Occupational vocal cord dysfunction due to exposure to wood dust and xerographic toner.

PubMed

Muñoz, Xavier; Roger, Alex; De la Rosa, David; Morell, Ferran; Cruz, Maria J

2007-04-01

Vocal cord dysfunction is a poorly understood entity that is often misdiagnosed as asthma. Both irritant and non-irritant vocal cord dysfunction have been described. This report presents two cases of irritant vocal cord dysfunction secondary to specific environmental exposure, the first to iroko and western red cedar wood (a carpenter) and the second to xerographic printing toner (a secretary). Several tests were performed, including chest radiographs, measurements of total serum immunoglobulin E, skin prick tests with common pneumoallergens (as well as iroko and western red cedar in the first case), pulmonary function studies, methacholine challenge testing, specific inhalation challenge performed with suspected agents in a single-blinded fashion, and peak expiratory flow testing and fiberoptic rhinolaryngoscopy (in case 1). During the specific inhalation challenge, the patients showed dysphonia, chest tightness, inspiratory stridor, and flattening of the inspiratory limb of the maximum flow-volume loop in spirometry, with no significant decreases in the level of forced expiratory volume in 1 second; fiberoptic rhinolaryngoscopy confirmed the diagnosis of vocal cord dysfunction in case 1. It is important to know that agents that can cause occupational asthma can also cause vocal cord dysfunction. The mechanisms by which these agents produce vocal cord dysfunction are unknown. The differences in the clinical presentation of the patients described relative to the reported cases suggest that more than one pathophysiological mechanism may be implicated in the genesis of this entity.

Revisiting an old concept: the coupled oscillator model for VCD. Part 2: implications of the generalised coupled oscillator mechanism for the VCD robustness concept.

PubMed

Nicu, Valentin Paul

2016-08-03

Using two illustrative examples it is shown that the generalised coupled oscillator (GCO) mechanism implies that the stability of the VCD sign computed for a given normal mode is not reflected by the magnitude of the ratio ζ between the rotational strength and dipole strength of the respective mode, i.e., the VCD robustness criterium proposed by Góbi and Magyarfalvi. The performed VCD GCO analysis brings further insight into the GCO mechanism and also into the VCD robustness concept. First, it shows that the GCO mechanism can be interpreted as a VCD resonance enhancement mechanism, i.e. very large VCD signals can be observed when the interacting molecular fragments are in favourable orientation. Second, it shows that the uncertainties observed in the computed VCD signs are associated to uncertainties in the relative orientation of the coupled oscillator fragments and/or to uncertainties in the predicted nuclear displacement vectors, i.e. not uncertainties in the computed magnetic dipole transition moments as was originally assumed. Since it is able to identify such situations easily, the VCD GCO analysis can be used as a VCD robustness analysis.

Glutathione S-transferase class mu regulation of apoptosis signal-regulating kinase 1 protein during VCD-induced ovotoxicity in neonatal rat ovaries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattacharya, Poulomi; Madden, Jill A.; Sen, Nivedita

2013-02-15

4-Vinylcyclohexene diepoxide (VCD) destroys ovarian primordial and small primary follicles via apoptosis. In mice, VCD exposure induces ovarian mRNA expression of glutathione S-transferase (GST) family members, including isoform mu (Gstm). Extra-ovarian GSTM negatively regulates pro-apoptotic apoptosis signal-regulating kinase 1 (ASK1) through protein complex formation, which dissociates during stress, thereby initiating ASK1-induced apoptosis. The present study investigated the ovarian response of Gstm mRNA and protein to VCD. Induction of Ask1 mRNA at VCD-induced follicle loss onset was determined. Ovarian GSTM:ASK1 protein complex formation was investigated and VCD exposure effects thereon evaluated. Phosphatidylinositol-3 kinase (PI3K) regulation of GSTM protein was also studied.more » Postnatal day (PND) 4 rat ovaries were cultured in control media ± 1) VCD (30 μM) for 2–8 days; 2) VCD (30 μM) for 2 days, followed by incubation in control media for 4 days (acute VCD exposure); or 3) LY294002 (20 μM) for 6 days. VCD exposure did not alter Gstm mRNA expression, however, GSTM protein increased (P < 0.05) after 6 days of both the acute and chronic treatments. Ask1 mRNA increased (0.33-fold; P < 0.05) relative to control after 6 days of VCD exposure. Ovarian GSTM:ASK1 protein complex formation was confirmed and, relative to control, the amount of GSTM bound to ASK1 increased 33% (P < 0.05) by chronic but with no effect of acute VCD exposure. PI3K inhibition increased (P < 0.05) GSTM protein by 40% and 71% on d4 and d6, respectively. These findings support involvement of GSTM in the ovarian response to VCD exposure, through regulation of pro-apoptotic ASK1. - Highlights: ► GSTM protein increases in response to ovarian VCD exposure. ► VCD increases Ask1 mRNA at the onset of follicle loss. ► Ovarian GSTM binds more ASK1 protein during VCD-induced ovotoxicity. ► PI3K regulates ovarian GSTM protein.« less

Loss of ovarian function in the VCD mouse-model of menopause leads to insulin resistance and a rapid progression into the metabolic syndrome.

PubMed

Romero-Aleshire, Melissa J; Diamond-Stanic, Maggie K; Hasty, Alyssa H; Hoyer, Patricia B; Brooks, Heddwen L

2009-09-01

Factors comprising the metabolic syndrome occur with increased incidence in postmenopausal women. To investigate the effects of ovarian failure on the progression of the metabolic syndrome, female B(6)C(3)F(1) mice were treated with 4-vinylcyclohexene diepoxide (VCD) and fed a high-fat (HF) diet for 16 wk. VCD destroys preantral follicles, causing early ovarian failure and is a well-characterized model for the gradual onset of menopause. After 12 wk on a HF diet, VCD-treated mice had developed an impaired glucose tolerance, whereas cycling controls were unaffected [12 wk AUC HF mice 13,455 +/- 643 vs. HF/VCD 17,378 +/- 1140 mg/dl/min, P < 0.05]. After 16 wk on a HF diet, VCD-treated mice had significantly higher fasting insulin levels (HF 5.4 +/- 1.3 vs. HF/VCD 10.1 +/- 1.4 ng/ml, P < 0.05) and were significantly more insulin resistant (HOMA-IR) than cycling controls on a HF diet (HF 56.2 +/- 16.7 vs. HF/VCD 113.1 +/- 19.6 mg/dl x microU/ml, P < 0.05). All mice on a HF diet gained more weight than mice on a standard diet, and weight gain in HF/VCD mice was significantly increased compared with HF cycling controls. Interestingly, even without a HF diet, progression into VCD-induced menopause caused a significant increase in cholesterol and free fatty acids. Furthermore, in mice fed a standard diet (6% fat), insulin resistance developed 4 mo after VCD-induced ovarian failure. Insulin resistance following ovarian failure (menopause) was prevented by estrogen replacement. Studies here demonstrate that ovarian failure (menopause) accelerates progression into the metabolic syndrome and that estrogen replacement prevents the onset of insulin resistance in VCD-treated mice. Thus, the VCD model of menopause provides a physiologically relevant means of studying how sex hormones influence the progression of the metabolic syndrome.

Application of improved technology to a preprototype vapor compression distillation /VCD/ water recovery subsystem

NASA Technical Reports Server (NTRS)

Johnson, K. L.; Reysa, R. P.; Fricks, D. H.

1981-01-01

Vapor compression distillation (VCD) is considered the most efficient water recovery process for spacecraft application. This paper reports on a preprototype VCD which has undergone the most extensive operational and component development testing of any VCD subsystem to date. The component development effort was primarily aimed at eliminating corrosion and the need for lubrication, upgrading electronics, and substituting nonmetallics in key rotating components. The VCD evolution is documented by test results on specific design and/or materials changes. Innovations worthy of further investigation and additional testing are summarized for future VCD subsystem development reference. Conclusions on experience gained are presented.

Evaluating diagnosis-based risk-adjustment methods in a population with spinal cord dysfunction.

PubMed

Warner, Grace; Hoenig, Helen; Montez, Maria; Wang, Fei; Rosen, Amy

2004-02-01

To examine performance of models in predicting health care utilization for individuals with spinal cord dysfunction. Regression models compared 2 diagnosis-based risk-adjustment methods, the adjusted clinical groups (ACGs) and diagnostic cost groups (DCGs). To improve prediction, we added to our model: (1) spinal cord dysfunction-specific diagnostic information, (2) limitations in self-care function, and (3) both 1 and 2. Models were replicated in 3 populations. Samples from 3 populations: (1) 40% of veterans using Veterans Health Administration services in fiscal year 1997 (FY97) (N=1,046,803), (2) veteran sample with spinal cord dysfunction identified by codes from the International Statistical Classification of Diseases, 9th Revision, Clinical Modifications (N=7666), and (3) veteran sample identified in Veterans Affairs Spinal Cord Dysfunction Registry (N=5888). Not applicable. Inpatient, outpatient, and total days of care in FY97. The DCG models (R(2) range,.22-.38) performed better than ACG models (R(2) range,.04-.34) for all outcomes. Spinal cord dysfunction-specific diagnostic information improved prediction more in the ACG model than in the DCG model (R(2) range for ACG,.14-.34; R(2) range for DCG,.24-.38). Information on self-care function slightly improved performance (R(2) range increased from 0 to.04). The DCG risk-adjustment models predicted health care utilization better than ACG models. ACG model prediction was improved by adding information.

Results of the Vapor Compression Distillation Flight Experiment (VCD-FE)

NASA Technical Reports Server (NTRS)

Hutchens, Cindy; Graves, Rex

2004-01-01

Vapor Compression Distillation (VCD) is the chosen technology for urine processing aboard the International Space Station (ISS). Key aspects of the VCD design have been verified and significant improvements made throughout the ground;based development history. However, an important element lacking from previous subsystem development efforts was flight-testing. Consequently, the demonstration and validation of the VCD technology and the investigation of subsystem performance in micro-gravity were the primary goals of the VCD-FE. The Vapor Compression Distillation Flight Experiment (VCD-E) was a flight experiment aboard the Space Shuttle Columbia during the STS-107 mission. The VCD-FE was a full-scale developmental version of the Space Station Urine Processor Assembly (UPA) and was designed to test some of the potential micro-gravity issues with the design. This paper summarizes the experiment results.

Effects of 4-Vinylcyclohexene Diepoxide on Peripubertal and Adult Sprague–Dawley Rats: Ovarian, Clinical, and Pathologic Outcomes

PubMed Central

Muhammad, F Salih; Goode, Amanda K; Kock, Nancy D; Arifin, Esther A; Cline, J Mark; Adams, Michael R; Hoyer, Patricia B; Christian, Patricia J; Isom, Scott; Kaplan, Jay R; Appt, Susan E

2009-01-01

Young rats treated daily with intraperitoneal 4-vinylcyclohexene diepoxide (VCD) undergo selective destruction of primordial follicles, resulting in gradual ovarian failure resembling the menopausal transition in women. To determine whether VCD has similar effects on ovaries of older rats, adult and peripubertal Sprague–Dawley rats were injected intraperitoneally daily for 30 d with vehicle or VCD at 40 or 80 mg/kg. Body weight, food intake, complete blood counts, and markers of liver injury and renal function were measured during VCD treatment. Complete gross necropsy and microscopic observations were performed on day 31, and ovarian follicles were counted. At 80 mg/kg, VCD destroyed primordial and primary follicles to a similar extent in both adult and peripubertal animals, although adult rats likely started with fewer follicles and therefore approached follicle depletion. Treatment with VCD did not affect body weight, but food intake was reduced in both adult and peripubertal rats treated with 80 mg/kg VCD. Adult rats treated with 80 mg/kg VCD had neutrophilia and increased BUN and creatinine; in addition, 4 of these rats were euthanized on days 25 or 26 due to peritonitis. VCD treatment did not increase alanine aminotransferase levels, a marker of liver injury, although the 80-mg/kg dose increased liver weights. In conclusion, VCD effectively destroys small preantral follicles in adult Sprague–Dawley rats, making them a suitable model of the menopausal transition of women. However, because adult rats were more sensitive to the irritant properties of VCD, the use of a lower dose should be considered. PMID:19295054

Dual protective role for Glutathione S-transferase class pi against VCD-induced ovotoxicity in the rat ovary

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keating, Aileen F.; Sen, Nivedita; Sipes, I. Glenn

2010-09-01

The occupational chemical 4-vinylcyclohexene diepoxide (VCD) selectively destroys ovarian small pre-antral follicles in rats and mice via apoptosis. Detoxification of VCD can occur through glutathione conjugation, catalyzed by glutathione S-transferase (GST) enzymes. Further, GST class pi (GSTp) can negatively regulate JNK activity through protein:protein interactions in extra-ovarian tissues. Dissociation of this protein complex in the face of chemical exposure releases the inhibition of pro-apoptotic JNK. Increased JNK activity during VCD-induced ovotoxicity has been shown in isolated ovarian small pre-antral follicles following in vivo dosing of rats (80 mg/kg/day; 15 days, i.p.). The present study investigated the pattern of ovarian GSTpmore » expression during VCD exposure. Additionally, the effect of VCD on an ovarian GSTp:JNK protein complex was investigated. PND4 F344 rat ovaries were incubated in control medium {+-} VCD (30 {mu}M) for 2-8 days. VCD increased ovarian GSTp mRNA (P < 0.05) relative to control on d4-d8; whereas GSTp protein was increased (P < 0.05) on d6-d8. A GSTp:JNK protein complex was detected by immunoprecipitation and Western blotting in ovarian tissues. Relative to control, the amount of GSTp-bound JNK was increased (P = 0.09), while unbound JNK was decreased (P < 0.05) on d6 of VCD exposure. The VCD-induced decrease in unbound JNK was preceded by a decrease in phosphorylated c-Jun which occurred on d4. These findings are in support of a possible dual protective role for GSTp in the rat ovary, consisting of metabolism of VCD and inhibition of JNK-initiated apoptosis.« less

Expression of ovarian microsomal epoxide hydrolase and glutathione S-transferase during onset of VCD-induced ovotoxicity in B6C3F{sub 1} mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keating, Aileen F.; Sipes, I. Glenn; Hoyer, Patricia B.

2008-07-01

4-vinylcyclohexene diepoxide (VCD) specifically destroys small pre-antral follicles in the rodent ovary. VCD can be detoxified to an inactive tetrol by microsomal epoxide hydrolase (mEH), or by conjugation to glutathione (GSH) by glutathione S-transferase (GST). Formation of VCD-GSH adducts in the mouse ovary 4 h after VCD exposure (0.57 mmol/kg/day) has been demonstrated. Because the mouse ovary expresses both mEH and GST, expression of mEH and GST pi and mu during a time-course of VCD-induced ovotoxicity was evaluated in a neonatal mouse ovarian culture system. Ovaries from postnatal day 4 (PND4) B6C3F{sub 1} mice were incubated with VCD (15 {mu}M)more » for 2, 4, 6, 8, 10, 12, or 15 days. Following incubation, ovaries were histologically evaluated, or assessed for mRNA or protein expression. VCD did not cause follicle loss (p > 0.05) on days 2, 4, or 6 of culture. At days 8, 10, 12, and 15, VCD reduced (p < 0.05) both primordial and primary follicle numbers. Increased (p < 0.05) expression of mEH, GST pi and GST mu mRNA was detected after 4 days of VCD exposure. This expression was reduced on days 6 and 8, when follicle loss was underway, but increased (p < 0.05) after 10 days of exposure. mEH and GST pi proteins were elevated (p < 0.05) following 8 days of VCD-exposure however there was no increase in GST mu protein. These findings suggest that with continuous exposure to VCD, increased expression of detoxification enzymes may participate in retarding the onset of follicle loss, but that this loss cannot ultimately be prevented.« less

Sexuality and sexual dysfunction in spinal cord-injured men in Turkey.

PubMed

Akman, Ramazan Yavuz; Coşkun Çelik, Evrim; Karataş, Metin

2015-01-01

To provide a comprehensive evaluation of sexual function and dysfunction in spinal cord-injured men based on self-reports of patients. Forty-seven spinal cord-injured men who completed the spinal shock and rehabilitation period were included. Patients were asked to complete a questionnaire developed to assess social status, sexual activities, abilities, and sexuality education after injury. Neurologic levels of patients were classified according to American Spinal Cord Injury Association protocol. Erectile function was evaluated by International Index of Erectile Function-5 (IIEF-5) questionnaire. Patients were aged between 20 and 62 years (mean: 35.2). Twenty-eight patients had T10 and above, 15 between T11 and L2, and 4 cauda conus injury. While 61.7% of the patients declared sexual activity, 93.6% declared some degree of erection. Mean IIEF-5 score was 5.3 and 87.3% of the patients had moderate to severe erectile dysfunction. Continuation of sexual activity after injury is very important and has a great impact on quality of life and interpersonal relationships for spinal cord-injured men. More attention must be given to sexuality after spinal cord injury. A very high rate of sexual dysfunction in spinal cord-injured patients was found and the importance of sexual education was emphasized in this study.

On vibrational circular dichroism chirality transfer in electron donor-acceptor complexes: a prediction for the quinine···BF3 system.

PubMed

Rode, Joanna E; Jamróz, Michał H; Dobrowolski, Jan Cz; Sadlej, Joanna

2012-08-02

Vibrational circular dichroism (VCD) chirality transfer occurs when an achiral molecule interacts with a chiral one and becomes VCD-active. Unlike for H-bonds, for organic electron donor-acceptor (EDA) complexes this phenomenon remains almost unknown. Here, the VCD chirality transfer from chiral quinine to achiral BF3 is studied at the B3LYP/aug-cc-pVDZ level. Accessibility of four quinine electron donor sites changes with conformation. Therefore, the quinine conformational landscape was explored and a considerable agreement between X-ray and the most stable conformer geometries was achieved. The BF3 complex through the aliphatic quinuclidine N atom is definitely dominating and is predicted to be easily recognizable in the VCD spectrum. Out of several VCD chirality transfer modes, the ν(s)(BF3) mode, the most intense in the entire VCD spectrum, satisfies the VCD mode robustness criterion and can be used for monitoring the chirality transfer phenomenon in quinine···BF3 system.

VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial.

PubMed

Moreau, Philippe; Hulin, Cyrille; Macro, Margaret; Caillot, Denis; Chaleteix, Carine; Roussel, Murielle; Garderet, Laurent; Royer, Bruno; Brechignac, Sabine; Tiab, Mourad; Puyade, Mathieu; Escoffre, Martine; Stoppa, Anne-Marie; Facon, Thierry; Pegourie, Brigitte; Chaoui, Driss; Jaccard, Arnaud; Slama, Borhane; Marit, Gerald; Laribi, Karim; Godmer, Pascal; Luycx, Odile; Eisenmann, Jean-Claude; Allangba, Olivier; Dib, Mamoun; Araujo, Carla; Fontan, Jean; Belhadj, Karim; Wetterwald, Marc; Dorvaux, Véronique; Fermand, Jean-Paul; Rodon, Philippe; Kolb, Brigitte; Glaisner, Sylvie; Malfuson, Jean-Valere; Lenain, Pascal; Biron, Laetitia; Planche, Lucie; Caillon, Helene; Avet-Loiseau, Herve; Dejoie, Thomas; Attal, Michel

2016-05-26

The Intergroupe Francophone du Myélome conducted a randomized trial to compare bortezomib-thalidomide-dexamethasone (VTD) with bortezomib-cyclophosphamide-dexamethasone (VCD) as induction before high-dose therapy and autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma. Overall, a total of 340 patients were centrally randomly assigned to receive VTD or VCD. After 4 cycles, on an intent-to-treat basis, 66.3% of the patients in the VTD arm achieved at least a very good partial response (primary end point) vs 56.2% in the VCD arm (P = .05). In addition, the overall response rate was significantly higher in the VTD arm (92.3% vs 83.4% in the VCD arm; P = .01). Hematologic toxicity was higher in the VCD arm, with significantly increased rates of grade 3 and 4 anemia, thrombocytopenia, and neutropenia. On the other hand, the rate of peripheral neuropathy (PN) was significantly higher in the VTD arm. With the exception of hematologic adverse events and PN, other grade 3 or 4 toxicities were rare, with no significant differences between the VTD and VCD arms. Our data support the preferential use of VTD rather than VCD in preparation for ASCT. This trial was registered at www.clinicaltrials.gov as #NCT01564537 and at EudraCT as #2013-003174-27. © 2016 by The American Society of Hematology.

The temporal profile of the reaction of microglia, astrocytes, and macrophages in the delayed onset paraplegia after transient spinal cord ischemia in rabbits.

PubMed

Matsumoto, Satoshi; Matsumoto, Mishiya; Yamashita, Atsuo; Ohtake, Kazunobu; Ishida, Kazuyoshi; Morimoto, Yasuhiro; Sakabe, Takefumi

2003-06-01

In the present study, we sought to elucidate the temporal profile of the reaction of microglia, astrocytes, and macrophages in the progression of delayed onset motor dysfunction after spinal cord ischemia (15 min) in rabbits. At 2, 4, 8, 12, 24, and 48 h after reperfusion (9 animals in each), hind limb motor function was assessed, and the lumbar spinal cord was histologically examined. Delayed motor dysfunction was observed in most animals at 48 h after ischemia, which could be predicted by a poor recovery of segmental spinal cord evoked potentials at 15 min of reperfusion. In the gray matter of the lumbar spinal cord, both microglia and astrocytes were activated early (2 h) after reperfusion. Microglia were diffusely activated and engulfed motor neurons irrespective of the recovery of segmental spinal cord evoked potentials. In contrast, early astrocytic activation was confined to the area where neurons started to show degeneration. Macrophages were first detected at 8 h after reperfusion and mainly surrounded the infarction area later. Although the precise roles of the activation of microglia, astrocytes, and macrophages are to be further determined, the results indicate that understanding functional changes of astrocytes may be important in the mechanism of delayed onset motor dysfunction including paraplegia. Microglia and macrophages play a role in removing tissue debris after transient spinal cord ischemia. Disturbance of astrocytic defense mechanism, breakdown of the blood-spinal cord barrier, or both seemed to be involved in the development of delayed motor dysfunction.

Lanthanide tris(β-diketonates) as useful probes for chirality determination of biological amino alcohols in vibrational circular dichroism: ligand to ligand chirality transfer in lanthanide coordination sphere.

PubMed

Miyake, Hiroyuki; Terada, Keiko; Tsukube, Hiroshi

2014-06-01

A series of lanthanide tris(β-diketonates) functioned as useful chirality probes in the vibrational circular dichroism (VCD) characterization of biological amino alcohols. Various chiral amino alcohols induced intense VCD signals upon ternary complexation with racemic lanthanide tris(β-diketonates). The VCD signals observed around 1500 cm(-1) (β-diketonate IR absorption region) correlated well with the stereochemistry and enantiomeric purity of the targeted amino alcohol, while the corresponding monoalcohol, monoamine, and diol substrates induced very weak VCD signals. The high-coordination number and dynamic property of the lanthanide complex offer an effective chirality VCD probing of biological substrates. © 2014 Wiley Periodicals, Inc.

Effectiveness of brain-based learning and animated cartoons for enhancing healthy habits among school children in Khon Kaen, Thailand.

PubMed

Banchonhattakit, Pannee; Duangsong, Rujira; Muangsom, Niramon; Kamsong, Theppamon; Phangwan, Krittiya

2015-03-01

The objective of this study was to investigate the effectiveness of brain-based learning (BBL) and animated cartoons on video compact discs (VCDs) in enhancing the healthy habits of school children. A representative sample of 1085 school children in the first through the third grades at 16 schools was selected by multistage random sampling. Knowledge of healthy habits and self-reported adoption of practices were assessed by a questionnaire. BBL and VCD, either combined or as single-intervention techniques, led to improved knowledge and practice of healthy behavior, whereas conventional teaching did not. As a single-intervention technique, BBL on its own led to a greater improvement in healthy practices than VCD, but the addition of BBL to VCD made no difference, and there was no difference between BBL and VCD in terms of improvements in knowledge. In conclusion, both BBL and VCD are effective, but VCD requires fewer resources. Recommendations are made for further research. © 2012 APJPH.

In vivo three-dimensional optical coherence tomography and multiphoton microscopy in a mouse model of ovarian neoplasia

NASA Astrophysics Data System (ADS)

Watson, Jennifer M.; Marion, Samuel L.; Rice, Photini Faith; Bentley, David L.; Besselsen, David; Utzinger, Urs; Hoyer, Patricia B.; Barton, Jennifer K.

2013-03-01

Our goal is to use optical coherence tomography (OCT) and multiphoton microscopy (MPM) to detect early tumor development in a mouse model of ovarian neoplasia. We hope to use information regarding early tumor development to create a diagnostic test for high-risk patients. In this study we collect in vivo images using OCT, second harmonic generation and two-photon excited fluorescence from non-vinylcyclohexene diepoxide (VCD)-dosed and VCD-dosed mice. VCD causes follicular apoptosis (simulating menopause) and leads to tumor development. Using OCT and MPM we visualized the ovarian microstructure and were able to see differences between non-VCD-dosed and VCD-dosed animals. This leads us to believe that OCT and MPM may be useful for detecting changes due to early tumor development.

Annual variations of monsoon and drought detected by GPS: A case study in Yunnan, China.

PubMed

Jiang, Weiping; Yuan, Peng; Chen, Hua; Cai, Jianqing; Li, Zhao; Chao, Nengfang; Sneeuw, Nico

2017-07-19

The Global Positioning System (GPS) records monsoonal precipitable water vapor (PWV) and vertical crustal displacement (VCD) due to hydrological loading, and can thus be applied jointly to diagnose meteorological and hydrological droughts. We have analyzed the PWV and VCD observations during 2007.0-2015.0 at 26 continuous GPS stations located in Yunnan province, China. We also obtained equivalent water height (EWH) derived from the Gravity Recovery And Climate Experiment (GRACE) and precipitation at these stations with the same period. Then, we quantified the annual variations of PWV, precipitation, EWH and VCD and provided empirical relationships between them. We found that GPS-derived PWV and VCD (positive means downward movement) are in phase with precipitation and GRACE-derived EWH, respectively. The annual signals of VCD and PWV show linearly correlated amplitudes and a two-month phase lag. Furthermore, the results indicate that PWV and VCD anomalies can also be used to explore drought, such as the heavy drought during winter/spring 2010. Our analysis results verify the capability of GPS to monitor monsoon variations and drought in Yunnan and show that a more comprehensive understanding of the characteristics of regional monsoon and drought can be achieved by integrating GPS-derived PWV and VCD with precipitation and GRACE-derived EWH.

Ovarian expressed microsomal epoxide hydrolase: Role in detoxification of 4-vinylcyclohexene diepoxide and regulation by phosphatidylinositol-3 kinase signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattacharya, Poulomi, E-mail: poulomib@iastate.edu; Sen, Nivedita, E-mail: nsen@email.arizona.edu; Hoyer, Patricia B., E-mail: Hoyer@u.arizona.edu

2012-01-01

4-vinylcyclohexene diepoxide (VCD) is a metabolite of 4-vinylcyclohexene (VCH) which has the potential to be formed in the ovary through CYP2E1 activity. VCD specifically destroys primordial and small primary follicles in the rodent ovary. Mouse ovaries exposed to VCD demonstrate increased mRNA and protein expression of microsomal epoxide hydrolase (mEH), and an inactive tetrol metabolite (4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane) can be formed in mouse ovarian follicles, potentially through detoxification action of mEH. In contrast, mEH can bioactivate another ovotoxic chemical, 7,12-dimethylbenz[a]anthracene (DMBA) to a more toxic compound, DMBA-3,4-diol-1,2-epoxide. Thus, the present study evaluated a functional role for mEH during detoxification of VCD. Additionally,more » because inhibition of the phosphatidyinositol-3 kinase (PI3K) signaling pathway in a previous study protected primordial follicles from VCD-induced destruction, but accelerated DMBA-induced ovotoxicity, a role for PI3K in ovarian mEH regulation was evaluated. Using a post-natal day (PND) 4 Fischer 344 rat whole ovary culture system inhibition of mEH using cyclohexene oxide during VCD exposure resulted in a greater (P < 0.05) loss of primordial and small primary follicles relative to VCD-treated ovaries. Also, relative to controls, meh mRNA was increased (P < 0.05) on day 4 of VCD (30 μM) exposure, followed by increased (P < 0.05) mEH protein after 6 days. Furthermore, inhibition of PI3K signaling increased mEH mRNA and protein expression. Thus, these results support a functional role for mEH in the rat ovary, and demonstrate the involvement of PI3K signaling in regulation of ovarian xenobiotic metabolism by mEH. -- Highlights: ► Ovarian mEH functions to metabolize VCD to a less toxic compound. ► mEH expression is increased in a temporal pattern in response to VCD exposure. ► PI3K signaling is involved in regulation of ovarian mEH expression.« less

7,12-dimethylbenz[a]anthracene-induced malignancies in a mouse model of menopause.

PubMed

Marion, Samuel L; Watson, Jennifer; Sen, Nivedita; Brewer, Molly A; Barton, Jennifer K; Hoyer, Patricia B

2013-02-01

Ovarian cancer has a high mortality rate because there are few symptoms in early disease development. The incidence of ovarian cancer increases in women after menopause. Understanding early events in this disease can best be achieved by using animal models. Therefore, the objective of this study was to develop and track the onset of ovarian tumorigenesis in mice mimicking characteristics of postmenopausal epithelial cancer in women. Female B6C3F1 mice (age, 28 d) received 4-vinylcyclohexene diepoxide (VCD, 160 mg/kg IV daily for 20 d) to cause ovarian failure. Four months after VCD treatment, via surgical intervention, each mouse received a single injection of 7,12-dimethylbenz[a]anthracene (DMBA) or vehicle control (sesame oil) under the bursa of the right ovary to cause ovarian neoplasms. The experimental groups were untreated controls (Con-Con), DMBA-treatment only (Con-DMBA), VCD treatment only (VCD-Con), and VCD+DMBA-treated (VCD+DMBA) mice. At 3, 5, 7, and 9 mo after DMBA injection, ovaries were collected for histologic and immunohistochemical evaluation. No tumors developed in Con-Con mice. All VCD-treated mice (with or without DMBA) exhibited ovarian failure. Mice that received both VCD and DMBA exhibited tumors at 3 mo (50%), 5 mo (14%), 7 mo (90%), and 9 mo (57%) after DMBA treatment; 31% of the tumors were epithelial in origin. Our findings confirm that inducing ovarian tumors in mice by chemical means is an effective method for studying early stages of tumor development that may be relevant to epithelial ovarian cancers that arise in postmenopausal women.

Spinal cord injury following operative shoulder intervention: A case report.

PubMed

Cleveland, Christine; Walker, Heather

2015-07-01

Cervical myelopathy is a spinal cord dysfunction that results from extrinsic compression of the spinal cord, its blood supply, or both. It is the most common cause of spinal cord dysfunction in patients greater than 55 years of age. A 57-year-old male with right shoulder septic arthritis underwent surgical debridement of his right shoulder and sustained a spinal cord injury intraoperatively. The most likely etiology is damage to the cervical spinal cord during difficult intubation requiring multiple attempts in this patient with underlying asymptomatic severe cervical stenosis. Although it is not feasible to perform imaging studies on all patients undergoing intubation for surgery, this patient's outcome would suggest consideration of inclusion of additional pre-surgical screening examination techniques, such as testing for a positive Hoffman's reflex, is appropriate to detect asymptomatic patients who may have underlying cervical stenosis.

Management of bladder dysfunction and satisfaction of life after spinal cord injury in Norway

PubMed Central

Hagen, Ellen Merete; Rekand, Tiina

2014-01-01

Background There is limited knowledge about bladder dysfunction and bladder management in persons with spinal cord injury (SCI) after discharge from the hospital in Norway. The impact of bladder dysfunction on satisfaction of life has been rarely explored. Setting Community-based survey from Norway. Methods An anonymous cross-sectional postal survey. A questionnaire was sent to the registered members of the Norwegian Spinal Cord Injuries Association. A total of 400 participants, with traumatic or non-traumatic SCI, received the questionnaire. Results A total of 248 subjects (62%), 180 men and 68 women, answered the questionnaire. Mean age was 54 years and mean time since injury 13.4 years. A total of 164 participants (66.1%) used intermittent catheterization for bladder emptying (48.5% women versus 72.8% men); more paraplegics than tetraplegics (77.2% versus 55.7%). Recommendations given at the Spinal Cord Units were thoroughly followed by persons who had used catheters more than 5 years. Use of incontinence pads were associated with reduced satisfaction of life. Conclusions The most common method of management of bladder dysfunction is clean intermittent catheterization in Norway. Recommendations were followed more thoroughly by persons who have used intermittent catheterization for more than 5 years. Spinal Cord Units are important source for information and guidance. PMID:24621024

Management of bladder dysfunction and satisfaction of life after spinal cord injury in Norway.

PubMed

Hagen, Ellen Merete; Rekand, Tiina

2014-05-01

There is limited knowledge about bladder dysfunction and bladder management in persons with spinal cord injury (SCI) after discharge from the hospital in Norway. The impact of bladder dysfunction on satisfaction of life has been rarely explored. Community-based survey from Norway. An anonymous cross-sectional postal survey. A questionnaire was sent to the registered members of the Norwegian Spinal Cord Injuries Association. A total of 400 participants, with traumatic or non-traumatic SCI, received the questionnaire. A total of 248 subjects (62%), 180 men and 68 women, answered the questionnaire. Mean age was 54 years and mean time since injury 13.4 years. A total of 164 participants (66.1%) used intermittent catheterization for bladder emptying (48.5% women versus 72.8% men); more paraplegics than tetraplegics (77.2% versus 55.7%). Recommendations given at the Spinal Cord Units were thoroughly followed by persons who had used catheters more than 5 years. Use of incontinence pads were associated with reduced satisfaction of life. The most common method of management of bladder dysfunction is clean intermittent catheterization in Norway. Recommendations were followed more thoroughly by persons who have used intermittent catheterization for more than 5 years. Spinal Cord Units are important source for information and guidance.

Life Testing of the Vapor Compression Distillation/Urine Processing Assembly (VCD/UPA) at the Marshall Space Flight Center (1993 to 1997)

NASA Technical Reports Server (NTRS)

Wieland, P.; Hutchens, C.; Long, D.; Salyer, B.

1998-01-01

Wastewater and urine generated on the International Space Station will be processed to recover pure water using vapor compression distillation (VCD). To verify the long-term reliability and performance of the VCD Urine Processor Assembly (UPA), life testing was performed at the Marshall Space Flight Center (MSFC) from January 1993 to April 1996. Two UPA'S, the VCD-5 and VCD-5A, were tested for 204 days and 665 days, respectively. The compressor gears and the distillation centrifuge drive belt were found to have operating lives of approximately 4,800 hours, equivalent to 3.9 years of operation on ISS for a crew of three at an average processing rate of 1.76 kg/h (3.97 lb/h). Precise alignment of the flex-splines of the fluids and purge pump motor drives is essential to avoid premature failure after about 400 hours of operation. Results indicate that, with some design and procedural modifications and suitable quality control, the required performance and operational life can be met with the VCD/UPA.

Life Testing of the Vapor Compression Distillation Urine Processing Assembly (VCD/UPA) at the Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

Wieland, Paul O.

1998-01-01

Wastewater and urine generated on the International Space Station will be processed to recover pure water. The method selected is vapor compression distillation (VCD). To verify the long-term reliability and performance of the VCD Urine Processing Assembly (UPA), accelerated life testing was performed at the Marshall Space Flight Center (MSFC) from January 1993 to April 1996. Two UPAS, the VCD-5 and VCD-5A, were tested for 204 days and 665 days, respectively. The compressor gears and the distillation centrifuge drive belt were found to have an operating life of approximately 4800 hours. Precise alignment of the flex-spline of the fluids pump is essential to avoid failure of the pump after about 400 hours of operation. Also, leakage around the seals of the drive shaft of the fluids pump and purge pump must be eliminated for continued good performance. Results indicate that, with some design and procedural modifications and suitable quality control, the required performance and operational life can be met with the VCD/UPA.

Asthma mimic: Case report and literature review of vocal cord nodule associated with wheezing.

PubMed

Kashif, Muhammad; Singh, Tushi; Aslam, Ahsan; Khaja, Misbahuddin

2017-01-01

Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. Various clinical conditions can mimic asthma, such as foreign body aspiration, subglottic stenosis, congestive heart failure, diffuse panbronchiolitis, aortic arch anomalies, reactive airway dysfunction syndrome, chronic obstructive pulmonary disease, retrosternal goiter, vocal cord tumors, other airway tumors, and vocal cord dysfunction. Upper airway obstruction can be a life-threatening emergency. Here, we present the case of a 58-year-old female with recurrent hospital visits for wheezing and exacerbations of asthma, who was later found to have a vocal cord nodule confirmed to be squamous cell carcinoma, which was mimicking like asthma.

[The Effectiveness of Abdominal Massage on Neurogenic Bowel Dysfunction in Patients With Spinal Cord Injury: A Systematic Review].

PubMed

Wu, Tzu-Jung; Lin, Chiu-Chu; Wang, Hsiu-Hung

2017-02-01

Neurogenic bowel dysfunction is a common comorbidity in spinal cord injury patients that may result in fecal incontinence. Abdominal massage is one intestinal training method that is used to improve bowel movement and defecation. To review the effectiveness of abdominal massage on neurogenic bowel dysfunction in patients with spinal cord injury. A systematic review of Chinese and English-language articles was performed in six databases using the following key words: spinal cord injury, abdominal massage, neurogenic bowel dysfunction, and bowel training. Relevant studies published prior to June 2016 that met the inclusion and exclusion criteria were selected. The Downs and Black scale was used to appraise the quality of each of the included studies. Eight studies were included in the final analysis. Four of these studies indicated that abdominal massage significantly improved bowel functions and the regularity and frequency of bowel movements. Although two of the studies indicated that abdominal massage significantly reduced the use of glycerin and laxatives, the remaining six did not. The eight studies earned respective quality scores ranging between 13 and 25. The current literature lacks consensus on the efficacy of abdominal massage in terms of improving bowel dysfunction in patients with spinal cord injuries. Future studies should use more stringent experimental designs such as randomized controlled studies to explore the correlations among massage time and frequency and bowel function improvements in order to provide guidelines for clinical care applications.

Rationale and design of a randomised clinical trial comparing vascular closure device and manual compression to achieve haemostasis after diagnostic coronary angiography: the Instrumental Sealing of ARterial puncture site - CLOSURE device versus manual compression (ISAR-CLOSURE) trial.

PubMed

Xhepa, Erion; Byrne, Robert A; Schulz, Stefanie; Helde, Sandra; Gewalt, Senta; Cassese, Salvatore; Linhardt, Maryam; Ibrahim, Tareq; Mehilli, Julinda; Hoppe, Katharina; Grupp, Katharina; Kufner, Sebastian; Böttiger, Corinna; Hoppmann, Petra; Burgdorf, Christof; Fusaro, Massimiliano; Ott, Ilka; Schneider, Simon; Hengstenberg, Christian; Schunkert, Heribert; Laugwitz, Karl-Ludwig; Kastrati, Adnan

2014-06-01

Vascular closure devices (VCD) have been introduced into clinical practice with the aim of increasing the procedural efficiency and clinical safety of coronary angiography. However, clinical studies comparing VCD and manual compression have yielded mixed results, and large randomised clinical trials comparing the two strategies are missing. Moreover, comparative efficacy studies between different VCD in routine clinical use are lacking. The Instrumental Sealing of ARterial puncture site - CLOSURE device versus manual compression (ISAR-CLOSURE) trial is a prospective, randomised clinical trial designed to compare the outcomes associated with the use of VCD or manual compression to achieve femoral haemostasis. The test hypothesis is that femoral haemostasis after coronary angiography achieved using VCD is not inferior to manual compression in terms of access-site-related vascular complications. Patients undergoing coronary angiography via the common femoral artery will be randomised in a 1:1:1 fashion to receive FemoSeal VCD, EXOSEAL VCD or manual compression. The primary endpoint is the incidence of the composite of arterial access-related complications (haematoma ≥5 cm, pseudoaneurysm, arteriovenous fistula, access-site-related bleeding, acute ipsilateral leg ischaemia, the need for vascular surgical/interventional treatment or documented local infection) at 30 days after randomisation. According to power calculations based on non-inferiority hypothesis testing, enrolment of 4,500 patients is planned. The trial is registered at www.clinicaltrials.gov (study identifier: NCT01389375). The safety of VCD as compared to manual compression in patients undergoing transfemoral coronary angiography remains an issue of clinical equipoise. The aim of the ISAR-CLOSURE trial is to assess whether femoral haemostasis achieved through the use of VCD is non-inferior to manual compression in terms of access-site-related vascular complications.

Testing the impact of a multimedia video CD of patient-controlled analgesia on pain knowledge and pain relief in patients receiving surgery.

PubMed

Chen, Hsing-Hsia; Yeh, Mei-Ling; Yang, Hui-Ju

2005-07-01

This study aimed to develop a multimedia video CD (VCD) of patient-controlled analgesia (PCA) and test its effects on pain knowledge and pain relief in patients receiving surgery. This multimedia VCD of PCA was created to convey fundamental knowledge to both patients and their family members and help patients properly utilize PCA devices to relieve pain and improve recovery. The content of multimedia VCD of PCA included pre-admission pain education, introduction of PCA, nursing care procedures, and questions and answers. This study used a quasi-experimental research design to test effects of the multimedia education program in the experimental group of 30 subjects compared to the control subjects of equal number (without the multimedia VCD of PCA). (1) The intervention of multimedia VCD of PCA resulted in a statistically significant difference in pain knowledge between the experimental and control groups. (2) Subjects in the experimental group obtained a better outcome of pain relief compared to control subjects. (3) Subjects in the experimental group indicated that the multimedia VCD of PCA indeed helped them effectively operate their PCA devices to relieve surgery pain. The clinical application of the multimedia VCD of PCA could help patients improve knowledge on pain, learn how to use PCA devices, achieve proper pain relief, and increase effectiveness of recovery activities.

Analysis of the major chiral compounds of Artemisia herba-alba essential oils (EOs) using reconstructed vibrational circular dichroism (VCD) spectra: En route to a VCD chiral signature of EOs.

PubMed

Said, Mohammed El-Amin; Vanloot, Pierre; Bombarda, Isabelle; Naubron, Jean-Valère; Dahmane, El Montassir; Aamouche, Ahmed; Jean, Marion; Vanthuyne, Nicolas; Dupuy, Nathalie; Roussel, Christian

2016-01-15

An unprecedented methodology was developed to simultaneously assign the relative percentages of the major chiral compounds and their prevailing enantiomeric form in crude essential oils (EOs). In a first step the infrared (IR) and vibrational circular dichroism (VCD) spectra of the crude essential oils were recorded and in a second step they were modelized as a linear weighted combination of the IR and VCD spectra of the individual spectra of pure enantiomer of the major chiral compounds present in the EOs. The VCD spectra of enantiomer of known enantiomeric excess shall be recorded if they are not yet available in a library of VCD spectra. For IR, the spectra of pure enantiomer or racemic mixture can be used. The full spectra modelizations were performed using a well known and powerful mathematical model (least square estimation: LSE) which resulted in a weighting of each contributing compound. For VCD modelization, the absolute value of each weighting represented the percentage of the associate compound while the attached sign addressed the correctness of the enantiomeric form used to build the model. As an example, a model built with the non-prevailing enantiomer will show a negative sign of the weighting value. For IR spectra modelization, the absolute value of each weighting represented the percentage of the compounds without of course accounting for the chirality of the prevailing enantiomers. Comparison of the weighting values issuing from IR and VCD spectra modelizations is a valuable source of information: if they are identical, the EOs are composed of nearly pure enantiomers, if they are different the chiral compounds of the EOs are not in an optically pure form. The method was applied on four samples of essential oil of Artemisia herba-alba in which the three major compounds namely (-)-α-thujone, (+)-β-thujone and (-)-camphor were found in different proportions as determined by GC-MS and chiral HPLC using polarimetric detector. In order to validate the methodology, the modelization of the VCD spectra was performed on purpose using the individual VCD spectra of (-)-α-thujone, (+)-β-thujone and (+)-camphor instead of (-)-camphor. During this work, the absolute configurations of (-)-α-thujone and (+)-β-thujone were confirmed by comparison of experimental and calculated VCD spectra as being (1S,4R,5R) and (1S,4S,5R) respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison of cyclophosphamide-thalidomide-dexamethasone to bortezomib-cyclophosphamide-dexamethasone as induction therapy for multiple myeloma patients in Brazil.

PubMed

Vigolo, Suelen; Zuckermann, Joice; Bittencourt, Rosane Isabel; Silla, Lúcia; Pilger, Diogo André

2017-09-01

Chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) remains the standard treatment for multiple myeloma (MM). Thalidomide or bortezomib may be combined with cyclophosphamide and dexamethasone, in what are known as the CTD and VCD protocols, respectively. The objective of this study was to evaluate the clinical characteristics and response rates obtained with CTD and VCD, observing whether the inclusion of bortezomib to treat MM patients in Brazil increases therapeutic efficiency. Forty-three MM patients treated with induction protocols CTD and VCD between January 2010 and March 2015 were included. The parameters analyzed were staging, frequency of comorbidities prior to treatment, response rates obtained at each induction cycle, progression-free survival, and overall survival of patients. Very good partial response and complete response obtained with the VCD protocol were superior, compared with the CTD treatment. The presence of comorbidities was similar in the two groups, except kidney failure, which prevailed in the VCD group. Also, 78.3% and 48.3% of patients treated with the VCD and CTD protocols underwent autologous HSCT, respectively. In patients given the VCD protocol, 45.5% had complete response before autologous HSCT. Among those given CTD, this number was only 7.1% (p=0.023). Disease progression after autologous HSCT did not differ between the two groups. VCD afforded better responses than the CTD protocol, and improved patient condition before autologous HSCT. However, more studies are necessary including more patients and addressing various clinical conditions, besides the analysis of cost-effectiveness of these treatments. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

Psychogenic Respiratory Distress: A Case of Paradoxical Vocal Cord Dysfunction and Literature Review

PubMed Central

Leo, Raphael J.; Konakanchi, Ramesh

1999-01-01

Background: Pulmonary disease such as asthma is a psychosomatic disorder vulnerable to exacerbations precipitated by psychological factors. A case is described in which a patient thought to have treatment-refractory asthma was discovered to have a conversion reaction, specifically paradoxical vocal cord dysfunction (PVCD), characterized by abnormal vocal cord adduction during inspiration. Data Sources: Reports of PVCD were located using a MEDLINE search and review of bibliographies. MEDLINE (English language only) was searched from 1966 through December 1998 using the terms functional asthma, functional upper airway obstruction, laryngeal diseases, Munchausen's stridor, paradoxical vocal cord dysfunction, psychogenic stridor, respiratory stridor, vocal cord dysfunction, and vocal cord paralysis. A total of 170 cases of PVCD were reviewed. Study Findings: PVCD appears to be significantly more common among females. PVCD spans all age groups, including pediatric, adolescent, and adult patients. PVCD was most often misdiagnosed as asthma or upper airway disease. Because patients present with atypical and/or refractory symptoms, several diagnostic tests are employed to evaluate patients with PVCD; laryngoscopy is the most common. Direct visualization of abnormal vocal cord movement is the most definitive means of establishing the diagnosis of PVCD. A number of psychiatric disturbances are related to PVCD, including conversion and anxiety disorders. PVCD is associated with severe psychosocial stress and difficulties with modulation of intense emotional states. Conclusions: Psychogenic respiratory distress produced by PVCD can be easily misdiagnosed as severe or refractory asthma or other pulmonary disease states. Recognition of PVCD is important to avoid unnecessary medications and invasive treatments. Primary care physicians can detect cases of PVCD by attending to clinical symptoms, implementing appropriate laboratory investigations, and examining the psychological covariates of the disorder. Psychotherapy and speech therapy are effective in treating most cases of PVCD. PMID:15014694

Complications with Angio-Seal™ vascular closure devices compared with manual compression after diagnostic cardiac catheterization and percutaneous coronary intervention.

PubMed

Gregory, Deborah; Midodzi, William; Pearce, Neil

2013-12-01

This study assessed and compared vascular complications in CATHs and PCIs using an Angio-Seal™ vascular closure device (VCD) versus manual compression (MC). Secondary data analysis of a population-based multiyear cohort database was conducted to compare femoral access-related vascular outcomes in cardiac procedures using VCD and MC between May 1, 2006 and December 31, 2010. The primary outcome was any vascular complication. Propensity score adjusted analysis was conducted to reduce bias associated with covariate imbalance between the groups compared. Of the 11,897 procedures, 7,063 (59.4%) used a VCD. Vascular complications occurred in 174/8,796 (2.0%) of CATHs and 82/3,004 (2.7%) of PCIs. In the CATH sample, the odds of vascular complication were 57% lower if a VCD was used (OR = 0.43, 95% CI 0.31-0.60). For the PCI sample, the risk was 49% lower if a VCD was used (OR = 0.51, 95% CI 0.31-0.81). A low incidence of vascular complications was observed with the use of an Angio-Seal VCD relative to MC for both procedures. © 2013, Wiley Periodicals, Inc.

Sexual Functioning in Men Living with a Spinal Cord Injury-A Narrative Literature Review.

PubMed

Sunilkumar, M M; Boston, Patricia; Rajagopal, M R

2015-01-01

Sexual dysfunction is a major concern for Indian men living with a spinal cord injury. To examine the literature related to sexuality traumatic cord injury and its impact on sexual functioning. Databases using Cumulative Index to Nursing and Allied Health Literature (CINAHL) 2000-2012, Medline 1989-2012, Applied Social Sciences Index and Abstracts (ASSIA) 1989-2012 and Google Scholar were the search engines used used for literature review. The search yielded a total of 457 articles and only 75 of them were found relevant. The minimum number of articles required to meet the inclusion criteria for this review was 25-30 articles. Out of the 75 articles, 33 were considered relevant or related to the topic of sexual functioning, spinal cord injury, and paraplegia. Six areas were identified: Sexual stigmatization, physiological barriers to sexual satisfaction, clinical aspects of sexual functioning, biomedical approaches to sexual dysfunction, partner satisfaction, and lack of accessibility to sexual education. Spinal cord injury and sexual functioning affects a large segment of the male Indian population, yet most current research focuses on quantitative measurement with the emphasis on ejaculatory dysfunction, orgasm impairment, incontinence, and other physiological dysfunction. Further research is needed to address the subjective accounts of patients themselves with respect to the emotional and social impact of sexual disability. This would help to identify the best possible outcomes for both treatment and rehabilitation.

Survey of spinal cord injury-induced neurogenic bladder studies using the Web of Science.

PubMed

Zou, Benjing; Zhang, Yongli; Li, Yucheng; Wang, Zantao; Zhang, Ping; Zhang, Xiyin; Wang, Bingdong; Long, Zhixin; Wang, Feng; Song, Guo; Wang, Yan

2012-08-15

To identify global trends in research on spinal cord injury-induced neurogenic bladder, through a bibliometric analysis using the Web of Science. We performed a bibliometric analysis of studies on spinal cord injury-induced neurogenic bladder using the Web of Science. Data retrieval was performed using key words "spinal cord injury", "spinal injury", "neurogenic bladder", "neuropathic bladder", "neurogenic lower urinary tract dysfunction", "neurogenic voiding dysfunction", "neurogenic urination disorder" and "neurogenic vesicourethral dysfunction". (a) published peer-reviewed articles on spinal cord injury-induced neurogenic bladder indexed in the Web of Science; (b) type of articles: original research articles and reviews; (c) year of publication: no limitation. (a) articles that required manual searching or telephone access; (b) Corrected papers and book chapters. (1) Annual publication output; (2) distribution according to journals; (3) distribution according to subject areas; (4) distribution according to country; (5) distribution according to institution; and (6) top cited publications. There were 646 research articles addressing spinal cord injury-induced neurogenic bladder in the Web of Science. Research on spinal cord injury-induced neurogenic bladder was found in the Science Citation Index-Expanded as of 1946. The United States, Ireland and Switzerland were the three major countries contributing to studies in spinal cord injury-induced neurogenic bladder in the 1970s. However, in the 1990s, the United States, the United Kingdom, the Netherlands, Germany and Japan published more papers on spinal cord injury-induced neurogenic bladder than Switzerland, and Ireland fell off the top ten countries list. In this century, the United States ranks first in spinal cord injury-induced neurogenic bladder studies, followed by France, the United Kingdom, Germany, Switzerland and Japan. Subject categories including urology, nephrology and clinical neurology, as well as rehabilitation, are represented in spinal cord injury-induced neurogenic bladder studies. From our analysis of the literature and research trends, we conclude that spinal cord injury-induced neurogenic bladder is a hot topic that will continue to generate considerable research interest in the future.

Vapor Compression Distillation Urine Processor Lessons Learned from Development and Life Testing

NASA Technical Reports Server (NTRS)

Hutchens, Cindy F.; Long, David A.

1999-01-01

Vapor Compression Distillation (VCD) is the chosen technology for urine processing aboard the International Space Station (155). Development and life testing over the past several years have brought to the forefront problems and solutions for the VCD technology. Testing between 1992 and 1998 has been instrumental in developing estimates of hardware life and reliability. It has also helped improve the hardware design in ways that either correct existing problems or enhance the existing design of the hardware. The testing has increased the confidence in the VCD technology and reduced technical and programmatic risks. This paper summarizes the test results and changes that have been made to the VCD design.

Optical spectroscopic elucidation of beta-turns in disulfide bridged cyclic tetrapeptides.

PubMed

Borics, Attila; Murphy, Richard F; Lovas, Sándor

2007-01-01

Vibrational circular dichroism (VCD) spectroscopic features of type II beta-turns were characterized previously, but, criteria for differentiation between beta-turn types had not been established yet. Model tetrapeptides, cyclized through a disulfide bridge, were designed on the basis of previous experimental results and the observed incidence of amino acid residues in the i + 1 and i + 2 positions in beta-turns, to determine the features of VCD spectra of type I and II beta-turns. The results were correlated with electronic circular dichroism (ECD) spectra and VCD spectra calculated from conformational data obtained by molecular dynamics (MD) simulations. All cyclic tetrapeptides yielded VCD signals with a higher frequency negative and a lower frequency positive couplet with negative lobes overlapping. MD simulations confirmed the conformational homogeneity of these peptides in solution. Comparison with ECD spectroscopy, MD, and quantum chemical calculation results suggested that the low frequency component of VCD spectra originating from the tertiary amide vibrations could be used to distinguish between types of beta-turn structures. On the basis of this observation, VCD spectroscopic features of type II and VIII beta-turns and ECD spectroscopic properties of a type VIII beta-turn were suggested. The need for independent experimental as well as theoretical investigations to obtain decisive conformational information was recognized. Copyright 2006 Wiley Periodicals, Inc.

Valnoctamide, which reduces rat brain arachidonic acid turnover, is a potential non-teratogenic valproate substitute to treat bipolar disorder.

PubMed

Modi, Hiren R; Ma, Kaizong; Chang, Lisa; Chen, Mei; Rapoport, Stanley I

2017-08-01

Valproic acid (VPA), used for treating bipolar disorder (BD), is teratogenic by inhibiting histone deacetylase. In unanaesthetized rats, chronic VPA, like other mood stabilizers, reduces arachidonic acid (AA) turnover in brain phospholipids, and inhibits AA activation to AA-CoA by recombinant acyl-CoA synthetase-4 (Acsl-4) in vitro. Valnoctamide (VCD), a non-teratogenic constitutional isomer of VPA amide, reported effective in BD, also inhibits recombinant Acsl-4 in vitro. VCD like VPA will reduce brain AA turnover in unanaesthetized rats. A therapeutically relevant (50mg/kg i.p.) dose of VCD or vehicle was administered daily for 30 days to male rats. AA turnover and related parameters were determined using our kinetic model, following intravenous [1- 14 C]AA in unanaesthetized rats for 10min, and measuring labeled and unlabeled lipids in plasma and high-energy microwaved brain. VCD, compared with vehicle, increased λ, the ratio of brain AA-CoA to unesterified plasma AA specific activities; and decreased turnover of AA in individual and total brain phospholipids. VCD's ability like VPA to reduce rat brain AA turnover and inhibit recombinant Acsl-4, and its efficacy in BD, suggest that VCD be further considered as a non-teratogenic VPA substitute for treating BD. Published by Elsevier B.V.

[The design and content validity of an infection control health education program for adolescents with cancer].

PubMed

Wang, Huey-Yuh; Chen, Yueh-Chih; Lin, Dong-Tsamn; Gau, Bih-Shya

2005-06-01

The purpose of this article is to describe the process of designing an Infection Control Health Education Program (ICP) for adolescents with cancer, to describe the content of that program, and to evaluate its validity. The program consisted of an audiovisual "Infection Control Health Education Program in Video Compact Disc (VCD)" and "Self-Care Daily Checklist (SCDC)". The VCD was developed from systematic literature reviews and consultations with experts in pediatric oncology care. It addresses the main issues of infection control among adolescents. The content of the SCDC was designed to enhance adolescents' self-care capabilities by means of twice daily self-recording. The response format for content validity of the VCD and SCDC was a 5-point Likert scale. The mean score for content validity was 4.72 for the VCD and 4.82 for the SCDC. The percentage of expert agreement was 99% for the VCD and 98% for the SCDC. In summary, the VCD was effective in improving adolescents' capacity for self-care and the extensive reinforcement SCDC was also shown to be useful. In a subsequent pilot study, the authors used this program to increase adolescent cancer patients' self-care knowledge and behavior for, and decrease their levels of secondary infection.

7,12-Dimethylbenz[a]anthracene-Induced Malignancies in a Mouse Model of Menopause

PubMed Central

Marion, Samuel L; Watson, Jennifer; Sen, Nivedita; Brewer, Molly A; Barton, Jennifer K; Hoyer, Patricia B

2013-01-01

Ovarian cancer has a high mortality rate because there are few symptoms in early disease development. The incidence of ovarian cancer increases in women after menopause. Understanding early events in this disease can best be achieved by using animal models. Therefore, the objective of this study was to develop and track the onset of ovarian tumorigenesis in mice mimicking characteristics of postmenopausal epithelial cancer in women. Female B6C3F1 mice (age, 28 d) received 4-vinylcyclohexene diepoxide (VCD, 160 mg/kg IV daily for 20 d) to cause ovarian failure. Four months after VCD treatment, via surgical intervention, each mouse received a single injection of 7,12-dimethylbenz[a]anthracene (DMBA) or vehicle control (sesame oil) under the bursa of the right ovary to cause ovarian neoplasms. The experimental groups were untreated controls (Con–Con), DMBA-treatment only (Con–DMBA), VCD treatment only (VCD–Con), and VCD+DMBA-treated (VCD+DMBA) mice. At 3, 5, 7, and 9 mo after DMBA injection, ovaries were collected for histologic and immunohistochemical evaluation. No tumors developed in Con–Con mice. All VCD-treated mice (with or without DMBA) exhibited ovarian failure. Mice that received both VCD and DMBA exhibited tumors at 3 mo (50%), 5 mo (14%), 7 mo (90%), and 9 mo (57%) after DMBA treatment; 31% of the tumors were epithelial in origin. Our findings confirm that inducing ovarian tumors in mice by chemical means is an effective method for studying early stages of tumor development that may be relevant to epithelial ovarian cancers that arise in postmenopausal women. PMID:23561932

Sexual Functioning in Men Living with a Spinal Cord Injury–A Narrative Literature Review

PubMed Central

Sunilkumar, MM; Boston, Patricia; Rajagopal, MR

2015-01-01

Background: Sexual dysfunction is a major concern for Indian men living with a spinal cord injury Objectives: To examine the literature related to sexuality traumatic cord injury and its impact on sexual functioning. Materials and Methods: Databases using Cumulative Index to Nursing and Allied Health Literature (CINAHL) 2000–2012, Medline 1989–2012, Applied Social Sciences Index and Abstracts (ASSIA) 1989–2012 and Google Scholar were the search engines used used for literature review. Results: The search yielded a total of 457 articles and only 75 of them were found relevant. The minimum number of articles required to meet the inclusion criteria for this review was 25–30 articles. Out of the 75 articles, 33 were considered relevant or related to the topic of sexual functioning, spinal cord injury, and paraplegia. Six areas were identified: Sexual stigmatization, physiological barriers to sexual satisfaction, clinical aspects of sexual functioning, biomedical approaches to sexual dysfunction, partner satisfaction, and lack of accessibility to sexual education. Conclusion: Spinal cord injury and sexual functioning affects a large segment of the male Indian population, yet most current research focuses on quantitative measurement with the emphasis on ejaculatory dysfunction, orgasm impairment, incontinence, and other physiological dysfunction. Further research is needed to address the subjective accounts of patients themselves with respect to the emotional and social impact of sexual disability. This would help to identify the best possible outcomes for both treatment and rehabilitation. PMID:26600694

Long Term Outcome after Application of the Angio-Seal Vascular Closure Device in Minipigs

PubMed Central

Kabelitz, Lisa; Nonn, Andrea; Nolte, Kay W.; Nikoubashman, Omid; Othman, Ahmed; Heringer, Sarah; Kramer, Martin; Wiesmann, Martin; Brockmann, Marc A.

2016-01-01

Minipigs are frequently used in (neuro-)interventional research. Longitudinal experiments may require repeated vessel access via the femoral artery. Anticoagulation and incompliance of the animals necessitates the use of a vascular closure device (VCD). The effects of the Angio-Seal VCD in minipigs were longitudinally assessed. Minipig (42±8.4 kg body weight) femoral arteries were sealed using the 8F (n = 6) or 6F (n = 7) Angio-Seal VCD. The pre-interventional femoral artery diameter was 5.1±0.4 mm (4.3–5.8 mm). Sealed puncture sites were analysed angiographically as well as by computed tomography angiography (CTA) for a mean period of 14.1±8.0 weeks (1–22 weeks). All animals were constantly treated with acetylsalicylic acid (ASS) (450 mg/d (n = 7) or 100 mg/d (n = 1)) and clopidogrel (75 mg/d (n = 8)). Non-instrumented (n = 2) and arteries sealed using the VCD (n = 2) were examined histologically. No postoperative hemorrhagic complications were observed. Three arteries were occluded after VCD placement (1 animal diagnosed after 4 weeks (8F), 2 animals after 1 week (6F)) and remained so until the end of the experiments after 22, 12 and 4 weeks, respectively. In one artery a 50% stenosis 8 weeks after application of a 6F Angio-Seal was detected. In 69.2% (n = 9) the VCD was applied without complications. Histopathological analysis of the sealed arterial segments showed subtotal obliteration of the vessel lumen, formation of collagenous tissue and partial damage of the internal elastic lamina. The Angio-Seal VCD prevents relevant hemorrhagic complications in minipigs treated with dual platelet inhibition, but is associated with increased vessel occlusion rates. PMID:27682594

Repositioning of Verrucosidin, a Purported Inhibitor of Chaperone Protein GRP78, as an Inhibitor of Mitochondrial Electron Transport Chain Complex I

PubMed Central

Gonzalez, Reyna; Pao, Peng-Wen; Hofman, Florence M.; Chen, Thomas C.; Louie, Stan G.; Pirrung, Michael C.; Schönthal, Axel H.

2013-01-01

Verrucosidin (VCD) belongs to a group of fungal metabolites that were identified in screening programs to detect molecules that preferentially kill cancer cells under glucose-deprived conditions. Its mode of action was proposed to involve inhibition of increased GRP78 (glucose regulated protein 78) expression during hypoglycemia. Because GRP78 plays an important role in tumorigenesis, inhibitors such as VCD might harbor cancer therapeutic potential. We therefore sought to characterize VCD’s anticancer activity in vitro. Triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 were treated with VCD under different conditions known to trigger increased expression of GRP78, and a variety of cellular processes were analyzed. We show that VCD was highly cytotoxic only under hypoglycemic conditions, but not in the presence of normal glucose levels, and VCD blocked GRP78 expression only when glycolysis was impaired (due to hypoglycemia or the presence of the glycolysis inhibitor 2-deoxyglucose), but not when GRP78 was induced by other means (hypoxia, thapsigargin, tunicamycin). However, VCD’s strictly hypoglycemia-specific toxicity was not due to the inhibition of GRP78. Rather, VCD blocked mitochondrial energy production via inhibition of complex I of the electron transport chain. As a result, cellular ATP levels were quickly depleted under hypoglycemic conditions, and common cellular functions, including general protein synthesis, deteriorated and resulted in cell death. Altogether, our study identifies mitochondria as the primary target of VCD. The possibility that other purported GRP78 inhibitors (arctigenin, biguanides, deoxyverrucosidin, efrapeptin, JBIR, piericidin, prunustatin, pyrvinium, rottlerin, valinomycin, versipelostatin) might act in a similar GRP78-independent fashion will be discussed. PMID:23755268

A rapid alternative to X-ray crystallography for chiral determination: case studies of vibrational circular dichroism (VCD) to advance drug discovery projects.

PubMed

Wesolowski, Steven S; Pivonka, Don E

2013-07-15

The absolute stereochemistry of chiral drugs is usually established via X-ray crystallography. However, vibrational circular dichroism (VCD) spectroscopy coupled with quantum mechanics simulations offers a rapid alternative to crystallography and is readily applied to both crystalline and non-crystalline samples. VCD is an effective complement to X-ray analysis of drug candidates, and it can be used as a high-throughput means of assessing absolute stereochemistry at all phases of the discovery process (hundreds of assignments per year). The practical implementation (or fee-for-service outsourcing) of VCD and selected case studies are illustrated with an emphasis on providing utility and impact to pharmaceutical discovery programs. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Single Chiroptical Spectroscopic Method May Not Be Able To Establish the Absolute Configurations of Diastereomers: Dimethylesters of Hibiscus and Garcinia Acids

PubMed Central

Polavarapu, Prasad L.; Donahue, Emily A.; Shanmugam, Ganesh; Scalmani, Giovanni; Hawkins, Edward K.; Rizzo, Carmelo; Ibnusaud, Ibrahim; Thomas, Grace; Habel, Deenamma; Sebastian, Dellamol

2013-01-01

Electronic circular dichroism (ECD), optical rotatory dispersion (ORD), and vibrational circular dichroism (VCD) spectra of hibiscus acid dimethyl ester have been measured and analyzed in combination with quantum chemical calculations of corresponding spectra. These results, along with those reported previously for garcinia acid dimethyl ester, reveal that none of these three (ECD, ORD, or VCD) spectroscopic methods, in isolation, can unequivocally establish the absolute configurations of diastereomers. This deficiency is eliminated when a combined spectral analysis of either ECD and VCD or ORD and VCD methods is used. It is also found that the ambiguities in the assignment of absolute configurations of diastereomers may also be overcome when unpolarized vibrational absorption is included in the spectral analysis. PMID:21568330

Laryngopharyngeal Reflux and Children

MedlinePlus

... with the voice box (larynx) and causes the vocal cords to close to prevent aspiration of the material ... as a narrowing of the area below the vocal cords (subglottic stenosis), hoarseness, and possibly eustachian tube dysfunction ...

Revisiting an old concept: the coupled oscillator model for VCD. Part 1: the generalised coupled oscillator mechanism and its intrinsic connection to the strength of VCD signals.

PubMed

Nicu, Valentin Paul

2016-08-03

Motivated by the renewed interest in the coupled oscillator (CO) model for VCD, in this work a generalised coupled oscillator (GCO) expression is derived by introducing the concept of a coupled oscillator origin. Unlike the standard CO expression, the GCO expression is exact within the harmonic approximation. Using two illustrative example molecules, the theoretical concepts introduced here are demonstrated by performing a GCO decomposition of the rotational strengths computed using DFT. This analysis shows that: (1) the contributions to the rotational strengths that are normally neglected in the standard CO model can be comparable to or larger than the CO contribution, and (2) the GCO mechanism introduced here can affect the VCD intensities of all types of modes in symmetric and asymmetric molecules.

pH titration monitored by quantum cascade laser-based vibrational circular dichroism.

PubMed

Rüther, Anja; Pfeifer, Marcel; Lórenz-Fonfría, Víctor A; Lüdeke, Steffen

2014-04-10

Vibrational circular dichroism (VCD) spectra of aqueous solutions of proline were recorded in the course of titrations from basic to acidic pH using a spectrometer equipped with a quantum cascade laser (QCL) as an infrared light source in the spectral range from 1320 to 1220 cm(-1). The pH-dependent spectra were analyzed by singular value decomposition and global fitting of a two-pK Henderson-Hasselbalch model. The analysis delivered relative fractions of the three different protonation species. Their agreement with the relative fractions obtained from performing the same analysis on pH-dependent Fourier transform infrared (FT-IR) and QCL-IR spectra validates the quantitative results from QCL-VCD. Global fitting of the pH-dependent VCD spectra of L-proline allowed for extraction of pure spectra corresponding to anionic, zwitterionic, and cationic L-proline. From a static experiment, only pure spectra of the zwitterion would be accessible in a straightforward way. A comparison to VCD spectra calculated for all three species led to assignment of vibrational modes that are characteristic for the respective protonation states. The study demonstrates the applicability of QCL-VCD both for quantitative evaluation and for qualitative interpretation of dynamic processes in aqueous solutions.

Extension of fourier transform vibrational circular dichroism into the near-infrared region: continuous spectral coverage from 800 to 10 000 cm(-1).

PubMed

Cao, Xiaolin; Shah, Rekha D; Dukor, Rina K; Guo, Changning; Freedman, Teresa B; Nafie, Laurence A

2004-09-01

We report the first vibrational circular dichroism (VCD) spectra with continuous coverage from 800 cm(-1) in the mid-infrared (MIR) region to 10 000 cm(-1) in the near-infrared (NIR) region. This coverage is illustrated with MIR and NIR absorbance and VCD spectra of 2,2-dimethyl-dioxolane-4-methanol (DDM), alpha-pinene, and camphor that serve as calibration samples over this entire region. Commercially available, dual-source Fourier transform (FT) MIR and NIR VCD spectrometers were equipped with appropriate light sources, optics, and detectors, and were modified for dual-polarization-modulation (DPM) operation. The combination of liquid-nitrogen- and thermoelectric-cooled HgCdTe (MCT) detectors, as well as InGaAs and Germanium (Ge) detectors operating at room temperature, permitted collection of the desired absorbance and VCD spectra across the range of vibrational fundamental, combination band, and overtone frequencies. The spectra of DDM and alpha-pinene were measured as neat liquids and recorded for both enantiomers in the various spectral regions. Spectra for camphor were all measured in CCl(4) solution at a concentration of 0.6 M, except for the carbonyl-stretching region, where a more dilute concentration was used. The typical anisotropy ratios (g) of the three molecules were estimated with respect to their strongest VCD bands in each spectral region. It was found that for all three molecules in the spectral regions above 2000 cm(-1), anisotropy ratios are approximately the same order (10(-5)) of magnitude. However, in the MIR region, the typical anisotropy ratios are significantly different for the three molecules. This study demonstrates that with modern FT-VCD spectrometers modified for DPM operation, VCD spectra can be measured continuously across a wide spectral range from the MIR to nearly the visible region with an unsurpassed combination of signal-to-noise ratio and spectral resolution.

IR-Raman-VCD study of R-(+)-Pulegone: Influence of the solvent

NASA Astrophysics Data System (ADS)

Aviles-Moreno, Juan Ramón; Ureña Horno, Elena; Partal Ureña, Francisco; López González, Juan Jesús

2011-08-01

R-(+)-Pulegone is a natural monoterpene obtained from the essential oils of a variety of plants. It is used in flavouring agents, perfumery and aromatherapy. In this work, a study of the molecular structure and the infrared and Raman spectra of this chemical is presented. Theoretical calculations reveal the existence of two conformers depending on the position of the methyl group (axial and equatorial), being the equatorial conformer the most stable. A complete and reliable assignment of the IR and Raman spectra of the title compound is made, and the results are used to carry out a detailed interpretation of the VCD spectrum of this compound in the 4000-900 cm -1 region. Finally, the influence of the solvent in the VCD bands (intensity and sign) has been tested comparing the neat liquid spectrum with the VCD spectra recorded with four solvents.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Bingke; Cheng, Hui-Chun; Brautigam, Chad A.

Vibrio parahaemolyticus protein L (VopL) is an actin nucleation factor that induces stress fibers when injected into eukaryotic host cells. VopL contains three N-terminal Wiskott-Aldrich homology 2 (WH2) motifs and a unique VopL C-terminal domain (VCD). We describe crystallographic and biochemical analyses of filament nucleation by VopL. The WH2 element of VopL does not nucleate on its own and requires the VCD for activity. The VCD forms a U-shaped dimer in the crystal, stabilized by a terminal coiled coil. Dimerization of the WH2 motifs contributes strongly to nucleation activity, as do contacts of the VCD to actin. Our data leadmore » to a model in which VopL stabilizes primarily lateral (short-pitch) contacts between actin monomers to create the base of a two-stranded filament. Stabilization of lateral contacts may be a common feature of actin filament nucleation by WH2-based factors.« less

[Homogeneous spinal-shortening axial decompression procedure for tethered cord syndrome].

PubMed

Wang, Haibo; Sun, Jingchuan; Wang, Yuan; Wu, Zhao; Xu, Tao; Chen, Kefu; Shi, Guodong; Yuan, Wen; Jia, Lianshun; Shi, Jiangang

2015-06-16

Surgical detethering is a traditional treatment for symptomatic tethered cord syndrome. However, such complications as cerebrospinal fluid leakage and neurologic deterioration are common. Homogeneous spinal-shortening axial decompression (HSAD) is a modified procedure of monosegmental spinal-shortening osteotomy and it is a novel surgical alternative of reducing neural tension indirectly. The objective was to evaluate the surgical outcomes of HSAD for tethered cord syndrome. The surgical outcomes were examined for 15 consecutive patients with tethered cord syndrome undergoing HSAD from April 2010 to July 2014. Improvements of neurological symptoms including urinary dysfunction, lower-extremity motor and sensory disturbances and/or gait abnormalities, low-back and/or lower-extremity pain, bowel incontinence and sexual dysfunction were evaluated. Their average follow-up period was 21.5 months. The length of spinal column shortening was 17.2 ± 2.9 mm. Urinary dysfunction (n = 9) was the most common residual deficit. All 9 patients with urological symptoms reported improvements, although deficits persisted at the last follow-up. All patients with lower-extremity motor dysfunction improved and 4 (50.0%) noted complete resolution of preoperative lower-extremity sensory symptoms. All patients reported immediate low-back or lower-extremity pain relief after HSAD. One patient reported improved sexual functioning and regained complete erectile capabilities. Two patients (11%) experienced less satisfactory symptomatic or functional benefit from HSAD. However, the main objective of surgery was to prevent further worsening of neurological status. Complete bone union at osteotomy site was noted in all cases at the last follow-up. As a novel surgical option for tethered cord syndrome, HSAD may avoid such complications as cerebrospinal fluid leakage or neurologic deterioration commonly encountered during traditional detethering surgery. All patients gain satisfactory functional outcomes without complications compared to their preoperative symptoms.

The Clusters-in-a-Liquid Approach for Solvation: New Insights from the Conformer Specific Gas Phase Spectroscopy and Vibrational Optical Activity Spectroscopy

PubMed Central

Perera, Angelo S.; Thomas, Javix; Poopari, Mohammad R.; Xu, Yunjie

2016-01-01

Vibrational optical activity spectroscopies, namely vibrational circular dichroism (VCD) and Raman optical activity (ROA), have been emerged in the past decade as powerful spectroscopic tools for stereochemical information of a wide range of chiral compounds in solution directly. More recently, their applications in unveiling solvent effects, especially those associated with water solvent, have been explored. In this review article, we first select a few examples to demonstrate the unique sensitivity of VCD spectral signatures to both bulk solvent effects and explicit hydrogen-bonding interactions in solution. Second, we discuss the induced solvent chirality, or chiral transfer, VCD spectral features observed in the water bending band region in detail. From these chirality transfer spectral data, the related conformer specific gas phase spectroscopic studies of small chiral hydration clusters, and the associated matrix isolation VCD experiments of hydrogen-bonded complexes in cold rare gas matrices, a general picture of solvation in aqueous solution emerges. In such an aqueous solution, some small chiral hydration clusters, rather than the chiral solutes themselves, are the dominant species and are the ones that contribute mainly to the experimentally observed VCD features. We then review a series of VCD studies of amino acids and their derivatives in aqueous solution under different pHs to emphasize the importance of the inclusion of the bulk solvent effects. These experimental data and the associated theoretical analyses are the foundation for the proposed “clusters-in-a-liquid” approach to account for solvent effects effectively. We present several approaches to identify and build such representative chiral hydration clusters. Recent studies which applied molecular dynamics simulations and the subsequent snapshot averaging approach to generate the ROA, VCD, electronic CD, and optical rotatory dispersion spectra are also reviewed. Challenges associated with the molecular dynamics snapshot approach are discussed and the successes of the seemingly random “ad hoc explicit solvation” reported before are also explained. To further test and improve the “clusters-in-a-liquid” model in practice, future work in terms of conformer specific gas phase spectroscopy of sequential solvation of a chiral solute, matrix isolation VCD measurements of small chiral hydration clusters, and more sophisticated models for the bulk solvent effects would be highly valuable. PMID:26942177

Fourier transform vibrational circular dichroism of small pharmaceutical molecules

NASA Astrophysics Data System (ADS)

Long, Fujin; Freedman, Teresa B.; Nafie, Laurence A.

1998-06-01

Fourier transform vibrational circular dichroism (FT-VCD) spectra of the small pharmaceutical molecules propanolol, ibuprofen and naproxen have been measured in the hydrogen stretching and mid-infrared regions to obtain information on solution conformation and to identify markers for absolute configuration determination. Ab initio molecular orbital calculations of low energy conformations, vibrational frequencies and VCD intensities for fragments of the drugs were utilized in interpreting the spectra. Features characteristic of five conformers of propranolol were identified. The weak positive CH stretching VCD signal in ibuprofen and naproxen is characteristic of the S-configuration of the chiral center common to these two analgesics.

Osthole attenuates spinal cord ischemia-reperfusion injury through mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction in rats.

PubMed

Zhou, Yue-fei; Li, Liang; Feng, Feng; Yuan, Hua; Gao, Da-kuan; Fu, Luo-an; Fei, Zhou

2013-12-01

Osthole, the main bioactive compounds isolated from the traditional Chinese medical herb broad Cnidium monnieri (L.) cusson, has been shown to exert spectrum of pharmacologic activities. The aim of this study was to investigate the potential neuroprotective effects of osthole against spinal cord ischemia-reperfusion injury in rats. Osthole was administrated at the concentration of 0.1, 1, 10, 50, or 200 mg/kg (intraperitoneally) 1 h before spinal cord ischemia. The effects on spinal cord injury were measured by spinal cord water content, infarct volume, hematoxylin and eosin staining, and neurologic assessment. Mitochondria were purified from injured spinal cord tissue to determine mitochondrial function. We found that treatment with osthole (10 and 50 mg/kg) significantly decreased spinal cord water content and infarct volume, preserved normal motor neurons, and improved neurologic functions. These protective effects can be also observed even if the treatment was delayed to 4 h after reperfusion. Osthole treatment preserved mitochondrial membrane potential level, reduced reactive oxygen species production, increased adenosine triphosphate generation, and inhibited cytochrome c release in mitochondrial samples. Moreover, osthole increased mitochondria respiratory chain complex activities in spinal cord tissue, with no effect on mitochondrial DNA content and the expression of mitochondrial-specific transcription factors. All these findings demonstrate the neuroprotective effect of osthole in spinal cord ischemia-reperfusion injury model and suggest that oshtole-induced neuroprotection was mediated by mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

Psychological impact and sexual dysfunction in men with and without spinal cord injury.

PubMed

Cobo Cuenca, Ana I; Sampietro-Crespo, Antonio; Virseda-Chamorro, Miguel; Martín-Espinosa, Noelia

2015-02-01

The World Health Organization recognizes sexual health as a fundamental right that should be guaranteed to all individuals. Sexual dysfunction affects various aspects in the lives (physical, psychic, and social) of affected persons. To assess the different types of sexual dysfunction, the quality of life (QOL), depression, anxiety, and levels of self-esteem observed in 165 men with sexual dysfunction, both with and without spinal cord injury (SCI). Case control study of 85 men with SCI and sexual dysfunction, and 80 men without SCI that have sexual dysfunction. The Sexual Health Evaluation Scale, the Fugl-Meyer Life Satisfaction Questionnaire scale, the Hospital Anxiety and Depression Scale, the Evaluation of the Sexual Health Scale, and Rosenberg's Self-esteem Scale were all used for data collection. Of the members in group A (with SCI), 89.4% (76) showed erectile dysfunction, and 75.2% (64) reported anejaculation. In group B (without SCI), 75 (96.8%) showed erectile dysfunction, and 58.7% (47) had disorders of sexual desire. In group A, 16.47 % (14) showed signs of depression, and 35.3% (30) had signs of anxiety. In group B, 30% (24) had elevated scores regarding depression, and 48.75% (39) had high scores for anxiety. All of the participants reported a high general QOL and a high satisfaction with their QOL but reported that their satisfaction with their sexual lives was only at the acceptable level. Social QOL is significantly higher in the SCI group (t Student P=0.031). The QOL, self-esteem, and anxiety and depression levels are significantly correlated. Men with sexual dysfunction strive to adapt to their situations, with the relationship between the type of sexual dysfunction and the QOL, mood (depression), and self-esteem all being important considerations. Sexuality and employment status are the areas where men with spinal cord injuries report less satisfaction. © 2014 International Society for Sexual Medicine.

Discrete mitochondrial aberrations in the spinal cord of sporadic ALS patients.

PubMed

Delic, Vedad; Kurien, Crupa; Cruz, Josean; Zivkovic, Sandra; Barretta, Jennifer; Thomson, Avery; Hennessey, Daniel; Joseph, Jaheem; Ehrhart, Jared; Willing, Alison E; Bradshaw, Patrick; Garbuzova-Davis, Svitlana

2018-08-01

Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease characterized by progressive motor neuron degeneration in the brain and spinal cord leading to muscle atrophy, paralysis, and death. Mitochondrial dysfunction is a major contributor to motor neuron degeneration associated with ALS progression. Mitochondrial abnormalities have been determined in spinal cords of animal disease models and ALS patients. However, molecular mechanisms leading to mitochondrial dysfunction in sporadic ALS (sALS) patients remain unclear. Also, segmental or regional variation in mitochondrial activity in the spinal cord has not been extensively examined in ALS. In our study, the activity of mitochondrial electron transport chain complex IV was examined in post-mortem gray and white matter of the cervical and lumbar spinal cords from male and female sALS patients and controls. Mitochondrial distribution and density in spinal cord motor neurons, lateral funiculus, and capillaries in gray and white matter were analyzed by immunohistochemistry. Results showed that complex IV activity was significantly decreased only in gray matter in both cervical and lumbar spinal cords from ALS patients. In ALS cervical and lumbar spinal cords, significantly increased mitochondrial density and altered distribution were observed in motor neurons, lateral funiculus, and cervical white matter capillaries. Discrete decreased complex IV activity in addition to changes in mitochondria distribution and density determined in the spinal cord in sALS patients are novel findings. These explicit mitochondrial defects in the spinal cord may contribute to ALS pathogenesis and should be considered in development of therapeutic approaches for this disease. © 2018 Wiley Periodicals, Inc.

High-resolution NO2 remote sensing from the Airborne Prism EXperiment (APEX) imaging spectrometer

NASA Astrophysics Data System (ADS)

Popp, C.; Brunner, D.; Damm, A.; Van Roozendael, M.; Fayt, C.; Buchmann, B.

2012-09-01

We present and evaluate the retrieval of high spatial resolution maps of NO2 vertical column densities (VCD) from the Airborne Prism EXperiment (APEX) imaging spectrometer. APEX is a novel instrument providing airborne measurements of unique spectral and spatial resolution and coverage as well as high signal stability. In this study, we use spectrometer data acquired over Zurich, Switzerland, in the morning and late afternoon during a flight campaign on a cloud-free summer day in June 2010. NO2 VCD are derived with a two-step approach usually applied to satellite NO2 retrievals, i.e. a DOAS analysis followed by air mass factor calculations based on radiative transfer computations. Our analysis demonstrates that APEX is clearly sensitive to NO2 VCD above typical European tropospheric background abundances (>1 × 1015 molec cm-2). The two-dimensional maps of NO2 VCD reveal a very convincing spatial distribution with strong gradients around major NOx sources (e.g. Zurich airport, waste incinerator, motorways) and low NO2 in remote areas. The morning overflights resulted in generally higher NO2 VCD and a more distinct pattern than the afternoon overflights which can be attributed to the meteorological conditions prevailing during that day with stronger winds and hence larger dilution in the afternoon. The remotely sensed NO2 VCD are also in reasonably good agreement with ground-based in-situ measurements from air quality networks considering the limitations of comparing column integrals with point measurements. Airborne NO2 remote sensing using APEX will be valuable to detect NO2 emission sources, to provide input for NO2 emission modelling, and to establish links between in-situ measurements, air quality models, and satellite NO2 products.

High resolution NO2 remote sensing from the Airborne Prism EXperiment (APEX) imaging spectrometer

NASA Astrophysics Data System (ADS)

Popp, C.; Brunner, D.; Damm, A.; Van Roozendael, M.; Fayt, C.; Buchmann, B.

2012-03-01

We present and evaluate the retrieval of high spatial resolution maps of NO2 vertical column densities (VCD) from the Airborne Prism EXperiment (APEX) imaging spectrometer. APEX is a novel instrument providing airborne measurements of unique spectral and spatial resolution and coverage as well as high signal stability. In this study, we use spectrometer data acquired over Zurich, Switzerland, in the morning and late afternoon during a flight campaign on a cloud-free summer day in June 2010. NO2 VCD are derived with a two-step approach usually applied to satellite NO2 retrievals, i.e. a DOAS analysis followed by air mass factor calculations based on radiative transfer computations. Our analysis demonstrates that APEX is clearly sensitive to NO2 VCD above typical European tropospheric background abundances (>1 × 1015 molec cm-2). The two-dimensional maps of NO2 VCD reveal a very plausible spatial distribution with strong gradients around major NOx sources (e.g. Zurich airport, waste incinerator, motorways) and low NO2 in remote areas. The morning overflights resulted in generally higher NO2 VCD and a more distinct pattern than the afternoon overflights which can be attributed to the meteorological conditions prevailing during that day (development of the boundary layer and increased wind speed in the afternoon) as well as to photochemical loss of NO2. The remotely sensed NO2 VCD are also highly correlated with ground-based in-situ measurements from local and national air quality networks (R=0.73). Airborne NO2 remote sensing using APEX will be valuable to detect NO2 emission sources, to provide input for NO2 emission modeling, and to establish links between in-situ measurements, air quality models, and satellite NO2 products.

Gastrointestinal symptoms in spinal cord injury: relationships with level of injury and psychologic factors.

PubMed

Ng, Clinton; Prott, Gillian; Rutkowski, Susan; Li, Yueming; Hansen, Ross; Kellow, John; Malcolm, Allison

2005-08-01

Previous surveys of gastrointestinal symptoms after spinal cord injury have not used validated questionnaires and have not focused on the full spectrum of such symptoms and their relationship to factors, such as level of spinal cord injury and psychologic dysfunction. This study was designed to detail the spectrum and prevalence of gastrointestinal symptoms in spinal cord injury and to determine clinical and psychologic factors associated with such symptoms. Established spinal cord injury patients (>12 months) randomly selected from a spinal cord injury database completed the following three questionnaires: 1) Rome II Integrative Questionnaire, 2) Hospital Anxiety and Depression Scale, and 3) Burwood Bowel Dysfunction after spinal cord injury. A total of 110 patients participated. The prevalence of abdominal bloating and constipation were 22 and 46 percent, respectively. Bloating was associated with cervical (odds ratio = 9.5) and lumbar (odds ratio = 12.1) level but not with thoracic level of injury. Constipation was associated with a higher level of injury (cervical odds ratio = 5.6 vs. lumbar) but not with psychologic factors. In contrast, abdominal pain (33 percent) and fecal incontinence (41 percent) were associated with higher levels of anxiety (odds ratio = 6.8, and odds ratio = 2.4) but not with the level of injury. There is a high prevalence and wide spectrum of gastrointestinal symptoms in spinal cord injury. Abdominal bloating and constipation are primarily related to specific spinal cord levels of injury, whereas abdominal pain and fecal incontinence are primarily associated with higher levels of anxiety. Based on our findings, further physiologic and psychologic research studies in spinal cord injury patients should lead to more rational management strategies for the common gastrointestinal symptoms in spinal cord injury.

Retaining Residual Ovarian Tissue following Ovarian Failure Has Limited Influence on Bone Loss in Aged Mice

PubMed Central

Craig, Zelieann R.; Marion, Samuel L.; Funk, Janet L.; Bouxsein, Mary L.; Hoyer, Patricia B.

2010-01-01

Previous work showed that retaining residual ovarian tissue protects young mice from accelerated bone loss following ovarian failure. The present study was designed to determine whether this protection is also present in aged animals. Aged (9–12 months) C57BL/6Hsd female mice were divided into: CON (vehicle), VCD (160 mg/kg; 15d), or OVX (ovariectomized). Lumbar BMD was monitored by DXA and μCT used to assess vertebral microarchitecture. BMD was not different between VCD and CON at any time point but was lower (P < .05) than baseline, starting 1 month after ovarian failure in VCD and OVX mice. Following μCT analysis there were no differences between CON and VCD, but OVX mice had lower bone volume fraction, trabecular thickness, and a trend for decreased connectivity density. These findings provide evidence that retention of residual ovarian tissue may protect aged follicle-depleted mice from accelerated bone loss to a lesser extent than that observed in young mice. PMID:20948577

Efficacy of a tetravalent dengue vaccine in children in Latin America.

PubMed

Villar, Luis; Dayan, Gustavo Horacio; Arredondo-García, José Luis; Rivera, Doris Maribel; Cunha, Rivaldo; Deseda, Carmen; Reynales, Humberto; Costa, Maria Selma; Morales-Ramírez, Javier Osvaldo; Carrasquilla, Gabriel; Rey, Luis Carlos; Dietze, Reynaldo; Luz, Kleber; Rivas, Enrique; Miranda Montoya, Maria Consuelo; Cortés Supelano, Margarita; Zambrano, Betzana; Langevin, Edith; Boaz, Mark; Tornieporth, Nadia; Saville, Melanie; Noriega, Fernando

2015-01-08

In light of the increasing rate of dengue infections throughout the world despite vector-control measures, several dengue vaccine candidates are in development. In a phase 3 efficacy trial of a tetravalent dengue vaccine in five Latin American countries where dengue is endemic, we randomly assigned healthy children between the ages of 9 and 16 years in a 2:1 ratio to receive three injections of recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) or placebo at months 0, 6, and 12 under blinded conditions. The children were then followed for 25 months. The primary outcome was vaccine efficacy against symptomatic, virologically confirmed dengue (VCD), regardless of disease severity or serotype, occurring more than 28 days after the third injection. A total of 20,869 healthy children received either vaccine or placebo. At baseline, 79.4% of an immunogenicity subgroup of 1944 children had seropositive status for one or more dengue serotypes. In the per-protocol population, there were 176 VCD cases (with 11,793 person-years at risk) in the vaccine group and 221 VCD cases (with 5809 person-years at risk) in the control group, for a vaccine efficacy of 60.8% (95% confidence interval [CI], 52.0 to 68.0). In the intention-to-treat population (those who received at least one injection), vaccine efficacy was 64.7% (95% CI, 58.7 to 69.8). Serotype-specific vaccine efficacy was 50.3% for serotype 1, 42.3% for serotype 2, 74.0% for serotype 3, and 77.7% for serotype 4. Among the severe VCD cases, 1 of 12 was in the vaccine group, for an intention-to-treat vaccine efficacy of 95.5%. Vaccine efficacy against hospitalization for dengue was 80.3%. The safety profile for the CYD-TDV vaccine was similar to that for placebo, with no marked difference in rates of adverse events. The CYD-TDV dengue vaccine was efficacious against VCD and severe VCD and led to fewer hospitalizations for VCD in five Latin American countries where dengue is endemic. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01374516.).

Patient Satisfaction After Femoral Arterial Access Site Closure Using the ExoSeal{sup ®} Vascular Closure Device Compared to Manual Compression: A Prospective Intra-individual Comparative Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pieper, Claus Christian, E-mail: claus.christian.pieper@ukb.uni-bonn.de; Thomas, Daniel, E-mail: daniel.thomas@ukb.uni-bonn.de; Nadal, Jennifer, E-mail: jennifer.nadal@ukb.uni-bonn.de

PurposeTo intra-individually compare discomfort levels and patient satisfaction after arterial access closure using the ExoSeal{sup ®} vascular closure device (VCD) and manual compression (MC) in a prospective study design.MethodsPatients undergoing two planned interventions from 07/2013 to 09/2014 could participate in the study. Access closure was performed with an ExoSeal{sup ®}-VCD in one and MC in the other intervention. Patients were clinically and sonographically examined and were given questionnaires 1 day after intervention [groin- and back-pain during bedrest (100-point visual analog scale; 0: no pain); comfortability of bedrest (10-point Likert scale, 1: comfortable), satisfaction with closure (10-point Likert scale, 1: very satisfied)].more » Results were analyzed in a cross-over design.Results48 patients (29 male, median age 62.5 (32–88) years) were included. An ExoSeal{sup ®}-VCD was used first in 25 cases. As four of these subsequently refused MC as second intervention, data from 44 patients could be analyzed. All closures were technically successful (successful device deployment) without major complications. Groin- and back-pain after VCD-use/MC was 0 (0–15) vs. 10 (0–80) and 0 (0–75) vs. 25 (0–90), respectively (p < 0.0001). Bedrest after VCD-use was more comfortable than after MC [1 (range 1–7) vs. 6 (2–10); p < 0.0001]. Satisfaction with the closure procedure and with the intervention in general was higher after VCD-use compared to MC [1 (1–3) vs. 5 (2–10) and 1 (1–2) vs. 2 (1–4), respectively; p < 0.0001].ConclusionIntra-individual comparison showed pain levels and discomfort to be significantly lower after ExoSeal{sup ®} use compared to MC. VCD closure was associated with higher satisfaction both with the closure itself and with the intervention in general.« less

Assignment of absolute stereostructures through quantum mechanics electronic and vibrational circular dichroism calculations.

PubMed

Dai, Peng; Jiang, Nan; Tan, Ren-Xiang

2016-01-01

Elucidation of absolute configuration of chiral molecules including structurally complex natural products remains a challenging problem in organic chemistry. A reliable method for assigning the absolute stereostructure is to combine the experimental circular dichroism (CD) techniques such as electronic and vibrational CD (ECD and VCD), with quantum mechanics (QM) ECD and VCD calculations. The traditional QM methods as well as their continuing developments make them more applicable with accuracy. Taking some chiral natural products with diverse conformations as examples, this review describes the basic concepts and new developments of QM approaches for ECD and VCD calculations in solution and solid states.

On chirality transfer in electron donor-acceptor complexes. A prediction for the sulfinimine···BF3 system.

PubMed

Rode, Joanna E; Dobrowolski, Jan Cz

2012-01-01

Stabilization energies of the electron donor-acceptor sulfinimine···BF(3) complexes calculated at either the B3LYP/aug-cc-pVTZ or the MP2/aug-cc-pVTZ level do not allow to judge, whether the N- or O-atom in sulfinimine is stronger electron-donor to BF(3) . The problem seems to be solvable because chirality transfer phenomenon between chiral sulfinimine and achiral BF(3) is expected to be vibrational circular dichroism (VCD) active. Moreover, the bands associated with the achiral BF(3) molecule are predicted to be the most intense in the entire spectrum. However, the VCD band robustness analyses show that most of the chirality transfer modes of BF(3) are unreliable. Conversely, variation of VCD intensity with change of intermolecular distance, angle, and selected dihedrals between the complex partners shows that to establish the robustness of chirality transfer mode. It is also necessary to determine the influence of the potential energy surface (PES) shape on the VCD intensity. At the moment, there is still no universal criterion for the chirality transfer mode robustness and the conclusions formulated based on one system cannot be directly transferred even to a quite similar one. However, it is certain that more attention should be focused on relation of PES shape and the VCD mode robustness problem. Copyright © 2011 Wiley Periodicals, Inc.

Adenosine A1-Dopamine D1 Receptor Heteromers Control the Excitability of the Spinal Motoneuron.

PubMed

Rivera-Oliver, Marla; Moreno, Estefanía; Álvarez-Bagnarol, Yocasta; Ayala-Santiago, Christian; Cruz-Reyes, Nicole; Molina-Castro, Gian Carlo; Clemens, Stefan; Canela, Enric I; Ferré, Sergi; Casadó, Vicent; Díaz-Ríos, Manuel

2018-05-24

While the role of the ascending dopaminergic system in brain function and dysfunction has been a subject of extensive research, the role of the descending dopaminergic system in spinal cord function and dysfunction is just beginning to be understood. Adenosine plays a key role in the inhibitory control of the ascending dopaminergic system, largely dependent on functional complexes of specific subtypes of adenosine and dopamine receptors. Combining a selective destabilizing peptide strategy with a proximity ligation assay and patch-clamp electrophysiology in slices from male mouse lumbar spinal cord, the present study demonstrates the existence of adenosine A 1 -dopamine D 1 receptor heteromers in the spinal motoneuron by which adenosine tonically inhibits D 1 receptor-mediated signaling. A 1 -D 1 receptor heteromers play a significant control of the motoneuron excitability, represent main targets for the excitatory effects of caffeine in the spinal cord and can constitute new targets for the pharmacological therapy after spinal cord injury, motor aging-associated disorders and restless legs syndrome.

Biomechanical properties of the spinal cord: implications for tissue engineering and clinical translation.

PubMed

Bartlett, Richard D; Choi, David; Phillips, James B

2016-10-01

Spinal cord injury is a severely debilitating condition which can leave individuals paralyzed and suffering from autonomic dysfunction. Regenerative medicine may offer a promising solution to this problem. Previous research has focused primarily on exploring the cellular and biological aspects of the spinal cord, yet relatively little remains known about the biomechanical properties of spinal cord tissue. Given that a number of regenerative strategies aim to deliver cells and materials in the form of tissue-engineered therapies, understanding the biomechanical properties of host spinal cord tissue is important. We review the relevant biomechanical properties of spinal cord tissue and provide the baseline knowledge required to apply these important physical concepts to spinal cord tissue engineering.

Effects of Enhanced Oxygen Delivery by Perfluorocarbons in Spinal Cord Injury

DTIC Science & Technology

2013-10-01

been established, linking post- traumatic ischemia to axonal dysfunction.8 Decreased oxygen level in severe traumatic injuries appears to be implicated...rodent weight drop traumatic spinal cord injury model; ( 2 ) determine if enhanced oxygen delivery in spinal cord injury spares cellular elements, white...shown that ischemia /hypoxia play crucial role in the devastating effects of the secondary injury following SCI which translates into worse neurological

Effectiveness of Phosphodiesterase 5 Inhibitors in the Treatment of Erectile Dysfunction in Patients with Spinal Cord Trauma: Systematic Review and Meta-Analysis.

PubMed

García-Perdomo, Herney Andrés; Echeverría-García, Fernando; Tobías, Aurelio

2017-01-01

To determine the effectiveness of the Phosphodiesterase 5 (PDE5) Inhibitors for the treatment of erectile dysfunction in patients with spinal trauma. A systematic review and meta-analysis comparing PDE5 inhibitors versus placebo were carried out for clinical trials conducted between 1980 and 2014 that evaluated male patients older than 18 years, diagnosed with spinal cord trauma and erectile dysfunction. We designed a search strategy for Medline, CENTRAL, EMBASE and other electronic sources. Two investigators independently and blindly screened the studies for inclusion. A random effect meta-analysis was performed. Six studies involving 963 patients were included. Male patients over 18 years with ED attributable or subsequent to traumatic spinal cord injury (SCI) were included from these studies. In 4 of these studies, patients were randomized to the treatment group receiving sildenafil and the comparison group was placebo. Out of the remaining 2 trials, one compared tadalafil against the placebo and the other vardenafil versus placebo. The improvement on SCIs with PDE5 inhibitors was found to be large (standardized mean difference 0.71; 95% CI 0.39-1.03), with a high heterogeneity (I2 = 74.4%). PDE5 inhibitors are effective for the treatment of erectile dysfunction secondary to SCI. © 2016 S. Karger AG, Basel.

Brainstem dysfunction protects against syncope in multiple sclerosis.

PubMed

Habek, Mario; Krbot Skorić, Magdalena; Crnošija, Luka; Adamec, Ivan

2015-10-15

The aim of this study was to investigate the correlation between autonomic dysfunction in multiple sclerosis (MS) and brainstem dysfunction evaluated with the vestibular evoked myogenic potentials (VEMP) score and conventional MRI. Forty-five patients with the diagnosis of clinically isolated syndrome (CIS) suggestive of MS were enrolled. VEMP, heart rate, and blood pressure responses to the Valsalva maneuver, heart rate response to deep breathing, and pain provoked head-up tilt table test, as well as brain and spinal cord MRI were performed. There was no difference in the VEMP score between patients with and without signs of sympathetic or parasympathetic dysfunction. However, patients with syncope had significantly lower VEMP score compared to patients without syncope (p<0.01). Patients with orthostatic hypotension (OH) showed a trend of higher VEMP score compared to patients without OH (p=0.06). There was no difference in the presence of lesions in the brainstem or cervical spinal cord between patients with or without any of the studied autonomic parameters. The model consisting of a VEMP score of ≤5 and normal MRI of the midbrain and cervical spinal cord has sensitivity and specificity of 83% for the possibility that the patient with MS can develop syncope. Pathophysiological mechanisms underlying functional and structural disorders of autonomic nervous system in MS differ significantly. While preserved brainstem function is needed for development of syncope, structural disorders like OH could be associated with brainstem dysfunction. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of orally administered OP-1206 alpha-CD with loxoprofen-Na on walking dysfunction in the rat neuropathic intermittent claudication model.

PubMed

Nakai, Katsuhiko; Takenobu, Yoshifumi; Takimizu, Hideyuki; Akimaru, Shinji; Ito, Hidenori; Maegawa, Hitoshi; Marsala, Martin; Katsube, Nobuo

2003-10-01

An orally active prostaglandin E1 analogue, OP-1206 alpha-CD improves walking dysfunction in the rat spinal stenosis model. Loxoprofen-Na, a non-steroidal anti-inflammatory drug, is used to relieve chronic pain in patients with lumbar spinal canal stenosis. To determine whether the OP-1206 alpha-CD in combination with loxoprofen-Na could induce a greater therapeutical effect on walking dysfunction and spinal cord blood flow (SCBF) than OP-1206 alpha-CD treatment alone after chronic spinal stenosis in the rat. Spinal stenosis was induced by placing two pieces of silicon rubber strips in the lumbar (L4 and L6) epidural space of rats. After surgery, walking function was measured using a treadmill apparatus and SCBF was measured using a laser-Doppler flow meter. Drugs were administered orally twice a day for 11 days from the day 3 post-surgery. OP-1206 alpha-CD elicited a significant improvement of walking dysfunction on days 7 and 14 post-surgery and significantly increased spinal cord blood flow on day 15, whereas walking dysfunction and SCBF of rats treated with loxoprofen-Na alone remained unchanged. Combined treatment of OP-1206 alpha-CD with loxoprofen-Na did not provide additive therapeutical effect. These results suggest that a significant improvement seen after OP-1206 alpha-CD treatment is primarily mediated by improvement of the local spinal cord blood flow. This effect is not ameliorated or potentiated by a combined treatment with loxoprofen-Na.

The Animal Model of Spinal Cord Injury as an Experimental Pain Model

PubMed Central

Nakae, Aya; Nakai, Kunihiro; Yano, Kenji; Hosokawa, Ko; Shibata, Masahiko; Mashimo, Takashi

2011-01-01

Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models. PMID:21436995

Inhibition of Type 1 Cytokine–mediated Inflammation by a Soluble CD30 Homologue Encoded by Ectromelia (Mousepox) Virus

PubMed Central

Saraiva, Margarida; Smith, Philip; Fallon, Padraic G.; Alcami, Antonio

2002-01-01

CD30 is up-regulated in several human diseases and viral infections but its role in immune regulation is poorly understood. Here, we report the expression of a functional soluble CD30 homologue, viral CD30 (vCD30), encoded by ectromelia (mousepox) virus, a poxvirus that causes a severe disease related to human smallpox. We show that vCD30 is a 12-kD secreted protein that not only binds CD30L with high affinity and prevents its interaction with CD30, but it also induces reverse signaling in cells expressing CD30L. vCD30 blocked the generation of interferon γ–producing cells in vitro and was a potent inhibitor of T helper cell (Th)1- but not Th2-mediated inflammation in vivo. The finding of a CD30 homologue encoded by ectromelia virus suggests a role for CD30 in antiviral defense. Characterization of the immunological properties of vCD30 has uncovered a role of CD30–CD30L interactions in the generation of inflammatory responses. PMID:12235215

Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: A soluble, secreted CD30 homologue

PubMed Central

Panus, Joanne Fanelli; Smith, Craig A.; Ray, Caroline A.; Smith, Terri Davis; Patel, Dhavalkumar D.; Pickup, David J.

2002-01-01

Cowpox virus (Brighton Red strain) possesses one of the largest genomes in the Orthopoxvirus genus. Sequence analysis of a region of the genome that is type-specific for cowpox virus identified a gene, vCD30, encoding a soluble, secreted protein that is the fifth member of the tumor necrosis factor receptor family known to be encoded by cowpox virus. The vCD30 protein contains 110 aa, including a 21-residue signal peptide, a potential O-linked glycosylation site, and a 58-aa sequence sharing 51–59% identity with highly conserved extracellular segments of both mouse and human CD30. A vCD30Fc fusion protein binds CD153 (CD30 ligand) specifically, and it completely inhibits CD153/CD30 interactions. Although the functions of CD30 are not well understood, the existence of vCD30 suggests that the cellular receptor plays a significant role in normal immune responses. Viral inhibition of CD30 also lends support to the potential therapeutic value of targeting CD30 in human inflammatory and autoimmune diseases. PMID:12034885

IR, Raman and Vibrational Optical Activity Spectra of Methyl Glycidate in Chloroform and Water: The Clusters-in-a-Liquid Solvation Model.

PubMed

Xu, Yunjie; Perera, Angelo Shehan; Cheramy, Joseph; Merten, Christian; Thomas, Javix

2018-05-16

Solvent effects, in particular those involving water as the solvent, are of significant interest to chemistry and physics communities. IR, vibrational circular dichroism (VCD), Raman, and Raman optical activity (ROA) spectra of methyl glycidate in two very different solvents, namely CCl4 and water, have been measured experimentally and simulated theoretically. While the observed spectra in CCl4 could be well modelled using the polarizable continuum model for the solvent, the situation is much different in water. The experimental VCD spectrum of methyl glycidate in water reveals strong induced VCD signatures in the water bending region, indicating the presence of the relatively long-lived methyl glycidate-watern complexes. We applied the clusters-in-a-liquid approach to identify the dominant methyl glycidate-water1,2 complexes which are the long-lived species responsible for all the spectra observed in water. We examined the influences of solvent dielectric environment and the hydrogen-bonding interactions on the conformational distribution of methyl glycidate. The geometry optimizations, frequency calculations, IR, VCD, Raman and ROA intensity calculations were performed at the B3LYP/6-311++G(2d,p) and aug-cc-pVTZ levels of theory with D3BJ dispersion correction. It is particularly satisfying to note that the clusters-in-a-liquid approach has captured all main experimental features in IR, VCD, Raman and ROA spectra of methyl glycidate in water. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ultrasonography and optical low-coherence interferometry compared in the chicken eye.

PubMed

Penha, Alexandra Marcha; Burkhardt, Eva; Schaeffel, Frank; Feldkaemper, Marita P

2012-06-01

To compare ocular biometry [anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD), and axial length (AL)] using A-scan ultrasonography and optical low-coherence interferometry (OLCI) in the chicken eye. Two-week-old chicks (n = 42) were measured. Bland-Altman plots and repeatability and correlation analyses were calculated for both methods. There was a high correlation between both methods for ACD (r = 0.6144, p < 0.0001), VCD (r = 0.9595, p < 0.0001), and AL (r = 0.9290, p < 0.0001) but not for LT (r = 0.1604, p = 0.144). Measurements by OLCI were more consistent (smaller coefficients of variation and higher intraclass correlation). Bland-Altman plots showed that ultrasound provided larger values for LT, VCD, and AL but not for ACD [differences between ultrasound and OLCI (mean ± SD): ACD = -0.11 ± 0.12 mm; LT = 0.10 ± 0.09 mm; VCD = 0.25 ± 0.08 mm; AL = 0.50 ± 0.16 mm]. A high correlation between both techniques was found for three of the four parameters (ACD, VCD, and AL). However, as the absolute values were different, both techniques cannot replace each other mainly because (1) one is non-contact and the other contact and can induce a minor indentation of the cornea and (2) each device uses different types of waves that cross the ocular interfaces differently. While consistency and repeatability were better by OLCI, a disadvantage is that, different from humans, it can only be used in anesthetized chicks.

Determination of the absolute configurations of natural products via density functional theory calculations of optical rotation, electronic circular dichroism, and vibrational circular dichroism: the cytotoxic sesquiterpene natural products quadrone, suberosenone, suberosanone, and suberosenol A acetate.

PubMed

Stephens, P J; McCann, D M; Devlin, F J; Smith, A B

2006-07-01

The determination of the absolute configurations (ACs) of chiral molecules using the chiroptical techniques of optical rotation (OR), electronic circular dichroism (ECD), and vibrational circular dichroism (VCD) has been revolutionized by the development of density functional theory (DFT) methods for the prediction of these properties. Here, we demonstrate the significance of these advances for the stereochemical characterization of natural products. Time-dependent DFT (TDDFT) calculations of the specific rotations, [alpha](D), of four cytotoxic natural products, quadrone (1), suberosenone (2), suberosanone (3), and suberosenol A acetate (4), are used to assign their ACs. TDDFT calculations of the ECD of 1 are used to assign its AC. The VCD spectrum of 1 is reported and also used, together with DFT calculations, to assign its AC. The ACs of 1 derived from its [alpha](D), ECD, and VCD are identical and in agreement with the AC previously determined via total synthesis. The previously undetermined ACs of 2-4, derived from their [alpha](D) values, have absolute configurations of their tricyclic cores identical to that of 1. Further studies of the ACs of these molecules using ECD and, especially, VCD are recommended to establish more definitively this finding. Our studies of the OR, ECD, and VCD of quadrone are the first to utilize DFT calculations of all three properties for the determination of the AC of a chiral natural product molecule.

A method for the generation of ectromelia virus (ECTV) recombinants: in vivo analysis of ECTV vCD30 deletion mutants.

PubMed

Alejo, Ali; Saraiva, Margarida; Ruiz-Argüello, Maria Begoña; Viejo-Borbolla, Abel; de Marco, Mar Fernández; Salguero, Francisco Javier; Alcami, Antonio

2009-01-01

Ectromelia virus (ECTV) is the causative agent of mousepox, a lethal disease of mice with similarities to human smallpox. Mousepox progression involves replication at the initial site of infection, usually the skin, followed by a rapid spread to the secondary replicative organs, spleen and liver, and finally a dissemination to the skin, where the typical rash associated with this and other orthopoxviral induced diseases appears. Case fatality rate is genetically determined and reaches up to 100% in susceptible mice strains. Like other poxviruses, ECTV encodes a number of proteins with immunomodulatory potential, whose role in mousepox progression remains largely undescribed. Amongst these is a secreted homologue of the cellular tumour necrosis factor receptor superfamily member CD30 which has been proposed to modulate a Th1 immune response in vivo. To evaluate the contribution of viral CD30 (vCD30) to virus pathogenesis in the infected host, we have adapted a novel transient dominant method for the selection of recombinant ECTVs. Using this method, we have generated an ECTV vCD30 deletion mutant, its corresponding revertant control virus as well as a virus encoding the extracellular domain of murine CD30. These viruses contain no exogenous marker DNA sequences in their genomes, as opposed to other ECTVs reported up to date. We show that the vCD30 is expressed as a secreted disulfide linked trimer and that the absence of vCD30 does not impair mousepox induced fatality in vivo. Replacement of vCD30 by a secreted version of mouse CD30 caused limited attenuation of ECTV. The recombinant viruses generated may be of use in the study of the role of the cellular CD30-CD30L interaction in the development of the immune response. The method developed might be useful for the construction of ECTV mutants for the study of additional genes.

Differential Regulation of Disheveled in a Novel Vegetal Cortical Domain in Sea Urchin Eggs and Embryos: Implications for the Localized Activation of Canonical Wnt Signaling

PubMed Central

Peng, ChiehFu Jeff; Wikramanayake, Athula H.

2013-01-01

Pattern formation along the animal-vegetal (AV) axis in sea urchin embryos is initiated when canonical Wnt (cWnt) signaling is activated in vegetal blastomeres. The mechanisms that restrict cWnt signaling to vegetal blastomeres are not well understood, but there is increasing evidence that the egg’s vegetal cortex plays a critical role in this process by mediating localized “activation” of Disheveled (Dsh). To investigate how Dsh activity is regulated along the AV axis, sea urchin-specific Dsh antibodies were used to examine expression, subcellular localization, and post-translational modification of Dsh during development. Dsh is broadly expressed during early sea urchin development, but immunolocalization studies revealed that this protein is enriched in a punctate pattern in a novel vegetal cortical domain (VCD) in the egg. Vegetal blastomeres inherit this VCD during embryogenesis, and at the 60-cell stage Dsh puncta are seen in all cells that display nuclear β-catenin. Analysis of Dsh post-translational modification using two-dimensional Western blot analysis revealed that compared to Dsh pools in the bulk cytoplasm, this protein is differentially modified in the VCD and in the 16-cell stage micromeres that partially inherit this domain. Dsh localization to the VCD is not directly affected by disruption of microfilaments and microtubules, but unexpectedly, microfilament disruption led to degradation of all the Dsh pools in unfertilized eggs over a period of incubation suggesting that microfilament integrity is required for maintaining Dsh stability. These results demonstrate that a pool of differentially modified Dsh in the VCD is selectively inherited by the vegetal blastomeres that activate cWnt signaling in early embryos, and suggests that this domain functions as a scaffold for localized Dsh activation. Localized cWnt activation regulates AV axis patterning in many metazoan embryos. Hence, it is possible that the VCD is an evolutionarily conserved cytoarchitectural domain that specifies the AV axis in metazoan ova. PMID:24236196

Four-year safety follow-up of the tetravalent dengue vaccine efficacy randomized controlled trials in Asia and Latin America.

PubMed

Arredondo-García, J L; Hadinegoro, S R; Reynales, H; Chua, M N; Rivera Medina, D M; Chotpitayasunondh, T; Tran, N H; Deseda, C C; Wirawan, D N; Cortés Supelano, M; Frago, C; Langevin, E; Coronel, D; Laot, T; Perroud, A P; Sanchez, L; Bonaparte, M; Limkittikul, K; Chansinghakul, D; Gailhardou, S; Noriega, F; Wartel, T A; Bouckenooghe, A; Zambrano, B

2018-02-08

Our objective was to describe the risk of hospital admission for virologically confirmed dengue (VCD) and the risk of clinically severe hospitalized VCD occurring up to 4 years after the first dose (years 1 to 4) in three randomized clinical trials comparing tetravalent dengue vaccine with placebo. The relative risks (RR) for hospitalized VCD from first dose to year 4 were estimated by year and age-group in individual and combined studies. Overall, from Year 1 to Year 4, 233 and 228 participants had at least one episode of hospitalized VCD in the vaccinated (n = 22 603) and placebo (n = 11 301) groups, respectively (RR = 0.511, 95% CI 0.42-0.62). Among these, 48 and 47 cases, respectively, were classified as clinically severe. In children aged ≥9 years, 88 and 136 participants had at least one episode of hospitalized VCD in the vaccinated (n = 17 629) and placebo (n = 8821) groups, respectively (RR = 0.324; 95% CI 0.24-0.43). In vaccinated participants aged <9 years, particularly in those aged 2-5 years, there were more hospitalized VCD cases compared with the control participants in Year 3 but not in Year 4. The overall RR in those aged <9 years for Year 1 to Year 4 was 0.786 (95% CI 0.60-1.03), with a higher protective effect in the 6-8 year olds than in the 2-5 year olds. The overall benefit-risk remained positive in those aged ≥9 years up to year 4, although the protective effect was lower in years 3 and 4 than in years 1 and 2. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Symptomatic Dengue in Children in 10 Asian and Latin American Countries.

PubMed

L'Azou, Maïna; Moureau, Annick; Sarti, Elsa; Nealon, Joshua; Zambrano, Betzana; Wartel, T Anh; Villar, Luis; Capeding, Maria R Z; Ochiai, R Leon

2016-03-24

The control groups in two phase 3 trials of dengue vaccine efficacy included two large regional cohorts that were followed up for dengue infection. These cohorts provided a sample for epidemiologic analyses of symptomatic dengue in children across 10 countries in Southeast Asia and Latin America in which dengue is endemic. We monitored acute febrile illness and virologically confirmed dengue (VCD) in 3424 healthy children, 2 to 16 years of age, in Asia (Indonesia, Malaysia, the Philippines, Thailand, and Vietnam) from June 2011 through December 2013 and in 6939 children, 9 to 18 years of age, in Latin America (Brazil, Colombia, Honduras, Mexico, and Puerto Rico) from June 2011 through April 2014. Acute febrile episodes were determined to be VCD by means of a nonstructural protein 1 antigen immunoassay and reverse-transcriptase-polymerase-chain-reaction assays. Dengue hemorrhagic fever was defined according to 1997 World Health Organization criteria. Approximately 10% of the febrile episodes in each cohort were confirmed to be VCD, with 319 VCD episodes (4.6 episodes per 100 person-years) occurring in the Asian cohort and 389 VCD episodes (2.9 episodes per 100 person-years) occurring in the Latin American cohort; no trend according to age group was observed. The incidence of dengue hemorrhagic fever was less than 0.3 episodes per 100 person-years in each cohort. The percentage of VCD episodes requiring hospitalization was 19.1% in the Asian cohort and 11.1% in the Latin American cohort. In comparable age groups (9 to 12 years and 13 to 16 years), the burden of dengue was higher in Asia than in Latin America. The burdens of dengue were substantial in the two regions and in all age groups. Burdens varied widely according to country, but the rates were generally higher and the disease more frequently severe in Asian countries than in Latin American countries. (Funded by Sanofi Pasteur; CYD14 and CYD15 ClinicalTrials.gov numbers, NCT01373281 and NCT01374516.).

New Perspective on Visual Communication Design Education: An Empirical Study of Applying Narrative Theory to Graphic Design Courses

ERIC Educational Resources Information Center

Yang, Chao-Ming; Hsu, Tzu-Fan

2017-01-01

Visual communication design (VCD) is a form of nonverbal communication. The application of relevant linguistic or semiotic theories to VCD education renders graphic design an innovative and scientific discipline. In this study, actual teaching activities were examined to verify the feasibility of applying narrative theory to graphic design…

Enantiomeric characterization and structure elucidation of LH601A using vibrational circular dichroism spectroscopy

NASA Astrophysics Data System (ADS)

Shen, Jian; Magesh, Sadagopan; Chen, Lin; Hu, Longqin; He, Yanan

2018-03-01

LH601A is a novel non-reactive chiral molecule inhibiting Keap1-Nrf2 protein-protein interaction. The absolute configuration (AC) was independently determined in this study using vibrational circular dichroism (VCD) spectroscopy. Because of band overlapping and broadening in the IR spectrum, a direct VCD spectrum comparison method is devised without the conventional IR band alignment. Being an unbiased AC inquiry, all possible chiralities are evaluated based on the statistical analysis of VCD similarity, Sv. The AC of three-center stereoisomer LH601A is unambiguously assigned to (S,R,S). A comparative study was also carried out to investigate the structural and energy differences of calculated conformers using the polarized continuum model of dimethyl sulfoxide.

Spinal neoplasms in small animals.

PubMed

Bagley, Rodney S

2010-09-01

Tumors arising from or involving the spinal cord are important considerations in animals presented for pain and limb dysfunction. Clinical signs of spinal cord dysfunction, however, are not pathognomic for neoplastic disease in most instances. Advanced magnetic resonance imaging (MRI) often accurately identifies the location and extent of abnormalities. Although some spinal neoplasms have a characteristic appearance with MRI, in other instances the abnormalities may not be readily discernable as neoplastic. Histologic diagnosis, therefore, is imperative to provide information regarding potential treatment modalities and prognosis. Histologic diagnosis is most commonly performed following surgical biopsy and is often performed in combination with surgical removal. Copyright 2010 Elsevier Inc. All rights reserved.

Concomitance of cervical intramedullary traumatic neuroma and cervical cord herniation in a tetraplegic woman.

PubMed

Su, Hui-Yi; Wu, Yung-Tsan; Liu, Ming-Ying; Lin, Yu-Chun; Chu, Heng-Yi; Chang, Shin-Tsu

2013-01-01

We present the first case of concomitant intramedullary traumatic neuroma and spinal cord herniation. A 57-year-old woman injured her cervical spine with subluxation and cord compression at the C5-C6 level. After the operation, the patient received intensive rehabilitation for one year with well response. Unfortunately, she experienced weakness and progressive numbness extending to all the limbs later. Cervical magnetic resonance imaging revealed spinal cord herniation at the C5-C6 level and pathology proved intramedullary traumatic neuroma. After the second operation, the paresthesia over the trunk and limbs persisted, and the patient was nearly totally assisted in her activities of daily living. The intramedullary traumatic neuroma and spinal cord herniation are rare causes in patients with spinal cord dysfunction. The case presented here indicates the possibility of the coexisting conditions leading to progressive neurologic deficits in patients with old spinal cord injury.

Regulation of malonyl-CoA-acyl carrier protein transacylase network in umbilical cord blood affected by intrauterine hyperglycemia.

PubMed

Zhang, Yong; Ye, Jianping; Fan, Jianxia

2017-09-26

Gestational diabetes mellitus (GDM) has been shown to be associated with high risk of diabetes in offspring. However, the mechanisms involved in the insulin resistance in offspring are still unclear. Mitochondrial dysfunction is related with insulin resistance. In mitochondria, malonyl-CoA-acyl carrier protein transacylase (MCAT) is the key enzyme of mitochondrial fatty acid synthesis and is estimated to contribute to insulin resistance. In this study, we aimed to examine the role of MCAT and its network in the umbilical cord blood in GDM-induced offspring insulin resistance. We isolated lymphocytes from umbilical cord vein blood in 6 GDM patients and 6 controls and examined the differences of RNA by RNA sequencing. qRT-PCR and western blot were used to measure mRNA and protein changes. Bisulfite genomic sequencing PCR was applied to detect DNA methylation. We found more than 400 genes were differentially regulated in the lymphocytes of umbilical cord blood from GDM patients and these genes were mainly enriched in immune system and endocrine system, which relate to mitochondrial dysfunction and insulin resistance. MCAT closely related with PTPN1 (Protein Tyrosine Phosphatase, Non-Receptor Type1) and STAT5A (Signal Transducer And Activator of Transcription 5A), which were all increased in umbilical cord blood from GDM patients. Increase in MCAT may be due to decreased MCAT DNA methylation. MCAT and its network with PTPN1, STAT5A are regulated in umbilical cord blood affected by maternal intrauterine hyperglycemia.

Electrophysiologic monitoring characteristics of the recurrent laryngeal nerve preoperatively paralyzed or invaded with malignancy.

PubMed

Kamani, Dipti; Darr, E Ashlie; Randolph, Gregory W

2013-11-01

To elucidate electrophysiologic responses of the recurrent laryngeal nerves that were preoperatively paralyzed or invaded by malignancy and to use this information as an added functional parameter for intraoperative management of recurrent laryngeal nerves with malignant invasion. Case series with chart review. Academic, tertiary care center. All consecutive neck surgeries with nerve monitoring performed by senior author (GWR) between December 1995 and January 2007 were reviewed after obtaining Institutional Review Board approval from Massachusetts Eye and Ear Infirmary Human Subjects Committee and the Partners Human Research Committee. Electrophysiologic parameters in all cases with preoperative vocal cord paralysis/paresis, and the recurrent laryngeal nerve invasion by cancer, were studied. Of the 1138 surgeries performed, 25 patients (2.1%) had preoperative vocal cord dysfunction. In patients with preoperative vocal cord dysfunction, recognizable recurrent laryngeal nerve electrophysiologic activity was preserved in over 50% of cases. Malignant invasion of the recurrent laryngeal nerve was found in 22 patients (1.9%). Neural invasion of the recurrent laryngeal nerve was associated with preoperative vocal cord paralysis in only 50% of these patients. In nerves invaded by malignancy, 60% maintained recognizable electrophysiologic activity, which was more commonly present and robust when vocal cord function was preserved. Knowledge of electrophysiologic intraoperative neural monitoring provides additional functional information and, along with preoperative vocal cord function information, aids in constructing decision algorithms regarding intraoperative management of the recurrent laryngeal nerve, in prognosticating postoperative outcomes, and in patient counseling regarding postoperative expectations.

Regional modeling of tropospheric NO2 vertical column density over East Asia during the period 2000-2010: comparison with multisatellite observations

NASA Astrophysics Data System (ADS)

Itahashi, S.; Uno, I.; Irie, H.; Kurokawa, J.-I.; Ohara, T.

2014-04-01

Satellite observations of the tropospheric NO2 vertical column density (VCD) are closely correlated to, and thus can be used to estimate, surface NOx emissions. In this study, the NO2 VCD simulated by a regional chemical transport model with emissions data from the updated Regional Emission inventory in ASia (REAS) version 2.1 were validated through comparison with multisatellite observations during the period 2000-2010. Rapid growth in NO2 VCD (~11% year-1) driven by the expansion of anthropogenic NOx emissions was identified above the central eastern China (CEC) region, except for the period during the economic downturn. In contrast, slightly decreasing trends (~2% year-1) were identified above Japan accompanied by a decline in anthropogenic emissions. To systematically compare the modeled NO2 VCD, we estimated sampling bias and the effect of applying the averaging kernel information, with particular focus on the SCanning Imaging Absorption spectroMeter for Atmospheric CHartographY (SCIAMACHY) data. Using the updated REAS, the modeled NO2 VCD reasonably reproduced annual trends observed by multisatellites, suggesting that the rate of increase of NOx emissions estimated by the updated REAS inventory would be robust. Province-scale revision of emissions above CEC is needed to further refine emission inventories. Based on the close linear relationship between modeled and observed NO2 VCD and anthropogenic NOx emissions, NOx emissions in 2009 and 2010, which were not covered by the updated REAS inventory, were estimated. NOx emissions from anthropogenic sources in China in 2009 and 2010 were determined to be 26.4 and 28.5 Tg year-1, respectively, indicating that NOx emissions increased more than twofold between 2000 and 2010. This increase reflected the strong growth of anthropogenic emissions in China following the rapid recovery from the economic downturn from late 2008 until mid-2009. Our method consists of simple estimations from satellite observations and provides results that are consistent with the most recent inventory of emissions data for China.

Mobile MAX-DOAS observation of NO2 and comparison with OMI satellite data in the western coastal areas of the Korean peninsula.

PubMed

Chong, Jihyo; Kim, Young J; Gu, Myojeong; Wagner, Thomas; Song, Chul H

2016-01-01

Ground-based MAX-DOAS measurements have been used to retrieve column densities of atmospheric absorbers such as NO2, SO2, HCHO, and O3. In this study, mobile MAX-DOAS measurements were conducted to map the 2-D distributions of atmospheric NO2 in the western coastal areas of the Korean peninsula. A Mini-MAX-DOAS instrument was mounted on the rooftop of a mobile lab vehicle with a telescope mounted parallel to the driving direction, pointing forward. The measurements were conducted from 21 to 24 December 2010 along the western coastal areas from Gomso harbor (35.59N, 126.61E) to Gunsan harbor (35.98N, 126.67E). During mobile MAX-DOAS observations, high elevation angles were used to avoid shades from nearby obstacles. For the determination of the tropospheric vertical column density (VCD), the air mass factor (AMF) was retrieved by the so-called geometric approximation. The NO2 VCDs from 20 and 45 degree elevation angles were retrieved from mobile MAX-DOAS measurements. The tropospheric NO2 VCDs derived from mobile MAX-DOAS measurements were compared directly to those retrieved by the OMI satellite observations. Mobile MAX-DOAS VCD was in good agreement with OMI tropospheric VCD on most days. However, OMI tropospheric VCD was much higher than that of mobile MAX-DOAS on 23 December 2010. One probable reason for this difference is that OMI retrieval might overestimate NO2 VCD under haze conditions, when a pollution plume was transported over the measurement site. The mobile MAX-DOAS observations reveal much finer spatial patterns of NO2 distributions, which can provide useful information for the validation of satellite observation of atmospheric trace gases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantifying and Reducing Uncertainties in Estimating OMI Tropospheric Column NO2 Trend over The United States

NASA Astrophysics Data System (ADS)

Smeltzer, C. D.; Wang, Y.; Boersma, F.; Celarier, E. A.; Bucsela, E. J.

2013-12-01

We investigate the effects of retrieval radiation schemes and parameters on trend analysis using tropospheric nitrogen dioxide (NO2) vertical column density (VCD) measurements over the United States. Ozone Monitoring Instrument (OMI) observations from 2005 through 2012 are used in this analysis. We investigated two radiation schemes, provided by National Aeronautics and Space Administration (NASA TOMRAD) and Koninklijk Nederlands Meteorologisch Instituut (KNMI DAK). In addition, we analyzed trend dependence on radiation parameters, including surface albedo and viewing geometry. The cross-track mean VCD average difference is 10-15% between the two radiation schemes in 2005. As the OMI anomaly developed and progressively worsens, the difference between the two schemes becomes larger. Furthermore, applying surface albedo measurements from the Moderate Resolution Imaging Spectroradiometer (MODIS) leads to increases of estimated NO2 VCD trends over high-emission regions. We find that the uncertainties of OMI-derived NO2 VCD trends can be reduced by up to a factor of 3 by selecting OMI cross-track rows on the basis of their performance over the ocean [see abstract figure]. Comparison of OMI tropospheric VCD trends to those estimated based on the EPA surface NO2 observations indicate using MODIS surface albedo data and a more narrow selection of OMI cross-track rows greatly improves the agreement of estimated trends between satellite and surface data. This figure shows the reduction of uncertainty in OMI NO2 trend by selecting OMI cross-track rows based on the performance over the ocean. With this technique, uncertainties within the seasonal trend may be reduced by a factor of 3 or more (blue) compared with only removing the anomalous rows: considering OMI cross-track rows 4-24 (red).

Neuroanatomy, neurophysiology, and dysfunction of the female lower urinary tract: a review.

PubMed

Unger, Cécile A; Tunitsky-Bitton, Elena; Muffly, Tyler; Barber, Matthew D

2014-01-01

The 2 major functions of the lower urinary tract are the storage and emptying of urine. These processes are controlled by complex neurophysiologic mechanisms and are subject to injury and disease. When there is disruption of the neurologic control centers, dysfunction of the lower urinary tract may occur. This is sometimes referred to as the "neurogenic bladder." The manifestation of dysfunction depends on the level of injury and severity of disruption. Patients with lesions above the spinal cord often have detrusor overactivity with no disruption in detrusor-sphincter coordination. Patients with well-defined suprasacral spinal cord injuries usually present with intact reflex detrusor activity but have detrusor sphincter dyssynergia, whereas injuries to or below the sacral spinal cord usually lead to persistent detrusor areflexia. A complete gynecologic, urologic, and neurologic examination should be performed when evaluating patients with neurologic lower urinary tract dysfunction. In addition, urodynamic studies and neurophysiologic testing can be used in certain circumstances to help establish diagnosis or to achieve better understanding of a patient's vesicourethral functioning. In the management of neurogenic lower urinary tract dysfunction, the primary goal is improvement of a patient's quality of life. Second to this is the prevention of chronic damage to the bladder and kidneys, which can lead to worsening impairment and symptoms. Treatment is often multifactorial, including behavioral modifications, bladder training programs, and pharmacotherapy. Surgical procedures are often a last resort option for management. An understanding of the basic neurophysiologic mechanisms of the lower urinary tract can guide providers in their evaluation and treatment of patients who present with lower urinary tract disorders. As neurologic diseases progress, voiding function often changes or worsens, necessitating a good understanding of the underlying physiology in question.

Cardiac dysfunctions following spinal cord injury

PubMed Central

Sandu, AM; Popescu, M; Iacobini, MA; Stoian, R; Neascu, C; Popa, F

2009-01-01

The aim of this article is to analyze cardiac dysfunctions occurring after spinal cord injury (SCI). Cardiac dysfunctions are common complications following SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. We reviewed epidemiology of cardiac disturbances after SCI, and neuroanatomy and pathophysiology of autonomic nervous system, sympathetic and parasympathetic. SCI causes disruption of descendent pathways from central control centers to spinal sympathetic neurons, originating into intermediolateral nuclei of T1–L2 spinal cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant cardiac dysfunction. Impairment of autonomic nervous control system, mostly in patients with cervical or high thoracic SCI, causes cardiac dysrrhythmias, especially bradycardia and, rarely, cardiac arrest, or tachyarrhytmias and hypotension. Specific complication dependent on the period of time after trauma like spinal shock and autonomic dysreflexia are also reviewed. Spinal shock occurs during the acute phase following SCI and is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe bradycardia and hypotension. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Besides all this, additional cardiac complications, such as cardiac deconditioning and coronary heart disease may also occur. Proper prophylaxis, including nonpharmacologic and pharmacological strategies and cardiac rehabilitation diminish occurrence of the cardiac dysfunction following SCI. Each type of cardiac disturbance requires specific treatment. PMID:20108532

Factors associated with sexual functioning in women following spinal cord injury.

PubMed

Harrison, J; Glass, C A; Owens, R G; Soni, B M

1995-12-01

Research into sexuality following spinal cord injury (SCI) has tended to concentrate on male experiences and the physical capabilities for sexual intercourse. The sexuality of women following SCI has only recently been addressed and studies are limited to small numbers and the use of non-standardised measures. The present investigation utilised standard measures of affective state and body satisfaction together with pre and post-injury questionnaire information of sexual dysfunction, feelings about sex and importance of sexual activity in a group of 85 women with SCI. Sexual dysfunction increased significantly post-injury, whilst feelings about sex and it's importance were unaffected. Sexual dysfunction and the importance of sex were inversely correlated. General and Head satisfaction estimates were not significantly different to control samples, whilst Body Satisfaction was increased for women with disabilities. None of the body satisfaction measures were related to the sexual functioning measure. General dissatisfaction was associated depression. Both anxiety and depression were experienced by the same individuals, and anxiety related to current sexual dysfunction. Qualitative data supported previous findings concerning the effects of social and attitudinal barriers on sexual functioning.

Diagnostic criteria for vascular cognitive disorders: a VASCOG statement.

PubMed

Sachdev, Perminder; Kalaria, Raj; O'Brien, John; Skoog, Ingmar; Alladi, Suvarna; Black, Sandra E; Blacker, Deborah; Blazer, Dan G; Chen, Christopher; Chui, Helena; Ganguli, Mary; Jellinger, Kurt; Jeste, Dilip V; Pasquier, Florence; Paulsen, Jane; Prins, Niels; Rockwood, Kenneth; Roman, Gustavo; Scheltens, Philip

2014-01-01

Several sets of diagnostic criteria have been published for vascular dementia since the 1960s. The continuing ambiguity in vascular dementia definition warrants a critical reexamination. Participants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the fifth revision of Diagnostic and Statistical Manual (DSM-5) Task Force. Cognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent cooccurrence of Alzheimer disease pathology emphasized. The proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathologic validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved.

Structure elucidation and absolute stereochemistry of isomeric monoterpene chromane esters.

PubMed

Batista, João M; Batista, Andrea N L; Mota, Jonas S; Cass, Quezia B; Kato, Massuo J; Bolzani, Vanderlan S; Freedman, Teresa B; López, Silvia N; Furlan, Maysa; Nafie, Laurence A

2011-04-15

Six novel monoterpene chromane esters were isolated from the aerial parts of Peperomia obtusifolia (Piperaceae) using chiral chromatography. This is the first time that chiral chromane esters of this kind, ones with a tethered chiral terpene, have been isolated in nature. Due to their structural features, it is not currently possible to assess directly their absolute stereochemistry using any of the standard classical approaches, such as X-ray crystallography, NMR, optical rotation, or electronic circular dichroism (ECD). Herein we report the absolute configuration of these molecules, involving four chiral centers, using vibrational circular dichroism (VCD) and density functional theory (DFT) (B3LYP/6-31G*) calculations. This work further reinforces the capability of VCD to determine unambiguously the absolute configuration of structurally complex molecules in solution, without crystallization or derivatization, and demonstrates the sensitivity of VCD to specify the absolute configuration for just one among a number of chiral centers. We also demonstrate the sufficiency of using the so-called inexpensive basis set 6-31G* compared to the triple-ζ basis set TZVP for absolute configuration analysis of larger molecules using VCD. Overall, this work extends our knowledge of secondary metabolites in plants and provides a straightforward way to determine the absolute configuration of complex natural products involving a chiral parent moiety combined with a chiral terpene adduct.

Vascular dysfunctions following spinal cord injury

PubMed Central

Popa, F; Grigorean, VT; Onose, G; Sandu, AM; Popescu, M; Burnei, G; Strambu, V; Sinescu, C

2010-01-01

The aim of this article is to analyze the vascular dysfunctions occurring after spinal cord injury (SCI). Vascular dysfunctions are common complications of SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. Neuroanatomy and physiology of autonomic nervous system, sympathetic and parasympathetic, is reviewed. SCI implies disruption of descendent pathways from central centers to spinal sympathetic neurons, originating in intermediolateral nuclei of T1–L2 cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant vascular dysfunction. Spinal shock occurs during the acute phase following SCI and it is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe arterial hypotension and bradycardia. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Arterial hypotension with orthostatic hypotension occurs in both acute and chronic phases. The etiology is multifactorial. We described a few factors influencing the orthostatic hypotension occurrence in SCI: sympathetic nervous system dysfunction, low plasma catecholamine levels, rennin–angiotensin–aldosterone activity, peripheral alpha–adrenoceptor hyperresponsiveness, impaired function of baroreceptors, hyponatremia and low plasmatic volume, cardiovascular deconditioning, morphologic changes in sympathetic neurons, plasticity within spinal circuits, and motor deficit leading to loss of skeletal muscle pumping activity. Additional associated cardiovascular concerns in SCI, such as deep vein thrombosis and long–term risk for coronary heart disease and systemic atherosclerosis are also described. Proper prophylaxis, including non–pharmacologic and pharmacological strategies, diminishes the occurrence of the vascular dysfunction following SCI. Each vascular disturbance requires a specific treatment. PMID:20945818

Regulation of malonyl-CoA-acyl carrier protein transacylase network in umbilical cord blood affected by intrauterine hyperglycemia

PubMed Central

Zhang, Yong; Ye, Jianping; Fan, Jianxia

2017-01-01

Background Gestational diabetes mellitus (GDM) has been shown to be associated with high risk of diabetes in offspring. However, the mechanisms involved in the insulin resistance in offspring are still unclear. Mitochondrial dysfunction is related with insulin resistance. In mitochondria, malonyl-CoA-acyl carrier protein transacylase (MCAT) is the key enzyme of mitochondrial fatty acid synthesis and is estimated to contribute to insulin resistance. In this study, we aimed to examine the role of MCAT and its network in the umbilical cord blood in GDM-induced offspring insulin resistance. Methods We isolated lymphocytes from umbilical cord vein blood in 6 GDM patients and 6 controls and examined the differences of RNA by RNA sequencing. qRT-PCR and western blot were used to measure mRNA and protein changes. Bisulfite genomic sequencing PCR was applied to detect DNA methylation. Results We found more than 400 genes were differentially regulated in the lymphocytes of umbilical cord blood from GDM patients and these genes were mainly enriched in immune system and endocrine system, which relate to mitochondrial dysfunction and insulin resistance. MCAT closely related with PTPN1 (Protein Tyrosine Phosphatase, Non-Receptor Type1) and STAT5A (Signal Transducer And Activator of Transcription 5A), which were all increased in umbilical cord blood from GDM patients. Increase in MCAT may be due to decreased MCAT DNA methylation. Conclusion MCAT and its network with PTPN1, STAT5A are regulated in umbilical cord blood affected by maternal intrauterine hyperglycemia. PMID:29088862

Determination of the absolute configurations of synthetic daunorubicin analogues using vibrational circular dichroism spectroscopy and density functional theory.

PubMed

Yang, Guochun; Tran, Ha; Fan, Eric; Shi, Wei; Lowary, Todd L; Xu, Yunjie

2010-08-01

The absolute configurations of three synthesized anthracycline analogues have been determined using vibrational circular dichroism (VCD) spectroscopy and the density functional theory (DFT) calculations. The experimental VCD spectra of the three compounds have been measured for the first time in the film state, prepared from their CDCl(3) solutions. Conformational searches for the monomers and some dimers of the three compounds have been performed at the DFT level using the B3LYP functional and the 6-311G** and 6-311++G** basis sets. The corresponding vibrational absorption and VCD spectra have been calculated. The good agreement between the experimental and the calculated spectra allows one to assign the absolute configurations of the three compounds with high confidence. In addition, the dominant conformers of the three compounds have also been identified. Copyright 2010 Wiley-Liss, Inc.

Monitoring somatosensory evoked potentials in spinal cord ischemia-reperfusion injury

PubMed Central

Ji, Yiming; Meng, Bin; Yuan, Chenxi; Yang, Huilin; Zou, Jun

2013-01-01

It remains unclear whether spinal cord ischemia-reperfusion injury caused by ischemia and other non-mechanical factors can be monitored by somatosensory evoked potentials. Therefore, we monitored spinal cord ischemia-reperfusion injury in rabbits using somatosensory evoked potential detection technology. The results showed that the somatosensory evoked potential latency was significantly prolonged and the amplitude significantly reduced until it disappeared during the period of spinal cord ischemia. After reperfusion for 30–180 minutes, the amplitude and latency began to gradually recover; at 360 minutes of reperfusion, the latency showed no significant difference compared with the pre-ischemic value, while the somatosensory evoked potential amplitude in-creased, and severe hindlimb motor dysfunctions were detected. Experimental findings suggest that changes in somatosensory evoked potential latency can reflect the degree of spinal cord ischemic injury, while the amplitude variations are indicators of the late spinal cord reperfusion injury, which provide evidence for the assessment of limb motor function and avoid iatrogenic spinal cord injury. PMID:25206629

Effect of spinal anterior root stimulation and sacral deafferentation on bladder and sexual dysfunction in spinal cord injury.

PubMed

Zaer, Hamed; Rasmussen, Mikkel Mylius; Zepke, Franko; Bodin, Charlotte; Domurath, Burkhard; Kutzenberger, Johannes

2018-05-10

Spinal cord injury (SCI) is a highly devastating injury with a variety of complications; among them are neurogenic bladder, bowel, and sexual dysfunction. We aimed to evaluate the effect of sacral anterior root stimulation with sacral deafferentation (SARS-SDAF) on neurogenic bladder and sexual dysfunction in a large well-defined spinal cord injury cohort. In the manner of cross-sectional study, subjects undergone SARS-SDAF between September 1986 and July 2011 answered a questionnaire concerning conditions before and after surgery in the department of Neuro-Urology, Bad Wildungen, Germany. In total 287 of 587 subjects were analyzed. Median age was 49 years (range 19-80), median time from SCI to surgery was 10 years (range 0-49), and from surgery to follow-up 13 years (range 1-25). Of the analyzed subjects, 100% of both gender used SARS for bladder emptying. On the visual analogue scale (VAS) ranging from 0 to 10 (best), satisfaction with SARS-SDAF was 10 concerning bladder emptying, however 5 and 8 regarding sexual performance, for female and male users, respectively. Baseline and follow-up comparison showed a decline in self-intermittent catheterization (p < 0.0001), partial catheterization by attendant (p = 0.0125), complete catheterization and suprapubic catheterization (p < 0.0001), transurethral catheterization (p < 0.0011), and fewer cases of involuntary urine leakage (p < 0.0001). The SARS-SDAF is a beneficial multi-potential treatment method with simultaneous positive effect on multi-organ dysfunction among SCI subjects.

Sudden death and paroxysmal autonomic dysfunction in stiff-man syndrome.

PubMed

Mitsumoto, H; Schwartzman, M J; Estes, M L; Chou, S M; La Franchise, E F; De Camilli, P; Solimena, M

1991-04-01

Two women with typical stiff-man syndrome (SMS) developed increasingly frequent attacks of muscle spasms with severe paroxysmal autonomic dysfunctions such as transient hyperpyrexia, diaphoresis, tachypnea, tachycardia, pupillary dilation, and arterial hypertension. Autoantibodies to GABA-ergic neurons were identified in the serum of both patients and in the cerebrospinal fluid of one. Both died suddenly and unexpectedly. General autopsy did not reveal the cause of death. Neuropathological studies revealed perivascular gliosis in the spinal cord and brain stem of one patient and lymphocytic perivascular infiltration in the spinal cord, brain stem, and basal ganglia of the other. The occurrence of a chronic inflammatory reaction in one of the two patients supports the idea that an autoimmune disease against GABA-ergic neurons may be involved in SMS. A review of the literature indicates that functional impairment in SMS is severe and prognosis is unpredictable because of the potential for sudden and unexpected death. Both muscular abnormalities and autonomic dysfunctions may result from autoimmunity directed against GABA-ergic neurons.

Trend analysis of tropospheric NO2 column density over East Asia during 2000-2010: multi-satellite observations and model simulations with the updated REAS emission inventory

NASA Astrophysics Data System (ADS)

Itahashi, S.; Uno, I.; Irie, H.; Kurokawa, J.; Ohara, T.

2013-04-01

Satellite observations of the tropospheric NO2 vertical column density (VCD) are closely correlated to surface NOx emissions and can thus be used to estimate the latter. In this study, the NO2 VCDs simulated by a regional chemical transport model with data from the updated Regional Emission inventory in ASia (REAS) version 2.1 were validated by comparison with multi-satellite observations (GOME, SCIAMACHY, GOME-2, and OMI) between 2000 and 2010. Rapid growth in NO2 VCD driven by expansion of anthropogenic NOx emissions was revealed above the central eastern China region, except during the economic downturn. In contrast, slightly decreasing trends were captured above Japan. The modeled NO2 VCDs using the updated REAS emissions reasonably reproduced the annual trends observed by multi-satellites, suggesting that the NOx emissions growth rate estimated by the updated inventory is robust. On the basis of the close linear relationship of modeled NO2 VCD, observed NO2 VCD, and anthropogenic NOx emissions, the NOx emissions in 2009 and 2010 were estimated. It was estimated that the NOx emissions from anthropogenic sources in China beyond doubled between 2000 and 2010, reflecting the strong growth of anthropogenic emissions in China with the rapid recovery from the economic downturn during late 2008 and mid-2009.

Nonplanar tertiary amides in rigid chiral tricyclic dilactams. Peptide group distortions and vibrational optical activity.

PubMed

Pazderková, Markéta; Profant, Václav; Hodačová, Jana; Sebestík, Jaroslav; Pazderka, Tomáš; Novotná, Pavlína; Urbanová, Marie; Safařík, Martin; Buděšínský, Miloš; Tichý, Miloš; Bednárová, Lucie; Baumruk, Vladimír; Maloň, Petr

2013-08-22

We investigate amide nonplanarity in vibrational optical activity (VOA) spectra of tricyclic spirodilactams 5,8-diazatricyclo[6,3,0,0(1,5)]undecan-4,9-dione (I) and its 6,6',7,7'-tetradeuterio derivative (II). These rigid molecules constrain amide groups to nonplanar geometries with twisted pyramidal arrangements of bonds to amide nitrogen atoms. We have collected a full range vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectra including signals of C-H and C-D stretching vibrations. We report normal-mode analysis and a comparison of calculated to experimental VCD and ROA. The data provide band-to-band assignment and offer a possibility to evaluate roles of constrained nonplanar tertiary amide groups and rigid chiral skeletons. Nonplanarity shows as single-signed VCD and ROA amide I signals, prevailing the couplets expected to arise from the amide-amide interaction. Amide-amide coupling dominates amide II (mainly C'-N stretching, modified in tertiary amides by the absence of a N-H bond) transitions (strong couplet in VCD, no significant ROA) probably due to the close proximity of amide nitrogen atoms. At lower wavenumbers, ROA spectra exhibit another likely manifestation of amide nonplanarity, showing signals of amide V (δ(oop)(N-C) at ~570 cm(-1)) and amide VI (δ(oop)(C'═O) at ~700 cm(-1) and ~650 cm(-1)) vibrations.

Advanced Applications of Vibrational Circular Dichroism: from Small Chiral Molecules to Fibrils

NASA Astrophysics Data System (ADS)

Dukor, Rina K.

2017-06-01

Vibrational Circular Dichroism (VCD), first discovered in the early 1970s, and commercialized in the late 1990's, is finally coming of age! No longer a curiosity of the few selected academic groups, it is now used by all major pharmaceutical companies, regulatory agencies, government labs and academic institutions. The main application for the technology has been determination of absolute configuration of small pharmaceutical molecules. In more recent years, this has extended to more complicated molecules such as natural products with many chiral centers and conformational flexibility. Other applications include determination of enantiomeric purity, chiral polymers, and characterization of other biological molecules such as proteins, carohydrates and nucleic acids. One of the most fascinating discoveries in the VCD field has been been unusual enhancement in intensity for proteins that form fibrils. We have demonstrated sensitivity of VCD to in situ solution-phase probe of the process of fibrillogenesis and subsequent development that currently can only be studied in detail with dried samples by such techniques as scanning electron microscopy or atomic force microscopy. We have further shown that several different proteins, that in their native state have different secondary structures, have a very similar unique signature of mature fibrils. In this presentation, we will discuss fundamentals of VCD, demonstrate a few examples of different applications and showcase the sensitivity to structure of fibrils, including new results on micro-sampling.

Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib.

PubMed

Kastritis, E; Gavriatopoulou, M; Roussou, M; Fotiou, D; Ziogas, D C; Migkou, M; Eleutherakis-Papaiakovou, E; Panagiotidis, I; Kanellias, N; Psimenou, E; Papadopoulou, E; Pamboucas, C; Manios, E; Gakiopoulou, H; Ntalianis, A; Tasidou, A; Giannouli, S; Terpos, E; Dimopoulos, M A

2017-06-16

Bortezomib, in combination with dexamethasone (VD) or with the addition of cyclophosphamide (VCD), is highly effective in patients with amyloid light-chain (AL) amyloidosis. Currently, VCD is considered as a primary regimen for patients with AL, but it is not clear whether the addition of cyclophosphamide to VD further and significantly improves efficacy, given the substantial activity of bortezomib itself. We retrospectively compared the outcomes of 101 patients with AL amyloidosis who received VD (n=59) or VCD (n=42) in two consecutive periods. Early mortality after adjustment for Mayo stage was similar. On intent to treat, a hematologic response rate was 68% for patients treated with VD and 78% for VCD (P=0.26), while complete response+very good partial response (CR+VGPR) rate was 47.5% and 35%, respectively. Higher doses of dexamethasone or twice-weekly bortezomib were not associated with significantly higher CR+VGPR rates. Organ responses occurred in similar rates between the two groups. Median survival was similar (33 vs 36 months, P=0.45) even after adjustment for Mayo stage and dose and schedule of bortezomib and dexamethasone. In conclusion, bortezomib even with low doses of dexamethasone is effective for the treatment of AL amyloidosis; higher doses of dexamethasone and addition of cyclophosphamide do not seem to have a profound effect on efficacy and survival.

Application of dielectric spectroscopy for monitoring high cell density in monoclonal antibody producing CHO cell cultivations.

PubMed

Párta, László; Zalai, Dénes; Borbély, Sándor; Putics, Akos

2014-02-01

The application of dielectric spectroscopy was frequently investigated as an on-line cell culture monitoring tool; however, it still requires supportive data and experience in order to become a robust technique. In this study, dielectric spectroscopy was used to predict viable cell density (VCD) at industrially relevant high levels in concentrated fed-batch culture of Chinese hamster ovary cells producing a monoclonal antibody for pharmaceutical purposes. For on-line dielectric spectroscopy measurements, capacitance was scanned within a wide range of frequency values (100-19,490 kHz) in six parallel cell cultivation batches. Prior to detailed mathematical analysis of the collected data, principal component analysis (PCA) was applied to compare dielectric behavior of the cultivations. PCA analysis resulted in detecting measurement disturbances. By using the measured spectroscopic data, partial least squares regression (PLS), Cole-Cole, and linear modeling were applied and compared in order to predict VCD. The Cole-Cole and the PLS model provided reliable prediction over the entire cultivation including both the early and decline phases of cell growth, while the linear model failed to estimate VCD in the later, declining cultivation phase. In regards to the measurement error sensitivity, remarkable differences were shown among PLS, Cole-Cole, and linear modeling. VCD prediction accuracy could be improved in the runs with measurement disturbances by first derivative pre-treatment in PLS and by parameter optimization of the Cole-Cole modeling.

Diagnostic criteria for vascular cognitive disorders: a VASCOG statement

PubMed Central

Sachdev, Perminder; Kalaria, Raj; O’Brien, John; Skoog, Ingmar; Alladi, Suvarna; Black, Sandra E; Blacker, Deborah; Blazer, Dan; Chen, Christopher; Chui, Helena; Ganguli, Mary; Jellinger, Kurt; Jeste, Dilip V.; Pasquier, Florence; Paulsen, Jane; Prins, Niels; Rockwood, Kenneth; Roman, Gustavo; Scheltens, Philip

2014-01-01

Background Several sets of diagnostic criteria have been published for vascular dementia (VaD) since the 1960s. The continuing ambiguity in VaD definition warrants a critical re-examination. Methods Participants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the DSM-5 Task Force. Results Cognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent co-occurrence of Alzheimer’s disease pathology emphasized. Conclusions The proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathological validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved. PMID:24632990

Normal and reversed supramolecular chirality of insulin fibrils probed by vibrational circular dichroism at the protofilament level of fibril structure.

PubMed

Kurouski, Dmitry; Dukor, Rina K; Lu, Xuefang; Nafie, Laurence A; Lednev, Igor K

2012-08-08

Fibrils are β-sheet-rich aggregates that are generally composed of several protofibrils and may adopt variable morphologies, such as twisted ribbons or flat-like sheets. This polymorphism is observed for many different amyloid associated proteins and polypeptides. In a previous study we proposed the existence of another level of amyloid polymorphism, namely, that associated with fibril supramolecular chirality. Two chiral polymorphs of insulin, which can be controllably grown by means of small pH variations, exhibit opposite signs of vibrational circular dichroism (VCD) spectra. Herein, using atomic force microscopy (AFM) and scanning electron microscopy (SEM), we demonstrate that indeed VCD supramolecular chirality is correlated not only by the apparent fibril handedness but also by the sense of supramolecular chirality from a deeper level of chiral organization at the protofilament level of fibril structure. Our microscopic examination indicates that normal VCD fibrils have a left-handed twist, whereas reversed VCD fibrils are flat-like aggregates with no obvious helical twist as imaged by atomic force microscopy or scanning electron microscopy. A scheme is proposed consistent with observed data that features a dynamic equilibrium controlled by pH at the protofilament level between left- and right-twist fibril structures with distinctly different aggregation pathways for left- and right-twisted protofilaments. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Enhancement of IR and VCD intensities due to charge transfer.

PubMed

Nicu, Valentin Paul; Autschbach, Jochen; Baerends, Evert Jan

2009-03-14

Donor-acceptor interactions such as the one between the Cl(-) base and the N-H sigma* acceptor orbitals encountered in the complexation of Cl(-) counterions to the [Co(en)(3)](3+) transition metal complex, have been shown to cause huge enhancement (between 1 and 2 orders of magnitude) of the VCD intensities of N-H stretching modes. This effect has been fully analyzed, and could be attributed to increased charge flow from the Cl(-) donors when the N-H bonds become stretched. The transfer of charge counteracts the movement of negative electronic charge that happens along with the motion of the H nuclei, effectively reversing the electronic part of the electric dipole transition moment (EDTM) in the direction of the charge flow (z, say), and of the magnetic transition dipole moment (MDTM) in the perpendicular direction. The consequences for the IR and VCD intensity follow: IR intensity is strongly increased if the EDTM is polarized in the z direction, e.g. in A(2) modes, but not so much if it is polarized in the xy plane (E modes), the VCD is strongly enhanced if the EDTM and MTDM are polarized in the xy plane (in E modes), but less so when they are polarized in the z direction (in A(2) modes). The explanation holds generally for complexation phenomena of this sort, including the donor-acceptor part of hydrogen bonding interactions, e.g. with solvent molecules.

The VCD pattern of the ν(C=O) bands in isoindolinones.

PubMed

Rode, Joanna Ewa; Lyczko, Krzysztof; Jawiczuk, Magdalena; Kawęcki, Robert; Stańczyk, Wojciech; Jaglińska, Agnieszka; Dobrowolski, Jan Cz

2018-05-18

The IR and VCD spectra of both enantiomers of Me, iPr, nBu, Ph and CH2Ph substituted isoindolinones in solution and KBr pellets were measured and interpreted with DFT calculations. The spectra in solution revealed no important differences in the C=O stretching vibration region while the interpretation of very distinct spectra taken in pellets required determining the crystal structures. The studied compounds crystallized in the P212121 (Me, iPr, CH2Ph), P31 (nBu), and P21 (Ph) space groups. We found that the quality of simulated spectra strongly depends on the substituent, the structure of the molecular cluster assumed, basis set, and use of the dispersion correction. The IR spectra can be reproduced well based on the simplest linear arrangement of hydrogen-bonded chains mimicking the molecular arrangement in the crystals. We found no common approach to reproduce all the registered VCD spectra in the crystal phase. For the Me and nBu isoindolinones, the VCD pattern was the best reproduced by full optimization of the selected large molecular clusters. For iPr, Ph and CH2Ph derivatives optimizing only the position of H-atoms in a fragment frozen as in the crystal provides the best results. Such an approach can reduce the computation time from months to one week. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A valuable animal model of spinal cord injury to study motor dysfunctions, comorbid conditions, and aging associated diseases.

PubMed

Rouleau, Pascal; Guertin, Pierre A

2013-01-01

Most animal models of contused, compressed or transected spinal cord injury (SCI) require a laminectomy to be performed. However, despite advantages and disadvantages associated with each of these models, the laminectomy itself is generally associated with significant problems including longer surgery and anaesthesia (related post-operative complications), neuropathic pain, spinal instabilities, deformities, lordosis, and biomechanical problems, etc. This review provides an overview of findings obtained mainly from our laboratory that are associated with the development and characterization of a novel murine model of spinal cord transection that does not require a laminectomy. A number of studies successfully conducted with this model provided strong evidence that it constitutes a simple, reliable and reproducible transection model of complete paraplegia which is particularly useful for studies on large cohorts of wild-type or mutant animals - e.g., drug screening studies in vivo or studies aimed at characterizing neuronal and non-neuronal adaptive changes post-trauma. It is highly suitable also for studies aimed at identifying and developing new pharmacological treatments against aging associated comorbid problems and specific SCI-related dysfunctions (e.g., stereotyped motor behaviours such as locomotion, sexual response, defecation and micturition) largely related with 'command centers' located in lumbosacral areas of the spinal cord.

Male sexual dysfunction and infertility associated with neurological disorders

PubMed Central

Fode, Mikkel; Krogh-Jespersen, Sheila; Brackett, Nancy L; Ohl, Dana A; Lynne, Charles M; Sønksen, Jens

2012-01-01

Normal sexual and reproductive functions depend largely on neurological mechanisms. Neurological defects in men can cause infertility through erectile dysfunction, ejaculatory dysfunction and semen abnormalities. Among the major conditions contributing to these symptoms are pelvic and retroperitoneal surgery, diabetes, congenital spinal abnormalities, multiple sclerosis and spinal cord injury. Erectile dysfunction can be managed by an increasingly invasive range of treatments including medications, injection therapy and the surgical insertion of a penile implant. Retrograde ejaculation is managed by medications to reverse the condition in mild cases and in bladder harvest of semen after ejaculation in more severe cases. Anejaculation might also be managed by medication in mild cases while assisted ejaculatory techniques including penile vibratory stimulation and electroejaculation are used in more severe cases. If these measures fail, surgical sperm retrieval can be attempted. Ejaculation with penile vibratory stimulation can be done by some spinal cord injured men and their partners at home, followed by in-home insemination if circumstances and sperm quality are adequate. The other options always require assisted reproductive techniques including intrauterine insemination or in vitro fertilization with or without intracytoplasmic sperm injection. The method of choice depends largely on the number of motile sperm in the ejaculate. PMID:22138899

Measurements of tropospheric NO2 in Romania using a zenith-sky mobile DOAS system and comparisons with satellite observations.

PubMed

Constantin, Daniel-Eduard; Merlaud, Alexis; Van Roozendael, Michel; Voiculescu, Mirela; Fayt, Caroline; Hendrick, François; Pinardi, Gaia; Georgescu, Lucian

2013-03-20

In this paper we present a new method for retrieving tropospheric NO2 Vertical Column Density (VCD) from zenith-sky Differential Optical Absorption Spectroscopy (DOAS) measurements using mobile observations. This method was used during three days in the summer of 2011 in Romania, being to our knowledge the first mobile DOAS measurements peformed in this country. The measurements were carried out over large and different areas using a mobile DOAS system installed in a car. We present here a step-by-step retrieval of tropospheric VCD using complementary observations from ground and space which take into account the stratospheric contribution, which is a step forward compared to other similar studies. The detailed error budget indicates that the typical uncertainty on the retrieved NO2tropospheric VCD is less than 25%. The resulting ground-based data set is compared to satellite measurements from the Ozone Monitoring Instrument (OMI) and the Global Ozone Monitoring Experiment-2 (GOME-2). For instance, on 18 July 2011, in an industrial area located at 47.03°N, 22.45°E, GOME-2 observes a tropospheric VCD value of (3.4 ± 1.9) × 1015 molec./cm2, while average mobile measurements in the same area give a value of (3.4 ± 0.7) × 10(15) molec./cm2. On 22 August 2011, around Ploiesti city (44.99°N, 26.1°E), the tropospheric VCD observed by satellites is (3.3 ± 1.9) × 10(15) molec./cm2 (GOME-2) and (3.2 ± 3.2) × 10(15) molec./cm2 (OMI), while average mobile measurements give (3.8 ± 0.8) × 10(15) molec./cm2. Average ground measurements over "clean areas", on 18 July 2011, give (2.5 ± 0.6) × 10(15) molec./cm2 while the satellite observes a value of (1.8 ± 1.3) × 10(15) molec./cm2.

Measurements of Tropospheric NO2 in Romania Using a Zenith-Sky Mobile DOAS System and Comparisons with Satellite Observations

PubMed Central

Constantin, Daniel-Eduard; Merlaud, Alexis; Van Roozendael, Michel; Voiculescu, Mirela; Fayt, Caroline; Hendrick, François; Pinardi, Gaia; Georgescu, Lucian

2013-01-01

In this paper we present a new method for retrieving tropospheric NO2 Vertical Column Density (VCD) from zenith-sky Differential Optical Absorption Spectroscopy (DOAS) measurements using mobile observations. This method was used during three days in the summer of 2011 in Romania, being to our knowledge the first mobile DOAS measurements peformed in this country. The measurements were carried out over large and different areas using a mobile DOAS system installed in a car. We present here a step-by-step retrieval of tropospheric VCD using complementary observations from ground and space which take into account the stratospheric contribution, which is a step forward compared to other similar studies. The detailed error budget indicates that the typical uncertainty on the retrieved NO2tropospheric VCD is less than 25%. The resulting ground-based data set is compared to satellite measurements from the Ozone Monitoring Instrument (OMI) and the Global Ozone Monitoring Experiment-2 (GOME-2). For instance, on 18 July 2011, in an industrial area located at 47.03°N, 22.45°E, GOME-2 observes a tropospheric VCD value of (3.4 ± 1.9) × 1015 molec./cm2, while average mobile measurements in the same area give a value of (3.4 ± 0.7) × 1015 molec./cm2. On 22 August 2011, around Ploiesti city (44.99°N, 26.1°E), the tropospheric VCD observed by satellites is (3.3 ± 1.9) × 1015 molec./cm2 (GOME-2) and (3.2 ± 3.2) × 1015 molec./cm2 (OMI), while average mobile measurements give (3.8 ± 0.8) × 1015 molec./cm2. Average ground measurements over “clean areas”, on 18 July 2011, give (2.5 ± 0.6) × 1015 molec./cm2 while the satellite observes a value of (1.8 ± 1.3) × 1015 molec./cm2. PMID:23519349

Inflatable artificial sphincter - series (image)

MedlinePlus

... sphincter dysfunction related to spinal cord injury or multiple sclerosis. Most experts advise their patients to try medication and bladder retraining therapy first before resorting to this treatment. Alternatives to ...

Cardiovascular and temperature changes in spinal cord injured rats at rest and during autonomic dysreflexia

PubMed Central

Laird, A S; Carrive, P; Waite, P M E

2006-01-01

In patients with high spinal cord injuries autonomic dysfunction can be dangerous, leading to medical complications such as postural hypotension, autonomic dysreflexia and temperature disturbance. While animal models have been developed to study autonomic dysreflexia, associated temperature changes have not been documented. Our aim here was to use radiotelemetry and infrared thermography in rodents to record the development of cardiovascular and skin temperature changes following complete T4 transection. In adult male Wistar rats (n = 5), responses were assessed prior to spinal cord injury (intact) and for 6 weeks following injury. Statistical analysis by a repeated-measure ANOVA revealed that following spinal cord injury (SCI), rats exhibited decreased mean arterial pressure (MAP, average decrease of 26 mmHg; P < 0.035) and elevated heart rate (HR, average increase of 65 bpm, P < 0.035) at rest. The basal core body temperature following SCI was also significantly lower than intact levels (−0.9°C; P < 0.0035). Associated with this decreased basal core temperature following SCI was an increased skin temperature of the mid-tail and hindpaw (+5.6 and +4.0°C, respectively; P < 0.0003) consistent with decreased cutaneous vasoconstrictor tone. Autonomic dysreflexia, in response to a 1 min colorectal distension (25 mmHg), was fully developed by 4 weeks after spinal cord transection, producing increases in MAP greater than 25 mmHg (P < 0.0003). In contrast to the tachycardia seen in intact animals in response to colorectal distension, SCI animals exhibited bradycardia (P < 0.0023). During episodes of autonomic dysreflexia mid-tail surface temperature decreased (approx. −1.7°C, P < 0.012), consistent with cutaneous vasoconstriction. This is the first study to compare cardiovascular dysfunction with temperature changes following spinal cord transection in rats. PMID:16973703

Cooperative use of VCD and XRD for the determination of tetrahydrobenzoisoquinolines absolute configuration: a reliable proof of memory of chirality and retention of configuration in enediyne rearrangements.

PubMed

Mondal, Shovan; Naubron, Jean-Valère; Campolo, Damien; Giorgi, Michel; Bertrand, Michéle P; Nechab, Malek

2013-12-01

The absolute configurations (AC) of azaheterocylic compounds resulting from the cascade rearrangement of enediynes involving only light atoms were unambiguously assigned by the joint use of vibrational circular dichroism (VCD) and copper radiation single crystal X-ray diffraction (XRD). These AC determinations proved that the rearrangements of enediynes proceeded with memory of chirality and retention of configuration. © 2013 Wiley Periodicals, Inc.

Neurogenic bladder in spinal cord injury patients

PubMed Central

Taweel, Waleed Al; Seyam, Raouf

2015-01-01

Neurogenic bladder dysfunction due to spinal cord injury poses a significant threat to the well-being of patients. Incontinence, renal impairment, urinary tract infection, stones, and poor quality of life are some complications of this condition. The majority of patients will require management to ensure low pressure reservoir function of the bladder, complete emptying, and dryness. Management typically begins with anticholinergic medications and clean intermittent catheterization. Patients who fail this treatment because of inefficacy or intolerability are candidates for a spectrum of more invasive procedures. Endoscopic managements to relieve the bladder outlet resistance include sphincterotomy, botulinum toxin injection, and stent insertion. In contrast, patients with incompetent sphincters are candidates for transobturator tape insertion, sling surgery, or artificial sphincter implantation. Coordinated bladder emptying is possible with neuromodulation in selected patients. Bladder augmentation, usually with an intestinal segment, and urinary diversion are the last resort. Tissue engineering is promising in experimental settings; however, its role in clinical bladder management is still evolving. In this review, we summarize the current literature pertaining to the pathology and management of neurogenic bladder dysfunction in patients with spinal cord injury. PMID:26090342

[Persistent Bilateral Vocal Cord Paralysis after General Anesthesia in a Patient with Multiple System Atrophy: A Case Report].

PubMed

Konishi, Hanako; Mizota, Toshiyuki; Fukuda, Kazuhiko

2015-06-01

We report a case of persistent bilateral vocal cord paralysis which developed after spine surgery under general anesthesia in a patient with multiple system atrophy. A 64-year-old woman was scheduled to receive spinal fusion surgery for kyphoscoliosis. She did not have apparent symptoms of vocal cord paralysis such as hoarseness before surgery. The surgery was performed smoothly under general anesthesia with endotracheal intubation. However, immediately after extubation, the patient developed severe upper airway obstruction and was re-intubated. Fiberoptic laryngoscopy revealed bilateral vocal cord abductor paralysis. Vocal cord paralysis did not improve and she received tracheotomy on the 12th day after surgery. She also showed symptoms of autonomic nervous system dysfunction and cerebellar ataxia, and was diagnosed as multiple system atrophy on postoperative day 64. We discuss differential diagnosis of persistent vocal cord paralysis after general anesthesia, and anesthetic management of a patient with multiple system atrophy.

[Placental atherosclerosis and markers of endothelial dysfunction in infants born to mothers with gestational diabetes].

PubMed

López Morales, Cruz Mónica; Brito Zurita, Olga Rosa; González Heredia, Ricardo; Cruz López, Miguel; Méndez Padrón, Araceli; Matute Briseño, Juan Antonio

2016-08-05

The pathophysiology of gestational diabetes itself causes hyperstimulation of adipose tissue and of the placenta cells increasing the production of inflammatory cytokines, which cause changes in the tissues exposed such as the placenta and foetus. Therefore, the objective of this study was to compare metabolic markers and endothelial dysfunction in umbilical cord blood, as well as to determine the presence of atherosclerosis in the placentas of newborn infants of patients with gestational diabetes and in patients with normally progressing pregnancies. An analytical cross-sectional study was carried out in 84 patients, obtaining data such as age, smoking and weight gain in pregnancy; the gestational age of the newborns was determined by Capurro, and their weight and destination subsequent to birth, the placentas were also collected in order to look for atherosclerosis through histological studies and glucose, insulin, VLDL-C, HDL-C, triglycerides, cholesterol, fibrinogen, PCR and markers of endothelial dysfunction (adiponectin, VCAM-1, ICAM-1 and IL-6) were determined in blood samples obtained from the umbilical cord. Placental atherosclerosis presented in 28.94% of the group with gestational diabetes compared to 10.52% of the group with normally progressing pregnancies (P=.044); differences were found in glucose, cholesterol, triglycerides, fibrinogen, HOMA-IR, PCR-us, HDL-C, not in VLDL-C. Twenty-one point five percent of the newborns of the gestational diabetes patients required hospitalization, against 5.2% in the control group, Pregnancies that involve diabetes have higher proportion of atherosclerosis, hospitalization of the newborn, insulin resistance, as well as elevation of markers associated with inflammation and endothelial dysfunction in umbilical cord blood. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

VCD Robustness of the Amide-I and Amide-II Vibrational Modes of Small Peptide Models.

PubMed

Góbi, Sándor; Magyarfalvi, Gábor; Tarczay, György

2015-09-01

The rotational strengths and the robustness values of amide-I and amide-II vibrational modes of For(AA)n NHMe (where AA is Val, Asn, Asp, or Cys, n = 1-5 for Val and Asn; n = 1 for Asp and Cys) model peptides with α-helix and β-sheet backbone conformations were computed by density functional methods. The robustness results verify empirical rules drawn from experiments and from computed rotational strengths linking amide-I and amide-II patterns in the vibrational circular dichroism (VCD) spectra of peptides with their backbone structures. For peptides with at least three residues (n ≥ 3) these characteristic patterns from coupled amide vibrational modes have robust signatures. For shorter peptide models many vibrational modes are nonrobust, and the robust modes can be dependent on the residues or on their side chain conformations in addition to backbone conformations. These robust VCD bands, however, provide information for the detailed structural analysis of these smaller systems. © 2015 Wiley Periodicals, Inc.

STROKOG (stroke and cognition consortium): An international consortium to examine the epidemiology, diagnosis, and treatment of neurocognitive disorders in relation to cerebrovascular disease.

PubMed

Sachdev, Perminder S; Lo, Jessica W; Crawford, John D; Mellon, Lisa; Hickey, Anne; Williams, David; Bordet, Régis; Mendyk, Anne-Marie; Gelé, Patrick; Deplanque, Dominique; Bae, Hee-Joon; Lim, Jae-Sung; Brodtmann, Amy; Werden, Emilio; Cumming, Toby; Köhler, Sebastian; Verhey, Frans R J; Dong, Yan-Hong; Tan, Hui Hui; Chen, Christopher; Xin, Xu; Kalaria, Raj N; Allan, Louise M; Akinyemi, Rufus O; Ogunniyi, Adesola; Klimkowicz-Mrowiec, Aleksandra; Dichgans, Martin; Wollenweber, Frank A; Zietemann, Vera; Hoffmann, Michael; Desmond, David W; Linden, Thomas; Blomstrand, Christian; Fagerberg, Björn; Skoog, Ingmar; Godefroy, Olivier; Barbay, Mélanie; Roussel, Martine; Lee, Byung-Chul; Yu, Kyung-Ho; Wardlaw, Joanna; Makin, Stephen J; Doubal, Fergus N; Chappell, Francesca M; Srikanth, Velandai K; Thrift, Amanda G; Donnan, Geoffrey A; Kandiah, Nagaendran; Chander, Russell J; Lin, Xuling; Cordonnier, Charlotte; Moulin, Solene; Rossi, Costanza; Sabayan, Behnam; Stott, David J; Jukema, J Wouter; Melkas, Susanna; Jokinen, Hanna; Erkinjuntti, Timo; Mok, Vincent C T; Wong, Adrian; Lam, Bonnie Y K; Leys, Didier; Hénon, Hilde; Bombois, Stéphanie; Lipnicki, Darren M; Kochan, Nicole A

2017-01-01

The Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD). Longitudinal studies with ≥75 participants who had suffered or were at risk of stroke or TIA and which evaluated cognitive function were invited to join STROKOG. The consortium will facilitate projects investigating rates and patterns of cognitive decline, risk factors for VCD, and biomarkers of vascular dementia. Currently, STROKOG includes 25 (21 published) studies, with 12,092 participants from five continents. The duration of follow-up ranges from 3 months to 21 years. Although data harmonization will be a key challenge, STROKOG is in a unique position to reuse and combine international cohort data and fully explore patient level characteristics and outcomes. STROKOG could potentially transform our understanding of VCD and have a worldwide impact on promoting better vascular cognitive outcomes.

An atypical presentation of visual conversion disorder.

PubMed

Foutch, Brian K

2015-01-01

Nonorganic vision loss accounts for up to 5% of patients and presents in two forms, malingering and visual conversion disorder (VCD). It is described a case of VCD in a new mother struggling both with her husband being deployed overseas and the recent death of her father. In addition, she had been evaluated for a concussion secondary to a motor vehicle accident three months prior. An inexpensive series of clinical tests were performed to rule out organic disease and obtained equivocal results. Some tests revealed intact vision in the affected eye while others supported a neurological cause for the vision loss. However, the patient quickly recovered normal visual acuity when encouraged to discuss situations that have been causing emotional stress. This almost immediate recovery of vision confirmed the diagnosis of VCD. This report should make primary eye care professionals more aware of visual conversion disorder and its clinical evaluation. Copyright © 2014 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

Autonomic Nervous System in Paralympic Athletes with Spinal Cord Injury.

PubMed

Walter, Matthias; Krassioukov, Andrei V

2018-05-01

Individuals sustaining a spinal cord injury (SCI) frequently suffer from sensorimotor and autonomic impairment. Damage to the autonomic nervous system results in cardiovascular, respiratory, bladder, bowel, and sexual dysfunctions, as well as temperature dysregulation. These complications not only impede quality of life, but also affect athletic performance of individuals with SCI. This article summarizes existing evidence on how damage to the spinal cord affects the autonomic nervous system and impacts the performance in athletes with SCI. Also discussed are frequently used performance-enhancing strategies, with a special focus on their legal aspect and implication on the athletes' health. Copyright © 2018 Elsevier Inc. All rights reserved.

The Use of ExoSeal Vascular Closure Device for Direct Antegrade Superficial Femoral Artery Puncture Site Hemostasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rimon, Uri, E-mail: rimonu@sheba.health.gov.il; Khaitovich, Boris, E-mail: borislena@012.net.il; Yakubovich, Dmitry, E-mail: Dmitry.Yakubovitch@sheba.health.gov.il

2015-06-15

PurposeThis study was designed to assess the efficacy and safety of the ExoSeal vascular closure device (VCD) to achieve hemostasis in antegrade access of the superficial femoral artery (SFA).MethodsWe retrospectively reviewed the outcome of ExoSeal VCD used for hemostasis in 110 accesses to the SFA in 93 patients between July 2011 and July 2013. All patients had patent proximal SFA based on computer tomography angiography or ultrasound duplex. Arterial calcifications at puncture site were graded using fluoroscopy. The SFA was accessed in an antegrade fashion with ultrasound or fluoroscopic guidance. In all patients, 5–7F vascular sheaths were used. The ExoSealmore » VCD was applied to achieve hemostasis at the end of the procedure. All patients were clinically examined and had ultrasound duplex exam for any puncture site complications during the 24 h postprocedure.ResultsIn all procedures, the ExoSeal was applied successfully. We did not encounter any device-related technical failure. There were four major complications in four patients (3.6 %): three pseudoaneurysms, which were treated with direct thrombin injection, and one hematoma, which necessitated transfusion of two blood units. All patients with complications were treated with anticoagulation preprocedure or received thrombolytic therapy.ConclusionsThe ExoSeal VCD can be safely used for antegrade puncture of the SFA, with a high procedural success rate (100 %) and a low rate of access site complications (3.6 %)« less

Using Student Video Cases to Assess Pre-service Elementary Teachers' Engineering Teaching Responsiveness

NASA Astrophysics Data System (ADS)

Dalvi, Tejaswini; Wendell, Kristen

2017-10-01

Our study addresses the need for new approaches to prepare novice elementary teachers to teach both science and engineering, and for new tools to measure how well those approaches are working. This in particular would inform the teacher educators of the extent to which novice teachers are developing expertise in facilitating their students' engineering design work. One important dimension to measure is novice teachers' abilities to notice the substance of student thinking and to respond in productive ways. This teacher noticing is particularly important in science and engineering education, where students' initial, idiosyncratic ideas and practices influence the likelihood that particular instructional strategies will help them learn. This paper describes evidence of validity and reliability for the Video Case Diagnosis (VCD) task, a new instrument for measuring pre-service elementary teachers' engineering teaching responsiveness. To complete the VCD, participants view a 6-min video episode of children solving an engineering design problem, describe in writing what they notice about the students' science ideas and engineering practices, and propose how a teacher could productively respond to the students. The rubric for scoring VCD responses allowed two independent scorers to achieve inter-rater reliability. Content analysis of the video episode, systematic review of literature on science and engineering practices, and solicitation of external expert educator responses establish content validity for VCD. Field test results with three different participant groups who have different levels of engineering education experience offer evidence of construct validity.

New Developments in the SCIAMACHY Level 2 Ground Processor Towards Version 7

NASA Astrophysics Data System (ADS)

Meringer, Markus; Noël, Stefan; Lichtenberg, Günter; Lerot, Christophe; Theys, Nicolas; Fehr, Thorsten; Dehn, Angelika; Liebing, Patricia; Gretschany, Sergei

2016-07-01

SCIAMACHY (SCanning Imaging Absorption spectroMeter for Atmospheric ChartographY) aboard ESA's environmental satellite ENVISAT observed the Earth's atmosphere in limb, nadir, and solar/lunar occultation geometries covering the UV-Visible to NIR spectral range. It is a joint project of Germany, the Netherlands and Belgium and was launched in February 2002. SCIAMACHY doubled its originally planned in-orbit lifetime of five years before the communication to ENVISAT was severed in April 2012, and the mission entered its post-operational phase. In order to preserve the best quality of the outstanding data recorded by SCIAMACHY, data processors are still being updated. This presentation will highlight three new developments that are currently being incorporated into the forthcoming version 7 of ESA's operational level 2 processor: 1. Tropospheric BrO, a new retrieval based on the scientific algorithm of (Theys et al., 2011). This algorithm had originally been developed for the GOME-2 sensor and was later adapted for SCIAMACHY. The main principle of the new algorithm is to split BrO total columns, which are already an operational product, into stratospheric VCD_{strat} and tropospheric VCD_{trop} fractions. BrO VCD_{strat} is determined from a climatological approach, driven by SCIAMACHY O_3 and NO_2 observations. Tropospheric vertical column densities are then determined as difference VCD_{trop}=VCD_{total}-VCD_{strat}. 2. Improved cloud flagging using limb measurements (Liebing, 2015). Limb cloud flags are already part of the SCIAMACHY L2 product. They are currently calculated employing the scientific algorithm developed by (Eichmann et al., 2015). Clouds are categorized into four types: water, ice, polar stratospheric and noctilucent clouds. High atmospheric aerosol loadings, however, often lead to spurious cloud flags, when aerosols had been misidentified as clouds. The new algorithm will better discriminate between aerosol and clouds. It will also have a higher sensitivity w.r.t. thin clouds. 3. A new, future-proof file format for the level 2 product based on NetCDF. The data format will be aligned and harmonized with other missions, particularly GOME and Sentinels. The final concept for the new format is still under discussion within the SCIAMACHY Quality Working Group. References: K.-U. Eichmann et al.: Global cloud top height retrieval using SCIAMACHY limb spectra: model studies and first results, Atmos. Meas. Tech. Discuss., 8, 8295-8352, 2015. P. Liebing: New Limb Cloud Detection Algorithm Theoretical Basis Document, 2016. N. Theys et al.: Global observations of tropospheric BrO columns using GOME-2 satellite data, Atmos. Chem. Phys., 11, 1791-1811, 2011.

What's the Difference Between Vocal Cord Dysfunction and Asthma?

MedlinePlus

... of Privacy Practices Notice of Nondiscrimination Manage Cookies Advertising Mayo Clinic is a not-for-profit organization and proceeds from Web advertising help support our mission. Mayo Clinic does not ...

Important Clinical Rehabilitation Principles Unique to People with Non-traumatic Spinal Cord Dysfunction.

PubMed

New, Peter Wayne; Eriks-Hoogland, Inge; Scivoletto, Giorgio; Reeves, Ronald K; Townson, Andrea; Marshall, Ruth; Rathore, Farooq A

2017-01-01

Background: Non-traumatic spinal cord dysfunction (SCDys) is caused by a large range of heterogeneous etiologies. Although most aspects of rehabilitation for traumatic spinal cord injury and SCDys are the same, people with SCDys have some unique rehabilitation issues. Purpose: This article presents an overview of important clinical rehabilitation principles unique to SCDys. Methods: Electronic literature search conducted (January 2017) using MEDLINE and Embase (1990-2016) databases for publications regarding SCDys. The focus of the literature search was on identifying publications that present suggestions regarding the clinical rehabilitation of SCDys. Results: The electronic search of MEDLINE and Embase identified no relevant publications, and the publications included were from the authors' libraries. A number of important clinical rehabilitation principles unique to people with SCDys were identified, including classification issues, general rehabilitation issues, etiology-specific issues, and a role for the rehabilitation physician as a diagnostic clinician. The classification issues were regarding the etiology of SCDys and the International Standards for Neurological Classification of Spinal Cord Injury. The general rehabilitation issues were predicting survival, improvement, and rehabilitation outcomes; admission to spinal rehabilitation units, including selection decision issues; participation in rehabilitation; and secondary health conditions. The etiology-specific issues were for SCDys due to spinal cord degeneration, tumors, and infections. Conclusions: Although there are special considerations regarding the rehabilitation of people with SCDys, such as the potential for progression of the underlying condition, functional improvement is typically significant with adequate planning of rehabilitation programs and special attention regarding the clinical condition of patients with SCDys.

Kainate and metabolic perturbation mimicking spinal injury differentially contribute to early damage of locomotor networks in the in vitro neonatal rat spinal cord.

PubMed

Taccola, G; Margaryan, G; Mladinic, M; Nistri, A

2008-08-13

Acute spinal cord injury evolves rapidly to produce secondary damage even to initially spared areas. The result is loss of locomotion, rarely reversible in man. It is, therefore, important to understand the early pathophysiological processes which affect spinal locomotor networks. Regardless of their etiology, spinal lesions are believed to include combinatorial effects of excitotoxicity and severe stroke-like metabolic perturbations. To clarify the relative contribution by excitotoxicity and toxic metabolites to dysfunction of locomotor networks, spinal reflexes and intrinsic network rhythmicity, we used, as a model, the in vitro thoraco-lumbar spinal cord of the neonatal rat treated (1 h) with either kainate or a pathological medium (containing free radicals and hypoxic/aglycemic conditions), or their combination. After washout, electrophysiological responses were monitored for 24 h and cell damage analyzed histologically. Kainate suppressed fictive locomotion irreversibly, while it reversibly blocked neuronal excitability and intrinsic bursting induced by synaptic inhibition block. This result was associated with significant neuronal loss around the central canal. Combining kainate with the pathological medium evoked extensive, irreversible damage to the spinal cord. The pathological medium alone slowed down fictive locomotion and intrinsic bursting: these oscillatory patterns remained throughout without regaining their control properties. This phenomenon was associated with polysynaptic reflex depression and preferential damage to glial cells, while neurons were comparatively spared. Our model suggests distinct roles of excitotoxicity and metabolic dysfunction in the acute damage of locomotor networks, indicating that different strategies might be necessary to treat the various early components of acute spinal cord lesion.

Use of Optical Mapping to Evaluate Mechanisms and New Therapies for Bladder Dysfunction Due to Spinal Cord Injury

DTIC Science & Technology

2013-10-01

TERMS Lower urinary tract symptoms (LUTS), spinal cord injury (SCI), Botulinum Toxin Type A and β3 adrenoceptor agonists 16. SECURITY...focused on the therapeutic benefits of β3 adrenoceptor agonists, botulinum neurotoxin type A (BTX-A) intradetrusor injections and their combination...compromised by the toxin . Thus, β3 adrenoceptor agonists in combination with BTX-A are beneficial in improving bladder function in SCI patients. 15. SUBJECT

Cardiovascular dysfunction following spinal cord injury

PubMed Central

Partida, Elizabeth; Mironets, Eugene; Hou, Shaoping; Tom, Veronica J.

2016-01-01

Both sensorimotor and autonomic dysfunctions often occur after spinal cord injury (SCI). Particularly, a high thoracic or cervical SCI interrupts supraspinal vasomotor pathways and results in disordered hemodynamics due to deregulated sympathetic outflow. As a result of the reduced sympathetic activity, patients with SCI may experience hypotension, cardiac dysrhythmias, and hypothermia post-injury. In the chronic phase, changes within the CNS and blood vessels lead to orthostatic hypotension and life-threatening autonomic dysreflexia (AD). AD is characterized by an episodic, massive sympathetic discharge that causes severe hypertension associated with bradycardia. The syndrome is often triggered by unpleasant visceral or sensory stimuli below the injury level. Currently the only treatments are palliative – once a stimulus elicits AD, pharmacological vasodilators are administered to help reduce the spike in arterial blood pressure. However, a more effective means would be to mitigate AD development by attenuating contributing mechanisms, such as the reorganization of intraspinal circuits below the level of injury. A better understanding of the neuropathophysiology underlying cardiovascular dysfunction after SCI is essential to better develop novel therapeutic approaches to restore hemodynamic performance. PMID:27073353

PVCM, PVCD, EPL, and irritable larynx syndrome: what are we talking about and how do we treat it?

PubMed

Andrianopoulos, M V; Gallivan, G J; Gallivan, K H

2000-12-01

Paroxysmal vocal cord movement/motion (PVCM), paroxysmal vocal cord dysfunction (PVCD), episodic paroxysmal laryngospasm (EPL), and irritable larynx syndrome (ILS) are terms used to describe laryngeal dysfunction masquerading as asthma, upper airway obstruction, or functional and organic voice disorders. The differential diagnosis of PVCM, PVCD, EPL, and ILS is critical to successful medical and behavioral management of the patient. During the past 10 years, 27 subjects, ages 15-79 years, were identified to have paroxysms of inspiratory stridor, acute respiratory distress, associated aphonia and dysphonia, resulting in misdiagnosis and unnecessary emergency treatments, including endotracheal intubation, cardiopulmonary resuscitation, massive pharmacotherapy, or tracheostomy. A multifactorial management program is proposed utilizing principles of motor learning, neurolinguistic programming model, respiratory and phonatory synchronization, relaxation techniques, concurrent monitoring of behavioral adjustments, and formal psychological counseling.

Waste water processing technology for Space Station Freedom - Comparative test data analysis

NASA Technical Reports Server (NTRS)

Miernik, Janie H.; Shah, Burt H.; Mcgriff, Cindy F.

1991-01-01

Comparative tests were conducted to choose the optimum technology for waste water processing on SSF. A thermoelectric integrated membrane evaporation (TIMES) subsystem and a vapor compression distillation subsystem (VCD) were built and tested to compare urine processing capability. Water quality, performance, and specific energy were compared for conceptual designs intended to function as part of the water recovery and management system of SSF. The VCD is considered the most mature and efficient technology and was selected to replace the TIMES as the baseline urine processor for SSF.

Preliminary Design Program: Vapor Compression Distillation Flight Experiment Program

NASA Technical Reports Server (NTRS)

Schubert, F. H.; Boyda, R. B.

1995-01-01

This document provides a description of the results of a program to prepare a preliminary design of a flight experiment to demonstrate the function of a Vapor Compression Distillation (VCD) Wastewater Processor (WWP) in microgravity. This report describes the test sequence to be performed and the hardware, control/monitor instrumentation and software designs prepared to perform the defined tests. the purpose of the flight experiment is to significantly reduce the technical and programmatic risks associated with implementing a VCD-based WWP on board the International Space Station Alpha.

Herpes zoster with dysfunction of bladder and anus.

PubMed

Jellinek, E H; Tulloch, W S

1976-12-04

Herpes zoster may give rise to dysfunction of bladder and anus. Mucosal lesions have been reported, and 7 cases are described with retention, loss of sensation, or incontinence. Sacral shingles is associated with sensory loss and flaccid detrusor paralysis. Lumbar shingles may cause retention, and zoster at higher levels can also damage the spinal cord. Recovery is usually complete. The implication for schemes of bladder innervation is discussed.

Symptomatic arrhythmias due to syringomyelia-induced severe autonomic dysfunction.

PubMed

Riedlbauchová, Lucie; Nedělka, Tomáš; Schlenker, Jakub

2014-10-01

Syringomyelia is characterized by cavity formation in the spinal cord, most often at C2-Th9 level. Clinical manifestation reflects extent and localization of the spinal cord injury. 20-year old woman was admitted for recurrent rest-related presyncopes with sudden manifestation. Paroxysms of sinus bradycardia with SA and AV blocks were repeatedly documented during symptoms. There was normal echocardiographic finding, (para) infectious etiology was not proved. Character of the ECG findings raised suspicion on neurogenic cause. Autonomic nervous system testing demonstrated abnormalities reflecting predominant sympathetic dysfunction. Suspicion on incipient myelopathy was subsequently confirmed by MRI, which discovered syringomyelia at Th5 level as the only pathology. A 52-year old man with hypotrophic quadruparesis resulting from perinatal brain injury was sent for 2-years lasting symptoms (sudden palpitation, sweating, muscle tightness, shaking) with progressive worsening. Symptoms occurred in association with sudden increase of sinus rhythm rate and blood pressure that were provoked by minimal physical activity. Presence of significant autonomic dysregulation with baroreflex hyperreactivity in orthostatic test and symptomatic postural orthostatic tachycardia with verticalization-associated hypertension were proved. MRI revealed syringomyelia at C7 and Th7 level affecting sympathetic centers at these levels. Sympathetic fibers dysfunction at C-Th spinal level may cause significant autonomic dysfunction with arrhythmic manifestation.

Soluble TNFα Signaling within the Spinal Cord Contributes to the Development of Autonomic Dysreflexia and Ensuing Vascular and Immune Dysfunction after Spinal Cord Injury.

PubMed

Mironets, Eugene; Osei-Owusu, Patrick; Bracchi-Ricard, Valerie; Fischer, Roman; Owens, Elizabeth A; Ricard, Jerome; Wu, Di; Saltos, Tatiana; Collyer, Eileen; Hou, Shaoping; Bethea, John R; Tom, Veronica J

2018-04-25

Cardiovascular disease and susceptibility to infection are leading causes of morbidity and mortality for individuals with spinal cord injury (SCI). A major contributor to these is autonomic dysreflexia (AD), an amplified reaction of the autonomic nervous system (hallmarked by severe hypertension) in response to sensory stimuli below the injury. Maladaptive plasticity of the spinal sympathetic reflex circuit below the SCI results in AD intensification over time. Mechanisms underlying this maladaptive plasticity are poorly understood, restricting the identification of treatments. Thus, no preventative treatments are currently available. Neuroinflammation has been implicated in other pathologies associated with hyperexcitable neural circuits. Specifically, the soluble form of TNFα (sTNFα) is known to play a role in neuroplasticity. We hypothesize that persistent expression of sTNFα in spinal cord underlies AD exacerbation. To test this, we intrathecally administered XPro1595, a biologic that renders sTNFα nonfunctional, after complete, high-level SCI in female rats. This dramatically attenuated the intensification of colorectal distension-induced and naturally occurring AD events. This improvement is mediated via decreased sprouting of nociceptive primary afferents and activation of the spinal sympathetic reflex circuit. We also examined peripheral vascular function using ex vivo pressurized arterial preparations and immune function via flow cytometric analysis of splenocytes. Diminishing AD via pharmacological inhibition of sTNFα mitigated ensuing vascular hypersensitivity and immune dysfunction. This is the first demonstration that neuroinflammation-induced sTNFα is critical for altering the spinal sympathetic reflex circuit, elucidating a novel mechanism for AD. Importantly, we identify the first potential pharmacological, prophylactic treatment for this life-threatening syndrome. SIGNIFICANCE STATEMENT Autonomic dysreflexia (AD), a disorder that develops after spinal cord injury (SCI) and is hallmarked by sudden, extreme hypertension, contributes to cardiovascular disease and susceptibility to infection, respectively, two leading causes of mortality and morbidity in SCI patients. We demonstrate that neuroinflammation-induced expression of soluble TNFα plays a critical role in AD, elucidating a novel underlying mechanism. We found that intrathecal administration after SCI of a biologic that inhibits soluble TNFα signaling dramatically attenuates AD and significantly reduces AD-associated peripheral vascular and immune dysfunction. We identified mechanisms behind diminished plasticity of neuronal populations within the spinal sympathetic reflex circuit. This study is the first to pinpoint a potential pharmacological, prophylactic strategy to attenuate AD and ensuing cardiovascular and immune dysfunction. Copyright © 2018 the authors 0270-6474/18/384147-17$15.00/0.

The longitudinal orthokeratology research in children (LORIC) in Hong Kong: a pilot study on refractive changes and myopic control.

PubMed

Cho, Pauline; Cheung, Sin Wan; Edwards, Marion

2005-01-01

Myopia is a common ocular disorder, and progression of myopia in children is of increasing concern. Modern overnight orthokeratology (ortho-k) is effective for myopic reduction and has been claimed to be effective in slowing the progression of myopia (myopic control) in children, although scientific evidence for this has been lacking. This 2 year pilot study was conducted to determine whether ortho-k can effectively reduce and control myopia in children. We monitored the growth of axial length (AL) and vitreous chamber depth (VCD) in 35 children (7-12 years of age), undergoing ortho-k treatment and compared the rates of change with 35 children wearing single-vision spectacles from an earlier study (control). For the ortho-k subjects, we also determined the changes in corneal curvature and the relationships with changes of refractive errors, AL and VCD. The baseline spherical equivalent refractive errors (SER), the AL, and VCD of the ortho-k and control subjects were not statistically different. All the ortho-k subjects found post-ortho-k unaided vision acceptable in the daytime. The residual SER at the end of the study was -0.18 +/- 0.69 D (dioptre) and the reduction (less myopic) in SER was 2.09 +/- 1.34 D (all values are mean +/- SD). At the end of 24 months, the increases in AL were 0.29 +/- 0.27 mm and 0.54 +/- 0.27 mm for the ortho-k and control groups, respectively (unpaired t test; p = 0.012); the increases in VCD were 0.23 +/- 0.25 mm and 0.48 +/- 0.26 mm for the ortho-k and control groups, respectively (p = 0.005). There was significant initial corneal flattening in the ortho-k group but no significant relationships were found between changes in corneal power and changes in AL and VCD. Ortho-k can have both a corrective and preventive/control effect in childhood myopia. However, there are substantial variations in changes in eye length among children and there is no way to predict the effect for individual subjects.

The role of d-allo-isoleucine in the deposition of the anti-Leishmania peptide bombinin H4 as revealed by 31P solid-state NMR, VCD spectroscopy, and MD simulation.

PubMed

Mijiddorj, Batsaikhan; Kaneda, Shiho; Sato, Hisako; Kitahashi, Yuki; Javkhlantugs, Namsrai; Naito, Akira; Ueda, Kazuyoshi; Kawamura, Izuru

2018-07-01

Bombinin H4 is an antimicrobial peptide that was isolated from the toad Bombina variegata. Bombinin H family peptides are active against gram-positive, gram-negative bacteria, and fungi as well as the parasite Leishmania. Among them, bombinin H4 (H4), which contains d-allo-isoleucine (d-allo-Ile) as the second residue in its sequence, is the most active, and its l-isomer is bombinin H2 (H2). H4 has a significantly lower LC50 than H2 against Leishmania. However, the atomic-level mechanism of the membrane interaction and higher activity of H4 has not been clarified. In this work, we investigated the behavior of the conformations and interactions of H2 and H4 with the Leishmania membrane using 31 P solid-state nuclear magnetic resonance (NMR), vibrational circular dichroism (VCD) spectroscopy, and molecular dynamics (MD) simulations. The generation of isotropic 31 P NMR signals depending on the peptide concentration indicated the abilities of H2 and H4 to exert antimicrobial activity via membrane disruption. The VCD experiment and density functional theory calculation confirmed the different stability and conformations of the N-termini of H2 and H4. MD simulations revealed that the N-terminus of H4 is more stable than that of H2 in the membrane, in line with the VCD experiment data. VCD and MD analyses demonstrated that the first l-Ile and second d-allo-Ile of H4 tend to take a cis conformation. These residues function as an anchor and facilitate the easy winding of the helical conformation of H4 in the membrane. It may assist to quickly reach to the threshold concentration of H4 on the Leishmania membrane. This article is part of a Special Issue entitled: d-Amino acids: biology in the mirror, edited by Dr. Loredano Pollegioni, Dr. Jean-Pierre Mothet and Dr. Molla Gianluca. Copyright © 2018 Elsevier B.V. All rights reserved.

Cell therapy for spinal cord injury informed by electromagnetic waves.

PubMed

Finnegan, Jack; Ye, Hui

2016-10-01

Spinal cord injury devastates the CNS, besetting patients with symptoms including but not limited to: paralysis, autonomic nervous dysfunction, pain disorders and depression. Despite the identification of several molecular and genetic factors, a reliable regenerative therapy has yet to be produced for this terminal disease. Perhaps the missing piece of this puzzle will be discovered within endogenous electrotactic cellular behaviors. Neurons and stem cells both show mediated responses (growth rate, migration, differentiation) to electromagnetic waves, including direct current electric fields. This review analyzes the pathophysiology of spinal cord injury, the rationale for regenerative cell therapy and the evidence for directing cell therapy via electromagnetic waves shown by in vitro experiments.

Effect of a procedural video CD and study guide on the practical fixed prosthodontic performance of Iranian dental students.

PubMed

Nikzad, Sakineh; Azari, Abbas; Mahgoli, Hosseinali; Akhoundi, Nasrin

2012-03-01

Dental students in programs around the world typically pass preclinical courses before entering the clinic and working on actual patients. Since fixed prosthodontics is a preclinical course that requires a great deal of effort, students may experience a substantial amount of stress that may affect their self-confidence and/or clinical performance. In this study, an instructional video CD (VCD) and study guide depicting the step-by-step procedures involved in a metal-ceramic tooth preparation and provisional crown fabrication was prepared. Students at the Faculty of Dentistry, Tehran University of Medical Sciences, Tehran, Iran, were divided randomly into two groups. Group A students trained as usual with live patients, and Group B students were given a copy of the VCD and study guide following a lecture. The students in Group B were encouraged to read the study guide and watch the VCD after live demonstrations. Then, both groups practiced individually on mannequins. At the end of the course, the students completed a sixteen-item questionnaire about their stress level, self-confidence, and knowledge base. The results showed that the students exposed to the extra media performed significantly better on some practical phases, e.g., laboratory procedures. A moderate, insignificant correlation was detected between exposure to media and decreasing the students' stress and self-esteem. We concluded that supplementary teaching aids such as a VCD and study guide may improve the clinical performance of dental students to some extent, but the live demonstration is still preferred by students.

Effects of soil freezing and thawing on vegetation carbon density in Siberia: A modeling analysis with the Lund-Potsdam-Jena Dynamic Global Vegetation Model (LPJ-DGVM)

NASA Astrophysics Data System (ADS)

Beer, C.; Lucht, W.; Gerten, D.; Thonicke, K.; Schmullius, C.

2007-03-01

The current latitudinal gradient in biomass suggests a climate-driven limitation of biomass in high latitudes. Understanding of the underlying processes, and quantification of their relative importance, is required to assess the potential carbon uptake of the biosphere in response to anticipated warming and related changes in tree growth and forest extent in these regions. We analyze the hydrological effects of thawing and freezing of soil on vegetation carbon density (VCD) in permafrost-dominated regions of Siberia using a process-based biogeochemistry-biogeography model, the Lund-Potsdam-Jena Dynamic Global Vegetation Model (LPJ-DGVM). The analysis is based on spatially explicit simulations of coupled daily thaw depth, site hydrology, vegetation distribution, and carbon fluxes influencing VCD subject to climate, soil texture, and atmospheric CO2 concentration. LPJ represents the observed high spring peak of runoff of large Arctic rivers, and simulates a realistic fire return interval of 100 to 200 years in Siberia. The simulated VCD changeover from taiga to tundra is comparable to inventory-based information. Without the consideration of freeze-thaw processes VCD would be overestimated by a factor of 2 in southern taiga to a factor of 5 in northern forest tundra, mainly because available soil water would be overestimated with major effects on fire occurrence and net primary productivity. This suggests that forest growth in high latitudes is not only limited by temperature, radiation, and nutrient availability but also by the availability of liquid soil water.

Dysfunctional oligodendrocyte progenitor cell (OPC) populations may inhibit repopulation of OPC depleted tissue.

PubMed

Chari, D M; Huang, W L; Blakemore, W F

2003-09-15

We have attempted to extend a previously described rat model of focal oligodendrocyte progenitor cell (OPC) depletion, using 40 Gy X-irradiation (Chari and Blakemore [2002] Glia 37:307-313), to the adult mouse spinal cord, to examine the ability of OPCs present in adjacent normal areas to colonise areas of progenitor depletion. In contrast to rat, OPCs in the mouse spinal cord appeared to be a comparatively radiation-resistant population, as 30-35% of OPCs survived in X-irradiated tissue (whereas <1% of OPCs survive in X-irradiated rat spinal cord). The numbers of surviving OPCs remained constant with time indicating that this population was incapable of regenerating itself in response to OPC loss. Additionally, these OPCs did not contribute to remyelination of axons when demyelinating lesions were placed in X-irradiated tissue, suggesting that the surviving cells are functionally impaired. Importantly, the length of the OPC-depleted area did not diminish with time, as would be expected if progressive repopulation of OPC-depleted areas by OPCs from normal areas was occurring. Our findings therefore raise the possibility that the presence of a residual dysfunctional OPC population may inhibit colonisation of such areas by normal OPCs. Copyright 2003 Wiley-Liss, Inc.

Involvement of the Spinal Cord in Mitochondrial Disorders.

PubMed

Finsterer, Josef; Zarrouk-Mahjoub, Sinda

2018-01-01

This review aims at summarising and discussing the current status concerning the clinical presentation, pathogenesis, diagnosis, and treatment of spinal cord affection in mitochondrial disorders (MIDs). A literature search using the database Pubmed was carried out by application of appropriate search terms and their combinations. Involvement of the spinal cord in MIDs is more frequent than anticipated. It occurs in specific and non-specific MIDs. Among the specific MIDs it has been most frequently described in LBSL, LS, MERRF, KSS, IOSCA, MIRAS, and PCH and only rarely in MELAS, CPEO, and LHON. Clinically, spinal cord involvement manifests as monoparesis, paraparesis, quadruparesis, sensory disturbances, hypotonia, spasticity, urinary or defecation dysfunction, spinal column deformities, or as transverse syndrome. Diagnosing spinal cord involvement in MIDs requires a thoroughly taken history, clinical exam, and imaging studies. Additionally, transcranial magnetic stimulation, somato-sensory-evoked potentials, and cerebro-spinal fluid can be supportive. Treatment is generally not at variance compared to the underlying MID but occasionally surgical stabilisation of the spinal column may be necessary. It is concluded that spinal cord involvement in MIDs is more frequent than anticipated but may be missed if cerebral manifestations prevail. Spinal cord involvement in MIDs may strongly determine the mobility of these patients.

[Perinatal outcome and cardiac dysfunction in preterm growth-restricted neonates in relation to placental impairment severity].

PubMed

Candel Pau, Júlia; Castillo Salinas, Félix; Perapoch López, Josep; Carrascosa Lezcano, Antonio; Sánchez García, Olga; Llurba Olivé, Elisa

2016-10-01

Intrauterine growth restriction (IUGR) and prematurity have been associated with increased perinatal morbidity and mortality and also with cardiovascular foetal programming. However, there are few studies on the impact of placenta-related IUGR on perinatal outcomes and cardiovascular biomarkers in pre-term infants. To determine differences in neonatal morbidity, mortality and cord blood biomarkers of cardiovascular dysfunction between pre-term placenta-related IUGR and non-IUGR new-borns, and to analyse their relationship with the severity of IUGR according to foetal Doppler evaluation. Prospective cohort study: pre-term infants with placenta-related IUGR and matched pre-term infants without IUGR. A Doppler scan was performed, and placenta-IUGR was classified according to severity. Comparative analysis of perinatal outcomes, neonatal morbidity and mortality, and cord blood levels of biomarkers of cardiovascular dysfunction was performed. IUGR new-borns present lower weight, length, head circumference, and Apgar score at birth, as well as increased neonatal and cardiovascular dysfunction biomarker levels, compared with pre-term new-borns without IUGR. These differences increase with the severity of IUGR determined by prenatal umbilical artery Doppler scan. Placenta-related-IUGR pre-term infants, irrespective of gestational age, present increased neonatal morbidity and mortality that is significantly proportional to the severity of IUGR. Placental impairment and severity also determine levels of cardiovascular dysfunction biomarkers at birth. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Cl-doping of Te-rich CdTe: Complex formation, self-compensation and self-purification from first principles

NASA Astrophysics Data System (ADS)

Lindström, A.; Klintenberg, M.; Sanyal, B.; Mirbt, S.

2015-08-01

The coexistence in Te-rich CdTe of substitutional Cl-dopants, ClTe, which act as donors, and Cd vacancies, VC d - 1 , which act as electron traps, was studied from first principles utilising the HSE06 hybrid functional. We find ClTe to preferably bind to VC d - 1 and to form an acceptor complex, (ClTe-VCd)-1. The complex has a (0,-1) charge transfer level close to the valence band and shows no trap state (deep level) in the band gap. During the complex formation, the defect state of VCd-1 is annihilated and leaves the Cl-doped CdTe bandgap without any trap states (self-purification). We calculate Cl-doped CdTe to be semi-insulating with a Fermi energy close to midgap. We calculate the formation energy of the complex to be sufficiently low to allow for spontanous defect formation upon Cl-doping (self-compensation). In addition, we quantitatively analyse the geometries, DOS, binding energies and formation energies of the (ClTe-VCd) complexes.

Electrical and mechanical anharmonicities from NIR-VCD spectra of compounds exhibiting axial and planar chirality: the cases of (S)-2,3-pentadiene and methyl-d(3) (R)- and (S)-[2.2]paracyclophane-4-carboxylate.

PubMed

Abbate, Sergio; Longhi, Giovanna; Gangemi, Fabrizio; Gangemi, Roberto; Superchi, Stefano; Caporusso, Anna Maria; Ruzziconi, Renzo

2011-10-01

The IR and Near infrared (NIR) vibrational circular dichroism (VCD) spectra of molecules endowed with noncentral chirality have been investigated. Data for fundamental, first, and second overtone regions of (S)-2,3-pentadiene, exhibiting axial chirality, and methyl-d(3) (R)- and (S)-[2.2]paracyclophane-4-carboxylate, exhibiting planar chirality have been measured and analyzed. The analysis of NIR and IR VCD spectra was based on the local-mode model and the use of density functional theory (DFT), providing mechanical and electrical anharmonic terms for all CH-bonds. The comparison of experimental and calculated spectra is satisfactory and allows one to monitor fine details in the asymmetric charge distribution in the molecules: these details consist in the harmonic frequencies, in the principal anharmonicity constants, in both the atomic polar and axial tensors and in their first and second derivatives with respect to the CH-stretching coordinates. Copyright © 2011 Wiley-Liss, Inc.

[Vocal cord paralysis after endotracheal intubation: an uncommon complication of general anesthesia].

PubMed

Hurtado Nazal, Claudia; Araneda Vilches, Andrea; Vergara Marín, Carolina; García Contreras, Karen; Napolitano Valenzuela, Carla; Badía Ventí, Pedro

2018-04-05

General anesthesia is a safe, frequent procedure in clinical practice. Although it is very unusual in procedures not related to head and or neck surgery, vocal cord paralysis is a serious and important complication. Incidence has been associated with patient age and comorbidities, as well as the position of the endotracheal tube and cuff. It can become a dangerous scenario because it predisposes aspiration. To present a case and analyze the risk factors associated with increased risk of vocal cord paralysis described in the literature. 53 year-old diabetic man, who developed hoarseness in the postoperative period after receiving general anesthesia for an elective abdominal laparoscopic surgery. Otolaryngological evaluation showed left vocal cord paralysis. Vocal cord paralysis can be a serious complication of general anesthesia because of important voice dysfunction and risk of aspiration. The management is not yet fully established, so prevention and early diagnosis is essential. Copyright © 2018 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Malignant spinal cord compression in cancer patients may be mimicked by a primary spinal cord tumour.

PubMed

Mohammadianpanah, M; Vasei, M; Mosalaei, A; Omidvari, S; Ahmadloo, N

2006-12-01

Although it is quite rare, second primary neoplasms in cancer patients may present with the signs and symptoms of malignant spinal cord compression. Primary spinal cord tumours in the cancer patients may be deceptive and considered as the recurrent first cancer. Therefore, it should be precisely differentiated and appropriately managed. We report such a case of intramedullary ependymoma of the cervical spinal cord mimicking metatstatic recurrent lymphoma and causing cord compression. A 50-year-old man developed intramedullary ependymoma of the cervical spinal cord 1.5 years following chemoradiation for Waldeyer's ring lymphoma. He presented with a 2-month history of neck pain, progressive upper- and lower-extremity numbness and weakness, and bowel and bladder dysfunction. Magnetic resonance imaging revealed an intramedullary expansive lesion extending from C4 to C6 levels of the cervical spinal cord. The clinical and radiological findings were suggestive of malignant process. A comprehensive investigation failed to detect another site of disease. He underwent operation, and the tumour was subtotally resected. The patient's neurological deficits improved subsequently. The development of the intramedullary ependymoma following treating lymphoma has not been reported. We describe the clinical, radiological and pathological findings of this case and review the literature.

Behavioral Intervention, Exercise, and Nutrition Education to Improve Health and Fitness (BENEfit) in Adolescents With Mobility Impairment Due to Spinal Cord Dysfunction

PubMed Central

Liusuwan, Rungsinee Amanda; Widman, Lana M; Abresch, Richard Ted; Johnson, Allan J; McDonald, Craig M

2007-01-01

Background/Objective: Determine the effects of a nutrition education and exercise intervention on the health and fitness of adolescents with mobility impairment due to spinal cord dysfunction from myelomeningocele and spinal cord injury. Subjects participated in a 16-week intervention consisting of a behavioral approach to lifestyle change, exercise, and nutrition education to improve fitness (BENEfit) program. Participants were given a schedule of aerobic and strengthening exercises and attended nutrition education and behavior modification sessions every other week along with their parent(s). Subjects: Twenty adolescents (aged 11–18 years, mean 15.4 ± 2.2 years) with spinal cord dysfunction. Methods: Subjects were tested immediately prior to starting and upon completion of the program. Aerobic fitness was measured using a ramp protocol with an arm ergometer. Heart rate and oxygen uptake were measured. Values at anaerobic threshold and maximum oxygen uptake were recorded. Peak isokinetic arm and shoulder strength were determined with a dynamometer. Body composition was estimated with dual-energy x-ray absorptiometry. Serum chemistry included measures of cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides. Results: Fourteen individuals completed all testing sessions. There was no significant overall change in weight, body mass index, body mass index z-scores, or serum chemistry. Overall, there was a significant increase in whole body lean tissue without a concomitant increase in whole body fat. Fitness measures revealed a significant increase in maximum power output, work efficiency as measured by the amount of power output produced aerobically, and resting oxygen uptake. Strength measurements revealed a significant increase in shoulder extension strength and a trend towards increased shoulder flexion strength. There were no significant changes in high-density lipoprotein, low-density lipoprotein, total cholesterol, or triglycerides. Conclusions: The BENEfit program shows promise as a method for improving the health and fitness of adolescents with mobility impairments who are at high risk for obesity and obesity-related health conditions. PMID:17874697

Assessment of neurogenic bowel dysfunction impact after spinal cord injury using the International Classification of Functioning, Disability and Health.

PubMed

Pires, Jennifer M; Ferreira, Ana M; Rocha, Filipa; Andrade, Luis G; Campos, Inês; Margalho, Paulo; Laíns, Jorge

2018-05-09

Bowel function is frequently compromised after spinal cord injury (SCI). Regardless of this crucial importance in patients' lives, there is still scarce literature on the Neurogenic Bowel Dysfunction (NBD) deleterious impact on SCI patient's lives and only few studies correlating NBD severity with quality of life (QoL). To our knowledge there are no studies assessing the impact of NBD on the context of ICF domains. To assess NBD after SCI using ICF domains and to assess its impact in QoL. Retrospective data analysis and cross-sectional phone survey. Outpatient spinal cord injury setting. Portuguese adult spinal cord injury patients. Retrospective analysis of demographic data, lesion characteristics and bowel management methods at last inpatient discharge. Cross-sectional phone survey assessing current bowel management methods, the Neurogenic Bowel Dysfunction Score and a Likert scale questionnaire about the impact on ICF domains and QoL. 64 patients answered the questionnaire. The majority was male (65.6%), mean age 56.6±15.6 years, AIS A lesion (39.1%), with a traumatic cause (71.9%). The main bowel management methods were contact laxatives, suppositories and osmotic laxatives. 50.1% of patients scored moderate or severe NBD. Considering ICF domains, the greatest impact was in personal and environmental factors, with 39.1% reporting impact in financial costs, 45.3% in need of assistance, 45.3% in emotional health and 46.9% in loss of privacy. There was a significant association between severity of NBD and negative impact on QoL (p<0.05). The study confirms the major impact of NBD on personal and environmental factors of ICF and on the quality of life of SCI population. These findings confirm that it is relevant to identify the main ICF domains affected by NBD after SCI in order to address targeted interventions, working toward changes in health policies and psychosocial aspects.

Sports Ultrasound: Applications Beyond the Musculoskeletal System.

PubMed

Finnoff, Jonathan T; Ray, Jeremiah; Corrado, Gianmichael; Kerkhof, Deanna; Hill, John

2016-09-01

Traditionally, ultrasound has been used to evaluate musculoskeletal injuries in athletes; however, ultrasound applications extend well beyond musculoskeletal conditions, many of which are pertinent to athletes. Articles were identified in PubMed using the search terms ultrasound, echocardiogram, preparticipation physical examination, glycogen, focused assessment with sonography of trauma, optic nerve, and vocal cord dysfunction. No date restrictions were placed on the literature search. Clinical review. Level 4. Several potential applications of nonmusculoskeletal ultrasound in sports medicine are presented, including extended Focused Assessment with Sonography for Trauma (eFAST), limited echocardiographic screening during preparticipation physical examinations, assessment of muscle glycogen stores, optic nerve sheath diameter measurements in athletes with increased intracranial pressure, and assessment of vocal cord dysfunction in athletes. Ultrasound can potentially be used to assist athletes with monitoring their muscle glycogen stores and the diagnosis of multiple nonmusculoskeletal conditions within sports medicine. © 2016 The Author(s).

Vapor Compression Distillation Flight Experiment

NASA Technical Reports Server (NTRS)

Hutchens, Cindy F.

2002-01-01

One of the major requirements associated with operating the International Space Station is the transportation -- space shuttle and Russian Progress spacecraft launches - necessary to re-supply station crews with food and water. The Vapor Compression Distillation (VCD) Flight Experiment, managed by NASA's Marshall Space Flight Center in Huntsville, Ala., is a full-scale demonstration of technology being developed to recycle crewmember urine and wastewater aboard the International Space Station and thereby reduce the amount of water that must be re-supplied. Based on results of the VCD Flight Experiment, an operational urine processor will be installed in Node 3 of the space station in 2005.

The control of male sexual responses.

PubMed

Courtois, Frédérique; Carrier, Serge; Charvier, Kathleen; Guertin, Pierre A; Journel, Nicolas Morel

2013-01-01

Male sexual responses are reflexes mediated by the spinal cord and modulated by neural circuitries involving both the peripheral and central nervous system. While the brain interact with the reflexes to allow perception of sexual sensations and to exert excitatory or inhibitory influences, penile reflexes can occur despite complete transections of the spinal cord, as demonstrated by the reviewed animal studies on spinalization and human studies on spinal cord injury. Neurophysiological and neuropharmacological substrates of the male sexual responses will be discussed in this review, starting with the spinal mediation of erection and its underlying mechanism with nitric oxide (NO), followed by the description of the ejaculation process, its neural mediation and its coordination by the spinal generator of ejaculation (SGE), followed by the occurrence of climax as a multisegmental sympathetic reflex discharge. Brain modulation of these reflexes will be discussed through neurophysiological evidence involving structures such as the medial preoptic area of hypothalamus (MPOA), the paraventricular nucleus (PVN), the periaqueductal gray (PAG), and the nucleus para-gigantocellularis (nPGI), and through neuropharmacological evidence involving neurotransmitters such as serotonin (5-HT), dopamine and oxytocin. The pharmacological developments based on these mechanisms to treat male sexual dysfunctions will complete this review, including phosphodiesterase (PDE-5) inhibitors and intracavernous injections (ICI) for the treatment of erectile dysfunctions (ED), selective serotonin reuptake inhibitor (SSRI) for the treatment of premature ejaculation, and cholinesterase inhibitors as well as alpha adrenergic drugs for the treatment of anejaculation and retrograde ejaculation. Evidence from spinal cord injured studies will be highlighted upon each step.

Review of the History of Non-traumatic Spinal Cord Dysfunction.

PubMed

New, Peter Wayne; Biering-Sørensen, Fin

2017-01-01

Background: The incidence of non-traumatic spinal cord dysfunction (SCDys) is reported to be higher than traumatic spinal cord injury (SCI) in many countries. No formal review of the history of SCDys has been published. Objective: This article aims to identify key highlights in the history of SCDys. Method: An electronic literature search was conducted (January 2017) using MEDLINE (1946-2016) and Embase (1974-2016) databases for publications regarding the history of SCDys. Publications on the history of SCI and a selection of neurology textbooks and books on the history of neurology were reviewed for potentially relevant references. The focus of the literature search was on identifying publications that detail key highlights regarding the history of the diagnosis and management of the most common SCDys conditions, as well as those of historical significance. Results: The electronic search of MEDLINE and Embase identified 11 relevant publications. The majority of publications included were identified from the authors' libraries and a selection of books on neurology and the history of neurology. Conclusions: This review outlines the history of SCDys, taking a broader historical perspective and covering the increasing awareness of the role of the spinal cord and knowledge of neuroanatomy. Key milestones in the history of the diagnosis and management of the most common SCDys conditions are presented. An appreciation of the history of SCDys increases our understanding of the large number of people who contributed to our current knowledge of these conditions and in some situations helps guide efforts regarding prevention of SCDys.

Dendritic spine dysgenesis contributes to hyperreflexia after spinal cord injury

PubMed Central

Bandaru, Samira P.; Liu, Shujun; Waxman, Stephen G.

2014-01-01

Hyperreflexia and spasticity are chronic complications in spinal cord injury (SCI), with limited options for safe and effective treatment. A central mechanism in spasticity is hyperexcitability of the spinal stretch reflex, which presents symptomatically as a velocity-dependent increase in tonic stretch reflexes and exaggerated tendon jerks. In this study we tested the hypothesis that dendritic spine remodeling within motor reflex pathways in the spinal cord contributes to H-reflex dysfunction indicative of spasticity after contusion SCI. Six weeks after SCI in adult Sprague-Dawley rats, we observed changes in dendritic spine morphology on α-motor neurons below the level of injury, including increased density, altered spine shape, and redistribution along dendritic branches. These abnormal spine morphologies accompanied the loss of H-reflex rate-dependent depression (RDD) and increased ratio of H-reflex to M-wave responses (H/M ratio). Above the level of injury, spine density decreased compared with below-injury spine profiles and spine distributions were similar to those for uninjured controls. As expected, there was no H-reflex hyperexcitability above the level of injury in forelimb H-reflex testing. Treatment with NSC23766, a Rac1-specific inhibitor, decreased the presence of abnormal dendritic spine profiles below the level of injury, restored RDD of the H-reflex, and decreased H/M ratios in SCI animals. These findings provide evidence for a novel mechanistic relationship between abnormal dendritic spine remodeling in the spinal cord motor system and reflex dysfunction in SCI. PMID:25505110

Efficacy and safety of vardenafil in men with erectile dysfunction caused by spinal cord injury.

PubMed

Giuliano, F; Rubio-Aurioles, E; Kennelly, M; Montorsi, F; Kim, E D; Finkbeiner, A E; Pommerville, P J; Colopy, M W; Wilkins, H J; Wachs, B H

2006-01-24

To assess the efficacy and tolerability of vardenafil in men with erectile dysfunction (ED) due to traumatic spinal cord injury (SCI). In this multicenter, double-blind, placebo-controlled, parallel-group 12-week study, 418 men aged 18 years and older with ED for more than 6 months consequent to SCI were randomized to vardenafil (n = 207) or placebo (n = 211) (10 mg for 4 weeks, then maintained or titrated to 5 or 20 mg at weeks 4 and 8). Efficacy assessments included the erectile function (EF) domain score of the International Index of Erectile Function questionnaire and diary questions regarding penetration, maintenance of erection to completion of intercourse, and ejaculation. Baseline patient characteristics were similar in the vardenafil (mean age 40 years) and placebo (mean age 39 years) groups. Mean baseline EF domain scores were 11.6 in the vardenafil group and 12.1 (moderate ED) in the placebo group. EF domain score in the vardenafil group improved to 22.0 (mild ED) at last observation carried forward vs 13.5 in the placebo group (p < 0.001). Over 12 weeks of treatment, mean per-patient penetration (76% vs 41%), maintenance (59% vs 22%), and ejaculation (19% vs 10%) success rates were significantly greater vs placebo (all p < 0.001). The most frequently reported drug-related adverse events were headache (vardenafil 15%, placebo 4%), flushing (vardenafil 6%, placebo 0%), nasal congestion (vardenafil 5%, placebo 0%), and dyspepsia (vardenafil 4%, placebo 0%). Vardenafil significantly improved erectile and ejaculatory function and was generally well tolerated in men with erectile dysfunction due to spinal cord injury.

Measurements of C-reactive protein (CRP) and nerve-growth-factor (NGF) concentrations in serum and urine samples of dogs with neurologic disorders.

PubMed

Kordass, Ulrike; Carlson, Regina; Stein, Veronika Maria; Tipold, Andrea

2016-01-08

The purpose of this study was to prove the hypothesis that C-reactive protein (CRP) and nerve growth factor (NGF) may be potential biomarkers for lower urinary tract disorders and may be able to distinguish between micturition dysfunctions of different origin in dogs with spinal cord diseases. NGF- and CRP- concentrations were measured in serum and urine samples using specific ELISA-Kits. Results in urine were standardized by urine-creatinine levels. CRP in serum was detectable in 32/76 and in urine samples in 40/76 patients. NGF could be measured in all serum and in 70/76 urine samples. Urinary CRP concentrations were significantly higher in dogs with micturition dysfunction (p = 0.0009) and in dogs with different neurological diseases (p = 0.0020) compared to the control group. However, comparing dogs with spinal cord disorders with and without associated micturition dysfunction no significant difference could be detected for NGF and CRP values in urine or serum samples. Additionally, levels did not decrease significantly, when measured at the time when the dogs regained the ability to urinate properly (urinary NGF p = 0.7962; urinary CRP p = 0.078). Urine samples with bacteria and/or leukocytes had no significant increase in urinary NGF (p = 0.1112) or CRP (p = 0.0534) concentrations, but higher CRP-levels in urine from dogs with cystitis were found compared to dogs without signs of cystitis. From these data we conclude that neither CRP nor NGF in urine or serum can be considered as reliable biomarkers for micturition disorders in dogs with spinal cord disorders in a clinical setting, but their production might be part of the pathogenesis of such disorders. Significantly higher levels of CRP could be found in the urine of dogs with micturition dysfunctions compared to control dogs. This phenomenon could potentially be explained by unspecific extrahepatic CRP production by smooth muscle cells in the dilated bladder.

Vardenafil improves ejaculation success rates and self-confidence in men with erectile dysfunction due to spinal cord injury.

PubMed

Giuliano, Francois; Rubio-Aurioles, Eusebio; Kennelly, Michael; Montorsi, Francesco; Kim, Edward D; Finkbeiner, Alex E; Pommerville, Peter J; Colopy, Michael W; Wachs, Barton H

2008-04-01

Multicenter, double-blind, placebo-controlled, parallel-group study. To assess the effect of the oral phosphodiesterase type-5 inhibitor, vardenafil, on ejaculation rates and self-confidence in men with spinal cord injury (SCI). Spinal command of male sexual functions is often seriously impaired by traumatic spinal cord injury (SCI). A high proportion of men with SCI cannot ejaculate during sexual intercourse. SCI-related ejaculatory disorders are often responsible for male infertility. Sexual dysfunction associated with SCI can also affect men's self-confidence. In this 12-week study, 418 men aged >or=18 years with erectile dysfunction >6 months resulting from a traumatic SCI were randomized to vardenafil (n = 207) or placebo (n = 211) 10 mg for 4 weeks, then maintained or titrated to 5 or 20 mg at weeks 4 and 8. Assessments included questions of the International Index of Erectile Function (IIEF) about ejaculation success and orgasmic perception; the Global Confidence Question; and quality-of-life scales to measure psychological well-being, self-esteem, depression, and mental health status. Overall per patient ejaculation success rates were significantly greater with vardenafil than placebo over 12 weeks of treatment (19% vs. 10%; P < 0.001). At last observation carried forward, the IIEF "orgasmic function" score increased from 2.9 at baseline to 4.0 for vardenafil and from 3.0 at baseline to 3.4 for placebo. Sixteen percent of men receiving vardenafil and 8% receiving placebo felt orgasm "almost always" or "always" at weeks 8-12, compared with 4% and 6%, respectively, at baseline. Significant improvements in confidence scores were observed with vardenafil compared with placebo (P < 0.0001). There were no clinically significant differences between vardenafil and placebo in the quality-of-life measures at the study endpoint, but these had been in the normal range at baseline. Vardenafil significantly improved ejaculation and self-confidence in men with erectile dysfunction due to SCI.

Infertility in Men with Spinal Cord Injury: Research and Treatment

PubMed Central

Brackett, Nancy L.

2012-01-01

Spinal cord injury (SCI) occurs most often to young men. Following SCI, most men are infertile due to a combination of erectile dysfunction, ejaculatory dysfunction and semen abnormalities. Erectile dysfunction may be treated by the same therapies that are used in the general population. Similarly, the same treatments that are effective to assist conception in couples with non-SCI male factor patients are effective in assisting conception in SCI male-factor patients. The most apparent differences in male-factor symptoms between SCI and non-SCI patients are the high occurrences of anejaculation and atypical semen profiles in men with SCI. Methods available to assist ejaculation in men with SCI include penile vibratory stimulation and EEJ. Use of surgical sperm retrieval as the first line of treatment for anejaculation in men with SCI is controversial. Most men with SCI have a unique semen profile characterized by normal sperm concentration, but abnormally low sperm motility. Toxic substances in the semen contribute to this problem. Despite impaired sperm parameters, pregnancy outcomes using sperm from men with SCI are similar to pregnancy outcomes using sperm from non-SCI men. Future studies should focus on improving natural ejaculation and improving semen quality in these men. PMID:24278717

Vibrational and chiroptical spectroscopic characterization of gamma-turn model cyclic tetrapeptides containing two beta-Ala residues.

PubMed

Vass, Elemér; Majer, Zsuzsa; Kohalmy, Krisztina; Hollósi, Miklós

2010-08-01

The optical spectroscopic characterization of gamma-turns in solution is uncertain and their distinction from beta-turns is often difficult. This work reports systematic ECD and vibrational circular dichroism (VCD) spectroscopic studies on gamma-turn model cyclic tetrapeptides cyclo(Ala-beta-Ala-Pro-beta-Ala) (1), cyclo(Pro-beta-Ala-Pro-beta-Ala) (2) and cyclo(Ala-beta-Ala-Ala-beta-Ala) (3). Conformational analysis performed at the 6-31G(d)/B3LYP level of theory using an adequate PCM solvent model predicted one predominant conformer for 1-3, featuring two inverse gamma-turns. The ECD spectra in ACN of 1 and 2 are characterized by a negative n-->pi* band near 230 nm and a positive pi-->pi* band below 200 nm with a long wavelength shoulder. The ECD spectra in TFE of 1-3 show similar spectra with blue-shifted bands. The VCD spectra in ACN-d(3) of 1 and 2 show a +/-/+/- amide I sign pattern resulting from four uncoupled vibrations in the case of 1 and a sequence of two positive couplets in the case of 2. A -/+/+/- amide I VCD pattern was measured for 3 in TFE-d(2). All three peptides give a positive couplet or couplet-like feature (+/-) in the amide II region. VCD spectroscopy, in agreement with theoretical calculations revealed that low frequency amide I vibrations (at approximately 1630 cm(-1) or below) are indicative of a C(7) H-bonded inverse gamma-turns with Pro in position 2, while gamma-turns encompassing Ala absorb at higher frequency (above 1645 cm(-1)). Copyright 2010 Wiley-Liss, Inc.

Tetravalent Dengue Vaccine: A Review in the Prevention of Dengue Disease.

PubMed

Scott, Lesley J

2016-09-01

Tetravalent, live-attenuated, dengue vaccine (Dengvaxia(®); CYD-TDV) is the first vaccine approved for the prevention of dengue disease caused by dengue virus (DENV) serotypes 1-4 in individuals aged 9-45 or 9-60 years living in high dengue endemic areas. This narrative review discusses the immunogenicity, protective efficacy, reactogenicity and safety of CYD-TDV in the prevention of dengue disease. In Latin American and Asian phase 3 trials in children and adolescents (n > 30,000), the recommended three-dose CYD-TDV regimen was efficacious in preventing virologically-confirmed dengue (VCD) during the period from 28 days after the last dose (month 13) to month 25, meeting the primary endpoint criteria. Protective efficacy against VCD in the respective individual trials was 60.8 and 56.5 % (primary analysis). During the 25-month active surveillance phase, CYD-TDV also provided protective efficacy against VCD, severe dengue, any grade of dengue haemorrhagic fever and VCD-related hospitalization in children aged 9 years and older. CYD-TDV was generally well tolerated, with no safety concerns identified after up to 4 years' follow-up (i.e. from post dose 1) in ongoing long-term studies. Based on evidence from the dengue clinical trial program, the WHO SAGE recommended that countries with high dengue endemicity consider introducing CYD-TDV as part of an integrated disease prevention strategy to lower disease burden. Pharmacoeconomic considerations will be pivotal to implementing dengue vaccination prevention strategies in these countries. The availability of a dengue vaccine is considered essential if the 2012 WHO global strategy targets for reducing the burden of dengue disease by 2020 are to be attained. Hence, CYD-TDV represents a major advance for the prevention of dengue disease in high dengue endemic regions.

Starclose SE® hemostasis after 6F direct antegrade superficial femoral artery access distal to the femoral head for peripheral endovascular procedures in obese patients.

PubMed

Spiliopoulos, Stavros; Kitrou, Panagiotis; Christeas, Nikolaos; Karnabatidis, Dimitris

2016-01-01

Direct superficial femoral artery (SFA) antegrade puncture is a valid alternative to common femoral artery (CFA) access for peripheral vascular interventions. Data investigating vascular closure device (VCD) hemostasis of distant SFA 6F access are limited. We aimed to investigate the safety and effectiveness of the Starclose SE® VCD for hemostasis, following direct 6F antegrade SFA access distal to the femoral head. This prospective, single-center study included patients who were not suitable for CFA puncture and were scheduled to undergo peripheral endovascular interventions using direct antegrade SFA 6F access, at least 2 cm below the inferior edge of femoral head. Hemostasis was obtained with the Starclose SE® VCD (Abbott Laboratories). Primary endpoints were successful hemostasis rate and periprocedural (30-day) major complication rate. Secondary endpoint was the rate of minor complications. Clinical and Doppler ultrasound follow-up was performed at discharge and at one month. Between September 2014 and August 2015, a total of 30 patients (21 male; 70.0%) with a mean body mass index of 41.2 kg/m2 were enrolled. Mean age was 72±9 years (range, 67-88 years). Most patients suffered from critical limb ischemia (87.1%) and diabetes (61.3%). Calcifications were present in eight cases (26.6%). Reason for direct SFA puncture was obesity (100%). Successful hemostasis was achieved in 100% of the cases. No major complications were noted after one-month follow-up. Minor complications included two <5 cm hematomas (6.6%) not necessitating treatment. In this prospective study, Starclose SE® VCD was safe and effective for hemostasis of antegrade direct SFA puncture. Uncomplicated hemostasis was achieved even in cases of puncturing 2 to 7 cm below the inferior edge of the femoral head.

Is Supramolecular Filament Chirality the Underlying Cause of Major Morphology Differences in Amyloid Fibrils?

PubMed Central

2015-01-01

The unique enhanced sensitivity of vibrational circular dichroism (VCD) to the formation and development of amyloid fibrils in solution is extended to four additional fibril-forming proteins or peptides where it is shown that the sign of the fibril VCD pattern correlates with the sense of supramolecular filament chirality and, without exception, to the dominant fibril morphology as observed in AFM or SEM images. Previously for insulin, it has been demonstrated that the sign of the VCD band pattern from filament chirality can be controlled by adjusting the pH of the incubating solution, above pH 2 for “normal” left-hand-helical filaments and below pH 2 for “reversed” right-hand-helical filaments. From AFM or SEM images, left-helical filaments form multifilament braids of left-twisted fibrils while the right-helical filaments form parallel filament rows of fibrils with a flat tape-like morphology, the two major classes of fibril morphology that from deep UV resonance Raman scattering exhibit the same cross-β-core secondary structure. Here we investigate whether fibril supramolecular chirality is the underlying cause of the major morphology differences in all amyloid fibrils by showing that the morphology (twisted versus flat) of fibrils of lysozyme, apo-α-lactalbumin, HET-s (218–289) prion, and a short polypeptide fragment of transthyretin, TTR (105–115), directly correlates to their supramolecular chirality as revealed by VCD. The result is strong evidence that the chiral supramolecular organization of filaments is the principal underlying cause of the morphological heterogeneity of amyloid fibrils. Because fibril morphology is linked to cell toxicity, the chirality of amyloid aggregates should be explored in the widely used in vitro models of amyloid-associated diseases. PMID:24484302

Spectroscopic investigation of Ginkgo biloba terpene trilactones and their interaction with amyloid peptide Aβ(25-35)

NASA Astrophysics Data System (ADS)

He, Jiangtao; Petrovic, Ana G.; Dzyuba, Sergei V.; Berova, Nina; Nakanishi, Koji; Polavarapu, Prasad L.

2008-04-01

The beneficial effects of Ginkgo biloba extract in the "treatment" of dementia are attributed to its terpene trilactone (TTL) constituents. The interactions between TTLs and amyloid peptide are believed to be responsible in preventing the aggregation of peptide. These interactions have been investigated using infrared vibrational absorption (VA) and circular dichroism (VCD) spectra. Four TTLs, namely ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC) and bilobalide (BB) and amyloid Aβ(25-35) peptide, as a model for the full length peptide, are used in this study. GA-monoether and GA-diether have also been synthesized and investigated to help understand the role of individual carbonyl groups in these interactions. The precipitation and solubility issues encountered with the mixture of ginkgolide + Aβ peptide for VA and VCD studies were overcome using binary ethanol-D 2O solvent mixture. The experimental VA and VCD spectra of GA, GB, GC and BB, GA-monoether and GA-diether have been analyzed using the corresponding spectra predicted with density functional theory. The time-dependent experimental VA and VCD spectra of Aβ(25-35) peptide and the corresponding experimental spectra in the presence of TTLs indicated that the effect of the TTLs in modulating the aggregation of Aβ(25-35) peptide is relatively small. Such small effects might indicate the absence of a specific interaction between the TTLs and Aβ(25-35) peptide as a major force leading to the reduced aggregation of amyloid peptides. It is possible that the therapeutic effect of G. biloba extract does not originate from direct interactions between TTLs and the Aβ(25-35) peptide and is more complex.

Is supramolecular filament chirality the underlying cause of major morphology differences in amyloid fibrils?

PubMed

Kurouski, Dmitry; Lu, Xuefang; Popova, Ludmila; Wan, William; Shanmugasundaram, Maruda; Stubbs, Gerald; Dukor, Rina K; Lednev, Igor K; Nafie, Laurence A

2014-02-12

The unique enhanced sensitivity of vibrational circular dichroism (VCD) to the formation and development of amyloid fibrils in solution is extended to four additional fibril-forming proteins or peptides where it is shown that the sign of the fibril VCD pattern correlates with the sense of supramolecular filament chirality and, without exception, to the dominant fibril morphology as observed in AFM or SEM images. Previously for insulin, it has been demonstrated that the sign of the VCD band pattern from filament chirality can be controlled by adjusting the pH of the incubating solution, above pH 2 for "normal" left-hand-helical filaments and below pH 2 for "reversed" right-hand-helical filaments. From AFM or SEM images, left-helical filaments form multifilament braids of left-twisted fibrils while the right-helical filaments form parallel filament rows of fibrils with a flat tape-like morphology, the two major classes of fibril morphology that from deep UV resonance Raman scattering exhibit the same cross-β-core secondary structure. Here we investigate whether fibril supramolecular chirality is the underlying cause of the major morphology differences in all amyloid fibrils by showing that the morphology (twisted versus flat) of fibrils of lysozyme, apo-α-lactalbumin, HET-s (218-289) prion, and a short polypeptide fragment of transthyretin, TTR (105-115), directly correlates to their supramolecular chirality as revealed by VCD. The result is strong evidence that the chiral supramolecular organization of filaments is the principal underlying cause of the morphological heterogeneity of amyloid fibrils. Because fibril morphology is linked to cell toxicity, the chirality of amyloid aggregates should be explored in the widely used in vitro models of amyloid-associated diseases.

Vibrational and electronic circular dichroism study of the interactions of cationic porphyrins with (dG-dC)10 and (dA-dT)10.

PubMed

Nový, Jakub; Urbanová, Marie

2007-03-01

The interactions of two different porphyrins, without axial ligands-5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin-Cu(II) tetrachloride (Cu(II)TMPyP) and with bulky meso substituents-5,10,15,20-tetrakis(N,N,N-trimethylanilinium-4-yl)porphyrin tetrachloride (TMAP), with (dG-dC)10 and (dA-dT)10 were studied by combination of vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectroscopy at different [oligonucleotide]/[porphyrin] ratios, where [oligonucleotide] and [porphyrin] are the concentrations of oligonucleotide per base-pair and porphyrin, respectively. The combination of VCD and ECD spectroscopy enables us to identify the types of interactions, and to specify the sites of interactions: The intercalative binding mode of Cu(II)TMPyP with (dG-dC)(10), which has been well described, was characterized by a new VCD "marker" and it was shown that the interaction of Cu(II)TMPyP with (dA-dT)10 via external binding to the phosphate backbone and major groove binding caused transition from the B to the non-B conformer. TMAP interacted with the major groove of (dG-dC)10, was semi-intercalated into (dA-dT)10, and caused significant variation in the structure of both oligonucleotides at the higher concentration of porphyrin. The spectroscopic techniques used in this study revealed that porphyrin binding with AT sequences caused substantial variation of the DNA structure. It was shown that VCD spectroscopy is an effective tool for the conformational studies of nucleic acid-porphyrin complexes in solution. (c) 2007 Wiley Periodicals, Inc.

Neurogenic detrusor overactivity in patients with spinal cord injury: evaluation and management.

PubMed

Sahai, Arun; Cortes, Eduardo; Seth, Jai; Khan, Muhammad Shamim; Panicker, Jalesh; Kelleher, Cornelius; Kessler, Thomas M; Fowler, Clare J; Dasgupta, Prokar

2011-12-01

Lower urinary tract dysfunction can have a significant impact on patients with spinal cord injury. Over the years, many treatment options have become available. This article reviews the assessment and management of neurogenic detrusor overactivity, with a particular focus on articles from the recent literature. Recent guidelines on the subject will be discussed. Management options include antimuscarinics and bladder emptying measures, botulinum toxin A, and neuromodulation in refractory cases and surgery for intractable cases. Recent and relevant publications in these areas will be summarized and discussed.

Progress in Paralysis | NIH MedlinePlus the Magazine

MedlinePlus

... benefits from this research flowing to people with Parkinson's disease or other neurological disorders? The mechanism of dysfunction in spinal cord injury is not completely understood but is believed to be ... Parkinson's and some of the other neurological disorders. Consequently, ...

Clinical and imaging features of spinal cord type of neuro Behçet disease: A case report and systematic review.

PubMed

Liu, Hui-Miao; Dong, Ci; Zhang, Yong-Zhi; Tian, Ya-Yun; Chen, Hong-Xu; Zhang, Sai; Li, Na; Gu, Ping

2017-10-01

To investigate the clinical and MRI characteristics of spinal cord nerve Behçet's disease. One patient with spinal cord nerve Behçet's disease was admitted to our hospital at October 20, 2015. Spinal cord nerve Behçet's disease. Retrospective analysis was performed on such case as well as 16 cases of spinal cord nerve Behçet's disease reported in China or abroad. Seventeen cases of spinal cord type of neuro Behçet's disease include 13 men and 4 women, with an average age of onset of 34.8 years old. The mean time from Behçet's disease symptoms to spinal cord involvement were 10.8 years. The initial symptom in one case was spinal cord injury, and another 4 cases had a recurrence course. The most common performance of spinal cord injury was sensory disturbance (82.4%), following by weakness (76.5%), sphincter or sexual dysfunction (58.8%), and pain in back, backside of neck or lower chest (29.4%). The number of cells was slightly increased or the protein level was increased in cerebrospinal fluid test. And the water channel protein antibody and oligoclonal band of serum levels were all negative. The spinal cord injury involved more than 3 vertebral bodies in 10 cases, and involved more than half of spinal cord in sagittal plane in 8 cases. In acute stage, shock therapy with large dose of glucocorticoid was generally applied both in China and abroad. The clinical features of spinal cord nerve Behçet's disease were various, making it easily misdiagnosed. Longitudinal extensive transverse myelitis performs as a characteristic manifestation.

Determination of the absolute configuration of two estrogenic nonylphenols in solution by chiroptical methods

NASA Astrophysics Data System (ADS)

Reinscheid, Uwe M.

2009-01-01

The absolute configurations of two estrogenic nonylphenols were determined in solution. Both nonylphenols, NP35 and NP112 could not be crystallized so that only solution methods are able to solve directly the question of absolute configuration. The conclusion based on experimental and calculated optical rotation and VCD data for the nonylphenol NP35 was independently confirmed by another study using a camphanoyl derivative and X-ray analysis of the obtained crystals. In case of NP112, the experimental rotation data are inconclusive. However, the comparison between experimental and calculated VCD data allowed the determination of the absolute configuration.

Absolute configuration of (-)-myrtenal by vibrational circular dichroism.

PubMed

Burgueño-Tapia, Eleuterio; Zepeda, L Gerardo; Joseph-Nathan, Pedro

2010-07-01

The VCD spectrum of the monoterpene (-)-myrtenal (1) was compared with theoretical spectra using ab initio density functional theory (DFT) calculations at the B3LYP/6-31G(d,p), B3LYP/6-31G+(d,p), B3LYP/6-311G+(d,p), B3LYP/DGDZVP, and B3PW91/DGTZVP levels of theory. Conformational analysis of 1 indicated that the lowest energy conformer was s-trans-C2-C10, which contributes more than 98.5% to the total conformational population regardless of the employed level of theory. The use of a recently developed confidence level algorithm demonstrated that VCD spectra calculated for the main conformer, using the indicated hybrid functionals and basis set, gave no significant changes, from where it follows that B3LYP/DGDZVP calculations provide a superior balance between computer cost and VCD spectral accuracy. The DGDZVP basis set demanded around a quarter the time than the 6-311G+(d,p) basis set while providing similar results. The spectral comparison also provided evidence that the levorotatory enantiomer of myrtenal has the 1R absolute configuration. 2010 Elsevier Ltd. All rights reserved.

Intra- versus Intermolecular Hydrogen Bonding: Solvent-Dependent Conformational Preferences of a Common Supramolecular Binding Motif from 1 H NMR and Vibrational Circular Dichroism Spectra.

PubMed

Demarque, Daniel P; Merten, Christian

2017-12-19

When predicting binding properties of small molecules or larger supramolecular aggregates, intra- and intermolecular hydrogen bonds are often considered the most important factor. Spectroscopic techniques such as 1 H NMR spectroscopy are typically utilized to characterize such binding events, but interpretation is often qualitative and follows chemical intuition. In this study, we compare the effects of intramolecular hydrogen bonding and solvation on two chiral 2,6-pyridinediyl-dialkylamides. In comparison with 1 H NMR spectroscopy, vibrational circular dichroism (VCD) spectroscopy proved to be more sensitive to conformational changes. In fact, the change of the solvent from CDCl 3 to [D 6 ]DMSO generates mirror-image VCD spectra for the same enantiomer. Here, the common sense that the sterically less hindered group is more prone to solvation proved to be wrong according predicted VCD spectra, which clearly show that both asymmetric amide hydrogens are equally likely to be solvated, but never simultaneously. The competition between intra- and intermolecular hydrogen bonding and their importance for a correct prediction of spectral properties are discussed. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Spanish validation of the International Spinal Cord Injury Pulmonary Function Basic Data Set questionnaire for the study of the repercussion of spinal cord injury in the respiratory system].

PubMed

Gómez Garrido, Alba; León Espitia, Ana María; Montesinos Magraner, Lluïsa; Ramirez Galceran, Lucrecia; Soler Canudes, Emilia; González Viejo, Miguel Angel

2015-12-07

The dysfunction of the respiratory system and the breathing complications in persons with injured spinal cord has an effect on the morbidity and the mortality of the disease. The objectives were: 1) to translate to Spanish and validate the questionnaire of international consensus: International Spinal Cord Injury Pulmonary Function Basic Data Set, and 2) to determine the influence of chronic spinal cord injury in the respiratory system in terms of respiratory functionalism. Translation to Spanish and validation of the questionnaire of international consensus intended for the study of the pulmonary function in spinal cord injury disease. We tested the reliability of that questionnaire. We conducted a descriptive transversal study to determine the degree of involvement of the respiratory system in spinal cord injury. A percentage of 91.9 did not have any respiratory pathology before spinal cord injury and 54.8% of patients smoked. A percentage of 27.4 of patients presented breathing complications one year after the injury. Results of the respiratory function tests were: FVC 67%, FEV1 72% and PEF 70%. Concordance and reliability were 98%. The Spanish version of the questionnaire of international consensus about the pulmonary function is a useful tool for the study of the respiratory involvement in spinal cord injury. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Changes in Afferent Activity After Spinal Cord Injury

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2010-01-01

Aims To summarize the changes that occur in the properties of bladder afferent neurons following spinal cord injury. Methods Literature review of anatomical, immunohistochemical, and pharmacologic studies of normal and dysfunctional bladder afferent pathways. Results Studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through coordination centers (periaqueductal gray and pontine micturition center) located in the rostral brain stem. This reflex pathway, which is activated by small myelinated (Aδ) bladder afferent nerves, is in turn modulated by higher centers in the cerebral cortex involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary voiding, as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury, the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. The recovery of bladder function after spinal cord injury is dependent in part on the plasticity of bladder afferent pathways and the unmasking of reflexes triggered by unmyelinated, capsaicin-sensitive, C-fiber bladder afferent neurons. Plasticity is associated with morphologic, chemical, and electrical changes in bladder afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and the peripheral target organs. Conclusions Spinal cord injury at sites remote from the lumbosacral spinal cord can indirectly influence properties of bladder afferent neurons by altering the function and chemical environment in the bladder or the spinal cord. PMID:20025033

[Acute non-traumatic myelopathy in children and adolescents].

PubMed

Arroyo, Hugo A

2013-09-06

The term 'acute myelopathies'--referred to a spinal cord dysfunction--represent a heterogeneous group of disorders with distinct etiologies, clinical and radiologic features, and prognoses. The objective of this review is to discuss the non-traumatic acute myelopathies. Acute myelopathy can be due to several causes as infective agents or inflammatory processes, such as in acute myelitis, compressive lesions, vascular lesions, etc. The clinical presentation is often dramatic with tetraparesis or paraparesis, sensory disturbances and bladder and/or bowel dysfunction. History and physical examination are used to localize the lesion to the root or specific level of the cord, which can guide imaging. Different syndromes are recognized: complete transverse lesion, central grey matter syndrome, anterior horn syndrome, anterior spinal artery syndrome, etc). The first priority is to rule out a compressive lesion. If a myelopathy is suspected, a gadolinium-enhanced MRI of the spinal cord should be obtained as soon as possible. If there is no structural lesion such as epidural blood or a spinal mass, then the presence or absence of spinal cord inflammation should be documented with a lumbar puncture. The absence of pleocytosis would lead to consideration of non inflammatory causes of myelopathy such as arteriovenous malformations, fibrocartilaginous embolism, or possibly early inflammatory myelopathy. In the presence of an inflammatory process (defined by gadolinium enhancement, cerebrospinal fluid pleocytosis, or elevated cerebrospinal fluid immunoglobulin index), one should determine whether there is an inflammatory or an infectious cause. Different virus, bacterias, parasites and fungi have to be considered as autoimmune and inflammatory diseases that involve the central nervous system.

Clinical evaluation of an innovative operative procedure in the treatment of the tethered cord syndrome.

PubMed

Hou, Yang; Sun, Jingchuan; Shi, Jiangang; Guo, Yongfei; Wang, Yuan; Shi, Guodong; Xu, Guohua

2018-06-01

The tethered cord syndrome (TCS) characterized by urination dysfunction has long been a worldwide clinical problem, of which clinical effects remains controversial. The objective of this study was to evaluate the clinical effects of an innovative surgical method for the treatment of TCS. This is a retrospective clinical study. There were 15 patients included in this study. The visual analog scale (VAS) and the Japanese Orthopaedic Association (JOA) scores were evaluated. The incidence of complications after surgery was also analyzed. A total of 15 patients including 9 men and 6 women with TCS underwent homogeneous spinal-shortening axial decompression (HSAD) from September 2011 to February 2015. The average age at the time of surgery was 38.1±17.7 years. The average postoperative follow-up period was 21.5±7.5 months. The VAS and JOA scores were used to evaluate the clinical effects of the new operational procedure. In addition, the incidence of complications was also recorded and analyzed. The VAS scores decreased from 3.93±2.52 to 1.80±1.21 at the final follow-up after surgery with a significant statistical difference (p=.006). The JOA scores also significantly increased from 9.93±3.43 to 21.20±4.18 at the final follow-up (p<.001). Fourteen cases (93.3%) with bladder dysfunction and 7 cases with sensory dysfunction of the lower limbs (87.5%) had a significant improvement postoperatively. Complications such as infection, pulmonary embolism, nerve injury, and broken rod were not observed during the follow-up period. The operation of HSAD was an effective and safe surgical method for TCS, which can achieve direct decompression of the tethered spinal cord. Copyright © 2017. Published by Elsevier Inc.

The artificial somato-autonomic reflex arch does not improve lower urinary tract function in patients with spinal cord lesions.

PubMed

Rasmussen, Mikkel Mylius; Rawashdeh, Yazan F; Clemmensen, Dorte; Tankisi, Hatice; Fuglsang-Frederiksen, Anders; Krogh, Klaus; Christensen, Peter

2015-02-01

The artificial somato-autonomic reflex arch (Xiao procedure) was proposed as treatment for neurogenic bladder dysfunction. We investigated the effects of the procedure on lower urinary tract function. Seven and 3 patients with a median age of 46 years (range 19 to 64) had AIS A and B spinal cord injury, respectively. In these patients an anastomosis was created between the ventral (motor) part of L5 and the ventral part of the S2 root. Urodynamics were performed and a standard questionnaire was completed at baseline and 18 months postoperatively. Artificial reflex arch stimulation did not initiate voiding or increase bladder pressure. Maximum bladder capacity did not change significantly from baseline to followup (median 427.5 ml, range 168 to 581 vs 498.5, range 271 to 580, p = 0.09). Likewise, bladder compliance did not significantly differ at baseline and followup (median 16.9 ml/cm H2O, range 15.0 to 65.0 vs 25.1, range 17.5 to 50.0, p = 0.95). No difference was found in awareness of bladder emptying, incontinence episodes, bladder emptying method or medication use for neurogenic bladder dysfunction. The only statistically significant change was a decreased incidence of leakage at followup on urodynamics (p = 0.03). Postoperatively decreased genital sensation and erectile dysfunction developed in 1 patient and another experienced a minor cerebrovascular accident with no long-term complications. In contrast to earlier findings, creation of an artificial somato-autonomic reflex arch in patients with spinal cord injury had no clinically relevant effect on lower urinary tract function. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The forgotten cause of stridor in the emergency department.

PubMed

Ng, Tian-Tee

2017-01-01

Paradoxical Vocal Fold Movement Disorder is where the larynx exhibits paradoxical vocal cords closure during respiration, creating partial airway obstruction. Causes of vocal fold movement disorder are multifactorial, and patients describe tightness of throat, difficulty getting air in, have stridor, and do not respond to inhalers. We propose using transnasal laryngoscopy examination, which will show narrowing of vocal cords on inspiration, and The Pittsburgh Vocal Cord Dysfunction Index with a cutoff score of ≥4 to distinguish vocal fold movement disorder from asthma and other causes of stridor. Management of paradoxical vocal fold movement disorder involves a combination of pharmacological, psychological, psychiatric, and speech training. Paradoxical vocal fold movement disorder is a very treatable cause of stridor, so long as it is identified and other organic causes are excluded.

Cognitive performance of people with traumatic spinal cord injury: a cross-sectional study comparing people with subacute and chronic injuries.

PubMed

Molina, B; Segura, A; Serrano, J P; Alonso, F J; Molina, L; Pérez-Borrego, Y A; Ugarte, M I; Oliviero, A

2018-02-22

Cross-sectional study. To assess the impact of spinal cord injury (SCI) on cognitive function in individuals with subacute and chronic SCI. National Hospital for SCI patients (Spain). The present investigation was designed to determine the nature, pattern, and extent of cognitive deficits in a group of participants with subacute (n = 32) and chronic (n = 34) SCI, using a comprehensive battery of reliable and validated neuropsychological assessments to study a broad range of cognitive functions. Twenty-seven able-bodied subjects matched to the groups with SCI for age and educational level formed the control group. The neuropsychological assessment showed alterations in the domain of attention, processing speed, memory and learning, executive functions, and in recognition in participants with SCI. The prevalence of cognitive dysfunction in the chronic stage was also confirmed at the individual level. The comparison of the neuropsychological assessment between the groups with subacute and chronic SCI showed a worsening of cognitive functions in those with chronic SCI compared to the group with subacute SCI. In participants with SCI, cognitive dysfunctions are present in the subacute stage and worsen over time. From a clinical point of view, we confirmed the presence of cognitive dysfunction that may interfere with the first stage of rehabilitation which is the most intense and important. Moreover, cognitive dysfunction may be important beyond the end of the first stage of rehabilitation as it can affect an individual's quality of life and possible integration to society.

Pregnancy complicated with Alport syndrome: a good obstetric outcome and failure to diagnose an infant born to a mother with Alport syndrome by umbilical cord immunofluorescence staining.

PubMed

Matsubara, Shigeki; Ueda, Yoshihiko; Takahashi, Hisako; Nagai, Takashi; Kuwata, Tomoyuki; Muto, Shigeaki; Yamaguchi, Takehiko; Takizawa, Toshihiro; Suzuki, Mitsuaki

2009-12-01

Alport syndrome is a familial progressive nephritis. The most frequent type is X-linked Alport syndrome, caused by genetic abnormalities in the alpha 5 chain of type IV collagen. Skin biopsy is a useful tool for diagnosing this disease. It is not well known how this syndrome affects pregnancy and how it is affected by pregnancy, or whether the umbilical cord may provide material for detecting this collagen abnormality. We report a primigravida with Alport syndrome with mild proteinuria who gave birth abdominally to a term male infant without deteriorating renal function during pregnancy. The umbilical cord from not only this infant but also from an Alport (-) control infant showed negative immunofluorescence staining for the alpha 5 chain of type IV collagen. Women with Alport syndrome without renal dysfunction may follow an uneventful obstetrical course until term. The cord may not be suitable for diagnosing Alport syndrome with immunofluorescence staining.

Paradoxical Vocal Cord Motion in Pediatric Patients.

PubMed

Palla, John; Friedman, Aaron D

2016-05-01

Paradoxical vocal cord motion (PVCM), also termed vocal cord dysfunction, is a poorly understood disorder of episodic dyspnea characterized by inappropriate vocal cord adduction during inspiration and potentially during expiration. It can coexist or be confused with asthma, so appropriate diagnosis is key to optimizing treatment success. Although many patients with PVCM may have underlying psychologic issues, there is emerging evidence to suggest that this entity is not psychogenic in every patient. Both laryngeal irritants and exercise have been identified as additional contributing factors in PVCM. Diagnosis of PVCM requires awake laryngoscopic confirmation. However, many patients do not exhibit signs of PVCM during this examination, despite provocation during testing. Therefore, clinical history remains key in determining which patients should proceed with behavioral therapy under the guidance of a speech pathologist. In addition, treatment may include limiting patient exposure to potential sources of laryngeal irritation. Refractory patients may benefit from psychologic assessment and treatment. [Pediatr Ann. 2016;45(5):e184-e188.]. Copyright 2016, SLACK Incorporated.

The relationship of exposure to air pollutants in pregnancy with surrogate markers of endothelial dysfunction in umbilical cord.

PubMed

Poursafa, Parinaz; Baradaran-Mahdavi, Sadegh; Moradi, Bita; Haghjooy Javanmard, Shaghayegh; Tajadini, Mohammadhasan; Mehrabian, Ferdous; Kelishadi, Roya

2016-04-01

This study aims to investigate the association of exposure to ambient air pollution during pregnancy with cord blood concentrations of surrogate markers of endothelial dysfunction. This population-based cohort was conducted from March 2014 to March 2015 among 250 mother-neonate pairs in urban areas of Isfahan, the second large and air-polluted city in Iran. We analyzed the association between the ambient carbon monoxide (CO), ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), particular matter 10 (PM10), and air quality index (AQI) with cord blood levels of endothelin-1, vascular adhesion molecule (VCAM), and intercellular adhesion molecule (ICAM). Multiple regression analysis was conducted after adjustment for potential confounding factors and covariates. The regression coefficient (beta), standard error of the estimate (SE), and 95% confidence intervals for each regression coefficient (95% CI) are reported. Data of 233 mother-neonate pairs were complete, and included in the analysis. Multiple regression analyses showed that AQI, CO and O3 had significant correlation with cord blood ICAM-1 [Beta (SE), 95%CI: 2.93 (0.72), 1.33,5.54; 2.28(1.44), 1.56,5.12; and 2.02(0.01), 1.03,2.04, respectively] as well as with VCAM-1 [2.78(0.91), 1.69,4.57; 2.47(1.47), 1.43,5.37; and 2.01(0.01),1.07,2.04, respectively]. AQI, PM10, and SO2 were significantly associated with Endothelin-1 concentrations [Beta (SE), 95%CI: 10.16(5.08),7.61,14.28; 9.70(3.46), 2.88,16.52; and 1.07(0.02), 1.03,2.11, respectively]. The significant associations of air pollutants with markers of endothelial dysfunction during fetal period may provide another evidence on the adverse health effects of air pollutants on early stages of atherosclerosis from fetal period. Our findings underscore the importance of considering environmental factors in primordial prevention of chronic diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Chiroptical studies on supramolecular chirality of molecular aggregates.

PubMed

Sato, Hisako; Yajima, Tomoko; Yamagishi, Akihiko

2015-10-01

The attempts of applying chiroptical spectroscopy to supramolecular chirality are reviewed with a focus on vibrational circular dichroism (VCD). Examples were taken from gels, solids, and monolayers formed by low-molecular mass weight chiral gelators. Particular attention was paid to a group of gelators with perfluoroalkyl chains. The effects of the helical conformation of the perfluoroalkyl chains on the formation of chiral architectures are reported. It is described how the conformation of a chiral gelator was determined by comparing the experimental and theoretical VCD spectra together with a model proposed for the molecular aggregation in fibrils. The results demonstrate the potential utility of the chiroptical method in analyzing organized chiral aggregates. © 2015 Wiley Periodicals, Inc.

Fascia: A missing link in our understanding of the pathology of fibromyalgia.

PubMed

Liptan, Ginevra L

2010-01-01

Significant evidence exists for central sensitization in fibromyalgia, however the cause of this process in fibromyalgia-and how it relates to other known abnormalities in fibromyalgia-remains unclear. Central sensitization occurs when persistent nociceptive input leads to increased excitability in the dorsal horn neurons of the spinal cord. In this hyperexcited state, spinal cord neurons produce an enhanced responsiveness to noxious stimulation, and even to formerly innocuous stimulation. No definite evidence of muscle pathology in fibromyalgia has been found. However, there is some evidence for dysfunction of the intramuscular connective tissue, or fascia, in fibromyalgia. This paper proposes that inflammation of the fascia is the source of peripheral nociceptive input that leads to central sensitization in fibromyalgia. The fascial dysfunction is proposed to be due to inadequate growth hormone production and HPA axis dysfunction in fibromyalgia. Fascia is richly innervated, and the major cell of the fascia, the fibroblast, has been shown to secrete pro-inflammatory cytokines, particularly IL-6, in response to strain. Recent biopsy studies using immuno-histochemical staining techniques have found increased levels of collagen and inflammatory mediators in the connective tissue surrounding the muscle cells in fibromyalgia patients. The inflammation of the fascia is similar to that described in conditions such as plantar fasciitis and lateral epicondylitis, and may be better described as a dysfunctional healing response. This may explain why NSAIDs and oral steroids have not been found effective in fibromyalgia. Inflammation and dysfunction of the fascia may lead to central sensitization in fibromyalgia. If this hypothesis is confirmed, it could significantly expand treatment options to include manual therapies directed at the fascia such as Rolfing and myofascial release, and direct further research on the peripheral pathology in fibromyalgia to the fascia.

A Clinical Practice Guideline for the Management of Degenerative Cervical Myelopathy: Introduction, Rationale, and Scope.

PubMed

Fehlings, Michael G; Tetreault, Lindsay A; Riew, K Daniel; Middleton, James W; Wang, Jeffrey C

2017-09-01

Degenerative cervical myelopathy (DCM) is a progressive spine disease and the most common cause of spinal cord dysfunction in adults worldwide. Patients with DCM may present with common signs and symptoms of neurological dysfunction, such as paresthesia, abnormal gait, decreased hand dexterity, hyperreflexia, increased tone, and sensory dysfunction. Clinicians across several specialties encounter patients with DCM, including primary care physicians, rehabilitation specialists, therapists, rheumatologists, neurologists, and spinal surgeons. Currently, there are no guidelines that outline how to best manage patients with mild (defined as a modified Japanese Orthopedic Association (mJOA) score of 15-17), moderate (mJOA = 12-14), or severe (mJOA ≤ 11) myelopathy, or nonmyelopathic patients with evidence of cord compression. This guideline provides evidence-based recommendations to specify appropriate treatment strategies for these populations. The intent of our recommendations is to (1) help identify patients at high risk of neurological deterioration, (2) define the role of nonoperative and operative management in each patient population, and (3) determine which patients are most likely to benefit from surgical intervention. The ultimate goal of these guidelines is to improve outcomes and reduce morbidity in patients with DCM by promoting standardization of care and encouraging clinicians to make evidence-informed decisions.

Neuromodulation of lower limb motor control in restorative neurology.

PubMed

Minassian, Karen; Hofstoetter, Ursula; Tansey, Keith; Mayr, Winfried

2012-06-01

One consequence of central nervous system injury or disease is the impairment of neural control of movement, resulting in spasticity and paralysis. To enhance recovery, restorative neurology procedures modify altered, yet preserved nervous system function. This review focuses on functional electrical stimulation (FES) and spinal cord stimulation (SCS) that utilize remaining capabilities of the distal apparatus of spinal cord, peripheral nerves and muscles in upper motor neuron dysfunctions. FES for the immediate generation of lower limb movement along with current rehabilitative techniques is reviewed. The potential of SCS for controlling spinal spasticity and enhancing lower limb function in multiple sclerosis and spinal cord injury is discussed. The necessity for precise electrode placement and appropriate stimulation parameter settings to achieve therapeutic specificity is elaborated. This will lead to our human work of epidural and transcutaneous stimulation targeting the lumbar spinal cord for enhancing motor functions in spinal cord injured people, supplemented by pertinent human research of other investigators. We conclude that the concept of restorative neurology recently received new appreciation by accumulated evidence for locomotor circuits residing in the human spinal cord. Technological and clinical advancements need to follow for a major impact on the functional recovery in individuals with severe damage to their motor system. Copyright © 2012 Elsevier B.V. All rights reserved.

Neuromodulation of lower limb motor control in restorative neurology

PubMed Central

Minassian, Karen; Hofstoetter, Ursula; Tansey, Keith; Mayr, Winfried

2012-01-01

One consequence of central nervous system injury or disease is the impairment of neural control of movement, resulting in spasticity and paralysis. To enhance recovery, restorative neurology procedures modify altered, yet preserved nervous system function. This review focuses on functional electrical stimulation (FES) and spinal cord stimulation (SCS) that utilize remaining capabilities of the distal apparatus of spinal cord, peripheral nerves and muscles in upper motor neuron dysfunctions. FES for the immediate generation of lower limb movement along with current rehabilitative techniques is reviewed. The potential of SCS for controlling spinal spasticity and enhancing lower limb function in multiple sclerosis and spinal cord injury is discussed. The necessity for precise electrode placement and appropriate stimulation parameter settings to achieve therapeutic specificity is elaborated. This will lead to our human work of epidural and transcutaneous stimulation targeting the lumbar spinal cord for enhancing motor functions in spinal cord injured people, supplemented by pertinent human research of other investigators. We conclude that the concept of restorative neurology recently received new appreciation by accumulated evidence for locomotor circuits residing in the human spinal cord. Technological and clinical advancements need to follow for a major impact on the functional recovery in individuals with severe damage to their motor system. PMID:22464657

Stem Cell Therapy in Bladder Dysfunction: Where Are We? And Where Do We Have to Go?

PubMed Central

Lee, Sang-Rae; Song, Yun Seob; Lee, Hong Jun

2013-01-01

To date, stem cell therapy for the bladder has been conducted mainly on an experimental basis in the areas of bladder dysfunction. The therapeutic efficacy of stem cells was originally thought to be derived from their ability to differentiate into various cell types. Studies about stem cell therapy for bladder dysfunction have been limited to an experimental basis and have been less focused than bladder regeneration. Bladder dysfunction was listed in MESH as “urinary bladder neck obstruction”, “urinary bladder, overactive”, and “urinary bladder, neurogenic”. Using those keywords, several articles were searched and studied. The bladder dysfunction model includes bladder outlet obstruction, cryoinjured, diabetes, ischemia, and spinal cord injury. Adipose derived stem cells (ADSCs), bone marrow stem cells (BMSCs), and skeletal muscle derived stem cells (SkMSCs) are used for transplantation to treat bladder dysfunction. The main mechanisms of stem cells to reconstitute or restore bladder dysfunction are migration, differentiation, and paracrine effects. The aim of this study is to review the stem cell therapy for bladder dysfunction and to provide the status of stem cell therapy for bladder dysfunction. PMID:24151627

Dual modality imaging of a novel rat model of ovarian carcinogenesis

NASA Astrophysics Data System (ADS)

Kanter, Elizabeth; Walker, Ross; Marion, Sam; Brewer, Molly A.; Hoyer, Patricia B.; Barton, Jennifer K.

2006-07-01

Ovarian cancer is the fifth leading cause of cancer death in women, in part because of the limited knowledge about early stage disease. We develop a novel rat model of ovarian cancer and perform a pilot study to examine the harvested ovaries with complementary optical imaging modalities. Rats are exposed to repeated daily dosing (20 days) with 4-vinylcyclohexene diepoxide (VCD) to cause early ovarian failure (model for postmenopause), and ovaries are directly exposed to 7,12-dimethylbenz(a)anthracene (DMBA) to cause abnormal ovarian proliferation and neoplasia. Harvested ovaries are examined with optical coherence tomography (OCT) and light-induced fluorescence (LIF) at one, three, and five months post-DMBA treatment. VCD causes complete ovarian follicle depletion within 8 months after onset of dosing. DMBA induces abnormal size, cysts, and neoplastic changes. OCT successfully visualizes normal and abnormal structures (e.g., cysts, bursa, follicular remnant degeneration) and the LIF spectra show statistically significant changes in the ratio of average emission intensity at 390:450 nm between VCD-treated ovaries and both normal cycling and neoplastic DMBA-treated ovaries. Overall, this pilot study demonstrates the feasibility of both the novel animal model for ovarian cancer and the ability of optical imaging techniques to visualize ovarian function and health.

Successful Cord Blood Stem Cell Transplantation for Primary Cutaneous CD8-positive Aggressive Epidermotropic Cytotoxic T-cell Lymphoma Complicated with Cerebral Infiltration.

PubMed

Ichikawa, Satoshi; Fukuhara, Noriko; Hatta, Shunsuke; Himuro, Masahito; Katsushima, Hiroki; Nasu, Kentaro; Ono, Koya; Inokura, Kyoko; Kobayashi, Masahiro; Onishi, Yasushi; Fujii, Hiroshi; Ishizawa, Kenichi; Ichinohasama, Ryo; Harigae, Hideo

2018-03-09

A 16-year-old boy, who had been initially examined for bilateral blepharedema and slight eruption, presented with rapidly deteriorating symptoms in associating with headache and consciousness disturbance. He was diagnosed to have primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (PCAE-CTL) by a biopsy of the skin and brain. After whole-brain radiation and some courses of chemotherapy, cord blood transplantation was performed with myeloablative conditioning. After transplantation, the cerebral dysfunction gradually improved. Disease remission was confirmed by the disappearance of any abnormal findings on electroencephalogram and magnetic resonance imaging. PCAE-CTL is reported to be an extremely aggressive disease with a poor prognosis, but the timely performance of cord blood transplantation is considered to be a promising treatment strategy.

Cognitive Changes Across the Menopause Transition: A Longitudinal Evaluation of the Impact of Age and Ovarian Status on Spatial Memory

PubMed Central

Koebele, Stephanie V.; Mennenga, Sarah E.; Hiroi, Ryoko; Quihuis, Alicia M.; Hewitt, Lauren T.; Poisson, Mallori L.; George, Christina; Mayer, Loretta P.; Dyer, Cheryl A.; Aiken, Leona S.; Demers, Laurence M.; Carson, Catherine; Bimonte-Nelson, Heather A.

2017-01-01

Cognitive changes that occur during mid-life and beyond are linked to both aging and the menopause transition. Studies in women suggest that the age at menopause onset can impact cognitive status later in life; yet, little is known about memory changes that occur during the transitional period to the post-menopausal state. The 4-vinylcyclohexene diepoxide (VCD) model simulates transitional menopause in rodents by depleting the immature ovarian follicle reserve and allowing animals to retain their follicle-deplete ovarian tissue, resulting in a profile similar to the majority of perimenopausal women. Here, Vehicle or VCD treatment was administered to ovary-intact adult and middle-aged Fischer-344 rats to assess the trajectory of cognitive change across time with normal aging and aging with transitional menopause via VCD-induced follicular depletion, as well as to evaluate whether age at the onset of follicular depletion plays a role in cognitive outcomes. Animals experiencing the onset of menopause at a younger age exhibited impaired spatial memory early in the transition to a follicle-deplete state. Additionally, at the mid- and post- follicular depletion time points, VCD-induced follicular depletion amplified an age effect on memory. Overall, these findings suggest that the age at the onset of menopause is a critical parameter to consider when evaluating learning and memory across the transition to reproductive senescence. From a translational perspective, this study illustrates how age at menopause onset might impact cognition in menopausal women, and provides insight into time points to explore for the window of opportunity for hormone therapy during the menopause transition period. Hormone therapy during this critical juncture might be especially efficacious at attenuating age- and menopause- related cognitive decline, producing healthy brain aging profiles in women who retain their ovaries throughout their lifespan. PMID:27793768

Satellite-observed NO2, SO2, and HCHO Vertical Column Densities in East Asia: Recent Changes and Comparisons with Regional Model

NASA Astrophysics Data System (ADS)

Kim, H. C.; Lee, P.; Kim, S.; Mok, J.; Yoo, H. L.; Bae, C.; Kim, B. U.; Lim, Y. K.; Woo, J. H.; Park, R.

2015-12-01

This study reports the recent changes in tropospheric NO2, SO2, and HCHO vertical column densities (VCD) in East Asia observed from multiple satellites, highlighting especially the annual trend changes of NO2 and SO2 over Beijing-Tianjin-Hebei (BTH) region of China since 2010. Tropospheric VCD data from Global Ozone Monitoring Experiment (GOME), SCanning Imaging Absorption spectroMeter for Atmospheric CHartographY (SCIAMACHY), Ozone Monitoring Instrument (OMI) and GOME-2, retrieved from the Royal Netherlands Meteorological Institute (KNMI) and OMI National Aeronautics and Space Administration (NASA) standard products, are utilized to investigate the annual trends of NO2, SO2, and HCHO VCDs from 2001 to 2015. They are also compared with simulations from Community Multi-scale Air Quality Model (CMAQ) based forecast system by the Integrated Multi-scale Air Quality System for Korea (IMAQS-K) of Ajou University. Until 2011, the changes in NO2 VCD over East Asian countries agree well with the findings of previous research, including the impact of the economic downturn during 2008-2009 and the subsequent quick recovery in China. After peaking in 2011, the NO2 VCD observations from active instruments (OMI and GOME-2) over China started to show a slower decreasing trend, mostly led by the rapid changes in the BTH region in northern China. On the other hand, SO2 started to decline earlier, from 2007, but inclined back from 2010 to 2012, and then back to declining trend since 2012. While satellite observations show dramatic recent changes, the model could not reproduce those changes mostly due to its use of fixed emission inventory. We conclude that rapid update of latest emission inventory is necessary for an accurate forecast of regional air quality in east Asia, especially for upcoming international sports events in PyeongChang (Korea), Tokyo (Japan) and Beijing (China) in 2018, 2020 and 2022, respectively.

Cognitive changes across the menopause transition: A longitudinal evaluation of the impact of age and ovarian status on spatial memory.

PubMed

Koebele, Stephanie V; Mennenga, Sarah E; Hiroi, Ryoko; Quihuis, Alicia M; Hewitt, Lauren T; Poisson, Mallori L; George, Christina; Mayer, Loretta P; Dyer, Cheryl A; Aiken, Leona S; Demers, Laurence M; Carson, Catherine; Bimonte-Nelson, Heather A

2017-01-01

Cognitive changes that occur during mid-life and beyond are linked to both aging and the menopause transition. Studies in women suggest that the age at menopause onset can impact cognitive status later in life; yet, little is known about memory changes that occur during the transitional period to the postmenopausal state. The 4-vinylcyclohexene diepoxide (VCD) model simulates transitional menopause in rodents by depleting the immature ovarian follicle reserve and allowing animals to retain their follicle-deplete ovarian tissue, resulting in a profile similar to the majority of perimenopausal women. Here, Vehicle or VCD treatment was administered to ovary-intact adult and middle-aged Fischer-344 rats to assess the trajectory of cognitive change across time with normal aging and aging with transitional menopause via VCD-induced follicular depletion, as well as to evaluate whether age at the onset of follicular depletion plays a role in cognitive outcomes. Animals experiencing the onset of menopause at a younger age exhibited impaired spatial memory early in the transition to a follicle-deplete state. Additionally, at the mid- and post- follicular depletion time points, VCD-induced follicular depletion amplified an age effect on memory. Overall, these findings suggest that age at the onset of menopause is a critical parameter to consider when evaluating learning and memory across the transition to reproductive senescence. From a translational perspective, this study illustrates how age at menopause onset might impact cognition in menopausal women, and provides insight into time points to explore for the window of opportunity for hormone therapy during the menopause transition period. Hormone therapy during this critical juncture might be especially efficacious at attenuating age- and menopause- related cognitive decline, producing healthy brain aging profiles in women who retain their ovaries throughout their lifespan. Copyright © 2016 Elsevier Inc. All rights reserved.

Abdominal Manual Therapy Repairs Interstitial Cells of Cajal and Increases Colonic c-Kit Expression When Treating Bowel Dysfunction after Spinal Cord Injury

PubMed Central

Zhang, Wenyi; Zhu, Zhaojin; Xie, Bin; Yu, Jun

2017-01-01

Background This study aimed to evaluate the therapeutic effects of abdominal manual therapy (AMT) on bowel dysfunction after spinal cord injury (SCI), investigating interstitial cells of Cajal (ICCs) and related c-kit expression. Methods Model rats were divided as SCI and SCI with drug treatment (intragastric mosapride), low-intensity (SCI + LMT; 50 g, 50 times/min), and high-intensity AMT (SCI + HMT; 100 g, 150 times/min). After 14 days of treatment, weight, improved Basso-Beattie-Bresnahan (BBB) locomotor score, and intestinal movement were evaluated. Morphological structure of spinal cord and colon tissues were examined. Immunostaining, RT-PCR, and western blot were used to assess c-kit expression. Results In SCI rats, AMT could not restore BBB, but it significantly increased weight, shortened time to defecation, increased feces amounts, and improved fecal pellet traits and colon histology. AMT improved the number, distribution, and ultrastructure of colonic ICCs, increasing colonic c-kit mRNA and protein levels. Compared with the SCI + Drug and SCI + LMT groups, the SCI + HMT group showed better therapeutic effect in improving intestinal transmission function and promoting c-kit expression. Conclusions AMT is an effective therapy for recovery of intestinal transmission function. It could repair ICCs and increase c-kit expression in colon tissues after SCI, in a frequency-dependent and pressure-dependent manner. PMID:29349063

Alpha-1 adrenoceptor hyperresponsiveness in three neuropathic pain states: complex regional pain syndrome 1, diabetic peripheral neuropathic pain and central pain states following spinal cord injury.

PubMed

Teasell, Robert W; Arnold, J Malcolm O

2004-01-01

The pathophysiology of the pain associated with complex regional pain syndrome, spinal cord injury and diabetic peripheral neuropathy is not known. The pain of complex regional pain syndrome has often been attributed to abnormal sympathetic nervous system activity based on the presence of vasomotor instability and a frequently reported positive response, albeit a temporary response, to sympathetic blockade. In contrast, the pain below the level of spinal cord injury and diabetic peripheral neuropathy are generally seen as deafferentation phenomena. Each of these pain states has been associated with abnormal sympathetic nervous system function and increased peripheral alpha-1 adrenoceptor activity. This increased responsiveness may be a consequence of alpha-1 adrenoceptor postsynaptic hypersensitivity, or alpha-2 adrenoceptor presynaptic dysfunction with diminished noradrenaline reuptake, increased concentrations of noradrenaline in the synaptic cleft and increased stimulation of otherwise normal alpha-1 adrenoceptors. Plausible mechanisms based on animal research by which alpha-1 adrenoceptor hyperresponsiveness can lead to chronic neuropathic-like pain have been reported. This raises the intriguing possibility that sympathetic nervous system dysfunction may be an important factor in the generation of pain in many neuropathic pain states. Although results to date have been mixed, there may be a greater role for new drugs which target peripheral alpha-2 adrenoceptors (agonists) or alpha-1 adrenoceptors (antagonists).

Effects of Dietary Vitamin E Supplementation in Bladder Function and Spasticity during Spinal Cord Injury

PubMed Central

Cordero, Kathia; Coronel, Gemma G.; Serrano-Illán, Miguel; Cruz-Bracero, Jennifer

2018-01-01

Traumatic spinal cord injury (SCI) results in debilitating autonomic dysfunctions, paralysis and significant sensorimotor impairments. A key component of SCI is the generation of free radicals that contributes to the high levels of oxidative stress observed. This study investigates whether dietary supplementation with the antioxidant vitamin E (alpha-tocopherol) improves functional recovery after SCI. Female adult Sprague-Dawley rats were fed either with a normal diet or a dietary regiment supplemented with vitamin E (51 IU/g) for eight weeks. The rats were subsequently exposed either to a contusive SCI or sham operation, and evaluated using standard functional behavior analysis. We report that the rats that consumed the vitamin E-enriched diet showed an accelerated bladder recovery and significant improvements in locomotor function relative to controls, as determined by residual volumes and Basso, Beatie, and Bresnaham BBB scores, respectively. Interestingly, the prophylactic dietary intervention did not preserve neurons in the ventral horn of injured rats, but it significantly increased the numbers of oligodendrocytes. Vitamin E supplementation attenuated the depression of the H-reflex (a typical functional consequence of SCI) while increasing the levels of supraspinal serotonin immunoreactivity. Our findings support the potential complementary use of vitamin E to ameliorate sensory and autonomic dysfunctions associated with spinal cord injury, and identified promising new cellular and functional targets of its neuroprotective effects. PMID:29495419

Sexual responsiveness in women with spinal cord injuries: differential effects of anxiety-eliciting stimulation.

PubMed

Sipski, Marca L; Rosen, Raymond C; Alexander, Craig J; Gómez-Marín, Orlando

2004-06-01

Sexual dysfunction is a common problem in women after spinal cord injuries (SCIs). Recently, the use of anxiety-provoking stimulation has been explored as a means of improving sexual responses in able-bodied sexually functional and dysfunctional women. In this laboratory-based study, we assessed the sexual and autonomic responses of women with SCIs with varying degrees of preservation of sympathetic innervation to their genitals to respond to anxiety-provoking audiovisual (AV) stimulation. Subjects were 45 women with SCIs and 11 able-bodied women. For purposes of analysis, SCI subjects were grouped on the basis of the degree of preservation of sensation in the T11-L2 dermatomes. Results revealed that women with low sensory scores in these dermatomes achieved higher vaginal pulse amplitude (VPA) responses to audiovisual erotic stimulation after anxiety preexposure than after neutral preexposure; however, women with SCIs and the greatest degree of preservation of sensory function in the T11-L2 dermatomes, as well as able-bodied controls, did not. Moreover, these same 2 groups of subjects had a decrease in VPA responses during baseline periods in which an anxiety-provoking video sequence was shown, but not during the neutral sequence. It is concluded that these findings are due to the proximity of sensory and autonomic neurologic elements in the spinal cord. Moreover, they demonstrate the differential effects of sympathetic stimulation on genital sexual arousal.

Dietary omega-3 polyunsaturated fatty acids improve the neurolipidome and restore the DHA status while promoting functional recovery after experimental spinal cord injury.

PubMed

Figueroa, Johnny D; Cordero, Kathia; Llán, Miguel S; De Leon, Marino

2013-05-15

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) confer multiple health benefits and decrease the risk of neurological disorders. Studies are needed, however, to identify promising cellular targets and to assess their prophylactic value against neurodegeneration. The present study (1) examined the efficacy of a preventive diet enriched with ω-3 PUFAs to reduce dysfunction in a well-established spinal cord injury (SCI) animal model and (2) used a novel metabolomics data analysis to identify potential neurolipidomic targets. Rats were fed with either control chow or chow enriched with ω-3 PUFAs (750 mg/kg/day) for 8 weeks before being subjected to a sham or a contusion SCI operation. We report new evidence showing that rats subjected to SCI after being pre-treated with a diet enriched with ω-3 PUFAs exhibit significantly better functional outcomes. Pre-treated animals exhibited lower sensory deficits, autonomic bladder recovery, and early improvements in locomotion that persisted for at least 8 weeks after trauma. We found that SCI triggers a robust alteration in the cord PUFA neurolipidome, which was characterized by a marked docosahexaenoic acid (DHA) deficiency. This DHA deficiency was associated with dysfunction and corrected with the ω-3 PUFA-enriched diet. Multivariate data analyses revealed that the spinal cord of animals consuming the ω-3 PUFA-enriched diet had a fundamentally distinct neurolipidome, particularly increasing the levels of essential and long chain ω-3 fatty acids and lysolipids at the expense of ω-6 fatty acids and its metabolites. Altogether, dietary ω-3 PUFAs prophylaxis confers resiliency to SCI mediated, at least in part, by generating a neuroprotective and restorative neurolipidome.

Dietary Omega-3 Polyunsaturated Fatty Acids Improve the Neurolipidome and Restore the DHA Status while Promoting Functional Recovery after Experimental Spinal Cord Injury

PubMed Central

Figueroa, Johnny D.; Cordero, Kathia; llán, Miguel S.

2013-01-01

Abstract Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) confer multiple health benefits and decrease the risk of neurological disorders. Studies are needed, however, to identify promising cellular targets and to assess their prophylactic value against neurodegeneration. The present study (1) examined the efficacy of a preventive diet enriched with ω-3 PUFAs to reduce dysfunction in a well-established spinal cord injury (SCI) animal model and (2) used a novel metabolomics data analysis to identify potential neurolipidomic targets. Rats were fed with either control chow or chow enriched with ω-3 PUFAs (750 mg/kg/day) for 8 weeks before being subjected to a sham or a contusion SCI operation. We report new evidence showing that rats subjected to SCI after being pre-treated with a diet enriched with ω-3 PUFAs exhibit significantly better functional outcomes. Pre-treated animals exhibited lower sensory deficits, autonomic bladder recovery, and early improvements in locomotion that persisted for at least 8 weeks after trauma. We found that SCI triggers a robust alteration in the cord PUFA neurolipidome, which was characterized by a marked docosahexaenoic acid (DHA) deficiency. This DHA deficiency was associated with dysfunction and corrected with the ω-3 PUFA-enriched diet. Multivariate data analyses revealed that the spinal cord of animals consuming the ω-3 PUFA-enriched diet had a fundamentally distinct neurolipidome, particularly increasing the levels of essential and long chain ω-3 fatty acids and lysolipids at the expense of ω-6 fatty acids and its metabolites. Altogether, dietary ω-3 PUFAs prophylaxis confers resiliency to SCI mediated, at least in part, by generating a neuroprotective and restorative neurolipidome. PMID:23294084

The pathology of lumbosacral lipomas: macroscopic and microscopic disparity have implications for embryogenesis and mode of clinical deterioration.

PubMed

Jones, Victoria; Wykes, Victoria; Cohen, Nicki; Thompson, Dominic; Jacques, Tom S

2018-06-01

Lumbosacral lipomas (LSL) are congenital disorders of the terminal spinal cord region that have the potential to cause significant spinal cord dysfunction in children. They are of unknown embryogenesis with variable clinical presentation and natural history. It is unclear whether the spinal cord dysfunction reflects a primary developmental dysplasia or whether it occurs secondarily to mechanical traction (spinal cord tethering) with growth. While different anatomical subtypes are recognised and classified according to radiological criteria, these subtypes correlate poorly with clinical prognosis. We have undertaken an analysis of surgical specimens in order to describe the spectrum of histological changes that occur and have correlated the histology with the anatomical type of LSL to determine if there are distinct histological subtypes. The histopathology was reviewed of 64 patients who had undergone surgical resection of LSL. The presence of additional tissues and cell types were recorded. LSLs were classified from pre-operative magnetic resonance imaging (MRI) scans according to Chapman classification. Ninety-five per cent of the specimens consisted predominantly of mature adipocytes with all containing thickened bands of connective tissue and peripheral nerve fibres, 91% of samples contained ectatic blood vessels with thickened walls, while 22% contained central nervous system (CNS) glial tissue. Additional tissue was identified of both mesodermal and neuroectodermal origin. Our analysis highlights the heterogeneity of tissue types within all samples, not reflected in the nomenclature. The diversity of tissue types, consistent across all subtypes, challenges currently held notions regarding the embryogenesis of LSLs and the assumption that clinical deterioration is due simply to tethering. © 2018 The Authors. Histopathology Published by John Wiley & Sons Ltd.

Aging among the Disabled: A Neglected Area.

ERIC Educational Resources Information Center

Kemp, Bryan

The paper addresses issues involved in the aging of persons disabled earlier through spinal dysfunction (post-polio and spinal cord injury) and mental retardation. Biological, psychological, and social aspects of aging are examined separately. In a discussion of longevity and physical health, causes of functional aging are considered.…

Vibrational circular dichroism of a 2,5-diketopiperazine (DKP) peptide: Evidence for dimer formation in cyclo LL or LD diphenylalanine in the solid state.

PubMed

Pérez-Mellor, Ariel; Zehnacker, Anne

2017-02-01

The diastereomer diketopiperazine (DKP) peptides built on phenylalanine, namely, cyclo diphenylalanine LPhe-LPhe and LPhe-DPhe, were studied in the solid phase by vibrational circular dichroism (VCD) coupled to quantum chemical calculations. The unit structure of cyclo LPhe-LPhe in KBr pellets is a dimer bridged by two strong NH…O hydrogen bonds. The intense bisignate signature in the CO stretch region is interpreted in terms of two contributions arising from the free COs of the dimer and the antisymmetrical combination of the bound COs. In contrast, cyclo LPhe-DPhe shows no VCD signal in relation to its symmetric nature. © 2017 Wiley Periodicals, Inc.

Automatic 3D segmentation of spinal cord MRI using propagated deformable models

NASA Astrophysics Data System (ADS)

De Leener, B.; Cohen-Adad, J.; Kadoury, S.

2014-03-01

Spinal cord diseases or injuries can cause dysfunction of the sensory and locomotor systems. Segmentation of the spinal cord provides measures of atrophy and allows group analysis of multi-parametric MRI via inter-subject registration to a template. All these measures were shown to improve diagnostic and surgical intervention. We developed a framework to automatically segment the spinal cord on T2-weighted MR images, based on the propagation of a deformable model. The algorithm is divided into three parts: first, an initialization step detects the spinal cord position and orientation by using the elliptical Hough transform on multiple adjacent axial slices to produce an initial tubular mesh. Second, a low-resolution deformable model is iteratively propagated along the spinal cord. To deal with highly variable contrast levels between the spinal cord and the cerebrospinal fluid, the deformation is coupled with a contrast adaptation at each iteration. Third, a refinement process and a global deformation are applied on the low-resolution mesh to provide an accurate segmentation of the spinal cord. Our method was evaluated against a semi-automatic edge-based snake method implemented in ITK-SNAP (with heavy manual adjustment) by computing the 3D Dice coefficient, mean and maximum distance errors. Accuracy and robustness were assessed from 8 healthy subjects. Each subject had two volumes: one at the cervical and one at the thoracolumbar region. Results show a precision of 0.30 +/- 0.05 mm (mean absolute distance error) in the cervical region and 0.27 +/- 0.06 mm in the thoracolumbar region. The 3D Dice coefficient was of 0.93 for both regions.

Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level

PubMed Central

Brommer, Benedikt; Engel, Odilo; Kopp, Marcel A.; Watzlawick, Ralf; Müller, Susanne; Prüss, Harald; Chen, Yuying; DeVivo, Michael J.; Finkenstaedt, Felix W.; Dirnagl, Ulrich; Liebscher, Thomas; Meisel, Andreas

2016-01-01

Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient’s environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P < 0.001) independently from mechanical ventilation and preserved sensory function by multiple regression analysis. We present evidence that spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS (‘immune paralysis’), sufficient to propagate clinically relevant infection in an injury level dependent manner. PMID:26754788

Sildenafil effects on sexual and cardiovascular responses in women with spinal cord injury.

PubMed

Sipski, M L; Rosen, R C; Alexander, C J; Hamer, R M

2000-06-01

Sexual dysfunction is common in women with spinal cord injuries (SCIs) and other neurologic conditions. Sildenafil has previously been shown to be safe and effective in the treatment of erectile dysfunction due to SCI. This study is the first to evaluate the sexual and cardiovascular effects of sildenafil in women with SCIs in a controlled, laboratory setting. Nineteen premenopausal women with SCIs were randomly assigned to receive either sildenafil (50 mg) or placebo in a double-blind, crossover design study. Physiologic and subjective measures of sexual response, heart rate, and blood pressure were recorded during baseline and sexual stimulation conditions. Adverse events were also recorded. Significant increases in subjective arousal (SA) were observed with both drug (P <0.01) and sexual stimulation conditions (P <0.001), and a borderline significant (P <0.07) effect of drug administration on vaginal pulse amplitude (VPA) was noted. Maximal responses occurred when sildenafil was combined with visual and manual sexual stimulation. Cardiovascular data showed modest increases in heart rate (+/-5 bpm) and mild decreases in blood pressure (+/-4 mm Hg) across all stimulation conditions, consistent with the peripheral vasodilatory mechanism of the drug. Sildenafil was well tolerated with no evidence of significant adverse events. Findings suggest that sildenafil may partially reverse the sexual dysfunction commonly associated with SCI in women. Consistent with previous findings in men, the sexual effects of the drug were most evident under conditions of optimal stimulation. Mild, clinically insignificant cardiovascular effects were also noted. Further large-scale studies of sildenafil's effects in women with neurogenic sexual dysfunction are strongly indicated.

Perceptual Detection of Subtle Dysphonic Traits in Individuals with Cervical Spinal Cord Injury Using an Audience Response Systems Approach.

PubMed

Johansson, Kerstin; Strömbergsson, Sofia; Robieux, Camille; McAllister, Anita

2017-01-01

Reduced respiratory function following lower cervical spinal cord injuries (CSCIs) may indirectly result in vocal dysfunction. Although self-reports indicate voice change and limitations following CSCI, earlier efforts using global perceptual ratings to distinguish speakers with CSCI from noninjured speakers have not been very successful. We investigate the use of an audience response system-based approach to distinguish speakers with CSCI from noninjured speakers, and explore whether specific vocal traits can be identified as characteristic for speakers with CSCI. Fourteen speech-language pathologists participated in a web-based perceptual task, where their overt reactions to vocal dysfunction were registered during the continuous playback of recordings of 36 speakers (18 with CSCI, and 18 matched controls). Dysphonic events were identified through manual perceptual analysis, to allow the exploration of connections between dysphonic events and listener reactions. More dysphonic events, and more listener reactions, were registered for speakers with CSCI than for noninjured speakers. Strain (particularly in phrase-final position) and creak (particularly in nonphrase-final position) distinguish speakers with CSCI from noninjured speakers. For the identification of intermittent and subtle signs of vocal dysfunction, an approach where the temporal distribution of symptoms is registered offers a viable means to distinguish speakers affected by voice dysfunction from non-affected speakers. In speakers with CSCI, clinicians should listen for presence of final strain and nonfinal creak, and pay attention to self-reported voice function and voice problems, to identify individuals in need for clinical assessment and intervention. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

[HIV-associated myelopathy: an uncommon indicator of AIDS].

PubMed

Konaté, A; Ceballos, P; Rivière, S; Faucherre, V; Ciurana, A J; Le Quellec, A

2001-10-01

Spinal cord lesions are an uncommon mode of discovering acquired immunodeficiency syndrome because they usually appear at a later stage. We report a 58-year-old patient who had a spastic paraparesia and sphincter dysfunction. The spinal cord magnetic resonance imaging showed spontaneous hypersignals on T2-weighted images at the cervical and thoracic levels, enhanced with gadolinium, and without swelling. No cause was found. The HIV serology was positive and allowed us to consider an HIV-associated myelopathy. The antiretroviral therapy led to functional recovery. An HIV serology is suggested whenever an unexplained intramedullary lesion is discovered. Indeed, the diagnosis of HIV-associated myelopathy implies a specific therapeutic approach.

Hoarseness caused by arytenoid dislocation after surgery for lung cancer.

PubMed

Kurihara, Nobuyasu; Imai, Kazuhiro; Minamiya, Yoshihiro; Saito, Hajime; Takashima, Shinogu; Kudo, Satoshi; Kawaharada, Yasushi; Ogawa, Jun-Ichi

2014-12-01

The patient was a 64-year-old woman with no history of laryngeal disorders. She underwent video-assisted right lower lobectomy and node dissection for lung cancer. Using a stylet while the patient was under general anesthesia, tracheal intubation with a 35-French gauge left-sided double-lumen endobronchial tube was successfully performed on the first attempt. The patient developed slight hoarseness on postoperative day 1, and we initially suspected recurrent laryngeal nerve paralysis caused by the surgery, which we elected to treat conservatively. However, because her hoarseness had not improved 4 months after surgery, we evaluated her vocal cords using laryngoscopy. This revealed severe dysfunction of the right vocal cord and arytenoid dislocation, which we treated through reduction using a balloon catheter. By 6 months, the patient's vocal cord mobility had improved. Arytenoid dislocation is a rare complication, but should be suspected when patients have right vocal fold paralysis after lung cancer surgery.

QUAD fever: beware of non-infectious fever in high spinal cord injuries.

PubMed

Goyal, Jyoti; Jha, Rakesh; Bhatia, Paramjeet; Mani, Raj Kumar

2017-06-18

A case of cervical spinal cord injury and quadriparesis with prolonged fever is being described. Initially, the patient received treatment for well-documented catheter-related bloodstream infection. High spiking fever returned and persisted with no obvious evidence of infection. The usual non-infectious causes too were carefully excluded. QUAD fever or fever due to spinal cord injury itself was considered. The pathogenetic basis of QUAD fever is unclear but could be attributed to autonomic dysfunction and temperature dysregulation. Awareness of this little known condition could help in avoiding unnecessary antimicrobial therapy and in more accurate prognostication. Unlike several previous reported cases that ended fatally, the present case ran a relatively benign course. The spectrum of presentations may therefore be broader than hitherto appreciated. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Evaluation of an Acute RNAi-Mediated Therapeutic for Visual Dysfunction Associated with Traumatic Brain Injury

DTIC Science & Technology

2013-10-01

requiring pacemaker  Refusal of consent - Claustrophobia  Spinal Cord Injury  Unstable due to tracheal stenosis and lobar collapse  2 patients had...be stopped.  Heart Block necessitating pacemaker  Unstable from a respiratory point of view due to previous Left lower lobectomy, right upper

Mitochondrial-Based Therapeutics for the Treatment of Spinal Cord Injury: Mitochondrial Biogenesis as a Potential Pharmacological Target

PubMed Central

Scholpa, Natalie E.

2017-01-01

Spinal cord injury (SCI) is characterized by an initial trauma followed by a progressive cascade of damage referred to as secondary injury. A hallmark of secondary injury is vascular disruption leading to vasoconstriction and decreased oxygen delivery, which directly reduces the ability of mitochondria to maintain homeostasis and leads to loss of ATP-dependent cellular functions, calcium overload, excitotoxicity, and oxidative stress, further exacerbating injury. Restoration of mitochondria dysfunction during the acute phases of secondary injury after SCI represents a potentially effective therapeutic strategy. This review discusses the past and present pharmacological options for the treatment of SCI as well as current research on mitochondria-targeted approaches. Increased antioxidant activity, inhibition of the mitochondrial permeability transition, alternate energy sources, and manipulation of mitochondrial morphology are among the strategies under investigation. Unfortunately, many of these tactics address single aspects of mitochondrial dysfunction, ultimately proving largely ineffective. Therefore, this review also examines the unexplored therapeutic efficacy of pharmacological enhancement of mitochondrial biogenesis, which has the potential to more comprehensively improve mitochondrial function after SCI. PMID:28935700

Mitochondrial-Based Therapeutics for the Treatment of Spinal Cord Injury: Mitochondrial Biogenesis as a Potential Pharmacological Target.

PubMed

Scholpa, Natalie E; Schnellmann, Rick G

2017-12-01

Spinal cord injury (SCI) is characterized by an initial trauma followed by a progressive cascade of damage referred to as secondary injury. A hallmark of secondary injury is vascular disruption leading to vasoconstriction and decreased oxygen delivery, which directly reduces the ability of mitochondria to maintain homeostasis and leads to loss of ATP-dependent cellular functions, calcium overload, excitotoxicity, and oxidative stress, further exacerbating injury. Restoration of mitochondria dysfunction during the acute phases of secondary injury after SCI represents a potentially effective therapeutic strategy. This review discusses the past and present pharmacological options for the treatment of SCI as well as current research on mitochondria-targeted approaches. Increased antioxidant activity, inhibition of the mitochondrial permeability transition, alternate energy sources, and manipulation of mitochondrial morphology are among the strategies under investigation. Unfortunately, many of these tactics address single aspects of mitochondrial dysfunction, ultimately proving largely ineffective. Therefore, this review also examines the unexplored therapeutic efficacy of pharmacological enhancement of mitochondrial biogenesis, which has the potential to more comprehensively improve mitochondrial function after SCI. U.S. Government work not protected by U.S. copyright.

Determination of the absolute configurations at stereogenic centers in the presence of axial chirality.

PubMed

Polavarapu, Prasad L; Jeirath, Neha; Kurtán, Tibor; Pescitelli, Gennaro; Krohn, Karsten

2009-01-01

Cephalochromin, a homodimeric naphthpyranone natural product, contains both axial chirality due to the hindered rotation along the biaryl axis and central chirality due to the C-2, C-2' stereogenic centers of the fused pyranone ring. For determining the absolute configurations (ACs) of central chirality elements, different chiroptical spectroscopic methods, namely vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and optical rotation (OR), have been used. From these experimental data, in conjunction with corresponding quantum chemical predictions at B3LYP/6-311G* level, it is found that the ECD spectra of cephalochromin are dominated by its axial chirality and are not suitable to distinguish the (aS,2S,2'S) and (aS,2R,2'R) diastereomers and hence to determine the ACs of the central chirality elements. OR signs also did not distinguish the (aS,2S,2'S) and (aS,2R,2'R) diastereomers. On other hand, VCD spectrum of cephalochromin exhibited separate spectral features attributable to axial chirality and stereogenic centers, thereby allowing the determination of both types of chirality elements. This is the first investigation demonstrating that, because of vibrations specific to the studied stereogenic centers, VCD spectroscopy can be used to simultaneously determine the ACs of axial and central chirality elements whenever other chiroptical methods (ECD and OR) fail to report on them. (c) 2009 Wiley-Liss, Inc.

Trends of tropospheric NO2 over the Yangtze River Delta region and the possible linkage to rapid urbanization

NASA Astrophysics Data System (ADS)

Ma, Mingliang; Zhang, Deying; Liu, Qiyang; Song, Yue; Zhou, Jiayuan; Shi, Runhe; Gao, Wei

2017-09-01

Over the past decade, China has experienced a rapid increase in urbanization. The urban built-up areas (population) of Shanghai increased by 16.1% (22.9%) from 2006 to 2015. This study aims to analyze the variations of tropospheric NO2 over Yangtze River Delta region and the impacts of rapid urbanization during 2006-2015. The results indicate that tropospheric NO2 vertical column density (VCD) of all cities in the study area showed an increasing trend during 2006-2011 whereas a decreasing trend during 2011-2015. Most cities showed a lower tropospheric NO2 VCD value in 2015 compared to that in 2006, except for Changzhou and Nantong. Shanghai and Ningbo are two hotspots where the tropospheric NO2 VCD decreased most significantly, at a rate of 22% and 19%, respectively. This effect could be ascribed to the implementation of harsh emission control policies therein. Similar seasonal variability was observed over all cities, with larger values observed in the summer and smaller values shown in the winter. Further investigations show that the observed increasing trend of tropospheric NO2 during 2006-2011 could be largely explained by rapid urbanization linked to car ownership, GDP, power consumption, population and total industrial output. Such effect was not prominent after 2011, mainly due to the implementation of emission control strategies.

Women with high early pregnancy urinary iodine levels have an increased risk of hyperthyroid newborns: the population-based Generation R Study.

PubMed

Medici, Marco; Ghassabian, Akhgar; Visser, Willy; de Muinck Keizer-Schrama, Sabine M P F; Jaddoe, Vincent W V; Visser, W Edward; Hooijkaas, Herbert; Hofman, Albert; Steegers, Eric A P; Bongers-Schokking, Jacoba J; Ross, H Alec; Tiemeier, Henning; Visser, Theo J; de Rijke, Yolanda B; Peeters, Robin P

2014-04-01

Iodine deficiency during pregnancy results in thyroid dysfunction and has been associated with adverse obstetric and foetal effects, leading to worldwide salt iodization programmes. As nowadays 69% of the world's population lives in iodine-sufficient regions, we investigated the effects of variation in iodine status on maternal and foetal thyroid (dys)function in an iodine-sufficient population. Urinary iodine, serum TSH, free T4 (FT4) and TPO-antibody levels were determined in early pregnancy (13·3 (1·9) week; mean (SD)) in 1098 women from the population-based Generation R Study. Newborn cord serum TSH and FT4 levels were determined at birth. The median urinary iodine level was 222·5 μg/l, indicating an iodine-sufficient population. 30·8% and 11·5% had urinary iodine levels <150 and >500 μg/l, respectively. When comparing mothers with urinary iodine levels <150 vs ≥150 μg/l, and >500 vs ≤500 μg/l, there were no differences in the risk of maternal increased or decreased TSH, hypothyroxinaemia or hyperthyroidism. Mothers with urinary iodine levels >500 μg/l had a higher risk of a newborn with decreased cord TSH levels (5·6 ± 1·4 (mean ± SE) vs 2·1 ± 0·5%, P = 0·04), as well as a higher risk of a hyperthyroid newborn (3·1 ± 0·9 vs 0·6 ± 0·3%, P = 0·02). These mothers had newborns with higher cord FT4 levels (21·7 ± 0·3 vs 21·0 ± 0·1 pm, P = 0·04). Maternal urinary iodine levels <150 μg/l were not associated with newborn thyroid dysfunction. In an iodine-sufficient population, higher maternal urinary iodine levels are associated with an increased risk of a hyperthyroid newborn. © 2013 John Wiley & Sons Ltd.

Prediction of autonomic dysreflexia during urodynamics: a prospective cohort study.

PubMed

Walter, Matthias; Knüpfer, Stephanie C; Cragg, Jacquelyn J; Leitner, Lorenz; Schneider, Marc P; Mehnert, Ulrich; Krassioukov, Andrei V; Schubert, Martin; Curt, Armin; Kessler, Thomas M

2018-04-13

Autonomic dysreflexia is a severe and potentially life-threatening condition in patients with spinal cord injury, as it can lead to myocardial ischemia, brain hemorrhage, or even death. Urodynamic investigation is the gold standard to assess neurogenic lower urinary tract dysfunction due to spinal cord injury and reveal crucial pathological findings, such as neurogenic detrusor overactivity. However, neurogenic detrusor overactivity and urodynamic investigation are known to be leading triggers of autonomic dysreflexia. Therefore, we aimed to determine predictors of autonomic dysreflexia in individuals with spinal cord injury during urodynamic investigation. This prospective cohort study included 300 patients with spinal cord injuries and complete datasets of continuous non-invasive cardiovascular monitoring, recorded during same session repeat urodynamic investigation. We used logistic regression to reveal predictors of autonomic dysreflexia during urodynamic investigation. We found that level of injury and presence of neurogenic detrusor overactivity were the only two independent significant predictors for autonomic dysreflexia during urodynamic investigation. A lesion at spinal segment T6 or above (odds ratio (OR) 5.5, 95% CI 3.2-9.4) compared to one at T7 or below, and presence of neurogenic detrusor overactivity (OR 2.7, 95% confidence interval (CI) 1.4-4.9) were associated with a significant increased odds of autonomic dysreflexia during urodynamic investigation. Both odds persisted after adjustment for age, sex, and completeness and stage of injury (adjusted OR (AOR) 6.6, 95% CI 3.8-11.7, and AOR 2.2, 95% CI 1.1-4.5, respectively). Further stratification by lesion level showed level-dependent significantly increased adjusted odds of autonomic dysreflexia, i.e., from C1-C4 (AOR 16.2, 95% CI 5.9-57.9) to T4-T6 (AOR 2.6, 95% CI 1.3-5.2), compared to lesions at T7 or below. In patients with neurogenic lower urinary tract dysfunction due to spinal cord injury, autonomic dysreflexia is independently predicted by lesion level and presence of neurogenic detrusor overactivity. Considering the health risks associated with autonomic dysreflexia, such as seizures, stroke, retinal bleeding, or even death, we recommend both continuous cardiovascular monitoring during urodynamic investigation in all spinal cord-injured patients with emphasis on those with cervical lesions, and appropriate neurogenic detrusor overactivity treatment to reduce the probability of potentially life-threatening complications. ClinicalTrials.gov, NCT01293110 .

A Comparative Analysis of Phase-Change Wastewater Processing Approaches for Microgravity

NASA Technical Reports Server (NTRS)

Lange, Kevin

2016-01-01

Two phase-change wastewater processing candidates, the ISS Vapor Compression Distillation (VCD) System and the Cascade Distiller System (CDS), are compared based on dynamic modeling of both technologies. Differences in fluid handling and energy recovery for the technologies are described and contrasted. Model predictions are presented showing how temperatures, pressures, and compositions vary locally within each distiller. These dynamic variations are difficult to observe experimentally and have implications regarding non-condensable buildup and salt precipitation potential. Alternative architectures involving VCD and CDS components are analyzed in terms of predicted performance and equivalent system mass (ESM). The addition of a downstream brine processor to increase water recovery is also evaluated. Options for reducing overall ESM are discussed, including the possibility of developing a single precipitation-tolerant primary wastewater processor.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scherrer, Arne; UMR 8640 ENS-CNRS-UPMC, Département de Chimie, 24 rue Lhomond, École Normale Supérieure, 75005 Paris; UPMC Université Paris 06, 4, Place Jussieu, 75005 Paris

The nuclear velocity perturbation theory (NVPT) for vibrational circular dichroism (VCD) is derived from the exact factorization of the electron-nuclear wave function. This new formalism offers an exact starting point to include correction terms to the Born-Oppenheimer (BO) form of the molecular wave function, similar to the complete-adiabatic approximation. The corrections depend on a small parameter that, in a classical treatment of the nuclei, is identified as the nuclear velocity. Apart from proposing a rigorous basis for the NVPT, we show that the rotational strengths, related to the intensity of the VCD signal, contain a new contribution beyond-BO that canmore » be evaluated with the NVPT and that only arises when the exact factorization approach is employed. Numerical results are presented for chiral and non-chiral systems to test the validity of the approach.« less

In situ Raman spectroscopy for simultaneous monitoring of multiple process parameters in mammalian cell culture bioreactors.

PubMed

Whelan, Jessica; Craven, Stephen; Glennon, Brian

2012-01-01

In this study, the application of Raman spectroscopy to the simultaneous quantitative determination of glucose, glutamine, lactate, ammonia, glutamate, total cell density (TCD), and viable cell density (VCD) in a CHO fed-batch process was demonstrated in situ in 3 L and 15 L bioreactors. Spectral preprocessing and partial least squares (PLS) regression were used to correlate spectral data with off-line reference data. Separate PLS calibration models were developed for each analyte at the 3 L laboratory bioreactor scale before assessing its transferability to the same bioprocess conducted at the 15 L pilot scale. PLS calibration models were successfully developed for all analytes bar VCD and transferred to the 15 L scale. Copyright © 2012 American Institute of Chemical Engineers (AIChE).

Design and testing of a controlled electromagnetic spinal cord impactor for use in large animal models of acute traumatic spinal cord injury.

PubMed

Petteys, Rory J; Spitz, Steven M; Syed, Hasan; Rice, R Andrew; Sarabia-Estrada, Rachel; Goodwin, C Rory; Sciubba, Daniel M; Freedman, Brett A

2017-09-01

Spinal cord injury (SCI) causes debilitating neurological dysfunction and has been observed in warfighters injured in IED blasts. Clinical benefit of SCI treatment remains elusive and better large animal models are needed to assess treatment options. Here, we describe a controlled electromagnetic spinal cord impactor for use in large animal models of SCI. A custom spinal cord impactor and platform were fabricated for large animals (e.g., pig, sheep, dog, etc.). Impacts were generated by a voice coil actuator; force and displacement were measured with a load cell and potentiometer respectively. Labview (National Instruments, Austin, TX) software was used to control the impact cycle and import force and displacement data. Software finite impulse response (FIR) filtering was employed for all input data. Silicon tubing was used a surrogate for spinal cord in order to test the device; repeated impacts were performed at 15, 25, and 40 Newtons. Repeated impacts demonstrated predictable results at each target force. The average duration of impact was 71.2 ±6.1ms. At a target force of 40N, the output force was 41.5 ±0.7N. With a target of 25N, the output force was 23.5 ±0.6N; a target of 15Newtons revealed an output force of 15.2 ±1.4N. The calculated acceleration range was 12.5-21.2m/s 2 . This custom spinal cord impactor reliably delivers precise impacts to the spinal cord and will be utilized in future research to study acute traumatic SCI in a large animal. Published by Elsevier Ltd.

[Current status of neurostimulation and neuromodulation for vesicourethral dysfunction].

PubMed

González-Chamorro, F; Verdú Tartajo, F; Hernández Fernández, C

1997-01-01

To describe the current indications, techniques and results of sacral root stimulation in patients with spinal cord lesions as a treatment for patients with high pressure bladders and/or urinary incontinence despite conservative management, as well as sacral root neuromodulation with permanent stimulators for complex bladder dysfunction: vesical instability, sensory urgency, chronic pelvic pain and chronic voiding dysfunction. The literature is reviewed, both techniques are described and the results of the most significant series are discussed, with special reference to the first groups that utilized these techniques. There is ample experience in the application of sacral root electrical stimulation. The reported results are comparable with those achieved by other treatments, such as augmentation cystoplasty. Neurostimulation and neuromodulation techniques are simple, the complications are minimal and they do not prelude the use of other therapies.

Characterizing the Severity of Autonomic Cardiovascular Dysfunction after Spinal Cord Injury Using a Novel 24 Hour Ambulatory Blood Pressure Analysis Software.

PubMed

Popok, David W; West, Christopher R; Hubli, Michele; Currie, Katharine D; Krassioukov, Andrei V

2017-02-01

Cardiovascular disease is one of the leading causes of morbidity and mortality in the spinal cord injury (SCI) population. SCI may disrupt autonomic cardiovascular homeostasis, which can lead to persistent hypotension, irregular diurnal rhythmicity, and the development of autonomic dysreflexia (AD). There is currently no software available to perform automated detection and evaluation of cardiovascular autonomic dysfunction(s) such as those generated from 24 h ambulatory blood pressure monitoring (ABPM) recordings in the clinical setting. The objective of this study is to compare the efficacy of a novel 24 h ABPM Autonomic Dysfunction Detection Software against manual detection and to use the software to demonstrate the relationships between level of injury and the degree of autonomic cardiovascular impairment in a large cohort of individuals with SCI. A total of 46 individuals with cervical (group 1, n = 37) or high thoracic (group 2, n = 9) SCI participated in the study. Outcome measures included the frequency and severity of AD, frequency of hypotensive events, and diurnal variations in blood pressure and heart rate. There was good agreement between the software and manual detection of AD events (Bland-Altman limits of agreement = ±1.458 events). Cervical SCI presented with more frequent (p = 0.0043) and severe AD (p = 0.0343) than did high thoracic SCI. Cervical SCI exhibited higher systolic and diastolic blood pressure during the night and lower heart rate during the day than high thoracic SCI. In conclusion, our ABPM AD Detection Software was equally as effective in detecting the frequency and severity of AD and hypotensive events as manual detection, suggesting that this software can be used in the clinical setting to expedite ABPM analyses.

[Neuro-urological diagnosis and therapy of lower urinary tract dysfunction in patients with spinal cord injury : S2k Guideline of the German-Speaking Medical Society of Paraplegia (DMGP), AWMF register no. 179/001].

PubMed

Böthig, R; Domurath, B; Kaufmann, A; Bremer, J; Vance, W; Kurze, I

2017-06-01

Most patients with spinal cord injury (SCI) suffer from neurogenic lower urinary tract dysfunction (NLUTD), bowel dysfunction and sexual dysfunction. If these remain untreated, severe medical complications and serious limitations (restrictions) in quality of life are imminent. In the long term, there are considerable differences in the treatment results of highly specialized centers versus other treatment facilities. Against this background, a consensus-based guideline, according to the AWMF (Association of the Scientific Medical Societies in Germany) criteria (S2k), was developed by the neuro-urology working group of the DMPG (German-Speaking Medical Society of Paraplegia). The guideline defines the principles and objectives of the neuro-urological care of patients with SCI and discusses in detail the principles of diagnosis and therapy of NLUTD. The need for video-urodynamic studies as a basis for the classification of the NLUTD and as a foundation for the development of a treatment strategy is emphasized. Both conservative and surgical therapy options and their indications are explained in detail. Possible complications and their prevention in the long-term course of SCI are presented with a particular consideration of the specific features of urinary tract infections and autonomic dysreflexia. Finally, the principles of the provision of urological appliances are discussed. The presented S2k guideline provides the current standards in the neuro-urological care of patients with NLUTD due to SCI. Their consistent implementation both in the acute and chronic phase as well as in the context of lifelong surveillance of SCI patients should prevent the impending complications of NLUTD.

Neuroprotective effects of lycopene in spinal cord injury in rats via antioxidative and anti-apoptotic pathway.

PubMed

Hu, Wei; Wang, Hongbo; Liu, Zhenfeng; Liu, Yanlu; Wang, Rong; Luo, Xiao; Huang, Yifei

2017-03-06

Oxidative damage induced-mitochondrial dysfunction and apoptosis has been widely studied in spinal cord injury (SCI). Lycopene, a polyunsaturated hydrocarbon, has the highest antioxidant capacity compared to the other carotenoids. However, the role of lycopene in SCI is unknown. In the present study, we evaluated the antioxidant effects of lycopene on mitochondrial dysfunction and apoptosis following T10 contusion SCI in rats. The rats were randomized into 5 groups: the sham group, the SCI group and the SCI pre-treated with lycopene (5, 10, or 20mg/kg) group. The SCI group showed increased malondialdehyde (MDA) content, decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) ability, which indicated that SCI could induce oxidative damage. What's more, the SCI group showed decreased mRNA expression of cytochrome b and mitochondrial transcription factor A (Tfam), and decreased mitochondrial membrane potential (ΔYm), which indicated that SCI could induce mitochondrial dysfunction. Besides, the SCI group showed decreased protein expression of bcl-2 and mitochondrial cytochrome C, increased protein expression of cytosolic cytochrome C, cleaved caspase-9, cleaved caspase-3 and bax, and increased TUNEL-positive cell numbers, which indicated that SCI could induce cell apoptosis. Fortunately, the lycopene treatment significantly ameliorated oxidative damage, mitochondrial dysfunction and cell apoptosis via the reversion of those parameters described above in the dose of lycopene of 10 and 20mg/kg. In addition, lycopene significantly ameliorated the hind limb motor disturbances in the SCI+lyco10 group and the SCI+lyco20 group compared with the SCI group. These results suggested that lycopene administration could improve total antioxidant status and might have neuroprotective effects on SCI. Copyright © 2017 Elsevier B.V. All rights reserved.

Rhabdomyolysis and acute kidney injury in patients with traumatic spinal cord injury

PubMed Central

Galeiras, Rita; Mourelo, Mónica; Pértega, Sonia; Lista, Amanda; Ferreiro, Mª Elena; Salvador, Sebastián; Montoto, Antonio; Rodríguez, Antonio

2016-01-01

Background: Patients with acute traumatic spinal cord injuries (SCIs) exhibit factors that, in other populations, have been associated with rhabdomyolysis. Purpose: The aim of the study is to determine the incidence of rhabdomyolysis in patients with acute traumatic SCI admitted to the Intensive Care Unit (ICU), as well as the development of secondary acute kidney injury and associated factors. Study Design and Setting: This was an observational, retrospective study. Patient Sample: All adult patients admitted to the ICU with acute traumatic SCI who presented rhabdomyolysis, diagnosed through creatine phosphokinase (CPK) levels >500 IU/L. Outcome Measures: Incidence of rhabdomyolysis and subsequent renal dysfunction was calculated. Materials and Methods: Data about demographic variables, comorbidity, rhabdomyolysis risk factors, and variables involving SCI, severity scores, and laboratory parameters were obtained from clinical records. Multivariate logistic regression was used to identify renal injury risk factors. Results: In 2006–2014, 200 patients with acute SCI were admitted to ICU. Of these, 103 had rhabdomyolysis (incidence = 51.5%; 95% confidence interval [CI]: 44.3%–58.7%). The most typical American Spinal Injury Association classification was A (70.3%). The injury severity score was 30.3 ± 12.1 and sequential organ failure assessment (SOFA) score was 5.6 ± 3.3 points. During their stay, 57 patients (55.3%; 95% CI: 45.2%–65.4%) presented renal dysfunction (creatinine ≥1.2 mg/dL). In the multivariate analysis, variables associated with renal dysfunction were creatinine at admission (odds ratio [OR] = 9.20; P = 0.006) and hemodynamic SOFA score the day following admission (OR = 1.33; P = 0.024). Creatinine was a better predictor of renal dysfunction than the peak CPK value during the rhabdomyolysis (area under the receiver operating characteristic curve: 0.91 vs. 0.63, respectively). Conclusions: Rhabdomyolysis is a frequent condition in patients with acute traumatic SCI admitted to the ICU, and renal dysfunction occurs in half of the cases. Creatinine values should be requested starting at the admission while neither the peak CPK values nor the hemodynamic SOFA scores could be used to properly discriminate between patients with and without renal dysfunction. PMID:27688625

Vapor compression distillation module

NASA Technical Reports Server (NTRS)

Nuccio, P. P.

1975-01-01

A Vapor Compression Distillation (VCD) module was developed and evaluated as part of a Space Station Prototype (SSP) environmental control and life support system. The VCD module includes the waste tankage, pumps, post-treatment cells, automatic controls and fault detection instrumentation. Development problems were encountered with two components: the liquid pumps, and the waste tank and quantity gauge. Peristaltic pumps were selected instead of gear pumps, and a sub-program of materials and design optimization was undertaken leading to a projected life greater than 10,000 hours of continuous operation. A bladder tank was designed and built to contain the waste liquids and deliver it to the processor. A detrimental pressure pattern imposed upon the bladder by a force-operated quantity gauge was corrected by rearranging the force application, and design goals were achieved. System testing has demonstrated that all performance goals have been fulfilled.

Height, weight, body mass index and ocular biometry in patients with sickle cell disease.

PubMed

Osuobeni, Ebi Peter; Okpala, Iheanyi; Williamson, Tom H; Thomas, Peter

2009-03-01

To investigate the effects of physical size on refractive error and the dimensions of optical components in sickle cell disease (SCD). The design was cross sectional. Height and weight of adult patients suffering from SCD were measured, and body mass index (BMI) was calculated. Anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD) and axial length (AL) were measured using A-scan ultrasonography. Corneal radius of curvature (CR) was measured using a keratometer. Non-cycloplegic refractive error was determined subjectively. Subjects with SC genotype were significantly taller than those with SS genotype. In the unadjusted data, height was correlated with VCD [p = 0.02, 0.44 mm deeper per 10 cm increase in height, 95% CI (0.65, 8.25)] and AL [p = 0.03, 0.42 mm longer for every 10 cm increase in height, 95%CI (0.49, 7.99)]. The relationship between height, VCD and AL was absent after adjustment for age, gender, genotype and weight. BMI (kg m(-2)) was correlated with AL/CR ratio in both unadjusted (p = 0.04, -0.10 decrease per 1 kg m(-2), 95% CI (-0.018, -0.001) and adjusted data (p = 0.05, -0.10 decrease per 10 kg m(-2), 95% CI (-0.0189, 0.0001). Refractive error was not related to height, weight or BMI. Physical size does not affect refractive error or optical components in adult patients with SCD.

"Low-intensity laser therapy effect on the recovery of traumatic spinal cord injury".

PubMed

Paula, Alecsandra Araujo; Nicolau, Renata Amadei; Lima, Mario de Oliveira; Salgado, Miguel Angel Castillo; Cogo, José Carlos

2014-11-01

Scientific advances have been made to optimize the healing process in spinal cord injury. Studies have been developed to obtain effective treatments in controlling the secondary injury that occurs after spinal cord injury, which substantially changes the prognosis. Low-intensity laser therapy (LILT) has been applied in neuroscience due to its anti-inflammatory effects on biological tissue in the repairing process. Few studies have been made associating LILT to the spinal cord injury. The objective of this study was to investigate the effect of the LILT (GaAlAs laser-780 nm) on the locomotor functional recovery, histomorphometric, and histopathological changes of the spinal cord after moderate traumatic injury in rats (spinal cord injury at T9 and T10). Thirty-one adult Wistar rats were used, which were divided into seven groups: control without surgery (n = 3), control surgery (n = 3), laser 6 h after surgery (n = 5), laser 48 h after surgery (n = 5), medullar lesion (n = 5) without phototherapy, medullar lesion + laser 6 h after surgery (n = 5), and medullar lesion + laser 48 h after surgery (n = 5). The assessment of the motor function was performed using Basso, Beattie, and Bresnahan (BBB) scale and adapted Sciatic Functional Index (aSFI). The assessment of urinary dysfunction was clinically performed. After 21 days postoperative, the animals were euthanized for histological and histomorphometric analysis of the spinal cord. The results showed faster motor evolution in rats with spinal contusion treated with LILT, maintenance of the effectiveness of the urinary system, and preservation of nerve tissue in the lesion area, with a notorious inflammation control and increased number of nerve cells and connections. In conclusion, positive effects on spinal cord recovery after moderate traumatic spinal cord injury were shown after LILT.

[One-stage total en bloc spondylectomy and reconstruction via a single posterior approach for thoracic vertebral symptomatic hemangioma associated with spinal cord dysfunction].

PubMed

Song, Ruo-xian; Zhang, Yong-gang; Zhang, Xue-song; Zheng, Guo-quan; Wang, Yan

2012-04-01

To investigate the surgical results of one-stage total en bloc spondylectomy (TES) and reconstruction via a single posterior approach for thoracic symptomatic vertebral hemangioma associated with spinal cord dysfunction and evaluate its curative effect. A total of 9 patients treated with one-stage TES (7 cases) and total vertebrectomy (2 cases) by posterior approach from March 2006 to January 2010 were retrospectively reviewed. The cases included 2 males and 7 females with a median age of 33.6 years (range 14 to 77 years), and with 1 case of Grade A, 3 cases of Grade B, 3 cases of Grade C, 2 cases of Grade D according to Frankel grade system. All patients suffered from moderate to severe pain and neurological deficit with an average symptom duration of 14.4 months (range 3 - 24 months) MRI revealed severe spinal cord compression. The spinal reconstruction was obtained by titanium mesh filled with autograft and posterior internal fixation with rod-screw system. The operation time was 210 minutes on average (180 - 270 minutes) and the average blood loss was 1800 ml (1000 - 5000 ml). The follow-up period lasted from 18 months to 5 years. All cases with preoperative pain relieved after operation. The visual analogue scale pain scores decreased to 1.1 from 8.3 at 3 months after surgery. No disruption of dural mater, cerebrospinal fluid leakage, iatrogenic spinal cord injury and major vessel damage occurred. Up to now, there was no local recurrence in all cases. Significant neurological function improvement was achieved in all patients with one to three grades in Frankel grade system. Fusion of the autograft was well achieved and no internal fixation failure in all patients. One-stage TES and spine reconstruction by a single posterior approach is feasible, safe and effective to this disease. It is favourable in decreasing the hemangioma recurrence and improvement of the neurological function.

Increased excitability of spinal pain reflexes and altered frequency-dependent modulation in the dopamine D3-receptor knockout mouse.

PubMed

Keeler, Benjamin E; Baran, Christine A; Brewer, Kori L; Clemens, Stefan

2012-12-01

Frequency-dependent modulation and dopamine (DA) receptors strongly modulate neural circuits in the spinal cord. Of the five known DA receptor subtypes, the D3 receptor has the highest affinity to DA, and D3-mediated actions are mainly inhibitory. Using an animal model of spinal sensorimotor dysfunction, the D3 receptor knockout mouse (D3KO), we investigated the physiological consequences of D3 receptor dysfunction on pain-associated signaling pathways in the spinal cord, the initial integration site for the processing of pain signaling. In the D3KO spinal cord, inhibitory actions of DA on the proprioceptive monosynaptic stretch reflex are converted from depression to facilitation, but its effects on longer-latency and pain-associated reflex responses and the effects of FM have not been studied. Using behavioral approaches in vivo, we found that D3KO animals exhibit reduced paw withdrawal latencies to thermal pain stimulation (Hargreaves' test) over wild type (WT) controls. Electrophysiological and pharmacological approaches in the isolated spinal cord in vitro showed that constant current stimulation of dorsal roots at a pain-associated frequency was associated with a significant reduction in the frequency-dependent modulation of longer-latency reflex (LLRs) responses but not monosynaptic stretch reflexes (MSRs) in D3KO. Application of the D1 and D2 receptor agonists and the voltage-gated calcium-channel ligand, pregabalin, but not DA, was able to restore the frequency-dependent modulation of the LLR in D3KO to WT levels. Thus we demonstrate that nociception-associated LLRs and proprioceptive MSRs are differentially modulated by frequency, dopaminergics and the Ca(2+) channel ligand, pregabalin. Our data suggest a role for the DA D3 receptor in pain modulation and identify the D3KO as a possible model for increased nociception. Copyright © 2012 Elsevier Inc. All rights reserved.

Age Related Changes in Metabolite Concentrations in the Normal Spinal Cord

PubMed Central

Abdel-Aziz, Khaled; Solanky, Bhavana S.; Yiannakas, Marios C.; Altmann, Daniel R.; Wheeler-Kingshott, Claudia A. M.; Thompson, Alan J.; Ciccarelli, Olga

2014-01-01

Magnetic resonance spectroscopy (MRS) studies have previously described metabolite changes associated with aging of the healthy brain and provided insights into normal brain aging that can assist us in differentiating age-related changes from those associated with neurological disease. The present study investigates whether age-related changes in metabolite concentrations occur in the healthy cervical spinal cord. 25 healthy volunteers, aged 23–65 years, underwent conventional imaging and single-voxel MRS of the upper cervical cord using an optimised point resolved spectroscopy sequence on a 3T Achieva system. Metabolite concentrations normalised to unsuppressed water were quantified using LCModel and associations between age and spinal cord metabolite concentrations were examined using multiple regressions. A linear decline in total N-Acetyl-aspartate concentration (0.049 mmol/L lower per additional year of age, p = 0.010) and Glutamate-Glutamine concentration (0.054 mmol/L lower per additional year of age, p = 0.002) was seen within our sample age range, starting in the early twenties. The findings suggest that neuroaxonal loss and/or metabolic neuronal dysfunction, and decline in glutamate-glutamine neurotransmitter pool progress with aging. PMID:25310093

Degenerative Cervical Myelopathy: A Spectrum of Related Disorders Affecting the Aging Spine.

PubMed

Tetreault, Lindsay; Goldstein, Christina L; Arnold, Paul; Harrop, James; Hilibrand, Alan; Nouri, Aria; Fehlings, Michael G

2015-10-01

Cervical spinal cord dysfunction can result from either traumatic or nontraumatic causes, including tumors, infections, and degenerative changes. In this article, we review the range of degenerative spinal disorders resulting in progressive cervical spinal cord compression and propose the adoption of a new term, degenerative cervical myelopathy (DCM). DCM comprises both osteoarthritic changes to the spine, including spondylosis, disk herniation, and facet arthropathy (collectively referred to as cervical spondylotic myelopathy), and ligamentous aberrations such as ossification of the posterior longitudinal ligament and hypertrophy of the ligamentum flavum. This review summarizes current knowledge of the pathophysiology of DCM and describes the cascade of events that occur after compression of the spinal cord, including ischemia, destruction of the blood-spinal cord barrier, demyelination, and neuronal apoptosis. Important features of the diagnosis of DCM are discussed in detail, and relevant clinical and imaging findings are highlighted. Furthermore, this review outlines valuable assessment tools for evaluating functional status and quality of life in these patients and summarizes the advantages and disadvantages of each. Other topics of this review include epidemiology, the prevalence of degenerative changes in the asymptomatic population, the natural history and rates of progression, risk factors of diagnosis (clinical, imaging and genetic), and management strategies.

β-Blockade use for Traumatic Injuries and Immunomodulation: A Review of Proposed Mechanisms and Clinical Evidence.

PubMed

Loftus, Tyler J; Efron, Philip A; Moldawer, Lyle L; Mohr, Alicia M

2016-10-01

Sympathetic nervous system activation and catecholamine release are important events following injury and infection. The nature and timing of different pathophysiologic insults have significant effects on adrenergic pathways, inflammatory mediators, and the host response. Beta adrenergic receptor blockers (β-blockers) are commonly used for treatment of cardiovascular disease, and recent data suggests that the metabolic and immunomodulatory effects of β-blockers can expand their use. β-blocker therapy can reduce sympathetic activation and hypermetabolism as well as modify glucose homeostasis and cytokine expression. It is the purpose of this review to examine either the biologic basis for proposed mechanisms or to describe current available clinical evidence for the use of β-blockers in traumatic brain injury, spinal cord injury, hemorrhagic shock, acute traumatic coagulopathy, erythropoietic dysfunction, metabolic dysfunction, pulmonary dysfunction, burns, immunomodulation, and sepsis.

Subclinical respiratory dysfunction in chronic cervical cord compression: a pulmonary function test correlation.

PubMed

Bhagavatula, Indira Devi; Bhat, Dhananjaya I; Sasidharan, Gopalakrishnan M; Mishra, Rakesh Kumar; Maste, Praful Suresh; Vilanilam, George C; Sathyaprabha, Talakkad N

2016-06-01

OBJECTIVE Respiratory abnormalities are well documented in acute spinal cord injury; however, the literature available for respiratory dysfunction in chronic compressive myelopathy (CCM) is limited. Respiratory dysfunction in CCM is often subtle and subclinical. The authors studied the pattern of respiratory dysfunction in patients with chronic cord compression by using spirometry, and the clinical and surgical implications of this dysfunction. In this study they also attempted to address the postoperative respiratory function in these patients. METHODS A prospective study was done in 30 patients in whom cervical CCM due to either cervical spondylosis or ossification of the posterior longitudinal ligament (OPLL) was diagnosed. Thirty age-matched healthy volunteers were recruited as controls. None of the patients included in the study had any symptoms or signs of respiratory dysfunction. After clinical and radiological diagnosis, all patients underwent pulmonary function tests (PFTs) performed using a standardized Spirometry Kit Micro before and after surgery. The data were analyzed using Statistical Software SPSS version 13.0. Comparison between the 2 groups was done using the Student t-test. The Pearson correlation coefficient was used for PFT results and Nurick classification scores. A p value < 0.05 was considered significant. RESULTS Cervical spondylotic myelopathy (prolapsed intervertebral disc) was the predominant cause of compression (n = 21, 70%) followed by OPLL (n = 9, 30%). The average patient age was 45.06 years. Degenerative cervical spine disease has a relatively younger onset in the Indian population. The majority of the patients (n = 28, 93.3%) had compression at or above the C-5 level. Ten patients (33.3%) underwent an anterior approach and discectomy, 11 patients (36.7%) underwent decompressive laminectomy, and the remaining 9 underwent either corpectomy with fusion or laminoplasty. The mean preoperative forced vital capacity (FVC) (65%) of the patients was significantly lower than that of the controls (88%) (p < 0.001). The mean postoperative FVC (73.7%) in the patients showed significant improvement compared with the preoperative values (p = 0.003). The mean postoperative FVC was still significantly lower than the control value (p = 0.002). The mean preoperative forced expiratory volume in 1 second (FEV1) (72%) of the patients was significantly lower than that of the controls (96%) (p < 0.001). The mean postoperative FEV1 (75.3%) in the cases showed no significant improvement compared with the preoperative values (p = 0.212). The mean postoperative FEV1 was still significantly lower than the control value (p < 0.001). The mean postoperative FEV1/FVC was not significantly different from the control value (p = 0.204). The mean postoperative peak expiratory flow rate was significantly lower than the control value (p = 0.01). The mean postoperative maximal voluntary ventilation was still significantly lower than the control value (p < 0.001). On correlating the FVC and Nurick scores using the Pearson correlation coefficient, a negative correlation was found. CONCLUSIONS There is subclinical respiratory dysfunction and significant impairment of various lung capacities in patients with CCM. The FVC showed significant improvement postoperatively. Respiratory function needs to be evaluated and monitored to avoid potential respiratory complications.

Associations Between Pre-Implant Psychosocial Factors and Spinal Cord Stimulation Outcome: Evaluation Using the MMPI-2-RF.

PubMed

Block, Andrew R; Marek, Ryan J; Ben-Porath, Yossef S; Kukal, Deborah

2017-01-01

Spinal cord stimulation (SCS) has variable effectiveness in controlling chronic pain. Previous research has demonstrated that psychosocial factors are associated with diminished results of SCS. The objective of this investigation is to examine associations between pre-implant psychological functioning as measured by the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) and SCS outcomes. SCS candidates at two sites (total N = 319) completed the MMPI-2-RF and measures of pain, emotional distress, and functional ability as part of a pre-implant psychological evaluation. At an average of 5 months post-implant, patients completed the measures of pain and emotional distress a second time. Poorer SCS outcomes and poorer patient satisfaction were associated with higher pre-implant MMPI-2-RF scores on scales used to assess emotional dysfunction, somatic/cognitive complaints, and interpersonal problems. Ways through which pre-implant psychological evaluations of spinal cord stimulator candidates can be informed by MMPI-2-RF findings are discussed. © The Author(s) 2015.

Spinal dural arteriovenous fistulas: the most frequent vascular malformations of the spinal cord.

PubMed

Iglesias Gordo, J; Martínez García, R

Spinal dural arteriovenous fistulas are produced by direct communication between the arterial and venous systems of the spinal cord, causing hypertension in the latter with spinal cord dysfunction. It is a rare pathology with unknown etiology and non-specific clinical symptoms that usually results in a delayed diagnosis. Often radiologists are the first to guide the disease towards an adequate diagnosis. Characteristic findings can be seen through MR or MR angiography, and may even locate the fistula in a high percentage of cases, although the pathology must be confirmed by spinal angiography. There are two treatment modalities: endovascular and surgical therapy. Endovascular treatment has improved in recent years with the advantages of a less invasive approach and is therefore usually chosen as primary therapy. In this article we review the main clinical manifestations, imaging findings and treatment of this pathology. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Remarkable recovery in an infant presenting with extensive perinatal cervical cord injury.

PubMed

Ul Haq, Israr; Gururaj, A K

2012-12-10

Cervical-cord damage is a complication of a difficult delivery, and results in spinal shock with flaccidity progressing to spastic paralysis. Conventionally, outlook for such patients is extremely poor and most will recover only slightly from quadriplegia and autonomic dysfunction. Here, we report a case in which the extent of damage considerably contrasted with the outcome and recovery. A full-term baby girl born by difficult vaginal delivery displayed bilateral flaccid paralysis of the lower limbs with absent spontaneous movements, weakness of both upper limbs, hyporeflexia in all limbs and axial hypotonia. MRI of cervicothoracic spine exhibited raised signal intensity in the dorsal aspects of C7 to T1 signifying myelopathy. MRI at 4 months revealed a near-total transection of the cervical cord. However, at 6 months, the child could move all lower limbs independently with a marked increase in power. There was no spasticity, wasting or incontinence. Reflexes had also returned.

International spinal cord injury bowel function basic data set (Version 2.0).

PubMed

Krogh, K; Emmanuel, A; Perrouin-Verbe, B; Korsten, M A; Mulcahey, M J; Biering-Sørensen, F

2017-07-01

International expert working group. To revise the International Spinal Cord Injury (SCI) Bowel Function Basic Data Set as a standardized format for the collecting and reporting of a minimal amount of information on bowel function in clinical practice and research. Working group appointed by the American Spinal injury association (ASIA) and the International Spinal Cord Society (ISCoS). The draft prepared by the working group was reviewed by the International SCI Data Set Committee and later by members of the ISCoS Executive and Scientific Committees and the ASIA board. The revised data set was posted on the ASIA and ISCoS websites for 1 month to allow further comments and suggestions. Changes resulting from a Delphi process among experts in children with SCI were included. Members of ISCoS Executive and Scientific Committees and the ASIA board made a final review and approved the data set. The International SCI Bowel Function Basic Data Set (Version 2.0) consists of the following 16 items: date of data collection, gastrointestinal and anal sphincter dysfunction unrelated to SCI, surgical procedures on the gastrointestinal tract, defecation method and bowel-care procedures, average time required for defecation, frequency of defecation, uneasiness, headache or perspiration during defecation, digital stimulation or evacuation of the anorectum, frequency of fecal incontinence, flatus incontinence, need to wear pad or plug, oral laxatives and prokinetics, anti-diarrheal agents, perianal problems, abdominal pain and discomfort and the neurogenic bowel dysfunction score. The International SCI Bowel Function Basic Data Set (Version 2.0) has been developed.

Association of myelopathy scores with cervical sagittal balance and normalized spinal cord volume: analysis of 56 preoperative cases from the AOSpine North America Myelopathy study.

PubMed

Smith, Justin S; Lafage, Virginie; Ryan, Devon J; Shaffrey, Christopher I; Schwab, Frank J; Patel, Alpesh A; Brodke, Darrel S; Arnold, Paul M; Riew, K Daniel; Traynelis, Vincent C; Radcliff, Kris; Vaccaro, Alexander R; Fehlings, Michael G; Ames, Christopher P

2013-10-15

Post hoc analysis of prospectively collected data. Development of methods to determine in vivo spinal cord dimensions and application to correlate preoperative alignment, myelopathy, and health-related quality-of-life scores in patients with cervical spondylotic myelopathy (CSM). CSM is the leading cause of spinal cord dysfunction. The association between cervical alignment, sagittal balance, and myelopathy has not been well characterized. This was a post hoc analysis of the prospective, multicenter AOSpine North America CSM study. Inclusion criteria for this study required preoperative cervical magnetic resonance imaging (MRI) and neutral sagittal cervical radiography. Techniques for MRI assessment of spinal cord dimensions were developed. Correlations between imaging and health-related quality-of-life scores were assessed. Fifty-six patients met inclusion criteria (mean age = 55.4 yr). The modified Japanese Orthopedic Association (mJOA) scores correlated with C2-C7 sagittal vertical axis (SVA) (r = -0.282, P = 0.035). Spinal cord volume correlated with cord length (r = 0.472, P < 0.001) and cord average cross-sectional area (r = 0.957, P < 0.001). For all patients, no correlations were found between MRI measurements of spinal cord length, volume, mean cross-sectional area or surface area, and outcomes. For patients with cervical lordosis, mJOA scores correlated positively with cord volume (r = 0.366, P = 0.022), external cord area (r = 0.399, P = 0.012), and mean cross-sectional cord area (r = 0.345, P = 0.031). In contrast, for patients with cervical kyphosis, mJOA scores correlated negatively with cord volume (r = -0.496, P = 0.043) and mean cross-sectional cord area (r = -0.535, P = 0.027). This study is the first to correlate cervical sagittal balance (C2-C7 SVA) to myelopathy severity. We found a moderate negative correlation in kyphotic patients of cord volume and cross-sectional area to mJOA scores. The opposite (positive correlation) was found for lordotic patients, suggesting a relationship of cord volume to myelopathy that differs on the basis of sagittal alignment. It is interesting to note that sagittal balance but not kyphosis is tied to myelopathy score. Future work will correlate alignment changes to cord morphology changes and myelopathy outcomes. SUMMARY STATEMENTS: This is the first study to correlate sagittal balance (C2-C7 SVA) to myelopathy severity. We found a moderate negative correlation in kyphotic patients of cord volume and cross-sectional area to mJOA scores. The opposite (positive correlation) was found for lordotic patients, suggesting a relationship of cord volume to myelopathy that differs on the basis of sagittal alignment.

Economic and environmental benefits of reducing standby power lossin DVD/VCD players and copiers in China

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Jiang; Li, Tienan; Li, Aizhen

With the popularization of household electrical appliances and the rapid development of office automation and networking, a huge number of consumer electronic devices, computers, copiers, and fax machines have been put into use in China over the last two decades. These products almost all use a certain amount of standby power--the power that is consumed when a device is connected but not performing its primary function. The rapid growth of standby energy consumption due to these products--and the consequent environmental problems--has attracted more and more attentions from researchers and from many government and international agencies. Numerous countries have developed policiesmore » and measures to restrict and reduce standby energy consumption (US EPA, 2004, IEA, 2001, and GEEA, 2004). However, standby energy consumption is still a new concept for Chinese consumers and the phenomenon of ''unconscious waste of energy'' is still very common in the people's daily life and work. With the goal of reducing China's standby energy consumption, China Certification Center for Energy Conservation Products (CECP) and the Lawrence Berkeley National Laboratory (LBNL) have, under the sponsorship of the Energy Foundation (EF), entered into a collaboration to develop technical requirements for CECP's labeling program for consumer electronics and office equipment. These technical requirements will be used to qualify products for CECP's energy efficiency endorsement label in China. In the phase I of this collaborative project, CECP and LBNL conducted technical and economic research on televisions and printers in China. Based on the results of this research, CECP developed specifications for, and carried out corresponding energy conservation certifications for these two products. CECP's standby power certification program has made impressive gains in China. Leading manufacturers, such as Haier, Hesons, TCL, Chuangwei, Lenovo, EPSON, Fujitsu, and Brother have participated in CECP's certification activities. Media events organized by CECP have greatly improved the country's awareness of standby power loss. Reducing standby power loss has been formally incorporated into China's energy efficiency policy portfolio and in China's collaboration with the international community on the subject of energy efficiency (IEA, 2001). In phase II of the program, CECP's main task was to assess the market for DVD/VCD (Digital Versatile/Video Disc and Video Compact Disc) players and copiers to analyze the economic and technical benefits of energy conservation potential, and to develop technical specifications for DVD/VCD players and copiers, with technical assistance from LBNL. Having built on the success of Phase I, CECP paid great attention to the appraisal of market conditions and the economic and environmental benefits of reducing standby power loss in DVD/VCD players and copiers, and solicited inputs from stakeholders before finalizing the product certification requirements. This paper summarizes the expected energy conservation and environmental benefits due to the implementation of certification programs for DVD/VCD players and copiers in China.« less

The Prevalence and Phenotype of Activated Microglia/Macrophages within the Spinal Cord of the Hyperostotic Mouse (twy/twy) Changes in Response to Chronic Progressive Spinal Cord Compression: Implications for Human Cervical Compressive Myelopathy

PubMed Central

Hirai, Takayuki; Uchida, Kenzo; Nakajima, Hideaki; Guerrero, Alexander Rodriguez; Takeura, Naoto; Watanabe, Shuji; Sugita, Daisuke; Yoshida, Ai; Johnson, William E. B.; Baba, Hisatoshi

2013-01-01

Background Cervical compressive myelopathy, e.g. due to spondylosis or ossification of the posterior longitudinal ligament is a common cause of spinal cord dysfunction. Although human pathological studies have reported neuronal loss and demyelination in the chronically compressed spinal cord, little is known about the mechanisms involved. In particular, the neuroinflammatory processes that are thought to underlie the condition are poorly understood. The present study assessed the localized prevalence of activated M1 and M2 microglia/macrophages in twy/twy mice that develop spontaneous cervical spinal cord compression, as a model of human disease. Methods Inflammatory cells and cytokines were assessed in compressed lesions of the spinal cords in 12-, 18- and 24-weeks old twy/twy mice by immunohistochemical, immunoblot and flow cytometric analysis. Computed tomography and standard histology confirmed a progressive spinal cord compression through the spontaneously development of an impinging calcified mass. Results The prevalence of CD11b-positive cells, in the compressed spinal cord increased over time with a concurrent decrease in neurons. The CD11b-positive cell population was initially formed of arginase-1- and CD206-positive M2 microglia/macrophages, which later shifted towards iNOS- and CD16/32-positive M1 microglia/macrophages. There was a transient increase in levels of T helper 2 (Th2) cytokines at 18 weeks, whereas levels of Th1 cytokines as well as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and macrophage antigen (Mac) −2 progressively increased. Conclusions Spinal cord compression was associated with a temporal M2 microglia/macrophage response, which may act as a possible repair or neuroprotective mechanism. However, the persistence of the neural insult also associated with persistent expression of Th1 cytokines and increased prevalence of activated M1 microglia/macrophages, which may lead to neuronal loss and demyelination despite the presence of neurotrophic factors. This understanding of the aetiopathology of chronic spinal cord compression is of importance in the development of new treatment targets in human disease. PMID:23717624

Searching for Models Exhibiting High Circularly Polarized Luminescence: the Electroactive Inherently Chiral Oligothiophenes.

PubMed

Benincori, Tiziana; Appoloni, Giulio; Mussini, Patrizia Romana; Arnaboldi, Serena; Cirilli, Roberto; Quartapelle Procopio, Elsa; Panigati, Monica; Abbate, Sergio; Mazzeo, Giuseppe; Longhi, Giovanna

2018-05-02

Two new inherently chiral oligothiophenes characterized by the atropisomeric 3,3'-bithianaphtene scaffold functionalized with fused ring bithiophene derivatives, namely 4H-cyclopenta [2,1-b3:4b']dithiophene (CPDT) and dithieno[3,3-b:2',3'-d]pyrrole (DTP), were synthesized. The racemates were fully characterized and resolved into antipodes by enantioselective HPLC. The enantiomers were analyzed through different chiroptical techniques: electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) were employed to attribute the absolute configuration (AC). Comparison of experimental and calculated VCD spectra confirmed the DFT calculated conformational characteristics. The compound functionalized with two CPDT units was oxidized with FeCl3 and ECD and CPL of the resulting material were measured. Circularly Polarized Luminescence (CPL) was measured in order to verify if inherently chiral oligothiophenes could be promising systems for chiral photonics applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and Stereochemical Assignment of Crypto-Optically Active (2) H6 -Neopentane.

PubMed

Masarwa, Ahmad; Gerbig, Dennis; Oskar, Liron; Loewenstein, Aharon; Reisenauer, Hans Peter; Lesot, Philippe; Schreiner, Peter R; Marek, Ilan

2015-10-26

The determination of the absolute configuration of chiral molecules is at the heart of asymmetric synthesis. Here we probe the spectroscopic limits for chiral discrimination with NMR spectroscopy in chiral aligned media and with vibrational circular dichroism spectroscopy of the sixfold-deuterated chiral neopentane. The study of this compound presents formidable challenges since its stereogenicity is only due to small mass differences. For this purpose, we selectively prepared both enantiomers of (2) H6 -1 through a concise synthesis utilizing multifunctional intermediates. While NMR spectroscopy in chiral aligned media could be used to characterize the precursors to (2) H6 -1, the final assignment could only be accomplished with VCD spectroscopy, despite the fleetingly small dichroic properties of 1. Both enantiomers were assigned by matching the VCD spectra with those computed with density functional theory. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of experimental and calculated chiroptical spectra for chiral molecular structure determination.

PubMed

Polavarapu, Prasad L; Covington, Cody L

2014-09-01

For three different chiroptical spectroscopic methods, namely, vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and Raman optical activity (ROA), the measures of similarity of the experimental spectra to the corresponding spectra predicted using quantum chemical theories are summarized. In determining the absolute configuration and/or predominant conformations of chiral molecules, these similarity measures provide numerical estimates of agreement between experimental observations and theoretical predictions. Selected applications illustrating the similarity measures for absorption, circular dichroism, and corresponding dissymmetry factor (DF) spectra, in the case of VCD and ECD, and for Raman, ROA, and circular intensity differential (CID) spectra in the case of ROA, are presented. The analysis of similarity in DF or CID spectra is considered to be much more discerning and accurate than that in absorption (or Raman) and circular dichroism (or ROA) spectra, undertaken individually. © 2014 Wiley Periodicals, Inc.

Surgical Treatment of Congenital Scoliosis Associated With Tethered Cord by Thoracic Spine-shortening Osteotomy Without Cord Detethering.

PubMed

Huang, Jing-Hui; Yang, Wei-Zhou; Shen, Chao; Chang, Michael S; Li, Huan; Luo, Zhuo-Jing; Tao, Hui-Ren

2015-10-15

Retrospective case series. To investigate the safety and efficacy of spine-shortening osteotomy for congenital scoliosis with tethered cord. Conventional surgery for congenital scoliosis associated with tethered cord risks the complications of detethering. Spine-shortening osteotomy holds the potential to correct scoliosis and decrease spinal cord tension simultaneously without an extra detethering procedure, but no data on this issue is available. 21 patients (14 females and 7 males, average age 15.4 yr) underwent spine-shortening osteotomy without detethering. All of the patients had tethered cord. Patients with main curve more than 90° underwent vertebral column resection (VCR), whereas the others had pedicle subtraction osteotomy (PSO) performed. The average postoperative follow-up period was 45.2 months. The mean operation time was 544.5 min with average blood loss of 2769.1 ml. The deformity correction was 61.3% in the coronal plane and 43.9° in the sagittal plane. 10 patients had neurological deficits preoperatively. At the final follow-up, the deficits in 8 (80%) patients were significantly improved, whereas 2 (20%) remained unchanged. At final follow-up, 71.4% (5/7) patients reported improvement in motor function, 100% (3/3) had improved pain scores, and 75% (3/4) reported better sensory function after the spine-shortening osteotomy. Urinary dysfunction and bowel incontinence present preoperatively in 3 patients all recovered by final follow-up. 5 (23.8%) patients incurred complications including temporary neurological deterioration in 1 patient, urinary tract infection in 2 patients, cerebrospinal fluid leakage in 1 patient, and blood loss more than 5000 ml in 1 patient. Spine-shortening osteotomy is a safe and effective procedure for congenital scoliosis associated with tethered cord. Spine-shortening osteotomy at the thoracic apical vertebrae level not only corrects the spine deformity but also simultaneously releases the tension of the tethered cord, resulting in improved neurologic function.

Toward semantic-based retrieval of visual information: a model-based approach

NASA Astrophysics Data System (ADS)

Park, Youngchoon; Golshani, Forouzan; Panchanathan, Sethuraman

2002-07-01

This paper center around the problem of automated visual content classification. To enable classification based image or visual object retrieval, we propose a new image representation scheme called visual context descriptor (VCD) that is a multidimensional vector in which each element represents the frequency of a unique visual property of an image or a region. VCD utilizes the predetermined quality dimensions (i.e., types of features and quantization level) and semantic model templates mined in priori. Not only observed visual cues, but also contextually relevant visual features are proportionally incorporated in VCD. Contextual relevance of a visual cue to a semantic class is determined by using correlation analysis of ground truth samples. Such co-occurrence analysis of visual cues requires transformation of a real-valued visual feature vector (e.g., color histogram, Gabor texture, etc.,) into a discrete event (e.g., terms in text). Good-feature to track, rule of thirds, iterative k-means clustering and TSVQ are involved in transformation of feature vectors into unified symbolic representations called visual terms. Similarity-based visual cue frequency estimation is also proposed and used for ensuring the correctness of model learning and matching since sparseness of sample data causes the unstable results of frequency estimation of visual cues. The proposed method naturally allows integration of heterogeneous visual or temporal or spatial cues in a single classification or matching framework, and can be easily integrated into a semantic knowledge base such as thesaurus, and ontology. Robust semantic visual model template creation and object based image retrieval are demonstrated based on the proposed content description scheme.

Absolute configurations of phytotoxins seiricardine A and inuloxin A obtained by chiroptical studies.

PubMed

Santoro, Ernesto; Mazzeo, Giuseppe; Petrovic, Ana G; Cimmino, Alessio; Koshoubu, Jun; Evidente, Antonio; Berova, Nina; Superchi, Stefano

2015-08-01

The absolute configuration (AC) of the plant phytotoxin inuloxin A, produced by Inula viscosa, and of the fungal phytotoxin seiricardine A, obtained from Seiridium fungi, pathogen for cypress, has been determined by experimental measurements and theoretical simulations of chiroptical properties of three related methods, namely, Optical Rotatory Dispersion (ORD), Electronic Circular Dichroism (ECD), and Vibrational Circular Dichroism (VCD). Computational prediction by Density Functional Theory (DFT) of VCD spectra and by Time-dependent DFT (TDDFT) of ORD and ECD spectra allowed to assign (7R,8R,10S) AC to naturally occurring (+)-inuloxin A. In the case of compound (-)-seiricardine A, which lacks useful for the analysis UV-Vis absorption, and thus provides a hardly detectable ECD spectrum and quite low ORD values, an introduction of a suitable chromophore by chemical derivatization was performed. The corresponding derivative, 2-O-p-bromobenzoate ester, gave rise to an intense ECD spectrum and higher ORD and VCD values. The comparison of computed spectra with the experimental ones allowed to assign (1S,2R,3aS,4S,5R,7aS) AC to (-)-2-O-p-bromobenzoate ester of seiricardine A and then to (-)-seiricardine A. This study further supports a recent trend of concerted application of more than a single chiroptical technique toward an unambiguous assignment of AC of flexible and complex natural products. Moreover, the use of chemical derivatization, with insertion of suitable chromophoric moieties has allowed to treat also UV-Vis transparent molecules by ECD and ORD spectroscopies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ag(I)-mediated homo and hetero pairs of guanosine and cytidine: monitoring by circular dichroism spectroscopy.

PubMed

Goncharova, Iryna

2014-01-24

Ag(I)-containing compounds are attractive as antibacterial and antifungal agents. The renewed interest in the application of silver(I) compounds has led to the need for detailed knowledge of the mechanism of their action. One of the possible ways is the coordination of Ag(I) to G-C pairs of DNA, where Ag(+) ions form Ag(I)-mediated base pairs and inhibit the transcription. Herein, a systematic chiroptical study on silver(I)-mediated homo and mixed pairs of the C-G complementary-base derivatives cytidine(C) and 5'-guanosine monophosphate(G) in water is presented. Ag(I)-mediated homo and hetero pairs of G and C and their self-assembled species were studied under two pH levels (7.0 and 10.0) by vibrational (VCD) and electronic circular dichroism(ECD). VCD was used for the first time in this field and showed itself to be a powerful method for obtaining specific structural information in solution. Based on results of the VCD experiments, the different geometries of the homo pairs were proposed under pH 7.0 and 10.0. ECD was used as a diagnostic tool to characterize the studied systems and as a contact point between the previously defined structures of the metal or proton mediated pairs of nucleobases and the systems studied here. On the basis of the obtained data, the formation of the self-assembled species of cytidine with a structure similar to the i-motif structure in DNA was proposed at pH 10.0. Copyright © 2013 Elsevier B.V. All rights reserved.

Ag(I)-mediated homo and hetero pairs of guanosine and cytidine: Monitoring by circular dichroism spectroscopy

NASA Astrophysics Data System (ADS)

Goncharova, Iryna

2014-01-01

Ag(I)-containing compounds are attractive as antibacterial and antifungal agents. The renewed interest in the application of silver(I) compounds has led to the need for detailed knowledge of the mechanism of their action. One of the possible ways is the coordination of Ag(I) to G-C pairs of DNA, where Ag+ ions form Ag(I)-mediated base pairs and inhibit the transcription. Herein, a systematic chiroptical study on silver(I)-mediated homo and mixed pairs of the C-G complementary-base derivatives cytidine(C) and 5‧-guanosine monophosphate(G) in water is presented. Ag(I)-mediated homo and hetero pairs of G and C and their self-assembled species were studied under two pH levels (7.0 and 10.0) by vibrational (VCD) and electronic circular dichroism(ECD). VCD was used for the first time in this field and showed itself to be a powerful method for obtaining specific structural information in solution. Based on results of the VCD experiments, the different geometries of the homo pairs were proposed under pH 7.0 and 10.0. ECD was used as a diagnostic tool to characterize the studied systems and as a contact point between the previously defined structures of the metal or proton mediated pairs of nucleobases and the systems studied here. On the basis of the obtained data, the formation of the self-assembled species of cytidine with a structure similar to the i-motif structure in DNA was proposed at pH 10.0.

Central corneal thickness measurements and ultrasonographic study of the growing equine eye.

PubMed

Herbig, Lena E; Eule, J Corinna

2015-11-01

The aim of this study was to determine the central corneal thickness (CCT) of healthy equine eyes with high-frequency ultrasound (HF) and ultrasound biomicroscopy (UBM) and to measure the axial dimensions with B-mode ultrasound. Additionally, the influence of the age on the measured dimensions of the globe was analyzed. Fifty warm blood horses (mean age 23.0 ± 21.12 months) were divided into 3 age groups (group 1: 0-6 months; group 2: ≥7-30 months; and group 3: ≥31-78 months). Corneal measurements were performed with a 22-MHz and a 50-MHz transducer. Crystalline lens thickness (CLT), vitreous chamber depth (VCD), and axial globe length (AGL) were measured at a frequency of 10 MHz. Anterior chamber depth (ACD) was calculated. The eyes were measured under general anesthesia nonrelated to this study. The mean CCT of 50 eyes was 818 ± 41 μm. The mean values ± SD in mm for axial dimensions were AGL 34.7 ± 2.7, ACD 3.4 ± 0.7, CLT 10.0 ± 0.9, and VCD of 20.4 ± 1.5. A positive correlation with increasing age was found for all dimensions. No significant differences were found between the gender and the left or right eye. HF and UBM are valuable high-resolution imaging tools for CCT measurements in horses. The here-obtained values support previous findings that a positive correlation with increasing age exists for CCT, ACD, CLT, VCD, and AGL in horse. © 2015 American College of Veterinary Ophthalmologists.

Neurogenic bowel dysfunction: pathophysiology, clinical manifestations and treatment.

PubMed

Preziosi, Giuseppe; Emmanuel, Anton

2009-08-01

Bowel dysfunction (e.g., fecal incontinence, infrequent or difficult defecation) are both frequent and severely troubling problems for patients with spinal cord injury, multiple sclerosis and Parkinson's disease. The etiology of these symptoms is complex; there may be autonomic and pelvic nerve dysfunction (with attenuation of voluntary motor function and impaired anorectal sensation and anorectal reflexes), or generalized systemic factors (e.g., altered diet and behavior, impaired mobility, psychological disturbances or drug adverse effects). The mainstay of current treatment is adapting a conservative approach towards reversing the systemic effects and optimizing the mechanics of defecation through the use of laxatives and irrigation approaches. When successful, this approach improves both evacuation and incontinence symptoms, with associated improvements in quality of life and independence. Future therapies may be directed at modulating pelvic innervation through electrical stimulation. Stoma formation remains an option for patients refractory to other approaches.

β-blockade Use for Traumatic Injuries and Immunomodulation: A review of proposed mechanisms and clinical evidence

PubMed Central

Loftus, Tyler J.; Efron, Philip A.; Moldawer, Lyle L.; Mohr, Alicia M.

2016-01-01

Sympathetic nervous system activation and catecholamine release are important events following injury and infection. The nature and timing of different pathophysiologic insults have significant effects on adrenergic pathways, inflammatory mediators, and the host response. Beta adrenergic receptor blockers (β-blockers) are commonly used for treatment of cardiovascular disease but recent data suggests that the metabolic and immunomodulatory effects of β-blockers can expand their use. β-blocker therapy can reduce sympathetic activation and hypermetabolism as well as modify glucose homeostasis and cytokine expression. It is the purpose of this review to examine either the biologic basis for proposed mechanisms or to describe current available clinical evidence for the use of β-blockers in traumatic brain injury (TBI), spinal cord injury (SCI), hemorrhagic shock, acute traumatic coagulopathy, erythropoietic dysfunction, metabolic dysfunction, pulmonary dysfunction, burns, immunomodulation, and sepsis. PMID:27172161

Suitability of Gray Water for Hydroponic Crop Production Following Biological and Physical Chemical and Biological Subsystems

NASA Technical Reports Server (NTRS)

Bubenheim, David L.; Harper, Lynn D.; Wignarajah, Kanapathipillai; Greene, Catherine

1994-01-01

The water present in waste streams from a human habitat must be recycled in Controlled Ecological Life Support Systems (CELSS) to limit resupply needs and attain self-sufficiency. Plants play an important role in providing food, regenerating air, and producing purified water via transpiration. However, we have shown that the surfactants present in hygiene waste water have acute toxic effects on plant growth (Bubenheim et al. 1994; Greene et al., 1994). These phytotoxic affects can be mitigated by allowing the microbial population on the root surface to degrade the surfactant, however, a significant suppression (several days) in crop performance is experienced prior to reaching sub-toxic surfactant levels and plant recovery. An effective alternative is to stabilize the microbial population responsible for degradation of the surfactant on an aerobic bioreactor and process the waste water prior to utilization in the hydroponic solution (Wisniewski and Bubenheim, 1993). A sensitive bioassay indicates that the surfactant phytotoxicity is suppressed by more than 90% within 5 hours of introduction of the gray water to the bioreactor; processing for more than 12 hours degrades more than 99% of the phytotoxin. Vapor Compression Distillation (VCD) is a physical / chemical method for water purification which employees sequential distillation steps to separate water from solids and to volatilize contaminants. The solids from the waste water are concentrated in a brine and the pure product water (70 - 90% of the total waste water volume depending on operating conditions) retains non of the phytotoxic effects. Results of the bioassay were used to guide evaluations of the suitability of recovered gray water following biological and VCD processing for hydroponic lettuce production in controlled environments. Lettuce crops were grown for 28 days with 100% of the input water supplied with recovered water from the biological processor or VCD. When compared with the growth of plants in control hydroponic solution containing pure deionized water, no growth difference could be measured resulting from any of the recovered water treatments. Both biological treatment and VCD offer alternative technology approaches to recovering water from waste streams appropriate for input into a crop production system. A high level of crop performance (food, air, and water production) can be maintained with either processor; selection decisions can be based on other factors regarding system integration.

Is There an Association Between Markers of Cardiovascular Autonomic Dysfunction at Discharge From Rehabilitation and Participation 1 and 5 Years Later in Individuals With Spinal Cord Injury?

PubMed

Rianne Ravensbergen, H J; de Groot, Sonja; Post, Marcel W; Bongers-Janssen, Helma M; van der Woude, Lucas H; Claydon, Victoria E

2016-09-01

To determine whether physical activity and participation 1 and 5 years after discharge are associated with measures of cardiovascular autonomic function: prevalence of hypotension and reduced peak heart rate at discharge from initial inpatient spinal cord injury (SCI) rehabilitation. Prospective cohort study. Rehabilitation centers. Individuals with SCI (N=146). Not applicable. We recorded markers of cardiovascular autonomic dysfunction (resting blood pressure and peak heart rate) and personal and lesion characteristics at the time of discharge from rehabilitation. Parameters for participation (social health status dimension of the Sickness Impact Profile) and physical activity (Physical Activity Scale for Individuals with Physical Disabilities [PASIPD]) were measured 1 and 5 years after discharge. Effects of prevalence of cardiovascular autonomic dysfunction were analyzed using linear regression analysis while correcting for possible confounders. We found no significant association between hypotension and social health status dimension of the Sickness Impact Profile or PASIPD, either at 1 or at 5 years after discharge. A significant association between peak heart rate and social health status dimension of the Sickness Impact Profile was found at 1 year after discharge, showing poorer participation in individuals with low peak heart rate (ie, cardiovascular autonomic dysfunction). The unadjusted relation between peak heart rate and the social health status dimension of the Sickness Impact Profile was significant at 5 years, but not when adjusted for confounders. We found associations between peak heart rate and PASIPD for both 1 and 5 years after discharge; however, these were not significant after correction for potential confounding factors. Autonomic dysfunction after SCI is a crucial factor influencing quality of life. We found that cardiovascular autonomic impairment, assessed from low peak heart rate, was associated with reduced participation after 1 year. The results suggest that peak heart rate at discharge from rehabilitation after SCI should be used to identify those needing additional support to facilitate physical activity and participation after discharge. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Advances in the management of infertility in men with spinal cord injury

PubMed Central

Ibrahim, Emad; Brackett, Nancy L; Lynne, Charles M

2016-01-01

Couples with a spinal cord injured male partner require assisted ejaculation techniques to collect semen that can then be further used in various assisted reproductive technology methods to achieve a pregnancy. The majority of men sustaining a spinal cord injury regardless of the cause or the level of injury cannot ejaculate during sexual intercourse. Only a small minority can ejaculate by masturbation. Penile vibratory stimulation and electroejaculation are the two most common methods used to retrieve sperm. Other techniques such as prostatic massage and the adjunct application of other medications can be used, but the results are inconsistent. Surgical sperm retrieval should be considered as a last resort if all other methods fail. Special attention must be paid to patients with T6 and rostral levels of injury due to the risk of autonomic dysreflexia resulting from stimulation below the level of injury. Bladder preparation should be performed before stimulation if retrograde ejaculation is anticipated. Erectile dysfunction is ubiquitous in the spinal cord injured population but is usually easily managed and does not pose a barrier to semen retrieval in these men. Semen analysis parameters of men with spinal cord injury are unique for this population regardless of the method of retrieval, generally presenting as normal sperm concentration but abnormally low sperm motility and viability. When sperm retrieval is desired in this population, emphasis should be placed on initially trying the simple methods of penile vibratory stimulation or electroejaculation before resorting to more advanced and invasive surgical procedures. PMID:27048781

Calcineurin Dysregulation Underlies Spinal Cord Injury-Induced K+ Channel Dysfunction in DRG Neurons

PubMed Central

Zemel, Benjamin M.; Brown, Eric V.; Urban, Mark W.; Tymanskyj, Stephen R.; Lepore, Angelo C.

2017-01-01

Dysfunction of the fast-inactivating Kv3.4 potassium current in dorsal root ganglion (DRG) neurons contributes to the hyperexcitability associated with persistent pain induced by spinal cord injury (SCI). However, the underlying mechanism is not known. In light of our previous work demonstrating modulation of the Kv3.4 channel by phosphorylation, we investigated the role of the phosphatase calcineurin (CaN) using electrophysiological, molecular, and imaging approaches in adult female Sprague Dawley rats. Pharmacological inhibition of CaN in small-diameter DRG neurons slowed repolarization of the somatic action potential (AP) and attenuated the Kv3.4 current. Attenuated Kv3.4 currents also exhibited slowed inactivation. We observed similar effects on the recombinant Kv3.4 channel heterologously expressed in Chinese hamster ovary cells, supporting our findings in DRG neurons. Elucidating the molecular basis of these effects, mutation of four previously characterized serines within the Kv3.4 N-terminal inactivation domain eliminated the effects of CaN inhibition on the Kv3.4 current. SCI similarly induced concurrent Kv3.4 current attenuation and slowing of inactivation. Although there was little change in CaN expression and localization after injury, SCI induced upregulation of the native regulator of CaN 1 (RCAN1) in the DRG at the transcript and protein levels. Consistent with CaN inhibition resulting from RCAN1 upregulation, overexpression of RCAN1 in naive DRG neurons recapitulated the effects of pharmacological CaN inhibition on the Kv3.4 current and the AP. Overall, these results demonstrate a novel regulatory pathway that links CaN, RCAN1, and Kv3.4 in DRG neurons. Dysregulation of this pathway might underlie a peripheral mechanism of pain sensitization induced by SCI. SIGNIFICANCE STATEMENT Pain sensitization associated with spinal cord injury (SCI) involves poorly understood maladaptive modulation of neuronal excitability. Although central mechanisms have received significant attention, recent studies have identified peripheral nerve hyperexcitability as a driver of persistent pain signaling after SCI. However, the ion channels and signaling molecules responsible for this change in primary sensory neuron excitability are still not well defined. To address this problem, this study used complementary electrophysiological and molecular methods to determine how Kv3.4, a voltage-gated K+ channel robustly expressed in dorsal root ganglion neurons, becomes dysfunctional upon calcineurin (CaN) inhibition. The results strongly suggest that CaN inhibition underlies SCI-induced dysfunction of Kv3.4 and the associated excitability changes through upregulation of the native regulator of CaN 1 (RCAN1). PMID:28751455

EFFECTS OF METHYLMERCURY ON SPINAL CORD AFFERENTS AND EFFERENTS—A REVIEW

PubMed Central

Colón-Rodríguez, Alexandra; Hannon, Heidi E.; Atchison, William D.

2017-01-01

Methylmercury (MeHg) is an environmental neurotoxicant of public health concern. It readily accumulates in exposed humans, primarily in neuronal tissue. Exposure to MeHg, either acutely or chronically, causes severe neuronal dysfunction in the central nervous system and spinal neurons; dysfunction of susceptible neuronal populations results in neurodegeneration, at least in part through Ca2+-mediated pathways. Biochemical and morphologic changes in peripheral neurons precede those in central brain regions, despite the fact that MeHg readily crosses the blood-brain barrier. Consequently, it is suggested that unique characteristics of spinal cord afferents and efferents could heighten their susceptibility to MeHg toxicity. Transient receptor potential (TRP) ion channels are a class of Ca2+-permeable cation channels that are highly expressed in spinal afferents, among other sensory and visceral organs. These channels can be activated in numerous ways, including directly via chemical irritants or indirectly via Ca2+ release from intracellular storage organelles. Early studies demonstrated that MeHg interacts with heterologous TRPs, though definitive mechanisms of MeHg toxicity on sensory neurons may involve more complex interaction with, and among, differentially-expressed TRP populations. In spinal efferents, glutamate receptors of the N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and possibly kainic acid (KA) classes are thought to play a major role in MeHg-induced neurotoxicity. Specifically, the Ca2+-permeable AMPA receptors, which are abundant in motor neurons, have been identified as being involved in MeHg-induced neurotoxicity. In this review, we will describe the mechanisms that could contribute to MeHg-induced spinal cord afferent and efferent neuronal degeneration, including the possible mediators, such as uniquely expressed Ca2+-permeable ion channels. PMID:28041893

Urinary tract infections in patients with spinal cord injuries.

PubMed

D'Hondt, Frederiek; Everaert, Karel

2011-12-01

Spinal cord injuries (SCI) result in different lower urinary tract dysfunctions. Because of both the disease and the bladder drainage method, urinary tract infections (UTIs) are one of the most frequent conditions seen in SCI patients. Diagnosis is not always easy due to lack of symptoms. Asymptomatic bacteriuria needs no treatment. If symptoms occur, antibiotherapy is indicated. Duration depends mainly on severity of illness and upper urinary tract or prostatic involvement. Choice of antibiotherapy should be based on local resistance profiles, but fluoroquinolones seems to be an adequate empirical treatment. Prevention of UTI is important, as lots of complications can be foreseen. Catheter care, permanent low bladder pressure and clean intermittent catheterization (CIC) with hydrophilic catheters are interventions that can prevent UTI. Probiotics might be useful, but data are limited.

An experience of second-trimester anhydramnios salvaged by single amnioinfusion.

PubMed

Io, Shingo; Kondoh, Eiji; Chigusa, Yoshitsugu; Tani, Hirohiko; Hamanishi, Junzo; Konishi, Ikuo

2017-11-20

Second-trimester anhydramnios, which is primarily caused by ruptured membranes, placental dysfunction, or congenital renal malformations, is associated with high perinatal morbidity and mortality. Although amnioinfusion temporarily increases amniotic fluid volume, it does not generally provide a fundamental solution. We describe a case of second-trimester anhydramnios with an umbilical cord factor, wherein single amnioinfusion may have successfully broken a vicious circle involving non-reassuring fetal status. A 34-year-old primigravid woman was referred to our hospital because of anhydramnios at 22 weeks' gestation. Single amnioinfusion improved the fetal circulatory failure, and the patient delivered a healthy full-term newborn. Single amnioinfusion may be a therapeutic approach to improve the prognosis of pregnancy when second-trimester anhydramnios results from umbilical cord factors.

Early spinal cord and brainstem involvement in infantile Leigh syndrome possibly caused by a novel variant.

PubMed

Tenney, Jeffrey R; Prada, Carlos E; Hopkin, Robert J; Hallinan, Barbara E

2013-12-01

Leigh syndrome, due to a dysfunction of mitochondrial energy metabolism, is a genetically heterogeneous and progressive neurologic disorder that usually occurs in infancy and childhood. Its clinical presentation and neuroimaging findings can be variable, especially early in the course of the disease. This report presents a patient with infantile Leigh syndrome who had atypical radiologic findings on serial neuroimaging studies with early and severe involvement of the cervical spinal cord and brainstem and injury to the thalami and basal ganglia occurring only late in the clinical course. Postmortem microscopic examination supported this timing of injury within the central nervous system. In addition, mitochondrial deoxyribonucleic acid sequencing showed a novel homoplasmic variant that could be responsible for this unique lethal form of Leigh syndrome.

Clinical and Functional Impact of Hypogastric Artery Exclusion During EVAR.

PubMed

Mansour, Wassim; Capoccia, Laura; Sirignano, Pasqualino; Montelione, Nunzio; Pranteda, Chiara; Formiconi, Martina; Sbarigia, Enrico; Speziale, Francesco

2016-10-01

Hypogastric artery (HA) revascularization during endovascular aneurysm repair (EVAR) is still open to debate. Moreover, exclusion-related complication rates reported in literature are not negligible. The aim of this study is to present and analyze the outcomes in patients undergoing EVAR with exclusion of 1 or both HAs at our academic center. We retrospectively reviewed our results in patients submitted to EVAR and needing HA exclusion, in terms of perioperative (30-day) and follow-up rates of intestinal and spinal cord ischemia, buttock claudication, buttock skin necrosis, and sexual dysfunction. From January 2008 to December 2014, a total of 527 patients underwent elective standard infrarenal EVAR; among those 104 (19.7%) had iliac involvement needing HA exclusion. In 73 patients with unilateral iliac involvement (70.1%, group UH), many single HAs were excluded. Thirty-one patients (29.9%) had bilateral iliac involvement (group BH), of which 16 (51.6%) had 1 HA excluded with revascularization of the contralateral one (group BHR); in the remaining 15 patients (48.4%) both HAs were excluded (group BHE). No 30-day or follow-up aneurysm-related mortality, intestinal, or spinal cord ischemia were recorded. At 30 days, skin necrosis was observed in 2 patients. Buttock claudication and sexual dysfunction rates were significantly greater in group BHE than in group BHR (P < .05). At a mean 18.6 months follow-up (range: 4-47), buttock claudication and sexual dysfunction rates in group BHE were persistently higher than that in groups UH and BHR (P < .05); HA coil embolization was significantly associated with buttock claudication and sexual dysfunction (P < .05). Whenever anatomically feasible, at least 1 HA should be salvaged in case of bilateral involvement. In case of unilateral HA exclusion, the rate of complications is not negligible. Coil embolization is related to a higher complication rate. © The Author(s) 2016.

Accumulation of p62 in degenerated spinal cord under chronic mechanical compression

PubMed Central

Tanabe, Fumito; Yone, Kazunori; Kawabata, Naoya; Sakakima, Harutoshi; Matsuda, Fumiyo; Ishidou, Yasuhiro; Maeda, Shingo; Abematsu, Masahiko; Komiya, Setsuro

2011-01-01

Intracellular accumulation of altered proteins, including p62 and ubiquitinated proteins, is the basis of most neurodegenerative disorders. The relationship among the accumulation of altered proteins, autophagy, and spinal cord dysfunction by cervical spondylotic myelopathy has not been clarified. We examined the expression of p62 and autophagy markers in the chronically compressed spinal cord of tiptoe-walking Yoshimura mice. In addition, we examined the expression and roles of p62 and autophagy in hypoxic neuronal cells. Western blot analysis showed the accumulation of p62, ubiquitinated proteins, and microtubule-associated protein 1 light chain 3 (LC3), an autophagic marker, in the compressed spinal cord. Immunohistochemical examinations showed that p62 accumulated in neurons, axons, astrocytes, and oligodendrocytes. Electron microscopy showed the expression of autophagy markers, including autolysosomes and autophagic vesicles, in the compressed spinal cord. These findings suggest the presence of p62 and autophagy in the degenerated compressed spinal cord. Hypoxic stress increased the expression of p62, ubiquitinated proteins, and LC3-II in neuronal cells. In addition, LC3 turnover assay and GFP-LC3 cleavage assay showed that hypoxic stress increased autophagy flux in neuronal cells. These findings suggest that hypoxic stress induces accumulation of p62 and autophagy in neuronal cells. The forced expression of p62 decreased the number of neuronal cells under hypoxic stress. These findings suggest that p62 accumulation under hypoxic stress promotes neuronal cell death. Treatment with 3-methyladenine, an autophagy inhibitor decreased the number of neuronal cells, whereas lithium chloride, an autophagy inducer increased the number of cells under hypoxic stress. These findings suggest that autophagy promotes neuronal cell survival under hypoxic stress. Our findings suggest that pharmacological inducers of autophagy may be useful for treating cervical spondylotic myelopathy patients. PMID:22082874

The Blood-Testis Barrier and Male Sexual Dysfunction following Spinal Cord Injury

DTIC Science & Technology

2014-10-01

antigenic sperm and sperm cell-containing compartments within the testis. We also demonstrated that once failed, the BTB remains permeable, essentially...input into the male sexual organs. SCI-dependent male infertility is characterized by a significant reduction in numbers and quality of functional... sperm . The mechanism(s) underlying this deficit has previously been unknown. My laboratory has explored the effects of spinal trauma on tissues that

The Blood Testis Barrier and Male Sexual Dysfunction following Spinal Cord Injury

DTIC Science & Technology

2015-10-01

sensory and motor deficits . In addition to these well-described pathological outcomes, a majority of men will also experience greatly diminished...underlying this deficit has previously been unknown. We have explored the effects of spinal trauma on tissues that exhibit “barrier” properties, or...immune cell infiltration. The goal of this project is to: 1) further elaborate the early and long-term biochemical, molecular and structural deficits

Skeletal muscle mitochondrial health and spinal cord injury.

PubMed

O'Brien, Laura C; Gorgey, Ashraf S

2016-10-18

Mitochondria are the main source of cellular energy production and are dynamic organelles that undergo biogenesis, remodeling, and degradation. Mitochondrial dysfunction is observed in a number of disease states including acute and chronic central or peripheral nervous system injury by traumatic brain injury, spinal cord injury (SCI), and neurodegenerative disease as well as in metabolic disturbances such as insulin resistance, type II diabetes and obesity. Mitochondrial dysfunction is most commonly observed in high energy requiring tissues like the brain and skeletal muscle. In persons with chronic SCI, changes to skeletal muscle may include remarkable atrophy and conversion of muscle fiber type from oxidative to fast glycolytic, combined with increased infiltration of intramuscular adipose tissue. These changes contribute to a proinflammatory environment, glucose intolerance and insulin resistance. The loss of metabolically active muscle combined with inactivity predisposes individuals with SCI to type II diabetes and obesity. The contribution of skeletal muscle mitochondrial density and electron transport chain activity to the development of the aforementioned comorbidities following SCI is unclear. A better understanding of the mechanisms involved in skeletal muscle mitochondrial dynamics is imperative to designing and testing effective treatments for this growing population. The current editorial will review ways to study mitochondrial function and the importance of improving skeletal muscle mitochondrial health in clinical populations with a special focus on chronic SCI.

Critical effects of alkyl chain length on fibril structures in benzene-trans(RR)- or (SS)-N,N'-alkanoyl-1,2-diaminocyclohexane gels.

PubMed

Sato, Hisako; Nakae, Takahiro; Morimoto, Kazuya; Tamura, Kenji

2012-02-28

Vibrational circular dichroism (VCD) spectra were recorded on benzene-d(6) gels formed by chiral low molecular mass gelators (LMGs), trans(RR)- or trans(SS)-N,N'-alkanoyl-1,2-diaminocyclohexane (denoted by RR-C(n) or SS-C(n), respectively; n = the number of carbon atoms in an introduced alkanoyl group). Attention was focused on the effects of alkyl chain length on the structures of the gels. When n was changed from 6 to 12, the signs of the coupled peaks around 1550 cm(-1) in the VCD spectra, which were assigned to the symmetric and asymmetric C=O stretching vibrations from the higher to lower wavenumber, respectively, critically depended on the alkyl chain length. In the case of RR-C(n), for example, the signs of the couplet were plus and minus for n = 8, 9, 10 and 12, while the signs of the same couplet were reversed for n = 6 and 7. The conformations of LMGs in fibrils were determined by comparing the observed IR and VCD spectra with those calculated for a monomeric molecule. The observed reversal of signs in the C=O couplet was rationalized in terms of the different modes of hydrogen bonding. In the case of C(8), C(9), C(10) and C(12), gelator molecules were stacked with their cyclohexyl rings in parallel, forming double anti-parallel chains of intermolecular hydrogen bonds using two pairs of >NH and >C=O groups. In case of C(6) and C(7), gelator molecules were stacked through a single chain of intermolecular hydrogen bonds using a pair of >NH and >C=O groups. The remaining pair of >NH and >C=O groups formed an intramolecular hydrogen bond.

Impact of Dengue Vaccination on Serological Diagnosis: Insights From Phase III Dengue Vaccine Efficacy Trials

PubMed Central

Plennevaux, Eric; Moureau, Annick; Arredondo-García, José L; Villar, Luis; Pitisuttithum, Punnee; Tran, Ngoc H; Bonaparte, Matthew; Chansinghakul, Danaya; Coronel, Diana L; L’Azou, Maïna; Ochiai, R Leon; Toh, Myew-Ling; Noriega, Fernando; Bouckenooghe, Alain

2018-01-01

Abstract Background We previously reported that vaccination with the tetravalent dengue vaccine (CYD-TDV; Dengvaxia) may bias the diagnosis of dengue based on immunoglobulin M (IgM) and immunoglobulin G (IgG) assessments. Methods We undertook a post hoc pooled analysis of febrile episodes that occurred during the active surveillance phase (the 25 months after the first study injection) of 2 pivotal phase III, placebo-controlled CYD-TDV efficacy studies that involved ≥31000 children aged 2–16 years across 10 countries in Asia and Latin America. Virologically confirmed dengue (VCD) episode was defined with a positive test for dengue nonstructural protein 1 antigen or dengue polymerase chain reaction. Probable dengue episode was serologically defined as (1) IgM-positive acute- or convalescent-phase sample, or (2) IgG-positive acute-phase sample and ≥4-fold IgG increase between acute- and convalescent-phase samples. Results There were 1284 VCD episodes (575 and 709 in the CYD-TDV and placebo groups, respectively) and 17673 other febrile episodes (11668 and 6005, respectively). Compared with VCD, the sensitivity and specificity of probable dengue definition were 93.1% and 77.2%, respectively. Overall positive and negative predictive values were 22.9% and 99.5%, respectively, reflecting the much lower probability of correctly confirming probable dengue in a population including a vaccinated cohort. Vaccination-induced bias toward false-positive diagnosis was more pronounced among individuals seronegative at baseline. Conclusions Caution will be required when interpreting IgM and IgG data obtained during routine surveillance in those vaccinated with CYD-TDV. There is an urgent need for new practical, dengue-specific diagnostic algorithms now that CYD-TDV is approved in a number of dengue-endemic countries. Clinical Trials Registration NCT01373281 and NCT01374516. PMID:29300876

Impact of Dengue Vaccination on Serological Diagnosis: Insights From Phase III Dengue Vaccine Efficacy Trials.

PubMed

Plennevaux, Eric; Moureau, Annick; Arredondo-García, José L; Villar, Luis; Pitisuttithum, Punnee; Tran, Ngoc H; Bonaparte, Matthew; Chansinghakul, Danaya; Coronel, Diana L; L'Azou, Maïna; Ochiai, R Leon; Toh, Myew-Ling; Noriega, Fernando; Bouckenooghe, Alain

2018-04-03

We previously reported that vaccination with the tetravalent dengue vaccine (CYD-TDV; Dengvaxia) may bias the diagnosis of dengue based on immunoglobulin M (IgM) and immunoglobulin G (IgG) assessments. We undertook a post hoc pooled analysis of febrile episodes that occurred during the active surveillance phase (the 25 months after the first study injection) of 2 pivotal phase III, placebo-controlled CYD-TDV efficacy studies that involved ≥31000 children aged 2-16 years across 10 countries in Asia and Latin America. Virologically confirmed dengue (VCD) episode was defined with a positive test for dengue nonstructural protein 1 antigen or dengue polymerase chain reaction. Probable dengue episode was serologically defined as (1) IgM-positive acute- or convalescent-phase sample, or (2) IgG-positive acute-phase sample and ≥4-fold IgG increase between acute- and convalescent-phase samples. There were 1284 VCD episodes (575 and 709 in the CYD-TDV and placebo groups, respectively) and 17673 other febrile episodes (11668 and 6005, respectively). Compared with VCD, the sensitivity and specificity of probable dengue definition were 93.1% and 77.2%, respectively. Overall positive and negative predictive values were 22.9% and 99.5%, respectively, reflecting the much lower probability of correctly confirming probable dengue in a population including a vaccinated cohort. Vaccination-induced bias toward false-positive diagnosis was more pronounced among individuals seronegative at baseline. Caution will be required when interpreting IgM and IgG data obtained during routine surveillance in those vaccinated with CYD-TDV. There is an urgent need for new practical, dengue-specific diagnostic algorithms now that CYD-TDV is approved in a number of dengue-endemic countries. NCT01373281 and NCT01374516.

Effects of central metal ions on vibrational circular dichroism spectra of tris-(beta-diketonato)metal(III) complexes.

PubMed

Sato, Hisako; Taniguchi, Tohru; Nakahashi, Atsufumi; Monde, Kenji; Yamagishi, Akihiko

2007-08-06

Vibrational circular dichroism (VCD) spectra of a series of [M(III)(acac)3] (acac = acetylacetonato; M = Cr, Co, Ru, Rh, Ir, and Al) and [M(III)(acac)2(dbm)] (dbm = dibenzoylmethanato; M = Cr, Co, and Ru) have been investigated experimentally and/or theoretically in order to see the effect of the central metal ion on the vibrational dynamics of ligands. The optical antipodes give the mirror-imaged spectra in the region of 1700-1000 cm(-1). The remarkable effect of the central metal ion is observed experimentally on the VCD peaks due to C-O stretches (1500-1300 cm(-1)) for both [M(III)(acac)3] and [M(III)(acac)2(dbm)]. In the case of Delta-[M(III)(acac)3], for example, the order of frequency of two C-O stretches (E and A2 symmetries) is dependent on the kind of a central metal ion as follows: E (-) > A2 (+) for M = Co, Rh, and Ir, while A2 (+) > E (-) for M = Cr and Ru. In the case of Delta-[M(III)(acac)2(dbm)], the order of frequency of three C-O stretches (A, B, and B symmetries) is as follows: A (-) > B (+) > B (+) for Co(III), B (+) > A (-) > B (-) for Cr(III), and A (-) > B (+) > B (-) for Ru(III). These results imply that the energy levels of C-O stretches are delicately affected by the kind of central metal ion. Since such detailed information is not obtained from the IR spectra alone, the VCD spectrum can probe the effect of the central metal ion on interligand cooperative vibration modes.

Molecules-in-molecules fragment-based method for the calculation of chiroptical spectra of large molecules: Vibrational circular dichroism and Raman optical activity spectra of alanine polypeptides.

PubMed

Jose, K V Jovan; Raghavachari, Krishnan

2016-12-01

The molecules-in-molecules (MIM) fragment-based method has recently been adapted to evaluate the chiroptical (vibrational circular dichroism [VCD] and Raman optical activity [ROA]) spectra of large molecules such as peptides. In the MIM-VCD and MIM-ROA methods, the relevant higher energy derivatives of the parent molecule are assembled from the corresponding derivatives of smaller fragment subsystems. In addition, the missing long-range interfragment interactions are accounted at a computationally less expensive level of theory (MIM2). In this work we employed the MIM-VCD and MIM-ROA fragment-based methods to explore the evolution of the chiroptical spectroscopic characteristics of 3 10 -helix, α-helix, β-hairpin, γ-turn, and β-extended conformers of gas phase polyalanine (chain length n = 6-14). The different conformers of polyalanine show distinctive features in the MIM chiroptical spectra and the associated spectral intensities increase with evolution of system size. For a better understanding the site-specific effects on the vibrational spectra, isotopic substitutions were also performed employing the MIM method. An increasing redshift with the number of isotopically labeled 13 C=O functional groups in the peptide molecule was seen. For larger polypeptides, we implemented the two-step-MIM model to circumvent the high computational expense associated with the evaluation of chiroptical spectra at a high level of theory using large basis sets. The chiroptical spectra of α-(alanine) 20 polypeptide obtained using the two-step-MIM model, including continuum solvation effects, show good agreement with the full calculations and experiment. This benchmark study suggests that the MIM-fragment approach can assist in predicting and interpreting chiroptical spectra of large polypeptides. © 2016 Wiley Periodicals, Inc.

Weekly cycle of NO2 by GOME measurements: A signature of anthropogenic sources

NASA Astrophysics Data System (ADS)

Beirle, S.; Platt, U.; Wenig, M.; Wagner, T.

2003-07-01

Nitrogen oxides (NO+NO2=NOx) are important trace gases in the troposphere with impact on human health, atmospheric chemistry and climate. Besides natural sources (lightning, soil emissions) and biomass burning, fossil fuel combustion is estimated to be responsible for about 50% of the total production of NOx. Since human activity in industrialized countries largely follows an artificial seven-day cycle, fossil fuel combustion is expected to be reduced during weekends. This "weekend effect" is well known from local, ground based measurements, but has never been analysed on a global scale before. The Global Ozone Monitoring Experiment (GOME) on board the ESA-satellite ERS-2 allows measurements of NO2 column densities. Applying sophisticated algorithms, vertical column densities (VCD) of tropospheric NO2 can be determined. We demonstrate the statistical analysis of weekly cycles of tropospheric NO2 VCDs for different regions of the world. In the cycles of the industrialized regions and cities in the US, Europe and Japan a clear Sunday minimum of tropospheric NO2 VCD can be seen. Sunday NO2 VCDs are about 25-50% lower than working day levels. Metropolitan areas with other religious and cultural backgrounds (Jerusalem, Mecca) show different weekly patterns corresponding to different days of rest. In China, no weekly pattern can be found. The presence of a weekly cycle in the measured tropospheric NO2 VCD allows the identification of anthropogenic sources. In addition, the fraction of emissions subjected to a weekly cycle (mainly transport, power generation) with respect to a constant background (all kind of natural sources, biomass burning, heavy industry) can be estimated. Furthermore, we estimated the lifetime of tropospheric NO2 by analysing the mean weekly cycle over Germany in detail, obtaining a value of about 12 h.

Weekly cycle of NO2 by GOME measurements: a signature of anthropogenic sources

NASA Astrophysics Data System (ADS)

Beirle, S.; Platt, U.; Wenig, M.; Wagner, T.

2003-12-01

Nitrogen oxides (NO+NO2=NOx and reservoir species) are important trace gases in the troposphere with impact on human health, atmospheric chemistry and climate. Besides natural sources (lightning, soil emissions) and biomass burning, fossil fuel combustion is estimated to be responsible for about 50% of the total production of NOx. Since human activity in industrialized countries largely follows a seven-day cycle, fossil fuel combustion is expected to be reduced during weekends. This "weekend effect" is well known from local, ground based measurements, but has never been analysed on a global scale before. The Global Ozone Monitoring Experiment (GOME) on board the ESA-satellite ERS-2 allows measurements of NO2 column densities. By estimating and subtracting the stratospheric column, and considering radiative transfer, vertical column densities (VCD) of tropospheric NO2 can be determined (e.g. Leue et al., 2001). We demonstrate the statistical analysis of weekly cycles of tropospheric NO2 VCDs for different regions of the world. In the cycles of the industrialized regions and cities in the US, Europe and Japan a clear Sunday minimum of tropospheric NO2 VCD can be seen. Sunday NO2 VCDs are about 25-50% lower than working day levels. Metropolitan areas with other religious and cultural backgrounds (Jerusalem, Mecca) show different weekly patterns corresponding to different days of rest. In China, no weekly pattern can be found. The presence of a weekly cycle in the measured tropospheric NO2 VCD may help to identify the different anthropogenic source categories. Furthermore, we estimated the lifetime of tropospheric NO2 by analysing the mean weekly cycle exemplarily over Germany, obtaining a value of about 6 h in summer and 18-24 h in winter.

Diabetes-induced microvascular complications at the level of the spinal cord; a contributing factor in diabetic neuropathic pain.

PubMed

Ved, N; Da Vitoria Lobo, M E; Bestall, S M; L Vidueira, C; Beazley-Long, N; Ballmer-Hofer, K; Hirashima, M; Bates, D O; Donaldson, L F; Hulse, R P

2018-05-17

Abnormalities of neurovascular interactions within the central nervous system of diabetic patients is associated with the onset of many neurological disease states. However, to date, the link between the neurovascular network within the spinal cord and regulation of nociception has not been investigated despite neuropathic pain being common in diabetes. We hypothesised that hyperglycaemia-induced endothelial degeneration in the spinal cord, due to suppression of VEGF-A/VEGFR2 signalling, induces diabetic neuropathic pain. Nociceptive pain behaviour was investigated in a chemically induced model of type 1 diabetes (streptozotocin induced, insulin supplemented; either vehicle or VEGF-A 165 b treated) and an inducible endothelial knockdown of VEGFR2 (tamoxifen induced). Diabetic animals developed mechanical allodynia and heat hyperalgesia. This was associated with a reduction in the number of blood vessels and reduction in Evans blue extravasation in the lumbar spinal cord of diabetic animals versus age-matched controls. Endothelial markers occludin, CD31 and VE-cadherin were downregulated in the spinal cord of the diabetic group versus controls, as well as a concurrent reduction of VEGF-A 165 b expression. In diabetic animals, VEGF-A 165 b treatment (biweekly intraperitoneal, 20 ng g -1 ) restored normal Evans blue extravasation and prevented vascular degeneration, diabetes-induced central neuron activation and neuropathic pain. Inducible knockdown of VEGFR2 (tamoxifen treated Tie2CreER T2 -vegfr2 flfl mice) led to a reduction in blood vessel network volume in the lumbar spinal cord and development of heat hyperalgesia. These findings indicate that hyperglycaemia leads to a reduction in the VEGF-A/VEGFR2 signalling cascade resulting in endothelial dysfunction in the spinal cord, which could be an undiscovered contributing factor to diabetic neuropathic pain. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Plasticity in reflex pathways to the lower urinary tract following spinal cord injury

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2013-01-01

The lower urinary tract has two main functions, storage and periodic expulsion of urine, that are regulated by a complex neural control system in the brain and lumbosacral spinal cord. This neural system coordinates the activity of two functional units in the lower urinary tract: (1) a reservoir (the urinary bladder) and (2) an outlet (consisting of bladder neck, urethra and striated muscles of the external urethra sphincter). During urine storage the outlet is closed and the bladder is quiescent to maintain a low intravesical pressure. During micturition the outlet relaxes and the bladder contracts to promote efficient release of urine. This reciprocal relationship between bladder and outlet is generated by reflex circuits some of which are under voluntary control. Experimental studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through a coordination center (the pontine micturition center) located in the rostral brainstem. This reflex pathway is in turn modulated by higher centers in the cerebral cortex that are involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary control of voiding as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. However the bladder does not empty efficiently because coordination between the bladder and urethral outlet is lost. Studies in animals indicate that dysfunction of the lower urinary tract after spinal cord injury is dependent in part on plasticity of bladder afferent pathways as well as reorganization of synaptic connections in the spinal cord. Reflex plasticity is associated with changes in the properties of ion channels and electrical excitability of afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and/or the peripheral target organs. PMID:21596038

Synthesis of the natural product building block 5-(3-bromophenyl)-4-hydroxy-5-methylhexan-2-one and its chiral characterization by using chiroptical spectroscopy.

PubMed

De Gussem, Ewoud; Cornelus, Jelle; Pieters, Sam; Van den Bossche, Dries; Van der Eycken, Johan; Herrebout, Wouter; Bultinck, Patrick

2013-10-07

The absolute configuration of 5-(3-bromophenyl)-4-hydroxy-5-methylhexan-2-one, an intermediate in the synthesis of various natural products, is assigned by using vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and optical rotatory dispersion (ORD). Experimental spectra were compared to density functional theory (DFT) calculations of the molecule with known configuration. These three techniques independently confirm that the absolute configuration is (S)-5-(3-bromophenyl)-4-hydroxy-5-methylhexan-2-one, thus enabling us to assign the absolute configuration with high reliability. The reliability of the VCD analysis was assessed quantitatively by using the CompareVOA program. We found that, in cases in which the agreement between theory and experiment was very good, a value of 10 cm(-1) for the triangular weighting function gave a more-realistic discriminative power between enantiomers than the default value of 20 cm(-1). Copyright © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Helical Inversion of Gel Fibrils by Elongation of Perfluoroalkyl Chains as Studied by Vibrational Circular Dichroism.

PubMed

Sato, Hisako; Yajima, Tomoko; Yamagishi, Akihiko

2016-05-01

Vibrational circular dichroism (VCD) spectroscopy was applied to gelation by a chiral low-molecular mass weight gelator, N,N'-diperfluoroalkanoyl-1,2-trans-diaminocyclohexane. Attention was focused on the winding effects of (-CF2 )n chains on the gelating ability. For this purpose, a series of gelators were synthesized with perfluoroalkyl chains of different length (n = 6-8). When gelation was studied using acetonitrile as a solvent, the fibrils took different morphologies, depending on the chain length: twisted saddle-like ribbon or helical ribbon from fibril (n = 6) and a helical ribbon from platelet (n = 8). The signs of VCD peaks assigned to the couplet of C=O stretching and to the C-F stretching were also dependent on n, indicating that a gelator molecule changed conformation on elongating perfluoroalkyl chains. A model is proposed for the aggregation modes in fibrils. Chirality 28:361-364, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A Community Perspective on Bowel Management and Quality of Life after Spinal Cord Injury: The Influence of Autonomic Dysreflexia.

PubMed

Inskip, Jessica A; Lucci, Vera-Ellen M; McGrath, Maureen S; Willms, Rhonda; Claydon, Victoria E

2018-05-01

Autonomic dysfunction is common in individuals with spinal cord injury (SCI) and leads to numerous abnormalities, including profound cardiovascular and bowel dysfunction. In those with high-level lesions, bowel management is a common trigger for autonomic dysreflexia (AD; hypertension provoked by sensory stimuli below the injury level). Improving bowel care is integral for enhancing quality of life (QoL). We aimed to describe the relationships between bowel care, AD, and QoL in individuals with SCI. We performed an online community survey of individuals with SCI. Those with injury at or above T7 were considered at risk for AD. Responses were received from 287 individuals with SCI (injury levels C1-sacral and average duration of injury 17.1 ± 12.9 [standard deviation] years). Survey completion rate was 73% (n = 210). Bowel management was a problem for 78%: it interfered with personal relationships (60%) and prevented staying (62%) and working (41%) away from home. The normal bowel care duration was >60 min in 24% and most used digital rectal stimulation (59%); 33% reported bowel incontinence at least monthly. Of those at risk for AD (n = 163), 74% had AD symptoms during bowel care; 32% described palpitations. AD interfered with activities of daily living in 51%. Longer durations of bowel care (p < 0.001) and more severe AD (p = 0.04) were associated with lower QoL. Bowel management is a key concern for individuals with SCI and is commonly associated with symptoms of AD. Further studies should explore ways to manage bowel dysfunction, increase self-efficacy, and ameliorate the impact of AD to improve QoL.

The Vocal Cord Dysfunction Questionnaire: Validity and Reliability of the Persian Version.

PubMed

Ghaemi, Hamide; Khoddami, Seyyedeh Maryam; Soleymani, Zahra; Zandieh, Fariborz; Jalaie, Shohreh; Ahanchian, Hamid; Khadivi, Ehsan

2017-12-25

The aim of this study was to develop, validate, and assess the reliability of the Persian version of Vocal Cord Dysfunction Questionnaire (VCDQ P ). The study design was cross-sectional or cultural survey. Forty-four patients with vocal fold dysfunction (VFD) and 40 healthy volunteers were recruited for the study. To assess the content validity, the prefinal questions were given to 15 experts to comment on its essential. Ten patients with VFD rated the importance of VCDQ P in detecting face validity. Eighteen of the patients with VFD completed the VCDQ 1 week later for test-retest reliability. To detect absolute reliability, standard error of measurement and smallest detected change were calculated. Concurrent validity was assessed by completing the Persian Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) by 34 patients with VFD. Discriminant validity was measured from 34 participants. The VCDQ was further validated by administering the questionnaire to 40 healthy volunteers. Validation of the VCDQ as a treatment outcome tool was conducted in 18 patients with VFD using pre- and posttreatment scores. The internal consistency was confirmed (Cronbach α = 0.78). The test-retest reliability was excellent (intraclass correlation coefficient = 0.97). The standard error of measurement and smallest detected change values were acceptable (0.39 and 1.08, respectively). There was a significant correlation between the VCDQ P and the CAT total scores (P < 0.05). Discriminative validity was significantly different. The VCDQ scores in patients with VFD before and after treatment was significantly different (P < 0.001). The VCDQ was cross-culturally adapted to Persian and demonstrated to be a valid and reliable self-administered questionnaire in Persian-speaking population. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Assessments of sensory plasticity after spinal cord injury across species.

PubMed

Haefeli, Jenny; Huie, J Russell; Morioka, Kazuhito; Ferguson, Adam R

2017-06-23

Spinal cord injury (SCI) is a multifaceted phenomenon associated with alterations in both motor function and sensory function. A majority of patients with SCI report sensory disturbances, including not only loss of sensation, but in many cases enhanced abnormal sensation, dysesthesia and pain. Development of therapeutics to treat these abnormal sensory changes require common measurement tools that can enable cross-species translation from animal models to human patients. We review the current literature on translational nociception/pain measurement in SCI and discuss areas for further development. Although a number of tools exist for measuring both segmental and affective sensory changes, we conclude that there is a pressing need for better, integrative measurement of nociception/pain outcomes across species to enhance precise therapeutic innovation for sensory dysfunction in SCI. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Methane ameliorates spinal cord ischemia-reperfusion injury in rats: Antioxidant, anti-inflammatory and anti-apoptotic activity mediated by Nrf2 activation.

PubMed

Wang, Liping; Yao, Ying; He, Rong; Meng, Yan; Li, Na; Zhang, Dan; Xu, Jiajun; Chen, Ouyang; Cui, Jin; Bian, Jinjun; Zhang, Yan; Chen, Guozhong; Deng, Xiaoming

2017-02-01

Methane is reported to have antioxidant, anti-inflammatory and anti-apoptotic properties. We investigated the potential neuroprotective effects of methane-rich saline (MS) on spinal cord ischemia-reperfusion injury and determined that its therapeutic benefits are associated with the activation of nuclear factor erythroid 2-related factor 2 (Nrf2). Rats received 9min of spinal cord ischemia induced by occlusion of the descending thoracic aorta plus systemic hypotension followed by a single MS treatment (10ml/kg, ip) and 72h reperfusion. MS treatment attenuated motor sensory deficits and produced high concentrations of methane in spinal cords during reperfusion, which increased Nrf2 expression and transcriptional activity in neurons, microglia and astrocytes in the ventral, intermediate and dorsal gray matter of lumbar segments. Heme oxygenase-1, superoxide dismutase, catalase and glutathione were upregulated; and glutathione disulfide, superoxide, hydrogen peroxide, malondialdehyde, 8-hydroxy-2-deoxyguanosine and 3-nitrotyrosine were downregulated in MS-treated spinal cords. MS treatment reduced neuronal apoptosis in gray matter zones, which was consistent with the suppression of cytochrome c release to the cytosol from the mitochondria and the activation of caspase-9 and -3. Throughout the gray matter, the activation of microglia and astrocytes was inhibited; the nuclear accumulation of phosphorylated nuclear factor-kappa B p65 was reduced; and tumor necrosis factor α, interleukin 1β, chemokine (C-X-C motif) ligand 1, intercellular adhesion molecule 1 and myeloperoxidase were decreased. MS treatment attenuated blood-spinal cord barrier dysfunction by preventing the expression and activity of matrix metallopeptidase-9 and disrupting tight junction proteins. Consecutive intrathecal injection of specific siRNAs targeting Nrf2 at 24-h intervals 3 days before ischemia reduced the beneficial effects of MS. Our data indicate that MS treatment prevents IR-induced spinal cord damage via antioxidant, anti-inflammatory and anti-apoptotic activities that involve the activation of Nrf2 signaling. Thus, methane may serve as a novel promising therapeutic agent for treating ischemic spinal cord injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Inflammatory cascades mediate synapse elimination in spinal cord compression

PubMed Central

2014-01-01

Background Cervical compressive myelopathy (CCM) is caused by chronic spinal cord compression due to spondylosis, a degenerative disc disease, and ossification of the ligaments. Tip-toe walking Yoshimura (twy) mice are reported to be an ideal animal model for CCM-related neuronal dysfunction, because they develop spontaneous spinal cord compression without any artificial manipulation. Previous histological studies showed that neurons are lost due to apoptosis in CCM, but the mechanism underlying this neurodegeneration was not fully elucidated. The purpose of this study was to investigate the pathophysiology of CCM by evaluating the global gene expression of the compressed spinal cord and comparing the transcriptome analysis with the physical and histological findings in twy mice. Methods Twenty-week-old twy mice were divided into two groups according to the magnetic resonance imaging (MRI) findings: a severe compression (S) group and a mild compression (M) group. The transcriptome was analyzed by microarray and RT-PCR. The cellular pathophysiology was examined by immunohistological analysis and immuno-electron microscopy. Motor function was assessed by Rotarod treadmill latency and stride-length tests. Results Severe cervical calcification caused spinal canal stenosis and low functional capacity in twy mice. The microarray analysis revealed 215 genes that showed significantly different expression levels between the S and the M groups. Pathway analysis revealed that genes expressed at higher levels in the S group were enriched for terms related to the regulation of inflammation in the compressed spinal cord. M1 macrophage-dominant inflammation was present in the S group, and cysteine-rich protein 61 (Cyr61), an inducer of M1 macrophages, was markedly upregulated in these spinal cords. Furthermore, C1q, which initiates the classical complement cascade, was more upregulated in the S group than in the M group. The confocal and electron microscopy observations indicated that classically activated microglia/macrophages had migrated to the compressed spinal cord and eliminated synaptic terminals. Conclusions We revealed the detailed pathophysiology of the inflammatory response in an animal model of chronic spinal cord compression. Our findings suggest that complement-mediated synapse elimination is a central mechanism underlying the neurodegeneration in CCM. PMID:24589419

Brain and spinal cord interaction: a dietary curcumin derivative counteracts locomotor and cognitive deficits after brain trauma.

PubMed

Wu, Aiguo; Ying, Zhe; Schubert, David; Gomez-Pinilla, Fernando

2011-05-01

In addition to cognitive dysfunction, locomotor deficits are prevalent in traumatic brain injured (TBI) patients; however, it is unclear how a concussive injury can affect spinal cord centers. Moreover, there are no current efficient treatments that can counteract the broad pathology associated with TBI. The authors have investigated potential molecular basis for the disruptive effects of TBI on spinal cord and hippocampus and the neuroprotection of a curcumin derivative to reduce the effects of experimental TBI. The authors performed fluid percussion injury (FPI) and then rats were exposed to dietary supplementation of the curcumin derivative (CNB-001; 500 ppm). The curry spice curcumin has protective capacity in animal models of neurodegenerative diseases, and the curcumin derivative has enhanced brain absorption and biological activity. The results show that FPI in rats, in addition to reducing learning ability, reduced locomotor performance. Behavioral deficits were accompanied by reductions in molecular systems important for synaptic plasticity underlying behavioral plasticity in the brain and spinal cord. The post-TBI dietary supplementation of the curcumin derivative normalized levels of BDNF, and its downstream effectors on synaptic plasticity (CREB, synapsin I) and neuronal signaling (CaMKII), as well as levels of oxidative stress-related molecules (SOD, Sir2). These studies define a mechanism by which TBI can compromise centers related to cognitive processing and locomotion. The findings also show the influence of the curcumin derivative on synaptic plasticity events in the brain and spinal cord and emphasize the therapeutic potential of this noninvasive dietary intervention for TBI.

Lower urinary tract and sexual dysfunction in neurological patients.

PubMed

Vodušek, David B

2014-01-01

Lower urinary tract dysfunction (LUTD) and sexual dysfunction (SD) are common in neurological patients due to a combination of lesions affecting relevant neural control, constraints imposed by sensorimotor and cognitive deficits and--particularly for SD--psychosocial consequences of chronic neurological disease. This review summarizes the etiology, diagnosis and treatment of LUTD and SD in neurological patients. LUTD may lead to serious health problems; both LUTD and SD significantly affect quality of life. Management of patients with spinal cord injury and dysraphism is undertaken in specialized centers according to established guidelines. Treatment of neurological patients with noncomplicated neurogenic LUTD or SD should preferentially be guided by a neurologist. For rational treatment of urinary symptoms, an accurate assessment is mandatory; the bladder and the sphincter need to be defined as normal, over- or underactive. Urodynamic testing is the gold standard for functional diagnosis; assessment of residual urine and uroflow are the minimal requirements before considering management. Dysfunction of desire, arousal and orgasm (ejaculation) may be diagnosed by medical history and are amenable to counselling and treatment, which is--in the case of erectile dysfunction--evidence based. Further high-quality studies are necessary to test the best approaches for diagnosing and managing particular types of neurogenic LUTD and SD in the different neurological patient populations. © 2014 S. Karger AG, Basel.

Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury.

PubMed

Kabu, Shushi; Gao, Yue; Kwon, Brian K; Labhasetwar, Vinod

2015-12-10

Spinal cord injury (SCI) results in devastating neurological and pathological consequences, causing major dysfunction to the motor, sensory, and autonomic systems. The primary traumatic injury to the spinal cord triggers a cascade of acute and chronic degenerative events, leading to further secondary injury. Many therapeutic strategies have been developed to potentially intervene in these progressive neurodegenerative events and minimize secondary damage to the spinal cord. Additionally, significant efforts have been directed toward regenerative therapies that may facilitate neuronal repair and establish connectivity across the injury site. Despite the promise that these approaches have shown in preclinical animal models of SCI, challenges with respect to successful clinical translation still remain. The factors that could have contributed to failure include important biologic and physiologic differences between the preclinical models and the human condition, study designs that do not mirror clinical reality, discrepancies in dosing and the timing of therapeutic interventions, and dose-limiting toxicity. With a better understanding of the pathobiology of events following acute SCI, developing integrated approaches aimed at preventing secondary damage and also facilitating neuroregenerative recovery is possible and hopefully will lead to effective treatments for this devastating injury. The focus of this review is to highlight the progress that has been made in drug therapies and delivery systems, and also cell-based and tissue engineering approaches for SCI. Copyright © 2015 Elsevier B.V. All rights reserved.

The excitatory amino acid receptor antagonist MK-801 prevents the hypersensitivity induced by spinal cord ischemia in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hao, J.X.; Xu, X.J.; Aldskogius, H.

1991-08-01

Protection by the NMDA receptor antagonist MK-801 against transient spinal cord ischemia-induced hypersensitivity was studied in rats. The spinal ischemia was initiated by vascular occlusion resulting from the interaction between the photosensitizing dye Erythrosin B and an argon laser beam. The hypersensitivity, termed allodynia, where the animals reacted by vocalization to nonnoxious mechanical stimuli in the flank area, was consistently observed during several days after induction of the ischemia. Pretreatment with MK-801 (0.1-0.5 mg/kg, iv) 10 min before laser irradiation dose dependently prevented the occurrence of allodynia. The neuroprotective effect of MK-801 was not reduced by maintaining normal body temperaturemore » during and after irradiation. There was a significant negative correlation between the delay in the administration of MK-801 after irradiation and the protective effect of the drug. Histological examination revealed slight morphological damage in the spinal cord in 38% of control rats after 1 min of laser irradiation without pretreatment with MK-801. No morphological abnormalities were observed in rats after pretreatment with MK-801 (0.5 mg/kg). The present results provide further evidence for the involvement of excitatory amino acids, through activation of the NMDA receptor, in the development of dysfunction following ischemic trauma to the spinal cord.« less

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL): assessment of the involved white matter tracts by MRI.

PubMed

Kassem, Hassan; Wafaie, Ahmed; Abdelfattah, Sherif; Farid, Tarek

2014-01-01

Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is a recently identified autosomal recessive disorder with early onset of symptoms and slowly progressive pyramidal, cerebellar and dorsal column dysfunction. LBSL is characterized by distinct white matter abnormalities and selective involvement of brainstem and spinal cord tracts. The purpose of this study is to assess the imaging features of the involved white matter tracts in cases of LBSL by MRI. We retrospectively reviewed the imaging features of the selectively involved white matter tracts in sixteen genetically proven cases of leukoencephalopathy with brainstem and spinal cord involvement and elevated brain lactate (LBSL). All patients presented with slowly progressive cerebellar sensory ataxia with spasticity and dorsal column dysfunction. MRI of the brain and spine using 1.5 T machine and proton magnetic resonance spectroscopy (1H MRS) on the abnormal white matter were done to all patients. The MRI and MRS data sets were analyzed according to lesion location, extent, distribution and signal pattern as well as metabolite values and ratios in MRS. Laboratory examinations ruled out classic leukodystrophies. In all cases, MRI showed high signal intensity in T2-weighted and FLAIR images within the cerebral subcortical, periventricular and deep white matter, posterior limbs of internal capsules, centrum semiovale, medulla oblongata, intraparenchymal trajectory of trigeminal nerves and deep cerebellar white matter. In the spine, the signal intensity of the dorsal column and lateral cortico-spinal tracts were altered in all patients. The subcortical U fibers, globi pallidi, thalami, midbrain and transverse pontine fibers were spared in all cases. In 11 cases (68.8%), the signal changes were inhomogeneous and confluent whereas in 5 patients (31.2%), the signal abnormalities were spotty. MRI also showed variable signal abnormalities in the sensory and pyramidal tracts in addition to the brainstem and cerebellar connections. Proton MRS showed consistent elevation of the lactate within the abnormal white matter. Distinct MRI findings in the form of selective affection of subcortical and deep white matter tracts of the brain (involving the posterior limb of internal capsules and sparing the subcortical U fibers), dorsal column and lateral cortico-spinal tracts of the spinal cord should lead to the diagnosis of LBSL supported by the presence of lactate peak in 1H MRS. The disease can be confirmed by the analysis of the disease gene DARS2.

U.S. EPA, Pesticide Product Label, RCI CHLOROPHEN 49-411, 10/05/1972

EPA Pesticide Factsheets

2011-04-14

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Neurogenic Causes of Detrusor Underactivity

PubMed Central

Kadow, Brian T.; Tyagi, Pradeep; Chermansky, Christopher J.

2015-01-01

Detrusor underactivity (DU) is a poorly understood dysfunction of the lower urinary tract which arises from multiple etiologies. Symptoms of DU are non-specific, and a pressure-flow urodynamic study is necessary to differentiate DU from other conditions such as overactive bladder (OAB) or bladder outlet obstruction (BOO). The prevalence of DU ranges from 10–48%, and DU is most prevalent in elderly males. The pathophysiology underlying DU can be from both neurogenic and non-neurogenic causes. In this article, we review the neurogenic causes of detrusor underactivity, including diabetic bladder dysfunction, spinal cord injury, multiple sclerosis, Parkinson’s disease, cerebrovascular accident, traumatic brain injury, and Fowler’s syndrome. As knowledge about the underlying causes of DU advances, there have been several potential therapeutic approaches proposed to help those who suffer from this condition. PMID:26715948

Calcineurin Dysregulation Underlies Spinal Cord Injury-Induced K+ Channel Dysfunction in DRG Neurons.

PubMed

Zemel, Benjamin M; Muqeem, Tanziyah; Brown, Eric V; Goulão, Miguel; Urban, Mark W; Tymanskyj, Stephen R; Lepore, Angelo C; Covarrubias, Manuel

2017-08-23

Dysfunction of the fast-inactivating Kv3.4 potassium current in dorsal root ganglion (DRG) neurons contributes to the hyperexcitability associated with persistent pain induced by spinal cord injury (SCI). However, the underlying mechanism is not known. In light of our previous work demonstrating modulation of the Kv3.4 channel by phosphorylation, we investigated the role of the phosphatase calcineurin (CaN) using electrophysiological, molecular, and imaging approaches in adult female Sprague Dawley rats. Pharmacological inhibition of CaN in small-diameter DRG neurons slowed repolarization of the somatic action potential (AP) and attenuated the Kv3.4 current. Attenuated Kv3.4 currents also exhibited slowed inactivation. We observed similar effects on the recombinant Kv3.4 channel heterologously expressed in Chinese hamster ovary cells, supporting our findings in DRG neurons. Elucidating the molecular basis of these effects, mutation of four previously characterized serines within the Kv3.4 N-terminal inactivation domain eliminated the effects of CaN inhibition on the Kv3.4 current. SCI similarly induced concurrent Kv3.4 current attenuation and slowing of inactivation. Although there was little change in CaN expression and localization after injury, SCI induced upregulation of the native regulator of CaN 1 (RCAN1) in the DRG at the transcript and protein levels. Consistent with CaN inhibition resulting from RCAN1 upregulation, overexpression of RCAN1 in naive DRG neurons recapitulated the effects of pharmacological CaN inhibition on the Kv3.4 current and the AP. Overall, these results demonstrate a novel regulatory pathway that links CaN, RCAN1, and Kv3.4 in DRG neurons. Dysregulation of this pathway might underlie a peripheral mechanism of pain sensitization induced by SCI. SIGNIFICANCE STATEMENT Pain sensitization associated with spinal cord injury (SCI) involves poorly understood maladaptive modulation of neuronal excitability. Although central mechanisms have received significant attention, recent studies have identified peripheral nerve hyperexcitability as a driver of persistent pain signaling after SCI. However, the ion channels and signaling molecules responsible for this change in primary sensory neuron excitability are still not well defined. To address this problem, this study used complementary electrophysiological and molecular methods to determine how Kv3.4, a voltage-gated K + channel robustly expressed in dorsal root ganglion neurons, becomes dysfunctional upon calcineurin (CaN) inhibition. The results strongly suggest that CaN inhibition underlies SCI-induced dysfunction of Kv3.4 and the associated excitability changes through upregulation of the native regulator of CaN 1 (RCAN1). Copyright © 2017 the authors 0270-6474/17/378257-17$15.00/0.

Neuroprosthetics and Solutions for Spinal Cord Dysfunctions

DTIC Science & Technology

2012-08-01

SSNI. 0 1 2 3 4 5 60 0.2 0.4 0.6 0.8 1 Stimulus amplitude (µA) P( rec rui tin g a t le ast n ne uro ns ) P(n=0|I) P(n=1|I) P(n=2|I) P(n=3|I) P(n=4|I...Annual Fall Meeting. Los Angeles, CA: 2007. 15 Bourbeau DJ, Hokanson J, Weber DJ. (2008). A computational model for examining activation of peripheral

A quadriplegic patient's cholescintigraphic findings: delayed gallbladder visualization and common bile duct dilation.

PubMed Central

Shih, W. J.; Magoun, S.; Lu, G.

1996-01-01

A Tc-99m DISIDA cholescintigraphic study of a 37-year-old patient with a 20-year history of quadriplegia demonstrated dilation of the common bile duct and delayed gallbladder visualization. A concurrent sonographic study showed an enlarged gallbladder with stones and dilation of the common bile duct. These findings were proved by autopsy. Quadriplegia secondary to a high level of spinal cord injury may result in gallbladder dysfunction. Images Figure PMID:8776068

[Oswald Schwarz: a pioneer in psychosomatic urology and sexual medicine].

PubMed

Berberich, H J; Schultheiss, D; Kieser, B

2015-01-01

Oswald Schwarz, a urologist from Vienna, was a scholar of Anton Ritter von Frisch and Hans Rubritius. As a physician during World War I, he was confronted with numerous bullet wounds to the spinal cord. In 1919, he completed his professorial thesis"Bladder dysfunction as a result of bullet wounds to the spinal cord". Oswald Schwarz was known as a committed surgeon. As an urologist he also treated patients with sexual dysfunction. Besides his practical and scientific urology-related work, he was also interested in psychology and philosophy. He held lectures on both subjects earning himself the nickname, the Urosoph. In the 1920s, Oswald Schwarz belonged to the inner circle of Alfred Adler, the founder of Individual Psychology, and was editor of the first psychosomatic textbook published in German, "Psychological origin and psychotherapy of physical symptoms" (1925). In addition, Schwarz wrote numerous articles and several books on sexual medicine. He also made many valuable contributions to the development of medical anthropology. Altogether, his work includes over 130 publications. Faced with the rise of fascism and National Socialism in Europe, Oswald Schwarz, who was of Jewish origin, emigrated to England in 1934. There he died in 1949. Unfortunately his scientific work has largely been forgotten. The aim of the following article is to remind us of his important contributions to the field.

Sexual concerns after Spinal Cord Injury: An update on management.

PubMed

Alexander, Marcalee Sipski; Aisen, Carrie Mlynarczyk; Alexander, Sterling Morrison; Aisen, Mindy Lipson

2017-01-01

Spinal Cord Injury (SCI) causes neurological impairment with resultant neurogenic sexual dysfunction which can compound preexisting psychological and medical sexual concerns. Understanding these concerns is important in managing the lifelong needs of persons with SCIs. To provide an overview of the impact of SCI on sexuality along with a framework for treatment of sexual concerns. To briefly review male infertility and its treatments and pregnancy in females after SCI. Interdisciplinary literature review and synthesis of information. The average age at SCI is increased, thus persons with SCIs may have preexisting sexual concerns. Sexual activity and satisfaction are decreased after SCI. Psychogenic sexual arousal is related to remaining sensation in the T11-L2 dermatomes. Orgasm occurs in approximately 50% of persons with SCIs with all injuries except subjects with complete lower motor neuron (LMN) injuries affecting the lowest sacral segments A structured approach to treatment including assessing preinjury function, determining the impact of injury, education, assessing and treating iatrogenic sexual dysfunction and treatment of concomitant problems is recommended. Basic and advanced methods to improve sexual arousal and orgasm are discussed and treatment of anejaculation and issues associated with pregnancy and SCI are reviewed. Sexual satisfaction is impaired after SCI; however, education and new therapies can improve responsiveness. Future research is warranted to improve sexual function and fertility potential in persons with SCIs.

Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case with distinct MRI findings.

PubMed

Uluc, Kayihan; Baskan, Ozdil; Yildirim, Kadriye Agan; Ozsahin, Selda; Koseoglu, Mesrure; Isak, Baris; Scheper, G C; Gunal, Dilek Ince; van der Knaap, M S

2008-10-15

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a recently described disorder with autosomal recessive mode of inheritance. Lately, mutations in the DARS2 gene, which encodes mitochondrial aspartyl-tRNA synthetase, have been found as the underlying defect. We report a 19-year-old male patient with cerebellar, pyramidal and dorsal column dysfunctions and specific magnetic resonance imaging (MRI) and characteristic magnetic resonance spectroscopy (MRS) abnormalities. The patient was compound-heterozygous for two mutations in DARS2. MRI showed selective involvement of cerebral and cerebellar white matter and superior and inferior cerebellar peduncles, without contrast enhancement. The U-fibers were spared. The sensory and the pyramidal tracts were affected over their entire length. Involvement of the intraparenchymal trajectories of the trigeminal nerves and mesencephalic trigeminal tracts was demonstrated. In the spinal cord, signal abnormalities were identified in the dorsal columns and the lateral corticospinal tracts. Proton-MRS of the frontal and cerebellar white matter showed elevated lactate, reduced N-acetylaspartate, increased myoinositol and mildly elevated choline. In LBSL, distinct MRI findings should lead to the diagnosis, which can be confirmed by the analysis of the disease gene DARS2.

Gestational diabetes mellitus alters maternal and neonatal circulating endothelial progenitor cell subsets.

PubMed

Acosta, Juan C; Haas, David M; Saha, Chandan K; Dimeglio, Linda A; Ingram, David A; Haneline, Laura S

2011-03-01

The purpose of this study was to examine whether women with gestational diabetes mellitus (GDM) and their offspring have reduced endothelial progenitor cell subsets and vascular reactivity. Women with GDM, healthy control subjects, and their infants participated. Maternal blood and cord blood were assessed for colony-forming unit-endothelial cells and endothelial progenitor cell subsets with the use of polychromatic flow cytometry. Cord blood endothelial colony-forming cells were enumerated. Vascular reactivity was tested by laser Doppler imaging. Women with GDM had fewer CD34, CD133, CD45, and CD31 cells (circulating progenitor cells [CPCs]) at 24-32 weeks' gestation and 1-2 days after delivery, compared with control subjects. No differences were detected in colony-forming unit-endothelial cells or colony-forming unit-endothelial cells. In control subjects, CPCs were higher in the third trimester, compared with the postpartum period. Cord blood from GDM pregnancies had reduced CPCs. Vascular reactivity was not different between GDM and control subjects. The normal physiologic increase in CPCs during pregnancy is impaired in women with GDM, which may contribute to endothelial dysfunction and GDM-associated morbidities. Copyright © 2011 Mosby, Inc. All rights reserved.

Therapeutic Hypothermia in Spinal Cord Injury: The Status of Its Use and Open Questions.

PubMed

Wang, Jiaqiong; Pearse, Damien D

2015-07-24

Spinal cord injury (SCI) is a major health problem and is associated with a diversity of neurological symptoms. Pathophysiologically, dysfunction after SCI results from the culmination of tissue damage produced both by the primary insult and a range of secondary injury mechanisms. The application of hypothermia has been demonstrated to be neuroprotective after SCI in both experimental and human studies. The myriad of protective mechanisms of hypothermia include the slowing down of metabolism, decreasing free radical generation, inhibiting excitotoxicity and apoptosis, ameliorating inflammation, preserving the blood spinal cord barrier, inhibiting astrogliosis, promoting angiogenesis, as well as decreasing axonal damage and encouraging neurogenesis. Hypothermia has also been combined with other interventions, such as antioxidants, anesthetics, alkalinization and cell transplantation for additional benefit. Although a large body of work has reported on the effectiveness of hypothermia as a neuroprotective approach after SCI and its application has been translated to the clinic, a number of questions still remain regarding its use, including the identification of hypothermia's therapeutic window, optimal duration and the most appropriate rewarming rate. In addition, it is necessary to investigate the neuroprotective effect of combining therapeutic hypothermia with other treatment strategies for putative synergies, particularly those involving neurorepair.

Neurogenic bowel management after spinal cord injury: Malaysian experience.

PubMed

Engkasan, Julia Patrick; Sudin, Siti Suhaida

2013-02-01

To describe the bowel programmes utilized by individuals with spinal cord injury; and to determine the association between the outcome of the bowel programmes and various interventions to facilitate defecation. A cross-sectional study. Individuals with spinal cord injury who have neurogenic bowel dysfunction. Face-to-face interviews were conducted using a self-constructed questionnaire that consisted of: (i) demographic and clinical characteristics of the participants; (ii) interventions to facilitate defecation; (iii) bowel care practices; (iv) outcome of the bowel programme (incidence of incontinence and duration of the evacuation procedure); and (v) participant satisfaction with their bowel programme. The majority (79.2%) of subjects used multiple interventions for bowel care. Duration of the evacuation procedure was more than 60 min in 28.0% of participants. Water intake of more than 2 l/day was associated with longer duration of bowel care. Only 8.0% of participants had at least one episode of incontinence per month. The majority of participants (84.8%) were satisfied with their bowel programme. Patients used multiple interventions to manage their bowels and spent a substantial amount of time performing bowel care. Nevertheless, the incidence of incontinence was low and satisfaction with their bowel programme was high.

The crossed phrenic phenomenon

PubMed Central

Ghali, Michael George Zaki

2017-01-01

The cervical spine is the most common site of traumatic vertebral column injuries. Respiratory insufficiency constitutes a significant proportion of the morbidity burden and is the most common cause of mortality in these patients. In seeking to enhance our capacity to treat specifically the respiratory dysfunction following spinal cord injury, investigators have studied the “crossed phrenic phenomenon”, wherein contraction of a hemidiaphragm paralyzed by a complete hemisection of the ipsilateral cervical spinal cord above the phrenic nucleus can be induced by respiratory stressors and recovers spontaneously over time. Strengthening of latent contralateral projections to the phrenic nucleus and sprouting of new descending axons have been proposed as mechanisms contributing to the observed recovery. We have recently demonstrated recovery of spontaneous crossed phrenic activity occurring over minutes to hours in C1-hemisected unanesthetized decerebrate rats. The specific neurochemical and molecular pathways underlying crossed phrenic activity following injury require further clarification. A thorough understanding of these is necessary in order to develop targeted therapies for respiratory neurorehabilitation following spinal trauma. Animal studies provide preliminary evidence for the utility of neuropharmacological manipulation of serotonergic and adenosinergic pathways, nerve grafts, olfactory ensheathing cells, intraspinal microstimulation and a possible role for dorsal rhizotomy in recovering phrenic activity following spinal cord injury PMID:28761411

Thrombospondin-1 modified bone marrow mesenchymal stem cells (BMSCs) promote neurite outgrowth and functional recovery in rats with spinal cord injury

PubMed Central

Pu, Yujie; Meng, Ke; Gu, Chuanlong; Wang, Linlin; Zhang, Xiaoming

2017-01-01

Stem cell therapies are currently gaining momentum in the treatment of spinal cord injury (SCI). However, unsatisfied intrinsic neurite growth capacity constitutes significant obstacles for injured spinal cord repair and ultimately results in neurological dysfunction. The present study assessed the efficacy of thrombospondin-1 (TSP-1), a neurite outgrowth-promoting molecule, modified bone marrow mesenchymal stem cells (BMSCs) on promoting neurite outgrowth in vitro and in vivo of Oxygen–Glucose Deprivation (OGD) treated motor neurons and SCI rat models. The present results demonstrated that the treatment of BMSCs+TSP-1 could promote the neurite length, neuronal survival, and functional recovery after SCI. Additionally, TSP-1 could activate transforming growth factor-β1 (TGF-β1) then induced the smad2 phosphorylation, and expedited the expression of GAP-43 to promote neurite outgrowth. The present study for the first time demonstrated that BMSCs+TSP-1 could promote neurite outgrowth and functional recovery after SCI partly through the TGF-β1/p-Samd2 pathway. The study provided a novel encouraging evidence for the potential treatment of BMSCs modification with TSP-1 in patients with SCI. PMID:29221205

Dendritic spine remodeling following early and late Rac1 inhibition after spinal cord injury: evidence for a pain biomarker

PubMed Central

Zhao, Peng; Hill, Myriam; Liu, Shujun; Chen, Lubin; Bangalore, Lakshmi; Waxman, Stephen G.

2016-01-01

Neuropathic pain is a significant complication following spinal cord injury (SCI) with few effective treatments. Drug development for neuropathic pain often fails because preclinical studies do not always translate well to clinical conditions. Identification of biological characteristics predictive of disease state or drug responsiveness could facilitate more effective clinical translation. Emerging evidence indicates a strong correlation between dendritic spine dysgenesis and neuropathic pain. Because dendritic spines are located on dorsal horn neurons within the spinal cord nociceptive system, dendritic spine remodeling provides a unique opportunity to understand sensory dysfunction after SCI. In this study, we provide support for the postulate that dendritic spine profiles can serve as biomarkers for neuropathic pain. We show that dendritic spine profiles after SCI change to a dysgenic state that is characteristic of neuropathic pain in a Rac1-dependent manner. Suppression of the dysgenic state through inhibition of Rac1 activity is accompanied by attenuation of neuropathic pain. Both dendritic spine dysgenesis and neuropathic pain return when inhibition of Rac1 activity is lifted. These findings suggest the utility of dendritic spines as structural biomarkers for neuropathic pain. PMID:26936986

A Toll-Like Receptor 9 Antagonist Improves Bladder Function and White Matter Sparing in Spinal Cord Injury

PubMed Central

David, Brian T.; Sampath, Sujitha; Dong, Wei; Heiman, Adee; Rella, Courtney E.; Elkabes, Stella

2014-01-01

Abstract Spinal cord injury (SCI) affects motor, sensory, and autonomic functions. As current therapies do not adequately alleviate functional deficits, the development of new and more effective approaches is of critical importance. Our earlier investigations indicated that intrathecal administration of a toll-like receptor 9 (TLR9) antagonist, cytidine-phosphate-guanosine oligodeoxynucleotide 2088 (CpG ODN 2088), to mice sustaining a severe, mid-thoracic contusion injury diminished neuropathic pain but did not alter locomotor deficits. These changes were paralleled by a decrease in the pro-inflammatory response at the injury epicenter. Using the same SCI paradigm and treatment regimen, the current studies investigated the effects of the TLR9 antagonist on bladder function. We report that the TLR9 antagonist decreases SCI-elicited urinary retention and ameliorates bladder morphopathology without affecting kidney function. A significant improvement in white matter sparing was also observed, most likely due to alterations in the inflammatory milieu. These findings indicate that the TLR9 antagonist has beneficial effects not only in reducing sensory deficits, but also on bladder dysfunction and tissue preservation. Thus, modulation of innate immune receptor signaling in the spinal cord can impact the effects of SCI. PMID:24936867

A toll-like receptor 9 antagonist improves bladder function and white matter sparing in spinal cord injury.

PubMed

David, Brian T; Sampath, Sujitha; Dong, Wei; Heiman, Adee; Rella, Courtney E; Elkabes, Stella; Heary, Robert F

2014-11-01

Spinal cord injury (SCI) affects motor, sensory, and autonomic functions. As current therapies do not adequately alleviate functional deficits, the development of new and more effective approaches is of critical importance. Our earlier investigations indicated that intrathecal administration of a toll-like receptor 9 (TLR9) antagonist, cytidine-phosphate-guanosine oligodeoxynucleotide 2088 (CpG ODN 2088), to mice sustaining a severe, mid-thoracic contusion injury diminished neuropathic pain but did not alter locomotor deficits. These changes were paralleled by a decrease in the pro-inflammatory response at the injury epicenter. Using the same SCI paradigm and treatment regimen, the current studies investigated the effects of the TLR9 antagonist on bladder function. We report that the TLR9 antagonist decreases SCI-elicited urinary retention and ameliorates bladder morphopathology without affecting kidney function. A significant improvement in white matter sparing was also observed, most likely due to alterations in the inflammatory milieu. These findings indicate that the TLR9 antagonist has beneficial effects not only in reducing sensory deficits, but also on bladder dysfunction and tissue preservation. Thus, modulation of innate immune receptor signaling in the spinal cord can impact the effects of SCI.

Thiazide use is associated with reduced risk for incident lower extremity fractures in men with spinal cord injury.

PubMed

Carbone, Laura D; Chin, Amy S; Lee, Todd A; Burns, Stephen P; Svircev, Jelena N; Hoenig, Helen M; Bailey, Lauren; Weaver, Frances M

2014-06-01

To determine the association between thiazide use and lower extremity fractures in patients who are men with a spinal cord injury (SCI). Cohort study from fiscal years 2002 to 2007. Medical centers. Men (N=6969) with an SCI from the Veterans Affairs (VA) Spinal Cord Dysfunction (SCD) Registry, including 1433 users of thiazides and 5536 nonusers of thiazides. Thiazide use versus nonuse. Incident lower extremity fractures. Among the men, 21% in the VA SCD Registry (fiscal years 2002-2007) included in these analyses used thiazide diuretics. There were 832 incident lower extremity fractures over the time period of this study: 110 fractures (7.7%) in 1433 thiazide users and 722 fractures (13%) in 5536 nonusers of thiazides. In unadjusted and adjusted models alike, thiazide use was associated with at least a one-quarter risk reduction in lower extremity fracture at any given point in time (unadjusted: hazard ratio (HR)=.75; 95% confidence interval (CI), .59-.94; adjusted: HR=.74; 95% CI, .58-.95). Thiazide use is common in men with SCI and is associated with a decreased likelihood for lower extremity fractures. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Management and outcomes of spinal epidural hematoma during vertebroplasty: Case series.

PubMed

Fang, Miao; Zhou, Jiaojiao; Yang, Dongjun; He, Yu; Xu, Yong; Liu, Xin; Zeng, Yong

2018-05-01

Spinal cord injury (SCI) is one of the common complications of spinal surgery. There is no definite treatment and time of decompression for spinal cord induced by epidural hematoma during vertebroplasty. A total of 6 patients with SCI during vertebroplasty were included in our research. All of them occurred sensory disturbance and motor dysfunction due to a lower or same level operative vertebral body lesion in vertebroplasty. Neurological manifestations during vertebroplasty, postoperative magnetic resonance imaging and computed tomography. Once SCI occurred in vertebroplasty, four patients were underwent spinal cord decompression immediately, and two patients were done after 14 and 22 hours, respectively. Before decompression operation, one patient was Frankel A, three were Frankel B, and two were Frankel C. One day after evacuation of the SEH, three patients recovered to normal neurological function (Frankel E), one to Frankel C, and one to Frankel D, but the other one did not recover. At the last follow-up, five patients had recovered to Frankel E and one patient to Frankel D. According to our experience, when SCI occurs during vertebroplasty, neurological deficits are always secondary to acute SEH. Timely decompression, particularly transfer surgery, can shorten recovery time.

Delayed Unilateral Soft Palate Palsy without Vocal Cord Involvement after Microvascular Decompression for Hemifacial Spasm

PubMed Central

Park, Jae Han; Jo, Kyung Il

2013-01-01

Microvascular decompression is a very effective and relatively safe surgical modality in the treatment of hemifacial spasm. But rare debilitating complications have been reported such as cranial nerve dysfunctions. We have experienced a very rare case of unilateral soft palate palsy without the involvement of vocal cord following microvascular decompression. A 33-year-old female presented to our out-patient clinic with a history of left hemifacial spasm for 5 years. On postoperative 5th day, patient started to exhibit hoarsness with swallowing difficulty. Symptoms persisted despite rehabilitation. Various laboratory work up with magnetic resonance image showed no abnormal lesions. Two years after surgery patient showed complete recovery of unitaleral soft palate palsy. Various etiologies of unilateral soft palate palsy are reviewed as the treatment and prognosis differs greatly on the cause. Although rare, it is important to keep in mind that such complication could occur after microvascular decompression. PMID:24003372

Sudden death in Leigh syndrome: an autopsy case.

PubMed

Ventura, Francesco; Rocca, Gabriele; Gentile, Raffaella; De Stefano, Francesco

2012-09-01

The present report describes the sudden death of a 3-year-old female child who had been clinically diagnosed with Leigh syndrome.Leigh syndrome is a heterogeneous progressive neurodegenerative disorder, which is characterized by focal or bilateral lesions in the thalamus, basal ganglia, brainstem, cerebellum, and spinal cord. Affected patients exhibit a variable clinical picture that frequently includes psychomotor retardation or regression, recurrent episodes of vomiting, failure to thrive, and signs of brainstem and basal ganglia dysfunction.The child was found dead in bed. Autopsy described the presence of symmetrical, necrotizing lesions scattered within the basal ganglia, thalamus, diencephalon, brainstem, and spinal-cord gray matter and revealed the presence of gastric contents in the upper and lower airways. We report the results of genetic investigations and describe the histological and immunohistochemical features that confirmed the diagnosis. These findings suggest that Leigh syndrome should be regarded as predisposing children to sudden death, especially by asphyxia secondary to the neurological disorder.

Cord Blood Bisphenol A Levels and Reproductive and Thyroid Hormone Levels of Neonates: The Hokkaido Study on Environment and Children's Health.

PubMed

Minatoya, Machiko; Sasaki, Seiko; Araki, Atsuko; Miyashita, Chihiro; Itoh, Sachiko; Yamamoto, Jun; Matsumura, Toru; Mitsui, Takahiko; Moriya, Kimihiko; Cho, Kazutoshi; Morioka, Keita; Minakami, Hisanori; Shinohara, Nobuo; Kishi, Reiko

2017-10-01

Bisphenol A (BPA) is widely used and BPA exposure is nearly ubiquitous in developed countries. While animal studies have indicated adverse health effects of prenatal BPA exposure including reproductive dysfunction and thyroid function disruption possibly in a sex-specific manner, findings from epidemiologic studies have not been enough to prove these adverse effects. Given very limited research on human, the aim of this study was to investigate associations between cord blood BPA levels and reproductive and thyroid hormone levels of neonates and whether associations differed by neonate sex. The study population included 514 participants of the Hokkaido study recruited from 2002 to 2005 at one hospital in Sapporo, Japan. The BPA level in cord blood was determined by ID-LC/MS/MS, and the limit of quantification was 0.040 ng/ml. We measured nine types of reproductive hormone levels in cord blood, and thyroid hormone levels were obtained from neonate mass screening test data. There were 283 subjects, who had both BPA and hormone levels measurements, included for the final analyses. The geometric mean of cord blood BPA was 0.051 ng/ml. After adjustment, BPA level was negatively associated with prolactin (PRL) (β = -0.38). There was an interaction between infant sex and BPA levels on PRL; a weak negative association was found in boys (β = -0.12), whereas a weak positive association was found in girls (β = 0.14). BPA level showed weak positive association with testosterone, estradiol, and progesterone levels in boys. No association was found between BPA and thyroid hormone levels. Our findings suggested that fetal BPA levels might be associated with changes in certain reproductive hormone levels of neonates in a sex-specific manner, though further investigations are necessary.

Spinal cord injury and women's sexual life: case-control study.

PubMed

Merghati-Khoei, E; Emami-Razavi, S H; Bakhtiyari, M; Lamyian, M; Hajmirzaei, S; Ton-Tab Haghighi, S; Korte, J E; Maasoumi, R

2017-03-01

Study design :This is a case-control study. The objective of this study was to estimate the magnitude of association between spinal cord injury (SCI) and women's quality of sexual life and sexual function. This study was conducted in the Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran. From the referral university-based clinics, we used simple random sampling to recruit 62 women: 31 women with SCI and 31 women without SCI. Socio-demographic and reproductive traits questionnaire, Sexual Quality of life-Female (SQOL-F), Female Sexual Function Index (FSFI) and Spinal Cord Independence Measure (SCIM) were completed using telephone and face-to-face interviews in the cases and controls. After univariate analyses, multivariate linear and proportional odds regression models were conducted to investigate the relation between SCI and women's quality of sexual life, as well as sexual function. The mean age of cases and controls was 35.42±6.51 and 33.77±4.02 years. Most women were high school-educated and housewives. Adjusting for probable confounders, the proportional odds regression model showed a significant relationship between the spinal cord injury (AOR=4.2, 95% CI: 1.8-9.2), non-college-educated (AOR=3.1, 95% CI: 1.2-5.9) and employed (AOR=1.8, 95% CI: 1.1-1.8) variables and being in one of the moderate or poor quality of life classes. Scores of SQOL-F and FSFI domains, except satisfaction, were significantly worse in cases versus controls (P<0.001). Although our participants showed low sexual dysfunction, they tended to report moderate to poor quality of sexual life. Our findings support the implication that sexual rehabilitation must be provided for women with SCI soon after injury.

Human Glial-Restricted Progenitor Transplantation into Cervical Spinal Cord of the SOD1G93A Mouse Model of ALS

PubMed Central

Lepore, Angelo C.; O'Donnell, John; Kim, Andrew S.; Williams, Timothy; Tuteja, Alicia; Rao, Mahendra S.; Kelley, Linda L.; Campanelli, James T.; Maragakis, Nicholas J.

2011-01-01

Cellular abnormalities are not limited to motor neurons in amyotrophic lateral sclerosis (ALS). There are numerous observations of astrocyte dysfunction in both humans with ALS and in SOD1G93A rodents, a widely studied ALS model. The present study therapeutically targeted astrocyte replacement in this model via transplantation of human Glial-Restricted Progenitors (hGRPs), lineage-restricted progenitors derived from human fetal neural tissue. Our previous findings demonstrated that transplantation of rodent-derived GRPs into cervical spinal cord ventral gray matter (in order to target therapy to diaphragmatic function) resulted in therapeutic efficacy in the SOD1G93A rat. Those findings demonstrated the feasibility and efficacy of transplantation-based astrocyte replacement for ALS, and also show that targeted multi-segmental cell delivery to cervical spinal cord is a promising therapeutic strategy, particularly because of its relevance to addressing respiratory compromise associated with ALS. The present study investigated the safety and in vivo survival, distribution, differentiation, and potential efficacy of hGRPs in the SOD1G93A mouse. hGRP transplants robustly survived and migrated in both gray and white matter and differentiated into astrocytes in SOD1G93A mice spinal cord, despite ongoing disease progression. However, cervical spinal cord transplants did not result in motor neuron protection or any therapeutic benefits on functional outcome measures. This study provides an in vivo characterization of this glial progenitor cell and provides a foundation for understanding their capacity for survival, integration within host tissues, differentiation into glial subtypes, migration, and lack of toxicity or tumor formation. PMID:21998733

Evaluation of the thoraco-laryngeal reflex ('slap test') as an aid to the diagnosis of cervical spinal cord and brainstem disease in horses.

PubMed

Newton-Clarke, M J; Divers, T J; Delahunta, A; Mohammed, H O

1994-09-01

A study was conducted over a 12 month period to assess the specificity and sensitivity of the 'slap test', using endoscopic evaluation, in the detection of cervical spinal cord and caudal brainstem lesions in horses. Fifteen ataxic horses were subjected to the 'slap test' and subsequently examined post mortem. Twelve out of the 15 had histopathological lesions consistent with their clinical signs. Thirteen horses with no history of neurological dysfunction and no histopathological evidence of cervical spinal cord or brainstem disease were used as controls. The laryngeal adductory responses exhibited by all horses were filmed and later scored independently by 3 assessors. The proportion of animals diagnosed with cervical spinal cord and/or brainstem disease, defined by histopathological criteria, was found to be statistically similar to the proportion with abnormal 'slap test' responses, using the McNemar chi-Square test. Despite statistical significance between proportions, sensitivity of the 'slap test' was low, 50% for the left side on both days and 58% for the right side. Specificity was higher, 69% (Day 1) and 75% (Day 2) for the left side and 75% (Day 1) and 69% (Day 2) for the right side. In contrast to this, conventional neurological examination was found to be 100% sensitive and 81% specific in the detection of lesions of histopathological significance in the cervical spinal cord/caudal brainstem. Agreement between scores for the 'slap test' from the same assessor on different days was good, with values for kappa of 0.59 to 0.85. In contrast, agreement between assessors on the 'slap test' score was poor, with kappa 0.35.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrical stimulation and motor recovery.

PubMed

Young, Wise

2015-01-01

In recent years, several investigators have successfully regenerated axons in animal spinal cords without locomotor recovery. One explanation is that the animals were not trained to use the regenerated connections. Intensive locomotor training improves walking recovery after spinal cord injury (SCI) in people, and >90% of people with incomplete SCI recover walking with training. Although the optimal timing, duration, intensity, and type of locomotor training are still controversial, many investigators have reported beneficial effects of training on locomotor function. The mechanisms by which training improves recovery are not clear, but an attractive theory is available. In 1949, Donald Hebb proposed a famous rule that has been paraphrased as "neurons that fire together, wire together." This rule provided a theoretical basis for a widely accepted theory that homosynaptic and heterosynaptic activity facilitate synaptic formation and consolidation. In addition, the lumbar spinal cord has a locomotor center, called the central pattern generator (CPG), which can be activated nonspecifically with electrical stimulation or neurotransmitters to produce walking. The CPG is an obvious target to reconnect after SCI. Stimulating motor cortex, spinal cord, or peripheral nerves can modulate lumbar spinal cord excitability. Motor cortex stimulation causes long-term changes in spinal reflexes and synapses, increases sprouting of the corticospinal tract, and restores skilled forelimb function in rats. Long used to treat chronic pain, motor cortex stimuli modify lumbar spinal network excitability and improve lower extremity motor scores in humans. Similarly, epidural spinal cord stimulation has long been used to treat pain and spasticity. Subthreshold epidural stimulation reduces the threshold for locomotor activity. In 2011, Harkema et al. reported lumbosacral epidural stimulation restores motor control in chronic motor complete patients. Peripheral nerve or functional electrical stimulation (FES) has long been used to activate sacral nerves to treat bladder and pelvic dysfunction and to augment motor function. In theory, FES should facilitate synaptic formation and motor recovery after regenerative therapies. Upcoming clinical trials provide unique opportunities to test the theory.

Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury.

PubMed

Ryge, Jesper; Winther, Ole; Wienecke, Jacob; Sandelin, Albin; Westerdahl, Ann-Charlotte; Hultborn, Hans; Kiehn, Ole

2010-06-09

Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation of which potentially could be used to alter the transcriptional response to prevent the motor neurons from entering a state of hyper-excitability.

Accumulation of p62 in degenerated spinal cord under chronic mechanical compression: functional analysis of p62 and autophagy in hypoxic neuronal cells.

PubMed

Tanabe, Fumito; Yone, Kazunori; Kawabata, Naoya; Sakakima, Harutoshi; Matsuda, Fumiyo; Ishidou, Yasuhiro; Maeda, Shingo; Abematsu, Masahiko; Komiya, Setsuro; Setoguchi, Takao

2011-12-01

Intracellular accumulation of altered proteins, including p62 and ubiquitinated proteins, is the basis of most neurodegenerative disorders. The relationship among the accumulation of altered proteins, autophagy, and spinal cord dysfunction by cervical spondylotic myelopathy has not been clarified. We examined the expression of p62 and autophagy markers in the chronically compressed spinal cord of tiptoe-walking Yoshimura mice. In addition, we examined the expression and roles of p62 and autophagy in hypoxic neuronal cells. Western blot analysis showed the accumulation of p62, ubiquitinated proteins, and microtubule-associated protein 1 light chain 3 (LC3), an autophagic marker, in the compressed spinal cord. Immunohistochemical examinations showed that p62 accumulated in neurons, axons, astrocytes, and oligodendrocytes. Electron microscopy showed the expression of autophagy markers, including autolysosomes and autophagic vesicles, in the compressed spinal cord. These findings suggest the presence of p62 and autophagy in the degenerated compressed spinal cord. Hypoxic stress increased the expression of p62, ubiquitinated proteins, and LC3-II in neuronal cells. In addition, LC3 turnover assay and GFP-LC3 cleavage assay showed that hypoxic stress increased autophagy flux in neuronal cells. These findings suggest that hypoxic stress induces accumulation of p62 and autophagy in neuronal cells. The forced expression of p62 decreased the number of neuronal cells under hypoxic stress. These findings suggest that p62 accumulation under hypoxic stress promotes neuronal cell death. Treatment with 3-methyladenine, an autophagy inhibitor decreased the number of neuronal cells, whereas lithium chloride, an autophagy inducer increased the number of cells under hypoxic stress. These findings suggest that autophagy promotes neuronal cell survival under hypoxic stress. Our findings suggest that pharmacological inducers of autophagy may be useful for treating cervical spondylotic myelopathy patients.

Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury

PubMed Central

2010-01-01

Background Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. Results Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. Conclusions This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation of which potentially could be used to alter the transcriptional response to prevent the motor neurons from entering a state of hyper-excitability. PMID:20534130

Human umbilical cord plasma proteins revitalize hippocampal function in aged mice

PubMed Central

Castellano, Joseph M.; Mosher, Kira I.; Abbey, Rachelle J.; McBride, Alisha A.; James, Michelle L.; Berdnik, Daniela; Shen, Jadon C.; Zou, Bende; Xie, Xinmin S.; Tingle, Martha; Hinkson, Izumi V.; Angst, Martin S.; Wyss-Coray, Tony

2017-01-01

Ageing drives changes in neuronal and cognitive function, the decline of which is a major feature of many neurological disorders. The hippocampus, a brain region subserving roles of spatial and episodic memory and learning, is sensitive to the detrimental effects of ageing at morphological and molecular levels. With advancing age, synapses in various hippocampal subfields exhibit impaired long-term potentiation1, an electrophysiological correlate of learning and memory. At the molecular level, immediate early genes are among the synaptic plasticity genes that are both induced by long-term potentiation2, 3, 4 and downregulated in the aged brain5, 6, 7, 8. In addition to revitalizing other aged tissues9, 10, 11, 12, 13, exposure to factors in young blood counteracts age-related changes in these central nervous system parameters14, 15, 16, although the identities of specific cognition-promoting factors or whether such activity exists in human plasma remains unknown17. We hypothesized that plasma of an early developmental stage, namely umbilical cord plasma, provides a reservoir of such plasticity-promoting proteins. Here we show that human cord plasma treatment revitalizes the hippocampus and improves cognitive function in aged mice. Tissue inhibitor of metalloproteinases 2 (TIMP2), a blood-borne factor enriched in human cord plasma, young mouse plasma, and young mouse hippocampi, appears in the brain after systemic administration and increases synaptic plasticity and hippocampal-dependent cognition in aged mice. Depletion experiments in aged mice revealed TIMP2 to be necessary for the cognitive benefits conferred by cord plasma. We find that systemic pools of TIMP2 are necessary for spatial memory in young mice, while treatment of brain slices with TIMP2 antibody prevents long-term potentiation, arguing for previously unknown roles for TIMP2 in normal hippocampal function. Our findings reveal that human cord plasma contains plasticity-enhancing proteins of high translational value for targeting ageing- or disease-associated hippocampal dysfunction. PMID:28424512

Metabolite profile of a mouse model of Charcot–Marie–Tooth type 2D neuropathy: implications for disease mechanisms and interventions

PubMed Central

Bais, Preeti; Beebe, Kirk; Morelli, Kathryn H.; Currie, Meagan E.; Norberg, Sara N.; Evsikov, Alexei V.; Miers, Kathy E.; Seburn, Kevin L.; Guergueltcheva, Velina; Kremensky, Ivo; Jordanova, Albena; Bult, Carol J.

2016-01-01

ABSTRACT Charcot–Marie–Tooth disease encompasses a genetically heterogeneous class of heritable polyneuropathies that result in axonal degeneration in the peripheral nervous system. Charcot–Marie–Tooth type 2D neuropathy (CMT2D) is caused by dominant mutations in glycyl tRNA synthetase (GARS). Mutations in the mouse Gars gene result in a genetically and phenotypically valid animal model of CMT2D. How mutations in GARS lead to peripheral neuropathy remains controversial. To identify putative disease mechanisms, we compared metabolites isolated from the spinal cord of Gars mutant mice and their littermate controls. A profile of altered metabolites that distinguish the affected and unaffected tissue was determined. Ascorbic acid was decreased fourfold in the spinal cord of CMT2D mice, but was not altered in serum. Carnitine and its derivatives were also significantly reduced in spinal cord tissue of mutant mice, whereas glycine was elevated. Dietary supplementation with acetyl-L-carnitine improved gross motor performance of CMT2D mice, but neither acetyl-L-carnitine nor glycine supplementation altered the parameters directly assessing neuropathy. Other metabolite changes suggestive of liver and kidney dysfunction in the CMT2D mice were validated using clinical blood chemistry. These effects were not secondary to the neuromuscular phenotype, as determined by comparison with another, genetically unrelated mouse strain with similar neuromuscular dysfunction. However, these changes do not seem to be causative or consistent metabolites of CMT2D, because they were not observed in a second mouse Gars allele or in serum samples from CMT2D patients. Therefore, the metabolite ‘fingerprint’ we have identified for CMT2D improves our understanding of cellular biochemical changes associated with GARS mutations, but identification of efficacious treatment strategies and elucidation of the disease mechanism will require additional studies. PMID:27288508

Pain outcomes after surgery in patients with intramedullary spinal cord cavernous malformations.

PubMed

Deutsch, Harel

2010-09-01

The objective of the study was to quantify the improvement in pain levels for patients who have undergone surgery for intramedullary spinal cord cavernous malformations (SCCMs). The author reviewed medical records of patients who underwent surgery for an intramedullary SCCM between 2003 and 2010. Numerical pain scores (range 0-10) were recorded preoperatively and at follow-up. The follow-up period exceeded 1 year. Neurological status and subjective outcomes were assessed. Each patient underwent follow-up MR imaging. Five patients were identified with SCCMs who underwent surgery: 4 with thoracic and 1 with cervical lesions. Patients had been conservatively managed for an average of 5 years prior to surgery, and none had a history of acute hemorrhage or neurological deterioration during the observation period. The primary indication for surgery in each patient was pain, although 4 of 5 patients had some evidence of myelopathy on examination. Pain improved from a mean preoperative score of 8.6 to mean score of 2.0 (p < 0.01) at 1 month. Pain scores then increased to 3.7 (p < 0.01) at 1 year. All patients had some improvement in pain. No new motor weakness was noted, but all patients had increased symptoms of posterior-column dysfunction and numbness after surgery. Spinal cord intramedullary cavernous malformations are increasingly being diagnosed early with patients presenting with mostly pain symptoms. Removal of the lesion is reliably associated with improvement in pain scores but often the pain improvement is transient. While long-term worsening of pain scores occurs, at 1-year follow-up, patients reported pain scores were improved over preoperative scores. In all patients some degree of postoperative posterior-column dysfunction was present. Some of the immediate pain relief may be due to analgesia related to the myelotomy of newly described posterior column pain pathways. In patients with severe pain, surgery to remove SCCMs reduced the overall pain level at 1 year.

Environmental Control and Life Support Systems Testing Facility at MSFC

NASA Technical Reports Server (NTRS)

2001-01-01

The Marshall Space Flight Center (MSFC) is responsible for designing and building the life support systems that will provide the crew of the International Space Station (ISS) a comfortable environment in which to live and work. Scientists and engineers at the MSFC are working together to provide the ISS with systems that are safe, efficient, and cost-effective. These compact and powerful systems are collectively called the Environmental Control and Life Support Systems, or simply, ECLSS. This photograph shows the Urine Processor Assembly (UPA) which utilizes the Vapor Compression Distillation (VCD) technology. The VCD is used for integrated testing of the entire Water Recovery System (WRS) and development testing of the Urine Processor Assembly. The UPA accepts and processes pretreated crewmember urine to allow it to be processed along with other wastewaters in the Water Processor Assembly (WPA). The WPA removes free gas, organic, and nonorganic constituents before the water goes through a series of multifiltration beds for further purification. Product water quality is monitored primarily through conductivity measurements. Unacceptable water is sent back through the WPA for reprocessing. Clean water is sent to a storage tank.

Performance Assessment of the Exploration Water Recovery System

NASA Technical Reports Server (NTRS)

Carter. D. Layne; Tabb, David; Perry, Jay

2008-01-01

A new water recovery system architecture designed to fulfill the National Aeronautics and Space Administration s (NASA) Space Exploration Policy has been tested at the Marshall Space Flight Center (MSFC). This water recovery system architecture evolved from the current state-of-the-art system developed for the International Space Station (ISS). Through novel integration of proven technologies for air and water purification, this system promises to elevate existing system optimization. The novel aspect of the system is twofold. First, volatile organic compounds (VOC) are removed from the cabin air via catalytic oxidation in the vapor phase, prior to their absorption into the aqueous phase. Second, vapor compression distillation (VCD) technology processes the condensate and hygiene waste streams in addition to the urine waste stream. Oxidation kinetics dictate that removing VOCs from the vapor phase is more efficient. Treating the various waste streams by VCD reduces the load on the expendable ion exchange and adsorption media which follows, as well as the aqueous-phase catalytic oxidation process further downstream. This paper documents the results of testing this new architecture.

Effect of intermixing at CdS/CdTe interface on defect properties

NASA Astrophysics Data System (ADS)

Park, Ji-Sang; Yang, Ji-Hui; Barnes, Teresa; Wei, Su-Huai

2016-07-01

We investigated the stability and electronic properties of defects in CdTe1-xSx that can be formed at the CdS/CdTe interface. As the anions mix at the interface, the defect properties are significantly affected, especially those defects centered at cation sites like Cd vacancy, VCd, and Te on Cd antisite, TeCd, because the environment surrounding the defect sites can have different configurations. We show that at a given composition, the transition energy levels of VCd and TeCd become close to the valence band maximum when the defect has more S atoms in their local environment, thus improving the device performance. Such beneficial role is also found at the grain boundaries when the Te atom is replaced by S in the Te-Te wrong bonds, reducing the energy of the grain boundary level. On the other hand, the transition levels with respect to the valence band edge of CdTe1-xSx increases with the S concentration as the valence band edge decreases with the S concentration, resulting in the reduced p-type doping efficiency.

On stability, chirality measures, and theoretical VCD spectra of the chiral C58X2 fullerenes (X = N, B).

PubMed

Ostrowski, Sławomir; Jamróz, Michał H; Rode, Joanna E; Dobrowolski, Jan Cz

2012-01-12

The stability of all 23 C(58)N(2) and C(58)B(2) heterofullerenes in the singlet and triplet states was determined at the B3LYP/6-31G** level. In equilibrium mixture the achiral (1,4) C(58)N(2) isomer would be populated in ca. 95.8%, the chiral (1,16) one in ca. 3.3%, and the achiral (1,4) C(58)B(2) in 100%, whereas all triplet state isomers are less stable. Fourteen out of 23 C(58)X(2) are chiral. Four different chirality measures were calculated by our own CHIMEA program: pure geometrical, labeled, mass, and charge. Intercorrelations between the measures for all chiral compounds indicate that the pure geometrical chirality measure is unstable and should not be used in QSAR predictions of the other molecular properties, while the labeled and mass-weighted ones are promising QSAR descriptors. For each chiral C(58)N(2) molecule, some very strong VCD bands, of intensity comparable with that in the IR spectra, can serve in identification and characterization of the isomers.

Study on the mechanism of using IR illumination to improve the carrier transport performance of CdZnTe detector

NASA Astrophysics Data System (ADS)

Mao, Yifei; Zhang, Jijun; Lin, Liwen; Lai, Jianming; Min, Jiahua; Liang, Xiaoyan; Huang, Jian; Tang, Ke; Wang, Linjun

2018-04-01

Different wavelength IR light (770-1150 nm) was used to evaluate the effect of IR light on the carrier transport performance of CdZnTe detector. The effective mobility-lifetime product (μτ*) of CdZnTe achieved 10-2 cm2 V-1 when the IR wavelength was in the range of 820-920 nm, but decreased to 1 × 10-4 cm2 V-1 when the wavelength was longer than 920 nm. The mechanism about how IR light affecting the carrier transport property of CdZnTe detector was analyzed with Shockley-Read-Hall model. The defect of doubly ionized Cd vacancy ([VCd]2-) was found to be the main factor that assist IR light affecting the μτ of CdZnTe detector. The photoconductive experiment under 770-1150 nm IR illumination was carried out, and three kinds of photocurrent curve were detected and analyzed by solving the Hecht equation. The experiments demonstrated the effect of [VCd]2- defect on the carrier transport property of CdZnTe detector under IR illumination.

Microbiological test results of the environmental control and life support systems vapors compression distillation subsystem recycle tank components following various pretreatment protocols

NASA Technical Reports Server (NTRS)

Huff, Tim

1993-01-01

Microbiological samples were collected from the recycle tank of the vapor compression distillation (VCD) subsystem of the water recovery test at NASA MSFC following a 68-day run. The recycle tank collects rejected urine brine that was pretreated with a commercially available oxidant (Oxone) and sulfuric acid and pumps it back to the processing component of the VCD. Samples collected included a water sample and two swab samples, one from the particulate filter surface and a second from material floating on the surface of the water. No bacteria were recovered from the water sample. Both swab samples contained a spore-forming bacterium, Bacillus insolitus. A filamentous fungus was isolated from the floating material. Approximately 1 month after the pretreatment chemicals were changed to sodium hypochlorite and sulfuric acid, a swab of the particulate filter was again analyzed for microbial content. One fungus was isolated, and spore-forming bacteria were observed. These results indicate the inability of these pretreatments to inhibit surface attachment. The implications of the presence of these organisms are discussed.

Conformational study of melectin and antapin antimicrobial peptides in model membrane environments

NASA Astrophysics Data System (ADS)

Kocourková, Lucie; Novotná, Pavlína; Čujová, Sabína; Čeřovský, Václav; Urbanová, Marie; Setnička, Vladimír

2017-01-01

Antimicrobial peptides have long been considered as promising compounds against drug-resistant pathogens. In this work, we studied the secondary structure of antimicrobial peptides melectin and antapin using electronic (ECD) and vibrational circular dichroism (VCD) spectroscopies that are sensitive to peptide secondary structures. The results from quantitative ECD spectral evaluation by Dichroweb and CDNN program and from the qualitative evaluation of the VCD spectra were compared. The antimicrobial activity of the selected peptides depends on their ability to adopt an amphipathic α-helical conformation on the surface of the bacterial membrane. Hence, solutions of different zwitterionic and negatively charged liposomes and micelles were used to mimic the eukaryotic and bacterial biological membranes. The results show a significant content of α-helical conformation in the solutions of negatively charged liposomes mimicking the bacterial membrane, thus correlating with the antimicrobial activity of the studied peptides. On the other hand in the solutions of zwitterionic liposomes used as models of the eukaryotic membranes, the fraction of α-helical conformation was lower, which corresponds with their moderate hemolytic activity.

Intraoperative monitoring of somatosensory (SSEPs) and transcranial electric motor-evoked potentials (tce-MEPs) during surgical correction of neuromuscular scoliosis in patients with central or peripheral nervous system diseases.

PubMed

Pastorelli, F; Di Silvestre, M; Vommaro, F; Maredi, E; Morigi, A; Bacchin, M R; Bonarelli, S; Plasmati, R; Michelucci, R; Greggi, T

2015-11-01

Combined intraoperative monitoring (IOM) of transcranial electric motor-evoked potentials (tce-MEPs) and somatosensory-evoked potentials (SSEPs) is safe and effective for spinal cord monitoring during scoliosis surgery. However, the literature data regarding the reliability of spinal cord monitoring in patients with neuromuscular scoliosis are conflicting and need to be confirmed. We reviewed IOM records of 40 consecutive patients with neuromuscular scoliosis related to central nervous system (CNS) (29 pts) or peripheral nervous system (PNS) (11 patients) diseases, who underwent posterior fusion with instrumentation surgery for spinal deformity. Multimodalitary IOM with SSEPs and tce-MEPs was performed. Spinal cord monitoring using at least one modality was attempted in 38/40 (95 %) patients. No false-negative results were present in either group, but a relatively high incidence of false-positive cases (4/29, 13.8 %) was noted in the CNS group. Two patients in the CNS group and one patient in the PNS group presented transient postoperative motor deficits (true positive), related to surgical manoeuvres in two cases and to malposition in the other one. Multimodalitary IOM is safe and effective to detect impending spinal cord and peripheral nerves dysfunction in neuromuscular scoliosis surgery. However, the interpretation of neurophysiological data may be challenging in such patients, and the rate of false-positive results is high when pre-operatory motor deficits are severe.

The effect of thalidomide on spinal cord ischemia/reperfusion injury in a rabbit model.

PubMed

Lee, C-J; Kim, K-W; Lee, H-M; Nahm, F S; Lim, Y-J; Park, J-H; Kim, C-S

2007-02-01

Randomized study. To evaluate the effects of thalidomide on spinal cord ischemia/reperfusion injury via reduced TNF-alpha production. Animal experimental laboratory, Clinical Research Institute of Seoul National University Hospital, Seoul, Korea. Spinal cord ischemia was induced in rabbits by occluding the infrarenal aorta. Rabbits in group N did not undergo ischemic insult, but rabbits in groups C (the untreated group), THA, and THB underwent ischemic insult for 15 min. The THA and THB groups received thalidomide (20 mg/kg) intraperitoneally (i.p.) before ischemia, but only the THB group received thalidomide (i.p., 20 mg/kg) after 24 and 48 h of reperfusion. After evaluating neurologic functions at 1.5 h, 3, and 5 days of reperfusion, rabbits were killed for histopathologic examination and Western blot analysis of TNF-alpha. The THA and THB groups showed significantly less neurologic dysfunction than the C group at 1.5 h, 3, and 5 days of reperfusion. The number of normal spinal motor neurons in ventral gray matter was higher in THA and THB than in C, but no difference was observed between THA and THB. Western blot analysis showed a significantly higher level of TNF-alpha in C than in THA and THB at 1.5 h of reperfusion, but no difference was observed between C, THA, or THB at 3 or 5 days of reperfusion. Thalidomide treatment before ischemic insult reduces early phase ischemia/reperfusion injury of the spinal cord in rabbits.

Initiation of bladder voiding with epidural stimulation in paralyzed, step trained rats.

PubMed

Gad, Parag N; Roy, Roland R; Zhong, Hui; Lu, Daniel C; Gerasimenko, Yury P; Edgerton, V Reggie

2014-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury.

Initiation of Bladder Voiding with Epidural Stimulation in Paralyzed, Step Trained Rats

PubMed Central

Gad, Parag N.; Roy, Roland R.; Zhong, Hui; Lu, Daniel C.; Gerasimenko, Yury P.; Edgerton, V. Reggie

2014-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury. PMID:25264607

Focal dysfunction of the proteasome: a pathogenic factor in a mouse model of amyotrophic lateral sclerosis.

PubMed

Kabashi, Edor; Agar, Jeffrey N; Taylor, David M; Minotti, Sandra; Durham, Heather D

2004-06-01

Mutations in the Cu/Zn-superoxide dismutase (SOD-1) gene are responsible for a familial form of amyotrophic lateral sclerosis (fALS). The present study demonstrated impaired proteasomal function in the lumbar spinal cord of transgenic mice expressing human SOD-1 with the ALS-causing mutation G93A (SOD-1(G93A)) compared to non-transgenic littermates (LM) and SOD-1(WT) transgenic mice. Chymotrypsin-like activity was decreased as early as 45 days of age. By 75 days, chymotrypsin-, trypsin-, and caspase-like activities of the proteasome were impaired, at about 50% of control activity in lumbar spinal cord, but unchanged in thoracic spinal cord and liver. Both total and specific activities of the proteasome were reduced to a similar extent, indicating that a change in proteasome function, rather than a decrease in proteasome levels, had occurred. Similar decreases of total and specific activities of the proteasome were observed in NIH 3T3 cell lines expressing fALS mutants SOD-1(G93A) and SOD-1(G41S), but not in SOD-1(WT) controls. Although overall levels of proteasome were maintained in spinal cord of SOD-1(G93A) transgenic mice, the level of 20S proteasome was substantially reduced in lumbar spinal motor neurons relative to the surrounding neuropil. It is concluded that impairment of the proteasome is an early event and contributes to ALS pathogenesis.

Amelioration of motor/sensory dysfunction and spasticity in a rat model of acute lumbar spinal cord injury by human neural stem cell transplantation

PubMed Central

2013-01-01

Introduction Intraspinal grafting of human neural stem cells represents a promising approach to promote recovery of function after spinal trauma. Such a treatment may serve to: I) provide trophic support to improve survival of host neurons; II) improve the structural integrity of the spinal parenchyma by reducing syringomyelia and scarring in trauma-injured regions; and III) provide neuronal populations to potentially form relays with host axons, segmental interneurons, and/or α-motoneurons. Here we characterized the effect of intraspinal grafting of clinical grade human fetal spinal cord-derived neural stem cells (HSSC) on the recovery of neurological function in a rat model of acute lumbar (L3) compression injury. Methods Three-month-old female Sprague–Dawley rats received L3 spinal compression injury. Three days post-injury, animals were randomized and received intraspinal injections of either HSSC, media-only, or no injections. All animals were immunosuppressed with tacrolimus, mycophenolate mofetil, and methylprednisolone acetate from the day of cell grafting and survived for eight weeks. Motor and sensory dysfunction were periodically assessed using open field locomotion scoring, thermal/tactile pain/escape thresholds and myogenic motor evoked potentials. The presence of spasticity was measured by gastrocnemius muscle resistance and electromyography response during computer-controlled ankle rotation. At the end-point, gait (CatWalk), ladder climbing, and single frame analyses were also assessed. Syrinx size, spinal cord dimensions, and extent of scarring were measured by magnetic resonance imaging. Differentiation and integration of grafted cells in the host tissue were validated with immunofluorescence staining using human-specific antibodies. Results Intraspinal grafting of HSSC led to a progressive and significant improvement in lower extremity paw placement, amelioration of spasticity, and normalization in thermal and tactile pain/escape thresholds at eight weeks post-grafting. No significant differences were detected in other CatWalk parameters, motor evoked potentials, open field locomotor (Basso, Beattie, and Bresnahan locomotion score (BBB)) score or ladder climbing test. Magnetic resonance imaging volume reconstruction and immunofluorescence analysis of grafted cell survival showed near complete injury-cavity-filling by grafted cells and development of putative GABA-ergic synapses between grafted and host neurons. Conclusions Peri-acute intraspinal grafting of HSSC can represent an effective therapy which ameliorates motor and sensory deficits after traumatic spinal cord injury. PMID:23710605

Use of a small molecule cell cycle inhibitor to control cell growth and improve specific productivity and product quality of recombinant proteins in CHO cell cultures.

PubMed

Du, Zhimei; Treiber, David; McCarter, John D; Fomina-Yadlin, Dina; Saleem, Ramsey A; McCoy, Rebecca E; Zhang, Yuling; Tharmalingam, Tharmala; Leith, Matthew; Follstad, Brian D; Dell, Brad; Grisim, Brent; Zupke, Craig; Heath, Carole; Morris, Arvia E; Reddy, Pranhitha

2015-01-01

The continued need to improve therapeutic recombinant protein productivity has led to ongoing assessment of appropriate strategies in the biopharmaceutical industry to establish robust processes with optimized critical variables, that is, viable cell density (VCD) and specific productivity (product per cell, qP). Even though high VCD is a positive factor for titer, uncontrolled proliferation beyond a certain cell mass is also undesirable. To enable efficient process development to achieve consistent and predictable growth arrest while maintaining VCD, as well as improving qP, without negative impacts on product quality from clone to clone, we identified an approach that directly targets the cell cycle G1-checkpoint by selectively inhibiting the function of cyclin dependent kinases (CDK) 4/6 with a small molecule compound. Results from studies on multiple recombinant Chinese hamster ovary (CHO) cell lines demonstrate that the selective inhibitor can mediate a complete and sustained G0/G1 arrest without impacting G2/M phase. Cell proliferation is consistently and rapidly controlled in all recombinant cell lines at one concentration of this inhibitor throughout the production processes with specific productivities increased up to 110 pg/cell/day. Additionally, the product quality attributes of the mAb, with regard to high molecular weight (HMW) and glycan profile, are not negatively impacted. In fact, high mannose is decreased after treatment, which is in contrast to other established growth control methods such as reducing culture temperature. Microarray analysis showed major differences in expression of regulatory genes of the glycosylation and cell cycle signaling pathways between these different growth control methods. Overall, our observations showed that cell cycle arrest by directly targeting CDK4/6 using selective inhibitor compound can be utilized consistently and rapidly to optimize process parameters, such as cell growth, qP, and glycosylation profile in recombinant antibody production cultures. © 2014 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.

Role of Side Chains in β-Sheet Self-Assembly into Peptide Fibrils. IR and VCD Spectroscopic Studies of Glutamic Acid-Containing Peptides.

PubMed

Tobias, Fernando; Keiderling, Timothy A

2016-05-10

Poly(glutamic acid) at low pH self-assembles after incubation at higher temperature into fibrils composed of antiparallel sheets that are stacked in a β2-type structure whose amide carbonyls have bifurcated H-bonds involving the side chains from the next sheet. Oligomers of Glu can also form such structures, and isotope labeling has provided insight into their out-of-register antiparallel structure [ Biomacromolecules 2013 , 14 , 3880 - 3891 ]. In this paper we report IR and VCD spectra and transmission electron micrograph (TEM) images for a series of alternately sequenced oligomers, Lys-(Aaa-Glu)5-Lys-NH2, where Aaa was varied over a variety of polar, aliphatic, or aromatic residues. Their spectral and TEM data show that these oligopeptides self-assemble into different structures, both local and morphological, that are dependent on both the nature of the Aaa side chains and growth conditions employed. Such alternate peptides substituted with small or polar residues, Ala and Thr, do not yield fibrils; but with β-branched aliphatic residues, Val and Ile, that could potentially pack with Glu side chains, these oligopeptides do show evidence of β2-stacking. By contrast, for Leu, with longer side chains, only β1-stacking is seen while with even larger Phe side chains, either β-form can be detected separately, depending on preparation conditions. These structures are dependent on high temperature incubation after reducing the pH and in some cases after sonication of initial fibril forms and reincubation. Some of these fibrillar peptides, but not all, show enhanced VCD, which can offer evidence for formation of long, multistrand, often twisted structures. Substitution of Glu with residues having selected side chains yields a variety of morphologies, leading to both β1- and β2-structures, that overall suggests two different packing modes for the hydrophobic side chains depending on size and type.

Better Contract Oversight Could Have Prevented Deficiencies in the Detention Facility in Parwan, Afghanistan

DTIC Science & Technology

2012-05-17

a visitation center, a water treatment plant, and vocational buildings where detainees can learn carpentry and culinary skills. The facility also...room not connected MHU PPI 69 DCID HVAC unit is inoperable Ml DAB PPI has o rdered p arts and w ill fix w hen it arrives 70 Access broken to VCD

Mass psychogenic illness: psychological predisposition and iatrogenic pseudo-vocal cord dysfunction and pseudo-reactive airways disease syndrome.

PubMed

Staudenmayer, Herman; Christopher, Kent L; Repsher, Lawrence; Hill, Ronald H

2011-06-01

A multidisciplinary team assessed five patients who alleged chronic medically unexplained multiorgan system symptoms described by idiopathic environmental intolerance allegedly triggered by exposure to solvents used in membrane roofing repair work on an office building. The event precipitated an incident of mass psychogenic illness (MPI). Treating physicians diagnosed irritant-associated vocal cord dysfunction (IVCD) and reactive airways disease syndrome (RADS) resulting from exposure. The authors conducted medical, psychological, and industrial hygiene evaluations. Air monitoring data for total volatile organic compounds obtained during the 2-day exposure period, measurements of emissions during membrane roofing repair at a similar site, mathematical modeling of air contaminant concentrations, and injection of tracer gas into the incident building revealed exposure levels well below those doses anticipated to cause clinical symptoms. There was no objective medical evidence validating symptoms. Review of the medical records indicated that the video laryngoscopy data, pulmonary function tests, and medical examinations relied upon by the treating physicians were inconsistent with published criteria for IVCD and RADS. Psychological evaluation identified defensiveness and self-serving misrepresentations of exaggerated health concerns associated with somatization and malingering. Each case had personality traits associated with at least one personality disorder. Social histories identified premorbid life events and stressors associated with distress. This is the first study to assess psychological predisposition, social interaction among the plaintiffs, and iatrogenic reinforcement of beliefs by diagnoses of pseudo-disorders associated with patient misrepresentation of exaggerated health concerns in an incident of MPI.

The nasogastric tube syndrome: two case reports and review of the literature.

PubMed

Apostolakis, L W; Funk, G F; Urdaneta, L F; McCulloch, T M; Jeyapalan, M M

2001-01-01

The nasogastric tube syndrome is a potentially life-threatening complication of an indwelling nasogastric (NG) tube. The syndrome is thought to result from ulceration and infection of the posterior cricoid region with subsequent dysfunction of vocal cord abduction. This dysfunction may present as complete loss of vocal cord abduction manifested as serious airway compromise. Reports of this syndrome are infrequent, with only 29 cases published to date. Two additional cases of nasogastric tube syndrome diagnosed at the University of Iowa Hospitals and Clinics over a 2-year period are presented. A search of MEDLINE (1966 through February 1999), including review of those articles' references identified seven previous publications, including 29 case reports. These 29 cases are reviewed and the findings summarized. Twenty-nine cases of NG tube syndrome are identified, with 16 of these occurring in the preantibiotic period. Including the two cases presented here, 15 contemporary patients are examined. Among these 15 cases, 10 required tracheostomy, on average 8.5 days after NG tube placement. Although the fully manifested syndrome presents quite dramatically, we suspect that a clinical spectrum of severity exists with less severe cases going unrecognized. Consistent with previous reports, we found that direct visualization of the postcricoid region is required to rule out the diagnosis and recommend such action be taken whenever the diagnosis is suspected. Treatment should include establishment of a safe airway, removal of the tube whenever possible, antibiotic therapy, and antireflux therapy.

Randomized Trial of Clitoral Vacuum Suction Versus Vibratory Stimulation in Neurogenic Female Orgasmic Dysfunction.

PubMed

Alexander, Marcalee; Bashir, Khurram; Alexander, Craig; Marson, Lesley; Rosen, Raymond

2018-02-01

To examine the safety and efficacy of using a clitoral vacuum suction device (CVSD) versus vibratory stimulation (V) to treat orgasmic dysfunction in women with multiple sclerosis (MS) or spinal cord injury (SCI). Randomized clinical trial. Two academic medical centers. Women (N=31) including 20 with MS and 11 with SCI. A 12-week trial of the use of a CVSD versus V. Female Sexual Function Inventory (FSFI) and Female Sexual Distress Scale (FSDS). Twenty-three women (18 MS, 5 SCI) completed the study including 13 of 16 randomized to CVSD and 10 of 15 randomized to V. There was a statistically significant increase in total FSFI score (P=.011), desire (P=.009), arousal (P=.009), lubrication (P=.008), orgasm (P=.012), and satisfaction (P=.049), and a significant decrease in distress as measured by FSDS (P=.020) in subjects using the CVSD. In subjects who used V, there was a statistically significant increase in the orgasm subscale of the FSFI (P=.028). Subjects using the CVSD maintained improvements 4 weeks after treatment. CVSD is safe and overall efficacious to treat female neurogenic sexual dysfunction related to MS and SCI. V is also safe and efficacious for female neurogenic orgasmic dysfunction; however, results were limited to the active treatment period. Because of ease of access and cost, clinicians can consider use of V for women with MS or SCI with orgasmic dysfunction. CVSD is recommended for women with multiple sexual dysfunctions or for whom V is ineffective. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Neuroprotective effects of the mitochondria-targeted antioxidant MitoQ in a model of inherited amyotrophic lateral sclerosis.

PubMed

Miquel, Ernesto; Cassina, Adriana; Martínez-Palma, Laura; Souza, José M; Bolatto, Carmen; Rodríguez-Bottero, Sebastián; Logan, Angela; Smith, Robin A J; Murphy, Michael P; Barbeito, Luis; Radi, Rafael; Cassina, Patricia

2014-05-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motor neuron degeneration that ultimately results in progressive paralysis and death. Growing evidence indicates that mitochondrial dysfunction and oxidative stress contribute to motor neuron degeneration in ALS. To further explore the hypothesis that mitochondrial dysfunction and nitroxidative stress contribute to disease pathogenesis at the in vivo level, we assessed whether the mitochondria-targeted antioxidant [10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl]triphenylphosphonium methane sulfonate (MitoQ) can modify disease progression in the SOD1(G93A) mouse model of ALS. To do this, we administered MitoQ (500 µM) in the drinking water of SOD1(G93A) mice from a time when early symptoms of neurodegeneration become evident at 90 days of age until death. This regime is a clinically plausible scenario and could be more easily translated to patients as this corresponds to initiating treatment of patients after they are first diagnosed with ALS. MitoQ was detected in all tested tissues by liquid chromatography/mass spectrometry after 20 days of administration. MitoQ treatment slowed the decline of mitochondrial function, in both the spinal cord and the quadriceps muscle, as measured by high-resolution respirometry. Importantly, nitroxidative markers and pathological signs in the spinal cord of MitoQ-treated animals were markedly reduced and neuromuscular junctions were recovered associated with a significant increase in hindlimb strength. Finally, MitoQ treatment significantly prolonged the life span of SOD1(G93A) mice. Our results support a role for mitochondrial nitroxidative damage and dysfunction in the pathogenesis of ALS and suggest that mitochondria-targeted antioxidants may be of pharmacological use for ALS treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Challenges in clinical applications of brain computer interfaces in individuals with spinal cord injury

PubMed Central

Rupp, Rüdiger

2014-01-01

Brain computer interfaces (BCIs) are devices that measure brain activities and translate them into control signals used for a variety of applications. Among them are systems for communication, environmental control, neuroprostheses, exoskeletons, or restorative therapies. Over the last years the technology of BCIs has reached a level of matureness allowing them to be used not only in research experiments supervised by scientists, but also in clinical routine with patients with neurological impairments supervised by clinical personnel or caregivers. However, clinicians and patients face many challenges in the application of BCIs. This particularly applies to high spinal cord injured patients, in whom artificial ventilation, autonomic dysfunctions, neuropathic pain, or the inability to achieve a sufficient level of control during a short-term training may limit the successful use of a BCI. Additionally, spasmolytic medication and the acute stress reaction with associated episodes of depression may have a negative influence on the modulation of brain waves and therefore the ability to concentrate over an extended period of time. Although BCIs seem to be a promising assistive technology for individuals with high spinal cord injury systematic investigations are highly needed to obtain realistic estimates of the percentage of users that for any reason may not be able to operate a BCI in a clinical setting. PMID:25309420

Prophylactic neuroprotective efficiency of co-administration of Ginkgo biloba and Trifolium pretense against sodium arsenite-induced neurotoxicity and dementia in different regions of brain and spinal cord of rats.

PubMed

Abdou, Heba M; Yousef, Mokhtar I; El Mekkawy, Desouki A; Al-Shami, Ahmed S

2016-08-01

The present study was carried out to evaluate the potential protective role of co-administration of Ginkgo biloba, Trifolium pretenseagainst sodium arsenite-induced neurotoxicity in different parts of brain (Cerebral cortex, Hippocampus, striatum and Hind brain) and in the spinal cord of rats. Sodium arsenite caused impairment in the acquisition and learning in all the behavioral tasks and caused significant increase in tumor necrosis factor-α,thiobarbituric acid-reactive substances andlipid profile, while caused significant decrease in glutathione, total thiol content, total antioxidant capacity, acetylcholinesterase, monoamine oxidase and ATPases activities. These results were confirmed by histopathological, fluorescence and scanning electron microscopy examination of different regions of brain. From these results sodium arsenite-induced neurodegenerative disorder in different regions of brain and spinal cord and this could be mediated through modifying the intracellular brain ions homeostasis, cholinergic dysfunction and oxidative damage. The presence of Ginkgo biloba and/orTrifolium pretense with sodium arsenite minimized its neurological damages. It was pronounced that using Ginkgo biloba and Trifolium pretense in combination was more effective as protective agents compared to use eachone of them alone. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spinal cord gliomas: management and outcome with reference to adjuvant therapy.

PubMed

Nishio, S; Morioka, T; Fujii, K; Inamura, T; Fukui, M

2000-01-01

The authors review their experience with 19 consecutive cases with either astrocytic tumour (glioblastoma multiforme one, anaplastic astrocytoma one, astrocytoma 4, pilocytic astrocytoma 4) or ependymoma (10 tumours in 9 patients) of the spinal cord who were treated during the period from 1982 to 1996. The patients included 10 male and 9 female patients with a median age of 38 years. The main tumour locations included the cervicomedullary region 5 the cervical cord (8), the thoracic cord (5) and one each in the thoracolumbar region and conus medullaris. While a total removal of the tumour was achieved in 8 out of 10 ependymomas, the initial treatment for astrocytic tumours was a partial resection in 5, and biopsy in the remaining 5. As adjuvant treatment, 8 patients received radiation therapy and 2 received chemotherapy. Two patients with an astrocytic tumour received chemotherapy only, while the remaining 9 received neither radiation therapy nor chemotherapy initially. After these treatments, 6 out of the 8 patients with low grade astrocytoma have remained alive for 1.3-12.6 years, while 2 patients with high grade astrocytic tumours died within 15 months following surgery. Eight out of 9 patients with an ependymoma have remained alive for 3.0-12.3 years, while one committed suicide 2 years after surgery. As a result, 14 patients are still alive; half of them are accompanied by a mild neurological dysfunction, while the remaining one has a moderate deficit. The postoperative results and the rationale for surgery is discussed, and an approach for utilising adjuvant therapy for high grade tumours is also suggested.

Neuroprotective Effects of Sulforaphane after Contusive Spinal Cord Injury

PubMed Central

Benedict, Andrea L.; Mountney, Andrea; Hurtado, Andres; Bryan, Kelley E.; Schnaar, Ronald L.; Dinkova-Kostova, Albena T.

2012-01-01

Abstract Traumatic spinal cord injury (SCI) leads to oxidative stress, calcium mobilization, glutamate toxicity, the release of proinflammatory factors, and depletion of reduced glutathione (GSH) at the site of injury. Induction of the Keap1/Nrf2/ARE pathway can alleviate neurotoxicity by protecting against GSH depletion, oxidation, intracellular calcium overload, mitochondrial dysfunction, and excitotoxicity. Sulforaphane (SF), an isothiocyanate derived from broccoli, is a potent naturally-occurring inducer of the Keap1/Nrf2/ARE pathway, leading to upregulation of genes encoding cytoprotective proteins such as NAD(P)H: quinone oxidoreductase 1, and GSH-regulatory enzymes. Additionally, SF can attenuate inflammation by inhibiting the nuclear factor-κB (NF-κB) pathway, and the enzymatic activity of the proinflammatory cytokine macrophage inhibitory factor (MIF). Our study examined systemic administration of SF in a rat model of contusion SCI, in an effort to utilize its indirect antioxidant and anti-inflammatory properties to decrease secondary injury. Two doses of SF (10 or 50 mg/kg) were administered at 10 min and 72 h after contusion SCI. SF (50 mg/kg) treatment resulted in both acute and long-term beneficial effects, including upregulation of the phase 2 antioxidant response at the injury site, decreased mRNA levels of inflammatory cytokines (i.e., MMP-9) in the injured spinal cord, inactivation of urinary MIF tautomerase activity, enhanced hindlimb locomotor function, and an increased number of serotonergic axons caudal to the lesion site. These findings demonstrate that SF provides neuroprotective effects in the spinal cord after injury, and could be a candidate for therapy of SCI. PMID:22853439

Neuroprotective effects of sulforaphane after contusive spinal cord injury.

PubMed

Benedict, Andrea L; Mountney, Andrea; Hurtado, Andres; Bryan, Kelley E; Schnaar, Ronald L; Dinkova-Kostova, Albena T; Talalay, Paul

2012-11-01

Traumatic spinal cord injury (SCI) leads to oxidative stress, calcium mobilization, glutamate toxicity, the release of proinflammatory factors, and depletion of reduced glutathione (GSH) at the site of injury. Induction of the Keap1/Nrf2/ARE pathway can alleviate neurotoxicity by protecting against GSH depletion, oxidation, intracellular calcium overload, mitochondrial dysfunction, and excitotoxicity. Sulforaphane (SF), an isothiocyanate derived from broccoli, is a potent naturally-occurring inducer of the Keap1/Nrf2/ARE pathway, leading to upregulation of genes encoding cytoprotective proteins such as NAD(P)H: quinone oxidoreductase 1, and GSH-regulatory enzymes. Additionally, SF can attenuate inflammation by inhibiting the nuclear factor-κB (NF-κB) pathway, and the enzymatic activity of the proinflammatory cytokine macrophage inhibitory factor (MIF). Our study examined systemic administration of SF in a rat model of contusion SCI, in an effort to utilize its indirect antioxidant and anti-inflammatory properties to decrease secondary injury. Two doses of SF (10 or 50 mg/kg) were administered at 10 min and 72 h after contusion SCI. SF (50 mg/kg) treatment resulted in both acute and long-term beneficial effects, including upregulation of the phase 2 antioxidant response at the injury site, decreased mRNA levels of inflammatory cytokines (i.e., MMP-9) in the injured spinal cord, inactivation of urinary MIF tautomerase activity, enhanced hindlimb locomotor function, and an increased number of serotonergic axons caudal to the lesion site. These findings demonstrate that SF provides neuroprotective effects in the spinal cord after injury, and could be a candidate for therapy of SCI.

Persistent Outpatient Hypertension Is Independently Associated with Spinal Cord Dysfunction and Imaging Characteristics of Spinal Cord Damage among Patients with Cervical Spondylosis.

PubMed

Kalb, Samuel; Zaidi, Hasan A; Ribas-Nijkerk, Juan C; Sindhwani, Maughan K; Clark, Justin C; Martirosyan, Nikolay L; Theodore, Nicholas

2015-08-01

Hypertension and cervical spondylosis are diseases of the adult population that are approaching near pandemic proportions. However, the interactions between these two disease processes are poorly understood. We set out to determine the associations among systemic hypertension, clinical status, and imaging findings of spinal cord damage for patients with cervical stenosis. A retrospective chart review was performed on patients with symptomatic cervical stenosis related to degenerative disease and divided on the basis of outpatient blood pressure control (normal <140/<90 mm Hg). Sagittal T2-weighted magnetic resonance imaging (MRI) of the cervical spine was analyzed to determine the degree of maximal canal stenosis (MCS; %), surface area of increased signal intensity (ISI; cm(2)), and signal intensity ratio (SIR). Functional status was evaluated using the modified Japanese Orthopaedic Association (mJOA) scale and the Nurick scale. One hundred twenty-two patients were identified (64 hypertensive, 58 nonhypertensive). Likelihood of ISI was higher in hypertensive patients (P < 0.05). Average ISI was significantly higher in patients with uncontrolled blood pressure (P = 0.02) despite MCS being identical between the two groups. The mJOA and Nurick scores were worse for patients with systemic hypertension (P < 0.02). Diabetes mellitus and smoking history did not affect these findings. Persistent hypertension in outpatients is associated with worsened clinical status and increased markers of spinal cord damage on MRI. Perioperative management of blood pressure may serve to improve clinical outcomes. Larger prospective trials are necessary to further validate these findings. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of spinal cord level on sexual function in the spina bifida population.

PubMed

Lee, N G; Andrews, E; Rosoklija, I; Logvinenko, T; Johnson, E K; Oates, R D; Estrada, C R

2015-06-01

Sexual dysfunction and infertility are prevalent in the spina bifida (SB) population; however, the mechanism of how they affect a person with spina bifida is poorly understood. Additionally, the management of children with spina bifida becomes more difficult as they exit from pediatric institutes. The present study sought to evaluate sexual health (using validated questionnaires) and fertility in adults with spina bifida and to correlate spinal cord level and ambulatory status with degree of sexual function. After institutional board review approval, 199 adult patients with SB, aged 18 and older and who were followed in one pediatric institution, were identified. Patients who were non-English speaking, cognitively and/or developmentally delayed, or unable to be contacted were excluded. Surveys regarding demographics, sexual health and infertility were mailed to the patients and administered in the clinic with the option to opt-out of the survey. Survey questions regarding sexual health were constructed using validated questionnaires: Female Sexual Function Index (FSFI) for females, and International Index of Erectile Function (IIEF) and Sexual Health Inventory for Men (SHIM) for males. Sexual dysfunction scores were correlated to the patients' spinal level and ambulatory status. Of the 121 eligible patients, 45 replied, with a response rate of 39%. For females, using a cut-off value of 26.5 for FSFI scoring, 25 out of 28 (89%) had sexual dysfunction. No association was seen between spinal level or ambulatory status and overall FSFI, satisfaction, or desire scores. For males, 10 out of 17 (59%) had severe erectile dysfunction (ED), and one out of 17 (6%) had no ED. No association was seen between ambulatory status and sexual function scores for the males. However, SHIM, satisfaction, and ED scores were higher in males with lower spinal lesions. People with spina bifida of both genders tended to have more severe dysfunction compared to those with sexual dysfunction of other etiologies, except with similar sexual desire scores. Regarding questions on fertility, no participant attempted to have children; thus, there was no infertility reported. Few studies have been conducted on sexual health and fertility in adults with SB. Three studies have utilized validated questionnaires and found varying degrees of sexual dysfunction in this subset of patients; however, only one study found sexual activity to be more likely in patients with more caudal levels of neurologic impairment. The present study also showed that SHIM, satisfaction, and ED scores were higher in males with lower spinal lesions. Limitations to this study primarily included the small sample size and low survey response rate. Limited information is known about adults with SB, and sexual function and fertility. While expressing sexual desire, adults with SB appear to experience high rates of sexual dysfunction. Fertility rates were inadequately assessed; this was possibly due to the high rate of sexual dysfunction. Sexual health in the SB population is an important component of the myriad of urologic care issues for these people. Due to the disparity in their care after reaching adulthood, it is prudent to follow these patients and understand their pathophysiology as they continue to mature through life. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Role of calpains in the injury-induced dysfunction and degeneration of the mammalian axon.

PubMed

Ma, Marek

2013-12-01

Axonal injury and degeneration, whether primary or secondary, contribute to the morbidity and mortality seen in many acquired and inherited central nervous system (CNS) and peripheral nervous system (PNS) disorders, such as traumatic brain injury, spinal cord injury, cerebral ischemia, neurodegenerative diseases, and peripheral neuropathies. The calpain family of proteases has been mechanistically linked to the dysfunction and degeneration of axons. While the direct mechanisms by which transection, mechanical strain, ischemia, or complement activation trigger intra-axonal calpain activity are likely different, the downstream effects of unregulated calpain activity may be similar in seemingly disparate diseases. In this review, a brief examination of axonal structure is followed by a focused overview of the calpain family. Finally, the mechanisms by which calpains may disrupt the axonal cytoskeleton, transport, and specialized domains (axon initial segment, nodes, and terminals) are discussed. © 2013.

Use of Optical Mapping to Evaluate Mechanisms and New Therapies for Bladder Dysfunction Due to Spinal Cord Injury

DTIC Science & Technology

2014-12-01

and the dome connected to tension transducers. Preparations were stretched to optimal resting tension ( Lo ) and allowed to equilibrate for 30 min...B SCT (200x) Uro LumenA Red: P2Y6 Green: vimentin Blue: DAPI Figure 11 13 This suggests there are different populations of IC within the bladder...Lumen Uro Control (200x) SCT (600x) Green: CD34 Blue: DAPI Red: P2Y6 Green: CD34 Blue: DAPI Figure 12 14 It was the first animal model

Perspectives on the rapid eye movement sleep switch in rapid eye movement sleep behavior disorder.

PubMed

Ramaligam, Vetrivelan; Chen, Michael C; Saper, Clifford B; Lu, Jun

2013-08-01

Rapid eye movement (REM) sleep in mammals is associated with wakelike cortical and hippocampal activation and concurrent postural muscle atonia. Research during the past 5 decades has revealed the details of the neural circuitry regulating REM sleep and muscle atonia during this state. REM-active glutamatergic neurons in the sublaterodorsal nucleus (SLD) of the dorsal pons are critical for generation for REM sleep atonia. Descending projections from SLD glutamatergic neurons activate inhibitory premotor neurons in the ventromedial medulla (VMM) and in the spinal cord to antagonize the glutamatergic supraspinal inputs on the motor neurons during REM sleep. REM sleep behavior disorder (RBD) consists of simple behaviors (i.e., twitching, jerking) and complex behaviors (i.e., defensive behavior, talking). Animal research has lead to the hypothesis that complex behaviors in RBD are due to SLD pathology, while simple behaviors of RBD may be due to less severe SLD pathology or dysfunction of the VMM, ventral pons, or spinal cord. Copyright © 2013 Elsevier B.V. All rights reserved.

The Perceived Role of ICTs in Quality of Life in Three Chinese Cities

ERIC Educational Resources Information Center

Lee, Paul S. N.; Leung, Louis; Lo, Venhwei; Xiong, Chengyu

2008-01-01

This study assesses the perceived role of information and communication technologies (ICTs) including the Internet, mobile telephone, CD/MD/MP3, television and VCR/VCD/DVD in raising quality of life (QoL). A comparison is made between three Chinese cities, namely, Beijing, Taipei and Hong Kong, to see if differences exist in the perceived value of…

Investigation of guanosine-quartet assemblies by vibrational and electronic circular dichroism spectroscopy, a novel approach for studying supramolecular entities.

PubMed

Setnicka, Vladimír; Urbanová, Marie; Volka, Karel; Nampally, Sreenivasachary; Lehn, Jean-Marie

2006-11-24

The self-assembly of guanosine-5'-hydrazide G-1 in D(2)O, in the presence and absence of sodium cations, has been investigated by chiroptical techniques: electronic (ECD) and the newly introduced vibrational (VCD) circular dichroism spectroscopy. Using a combination of ECD and VCD with other methods such as IR, electron microscopy, and electrospray ionization mass spectrometry (ESI-MS) it was found that G-1 produces long-range chiral aggregates consisting of G-quartets, (G-1)(4), subsequently stacked into columns, [(G-1)(4)](n), induced by binding of metal cations between the (G-1)(4) species. This process, accompanied by gelation of the sample, is highly efficient in the presence of an excess of sodium cations, leading to aggregates with strong quartet-quartet interaction. Thermally induced conformational changes and conformational stability of guanosine-5'-hydrazide assemblies were studied by chiroptical techniques and the melting temperature of the hydrogels formed was obtained. The temperature-dependent experiments indicate that the long-range supramolecular aggregates are dissociated by increasing temperature into less ordered species, monomers, or other intermediates in equilibrium, as indicated by MS experiments.

Sensing site-specific structural characteristics and chirality using vibrational circular dichroism of isotope labeled peptides.

PubMed

Keiderling, Timothy A

2017-12-01

Isotope labeling has a long history in chemistry as a tool for probing structure, offering enhanced sensitivity, or enabling site selection with a wide range of spectroscopic tools. Chirality sensitive methods such as electronic circular dichroism are global structural tools and have intrinsically low resolution. Consequently, they are generally insensitive to modifications to enhance site selectivity. The use of isotope labeling to modify vibrational spectra with unique resolvable frequency shifts can provide useful site-specific sensitivity, and these methods have been recently more widely expanded in biopolymer studies. While the spectral shifts resulting from changes in isotopic mass can provide resolution of modes from specific parts of the molecule and can allow detection of local change in structure with perturbation, these shifts alone do not directly indicate structure or chirality. With vibrational circular dichroism (VCD), the shifted bands and their resultant sign patterns can be used to indicate local conformations in labeled biopolymers, particularly if multiple labels are used and if their coupling is theoretically modeled. This mini-review discusses selected examples of the use of labeling specific amides in peptides to develop local structural insight with VCD spectra. © 2017 Wiley Periodicals, Inc.

Chirality and chiroptical properties of amyloid fibrils.

PubMed

Dzwolak, Wojciech

2014-09-01

Chirality of amyloid fibrils-linear beta-sheet-rich aggregates of misfolded protein chains-often manifests in morphological traits such as helical twist visible in atomic force microscopy and in chiroptical properties accessible to vibrational circular dichroism (VCD). According to recent studies the relationship between molecular chirality of polypeptide building blocks and superstructural chirality of amyloid fibrils may be more intricate and less deterministic than previously assumed. Several puzzling experimental findings have put into question earlier intuitive ideas on: 1) the bottom-up chirality transfer upon amyloidogenic self-assembly, and 2) the structural origins of chiroptical properties of protein aggregates. For example, removal of a single amino acid residue from an amyloidogenic all-L peptide was shown to reverse handedness of fibrils. On the other hand, certain types of amyloid aggregates revealed surprisingly strong VCD spectra with the sign and shape dependent on the conditions of fibrillation. Hence, microscopic and chiroptical studies have highlighted chirality as one more aspect of polymorphism of amyloid fibrils. This brief review is intended to outline the current state of research on amyloid-like fibrils from the perspective of their structural and superstructural chirality and chiroptical properties. © 2014 Wiley Periodicals, Inc.

Bifurcatriol, a New Antiprotozoal Acyclic Diterpene from the Brown Alga Bifurcaria bifurcata

PubMed Central

Smyrniotopoulos, Vangelis; Merten, Christian; Kaiser, Marcel; Tasdemir, Deniz

2017-01-01

Linear diterpenes that are commonly found in brown algae are of high chemotaxonomic and ecological importance. This study reports bifurcatriol (1), a new linear diterpene featuring two stereogenic centers isolated from the Irish brown alga Bifurcaria bifurcata. The gross structure of this new natural product was elucidated based on its spectroscopic data (IR, 1D and 2D-NMR, HRMS). Its absolute configuration was identified by experimental and computational vibrational circular dichroism (VCD) spectroscopy, combined with the calculation of 13C-NMR chemical shielding constants. Bifurcatriol (1) was tested for in vitro antiprotozoal activity towards a small panel of parasites (Plasmodium falciparum, Trypanosoma brucei rhodesiense, T. cruzi, and Leishmania donovani) and cytotoxicity against mammalian primary cells. The highest activity was exerted against the malaria parasite P. falciparum (IC50 value 0.65 μg/mL) with low cytotoxicity (IC50 value 56.6 μg/mL). To our knowledge, this is the first successful application of VCD and DP4 probability analysis of the calculated 13C-NMR chemical shifts for the simultaneous assignment of the absolute configuration of multiple stereogenic centers in a long-chain acyclic natural product. PMID:28767061

J-R fracture characteristics of ferritic steels for RPVs and RCS piping of nuclear power plants

NASA Astrophysics Data System (ADS)

Yoon, Ji-Hyun; Lee, Bong-Sang; Hong, Jun-Hwa

2001-10-01

J-R fracture resistance tests have been performed on 3 heats of SA508-Gr.3 nuclear reactor pressure vessel (RPV) steel as well as 2 heats of SA516-Gr.70 and a heat of SA508-Gr.1a steels for nuclear reactor coolant system (RCS) piping. For the latter two steels, dynamic in addition to static J-R fracture resistances were investigated. From the test results of the SA508-Gr.3 steels, the J-R fracture resistance was superior in the following order: Si-killing steel, modified VCD steel and VCD steel. Microstructural analyses were carried out to correlate J-R fracture resistances with microstructural characteristics. According to the test results for SA508-Gr.1a and SA516-Gr.70 steels, all of the tested steels showed steep drops in fracture resistance at certain temperature and loading rate combinations. One heat of SA516-Gr.70 steel was very sensitive to dynamic strain aging and its fracture resistance was significantly low. It was concluded that microstructural and chemical factors affect the J-R fracture and DSA characteristics of SA516-Gr.70 steels.

Including thermal disorder of hydrogen bonding to describe the vibrational circular dichroism spectrum of zwitterionic L-alanine in water.

PubMed

Orestes, Ednilsom; Bistafa, Carlos; Rivelino, Roberto; Canuto, Sylvio

2015-05-28

The vibrational circular dichroism (VCD) spectrum of l-alanine amino acid in aqueous solution in ambient conditions has been studied. The emphasis has been placed on the inclusion of the thermal disorder of the solute-solvent hydrogen bonds that characterize the aqueous solution condition. A combined and sequential use of molecular mechanics and quantum mechanics was adopted. To calculate the average VCD spectrum, the DFT B3LYP/6-311++G(d,p) level of calculation was employed, over one-hundred configurations composed of the solute plus all water molecules making hydrogen bonds with the solute. Simplified considerations including only four explicit solvent molecules and the polarizable continuum model were also made for comparison. Considering the large number of vibration frequencies with only limited experimental results a direct comparison is presented, when possible, and in addition a statistical analysis of the calculated values was performed. The results are found to be in line with the experiment, leading to the conclusion that including thermal disorder may improve the agreement of the vibrational frequencies with experimental results, but the thermal effects may be of greater value in the calculations of the rotational strengths.

Intraperitoneally administered IgG from patients with amyotrophic lateral sclerosis or from an immune-mediated goat model increase the levels of TNF-α, IL-6, and IL-10 in the spinal cord and serum of mice.

PubMed

Obál, Izabella; Klausz, Gergely; Mándi, Yvette; Deli, Mária; Siklós, László; Engelhardt, József I

2016-05-24

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that involves the selective loss of the upper and lower motor neurons (MNs). Neuroinflammation has been implicated in the pathogenesis of the sporadic form of the disease. We earlier developed immune-mediated animal models of ALS and demonstrated humoral and cellular immune reactions in the nervous system and in the sera of patients and animals. The accumulation of immunoglobulin G (IgG), an elevated intracellular level of calcium, ultrastructural alterations in the MNs, and activation of the microglia were noted in the spinal cord of ALS patients. Similar alterations developed in mice inoculated intraperitoneally with IgG from ALS patients or from an immune-mediated goat model. We have now examined whether the intraperitoneal injection of mice with IgG from sporadic ALS patients or from immunized goats with the homogenate of the anterior horn of the bovine spinal cord is associated with changes in the pro-inflammatory (TNF-α and IL-6) and anti-inflammatory (IL-10) cytokines in the spinal cord and serum of the mice. The levels of cytokines were measured by ELISA. Intraperitoneally administered IgG from the ALS patients induced subclinical signs of MN disease, while the injection of IgG from immunized goats resulted in a severe respiratory dysfunction and limb paralysis 24 h after the injections. Significantly increased levels of TNF-α and IL-10 were detected in the spinal cord of the mice injected with the human ALS IgG. The level of IL-6 increased primarily in the serum. The IgG from the immunized goats induced highly significant increases in the levels of all three cytokines in the serum and the spinal cord of mice. Our earlier experiments had proved that when ALS IgG or IgG from immune-mediated animal models was inoculated into mice, it was taken up in the MNs and had the ability to initiate damage in them. The pathological process was paralleled by microglia recruitment and activation in the spinal cord. The present experiment revealed that these forms of IgG cause significant increases in certain cytokine levels locally in the spinal cord and in the serum of the inoculated mice. These results suggest that IgG directed to the MNs may be an initial element in the damage to the MNs both in human ALS and in its immune-mediated animal models.

[Umbilical cord collision in the first trimester in a monoamniotic twin pregnancy--does it really matter?].

PubMed

Ropacka-Lesiak, Mariola; Lebioda, Anna; Breborowicz, Grzegorz

2012-09-01

A case of an umbilical cord collision diagnosed in the first trimester of a monochorionic monoamniotic twin pregnancy is presented. An intensive surveillance included ultrasound monitoring with color and spectral Doppler and fetal echocardiography. The first signs of fetal distress were observed at 31 weeks of gestation. The brain sparing effect as well as a periodic appearance of the "notch" in the wave forms obtained from the umbilical artery from the collision region were observed. In the first ultrasound scan there were no abnormalities in twin I. In contrast, in twin II a vascular resistance in the umbilical artery was at the upper limit for the gestational age. Five days later, decreased vascular resistance in the middle cerebral artery, which fluctuated at the lower limit, was noticed in twin II. After the next four days, PI in the middle cerebral artery decreased below the lower limit and tricuspid regurgitation appeared. In twin I the vascular resistance in the umbilical artery increased and remained at the upper limit of the reference ranges. Cardiotocographic records did not reveal signs of fetal distress. After a week the signs of brain sparing effect were visible in both fetuses. However, twin II showed features of umbilical cord clamping in the form of abnormal blood flow waveforms in the umbilical artery ("notch"). Therefore, despite the absence of signs of fetal distress in CTG in monochorionic monoamniotic twins with growth discordance of 20% and exponents of periodical clamping of the umbilical cord in twin II at 34 weeks, the decision to perform a caesarean section was made. The patient gave birth to two daughters (twin I: weight 1780g, Ap 10, pH 7.39, 7.40, BE -3.0, -2.6, and twin II: weight 1860g, Ap 10, pH 7.29, 7.35, BE -1.4, -2.4). During the delivery the umbilical cords collision was found at the region close to the body of twins. This case presents the possibility of using ultrasound and Doppler in the early diagnosis, monitoring and surveillance of pregnancies complicated by umbilical cords collision in monochorionic monoamniotic twins from the first trimester. Application of these methods allowed a safe monitoring of the fetuses and the identification of the onset of the cords collision. This in turn allowed the achievement of fetal maturity at 34 weeks, when both the risk of death and neonatal morbidity are significantly minimized. The use of Doppler blood flow velocimetry allowed the diagnosis of umbilical cords tightening before there were any signs of cardiac dysfunction in the CTG. This enabled to determine the most favorable, earlier time for delivery. The paper presents diagnostic management and surveillance in monochorionic monoamniotic pregnancy complicated by umbilical cord collision since the early pregnancy.

Spinal inhibition and motor function in adults with spastic cerebral palsy

PubMed Central

Condliffe, E. G.; Jeffery, D. T.; Emery, D. J.

2016-01-01

Key points Abnormal activation of motoneurons in the spinal cord by sensory pathways is thought to contribute to impaired movement control and spasticity in individuals with cerebral palsy.Here we use single motor unit recordings to show how individual motoneurons in the spinal cord respond to sensory inputs in a group of participants with cerebral palsy having different degrees of motor dysfunction.In participants who had problems walking independently and required assistive devices such as wheelchairs, sensory pathways only excited motoneurons in the spinal cord.In contrast, in participants with cerebral palsy who walked independently for long distances, sensory inputs both inhibited and excited motoneurons in the spinal cord, similar to what we found in uninjured control participants.These findings demonstrate that in individuals with severe cerebral palsy, inhibitory control of motoneurons from sensory pathways is reduced and may contribute to motor dysfunction and spasticity. Abstract Reduced inhibition of spinal motoneurons by sensory pathways may contribute to heightened reflex activity, spasticity and impaired motor function in individuals with cerebral palsy (CP). To measure if the activation of inhibitory post‐synaptic potentials (IPSPs) by sensory inputs is reduced in CP, the tonic discharge rate of single motor units from the soleus muscle was plotted time‐locked to the occurrence of a sensory stimulation to produce peri‐stimulus frequencygrams (PSFs). Stimulation to the medial arch of the foot was used to activate cutaneomuscular afferents in 17 adults with bilateral spastic CP and 15 neurologically intact (NI) peers. Evidence of IPSP activation from the PSF profiles, namely a marked pause or reduction in motor unit firing rates at the onset of the cutaneomuscular reflex, was found in all NI participants but in only half of participants with CP. In the other half of the participants with CP, stimulation of cutaneomuscular afferents produced a PSF profile indicative of a pure excitatory post‐synaptic potential, with firing rates increasing above the mean pre‐stimulus rate for 300 ms or more. The amplitude of motoneuron inhibition during the period of IPSP activation, as measured from the surface EMG, was less in participants with poor motor function as evaluated with the Gross Motor Functional Classification System (r = 0.72, P < 0.001) and the Functional Mobility Scale (r = −0.82, P < 0.001). These findings demonstrate that in individuals with CP, reduced activation of motoneuron IPSPs by sensory inputs is associated with reduced motor function and may contribute to enhanced reflexes and spasticity in CP. PMID:26842905

[Spinal cord injury with neurogenic lower urinary tract dysfunction as a potential risk factor for bladder carcinoma].

PubMed

Böthig, Ralf; Fiebag, Kai; Kowald, Birgitt; Hirschfeld, Sven; Thietje, Roland; Kurze, Ines; Schöps, Wolfgang; Böhme, Holger; Kaufmann, Albert; Zellner, Michael; Kadhum, Thura; Golka, Klaus

2018-05-29

 Life expectancy for people with spinal cord injury/disease (SCI/D) is increasing, due to modern advances in treatment methods and in neuro-urology. However, with the increased life expectancy the risk of developing urinary bladder cancer is gaining importance. How is this patient group different from the general population?  Single-centre retrospective evaluation of consecutive patient data with spinal cord injury and proven urinary bladder cancer.  Between January 1st 1998 and March 31st 2017, 32 (3 female, 29 male) out of a total of 6432 patients with SCI/D were diagnosed with bladder cancer.The average age at bladder cancer diagnosis was 54.5 years, which is well below the average for bladder cancer cases in the general population (male: 74, female: 75).Twenty-seven patients suffered from urodynamically confirmed neurogenic detrusor overactivity, while five patients (all male) had detrusor acontractility.The median latency period between the onset of SCI/D and tumor diagnosis was 29.5 years. Temporary indwelling catheterisation was found in four patients for only 1.61 % of the overall latency period of all patients.The majority of the patients (n = 27) had transitional cell carcinoma, while five had squamous cell carcinoma. Of the 32 patients, 25 (78 %) had muscle invasive bladder cancer at ≥ T2 at the time of diagnosis. Regarding tumour grading, 23 out of 32 patients showed a histologically poorly differentiated G3 carcinoma; two patients each had G2 and G1 tumours repectively (no information on tumour grading was available in five patients).The median survival for all patients was 11.5 months. The prognosis of patients with squamous cell carcinoma was even worse; 4 out of 5 died within 7 months (median 4 months).  The significantly younger age at onset and the frequency of invasive, poorly differentiated tumour at diagnosis indicate that SCI/D influences both bladder cancer risk and prognosis significantly. The latency period between paralysis and tumour disease seems to be a decisive risk parameter.The type of neurogenic bladder dysfunction and the form of bladder drainage do not appear to influence the risk. Long-term indwelling catheter drainage played only a minor role in the investigated patients.Early detection of bladder cancer in patients with spinal cord injury remains a challenge. © Georg Thieme Verlag KG Stuttgart · New York.

Neurogenic bowel dysfunction: Clinical management recommendations of the Neurologic Incontinence Committee of the Fifth International Consultation on Incontinence 2013.

PubMed

Cotterill, Nikki; Madersbacher, Helmut; Wyndaele, Jean J; Apostolidis, Apostolos; Drake, Marcus J; Gajewski, Jerzy; Heesakkers, John; Panicker, Jalesh; Radziszewski, Piotr; Sakakibara, Ryuji; Sievert, Karl-Dietrich; Hamid, Rizwan; Kessler, Thomas M; Emmanuel, Anton

2018-01-01

Evidence-based guidelines for the management of neurological disease and lower bowel dysfunction have been produced by the International Consultations on Incontinence (ICI). These are comprehensive guidelines, and were developed to have world-wide relevance. To update clinical management of neurogenic bowel dysfunction from the recommendations of the 4th ICI, 2009. A series of evidence reviews and updates were performed by members of the working group. The resulting guidelines were presented at the 2012 meeting of the European Association of Urology for consultation, and modifications applied to deliver evidence based conclusions and recommendations for the scientific report of the 5th edition of the ICI in 2013. The current review is a synthesis of the conclusions and recommendations, including the algorithms for initial and specialized management of neurogenic bowel dysfunction. The pathophysiology is described in terms of spinal cord injury, multiple sclerosis, and Parkinson's disease. Assessment requires detailed history and clinical assessment, general investigations, and specialized testing, if required. Treatment primarily focuses on optimizing stool consistency and regulating bowel evacuation to improve quality of life. Symptom management covers conservative and interventional measures to promote good habits and assist stool evacuation, along with prevention of incontinence. Education is essential to achieving optimal bowel management. The review offers a pragmatic approach to management in the context of complex pathophysiology and varied evidence base. © 2017 Wiley Periodicals, Inc.

Spinal Disinhibition in Experimental and Clinical Painful Diabetic Neuropathy

PubMed Central

Marshall, Andrew G.; Lee-Kubli, Corinne; Azmi, Shazli; Zhang, Michael; Ferdousi, Maryam; Mixcoatl-Zecuatl, Teresa; Petropoulos, Ioannis N.; Ponirakis, Georgios; Fineman, Mark S.; Fadavi, Hassan; Frizzi, Katie; Tavakoli, Mitra; Jolivalt, Corinne G.; Boulton, Andrew J.M.; Efron, Nathan; Calcutt, Nigel A.

2017-01-01

Impaired rate-dependent depression (RDD) of the Hoffman reflex is associated with reduced dorsal spinal cord potassium chloride cotransporter expression and impaired spinal γ-aminobutyric acid type A receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin supplementation that did not restore normoglycemia. Impaired RDD in diabetic rats was rapidly normalized by spinal delivery of duloxetine acting via 5-hydroxytryptamine type 2A receptors and temporally coincident with the alleviation of allodynia. Deficits in RDD and corneal nerve density were demonstrated in patients with painful diabetic neuropathy compared with healthy control subjects and patients with painless diabetic neuropathy. Spinal inhibitory dysfunction and peripheral small fiber pathology may contribute to the clinical phenotype in painful diabetic neuropathy. Deficits in RDD may help identify patients with spinally mediated painful diabetic neuropathy who may respond optimally to therapies such as duloxetine. PMID:28202580

Relative shortening and functional tethering of spinal cord in adolescent scoliosis - Result of asynchronous neuro-osseous growth, summary of an electronic focus group debate of the IBSE.

PubMed

Chu, Winnie Cw; Lam, Wynnie Mw; Ng, Bobby Kw; Tze-Ping, Lam; Lee, Kwong-Man; Guo, Xia; Cheng, Jack Cy; Burwell, R Geoffrey; Dangerfield, Peter H; Jaspan, Tim

2008-06-27

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The Statement for this debate was written by Dr WCW Chu and colleagues who examine the spinal cord to vertebral growth interaction during adolescence in scoliosis. Using the multi-planar reconstruction technique of magnetic resonance imaging they investigated the relative length of spinal cord to vertebral column including ratios in 28 girls with AIS (mainly thoracic or double major curves) and 14 age-matched normal girls. Also evaluated were cerebellar tonsillar position, somatosensory evoked potentials (SSEPs), and clinical neurological examination. In severe AIS compared with normal controls, the vertebral column is significantly longer without detectable spinal cord lengthening. They speculate that anterior spinal column overgrowth relative to a normal length spinal cord exerts a stretching tethering force between the two ends, cranially and caudally leading to the initiation and progression of thoracic AIS. They support and develop the Roth-Porter concept of uncoupled neuro-osseous growth in the pathogenesis of AIS which now they prefer to term 'asynchronous neuro-osseous growth'. Morphological evidence about the curve apex suggests that the spinal cord is also affected, and a 'double pathology' is suggested. AIS is viewed as a disorder with a wide spectrum and a common neuroanatomical abnormality namely, a spinal cord of normal length but short relative to an abnormally lengthened anterior vertebral column. Neuroanatomical changes and/or abnormal neural function may be expressed only in severe cases. This asynchronous neuro-osseous growth concept is regarded as one component of a larger concept. The other component relates to the brain and cranium of AIS subjects because abnormalities have been found in brain (infratentorial and supratentorial) and skull (vault and base). The possible relevance of systemic melatonin-signaling pathway dysfunction, platelet calmodulin levels and putative vertebral vascular biology to the asynchronous neuro-osseous growth concept is discussed. A biomechanical model to test the spinal component of the concept is in hand. There is no published research on the biomechanical properties of the spinal cord for scoliosis specimens. Such research on normal spinal cords includes movements (kinematics), stress-strain responses to uniaxial loading, and anterior forces created by the stretched cord in forward flexion that may alter sagittal spinal shape during adolescent growth. The asynchronous neuro-osseous growth concept for the spine evokes controversy. Dr Chu and colleagues respond to five other concepts of pathogenesis for AIS and suggest that relative anterior spinal overgrowth and biomechanical growth modulation may also contribute to AIS pathogenesis.

Spinal cord compression in pseudohypoparathyroidism.

PubMed

Roberts, Timothy T; Khasnavis, Siddharth; Papaliodis, Dean N; Citone, Isabella; Carl, Allen L

2013-12-01

Spinal cord compression associated with pseudohypoparathyroidism (PHP) is an increasingly reported sequelae of the underlying metabolic syndrome. The association of neurologic dysfunction with PHP is not well appreciated. We believe this to be secondary to a combination of underlying congenital stenosis, manifest by short pedicles secondary to premature physeal closure, and hypertrophic ossification of the vertebral bony and ligamentous complexes. The purpose of this case report is to review the case of spinal stenosis in a child with PHP Type Ia. We are aware of only eight published reports of patients with PHP Type Ia and spinal stenosis-there are only two previously known cases of pediatric spinal stenosis secondary to PHP. This is a case report detailing the symptoms, diagnosis, interventions, complications, and ultimate outcomes of a pediatric patient undergoing spinal decompression and fusion for symptomatic stenosis secondary to PHP Type Ia. Literature search was reviewed regarding the reports of spinal stenosis and PHP, and the results are culminated and discussed. We report on a 14-year-old obese male with PHP and progressive lower extremity weakness secondary to congenital spinal stenosis. Examination revealed functional upper extremities with spastic paraplegia of bilateral lower extremities. The patient's neurologic function was cautiously monitored, but he deteriorated to a bed-bound state, preoperatively. The patient's chart was reviewed, summarized, and presented. Literature was searched using cross-reference of PHP and the terms "spinal stenosis," "myelopathy", "myelopathic," and "spinal cord compression." All relevant case reports were reviewed, and the results are discussed herein. The patient underwent decompression and instrumented fusion of T2-T11. He improved significantly with regard to lower extremity function, achieving unassisted ambulation function after extensive rehabilitation. Results from surgical decompression in previously reported cases are mixed, ranging from full recovery to iatrogenic paraplegia. The association of neurologic dysfunction with PHP is not well appreciated. It is important to highlight this rare association. Surgical decompression in patients with PHP yields mixed results but may be of greatest efficacy in younger patients who receive early intervention. Copyright © 2013 Elsevier Inc. All rights reserved.

Spinal Cord Injury Causes Chronic Liver Pathology in Rats

PubMed Central

Sauerbeck, Andrew D.; Laws, J. Lukas; Bandaru, Veera V.R.; Popovich, Phillip G.; Haughey, Norman J.

2015-01-01

Abstract Traumatic spinal cord injury (SCI) causes major disruption to peripheral organ innervation and regulation. Relatively little work has investigated these post-SCI systemic changes, however, despite considerable evidence that multiple organ system dysfunction contributes to chronic impairments in health. Because metabolic dysfunction is common after SCI and the liver is a pivotal site for metabolic homeostasis, we sought to determine if liver pathology occurs as a result of SCI in a rat spinal contusion model. Histologic evidence showed excess lipid accumulation in the liver for at least 21 days post-injury after cervical or midthoracic SCI. Lipidomic analysis revealed an acute increase in hepatic ceramides as well as chronically elevated lactosylceramide. Post-SCI hepatic changes also included increased proinflammatory gene expression, including interleukin (IL)-1α, IL-1β, chemokine ligand-2, and tumor necrosis factor-α mRNA. These were coincident with increased CD68+ macrophages in the liver through 21 days post-injury. Serum alanine transaminase, used clinically to detect liver damage, was significantly increased at 21 days post-injury, suggesting that early metabolic and inflammatory damage preceded overt liver pathology. Surprisingly, liver inflammation was even detected after lumbar SCI. Collectively, these results suggest that SCI produces chronic liver injury with symptoms strikingly similar to those of nonalcoholic steatohepatitis (fatty liver disease). These clinically significant hepatic changes after SCI are known to contribute to systemic inflammation, cardiovascular disease, and metabolic syndrome, all of which are more prevalent in persons with SCI. Targeting acute and prolonged hepatic pathology may improve recovery and reduce long-term complications after SCI. PMID:25036371

Early presymptomatic cholinergic dysfunction in a murine model of amyotrophic lateral sclerosis

PubMed Central

Casas, Caty; Herrando-Grabulosa, Mireia; Manzano, Raquel; Mancuso, Renzo; Osta, Rosario; Navarro, Xavier

2013-01-01

Sporadic and familiar amyotrophic lateral sclerosis (ALS) cases presented lower cholinergic activity than in healthy individuals in their still preserved spinal motoneurons (MNs) suggesting that cholinergic reduction might occur before MN death. To unravel how and when cholinergic function is compromised, we have analyzed the spatiotemporal expression of choline acetyltransferase (ChAT) from early presymptomatic stages of the SOD1G93A ALS mouse model by confocal immunohistochemistry. The analysis showed an early reduction in ChAT content in soma and presynaptic boutons apposed onto MNs (to 76%) as well as in cholinergic interneurons in the lumbar spinal cord of the 30-day-old SOD1G93A mice. Cholinergic synaptic stripping occurred simultaneously to the presence of abundant surrounding major histocompatibility complex II (MHC-II)-positive microglia and the accumulation of nuclear Tdp-43 and the appearance of mild oxidative stress within MNs. Besides, there was a loss of neuronal MHC-I expression, which is necessary for balanced synaptic stripping after axotomy. These events occurred before the selective raise of markers of denervation such as ATF3. By the same time, alterations in postsynaptic cholinergic-related structures were also revealed with a loss of the presence of sigma-1 receptor, a Ca2+ buffering chaperone in the postsynaptic cisternae. By 2 months of age, ChAT seemed to accumulate in the soma of MNs, and thus efferences toward Renshaw interneurons were drastically diminished. In conclusion, cholinergic dysfunction in the local circuitry of the spinal cord may be one of the earliest events in ALS etiopathogenesis. PMID:23531559

Reduced Activity of AMP-Activated Protein Kinase Protects against Genetic Models of Motor Neuron Disease

PubMed Central

Lim, M. A.; Selak, M. A.; Xiang, Z.; Krainc, D.; Neve, R. L.; Kraemer, B. C.; Watts, J. L.

2012-01-01

A growing body of research indicates that amyotrophic lateral sclerosis (ALS) patients and mouse models of ALS exhibit metabolic dysfunction. A subpopulation of ALS patients possesses higher levels of resting energy expenditure and lower fat-free mass compared to healthy controls. Similarly, two mutant copper zinc superoxide dismutase 1 (mSOD1) mouse models of familial ALS possess a hypermetabolic phenotype. The pathophysiological relevance of the bioenergetic defects observed in ALS remains largely elusive. AMP-activated protein kinase (AMPK) is a key sensor of cellular energy status and thus might be activated in various models of ALS. Here, we report that AMPK activity is increased in spinal cord cultures expressing mSOD1, as well as in spinal cord lysates from mSOD1 mice. Reducing AMPK activity either pharmacologically or genetically prevents mSOD1-induced motor neuron death in vitro. To investigate the role of AMPK in vivo, we used Caenorhabditis elegans models of motor neuron disease. C. elegans engineered to express human mSOD1 (G85R) in neurons develops locomotor dysfunction and severe fecundity defects when compared to transgenic worms expressing human wild-type SOD1. Genetic reduction of aak-2, the ortholog of the AMPK α2 catalytic subunit in nematodes, improved locomotor behavior and fecundity in G85R animals. Similar observations were made with nematodes engineered to express mutant tat-activating regulatory (TAR) DNA-binding protein of 43 kDa molecular weight. Altogether, these data suggest that bioenergetic abnormalities are likely to be pathophysiologically relevant to motor neuron disease. PMID:22262909

Disrupted autophagy after spinal cord injury is associated with ER stress and neuronal cell death

PubMed Central

Liu, S; Sarkar, C; Dinizo, M; Faden, A I; Koh, E Y; Lipinski, M M; Wu, J

2015-01-01

Autophagy is a catabolic mechanism facilitating degradation of cytoplasmic proteins and organelles in a lysosome-dependent manner. Autophagy flux is necessary for normal neuronal homeostasis and its dysfunction contributes to neuronal cell death in several neurodegenerative diseases. Elevated autophagy has been reported after spinal cord injury (SCI); however, its mechanism, cell type specificity and relationship to cell death are unknown. Using a rat model of contusive SCI, we observed accumulation of LC3-II-positive autophagosomes starting at posttrauma day 1. This was accompanied by a pronounced accumulation of autophagy substrate protein p62, indicating that early elevation of autophagy markers reflected disrupted autophagosome degradation. Levels of lysosomal protease cathepsin D and numbers of cathepsin-D-positive lysosomes were also decreased at this time, suggesting that lysosomal damage may contribute to the observed defect in autophagy flux. Normalization of p62 levels started by day 7 after SCI, and was associated with increased cathepsin D levels. At day 1 after SCI, accumulation of autophagosomes was pronounced in ventral horn motor neurons and dorsal column oligodendrocytes and microglia. In motor neurons, disruption of autophagy strongly correlated with evidence of endoplasmic reticulum (ER) stress. As autophagy is thought to protect against ER stress, its disruption after SCI could contribute to ER-stress-induced neuronal apoptosis. Consistently, motor neurons showing disrupted autophagy co-expressed ER-stress-associated initiator caspase 12 and cleaved executioner caspase 3. Together, these findings indicate that SCI causes lysosomal dysfunction that contributes to autophagy disruption and associated ER-stress-induced neuronal apoptosis. PMID:25569099

Analytical Methods for Determining the Motion of a Rigid Body Equipped with Internal Motion-Sensing Transducers

DTIC Science & Technology

1976-10-01

should be easily converted into software for use on high-speed digital computers. Since no readily available references were found containing relationships...L31 Library 1 ONR Boston 4 NSWC, White Oak 1 J.E. Goeller 1 ONR Chicago 1 V.C.D. Dawson 1 H.K. Steves 1 ONR Pasadena 1 Libary 1 NRL/CODE 2627 Lib 1

Impact of vocal cord ultrasonography on endocrine surgery practices.

PubMed

Carneiro-Pla, Denise; Solorzano, Carmen C; Wilhelm, Scott M

2016-01-01

It is common practice to perform flexible laryngoscopy (FL) to ensure true vocal cord (TVC) mobility in patients with previous neck operations or patients with suspected VC dysfunction. Vocal cord ultrasonography (VCUS) is accurate in identifying TVC paralysis. The goal of this study is to evaluate the impact of VCUS as the initial study to confirm TVC mobility in patients requiring preoperative FL. A total of 194 consecutive patients with indications for preoperative FL underwent VCUS. In group 1, 52 patients had FL regardless of the results of VCUS, whereas in group 2, 142 patients had VCUS followed by FL only when VCUS was unsatisfactory. VCUS visualized TVC/arytenoids in 164 of 194 (85%) patients. TVC visualization was more common in women (95%) and in patients without thyroid cartilage calcification (92%) (P < .0005). VCUS predicted all paralyzed TVC. In group 2, 76% of patients had adequate VCUS and avoided preoperative FL. Among 24% of patients in whom VCUS was inadequate, 16 had preoperative FL attributable to a lack of TVC visualization, 6 had abnormal TVC mobility, 11 needed additional confirmations, and 2 had previous FL for another reason. VCUS changed surgeon practices by avoiding the need for preoperative FL in the majority of patients. This noninvasive and sensitive method demonstrates TVC mobility and safely precludes preoperative FL in most patients. Copyright © 2016 Elsevier Inc. All rights reserved.

International bowel function basic spinal cord injury data set.

PubMed

Krogh, K; Perkash, I; Stiens, S A; Biering-Sørensen, F

2009-03-01

International expert working group. To develop an International Bowel Function Basic Spinal Cord Injury (SCI) Data Set presenting a standardized format for the collection and reporting of a minimal amount of information on bowel function in daily practice or in research. Working group consisting of members appointed by the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS). A draft prepared by the working group was reviewed by Executive Committee of the International SCI Standards and Data Sets, and later by ISCoS Scientific Committee and the ASIA Board. Relevant and interested scientific and professional (international) organizations and societies (approximately 40) were also invited to review the data set and it was posted on the ISCoS and ASIA websites for 3 months to allow comments and suggestions. The ISCoS Scientific Committee, Council and ASIA Board received the data set for final review and approval. The International Bowel Function Basic SCI Data Set includes the following 12 items: date of data collection, gastrointestinal or anal sphincter dysfunction unrelated to SCI, surgical procedures on the gastrointestinal tract, awareness of the need to defecate, defecation method and bowel care procedures, average time required for defecation, frequency of defecation, frequency of fecal incontinence, need to wear pad or plug, medication affecting bowel function/constipating agents, oral laxatives and perianal problems. An International Bowel Function Basic SCI Data Set has been developed.

Maternal Pre-Gravid Obesity Changes Gene Expression Profiles Towards Greater Inflammation and Reduced Insulin Sensitivity in Umbilical Cord

PubMed Central

Thakali, Keshari M.; Saben, Jessica; Faske, Jennifer B.; Lindsey, Forrest; Gomez-Acevedo, Horacio; Lowery, Curtis L.; Badger, Thomas M.; Andres, Aline; Shankar, Kartik

2014-01-01

Background Maternal obesity is associated with unfavorable outcomes, which may be reflected in the as yet undiscovered gene expression profiles of the umbilical cord (UC). Methods UCs from 12 lean (pre-gravid BMI < 24.9) and 10 overweight/obese (OW/OB, pre-gravid BMI ≥25) women without gestational diabetes were collected for gene expression analysis using Human Primeview microarrays (Affymetrix). Metabolic parameters were assayed in mother’s plasma and cord blood. Results Although offspring birth weight and adiposity (at 2-wk) did not differ between groups, expression of 232 transcripts was affected in UC from OW/OB compared to those of lean mothers. GSEA analysis revealed an up-regulation of genes related to metabolism, stimulus and defense response and inhibitory to insulin signaling in the OW/OB group. We confirmed that EGR1, periostin, and FOSB mRNA expression was induced in UCs from OW/OB moms, while endothelin receptor B, KFL10, PEG3 and EGLN3 expression was decreased. Messenger RNA expression of EGR1, FOSB, MEST and SOCS1 were positively correlated (p<0.05) with mother’s first trimester body fat mass (%). Conclusions Our data suggest a positive association between maternal obesity and changes in UC gene expression profiles favoring inflammation and insulin resistance, potentially predisposing infants to develop metabolic dysfunction later on in life. PMID:24819376

In silico modeling of axonal reconnection within a discrete fiber tract after spinal cord injury.

PubMed

Woolfe, Franco; Waxman, Stephen G; Hains, Bryan C

2007-02-01

Following spinal cord injury (SCI), descending axons that carry motor commands from the brain to the spinal cord are injured or transected, producing chronic motor dysfunction and paralysis. Reconnection of these axons is a major prerequisite for restoration of function after SCI. Thus far, only modest gains in motor function have been achieved experimentally or in the clinic after SCI, identifying the practical limitations of current treatment approaches. In this paper, we use an ordinary differential equation (ODE) to simulate the relative and synergistic contributions of several experimentally-established biological factors related to inhibition or promotion of axonal repair and restoration of function after SCI. The factors were mathematically modeled by the ODE. The results of our simulation show that in a model system, many factors influenced the achievability of axonal reconnection. Certain factors more strongly affected axonal reconnection in isolation, and some factors interacted in a synergistic fashion to produce further improvements in axonal reconnection. Our data suggest that mathematical modeling may be useful in evaluating the complex interactions of discrete therapeutic factors not possible in experimental preparations, and highlight the benefit of a combinatorial therapeutic approach focused on promoting axonal sprouting, attraction of cut ends, and removal of growth inhibition for achieving axonal reconnection. Predictions of this simulation may be of utility in guiding future experiments aimed at restoring function after SCI.

Inherited neuroaxonal dystrophy in dogs causing lethal, fetal-onset motor system dysfunction and cerebellar hypoplasia

PubMed Central

Fyfe, John C.; Al-Tamimi, Raba' A.; Castellani, Rudy J.; Rosenstein, Diana; Goldowitz, Daniel; Henthorn, Paula S.

2010-01-01

Neuroaxonal dystrophy in brainstem, spinal cord tracts, and spinal nerves accompanied by cerebellar hypoplasia was observed in a colony of laboratory dogs. Fetal akinesia was documented by ultrasonographic examination. At birth, affected puppies exhibited stereotypical positioning of limbs, scoliosis, arthrogryposis, pulmonary hypoplasia, and respiratory failure. Regional hypoplasia in the central nervous system was apparent grossly, most strikingly as underdeveloped cerebellum and spinal cord. Histopathologic abnormalities included swollen axons and spheroids in brainstem and spinal cord tracts; reduced cerebellar foliation, patchy loss of Purkinje cells, multifocal thinning of the external granular cell layer, and loss of neurons in the deep cerebellar nuclei; spheroids and loss of myelinated axons in spinal roots and peripheral nerves; increased myocyte apoptosis in skeletal muscle; and fibrofatty connective tissue proliferation around joints. Breeding studies demonstrated that the canine disorder is a fully penetrant, simple autosomal recessive trait. The disorder demonstrated a type and distribution of lesions homologous to that of human infantile neuroaxonal dystrophy (INAD), most commonly caused by mutations of PLA2G6, but alleles of informative markers flanking the canine PLA2G6 locus did not associate with the canine disorder. Thus, fetal-onset neuroaxonal dystrophy in dogs, a species with well-developed genome mapping resources, provides a unique opportunity for additional disease gene discovery and understanding of this pathology. PMID:20653033

Effects of cathodal trans-spinal direct current stimulation on lower urinary tract function in normal and spinal cord injury mice with overactive bladder

NASA Astrophysics Data System (ADS)

Ahmed, Zaghloul

2017-10-01

Objective. Lower urinary tract (LUT) dysfunction is a monumental problem affecting quality of life following neurotrauma, such as spinal cord injury (SCI). Proper function of the bladder and its associated structures depends on coordinated activity of the neuronal circuitry in the spinal cord and brain. Disconnection between the spinal and brain centers controlling the LUT causes fundamental changes in the mechanisms involved in the micturition and storage reflexes. We investigated the effects of cathodal trans-spinal direct current stimulation (c-tsDCS) of the lumbosacral spine on bladder and external urinary sphincter (EUS) functions. Approach. We used cystometry and electromyography (EMG), in mice with and without SCI. Main results. c-tsDCS caused initiation of the micturition reflex in urethane-anesthetized normal mice with depressed micturition reflexes. This effect was associated with normalized EUS-EMG activity. Moreover, in urethane-anesthetized normal mice with expressed micturition reflexes, c-tsDCS increased the firing frequency, amplitude, and duration of EUS-EMG activity. These effects were associated with increased maximum intravesical pressure (P max) and intercontraction interval (ICI). In conscious normal animals, c-tsDCS caused significant increases in P max, ICI, threshold pressure (P thres), baseline pressure (P base), and number and amplitude of non-voiding contractions (NVCnumb and P im, respectively). In conscious mice with severe contusive SCI and overactive bladder, c-tsDCS increased P max, ICI, and P thres, but decreased P base, NVCnumb, and P im. c-tsDCS reduced the detrusor-overactivity/cystometry ratio, which is a measure of bladder overactivity associated with renal deterioration. Significance. These results indicate that c-tsDCS induces robust modulation of the lumbosacral spinal-cord circuitry that controls the LUT.

Clinical presentation, imaging findings, and prognosis of spinal dural arteriovenous fistula.

PubMed

Lee, Jookyung; Lim, Young-Min; Suh, Dae Chul; Rhim, Seung Chul; Kim, Sang Joon; Kim, Kwang-Kuk

2016-04-01

Spinal dural arteriovenous fistula (SDAVF) is a relatively common acquired vascular malformation of the spinal cord. Assessment of a SDAVF is often difficult because of non-specific findings on non-invasive imaging modalities. Diagnosis of a SDAVF is often delayed, and some patients receive unnecessary treatment and treatment delays, often resulting in a poor outcome. The aim of this study was to characterize the clinical presentation, typical imaging findings, and long-term outcome of SDAVF. Forty patients (13 women, 27 men; mean age 58.18 ± standard deviation 14.75 years) who were treated at our hospital from June 1992 to March 2014 were retrospectively reviewed. We investigated the baseline characteristics, clinical presentation, imaging findings, treatment modalities, and outcome of the patients. The most common clinical presentation was a sensory symptom (80%), followed by motor weakness (70%), and sphincter dysfunction (62.5%). Roughly one-third (32.5%) of patients had a stepwise progression of fluctuating weakness and sensory symptoms, but the most common presentation was chronic progressive myelopathic symptoms (47.5%). Thirty-four patients (85%) had T2 signal change on the spinal cord MRI, indicative of cord edema. Thirty-eight patients had typical perimedullary vessel flow voids on T2-weighted MRI. Twenty-eight patients were treated with endovascular embolization, five patients underwent surgery, and four patients underwent both. Clinical outcome was determined by severity of initial deficit (p=0.008), extent of cord edema (p=0.010), treatment failure (p=0.004), and a residual fistula (p=0.017). SDAVF causes a treatable myelopathy, so early diagnosis and intervention is essential. Copyright © 2015 Elsevier Ltd. All rights reserved.

Detecting bladder fullness through the ensemble activity patterns of the spinal cord unit population in a somatovisceral convergence environment.

PubMed

Park, Jae Hong; Kim, Chang-Eop; Shin, Jaewoo; Im, Changkyun; Koh, Chin Su; Seo, In Seok; Kim, Sang Jeong; Shin, Hyung-Cheul

2013-10-01

Chronic monitoring of the state of the bladder can be used to notify patients with urinary dysfunction when the bladder should be voided. Given that many spinal neurons respond both to somatic and visceral inputs, it is necessary to extract bladder information selectively from the spinal cord. Here, we hypothesize that sensory information with distinct modalities should be represented by the distinct ensemble activity patterns within the neuronal population and, therefore, analyzing the activity patterns of the neuronal population could distinguish bladder fullness from somatic stimuli. We simultaneously recorded 26-27 single unit activities in response to bladder distension or tactile stimuli in the dorsal spinal cord of each Sprague-Dawley rat. In order to discriminate between bladder fullness and tactile stimulus inputs, we analyzed the ensemble activity patterns of the entire neuronal population. A support vector machine (SVM) was employed as a classifier, and discrimination performance was measured by k-fold cross-validation tests. Most of the units responding to bladder fullness also responded to the tactile stimuli (88.9-100%). The SVM classifier precisely distinguished the bladder fullness from the somatic input (100%), indicating that the ensemble activity patterns of the unit population in the spinal cord are distinct enough to identify the current input modality. Moreover, our ensemble activity pattern-based classifier showed high robustness against random losses of signals. This study is the first to demonstrate that the two main issues of electroneurographic monitoring of bladder fullness, low signals and selectiveness, can be solved by an ensemble activity pattern-based approach, improving the feasibility of chronic monitoring of bladder fullness by neural recording.

Top ten research priorities for spinal cord injury: the methodology and results of a British priority setting partnership.

PubMed

van Middendorp, J J; Allison, H C; Ahuja, S; Bracher, D; Dyson, C; Fairbank, J; Gall, A; Glover, A; Gray, L; Masri, W El; Uttridge, A; Cowan, K

2016-05-01

This is a mixed-method consensus development project. The objective of this study was to identify a top ten list of priorities for future research into spinal cord injury (SCI). The British Spinal Cord Injury Priority Setting Partnership was established in 2013 and completed in 2014. Stakeholders included consumer organisations, healthcare professional societies and caregivers. This partnership involved the following four key stages: (i) gathering of research questions, (ii) checking of existing research evidence, (iii) interim prioritisation and (iv) a final consensus meeting to reach agreement on the top ten research priorities. Adult individuals with spinal cord dysfunction because of trauma or non-traumatic causes, including transverse myelitis, and individuals with a cauda equina syndrome (henceforth grouped and referred to as SCI) were invited to participate in this priority setting partnership. We collected 784 questions from 403 survey respondents (290 individuals with SCI), which, after merging duplicate questions and checking systematic reviews for evidence, were reduced to 109 unique unanswered research questions. A total of 293 people (211 individuals with SCI) participated in the interim prioritisation process, leading to the identification of 25 priorities. At a final consensus meeting, a representative group of individuals with SCI, caregivers and health professionals agreed on their top ten research priorities. Following a comprehensive, rigorous and inclusive process, with participation from individuals with SCI, caregivers and health professionals, the SCI research agenda has been defined by people to whom it matters most and should inform the scope and future activities of funders and researchers for the years to come. The NIHR Oxford Biomedical Research Centre provided core funding for this project.

Ground zero: not asthma at all.

PubMed

de Benedictis, Fernando Maria; de Benedictis, Diletta; Mirabile, Lorenzo; Pozzi, Marco; Guerrieri, Arcangela; Di Pillo, Sabrina

2015-09-01

Upper airway obstruction is commonly misdiagnosed as asthma. We report on four children with recurrent respiratory symptoms who had been erroneously diagnosed as having asthma and who received anti-asthma medication for several years. The evaluation of spirometry tracing was neglected in all cases. Subglottic stenosis, tracheomalacia secondary to tracheo-esophageal fistula, double aortic arch, and vocal cord dysfunction were suspected by direct inspection of the flow-volume curves and eventually diagnosed. The value of clinical history and careful evaluation of spirometry tracing in children with persistent respiratory symptoms is critically discussed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Excessive daytime somnolence in spinocerebellar ataxia type 1.

PubMed

Dang, Dien; Cunnington, David

2010-03-15

Autosomal dominant spinocerebellar ataxias (SCAs) are progressive neurodegenerative disorders which result in dysfunction of the neuronal systems of the spinal cord, brainstem, and cerebellum. The manifestations of daytime somnolence and abnormal sleep behavior have been described in SCA type 3 (SCA3) and SCA type 6 (SCA6), but as yet have not been described in SCA type 1 (SCA1). We report two cases of sleep disturbance, fatigue and excessive daytime somnolence in individuals with SCA1 and their progress through several therapies. These case studies are unique as they describe excessive daytime somnolence and sleep abnormalities in SCA1.

Determination of the weak phase γ from color-allowed B+/-u-->DK+/- decays

NASA Astrophysics Data System (ADS)

Xing, Zhi-Zhong

1998-11-01

We show that it is possible to determine the weak phase γ≡arg(-V*ubVud/V*cbVcd) of the Cabibbo-Kobayashi-Maskawa flavor mixing matrix only from the measurement of the color-allowed B+/-u-->DK+/- decay rates. The uncertainty of this method, arising mainly from the factorization approximation for two tree-level spectator quark transitions, may be well controlled.

The effects of Fu Zi on changes in the body heat of dogs.

PubMed

Chen, Tian-Tian; Qi, Chunhua; Guo, Huijun; Cheng, Ziqiang; Zhou, Dong; Liu, Haitao; Liu, Jianzhu

2009-03-01

The aim of the present study was to investigate the effects of Fu Zi on changes in the body heat of dogs. Twelve clinically healthy dogs were divided into two groups: the control group (six dogs) and the experimental group (six dogs). The control group was made to ingest normal saline mixed with canned meat, while the experimental group was made to ingest the Fu Zi solution mixed with canned meat. The infrared thermographic system was used to determine the level of body heat generated by these dogs. These areas include the dorsocranial (DCr), dorsocaudal (DCd), ventrocranial (VCr), and ventrocaudal (VCd) regions at pretreatment and were determined at 10, 20, 30, 50, 90, 120, 240, and 360 minutes after treatment for each of these areas. The results showed a tendency toward increased body heat until 30 minutes after ingestion of the Fu Zi powder mixed with canned meat. The significant differences in the changes of body heat were detected at 360 minutes in the DCd regions, 20 minutes in the VCr regions, and 30 minutes in the VCd regions between the experimental and control groups (p < 0.05). Based from our results, we find that Fu Zi can increase and maintain the dogs' body heat for at least 6 hours.

Absolute Configuration of 3-METHYLCYCLOHEXANONE by Chiral Tag Rotational Spectroscopy and Vibrational Circular Dichroism

NASA Astrophysics Data System (ADS)

Evangelisti, Luca; Holdren, Martin S.; Mayer, Kevin J.; Smart, Taylor; West, Channing; Pate, Brooks

2017-06-01

The absolute configuration of 3-methylcyclohexanone was established by chiral tag rotational spectroscopy measurements using 3-butyn-2-ol as the tag partner. This molecule was chosen because it is a benchmark measurement for vibrational circular dichroism (VCD). A comparison of the analysis approaches of chiral tag rotational spectroscopy and VCD will be presented. One important issue in chiral analysis by both methods is the conformational flexibility of the molecule being analyzed. The analysis of conformational composition of samples will be illustrated. In this case, the high spectral resolution of molecular rotational spectroscopy and potential for spectral simplification by conformational cooling in the pulsed jet expansion are advantages for chiral tag spectroscopy. The computational chemistry requirements for the two methods will also be discussed. In this case, the need to perform conformer searches for weakly bound complexes and to perform reasonably high level quantum chemistry geometry optimizations on these complexes makes the computational time requirements less favorable for chiral tag rotational spectroscopy. Finally, the issue of reliability of the determination of the absolute configuration will be considered. In this case, rotational spectroscopy offers a "gold standard" analysis method through the determination of the ^{13}C-subsitution structure of the complex between 3-methylcyclohexanone and an enantiopure sample of the 3-butyn-2-ol tag.

Electronic and vibrational exciton coupling in oxidized trianglimines.

PubMed

Szymkowiak, Joanna; Kwit, Marcin

2018-02-01

Readily available chiral trianglimine and their (poly)oxygenated congeners represent a unique class of macrocyclic rigid compounds optimal for testing electronic and vibrational circular dichroism exciton chirality methods. Electronic and vibrational circular dichroism spectra of such trianglimines are strongly affected by polar substituents in macrocycle skeletons. Double substitution by OH groups in each aromatic fragment of the macrocycle causes sign reversal of the exciton couplet in the region of the strongest UV absorption. On the other hand, electronic circular dichroism spectrum of the macrocycle having 2 methoxy groups shows 2 exciton couplets-the long-wavelength positive and the second of the negative sign, observed at the shorter wavelengths. VCD spectra of macrocyclic imines show vibrational exciton couplets in the region of strong C=N stretches. The signs of these couplets are positive and the opposite of the diamine chirality. For trianglimine macrocycles the interpretation of VCD spectra in terms of excitons is much more convincing than for electronic circular dichroism spectra. By contrast, trans-1,2-diaminocyclohexane-based vicinal diimines, being a one-third of the respective macrocycle, do not exhibit any vibrational exciton effect. Experimental data were confronted with DFT calculations. We observed good-to-excellent agreement between experimental and computed data. © 2017 Wiley Periodicals, Inc.

SMN regulates axonal local translation via miR-183/mTOR pathway

PubMed Central

Kye, Min Jeong; Niederst, Emily D.; Wertz, Mary H.; Gonçalves, Inês do Carmo G.; Akten, Bikem; Dover, Katarzyna Z.; Peters, Miriam; Riessland, Markus; Neveu, Pierre; Wirth, Brunhilde; Kosik, Kenneth S.; Sardi, S. Pablo; Monani, Umrao R.; Passini, Marco A.; Sahin, Mustafa

2014-01-01

Reduced expression of SMN protein causes spinal muscular atrophy (SMA), a neurodegenerative disorder leading to motor neuron dysfunction and loss. However, the molecular mechanisms by which SMN regulates neuronal dysfunction are not fully understood. Here, we report that reduced SMN protein level alters miRNA expression and distribution in neurons. In particular, miR-183 levels are increased in neurites of SMN-deficient neurons. We demonstrate that miR-183 regulates translation of mTor via direct binding to its 3′ UTR. Interestingly, local axonal translation of mTor is reduced in SMN-deficient neurons, and this can be recovered by miR-183 inhibition. Finally, inhibition of miR-183 expression in the spinal cord of an SMA mouse model prolongs survival and improves motor function of Smn-mutant mice. Together, these observations suggest that axonal miRNAs and the mTOR pathway are previously unidentified molecular mechanisms contributing to SMA pathology. PMID:25055867

Descending pain modulation in irritable bowel syndrome (IBS): a systematic review and meta-analysis.

PubMed

Chakiath, Rosemary J; Siddall, Philip J; Kellow, John E; Hush, Julia M; Jones, Mike P; Marcuzzi, Anna; Wrigley, Paul J

2015-12-10

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. While abdominal pain is a dominant symptom of IBS, many sufferers also report widespread hypersensitivity and present with other chronic pain conditions. The presence of widespread hypersensitivity and extra-intestinal pain conditions suggests central nervous dysfunction. While central nervous system dysfunction may involve the spinal cord (central sensitisation) and brain, this review will focus on one brain mechanism, descending pain modulation. We will conduct a comprehensive search for the articles indexed in the databases Ovid MEDLINE, Ovid Embase, Ovid PsycINFO and Cochrane Central Register of Controlled Trial (CENTRAL) from their inception to August 2015, that report on any aspect of descending pain modulation in irritable bowel syndrome. Two independent reviewers will screen studies for eligibility, assess risk of bias and extract relevant data. Results will be tabulated and, if possible, a meta-analysis will be carried out. The systematic review outlined in this protocol aims to summarise current knowledge regarding descending pain modulation in IBS. PROSPERO CRD42015024284.

Virtual reality training improves balance function.

PubMed

Mao, Yurong; Chen, Peiming; Li, Le; Huang, Dongfeng

2014-09-01

Virtual reality is a new technology that simulates a three-dimensional virtual world on a computer and enables the generation of visual, audio, and haptic feedback for the full immersion of users. Users can interact with and observe objects in three-dimensional visual space without limitation. At present, virtual reality training has been widely used in rehabilitation therapy for balance dysfunction. This paper summarizes related articles and other articles suggesting that virtual reality training can improve balance dysfunction in patients after neurological diseases. When patients perform virtual reality training, the prefrontal, parietal cortical areas and other motor cortical networks are activated. These activations may be involved in the reconstruction of neurons in the cerebral cortex. Growing evidence from clinical studies reveals that virtual reality training improves the neurological function of patients with spinal cord injury, cerebral palsy and other neurological impairments. These findings suggest that virtual reality training can activate the cerebral cortex and improve the spatial orientation capacity of patients, thus facilitating the cortex to control balance and increase motion function.

Virtual reality training improves balance function

PubMed Central

Mao, Yurong; Chen, Peiming; Li, Le; Huang, Dongfeng

2014-01-01

Virtual reality is a new technology that simulates a three-dimensional virtual world on a computer and enables the generation of visual, audio, and haptic feedback for the full immersion of users. Users can interact with and observe objects in three-dimensional visual space without limitation. At present, virtual reality training has been widely used in rehabilitation therapy for balance dysfunction. This paper summarizes related articles and other articles suggesting that virtual reality training can improve balance dysfunction in patients after neurological diseases. When patients perform virtual reality training, the prefrontal, parietal cortical areas and other motor cortical networks are activated. These activations may be involved in the reconstruction of neurons in the cerebral cortex. Growing evidence from clinical studies reveals that virtual reality training improves the neurological function of patients with spinal cord injury, cerebral palsy and other neurological impairments. These findings suggest that virtual reality training can activate the cerebral cortex and improve the spatial orientation capacity of patients, thus facilitating the cortex to control balance and increase motion function. PMID:25368651

Development of an Algorithm to Perform a Comprehensive Study of Autonomic Dysreflexia in Animals with High Spinal Cord Injury Using a Telemetry Device.

PubMed

Popok, David; West, Christopher; Frias, Barbara; Krassioukov, Andrei V

2016-07-29

Spinal cord injury (SCI) is a debilitating neurological condition characterized by somatic and autonomic dysfunctions. In particular, SCI above the mid-thoracic level can lead to a potentially life-threatening hypertensive condition called autonomic dysreflexia (AD) that is often triggered by noxious or non-noxious somatic or visceral stimuli below the level of injury. One of the most common triggers of AD is the distension of pelvic viscera, such as during bladder and bowel distension or evacuation. This protocol presents a novel pattern recognition algorithm developed for a JAVA platform software to study the fluctuations of cardiovascular parameters as well as the number, severity and duration of spontaneously occurring AD events. The software is able to apply a pattern recognition algorithm on hemodynamic data such as systolic blood pressure (SBP) and heart rate (HR) extracted from telemetry recordings of conscious and unrestrained animals before and after thoracic (T3) complete transection. With this software, hemodynamic parameters and episodes of AD are able to be detected and analyzed with minimal experimenter bias.

CD4+ T Cells Coexpressing CD134 (OX40) Harbor Significantly Increased Levels of Human Herpesvirus 6B DNA Following Umbilical Cord Blood Transplantation.

PubMed

Pritchett, Joshua C; Green, Jaime S; Thomm, Angela M; Knox, Konstance K; Verneris, Michael R; Lund, Troy C

2016-12-15

Human herpesvirus 6B (HHV-6B) commonly reactivates after umbilical cord blood transplantation (UCBT) and is associated with delayed engraftment, fever, rash, and central nervous system dysfunction. Recently, CD134 (OX40) has been implicated as a potential viral entry receptor. We evaluated CD4 + CD134 + / neg-lo and CD8 + CD134 + / neg-lo cells at day 28 after UCBT in 20 subjects with previously documented HHV-6 reactivation and persistent viremia. Analysis of CD4 + CD134 + cells as compared to CD4 + CD134 neg-lo cells showed 0.308 versus 0.129 copies of HHV-6B/cell (P = .0002). CD8 + CD134 +/neg-lo cells contained little to no HHV-6B copies. Following UCBT, CD4 + CD134 + cells harbor significantly increased levels of HHV-6B, suggesting that CD134 (OX40) may facilitate viral entry. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Inducible laryngeal obstruction during exercise: moving beyond vocal cords with new insights.

PubMed

Olin, James Tod; Clary, Matthew S; Deardorff, Emily H; Johnston, Kristina; Morris, Michael J; Sokoya, Mofiyinfolu; Staudenmayer, Herman; Christopher, Kent L

2015-02-01

Exercise as an important part of life for the health and wellness of children and adults. Inducible laryngeal obstruction (ILO) is a consensus term used to describe a group of disorders previously called vocal cord dysfunction, paradoxical vocal fold motion, and numerous other terms. Exercise-ILO can impair one's ability to exercise, can be confused with asthma, leading to unnecessary prescription of asthma controller and rescue medication, and results in increased healthcare resource utilization including (rarely) emergency care. It is characterized by episodic shortness of breath and noisy breathing that generally occurs at high work rates. The present diagnostic gold standard for all types of ILO is laryngoscopic visualization of inappropriate glottic or supraglottic movement resulting in airway narrowing during a spontaneous event or provocation challenge. A number of different behavioral techniques, including speech therapy, biofeedback, and cognitive-behavioral psychotherapy, may be appropriate to treat individual patients. A consensus nomenclature, which will allow for better characterization of patients, coupled with new diagnostic techniques, may further define the epidemiology and etiology of ILO as well as enable objective evaluation of therapeutic modalities.

Early, but not late, treatment with human umbilical cord blood-derived mesenchymal stem cells attenuates cisplatin nephrotoxicity through immunomodulation.

PubMed

Park, Ji Hyeon; Jang, Hye Ryoun; Kim, Do Hee; Kwon, Ghee Young; Lee, Jung Eun; Huh, Wooseong; Choi, Soo Jin; Oh, Wonil; Oh, Ha Young; Kim, Yoon-Goo

2017-10-01

Preemptive treatment with mesenchymal stem cells (MSCs) can attenuate cisplatin-induced acute kidney injury (AKI). However, it is uncertain whether MSC treatment after the development of renal dysfunction prevents AKI progression or if MSC immunomodulatory properties contribute to MSC therapy. In this study, human umbilical cord blood (hUCB)-derived MSCs were used to compare the effects and mechanisms of early and late MSC therapy in a murine model. After cisplatin injection into C57BL/6 mice, hUCB-MSCs were administered on day 1 (early treatment) or day 3 (late treatment). With early treatment, cisplatin nephrotoxicity was attenuated as evidenced by decreased blood urea nitrogen (BUN) and reduced apoptosis and tubular injury scores on day 3 Early treatment resulted in downregulation of intrarenal monocyte chemotactic protein-1 and IL-6 expression and upregulation of IL-10 and VEGF expression. Flow cytometric analysis showed similar populations of infiltrated immune cells in both groups; however, regulatory T-cell (Treg) infiltration was 2.5-fold higher in the early treatment group. The role of Tregs was confirmed by the blunted effect of early treatment on renal injury after Treg depletion. In contrast, late treatment (at a time when BUN levels were 2-fold higher than baseline levels) showed no renoprotective effects on day 6 Neither the populations of intrarenal infiltrating immune cells (including Tregs) nor cytokine expression levels were affected by late treatment. Our results suggest that early MSC treatment attenuates renal injury by Treg induction and immunomodulation, whereas a late treatment (i.e., after the development of renal dysfunction) does not prevent AKI progression or alter the intrarenal inflammatory micromilieu. Copyright © 2017 the American Physiological Society.

Effectiveness of an upper extremity exercise device integrated with computer gaming for aerobic training in adolescents with spinal cord dysfunction.

PubMed

Widman, Lana M; McDonald, Craig M; Abresch, R Ted

2006-01-01

To determine whether a new upper extremity exercise device integrated with a video game (GameCycle) requires sufficient metabolic demand and effort to induce an aerobic training effect and to explore the feasibility of using this system as an exercise modality in an exercise intervention. Pre-post intervention. University-based research facility. SUBJECT POPULATION: A referred sample of 8 adolescent subjects with spina bifida (4 girls, 15.5 +/- 0.6 years; 4 boys, 17.5 +/- 0.9 years) was recruited to participate in the project. All subjects had some level of mobility impairment that did not allow them to participate in mainstream sports available to their nondisabled peers. Five subjects used a wheelchair full time, one used a wheelchair occasionally, but walked with forearm crutches, and 2 were fully ambulatory, but had impaired gait. Peak oxygen uptake, maximum work output, aerobic endurance, peak heart rate, rating of perceived exertion, and user satisfaction. Six of the 8 subjects were able to reach a Vo2 of at least 50% of their Vo2 reserve while using the GameCycle. Seven of the 8 subjects reached a heart rate of at least 50% of their heart rate reserve. One subject did not reach either 50% of Vo2 reserve or 50% of heart rate reserve. Seven of the 8 subjects increased their maximum work capability after training with the GameCycle at least 3 times per week for 16 weeks. The data suggest that the GameCycle seems to be adequate as an exercise device to improve oxygen uptake and maximum work capability in adolescents with lower extremity disability caused by spinal cord dysfunction. The subjects in this study reported that the video game component was enjoyable and provided a motivation to exercise.

Contemporary Cardiovascular Concerns after Spinal Cord Injury: Mechanisms, Maladaptations, and Management.

PubMed

Phillips, Aaron A; Krassioukov, Andrei V

2015-12-15

Cardiovascular (CV) issues after spinal cord injury (SCI) are of paramount importance considering they are the leading cause of death in this population. Disruption of autonomic pathways leads to a highly unstable CV system, with impaired blood pressure (BP) and heart rate regulation. In addition to low resting BP, on a daily basis the majority of those with SCI suffer from transient episodes of aberrantly low and high BP (termed orthostatic hypotension and autonomic dysreflexia, respectively). In fact, autonomic issues, including resolution of autonomic dysreflexia, are frequently ranked by individuals with high-level SCI to be of greater priority than walking again. Owing to a combination of these autonomic disturbances and a myriad of lifestyle factors, the pernicious process of CV disease is accelerated post-SCI. Unfortunately, these secondary consequences of SCI are only beginning to receive appropriate clinical attention. Immediately after high-level SCI, major CV abnormalities present in the form of neurogenic shock. After subsiding, new issues related to BP instability arise, including orthostatic hypotension and autonomic dysreflexia. This review describes autonomic control over the CV system before injury and the mechanisms underlying CV abnormalities post-SCI, while also detailing the end-organ consequences, including those of the heart, as well as the systemic and cerebral vasculature. The tertiary impact of CV dysfunction will also be discussed, such as the potential impediment of rehabilitation, and impaired cognitive function. In the recent past, our understanding of autonomic dysfunctions post-SCI has been greatly enhanced; however, it is vital to further develop our understanding of the long-term consequences of these conditions, which will equip us to better manage CV disease morbidity and mortality in this population.

Human umbilical cord mesenchymal stem cells alleviate interstitial fibrosis and cardiac dysfunction in a dilated cardiomyopathy rat model by inhibiting TNF-α and TGF-β1/ERK1/2 signaling pathways

PubMed Central

Zhang, Changyi; Zhou, Guichi; Chen, Yezeng; Liu, Sizheng; Chen, Fen; Xie, Lichun; Wang, Wei; Zhang, Yonggang; Wang, Tianyou; Lai, Xiulan; Ma, Lian

2018-01-01

Dilated cardiomyopathy (DCM) is a disease of the heart characterized by pathological remodeling, including patchy interstitial fibrosis and degeneration of cardiomyocytes. In the present study, the beneficial role of human umbilical cord-derived mesenchymal stem cells (HuMSCs) derived from Wharton's jelly was evaluated in the myosin-induced rat model of DCM. Male Lewis rats (aged 8-weeks) were injected with porcine myosin to induce DCM. Cultured HuMSCs (1×106 cells/rat) were intravenously injected 28 days after myosin injection and the effects on myocardial fibrosis and the underlying signaling pathways were investigated and compared with vehicle-injected and negative control rats. Myosin injections in rats (vehicle group and experimental group) for 28 days led to severe fibrosis and significant deterioration of cardiac function indicative of DCM. HuMSC treatment reduced fibrosis as determined by Masson's staining of collagen deposits, as well as quantification of molecular markers of myocardial fibrosis such as collagen I/III, profibrotic factors transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), and connective tissue growth factor (CTGF). HuMSC treatment restored cardiac function as observed using echocardiography. In addition, western blot analysis indicated that HuMSC injections in DCM rats inhibited the expression of TNF-α, extracellular-signal regulated kinase 1/2 (ERK1/2) and TGF-β1, which is a master switch for inducing myocardial fibrosis. These findings suggested that HuMSC injections attenuated myocardial fibrosis and dysfunction in a rat model of DCM, likely by inhibiting TNF-α and the TGF-β1/ERK1/2 fibrosis pathways. Therefore, HuMSC treatment may represent a potential therapeutic method for treatment of DCM. PMID:29115435

Neural Mechanisms Underlying Lower Urinary Tract Dysfunction

PubMed Central

Ogawa, Teruyuki; Miyazato, Minoru; Kitta, Takeya; Furuta, Akira; Chancellor, Michael B.; Tyagi, Pradeep

2014-01-01

This article summarizes anatomical, neurophysiological, and pharmacological studies in humans and animals to provide insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract and alterations in these mechanisms in lower urinary tract dysfunction. The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the bladder, urethra, and external urethral sphincter. During urine storage, the outlet is closed and the bladder smooth muscle is quiescent. When bladder volume reaches the micturition threshold, activation of a micturition center in the dorsolateral pons (the pontine micturition center) induces a bladder contraction and a reciprocal relaxation of the urethra, leading to bladder emptying. During voiding, sacral parasympathetic (pelvic) nerves provide an excitatory input (cholinergic and purinergic) to the bladder and inhibitory input (nitrergic) to the urethra. These peripheral systems are integrated by excitatory and inhibitory regulation at the levels of the spinal cord and the brain. Therefore, injury or diseases of the nervous system, as well as disorders of the peripheral organs, can produce lower urinary tract dysfunction, leading to lower urinary tract symptoms, including both storage and voiding symptoms, and pelvic pain. Neuroplasticity underlying pathological changes in lower urinary tract function is discussed. PMID:24578802

A single dose of a neuron-binding human monoclonal antibody improves brainstem NAA concentrations, a biomarker for density of spinal cord axons, in a model of progressive multiple sclerosis.

PubMed

Wootla, Bharath; Denic, Aleksandar; Watzlawik, Jens O; Warrington, Arthur E; Rodriguez, Moses

2015-04-29

Intracerebral infection of susceptible mouse strains with Theiler's murine encephalomyelitis virus (TMEV) results in chronic demyelinating disease with progressive axonal loss and neurologic dysfunction similar to progressive forms of multiple sclerosis (MS). We previously showed that as the disease progresses, a marked decrease in brainstem N-acetyl aspartate (NAA; metabolite associated with neuronal integrity) concentrations, reflecting axon health, is measured. We also demonstrated stimulation of neurite outgrowth by a neuron-binding natural human antibody, IgM12. Treatment with either the serum-derived or recombinant human immunoglobulin M 12 (HIgM12) preserved functional motor activity in the TMEV model. In this study, we examined IgM-mediated changes in brainstem NAA concentrations and central nervous system (CNS) pathology. (1)H-magnetic resonance spectroscopy (MRS) showed that treatment with HIgM12 significantly increased brainstem NAA concentrations compared to controls in TMEV-infected mice. Pathologic analysis demonstrated a significant preservation of axons in the spinal cord of animals treated with HIgM12. This study links drug efficacy of slowing deficits with axon preservation and NAA concentrations in the brainstem in a model of progressive MS. HIgM12-mediated changes of NAA concentrations in the brainstem are a surrogate marker of axon injury/preservation throughout the spinal cord. This study provides proof-of-concept that a neuron-reactive human IgM can be therapeutic and provides a biomarker for clinical trials.

A combined deficiency of vitamins E and C causes severe central nervous system damage in guinea pigs.

PubMed

Burk, Raymond F; Christensen, Joani M; Maguire, Mark J; Austin, Lori M; Whetsell, William O; May, James M; Hill, Kristina E; Ebner, Ford F

2006-06-01

A short period of combined deficiency of vitamins E and C causes profound central nervous system (CNS) dysfunction in guinea pigs. For this report, CNS histopathology was studied to define the nature and extent of injury caused by this double deficiency. Weanling guinea pigs were fed a vitamin E-deficient or -replete diet for 14 d. Then vitamin C was withdrawn from the diet of some guinea pigs. Four diet groups were thus formed: replete, vitamin E deficient, vitamin C deficient, and both vitamin E and C deficient. From 5 to 11 d after institution of the doubly deficient diet, 9 of 12 guinea pigs developed paralysis, and 2 more were found dead. The remaining guinea pig in the doubly deficient group and all animals in the other 3 groups survived without clinical impairment until the experiment was terminated at 13-15 d. Brains and spinal cords were serially sectioned and stained for examination. Only the combined deficiency produced damage in the CNS. The damage consisted mainly of nerve cell death, axonal degeneration, vascular injury, and associated glial cell responses. The spinal cord and the ventral pons in the brainstem were most severely affected, often exhibiting asymmetric cystic lesions. Several features of the lesions suggest that the primary damage was to blood vessels. These results indicate that the paralysis and death caused by combined deficiency of vitamins E and C in guinea pigs is caused by severe damage in the brainstem and spinal cord.

Alterations in Mouse Hypothalamic Adipokine Gene Expression and Leptin Signaling following Chronic Spinal Cord Injury and with Advanced Age

PubMed Central

Bigford, Gregory E.; Bracchi-Ricard, Valerie C.; Nash, Mark S.; Bethea, John R.

2012-01-01

Chronic spinal cord injury (SCI) results in an accelerated trajectory of several cardiovascular disease (CVD) risk factors and related aging characteristics, however the molecular mechanisms that are activated have not been explored. Adipokines and leptin signaling are known to play a critical role in neuro-endocrine regulation of energy metabolism, and are now implicated in central inflammatory processes associated with CVD. Here, we examine hypothalamic adipokine gene expression and leptin signaling in response to chronic spinal cord injury and with advanced age. We demonstrate significant changes in fasting-induced adipose factor (FIAF), resistin (Rstn), long-form leptin receptor (LepRb) and suppressor of cytokine-3 (SOCS3) gene expression following chronic SCI and with advanced age. LepRb and Jak2/stat3 signaling is significantly decreased and the leptin signaling inhibitor SOCS3 is significantly elevated with chronic SCI and advanced age. In addition, we investigate endoplasmic reticulum (ER) stress and activation of the uncoupled protein response (UPR) as a biological hallmark of leptin resistance. We observe the activation of the ER stress/UPR proteins IRE1, PERK, and eIF2alpha, demonstrating leptin resistance in chronic SCI and with advanced age. These findings provide evidence for adipokine-mediated inflammatory responses and leptin resistance as contributing to neuro-endocrine dysfunction and CVD risk following SCI and with advanced age. Understanding the underlying mechanisms contributing to SCI and age related CVD may provide insight that will help direct specific therapeutic interventions. PMID:22815920

Positive and negative affect in individuals with spinal cord injuries.

PubMed

Salter, J E; Smith, S D; Ethans, K D

2013-03-01

Participants with spinal cord injuries (SCIs) and healthy controls completed standardized questionnaires assessing depression level, positive and negative affect, and personality traits. To identify the specific characteristics of emotional experiences affected by spinal cord injury. A Canadian rehabilitation center. Individuals with SCIs were recruited from a list of patients who had volunteered to participate in studies being conducted by the SCI clinic. Healthy controls were recruited from the community, but tested in the SCI clinic. Thirty-six individuals with complete (ASIA A) SCIs and 36 age-, gender- and education-matched controls participated in this study. SCI participants were classified as cervical (C1-C7), upper thoracic (T1-T5) or lower thoracic/upper lumbar (T6-L2). All participants completed the Beck Depression Inventory, the Positive and Negative Affect Schedules, the NEO Neuroticism Questionnaire, and the harm avoidance scale of the Tridimensional Personality Questionnaire. Data were analyzed using independent-samples t-tests (when contrasting SCI and controls) and analysis of variance (when comparing across SCI groups). Participants with SCIs experienced significantly less positive affect than controls. The two groups did not differ in their experience of negative affect. Participants with SCIs also reported greater levels of depression. Depression scores improved with an increasing number of years post injury. Individuals with SCIs are characterized by specific emotional dysfunction related to the experience of positive emotions, rather than a tendency to ruminate on negative emotions. The results suggest that these individuals would benefit from rehabilitation programs that include training in positive psychology.

Intestinal diversion (colostomy or ileostomy) in patients with severe bowel dysfunction following spinal cord injury.

PubMed

Hocevar, Barbara; Gray, Mikel

2008-01-01

Spinal cord injury (SCI) affects motor and sensory nervous integrity resulting in paralysis of lower or both upper and lower extremities, as well as autonomic nervous system function resulting in neurogenic bowel. SCI leads to diminished or lost sensations of the need to defecate or inability to distinguish the presence of gas versus liquid versus solid stool in the rectal vault. Sensory loss, incomplete evacuation of stool from the rectal vault, immobility, and reduced anal sphincter tone increase the risk of fecal incontinence. Gastrointestinal symptoms are associated with depression, anxiety, and significant impairments in quality of life (QOL) in a significant portion of persons with SCI. 1. To compare clinical, functional, or quality of life outcomes in spinal cord injured patients with gastrointestinal symptoms managed by conservative measures versus intestinal diversion (colostomy or ileostomy). 2. To identify complications associated with ostomy surgery in patients with bowel dysfunction and SCI. A systematic review of electronic databases MEDLINE and CINAHL (from January 1960 to November 2007) was undertaken using the following key words: (1) ostomy, (2) stoma, (3) colostomy, and (4) ileostomy. Boolean features of these databases were used to combine these terms with the key word "spinal cord injuries." Prospective and retrospective studies that directly compared clinical, functional, QOL outcomes or satisfaction among patients with intestinal diversions to patients managed by conservative means were included. Creation of an ostomy in selected patients provides equivocal or superior QOL outcomes when compared to conservative bowel management strategies. Both colostomy and ileostomy surgery significantly reduce the amount of time required for bowel management. Patients who undergo ostomy surgery tend to be satisfied with their surgery, and a significant portion report a desire to be counseled about this option earlier. There are no clear advantages when functional, clinical, or QOL outcomes associated with colostomy are compared to those seen in SCI patients undergoing ileostomy. 1. The WOC nurse plays a pivotal role in both conservative bowel management and the decision to undergo ostomy surgery. 2. Preoperative stoma site marking is vital for the best surgical outcome. 3. The system best suited to an individual is based on a variety of factors including but not limited to stoma location, type of effluent, peristomal plane and contours, and the individual's capabilities and preferences. 4. Some individuals with a sigmoid or descending colostomy may benefit from colostomy irrigation as a management method. 5. Postoperatively, assessment of pressure points for signs of tissue breakdown, evaluation of treatment methods for existing pressure ulcers with suitable modification, and support surface assessment should be included in ongoing annual follow-up visits.

Human iPS cell-derived astrocyte transplants preserve respiratory function after spinal cord injury

PubMed Central

Li, Ke; Javed, Elham; Scura, Daniel; Hala, Tamara J.; Seetharam, Suneil; Falnikar, Aditi; Richard, Jean-Philippe; Chorath, Ashley; Maragakis, Nicholas J.; Wright, Megan C.; Lepore, Angelo C.

2015-01-01

Transplantation-based replacement of lost and/or dysfunctional astrocytes is a promising therapy for spinal cord injury (SCI) that has not been extensively explored, despite the integral roles played by astrocytes in the central nervous system (CNS). Induced pluripotent stem (iPS) cells are a clinically-relevant source of pluripotent cells that both avoid ethical issues of embryonic stem cells and allow for homogeneous derivation of mature cell types in large quantities, potentially in an autologous fashion. Despite their promise, the iPS cell field is in its infancy with respect to evaluating in vivo graft integration and therapeutic efficacy in SCI models. Astrocytes express the major glutamate transporter, GLT1, which is responsible for the vast majority of glutamate uptake in spinal cord. Following SCI, compromised GLT1 expression/function can increase susceptibility to excitotoxicity. We therefore evaluated intraspinal transplantation of human iPS cell-derived astrocytes (hIPSAs) following cervical contusion SCI as a novel strategy for reconstituting GLT1 expression and for protecting diaphragmatic respiratory neural circuitry. Transplant-derived cells showed robust long-term survival post-injection and efficiently differentiated into astrocytes in injured spinal cord of both immunesuppressed mice and rats. However, the majority of transplant-derived astrocytes did not express high levels of GLT1, particularly at early times post-injection. To enhance their ability to modulate extracellular glutamate levels, we engineered hIPSAs with lentivirus to constitutively express GLT1. Overexpression significantly increased GLT1 protein and functional GLT1-mediated glutamate uptake levels in hIPSAs both in vitro and in vivo post-transplantation. Compared to human fibroblast control and unmodified hIPSA transplantation, GLT1-overexpressing hIPSAs reduced (1) lesion size within the injured cervical spinal cord, (2) morphological denervation by respiratory phrenic motor neurons at the diaphragm neuromuscular junction, and (3) functional diaphragm denervation as measured by recording of spontaneous EMGs and evoked compound muscle action potentials. Our findings demonstrate that hiPSA transplantation is a therapeutically-powerful approach for SCI. PMID:26216662

Human iPS cell-derived astrocyte transplants preserve respiratory function after spinal cord injury.

PubMed

Li, Ke; Javed, Elham; Scura, Daniel; Hala, Tamara J; Seetharam, Suneil; Falnikar, Aditi; Richard, Jean-Philippe; Chorath, Ashley; Maragakis, Nicholas J; Wright, Megan C; Lepore, Angelo C

2015-09-01

Transplantation-based replacement of lost and/or dysfunctional astrocytes is a promising therapy for spinal cord injury (SCI) that has not been extensively explored, despite the integral roles played by astrocytes in the central nervous system (CNS). Induced pluripotent stem (iPS) cells are a clinically-relevant source of pluripotent cells that both avoid ethical issues of embryonic stem cells and allow for homogeneous derivation of mature cell types in large quantities, potentially in an autologous fashion. Despite their promise, the iPS cell field is in its infancy with respect to evaluating in vivo graft integration and therapeutic efficacy in SCI models. Astrocytes express the major glutamate transporter, GLT1, which is responsible for the vast majority of glutamate uptake in spinal cord. Following SCI, compromised GLT1 expression/function can increase susceptibility to excitotoxicity. We therefore evaluated intraspinal transplantation of human iPS cell-derived astrocytes (hIPSAs) following cervical contusion SCI as a novel strategy for reconstituting GLT1 expression and for protecting diaphragmatic respiratory neural circuitry. Transplant-derived cells showed robust long-term survival post-injection and efficiently differentiated into astrocytes in injured spinal cord of both immunesuppressed mice and rats. However, the majority of transplant-derived astrocytes did not express high levels of GLT1, particularly at early times post-injection. To enhance their ability to modulate extracellular glutamate levels, we engineered hIPSAs with lentivirus to constitutively express GLT1. Overexpression significantly increased GLT1 protein and functional GLT1-mediated glutamate uptake levels in hIPSAs both in vitro and in vivo post-transplantation. Compared to human fibroblast control and unmodified hIPSA transplantation, GLT1-overexpressing hIPSAs reduced (1) lesion size within the injured cervical spinal cord, (2) morphological denervation by respiratory phrenic motor neurons at the diaphragm neuromuscular junction, and (3) functional diaphragm denervation as measured by recording of spontaneous EMGs and evoked compound muscle action potentials. Our findings demonstrate that hiPSA transplantation is a therapeutically-powerful approach for SCI. Copyright © 2015 Elsevier Inc. All rights reserved.

Anaphylaxis to drugs.

PubMed

Kuruvilla, Merin; Khan, David A

2015-05-01

Drug-induced anaphylaxis is a common cause of anaphylaxis and a leading cause of fatal anaphylaxis. Antibiotics, radiocontrast, and nonsteroidal anti-inflammatory drugs are commonly implicated drugs. Vocal cord dysfunction can mimic anaphylaxis and is often overlooked. β-Lactams are a common cause of anaphylaxis; however, skin testing and drug challenge can usually determine tolerability of other classes of β-lactams. Nonionic contrast agents cause anaphylaxis less frequently than ionic contrast, and immunoglobulin E-mediated mechanisms may have a role in some of these reactions. Skin testing with radiocontrast may have a role in evaluating patients with anaphylaxis to nonionic contrast. Copyright © 2015 Elsevier Inc. All rights reserved.

Acute lower motor neuron tetraparesis.

PubMed

Añor, Sònia

2014-11-01

Flaccid nonambulatory tetraparesis or tetraplegia is an infrequent neurologic presentation; it is characteristic of neuromuscular disease (lower motor neuron [LMN] disease) rather than spinal cord disease. Paresis beginning in the pelvic limbs and progressing to the thoracic limbs resulting in flaccid tetraparesis or tetraplegia within 24 to 72 hours is a common presentation of peripheral nerve or neuromuscular junction disease. Complete body flaccidity develops with severe decrease or complete loss of spinal reflexes in pelvic and thoracic limbs. Animals with acute generalized LMN tetraparesis commonly show severe motor dysfunction in all limbs and severe generalized weakness in all muscles. Copyright © 2014 Elsevier Inc. All rights reserved.

The interplay of aggregation, fibrillization and gelation of an unexpected low molecular weight gelator: glycylalanylglycine in ethanol/water.

PubMed

Farrell, Stefanie; DiGuiseppi, David; Alvarez, Nicolas; Schweitzer-Stenner, Reinhard

2016-07-13

Hydrogels formed by polypeptides could be much-favored tools for drug delivery because their main ingredients are generally biodegradable. However, the gelation of peptides in aqueous solution generally requires a minimal length of the peptide as well as distinct sequences of hydrophilic and hydrophobic residues. The aggregation of short peptides like tripeptides, which are relatively cheap and offer a high degree of biodegradability, are generally thought to require a high hydrophobicity of their residues. We found that contrary to this expectation cationic glycylalanylglycine in 55 mol% ethanol/45 mol% water forms a gel below a melting temperature of ca. 36 °C. A pure hydrogel state can be obtained after allowing the ethanol component to evaporate. The gel phase consists of crystalline fibrils of several 100 μm, which form a sample-spanning network. Rheological data reveal a soft elastic solid gel. We investigated the kinetics of the various processes that lead to the final gel state of the ternary mixture by a unique combination of UV circular dichroism, infrared, vibrational circular dichroism (VCD) and rheological measurements. A mathematical analysis of our data show that gelation is preceded by the formation of peptide β-sheet like tapes or ribbons, which give rise to a significant enhancement of the amide I' VCD signal, and the subsequent formation of rather thick and long fibrils. The VCD signals indicate that the tapes exhibit a right-handed helicity at temperatures above 16 °C and a left-handed helicity below. The tapes'/ribbons' helicity change occurs at a temperature where the UVCD data reflect a relatively long nucleation process. The kinetics of gel formation probed by the storage and loss moduli are composed of a fast process that follows tape/ribbon/fibril formation and is clearly identifiable in a movie that shows the gelation process and a slow process that causes an additional gel stabilization. The rheological data indicate that left-handed fibrils observed at low temperatures form a more solid-like structure than their right-handed counterparts formed at higher temperatures. Taken together our data reveal GAG as an unexpected gelator, the formation of which is underlied by a set of distinguishable kinetic processes.

[Efficacy of cultural-appropriate health education on information, motivation and behavioral skills of fever management for children in new immigrant Vietnamese mothers].

PubMed

Hsu, Hsian-Chou; Chen, Su-Jun; Huang, Mei-Chih

2012-12-01

Fever is the most common symptom in pediatric healthcare. Providing parents with better information on childhood fever management can improve their cognition and home-care abilities. Vietnamese female spouse comprise the largest segment of women who have emigrated from Southeast Asia to Taiwan over the past two decades. After arrival to Taiwan, they have to encounter the events of pregnancy and being a mother. In health care services, language barriers and cultural issues are key healthcare-related barriers to the adaptation of these women to Taiwan society. This study assessed the efficacy of using Vietnamese-language fever management education materials in changing the fever management behaviors of Vietnamese mothers living in Taiwan. This experimental study used a randomly assigned, pre- and post-test approach. A snowball method was used to recruit Vietnamese women living in southern Taiwan with children under 6 years of age. Participants were randomly assigned to experimental (n = 31, Vietnamese-language fever management brochure + VCD) and comparison (n = 30, Chinese-language brochure + VCD) groups. Both groups achieved significantly improvement scores in (fever) information, attitudes, self-efficacy and skills, with improvements significantly higher in the experimental group than the comparison group. This study supports that fever management education presented in the recipient's primary language effectively improves recipient fever management knowledge, attitudes, skills, and self-efficacy.

Energy efficiency of acetone, butanol, and ethanol (ABE) recovery by heat-integrated distillation.

PubMed

Grisales Diaz, Victor Hugo; Olivar Tost, Gerard

2018-03-01

Acetone, butanol, and ethanol (ABE) is an alternative biofuel. However, the energy requirement of ABE recovery by distillation is considered elevated (> 15.2 MJ fuel/Kg-ABE), due to the low concentration of ABE from fermentation broths (between 15 and 30 g/l). In this work, to reduce the energy requirements of ABE recovery, four processes of heat-integrated distillation were proposed. The energy requirements and economic evaluations were performed using the fermentation broths of several biocatalysts. Energy requirements of the processes with four distillation columns and three distillation columns were similar (between 7.7 and 11.7 MJ fuel/kg-ABE). Double-effect system (DED) with four columns was the most economical process (0.12-0.16 $/kg-ABE). ABE recovery from dilute solutions by DED achieved energy requirements between 6.1 and 8.7 MJ fuel/kg-ABE. Vapor compression distillation (VCD) reached the lowest energy consumptions (between 4.7 and 7.3 MJ fuel/kg-ABE). Energy requirements for ABE recovery DED and VCD were lower than that for integrated reactors. The energy requirements of ABE production were between 1.3- and 2.0-fold higher than that for alternative biofuels (ethanol or isobutanol). However, the energy efficiency of ABE production was equivalent than that for ethanol and isobutanol (between 0.71 and 0.76) because of hydrogen production in ABE fermentation.

Heidelberg Retina Tomograph 3 machine learning classifiers for glaucoma detection

PubMed Central

Townsend, K A; Wollstein, G; Danks, D; Sung, K R; Ishikawa, H; Kagemann, L; Gabriele, M L; Schuman, J S

2010-01-01

Aims To assess performance of classifiers trained on Heidelberg Retina Tomograph 3 (HRT3) parameters for discriminating between healthy and glaucomatous eyes. Methods Classifiers were trained using HRT3 parameters from 60 healthy subjects and 140 glaucomatous subjects. The classifiers were trained on all 95 variables and smaller sets created with backward elimination. Seven types of classifiers, including Support Vector Machines with radial basis (SVM-radial), and Recursive Partitioning and Regression Trees (RPART), were trained on the parameters. The area under the ROC curve (AUC) was calculated for classifiers, individual parameters and HRT3 glaucoma probability scores (GPS). Classifier AUCs and leave-one-out accuracy were compared with the highest individual parameter and GPS AUCs and accuracies. Results The highest AUC and accuracy for an individual parameter were 0.848 and 0.79, for vertical cup/disc ratio (vC/D). For GPS, global GPS performed best with AUC 0.829 and accuracy 0.78. SVM-radial with all parameters showed significant improvement over global GPS and vC/ D with AUC 0.916 and accuracy 0.85. RPART with all parameters provided significant improvement over global GPS with AUC 0.899 and significant improvement over global GPS and vC/D with accuracy 0.875. Conclusions Machine learning classifiers of HRT3 data provide significant enhancement over current methods for detection of glaucoma. PMID:18523087

Effect of spinal monoaminergic neuronal system dysfunction on pain threshold in rats, and the analgesic effect of serotonin and norepinephrine reuptake inhibitors.

PubMed

Tamano, Ryuta; Ishida, Mitsuhiro; Asaki, Toshiyuki; Hasegawa, Minoru; Shinohara, Shunji

2016-02-26

Dysfunction in the central serotonin (5-HT) and norepinephrine (NE) systems cause depression and pain. Descending spinal pain modulatory pathways are important in the analgesic mechanisms of antidepressants, particularly serotonin and norepinephrine reuptake inhibitors (SNRIs). While many non-clinical studies have demonstrated the roles of central monoaminergic systems in pain, there is little evidence to illuminate the direct contribution of spinal descending pain modulatory systems independently of depressive-like behavior. To examine the effects of dysfunction of spinal monoaminergic systems on pain sensitivity, we established a rat chronic pain model by administering lumbar-intrathecal reserpine to minimize its influence on brain. Lumbar-intrathecal reserpine evoked persistent mechanical hypersensitivity and corresponding reductions in spinal 5-HT and NE concentrations (from 767.2 to 241.6ng/g and from 455.9 to 41.7ng/g, respectively after reserpine 30nmol). Lumbar-intrathecal reserpine did not deplete brain monoamines or bring about depressive-like behavior in the forced swim test. Spinal monoamines depletion-induced pain sensitivity was ameliorated by lumbar-intrathecal administration of the SNRIs (duloxetine and milnacipran) in dose-dependent manners. These suggest that increased pain sensitivity could be induced by dysfunction solely of the descending pain modulatory system, regardless of depressive-like behavior, and lumbar-intrathecal administration of SNRIs could ameliorate the pain sensitivity which might be mediated by affecting the descending pain modulatory system in the spinal cord, not via their antidepressant effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Oral administration of metal chelator ameliorates motor dysfunction after a small hemorrhage near the internal capsule in rat.

PubMed

Masuda, Tadashi; Hida, Hideki; Kanda, Yoshie; Aihara, Noritaka; Ohta, Kengo; Yamada, Kazuo; Nishino, Hitoo

2007-01-01

Cerebral hemorrhage leads to local production of free iron, radicals, cytokines, etc. To investigate whether a decrease of iron-mediated radical production influences functional recovery after intracerebral hemorrhage (ICH), a modified ICH rat model with a small hemorrhage near the internal capsule (IC) accompanied with relatively severe motor dysfunction was first developed. Then clioquinol (CQ), an iron chelator that reduces hydroxyl radical production, was orally administrated. Injection of different doses of Type IV collagenase (1.4 mul 1-200 U/ml) into the left striatum near the IC in Wistar rats showed that injection of 7.5 U/ml collagenase resulted in a small hemorrhoidal lesion near the IC with relatively severe motor dysfunction (IC model). Retrograde labeling of neurons in the sensory-motor cortex and axons in the corticospinal tract using Fluoro-gold (FG) injection into the spinal cord (C3-C4) showed that few labeled neurons in the sensory-motor cortex were detected in the IC model, FG-labeled axons disappeared, and FG-including ED-1-positive cells appeared within 24 hr in the IC. Assessments of behavior and histologic analysis after oral administration of CQ in the IC model indicated that oral administration of CQ prevented a decrease of FG-labeled neurons, and resulted in better motor-function recovery. CQ inhibited hydrogen peroxide-induced cell toxicity in oligodendrocytes in vitro, but not in neurons. Our data suggests that CQ ameliorated motor dysfunction after a small hemorrhage near the IC by a mechanism that is related to reduction of chain-reactive hydroxyl radical production in oligodendrocytes.

Evaluation of purinergic mechanism for the treatment of voiding dysfunction: a study in conscious spinal cord-injured rats.

PubMed

Lu, Shing-Hwa; Groat, William C de; Lin, Alex T L; Chen, Kuang-Kuo; Chang, Luke S

2007-10-01

To investigate the effect of a selective P2X(3-)P2X(2/3) purinergic receptor antagonist (a-317491) on detrusor hyperreflexia in conscious chronic spinal cord-injured female rats. Six chronic spinal cord-transected female Sprague-Dawley rats (290-336 g) were used in this study. Spinal transection at the T8-T9 segmental level was performed using aseptic techniques under halothane anesthesia. Fourteen to 16 weeks after spinal transection, A-317491, a selective P2X(3-)P2X(2/3) purinergic receptor antagonist, was administered intravenously in cystometry studies at increasing doses of 0.03, 0.1, 0.3, 1, 3, 10 and 30 micromol/kg at 40-50 minute intervals. Cystometrograms (CMGs) were performed before and after the administration of each dose of the drug. The continuous filling of CMGs revealed a large number of small-amplitude (> 8 cmH(2)O), non-voiding contractions (NVCs) (average, 9.7 per voiding cycle) preceding voiding contractions (mean amplitude, 31 cmH(2)O; duration, 2.5 minutes), which occurred at an interval of 539 seconds and at a pressure threshold of 5.7 cmH(2)O. When tested in a range of doses (0.03-30 micromol/kg, intravenous), A-317491 in doses between 1 and 30 micromol/kg significantly (p < 0.05) increased the interval between voids by 25%, reduced the number of NVCs by 42-62%, and increased the pressure threshold for voiding by 53-73%, but did not change the amplitude of the duration of the voiding contractions. The effects of the drug were apparent within 10 minutes following administration. These results indicate that purinergic mechanisms, presumably involving P2X(3) or P2X(2/3) receptors on bladder C-fiber afferent nerves, play an important role in the detrusor hyperreflexia that occurs after spinal cord injury in rats.

Neurological function after total en bloc spondylectomy for thoracic spinal tumors.

PubMed

Murakami, Hideki; Kawahara, Norio; Demura, Satoru; Kato, Satoshi; Yoshioka, Katsuhito; Tomita, Katsuro

2010-03-01

Total en bloc spondylectomy (TES) for thoracic spinal tumors may in theory produce neurological dysfunction as a result of ischemic or mechanical damage to the spinal cord. Potential insults include preoperative embolization at 3 levels, intraoperative ligation of segmental arteries, nerve root ligation, and circumferential dural dissection. The purpose of this study was to assess neurological function after thoracic TES. The authors performed a retrospective review of 79 patients with thoracic-level spinal tumors that had been treated with TES between 1989 and 2006. Neurological function was retrospectively analyzed according to the Frankel grading system. Of the 79 cases, 26 involved primary tumors and 53 involved metastatic tumors. The number of excised vertebrae was 1 in 60 cases, 2 in 13, and >or= 3 in 6. The Frankel grade before surgery was B in 1 case, C in 16, D in 29, and E in 33. At the follow-up, the Frankel grade was C in 2 cases, D in 24, and E in 53. Of 46 cases with neurological deficits before surgery, neurological improvement of at least 1 Frankel grade was achieved in 25 cases (54.3%). Although the Frankel grade did not change in 21 patients, improvement in neurological symptoms within the same Frankel grade did occur in these patients. There were no cases of neurological deterioration. There was no neurological deterioration due to preoperative embolization, ligation of segmental arteries, or ligation of thoracic nerve roots. Each of the cases with preoperative neurological deficits showed improvement in neurological symptoms. Data in the current study clinically proved that TES is a safe operation with respect to spinal cord blood flow. In TES, the spinal cord is circumferentially decompressed and the spinal column is shortened. An increase in spinal cord blood flow due to spinal shortening in addition to decompression was considered to have brought about a resolution of neurological symptoms with TES.

Examination of temporal and spatial variability of NO2 VCDs measured using mobile-MAX-DOAS in Toronto, Canada.

NASA Astrophysics Data System (ADS)

Davis, Zoe; Baray, Sabour; Khanbabkhani, Aida; Fujs, William; Csukat, Csilla; McLaren, Robert

2017-04-01

Mobile-MAX-DOAS is an innovative technique used to estimate pollutant emission rates and validate satellite measurements and air quality models. It is essential to identify and examine factors that can significantly impact the accuracy of this developing technique. Mobile-MAX-DOAS measurements were conducted in Toronto, Canada with a mini-MAX-DOAS instrument mounted (pointing backwards) on top of a car during August and September, 2016. Scattered sunlight spectra were collected every 45 seconds in the continuously repeated sequence of elevation angles of 30o, 30o, 30o, 30o, 40o, 30o, 90o. Tropospheric VCDs were determined using the geometric approximation from DSCDs fitted using a near-noon, low NO2 VCD FRS spectrum. The study goal was to examine the validity of the assumption that VCDs remain relatively constant at each measured location on a driving route encircling an urban area of interest with typical time periods of 1.5-3 hours to estimate emissions and whether driving direction significantly impacts results. NO2 VCD temporal variability was therefore determined by repeating driving routes in both directions in quick succession on multiple days. Strong temporal variability in NO2 VCDs of up to a factor of two were observed for some routes for the same vehicle locations under constant prevailing wind conditions within <2 hours. These differences may be due to the effects of transport, changing tropospheric chemistry and/or diurnal trends in emissions rates. Under these conditions measurements along different portions of the encircled area in a large city may not be representative of the entire measurement period, introducing error into the final emission estimate. Certain straight roads exhibited significantly different VCDs within < 30 minutes when the instrument azimuth pointing direction was changed by 180o. The weighted average VCD was ˜8(±3x) x1016molec. cm-1 from driving in one direction but ˜4 (± 1.5) x1016molec. cm-1 from driving in the opposite direction. This indicates sufficient horizontal inhomogeneity for the instrument to view significantly different NO2 regimes while at the same vehicle geographical location due to the different azimuth direction. NO2line fluxes were determined during weekday afternoon rush-hours by driving repeatedly in both directions under tangential prevailing winds conditions on a road that is 8km downwind of Toronto and 4km downwind of a major highway. During one afternoon the average NO2 VCD was 6(±2)x1016 molec. cm-2with a standard deviation of 3x1015 molec. cm-2. This average value is consistent with NO2 VCDs retrieved using optimal estimation methods from stationary MAX-DOAS measurements at nearby York University. Using a 10m elevation measured wind-speed of 16km hr-1, the NO2 line flux was 3(± 9) x1018molec. cm-1s-1, approximately 6 times that determined by Halla et al. (2011) for a line flux measured in a rural area of southwestern Ontario, downwind of pollution sources in Michigan and Ohio. Our resulting average NO2 flux of 84 (+/-25) mg m-2hr-1 is consistent with NOx fluxes measured in major European cities of up to 90 mg m-2hr-1. This work will be used as a baseline experiment to apply this method in other Canadian cities.

[Is subtotal bilateral thyroidectomy still indicated in patients with Grave's disease?].

PubMed

Bilosi, M; Binquet, C; Goudet, P; Lalanne-Mistrih, M L; Brun, J M; Cougard, P

2002-02-01

To evaluate the morbidity and the functional results of subtotal bilateral thyroidectomy in patients (TST) with Graves' disease. A retrospective study was performed in 128 patients. They were 23 males and 105 females with a median age of 34 years (range: 14-68). Weight of remnant tissue was between 4 and 5 g. Thyroid functional status was evaluated, at 3 months and after a follow-up period ranged from 1 to 5 years, by measurement of serum concentration of free T4 and/or free T3 and TSH. They were no post-operative death. Surgical complications were 2 vocal cord palsies and 17 hypocalcemia (inf. to 2 mmol/L). After a median follow-up of 2 years, they were no longer any cases of vocal cord dysfunction and no case of permanent hypoparathyroidism. Functional results were established in 118 patients: 46 patients had clinical hypothyroidism (39%), 64 patients had latent hypothyroidism or euthyroidism (54.2%), and 8 had recurrent hyperthyroidism (6.8%). These results suggest that TST with a remnant mass inferior to 5 g provides a low level of recurrent hyperthyroidism and allows to give no drug therapy to half patients. In our opinion, TST is still indicated in Graves' disease.

[Vocal cord paralysis after thyroid surgery : Current medicolegal aspects of intraoperative neuromonitoring].

PubMed

Dralle, H; Schneider, R; Lorenz, K; Phuong, N Thanh; Sekulla, C; Machens, A

2015-07-01

Intraoperative neuromonitoring (IONM) has been commercially available for approximately 15 years and is highly predictive in thyroid gland surgery concerning either postoperative vocal fold mobility in the case of an intact signal for muscle action electromyogram (EMG, > 99 % right negative) or vocal fold dysfunction in the case of loss of signal (> 70 % right positive). The use of IONM improves the intraoperative identification of recurrent laryngeal nerve function and due to the high predictive value with respect to the expected vocal cord function the result of IONM has to be integrated into the surgical concept of thyroidectomy. Unilateral loss of function of the recurrent laryngeal nerve cannot be completely avoided despite correct application of IONM; however, bilateral vocal fold palsy can be safely avoided when contralateral surgery is cancelled after a loss of signal occurs during resection of the first side in planned bilateral surgery (alternative strategy). Patients have to be informed preoperatively about the limitations of IONM and potential strategy changes during planned bilateral surgery. Surgeons should apply IONM according to the published current recommendations and by selecting a risk-oriented intraoperative strategy in the case of loss of signal from the recurrent laryngeal nerve.

The injury of fine particulate matter from cooking oil fumes on umbilical cord blood vessels in vitro.

PubMed

Hou, Lijuan; Zhang, Jian; Zhang, Chao; Xu, Yachun; Zhu, Xiaoxia; Yao, Cijiang; Liu, Ying; Li, Tao; Cao, Jiyu

2017-01-01

Cooking oil fumes (COFs) derived PM 2.5 is the major source of indoor air pollution in Asia. For this, a pregnant rat model within different doses of cooking oil fumes (COFs) derived PM 2.5 was established in pregnancy in our research. Our previous studies have showed that exposure to COFs-derived PM 2.5 was related to adverse pregnancy outcomes. However, the mechanisms of signaling pathways remain unknown. Therefore, this study aimed to investigate the underlying mechanisms induced by COFs-derived PM2.5 injury on umbilical cord blood vessels (UCs) in vitro. Exposure to COFs-derived PM 2.5 resulted in changing the expression of eNOS, ET-1, ETRA, and ETRB. In additions, western blot analysis indicated that the HIF-1α/iNOS/NO signaling pathway and VEGF/VEGFR1/iNOS signaling pathway were involved in UCs injury triggered by COFs-derived PM 2.5 . In conclusion, our data suggested that exposure to COFs-derived PM 2.5 resulted in increasing of oxidative stress and inflammation, as well as dysfunction of UCs. Copyright © 2016 Elsevier B.V. All rights reserved.

Redox susceptibility of SOD1 mutants is associated with the differential response to CCS over-expression in vivo.

PubMed

Son, Marjatta; Fu, Qiao; Puttaparthi, Krishna; Matthews, Christina M; Elliott, Jeffrey L

2009-04-01

Over-expression of CCS in G93A SOD1 mice accelerates neurological disease and enhances mitochondrial pathology. We studied the effect of CCS over-expression in transgenic mice expressing G37R, G86R or L126Z SOD1 mutations in order to understand factors which influence mitochondrial dysfunction. Over-expression of CCS markedly decreased survival and produced mitochondrial vacuolation in G37R SOD1 mice but not in G86R or L126Z SOD1 mice. Moreover, CCS/G37R SOD1 spinal cord showed specific reductions in mitochondrial complex IV subunits consistent with an isolated COX deficiency, while no such reductions were detected in CCS/G86R or CCS/L126Z SOD1 mice. CCS over-expression increased the ratio of reduced to oxidized SOD1 monomers in the spinal cords of G37R SOD1 as well as G93A SOD1 mice, but did not influence the redox state of G86R or L126Z SOD1 monomers. The effects of CCS on disease are SOD1 mutation dependent and correlate with SOD1 redox susceptibility.

Are Multidimensional Pain Inventory Coping Strategy Profiles Associated with Long-Term Spinal Cord Stimulation Effectiveness?

PubMed

Paroli, Mery; Bernini, Olivia; De Carolis, Giuliano; Tollapi, Lara; Bondi, Franca; Martini, Antonella; Dario, Alessandro; Paolicchi, Adriana

2018-05-01

It is acknowledged that the way patients cope with pain may influence treatment outcome. In particular, psychological factors are deemed important when considering patients for suitability for spinal cord stimulation (SCS). The aim of the study is to observe how pre-implantation psychological characteristics impact the effectiveness of SCS for chronic pain. The analysis comprised data from 137 patients who underwent an SCS implant. Screening evaluation included a coping strategies profile (Multidimensional Pain Inventory) and psychiatric disorders (Mini-International Neuropsychiatric Interview). Based on SCS implant outcome collected during follow-up visits, patients were divided into three groups: subjects with long-term pain relief (long-term group), subjects who failed the SCS treatment and decided to explant trial device (trial explanter group [TE]), and those who chose a permanent device (permanent explanter group [PE]). Results showed that most of the patients who failed with the SCS (TE and PE groups) demonstrated a dysfunctional coping profile and showed a higher presence of psychiatric disorders, which significantly influenced the experience and perception of pain. The findings of this study support the value of a multidisciplinary screening. Addressing psychological issues before SCS implantation can reduce the failure rate of SCS.

Relationship of BK polyoma virus (BKV) in the urine with hemorrhagic cystitis and renal function in recipients of T-cell depleted peripheral blood and cord blood stem cell transplants

PubMed Central

Lee, Yeon Joo; Zheng, Junting; Kolitsopoulos, Yovanna; Chung, Dick; Amigues, Isabelle; Son, Tammy; Choo, Kathleen; Hester, Jeff; Giralt, Sergio A.; Glezerman, Ilya G.; Jakubowski, Ann A.; Papanicolaou, Genovefa A.

2014-01-01

Hematopoietic stem cell transplant (HSCT) recipients are at significant risk for BKV reactivation, hemorrhagic cystitis (HC) and renal dysfunction. We prospectively monitored 98 HSCT by serial BKV PCR in the urine through Day (D) +100 to analyze the relationship between BKV viruria and HC, serum creatinine (Cr) and creatinine clearance (CrCl) through D +180 or death. Patients, median age 52 years, range 20-73, received T-cell depleted (50%) or cord blood allografts (21%). Median pre-HSCT BKV IgG titers were 1:10,240. Incremental increase in BKV IgG titers correlated with developing BKV viruria ≥ 107 copies/mL. By D +100, 53 (54%) patients had BKV viruria. BKV viral load in the urine increased at engraftment and persisted throughout D +100. HC developed in 10 patients (10%); 7/10 with BKV viruria. In competing risk analyses, BKV viruria ≥ 107 copies/mL, older age, CMV reactivation and foscarnet use were risk factors for HC. Cr and CrCl at 2, 3 and 6 months post-HSCT were similar between patients with and without BKV viruria. PMID:24769326

Cervical spondylotic myelopathy.

PubMed

Tracy, Jennifer A; Bartleson, J D

2010-05-01

Cervical spondylosis is part of the aging process and affects most people if they live long enough. Degenerative changes affecting the intervertebral disks, vertebrae, facet joints, and ligamentous structures encroach on the cervical spinal canal and damage the spinal cord, especially in patients with a congenitally small cervical canal. Cervical spondylotic myelopathy (CSM) is the most common cause of myelopathy in adults. The anatomy, pathophysiology, clinical presentation, differential diagnosis, diagnostic investigation, natural history, and treatment options for CSM are summarized. Patients present with signs and symptoms of cervical spinal cord dysfunction with or without cervical nerve root injury. The condition may or may not be accompanied by pain in the neck and/or upper limb. The differential diagnosis is broad. Imaging, typically with magnetic resonance imaging, is the most useful diagnostic tool. Electrophysiologic testing can help exclude alternative diagnoses. The effectiveness of conservative treatments is unproven. Surgical decompression improves neurologic function in some patients and prevents worsening in others, but is associated with risk. Neurologists should be familiar with this very common condition. Patients with mild signs and symptoms of CSM can be monitored. Surgical decompression from an anterior or posterior approach should be considered in patients with progressive and moderate to severe neurologic deficits.

Peroxisome proliferator activator receptor gamma coactivator-1alpha (PGC-1α) improves motor performance and survival in a mouse model of amyotrophic lateral sclerosis

PubMed Central

2011-01-01

Background Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that affects spinal cord and cortical motor neurons. An increasing amount of evidence suggests that mitochondrial dysfunction contributes to motor neuron death in ALS. Peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) is a principal regulator of mitochondrial biogenesis and oxidative metabolism. Results In this study, we examined whether PGC-1α plays a protective role in ALS by using a double transgenic mouse model where PGC-1α is over-expressed in an SOD1 transgenic mouse (TgSOD1-G93A/PGC-1α). Our results indicate that PGC-1α significantly improves motor function and survival of SOD1-G93A mice. The behavioral improvements were accompanied by reduced blood glucose level and by protection of motor neuron loss, restoration of mitochondrial electron transport chain activities and inhibition of stress signaling in the spinal cord. Conclusion Our results demonstrate that PGC-1α plays a beneficial role in a mouse model of ALS, suggesting that PGC-1α may be a potential therapeutic target for ALS therapy. PMID:21771318

Extravasation of the contrast media during voiding cystourethrography in a long-term spinal cord injury patient.

PubMed

Kovindha, A; Sivasomboon, C; Ovatakanont, P

2005-07-01

To present complications and pitfalls in voiding cystourethrography (VCUG) and introduce a guideline for performing VCUG in a long-term spinal cord injury (SCI) patient with neurogenic bladder dysfunction (NBD) and contracted bladder. A case report. Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand. We describe a chronic C(5) tetraplegic man with NBD and contracted bladder, who developed autonomic dysreflexia (AD), gross hematuria and extravasation of contrast median during VCUG. A foley catheter was retained after VCUG. AD was resolved and urine cleared after a week of continuous bladder irrigation. VCUG should be performed with caution in a long-term SCI patient with NBD and contracted bladder. Forceful pushing of the contrast media by the hand-injection method caused abrupt distention of the contracted bladder, damaged bladder mucosa and aggrevated AD. We suggest a guideline as follows: report bladder capacity and AD, if present, in an X-ray requisition form; use the gravity-drip method, stop the drip and drain the contrast media if a sudden headache and rising of blood pressure (BP) develop; observe urine colour, and report if bleeding or AD occurs.

International Spinal Cord Injury Core Data Set (version 2.0)-including standardization of reporting.

PubMed

Biering-Sørensen, F; DeVivo, M J; Charlifue, S; Chen, Y; New, P W; Noonan, V; Post, M W M; Vogel, L

2017-08-01

The study design includes expert opinion, feedback, revisions and final consensus. The objective of the study was to present the new knowledge obtained since the International Spinal Cord Injury (SCI) Core Data Set (Version 1.0) published in 2006, and describe the adjustments made in Version 2.0, including standardization of data reporting. International. Comments received from the SCI community were discussed in a working group (WG); suggestions from the WG were reviewed and revisions were made. All suggested revisions were considered, and a final version was circulated for final approval. The International SCI Core Data Set (Version 2.0) consists of 25 variables. Changes made to this version include the deletion of one variable 'Total Days Hospitalized' and addition of two variables 'Date of Rehabilitation Admission' and 'Date of Death.' The variable 'Injury Etiology' was extended with six non-traumatic categories, and corresponding 'Date of Injury' for non-traumatic cases, was defined as the date of first physician visit for symptoms related to spinal cord dysfunction. A category reflecting transgender was added. A response category was added to the variable on utilization of ventilatory assistance to document the use of continuous positive airway pressure for sleep apnea. Other clarifications were made to the text. The reporting of the pediatric SCI population was updated as age groups 0-5, 6-12, 13-14, 15-17 and 18-21. Collection of the core data set should be a basic requirement of all studies of SCI to facilitate accurate descriptions of patient populations and comparison of results across published studies from around the world.

Epstein-Barr Virus-positive T-cell Lymphoproliferative Disease Following Umbilical Cord Blood Transplantation for Acute Myeloid Leukemia.

PubMed

Yui, Shunsuke; Yamaguchi, Hiroki; Imadome, Ken-ichi; Arai, Ayako; Takahashi, Mikiko; Ohashi, Ryuji; Tamai, Hayato; Moriya, Keiichi; Nakayama, Kazutaka; Shimizu, Akira; Inokuchi, Koiti

2016-01-01

We report a case of the extremely rare condition Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease (LPD) which occurred after umbilical cord blood transplantation. A 25-year-old Japanese man underwent cord blood transplantation from a male human leukocyte antigen 4/6-matched donor due to acute myeloid leukemia with trisomy 8. Bone marrow examination on day 30 showed chimerism with at least 90% donor cells and complete hematological response. Chronic symptoms of graft-versus-host disease appeared only on the skin and were successfully treated with cyclosporine alone. Three years later, however, the patient experienced repeated cold-like symptoms and was hospitalized with liver dysfunction. A high fever developed and was followed by significant edema of the right side of the face. The EBV DNA copy number in whole peripheral blood was 2×10(4)/mL. Liver biopsy showed invasion of EBV-infected CD8-positive T cells. Southern blotting analysis of the whole peripheral blood showed that the T-cell receptor Cβ1 rearrangement was positive. On the basis of these results, EBV-positive T-cell LPD was diagnosed and treated with prednisolone, cyclosporine, and etoposide, followed by cyclophosphamide, doxorubicin, vincristine, and prednisone. However, the patient died of cardiac function failure, pneumonia, and pulmonary hemorrhage, all of unidentified cause. Most cases of EBV-related LPD after hematopoietic stem cell transplantation consist of EBV-positive B-cell LPD, and, to our knowledge, de novo EBV-positive T-cell LPD subsequent to transplantation has not been previously reported.

31st G. Heiner Sell Lectureship: Secondary Medical Consequences of Spinal Cord Injury

PubMed Central

Bauman, William A.; Korsten, Mark A.; Radulovic, Miroslav; Schilero, Gregory J.; Wecht, Jill M.; Spungen, Ann M.

2012-01-01

Persons with spinal cord injury (SCI) have secondary medical consequences of paralysis and/or the consequences of extreme inactivity. The metabolic changes that result from reduced activity include insulin resistance with carbohydrate disorders and dyslipidemia. A higher prevalence of coronary artery calcification was found in persons with SCI than that in matched able-bodied controls. A depression in anabolic hormones, circulating testosterone and growth hormone, has been described. Adverse soft tissue body composition changes of increased adiposity and reduced skeletal muscle are appreciated. Immobilization is the cause for sublesional disuse osteoporosis with an associated increased risk of fragility fracture. Bowel dysmotility affects all segments of the gastrointestinal tract, with an interest in better defining and addressing gastroesophageal reflux disease and difficulty with evacuation. Developing and testing more effective approaches to cleanse the bowel for elective colonoscopy are being evaluated. The extent of respiratory dysfunction depends on the level and completeness of SCI. Individuals with higher spinal lesions have both restrictive and obstructive airway disease. Pharmacological approaches and expiratory muscle training are being studied as interventions to improve pulmonary function and cough strength with the objective of reducing pulmonary complications. Persons with spinal lesions above the 6th thoracic level lack both cardiac and peripheral vascular mechanisms to maintain blood pressure, and they are frequently hypotensive, with even worse hypotension with upright posture. Persistent and/or orthostatic hypotension may predispose those with SCI to cognitive impairments. The safety and efficacy of anti-hypotensive agents to normalize blood pressure in persons with higher level cord lesions is being investigated. PMID:23459498

Objective measures of motor dysfunction after compression spinal cord injury in adult rats: correlations with locomotor rating scores.

PubMed

Semler, Joerg; Wellmann, Katharina; Wirth, Felicitas; Stein, Gregor; Angelova, Srebrina; Ashrafi, Mahak; Schempf, Greta; Ankerne, Janina; Ozsoy, Ozlem; Ozsoy, Umut; Schönau, Eckhard; Angelov, Doychin N; Irintchev, Andrey

2011-07-01

Precise assessment of motor deficits after traumatic spinal cord injury (SCI) in rodents is crucial for understanding the mechanisms of functional recovery and testing therapeutic approaches. Here we analyzed the applicability to a rat SCI model of an objective approach, the single-frame motion analysis, created and used for functional analysis in mice. Adult female Wistar rats were subjected to graded compression of the spinal cord. Recovery of locomotion was analyzed using video recordings of beam walking and inclined ladder climbing. Three out of four parameters used in mice appeared suitable: the foot-stepping angle (FSA) and the rump-height index (RHI), measured during beam walking, and for estimating paw placement and body weight support, respectively, and the number of correct ladder steps (CLS), assessing skilled limb movements. These parameters, similar to the Basso, Beattie, and Bresnahan (BBB) locomotor rating scores, correlated with lesion volume and showed significant differences between moderately and severely injured rats at 1-9 weeks after SCI. The beam parameters, but not CLS, correlated well with the BBB scores within ranges of poor and good locomotor abilities. FSA co-varied with RHI only in the severely impaired rats, while RHI and CLS were barely correlated. Our findings suggest that the numerical parameters estimate, as intended by design, predominantly different aspects of locomotion. The use of these objective measures combined with BBB rating provides a time- and cost-efficient opportunity for versatile and reliable functional evaluations in both severely and moderately impaired rats, combining clinical assessment with precise numerical measures.

Rehabilitation of people with spinal cord damage due to tumor: literature review, international survey and practical recommendations for optimizing their rehabilitation.

PubMed

New, Peter Wayne; Marshall, Ruth; Stubblefield, Michael D; Scivoletto, Giorgio

2017-03-01

People with spinal cord dysfunction (SCDys) due to tumor (benign and malignant) pose enormous rehabilitation challenges. Objectives were: conduct literature search regarding epidemiology, clinical features and outcomes for SCDys due to tumor following rehabilitation, the ideal setting for rehabilitation and practical considerations for rehabilitation; and propose framework and practical considerations for managing people with SCDys due to tumor in spinal rehabilitation units (SRUs). Survey of rehabilitation health care professionals, consensus opinion from experts and literature search. Workshop at International Spinal Cord Society and American Spinal Injury Association combined annual meeting, May 16, 2015, Montréal, Canada. Workshop attendees and experts in the rehabilitation of people with SCDys due to tumor. Reports of services offered to people with SCDys due to tumor, including whether those with benign and malignant tumors are admitted into rehabilitation, any admission criteria used and the rational for declining admission. Most respondents (n = 33, 83%) reported that people with benign tumors were routinely admitted for rehabilitation but only 18 (45%) reported that people with malignant tumors were routinely admitted. A range of criteria and reasons for declining admission were given. Evidence from the literature and the opinion of experts support the admission of people with SCDys due to tumor into specialist SRUs. A framework and practical considerations for managing people with SCDys due to tumor in SRUs are proposed. Patients with tumor causing SCDys should be given greater access to specialist SRU in order to achieve the best outcomes.

Mutations in FLVCR1 Cause Posterior Column Ataxia and Retinitis Pigmentosa

PubMed Central

Rajadhyaksha, Anjali M.; Elemento, Olivier; Puffenberger, Erik G.; Schierberl, Kathryn C.; Xiang, Jenny Z.; Putorti, Maria L.; Berciano, José; Poulin, Chantal; Brais, Bernard; Michaelides, Michel; Weleber, Richard G.; Higgins, Joseph J.

2010-01-01

The study of inherited retinal diseases has advanced our knowledge of the cellular and molecular mechanisms involved in sensory neural signaling. Dysfunction of two specific sensory modalities, vision and proprioception, characterizes the phenotype of the rare, autosomal-recessive disorder posterior column ataxia and retinitis pigmentosa (PCARP). Using targeted DNA capture and high-throughput sequencing, we analyzed the entire 4.2 Mb candidate sequence on chromosome 1q32 to find the gene mutated in PCARP in a single family. Employing comprehensive bioinformatic analysis and filtering, we identified a single-nucleotide coding variant in the feline leukemia virus subgroup C cellular receptor 1 (FLVCR1), a gene encoding a heme-transporter protein. Sanger sequencing confirmed the FLVCR1 mutation in this family and identified different homozygous missense mutations located within the protein's transmembrane channel segment in two other unrelated families with PCARP. To determine whether the selective pathologic features of PCARP correlated with FLVCR1 expression, we examined wild-type mouse Flvcr1 mRNA levels in the posterior column of the spinal cord and the retina via quantitative real-time reverse-transcriptase PCR. The Flvcr1 mRNA levels were most abundant in the retina, followed by the posterior column of the spinal cord and other brain regions. These results suggest that aberrant FLVCR1 causes a selective degeneration of a subpopulation of neurons in the retina and the posterior columns of the spinal cord via dysregulation of heme or iron homeostasis. This finding broadens the molecular basis of sensory neural signaling to include common mechanisms that involve proprioception and vision. PMID:21070897

Rehabilitation of people with spinal cord damage due to tumor: literature review, international survey and practical recommendations for optimizing their rehabilitation

PubMed Central

Marshall, Ruth; Stubblefield, Michael D.; Scivoletto, Giorgio

2017-01-01

Background People with spinal cord dysfunction (SCDys) due to tumor (benign and malignant) pose enormous rehabilitation challenges. Objectives were: conduct literature search regarding epidemiology, clinical features and outcomes for SCDys due to tumor following rehabilitation, the ideal setting for rehabilitation and practical considerations for rehabilitation; and propose framework and practical considerations for managing people with SCDys due to tumor in spinal rehabilitation units (SRUs). Design Survey of rehabilitation health care professionals, consensus opinion from experts and literature search. Setting Workshop at International Spinal Cord Society and American Spinal Injury Association combined annual meeting, May 16, 2015, Montréal, Canada. Participants Workshop attendees and experts in the rehabilitation of people with SCDys due to tumor. Outcomes Measures Reports of services offered to people with SCDys due to tumor, including whether those with benign and malignant tumors are admitted into rehabilitation, any admission criteria used and the rational for declining admission. Results Most respondents (n = 33, 83%) reported that people with benign tumors were routinely admitted for rehabilitation but only 18 (45%) reported that people with malignant tumors were routinely admitted. A range of criteria and reasons for declining admission were given. Evidence from the literature and the opinion of experts support the admission of people with SCDys due to tumor into specialist SRUs. Conclusions A framework and practical considerations for managing people with SCDys due to tumor in SRUs are proposed. Patients with tumor causing SCDys should be given greater access to specialist SRU in order to achieve the best outcomes. PMID:27088581

The Amnioscope Strikes Back as a Useful Device for Pinhole Amniotomy in the Management of Polyhydramnios

PubMed Central

Koyama, Shinsuke; Tomimatsu, Takuji; Kanagawa, Takeshi; Tsutsui, Tateki; Kimura, Tadashi

2011-01-01

Polyhydramnios is associated with many serious maternal complications such as placental abruption or cord prolapse at rupture of membranes, uterine dysfunction at delivery, and postpartum hemorrhage. When considering uterine dysfunction caused by overstretched uterine muscles, active artificial amniotomy for more efficient labor seems to be a preferred obstetric management, but the potential adverse complications make obstetricians hesitate to perform this procedure. In such a challenging situation, a new strategy is required. We recently performed pinhole artificial amniotomy using an amnioscope in four women with polyhydramnios, not only to accelerate of labor but also to more slowly and safely reduce amniotic fluid volume. We had no complications using this procedure, and all women were able to have a vaginal delivery without postpartum hemorrhage and neonatal asphyxia. Pinhole artificial amniotomy using an amnioscope may be more convenient and safer than conventional artificial amniotomy. The significance of the amnioscope has been practically nil in modern obstetric management. In this pilot clinical study, we identified a new value for the amnioscope as a promising device for safer amniotomy in women with polyhydramnios. PMID:23705096

Co-morbidities in severe asthma: Clinical impact and management.

PubMed

Porsbjerg, Celeste; Menzies-Gow, Andrew

2017-05-01

Patients with severe asthma represent a minority of the total asthma population, but carry a majority of the morbidity and healthcare costs. Achieving better asthma control in this group of patients is therefore of key importance. Systematic assessment of patients with possible severe asthma to identify treatment barriers and triggers of asthma symptoms, including co-morbidities, improves asthma control and reduces healthcare costs and is recommended by international guidelines on management of severe asthma. This review provides the clinician with an overview of the prevalence and clinical impact of the most common co-morbidities in severe asthma, including chronic rhinosinusitis, nasal polyposis, allergic rhinitis, dysfunctional breathing, vocal cord dysfunction, anxiety and depression, obesity, obstructive sleep apnoea syndrome (OSAS), gastroesophageal reflux disease (GERD), bronchiectasis, allergic bronchopulmonary aspergillosis (ABPA) and eosinophilic granulomatous with polyangiitis (EGPA). Furthermore, the review offers a summary of recommended diagnostic and management approaches for each co-morbidity. Finally, the review links co-morbid conditions to specific phenotypes of severe asthma, in order to guide the clinician on which co-morbidities to look for in specific patients. © 2017 Asian Pacific Society of Respirology.

[Evaluation of the management of erectile and ejaculatory dysfunction in a series of 90 patients with spinal cord injuries].

PubMed

Hadiji, N; Benbouzid, R; Previnaire, J G; Leblond, C; Mieusset, R; Enjalbert, M; Soler, J M

2013-12-01

To evaluate the erectile dysfunction and ejaculatory on patients injured in conus medullaris (CMI) and the efficacy of treatment. Ninety patients with injured conus medullaris underwent a retrospective and monocentric study. They have all an assessment of erectile dysfunction and ejaculatory by the International Index of Erectile Function (IIEF-15) and a clinic scenario. We evaluated the erection by a clinical scoring scale (Shrameck). Seventy-seven out of 90 (85.55%) had therapeutic tests to restore erection: prostaglandin (PGE1), phosphodiesterase type 5 inhibitors (PDE5) and Papaverine. Seventy-four out of 90 (82.22%) underwent a penile stimulation tests (VM) more or less associated with Midodrine(®) (alpha mimetic) to cause ejaculation with a systematic search of spermatozoa in urine. Data were entered and analyzed using Microsoft Office Excel. Ninety patients with a complete lesion of the sacral metameres (S2S3S4) were included. They were responding to PGE1, PDE5, respectively 81.63% and 30.76%. The association VM/Midodrine(®) improves ejaculation in 52.63% of cases. Orgasm is absent in all our CMI. In this series of BCM patients, we observed a good efficacy of PGE1 and PDE 5 on erection. We also observed positive results of vibromassage and alpha-agonists on ejaculation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Sudden Death: An Uncommon Occurrence in Dementia with Lewy Bodies.

PubMed

Molenaar, Joery P; Wilbers, Joyce; Aerts, Marjolein B; Leijten, Quinten H; van Dijk, Jan G; Esselink, Rianne A; Bloem, Bastiaan R

2016-01-01

We present a 75-year-old woman with dementia and parkinsonism who developed severe orthostatic hypotension and eventually died. Autopsy revealed extensive Lewy body formation in the midbrain, limbic system, intermediate spinal cord, and medulla oblongata. Furthermore, a vast amount of Lewy bodies was seen in the paravertebral sympathetic ganglia which likely explained the severe autonomic failure. We speculate that this autonomic failure caused sudden death through dysregulation of respiration or heart rhythm, reminiscent of sudden death in multiple system atrophy (MSA). Clinicians should be aware of this complication in patients presenting with parkinsonism and autonomic dysfunction, and that sudden death may occur in dementia with Lewy bodies (DLB) as it does in MSA.

Functional neuroanatomy of human cortex cerebri in relation to wanting sex and having it.

PubMed

Georgiadis, Janniko R

2015-04-01

Neuroanatomical textbooks typically restrict the central nervous system control of sexual responsiveness to the hypothalamus, brainstem and spinal cord. However, for all its primitive functions human sex is surprisingly complex and versatile. This review aims to extend the neuroanatomy of sexual responsiveness by providing a comprehensive overview of the empirical evidence for cerebral cortical involvement. To this end I will structure relevant human brain research data to fit the sexual pleasure cycle template-wanting sex, having sex, inhibiting sex-arguing that going through these sexual response phases requires adequate shifting between functional cortical networks. The relevance of this notion for understanding certain sexual dysfunctions is discussed. © 2015 Wiley Periodicals, Inc.

Energy Homeostasis and Abnormal RNA Metabolism in Amyotrophic Lateral Sclerosis

PubMed Central

Liu, Yu-Ju; Tsai, Po-Yi; Chern, Yijuang

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that is clinically characterized by progressive muscle weakness and impaired voluntary movement due to the loss of motor neurons in the brain, brain stem and spinal cord. To date, no effective treatment is available. Ample evidence suggests that impaired RNA homeostasis and abnormal energy status are two major pathogenesis pathways in ALS. In the present review article, we focus on recent studies that report molecular insights of both pathways, and discuss the possibility that energy dysfunction might negatively regulate RNA homeostasis via the impairment of cytoplasmic-nuclear shuttling in motor neurons and subsequently contribute to the development of ALS. PMID:28522961

Ultrasonographic and macroscopic anatomy of the enucleated eyes of the buffalo (Bos bubalis) and the one-humped camel (Camelus dromedarius) of different ages.

PubMed

Kassab, A

2012-02-01

The ultrasonographic appearance and measurements of the normal buffalo and camel eye globes were described in 60 buffaloes (Bos bubalis) aged 1 year (28 eyes) and 10 years (32 eyes), and in 51 humped camels (Camelus dromedarius) aged 1 year (26 eyes) and 10 years (24 eyes). Ocular measurements were recorded by A- and B-scan ultrasonographic examination of 40 buffalo eyes (18 young and 22 adult eyes) and 34 camel eyes (14 young and 20 adult eyes) using a KANGH ultrasound scanner equipped with 10 MHz probe. For gross measurements, 20 buffalo and 16 camel eye globes were frozen and dissected and the same measurements were made using fine callipers macroscopically. The aqueous and vitreous humour of the buffalo and camel eyes appeared anechoic. The cornea, anterior and posterior lens capsule and iris appeared hyperechoic. The ocular measurements for the axial length, vitreous chamber depth (VCD), corneal thickness, lens thickness and scleroretinal rim thickness increase with the advance of age in both buffaloes and camels. Except for the anterior chamber depth, VCD and lens thickness, which were larger in adult camels than in adult buffaloes, no other differences between ocular dimensions were observed in both species. The results of this study are valuable for comparative ocular anatomy and will be useful for ultrasonographic evaluation of ocular diseases in buffaloes and camels. © 2011 Blackwell Verlag GmbH.

A variable-collimation display system

NASA Astrophysics Data System (ADS)

Batchko, Robert; Robinson, Sam; Schmidt, Jack; Graniela, Benito

2014-03-01

Two important human depth cues are accommodation and vergence. Normally, the eyes accommodate and converge or diverge in tandem; changes in viewing distance cause the eyes to simultaneously adjust both focus and orientation. However, ambiguity between accommodation and vergence cues is a well-known limitation in many stereoscopic display technologies. This limitation also arises in state-of-the-art full-flight simulator displays. In current full-flight simulators, the out-the-window (OTW) display (i.e., the front cockpit window display) employs a fixed collimated display technology which allows the pilot and copilot to perceive the OTW training scene without angular errors or distortions; however, accommodation and vergence cues are limited to fixed ranges (e.g., ~ 20 m). While this approach works well for long-range, the ambiguity of depth cues at shorter range hinders the pilot's ability to gauge distances in critical maneuvers such as vertical take-off and landing (VTOL). This is the first in a series of papers on a novel, variable-collimation display (VCD) technology that is being developed under NAVY SBIR Topic N121-041 funding. The proposed VCD will integrate with rotary-wing and vertical take-off and landing simulators and provide accurate accommodation and vergence cues for distances ranging from approximately 3 m outside the chin window to ~ 20 m. A display that offers dynamic accommodation and vergence could improve pilot safety and training, and impact other applications presently limited by lack of these depth cues.

A comparison of point defects in Cd1-xZnxTe1-ySey crystals grown by Bridgman and traveling heater methods

NASA Astrophysics Data System (ADS)

Gul, R.; Roy, U. N.; Camarda, G. S.; Hossain, A.; Yang, G.; Vanier, P.; Lordi, V.; Varley, J.; James, R. B.

2017-03-01

In this paper, the properties of point defects in Cd1-xZnxTe1-ySey (CZTS) radiation detectors are characterized using deep-level transient spectroscopy and compared between materials grown using two different methods, the Bridgman method and the traveling heater method. The nature of the traps was analyzed in terms of their capture cross-sections and trap concentrations, as well as their effects on the measured charge-carrier trapping and de-trapping times, and then compared for the two growth techniques. The results revealed that Se addition to CdZnTe can reduce the VCd- concentration. In Travelling Heater Method (THM) and Bridgman Method (BM) grown CZTS detectors, besides a few similarities in the shallow and medium energy traps, there were major differences in the deep traps. It was observed that the excess-Te and lower growth-temperature conditions in THM-grown CZTS led to a complete compensation of VCd- and two additional traps (attributed to Tei- and TeCd++ appearing at around Ev + 0.26 eV and Ec - 0.78 eV, respectively). The 1.1-eV deep trap related to large Te secondary phases was a dominant trap in the BM-grown CZTS crystals. In addition to i-DLTS data, the effects of point defects induced due to different processing techniques on the detector's resistivity, spectral response to gammas, and μτ product were determined.

Prospective study of the impact on quality of life of cystectomy with ileal conduit urinary diversion for neurogenic bladder dysfunction.

PubMed

Guillotreau, Julien; Castel-Lacanal, Evelyne; Roumiguié, Mathieu; Bordier, Benoit; Doumerc, Nicolas; De Boissezon, Xavier; Malavaud, Bernard; Marque, Philippe; Rischmann, Pascal; Gamé, Xavier

2011-11-01

Neurogenic bladder dysfunction has a negative impact on the patient's quality of life (QoL). Cystectomy with ileal conduit urinary diversion is a treatment option in patients in failure after conservative management. The objective of this study was to evaluate the impact of ileal conduit urinary diversion on the QoL of patients with neurogenic bladder dysfunction. From March 2004 to November 2010, 48 patients (36 women and 12 men with a mean age of 50.6  ±  11.8 years) treated by cystectomy with ileal conduit urinary diversion for neurogenic bladder dysfunction, prospectively completed, before and after surgery, two self-administered QoL questionnaires. Neurological diseases were multiple sclerosis in 38 cases, spinal cord injury in 7 cases, and other neurological disease in 3 cases. Cystectomy was performed by laparoscopy in all patients. QoL was measured by using two self-administered questionnaires, one questionnaire specific for urinary disorders validated in neurological patients, Qualiveen®, and the generic SF36-v2® questionnaire. Data were compared by Student's t test. Comparison of the Qualiveen® self-administered questionnaire scores and indices before and after surgery showed that, after surgery, patients presented a significant reduction of limitations (0.57 ± 0.64 vs. 1.55 ± 1.35, P < 0.001), constraints (2.12  ±  0.83 vs. 2.64  ±  1.12, P = 0.046) scores and the SIUP index (1.29 ± 0.65 vs. 1.79 ± 0.95, P = 0.015). No significant change in SF36-v2® scores was observed postoperatively. Ileal conduit urinary diversion improves the urinary QoL of patients with neurogenic bladder dysfunction by decreasing limitations and constraints induced by urinary disorders, but has no impact on general QoL. Copyright © 2011 Wiley Periodicals, Inc.

Synaptic dysfunction and altered excitability in C9ORF72 ALS/FTD.

PubMed

Starr, Alexander; Sattler, Rita

2018-08-15

Amyotrophic lateral sclerosis (ALS) is characterized by a progressive degeneration of upper and lower motor neurons, resulting in fatal paralysis due to denervation of the muscle. Due to genetic, pathological and symptomatic overlap, ALS is now considered a spectrum disease together with frontotemporal dementia (FTD), the second most common cause of dementia in individuals under the age of 65. Interestingly, in both diseases, there is a large prevalence of RNA binding proteins (RBPs) that are mutated and considered disease-causing, or whose dysfunction contribute to disease pathogenesis. The most common shared genetic mutation in ALS/FTD is a hexanucleuotide repeat expansion within intron 1 of C9ORF72 (C9). Three potentially overlapping, putative toxic mechanisms have been proposed: loss of function due to haploinsufficient expression of the C9ORF72 mRNA, gain of function of the repeat RNA aggregates, or RNA foci, and repeat-associated non-ATG-initiated translation (RAN) of the repeat RNA into toxic dipeptide repeats (DPRs). Regardless of the causative mechanism, disease symptoms are ultimately caused by a failure of neurotransmission in three regions: the brain, the spinal cord, and the neuromuscular junction. Here, we review C9 ALS/FTD-associated synaptic dysfunction and aberrant neuronal excitability in these three key regions, focusing on changes in morphology and synapse formation, excitability, and excitotoxicity in patients, animal models, and in vitro models. We compare these deficits to those seen in other forms of ALS and FTD in search of shared pathways, and discuss the potential targeting of synaptic dysfunctions for therapeutic intervention in ALS and FTD patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Cerebrovascular dysfunction is an attractive target for therapy in heat stroke.

PubMed

Chen, Sheng-Hsien; Niu, Ko-Chi; Lin, Mao-Tsun

2006-08-01

1. The aim of the present review is to summarize clinical observations and results of animal models that advance the knowledge of the attenuation of cerebrovascular dysfunction in the setting of heat stroke. It is a narrative review of selected published literature from Medline over the period 1959-2005. 2. All heat-stressed rodents, even under general anaesthesia, have hyperthermia, systemic inflammation, hypercoagulable state, arterial hypotension and tissue ischaemia and injury in multiple organs. These findings demonstrate that rodent heat stroke models can nearly mirror the full spectrum of human heat stroke. Experimental heat stroke fulfills the empirical triad used for the diagnosis of classical human heat stroke, namely hyperthermia, central nervous system alterations and a history of heat stress. 3. These physiological dysfunctions and survival during heat stroke can be improved by whole-body or brain cooling therapy adopted immediately after the onset of heat stroke. 4. However, in the absence of body or brain cooling, these heat stroke reactions can still be reduced by the following measures: (i) fluid replacement with 3% NaCl solution, 10% human albumin or hydroxyethyl starch; (ii) intravenous delivery of anti-inflammatory drugs, free radical scavengers or interleukin-1 receptor antagonists; (iii) hyperbaric oxygen therapy; or (iv) transplantation of human umbilical cord blood cells. 5. In addition, before initiation of heat stress, prior manipulations with one of the following measures was found to be able to protect against heat stroke reactions: (i) systemic delivery of alpha-tocopherol, mannitol, inducible nitric oxide synthase inhibitors, mu-opioid receptor antagonists, endothelin ETA receptor antagonists, serotoninergic nerve depletors or receptor antagonists, or glutamate receptor antagonists; or (ii) heat shock protein 72 preconditioning. 6. There is compelling evidence that cerebrovascular dysfunction is an attractive target for therapy in heat stroke.

High-resolution mapping of the NO2 spatial distribution over Belgian urban areas based on airborne APEX remote sensing

NASA Astrophysics Data System (ADS)

Tack, Frederik; Merlaud, Alexis; Iordache, Marian-Daniel; Danckaert, Thomas; Yu, Huan; Fayt, Caroline; Meuleman, Koen; Deutsch, Felix; Fierens, Frans; Van Roozendael, Michel

2017-05-01

We present retrieval results of tropospheric nitrogen dioxide (NO2) vertical column densities (VCDs), mapped at high spatial resolution over three Belgian cities, based on the DOAS analysis of Airborne Prism EXperiment (APEX) observations. APEX, developed by a Swiss-Belgian consortium on behalf of ESA (European Space Agency), is a pushbroom hyperspectral imager characterised by a high spatial resolution and high spectral performance. APEX data have been acquired under clear-sky conditions over the two largest and most heavily polluted Belgian cities, i.e. Antwerp and Brussels on 15 April and 30 June 2015. Additionally, a number of background sites have been covered for the reference spectra. The APEX instrument was mounted in a Dornier DO-228 aeroplane, operated by Deutsches Zentrum für Luft- und Raumfahrt (DLR). NO2 VCDs were retrieved from spatially aggregated radiance spectra allowing urban plumes to be resolved at the resolution of 60 × 80 m2. The main sources in the Antwerp area appear to be related to the (petro)chemical industry while traffic-related emissions dominate in Brussels. The NO2 levels observed in Antwerp range between 3 and 35 × 1015 molec cm-2, with a mean VCD of 17.4 ± 3.7 × 1015 molec cm-2. In the Brussels area, smaller levels are found, ranging between 1 and 20 × 1015 molec cm-2 and a mean VCD of 7.7 ± 2.1 × 1015 molec cm-2. The overall errors on the retrieved NO2 VCDs are on average 21 and 28 % for the Antwerp and Brussels data sets. Low VCD retrievals are mainly limited by noise (1σ slant error), while high retrievals are mainly limited by systematic errors. Compared to coincident car mobile-DOAS measurements taken in Antwerp and Brussels, both data sets are in good agreement with correlation coefficients around 0.85 and slopes close to unity. APEX retrievals tend to be, on average, 12 and 6 % higher for Antwerp and Brussels, respectively. Results demonstrate that the NO2 distribution in an urban environment, and its fine-scale variability, can be mapped accurately with high spatial resolution and in a relatively short time frame, and the contributing emission sources can be resolved. High-resolution quantitative information about the atmospheric NO2 horizontal variability is currently rare, but can be very valuable for (air quality) studies at the urban scale.

A Review of Fibrocartilaginous Embolic Myelopathy and Different Types of Peracute Non-Compressive Intervertebral Disk Extrusions in Dogs and Cats

PubMed Central

De Risio, Luisa

2015-01-01

This review discusses terminology, pathological, clinical, and magnetic resonance imaging (MRI) findings, treatment, outcome, and prognostic factors of fibrocartilaginous embolic myelopathy (FCEM), acute non-compressive nucleus pulposus extrusion (ANNPE), and intradural/intramedullary intervertebral disk extrusion (IIVDE). FCEM, ANNPE, and IIVDE have a similar clinical presentation characterized by peracute onset of neurological dysfunction that is generally non-progressive after the initial 24–48 h. Differentiating between these conditions can be challenging, however, certain clinical and imaging findings can help. FCEM can occur in both adult and immature animals, whereas ANNPE or IIVDE have been reported only in animals older than 1 year. In dogs, ANNPE and IIVDE most commonly occur in the intervertebral disk spaces between T12 and L2, whereas FCEM has not such site predilection. In cats, FCEM occurs more frequently in the cervical spinal cord than in other locations. Data on cats with ANNPE and IIVDE are limited. Optimal MRI definition and experience in neuroimaging can help identify the findings that allow differentiation between FCEM, ANNPE, and IIVDE. In animals with ANNPE and IIVDE, the affected intervertebral disk space is often narrowed and the focal area of intramedullary hyperintensity on T2-weighted images is located above the affected intervertebral disk space. In dogs with ANNPE signal changes associated with the extruded nucleus pulposus and epidural fat disruption can be identified in the epidural space dorsal to the affected intervertebral disk. Identification of a linear tract (predominantly hyperintense on T2-weighted images, iso to hypointense on T1-weighted images and hypointense on T2*-weighted gradient recall echo images) extending from the intervertebral disk into the spinal cord parenchyma is highly suggestive of IIVDE. Treatment of FCEM and ANNPE is conservative. Dogs reported with IIVDE have been managed either conservatively or surgically. Prognostic factors include degree of neurological dysfunction (particularly loss of nociception) and disease-specific MRI variables. PMID:26664953

Concepts on the pathogenesis of adolescent idiopathic scoliosis. Bone growth and mass, vertebral column, spinal cord, brain, skull, extra-spinal left-right skeletal length asymmetries, disproportions and molecular pathogenesis.

PubMed

Burwell, R Geoffrey; Dangerfield, Peter H; Freeman, Brian J C

2008-01-01

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). Encouraging advances thought to be related to AIS pathogenesis have recently been made in several fields including anthropometry of bone growth, bone mass, spinal growth modulation, extra-spinal left-right skeletal length asymmetries and disproportions, magnetic resonance imaging of vertebral column, spinal cord, brain, skull, and molecular pathogenesis. These advances are leading to the evaluation of new treatments including attempts at minimally invasive surgery on the spine and peri-apical ribs. Several concepts of AIS are outlined indicating their clinical applications but not their research potential. The concepts, by derivation morphological, molecular and mathematical, are addressed in 15 sections: 1) initiating and progressive factors; 2) relative anterior spinal overgrowth; 3) dorsal shear forces that create axial rotational instability; 4) rotational preconstraint; 5) uncoupled, or asynchronous, spinal neuro-osseous growth; 6) brain, nervous system and skull; 7) a novel neuro-osseous escalator concept based on a putative abnormality of two normal polarized processes namely, a) increasing skeletal dimensions, and b) the CNS body schema - both contained within a neuro-osseous timing of maturation (NOTOM) concept; 8) transverse plane pelvic rotation, skeletal asymmetries and developmental theory; 9) thoraco-spinal concept; 10) origin in contracture at the hips; 11) osteopenia; 12) melatonin deficiency; 13) systemic melatonin-signaling pathway dysfunction; 14) platelet calmodulin dysfunction; and 15) biomechanical spinal growth modulation. From these concepts, a collective model for AIS pathogenesis is formulated. The central concept of this model includes the body schema of the neural systems, widely-studied in adults, that control normal posture and coordinated movements with frames of reference in the posterior parietal cortex. The escalator concept has implications for the normal development of upright posture, and the evolution in humans of neural control, the trunk and unique bipedal gait.

Myxopapillary ependymoma as a cause of back pain in a young male – A case report

PubMed Central

Ngo, Trung P; Dufton, John; Stern, Paula J; Islam, Omar

2013-01-01

Objective: Primary spinal cord tumours are rare causes of low back pain but can be a significant cause of morbidity if undiagnosed and untreated. The following is a case of a young male patient presenting with low back pain and radicular symptoms caused by myxopapillary ependymoma. Clinical Features: A nineteen year old male presented to an orthopaedic surgeon with a long history of back pain. He was initially diagnosed with soft tissue injuries and discharged. He began to experience erectile and bowel dysfunction two years later and was re-referred to the orthopaedic surgeon by his family physician but was lost to follow-up. The patient did not present to the surgeon until two years after his symptom profile changed. At that point, MRI examinations revealed a large myxopapillary ependymoma extending from T12 to L4 that was confirmed by a pathologist. Intervention and Outcome: The tumour was surgically resected with subsequent adjuvant radiotherapy. After one year, the patient required continued catheterization and had poor anal tone. His back and leg complaints were almost normal. Follow-up MRI examinations revealed no disease progression or new spinal lesions at 4 years after the initial diagnosis. Conclusion: The clinical presentation of primary spinal cord tumours is non-specific and can easily be missed. In cases of chronic back pain, signs and symptoms should be regularly monitored for changes indicative of progressive neurological compromise such as sensory, motor and bowel/bladder dysfunction. If there is deterioration of clinical signs and symptoms, a spinal tumour should be considered in the list of differential diagnoses. Delayed diagnosis and treatment of these rare causes of back pain could lead to poor outcomes; therefore, a referral to a surgeon should be done immediately with proper follow up to ensure continuity of care. PMID:23754860

Urothelial dysfunction and chronic inflammation in patients with spinal cord injuries at different levels and correlation with urodynamic findings.

PubMed

Jiang, Yuan-Hong; Liu, Hsin-Tzu; Kuo, Hann-Chorng

2015-11-01

To investigate urothelial dysfunction and suburothelial inflammation in patients with chronic SCI at different spinal cord levels. Immunofluorescence staining of E-cadherin, zonula occludens-1 (ZO-1), tryptase (mast cell activation), and apoptosis tests on bladder biopsy specimens including urothelium and suburothelium were performed in 34 chronic SCI patients and 10 controls. Video-urodynamic studies were also analyzed and correlated with immunofluorescence findings. The mean interval from SCI to bladder biopsy was 9.3 ± 8.4 years. Patients with chronic SCI had significantly lower expression of E-cadherin (20.86 ± 14.07 vs. 42.40 ± 16.73, the fluorescence intensity per 4 µm(2)) and ZO-1 (5.54 ± 3.73 vs. 11.01 ± 5.66, the fluorescence intensity per 4 µm(2)) than controls (both P < 0.05). Additionally, suburothelial activated mast cells (16.60 ± 6.85 vs. 1.25 ± 1.15, positive cells per 100 cells) and apoptotic cell numbers (5.39 ± 4.86 vs. 0.08 ± 0.26, positive cells per 100 cells) were significantly higher than in controls (both P < 0.05). Immunofluorescence characteristics and video-urodynamic findings did not differ between patients with 15 cervical and 19 thoracic SCIs. Suburothelial activated mast cell numbers correlated negatively to E-cadherin expression in the urothelium (r = -0.559, P < 0.05). Additionally, apoptotic cell number correlated negatively with cystometric bladder capacity (r = -0.535, P < 0.05). Decreased expression of urothelial adhesion and junction proteins and increased suburothelial inflammation and apoptosis were found in patients with chronic SCI, regardless of injury level. Such mechanisms might contribute to the vulnerability of patients with SCI to cystitis and recurrent bacterial infections. © 2014 Wiley Periodicals, Inc.

Lysosomal damage after spinal cord injury causes accumulation of RIPK1 and RIPK3 proteins and potentiation of necroptosis.

PubMed

Liu, Shuo; Li, Yun; Choi, Harry M C; Sarkar, Chinmoy; Koh, Eugene Y; Wu, Junfang; Lipinski, Marta M

2018-04-23

Necroptosis, a regulated necrosis pathway mediated by the receptor-interacting protein kinases 1 and 3 (RIPK1 and RIPK3), is induced following spinal cord injury (SCI) and thought to contribute to neuronal and glial cell death. However, mechanisms leading to activation of necroptosis after SCI remain unclear. We have previously shown that autophagy, a catabolic pathway facilitating degradation of cytoplasmic proteins and organelles in a lysosome-dependent manner, is inhibited following SCI in rats. Our current data confirm that inhibition of autophagy also occurs after thoracic contusive SCI in the mouse model, as indicated by accumulation of both the autophagosome marker, LC3-II and autophagy cargo protein, p62/SQSTM1. This was most pronounced in the ventral horn neurons and was caused by rapid inhibition of lysosomal function after SCI. Interestingly, RIPK1, RIPK3, and the necroptosis effector protein MLKL also rapidly accumulated after SCI and localized to neurons with disrupted autophagy, suggesting that these events may be related. To determine if lysosomal dysfunction could contribute to induction of necroptosis, we treated PC12 cells and primary rat cortical neurons with lysosomal inhibitors. This led to rapid accumulation of RIPK1 and RIPK3, confirming that they are normally degraded by the lysosomal pathway. In PC12 cells lysosomal inhibition also sensitized cells to necroptosis induced by tumor necrosis factor α (TNFα) and caspase inhibitor. Imaging studies confirmed that RIPK1 partially localized to lysosomes in both untreated and lysosomal inhibitor treated cells. Similarly, we detected presence of RIPK1, RIPK3 and MLKL in both cytosol and at lysosomes after SCI in vivo. Furthermore, stimulation of autophagy and lysosomal function with rapamycin treatment led to decreased accumulation of RIPK1 and attenuated cell death after SCI. These data suggest that lysosomal dysfunction after SCI may contribute to both inhibition of autophagy and sensitize cells to necroptosis by promoting RIPK1 and RIPK3 accumulation.

Regional deficiencies in chaperone-mediated autophagy underlie α-synuclein aggregation and neurodegeneration

PubMed Central

Malkus, Kristen A.; Ischiropoulos, Harry

2012-01-01

In neurodegenerative diseases, it remains unclear why certain brain regions are selectively vulnerable to protein aggregation. In transgenic mice expressing human A53T α-synuclein, the brainstem and spinal cord develop the most prominent α-synuclein inclusions which correlate with age-dependent motor dysfunction. Herein we present the novel finding that this selective aggregation is in part dependent on the inability of chaperone-mediated autophagy (CMA) to effectively degrade α-synuclein in these brain regions. Lysosomal assays revealed that CMA activity was significantly decreased in aggregation-prone regions compared to the remainder of the brain. Previously, CMA activity has been shown to be proportional to levels of the CMA receptor Lamp-2a. Using antibodies, brain tissue from Lamp-2a null mice, enzymatic deglycosylation, and mass spectrometry, we identified Lamp2a as a novel 72 kDa glycoprotein in the mouse brain. Examination of Lamp-2a levels revealed differences in expression across brain regions. The brainstem and the spinal cord had a more than three-fold greater levels of Lamp-2a as compared to regions less vulnerable to aggregation and exhibited a selective upregulation of Lamp-2a during development of α-synuclein inclusions. Despite this dynamic response of Lamp-2a, the levels of substrates bound to the brain lysosomes as well as the rates of substrate uptake and degradation were not proportional to the levels of Lamp-2a. These regional differences in CMA activity and Lamp-2a expression were found in both non-transgenic mice as well as A53T α-syn mice. Therefore, these are inherent variations and not a transgene-specific effect. However, differences in CMA activity may render select brain regions vulnerable to homeostatic dysfunction in the presence of stressors such as overexpression of human A53T α-syn. Collectively, the data provide a potential mechanism to explain the dichotomy of vulnerability or resistance that underlies brain regions during aggregate formation in neurodegenerative disease. PMID:22426402

Urodynamic results, clinical efficacy, and complication rates of sacral intradural deafferentation and sacral anterior root stimulation in patients with neurogenic lower urinary tract dysfunction resulting from complete spinal cord injury.

PubMed

Krasmik, D; Krebs, Jörg; van Ophoven, Arndt; Pannek, Jürgen

2014-11-01

To investigate the outcome and complications of sacral deafferentation (SDAF) and sacral anterior root stimulation (SARS) in patients with neurogenic lower urinary tract dysfunction (NLUTD) resulting from complete spinal cord injury (SCI). Retrospective chart analysis of 137 patients who underwent SDAF/SARS at a single institution. Patients were categorized as being at risk of renal damage when the maximum detrusor pressure was >40 cmH2 O or detrusor compliance was <20 ml/cmH2 O. After a mean follow-up time of 14.8 ± 5.3 years, SDAF/SARS treatment significantly (P < 0.001) reduced the number of patients suffering from elevated detrusor pressure from 65 to 2, and from low detrusor compliance from 62 to 13, respectively. Mean bladder capacity significantly (P < 0.001) improved from 272.4 ± 143.0 to 475.0 ± 82.7 ml. The mean number of symptomatic UTI also decreased significantly (P < 0.001) from 6.2 ± 4.5 to 2.5 ± 2.6 per year. The number of patients suffering from incontinence had significantly (P < 0.001) decreased from 70 to 44. At the last follow-up visit, 107 (78.1%) patients were still using the stimulator. A total of 84 complications requiring surgical revision were observed. Defects of the stimulator cables or the receiver plate were the most common events (n = 38). The retrospective design pertains to the limitations of the study. Sacral deafferentation and SARS are an effective treatment option for refractory NLUTD in patients with complete SCI, despite a substantial long-term complication rate. © 2014 Wiley Periodicals, Inc.

Effectiveness of an Upper Extremity Exercise Device Integrated With Computer Gaming for Aerobic Training in Adolescents With Spinal Cord Dysfunction

PubMed Central

Widman, Lana M; McDonald, Craig M; Abresch, R. Ted

2006-01-01

Background/Objective: To determine whether a new upper extremity exercise device integrated with a video game (GameCycle) requires sufficient metabolic demand and effort to induce an aerobic training effect and to explore the feasibility of using this system as an exercise modality in an exercise intervention. Design: Pre-post intervention. Setting: University-based research facility. Subject Population: A referred sample of 8 adolescent subjects with spina bifida (4 girls, 15.5 ± 0.6 years; 4 boys, 17.5 ± 0.9 years) was recruited to participate in the project. All subjects had some level of mobility impairment that did not allow them to participate in mainstream sports available to their nondisabled peers. Five subjects used a wheelchair full time, one used a wheelchair occasionally, but walked with forearm crutches, and 2 were fully ambulatory, but had impaired gait. Main Outcome Measures: Peak oxygen uptake, maximum work output, aerobic endurance, peak heart rate, rating of perceived exertion, and user satisfaction. Results: Six of the 8 subjects were able to reach a Vo2 of at least 50% of their Vo2 reserve while using the GameCycle. Seven of the 8 subjects reached a heart rate of at least 50% of their heart rate reserve. One subject did not reach either 50% of Vo2 reserve or 50% of heart rate reserve. Seven of the 8 subjects increased their maximum work capability after training with the GameCycle at least 3 times per week for 16 weeks. Conclusions: The data suggest that the GameCycle seems to be adequate as an exercise device to improve oxygen uptake and maximum work capability in adolescents with lower extremity disability caused by spinal cord dysfunction. The subjects in this study reported that the video game component was enjoyable and provided a motivation to exercise. PMID:17044386

Pigmented Creatine Deposits in Amyotrophic Lateral Sclerosis Central Nervous System Tissues Identified by Synchrotron Fourier Transform Infrared Microspectroscopy and X-ray Fluorescence Spectromicroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kastyak, M.; Szczerbowska-Boruchowska, M; Adamek, D

2010-01-01

Amyotrophic Lateral Sclerosis (ALS) is an untreatable, neurodegenerative disease of motor neurons characterized by progressive muscle atrophy, limb paralysis, dysarthria, dysphagia, dyspnae and finally death. Large motor neurons in ventral horns of spinal cord and motor nuclei in brainstem, large pyramidal neurons of motor cortex and/or large myelinated axons of corticospinal tracts are affected. In recent synchrotron Fourier Transform Infrared microspectroscopy (sFTIR) studies of ALS CNS autopsy tissue, we discovered a small deposit of crystalline creatine, which has a crucial role in energy metabolism. We have now examined unfixed, snap frozen, post-autopsy tissue sections of motor cortex, brain stem, spinalmore » cord, hippocampus and substantia nigra from six ALS and three non-degenerated cases with FTIR and micro-X-ray fluorescence (XRF). Heterogeneous pigmented deposits were discovered in spinal cord, brain stem and motor neuron cortex of two ALS cases. The FTIR signature of creatine has been identified in these deposits and in numerous large, non-pigmented deposits in four of the ALS cases. Comparable pigmentation and creatine deposits were not found in controls or in ALS hippocampus and substantia nigra. Ca, K, Fe, Cu and Zn, as determined by XRF, were not correlated with the pigmented deposits; however, there was a higher incidence of hot spots (Ca, Zn, Fe and Cu) in the ALS cases. The identity of the pigmented deposits remains unknown, although the absence of Fe argues against both erythrocytes and neuromelanin. We conclude that elevated creatine deposits may be indicators of dysfunctional oxidative processes in some ALS cases.« less

Neurologic outcome after thoracolumbar partial lateral corpectomy for intervertebral disc disease in 72 dogs.

PubMed

Salger, Florian; Ziegler, Luisa; Böttcher, Irene Christine; Oechtering, Gerhard; Böttcher, Peter; Flegel, Thomas

2014-07-01

To determine neurologic outcome and factors influencing outcome after thoracolumbar partial lateral corpectomy (PLC) in dogs with intervertebral disc disease (IVDD) causing ventral spinal cord compression. Retrospective case series. Dogs with IVDD (n = 72; 87 PLC). Dogs with IVDD between T9 and L5 were included if treated by at least 1 PLC. Exclusion criteria were: previous spinal surgery, combination of PLC with another surgical procedure. Neurologic outcome was assessed by: (1) modified Frankel score (MFS) based on neurologic examinations at 4 time points (before surgery, immediately after PLC, at discharge and 4 weeks after PLC); and (2) owner questionnaire. The association of the following factors with neurologic outcome was analyzed: age, body weight, duration of current neurologic dysfunction (acute, chronic), IVDD localization, breed (chondrodystrophic, nonchondrodystrophic), number of PLCs, degree of presurgical spinal cord compression and postsurgical decompression, slot depth, presurgical MFS. Presurgical spinal cord compression was determined by CT myelography (71 dogs) or MRI (1 dog), whereas postsurgical decompression and slot depth were determined on CT myelography (69 dogs). MFS was improved in 18.7%, 31.7%, and 64.2% of dogs at the 3 postsurgical assessments, whereas it was unchanged in 62.6%, 52.8%, and 32.0% at corresponding time points. Based on owner questionnaire, 91.4% of dogs were ambulatory 6 months postsurgically with 74.5% having a normal gait. Most improvement in neurologic function developed within 6 months after surgery. Presurgical MFS was the only variable significantly associated with several neurologic outcome measurements (P < .01). PLC is an option for decompression in ventrally compressing thoracolumbar IVDD. Prognosis is associated with presurgical neurologic condition. © Copyright 2014 by The American College of Veterinary Surgeons.

New insights into the mechanisms of itch: are pain and itch controlled by distinct mechanisms?

PubMed Central

Liu, Tong; Ji, Ru-Rong

2013-01-01

Itch and pain are closely related but distinct sensations. They share largely overlapping mediators and receptors, and itch-responding neurons are also sensitive to pain stimuli. Itch-mediating primary sensory neurons are equipped with distinct receptors and ion channels for itch transduction, including Mas-related G protein-coupled receptors (Mrgprs), protease-activated receptors (PARs), histamine receptors, bile acid receptor (TGR5), toll-like receptors (TLRs), and transient receptor potential subfamily V1/A1 (TRPV1/A1). Recent progress has indicated the existence of an itch-specific neuronal circuitry. The MrgprA3-expressing primary sensory neurons exclusively innervate the epidermis of skin and their central axons connect with gastrin-releasing peptide receptor (GRPR)-expressing neurons in the superficial spinal cord. Notably, ablation of MrgprA3-expressing primary sensory neurons or GRPR-expressing spinal cord neurons results in selective reduction in itch but not pain. Chronic itch results from dysfunction of the immune and nervous system and can manifest as neural plasticity, despite the fact that chronic itch is often treated by dermatologists. While differences between acute pain and acute itch are striking, chronic itch and chronic pain share many similar mechanisms, including peripheral sensitization (increased responses of primary sensory neurons to itch and pain mediators), central sensitization (hyperactivity of spinal projection neurons and excitatory interneurons), loss of inhibitory control in the spinal cord, and neuro-immune and neuro-glial interactions. Notably, painful stimuli can elicit itch in some chronic conditions (e.g., atopic dermatitis) and some drugs for treating chronic pain are also effective in chronic itch. Thus, itch and pain have more similarities in pathological and chronic conditions. PMID:23636773

Degeneration of Phrenic Motor Neurons Induces Long-Term Diaphragm Deficits following Mid-Cervical Spinal Contusion in Mice

PubMed Central

Nicaise, Charles; Putatunda, Rajarshi; Hala, Tamara J.; Regan, Kathleen A.; Frank, David M.; Brion, Jean-Pierre; Leroy, Karelle; Pochet, Roland; Wright, Megan C.

2012-01-01

Abstract A primary cause of morbidity and mortality following cervical spinal cord injury (SCI) is respiratory compromise, regardless of the level of trauma. In particular, SCI at mid-cervical regions targets degeneration of both descending bulbospinal respiratory axons and cell bodies of phrenic motor neurons, resulting in deficits in the function of the diaphragm, the primary muscle of inspiration. Contusion-type trauma to the cervical spinal cord is one of the most common forms of human SCI; however, few studies have evaluated mid-cervical contusion in animal models or characterized consequent histopathological and functional effects of degeneration of phrenic motor neuron–diaphragm circuitry. We have generated a mouse model of cervical contusion SCI that unilaterally targets both C4 and C5 levels, the location of the phrenic motor neuron pool, and have examined histological and functional outcomes for up to 6 weeks post-injury. We report that phrenic motor neuron loss in cervical spinal cord, phrenic nerve axonal degeneration, and denervation at diaphragm neuromuscular junctions (NMJ) resulted in compromised ipsilateral diaphragm function, as demonstrated by persistent reduction in diaphragm compound muscle action potential amplitudes following phrenic nerve stimulation and abnormalities in spontaneous diaphragm electromyography (EMG) recordings. This injury paradigm is reproducible, does not require ventilatory assistance, and provides proof-of-principle that generation of unilateral cervical contusion is a feasible strategy for modeling diaphragmatic/respiratory deficits in mice. This study and its accompanying analyses pave the way for using transgenic mouse technology to explore the function of specific genes in the pathophysiology of phrenic motor neuron degeneration and respiratory dysfunction following cervical SCI. PMID:23176637

Vitamin D rescues dysfunction of fetal endothelial colony forming cells from individuals with gestational diabetes.

PubMed

Gui, J; Rohrbach, A; Borns, K; Hillemanns, P; Feng, L; Hubel, C A; von Versen-Höynck, F

2015-04-01

Gestational diabetes (GDM) is associated with long-term cardiovascular and metabolic diseases in offspring. However, the mechanisms are not well understood. We explored whether fetal exposure to a diabetic environment is associated with fetal endothelial progenitor cell dysfunction, and whether vitamin D can reverse the impairment. Nineteen women with uncomplicated pregnancies and 18 women with GDM were recruited before delivery. Time to first appearance of endothelial colony forming cell (ECFC) colonies and number of ECFC colonies formed from culture of cord peripheral blood mononuclear cells were determined. Angiogenesis-related functions of ECFCs in vitro were tested in the presence or absence of vitamin D. Fetal ECFCs from GDM pregnancies formed fewer colonies in culture (P = 0.04) and displayed reduced proliferation (P = 0.02), migration (P = 0.04) and tubule formation (P = 0.03) compared to uncomplicated pregnancies. Fetal ECFCs exposed to hyperglycemia in vitro exhibited less migration (P < 0.05) and less tubule formation (P < 0.05) than normoglycemic control. Vitamin D significantly improved the dysfunction of fetal ECFCs from pregnancies complicated by GDM or after exposure of healthy ECFCs to hyperglycemia. Fetal ECFCs from GDM pregnancies or ECFCs exposed to hyperglycemia in vitro exhibit reduced quantity and impaired angiogenesis-related functions. Vitamin D significantly rescues these functions. These findings may have implications for vascular function of infants exposed to a diabetic intrauterine environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

COMBINED USE OF α-ADRENERGIC AND MUSCARINIC ANTAGONISTS FOR THE TREATMENT OF VOIDING DYSFUNCTION

PubMed Central

RUGGIERI, MICHAEL R.; BRAVERMAN, ALAN S.; PONTARI, MICHEL A.

2012-01-01

Purpose We provide an overview of the medical literature supporting the combined use of muscarinic and α-adrenergic antagonist therapy for the treatment of voiding dysfunction. Materials and Methods The MEDLINE database (1966 to 2004) of the United States National Library of Medicine was searched for pertinent studies. Results Although the mechanism of action of α-adrenergic antagonist therapy for voiding dysfunction has traditionally been assumed to be relaxation of the periurethral, prostatic and bladder neck smooth muscle, substantial evidence supports action at extraprostatic sites involved in micturition, including the bladder dome smooth muscle, peripheral ganglia, spinal cord and brain. Likewise the mechanism of action of anticholinergic therapy has been traditionally assumed to be inhibition of the M3 muscarinic receptor subtypes that mediate normal bladder contractions. However, M2 receptor mediates hypertrophied bladder contractions and there is evidence for an M2 component to the suprasacral control of voiding. Conclusions Based on the physiology of α-adrenergic and muscarinic receptors the inhibition of each one would be expected to be more beneficial than that of either alone because they would work on 2 components of detrusor function. Patients who would likely benefit from this combination therapy are men with lower urinary tract symptoms, women with urgency/frequency syndrome (overactive bladder), patients with uninhibited bladder contractions due to neurogenic bladder, and patients with pelvic pain and voiding symptoms, ie interstitial cystitis and chronic prostatitis/chronic pelvic pain syndrome. PMID:16217275

Transverse myelitis caused by hepatitis E: previously undescribed in adults

PubMed Central

Sarkar, Pamela; Morgan, Catherine; Ijaz, Samreen

2015-01-01

We report the case of a 62-year-old Caucasian woman who was admitted with urinary retention and lower limb paraesthesia following a week's prodromal illness of headache and malaise. Liver function tests showed a picture of acute hepatocellular dysfunction. She developed reduced lower limb power, brisk reflexes, extensor plantars, a sensory level at T8 and reduced anal sphincter tone, establishing a clinical diagnosis of transverse myelitis. A spinal MRI showed no evidence of cauda equina or spinal cord compression. Cerebrospinal fluid (CSF) analysis showed raised protein and raised white cell count. Hepatitis E IgM and IgG were positive and hepatitis E virus was found in her CSF. She was treated with methylprednisolone and is slowly recovering with physiotherapy. PMID:26150621

Postinfarction Functional Recovery Driven by a Three-Dimensional Engineered Fibrin Patch Composed of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells.

PubMed

Roura, Santiago; Soler-Botija, Carolina; Bagó, Juli R; Llucià-Valldeperas, Aida; Férnandez, Marco A; Gálvez-Montón, Carolina; Prat-Vidal, Cristina; Perea-Gil, Isaac; Blanco, Jerónimo; Bayes-Genis, Antoni

2015-08-01

Considerable research has been dedicated to restoring myocardial cell slippage and limiting ventricular remodeling after myocardial infarction (MI). We examined the ability of a three-dimensional (3D) engineered fibrin patch filled with human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) to induce recovery of cardiac function after MI. The UCBMSCs were modified to coexpress luciferase and fluorescent protein reporters, mixed with fibrin, and applied as an adhesive, viable construct (fibrin-cell patch) over the infarcted myocardium in mice (MI-UCBMSC group). The patch adhered well to the heart. Noninvasive bioluminescence imaging demonstrated early proliferation and differentiation of UCBMSCs within the construct in the postinfarct mice in the MI-UCBMSC group. The implanted cells also participated in the formation of new, functional microvasculature that connected the fibrin-cell patch to both the subjacent myocardial tissue and the host circulatory system. As revealed by echocardiography, the left ventricular ejection fraction and fractional shortening at sacrifice were improved in MI-UCBMSC mice and were markedly reduced in mice treated with fibrin alone and untreated postinfarction controls. In conclusion, a 3D engineered fibrin patch composed of UCBMSCs attenuated infarct-derived cardiac dysfunction when transplanted locally over a myocardial wound. ©AlphaMed Press.

IGF-1 and BDNF promote chick bulbospinal neurite outgrowth in vitro.

PubMed

Salie, Rishard; Steeves, John D

2005-11-01

Injured neurons in the CNS do not experience significant functional regeneration and so spinal cord insult often results in permanently compromised locomotor ability. The capability of a severed axon to re-grow is thought to depend on numerous factors, one of which is the decreased availability of neurotrophic factors. Application of trophic factors to axotomized neurons has been shown to enhance survival and neurite outgrowth. Although brainstem-spinal connections play a pivotal role in motor dysfunction after spinal cord injury, relatively little is known about the trophic sensitivity of these populations. This study explores the response of bulbospinal populations to various trophic factors. Several growth factors were initially examined for potential trophic effects on the projection neurons of the brainstem. Brain derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF-1) significantly enhance mean process length in both the vestibulospinal neurons and spinal projection neurons from the raphe nuclei. Nerve growth factor (NGF), neurotrophin-4 (NT-4) and glial derived neurotrophic factor (GDNF) did not effect process outgrowth in vestibulospinal neurons. At the developmental stages used in this study, it was determined that receptors for BDNF and IGF-1 were present both on bulbospinal neurons and on surrounding cells with a non-neuronal morphology.

Griffonia simplicifolia Isolectin B4 Identifies a Specific Subpopulation of Angiogenic Blood Vessels Following Contusive Spinal Cord Injury in the Adult Mouse

PubMed Central

BENTON, RICHARD L.; MADDIE, MELISSA A.; MINNILLO, DANIELLE R.; HAGG, THEO; WHITTEMORE, SCOTT R.

2009-01-01

After traumatic spinal cord injury (SCI), disruption and plasticity of the microvasculature within injured spinal tissue contribute to the pathological cascades associated with the evolution of both primary and secondary injury. Conversely, preserved vascular function most likely results in tissue sparing and subsequent functional recovery. It has been difficult to identify subclasses of damaged or regenerating blood vessels at the cellular level. Here, adult mice received a single intravenous injection of the Griffonia simplicifolia isolectin B4 (IB4) at 1–28 days following a moderate thoracic (T9) contusion. Vascular binding of IB4 was maximally observed 7 days following injury, a time associated with multiple pathologic aspects of the intrinsic adaptive angiogenesis, with numbers of IB4 vascular profiles decreasing by 21 days postinjury. Quantitative assessment of IB4 binding shows that it occurs within the evolving lesion epicenter, with affected vessels expressing a temporally specific dysfunctional tight junctional phenotype as assessed by occludin, claudin-5, and ZO-1 immunoreactivities. Taken together, these results demonstrate that intravascular lectin delivery following SCI is a useful approach not only for observing the functional status of neovascular formation but also for definitively identifying specific subpopulations of reactive spinal microvascular elements. PMID:18092342

Glycinergic dysfunction in a subpopulation of dorsal horn interneurons in a rat model of neuropathic pain

PubMed Central

Imlach, Wendy L.; Bhola, Rebecca F.; Mohammadi, Sarasa A.; Christie, Macdonald J.

2016-01-01

The development of neuropathic pain involves persistent changes in signalling within pain pathways. Reduced inhibitory signalling in the spinal cord following nerve-injury has been used to explain sensory signs of neuropathic pain but specific circuits that lose inhibitory input have not been identified. This study shows a specific population of spinal cord interneurons, radial neurons, lose glycinergic inhibitory input in a rat partial sciatic nerve ligation (PNL) model of neuropathic pain. Radial neurons are excitatory neurons located in lamina II of the dorsal horn, and are readily identified by their morphology. The amplitude of electrically-evoked glycinergic inhibitory post-synaptic currents (eIPSCs) was greatly reduced in radial neurons following nerve-injury associated with increased paired-pulse ratio. There was also a reduction in frequency of spontaneous IPSCs (sIPSCs) and miniature IPSCs (mIPSC) in radial neurons without significantly affecting mIPSC amplitude. A subtype selective receptor antagonist and western blots established reversion to expression of the immature glycine receptor subunit GlyRα2 in radial neurons after PNL, consistent with slowed decay times of IPSCs. This study has important implications as it identifies a glycinergic synaptic connection in a specific population of dorsal horn neurons where loss of inhibitory signalling may contribute to signs of neuropathic pain. PMID:27841371

Somatic genital reflexes in rats with a nod to humans: anatomy, physiology, and the role of the social neuropeptides

PubMed Central

Normandin, Joseph J.; Murphy, Anne Z.

2011-01-01

Somatic genital reflexes such as ejaculation and vaginocervical contractions are produced through the striated muscles associated with the genitalia. The coordination of these reflexes is surprisingly complex and involves a number of lumbosacral spinal and supraspinal systems. The rat model has proved to be an excellent source of information regarding these mechanisms, and many parallels to research in humans can be drawn. An understanding of the spinal systems involving the lumbosacral spinal cord, both efferent and afferent, has been generated through decades of research. Spinal and supraspinal mechanisms of descending excitation, through a spinal ejaculation generator in the lumbar spinal cord and thalamus, and descending inhibition, through the ventrolateral medulla, have been identified and characterized both anatomically and physiologically. In addition, delineation of the neural circuits whereby ascending genitosensory information regarding the regulation of somatic genital reflexes is relayed supraspinally has also been the topic of recent investigation. Lastly, the importance of the “social neuropeptides” oxytocin and vasopressin in the regulation of somatic genital reflexes, and associated sociosexual behaviors, is emerging. This work not only has implications for understanding how nervous systems generate sexual behavior, but also provides treatment targets for sexual dysfunction in people. PMID:21338605

Breakthrough infection of Geotrichum capitatum during empirical caspofungin therapy after umbilical cord blood transplantation.

PubMed

Oya, Shuki; Muta, Tsuyoshi

2018-06-20

We experienced a breakthrough fungal infection caused by Geotrichum capitatum during empirical therapy with caspofungin. A 68-year-old male patient with refractory acute lymphoblastic leukemia had received umbilical cord blood transplantation after two courses of induction therapy. Empirical therapy with caspofungin was initiated 5 days before transplantation. Tacrolimus was continuously infused to prevent graft-versus-host disease. A minidose of methotrexate was intravenously administered on days 1 and 3 post-transplantation, which was changed to prednisolone from day 7 due to severe mucositis. During a recurrence of fever on day 11, blood cultures were found to be positive for a yeast-like organism, which was later confirmed by mass spectrometry to be G. capitatum. The serum levels of beta-D-glucan were elevated to 747 pg/mL. Caspofungin was switched to liposomal amphotericin B; however, radiological findings revealed pulmonary, splenic, and central nervous system involvement. Progressive renal and hepatic dysfunction subsequently developed. The patient died on day 25 post-transplantation secondary to the development of hemophagocytic syndrome and respiratory failure. We emphasize that recurrent febrile episodes, prolonged neutropenia, and underlying gastrointestinal mucosal damage require extreme caution due to the possibility of breakthrough infection caused by new fungal pathogens during empirical therapy with caspofungin.

Induction of mice adult bone marrow mesenchymal stem cells into functional motor neuron-like cells.

PubMed

Abdullah, Rafal H; Yaseen, Nahi Y; Salih, Shahlaa M; Al-Juboory, Ahmad Adnan; Hassan, Ayman; Al-Shammari, Ahmed Majeed

2016-11-01

The differentiation of mesenchymal stem cells (MSC) into acetylcholine secreted motor neuron-like cells, followed by elongation of the cell axon, is a promising treatment for spinal cord injury and motor neuron cell dysfunction in mammals. Differentiation is induced through a pre-induction step using Beta- mercaptoethanol (BME) followed by four days of induction with retinoic acid and sonic hedgehog. This process results in a very efficient differentiation of BM-MSCs into motor neuron-like cells. Immunocytochemistry showed that these treated cells had specific motor neural markers: microtubule associated protein-2 and acetylcholine transferase. The ability of these cells to function as motor neuron cells was assessed by measuring acetylcholine levels in a culture media during differentiation. High-performance liquid chromatography (HPLC) showed that the differentiated cells were functional. Motor neuron axon elongation was then induced by adding different concentrations of a nerve growth factor (NGF) to the differentiation media. Using a collagen matrix to mimic the natural condition of neural cells in a three-dimensional model showed that the MSCs were successfully differentiated into motor neuron-like cells. This process can efficiently differentiate MSCs into functional motor neurons that can be used for autologous nervous system therapy and especially for treating spinal cord injuries. Copyright © 2016 Elsevier B.V. All rights reserved.

Neural Control and Physiology of Sexual Function: Effect of Spinal Cord Injury.

PubMed

Krassioukov, Andrei; Elliott, Stacy

2017-01-01

Objective: To present the current understanding of normal anatomy, physiology, sexual physiology, pathophysiology and the consequential sexual changes and dysfunctions following a spinal cord injury (SCI). Methods: Narrative review of the latest literature. Results: Peripheral innervations of the pelvis involve 3 sets of efferent neurons coordinated though the pelvic plexus (somatic, thoracolumbar sympathetic, and sacral parasympathetic), and these are under cerebral descending excitatory and inhibitory control. SCI, depending on the level of lesion and completeness, can alter this cerebral control, affecting the psychological and reflexogenic potential for genital arousal and also ejaculation and orgasm. During arousal, nitric oxide is the main neurotransmitter for smooth muscle relaxation in both male and female erectile tissue. In men, erection, ejaculation, and orgasm are under separate neurological control and can be individually affected by SCI. Conclusions: Since sexual function is rated amongst the highest priorities by individuals living with SCI, methods employed to affect the neurological changes to maximize sexual neurophysiology prior to initiating medical therapies including paying attention to sexual sensate areas and visceral signals with mindfulness techniques, practicing body mapping, and sexual stimulation of sensate areas to encourage neuroplasticity. Attention should be paid to the biopsychosocial sexual contexts within which persons with SCI live to maximize their sexual and fertility rehabilitation.

Neural Control and Physiology of Sexual Function: Effect of Spinal Cord Injury

PubMed Central

Elliott, Stacy

2017-01-01

Objective: To present the current understanding of normal anatomy, physiology, sexual physiology, pathophysiology and the consequential sexual changes and dysfunctions following a spinal cord injury (SCI). Methods: Narrative review of the latest literature. Results: Peripheral innervations of the pelvis involve 3 sets of efferent neurons coordinated though the pelvic plexus (somatic, thoracolumbar sympathetic, and sacral parasympathetic), and these are under cerebral descending excitatory and inhibitory control. SCI, depending on the level of lesion and completeness, can alter this cerebral control, affecting the psychological and reflexogenic potential for genital arousal and also ejaculation and orgasm. During arousal, nitric oxide is the main neurotransmitter for smooth muscle relaxation in both male and female erectile tissue. In men, erection, ejaculation, and orgasm are under separate neurological control and can be individually affected by SCI. Conclusions: Since sexual function is rated amongst the highest priorities by individuals living with SCI, methods employed to affect the neurological changes to maximize sexual neurophysiology prior to initiating medical therapies including paying attention to sexual sensate areas and visceral signals with mindfulness techniques, practicing body mapping, and sexual stimulation of sensate areas to encourage neuroplasticity. Attention should be paid to the biopsychosocial sexual contexts within which persons with SCI live to maximize their sexual and fertility rehabilitation. PMID:29339872

Effects of level and degree of spinal cord injury on male orgasm.

PubMed

Sipski, M; Alexander, C J; Gómez-Marín, O

2006-12-01

Controlled, laboratory-based analysis. To determine the impact of spinal cord injuries (SCIs) on the ability to achieve male orgasm. US academic medical center. A laboratory-based analysis of the ability of 45 men with SCIs and 16 able-bodied control subjects to achieve orgasm coupled with a detailed neurologic examination, history and physical examination, and administration of the International Index of Erectile Function. Men with SCIs were less likely than controls to achieve orgasm. Mean latency to orgasm, blood pressure and heart rates at orgasm were not significantly different between controls and SCI subjects. Men with incomplete SCIs were more likely to achieve orgasm than those with complete SCIs. A disconnect was noted between the presence of orgasm and the presence of ejaculation. Men with complete lower motor neuron dysfunction affecting their sacral segments were less likely to achieve orgasm than men with any other patterns of SCI. These results document the ability of men with complete SCIs to achieve orgasm. Characteristics of orgasm in men with SCIs as compared to able-bodied subjects are similar. Although orgasm and ejaculation are more likely to occur together, a number of men with SCIs achieve orgasm without ejaculation. Further research should explore the possibility of retraining ejaculatory and orgasmic responses in men with SCIs.

Astrocytes influence the severity of spinal muscular atrophy

PubMed Central

Rindt, Hansjörg; Feng, Zhihua; Mazzasette, Chiara; Glascock, Jacqueline J.; Valdivia, David; Pyles, Noah; Crawford, Thomas O.; Swoboda, Kathryn J.; Patitucci, Teresa N.; Ebert, Allison D.; Sumner, Charlotte J.; Ko, Chien-Ping; Lorson, Christian L.

2015-01-01

Systemically low levels of survival motor neuron-1 (SMN1) protein cause spinal muscular atrophy (SMA). α-Motor neurons of the spinal cord are considered particularly vulnerable in this genetic disorder and their dysfunction and loss cause progressive muscle weakness, paralysis and eventually premature death of afflicted individuals. Historically, SMA was therefore considered a motor neuron-autonomous disease. However, depletion of SMN in motor neurons of normal mice elicited only a very mild phenotype. Conversely, restoration of SMN to motor neurons in an SMA mouse model had only modest effects on the SMA phenotype and survival. Collectively, these results suggested that additional cell types contribute to the pathogenesis of SMA, and understanding the non-autonomous requirements is crucial for developing effective therapies. Astrocytes are critical for regulating synapse formation and function as well as metabolic support for neurons. We hypothesized that astrocyte functions are disrupted in SMA, exacerbating disease progression. Using viral-based restoration of SMN specifically to astrocytes, survival in severe and intermediate SMA mice was observed. In addition, neuromuscular circuitry was improved. Astrogliosis was prominent in end-stage SMA mice and in post-mortem patient spinal cords. Increased expression of proinflammatory cytokines was partially normalized in treated mice, suggesting that astrocytes contribute to the pathogenesis of SMA. PMID:25911676

KARS-related diseases: progressive leukoencephalopathy with brainstem and spinal cord calcifications as new phenotype and a review of literature.

PubMed

Ardissone, Anna; Tonduti, Davide; Legati, Andrea; Lamantea, Eleonora; Barone, Rita; Dorboz, Imen; Boespflug-Tanguy, Odile; Nebbia, Gabriella; Maggioni, Marco; Garavaglia, Barbara; Moroni, Isabella; Farina, Laura; Pichiecchio, Anna; Orcesi, Simona; Chiapparini, Luisa; Ghezzi, Daniele

2018-04-04

KARS encodes lysyl- transfer ribonucleic acid (tRNA) synthetase, which catalyzes the aminoacylation of tRNA-Lys in the cytoplasm and mitochondria. Eleven families/sporadic patients and 16 different mutations in KARS have been reported to date. The associated clinical phenotype is heterogeneous ranging from early onset encephalopathy to isolated peripheral neuropathy or nonsyndromic hearing impairment. Recently additional presentations including leukoencephalopathy as predominant cerebral involvement or cardiomyopathy, isolated or associated with muscular and cerebral involvement, have been reported. A progressive Leukoencephalopathy with brainstem and spinal cord calcifications was previously described in a singleton patient and in two siblings, without the identification of the genetic cause. We reported here about a new severe phenotype associated with biallelic KARS mutations and sharing some common points with the other already reported phenotypes, but with a distinct clinical and neuroimaging picture. Review of KARS mutant patients published to date will be also discussed. Herein, we report the clinical, biochemical and molecular findings of 2 unreported Italian patients affected by developmental delay, acquired microcephaly, spastic tetraparesis, epilepsy, sensory-neural hypoacusia, visual impairment, microcytic hypochromic anaemia and signs of hepatic dysfunction. MRI pattern in our patients was characterized by progressive diffuse leukoencephalopathy and calcifications extending in cerebral, brainstem and cerebellar white matter, with spinal cord involvement. Genetic analysis performed on these 2 patients and in one subject previously described with similar MRI pattern revealed the presence of biallelic mutations in KARS in all 3 subjects. With our report we define the molecular basis of the previously described Leukoencephalopathy with Brainstem and Spinal cord Calcification widening the spectrum of KARS related disorders, particularly in childhood onset disease suggestive for mitochondrial impairment. The review of previous cases does not suggest a strict and univocal genotype/phenotype correlation for this highly heterogeneous entity. Moreover, our cases confirm the usefulness of search for common brain and spine MR imaging pattern and of broad genetic screening, in syndromes clinically resembling mitochondrial disorders in spite of normal biochemical assay.

Radiation-induced changes in the profile of spinal cord serotonin, prostaglandin synthesis, and vascular permeability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siegal, T.; Pfeffer, M.R.

To investigate the profile of biochemical and physiological changes induced in the rat spinal cord by radiation, over a period of 8 months. The thoraco-lumbar spinal cords of Fisher rats were irradiated to a dose of 15 Gy. The rats were then followed and killed at various times afterward. Serotonin (5-HT) and its major metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) were assayed as well as prostaglandin synthesis. Microvessel permeability was assessed by quantitative evaluation of Evans blue dye extravasation. None of the rats developed neurologic dysfunction, and histologic examination revealed only occasional gliosis in the ventral white matter at 240 days aftermore » irradiation. Serotonin levels were unchanged at 2, 14, and 56 days after radiation but increased at 120 and 240 days in the irradiated cord segments when compared to both the nonirradiated thoracic and cervical segments (p < 0.01) and age-matched controls (p < 0.03). The calculated utilization ratio of serotonin (5-HIAA/5-HT) remained unchanged. Immediately after radiation (at 3 and 24 h) an abrupt but brief increase in the synthesis of prostaglandin-E{sub 2} (PGE{sub 2}), thromboxane (TXB{sub 2}), and prostacyclin [6 keto-PGF1{alpha} (6KPGF)] was noted, which returned to normal at 3 days. This was followed after 7 and 14 days by a significant fall off in synthesis of all three prostaglandins. Thereafter, at 28, 56, 120, and 240 days, escalated production of thromboxane followed, white prostacyclin synthesis remained markedly reduced (-88% of control level at 240 days). Up to 7 days after radiation the calculated TXB{sub 2}/6KPGF ratio remained balanced, regardless of the observed abrupt early fluctuations in their rate of synthesis. Later, between 7 and 240 days after radiation, a significant imbalance was present which became more pronounced over time. In the first 24 h after radiation, a 104% increase in microvessel permeability was observed which returned to normal by 3 days. 57 refs., 3 figs.« less

Comparison of the scoliosis curve patterns and MRI syrinx cord characteristics of idiopathic syringomyelia versus Chiari I malformation.

PubMed

Zhu, Zezhang; Sha, Shifu; Chu, Winnie C C; Yan, Huang; Xie, Dingding; Liu, Zhen; Sun, Xu; Zhu, Weiguo; Cheng, Jack C Y; Qiu, Yong

2016-02-01

Although the more readily available MR imaging has brought about more incidental findings of idiopathic syringomyelia (IS), no published study has specifically addressed the clinical and imaging features of IS-associated scoliosis. Since IS and Chiari I malformation (CMI)-type syringomyelia are hypothesized to share a common underlying developmental pathomechanism, this study aimed to investigate the scoliosis curve patterns and MRI syrinx cord characteristics of patients with IS comparing with those seen in CMI. Sixty-one patients with scoliosis secondary to IS were identified and reviewed retrospectively. The curve pattern and specific curve features were recorded and compared with historic CMI controls. Location, size, and morphological appearance of the syrinx were systematically assessed on MR images. The maximal syrinx/cord ratio and rostrocaudal length of the syrinx in IS averaged 0.43 ± 0.16 (range 0.17-0.78) and 4.6 ± 2.5 (range 2-15) vertebral levels, respectively, both of which were smaller than those reported in CMI-type syringomyelia. Regarding the characteristics of IS-related scoliosis, sagittal profiles as well as the frequency of curve patterns and atypical features were all found to resemble those in patients with CMI (P > .05). Among the 47 individuals with a single thoracic curve, Fisher exact test revealed a significant correlation between curve convexity and the dominant side of deviated syrinx (83.3 % concordance rate, P = .021). In addition, apex of the thoracic curve trended toward being significantly correlated with the level of maximum expansion of the syrinx (P = .066). Radiological characteristics of scoliosis were found to be similar between idiopathic and CMI-type syrinx in both the coronal and sagittal planes, adding further evidence to the concept that these entities may be part of a spectrum of disease sharing a common pathophysiological mechanism. The thoracic spine in IS patients tended to be convex to the deviated side of syrinx, which indirectly supported the likely role of spinal cord dysfunction in the pathogenesis of syrinx-associated spinal deformities.

Metabolic Dysfunctions in Amyotrophic Lateral Sclerosis Pathogenesis and Potential Metabolic Treatments

PubMed Central

Tefera, Tesfaye W.; Borges, Karin

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease primarily characterized by loss of motor neurons in brain and spinal cord. The death of motor neurons leads to denervation of muscle which in turn causes muscle weakness and paralysis, decreased respiratory function and eventually death. Growing evidence indicates disturbances in energy metabolism in patients with ALS and animal models of ALS, which are likely to contribute to disease progression. Particularly, defects in glucose metabolism and mitochondrial dysfunction limit the availability of ATP to CNS tissues and muscle. Several metabolic approaches improving mitochondrial function have been investigated in vitro and in vivo and showed varying effects in ALS. The effects of metabolic approaches in ALS models encompass delays in onset of motor symptoms, protection of motor neurons and extension of survival, which signifies an important role of metabolism in the pathogenesis of the disease. There is now an urgent need to test metabolic approaches in controlled clinical trials. In addition, more detailed studies to better characterize the abnormalities in energy metabolism in patients with ALS and ALS models are necessary to develop metabolically targeted effective therapies that can slow the progression of the disease and prolong life for patients with ALS. PMID:28119559

Neurogenic bowel dysfunction (NBD) translation and linguistic validation to classical Arabic.

PubMed

Mallek, A; Elleuch, M H; Ghroubi, S

2016-09-01

To translate and linguistically validate in classical Arabic; the French version of the neurogenic bowel dysfunction (NBD). Arabic translation of the NBD score was obtained by the "forward translation/backword translation" method. Patients with multiple sclerosis (MS) and spinal cord injury were included. Evaluation of intestinal and anorectal disorders was conducted by the self-administered questionnaire NBD, which was filled twice two weeks apart. An item-by-item analysis was made. The feasibility, acceptability, internal consistency using Cronbach's alpha, and test-retest repeatability by non-parametric Spearman correlation were studied. Twenty-three patients with colorectal disorders secondary to neurological disease were included, the average age was 40.79±9.16years and the sex-ratio was 1.85. The questionnaire was feasible and acceptable, no items were excluded. The spearman correlation was of 0.842. Internal consistency was judged good through the Cronbach's alpha was of 0.896. The Arabic version of NBD was reproducible and construct validity was satisfactory. The study of its responsiveness to change with a larger number of patients will be the subject of further work. 4. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Novel Neuroprotective Multicomponent Therapy for Amyotrophic Lateral Sclerosis Designed by Networked Systems

PubMed Central

Herrando-Grabulosa, Mireia; Mulet, Roger; Pujol, Albert; Mas, José Manuel; Navarro, Xavier; Aloy, Patrick; Coma, Mireia; Casas, Caty

2016-01-01

Amyotrophic Lateral Sclerosis is a fatal, progressive neurodegenerative disease characterized by loss of motor neuron function for which there is no effective treatment. One of the main difficulties in developing new therapies lies on the multiple events that contribute to motor neuron death in amyotrophic lateral sclerosis. Several pathological mechanisms have been identified as underlying events of the disease process, including excitotoxicity, mitochondrial dysfunction, oxidative stress, altered axonal transport, proteasome dysfunction, synaptic deficits, glial cell contribution, and disrupted clearance of misfolded proteins. Our approach in this study was based on a holistic vision of these mechanisms and the use of computational tools to identify polypharmacology for targeting multiple etiopathogenic pathways. By using a repositioning analysis based on systems biology approach (TPMS technology), we identified and validated the neuroprotective potential of two new drug combinations: Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine. In addition, we estimated their molecular mechanisms of action in silico and validated some of these results in a well-established in vitro model of amyotrophic lateral sclerosis based on cultured spinal cord slices. The results verified that Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine promote neuroprotection of motor neurons and reduce microgliosis. PMID:26807587

[New diagnostic approach can improve treatment of whiplash injuries. Functional magnetic resonance tomography makes visualization of the injuries possible].

PubMed

Bergholm, Ulla; Johansson, Bengt H

2003-11-20

Patients suffering from chronic pain and dysfunction after acceleration/deceleration trauma to the cervical spine often present reliability problems. This is partly due to inadequate possibilities of diagnosing of the soft tissue structures in this area. A new diagnostic method--functional magnetic resonance imaging (fMRI) has made it possible to detect injuries in ligaments and capsules at the craniocervical junction. Not only do these structures stabilize the head during rotation movements, but they also contain receptors of the central nervous system, and thus have the most important function in position perception (i.e. proprioception) and movement control. The late onset of symptoms in this patient group can now be explained by the functional stenosis of the spinal cord and brainstem due to scar formation around the dens axis after injury. Modern neurophysiology can now explain the background of the generalized and complex picture of chronic pain and muscular and cognitive dysfunction. This new knowledge has prepared the way for more specific therapy in patients suffering from craniocervical instability symptoms and pain from disks and facet joints in the cervical spine after whiplash trauma.

Detection from space of a reduction in anthropogenic emissions of nitrogen oxides during the Chinese economic downturn

NASA Astrophysics Data System (ADS)

Lin, J.-T.; McElroy, M. B.

2011-01-01

Rapid economic and industrial development in China and relatively weak emission controls have resulted in significant increases in emissions of nitrogen oxides (NOx) in recent years, with the exception of late 2008 to mid 2009 when the economic downturn led to emission reductions detectable from space. Here vertical column densities (VCDs) of tropospheric NO2 retrieved from satellite observations by SCIAMACHY, GOME-2 and OMI (both by KNMI and by NASA) are used to evaluate changes in emissions of NOx from October 2004 to February 2010 identifying impacts of the economic downturn. Data over polluted regions of Northern East China suggest an increase of 27-33% in annual mean VCD of NO2 prior to the downturn, consistent with an increase of 49% in thermal power generation (TPG) reflecting the economic growth. More detailed analysis is used to quantify changes in emissions of NOx in January over the period 2005-2010 when the effect of the downturn was most evident. The GEOS-Chem model is employed to evaluate the effect of changes in chemistry and meteorology on VCD of NO2. This analysis indicates that emissions decreased by 20% from January 2008 to January 2009, close to the reduction of 18% in TPG that occurred over the same interval. A combination of three relatively independent approaches indicates that the economic downturn was responsible for a~reduction in emissions by 9-11% in January 2009 with an additional decrease of 10% attributed to the slow-down in industrial activity associated with the coincident celebration of the Chinese New Year.

Methodology for the Absolute Configuration Determination of Epoxythymols Using the Constituents of Ageratina glabrata.

PubMed

Arreaga-González, Héctor M; Pardo-Novoa, Julio C; Del Río, Rosa E; Rodríguez-García, Gabriela; Torres-Valencia, J Martín; Manríquez-Torres, J Jesús; Cerda-García-Rojas, Carlos M; Joseph-Nathan, Pedro; Gómez-Hurtado, Mario A

2018-01-26

A methodology to determine the enantiomeric excess and the absolute configuration (AC) of natural epoxythymols was developed and tested using five constituents of Ageratina glabrata. The methodology is based on enantiomeric purity determination employing 1,1'-bi-2-naphthol (BINOL) as a chiral solvating agent combined with vibrational circular dichroism (VCD) measurements and calculations. The conformational searching included an extensive Monte Carlo protocol that considered the rotational barriers to cover the whole conformational spaces. (+)-(8S)-10-Benzoyloxy-6-hydroxy-8,9-epoxythymol isobutyrate (1), (+)-(8S)-10-acetoxy-6-methoxy-8,9-epoxythymol isobutyrate (4), and (+)-(8S)-10-benzoyloxy-6-methoxy-8,9-epoxythymol isobutyrate (5) were isolated as enantiomerically pure constituents, while 10-isobutyryloxy-8,9-epoxythymol isobutyrate (2) was obtained as a 75:25 (8S)/(8R) scalemic mixture. In the case of 10-benzoyloxy-8,9-epoxythymol isobutyrate (3), the BINOL methodology revealed a 56:44 scalemic mixture and the VCD measurement was beyond the limit of sensitivity since the enantiomeric excess is only 12%. The racemization process of epoxythymol derivatives was studied using compound 1 and allowed the clarification of some stereochemical aspects of epoxythymol derivatives since their ACs have been scarcely analyzed and a particular behavior in their specific rotations was detected. In more than 30 oxygenated thymol derivatives, including some epoxythymols, the reported specific rotation values fluctuate from -1.6 to +1.4 passing through zero, suggesting the presence of scalemic and close to racemic mixtures, since enantiomerically pure natural constituents showed positive or negative specific rotations greater than 10 units.

Chiral detection in high-performance liquid chromatography by vibrational circular dichroism.

PubMed

Tran, C D; Grishko, V I; Huang, G

1994-09-01

A novel chiral detector for high-performance liquid chromatography has been developed. This detector is based on the measurement of circular dichroism of chiral effluents in the infrared region, i.e., vibrational circular dichroism (VCD). In this instrument, a solid-state spectral tunable (from 2.4 to 3.5 microns) F-center laser was used as the light source. The linearly polarized laser beam was converted into left circularly polarized light (LCPL) and right circularly polarized light (RCPL) at 42 kHz by means of a photoelastic modulator. The intensity of the LCPL and RCPL transmitted through the sample was measured by a liquid nitrogen cooled indium antimonide detector. Double modulation was employed to reduce the noise associated with the laser beam. Specifically, the linearly polarized laser beam, prior to being converted to CPL, was modulated at 85 Hz by a mechanical chopper. Demodulation and amplification were accomplished with the use of two lock-in amplifiers. In its present configuration, the instrument can be used to measure the VCD of O-H groups. Its sensitivity is so high that it was able, for the first time, to detect chirally (with limits of detection of micrograms) (R)- and (S)-2,2,2-trifluoro-1-(9- anthryl)ethanol and (R)- and (S)-benzoin when these compounds were chromatographically separated from the corresponding racemic mixtures by a Chiralcel-OD column. The main advantage of this chiral detector is, however, its universality; i.e., it can be used to virtually detect any chiral compounds which has O-H group (e.g, aliphatic alcohols such as 2-octanol).

Preprototype Vapor Compression Distillation Subsystem development

NASA Technical Reports Server (NTRS)

Thompson, C. D.; Ellis, G. S.; Schubert, F. H.

1981-01-01

Vapor Compression Distillation (VCD) has evolved as the most promising approach to reclaim potable water from wastewater for future long-term manned space missions. Life Systems, Inc. (LSI), working with NASA, has developed a preprototype Vapor Compression Distillation Subsystem (VCDS) which processes wastewater at 1.4 kg/h. The preprototype unit weighs 143 kg, occupies a volume of 0.47 cu m, and will reclaim 96 percent of the available wastewater. This unit has been tested by LSI and is scheduled for further testing at NASA-JSC. This paper presents the preprototype VCDS design, configuration, performance data, test results and flight system projections.