Red blood cells carry out T cell growth and survival bioactivities that are sensitive to cyclosporine A.

PubMed

Antunes, Ricardo F; Brandão, Cláudia; Carvalho, Gonçalo; Girão, Cristina; Arosa, Fernando A

2009-10-01

Red blood cells (RBC) have emerged as a novel regulatory cell type endowed with bioactivities toward activated human T cells. Herein we show that the RBC bioactivities act on intracellular pathways initiated by T cell receptor (TCR)-dependent and -independent stimuli,including IL-2, IL-15, and the mixture of phorbol dibutyrate and ionomycin. The RBC bioactivities preserve the antioxidant status and are capable of rescuing activated T cells from cell death induced by serum deprivation. They are not mediated by glycosylphosphatidylinositol-linked receptors or sialic acids, and kinetic studies revealed that they hasten the entrance into the cell cycle. By using cyclosporine A (CsA) and rapamycin (Rapa) we show that the RBC bioactivities are calcineurin-dependent. Thus, treatment of T cells with CsA, but not Rapa, impaired RBC bioactivities, and preincubation of RBC with CsA completely abolished their bioactivities. We have demonstrated that RBC carry out bioactivities that are sensitive to CsA.

Cyclosporine A and palmitic acid treatment synergistically induce cytotoxicity in HepG2 cells

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

Luo, Yi, E-mail: yi.luo@pfizer.com; Rana, Payal; Will, Yvonne

Immunosuppressant cyclosporine A (CsA) treatment can cause severe side effects. Patients taking immunosuppressant after organ transplantation often display hyperlipidemia and obesity. Elevated levels of free fatty acids have been linked to the etiology of metabolic syndromes, nonalcoholic fatty liver and steatohepatitis. The contribution of free fatty acids to CsA-induced toxicity is not known. In this study we explored the effect of palmitic acid on CsA-induced toxicity in HepG2 cells. CsA by itself at therapeutic exposure levels did not induce detectible cytotoxicity in HepG2 cells. Co-treatment of palmitic acid and CsA resulted in a dose dependent increase in cytotoxicity, suggesting thatmore » fatty acid could sensitize cells to CsA-induced cytotoxicity at the therapeutic doses of CsA. A synergized induction of caspase-3/7 activity was also observed, indicating that apoptosis may contribute to the cytotoxicity. We demonstrated that CsA reduced cellular oxygen consumption which was further exacerbated by palmitic acid, implicating that impaired mitochondrial respiration might be an underlying mechanism for the enhanced toxicity. Inhibition of c-Jun N-terminal kinase (JNK) attenuated palmitic acid and CsA induced toxicity, suggesting that JNK activation plays an important role in mediating the enhanced palmitic acid/CsA-induced toxicity. Our data suggest that elevated FFA levels, especially saturated FFA such as palmitic acid, may be predisposing factors for CsA toxicity, and patients with underlying diseases that would elevate free fatty acids may be susceptible to CsA-induced toxicity. Furthermore, hyperlipidemia/obesity resulting from immunosuppressive therapy may aggravate CsA-induced toxicity and worsen the outcome in transplant patients. -- Highlights: ► Palmitic acid and cyclosporine (CsA) synergistically increased cytotoxicity. ► The impairment of mitochondrial functions may contribute to the enhanced toxicity. ► Inhibition of JNK activity attenuated palmitate/ CsA induced toxicity. ► Palmitate sensitizes cells to the toxicity induced by CsA at therapeutic exposure. ► Elevated free fatty acids may predispose the patients to CsA-induced toxicity.« less

77 FR 18298 - Improvements to the Compliance, Safety, Accountability (CSA) Motor Carrier Safety Measurement...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-27

... effectively identify and prioritize high-risk and other unsafe motor carriers for enforcement interventions... interventions by more accurately identifying safety sensitive carriers (i.e., carriers transporting people and carriers hauling hazardous materials (HM)), so that such firms can be selected for CSA interventions at...

Professionals' Attitude Toward Reporting Child Sexual Abuse in Saudi Arabia.

PubMed

Al-Saif, Dalia M; Al-Eissa, Majid; Saleheen, Hassan; Al-Mutlaq, Huda; Everson, Mark D; Almuneef, Maha A

2018-01-01

Child sexual abuse (CSA) requires specialized knowledge and training that includes forensic interview skills. The aim of this study was to determine variations in professionals' attitudes toward CSA by measuring three aspects of forensic attitudes (sensitivity, specificity, and skepticism) and evaluating disagreements concerning the assessment of CSA cases in Saudi Arabia. A cross-sectional, web-based study, in which the Child Forensic Attitude Scale was used to measure professionals' attitudes, was conducted. Professionals who dealt with suspected cases of CSA as part of their jobs or were in professions that necessitated involvement with such cases, were selected as participants. Of 327 participants, 53% were aged ≤40 years, and 54% were men. In addition, 24% were doctors/nurses, 20% were therapists/psychiatrists, 24% were social workers, 17% were educators, 9% were law enforcement professionals, and 5% were medical examiners. Attitude subscale scores differed significantly according to participants' sex, specialty, and training. Women, healthcare professionals, and those who had participated in more than five training courses were more concerned about the underreporting of abuse (high sensitivity) relative to other professionals. In comparison, men, medical examiners, law enforcement officers, and undertrained professionals tended to underreport suspected sexual abuse cases (high specificity). High specificity in attitudes toward suspected cases of CSA could affect professionals' judgment and contribute to low reporting rates. Certain strategies, including increasing self-awareness of personal bias, specific CSA recognition courses, and team approaches to case assessment and management, should be implemented to control the influence of subjective factors.

The influence of radiographic viewing perspective and demographics on the Critical Shoulder Angle

PubMed Central

Suter, Thomas; Popp, Ariane Gerber; Zhang, Yue; Zhang, Chong; Tashjian, Robert Z.; Henninger, Heath B.

2014-01-01

Background Accurate assessment of the critical shoulder angle (CSA) is important in clinical evaluation of degenerative rotator cuff tears. This study analyzed the influence of radiographic viewing perspective on the CSA, developed a classification system to identify malpositioned radiographs, and assessed the relationship between the CSA and demographic factors. Methods Glenoid height, width and retroversion were measured on 3D CT reconstructions of 68 cadaver scapulae. A digitally reconstructed radiograph was aligned perpendicular to the scapular plane, and retroversion was corrected to obtain a true antero-posterior (AP) view. In 10 scapulae, incremental anteversion/retroversion and flexion/extension views were generated. The CSA was measured and a clinically applicable classification system was developed to detect views with >2° change in CSA versus true AP. Results The average CSA was 33±4°. Intra- and inter-observer reliability was high (ICC≥0.81) but decreased with increasing viewing angle. Views beyond 5° anteversion, 8° retroversion, 15° flexion and 26° extension resulted in >2° deviation of the CSA compared to true AP. The classification system was capable of detecting aberrant viewing perspectives with sensitivity of 95% and specificity of 53%. Correlations between glenoid size and CSA were small (R≤0.3), and CSA did not vary by gender (p=0.426) or side (p=0.821). Conclusions The CSA was most susceptible to malposition in ante/retroversion. Deviations as little as 5° in anteversion resulted in a CSA >2° from true AP. A new classification system refines the ability to collect true AP radiographs of the scapula. The CSA was unaffected by demographic factors. PMID:25591458

Muscle Weakness in the Empty and Full Can Tests Cannot Differentiate Rotator Cuff Tear from Cervical Spondylotic Amyotrophy: Pain Provocation is a Useful Finding.

PubMed

Iwata, Eiichiro; Shigematsu, Hideki; Inoue, Kazuya; Egawa, Takuya; Sakamoto, Yoshihiro; Tanaka, Yasuhito

2017-01-01

Rotator cuff tears and cervical spondylotic amyotrophy (CSA) are often confused as the main symptom in those with difficulty in shoulder elevation. Empty and full can tests are frequently used for the clinical diagnosis of rotator cuff tears. The aim of the present study was to investigate whether the empty and full can test results can help differentiate rotator cuff tears from CSA. Twenty-seven consecutive patients with rotator cuff tears and 25 with CSA were enrolled. We prospectively performed empty and full can tests in patients with rotator cuff tears and CSA. The following signs were considered positive: (a) muscle weakness during the empty can test, (b) muscle weakness during the full can test, (c) pain provocation during the empty can test, and (d) pain provocation during the full can test. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of rotator cuff tears for each positive finding. The sensitivity and specificity of each index were as follows (sensitivity, specificity, PPV, NPV): (a) 77.8%, 0%, 45.7%, 0%; (b) 66.7%, 4.0%, 42.9%, 10.0%; (c) 88.9%, 96.0%, 96.0%, 88.9%; and (d) 74.1%, 96.0%, 95.2%, 77.4%. There were significant differences for each index. Muscle weakness during the empty and full can tests was not useful in differentiating rotator cuff tears from CSA because of low specificity and PPV. However, pain provocation was useful in differentiating these two conditions because of high specificity and PPV.

Infant feeding experiences of women who were sexually abused in childhood.

PubMed

Wood, Karen; Van Esterik, Penny

2010-04-01

To explore the effects of childhood sexual abuse (CSA) on women's breastfeeding and infant feeding decisions and experiences. Qualitative, participatory study using semistructured in-depth interviews. Tamara's House, a healing centre for women who were sexually abused in childhood, located in Saskatoon, Sask. Six mothers who were sexually abused in childhood. In-depth interviews were conducted and transcribed verbatim. Thematic analysis was iterative and participatory. The emerging themes that resulted from initial analysis by the researchers were presented at a meeting held jointly with academics, survivors, and professionals in the field to achieve consensus. Throughout the process, findings were considered in relation to related literature on breasts, breastfeeding, and CSA. History of CSA complicated the women's infant feeding decisions and experiences. For 2 women, birthing and breastfeeding facilitated healing from the effects of the abuse. Shame, touch, breasts, dissociation, medical care, and healing emerged as analytic themes. A history of CSA can affect a woman's experience of breastfeeding, including acting as a trigger for remembering or reexperiencing the abuse. Women who were sexually abused as children need to experience a sense of safety, acceptance, sensitivity, and understanding. Physicians need to be aware of the effects of CSA on infant feeding and women's health, and might need to be trained in a sensitive-practice approach to working with patients who were sexually abused as children.

Cardiovascular actions of L-cysteine and L-cysteine sulfinic acid in the nucleus tractus solitarius of the rat.

PubMed

Takemoto, Yumi

2014-07-01

The sulfur-containing excitatory amino acid (EAA) L-cysteine sulfinic acid (CSA), a neurotransmitter candidate, is endogenously synthesized from L-cysteine (Cys). Exogenous Cys administration into the brain produces cardiovascular effects; these effects likely occur via synaptic stimulation of central nervous system (CNS) neurons that regulate peripheral cardiovascular function. However, the cardiovascular responses produced by CNS Cys administration could result from CSA biosynthesized in synapse. The present study examined the role of CSA in Cys-induced cardiovascular responses within the nucleus tractus solitarius (NTS) of anesthetized rats. The NTS receives input from various visceral afferents that gate autonomic reflexes, including cardiovascular reflexes. Within the NTS, both Cys and CSA microinjections produced decrease responses in arterial blood pressure and heart rate that were similar to those produced by L-glutamate. Co-injection of the ionotropic EAA receptor antagonist kynurenic acid abolished Cys-, but not CSA-, induced cardiovascular responses. This finding suggests that only Cys-induced cardiovascular responses are mediated by kynurenate-sensitive receptors. This study provides the first demonstration that Cys- and CSA-induced cardiovascular responses occur via different mechanisms in the NTS of rats. Further, this study also indicates that Cys-induced cardiovascular responses do not occur via CSA. Thus, within the NTS, endogenous Cys and/or CSA might be involved in cardiovascular regulation.

A Cosmic Dust Sensor Based on an Array of Grid Electrodes

NASA Astrophysics Data System (ADS)

Li, Y. W.; Bugiel, S.; Strack, H.; Srama, R.

2014-04-01

We described a low mass and high sensitivity cosmic dust trajectory sensor using a array of grid segments[1]. the sensor determines the particle velocity vector and the particle mass. An impact target is used for the detection of the impact plasma of high speed particles like interplanetary dust grains or high speed ejecta. Slower particles are measured by three planes of grid electrodes using charge induction. In contrast to conventional Dust Trajectory Sensor based on wire electrodes, grid electrodes a robust and sensitive design with a trajectory resolution of a few degree. Coulomb simulation and laboratory tests were performed in order to verify the instrument design. The signal shapes are used to derive the particle plane intersection points and to derive the exact particle trajectory. The accuracy of the instrument for the incident angle depends on the particle charge, the position of the intersection point and the signal-to-noise of the charge sensitive amplifier (CSA). There are some advantages of this grid-electrodes based design with respect to conventional trajectory sensor using individual wire electrodes: the grid segment electrodes show higher amplitudes (close to 100%induced charge) and the overall number of measurement channels can be reduced. This allows a compact instrument with low power and mass requirements.

Using pre-operative MRI to predict intraoperative hamstring graft size for anterior cruciate ligament reconstruction.

PubMed

Leiter, Jeff; Elkurbo, Mohamed; McRae, Sheila; Chiu, James; Froese, Warren; MacDonald, Peter

2017-01-01

Large variation in tendon size between individuals makes hamstring graft diameter for anterior cruciate ligament (ACL) reconstruction unpredictable. Inadequate graft diameter may necessitate an alternative source of tissue requiring pre-operative planning. The purpose of this study was to determine whether magnetic resonance image (MRI) measurements and clinical anthropometric data are predictive of hamstring tendon graft diameter. Data from 109 patients having ACL reconstruction with semitendinosus-gracilis (STGT) autograft were retrospectively evaluated. Cross-sectional area (CSA) of the gracilis tendon (GT) and semitendinosus tendon (ST) were determined from pre-operative MRI scans. Variables included pre-operative height, weight, body mass index (BMI), age and gender; and intra-operative graft diameter. Correlations between anthropometric variables, hamstring tendons CSA and intra-operative graft diameter were calculated. Multiple stepwise regression was performed to assess the predictive value of these variables to graft diameter. Sensitivity and specificity were calculated to evaluate the utility of MRI CSA measurements in accurately identifying inadequate graft diameter (<8 mm). All anthropometric variables were positively correlated with intraoperative graft diameter (p < 0.01). Semitendinosus-gracilis tendon CSA (p < 0.001) and STGT CSA and weight (p < 0.001) were significantly predictive models of graft diameter. Sensitivity and specificity were 79 and 74 %, respectively. The strongest indicators of a four-stranded STGT graft for primary ACL reconstruction were STGT CSA on MRI plus weight. Measurement of graft diameter can be performed pre-operatively via MRI to identify tendons that may be of inadequate size for ACL reconstruction. This can assist with surgical planning to determine the most appropriate graft choice. III.

Tensor sufficient dimension reduction

PubMed Central

Zhong, Wenxuan; Xing, Xin; Suslick, Kenneth

2015-01-01

Tensor is a multiway array. With the rapid development of science and technology in the past decades, large amount of tensor observations are routinely collected, processed, and stored in many scientific researches and commercial activities nowadays. The colorimetric sensor array (CSA) data is such an example. Driven by the need to address data analysis challenges that arise in CSA data, we propose a tensor dimension reduction model, a model assuming the nonlinear dependence between a response and a projection of all the tensor predictors. The tensor dimension reduction models are estimated in a sequential iterative fashion. The proposed method is applied to a CSA data collected for 150 pathogenic bacteria coming from 10 bacterial species and 14 bacteria from one control species. Empirical performance demonstrates that our proposed method can greatly improve the sensitivity and specificity of the CSA technique. PMID:26594304

Novel active signal compression in low-noise analog readout at future X-ray FEL facilities

NASA Astrophysics Data System (ADS)

Manghisoni, M.; Comotti, D.; Gaioni, L.; Lodola, L.; Ratti, L.; Re, V.; Traversi, G.; Vacchi, C.

2015-04-01

This work presents the design of a low-noise front-end implementing a novel active signal compression technique. This feature can be exploited in the design of analog readout channels for application to the next generation free electron laser (FEL) experiments. The readout architecture includes the low-noise charge sensitive amplifier (CSA) with dynamic signal compression, a time variant shaper used to process the signal at the preamplifier output and a 10-bit successive approximation register (SAR) analog-to-digital converter (ADC). The channel will be operated in such a way to cope with the high frame rate (exceeding 1 MHz) foreseen for future XFEL machines. The choice of a 65 nm CMOS technology has been made in order to include all the building blocks in the target pixel pitch of 100 μm. This work has been carried out in the frame of the PixFEL Project funded by the Istituto Nazionale di Fisica Nucleare (INFN), Italy.

Comparison of pedometer and accelerometer measures of free-living physical activity.

PubMed

Tudor-Locke, Catrine; Ainsworth, Barbara E; Thompson, Raymond W; Matthews, Charles E

2002-12-01

The purpose of this investigation was 1) to evaluate agreement between dual-mode CSA accelerometer outputs and Yamax pedometer outputs assessed concurrently under free-living conditions; 2) to determine the relationship between pedometer-steps per day and CSA-time spent in inactivity and in light-, moderate-, and vigorous-intensity activities; and 3) to identify a value of pedometer-steps per day that corresponds with a minimum of 30 CSA-min x d(-1) of moderate ambulatory activity. Data were analyzed from 52 participants (27 men, 25 women; mean age = 38.2 +/- 12.0 yr; mean BMI = 26.4 +/- 4.5 kg x m(-2)) who were enrolled in the International Physical Activity Questionnaire study and wore both motion sensors during waking hours for 7 consecutive days. Participants averaged 415.0+/-159.5 CSA-counts x min(-1) x d(-1), 357,601 +/- 138,425 CSA-counts x d(-1), 11,483 +/- 3,856 CSA-steps x d(-1), and 9,638 +/- 4,030 pedometer-steps x d(-1). There was a strong relationship between all CSA outputs and pedometer outputs (r = 0.74-0.86). The mean difference in steps detected between instruments was 1845+/-2116 steps x d(-1) (CSA > pedometer; t = 6.29, P < 0.0001). There were distinct differences (effect sizes >0.80) in mean CSA-time (min x d(-1)) in moderate and vigorous activity with increasing pedometer-determined activity quartiles; no differences were noted for inactivity or light activity. Approximately 33 CSA-min x d(-1) of moderate activity corresponded with 8000 pedometer-steps x d(-1). Differences in mean steps per day detected may be due to differences in set instrument sensitivity thresholds and/or attachment. Additional studies with different populations are needed to confirm a recommended number of steps per day associated with the duration and intensity of public health recommendations for ambulatory activity.

Rapid Diagnosis of Tuberculosis from Analysis of Urine Volatile Organic Compounds

PubMed Central

Lim, Sung H.; Martino, Raymond; Anikst, Victoria; Xu, Zeyu; Mix, Samantha; Benjamin, Robert; Schub, Herbert; Eiden, Michael; Rhodes, Paul A.; Banaei, Niaz

2017-01-01

The World Health Organization has called for simple, sensitive, and non-sputum diagnostics for tuberculosis. We report development of a urine tuberculosis test using a colorimetric sensor array (CSA). The sensor comprised of 73 different indicators captures high-dimensional, spatiotemporal signatures of volatile chemicals emitted by human urine samples. The sensor responses to 63 urine samples collected from 22 tuberculosis cases and 41 symptomatic controls were measured under five different urine test conditions. Basified testing condition yielded the best accuracy with 85.5% sensitivity and 79.5% specificity. The CSA urine assay offers desired features needed for tuberculosis diagnosis in endemic settings. PMID:29057329

Identification and characterization of a cyclosporin binding cyclophilin from Staphylococcus aureus Newman

PubMed Central

Polley, Soumitra; Seal, Soham; Mahapa, Avisek; Jana, Biswanath; Biswas, Anindya; Mandal, Sukhendu; Sinha, Debabrata; Sau, Keya; Sau, Subrata

2017-01-01

Cyclophilins, a class of peptidyl-prolyl cis-trans isomerase (PPIase) enzymes, are inhibited by cyclosporin A (CsA), an immunosuppressive drug. Staphylococcus aureus Newman, a pathogenic bacterium, carries a gene for encoding a putative cyclophilin (SaCyp). SaCyp shows significant homology with other cyclophilins at the sequence level. A three-dimensional model structure of SaCyp harbors a binding site for CsA. To verify whether SaCyp possesses both the PPIase activity and the CsA binding ability, we have purified and investigated a recombinant SaCyp (rCyp) using various in vitro tools. Our RNase T1 refolding assay indicates that rCyp has a substantial extent of PPIase activity. rCyp that exists as a monomer in the aqueous solution is truly a cyclophilin as its catalytic activity specifically shows sensitivity to CsA. rCyp appears to bind CsA with a reasonably high affinity. Additional investigations reveal that binding of CsA to rCyp alters its structure and shape to some extent. Both rCyp and rCyp-CsA are unfolded via the formation of at least one intermediate in the presence of guanidine hydrochloride. Unfolding study also indicates that there is substantial extent of thermodynamic stabilization of rCyp in the presence of CsA as well. The data suggest that rCyp may be exploited to screen the new antimicrobial agents in the future. PMID:28584448

Forensic child sexual abuse evaluations: assessing subjectivity and bias in professional judgements.

PubMed

Everson, Mark D; Sandoval, Jose Miguel

2011-04-01

Evaluators examining the same evidence often arrive at substantially different conclusions in forensic assessments of child sexual abuse (CSA). This study attempts to identify and quantify subjective factors that contribute to such disagreements so that interventions can be devised to improve the reliability of case decisions. Participants included 1106 professionals in the field of child maltreatment representing a range of professional positions or job titles and years of experience. Each completed the Child Forensic Attitude Scale (CFAS), a 28-item survey assessing 3 forensic attitudes believed to influence professional judgments about CSA allegations: emphasis-on-sensitivity (i.e., a focus on minimizing false negatives or errors of undercalling abuse); emphasis-on-specificity (i.e., a focus on minimizing false positives or errors of overcalling abuse); and skepticism toward child and adolescent reports of CSA. A subset of 605 professionals also participated in 1 of 3 diverse decision exercises to assess the influence of the 3 forensic attitudes on ratings of case credibility. Exploratory factor analysis identified 4 factors or attitude subscales that corresponded closely with the original CFAS scales: 2 subscales for emphasis-on-sensitivity and 1 each for emphasis-on-specificity and skepticism. Attitude subscale scores differed significantly by sample source (in-state trainings vs. national conferences), gender, years of experience, and professional position, with Child Protective Service workers unexpectedly more concerned about overcalling abuse and more skeptical of child disclosures than other professionals-a pattern of scores associated with an increased probability of disbelieving CSA allegations. The 3 decision exercises offered validation of the attitude subscales as predictors of professional ratings of case credibility, with adjusted R(2)s for the three exercises ranging from .06 to .24, suggesting highly variable effect sizes. Evaluator disagreements about CSA allegations can be explained, in part, by individual differences in 3 attitudes related to forensic decision-making: emphasis-on-sensitivity, emphasis-on-specificity, and skepticism toward child reports of abuse. These attitudes operate as predispositions or biases toward viewing CSA allegations as likely true or likely false. Several strategies for curbing the influence of subjective factors are highlighted including self-awareness of personal biases and team approaches to assessment. Copyright © 2011 Elsevier Ltd. All rights reserved.

Comparison of the BBL CHROMagar Staph aureus Agar Medium to Conventional Media for Detection of Staphylococcus aureus in Respiratory Samples

PubMed Central

Flayhart, Diane; Lema, Clara; Borek, Anita; Carroll, Karen C.

2004-01-01

Screening for Staphylococcus aureus has become routine in certain patient populations. This study is the first clinical evaluation of the BBL CHROMagar Staph aureus agar (CSA) medium (BD Diagnostics, Sparks, Md.) for detection of S. aureus in nasal surveillance cultures and in respiratory samples from cystic fibrosis (CF) patients. S. aureus colonies appear mauve on CSA. Other organisms are inhibited or produce a distinctly different colony color. S. aureus was identified from all media by slide coagulase, exogenous DNase, and mannitol fermentation assays. Susceptibility testing was performed using the agar dilution method. A total of 679 samples were evaluated. All samples were inoculated onto CSA. Nasal surveillance cultures were inoculated onto sheep blood agar (SBA) (BD Diagnostics), and samples from CF patients were inoculated onto mannitol salt agar (MSA) (BD Diagnostics). Of the 679 samples cultured, 200 organisms produced a mauve color on CSA (suspicious for S. aureus) and 180 were positive for S. aureus on SBA or MSA. Of 200 CSA-positive samples 191 were identified as S. aureus. Nine mauve colonies were slide coagulase negative and were subsequently identified as Staphylococcus lugdunensis (one), Staphylococcus epidermidis (three), Staphylococcus haemolyticus (one), and Corynebacterium species (four). CSA improved the ability to detect S. aureus by recovering 12 S. aureus isolates missed by conventional media. Of the 192 S. aureus isolates recovered, 122 were methicillin susceptible and 70 were methicillin resistant. Overall, the sensitivity and specificity of CSA in this study were 99.5 and 98%, respectively. There was no difference in the performance of the slide coagulase test or in susceptibility testing performed on S. aureus recovered from CSA compared to SBA or MSA. Our data support the use of CSA in place of standard culture media for detection of S. aureus in heavily contaminated respiratory samples. PMID:15297498

C-reactive protein is elevated in heart failure patients with central sleep apnea and Cheyne-Stokes respiration.

PubMed

Schmalgemeier, Heidi; Bitter, Thomas; Fischbach, Thomas; Horstkotte, Dieter; Oldenburg, Olaf

2014-01-01

Manifestation of central sleep apnea (CSA) with Cheyne-Stokes respiration is of major prognostic impact in chronic heart failure (CHF). Inflammatory processes have been linked to a progression of cardiovascular diseases, including heart failure. While an association of C-reactive protein (CRP) levels to obstructive sleep apnea has been documented before, there is a lack of information regarding variation of CRP levels in patients with CSA. The objective of this study was to investigate a potential association of CRP levels to CSA severity in CHF patients. High sensitivity CRP levels were analyzed in 966 patients with CHF (BMI 26.3 ± 4.6, New York Heart Association class 2.6 ± 0.5, left ventricular ejection fraction 29.4 ± 7.9%, N-terminal pro-brain natriuretic peptide, NT-proBNP, level 2,209 ± 3,315 pg/ml) without sleep-disordered breathing (SDB; Apnea-Hypopnea Index, AHI, <5/h) or various degrees of CSA, documented by in-hospital cardiorespiratory polygraphy or polysomnography. The CRP concentration in CHF patients was 0.550 ± 0.794 mg/dl in patients without SDB (AHI 0-4/h, n = 403) versus 0.488 ± 0.708 mg/dl in patients with mild CSA (AHI 5-14/h, n = 123, p = n.s.) and 0.660 ± 0.963 mg/dl in patients with moderate CSA (AHI 15-29/h, n = 160, p = n.s.). In patients with severe CSA (AHI ≥ 30/h, n = 280), significantly higher CRP concentrations were documented (0.893 ± 1.384 mg/dl, p < 0.05). Stepwise regression analysis revealed AHI, NT-proBNP and heart rate to be independently associated with elevated CRP levels. Severe CSA in CHF patients is associated with elevated levels of CRP, a systemic marker of inflammation and cardiovascular risk. This might explain in part the negative prognostic impact of CSA in these patients. Copyright © 2013 S. Karger AG, Basel.

Validation of the EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis.

PubMed

Burgers, Leonie E; Siljehult, Filip; Ten Brinck, Robin M; van Steenbergen, Hanna W; Landewé, Robert B M; Rantapää-Dahlqvist, Solbritt; van der Helm-van Mil, Annette H M

2017-12-01

Recently a EULAR-taskforce defined arthralgia suspicious for progression to RA, in order to allow inclusion of homogeneous sets of arthralgia patients in clinical studies. This longitudinal study aimed (i) to validate this definition in arthralgia patients in whom rheumatologists felt that imminent RA was more likely than other arthralgias [clinically suspect arthralgia (CSA)], that is, the target population fulfilling the entry criterion, and (ii) to explore the performance in arthralgia patients who were referred to secondary care prior to rheumatological evaluation, hence ignoring the entry criterion. The definition was assessed in 241 Dutch patients identified with CSA by rheumatologists and 113 patients referred to the Umeå university hospital with recent-onset arthralgia in small joints. The external reference was arthritis development <2 years' follow-up. CSA patients with a positive definition (⩾3/7 parameters present) had an increased risk for developing arthritis compared with definition-negative CSA patients (hazard ratio = 2.1, 95% CI: 0.9, 4.7). The sensitivity was 84% and the positive predictive value 30%. In arthralgia patients in whom the definition was applied before rheumatological evaluation, a positive definition was neither sensitive (10%) nor predictive (positive predictive value 3%). The EULAR definition of arthralgia suspicious for progression to RA is sensitive when used to support the rheumatologist's opinion on imminent RA. This validation study shows that the definition, when used as designed, further homogenizes patients that rheumatologists consider at risk for RA. To arrive at a high specificity, the clinical definition needs to be combined with biomarkers. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Distribution of cyclophilin B-binding sites in the subsets of human peripheral blood lymphocytes.

PubMed

Denys, A; Allain, F; Foxwell, B; Spik, G

1997-08-01

Cyclophilin B (CyPB) is a cyclosporin A (CsA)-binding protein, mainly associated with the secretory pathway and released in biological fluids. We have recently demonstrated that both free CyPB and CyPB-CsA complex specifically bind to peripheral blood T lymphocytes and are internalized. These results suggest that CyPB might promote the targeting of the drug into sensitive cells. Peripheral blood lymphocytes are subdivided in several populations according to their biological functions and sensitivity to CsA. We have investigated the binding of CyPB to these different subsets using a CyPB derivatized by fluorescein through its single cysteine which retains its binding properties. We have confirmed that only T cells were involved in the interaction with CyPB. The ligand binding was found to be heterogeneously distributed on the different T-cell subsets and surface-bound CyPB was mainly associated with the CD4-positive cells. No significant difference was noted between the CD45RA and CD45RO subsets, demonstrating that CyPB-binding sites were equally distributed between native and memory T cells. CD3 stimulation of T lymphocytes led to a decrease in the CyPB-binding capacity, that may be explained by a down-regulation of the CyPB-receptor expression upon T-cell activation. Finally, we demonstrated that CyPB-receptor-positive cells, isolated on CyPB sulphydryl-coupled affinity matrices, are more sensitive to CyPB-complexed CsA than mixed peripheral blood lymphocytes, suggesting that CyPB potentiates CsA activity through the binding of the complex. Taken together, our results demonstrate that CyPB-binding sites are mainly associated with resting cells of the helper T lymphocyte, and that CyPB might modulate the distribution of CsA through the drug targeting to sensitive cells.

Mass spectrometer calibration of Cosmic Dust Analyzer

NASA Astrophysics Data System (ADS)

Ahrens, Thomas J.; Gupta, Satish C.; Jyoti, G.; Beauchamp, J. L.

2003-02-01

The time-of-flight (TOF) mass spectrometer (MS) of the Cosmic Dust Analyzer (CDA) instrument aboard the Cassini spacecraft is expected to be placed in orbit about Saturn to sample submicrometer-diameter ring particles and impact ejecta from Saturn's satellites. The CDA measures a mass spectrum of each particle that impacts the chemical analyzer sector of the instrument. Particles impact a Rh target plate at velocities of 1-100 km/s and produce some 10-8 to 10-5 times the particle mass of positive valence, single-charged ions. These are analyzed via a TOF MS. Initial tests employed a pulsed N2 laser acting on samples of kamacite, pyrrhotite, serpentine, olivine, and Murchison meteorite induced bursts of ions which were detected with a microchannel plate and a charge sensitive amplifier (CSA). Pulses from the N2 laser (1011 W/cm2) are assumed to simulate particle impact. Using aluminum alloy as a test sample, each pulse produces a charge of ~4.6 pC (mostly Al+1), whereas irradiation of a stainless steel target produces a ~2.8 pC (Fe+1) charge. Thus the present system yields ~10-5% of the laser energy in resulting ions. A CSA signal indicates that at the position of the microchannel plate, the ion detector geometry is such that some 5% of the laser-induced ions are collected in the CDA geometry. Employing a multichannel plate detector in this MS yields for Al-Mg-Cu alloy and kamacite targets well-defined peaks at 24 (Mg+1), 27(Al+1), and 64 (Cu+1) and 56 (Fe+1), 58 (Ni+1), and 60 (Ni+1) dalton, respectively.

Body mass index and anxiety/depression as mediators of the effects of child sexual and physical abuse on physical health disorders in women.

PubMed

McCarthy-Jones, Simon; McCarthy-Jones, Roseline

2014-12-01

The relation between childhood sexual abuse (CSA) and physical health disorders in adulthood, and what factors may serve as mediators, remains poorly understood. Using data from the 2007 Adult Psychiatric Morbidity Survey (N=3,486), we tested whether CSA was associated with physical health disorders in adult women and if mediated effects via body mass index (BMI), anxiety/depression, alcohol dependence, and smoking were present. Compared to women with no CSA, women who had experienced CSA involving intercourse had more than twice the odds of being obese, more than 3 times the odds of experiencing mental health disorders, more than 4 times the odds of being alcohol dependent, more than 5 times the odds of being drug dependent, and more than 6 times the odds of attempting suicide. Those experiencing both CSA and child physical abuse (CPA) were on average over 11kg heavier than those with neither CSA nor CPA. After controlling for demographics, CPA, and childhood bullying, CSA was associated with the majority of physical health disorders studied (typically 50-100% increases in odds). Evidence was found consistent with mediation by BMI (typically accounting for 5-20% increases in odds) and anxiety/depression (typically accounting for 8-40% increases in odds), in a dose-response manner, for the majority of physical health disorders. Bidirectional relations among these mediators and physical health disorders, and residual confounding, may have led to overestimation of mediation through BMI and anxiety/depression and underestimation of mediation through alcohol/smoking. Relations between both CPA and childhood bullying and physical health disorders in adulthood were also found. Longitudinal studies employing more sensitive measures of potential mediators are now required. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Significant expression of thyroid transcription factor-1 in pulmonary squamous cell carcinoma detected by SPT24 monoclonal antibody and CSA-II system.

PubMed

Kashima, Kenji; Hashimoto, Hisashi; Nishida, Haruto; Arakane, Motoki; Yada, Naomi; Daa, Tsutomu; Yokoyama, Shigeo

2014-01-01

In contrast to the usefulness of thyroid transcription factor-1 (TTF-1) in distinguishing primary adenocarcinoma of the lung from metastatic lesions, TTF-1 expression in pulmonary squamous cell carcinoma is reported to be at low level and not a suitable immunohistochemical marker. We hypothesized that the highly sensitive detection system, CSA-II, can visualize even faint expression of TTF-1 in pulmonary squamous cell carcinoma. In this study, 2 commercially available clones of TTF-1 monoclonal antibody, 8G7G3/1 and SPT24, were used for staining 38 cases of pulmonary squamous cell carcinoma, in combination with the CSA-II and the conventional detection system, EnVision. The combined use of the 8G7G3/1 clone with EnVision and CSA-II showed a positive reaction in only 1 and 4 cases, respectively. The use of SPT24 clone showed positive staining in 5 cases with EnVision and in 20 of 38 cases (52.6%) with the CSA-II. Interestingly, positive staining by the SPT24-CSA-II technique of samples from tissue blocks preserved for <2 years was 73.6% compared with only 31.5% in those preserved for >2 years. In addition, a 6-month preservation of the cut sections resulted in stain fading and decreased positivity (50%), compared with freshly cut sections. We conclude that the use of the SPT24 monoclonal antibody with the CSA-II system can detect even weak expression of TTF-1 in pulmonary squamous cell carcinoma. This staining technique can potentially allow the discrimination of primary squamous cell carcinoma of the lung from metastatic lesions, especially in freshly prepared paraffin sections.

The Diagnostic Utility of the Child Sexual Behavior Inventory for Sexual Abuse: A Systematic Review.

PubMed

Vrolijk-Bosschaart, Thekla F; Verlinden, Eva; Langendam, Miranda W; De Smet, Vivienne; Teeuw, Arianne H; Brilleslijper-Kater, Sonja N; Benninga, Marc A; Lindauer, Ramón J L

2018-06-11

Children with alleged child sexual abuse (CSA) need to be assessed systematically. The use of validated instruments during the assessment, like the Child Sexual Behavior Inventory (CSBI), could add diagnostic value. We aim to assess the diagnostic utility of the CSBI to differentiate between sexually abused and non-abused children. We conducted a systematic review. We searched the electronic databases MEDLINE and PsychInfo for studies comparing CSBI scores in sexually abused children and non-abused children (2-12 years old). Two independent reviewers extracted data and assessed the methodological quality. We included 7 (out of 1048) articles. The CSBI total scores were significantly higher in CSA-victims compared with non-abused children (in case-control settings). However, in children with suspected CSA, the results were ambiguous. One study reported significant differences. Another study reported weak diagnostic ability for the CSBI-3 in children with suspected CSA (a sensitivity and specificity of 0.50, with a positive predictive value of 0.28, and a negative predictive value of 0.72). Research on the diagnostic utility of the CSBI for suspected CSA is limited and shows disappointing results. Until more research is done, the CSBI should not be used on its own to differentiate between sexually abused and non-abused children.

KIAA1530 Protein Is Recruited by Cockayne Syndrome Complementation Group Protein A (CSA) to Participate in Transcription-coupled Repair (TCR)

PubMed Central

Fei, Jia; Chen, Junjie

2012-01-01

Transcription-coupled repair (TCR) is the major pathway involved in the removal of UV-induced photolesions from the transcribed strand of active genes. Two Cockayne syndrome (CS) complementation group proteins, CSA and CSB, are important for TCR repair. The molecular mechanisms by which CS proteins regulate TCR remain elusive. Here, we report the characterization of KIAA1530, an evolutionarily conserved protein that participates in this pathway through its interaction with CSA and the TFIIH complex. We found that UV irradiation led to the recruitment of KIAA1530 onto chromatin in a CSA-dependent manner. Cells lacking KIAA1530 were highly sensitive to UV irradiation and displayed deficiency in TCR. In addition, KIAA1530 depletion abrogated stability of the CSB protein following UV irradiation. More excitingly, we found that a unique CSA mutant (W361C), which was previously identified in a patient with UVsS syndrome, showed defective KIAA1530 binding and resulted in a failure of recruiting KIAA1530 and stabilizing CSB after UV treatment. Together, our data not only reveal that KIAA1530 is an important player in TCR but also lead to a better understanding of the molecular mechanism underlying UVsS syndrome. PMID:22902626

Community supported agriculture membership in Arizona. An exploratory study of food and sustainability behaviours.

PubMed

MacMillan Uribe, Alexandra L; Winham, Donna M; Wharton, Christopher M

2012-10-01

Community supported agriculture (CSA) programs have become a viable source of locally produced foods and represent a new way to increase fruit and vegetable consumption among individuals. Because CSAs represent a way for consumers to acquire healthy foods while providing financial support to local farmers, CSA involvement could reflect, and be related to, greater concern with both health and environmental impact of food choice. As such, the aim of this study was to examine whether ecological attitudes of CSA members could predict food- and sustainability-related behaviours. Using an online survey, respondents answered questions about attitudes towards the environment, as well behaviours related to food purchases, family food preparation, composting, recycling and minimising food-packaging waste. A total of 115 CSA member responses were collected. Ordinary least squares (OLS) multivariate regression analysis was used to investigate the predictive validity of environmental attitudes on measures of behaviours. A large portion of participants reported the amount and variety of fruits and vegetables their households ate increased as a result of joining a CSA program. Ecological sensitivity was a significant predictor of sustainability-related behaviours as well as money spent eating out and times eaten away from home per week. However, it was not predictive of family involvement in home food preparation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Brain natriuretic peptide in patients with congestive heart failure and central sleep apnea.

PubMed

Carmona-Bernal, Carmen; Quintana-Gallego, Esther; Villa-Gil, Manuel; Sánchez-Armengol, Angeles; Martínez-Martínez, Angel; Capote, Francisco

2005-05-01

To assess the possible relationship between Cheyne-Stokes respiration (CSR) associated with central sleep apnea (CSA) syndrome and brain natriuretic peptide (BNP) in an outpatient population presenting with stable congestive heart failure (CHF). Ninety patients with CHF due to systolic dysfunction (left ventricular ejection fraction

Comparison of functional assays used in the clinical development of a placental malaria vaccine.

PubMed

Pehrson, Caroline; Heno, Kristine K; Adams, Yvonne; Resende, Mafalda; Mathiesen, Line; Soegaard, Max; de Jongh, Willem A; Theander, Thor G; Salanti, Ali; Nielsen, Morten A

2017-01-23

Malaria in pregnancy is associated with significant morbidity in pregnant women and their offspring. Plasmodium falciparum infected erythrocytes (IE) express VAR2CSA that mediates binding to chondroitin sulphate A (CSA) in the placenta. Two VAR2CSA-based vaccines for placental malaria are in clinical development. The purpose of this study was to evaluate the robustness and comparability of binding inhibition assays used in the clinical development of placental malaria vaccines. The ability of sera from animals immunised with different VAR2CSA constructs to inhibit IE binding to CSA was investigated in three in vitro assays using 96-well plates, petri dishes, capillary flow and an ex vivo placental perfusion assay. The inter-assay variation was not uniform between assays and ranged from above ten-fold in the flow assay to two-fold in the perfusion assay. The intra-assay variation was highest in the petri dish assay. A positive correlation between IE binding avidity and the level of binding after antibody inhibition in the petri dish assay indicate that high avidity IE binding is more difficult to inhibit. The highest binding inhibition sensitivity was found in the 96-well and petri dish assays compared to the flow and perfusion assays where binding inhibition required higher antibody titers. The inhibitory capacity of antibodies is not easily translated between assays and the high sensitivity of the 96-well and petri dish assays stresses the need for comparing serial dilutions of serum. Furthermore, IE binding avidity must be in the same range when comparing data from different days. There was an overall concordance in the capacity of antibody-mediated inhibition, when comparing the in vitro assays with the perfusion assay, which more closely represents in vivo conditions. Importantly the ID1-ID2a protein in a liposomal formulation, currently in a phase I trial, effectively induced antibodies that inhibited IE adhesion in placental tissue. Copyright © 2016. Published by Elsevier Ltd.

Characterization of anti-Toxoplasma activity of SDZ 215-918, a cyclosporin derivative lacking immunosuppressive and peptidyl-prolyl-isomerase-inhibiting activity: possible role of a P glycoprotein in Toxoplasma physiology.

PubMed Central

Silverman, J A; Hayes, M L; Luft, B J; Joiner, K A

1997-01-01

The immunosuppressive agent cyclosporin A (CsA) also possesses broad-spectrum antimicrobial activity. Previous investigators have reported that the obligate intracellular protozoan Toxoplasma gondii is sensitive to CsA. We have measured the sensitivity of Toxoplasma to 26 CsA derivatives that maintain only a subset of the parent compound's activity. We identified one compound, SDZ 215-918, that is a particularly potent inhibitor of parasite invasion and replication, with a 50% inhibitory concentration of 0.45 microg/ml, which is 10-fold lower than that of CsA. Kinetic studies demonstrate that activity has a rapid onset (half-life, < or = 20 min) and is initially reversible, although long-term exposure (> 24 h) to 5 microg/ml is lethal; in contrast, this concentration had no effect on host cell protein synthesis or cell division. SDZ 215-918 acts directly on the parasite, as demonstrated by inhibition of macromolecular synthesis in host-free extracellular parasites. Inhibition of invasion is due to a reduction in parasite motility. SDZ 215-918 does not bind to cyclophilins, the ubiquitous cyclosporin-binding proteins, but is a potent inhibitor of the mammalian P glycoprotein, a member of the ATP binding cassette transporter superfamily and the pump responsible for multidrug resistance in cancer and parasite cell lines. SDZ 215-918 blocks the efflux of rhodamine 123 from extracellular parasites, consistent with inhibition of a P glycoprotein-like pump. We suggest that a P glycoprotein or a related transporter plays a crucial role in the biology of Toxoplasma and may be a novel target for antiparasitic compounds. Preliminary studies with animals indicate that SDZ 215-918 inhibits parasite growth in vivo; its relationship to CsA may make it suitable for clinical development. PMID:9303374

Identification of cellular and viral factors related to anti-hepatitis C virus activity of cyclophilin inhibitor.

PubMed

Goto, Kaku; Watashi, Koichi; Inoue, Daisuke; Hijikata, Makoto; Shimotohno, Kunitada

2009-10-01

We have so far reported that an immunosuppressant cyclosporin A (CsA), a well-known cyclophilin (CyP) inhibitor (CPI), strongly suppressed hepatitis C virus (HCV) replication in cell culture, and that CyPB was a cellular cofactor for viral replication. To further investigate antiviral mechanisms of CPI, we here developed cells carrying CsA-resistant HCV replicons, by culturing the HCV subgenomic replicon cells for 4 weeks in the presence of CsA with G418. Transfection of total RNA from the isolated CsA-resistant cells to naïve Huh7 cells conferred CsA resistance, suggesting that the replicon RNA itself was responsible for the resistant phenotype. Of the identified amino acid mutations, D320E in NS5A conferred the CsA resistance. The replicon carrying the D320E mutation was sensitive to interferon-alpha, but was resistant to CsA and other CPIs including NIM811 and sanglifehrin A. Knockdown of individual CyP subtypes revealed CyP40, in addition to CyPA and CyPB, contributed to viral replication, and CsA-resistant replicons acquired independence from CyPA for efficient replication. These data provide important evidence on the mechanisms underlying the regulation of HCV replication by CyP and for designing novel and specific anti-HCV strategies with CPIs.

An Introduction to Phase-Sensitive Amplifiers: An Inexpensive Student Instrument

ERIC Educational Resources Information Center

Temple, Paul A.

1975-01-01

Discusses the principle of operation of phase-sensitive amplifiers. Gives three examples, suitable for undergraduate laboratory use, of the use of phase-sensitive, or "lock-in" amplifiers. Concludes with a description of an inexpensive lock-in amplifier which has an overall voltage gain of 1000. (Author/MLH)

Colon-targeted delivery of cyclosporine A using dual-functional Eudragit® FS30D/PLGA nanoparticles ameliorates murine experimental colitis.

PubMed

Naeem, Muhammad; Bae, Junhwan; Oshi, Murtada A; Kim, Min-Soo; Moon, Hyung Ryong; Lee, Bok Luel; Im, Eunok; Jung, Yunjin; Yoo, Jin-Wook

2018-01-01

Colon-targeted oral nanoparticles (NPs) have emerged as an ideal, safe, and effective therapy for ulcerative colitis (UC) owing to their ability to selectively accumulate in inflamed colonic mucosa. Cyclosporine A (CSA), an immunosuppressive agent, has long been used as rescue therapy in severe steroid-refractory UC. In this study, we developed CSA-loaded dual-functional polymeric NPs composed of Eudragit ® FS30D as a pH-sensitive polymer for targeted delivery to the inflamed colon, and poly(lactic-co-glycolic acid) (PLGA) as a sustained-release polymer. CSA-loaded Eudragit FS30D nanoparticles (ENPs), PLGA nanoparticles (PNPs), and Eudragit FS30D/PLGA nanoparticles (E/PNPs) were prepared using the oil-in-water emulsion method. Scanning electron microscope images and zeta size data showed successful preparation of CSA-loaded NPs. PNPs exhibited a burst drug release of >60% at pH 1.2 (stomach pH) in 0.5 h, which can lead to unwanted systemic absorption and side effects. ENPs effectively inhibited the burst drug release at pH 1.2 and 6.8 (proximal small intestine pH); however, nearly 100% of the CSA in ENPs was released rapidly at pH 7.4 (ileum-colon pH) owing to complete NP dissolution. In contrast to single-functional PNPs and ENPs, the dual-functional E/PNPs minimized burst drug release (only 18%) at pH 1.2 and 6.8, and generated a sustained release at pH 7.4 thereafter. Importantly, in distribution studies in the gastrointestinal tracts of mice, E/PNPs significantly improved CSA distribution to the colon compared with PNPs or ENPs. In a mouse model of colitis, E/PNP treatment improved weight loss and colon length, and decreased rectal bleeding, spleen weight, histological scoring, myeloperoxidase activity, macrophage infiltration, and expression of proinflammatory cytokines compared with PNPs or ENPs. Overall, this work confirms the benefits of CSA-loaded E/PNPs for efficiently delivering CSA to the colon, suggesting their potential for UC therapy.

The combined rapid detection and species-level identification of yeasts in simulated blood culture using a colorimetric sensor array

PubMed Central

Lim, Sung H.; Wilson, Deborah A.; SalasVargas, Ana Victoria; Churi, Yair S.; Rhodes, Paul A.; Mazzone, Peter J.; Procop, Gary W.

2017-01-01

Background A colorimetric sensor array (CSA) has been demonstrated to rapidly detect and identify bacteria growing in blood cultures by obtaining a species-specific “fingerprint” of the volatile organic compounds (VOCs) produced during growth. This capability has been demonstrated in prokaryotes, but has not been reported for eukaryotic cells growing in culture. The purpose of this study was to explore if a disposable CSA could differentially identify 7 species of pathogenic yeasts growing in blood culture. Methods Culture trials of whole blood inoculated with a panel of clinically important pathogenic yeasts at four different microorganism loads were performed. Cultures were done in both standard BacT/Alert and CSA-embedded bottles, after adding 10 mL of spiked blood to each bottle. Color changes in the CSA were captured as images by an optical scanner at defined time intervals. The captured images were analyzed to identify the yeast species. Time to detection by the CSA was compared to that in the BacT/Alert system. Results One hundred sixty-two yeast culture trials were performed, including strains of several species of Candida (Ca. albicans, Ca. glabrata, Ca. parapsilosis, and Ca. tropicalis), Clavispora (synonym Candida) lusitaniae, Pichia kudriavzevii (synonym Candida krusei) and Cryptococcus neoformans, at loads of 8.2 × 105, 8.3 × 103, 8.5 × 101, and 1.7 CFU/mL. In addition, 8 negative trials (no yeast) were conducted. All negative trials were correctly identified as negative, and all positive trials were detected. Colorimetric responses were species-specific and did not vary by inoculum load over the 500000-fold range of loads tested, allowing for accurate species-level identification. The mean sensitivity for species-level identification by CSA was 74% at detection, and increased with time, reaching almost 95% at 4 hours after detection. At an inoculum load of 1.7 CFU/mL, mean time to detection with the CSA was 6.8 hours (17%) less than with the BacT/Alert platform. Conclusion The CSA combined rapid detection of pathogenic yeasts in blood culture with accurate species-level identification. PMID:28296967

The combined rapid detection and species-level identification of yeasts in simulated blood culture using a colorimetric sensor array.

PubMed

Shrestha, Nabin K; Lim, Sung H; Wilson, Deborah A; SalasVargas, Ana Victoria; Churi, Yair S; Rhodes, Paul A; Mazzone, Peter J; Procop, Gary W

2017-01-01

A colorimetric sensor array (CSA) has been demonstrated to rapidly detect and identify bacteria growing in blood cultures by obtaining a species-specific "fingerprint" of the volatile organic compounds (VOCs) produced during growth. This capability has been demonstrated in prokaryotes, but has not been reported for eukaryotic cells growing in culture. The purpose of this study was to explore if a disposable CSA could differentially identify 7 species of pathogenic yeasts growing in blood culture. Culture trials of whole blood inoculated with a panel of clinically important pathogenic yeasts at four different microorganism loads were performed. Cultures were done in both standard BacT/Alert and CSA-embedded bottles, after adding 10 mL of spiked blood to each bottle. Color changes in the CSA were captured as images by an optical scanner at defined time intervals. The captured images were analyzed to identify the yeast species. Time to detection by the CSA was compared to that in the BacT/Alert system. One hundred sixty-two yeast culture trials were performed, including strains of several species of Candida (Ca. albicans, Ca. glabrata, Ca. parapsilosis, and Ca. tropicalis), Clavispora (synonym Candida) lusitaniae, Pichia kudriavzevii (synonym Candida krusei) and Cryptococcus neoformans, at loads of 8.2 × 105, 8.3 × 103, 8.5 × 101, and 1.7 CFU/mL. In addition, 8 negative trials (no yeast) were conducted. All negative trials were correctly identified as negative, and all positive trials were detected. Colorimetric responses were species-specific and did not vary by inoculum load over the 500000-fold range of loads tested, allowing for accurate species-level identification. The mean sensitivity for species-level identification by CSA was 74% at detection, and increased with time, reaching almost 95% at 4 hours after detection. At an inoculum load of 1.7 CFU/mL, mean time to detection with the CSA was 6.8 hours (17%) less than with the BacT/Alert platform. The CSA combined rapid detection of pathogenic yeasts in blood culture with accurate species-level identification.

Genetics Home Reference: UV-sensitive syndrome

MedlinePlus

... damaged, the enzyme that carries out gene transcription (RNA polymerase) gets stuck, and the process stalls. Researchers ... the CSB, CSA, and UVSSA proteins help remove RNA polymerase from the damaged site, so the DNA ...

Potential pathways from stigmatization and externalizing behavior to anger and dating aggression in sexually abused youth.

PubMed

Feiring, Candice; Simon, Valerie A; Cleland, Charles M; Barrett, Ellen P

2013-01-01

Although experiencing childhood sexual abuse (CSA) puts youth at risk for involvement in relationship violence, research is limited on the potential pathways from CSA to subsequent dating aggression. The current study examined prospective pathways from externalizing behavior problems and stigmatization (abuse-specific shame and self-blame attributions) to anger and dating aggression. One hundred sixty youth (73% female, 69% ethnic/racial minorities) with confirmed CSA histories were interviewed at the time of abuse discovery (T1, when they were 8-15 years of age), and again 1 and 6 years later (T2 and T3). Externalizing behavior and abuse-specific stigmatization were assessed at T1 and T2. Anger and dating aggression were assessed at T3. The structural equation model findings supported the proposed relations from stigmatization following the abuse to subsequent dating aggression through anger. Only externalizing behavior at T1 was related to later dating aggression, and externalizing was not related to subsequent anger. This longitudinal research suggests that clinical interventions for victims of CSA be sensitive to the different pathways by which youth come to experience destructive conflict behavior in their romantic relationships.

Identification of a novel cyclosporin-sensitive element in the human tumor necrosis factor alpha gene promoter

PubMed Central

1993-01-01

Tumor necrosis factor alpha (TNF-alpha), a cytokine with pleiotropic biological effects, is produced by a variety of cell types in response to induction by diverse stimuli. In this paper, TNF-alpha mRNA is shown to be highly induced in a murine T cell clone by stimulation with T cell receptor (TCR) ligands or by calcium ionophores alone. Induction is rapid, does not require de novo protein synthesis, and is completely blocked by the immunosuppressant cyclosporin A (CsA). We have identified a human TNF-alpha promoter element, kappa 3, which plays a key role in the calcium-mediated inducibility and CsA sensitivity of the gene. In electrophoretic mobility shift assays, an oligonucleotide containing kappa 3 forms two DNA protein complexes with proteins that are present in extracts from unstimulated T cells. These complexes appear in nuclear extracts only after T cell stimulation. Induction of the inducible nuclear complexes is rapid, independent of protein synthesis, and blocked by CsA, and thus, exactly parallels the induction of TNF-alpha mRNA by TCR ligands or by calcium ionophore. Our studies indicate that the kappa 3 binding factor resembles the preexisting component of nuclear factor of activated T cells. Thus, the TNF-alpha gene is an immediate early gene in activated T cells and provides a new model system in which to study CsA-sensitive gene induction in activated T cells. PMID:8376940

Multisite analytical evaluation of the Abbott ARCHITECT cyclosporine assay.

PubMed

Wallemacq, Pierre; Maine, Gregory T; Berg, Keith; Rosiere, Thomas; Marquet, Pierre; Aimo, Giuseppe; Mengozzi, Giulio; Young, Julianna; Wonigeit, Kurt; Kretschmer, Robert; Wermuth, Bendicht; Schmid, Rainer W

2010-04-01

The objective of this study was to evaluate the analytical performance of the Abbott ARCHITECT Cyclosporine (CsA) immunoassay in 7 clinical laboratories in comparison to liquid chromatography/tandem mass spectrometry (LC/MS/MS), Abbott TDx, Cobas Integra 800, and the Dade Dimension Xpand immunoassay. The ARCHITECT assay uses a whole blood specimen, a pretreatment step with organic reagents to precipitate proteins and extract the drug, followed by a 2-step automated immunoassay with magnetic microparticles coated with anti-CsA antibody and an acridinium-CsA tracer. Imprecision testing at the 7 evaluation sites gave a range of total % coefficient of variations of 7.5%-12.2% at 87.5 ng/mL, 6.6%-14.3% at 411 ng/mL, and 5.2%-10.7% at 916 ng/mL. The lower limit of quantification ranged from 12 to 20 ng/mL. Purified CsA metabolites AM1, AM1c, AM4N, AM9, and AM19 were tested in whole blood by the ARCHITECT assay and showed minimal cross-reactivity at all 7 sites. In particular, AM1 and AM9 cross-reactivity in the ARCHITECT assay, ranged from -2.5% to 0.2% and -0.8% to 2.2%, respectively, and was significantly lower than for the TDx assay, in which the values were 3.2% and 16.1%, respectively. Comparable testing of metabolites in the Dade Dimension Xpand assay at 2 evaluation sites showed cross-reactivity to AM4N (6.4% and 6.8%) and AM9 (2.6% and 3.6%) and testing on the Roche Integra 800 showed cross-reactivity to AM1c (2.4%), AM9 (10.7%), and AM19 (2.8%). Cyclosporine International Proficiency Testing Scheme samples, consisting of both pooled specimens from patients receiving CsA therapy as well as whole-blood specimens supplemented with CsA, were tested by the ARCHITECT assay at 6 sites and showed an average bias of -24 to -58 ng/mL versus LC/MSMS CsA and -2 to -37 ng/mL versus AxSYM CsA. Studies were performed with the ARCHITECT CsA assay on patient specimens with the following results: ARCHITECT CsA assay versus LC/MSMS, average bias of 31 ng/mL; ARCHITECT versus the Dade Dimension assay (4 sites), average biases of -7 to -228 ng/mL; ARCHITECT versus AxSYM and TDx, average biases of -4 and -53 ng/mL, respectively. Spearman correlation coefficients were >or=0.89. The ARCHITECT CsA assay has significantly reduced CsA metabolite interference relative to other immunoassays and is a convenient and sensitive semiautomated method to measure CsA in whole blood.

Development of Ultra-Super Sensitive Immunohistochemistry and Its Application to the Etiological Study of Adult T-Cell Leukemia/Lymphoma

PubMed Central

Hasui, Kazuhisa; Wang, Jia; Tanaka, Yuetsu; Izumo, Shuji; Eizuru, Yoshito; Matsuyama, Takami

2012-01-01

Antigen retrieval (AR) and ultra-super sensitive immunohistochemistry (ultra-IHC) have been established for application to archival human pathology specimens. The original ultra-IHC was the ImmunoMax method or the catalyzed signal amplification system (ImmunoMax/CSA method), comprising the streptavidin-biotin complex (sABC) method and catalyzed reporter deposition (CARD) reaction with visualization of its deposition. By introducing procedures to diminish non-specific staining in the original ultra-IHC method, we developed the modified ImmunoMax/CSA method with AR heating sections in an AR solution (heating-AR). The heating-AR and modified ImmunoMax/CSA method visualized expression of the predominantly simple present form of HTLV-1 proviral DNA pX region p40Tax protein (Tax) in adult T-cell leukemia/lymphoma (ATLL) cells in archival pathology specimens in approximately 75% of cases. The simple present form of Tax detected exhibited a close relation with ATLL cell proliferation. We also established a new simplified CSA (nsCSA) system by replacing the sABC method with the secondary antibody- and horse radish peroxidase-labeled polymer reagent method, introducing the pretreatments blocking non-specific binding of secondary antibody reagent, and diminishing the diffusion of deposition in the CARD reaction. Combined with AR treating sections with proteinase K solution (enzymatic-AR), the nsCSA system visualized granular immunostaining of the complex present form of Tax in a small number of ATLL cells in most cases, presenting the possibility of etiological pathological diagnosis of ATLL and suggesting that the complex present form of Tax-positive ATLL cells were young cells derived from ATLL stem cells. The heating-AR and ultra-IHC detected physiological expression of the p53 protein and its probable phosphorylation by Tax in peripheral blood mononuclear cells of peripheral blood tissue specimens from HTLV-1 carriers, as well as physiological and pathological expression of the molecules involved with G1 phase progression and G1–S phase transition (E2F-1, E2F-4, DP-1, and cyclin E) in ATLL and peripheral T-cell lymphoma cells. The ultra-IHC with AR is useful for etiological pathological diagnosis of ATLL since HTLV-1 pathogenicity depends on that of Tax, and can be a useful tool for studies translating advanced molecular biology and pathology to human pathology. PMID:22685351

End-Tidal CO2 Tension Is Predictive of Effective Nocturnal Oxygen Therapy in Patients with Chronic Heart Failure and Central Sleep Apnea.

PubMed

Sugimura, Koichiro; Shinozaki, Tsuyoshi; Fukui, Shigefumi; Ogawa, Hiromasa; Shimokawa, Hiroaki

2016-05-01

Central sleep apnea (CSA) is characterized by recurring cycles of crescendo-decrescendo ventilation during sleep, and enhances sympathetic nerve activity. Thus CSA has a prognostic impact in patients with chronic heart failure (CHF). Although nocturnal oxygen (O2) therapy decreases frequency of CSA and improves functional exercise capacity, it is also known that some non-responders to the therapy exist. We thus aimed to identify predictors of responders to nocturnal O2 therapy in CHF patients with CSA. In 12 CHF patients with CSA hospitalized at our department, sleep study was performed at 2 consecutive nights. Patients nasally inhaled O2 at either the first or second night in a randomized manner. To predict the percentage reduction in apnea-hypopnea index (%ΔAHI) in response to the nocturnal O2 therapy, we performed multiple regression analysis with a stepwise method with variables including age, brain-natriuretic peptide, circulation time, baseline AHI, hypercapnic ventilatory response and end-tidal carbon dioxide tension (PETCO2). Nocturnal O2 therapy significantly decreased AHI (from 32 ± 13 /h to 12 ± 10 /h, P < 0.0001). Among the possible predictors, PETCO2 was the only variable that is predictive of % changes in AHI. Receiver operating characteristics analysis determined 4.25% as the optimal cutoff PETCO2 level to identify responder to nocturnal O2 therapy (> 50% reduction of AHI), with 88.9% of sensitivity and 66.7% of specificity. In conclusion, PETCO2 is useful to predict the efficacy of O2 therapy in CHF patients with CSA, providing important information to the current nocturnal O2 therapy.

[Child sexual abuse: a study among 892 female students of a medical school].

PubMed

Chen, Jing-qi; Han, Ping; Dunne, Michael P

2004-01-01

This study was designed to ascertain the prevalence of child sexual abuse (CSA) among female students of a medical school and to explore the impact of CSA on the mental health and health related risk behaviors of the victims being sexually abused and to provide useful reference for CSA prevention. A cross-sectional survey was carried out among 892 female students from a medical school by anonymous self-administered questionnaire during Oct. 2002. The questionnaire used for this study mainly included (1) general demographic information; (2) sexual experiences; (3) 12 forms of CSA. In this study, cases of CSA were defined as those who answered positively to one or more of the 12 questions relating to childhood sexual experiences (including non-physical contact CSA and physical contact CSA) occurring before age 16 with a person when a child did not want to. (4) Center for Epidemiologic Studies (CES)-Depression Scale; (5) Self Esteem Scale; (6) Risk Behaviors; (7) Health status' self-evaluation. Survey procedures were designed to protect students' privacy by allowing anonymous and voluntary participation. Students were seated separately, completed the self-administered questionnaire in their classrooms during a regular class period. Respondents were encouraged to participate in this survey, but given the sensitive nature of the subject, they could skip portion of the questionnaire if they were not comfortable with the questions. The completed questionnaires were sealed in envelopes by students themselves (the envelope was distributed with questionnaire at the same time), and then collected together. Data were analysed by using the Statistical Package for the Social Sciences software. Frequency, percentage, Chi-square test and t-test of statistics were used to analyze the CSA prevalence and explore the influence of CSA on mental health of students. Among 892 female students, 25.6% reported having experienced CSA (any one of 12 forms non-physical contact and physical contact CSA) before the age of 16 years. The median age at first episode was 12 years. Comparing the rates of CSA of female students in different parents' education level, between one-child in a family and more than one-child in a family, among rural area, county and city, there were no significant differences. Compared to the students who had not experienced CSA, the students who had experienced CSA reported higher levels of depression (CES-D score 18.78 vs. 16.68, t = 2.81, P = 0.005), lower levels of health status self-evaluation (score 3.53 vs. 3.78, t = 2.94, P = 0.003); higher proportion of subjects who reported drinking alcohol and having ever smoked during the past 30 days (drinking 32.7% vs. 22.9%, chi(2) = 8.51, P = 0.004; smoking 8.8% vs. 4.4%, chi(2) = 6.17, P = 0.013); a higher percentage engaged in sexual intercourse (19.3% vs. 5.9%, chi(2) = 33.48, P = 0.000); ever seriously considered attempting suicide (23.7% vs. 15.4%, chi(2) = 8.09, P = 0.004), making a plan about how would attempt suicide (17.9% vs. 9.7%, chi(2) = 10.62, P = 0.001), being threatened or injured by someone with a weapon such as a knife, or club on school property (3.5% vs. 1.1%, chi(2) = 6.17, P = 0.013), being involved in physical fight (16.7% vs. 5.6%, chi(2) = 27.05, P = 0.000) during the 12 months preceding the survey. The results further showed that the CSA of girls in our country is not uncommon, as reported before in our country and in the other countries and is associated with poor mental health and risky behaviors. The findings highlight the urgent need for the further research into CSA epidemiological characteristics, health services for the victims abused sexually, sexual abuse prevention programs in schools and the general community in China.

Pedophilic sexual interests and psychopathy in child sexual abusers working with children.

PubMed

Turner, Daniel; Rettenberger, Martin; Lohmann, Lena; Eher, Reinhard; Briken, Peer

2014-02-01

Research has identified stable and dynamic characteristics in child sexual abusers working with children (CSA-W) that may distinguish them from other child sexual abusers (CSA). However, in previous research CSA-W have usually been included in the group of extra-familial CSA (CSA-E). Two hundred and forty-eight forensic-sexological reports about CSA conducted by the Federal Evaluation Centre for Violent and Sexual Offenders in the Austrian Prison System were evaluated retrospectively. One hundred and nineteen intra-familial CSA (CSA-I), 66 CSA-E, and 38 CSA-W were compared with regard to static risk factors, indicators of psychopathy, and pedophilic sexual interests. CSA-E had the highest risk of recidivism as measured by the Static-99 total score, followed by CSA-W. Furthermore, CSA-E had more previous convictions than CSA-W. Both CSA-E and CSA-I had higher total scores on the Psychopathy Checklist-Revised than CSA-W. CSA-W had the highest prevalence of pedophilia diagnoses according to DSM-IV-TR criteria, as well as the highest rate of pedophilia with an orientation toward male children, and the highest frequency of male victims. CSA-W also had the highest total scores in the Screening Scale for Pedophilic Interests. CSA-W seem to constitute a group with particular risk factors and criminogenic needs, that is, they show more indicators of pedophilic sexual interests but less general antisociality and psychopathy, and would thus seem to be distinguishable from other CSA. Future research should focus in particular on evaluating differences in the grooming strategies used by CSA-W to commit and disclose child sexual abuse, as well as on the resources of this particular offender group. Copyright © 2013 Elsevier Ltd. All rights reserved.

Muscle atrophy and recovery of individual thigh muscles as measured by magnetic resonance imaging scan during treatment with cast for ankle or foot fracture.

PubMed

Yamauchi, Koun; Yoshiko, Akito; Suzuki, Shigetoshi; Kato, Chisato; Akima, Hiroshi; Kato, Takayuki; Ishida, Koji

2017-01-01

We aimed to longitudinally investigate individual thigh muscle changes using magnetic resonance imaging (MRI) during treatment with cast of ankle or foot fracture. Moreover, we aimed to demonstrate whether measurements of muscle cross-sectional area (CSA) are sensitive to muscle changes, contributing to simpler methods in clinical application . Ten patients undergoing treatment with cast of acute ankle or foot fractures were studied. Axial MRI (1.5 T) was conducted around the affected mid-thigh region after the injury (Pre), after maintaining a nonweight-bearing (NWB) period (approximately 28 days), and after finishing rehabilitation (recovery). Regarding individual thigh muscles, the total CSAs corresponding to 40% of the femoral length (FL) and the CSAs at 5% interval of the FL were longitudinally measured. Standardized response means (SRMs) were accessed for sensitivity in the muscle changes. The total CSAs at NWB were significantly lower than those at Pre in vastus lateralis (10.9% ± 5.4%), vastus intermedius (8.4% ± 6.7%), and vastus medialis (11.2% ± 6.9%) ( p < 0.01 for all). In contrast, at recovery, the only significant muscle atrophy relative to that at Pre was observed in the semitendinosus of the proximal 15% and 10% CSAs ( p < 0.01 and p = 0.01, respectively). In all muscles, SRM using a single-slice CSA at or near the muscle belly was high. Thigh muscle changes differ according to the variations in individual muscles. CSA measurements at or near the muscle belly are simple methods and sensitive indicators of these muscle changes.

In vitro chemo-sensitivity assay guided chemotherapy is associated with prolonged overall survival in cancer patients.

PubMed

Udelnow, Andrej; Schönfęlder, Manfred; Würl, Peter; Halloul, Zuhir; Meyer, Frank; Lippert, Hans; Mroczkowski, Paweł

2013-06-01

The overall survival (OS) of patients suffering From various tumour entities was correlated with the results of in vitro-chemosensitivity assay (CSA) of the in vivo applied drugs. Tumour specimen (n=611) were dissected in 514 patients and incubated for primary tumour cell culture. The histocytological regression assay was performed 5 days after adding chemotherapeutic substances to the cell cultures. n=329 patients undergoing chemotherapy were included in the in vitro/in vivo associations. OS was assessed and in vitro response groups compared using survival analysis. Furthermore Cox-regression analysis was performed on OS including CSA, age, TNM classification and treatment course. The growth rate of the primary was 73-96% depending on tumour entity. The in-vitro response rate varied with histology and drugs (e.g. 8-18% for methotrexate and 33-83% for epirubicine). OS was significantly prolonged for patients treated with in vitro effective drugs compared to empiric therapy (log-rank-test, p=0.0435). Cox-regression revealed that application of in vitro effective drugs, residual tumour and postoperative radiotherapy determined the death risk independently. When patients were treated with drugs effective in our CSA, OS was significantly prolonged compared to empiric therapy. CSA guided chemotherapy should be compared to empiric treatment by a prospective randomized trial.

Design of a Multi-Channel Front-End Readout ASIC With Low Noise and Large Dynamic Input Range for APD-Based PET Imaging

NASA Astrophysics Data System (ADS)

Fang, X. C.; Hu-Guo, Ch.; Ollivier-Henry, N.; Brasse, D.; Hu, Y.

2010-06-01

This paper represents the design of a low-noise, wide band multi-channel readout integrated circuit (IC) used as front end readout electronics of avalanche photo diodes (APD) dedicated to a small animal positron emission tomography (PET) system. The first ten-channel prototype chip (APD-Chip) of the analog parts has been designed and fabricated in a 0.35 μm CMOS process. Every channel of the APD_Chip includes a charge-sensitive preamplifier (CSA), a CR-(RC)2 shaper, and an analog buffer. In a channel, the CSA reads charge signals (10 bits dynamic range) from an APD array having 10 pF of capacitance per pixel. A linearized degenerated differential pair which ensures high linearity in all dynamical range is used as the high feedback resistor for preventing pile up of signals. The designed CSA has the capability of compensating automatically up to 200 nA leakage current from the detector. The CR-(RC)2 shaper filters and shapes the output signal of the CSA. An equivalent input noise charge obtained from test is 275 e -+ 10 e-/pF. In this paper the prototype is presented for both its theoretical analysis and its test results.

10 CFR 95.31 - Protective personnel.

Code of Federal Regulations, 2010 CFR

2010-01-01

... equivalent) if the licensee, certificate holder, or other person possesses information classified... Information. (b) Possess a “Q” access authorization (or CSA equivalent) if the licensee, certificate holder... vulnerability information; and certain particularly sensitive Naval Nuclear Propulsion Program information (e.g...

10 CFR 95.31 - Protective personnel.

Code of Federal Regulations, 2011 CFR

2011-01-01

... equivalent) if the licensee, certificate holder, or other person possesses information classified... Information. (b) Possess a “Q” access authorization (or CSA equivalent) if the licensee, certificate holder... vulnerability information; and certain particularly sensitive Naval Nuclear Propulsion Program information (e.g...

Active rc filter permits easy trade-off of amplifier gain and sensitivity to gain

NASA Technical Reports Server (NTRS)

Kerwin, W. J.; Shaffer, C. V.

1968-01-01

Passive RC network was designed with zeros of transmission in the right half of the complex frequency plane in the feedback loop of a simple negative-gain amplifier. The proper positioning provides any desired trade-off between amplifier gain and sensitivity to amplifier gain.

Shortened Time to Identify Staphylococcus Species from Blood Cultures and Methicillin Resistance Testing Using CHROMAgar

PubMed Central

Chihara, Shingo; Hayden, Mary K.; Minogue-Corbett, Eileen; Singh, Kamaljit

2009-01-01

The ability to rapidly differentiate coagulase-negative staphylococcus (CoNS) from Staphylococcus aureus and to determine methicillin resistance is important as it affects the decision to treat empiric antibiotic selection. The objective of this study was to evaluate CHROMagar S. aureus and CHROMagar MRSA (Becton Dickinson) for rapid identification of Staphylococcus spp. directly from blood cultures. Consecutive blood culture bottles (BacT Alert 3D SA and SN, bioMérieux) growing gram-positive cocci in clusters were evaluated. An aliquot was plated onto CHROMagar MRSA (C-MRSA) and CHROMagar S. aureus (C-SA) plates, which were read at 12 to 16 hours. C-SA correctly identified 147/147 S. aureus (100% sensitivity); 2 CoNS were misidentified as S. aureus (98% specificity). C-MRSA correctly identified 74/77 MRSA (96% sensitivity). None of the MSSA isolates grew on C-MRSA (100% specificity). In conclusion, CHROMagar is a rapid and sensitive method to distinguish MRSA, MSSA, and coagulase-negative Staphylococcus and may decrease time of reporting positive results. PMID:20016679

Top-down attentional control in spatially coincident stimuli enhances activity in both task-relevant and task-irrelevant regions of cortex

PubMed Central

Erickson, Kirk I.; Prakash, Ruchika Shaurya; Kim, Jennifer S.; Sutton, Bradley P.; Colcombe, Stanley J.; Kramer, Arthur F.

2010-01-01

Models of selective attention predict that focused attention to spatially contiguous stimuli may result in enhanced activity in areas of cortex specialized for processing task-relevant and task-irrelevant information. We examined this hypothesis by localizing color-sensitive areas (CSA) and word and letter sensitive areas of cortex and then examining modulation of these regions during performance of a modified version of the Stroop task in which target and distractors are spatially coincident. We report that only the incongruent condition with the highest cognitive demand showed increased activity in CSA relative to other conditions, indicating an attentional enhancement in target processing areas. We also found an enhancement of activity in one region sensitive to word/letter processing during the most cognitively demanding incongruent condition indicating greater processing of the distractor dimension. Correlations with performance revealed that top-down modulation during the task was critical for effective filtering of irrelevant information in conflict conditions. These results support predictions made by models of selective attention and suggest an important mechanism of top-down attentional control in spatially contiguous stimuli. PMID:18804123

A high-resolution (13)C 3D CSA-CSA-CSA correlation experiment by means of magic angle turning.

PubMed

Hu, J Z; Ye, C; Pugmire, R J; Grant, D M

2000-08-01

It is shown in this paper that a previously reported 90 degrees sample flipping (13)C 2D CSA-CSA correlation experiment may be carried out alternatively by employing constant slow sample rotation about the magic angle axis and by synchronizing the read pulse to 13 of the rotor cycle. A high-resolution 3D CSA-CSA-CSA correlation experiment based on the magic angle turning technique is reported in which the conventional 90 degrees 2D CSA-CSA powder pattern for each carbon in a system containing a number of inequivalent carbons may be separated according to the isotropic chemical shift value. The technique is demonstrated on 1,2,3-trimethoxybenzene in which all of the overlapping powder patterns that cannot be segregated by the 2D CSA-CSA experiment are resolved successfully by the 3D CSA-CSA-CSA experiment, including even the two methoxy groups (M(1) and M(3)) whose isotropic shifts, confirmed by high-speed MAS, are separated by only 1 ppm. A difference of 4 ppm in the principal value component (delta(33)) between M(1) and M(3) is readily obtained. Copyright 2000 Academic Press.

Cardiac surgery-associated acute kidney injury

PubMed Central

Ortega-Loubon, Christian; Fernández-Molina, Manuel; Carrascal-Hinojal, Yolanda; Fulquet-Carreras, Enrique

2016-01-01

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a well-recognized complication resulting with the higher morbid-mortality after cardiac surgery. In its most severe form, it increases the odds ratio of operative mortality 3–8-fold, length of stay in the Intensive Care Unit and hospital, and costs of care. Early diagnosis is critical for an optimal treatment of this complication. Just as the identification and correction of preoperative risk factors, the use of prophylactic measures during and after surgery to optimize renal function is essential to improve postoperative morbidity and mortality of these patients. Cardiopulmonary bypass produces an increased in tubular damage markers. Their measurement may be the most sensitive means of early detection of AKI because serum creatinine changes occur 48 h to 7 days after the original insult. Tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 are most promising as an early diagnostic tool. However, the ideal noninvasive, specific, sensitive, reproducible biomarker for the detection of AKI within 24 h is still not found. This article provides a review of the different perspectives of the CSA-AKI, including pathogenesis, risk factors, diagnosis, biomarkers, classification, postoperative management, and treatment. We searched the electronic databases, MEDLINE, PubMed, EMBASE using search terms relevant including pathogenesis, risk factors, diagnosis, biomarkers, classification, postoperative management, and treatment, in order to provide an exhaustive review of the different perspectives of the CSA-AKI. PMID:27716701

Brainstem Involvement as a Cause of Central Sleep Apnea: Pattern of Microstructural Cerebral Damage in Patients with Cerebral Microangiopathy

PubMed Central

Duning, Thomas; Deppe, Michael; Brand, Eva; Stypmann, Jörg; Becht, Charlotte; Heidbreder, Anna; Young, Peter

2013-01-01

Background The exact underlying pathomechanism of central sleep apnea with Cheyne-Stokes respiration (CSA-CSR) is still unclear. Recent studies have demonstrated an association between cerebral white matter changes and CSA. A dysfunction of central respiratory control centers in the brainstem was suggested by some authors. Novel MR-imaging analysis tools now allow far more subtle assessment of microstructural cerebral changes. The aim of this study was to investigate whether and what severity of subtle structural cerebral changes could lead to CSA-CSR, and whether there is a specific pattern of neurodegenerative changes that cause CSR. Therefore, we examined patients with Fabry disease (FD), an inherited, lysosomal storage disease. White matter lesions are early and frequent findings in FD. Thus, FD can serve as a "model disease" of cerebral microangiopathy to study in more detail the impact of cerebral lesions on central sleep apnea. Patients and Methods Genetically proven FD patients (n = 23) and age-matched healthy controls (n = 44) underwent a cardio-respiratory polysomnography and brain MRI at 3.0 Tesla. We applied different MR-imaging techniques, ranging from semiquantitative measurement of white matter lesion (WML) volumes and automated calculation of brain tissue volumes to VBM of gray matter and voxel-based diffusion tensor imaging (DTI) analysis. Results In 5 of 23 Fabry patients (22%) CSA-CSR was detected. Voxel-based DTI analysis revealed widespread structural changes in FD patients when compared to the healthy controls. When calculated as a separate group, DTI changes of CSA-CSR patients were most prominent in the brainstem. Voxel-based regression analysis revealed a significant association between CSR severity and microstructural DTI changes within the brainstem. Conclusion Subtle microstructural changes in the brainstem might be a neuroanatomical correlate of CSA-CSR in patients at risk of WML. DTI is more sensitive and specific than conventional structural MRI and other advanced MR analyses tools in demonstrating these abnormalities. PMID:23637744

Nano strain-amplifier: Making ultra-sensitive piezoresistance in nanowires possible without the need of quantum and surface charge effects

NASA Astrophysics Data System (ADS)

Phan, Hoang-Phuong; Dinh, Toan; Kozeki, Takahiro; Nguyen, Tuan-Khoa; Qamar, Afzaal; Namazu, Takahiro; Nguyen, Nam-Trung; Dao, Dzung Viet

2016-09-01

This paper presents an innovative nano strain-amplifier employed to significantly enhance the sensitivity of piezoresistive strain sensors. Inspired from the dogbone structure, the nano strain-amplifier consists of a nano thin frame released from the substrate, where nanowires were formed at the centre of the frame. Analytical and numerical results indicated that a nano strain-amplifier significantly increases the strain induced into a free standing nanowire, resulting in a large change in their electrical conductance. The proposed structure was demonstrated in p-type cubic silicon carbide nanowires fabricated using a top down process. The experimental data showed that the nano strain-amplifier can enhance the sensitivity of SiC strain sensors at least 5.4 times larger than that of the conventional structures. This result indicates the potential of the proposed strain-amplifier for ultra-sensitive mechanical sensing applications.

Lower bone turnover and relative bone deficits in men with metabolic syndrome: a matter of insulin sensitivity? The European Male Ageing Study.

PubMed

Laurent, M R; Cook, M J; Gielen, E; Ward, K A; Antonio, L; Adams, J E; Decallonne, B; Bartfai, G; Casanueva, F F; Forti, G; Giwercman, A; Huhtaniemi, I T; Kula, K; Lean, M E J; Lee, D M; Pendleton, N; Punab, M; Claessens, F; Wu, F C W; Vanderschueren, D; Pye, S R; O'Neill, T W

2016-11-01

We examined cross-sectional associations of metabolic syndrome and its components with male bone turnover, density and structure. Greater bone mass in men with metabolic syndrome was related to their greater body mass, whereas hyperglycaemia, hypertriglyceridaemia or impaired insulin sensitivity were associated with lower bone turnover and relative bone mass deficits. Metabolic syndrome (MetS) has been associated with lower bone turnover and relative bone mass or strength deficits (i.e. not proportionate to body mass index, BMI), but the relative contributions of MetS components related to insulin sensitivity or obesity to male bone health remain unclear. We determined cross-sectional associations of MetS, its components and insulin sensitivity (by homeostatic model assessment-insulin sensitivity (HOMA-S)) using linear regression models adjusted for age, centre, smoking, alcohol, and BMI. Bone turnover markers and heel broadband ultrasound attenuation (BUA) were measured in 3129 men aged 40-79. Two centres measured total hip, femoral neck, and lumbar spine areal bone mineral density ( a BMD, n = 527) and performed radius peripheral quantitative computed tomography (pQCT, n = 595). MetS was present in 975 men (31.2 %). Men with MetS had lower β C-terminal cross-linked telopeptide (β-CTX), N-terminal propeptide of type I procollagen (PINP) and osteocalcin (P < 0.0001) and higher total hip, femoral neck, and lumbar spine a BMD (P ≤ 0.03). Among MetS components, only hypertriglyceridaemia and hyperglycaemia were independently associated with PINP and β-CTX. Hyperglycaemia was negatively associated with BUA, hypertriglyceridaemia with hip a BMD and radius cross-sectional area (CSA) and stress-strain index. HOMA-S was similarly associated with PINP and β-CTX, BUA, and radius CSA in BMI-adjusted models. Men with MetS have higher a BMD in association with their greater body mass, while their lower bone turnover and relative deficits in heel BUA and radius CSA are mainly related to correlates of insulin sensitivity. Our findings support the hypothesis that underlying metabolic complications may be involved in the bone's failure to adapt to increasing bodily loads in men with MetS.

Correlation of embryonic skeletal muscle myotube physical characteristics with contractile force generation on an atomic force microscope-based bio-microelectromechanical systems device

NASA Astrophysics Data System (ADS)

Pirozzi, K. L.; Long, C. J.; McAleer, C. W.; Smith, A. S. T.; Hickman, J. J.

2013-08-01

Rigorous analysis of muscle function in in vitro systems is needed for both acute and chronic biomedical applications. Forces generated by skeletal myotubes on bio-microelectromechanical cantilevers were calculated using a modified version of Stoney's thin-film equation and finite element analysis (FEA), then analyzed for regression to physical parameters. The Stoney's equation results closely matched the more intensive FEA and the force correlated to cross-sectional area (CSA). Normalizing force to measured CSA significantly improved the statistical sensitivity and now allows for close comparison of in vitro data to in vivo measurements for applications in exercise physiology, robotics, and modeling neuromuscular diseases.

Reports of child sexual abuse of boys and girls: Longitudinal trends over a 20-year period in Victoria, Australia.

PubMed

Mathews, Ben; Bromfield, Leah; Walsh, Kerryann; Cheng, Qinglu; Norman, Rosana E

2017-04-01

Although prevalence studies show girls are more frequently sexually abused than boys, a significant proportion of boys also experience child sexual abuse (CSA). The challenges for public policy are amplified for boys due to less developed public and professional sensitisation to boys' experiences, conceptions of masculinity, and less research on boys including into reporting trends and outcomes. We conducted a 20-year longitudinal time-trend analysis of government data to identify reporting trends and report outcomes for CSA in Victoria, Australia from 1993 to 2012. We stratified by child gender and reporter status. Results indicate a new sensitisation to CSA, especially for boys, although this trend was not stable. Marked change occurred in the last five years, likely influenced by major social and political events. Comparison over time revealed that from 1993 to 2012, the rate of reporting of boys increased 2.6-fold whereas there was a 1.5-fold increase for girls. Comparing genders, with regards to rate of reporting, in 1993, the sex ratio of girls to boys was 2:1, while by 2012 this ratio changed to 1.14:1. Reports by police and other mandated reporters accounted for the majority of the increase in reports over the 20-year period, suggesting unequal sensitisation. Positive report outcomes (i.e. substantiations, findings of harm, and referral to services) increased twelve-fold for boys, and nearly five-fold for girls, indicating the increased levels of reports were based in actual clinical need. Most of this increase occurred from 2009 to 2012, influenced by a compound of social, political and agency-related factors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Predicting distant failure in early stage NSCLC treated with SBRT using clinical parameters.

PubMed

Zhou, Zhiguo; Folkert, Michael; Cannon, Nathan; Iyengar, Puneeth; Westover, Kenneth; Zhang, Yuanyuan; Choy, Hak; Timmerman, Robert; Yan, Jingsheng; Xie, Xian-J; Jiang, Steve; Wang, Jing

2016-06-01

The aim of this study is to predict early distant failure in early stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT) using clinical parameters by machine learning algorithms. The dataset used in this work includes 81 early stage NSCLC patients with at least 6months of follow-up who underwent SBRT between 2006 and 2012 at a single institution. The clinical parameters (n=18) for each patient include demographic parameters, tumor characteristics, treatment fraction schemes, and pretreatment medications. Three predictive models were constructed based on different machine learning algorithms: (1) artificial neural network (ANN), (2) logistic regression (LR) and (3) support vector machine (SVM). Furthermore, to select an optimal clinical parameter set for the model construction, three strategies were adopted: (1) clonal selection algorithm (CSA) based selection strategy; (2) sequential forward selection (SFS) method; and (3) statistical analysis (SA) based strategy. 5-cross-validation is used to validate the performance of each predictive model. The accuracy was assessed by area under the receiver operating characteristic (ROC) curve (AUC), sensitivity and specificity of the system was also evaluated. The AUCs for ANN, LR and SVM were 0.75, 0.73, and 0.80, respectively. The sensitivity values for ANN, LR and SVM were 71.2%, 72.9% and 83.1%, while the specificity values for ANN, LR and SVM were 59.1%, 63.6% and 63.6%, respectively. Meanwhile, the CSA based strategy outperformed SFS and SA in terms of AUC, sensitivity and specificity. Based on clinical parameters, the SVM with the CSA optimal parameter set selection strategy achieves better performance than other strategies for predicting distant failure in lung SBRT patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ca(2+)-dependent nonspecific permeability of the inner membrane of liver mitochondria in the guinea fowl (Numida meleagris).

PubMed

Vedernikov, Aleksander A; Dubinin, Mikhail V; Zabiakin, Vladimir A; Samartsev, Victor N

2015-06-01

This comparative study presents the results of the induction of Ca(2+)-dependent nonspecific permeability of the inner membrane (pore opening) of rat and guinea fowl liver mitochondria by mechanisms that are both sensitive and insensitive to cyclosporin A (CsA). It was established that energized rat and guinea fowl liver mitochondria incubated with 1 mM of inorganic phosphate (Pi) are capable of swelling upon addition of at least 125 and 875 nmol of CaCl2 per 1 mg protein, respectively. Under these conditions, the Ca(2+) release from the mitochondria of these animals and a drop in Δψ are observed. All of these processes are inhibited by 1 μM of CsA. FCCP, causing organelle de-energization, induces pore opening in rat and guinea fowl liver mitochondria upon addition of 45 и 625 nmol of CaCl2 per 1 mg protein, respectively. These results suggest the existence of a CsA-sensitive mechanism for the induction of Ca(2+)-dependent pores in guinea fowl liver mitochondria, which has been reported in rat liver mitochondria. However, guinea fowl liver mitochondria have a significantly greater resistance to Ca(2+) as a pore inducer compared to rat liver mitochondria. It was found that the addition of α,ω-hexadecanedioic acid (HDA) to rat and guinea fowl liver mitochondria incubated with CsA and loaded with Ca(2+) causes organelle swelling and Ca(2+) release from the matrix. It is assumed that in contrast to the CsA-sensitive pore, the CsA-insensitive pore induced by HDA in the inner membrane of guinea fowl liver mitochondria, as well as in rat liver mitochondria, is lipid in nature.

Development of a compact radiation-hardened low-noise front-end readout ASIC for CZT-based hard X-ray imager

NASA Astrophysics Data System (ADS)

Gao, W.; Gan, B.; Li, X.; Wei, T.; Gao, D.; Hu, Y.

2015-04-01

In this paper, we present the development and performances of a radiation-hardened front-end readout application-specific integrated circuit (ASIC) dedicated to CZT detectors for a hard X-ray imager in space applications. The readout channel consists of a charge sensitive amplifier (CSA), a CR-RC shaper, a fast shaper, a discriminator and a driving buffer. With the additional digital filtering, the readout channel can achieve very low noise performances and low power dissipation. An eight-channel prototype ASIC is designed and fabricated in 0.35 μm CMOS process. The energy range of the detected X-rays is evaluated as 1.45 keV to 281 keV. The gain is larger than 100 mV/fC. The equivalent noise charge (ENC) of the ASIC is 53 e- at zero farad plus 10 e- per picofarad. The power dissipation is less than 4.4 mW/channel. Through the measurement with a CZT detector, the energy resolution is less than 3.45 keV (FWHM) under the irradiation of the radioactive source 241Am. The radiation effect experiments indicate that the proposed ASIC can resist the total ionization dose (TID) irradiation of higher than 200 krad (Si).

PFM2: a 32 × 32 processor for X-ray diffraction imaging at FELs

NASA Astrophysics Data System (ADS)

Manghisoni, M.; Fabris, L.; Re, V.; Traversi, G.; Ratti, L.; Grassi, M.; Lodola, L.; Malcovati, P.; Vacchi, C.; Pancheri, L.; Benkechcache, M. E. A.; Dalla Betta, G.-F.; Xu, H.; Verzellesi, G.; Ronchin, S.; Boscardin, M.; Batignani, G.; Bettarini, S.; Casarosa, G.; Forti, F.; Giorgi, M.; Paladino, A.; Paoloni, E.; Rizzo, G.; Morsani, F.

2016-11-01

This work is concerned with the design of a readout chip for application to experiments at the next generation X-ray Free Electron Lasers (FEL). The ASIC, named PixFEL Matrix (PFM2), has been designed in a 65 nm CMOS technology and consists of 32 × 32 pixels. Each cell covers an area of 110 × 110 μm2 and includes a low-noise charge sensitive amplifier (CSA) with dynamic signal compression, a time-variant shaper used to process the preamplifier output signal, a 10-bit successive approximation register (SAR) analog-to-digital converter (ADC) and digital circuitry for channel control and data readout. Two different solutions for the readout channel, based on different versions of the time-variant filter, have been integrated in the chip. Both solutions can be operated in such a way to cope with the high frame rate (exceeding 1 MHz) foreseen for future X-ray FEL machines. The ASIC will be bump bonded to a slim/active edge pixel sensor to form the first demonstrator for the PixFEL X-ray imager. This work has been carried out in the frame of the PixFEL project funded by Istituto Nazionale di Fisica Nucleare (INFN), Italy.

Evaluation of the in vitro activity of ceragenins against Trichomonas vaginalis.

PubMed

Polat, Zubeyde Akin; Cetin, Ali; Savage, Poul B

2016-03-01

Trichomonosis, caused by the protozoan parasite Trichomonas vaginalis, is a curable sexually transmitted disease that is most commonly encountered worldwide. Increasing importance of trichomoniasis and emerging of resistance against metronidazole lead to search for alternative drugs with different mode of activity. The purpose of this study was to determine in vitro activity of ceragenins (CSA-13, CSA-44, CSA-13, and CSA-138) against the metronidazole-susceptible (ATCC 30001) and metronidazole-resistant (ATCC 50138) strains of T. vaginalis. The effective concentrations were evaluated using two strains of T. vaginalis with different metronidazole susceptibilities (ATCC 30001 and ATCC 50138) in the presence of dilution series of ceragenins in 24-well microtitre assays. Overall, all the ceragenins killed the metronidazole-susceptible (ATCC 30001) and metronidazole-resistant (ATCC 50138) strains of T. vaginalis (p>0.05). With regard to the their effects against the studied strains of T. vaginalis, in order of effectiveness, overall, the ceragenins ordered as CSA-13 (the most effective), CSA-131 and CSA-138 (effective similarly), and CSA-44 (the least effective) (p<0.05). All of the ceragenins reduced the trophozoite numbers of both of studied strains of T. vaginalis with a time- and dose- dependent manner (p<0.05). Although all of the study ceragenins, CSA-13, CSA-44, CSA-13, and CSA-138, killed the studied strains of T. vaginalis. CSA-13 is the leading ceragenin as the most effective anti-trichomonas compound, followed by CSA-131 and CSA-138. They have a potential to have a place in the armemantarium of gynecologic and urologic practice for the management of sexually transmitted diseases.

The effect of cyclosporin A, FK506 and rapamycin on the murine contact sensitivity reaction

PubMed Central

Salerno, A; Bonanno, C T; Caccamo, N; Cigna, D; Dominici, R; Ferro, C; Sireci, G; Dieli, F

1998-01-01

We have evaluated the effects of three potent immunosuppressive agents, cyclosporin A (CsA), FK506 and rapamycin, on the murine contact sensitivity (CS) reaction to the hapten trinitrochlorobenzene. Development of CS reaction requires participation of three distinct T cell subsets: αβ+, CD4+ T lymphocytes, which are the classical effector cell of the CS reaction, γδ+ T lymphocytes, and αβ+, double-negative (CD4− CD8−) T lymphocytes that express the B220 molecule and produce IL-4. We found that all three drugs inhibit the development of the CS reaction, but they affect different target cells. In fact, rapamycin and FK-506 block both αβ+, CD4+ and γδ+ T lymphocytes, while CsA inhibits only the αβ+, CD4+ T lymphocyte. None of the three drugs exerted any inhibitory activity on the αβ+, double-negative (CD4− CD8−) T lymphocytes. Hapten-immune lymph node cells from mice treated in vivo with CsA or FK506 failed to proliferate and to produce IL-2 when re-exposed to the specific antigen in vitro. In contrast, immune lymph node cells from mice that had been treated in vivo with rapamycin gave optimal antigen-specific proliferation and IL-2 production in vitro. The implications of these observations are discussed in relation to the use of these immunosuppressive agents for prevention of allograft rejection. PMID:9566798

How Much Child Sexual Abuse is “Below the Surface,” and Can We Help Adults Identify it Early?

PubMed Central

Martin, Erin K.; Silverstone, Peter H.

2013-01-01

Child sexual abuse (CSA) occurs frequently in society to children aged between 2 and 17. It is significantly more common in girls than boys, with the peak age for CSA occurring when girls are aged 13–17. Many children experience multiple episodes of CSA, as well as having high rates of other victimizations (such as physical assaults). One of the problems for current research in CSA is different definitions of what this means, and no recent review has clearly differentiated more severe forms of CSA, and how commonly this is disclosed. In general we suggest there are four types of behavior that should be included as CSA, namely (1) non-contact, (2) genital touching, (3) attempted vaginal and anal penetrative acts, and (4) vaginal and anal penetrative acts. Evidence suggests that CSA involving types (2), (3), and (4) is more likely to have significant long-term outcomes, and thus can be considered has having higher-impact. From the research to date approximately 15% of girls aged 2–17 experience higher-impact CSA (with most studies suggesting that between 12 and 18% of girls experience higher-impact CSA). Approximately 6% of boys experience higher-impact CSA (with most studies suggesting that between 5 and 8% experience higher-impact CSA). The data also suggests that in over 95% of cases the CSA is never disclosed to authorities. Thus, CSA is frequent but often not identified, and occurs “below the surface” in the vast majority of higher-impact cases. Helping adults to understand “below the surface” CSA might help them to recognize it early, but there are very few indicators specific to CSA, making this a challenging goal to achieve. Nonetheless, given that CSA frequently occurs with other types of abuse, a training program that focuses on both CSA and other abuse may offer a method to allow both early recognition and prevention by adults in the general population. PMID:23874306

Formative assessment of GP trainees' clinical skills.

PubMed

Wiener-Ogilvie, Sharon; Begg, Drummond

2012-03-01

Clinical skill assessment (CSA) has been an integral part of the Royal College of General Practitioners' membership examination (MRCGP) since 2008. It is an expensive, high-stakes examination with first time pass rates ranging from 76.4 to 81.3. In this paper we describe the South East Scotland Deanery, NHS Education Scotland, pilot of a formative clinical skills assessment (fCSA) using the principles of formative assessment and OSCE. The purpose of the study was to assess the acceptability of the fCSA and to examine whether trainees, identified during the fCSA as 'at risk of failing the MRCGP CSA exam', are more likely to fail the MRCGP CSA exam later on in the year. Trainees were assessed in four clinical skills stations under exam conditions. After each station they were given verbal feedback and subsequently both trainee and their trainer received written feedback. We assessed the value of the exercise through written feedback from trainees and trainers. Each trainee's performance in fCSA was triangulated with trainer assessment to identify 'flagged trainees'. We compared flagged and non-flagged trainees' performance in MRCGP CSA. Both trainees and trainers highly rated the fCSA. Overall 97% of non-flagged trainees have passed the RCGP CSA exam by May of that year in comparison to 80% of flagged trainees who have passed the RCGP CSA (P = 0.005). Trainers and trainees rated the fCSA as excellent and useful. We were able to demonstrate that the fCSA can be used to identify those trainees likely to fail the RCGP CSA. Contrary to reservations about the potential to demoralise trainees, the fCSA was viewed as a useful and a positive experience by both trainees and trainers. In addition, we suggest that feedback from fCSA was useful in triggering appropriate educational interventions. Early intervention with trainees who are predicted to fail the CSA has the potential to reduce deaneries overall fail rate. Preventing one trainee failure could save over £30 000.

10 CFR 95.17 - Processing facility clearance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... existing facility clearance granted by a current CSA and authorize possession of license or certificate... concerning the foreign intelligence threat, risk of unauthorized technology transfer, type and sensitivity of..., certificate holder, or other person must advise the NRC within 30 days of any significant events or changes...

10 CFR 95.17 - Processing facility clearance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... existing facility clearance granted by a current CSA and authorize possession of license or certificate... concerning the foreign intelligence threat, risk of unauthorized technology transfer, type and sensitivity of..., certificate holder, or other person must advise the NRC within 30 days of any significant events or changes...

Spectroscopic (FT-IR, FT-Raman and UV-Visible) investigations, NMR chemical shielding anisotropy (CSA) parameters of 2,6-Diamino-4-chloropyrimidine for dye sensitized solar cells using density functional theory.

PubMed

Gladis Anitha, E; Joseph Vedhagiri, S; Parimala, K

2015-02-05

The molecular structure, geometry optimization, vibrational frequencies of organic dye sensitizer 2,6-Diamino-4-chloropyrimidine (DACP) were studied based on Hartree-Fock (HF) and density functional theory (DFT) using B3LYP methods with 6-311++G(d,p) basis set. Ultraviolet-Visible (UV-Vis) spectrum was investigated by time dependent DFT (TD-DFT). Features of the electronic absorption spectrum in the UV-Visible regions were assigned based on TD-DFT calculation. The absorption bands are assigned to transitions. The interfacial electron transfer between semiconductor TiO2 electrode and dye sensitizer DACP is due to an electron injection process from excited dye to the semiconductor's conduction band. The observed and the calculated frequencies are found to be in good agreement. The energies of the frontier molecular orbitals (FMOS) have also been determined. The chemical shielding anisotropic (CSA) parameters are calculated from the NMR analysis, Stability of the molecule arising from hyperconjugative interactions and charge delocalization has been analyzed using natural bond orbital (NBO) analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Placenta-specific drug delivery by trophoblast-targeted nanoparticles in mice

PubMed Central

Zhang, Baozhen; Tan, Lunbo; Yu, Yan; Wang, Baobei; Chen, Zhilong; Han, Jinyu; Li, Mengxia; Chen, Jie; Xiao, Tianxia; Ambati, Balamurali K; Cai, Lintao; Yang, Qing; Nayak, Nihar R; Zhang, Jian; Fan, Xiujun

2018-01-01

Rationale: The availability of therapeutics to treat pregnancy complications is severely lacking, mainly due to the risk of harm to the fetus. In placental malaria, Plasmodium falciparum-infected erythrocytes (IEs) accumulate in the placenta by adhering to chondroitin sulfate A (CSA) on the surfaces of trophoblasts. Based on this principle, we have developed a method for targeted delivery of payloads to the placenta using a synthetic placental CSA-binding peptide (plCSA-BP) derived from VAR2CSA, a CSA-binding protein expressed on IEs. Methods: A biotinylated plCSA-BP was used to examine the specificity of plCSA-BP binding to mouse and human placental tissue in tissue sections in vitro. Different nanoparticles, including plCSA-BP-conjugated nanoparticles loaded with indocyanine green (plCSA-INPs) or methotrexate (plCSA-MNPs), were administered intravenously to pregnant mice to test their efficiency at drug delivery to the placenta in vivo. The tissue distribution and localization of the plCSA-INPs were monitored in live animals using an IVIS imaging system. The effect of plCSA-MNPs on fetal and placental development and pregnancy outcome were examined using a small-animal high-frequency ultrasound (HFUS) imaging system, and the concentrations of methotrexate in fetal and placental tissues were measured using high-performance liquid chromatography (HPLC). Results: plCSA-BP binds specifically to trophoblasts and not to other cell types in the placenta or to CSA-expressing cells in other tissues. Moreover, we found that intravenously administered plCSA-INPs accumulate in the mouse placenta, and ex vivo analysis of the fetuses and placentas confirmed placenta-specific delivery of these nanoparticles. We also demonstrate successful delivery of methotrexate specifically to placental cells by plCSA-BP-conjugated nanoparticles, resulting in dramatic impairment of placental and fetal development. Importantly, plCSA-MNPs treatment had no apparent adverse effects on maternal tissues. Conclusion: These results demonstrate that plCSA-BP-guided nanoparticles could be used for the targeted delivery of payloads to the placenta and serve as a novel placenta-specific drug delivery option. PMID:29774074

A Second Quorum-Sensing System Regulates Cell Surface Properties but Not Phenazine Antibiotic Production in Pseudomonas aureofaciens

PubMed Central

Zhang, Zhongge; Pierson, Leland S.

2001-01-01

The root-associated biological control bacterium Pseudomonas aureofaciens 30-84 produces a range of exoproducts, including protease and phenazines. Phenazine antibiotic biosynthesis by phzXYFABCD is regulated in part by the PhzR-PhzI quorum-sensing system. Mutants defective in phzR or phzI produce very low levels of phenazines but wild-type levels of exoprotease. In the present study, a second genomic region of strain 30-84 was identified that, when present in trans, increased β-galactosidase activity in a genomic phzB::lacZ reporter and partially restored phenazine production to a phzR mutant. Sequence analysis identified two adjacent genes, csaR and csaI, that encode members of the LuxR-LuxI family of regulatory proteins. No putative promoter region is present upstream of the csaI start codon and no lux box-like element was found in either the csaR promoter or the 30-bp intergenic region between csaR and csaI. Both the PhzR-PhzI and CsaR-CsaI systems are regulated by the GacS-GacA two-component regulatory system. In contrast to the multicopy effects of csaR and csaI in trans, a genomic csaR mutant (30-84R2) and a csaI mutant (30-84I2) did not exhibit altered phenazine production in vitro or in situ, indicating that the CsaR-CsaI system is not involved in phenazine regulation in strain 30-84. Both mutants also produced wild-type levels of protease. However, disruption of both csaI and phzI or both csaR and phzR eliminated both phenazine and protease production completely. Thus, the two quorum-sensing systems do not interact for phenazine regulation but do interact for protease regulation. Additionally, the CsaI N-acylhomoserine lactone (AHL) signal was not recognized by the phenazine AHL reporter 30-84I/Z but was recognized by the AHL reporters Chromobacterium violaceum CV026 and Agrobacterium tumefaciens A136(pCF240). Inactivation of csaR resulted in a smooth mucoid colony phenotype and formation of cell aggregates in broth, suggesting that CsaR is involved in regulating biosynthesis of cell surface components. Strain 30-84I/I2 exhibited mucoid colony and clumping phenotypes similar to those of 30-84R2. Both phenotypes were reversed by complementation with csaR-csaI or by the addition of the CsaI AHL signal. Both quorum-sensing systems play a role in colonization by strain 30-84. Whereas loss of PhzR resulted in a 6.6-fold decrease in colonization by strain 30-84 on wheat roots in natural soil, a phzR csaR double mutant resulted in a 47-fold decrease. These data suggest that gene(s) regulated by the CsaR-CsaI system also plays a role in the rhizosphere competence of P. aureofaciens 30-84. PMID:11526037

Difficulties in estimating muscle forces from muscle cross-sectional area. An example using the psoas major muscle.

PubMed

Gatton, M L; Pearcy, M J; Pettet, G J

1999-07-15

Most biomechanical models use muscle cross-sectional area (CSA) as an indicator of maximum isometric muscle force. In general, there are multiple estimates of CSA for the same muscle. For example, numerous studies have estimated the CSA of the psoas major muscle using different subject populations and positions. However, few studies have combined the available information to obtain an overall estimate of CSA or investigated the effect different subject characteristics may have on CSA. In the present update, nine studies that reported psoas major CSA or physiologic CSA were compared with respect to subject characteristics, methodology, and results. Corrections to cadaveric data were made to adjust physiologic CSA to CSA. Comparison of reported values for living subjects indicated that females have smaller mean CSA than males for the psoas major muscle and that body size does not significantly influence muscle CSA in males. Areas derived from cadaveric data were smaller than similar studies on living subjects, possibly because of subject age, removal of tendinous and fatty components of fascicles, and lack of detailed data for fascicle angles in the supine position. Results indicate that researchers who use muscle CSA in biomechanical models should carefully assess the appropriateness of the data used, particularly in relation to potential sex differences and the influence of postural changes on CSA.

Pulmonary hypertension and computed tomography measurement of small pulmonary vessels in severe emphysema.

PubMed

Matsuoka, Shin; Washko, George R; Yamashiro, Tsuneo; Estepar, Raul San Jose; Diaz, Alejandro; Silverman, Edwin K; Hoffman, Eric; Fessler, Henry E; Criner, Gerard J; Marchetti, Nathaniel; Scharf, Steven M; Martinez, Fernando J; Reilly, John J; Hatabu, Hiroto

2010-02-01

Vascular alteration of small pulmonary vessels is one of the characteristic features of pulmonary hypertension in chronic obstructive pulmonary disease. The in vivo relationship between pulmonary hypertension and morphological alteration of the small pulmonary vessels has not been assessed in patients with severe emphysema. We evaluated the correlation of total cross-sectional area of small pulmonary vessels (CSA) assessed on computed tomography (CT) scans with the degree of pulmonary hypertension estimated by right heart catheterization. In 79 patients with severe emphysema enrolled in the National Emphysema Treatment Trial (NETT), we measured CSA less than 5 mm(2) (CSA(<5)) and 5 to 10 mm(2) (CSA(5-10)), and calculated the percentage of total CSA for the lung area (%CSA(<5) and %CSA(5-10), respectively). The correlations of %CSA(<5) and %CSA(5-10) with pulmonary arterial mean pressure (Ppa) obtained by right heart catheterization were evaluated. Multiple linear regression analysis using Ppa as the dependent outcome was also performed. The %CSA(<5) had a significant negative correlation with Ppa (r = -0.512, P < 0.0001), whereas the correlation between %CSA(5-10) and Ppa did not reach statistical significance (r = -0.196, P = 0.083). Multiple linear regression analysis showed that %CSA(<5) and diffusing capacity of carbon monoxide (DL(CO)) % predicted were independent predictors of Ppa (r(2) = 0.541): %CSA (<5) (P < 0.0001), and DL(CO) % predicted (P = 0.022). The %CSA(<5) measured on CT images is significantly correlated to Ppa in severe emphysema and can estimate the degree of pulmonary hypertension.

A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis.

PubMed

Gilger, Brian C; Salmon, Jacklyn H; Wilkie, David A; Cruysberg, Lars P J; Kim, Jonghyeon; Hayat, Matt; Kim, Hyuncheol; Kim, Stephanie; Yuan, Peng; Lee, Susan S; Harrington, Susan M; Murray, Patrick R; Edelhauser, Henry F; Csaky, Karl G; Robinson, Michael R

2006-06-01

To determine the feasibility, safety, and effectiveness of an episcleral or deep scleral lamellar sustained release cyclosporine (CsA) device in a naturally occurring animal model of uveitis. A two-compartment perfusion chamber was used to assess in vitro human and equine scleral permeability of fluorescein, dexamethasone-fluorescein, or CsA. A biodegradable, matrix-reservoir CsA implant was designed, and release rates of CsA were determined in vitro. Tissue CsA levels were measured in eyes with the implant. Horses with equine recurrent uveitis (ERU) received episcleral or deep scleral lamellar CsA implants and were monitored for up to 3 years. Dexamethasone-fluorescein and CsA penetrated the in vitro equine sclera poorly; however, low but detectable levels of CsA were detected intraocularly in vivo. The implant placed episclerally failed to control inflammatory episodes in ERU. CsA implants placed in the deep sclera adjacent to the suprachoroidal space resulted in high levels of CsA in most ocular tissues. In clinical equine patients with ERU, frequency of uveitic flare-ups was significantly decreased after implantation of a deep scleral lamellar CsA implant. Diffusion of CsA across the sclera from the episcleral space was not a feasible method of drug delivery to the equine eye. However, placing a deep scleral lamellar CsA implant adjacent to the suprachoroidal space was effective in achieving therapeutic ocular drug concentrations and controlling uveitis in horses with ERU.

Evidence for globally shared, cross-reacting polymorphic epitopes in the pregnancy-associated malaria vaccine candidate VAR2CSA.

PubMed

Avril, Marion; Kulasekara, Bridget R; Gose, Severin O; Rowe, Chris; Dahlbäck, Madeleine; Duffy, Patrick E; Fried, Michal; Salanti, Ali; Misher, Lynda; Narum, David L; Smith, Joseph D

2008-04-01

Pregnancy-associated malaria (PAM) is characterized by the placental sequestration of Plasmodium falciparum-infected erythrocytes (IEs) with the ability to bind to chondroitin sulfate A (CSA). VAR2CSA is a leading candidate for a pregnancy malaria vaccine, but its large size ( approximately 350 kDa) and extensive polymorphism may pose a challenge to vaccine development. In this study, rabbits were immunized with individual VAR2CSA Duffy binding-like (DBL) domains expressed in Pichia pastoris or var2csa plasmid DNA and sera were screened on different CSA-binding parasite lines. Rabbit antibodies to three recombinant proteins (DBL1, DBL3, and DBL6) and four plasmid DNAs (DBL1, DBL3, DBL5, and DBL6) reacted with homologous FCR3-CSA IEs. By comparison, antibodies to the DBL4 domain were unable to react with native VAR2CSA protein unless it was first partially proteolyzed with trypsin or chymotrypsin. To investigate the antigenic relationship of geographically diverse CSA-binding isolates, rabbit immune sera were screened on four heterologous CSA-binding lines from different continental origins. Antibodies did not target conserved epitopes exposed in all VAR2CSA alleles; however, antisera to several DBL domains cross-reacted on parasite isolates that had polymorphic loops in common with the homologous immunogen. This study demonstrates that VAR2CSA contains common polymorphic epitopes that are shared between geographically diverse CSA-binding lines.

Complexity of childhood sexual abuse: predictors of current post-traumatic stress disorder, mood disorders, substance use, and sexual risk behavior among adult men who have sex with men.

PubMed

Boroughs, Michael S; Valentine, Sarah E; Ironson, Gail H; Shipherd, Jillian C; Safren, Steven A; Taylor, S Wade; Dale, Sannisha K; Baker, Joshua S; Wilner, Julianne G; O'Cleirigh, Conall

2015-10-01

Men who have sex with men (MSM) are the group most at risk for HIV and represent the majority of new infections in the United States. Rates of childhood sexual abuse (CSA) among MSM have been estimated as high as 46 %. CSA is associated with increased risk of HIV and greater likelihood of HIV sexual risk behavior. The purpose of this study was to identify the relationships between CSA complexity indicators and mental health, substance use, sexually transmitted infections, and HIV sexual risk among MSM. MSM with CSA histories (n = 162) who were screened for an HIV prevention efficacy trial completed comprehensive psychosocial assessments. Five indicators of complex CSA experiences were created: CSA by family member, CSA with penetration, CSA with physical injury, CSA with intense fear, and first CSA in adolescence. Adjusted regression models were used to identify relationships between CSA complexity and outcomes. Participants reporting CSA by family member were at 2.6 odds of current alcohol use disorder (OR 2.64: CI 1.24-5.63), two times higher odds of substance use disorder (OR 2.1: CI 1.02-2.36), and 2.7 times higher odds of reporting an STI in the past year (OR 2.7: CI 1.04-7.1). CSA with penetration was associated with increased likelihood of current PTSD (OR 3.17: CI 1.56-6.43), recent HIV sexual risk behavior (OR 2.7: CI 1.16-6.36), and a greater number of casual sexual partners (p = 0.02). Both CSA with Physical Injury (OR 4.05: CI 1.9-8.7) and CSA with Intense Fear (OR 5.16: CI 2.5-10.7) were related to increased odds for current PTSD. First CSA in adolescence was related to increased odds of major depressive disorder. These findings suggest that CSA, with one or more complexities, creates patterns of vulnerabilities for MSM, including post-traumatic stress disorder, substance use, and sexual risk taking, and suggests the need for detailed assessment of CSA and the development of integrated HIV prevention programs that address mental health and substance use comorbidities.

Complexity of childhood sexual abuse: Predictors of current PTSD, mood disorders, substance use, and sexual risk behavior among adult men who have sex with men

PubMed Central

Boroughs, Michael S.; Valentine, Sarah E.; Ironson, Gail H.; Shipherd, Jillian C.; Safren, Steven A.; Taylor, S. Wade; Dale, Sannisha K.; Baker, Joshua S.; Wilner, Julianne G.; O'Cleirigh, Conall

2016-01-01

Men who have sex with men (MSM) are the group most at risk for HIV and represent the majority of new infections in the United States. Rates of childhood sexual abuse (CSA) among MSM have been estimated as high as 46%. CSA is associated with increased risk of HIV and greater likelihood of HIV sexual risk behavior. The purpose of this study was to identify the relationships between CSA complexity indicators and mental health, substance use, sexually transmitted infections (STIs) and HIV sexual risk among MSM. MSM with CSA histories (n = 162) who were screened for an HIV-prevention efficacy trial completed comprehensive psychosocial assessments. Five indicators of complex CSA experiences were created: CSA by family member, CSA with penetration, CSA with physical injury, CSA with intense fear, and first CSA in adolescence. Adjusted regression models were used to identify relationships between CSA complexity and outcomes. Participants reporting CSA by family member were at 2.6 odds of current alcohol use disorder (OR: 2.64: CI 1.24 – 5.63), 2 times higher odds of substance use disorder (OR 2.1: CI 1.02 – 2.36), and 2.7 times higher odds of reporting an STI in the past year (OR 2.7: CI 1.04 – 7.1). CSA with penetration was associated with increased likelihood of current PTSD (OR 3.17: CI 1.56 – 6.43), recent HIV sexual risk behavior (OR 2.7: CI 1.16 – 6.36) and a greater number of casual sexual partners (p = .02). Both CSA with Physical Injury (OR 4.05: CI 1.9 – 8.7) and CSA with Intense Fear (OR 5.16: CI 2.5 – 10.7) were related to increased odds for current PTSD. First CSA in adolescence was related to increased odds of major depressive disorder. These findings suggest that CSA, with one or more complexities, creates patterns of vulnerabilities for MSM, including PTSD, substance use, and sexual risk taking and suggests the need for detailed assessment of CSA and the development of integrated HIV prevention programs that address mental health and substance use comorbidities. PMID:26159863

Relation of Natriuretic Peptide Concentrations to Central Sleep Apnea in Patients With Heart Failure

PubMed Central

Calvin, Andrew D.; Somers, Virend K.; van der Walt, Christelle; Scott, Christopher G.

2011-01-01

Background: Central sleep apnea (CSA) is frequent among patients with heart failure (HF) and associated with increased morbidity and mortality. Elevated cardiac filling pressures promote CSA and atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) secretion. We hypothesized that circulating natriuretic peptide concentrations predict CSA. Methods: Consecutive patients with HF (n = 44) with left ventricular ejection fraction (LVEF) ≤ 35% underwent polysomnography for detection of CSA. CSA was defined as an apnea-hypopnea index ≥ 15 with ≥ 50% central apneic events. The relation of natriuretic peptide concentrations to CSA was evaluated by estimation of ORs and receiver operator characteristics (ROCs). Results: Twenty-seven subjects (61%) had CSA, with men more frequently affected than women (73% vs 27%; OR, 7.1; P = .01); given that only three women had CSA, further analysis was restricted to men. Subjects with CSA had higher mean ANP (4,336 pg/mL vs 2,510 pg/mL, P = .03) and BNP concentrations (746 pg/mL vs 379 pg/mL, P = .05). ANP and BNP concentrations were significantly related to CSA (OR, 3.7 per 3,000 pg/mL, P = .03 and OR, 1.5 per 200 pg/mL, P = .04, respectively), whereas age, LVEF, and New York Heart Association functional class were not. Concentrations of ANP and BNP were predictive of CSA as ROC demonstrated areas under the curve of 0.75 and 0.73, respectively. Conclusions: Risk of CSA is related to severity of HF. ANP and BNP concentrations performed similarly for detection of CSA; low concentrations appear associated with low risk for CSA in men. PMID:21636668

78 FR 79423 - Energy Efficiency Program for Industrial Equipment: Petition of CSA Group for Classification as a...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-30

.... Evaluation and Testing CSA Group with the manufacturer's assistance prepares a motor control list...-0053] Energy Efficiency Program for Industrial Equipment: Petition of CSA Group for Classification as a...: This notice announces receipt of a petition from CSA Group (CSA) seeking classification as a nationally...

Amorphous solid dispersion of cyclosporine A prepared with fine droplet drying process: Physicochemical and pharmacokinetic characterization.

PubMed

Suzuki, Hiroki; Moritani, Tatsuru; Morinaga, Tadahiko; Seto, Yoshiki; Sato, Hideyuki; Onoue, Satomi

2017-03-15

The present study aimed to develop an amorphous solid dispersion (ASD) of cyclosporine A (CsA) by a fine droplet drying (FDD) process for improvement in oral absorption of CsA. CsA and hydroxypropyl cellulose-SSL were dissolved in 1,4-dioxane, and the solution was powdered by the FDD process to obtain the ASD formulation of CsA (ASD/CsA). The ASD/CsA was characterized in terms of morphology, particle size distribution, crystallinity, dissolution behavior, physicochemical stability, and pharmacokinetic behavior in rats. The ASD/CsA was obtained in the form of uniform spherical particles, and the span factor was calculated to be ca. 0.4. CsA in the formulation existed in an amorphous state. The ASD/CsA exhibited a higher dissolution behavior of CsA than amorphous CsA, whereas storage of the ASD/CsA under accelerated conditions led to impairment in the dissolution behavior. The constant release of CsA from non-aged ASD/CsA was observed during dissolution testing. After oral administration of CsA samples (10mg-CsA/kg) in rats, the ASD/CsA showed a high and sustained plasma concentration of CsA as evidenced by a 18-fold increase in the oral bioavailability of CsA compared with amorphous CsA. From these findings, the FDD process might be an efficacious option for the ASD formulation of CsA with enhanced biopharmaceutics properties. Copyright © 2017 Elsevier B.V. All rights reserved.

Structure of the DBL3x domain of pregnancy-associated malaria protein VAR2CSA complexed with chondroitin sulfate A

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

Singh, K.; Gittis, A.G.; Nguyen, P.

Plasmodium falciparum-infected erythrocytes bind to chondroitin sulfate A (CSA) in the placenta via the VAR2CSA protein, a member of the P. falciparum erythrocyte membrane protein-1 family, leading to life-threatening malaria in pregnant women with severe effects on their fetuses and newborns. Here we describe the structure of the CSA binding DBL3x domain, a Duffy binding-like (DBL) domain of VAR2CSA. By forming a complex of DBL3x with CSA oligosaccharides and determining its structure, we have identified the CSA binding site to be a cluster of conserved positively charged residues on subdomain 2 and subdomain 3. Mutation or chemical modification of lysinemore » residues at the site markedly diminished CSA binding to DBL3x. The location of the CSA binding site is an important step forward in the molecular understanding of pregnancy-associated malaria and offers a new target for vaccine development.« less

VAR2CSA domains expressed in Escherichia coli induce cross-reactive antibodies to native protein.

PubMed

Oleinikov, Andrew V; Francis, Susan E; Dorfman, Jeffrey R; Rossnagle, Eddie; Balcaitis, Stephanie; Getz, Tony; Avril, Marion; Gose, Severin; Smith, Joseph D; Fried, Michal; Duffy, Patrick E

2008-04-15

The variant surface antigen VAR2CSA is a pregnancy malaria vaccine candidate, but its size and polymorphism are obstacles to development. We expressed 3D7-type VAR2CSA domains in Escherichia coli as insoluble His-tagged proteins (Duffy binding-like [DBL] domains DBL1, DBL3, DBL4, and DBL5) that were denatured and refolded or as soluble glutathione S-transferase-tagged protein (DBL6). Anti-DBL5 antiserum cross-reacted with surface proteins of chondroitin sulfate A (CSA)-binding laboratory strains (3D7-CSA and FCR3-CSA) and a clinical pregnancy malaria isolate, whereas anti-DBL6 antiserum reacted only to 3D7 surface protein. This is the first report that E. coli-expressed VAR2CSA domains induce antibody to native VAR2CSA.

Effects of sex, parity, and sequence variation on seroreactivity to candidate pregnancy malaria vaccine antigens.

PubMed

Oleinikov, Andrew V; Rossnagle, Eddie; Francis, Susan; Mutabingwa, Theonest K; Fried, Michal; Duffy, Patrick E

2007-07-01

Plasmodium falciparum-infected erythrocytes adhere to chondroitin sulfate A (CSA) to sequester in the human placenta, and pregnancy malaria (PM) is associated with the development of disease in and the death of both mother and child. A PM vaccine appears to be feasible, because women become protected as they develop antibodies against placental infected erythrocytes (IEs). Two IE surface molecules, VAR1CSA and VAR2CSA, bind CSA in vitro and are potential vaccine candidates. We expressed all domains of VAR1CSA and VAR2CSA as mammalian cell surface proteins, using a novel approach that allows rapid purification, immobilization, and quantification of target antigen. For serum samples from East Africa, we measured reactivity to all domains, and we examined the effects of host sex and parity, as well as the effects of parasite antigenic variation. Serum samples obtained from multigravid women had a higher reactivity to all VAR2CSA domains than did those obtained from primigravid women or from men. Conversely, serum samples obtained from men had consistently higher reactivity to VAR1CSA domains than did those obtained from gravid women. Seroreactivity was strongly influenced by antigenic variation of VAR2CSA Duffy binding-like domains. Women acquire antibodies to VAR2CSA over successive pregnancies, but they lose reactivity to VAR1CSA. Serum reactivity to VAR2CSA is variant specific, and future studies should examine the degree to which functional antibodies, such as binding-inhibition antibodies, are variant specific.

Evidence for Globally Shared, Cross-Reacting Polymorphic Epitopes in the Pregnancy-Associated Malaria Vaccine Candidate VAR2CSA▿

PubMed Central

Avril, Marion; Kulasekara, Bridget R.; Gose, Severin O.; Rowe, Chris; Dahlbäck, Madeleine; Duffy, Patrick E.; Fried, Michal; Salanti, Ali; Misher, Lynda; Narum, David L.; Smith, Joseph D.

2008-01-01

Pregnancy-associated malaria (PAM) is characterized by the placental sequestration of Plasmodium falciparum-infected erythrocytes (IEs) with the ability to bind to chondroitin sulfate A (CSA). VAR2CSA is a leading candidate for a pregnancy malaria vaccine, but its large size (∼350 kDa) and extensive polymorphism may pose a challenge to vaccine development. In this study, rabbits were immunized with individual VAR2CSA Duffy binding-like (DBL) domains expressed in Pichia pastoris or var2csa plasmid DNA and sera were screened on different CSA-binding parasite lines. Rabbit antibodies to three recombinant proteins (DBL1, DBL3, and DBL6) and four plasmid DNAs (DBL1, DBL3, DBL5, and DBL6) reacted with homologous FCR3-CSA IEs. By comparison, antibodies to the DBL4 domain were unable to react with native VAR2CSA protein unless it was first partially proteolyzed with trypsin or chymotrypsin. To investigate the antigenic relationship of geographically diverse CSA-binding isolates, rabbit immune sera were screened on four heterologous CSA-binding lines from different continental origins. Antibodies did not target conserved epitopes exposed in all VAR2CSA alleles; however, antisera to several DBL domains cross-reacted on parasite isolates that had polymorphic loops in common with the homologous immunogen. This study demonstrates that VAR2CSA contains common polymorphic epitopes that are shared between geographically diverse CSA-binding lines. PMID:18250177

Early-age hydration and volume change of calcium sulfoaluminate cement-based binders

NASA Astrophysics Data System (ADS)

Chaunsali, Piyush

Shrinkage cracking is a predominant deterioration mechanism in structures with high surface-to-volume ratio. One way to allay shrinkage-induced stresses is to use calcium sulfoaluminate (CSA) cement whose early-age expansion in restrained condition induces compressive stress that can be utilized to counter the tensile stresses due to shrinkage. In addition to enhancing the resistance against shrinkage cracking, CSA cement also has lower carbon footprint than that of Portland cement. This dissertation aims at improving the understanding of early-age volume change of CSA cement-based binders. For the first time, interaction between mineral admixtures (Class F fly ash, Class C fly ash, and silica fume) and OPC-CSA binder was studied. Various physico-chemical factors such as the hydration of ye'elimite (main component in CSA cement), amount of ettringite (the main phase responsible for expansion in CSA cement), supersaturation with respect to ettringite in cement pore solution, total pore volume, and material stiffness were monitored to examine early-age expansion characteristics. This research validated the crystallization stress theory by showing the presence of higher supersaturation level of ettringite, and therefore, higher crystallization stress in CSA cement-based binders. Supersaturation with respect to ettringite was found to increase with CSA dosage and external supply of gypsum. Mineral admixtures (MA) altered the expansion characteristics in OPC-CSA-MA binders with fixed CSA cement. This study reports that fly ash (FA) behaves differently depending on its phase composition. The Class C FA-based binder (OPC-CSA-CFA) ceased expanding beyond two days unlike other OPC-CSA-MA binders. Three factors were found to govern expansion of CSA cement-based binders: 1) volume fraction of ettringite in given pore volume, 2) saturation level of ettringite, and 3) dynamic modulus. Various models were utilized to estimate the macroscopic tensile stress in CSA cement-based binders without taking into account the viscoelastic effects. For the first time, model based on poromechanics was used to calculate the macroscopic tensile stress that develops in CSA cement-based binders due to crystallization of ettringite. The models enabled a reasonable prediction of tensile stress due to crystallization of ettringite including the failure of an OPC-CSA binder which had high CSA cement content. Elastic strain based on crystallization stress was calculated and compared with the observed strain. A mismatch between observed and calculated elastic strain indicated the presence of early-age creep. Lastly, the application of CSA cement in concretes is discussed to link the paste and concrete behavior.

Childhood Sexual Abuse in Adolescents Adjudicated for Sexual Offenses: Mental Health Consequences and Sexual Offending Behaviors.

PubMed

Morais, Hugo B; Alexander, Apryl A; Fix, Rebecca L; Burkhart, Barry R

2018-02-01

Most studies on the mental health consequences of childhood sexual abuse (CSA) focus predominantly on CSA survivors who do not commit sexual offenses. The current study examined the effects of CSA on 498 male adolescents adjudicated for sexual offenses who represent the small portion of CSA survivors who engage in sexual offenses. The prevalence of internalizing symptoms, parental attachment difficulties, specific sexual offending behaviors, and risk for sexually offending were compared among participants with and without a history of CSA. Results indicated that participants with a history of CSA were more likely to be diagnosed with major depression and posttraumatic stress disorder than those who did not report a history of CSA. A history of CSA was also positively correlated with risk for sexually offending and with specific offense patterns and consensual sexual behaviors. No significant differences emerged on parental attachment difficulties. These results highlight that adolescents adjudicated for sexual offenses with a history of CSA present with differences in sexual and psychological functioning as well as markedly different offending patterns when compared with those without a CSA history. Clinical implications and future directions are discussed.

Left Atrial Size, Chemosensitivity, and Central Sleep Apnea in Heart Failure

PubMed Central

Calvin, Andrew D.; Somers, Virend K.; Johnson, Bruce D.; Scott, Christopher G.

2014-01-01

BACKGROUND: Central sleep apnea (CSA) is common among patients with heart failure (HF) and is promoted by elevated CO2 chemosensitivity. Left atrial size is a marker of the hemodynamic severity of HF. The aim of this study was to determine if left atrial size predicts chemosensitivity to CO2 and CSA in patients with HF. METHODS: Patients with HF with left ventricular ejection fraction ≤ 35% underwent polysomnography for detection of CSA, echocardiography, and measurement of CO2 chemosensitivity. CSA was defined as an apnea-hypopnea index (AHI) ≥ 15/h with ≥ 50% central apneic events. The relation of clinical and echocardiographic parameters to chemosensitivity and CSA were evaluated by linear regression, estimation of ORs, and receiver operator characteristics. RESULTS: Of 46 subjects without OSA who had complete data for analysis, 25 had CSA. The only parameter that significantly correlated with chemosensitivity was left atrial volume index (LAVI) (r = 0.40, P < .01). LAVI was greater in those with CSA than those without CSA (59.2 mL/m2 vs 36.4 mL/m2, P < .001) and significantly correlated with log-transformed AHI (r = 0.46, P = .001). LAVI was the best predictor of CSA (area under the curve = 0.83). A LAVI ≤ 33 mL/m2 was associated with 22% risk for CSA, while LAVI ≥ 53 mL/m2 was associated with 92% risk for CSA. CONCLUSIONS: Increased LAVI is associated with heightened CO2 chemosensitivity and greater frequency of CSA. LAVI may be useful to guide referral for polysomnography for detection of CSA in patients with HF. PMID:24522490

Use of the local lymph node assay in assessment of immune function.

PubMed

van den Berg, Femke A; Baken, Kirsten A; Vermeulen, Jolanda P; Gremmer, Eric R; van Steeg, Harry; van Loveren, Henk

2005-07-01

The murine local lymph node assay (LLNA) was originally developed as a predictive test method for the identification of chemicals with sensitizing potential. In this study we demonstrated that an adapted LLNA can also be used as an immune function assay by studying the effects of orally administered immunomodulating compounds on the T-cell-dependent immune response induced by the contact sensitizer 2,4-dinitrochlorobenzene (DNCB). C57Bl/6 mice were treated with the immunotoxic compounds cyclosporin A (CsA), bis(tri-n-butyltin)oxide (TBTO) or benzo[a]pyrene, (B[a]P). Subsequently, cell proliferation and interferon-gamma (IFN-gamma) and interleukin (IL)-4 release were determined in the auricular lymph nodes (LNs) after DNCB application on both ears. Immunosuppression induced by CsA, TBTO and B[a]P was clearly detectable in this application of the LLNA. Cytokine release measurements proved valuable to confirm the results of the cell proliferation assay and to obtain an indication of the effect on Th1/Th2 balance. We believe to have demonstrated the applicability of an adapted LLNA as an immune function assay in the mouse.

Combined flurbiprofen and cyclosporin-A does not attenuate bone loss and exaggerates renal impairment.

PubMed

Sass, D A; Rucinski, B; Bryer, H P; Mann, G N; Yuan, Z; Ma, Y; Jee, W S; Epstein, S

1996-10-01

Cyclosporine (CsA) is a potent immunosuppressant that has revolutionized the success of organ transplantation. Flurbiprofen (FB), a propionic acid derivative NSAID, has been demonstrated in vivo to reduce osteoclast numbers in normal rats. The aim of this experiment was to determine whether addition of FB to CsA-treated rats could prevent the bone changes associated with CsA therapy. Forty-eight 10-12-week-old male Sprague-Dawley rats were randomized to receive, daily for 28 days: (1) CsA vehicle p.o. plus FB vehicle sc; (2) CsA (15 mg/kg) p.o. plus FB vehicle sc, (3) CsA vehicle p.o. plus FB (1.5 mg/kg) sc; and (4) CsA (15 mg/kg) p.o. plus FB (1.5 mg/kg) sc. Rats were weighed and venous blood sampled at baseline, 14 days, and 28 days for determination of glucose, Ca+2, BUN, creatinine, PTH, osteocalcin, and 1,25(OH)2 vitamin D. Tibiae were removed following killing, after double labeling for histomorphometry. Body mass was significantly lower than control in all rats receiving CsA on days 14 and 28 while blood glucose was only elevated in the CsA alone group. Day 28 BUN and creatinine were significantly elevated in the CsA group and the combination of CsA and FB revealed an exacerbation of this trend. Vitamin D and osteocalcin were consistently increased in the CsA and CsA/FB groups. Bone histomorphometry showed evidence of trabecular osteopenia in CsA and CsA/FB groups. CsA alone resulted in elevated bone turnover. FB was unable to prevent the trabecular bone loss induced by CsA therapy. This experiment indicates no role for FB as a therapeutic option in CsA-induced bone disease at the given doses and duration of treatment by virtue of its lack of bone sparing ability and adverse renal effects when the two drugs are administered concurrently.

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

El-Gowelli, Hanan M.; Helmy, Maged W.; Ali, Rabab M.

Endothelin (ET) signaling provokes nephrotoxicity induced by the immunosuppressant drug cyclosporine A (CSA). We tested the hypotheses that (i): celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, counterbalances renal derangements caused by CSA in rats and (ii) the COX-2/endothelin ET{sub B} receptor signaling mediates the CSA-celecoxib interaction. Ten-day treatment with CSA (20 mg/kg/day) significantly increased biochemical indices of renal function (serum urea, creatinine), inflammation (interleukin-2, IL-2) and fibrosis (transforming growth factor-β{sub 1}, TGF-β{sub 1}). Histologically, CSA caused renal tubular atrophy along with interstitial fibrosis. These detrimental renal effects of CSA were largely reduced in rats treated concurrently with celecoxib (10 mg/kg/day). Wemore » also report that cortical glomerular and medullary tubular protein expressions of COX-2 and ET{sub B} receptors were reduced by CSA and restored to near-control values in rats treated simultaneously with celecoxib. The importance of ET{sub B} receptors in renal control and in the CSA-celecoxib interaction was further verified by the findings (i) most of the adverse biochemical, inflammatory, and histopathological profiles of CSA were replicated in rats treated with the endothelin ET{sub B} receptor antagonist BQ788 (0.1 mg/kg/day, 10 days), and (ii) the BQ788 effects, like those of CSA, were alleviated in rats treated concurrently with celecoxib. Together, the data suggest that the facilitation of the interplay between the TGF-β1/IL-2/COX-2 pathway and the endothelin ET{sub B} receptors constitutes the cellular mechanism by which celecoxib ameliorates the nephrotoxic manifestations of CSA in rats. - Highlights: • Celecoxib abolishes nephrotoxic manifestations of CSA in rats. • Blockade of ETB receptors by BQ788 mimicked the nephrotoxic effects of CSA. • CSA or BQ788 reduces renal protein expression of COX-2 and endothelin ETB receptors. • Enhanced TGFβ1/IL-2/COX2/ETB signaling mediates celecoxib renoprotection.« less

Exploring the nature of the relationship between child sexual abuse and substance use among women.

PubMed

Jarvis, T J; Copeland, J; Walton, L

1998-06-01

This study investigated whether child abuse (CSA) was associated with earlier substance use and greater severity of substance dependence and what aspects of CSA might predict substance abuse. The study compared (a) drug and alcohol treatment clients with and without a history of CSA and (b) CSA survivors outside drug and alcohol treatment who did or did not have current substance abuse. Semi-structured interviews took place at participants' homes, treatment agencies or the research centre. Volunteer participants included 100 women recruited from drug and alcohol treatment programmes and 80 CSA survivors recruited through CSA counseling services and medial advertising. The results focus on data from the Opiate Treatment Index, Severity of Alcohol Dependence Questionnaire, Substance Dependence Scale, Self-Esteem Inventory and self-reported histories of CSA. There were no differences between CSA survivors and other drug and alcohol treatment clients in their severity of dependence. Women with a history of CSA more frequently identified stimulants as their main problem drug and reported an earlier age of first intoxication and earlier use of inhalants. Among abused CSA survivors outside drug and alcohol treatment, women with current substance abuse had typically been abused during adolescence by someone outside the family, whereas those without current substance abuse were typically abused by family members before adolescence. The results suggest that adolescence is a crucial time for the influence of CSA experiences on substance abuse.

Quantum-Limited Directional Amplifiers with Optomechanics

NASA Astrophysics Data System (ADS)

Malz, Daniel; Tóth, László D.; Bernier, Nathan R.; Feofanov, Alexey K.; Kippenberg, Tobias J.; Nunnenkamp, Andreas

2018-01-01

Directional amplifiers are an important resource in quantum-information processing, as they protect sensitive quantum systems from excess noise. Here, we propose an implementation of phase-preserving and phase-sensitive directional amplifiers for microwave signals in an electromechanical setup comprising two microwave cavities and two mechanical resonators. We show that both can reach their respective quantum limits on added noise. In the reverse direction, they emit thermal noise stemming from the mechanical resonators; we discuss how this noise can be suppressed, a crucial aspect for technological applications. The isolation bandwidth in both is of the order of the mechanical linewidth divided by the amplitude gain. We derive the bandwidth and gain-bandwidth product for both and find that the phase-sensitive amplifier has an unlimited gain-bandwidth product. Our study represents an important step toward flexible, on-chip integrated nonreciprocal amplifiers of microwave signals.

Adsorption and desorption performance of benzene over hierarchically structured carbon-silica aerogel composites.

PubMed

Dou, Baojuan; Li, Jinjun; Wang, Yufei; Wang, Hailin; Ma, Chunyan; Hao, Zhengping

2011-11-30

Hierarchically structured carbon-silica aerogel (CSA) composites were synthesized from cheap water glass precursors and granulated activated carbon via a post-synthesis surface modification with trimethylchlorosilane (TMCS) and a low-cost ambient pressure drying procedure. The resultant CSA composites possess micro/mesoporous structure and hydrophobic surface. The adsorption and desorption performance of benzene on carbon-silica aerogel composite (CSA-2) under static and dynamic conditions were investigated, comparing with pure silica aerogel (CSA-0) and microporous activated carbon (AC). It was found that CSA-2 has high affinity towards aromatic molecules and fast adsorption kinetics. Excellent performance of dynamic adsorption and desorption observed on CSA-2 is related to its higher adsorption capacity than CSA-0 and less mass transfer resistance than AC, arising from the well-developed microporosity and open foam mesostructure in the CSA composites. Copyright © 2011 Elsevier B.V. All rights reserved.

Linking vegetable preferences, health and local food systems through community-supported agriculture.

PubMed

Wilkins, Jennifer L; Farrell, Tracy J; Rangarajan, Anusuya

2015-09-01

The objective of the present study was to explore the influence of participation in community-supported agriculture (CSA) on vegetable exposure, vegetable intake during and after the CSA season, and preference related to locally produced vegetables acquired directly from CSA growers. Quantitative surveys were administered at three time points in two harvest seasons to four groups of CSA participants: new full-paying, returning full-paying, new subsidized and returning subsidized members. Questionnaires included a vegetable frequency measure and measures of new and changed vegetable preference. Comparisons were made between new and returning CSA members and between those receiving subsidies and full-paying members. The research was conducted in a rural county in New York, USA. CSA members who agreed to participate in the study. Analysis was based on 151 usable questionnaires. CSA participants reported higher intake of eleven different vegetables during the CSA season, with a sustained increase in some winter vegetables. Over half of the respondents reported trying at least one, and up to eleven, new vegetables. Sustained preferences for CSA items were reported. While those who choose to join a CSA may be more likely to acquire new and expanded vegetable preferences than those who do not, the CSA experience has the potential to enhance vegetable exposure, augment vegetable preference and increase overall vegetable consumption. Dietary patterns encouraged through CSA participation can promote preferences and consumer demand that support local production and seasonal availability. Emphasis on fresh and fresh stored locally produced vegetables is consistent with sustainable community-based food systems.

Enhanced colonic delivery of ciclosporin A self-emulsifying drug delivery system encapsulated in coated minispheres.

PubMed

Keohane, Kieran; Rosa, Mónica; Coulter, Ivan S; Griffin, Brendan T

2016-01-01

Investigate the potential of coated minispheres (SmPill®) to enhance localized Ciclosporin A (CsA) delivery to the colon. CsA self-emulsifying drug delivery systems (SEDDS) were encapsulated into SmPill® minispheres. Varying degrees of coating thickness (low, medium and high) were applied using ethylcellulose and pectin (E:P) polymers. In vitro CsA release was evaluated in simulated gastric and intestinal media. Bioavailability of CsA in vivo following oral administration to pigs of SmPill® minispheres was compared to Neoral® po and Sandimmun® iv in a pig model. CsA concentrations in blood and intestinal tissue were determined by HPLC-UV. In vitro CsA release from coated minispheres decreased with increasing coating thickness. A linear relationship was observed between in vitro CsA release and in vivo bioavailability (r(2) = 0.98). CsA concentrations in the proximal, transverse and distal colon were significantly higher following administration of SmPill®, compared to Neoral® po and Sandimmun® iv (p < 0.05). Analysis of transverse colon tissue subsections also revealed significantly higher CsA concentrations in the mucosa and submucosa using SmPill® minispheres (p < 0.05). Modulating E:P coating thickness controls release of CsA from SmPill® minispheres. Coated minispheres limited CsA release in the small intestine and enhanced delivery and uptake in the colon. These findings demonstrate clinical advantages of an oral coated minisphere-enabled CsA formulation in the treatment of inflammatory conditions of the large intestine.

Expression of renal distal tubule transporters TRPM6 and NCC in a rat model of cyclosporine nephrotoxicity and effect of EGF treatment.

PubMed

Ledeganck, Kristien J; Boulet, Gaëlle A; Horvath, Caroline A; Vinckx, Marleen; Bogers, Johannes J; Van Den Bossche, Rita; Verpooten, Gert A; De Winter, Benedicte Y

2011-09-01

Renal magnesium (Mg(2+)) and sodium (Na(+)) loss are well-known side effects of cyclosporine (CsA) treatment in humans, but the underlying mechanisms still remain unclear. Recently, it was shown that epidermal growth factor (EGF) stimulates Mg(2+) reabsorption in the distal convoluted tubule (DCT) via TRPM6 (Thébault S, Alexander RT, Tiel Groenestege WM, Hoenderop JG, Bindels RJ. J Am Soc Nephrol 20: 78-85, 2009). In the DCT, the final adjustment of renal sodium excretion is regulated by the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC), which is activated by the renin-angiotensin-aldosterone system (RAAS). The aim of this study was to gain more insight into the molecular mechanisms of CsA-induced hypomagnesemia and hyponatremia. Therefore, the renal expression of TRPM6, TRPM7, EGF, EGF receptor, claudin-16, claudin-19, and the NCC, and the effect of the RAAS on NCC expression, were analyzed in vivo in a rat model of CsA nephrotoxicity. Also, the effect of EGF administration on these parameters was studied. CsA significantly decreased the renal expression of TRPM6, TRPM7, NCC, and EGF, but not that of claudin-16 and claudin-19. Serum aldosterone was significantly lower in CsA-treated rats. In control rats treated with EGF, an increased renal expression of TRPM6 together with a decreased fractional excretion of Mg(2+) (FE Mg(2+)) was demonstrated. EGF did not show this beneficial effect on TRPM6 and FE Mg(2+) in CsA-treated rats. These data suggest that CsA treatment affects Mg(2+) homeostasis via the downregulation of TRPM6 in the DCT. Furthermore, CsA downregulates the NCC in the DCT, associated with an inactivation of the RAAS, resulting in renal sodium loss.

Molecular mechanisms of immunosuppression.

PubMed

Baumann, G; Zenke, G; Wenger, R; Hiestand, P; Quesniaux, V; Andersen, E; Schreier, M H

1992-04-01

The immunosuppressive drug cyclosporin A (CsA, Sandimmun, SIM) is currently being evaluated in a variety of autoimmune disorders with some remarkable successes. Despite the wide empiric application of CsA, the precise mechanism of action of this drug remains elusive. To identify the molecular mode of action of CsA in the process of T cell activation, we have compared the biological profile of cyclophilin-binding cyclosporin analogues (CBCA), which lack immunosuppressive properties, with CsA. We have found that CsA binding to its intracellular receptor (cyclophilin) is required but not sufficient for immunosuppression. Moreover, inhibition of the peptidyl-prolyl cis-trans isomerase activity of cyclophilin does not seem to be relevant for the inhibitory effects of CsA. In analogy to the immunosuppressants FK506 and rapamycin, a specific structure at the 'effector' domain of the CsA molecule different from the immunophilin 'binding' domain determines the biological activity. Overall, a significant understanding of the structure-activity relationship of CsA has emerged. This will have a major impact on the identification of the precise mechanism of action of CsA and its side effects in the process of immunosuppression.

Development of a HgCdTe photomixer and impedance matched GaAs FET amplifier

NASA Technical Reports Server (NTRS)

Shanley, J. F.; Paulauskas, W. A.; Taylor, D. R.

1982-01-01

A research program for the development of a 10.6 micron HgCdTe photodiode/GaAs field effect transistor amplifier package for use at cryogenic temperatures (77k). The photodiode/amplifier module achieved a noise equivalent power per unit bandwidth of 5.7 times 10 to the 20th power W/Hz at 2.0 GHz. The heterodyne sensitivity of the HgCdTe photodiode was improved by designing and building a low noise GaAs field effect transistor amplifier operating at 77K. The Johnson noise of the amplifier was reduced at 77K, and thus resulted in an increased photodiode heterodyne sensitivity.

Designing a VAR2CSA-based vaccine to prevent placental malaria.

PubMed

Fried, Michal; Duffy, Patrick E

2015-12-22

Placental malaria (PM) due to Plasmodium falciparum is a major cause of maternal, fetal and infant mortality, but the mechanisms of pathogenesis and protective immunity are relatively well-understood for this condition, providing a path for vaccine development. P. falciparum parasites bind to chondroitin sulfate A (CSA) to sequester in the placenta, and women become resistant over 1-2 pregnancies as they acquire antibodies that block adhesion to CSA. The protein VAR2CSA, a member of the PfEMP1 variant surface antigen family, mediates parasite adhesion to CSA, and is the leading target for a vaccine to prevent PM. Obstacles to PM vaccine development include the large size (∼ 350 kD), high cysteine content, and sequence variation of VAR2CSA. A number of approaches have been taken to identify the combination of VAR2CSA domains and alleles that can induce broadly active antibodies that block adhesion of heterologous parasite isolates to CSA. This review summarizes these approaches, which have examined VAR2CSA fragments for binding activity, antigenicity with naturally acquired antibodies, and immunogenicity in animals for inducing anti-adhesion or surface-reactive antibodies. Two products are expected to enter human clinical studies in the near future based on N-terminal VAR2CSA fragments that have high binding affinity for CSA, and additional proteins preferentially expressed by placental parasites are also being examined for their potential contribution to a PM vaccine. Copyright © 2015. Published by Elsevier Ltd.

Does the Critical Shoulder Angle Correlate With Rotator Cuff Tear Progression?

PubMed

Chalmers, Peter N; Salazar, Dane; Steger-May, Karen; Chamberlain, Aaron M; Yamaguchi, Ken; Keener, Jay D

2017-06-01

The critical shoulder angle (CSA) has been reported to be associated with rotator cuff disease and has been suggested as an etiology for cuff tears. However, it is unclear whether acromial morphologic characteristics such as CSA are a cause or effect because all studies to date have been retrospective. (1) How often can the CSA be reliably measured? (2) Is the CSA associated with rotator cuff disease? (3) Is the CSA correlated with baseline tear size or tear enlargement? (4) Does the CSA change with time? In this retrospective comparison of longitudinally collected data, patients with asymptomatic rotator cuff tears underwent ultrasonography and standardized AP radiographs at enrollment and yearly thereafter during a median of 4 years. Three hundred ninety-five patients were included, of whom 14 were excluded as they were not yet eligible for 2-year followup and 68 (18%) were lost to followup, leaving 313 study patients who were evaluated with 1433 radiographs. Patients with adhesive capsulitis with normal rotator cuffs and radiographically normal scapulae were included as control subjects (119 subjects). Two observers (PNC, DS) measured the CSA in a blinded fashion. Radiographs that met Suter-Henninger criteria for CSA measurement reliability were included. For the study group, 179 of the 313 (57%) patients with radiographs that met Suter-Henninger criteria were further analyzed; the remainder were excluded from this study. For the control group, 50 of 119 (42%) subjects met criteria and were further analyzed. Tear enlargement was found in 94 patients, and the CSA was compared in patients with tears and control subjects, and in tears with or without enlargement, and was correlated with tear size. In a subgroup of the study group in which 59 of 179 patients had a minimum of 3 years between initial and followup radiographs, two CSA measurements were performed to measure change. In total, of the 1552 radiographs evaluated, only 326 (21%) were of sufficient quality to measure the CSA. The CSA was higher among patients with cuff tears than control subjects (34° ± 4° versus 32° ± 4°; mean difference, 2.0°; 95% CI, 0.7°-3.2°; p = 0.003). The CSA did not correlate with baseline tear length (ρ = 0.22, p = 0.090) or width (ρ = 0.16, p = 0.229). The CSA was not different between tears that enlarged and those that were stable (34° ± 3° versus 34° ± 4°; mean difference, 0.2°; 95% CI, -0.9° to -1.4°; p = 0.683). The CSA did not change over time (CSA Time 1: mean 33° ± 4° SD; CSA Time 2: mean 33° ± 4° SD; mean difference, -0.2°; 95% CI, -0.6° to 0.1°; p = 0.253). Even with a longitudinal protocol, most radiographs are of insufficient quality for CSA measurement. Although patients with a history of degenerative cuff disease have higher CSA values than control subjects, the difference is small enough that it could be influenced by measurement error in practice; in any case, a difference of the magnitude we observed is likely to be clinically unimportant. The CSA is not correlated with tear size or tear progression, and does not seem to change with time. These results suggest that the CSA is unlikely to be related to rotator cuff disease. Level II, prognostic study.

Factors protecting against the development of adjustment difficulties in young adults exposed to childhood sexual abuse.

PubMed

Lynskey, M T; Fergusson, D M

1997-12-01

The aims of this study were to identify the factors which discriminated young people exposed to childhood sexual abuse (CSA) who developed psychiatric disorder or adjustment difficulties in young adulthood from those young people exposed to CSA who did not develop psychiatric disorder or adjustment difficulties by age 18. Data were gathered on a birth cohort of 1,025 New Zealand children studied from birth to the age of 18 on (a) exposure to CSA; (b) patterns of psychiatric disorder and adjustment difficulties at age 18 years; (c) factors that may have influenced responses to CSA including characteristics of the abuse, parental bonding, parental characteristics, and adolescent peer affiliations. Just over 10% of the cohort reported CSA. Those reporting CSA were at increased risks of a range of difficulties at age 18 (depression, anxiety, conduct disorder, alcohol abuse/dependence, other substance abuse/dependence, post sexual abuse trauma, attempted suicide). However, not all of those exposed to CSA developed difficulties and approximately a quarter of those exposed to CSA did not meet criteria for any adjustment difficulty. Further analysis suggested that the extent of adjustment difficulties in those exposed to CSA was influenced by two additional factors: (a) the extent of affiliations with delinquent or substance using peers in adolescence; and (b) the extent of paternal care or support in childhood. The findings of this study suggest that while young people exposed to CSA are at increased risks of psychiatric disorder and adjustment difficulties in young adulthood, not all individuals exposed to CSA will develop adjustment difficulties. Important factors protecting against the development of adjustment difficulties in young people experiencing CSA appear to be the nature and quality of peer and family relationships.

Exploring the role of child sexual abuse and posttraumatic stress disorder symptoms in gay and bisexual men reporting compulsive sexual behavior.

PubMed

Blain, Leah M; Muench, Fred; Morgenstern, Jon; Parsons, Jeffrey T

2012-05-01

Compulsive sexual behavior (CSB) is an impairing yet understudied clinical phenomenon. The experience of child sexual abuse (CSA) has been implicated as an etiological factor in the development of some cases of CSB (Kuzma & Black, 2008); however, research regarding the role of CSA and related psychopathology in CSB symptomatology has been limited in the literature. The present study aimed to examine the uniqueness of the association of CSA with CSB as compared to other experiences of child maltreatment; the role of posttraumatic stress disorder (PTSD) symptomatology in CSB symptoms for individuals reporting CSA; and clinical differences between individuals with and without histories of CSA. Hypotheses were tested using data from a sample of 182 gay and bisexual men reporting CSB symptoms. CSA prevalence was high in the tested sample (39%). CSA severity was a unique predictor of CSB symptoms, above child physical and emotional abuse, and poly-victimization status was not significantly related to CSB symptoms. Contrary to hypotheses, PTSD symptoms did not significantly mediate the role of CSA severity, although PTSD symptoms explained additional variance in CSB symptoms, with the final model accounting for over a quarter of the variance in CSB symptoms (27%). Finally, men with a history of CSA reported more CSB, depressive, and anxious symptoms than those without a history of CSA. Findings from the present study support the hypothesis that CSA may be uniquely related to CSB symptoms, above other forms of child maltreatment, and indicate that men with a CSA history are likely to present more severe clinical comorbidities. Clinical implications and future research directions are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Methodologic Considerations for the Study of Childhood Sexual Abuse in Sexual Health Outcome Research: A Comprehensive Review.

PubMed

Kilimnik, Chelsea D; Pulverman, Carey S; Meston, Cindy M

2018-04-01

Childhood sexual abuse (CSA) has been a topic of interest in sexual health research for decades, yet literature on the sexual health correlates of CSA has been hindered by methodologic inconsistencies that have resulted in discrepant samples and mixed results. To review the major methodologic inconsistencies in the field, explore the scientific and clinical impact of these inconsistencies, and propose methodologic approaches to increase consistency and generalizability to the general population of women with CSA histories. A comprehensive literature review was conducted to assess the methodologic practices used in examining CSA and sexual health outcomes. Methodologic decisions of researchers examining sexual health outcomes of CSA. There are a number of inconsistencies in the methods used to examine CSA in sexual health research across the domains of CSA operationalization, recruitment language, and measurement approaches to CSA experiences. The examination of CSA and sexual health correlates is an important research endeavor that needs rigorous methodologic approaches. We propose recommendations to increase the utility of CSA research in sexual health. We recommend the use of a developmentally informed operationalization of childhood and adolescence, rather than age cutoffs. Researchers are encouraged to use a broad operationalization of sexual abuse such that different abuse characteristics can be measured, reported, and examined in the role of sexual health outcomes. We recommend inclusive recruitment approaches to capture the full range of CSA experiences and transparency in reporting these methods. The field also could benefit from the validation of existing self-report instruments for assessing CSA and detailed reporting of the instruments used in research studies. The use of more consistent research practices could improve the state of knowledge on the relation between CSA and sexual health. Kilimnik CD, Pulverman CS, Meston CM. Methodologic Considerations for the Study of Childhood Sexual Abuse in Sexual Health Outcome Research: A Comprehensive Review. Sex Med Rev 2018;6:176-187. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

False Memory for Trauma-Related DRM Lists in Adolescents and Adults with Histories of Child Sexual Abuse

PubMed Central

Goodman, Gail S.; Ogle, Christin M.; Block, Stephanie D.; Harris, LaTonya S.; Larson, Rakel P.; Augusti, Else-Marie; Cho, Young Il; Beber, Jonathan; Timmer, Susan; Urquiza, Anthony

2014-01-01

The purpose of the present research was to examine Deese-Roediger-McDermott (DRM) false memory for trauma-related and nontrauma-related lists in adolescents and adults with and without documented histories of child sexual abuse (CSA). Individual differences in psychopathology and adult attachment were also explored. Participants were administered free recall and recognition tests after hearing CSA, negative, neutral, and positive DRM lists. In free recall, CSA and negative lists produced the most false memory. In sharp contrast, for recognition, CSA lists enjoyed the highest d’ scores. CSA-group adolescents who evinced greater PTSD symptoms had higher rates of false memory compared to: 1) nonCSA-group adolescents with higher PTSD symptom scores (free recall), and 2) CSA-group adolescents with lower PTSD symptom scores (recognition). Regression analyses revealed that individuals with higher PTSD scores and greater fearful-avoidant attachment tendencies showed less proficient memory monitoring for CSA lists. Implications for trauma and memory development and for translational research are discussed. PMID:23786687

Enhanced absorption of cyclosporin A by complexation with dimethyl-beta-cyclodextrin in bile duct-cannulated and -noncannulated rats.

PubMed

Miyake, K; Arima, H; Irie, T; Hirayama, F; Uekama, K

1999-01-01

The enhancing effects of dimethyl-beta-cyclodextrin (DM-beta-CyD) on the absorption of cyclosporin A (CsA) after oral administration to rats under bile duct-cannulated and -noncannulated conditions were investigated. The dissolution rate of CsA was markedly augmented by complexation with DM-beta-CyD. In a closed loop in situ study, DM-beta-CyD considerably increased the cumulative amounts of CsA in the mesenteric venous blood after injection of the aqueous CsA suspension into the small intestinal sac of rats. In addition, the cumulative amount ratio of M1, the dominant metabolite of CsA in rats, to CsA in the mesenteric venous blood for up to 40 min after the injection of the CsA-DM-beta-CyD suspension into the sac was lower than that of the CsA suspension alone. DM-beta-CyD inhibited the bioconversion of CsA in the small intestinal microsomes of rats. These results indicate that the bioconversion of CsA was abated by complexation with DM-beta-CyD. An in vivo study revealed that DM-beta-CyD increased the transfer of CsA to blood, not lymph, with low variability in the absorption after oral administration of the CsA suspension to rats. The variability of bioavailability of DM-beta-CyD complex was lower than that of Sandimmune, although the extent of bioavailability of DM-beta-CyD was only a little higher than that of Sandimmune. The bioavailability of CsA or its DM-beta-CyD complex was appreciably decreased by the cannulation of the bile duct of rats, and the extent of the lowering in the bioavailability in the presence of DM-beta-CyD was much less serious than that of CsA alone. The present results suggest that DM-beta-CyD is particularly useful in designing oral preparations of CsA with an enhanced bioavailability and a reduced variability in absorption.

Positive Selection of Plasmodium falciparum Parasites With Multiple var2csa-Type PfEMP1 Genes During the Course of Infection in Pregnant Women

PubMed Central

Salanti, Ali; Lavstsen, Thomas; Nielsen, Morten A.; Theander, Thor G.; Leke, Rose G. F.; Lo, Yeung Y.; Bobbili, Naveen; Arnot, David E.; Taylor, Diane W.

2011-01-01

Placental malaria infections are caused by Plasmodium falciparum–infected red blood cells sequestering in the placenta by binding to chondroitin sulfate A, mediated by VAR2CSA, a variant of the PfEMP1 family of adhesion antigens. Recent studies have shown that many P. falciparum genomes have multiple genes coding for different VAR2CSA proteins, and parasites with >1 var2csa gene appear to be more common in pregnant women with placental malaria than in nonpregnant individuals. We present evidence that, in pregnant women, parasites containing multiple var2csa-type genes possess a selective advantage over parasites with a single var2csa gene. Accumulation of parasites with multiple copies of the var2csa gene during the course of pregnancy was also correlated with the development of antibodies involved in blocking VAR2CSA adhesion. The data suggest that multiplicity of var2csa-type genes enables P. falciparum parasites to persist for a longer period of time during placental infections, probably because of their greater capacity for antigenic variation and evasion of variant-specific immune responses. PMID:21592998

The Effects of Arthroscopic Lateral Acromioplasty on the Critical Shoulder Angle and the Anterolateral Deltoid Origin: An Anatomic Cadaveric Study.

PubMed

Katthagen, J Christoph; Marchetti, Daniel Cole; Tahal, Dimitri S; Turnbull, Travis Lee; Millett, Peter J

2016-04-01

To investigate if (1) an anterolateral acromioplasty and (2) a lateral acromion resection alter the critical shoulder angle (CSA) without affecting the deltoid origin. First, the native CSAs of 10 human cadaveric shoulders (6 male and 4 female specimens; mean age, 54.2 years) were determined with the use of fluoroscopy. Setup allowed for consistent repetitive measurements. Next, a standard arthroscopic anterolateral acromioplasty was performed to create a type 1 acromion, and the CSA was reassessed fluoroscopically. Afterward, a lateral acromioplasty was performed with a 5-mm lateral acromion resection using a 5-mm burr, and the CSA was measured again. The native CSA was compared with (1) the CSA after acromioplasty and (2) the CSA after acromioplasty and lateral acromion resection using a paired t test. Finally, the acromial deltoid attachment was evaluated anatomically for damage to the anterolateral origin. The mean native CSA (34.3° ± 2.1°) was reduced significantly by acromioplasty (33.1° ± 2.0°, P < .001) and further reduced by lateral acromion resection (31.5° ± 1.7°, P < .001). Anterolateral acromioplasty reduced the CSA by a mean of 1.4° (95% confidence interval boundaries, 0.8° and 1.9°), and in combination with lateral acromion resection, the CSA was reduced by a mean of 2.8° (95% confidence interval boundaries, 2.1° and 3.5°). In all specimens (5 of 5) with a presurgery CSA of 35° or greater, the CSA was reduced to the range of 30° to 35° by the combination of both techniques. However, in 2 specimens with a CSA of approximately 32°, the CSA was reduced to less than 30°. The acromial deltoid attachment was found to be well preserved in all specimens. Arthroscopic anterolateral acromioplasty and a 5-mm lateral acromion resection each reduced the CSA significantly and did not damage the deltoid origin. The combination of both techniques could potentially be used in clinical practice to reduce a CSA greater than 35° to the desired range of 30° to 35°. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Large Critical Shoulder Angle Has Higher Risk of Tendon Retear After Arthroscopic Rotator Cuff Repair.

PubMed

Li, Hong; Chen, Yuzhou; Chen, Jiwu; Hua, Yinghui; Chen, Shiyi

2018-05-01

The critical shoulder angle (CSA) is the angle created between the superior and inferior bone margins of the glenoid and the most lateral border of the acromion. A few studies recently investigated the relation between CSA and functional outcomes after rotator cuff repair. However, there is a lack of research investigating the effect of CSA on postoperative tendon integrity after rotator cuff repair. To assess the effects of the CSA on postoperative tendon integrity after rotator cuff repair. Cohort study; Level of evidence, 3. All patients who underwent rotator cuff repair for full-thickness supraspinatus tears by 1 senior surgeon between January 2010 and January 2014 were included in this study. All patients had standardized anteroposterior shoulder radiographs the day before surgery. CSA and acromial index (AI) were measured. AI was derived by measuring the distance from the glenoid plane to the lateral border of the acromion and dividing it by the distance from the glenoid plane to the lateral aspect of the humeral head. Functional scores-including American Shoulder and Elbow Surgeons shoulder evaluation form, modified University of California at Los Angeles score, Constant-Murley score, and visual analog scale for pain-were used to evaluate shoulder function at a minimum follow-up of 2 years. Meanwhile, magnetic resonance imaging examinations were performed to evaluate rotator cuff integrity according to the Sugaya method and the signal/noise quotient (SNQ) of the rotator cuff tendon. A total of 90 patients were included in this study: 42 patients with a single-row repair and 48 with a double-row repair. There was a significant positive correlation between CSA or AI and tendon SNQ. On the basis of CSA, the patients were divided into 2 groups: large CSA (>38°) and control (CSA ≤38°). At final follow-up, the large CSA group and the control CSA group demonstrated no significant differences in American Shoulder and Elbow Surgeons, University of California at Los Angeles, Constant, and visual analog scale scores. Postoperative magnetic resonance imaging revealed that the large CSA group had 9 cases of retear, with a significantly higher retear rate than the control group (15% vs 0%, P = .03). Furthermore, the tendon SNQ of the large CSA group was significantly greater than that of the control group. CSA did not appear to influence postoperative functional outcomes, while those in the large CSA group had poor tendon integrity after rotator cuff repair. These findings indicate that a large CSA is associated with an increased risk of rotator cuff tendon retear after repair.

Response of human renal tubular cells to cyclosporine and sirolimus: A toxicogenomic study

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

Pallet, Nicolas; Rabant, Marion; Xu-Dubois, Yi-Chun

The molecular mechanisms involved in the potentially nephrotoxic response of tubular cells to immunosuppressive drugs remain poorly understood. Transcriptional profiles of human proximal tubular cells exposed to cyclosporine A (CsA), sirolimus (SRL) or their combination, were established using oligonucleotide microarrays. Hierarchical clustering of genes implicated in fibrotic processes showed a clear distinction between expression profiles with CsA and CsA + SRL treatments on the one hand and SRL treatment on the other. Functional analysis found that CsA and CsA + SRL treatments preferentially alter biological processes located at the cell membrane, such as ion transport or signal transduction, whereas SRLmore » modifies biological processes within the nucleus and related to transcriptional activity. Genome wide expression analysis suggested that CsA may induce an endoplasmic reticulum (ER) stress in tubular cells in vitro. Moreover we found that CsA exposure in vivo is associated with the upregulation of the ER stress marker BIP in kidney transplant biopsies. In conclusion, this toxicogenomic study highlights the molecular interaction networks that may contribute to the tubular response to CsA and SRL. These results may also offer a new working hypothesis for future research in the field of CsA nephrotoxicity. Further studies are needed to evaluate if ER stress detection in tubular cells in human biopsies can predict CsA nephrotoxicity.« less

[Association of childhood sexual abuse and disordered eating in a sample of Mexican adolescents].

PubMed

Unikel-Santoncini, Claudia; Ramos-Lira, Luciana; Juárez-García, Francisco

2011-01-01

To analyze the association between childhood sexual abuse (CSA) and disordered eating (DE). A probabilistic sample of 2,358 female high school students of public schools in the Estado de Mexico was used. DE was more prevalent among CSA sufferers (p < or = 0.05). Preoccupation with gaining weight, binging and restrictive behaviors were associated to CSA (p < or = 0.05). The probability of DE was 7 times higher when the CSA experience had not been revealed and 36 times when CSA happened before 14 years of age. The association between CSA and DE is clear in the sample studied, as well as with some of its specific characteristics, which highlights the need to deepen in this research field and to incorporate the evaluation of CSA and its consequences in adolescents' mental health.

Children's knowledge of sexual abuse prevention in El Salvador.

PubMed

Hurtado, Alicia; Katz, Craig L; Ciro, Dianne; Guttfreund, Daniel; Nosike, Digna

2014-01-01

Child sexual abuse (CSA) remains a global health problem that must be addressed. In a country with limited resources such as El Salvador, we sought an alternative way to disseminate CSA prevention information to elementary school children. The aim of this study was to evaluate the effectiveness of a child sexual abuse (CSA) prevention exhibit at a children's museum. We asked 189 children to answer a questionnaire about CSA prevention before entering a museum exhibit on the subject and then asked 59 different children to answer the questionnaire after visiting the exhibit. Children's knowledge scores on CSA prevention significantly improved after visiting the exhibit (P < .012). A museum exhibit that addresses CSA prevention is an effective way of communicating CSA prevention to children. Copyright © 2014 Icahn School of Medicine at Mount Sinai. Published by Elsevier Inc. All rights reserved.

When the face reveals what words do not: facial expressions of emotion, smiling, and the willingness to disclose childhood sexual abuse.

PubMed

Bonanno, George A; Keltner, Dacher; Noll, Jennie G; Putnam, Frank W; Trickett, Penelope K; LeJeune, Jenna; Anderson, Cameron

2002-07-01

For survivors of childhood sexual abuse (CSA), verbal disclosure is often complex and painful. The authors examined the voluntary disclosure-nondisclosure of CSA in relation to nonverbal expressions of emotion in the face. Consistent with hypotheses derived from recent theorizing about the moral nature of emotion, CSA survivors who did not voluntarily disclose CSA showed greater facial expressions of shame, whereas CSA survivors who voluntarily disclosed CSA expressed greater disgust. Expressions of disgust also signaled sexual abuse accompanied by violence. Consistent with recent theorizing about smiling behavior, CSA nondisclosers made more polite smiles, whereas nonabused participants expressed greater genuine positive emotion. Discussion addressed the implications of these findings for the study of disclosure of traumatic events, facial expression, and the links between morality and emotion.

Cyclosporine A-Sensitive, Cyclophilin B-Dependent Endoplasmic Reticulum-Associated Degradation

PubMed Central

Luban, Jeremy; Molinari, Maurizio

2010-01-01

Peptidyl-prolyl cis/trans isomerases (PPIs) catalyze cis/trans isomerization of peptide bonds preceding proline residues. The involvement of PPI family members in protein refolding has been established in test tube experiments. Surprisingly, however, no data is available on the involvement of endoplasmic reticulum (ER)-resident members of the PPI family in protein folding, quality control or disposal in the living cell. Here we report that the immunosuppressive drug cyclosporine A (CsA) selectively inhibits the degradation of a subset of misfolded proteins generated in the ER. We identify cyclophilin B (CyPB) as the ER-resident target of CsA that catalytically enhances disposal from the ER of ERAD-LS substrates containing cis proline residues. Our manuscript presents the first evidence for enzymatic involvement of a PPI in protein quality control in the ER of living cells. PMID:20927389

Clinical characteristic and risk factors of recurrent sexual abuse and delayed reported sexual abuse in childhood.

PubMed

Hu, Mei-Hua; Huang, Go-Shine; Huang, Jing-Long; Wu, Chang-Teng; Chao, An-Shine; Lo, Fu-Sung; Wu, Han-Ping

2018-04-01

Child sexual abuse (CSA) is a global problem that affects children of all ages, and the evaluation of these victims by psychologic and gynecologic experts in pediatric emergency departments is an important issue. Few data are available on the characteristics of children admitted to pediatric emergency department with recurrent CSA and delayed reported CSA. The aim of the present study was to describe the clinical features of, and risk factors for, recurrent CSA and delayed reported CSA. The study retrospectively analyzed victims of CSA who were admitted to a pediatric emergency department. Chi-square tests and univariate analyses were performed to assess the risk factors of recurrent or delayed reported CSA. Of the 91 CSA cases, 32 (35.2%) were recurrent assaults. Of the 70 cases recorded the duration of the event, 22 (31.4%) were delayed report cases. Comparisons of the non-recurrent and recurrent CSA assault groups revealed a significant increase in comorbidities (odds ratio [OR]: 4.46, 95% confidence interval [CI]: 1.54-12.93), acute psychiatric problems (OR: 3.18, CI: 1.26-8.06), attempted suicide (OR: 4.23, CI: 1.28-13.99), and the need for treatment with antipsychotic medications (OR: 5.57, CI: 1.37-22.65). Compared with non-delayed reported cases, the delay reported cases of CSA were significantly more likely to have anxiety (P < .05). The CSA victims in the present study exhibited acute medical and/or psychosocial problems, which indicate that pediatric emergency professionals have a responsibility to look for and recognize particular characteristics in these victims.

10 CFR 431.447 - Department of Energy recognition of nationally recognized certification programs.

Code of Federal Regulations, 2013 CFR

2013-01-01

... IEEE Std 112-2004 Test Methods A and B, IEEE Std 114-2010, CSA C390-10, and CSA C747 (incorporated by... IEEE Std 112-2004 Test Methods A and B, IEEE Std 114-2010, CSA C390-10, and CSA C747- (incorporated by...

10 CFR 431.447 - Department of Energy recognition of nationally recognized certification programs.

Code of Federal Regulations, 2014 CFR

2014-01-01

... IEEE Std 112-2004 Test Methods A and B, IEEE Std 114-2010, CSA C390-10, and CSA C747 (incorporated by... IEEE Std 112-2004 Test Methods A and B, IEEE Std 114-2010, CSA C390-10, and CSA C747- (incorporated by...

Serum and renal tissue markers of nephropathy in rats under immunosuppressive therapy: cyclosporine versus sirolimus.

PubMed

Sereno, J; Parada, B; Rodrigues-Santos, P; Lopes, P C; Carvalho, E; Vala, H; Teixeira-Lemos, E; Alves, R; Figueiredo, A; Mota, A; Teixeira, F; Reis, F

2013-04-01

Cyclosporin (CsA) has been progressively replaced by other drugs with putatively fever side effects, including nephrotoxicity and hypertension. Sirolimus (SRL) is one of the main options for management of kidney transplant patients in the post-CsA era. It shows identical efficacy with apparently less cardiorenal side effects than CsA. However, doubts remain concerning the mechanisms of putative renoprotection by SRL as well as the best serum and/or tissue markers for nephropathy, as assessed in this study employing CsA- and SRL-treated rats. Three groups (n = 6) were treated orally during a 6-week protocol: control (vehicle); CsA (5 mg/kg body weight per day Sandimmun Neoral); SRL (1 mg/kg body weight per day Rapamune). Blood pressure and heart rate were assessed with a "tail cuff". Renal dysfunction and morphology were characterized using serum creatinine and blood urea nitrogen (BUN) levels as well as hematoxylin and eosin and periodic acid Schiff staining, respectively. We examined serum concentrations of interleukin (IL)-2, IL-1β, high-sensitivity C-reactive protein, tumor necrosis factor TNF-α, and vascular endothelial growth factor and kidney mRNA expression of interleukin-1β (IL-1β), tumor protein 53 (TP53), mammalian target of rapamycin (mTOR) and proliferating cell nuclear antigen (PCNA), as well as markers of lipid peroxidation in the kidney and serum. Both CsA and SRL induced significant increases in systolic and diastolic blood pressure, but only CsA caused tachycardia. CsA-treated rats also displayed increased serum creatinine and BUN levels, accompanied by mild renal lesions, which were almost absent among SRL-treated rats, which presented hyperlipidemic and hyperglycemic profiles. CsA-induced nephrotoxicity was accompanied by kidney overexpression of inflammatory and proliferative mRNA markers (IL-1β, mTOR and PCNA), which were absent among SRL group. In conclusion, the antiproliferative and antifibrotic character of SRL may explain its less nephrotoxic profile. Renal over expression of mTOR in the CsA-treated group, associated with renal dysfunction and structural damage, reinforces the potential beneft of SRL as a strategy to reduce CsA-evoked nephrotoxicity. Copyright © 2013 Elsevier Inc. All rights reserved.

Autumnalamide targeted proteins of the immunophilin family.

PubMed

Sánchez, Jon Andoni; Alfonso, Amparo; Thomas, Olivier P; Botana, Luís M

2017-02-01

Previous works with autumnalamide reported that Store Operated Calcium (SOC) channels were blocked through mitochondrial modulation. In the present paper we studied the effect of autumnalamide on ionomycin Ca 2+ fluxes. Thus, autumnalamide did not modify ionomycin-sensitive intracellular pools while the ionomycin-induced Ca 2+ influx was blocked with similar potency whether the incubation was done before or after ionomycin-sensitive pools depletion. Nevertheless, autumnalamide was not able to inhibit ionomycin-induced Ca 2+ influx once the membrane channels were activated. Moreover, the compound efficiently inhibited flufenamic acid (FFA) Ca 2+ release induced in this organelle but no the next influx. Since in previous work the effect of autumnalamide was inhibited by cyclosporine A (CsA), structures that target this drug were studied. Therefore, the affinity of autumnalamide for cyclophilin D (Cyp D) was examined. The K D obtained for Cyp D- autumnalamide was 1.51±1.399. Moreover, the K D for Cyp A- autumnalamide was calculated. The peptide had a similar order of Cyp A binding affinity than CsA (8.08±1.23 and 6.85±1.1μM respectively). After testing autumnalamide-binding capacity for Cyp A, the activity of this compound on Cyp A pathway was tested. Thus, the effect on interleukin (IL)-2 release on activated T-lymphocytes was checked. Autumnalamide was able to reduce IL-2 levels near to T cells in resting conditions. Next, the effect over calcineurin and NFATc1 was also evaluated. While CsA inhibits both calcineurin and NFATc1, autumnalamide did not produce any effect. From these results we can conclude that, autumnalamide targeted mitochondrion and prevent T-cells from IL-2 production through the modulation of SOC Ca 2+ channels. Copyright © 2016 Elsevier GmbH. All rights reserved.

Low-sensitivity, frequency-selective amplifier circuits for hybrid and bipolar fabrication.

NASA Technical Reports Server (NTRS)

Pi, C.; Dunn, W. R., Jr.

1972-01-01

A network is described which is suitable for realizing a low-sensitivity high-Q second-order frequency-selective amplifier for high-frequency operation. Circuits are obtained from this network which are well suited for realizing monolithic integrated circuits and which do not require any process steps more critical than those used for conventional monolithic operational and video amplifiers. A single chip version using compatible thin-film techniques for the frequency determination elements is then feasible. Center frequency and bandwidth can be set independently by trimming two resistors. The frequency selective circuits have a low sensitivity to the process variables, and the sensitivity of the center frequency and bandwidth to changes in temperature is very low.

Electromagnetic shielding effectiveness studies on polyaniline/CSA-WO3 composites at KU band frequencies

NASA Astrophysics Data System (ADS)

Sastry, D. Nagesa; Revanasiddappa, M.; Suresh, T.; Kiran, Y. T. Ravi; Raghavendra, S. C.

2018-05-01

This paper highlights the Electromagnetic Interference (EMI) Shielding Effectiveness and electromagnetic wave attenuation behavior of Polyaniline/Camphor Sulphonic Acid (PANI-CSA) - tungsten oxide (WO3) composites. Insitu polymerization of aniline monomer with camphor sulphonic acid (CSA) as a dopant was carried out in the presence of ammonium persulphate an oxidizing agent to synthesize PANI-CSA tungsten oxide composites (PANI/CSA-WO3) by chemical oxidation method. The composites have been synthesized with various compositions (10, 20, 30, 40 and 50 wt %) of tungsten oxide in PANI/CSA matrix. The EMI shielding measurements were carried out in the broad microwave spectrum covering the frequency range from 12 to 18 GHz (Ku-Band). The results show the influence of tungsten oxide in PANI/CSA over the EMI shielding Effectiveness. The composites have shown excellent microwave absorption behavior confirmed by the EMI Shielding Effectiveness values of the order of -15 to -16 dB.

Magnetic hyaluronate hydrogels: preparation and characterization

NASA Astrophysics Data System (ADS)

Tóth, Ildikó Y.; Veress, Gábor; Szekeres, Márta; Illés, Erzsébet; Tombácz, Etelka

2015-04-01

A novel soft way of hyaluronate (HyA) based magnetic hydrogel preparation was revealed. Magnetite nanoparticles (MNPs) were prepared by co-precipitation. Since the naked MNPs cannot be dispersed homogenously in HyA-gel, their surface was modified with natural and biocompatible chondroitin-sulfate-A (CSA) to obtain CSA-coated MNPs (CSA@MNPs). The aggregation state of MNPs and that loaded with increasing amount of CSA up to 1 mmol/g was measured by dynamic light scattering at pH~6. Only CSA@MNP with ≥0.2 mmol/g CSA content was suitable for magnetic HyA-gel preparation. Rheological studies showed that the presence of CSA@MNP with up to 2 g/L did not affect the hydrogel's rheological behavior significantly. The results suggest that the HyA-based magnetic hydrogels may be promising formulations for future biomedical applications, e.g. as intra-articular injections in the treatment of osteoarthritis.

Household Risk and Child Sexual Abuse in a Low Income, Urban Sample of Women.

ERIC Educational Resources Information Center

Rowland, David L.; Zabin, Laurie S.; Emerson, Mark

2000-01-01

Explored the impact of household environment and childhood sexual abuse (CSA) on psychosocial development. Data on low-income, urban CSA victims, and non-CSA women indicated that household conditions indicative of parental dysfunction, antisocial behavior, and instability set the stage for CSA by interfering with parental protection. Victims'…

78 FR 32295 - Motor Carrier Safety Advisory Committee (MCSAC); Public Meetings of the CSA and Motorcoach...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-29

... subcommittee will meet to discuss ideas, concepts, and suggestions on FMCSA's CSA program. On Wednesday and... CSA Subcommittee will discuss information, concepts, and ideas concerning FMCSA's CSA program. The...: Motorcoach HOS The Motorcoach HOS Subcommittee will meet to discuss information, concepts, and ideas it...

Protective Antibodies against Placental Malaria and Poor Outcomes during Pregnancy, Benin

PubMed Central

Denoeud-Ndam, Lise; Doritchamou, Justin; Viwami, Firmine; Salanti, Ali; Nielsen, Morten A.; Fievet, Nadine; Massougbodji, Achille; Luty, Adrian J.F.; Deloron, Philippe

2015-01-01

Placental malaria is caused by Plasmodium falciparum–infected erythrocytes that bind to placental tissue. Binding is mediated by VAR2CSA, a parasite antigen coded by the var gene, which interacts with chondroitin sulfate A (CSA). Consequences include maternal anemia and fetal growth retardation. Antibody-mediated immunity to placental malaria is acquired during successive pregnancies, but the target of VAR2CSA-specific protective antibodies is unclear. We assessed VAR2CSA-specific antibodies in pregnant women and analyzed their relationships with protection against placental infection, preterm birth, and low birthweight. Antibody responses to the N-terminal region of VAR2CSA during early pregnancy were associated with reduced risks for infections and low birthweight. Among women infected during pregnancy, an increase in CSA binding inhibition was associated with reduced risks for placental infection, preterm birth, and low birthweight. These data suggest that antibodies against VAR2CSA N-terminal region mediate immunity to placental malaria and associated outcomes. Our results validate current vaccine development efforts with VAR2CSA N-terminal constructs. PMID:25898123

Endophytic fungi from pigeon pea [Cajanus cajan (L.) Millsp.] produce antioxidant Cajaninstilbene acid.

PubMed

Zhao, JinTong; Fu, YuJie; Luo, Meng; Zu, YuanGang; Wang, Wei; Zhao, ChunJian; Gu, ChengBo

2012-05-02

In this study, novel endophytic fungi producing cajaninstilbene acid (CSA) from pigeon pea [ Cajanus cajan (L.) Millsp.] were investigated and screened. CSA has prominent pharmacological activities. A total of 110 endophytic fungi isolates were grouped into 8 genera on the basis of morphological characteristics, and CSA-producing fungi were screened by liquid chromatography-tandem mass spectrometry (LC-MS/MS). According to ITS-rDNA sequences analysis, the CSA-producing fungi were identified as Fusarium solani (ERP-07), Fusarium oxysporum (ERP-10), and Fusarium proliferatum (ERP-13), respectively. The amount of CSA produced by the ERP-13 reached 504.8 ± 20.1 μg/L or 100.5 ± 9.4 μg/g dry weight of mycelium. In a DPPH radical-scavenging assay, when the concentration of fungal CSA was 500 μg/mL, inhibition percentage could reach 80%, which was almost the same as that of standard CSA. This study first reported the natural antioxidant CSA from endophytic fungi F. solani and F. proliferatum isolated from pigeon pea.

Methylation-sensitive amplified polymorphism (MSAP) marker to investigate drought-stress response in Montepulciano and Sangiovese grape cultivars.

PubMed

Albertini, Emidio; Marconi, Gianpiero

2014-01-01

Methylation-sensitive amplified polymorphism (MSAP) is a technique developed for assessing the extent and pattern of cytosine methylation and has been applied to genomes of several species (Arabidopsis, grape, maize, tomato, and pepper). The technique relies on the use of isoschizomers that differ in their sensitivity to methylation.

The effect of adaptive servo ventilation (ASV) on objective and subjective outcomes in Cheyne-Stokes respiration (CSR) with central sleep apnea (CSA) in heart failure (HF): A systematic review.

PubMed

Yang, Hyunju; Sawyer, Amy M

2016-01-01

To summarize the current evidence for adaptive servo ventilation (ASV) in Cheyne-Stokes respiration (CSR) with central sleep apnea (CSA) in heart failure (HF) and advance a research agenda and clinical considerations for ASV-treated CSR-CSA in HF. CSR-CSA in HF is associated with higher overall mortality, worse outcomes and lower quality of life (QOL) than HF without CSR-CSA. Five databases were searched using key words (n = 234). Randomized controlled trials assessed objective sleep quality, cardiac, and self-reported outcomes in adults (≥18 years) with HF (n = 10). ASV has a beneficial effect on the reduction of central sleep apnea in adult patients with CSR-CSA in HF, but it is not be superior to CPAP, bilevel PPV, or supplemental oxygen in terms of sleep quality defined by polysomnography, cardiovascular outcomes, subjective daytime sleepiness, and quality of life. ASV is not recommended for CSR-CSA in HF. It is important to continue to refer HF patients for sleep evaluation to clearly discern OSA from CSR-CSA. Symptom management research, inclusive of objective and subjective outcomes, in CSR-CSA in HF adults is needed. Copyright © 2016 Elsevier Inc. All rights reserved.

The independent effects of child sexual abuse and impulsivity on lifetime suicide attempts among female patients.

PubMed

Daray, Federico M; Rojas, Sasha M; Bridges, Ana J; Badour, Christal L; Grendas, Leandro; Rodante, Demián; Puppo, Soledad; Rebok, Federico

2016-08-01

Child sexual abuse (CSA) is a causal agent in many negative adulthood outcomes, including the risk for life-threatening behaviors such as suicide ideation and suicide attempts. Traumatic events such as CSA may pose risk in the healthy development of cognitive and emotional functioning during childhood. In fact, high impulsivity, a risk factor for suicidal behavior, is characteristic of CSA victims. The current study aims to understand the relations among CSA, impulsivity, and frequency of lifetime suicide attempts among a female patient sample admitted for suicidal behavior. Participants included 177 female patients between the ages of 18 and 63 years admitted at two hospitals in Buenos Aires, Argentina. Number of previous suicide attempts and CSA were assessed via structured interviews, while impulsivity was assessed with the Barratt Impulsiveness Scale (BIS-11). A model of structural equations was employed to evaluate the role of impulsivity in the relation between CSA and suicide attempts. CSA (β=.18, p<.05) and impulsivity (β=.24, p<.05) were associated with the number of previous suicide attempts. However, impulsivity was not significantly associated with CSA (β=.09, p>.05). CSA and impulsivity are independently associated with lifetime suicide attempts among female patients with recent suicidal behavior. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Cyclosporin A causes oxidative stress and mitochondrial dysfunction in renal tubular cells].

PubMed

Pérez de Hornedo, J; de Arriba, G; Calvino, M; Benito, S; Parra, T

2007-01-01

Reactive oxygen species (ROS) have been implicated in cyclosporin A (CsA) nephrotoxicity. As mitochondria are one of the main sources of ROS in cells, we evaluated the role of CsA in mitochondrial structure and function in LLC-PK1 cells. We incubated cells with CsA 1 microM for 24 hours and studies were performed with flow citometry and confocal microscopy. We studied mitochondrial NAD(P)H content, superoxide anion (O2.-) production (MitoSOX Red), oxidation of cardiolipin of inner mitochondrial membrane (NAO) and mitochondrial membrane potential (DIOC2(3)). Also we analyzed the intracellular ROS synthesis (H2DCF-DA) and reduced glutation (GSH) of cells. Our results showed that CsA decreased NAD(P)H and membrane potential, and increased O2.- in mitochondria. CsA also provoked oxidation of cardiolipin. Furthermore, CsA increased intracellular ROS production and decreased GSH content. These results suggest that CsA has crucial effects in mitochondria. CsA modified mitochondrial physiology through the decrease of antioxidant mitochondrial compounds as NAD(P)H and the dissipation of mitochondrial membrane potential and increase of oxidants as O2.-. Also, CsA alters lipidic structure of inner mitochondrial membrane through the oxidation of cardiolipin. These effects trigger a chain of events that favour intracellular synthesis of ROS and depletion of GSH that can compromise cellular viability. Nephrotoxic cellular effects of CsA can be explained, at least in part, through its influence on mitochondrial functionalism.

Symptomatology and health care utilization of women primary care patients who experienced childhood sexual abuse.

PubMed

Hulme, P A

2000-11-01

The purpose of this study was to (1) determine the symptomatology of women primary care patients who experienced childhood sexual abuse (CSA), using both a self-report survey and a chart review, and (2) determine their health care utilization patterns, using chart and information system reviews. An ex post facto research design was used. Women primary care patients who experienced CSA were compared with those who reported no CSA. Participants were recruited from a random sample of women patients from a large primary care clinic. They were mailed the survey; chart and information system reviews were conducted on those who returned surveys. Of the 395 participants, 23% reported past CSA on the survey. Women who experienced CSA reported 44 out of 51 physical and psychosocial symptoms more frequently than their counterparts who reported no past CSA. Further, they experienced these symptoms more intensely and in greater number. In their charts, however, far fewer differences in symptoms between groups were found. Nonetheless, women who experienced CSA visited the primary care clinic an average of 1.33 more times than women with no CSA, and they incurred an average of $150 more in primary care charges over a 2-year period. The findings indicate that many women primary care patients who experienced CSA suffer multiple symptoms that are not reflected in their charts. In addition, the findings demonstrate that not only is CSA associated with increased primary care visits, but also increased primary care costs, as measured by charges.

Clinical characteristic and risk factors of recurrent sexual abuse and delayed reported sexual abuse in childhood

PubMed Central

Hu, Mei-Hua; Huang, Go-Shine; Huang, Jing-Long; Wu, Chang-Teng; Chao, An-Shine; Lo, Fu-Sung; Wu, Han-Ping

2018-01-01

Abstract Child sexual abuse (CSA) is a global problem that affects children of all ages, and the evaluation of these victims by psychologic and gynecologic experts in pediatric emergency departments is an important issue. Few data are available on the characteristics of children admitted to pediatric emergency department with recurrent CSA and delayed reported CSA. The aim of the present study was to describe the clinical features of, and risk factors for, recurrent CSA and delayed reported CSA. The study retrospectively analyzed victims of CSA who were admitted to a pediatric emergency department. Chi-square tests and univariate analyses were performed to assess the risk factors of recurrent or delayed reported CSA. Of the 91 CSA cases, 32 (35.2%) were recurrent assaults. Of the 70 cases recorded the duration of the event, 22 (31.4%) were delayed report cases. Comparisons of the non-recurrent and recurrent CSA assault groups revealed a significant increase in comorbidities (odds ratio [OR]: 4.46, 95% confidence interval [CI]: 1.54–12.93), acute psychiatric problems (OR: 3.18, CI: 1.26–8.06), attempted suicide (OR: 4.23, CI: 1.28–13.99), and the need for treatment with antipsychotic medications (OR: 5.57, CI: 1.37–22.65). Compared with non-delayed reported cases, the delay reported cases of CSA were significantly more likely to have anxiety (P < .05). The CSA victims in the present study exhibited acute medical and/or psychosocial problems, which indicate that pediatric emergency professionals have a responsibility to look for and recognize particular characteristics in these victims. PMID:29620636

Optimizing expression of the pregnancy malaria vaccine candidate, VAR2CSA in Pichia pastoris.

PubMed

Avril, Marion; Hathaway, Marianne J; Cartwright, Megan M; Gose, Severin O; Narum, David L; Smith, Joseph D

2009-06-29

VAR2CSA is the main candidate for a vaccine against pregnancy-associated malaria, but vaccine development is complicated by the large size and complex disulfide bonding pattern of the protein. Recent X-ray crystallographic information suggests that domain boundaries of VAR2CSA Duffy binding-like (DBL) domains may be larger than previously predicted and include two additional cysteine residues. This study investigated whether longer constructs would improve VAR2CSA recombinant protein secretion from Pichia pastoris and if domain boundaries were applicable across different VAR2CSA alleles. VAR2CSA sequences were bioinformatically analysed to identify the predicted C11 and C12 cysteine residues at the C-termini of DBL domains and revised N- and C-termimal domain boundaries were predicted in VAR2CSA. Multiple construct boundaries were systematically evaluated for protein secretion in P. pastoris and secreted proteins were tested as immunogens. From a total of 42 different VAR2CSA constructs, 15 proteins (36%) were secreted. Longer construct boundaries, including the predicted C11 and C12 cysteine residues, generally improved expression of poorly or non-secreted domains and permitted expression of all six VAR2CSA DBL domains. However, protein secretion was still highly empiric and affected by subtle differences in domain boundaries and allelic variation between VAR2CSA sequences. Eleven of the secreted proteins were used to immunize rabbits. Antibodies reacted with CSA-binding infected erythrocytes, indicating that P. pastoris recombinant proteins possessed native protein epitopes. These findings strengthen emerging data for a revision of DBL domain boundaries in var-encoded proteins and may facilitate pregnancy malaria vaccine development.

Optimizing expression of the pregnancy malaria vaccine candidate, VAR2CSA in Pichia pastoris

PubMed Central

Avril, Marion; Hathaway, Marianne J; Cartwright, Megan M; Gose, Severin O; Narum, David L; Smith, Joseph D

2009-01-01

Background VAR2CSA is the main candidate for a vaccine against pregnancy-associated malaria, but vaccine development is complicated by the large size and complex disulfide bonding pattern of the protein. Recent X-ray crystallographic information suggests that domain boundaries of VAR2CSA Duffy binding-like (DBL) domains may be larger than previously predicted and include two additional cysteine residues. This study investigated whether longer constructs would improve VAR2CSA recombinant protein secretion from Pichia pastoris and if domain boundaries were applicable across different VAR2CSA alleles. Methods VAR2CSA sequences were bioinformatically analysed to identify the predicted C11 and C12 cysteine residues at the C-termini of DBL domains and revised N- and C-termimal domain boundaries were predicted in VAR2CSA. Multiple construct boundaries were systematically evaluated for protein secretion in P. pastoris and secreted proteins were tested as immunogens. Results From a total of 42 different VAR2CSA constructs, 15 proteins (36%) were secreted. Longer construct boundaries, including the predicted C11 and C12 cysteine residues, generally improved expression of poorly or non-secreted domains and permitted expression of all six VAR2CSA DBL domains. However, protein secretion was still highly empiric and affected by subtle differences in domain boundaries and allelic variation between VAR2CSA sequences. Eleven of the secreted proteins were used to immunize rabbits. Antibodies reacted with CSA-binding infected erythrocytes, indicating that P. pastoris recombinant proteins possessed native protein epitopes. Conclusion These findings strengthen emerging data for a revision of DBL domain boundaries in var-encoded proteins and may facilitate pregnancy malaria vaccine development. PMID:19563628

Celecoxib offsets the negative renal influences of cyclosporine via modulation of the TGF-β1/IL-2/COX-2/endothelin ET(B) receptor cascade.

PubMed

El-Gowelli, Hanan M; Helmy, Maged W; Ali, Rabab M; El-Mas, Mahmoud M

2014-03-01

Endothelin (ET) signaling provokes nephrotoxicity induced by the immunosuppressant drug cyclosporine A (CSA). We tested the hypotheses that (i): celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, counterbalances renal derangements caused by CSA in rats and (ii) the COX-2/endothelin ET(B) receptor signaling mediates the CSA-celecoxib interaction. Ten-day treatment with CSA (20 mg/kg/day) significantly increased biochemical indices of renal function (serum urea, creatinine), inflammation (interleukin-2, IL-2) and fibrosis (transforming growth factor-β₁, TGF-β₁). Histologically, CSA caused renal tubular atrophy along with interstitial fibrosis. These detrimental renal effects of CSA were largely reduced in rats treated concurrently with celecoxib (10 mg/kg/day). We also report that cortical glomerular and medullary tubular protein expressions of COX-2 and ET(B) receptors were reduced by CSA and restored to near-control values in rats treated simultaneously with celecoxib. The importance of ET(B) receptors in renal control and in the CSA-celecoxib interaction was further verified by the findings (i) most of the adverse biochemical, inflammatory, and histopathological profiles of CSA were replicated in rats treated with the endothelin ETB receptor antagonist BQ788 (0.1 mg/kg/day, 10 days), and (ii) the BQ788 effects, like those of CSA, were alleviated in rats treated concurrently with celecoxib. Together, the data suggest that the facilitation of the interplay between the TGF-β1/IL-2/COX-2 pathway and the endothelin ET(B) receptors constitutes the cellular mechanism by which celecoxib ameliorates the nephrotoxic manifestations of CSA in rats. Copyright © 2014 Elsevier Inc. All rights reserved.

Aluminum exacerbates cyclosporin induced nephrotoxicity in rats.

PubMed

Tariq, M; Morais, C; Sujata, B; Sobki, S; al Sulaiman, M; al Khader, A

1999-01-01

Cyclosporin (CSA) has been universally used as an immunosuppressant for the management of allotransplantation and autoimmune diseases. However, nephrotoxicity of CSA limits its use to optimum level. Aluminum (Al) is an extensively distributed element in the environment and human exposure to this metal is unavoidable. Recent studies suggest that even a slight impairment of renal function may increase the Al body burden significantly, which may lead to neurotoxicity, nephrotoxicity, osteodystrophy or hypochromic anemia. In the present study, an attempt was made to study the effect of concomitant use of Al and CSA on structure and function of kidney in rats. This study was undertaken in two steps. In the first set of experiments, the effect of single dose of Al (1% Al2(SO4)3 18H2O) on the nephrotoxicity of multiple doses of CSA (12.5 mg/kg, 25 mg/kg and 50 mg/kg) was studied, where as in the second set of experiments the effect of multiple doses of Al (0.25%, 0.5% and 1%) on single dose of CSA (50 mg/kg) was undertaken. Male Sprague-Dawley rats (weighing 230 +/- 20 g) were used in this study. CSA was given once a day by gavage for seven days, where as Al was given in drinking water for the same period. Twenty four hours after the last dose of CSA, animals were sacrificed and blood and kidney were collected for biochemical and histopathological studies. The bio-chemical parameters included blood urea nitrogen (BUN), serum creatinine (SCr), CSA and Al levels. The kidney homogenates were assayed for malondialdehyde (MDA) and lipid hydroperoxides (LPH). Treatment of rats with CSA alone produced dose-dependent structural and functional changes in kidney. Although Al alone failed to produce any deleterious effect on renal function, it significantly increased the bioavailability and nephrotoxicity of CSA. Al also exacerbated CSA induced increase in oxidative stress (as evident by increased MDA and LPH). Thus, the exacerbation of CSA nephrotoxicity by Al may be attributed to increased bioavailability of CSA and excessive generation of free radicals following concomitant use of these drugs.

Critical Shoulder Angle and Acromial Index Do Not Influence 24-Month Functional Outcome After Arthroscopic Rotator Cuff Repair.

PubMed

Lee, Merrill; Chen, Jerry Yongqian; Liow, Ming Han Lincoln; Chong, Hwei Chi; Chang, Paul; Lie, Denny

2017-11-01

Recent studies have shown a correlation between scapular geometry and the development of atraumatic rotator cuff tears. However, a paucity of literature is available on the effects of critical shoulder angle (CSA) and acromial index (AI) on functional outcomes after arthroscopic rotator cuff repair. Hypothesis/Purpose: The purpose was to investigate the influence of CSA and AI on 24-month functional outcomes after arthroscopic rotator cuff repair. The hypothesis was that a larger CSA or AI would result in poorer postoperative outcomes. Cohort study; Level of evidence, 3. The study included 147 patients who underwent arthroscopic double-row rotator cuff repair for radiologically documented full-thickness supraspinatus tears. An independent reviewer measured the CSA and AI on preoperative radiographs. These patients were prospectively enrolled and were evaluated preoperatively as well as at 3, 6, 12, and 24 months postoperatively. Functional outcome was assessed with the Constant Shoulder Score (CSS), Oxford Shoulder Score (OSS), and University of California at Los Angeles (UCLA) Shoulder Rating Scale. The patients were first divided based on CSA: (1) ≤35° (control CSA) and (2) >35° (increased CSA); and then based on AI: (1) ≤0.7 and (2) >0.7. The Student unpaired t test, Pearson chi-square test, and Pearson correlation were performed to examine the influence of CSA and AI on postoperative functional outcome scores. At 6 months of follow-up, the CSS, OSS, and UCLA Shoulder Rating Scale were 10 ± 1, 4 ± 2, and 3 ± 1 points poorer in the increased CSA group compared with the control CSA group ( P = .005, P = .030, and P = .035, respectively). These scores were not significantly different between both AI groups. By 24 months of follow-up, all outcome scores were comparable between both CSA groups as well as between both AI groups. No significant correlation was found between either CSA or AI when compared with CSS, OSS, or UCLA Shoulder Rating Scale at 24 months of follow-up. CSA and AI do not appear to influence 24-month functional outcomes postoperatively and hence are not contraindications to arthroscopic rotator cuff repair.

[Magnetic resonance imaging study of effects of accommodation on human lens morphological characters].

PubMed

Zheng, Sui-lian; Zhang, Ai; Shi, Jian-jing; Zhou, Yun-xin

2013-11-05

To evaluate the effects of accommodation on lens morphological characters. From January 2011 to June 2011, magnetic resonance images of eyes were acquired from 30 subjects aged 20 to 24 years during accommodation and at rest. The optimal images were analyzed by Autocad 2010 to obtain the total lens cross-sectional area (CSA) and CSA of anterior and posterior portions of lens, anterior chamber depth, lens thickness, lens diameter, vitreous chamber depth and axial length during accommodation and at rest. Paired-t test was performed. The anterior curvature radius (mm), posterior curvature radius (mm), CSA of anterior portion (mm(2)), CSA of posterior portion (mm(2)), total lens CSA (mm(2)) was (8.7 ± 0.8), (6.2 ± 0.5), (7.5 ± 2.1), (12.0 ± 2.6), (20 ± 4) during relaxed accommodation; anterior curvature radius (mm), posterior curvature radius (mm), CSA of anterior portion (mm(2)), CSA of posterior portion (mm(2)), total lens CSA (mm(2)) was (7.1 ± 1.3), (5.6 ± 0.5), (14.7 ± 2.9), (12.2 ± 2.1) and (27 ± 4) during accommodation. The total lens CSA (t = -11.556, P < 0.01) and CSA of anterior portion (t = -15.653, P < 0.01) both increased in accommodative states. The CSA of posterior portion of lens (t = -0.437, P > 0.05) under a statistically independent accommodative state. There was significant difference in the anterior chamber depth (t = 4.366, P < 0.01), lens thickness (t = -5.456, P < 0.01) and lens diameter (t = 4.597, P < 0.01) in accommodative states. There were insignificant differences both in vitreous chamber depth (t = 0.428, P > 0.05) and axial length (t = 0.418, P > 0.05) under accommodative states. During accommodation, the anterior chamber depth decreases, lens thickness increases and diameter of lens decreases while anterior portions and total lens CSA increase. There are insignificant changes in posterior portions of lens CSA, vitreous chamber depth and axial length. The accommodative changes in CSA indicate that the anterior portion of lens may be related with the properties of anterior capsule and lens material, the position of zonular attachments and the location of fetal nucleus. Helmholtz theory is supported.

The prevalence and impact of childhood sexual abuse on HIV-risk behaviors among men who have sex with men (MSM) in India.

PubMed

Tomori, Cecilia; McFall, Allison M; Srikrishnan, Aylur K; Mehta, Shruti H; Nimmagadda, Nymisha; Anand, Santhanam; Vasudevan, Canjeevaram K; Solomon, Suniti; Solomon, Sunil S; Celentano, David D

2016-08-12

Childhood sexual abuse (CSA) is a significant global public health problem, which is associated with negative psychosocial outcomes and high-risk sexual behaviors in adults. Men who have sex with men (MSM) often report higher prevalence of CSA history than the general population, and CSA may play a key role in MSM's greater vulnerability to HIV. This study examined the prevalence of CSA history and its impact on the number of recent HIV-related risk behaviors (unprotected anal intercourse, high number of male and female sexual partners, alcohol use, drug use, and sex work in prior 6 months) and lifetime risk behaviors and experiences (high number of lifetime male and female sexual partners, early sexual debut, injection drug use, sex work, and intimate partner violence) among 11,788 adult MSM recruited via respondent driven sampling across 12 sites in India, with additional insights from thematic analysis of qualitative research with 363 MSM from 15 sites. Nearly a quarter (22.4 %) of participants experienced CSA, with substantially higher prevalence of CSA in the South and among kothis (feminine sexual identity). Qualitative findings revealed that older, trusted men may target young and, especially, gender nonconforming boys, and perpetrators' social position facilitates nondisclosure. CSA may also initiate further same-sex encounters, including sex work. In multivariable analysis, MSM who experienced CSA had 21 % higher rate of recent (adjusted rate ratio [aRR = 1.21], 95 % confidence interval [CI]: 1.14-1.28), and 2.0 times higher lifetime (aRR = 2.04, 95 % CI: 1.75-2.38) HIV-related behaviors/experiences compared with those who did not. This large, mixed-methods study found high overall prevalence of CSA among MSM (22.4 %), with substantially higher prevalence among MSM residing in the South and among more feminine sexual identities. Qualitative findings highlighted boys' vulnerabilities to CSA, especially gender nonconformity, and CSA's role in further sexual encounters, including sex work. Additionally, CSA was associated with an elevated rate of recent, and an even higher rate of lifetime HIV-related risk factors. Our results suggest an acute need for the development of CSA prevention interventions and the integration of mental health services for MSM with histories of CSA as part of HIV-prevention efforts.

A Novel Virus-Like Particle Based Vaccine Platform Displaying the Placental Malaria Antigen VAR2CSA.

PubMed

Thrane, Susan; Janitzek, Christoph M; Agerbæk, Mette Ø; Ditlev, Sisse B; Resende, Mafalda; Nielsen, Morten A; Theander, Thor G; Salanti, Ali; Sander, Adam F

2015-01-01

Placental malaria caused by Plasmodium falciparum is a major cause of mortality and severe morbidity. Clinical testing of a soluble protein-based vaccine containing the parasite ligand, VAR2CSA, has been initiated. VAR2CSA binds to the human receptor chondroitin sulphate A (CSA) and is responsible for sequestration of Plasmodium falciparum infected erythrocytes in the placenta. It is imperative that a vaccine against malaria in pregnancy, if administered to women before they become pregnant, can induce a strong and long lasting immune response. While most soluble protein-based vaccines have failed during clinical testing, virus-like particle (VLP) based vaccines (e.g., the licensed human papillomavirus vaccines) have demonstrated high efficacy, suggesting that the spatial assembly of the vaccine antigen is a critical parameter for inducing an optimal long-lasting protective immune response. We have developed a VLP vaccine display platform by identifying regions of the HPV16 L1 coat protein where a biotin acceptor site (AviTagTM) can be inserted without compromising VLP-assembly. Subsequent biotinylation of Avi-L1 VLPs allow us to anchor monovalent streptavidin (mSA)-fused proteins to the biotin, thereby obtaining a dense and repetitive VLP-display of the vaccine antigen. The mSA-VAR2CSA antigen was delivered on the Avi-L1 VLP platform and tested in C57BL/6 mice in comparison to two soluble protein-based vaccines consisting of naked VAR2CSA and mSA-VAR2CSA. The mSA-VAR2CSA Avi-L1 VLP and soluble mSA-VAR2CSA vaccines induced higher antibody titers than the soluble naked VAR2CSA vaccine after three immunizations. The VAR2CSA Avi-L1 VLP vaccine induced statistically significantly higher endpoint titres compared to the soluble mSA-VAR2CSA vaccine, after 1st and 2nd immunization; however, this difference was not statistically significant after 3rd immunization. Importantly, the VLP-VAR2CSA induced antibodies were functional in inhibiting the binding of parasites to CSA. This study demonstrates that the described Avi-L1 VLP-platform may serve as a versatile system for facilitating optimal VLP-display of large and complex vaccine antigens.

Carpal tunnel syndrome assessment with ultrasonography: value of inlet-to-outlet median nerve area ratio in patients versus healthy volunteers.

PubMed

Fu, Tengfei; Cao, Manlin; Liu, Fang; Zhu, Jiaan; Ye, Dongmei; Feng, Xianxuan; Xu, Yiming; Wang, Gang; Bai, Yuehong

2015-01-01

To evaluate the diagnostic value of the Inlet-to-outlet median nerve area ratio (IOR) in patients with clinically and electrophysiologically confirmed carpal tunnel syndrome (CTS). Forty-six wrists in 46 consecutive patients with clinical and electrodiagnostic evidence of CTS and forty-four wrists in 44 healthy volunteers were examined with ultrasonography. The cross-sectional area (CSA) of the median nerve was measured at the carpal tunnel inlet (the level of scaphoid-pisiform) and outlet (the level of the hook of the hamate), and the IOR was calculated for each wrist. Ultrasonography and electrodiagnostic tests were performed under blinded conditions. Electrodiagnostic testing combined with clinical symptoms were considered to be the gold standard test. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value between the inlet CSA and IOR. The study population included 16 men and 30 women (mean age, 45.3 years; range, 18-83 years). The control population included 18 men and 26 women (mean age, 50.4 years; range, 18-79 years). The mean inlet CSA was 8.7 mm2 in healthy controls and 14.6mm2 in CTS group (P<0.001). The mean IOR in healthy volunteers (1.0) was smaller than that in patients (1.6, P<0.001). Receiver operating characteristic analysis revealed a diagnostic advantage to using the IOR rather than the inlet CSA (P<0.01). An IOR cutoff value of ≥ 1.3 would yield 93% specificity and 91% sensitivity in the diagnosis of CTS. The IOR of median nerve area promises to be an effective means in the diagnosis of CTS. A large-scale, randomized controlled trial is required to determine how and when this parameter will be used.

Shear-wave elastography: a new potential method to diagnose ulnar neuropathy at the elbow.

PubMed

Paluch, Łukasz; Noszczyk, Bartłomiej; Nitek, Żaneta; Walecki, Jerzy; Osiak, Katarzyna; Pietruski, Piotr

2018-06-01

The primary aim of this study was to verify if shear-wave elastography (SWE) can be used to diagnose ulnar neuropathy at the elbow (UNE). The secondary objective was to compare the cross-sectional areas (CSA) of the ulnar nerve in the cubital tunnel and to determine a cut-off value for this parameter accurately identifying persons with UNE. The study included 34 patients with UNE (mean age, 59.35 years) and 38 healthy controls (mean age, 57.42 years). Each participant was subjected to SWE of the ulnar nerve at three levels: in the cubital tunnel (CT) and at the distal arm (DA) and mid-arm (MA). The CSA of the ulnar nerve in the cubital tunnel was estimated by means of ultrasonographic imaging. Patients with UNE presented with significantly greater ulnar nerve stiffness in the cubital tunnel than the controls (mean, 96.38 kPa vs. 33.08 kPa, p < 0.001). Ulnar nerve stiffness of 61 kPa, CT to DA stiffness ratio equal 1.68, and CT to MA stiffness ratio of 1.75 provided 100% specificity, sensitivity, positive and negative predictive value in the detection of UNE. Mean CSA of the ulnar nerve in the cubital tunnel turned out to be significantly larger in patients with UNE than in healthy controls (p < 0.001). A weak positive correlation was found in the UNE group between the ulnar nerve CSA and stiffness (R = 0.31, p = 0.008). SWE seems to be a promising, reliable and simple quantitative adjunct test to support the diagnosis of UNE. • SWE enables reliable detection of cubital tunnel syndrome • Significant increase of entrapped ulnar nerve stiffness is observed in UNE • SWE is a perspective screening tool for early detection of compressive neuropathies.

Types and Characteristics of Childhood Sexual Abuse: How Do They Matter in HIV Sexual Risk Behaviors Among Women in Methadone Treatment in New York City?

PubMed

Engstrom, Malitta; Winham, Katherine; Gilbert, Louisa

2016-01-01

Childhood sexual abuse (CSA) is often considered an important distal factor in HIV sexual risk behaviors; however, there are limited and mixed findings regarding this relationship among women experiencing substance use problems. In addition, research with this population of women has yet to examine differences in observed CSA-HIV sexual risk behaviors relationships by CSA type and characteristics. This study examines relationships between CSA coding, type, and characteristics and HIV sexual risk behaviors with main intimate partners among a random sample of 390 women in methadone treatment in New York City who completed individual interviews with trained female interviewers. Findings from logistic regression analyses indicate that CSA predicts substance use with sexual activity, with variations by CSA coding, type, and characteristics; however, the role of CSA is more limited than expected. Having a main partner with HIV risk mediates some relationships between CSA and drinking four or more drinks prior to sex. Intimate partner violence is the most consistent predictor of sexual risk behaviors. Other salient factors include polysubstance use, depression, social support, recent incarceration, relationship characteristics, and HIV status. This study contributes to understanding of relationships between CSA and HIV sexual risk behaviors and key correlates associated with HIV sexual risk behaviors among women in methadone treatment. It also highlights the complexity of measuring CSA and its association with sexual risk behaviors and the importance of comprehensive approaches to HIV prevention that address psychological, relational, situational, and substance use experiences associated with sexual risk behaviors among this population.

A Quantitative Study on Gender Differences in Disclosing Child Sexual Abuse and Reasons for Nondisclosure.

PubMed

Okur, Pinar; van der Knaap, Leontien M; Bogaerts, Stefan

2017-07-01

Despite the available literature on disclosure of child sexual abuse (CSA), little is known about how gender affects disclosure. This article aims to quantitatively examine whether gender differences exist in formal (to legal or child protection authorities) and informal (to a family member or friend) disclosure of CSA and, if so, to assess whether this relation is associated with abuse characteristics and attitudes toward gender roles. The study also aimed to examine whether gender differences exist in reasons not to disclose CSA. Data of a sample of 586 participants, who reported to have experienced CSA committed by a single person, have been used for the analyses. There were no gender differences for formal disclosure, but the informal disclosure rate of CSA was 2.4 times higher for women than men, and this effect remained significant after controlling for abuse characteristics and attitudes, even though the gender difference decreased slightly. Furthermore, women and men reported different reasons for not disclosing CSA in their personal network. Women were more worried than men that family and friends would discover the abuse and reported more insecurity of what to do in this situation. Professionals in the field of CSA should consider a gender perspective when developing guidelines. Men have rarely been the subject of studies of disclosure after CSA. Professionals should focus more on general mental health outcomes of men that are not related with CSA directly, but where the effects of CSA may exert more indirectly through associations with other problems in life.

Ultrasonography has a diagnostic value in the assessment of cervical radiculopathy: A prospective pilot study.

PubMed

Takeuchi, Mikinobu; Wakao, Norimitsu; Hirasawa, Atsuhiko; Murotani, Kenta; Kamiya, Mitsuhiro; Osuka, Koji; Takayasu, Masakazu

2017-08-01

This study investigated the diagnostic accuracy of the difference in the cross-sectional areas (CSAs) of affected cervical nerve roots (NRs) for diagnosing cervical radiculopathy (CR). In total, 102 CR patients and 219 healthy volunteers were examined with ultrasound. The CSA of the cervical NR at each level was measured on the affected side and the contralateral side in CR patients by blinded ultrasonographic technicians. The difference between the CSAs of CR patients and normal volunteers and the difference in the laterality of CSA at the same affected level (ΔCSA) were calculated for each cervical level. The CSAs of the affected NRs in CR patients were significantly larger than those of the unaffected NRs in CR patients and those of the control group at the C5, C6 and C7 levels (P<0.005). ΔCSA was also significantly larger in the CR group at all levels (P<0.001). A receiver operating characteristic analysis demonstrated that the threshold values were 9.6 mm 2 (CSA) for C5NR and 15 mm 2 for both C6NR and C7NR. This study revealed that the CSAs of affected NRs were enlarged and that the laterality of the CSA (ΔCSA) was greater in CR patients than in control patients. • Cervical radiculopathy is diagnosed through ultrasonographic measurement of the CSAs. • The CSAs of affected nerve roots were significantly enlarged. • The ΔCSA in the CR group was significantly higher than in the control group. • Diagnostic CSA and ΔCSA thresholds were identified.

What Is the Most Representative Parameter for Describing the Size of the Atlas? CT Morphometric Analysis of the Atlas with Special Reference to Atlas Hypoplasia.

PubMed

Yamahata, Hitoshi; Hirano, Hirofumi; Yamaguchi, Satoshi; Mori, Masanao; Niiro, Tadaaki; Tokimura, Hiroshi; Arita, Kazunori

2017-09-15

The spinal canal diameter (SCD) is one of the most studied factors for the assessment of cervical spinal canal stenosis. The inner anteroposterior diameter (IAP), the SCD, and the cross-sectional area (CSA) of the atlas have been used for the evaluation of the size of the atlas in patients with atlas hypoplasia, a rare form of developmental spinal canal stenosis, however, there is little information on their relationship. The aim of this study was to identify the most useful parameter for depicting the size of the atlas. The CSA, the IAP, and the SCD were measured on computed tomography (CT) images at the C1 level of 213 patients and compared in this retrospective study. These three parameters increased with increasing patient height and weight. There was a strong correlation between IAP and SCD (r = 0.853) or CSA (r = 0.822), while correlation between SCD and CSA (r = 0.695) was weaker than between IAP and CSA. Partial correlation analysis showed that IAP was positively correlated with SCD (r = 0.687) and CSA (r = 0.612) when CSA or SCD were controlled. SCD was negatively correlated with CSA when IAP was controlled (r = -0.21). The IAP can serve as the CSA for the evaluation of the size of the atlas ring, while the SCD does not correlate with the CSA. As the patient height and weight affect the size of the atlas, analysis of the spinal canal at the C1 level should take into account physiologic patient data.

Allostatic Perspectives in Women Veterans With a History of Childhood Sexual Assault.

PubMed

Groër, Maureen Wimberly; Kostas-Polston, Elizabeth A; Dillahunt-Aspillaga, Christina; Beckie, Theresa M; Johnson-Mallard, Versie; Duffy, Allyson; Evans, Mary E

2016-07-01

Women veterans have increased reports of sexual victimization compared to women in general, including childhood sexual assault (CSA) before military service, increasing the risk of military sexual trauma. Findings from recent studies reveal negative health effects following a history of CSA. There is a strong relationship between CSA and revictimization in civilian and military life, which may contribute to allostatic load. (1) To determine the relationship between women veterans' CSA history and later sexual assault history and (2) to determine the relationships between women veterans' CSA and primary mediators and secondary and tertiary outcomes of allostasis. Cross-sectional. Women (N = 81), 18-70 years old, veterans of the U.S. Armed Services. Participants completed questionnaires and blood and hair samples were collected. Several scales were utilized: Posttraumatic Checklist-Military, Center for Epidemiological Studies-Depression Scale, Pain Outcomes Questionnaire-Short Form, Cohen's Perceived Stress Scale (PSS), Profile of Mood States, and an investigator-developed sexual harassment/assault instrument. Thirty-three percent of participants reported CSA; of these, 38.5% reported military sexual assault and 70.3% sexual assault during civilian life. Those with CSA had higher cholesterol, triglycerides, perceived stress scores, and greater pain and fatigue than those without CSA. Hair cortisol was marginally lower in women with CSA when PSS was controlled, suggesting a dampened hypothalamic-pituitary-adrenal axis. These data suggest that some women veterans with a history of CSA may have increased allostatic load and be at increased risk for a variety of later life illnesses. © The Author(s) 2016.

PTSD and marital satisfaction in military service members: examining the simultaneous roles of childhood sexual abuse and combat exposure.

PubMed

Miller, Adam B; Schaefer, Karen E; Renshaw, Keith D; Blais, Rebecca K

2013-11-01

Childhood sexual abuse (CSA) is relatively common and is associated with a multitude of negative outcomes in adulthood, including posttraumatic stress disorder (PTSD) and lower marital satisfaction. However, CSA has been understudied in military samples. The purpose of the present study was to examine the relative contributions of CSA and combat exposure to PTSD and marital satisfaction. Two hundred eighteen National Guard/Reserve veterans who deployed overseas between 2001 and 2008 completed self-report measures of CSA, marital satisfaction, combat exposure, and PTSD symptom severity. Data were analyzed using linear regression and path analysis to evaluate a comprehensive model including all variables. CSA accounted for unique variance in PTSD symptom severity independent of combat exposure. CSA also had a negative direct association with marital satisfaction, independent of combat exposure and PTSD symptom severity. In contrast, combat exposure had only a negative indirect association with marital satisfaction via PTSD when all variables were examined simultaneously. CSA accounted for unique variance in both PTSD symptom severity and marital satisfaction in this sample of combat veterans. Clinically, results suggest that assessment and treatment of CSA is indicated for military veterans suffering from PTSD. Further, treatment of CSA may improve marital satisfaction, which may positively affect psychological functioning in the veteran. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mechanism and Catalytic Site Atlas (M-CSA): a database of enzyme reaction mechanisms and active sites.

PubMed

Ribeiro, António J M; Holliday, Gemma L; Furnham, Nicholas; Tyzack, Jonathan D; Ferris, Katherine; Thornton, Janet M

2018-01-04

M-CSA (Mechanism and Catalytic Site Atlas) is a database of enzyme active sites and reaction mechanisms that can be accessed at www.ebi.ac.uk/thornton-srv/m-csa. Our objectives with M-CSA are to provide an open data resource for the community to browse known enzyme reaction mechanisms and catalytic sites, and to use the dataset to understand enzyme function and evolution. M-CSA results from the merging of two existing databases, MACiE (Mechanism, Annotation and Classification in Enzymes), a database of enzyme mechanisms, and CSA (Catalytic Site Atlas), a database of catalytic sites of enzymes. We are releasing M-CSA as a new website and underlying database architecture. At the moment, M-CSA contains 961 entries, 423 of these with detailed mechanism information, and 538 with information on the catalytic site residues only. In total, these cover 81% (195/241) of third level EC numbers with a PDB structure, and 30% (840/2793) of fourth level EC numbers with a PDB structure, out of 6028 in total. By searching for close homologues, we are able to extend M-CSA coverage of PDB and UniProtKB to 51 993 structures and to over five million sequences, respectively, of which about 40% and 30% have a conserved active site. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Antibody levels to recombinant VAR2CSA domains vary with Plasmodium falciparum parasitaemia, gestational age, and gravidity, but do not predict pregnancy outcomes.

PubMed

Fried, Michal; Kurtis, Jonathan D; Swihart, Bruce; Morrison, Robert; Pond-Tor, Sunthorn; Barry, Amadou; Sidibe, Youssoufa; Keita, Sekouba; Mahamar, Almahamoudou; Andemel, Naissem; Attaher, Oumar; Dembele, Adama B; Cisse, Kadidia B; Diarra, Bacary S; Kanoute, Moussa B; Narum, David L; Dicko, Alassane; Duffy, Patrick E

2018-03-09

Maternal malaria is a tropical scourge associated with poor pregnancy outcomes. Women become resistant to Plasmodium falciparum pregnancy malaria as they acquire antibodies to the variant surface antigen VAR2CSA, a leading vaccine candidate. Because malaria infection may increase VAR2CSA antibody levels and thereby confound analyses of immune protection, gravidity-dependent changes in antibody levels during and after infection, and the effect of VAR2CSA antibodies on pregnancy outcomes were evaluated. Pregnant women enrolled in a longitudinal cohort study of mother-infant pairs in Ouelessebougou, Mali provided plasma samples at enrollment, gestational week 30-32, and delivery. Antibody levels to VAR2CSA domains were measured using a multiplex bead-based assay. Antibody levels to VAR2CSA were higher in multigravidae than primigravidae. Malaria infection was associated with increased antibody levels to VAR2CSA domains. In primigravidae but not in secundigravidae or multigravidae, antibodies levels sharply declined after an infection. A relationship between any VAR2CSA antibody specificity and protection from adverse pregnancy outcomes was not detected. During malaria infection, primigravidae acquire short-lived antibodies. The lack of an association between VAR2CSA domain antibody reactivity and improved pregnancy outcomes suggests that the recombinant proteins may not present native epitopes targeted by protective antibodies.

Predicting Long-Term Outcomes for Women Sexually Abused in Childhood: Contribution of Abuse Severity Versus Family Environment

ERIC Educational Resources Information Center

Fassler, I.R.; Amodeo, M.; Griffin, M.L.; Clay, C.M.; Ellis, M.A.

2005-01-01

Objective:: Child sexual abuse (CSA) has been associated with adverse adult psychosocial outcomes, although some reports describe minimal long-term effects. The search for explanations for the heterogeneous outcomes in women with CSA has led to an examination of a range of CSA-related factors, from the severity of individual CSA incidents to the…

Relationships between childhood sexual abuse and substance use and sexual risk behaviors during adolescence: An integrative review.

PubMed

Draucker, Claire Burke; Mazurczyk, Jill

2013-01-01

Childhood sexual abuse (CSA) is thought to be a precursor to substance use and sexual risk behaviors during adolescence. To inform adolescent prevention efforts, information is needed to explicate the nature of the relationships between CSA and these health risks. The aim of this study was to summarize the current literature on the associations between a history of CSA and substance use and sexual risk behaviors during adolescence. We conducted a systematic literature search and an integrative review. Current evidence implicates CSA as a robust precursor to the use of a wide variety of substances and multiple sexual risk behaviors during adolescence. Screening for CSA in adolescents at risk and incorporating strategies that enhance CSA recovery in adolescent prevention programs are warranted. Future research that includes longitudinal designs, uses multiple methods of assessment, and identifies pathways between CSA and adolescent health risks is recommended. Copyright © 2013 Elsevier Inc. All rights reserved.

Long-term social status and intimate relationship in women with childhood sexual abuse who got outpatient psychotherapy for anxiety disorder and depression.

PubMed

Peleikis, Dawn E; Mykletun, Arnstein; Dahl, Alv A

2005-01-01

The aim of this paper was twofold: namely to examine current intimate relationships and social status of women with childhood sexual abuse (CSA) in the long term after outpatient psychotherapy, and to investigate the relative influence of CSA and family background risk factors (FBRF) on the indicators of this status. Fifty-six women with reported CSA and 56 without CSA, who had outpatient psychotherapy for anxiety disorders and/or depression, were personally examined 5 years after termination. Women with CSA had considerably greater sexual and mental health problems, but the same prevalence of partnerships, children and friends as the contrast. No differences were observed as to self-esteem, intimate bonds and physical quality of life. Sexual problems and low education were mainly explained by CSA, other measures by FBRF. Women treated with outpatient psychotherapy for anxiety disorders and depression had moderate problems at long-term follow-up, but more so for those women who had been exposed to CSA.

Poor Families Striving to Save in Matched Children's Savings Accounts: Findings from a Randomized Experimental Design in Uganda.

PubMed

Karimli, Leyla; Ssewamala, Fred M; Neilands, Torsten B

2014-12-01

This study examines participants' savings in children's savings accounts (CSAs) set up for AIDS-orphaned children ages 10-15 in Uganda. Using a cluster randomized experimental design, we examine the extent to which families participating in a CSA program report more savings than their counterparts not participating in the program, explore the extent to which families who participate in the CSA program report using formal financial institutions compared with families who do not have a CSA, and consider whether families participating in the CSA program bring new money into the CSA or whether they reshuffle existing household assets. We find that participating in a CSA increased families' likelihood to report having saved money. However, our results show no intervention effect either on the amount of self-reported savings or on the likelihood of using formal financial institutions. Further research is needed to understand whether use of a CSA helps families generate new wealth.

Poor Families Striving to Save in Matched Children’s Savings Accounts: Findings from a Randomized Experimental Design in Uganda

PubMed Central

Karimli, Leyla; Ssewamala, Fred M.; Neilands, Torsten B.

2014-01-01

This study examines participants’ savings in children’s savings accounts (CSAs) set up for AIDS-orphaned children ages 10–15 in Uganda. Using a cluster randomized experimental design, we examine the extent to which families participating in a CSA program report more savings than their counterparts not participating in the program, explore the extent to which families who participate in the CSA program report using formal financial institutions compared with families who do not have a CSA, and consider whether families participating in the CSA program bring new money into the CSA or whether they reshuffle existing household assets. We find that participating in a CSA increased families’ likelihood to report having saved money. However, our results show no intervention effect either on the amount of self-reported savings or on the likelihood of using formal financial institutions. Further research is needed to understand whether use of a CSA helps families generate new wealth. PMID:25525282

Anaerobic bacteria growth in the presence of cathelicidin LL-37 and selected ceragenins delivered as magnetic nanoparticles cargo.

PubMed

Durnaś, Bonita; Piktel, Ewelina; Wątek, Marzena; Wollny, Tomasz; Góźdź, Stanisław; Smok-Kalwat, Jolanta; Niemirowicz, Katarzyna; Savage, Paul B; Bucki, Robert

2017-07-26

Cationic antibacterial peptides (CAPs) and synthetic molecules mimicking the amphiphilic structure of CAPs, such as ceragenins, are promising compounds for the development of new antimicrobials. We tested the in vitro activity of ceragenins CSA-13 and CSA-131 against several anaerobic bacteria including Bacteroides spp. and Clostridium difficile. We compared results to the activity of cathelicidin LL-37, metronidazole and nanosystems developed by attachment of CSA-13 and CSA-131 to magnetic nanoparticles (MNPs). The antibacterial effect was tested using killing assay and modified CLSI broth microdilution assay. Ceragenins CSA-13 and CSA-131 displayed stronger bactericidal activity than LL-37 or metronidazole against all of the tested bacterial strains. Additionally CSA-131 revealed an enhanced ability to prevent the formation of Bacteroides fragilis and Propionibacterium acnes biofilms. These data confirmed that ceragenins display antimicrobial activity against a broad range of microorganisms including anaerobic bacteria and deserve further investigations as compounds serving to develop new treatment against anaerobic and mixed infections.

Antibodies among men and children to placental-binding Plasmodium falciparum-infected erythrocytes that express var2csa.

PubMed

Beeson, James G; Ndungu, Francis; Persson, Kristina E M; Chesson, Joanne M; Kelly, Greg L; Uyoga, Sophie; Hallamore, Sandra L; Williams, Thomas N; Reeder, John C; Brown, Graham V; Marsh, Kevin

2007-07-01

During pregnancy, specific variants of Plasmodium falciparum-infected erythrocytes (IEs) can accumulate in the placenta through adhesion to chondroitin sulfate A (CSA) mediated by expression of PfEMP1 encoded by var2csa-type genes. Antibodies against these variants are associated with protection from maternal malaria. We evaluated antibodies among Kenyan, Papua New Guinean, and Malawian men and Kenyan children against two different CSA-binding P. falciparum isolates expressing var2csa variants. Specific IgG was present at significant levels among some men and children from each population, suggesting exposure to these variants is not exclusive to pregnancy. However, the level and prevalence of antibodies was substantially lower overall than exposed multigravidas. IgG-binding was specific and did not represent antibodies to subpopulations of non-CSA-binding IEs, and some sera inhibited IE adhesion to CSA. These findings have significant implications for understanding malaria pathogenesis and immunity and may be significant for understanding the acquisition of immunity to maternal malaria.

Towards a common framework for assessing the activity and associations of groups who sexually abuse children

PubMed Central

Cockbain, Ella; Brayley, Helen; Sullivan, Joe

2013-01-01

Extensive social psychological research emphasises the importance of groups in shaping individuals’ thoughts and actions. Within the child sexual abuse (CSA) literature criminal organisation has been largely overlooked, with some key exceptions. This research was a novel collaboration between academia and the UK's Child Exploitation and Online Protection Centre (CEOP). Starting from the premise that the group is, in itself, a form of social situation affecting abuse, it offers the first systematic situational analysis of CSA groups. In-depth behavioural data from a small sample of convicted CSA group-offenders (n = 3) were analysed qualitatively to identify factors and processes underpinning CSA groups’ activities and associations: group formation, evolution, identity and resources. The results emphasise CSA groups’ variability, fluidity and dynamism. The foundations of a general framework are proposed for researching and assessing CSA groups and designing effective interventions. It is hoped that this work will stimulate discussion and development in this long-neglected area of CSA, helping to build a coherent knowledge-base. PMID:26494978

Children Seeking Refuge: A Review of the Escalating Humanitarian Crisis of Child Sexual Abuse and HIV/AIDS in Latin America.

PubMed

Thornton, Clifton P; Veenema, Tener Goodwin

2015-01-01

Early identification and intervention for victims of child sexual abuse (CSA) is essential to halting the spread of HIV in Latino populations because children who are sexually abused are at an increased risk of contracting HIV. The recent influx of unaccompanied children into the United States exposed histories of victimization, vulnerability to CSA, and suggested an epidemic of CSA in Latin America. CSA has been identified as a contributory event to HIV infection. The aim of our research was to identify factors associated with CSA and Latin Americans. A systematic review and a document search were conducted on factors associated with CSA in Latin America. Victimization was associated with lifelong risk factors for HIV. Males were consistently underrepresented in the published CSA literature and machismo attitudes may contribute to abuses of sexual power by males and contribute to males not reporting or under-reporting victimization. Copyright © 2015 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Amplified OTDR systems for multipoint corrosion monitoring.

PubMed

Nascimento, Jehan F; Silva, Marcionilo J; Coêlho, Isnaldo J S; Cipriano, Eliel; Martins-Filho, Joaquim F

2012-01-01

We present two configurations of an amplified fiber-optic-based corrosion sensor using the optical time domain reflectometry (OTDR) technique as the interrogation method. The sensor system is multipoint, self-referenced, has no moving parts and can measure the corrosion rate several kilometers away from the OTDR equipment. The first OTDR monitoring system employs a remotely pumped in-line EDFA and it is used to evaluate the increase in system reach compared to a non-amplified configuration. The other amplified monitoring system uses an EDFA in booster configuration and we perform corrosion measurements and evaluations of system sensitivity to amplifier gain variations. Our experimental results obtained under controlled laboratory conditions show the advantages of the amplified system in terms of longer system reach with better spatial resolution, and also that the corrosion measurements obtained from our system are not sensitive to 3 dB gain variations.

Amplified OTDR Systems for Multipoint Corrosion Monitoring

PubMed Central

Nascimento, Jehan F.; Silva, Marcionilo J.; Coêlho, Isnaldo J. S.; Cipriano, Eliel; Martins-Filho, Joaquim F.

2012-01-01

We present two configurations of an amplified fiber-optic-based corrosion sensor using the optical time domain reflectometry (OTDR) technique as the interrogation method. The sensor system is multipoint, self-referenced, has no moving parts and can measure the corrosion rate several kilometers away from the OTDR equipment. The first OTDR monitoring system employs a remotely pumped in-line EDFA and it is used to evaluate the increase in system reach compared to a non-amplified configuration. The other amplified monitoring system uses an EDFA in booster configuration and we perform corrosion measurements and evaluations of system sensitivity to amplifier gain variations. Our experimental results obtained under controlled laboratory conditions show the advantages of the amplified system in terms of longer system reach with better spatial resolution, and also that the corrosion measurements obtained from our system are not sensitive to 3 dB gain variations. PMID:22737017

Short-term systemic insulin-like growth factor-1 is unable to prevent cyclosporin A-induced osteopenia in the rat.

PubMed

Mann, G N; Sass, D A; Chen, H K; Buchinsky, F J; Bryer, H P; Ma, Y F; Jee, W S; Rucinski, B; Epstein, S

1996-07-01

Immunosuppression with cyclosporin A (CsA) is effective in a number of immune-mediated diseases and in preventing rejection following organ transplantation. We have repeatedly demonstrated that CsA in the rat model produces accelerated bone remodelling with net bone loss, best characterized in trabecular bone. IGF-I holds promise as a treatment for various osteopenic conditions. Although currently a subject of much controversy, various studies have suggested that in vivo it is anabolic to cortical as well as trabecular bone. The purpose of this study was, in part, to further characterize the effects of CsA and IGF-I on trabecular and cortical bone, and to see whether systemic IGF-I is able to modulate CsA's deleterious skeletal effects. Sixty 10 week-old, male, Sprague-Dawley rats were randomized to receive the following daily for 3 weeks: (1) CsA vehicle (veh) per os (po) + recombinant human (rh) IGF-1 veh subcutaneously (sc); (2) CsA 15 mg/kg po + rhIGF-I-veh; (3) CsA-veh + rhIGF-I 200 microg/kg sc; (4) CsA-veh + rhIGF-I 600 microg/kg sc; (5) CsA 15 mg/kg + rhIGF-I 200 microg/kg, and (6) CsA 15 mg/kg + rhIGF-I 600 microg/kg. Rats were weighed and venous blood was sampled serially for determination of glucose, ionized calcium (Ca2+), PTH, vitamin D, and osteocalcin. Following sacrifice on day 20, histomorphometry was performed on double calcein-labeled tibial metaphysis and diaphysis. All rats receiving CsA had elevated levels of blood glucose and osteocalcin by day 9 and vitamin D at day 20. PTH was similar in all groups, and Ca2+ was only raised in the CsA and CsA + IGF-I 200 microg/kg groups. Rats receiving IGF-I 200 microg/kg and IGF-I 600 microg/kg gained more weight than either vehicle- or CsA-treated animals, attesting to IGF-1's anabolic properties. CsA caused severe trabecular bone loss, not prevented by IGF-I; it even further increased the eroded surface. CsA and IGF-I had little effect on cortical bone volume or marrow area. IGF-I increased endocortical matrix synthesis, as evidenced by the increases in the percent endocortical osteoid perimeter, an effect negated by the addition of CsA. This experiment demonstrates that trabecular bone is more susceptible than cortical bone to the deleterious effects of CsA and indicates little role for IGF-1 in the pathophysiology or treatment of CsA-induced bone disease at the given doses and duration of treatment.

Enhanced force sensitivity and noise squeezing in an electromechanical resonator coupled to a nanotransistor

NASA Astrophysics Data System (ADS)

Mahboob, I.; Flurin, E.; Nishiguchi, K.; Fujiwara, A.; Yamaguchi, H.

2010-12-01

A nanofield-effect transistor (nano-FET) is coupled to a massive piezoelectricity based electromechanical resonator integrated with a parametric amplifier. The mechanical parametric amplifier can enhance the resonator's displacement and the resulting electrical signal is further amplified by the nano-FET. This hybrid amplification scheme yields an increase in the mechanical displacement signal by 70 dB resulting in a force sensitivity of 200 aN Hz-1/2 at 3 K. The mechanical parametric amplifier can also squeeze the displacement noise in one oscillation phase by 5 dB enabling a factor of 4 reduction in the thermomechanical noise force level.

A pharmacologically-based array to identify targets of cyclosporine A-induced toxicity in cultured renal proximal tubule cells

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

Sarró, Eduard, E-mail: eduard.sarro@vhir.org; Renal Physiopathology, CIBBIM-Nanomedicine, Vall d'Hebron Research Institute; Jacobs-Cachá, Conxita, E-mail: conxita.jacobs@vhir.org

2012-01-15

Mechanisms of cyclosporine A (CsA)-induced nephrotoxicity were generally thought to be hemodynamic in origin; however, there is now accumulating evidence of a direct tubular effect. Although genomic and proteomic experiments by our group and others provided overall information on genes and proteins up- or down-regulated by CsA in proximal tubule cells (PTC), a comprehensive view of events occurring after CsA exposure remains to be described. For this purpose, we applied a pharmacologic approach based on the use of known activities of a large panel of potentially protective compounds and evaluated their efficacy in preventing CsA toxicity in cultured mouse PTC.more » Our results show that compounds that blocked protein synthesis and apoptosis, together with the CK2 inhibitor DMAT and the PI3K inhibitor apigenin, were the most efficient in preventing CsA toxicity. We also identified GSK3, MMPs and PKC pathways as potential targets to prevent CsA damage. Additionally, heparinase-I and MAPK inhibitors afforded partial but significant protection. Interestingly, antioxidants and calcium metabolism-related compounds were unable to ameliorate CsA-induced cytotoxicity. Subsequent experiments allowed us to clarify the hierarchical relationship of targeted pathways after CsA treatment, with ER stress identified as an early effector of CsA toxicity, which leads to ROS generation, phenotypical changes and cell death. In summary, this work presents a novel experimental approach to characterizing cellular responses to cytotoxics while pointing to new targets to prevent CsA-induced toxicity in proximal tubule cells. Highlights: ► We used a novel pharmacological approach to elucidate cyclosporine (CsA) toxicity. ► The ability of a broad range of compounds to prevent CsA toxicity was evaluated. ► CsA toxicity was monitored using LDH release assay and PARP cleavage. ► Protein synthesis, PI3K, GSK3, MMP, PKC and caspase inhibitors prevented CsA toxicity. ► We also identified ER stress as an early effector of CsA toxicity.« less

CSA/AZA, in the absence of prednisone, improves linear growth in renal transplanted children.

PubMed

David-Neto, E; Nahas, W; Sampaio, E C; Ianhez, L E; Sabbaga, E; Arap, S

1992-01-01

We compared the results of 44 renal transplants in children, of whom 24 were treated with CSA/AZA and 20 with prednisone in combination with AZA and/or CSA. There were no differences in age distribution or mean ages at transplant between the two treatment groups. The CSA/AZA group had a longer follow-up (29 +/- 33 vs 17 +/- 18 months). At the last follow-up, five children in the CSA/AZA and none in the prednisone group had lost their grafts. Serum creatinine increased in both groups from 0.7 +/- 0.1 mg/dl and 0.9 +/- 0.1 mg/dl at the end of the first month to 1.1 +/- 0.2 mg/dl in the 36th month (CSA/AZA group) (P < 0.0001) and to 1.5 +/- 0.6 mg/dl in the 18th month (prednisone group) (P < 0.05), respectively. Total cholesterol level was 189 +/- 52 mg/dl and 178 +/- 60 mg/dl and LDL level was 117 +/- 48 mg/dl and 115 +/- 51 mg/dl for the prednisone and CSA/AZA groups, respectively. HDL was greater in the CSA/AZA group (50 +/- 10 vs 41 +/- 10 mg/dl) (P < 0.03), and VLDL was greater in the prednisone group (31 +/- 13 vs 22 +/- 8 mg/dl) (P < 0.05). Serum triglyceride was greater in the prednisone group (174 +/- 93 vs 112 +/- 50 mg/dl) (P < 0.03). The standard deviation score for height of the children in the prednisone group did not change (-2.4 +/- 1.4 vs -2.1 +/- 1.4 SDS), whereas the SDS height score for the CSA/AZA children increased from -3.1 +/- 1.7 to -2.6 +/- 1.5, -1.9 +/- 1.4 and -1.7 +/- 1.4, at 12, 24 and 36 months, respectively (P < 0.001). CSA/AZA is a good immunosuppressive regime for the first renal transplant in children, but only 75% tolerated AZA/CSA without same damage to their grafts.

Physical symptoms in very young children assessed for sexual abuse: a mixed method analysis from the ASAC study.

PubMed

Vrolijk-Bosschaart, Thekla F; Brilleslijper-Kater, Sonja N; Widdershoven, Guy A; Teeuw, Arianne Rian H; Verlinden, Eva; Voskes, Yolande; van Duin, Esther M; Verhoeff, Arnoud P; Benninga, Marc A; Lindauer, Ramón J L

2017-10-01

So far, a recognizable pattern of clinical symptoms for child sexual abuse (CSA), especially in young male children, is lacking. To improve early recognition of CSA, we reviewed physical complaints, physical examination, and tests on sexually transmitted infections (STIs) in confirmed victims (predominantly preschool boys) of CSA from the Amsterdam sexual abuse case (ASAC). We retrospectively analyzed the outcomes of the primary assessment using mixed methods: descriptive analysis of physical complaints, physical exams, and STI tests from medical files and a qualitative analysis on expert's interpretations of physical complaints and children's behavior during physical examination. We included 54 confirmed CSA victims, median age 3.2 (0-6) years, 43 boys (80%), and 11 girls (20%). Physical complaints were reported in 50%, of which gastrointestinal and anogenital complaints were most common. None of the children showed CSA-specific genital signs at physical examination. Most prominent finding during physical examination was a deviant behavioral response (anxiety, withdrawal, too outgoing) in 15 children (28%), especially in children who experienced anal/vaginal penetration. Testing for STIs was negative. Physical complaints and physical signs at examinations were non-specific for CSA. Deviant behavioral reactions during physical examination were the most prominent finding. Precise observation of a child's behavior during physical examination is needed. What is known • Child sexual abuse (CSA) affects many children on both the short and the long term but remains unrecognized in most cases. • So far, there is a lack of studies on symptom patterns of CSA in male, preschool children. What is new • None of the children showed CSA-specific findings at physical and anogenital examination; STIs were not found in the confirmed victims of CSA. • The most prominent finding was the deviant behavioral response of the children examined, especially in children who experienced anal/vaginal penetration; therefore, precise observation of a child's behavior during physical examination is a crucial part of the evaluation of suspected CSA.

Self-defining as sexually abused and adult sexual risk behavior: Results from a cross-sectional survey of women attending an STD clinic

PubMed Central

Carey, Michael P.; Coury-Doniger, Patricia

2011-01-01

Objective Childhood sexual abuse (CSA) is associated with increased sexual risk behavior in adulthood, and this association may be mediated by traumagenic dynamics constructs (i.e., traumatic sexualization, trust, guilt, and powerlessness). However, few studies have investigated whether such relationships hold for women who do not identify as having experienced CSA despite meeting objective criteria that CSA occurred. This study sought to determine whether individuals who met research criteria for CSA and who self-defined as sexually abused differed on traumagenic dynamics constructs and current sexual risk behavior from individuals who met research criteria for CSA and who did not self-define as sexually abused. Methods Participants were 481 women recruited from a publicly-funded STD clinic. Participants completed a computerized survey assessing childhood sexual experiences and adult sexual risk behavior. Results Of the total sample, 206 (43%) met research criteria for CSA. Of the women meeting research criteria for CSA, 142 (69%) self-defined as sexually abused. Women who met research criteria for CSA reported more traumatic sexualization, more trust of a partner, more powerlessness, less sexual guilt, more episodes of unprotected sex, more sex partners, and greater likelihood of sex trading, compared to women who did not meet research criteria for CSA. Among women meeting research criteria, those who self-defined as sexually abused did not differ from those who did not self-define on any of the traumagenic dynamics constructs or on current sexual risk behavior, controlling for CSA characteristics. Conclusions Individuals who were sexually abused as children by behavioral research criteria are at risk for engaging in sexual risk behavior as adults, regardless of whether or not they perceive the experience to be CSA. Future research is needed to understand how non-definers perceive these childhood sexual experiences. PMID:21620162

Resistor-less charge sensitive amplifier for semiconductor detectors

NASA Astrophysics Data System (ADS)

Pelczar, K.; Panas, K.; Zuzel, G.

2016-11-01

A new concept of a Charge Sensitive Amplifier without a high-value resistor in the feedback loop is presented. Basic spectroscopic parameters of the amplifier coupled to a coaxial High Purity Germanium detector (HPGe) are discussed. The amplifier signal input is realized with an n-channel J-FET transistor. The feedback capacitor is discharged continuously by the second, forward biased n-channel J-FET, driven by an RC low-pass filter. Both the analog-with a standard spectroscopy amplifier and a multi-channel analyzer-and the digital-by applying a Flash Analog to Digital Converter-signal readouts were tested. The achieved resolution in the analog and the digital readouts was 0.17% and 0.21%, respectively, at the Full Width at Half Maximum of the registered 60Co 1332.5 keV gamma line.

Cyclosporin A Inhibits Rotavirus Replication and Restores Interferon-Beta Signaling Pathway In Vitro and In Vivo

PubMed Central

He, Haiyang; Wu, Yuzhang

2013-01-01

Rotavirus (RV) is the most common cause of severe diarrhea among infants and young children. Currently, there is no specific drug available against rotavirus, largely due to the lack of an ideal target molecule which has hampered drug development. Our previous studies have revealed that cyclosporin A (CsA) might be potentially useful as an anti-RV drug. We therefore used both cellular and mouse models to study the immunological safety and effectiveness of CsA as an anti-RV drug. We found that CsA treatment of HT-29 cells before, during, and after viral infection efficiently inhibited Wa strain RV replication and restored IFN-β expression in a HT-29 cell line model. Exploring the underlying mechanisms showed that CsA promoted Interferon Regulatory Factor-5 (IRF-5) expression (a key positive regulator of the type I IFN signaling pathway), but not IRF-1, IRF-3, or IRF-7. Additionally, CsA inhibited SOCS-1 expression (the key negative regulator of IFN-α/β), but not SOCS-2 or SOCS-3. The antiviral effect of CsA was confirmed in an RV-infected neonatal mouse model by evaluation of antigen clearance and assessment of changes in intestinal tissue pathology. Also, no differences in T cell frequency or proliferation between the CsA- and vehicle-treated groups were observed. Thus, both our in vitro and in vivo findings suggest that CsA, through modulating the expression of key regulators in IFN signaling pathway, promote type I IFN-based intracellular innate immunity in RV host cells. These findings suggest that CsA may be a useful candidate to develop a new anti-RV strategy, although further evaluation and characterization of CsA on RV-induced diarrhea are warranted. PMID:23990993

Alterations in cyclosporin A pharmacokinetics and metabolism during treatment with St John's wort in renal transplant patients

PubMed Central

Bauer, Steffen; Störmer, Elke; Johne, Andreas; Krüger, Hagen; Budde, Klemens; Neumayer, Hans-Hellmut; Roots, Ivar; Mai, Ingrid

2003-01-01

Aim This study investigated the effects of St John's wort extract (SJW) on the pharmacokinetics and metabolism of the immunosuppressant cyclosporin A (CSA). Methods In an open-label study, 11 renal transplant patients received 600 mg SJW extract daily for 14 days in addition to their regular regimen of CSA. Blood concentrations of CSA and its metabolites AM1, AM1C, AM9, AM19, and AM4N were measured by HPLC. Results After 2 weeks of SJW coadministration, dose-corrected AUC0–12, Cmax and Ctrough values for CSA decreased significantly by 46%[geometric mean ratio baseline/SJW (95% CI): 1.83 (1.63–2.05)], 42%[1.72 (1.42–2.08)], and 41%[1.70 (1.17–2.47)], respectively. CSA doses were increased from a median of 2.7 mg day−1 kg−1 at baseline to 4.2 mg day−1 kg−1 at day 15, with the first dose adjustment required only 3 days after initiation of SJW treatment. Additionally, the metabolite pattern of CSA was substantially altered during SJW treatment. Whereas dose-corrected AUC values for AM1, AM1c and AM4N significantly decreased by 59%, 61%, and 23% compared with baseline, AUC values for AM9 and AM19 were unchanged. Following the increase in CSA dose, observed AUC and Cmax values for AM9, AM19, and AM4N increased by 20–51% and 43–90%, respectively. Conclusion Administration of SJW extract to patients receiving CSA treatment resulted in a rapid and significant reduction of plasma CSA concentrations. Additionally, the substantial alterations in CSA metabolite kinetics observed may affect the toxicity profile of the drug. PMID:12580993

Allometric scaling of biceps strength before and after resistance training in men.

PubMed

Zoeller, Robert F; Ryan, Eric D; Gordish-Dressman, Heather; Price, Thomas B; Seip, Richard L; Angelopoulos, Theodore J; Moyna, Niall M; Gordon, Paul M; Thompson, Paul D; Hoffman, Eric P

2007-06-01

The purposes of this study were 1) derive allometric scaling models of isometric biceps muscle strength using pretraining body mass (BM) and muscle cross-sectional area (CSA) as scaling variables in adult males, 2) test model appropriateness using regression diagnostics, and 3) cross-validate the models before and after 12 wk of resistance training. A subset of FAMuSS (Functional SNP Associated with Muscle Size and Strength) study data (N=136) were randomly split into two groups (A and B). Allometric scaling models using pretraining BM and CSA were derived and tested for group A. The scaling exponents determined from these models were then applied to and tested on group B pretraining data. Finally, these scaling exponents were applied to and tested on group A and B posttraining data. BM and CSA models produced scaling exponents of 0.64 and 0.71, respectively. Regression diagnostics determined both models to be appropriate. Cross-validation of the models to group B showed that the BM model, but not the CSA model, was appropriate. Removal of the largest six subjects (CSA>30 cm) from group B resulted in an appropriate fit for the CSA model. Application of the models to group A posttraining data showed that both models were appropriate, but only the body mass model was successful for group B. These data suggest that the application of scaling exponents of 0.64 and 0.71, using BM and CSA, respectively, are appropriate for scaling isometric biceps strength in adult males. However, the scaling exponent using CSA may not be appropriate for individuals with biceps CSA>30 cm. Finally, 12 wk of resistance training does not alter the relationship between BM, CSA, and muscular strength as assessed by allometric scaling.

Bullying victimization and child sexual abuse among left-behind and non-left-behind children in China.

PubMed

Yan, Li; Zhu, Qianqian; Tu, Xiaowen; Zuo, Xiayun; Yu, Chunyan; Lou, Chaohua; Lian, Qiguo

2018-01-01

Bullying is one of the most important factors associated with child abuse. However, robust tests supporting the assumption that being bullied can contribute to child sexual abuse (CSA) among left-behind children (LBC) remain sparse. This study aims to investigate the association of bullying victimization with CSA among LBC in China. A cross-sectional study was conducted in six middle schools of Sichuan and Anhui province in 2015. The bullying victimization was assessed by seven items from the Revised Olweus Bully/Victim Questionnaire. The experience of CSA was measured by ten items CSA scale with good consistency. A total of 1,030 children met the sampling criteria, including 284 LBC and 746 non-LBC. The prevalence of CSA was 22.89% in LBC and 20.19% in non-LBC ( p  > 0.05). Bullying victimization was related to CSA among both LBC (adjusted Odds Ratio [aOR] = 2.52, 95% CI [1.34-4.73]) and non-LBC (aOR = 2.35, 95% CI [1.58-3.53]). The association between bullying victimization and CSA was much higher among left-behind girls (left-behind girls: aOR = 7.36, 95% CI [2.16-24.99]; non-left-behind girls: aOR = 2.38, 95% CI [1.08-5.27]). Also, LBC of a young age (11-15), children with siblings, living in rural areas and non-traditional family structure who were bullied were more likely to suffer CSA than their non-LBC peers. Bullying victimization is associated with a significant increase in CSA among both LBC and non-LBC. Anti-bullying programs should target vulnerable populations including female LBC and LBC with siblings to reduce the risk of CSA.

Bullying victimization and child sexual abuse among left-behind and non-left-behind children in China

PubMed Central

Yan, Li; Zhu, Qianqian; Tu, Xiaowen; Zuo, Xiayun; Yu, Chunyan; Lou, Chaohua

2018-01-01

Background Bullying is one of the most important factors associated with child abuse. However, robust tests supporting the assumption that being bullied can contribute to child sexual abuse (CSA) among left-behind children (LBC) remain sparse. This study aims to investigate the association of bullying victimization with CSA among LBC in China. Methods A cross-sectional study was conducted in six middle schools of Sichuan and Anhui province in 2015. The bullying victimization was assessed by seven items from the Revised Olweus Bully/Victim Questionnaire. The experience of CSA was measured by ten items CSA scale with good consistency. Results A total of 1,030 children met the sampling criteria, including 284 LBC and 746 non-LBC. The prevalence of CSA was 22.89% in LBC and 20.19% in non-LBC (p > 0.05). Bullying victimization was related to CSA among both LBC (adjusted Odds Ratio [aOR] = 2.52, 95% CI [1.34–4.73]) and non-LBC (aOR = 2.35, 95% CI [1.58–3.53]). The association between bullying victimization and CSA was much higher among left-behind girls (left-behind girls: aOR = 7.36, 95% CI [2.16–24.99]; non-left-behind girls: aOR = 2.38, 95% CI [1.08–5.27]). Also, LBC of a young age (11–15), children with siblings, living in rural areas and non-traditional family structure who were bullied were more likely to suffer CSA than their non-LBC peers. Conclusions Bullying victimization is associated with a significant increase in CSA among both LBC and non-LBC. Anti-bullying programs should target vulnerable populations including female LBC and LBC with siblings to reduce the risk of CSA. PMID:29888125

Examining the relationship between a childhood history of sexual abuse and later dissociation, breast-feeding practices, and parenting anxiety.

PubMed

Bowman, Katherine Gail; Ryberg, Jacalyn Wickline; Becker, Heather

2009-08-01

The purpose of this study is to compare Mexican American adolescent mothers with and without childhood sexual abuse (CSA) histories to examine the influence of CSA on dissociation, selection of infant feeding method, and intimate parenting anxiety. Participants are 78 English-speaking adolescents between 15 and 19 years of age and recruited from the southwestern United States. Nearly one third of the sample ( n = 24, 30.77%) reports CSA histories. There is no correlation between CSA history and intimate parenting anxiety, no difference between breast-feeding and formula-feeding mothers in CSA severity, and intimate parenting anxiety does not predict dissociation. These findings are inconsistent with previous research. Supportive resources may explain the inconsistency and play a role in adolescent mothers' responses to CSA. Further research is necessary to explore these possibilities.

Bactericidal Activity of Ceragenin CSA-13 in Cell Culture and in an Animal Model of Peritoneal Infection.

PubMed

Bucki, Robert; Niemirowicz, Katarzyna; Wnorowska, Urszula; Byfield, Fitzroy J; Piktel, Ewelina; Wątek, Marzena; Janmey, Paul A; Savage, Paul B

2015-10-01

Ceragenins constitute a novel family of cationic antibiotics characterized by a broad spectrum of antimicrobial activities, which have mostly been assessed in vitro. Using a polarized human lung epithelial cell culture system, we evaluated the antibacterial activities of the ceragenin CSA-13 against two strains of Pseudomonas aeruginosa (PAO1 and Xen5). Additionally, the biodistribution and bactericidal activity of a CSA-13-IRDye 800CW derivate were assessed using an animal model of peritoneal infection after PAO1 challenge. In cell culture, CSA-13 bactericidal activities against PAO1 and Xen5 were higher than the activities of the human cathelicidin peptide LL-37. Increased CSA-13 activity was observed in polarized human lung epithelial cell cultures subjected to butyric acid treatment, which is known to increase endogenous LL-37 production. Eight hours after intravenous or intraperitoneal injection, the greatest CSA-13-IRDye 800CW accumulation was observed in mouse liver and kidneys. CSA-13-IRDye 800CW administration resulted in decreased bacterial outgrowth from abdominal fluid collected from animals subjected to intraperitoneal PAO1 infection. These observations indicate that CSA-13 may synergistically interact with antibacterial factors that are naturally present at mucosal surfaces and it maintains its antibacterial activity in the infected abdominal cavity. Cationic lipids such as CSA-13 represent excellent candidates for the development of new antibacterial compounds. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

High-resolution nerve ultrasound and magnetic resonance neurography as complementary neuroimaging tools for chronic inflammatory demyelinating polyneuropathy

PubMed Central

Pitarokoili, Kalliopi; Kronlage, Moritz; Bäumer, Philip; Schwarz, Daniel; Gold, Ralf; Bendszus, Martin; Yoon, Min-Suk

2018-01-01

Background: We present a clinical, electrophysiological, sonographical and magnetic resonance neurography (MRN) study examining the complementary role of two neuroimaging methods of the peripheral nervous system for patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Furthermore, we explore the significance of cross-sectional area (CSA) increase through correlations with MRN markers of nerve integrity. Methods: A total of 108 nerve segments on the median, ulnar, radial, tibial and fibular nerve, as well as the lumbar and cervical plexus of 18 CIDP patients were examined with high-resonance nerve ultrasound (HRUS) and MRN additionally to the nerve conduction studies. Results: We observed a fair degree of correlation of the CSA values for all nerves/nerve segments between the two methods, with a low random error in Bland–Altman analysis (bias = HRUS-CSA − MRN-CSA, −0.61 to −3.26 mm). CSA in HRUS correlated with the nerve T2-weighted (nT2) signal increase as well as with diffusion tensor imaging parameters such as fractional anisotropy, a marker of microstructural integrity. HRUS-CSA of the interscalene brachial plexus correlated significantly with the MRN-CSA and nT2 signal of the L5 and S1 roots of the lumbar plexus. Conclusions: HRUS allows for reliable CSA imaging of all peripheral nerves and the cervical plexus, and CSA correlates with markers of nerve integrity. Imaging of proximal segments as well as the estimation of nerve integrity require MRN as a complementary method. PMID:29552093

Mediators of the Relation between Childhood Sexual Abuse and Women’s Sexual Risk Behavior: A Comparison of Two Theoretical Frameworks

PubMed Central

Senn, Theresa E.; Carey, Michael P.; Coury-Doniger, Patricia

2012-01-01

Childhood sexual abuse (CSA) is associated with sexual risk behavior in adulthood, but little research has investigated processes that might mediate this relation. The purpose of this study was to investigate whether constructs suggested by the traumagenic dynamics (TD) model (a theory of the effects of CSA) or constructs suggested by the Information-Motivation-Behavioral skills (IMB) model (a theory of the antecedents of sexual risk behavior) better mediated the relation between CSA and sexual risk behavior in adulthood. Participants were 481 women attending an STI clinic (66% African American) who completed a computerized survey as well as behavioral simulations assessing condom application and sexual assertiveness skills. Forty-five percent of the sample met criteria for CSA and CSA was associated with sexual risk behavior in adulthood. In multiple mediator models, the TD constructs mediated the relation between CSA and the number of sexual partners whereas the IMB constructs mediated the relation between CSA and unprotected sex. In addition, the TD constructs better mediated the relation between CSA and the number of sexual partners; the TD and IMB constructs did not differ in their ability to mediate the relation between CSA and unprotected sex. Sexual risk reduction interventions for women who were sexually abused should target not only the constructs from health behavior models (e.g., motivation and skills to reduce sexual risk), but also constructs that are specific to sexual abuse (e.g., traumatic sexualization and guilt). PMID:22282323

Cyclosporine-induced changes in drug metabolizing enzymes in hyperlipemic rabbit kidneys could explain its toxicity.

PubMed

Elbarbry, Fawzy; Ragheb, Ahmed; Attia, Ahmed; Chibbar, Rajni; Marfleet, Travis; Shoker, Ahmed

2010-11-01

This study investigates the mechanism of cyclosporine A (CsA)-mediated nephrotoxicity by examining the hypothesis that CsA toxicity is mediated through its effect on the kidney drug metabolizing enzymes in a hyperlipemic rabbit model. Twenty-four female New Zealand white rabbits divided into four groups. Group 1 received regular diet. Group 2 received 1% cholesterol diet. Group 3 received CsA (25 mg/kg, orally once daily) and group 4 received 1% cholesterol diet and CsA (25 mg/kg, orally once daily). Cytochrome P450 2E1 (CYP2E1) activity in kidney microsomes was assessed by measuring p-nitrophenol hydroxylase activity. Generation of reactive oxygen species (ROS) was assessed by measuring malondialdehyde (MDA) and the protein carbonyl. Effect of CsA and hyperlipidemia on the antioxidant proteins were also assessed using standard techniques. CsA but not the high-cholesterol diet induced significant elevation in MDA, protein carbonyl and CYP2E1 activities in the kidney. The addition of cholesterol to CsA normalized ROS markers without affecting the CsA-enhanced CYP2E1 activity. Alone, CsA caused characteristic tubular injury, whereas the addition of high-cholesterol diet to CsA nearly abolished the tubular damage. CsA-enhanced rabbit kidney ROS and CYP2E1 activities. Hyperlipidemia attenuates CsA tubular injury, most probably due to normalization of renal ROS, but not CYP2E1 activity.

Preventing the Onset of Child Sexual Abuse by Targeting Young Adolescents With Universal Prevention Programming

PubMed Central

Letourneau, Elizabeth J.; Schaeffer, Cindy M.; Bradshaw, Catherine P.; Feder, Kenneth A.

2017-01-01

Child sexual abuse (CSA) is a serious public health problem that increases risk for physical and mental health problems across the life course. Young adolescents are responsible for a substantial portion of CSA offending, yet to our knowledge, no validated prevention programs that target CSA perpetration by youth exist. Most existing efforts to address CSA rely on reactive criminal justice policies or programs that teach children to protect themselves; neither approach is well validated. Given the high rates of desistance from sexual offending following a youth’s first CSA-related adjudication, it seems plausible that many youth could be prevented from engaging in their first offense. The goal of this article is to examine how school-based universal prevention programs might be used to prevent CSA perpetrated by adolescents. We review the literature on risk and protective factors for CSA perpetration and identify several promising factors to target in an intervention. We also summarize the literature on programs that have been effective at preventing adolescent dating violence and other serious problem behaviors. Finally, we describe a new CSA prevention program under development and early evaluation and make recommendations for program design characteristics, including unambiguous messaging, parental involvement, multisession dosage, skills practice, and bystander considerations. PMID:28413921

Transdiagnostic psychopathology mediates the relationship between childhood sexual abuse and HIV/AIDS and other sexually transmitted infections in adulthood.

PubMed

Latack, Jessica A; Rodriguez-Seijas, Craig; Stohl, Malka; Blanco, Carlos; Hasin, Deborah S; Eaton, Nicholas R

2015-10-01

Exposure to childhood sexual abuse (CSA) is associated with elevated rates of mental disorders, sexual risk behavior, and sexually transmitted infections (STIs) in adulthood. Mental disorders themselves are associated with an increased risk for HIV/AIDs and STIs as well, and thus may mediate the association between CSA and HIV/AIDS and other STIs. The links among CSA, disorders, and STIs are unclear, however. The current study tested the hypothesis that the association of CSA with STIs is mediated by adult transdiagnostic psychopathology. We examined the potential mediating role of transdiagnostic psychopathology factors-internalizing (INT) and externalizing (EXT)-in the association between CSA and receiving a past-year diagnosis of HIV, AIDS, or another STI in a large, national probability sample of adults (N=34,653). Using indirect effects modeling, we found that 54.4% of the association between CSA and subsequent HIV/AIDS/STI diagnosis operated through transdiagnostic psychopathology. The proposed mediation model was supported, indicating that individuals reporting CSA had higher estimated levels of latent general liabilities for INT and EXT disorders, and it was largely these liabilities that accounted for the link between CSA and heightened risk of adult HIV, AIDS, and STI diagnoses. Copyright © 2015 Elsevier Inc. All rights reserved.

Superior outcome using cyclosporin A alone versus cyclosporin A plus methotrexate for post-transplant immunosuppression in children with acute leukemia undergoing sibling hematopoietic stem cell transplantation.

PubMed

Weiss, Melissa; Steinbach, Daniel; Zintl, Felix; Beck, James; Gruhn, Bernd

2015-06-01

The outcome of cyclosporin A (CSA) alone (n = 19) as graft-versus-host disease (GVHD) prophylaxis was compared to that of CSA combined with methotrexate (MTX) (n = 43) in children with acute leukemia who underwent hematopoietic stem cell transplantation. All respective donors were HLA-identical siblings. All patients received CSA at a dose of 3 mg/kg/day starting on day -1. A CSA level of 80-130 ng/ml was aimed for. The 43 patients in the historical control were given an additional 10 mg/m(2) dosage of MTX on days 1, 3, 6, and 11. Patients who received CSA alone had a significantly reduced cumulative incidence of relapse (5 vs. 40 %; p = 0.002), a significantly increased 5-year event-free survival (84 vs. 35 %; p = 0.001), and a significantly increased 5-year overall survival (84 vs. 42 %; p = 0.004). The incidence of acute GVHD grade II-IV and chronic GVHD in patients in the CSA group was equivalent to the CSA+MTX group (26 vs. 19 %; p = 0.440, and 32 vs. 23 %; p = 0.428). In conclusion, post-transplant immunosuppression consisting of CSA alone is well tolerated and may contribute to a superior outcome.

[Chronobiological studies on effect of cyclosporin A (CsA) against adult male worms of Schistosoma mansoni in vitro].

PubMed

Liu, J; Chappell, L H

1998-01-01

To study the action mode of cyclosporin A (CsA) against Schistosoma mansoni in vitro. MF1 mice were infected with Schistosoma mansoni cercariae for 6 weeks when the adult worms were recovered by portal perfusion. The male worms of S. mansoni recovered were exposed to varying concentrations of CsA at 8, 16, and 24 h in vitro. Drug induced damage to the male worm surface was chrono-biologically observed throughout these experiments by SEM. After the male worms of S. mansoni were incubated with 1 microgram/ml CsA for 8-24 h, the tegument showed swelling of ridges with appearance of holes on their surface and detachment of a part of spines. The above damage of the tegument became more evident in male worms after incubation with 10, 15, 20 micrograms/ml CsA for 8-24 h. Moreover, incubation of male worms with 25 micrograms/ml CsA for 8-24 h resulted in significant deformation and disruption of tegument, rupture of ridges and detachment of spines. The tegumental damage of male worms of S. mansoni was dose- and time-dependent. The antischistosomal action of CsA is direct, the schistosome tegument appears to be the main site for CsA attack.

Patient and physician perspectives on the use of cyclosporine ophthalmic emulsion 0.05% for the management of chronic dry eye

PubMed Central

Deveney, Tatiana; Asbell, Penny A

2018-01-01

Dry eye disease (DED) is a multifactorial disease of the ocular surface and is one of the most common reasons for patients to visit an eye care provider. Cyclosporine A (CsA) is an immune modulating drug that was approved in the US for topical use in the treatment of DED in 2003, which led to a paradigm change in our understanding and treatment of DED, turning attention to control of inflammation for treatment. This review summarizes the literature to date regarding the impact of CsA on the treatment of DED. A special focus is given to the patient and physician perspectives of CsA, including dry eye symptom improvement, medication side effects, and overall patient satisfaction. Studies evaluating CsA in DED have considerable heterogeneity making generalized conclusions about the effect of CsA difficult. However, most studies have demonstrated improvement in at least some symptoms of dry eye in CsA-treated patients. Side effects, most commonly ocular burning on administration of CsA, are common. The literature is sparse regarding long-term follow-up of patients treated with CsA, optimal duration of treatment, and identifying which patients may receive the most benefit from CsA. PMID:29615833

Increased Advanced Oxidation Protein Products Generation by Cyclosporine-A and Angiotensin II in Human Gingival Fibroblasts – Ex-vivo Study

PubMed Central

Subbarayan, Rajasekaran; Ajitkumar, Supraja; Murugan Girija, Dinesh

2017-01-01

Introduction Cyclosporin-A (CsA), an immunosuppressant, induces renal fibrosis and Renin Angiotensin System (RAS) is known to play a major role. CsA has the potential to increase the oxidative stress; specifically through the Advanced Oxidation Protein Products (AOPP) which could possibly stimulate fibrosis. A similar type of pathology occurs even in the gingiva known as CsA Induced Gingival Overgrowth (CIGO). Aim This study was undertaken to estimate the AOPP generation by Human Gingival Fibroblasts (HGF) under the influence of CsA and Angiotensin II (Ang II). Materials and Methods Six healthy gingival tissue samples were obtained during crown lengthening procedure and primary HGF were cultured using enzymatic digestion method. The ideal non-cytotoxic concentrations of CsA and Ang II were identified using cytotoxicity assay. Later, HGF were incubated with CsA and Ang II for 12 hours and AOPP assay was performed at zero and one hour interval. Results There was a statistically significant increase in AOPP production in both the CsA and Ang II when compared to the control group with a p value<0.05. Conclusion CsA can induce oxidative stress and preventing/controlling it may be necessary to prevent untoward effect of the drug. PMID:28274044

Physiological stress responses predict sexual functioning and satisfaction differently in women who have and have not been sexually abused in childhood

PubMed Central

Meston, Cindy M.; Lorenz, Tierney A.

2012-01-01

Physiological responses to sexual stimuli may contribute to the increased rate of sexual problems seen in women with childhood sexual abuse (CSA) histories. We compared two physiological stress responses as predictors of sexual function and satisfaction, sympathetic nervous system (SNS) activation and cortisol in women with (CSA, N = 136) and without CSA histories (NSA, N = 102). In CSA survivors, cortisol response to sexual stimuli did not significantly predict sexual functioning; however, in NSA women, cortisol increases were associated with poorer sexual functioning, and decreases with higher functioning. For women with CSA histories, lower SNS activity was associated with poorer sexual functioning. For CSA survivors with low lifetime trauma, lower SNS activity was associated with higher sexual satisfaction; for women with high lifetime trauma, the reverse was true. Decreased SNS activity during sexual stimuli predicted higher sexual functioning in NSA women with low lifetime exposure to traumatic events, but lower sexual functioning in those with high exposure. Differences between women with and without CSA histories in the association between cortisol and SNS response and sexual functioning and satisfaction suggests that CSA causes disruptions in both short and long-term stress responses to sexual stimuli that perpetuate into adulthood. PMID:24748915

The effect of pre-existing affect on the sexual responses of women with and without a history of childhood sexual abuse.

PubMed

Rellini, Alessandra H; Elinson, Samantha; Janssen, Erick; Meston, Cindy M

2012-04-01

Women with a history of childhood sexual abuse (CSA) are at greater risk for experiencing sexual problems in their adult lives. Yet, little is known about the possible role of cognitive and affective mechanisms in the development of sexual arousal difficulties in this population. This study investigated the role of pre-existing affect (affect prior to exposure to sexual stimuli) on genital responses, subjective sexual arousal, and affect elicited during the presentation of erotic film excerpts in a community sample of 25 women with and 25 women without a history of CSA. The CSA group showed greater pre-existing negative affect and smaller genital responses to the erotic film stimuli compared to the NSA group. Findings support a moderating effect of CSA, in that pre-existing negative affect was associated with strength of genital responses in the NSA but not in the CSA group. The results did not support a mediation model of pre-existing negative affect as an explanation for smaller physiological sexual responses in the CSA group. Taken together, the findings suggest that pre-existing affect may be more relevant for women with no history of CSA and call for more research on factors implicated in impaired sexual responses in women with a history of CSA.

In vitro bactericidal and bacteriolytic activity of ceragenin CSA-13 against planktonic cultures and biofilms of Streptococcus pneumoniae and other pathogenic streptococci.

PubMed

Moscoso, Miriam; Esteban-Torres, María; Menéndez, Margarita; García, Ernesto

2014-01-01

Ceragenin CSA-13, a cationic steroid, is here reported to show a concentration-dependent bactericidal/bacteriolytic activity against pathogenic streptococci, including multidrug-resistant Streptococcus pneumoniae. The autolysis promoted by CSA-13 in pneumococcal cultures appears to be due to the triggering of the major S. pneumoniae autolysin LytA, an N-acetylmuramoyl-L-alanine amidase. CSA-13 also disintegrated pneumococcal biofilms in a very efficient manner, although at concentrations slightly higher than those required for bactericidal activity on planktonic bacteria. CSA-13 has little hemolytic activity which should allow testing its antibacterial efficacy in animal models.

Direct Current Amplifier. Report No. 92; AMPLIFICADOR DE CORRIENTE CONTINUA. Informe No. 92

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

Marazzi, C.

1963-01-01

A direct-current amplifier with low zero current and solid-state chopper for input is described. This amplifier can be used in control circuits and for general applications such as temperature measurement in thermocouples, amplifier for a photo-sensitive element, or zero amplifier in control systems. The input impedance is relatively low, serving principally as current amplifier. It is possible to obtain a symmetry characteristic for positive and negative values of the output voltage with respect to the input. (tr-auth)

Exploitation of the Apoptosis-Primed State of MYCN-Amplified Neuroblastoma to Develop a Potent and Specific Targeted Therapy Combination

PubMed Central

Ham, Jungoh; Costa, Carlotta; Sano, Renata; Lochmann, Timothy L.; Sennott, Erin M.; Patel, Neha U.; Dastur, Anahita; Gomez-Caraballo, Maria; Krytska, Kateryna; Hata, Aaron N.; Floros, Konstantinos V.; Hughes, Mark T.; Jakubik, Charles T.; Heisey, Daniel A.R.; Ferrell, Justin T.; Bristol, Molly L.; March, Ryan J.; Yates, Craig; Hicks, Mark A.; Nakajima, Wataru; Gowda, Madhu; Windle, Brad E.; Dozmorov, Mikhail G.; Garnett, Mathew J.; McDermott, Ultan; Harada, Hisashi; Taylor, Shirley M.; Morgan, Iain M.; Benes, Cyril H.; Engelman, Jeffrey A.; Mossé, Yael P.; Faber, Anthony C.

2016-01-01

Summary Fewer than half of children with high-risk neuroblastoma survive. Many of these tumors harbor high-level amplification of MYCN, which correlates with poor disease outcome. Using data from our large drug screen we predicted, and subsequently demonstrated, that MYCN-amplified neuroblastomas are sensitive to the BCL-2 inhibitor ABT-199. This sensitivity occurs in part through low anti-apoptotic BCL-xL expression, high pro-apoptotic NOXA expression, and paradoxical, MYCN-driven upregulation of NOXA. Screening for enhancers of ABT-199 sensitivity in MYCN-amplified neuroblastomas, we demonstrate that the Aurora Kinase A inhibitor MLN8237 combines with ABT-199 to induce widespread apoptosis. In diverse models of MYCN-amplified neuroblastoma, including a patient-derived xenograft model, this combination uniformly induced tumor shrinkage, and in multiple instances led to complete tumor regression. PMID:26859456

Delay in disclosure of non-parental child sexual abuse in the context of emotional and physical maltreatment: A pilot study.

PubMed

Tashjian, Sarah M; Goldfarb, Deborah; Goodman, Gail S; Quas, Jodi A; Edelstein, Robin

2016-08-01

The present pilot study sought to identify predictors of delays in child sexual abuse (CSA) disclosure, specifically whether emotional and physical abuse by a parental figure contributes to predicting delays over and above other important victim factors. Alleged CSA victims (N=79), whose parental figures were not the purported sexual abuse perpetrators, were interviewed and their case files reviewed, across two waves of a longitudinal study. Regression analyses indicated that experiencing both emotional and physical abuse by a parental figure was uniquely predictive of longer delays in disclosure of CSA perpetrated by someone other than a parental figure. Victim-CSA perpetrator relationship type and sexual abuse duration also significantly predicted CSA disclosure delay, whereas victim age at the time of the police report, victim gender, and victims' feelings of complicity were not significant unique predictors. Child abuse victims' expectations of lack of parental support may underlie these findings. Parent-child relationships are likely crucial to timely disclosure of CSA, even when a parent is not the CSA perpetrator. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of Child Sex Abuse on Adult Psychopathology: A Genetically and Epigenetically Informed Investigation

PubMed Central

Beach, Steven R. H.; Brody, Gene H.; Lei, Man Kit; Gibbons, Frederick X.; Gerrard, Meg; Simons, Ronald L.; Cutrona, Carolyn E.; Philibert, Robert A.

2013-01-01

Genetic, environmental, and epigenetic influences and their transactions were examined in a sample of 155 women from the Iowa Adoptee sample (IAS) who had been removed from their biological parents shortly after birth, and assessed when participants were an average of 41.10 years old. We observed an interactive effect of child sex abuse (CSA) and biological parent psychopathology (i.e., genetic load) on substance abuse as well as a main effect of CSA on substance abuse in adulthood. We also observed main effects of CSA and genetic load on depression and on antisocial characteristics. As predicted, CSA, but not genetic load or later substance abuse, was associated with epigenetic change. In addition, the interaction between genetic load and CSA predicted epigenetic change, indicating a potential genetic basis for differential impact of CSA on epigenetic change. Finally, epigenetic change partially mediated the effect of CSA on antisocial characteristics. The results suggest the relevance of genetic and epigenetic processes for future theorizing regarding marital and family precursors of several forms of adult psychopathology. Implications for preventive intervention are discussed. PMID:23421829

Initial Assessment of CSA Group Niobium Boron Based Coatings on 4340 Steel

DTIC Science & Technology

2017-07-01

Technical Report ARWSB-TR-17026 Initial Assessment of CSA Group Niobium- Boron Based Coatings on 4340 Steel C.P. Mulligan...REPORT TYPE Technical 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Initial Assessment of CSA Group Niobium- Boron Based Coatings on 4340...metallographic mounts reported as (1) thin and (2) thick Niobium- Boron (Nb-B) type coatings on steel. CSA Group is interested in providing coatings for potential

[Central sleep apnea syndrome].

PubMed

Sanner, B; Schäfer, T

2008-04-01

Central sleep apnea (CSA) is characterized by a lack of drive to inspire for at least 10 sec. In the CSA-syndrome accompanying arousals and desaturations of the arterial blood cause sleep disturbances and sympathetic nerve activations which lead to excessive daytime sleepiness and increase the risk for cardiovascular morbidity. There are six manifestations of CSA: a rare primary or idiopathic form, often in hypocapnic patients with an increased hypercapnic ventilatory drive; Cheyne-Stokes respiration, characterised by periodic CSA and a crescendo/decrescendo breathing pattern, often in patients with severe cardiac or neurological diseases; high altitude-induced periodic breathing (above 4000 m), CSA due to medical or neurological conditions; CSA due to drug or substance use; and primary sleep apnea of infancy. Besides the consequent treatment of the underlying medical conditions therapeutic options include the use of drugs, e. g. acetacolamide or oxygen, as well as non-invasive ventilation, e. g. continuous positive airway pressure (CPAP) or adaptive servo-ventilation.

Relationship between central sleep apnea and Cheyne-Stokes Respiration.

PubMed

Flinta, Irena; Ponikowski, Piotr

2016-03-01

Central sleep apnea (CSA) in patients with heart failure (HF) occurs frequently and shows a serious influence on prognosis in this population. The key elements in the pathophysiology of CSA are respiratory instability with chronic hyperventilation, changes of arterial carbon dioxide pressure (pCO2) and elongated circulation time. The main manifestation of CSA in patients with HF is Cheyne-Stokes Respiration (CSR). The initial treatment is the optimization of HF therapy. However, many other options of the therapeutic management have been studied, particularly those based on positive airway pressure methods. In patients with heart failure we often can observe the overlap of CSA and CSR; we will discuss the differences between these forms of breathing disorders during sleep. We will also discuss when CSA and CSR occur independently of each other and the importance of CSR occurring during the daytime in context of CSA during the nighttime. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Child sexual abuse in Japan: A systematic review and future directions.

PubMed

Tanaka, Masako; Suzuki, Yumi E; Aoyama, Ikuko; Takaoka, Kota; MacMillan, Harriet L

2017-04-01

Estimating the national prevalence of child sexual abuse (CSA) and its association with health and developmental outcomes is the first step in developing prevention strategies. While such data are available from many countries, less is known about the epidemiology of CSA in Japan. For this systematic review, we searched English databases: Embase, Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R), Ovid OLDMEDLINE(R), PsycINFO, and Japanese databases: Cinii, J-Stage, Children's Rainbow Center Japan, Japan Child and Family Research Institute, Japanese Journal of Child Abuse and Neglect to identify articles published before July 2015 examining the lifetime prevalence of CSA in Japan using non-clinical samples. Data were extracted from published reports. We initially identified 606 citations and after abstract review, retrieved 120 publications. Six studies that met the selection criteria and additional two relevant studies were reviewed. The range of contact CSA for females was 10.4%-60.7%, and the prevalence of this type of CSA for males was 4.1%. The range of penetrative CSA for females was 1.3%-8.3% and that for males was 0.5%-1.3%. A number of methodological issues were identified, including a lack of validated measures of CSA, and low response rates. In contrast to a lower prevalence of penetrative CSA, the prevalence of contact CSA among Japanese females may be comparable or higher in relation to international estimates. Future research on children's perceptions of and exposure to sexual abuse, crime and exploitation in Japan is discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparisons of four methods of estimating physical activity in adult women.

PubMed

Leenders NYJM; Sherman, W M; Nagaraja, H N

2000-07-01

To compare four different methods of measuring physical activity (PA) in adult women under free-living conditions. Twelve women participated in a 7-d period during which PA was assessed via self-report, accelerometry and step-counting. Subjects wore at the waist a Tritrac-R3D accelerometer, a Computer Science Application Inc. activity monitor (CSA), both of which measure bodily accelerations in various planes, and a Yamax Digi-Walker-500 that records steps. After the 7-d period subjects responded to a 7-d Physical Activity Recall interview (PAR). Physical activity-related energy expenditure (PAEE) determined from PAR was significantly higher than PAEE estimated from either the Tritrac, CSA, or the Yamax data. Time spent in light, moderate, and hard physical activity was not significantly different between PAR, CSA, and Tritrac. Log-transformed activity counts from CSA were highly correlated with log-transformed Tritrac results (r > 0.90). Number of steps recorded by the Yamax was significantly correlated with untransformed Tritrac and CSA results. Based upon comparisons with PAR, Tritrac, CSA, and Yamax underestimate the amount of PAEE by 25, 46, and 48%, respectively. The correspondence between the Tritrac and CSA results suggests that both devices produce similar estimates of bodily movement in free-living women. The relationships among results for Tritrac, CSA, and Yamax indicate that the number of steps recorded by the Yamax is representative of the amount of physical activity performed during the day as estimated by Tritrac and CSA. These results should be useful when selecting a method to measure PA in individuals under free-living conditions.

Prevalence, Defining Characteristics, and Related Factors of the Nursing Diagnosis of Anxiety in Hospitalized Medical-Surgical Patients.

PubMed

Sanson, Gianfranco; Perrone, Annalisa; Fascì, Adriana; D'Agostino, Fabio

2018-03-01

To document the prevalence of the nursing diagnosis of anxiety in hospital patients, based on its level of severity, defining characteristics (DCs), and other related factors, and to identify the key DCs that serve as predictors of clinically significant anxiety (CSA). Cross-sectional study. We enrolled 116 consecutive adult patients hospitalized from October 10 to 16, 2016, in medical-surgical wards within the first 48 hr of admission. The potential DCs and related factors of anxiety were collected based on the NANDA International terminology. Anxiety was considered clinically significant when presenting at moderate, severe, or panic level. The differences in DC prevalence among patients having or not having CSA were analyzed by unpaired student's t-test. Multivariate analysis was used to examine the independent association between the DCs and CSA. The prevalence of CSA was 36.2% and was significantly higher in patients who were older, female, and taking anxiolytic drugs, and among those who had cancer. The most frequent related factor for CSA was major change in health status. In the logistic regression, the presence of the DCs helplessness, altered attention or concentration, and anguish independently increased the odds of having CSA, whereas subjects presenting with Diminished ability to problem-solve had about a 96% reduction in the likelihood to suffer from such a condition. A high prevalence of CSA among medical-surgical patients was shown. Furthermore, a critical cluster of DCs useful to identify CSA was found. The ability to accurately diagnose CSA should help prescribe and deliver the appropriate nursing interventions. © 2018 Sigma Theta Tau International.

Diminished functional connectivity on the road to child sexual abuse in pedophilia.

PubMed

Kärgel, Christian; Massau, Claudia; Weiß, Simone; Walter, Martin; Kruger, Tillmann H C; Schiffer, Boris

2015-03-01

Pedophilia is a disorder recognized for its impairment to the individual and for the harm it may cause to others. However, the neurobiology of pedophilia and a possible propensity to sexually abuse children are not well understood. In this study, we thus aimed at providing new insights in how functional integration of brain regions may relate to pedophilia or child sexual abuse (CSA). By using functional magnetic resonance imaging (fMRI) technique, we compared functional connectivity at rest (RSFC) between pedophiles who engaged (P+CSA; N = 12) or did not engage (P-CSA; N = 14) in CSA and healthy controls (HCs; N = 14) within two networks: (i) the default mode network and (ii) the limbic network that has been linked to pedophilia before. Pedophiles who engaged in CSA show diminished RSFC in both networks compared with HC and P-CSA. Most importantly, they showed diminished RSFC between the left amygdala and orbitofrontal as well as anterior prefrontal regions. Though significant age differences between groups could not be avoided, correlation control analysis did not provide evidence for the assumption that the RSFC effects were related to age differences. We found significantly diminished RSFC in brain networks critically involved in widespread motivational and socio-emotional processes. These results extend existing models of the functional neuroanatomy of pedophilia and CSA as altered RSFC between these regions were related to CSA rather than pedophilia and thus may account for an increased propensity to engage in CSA in people suffering from pedophilia. © 2015 International Society for Sexual Medicine.

Burkitt lymphoma expresses oncofetal chondroitin sulfate without being a reservoir for placental malaria sequestration.

PubMed

Agerbaek, Mette Ø; Pereira, Marina A; Clausen, Thomas M; Pehrson, Caroline; Oo, Htoo Zarni; Spliid, Charlotte; Rich, Jamie R; Fung, Vincent; Nkrumah, Francis; Neequaye, Janet; Biggar, Robert J; Reynolds, Steven J; Tosato, Giovanna; Pullarkat, Sheeja T; Ayers, Leona W; Theander, Thor G; Daugaard, Mads; Bhatia, Kishor; Nielsen, Morten A; Mbulaiteye, Sam M; Salanti, Ali

2017-04-01

Burkitt lymphoma (BL) is a malignant disease, which is frequently found in areas with holoendemic Plasmodium falciparum malaria. We have previously found that the VAR2CSA protein is present on malaria-infected erythrocytes and facilitates a highly specific binding to the placenta. ofCS is absent in other non-malignant tissues and thus VAR2CSA generally facilitates parasite sequestration and accumulation in pregnant women. In this study, we show that the specific receptor for VAR2CSA, the oncofetal chondroitin sulfate (ofCS), is likewise present in BL tissue and cell lines. We therefore explored whether ofCS in BL could act as anchor site for VAR2CSA-expressing infected erythrocytes. In contrast to the placenta, we found no evidence of in vivo sequestering of infected erythrocytes in the BL tissue. Furthermore, we found VAR2CSA-specific antibody titers in children with endemic BL to be lower than in control children from the same malaria endemic region. The abundant presence of ofCS in BL tissue and the absence of ofCS in non-malignant tissue encouraged us to examine whether recombinant VAR2CSA could be used to target BL. We confirmed the binding of VAR2CSA to BL-derived cells and showed that a VAR2CSA drug conjugate efficiently killed the BL-derived cell lines in vitro. These results identify ofCS as a novel therapeutic BL target and highlight how VAR2CSA could be used as a tool for the discovery of novel approaches for directing BL therapy. © 2016 UICC.

Burkitt lymphoma express oncofetal Chondroitin Sulfate without being a reservoir for placental malaria sequestration

PubMed Central

Agerbæk, Mette Ø.; Pereira, Marina A.; Clausen, Thomas M.; Pehrson, Caroline; Oo, Htoo Zarni; Spliid, Charlotte; Rich, Jamie R.; Fung, Vincent; Nkrumah, Francis; Neequaye, Janet; Biggar, Robert J.; Reynolds, Steven J.; Tosato, Giovanna; Pullarkat, Sheeja T.; Ayers, Leona W.; Theander, Thor G.; Daugaard, Mads; Bhatia, Kishor; Nielsen, Morten A.; Mbulaiteye, Sam M.; Salanti, Ali

2016-01-01

Burkitt lymphoma (BL) is a malignant disease, which is frequently found in areas with holoendemic Plasmodium falciparum malaria. We have previously found that the VAR2CSA protein is present on malaria-infected erythrocytes and facilitates a highly specific binding to the placenta. OfCS is absent from other non-malignant tissues and thus VAR2CSA generally facilitates parasite sequestration and accumulation in pregnant women. In this study, we show that the specific receptor for VAR2CSA, the oncofetal chondroitin sulfate (ofCS), is likewise present in BL tissue and cell lines. We therefore explored whether ofCS in BL could act as anchor-site for VAR2CSA-expressing infected erythrocytes. In contrast to the placenta, we found no evidence of in vivo sequestering of infected erythrocytes in the BL tissue. Furthermore, we found VAR2CSA specific antibody titers in children with endemic BL to be lower than in control children from the same malaria endemic region. The abundant presence of ofCS in BL tissue and the absence of ofCS in non-malignant tissue, encouraged us to examine whether recombinant VAR2CSA could be used to target BL. We confirmed the binding of VAR2CSA to BL-derived cells and showed that a VAR2CSA drug conjugate efficiently killed the BL-derived cell lines in vitro. These results identify ofCS as a novel therapeutic BL target and highlight how VAR2CSA could be used as a tool for the discovery of novel approaches for directing BL therapy. PMID:27997697

Vitamin E protects against the mitochondrial damage caused by cyclosporin A in LLC-PK1 cells

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

Arriba, G. de; Seccion de Nefrologia del Hospital Universitario de Guadalajara; Departamento de Medicina de la Universidad de Alcala de Henares

Cyclosporin A (CsA) has nephrotoxic effects known to involve reactive oxygen species (ROS), since antioxidants prevent the kidney damage induced by this drug. Given that mitochondria are among the main sources of intracellular ROS, the aims of our study were to examine the mitochondrial effects of CsA in the porcine renal endothelial cell line LLC-PK1 and the influence of the antioxidant Vitamin E (Vit E). Following the treatment of LLC-PK1 cells with CsA, we assessed the mitochondrial synthesis of superoxide anion, permeability transition pore opening, mitochondrial membrane potential, cardiolipin peroxidation, cytochrome c release and cellular apoptosis, using flow cytometry andmore » confocal microscopy procedures. Similar experiments were done after Vit E preincubation of cells. CsA treatment increased superoxide anion in a dose-dependent way. CsA opened the permeability transition pores, caused Bax migration to mitochondria, and decreased mitochondrial membrane potential and cardiolipin content. Also CsA released cytochrome c into cytosol and provoked cellular apoptosis. Vit E pretreatment inhibited the effects that CsA induced on mitochondrial structure and function in LLC-PK1 cells and avoided apoptosis. CsA modifies mitochondrial LLC-PK1 cell physiology with loss of negative electrochemical gradient across the inner mitochondrial membrane and increased lipid peroxidation. These features are related to apoptosis and can explain the cellular damage that CsA induces. As Vit E inhibited these effects, our results suggest that they were mediated by an increase in ROS production by mitochondria.« less

Sexual abuse in childhood and sexual dysfunction in adulthood: an Australian population-based study.

PubMed

Najman, Jake M; Dunne, Michael P; Purdie, David M; Boyle, Francis M; Coxeter, Peter D

2005-10-01

This study examined self-reported adult sexual functioning in individuals reporting a history of childhood sexual abuse (CSA) in a representative sample of the Australian population. A sample of 1793 persons, aged 18-59 years, were randomly selected from the electoral roll for Australian states and territories in April 2000. Respondents were interviewed about their health status and sexual experiences, including unwanted sexual experiences before the age of 16 years. More than one-third of women and approximately one-sixth of men reported a history of CSA. Women were more likely than men to report both non-penetrative and penetrative experiences of CSA. For both sexes, there was a significant association between CSA and symptoms of sexual dysfunction. In assessing the specific nature of the relationship between sexual abuse and sexual dysfunction, statistically significant associations were, in general, evident for women only. CSA was not associated with the level of physical or emotional satisfaction respondents experienced with their sexual activity. The total number of lifetime sexual partners was significantly and positively associated with CSA for females, but not for males; however, the number of sexual partners in the last year was not related to CSA. CSA in the Australian population is common and contributes to significant impairment in the sexual functioning of adults, especially women. These consequences appear not to extend to the other areas of sexual activity considered in this study.

Maximum toe flexor muscle strength and quantitative analysis of human plantar intrinsic and extrinsic muscles by a magnetic resonance imaging technique.

PubMed

Kurihara, Toshiyuki; Yamauchi, Junichiro; Otsuka, Mitsuo; Tottori, Nobuaki; Hashimoto, Takeshi; Isaka, Tadao

2014-01-01

The aims of this study were to investigate the relationships between the maximum isometric toe flexor muscle strength (TFS) and cross-sectional area (CSA) of the plantar intrinsic and extrinsic muscles and to identify the major determinant of maximum TFS among CSA of the plantar intrinsic and extrinsic muscles. Twenty six young healthy participants (14 men, 12 women; age, 20.4 ± 1.6 years) volunteered for the study. TFS was measured by a specific designed dynamometer, and CSA of plantar intrinsic and extrinsic muscles were measured using magnetic resonance imaging (MRI). To measure TFS, seated participants optimally gripped the bar with their toes and exerted maximum force on the dynamometer. For each participant, the highest force produced among three trials was used for further analysis. To measure CSA, serial T1-weighted images were acquired. TFS was significantly correlated with CSA of the plantar intrinsic and extrinsic muscles. Stepwise multiple linear regression analyses identified that the major determinant of TFS was CSA of medial parts of plantar intrinsic muscles (flexor hallucis brevis, flexor digitorum brevis, quadratus plantae, lumbricals and abductor hallucis). There was no significant difference between men and women in TFS/CSA. CSA of the plantar intrinsic and extrinsic muscles is one of important factors for determining the maximum TFS in humans.

Measurement of anterior tibial muscle size using real-time ultrasound imaging.

PubMed

Martinson, H; Stokes, M J

1991-01-01

Cross-sectional images of the anterior tibial muscle group were obtained using real-time ultrasound scanning in 17 normal women. From photographs taken of the images, the cross-sectional area (CSA) and two linear measurements of muscle cross-section were determined. A measurement of the shortest distance of the muscle depth was termed DS, and a measurement of the longest distance through the muscle group was termed DL. Both linear dimensions showed a positive correlation with CSA and the best correlations were obtained when the dimensions were squared or combined (DS x DL). The correlation values were: CSA vs DS2, r = 0.9; CSA vs DL2, r = 0.75 and CSA vs DS x DL, r = 0.88. An approximate value for CSA could be calculated from DS2 by the equation 2 x DS2 + 1. A shape ratio, obtained by dividing DL by DS, was consistent within the group [mean 2.1 (SD 0.2)] and characterised the muscle geometrically. The CSA of repeated scans was assessed for repeatability between-days and between-scans by analysis of variance and the coefficient of variation (CV) calculated. Areas were repeatable between-days (CV 6.5%) and between-scans (CV 3.6%). Linear dimensions of the anterior tibial muscle group reflected CSA and their potential for assessing changes in muscle size with atrophy and hypertrophy have yet to be established.

The production of granulocyte-monocyte colony-stimulating activity by isolated human T lymphocyte subpopulations.

PubMed

Hesketh, P J; Sullivan, R; Valeri, C R; McCarroll, L A

1984-05-01

Isolated human T lymphocyte subpopulations were obtained by fluorescence-activated cell sorting using the murine monoclonal antibodies, OKT4 and OKT8. The capabilities of the isolated lymphocytes to produce granulocyte-monocyte colony-stimulating activity (CSA) in response to mitogen challenge were assessed by in vitro assays employing light density nonadherent bone marrow cells. Essentially, no CSA production was noted by any isolated T lymphocyte population [OKT4 positive (+) or OKT8 positive (+)] cultured alone or following the addition of 10(4) autologous monocytes/ml. When phytohemagglutinin (PHA) alone was added, OKT4+ lymphocytes elaborated small amounts of CSA. With the addition of concanavalin A (Con-A) alone, both OKT4+ and OKT8+ cells were able to produce modest amounts of CSA. Significantly enhanced CSA production was observed when either OKT4+ or OKT8+ lymphocytes were coincubated with autologous monocytes in the presence of mitogen. We conclude that highly purified T lymphocyte subpopulations, free of monocytes as assessed by nonspecific esterase staining, can elaborate small amounts of CSA in response to PHA or Con-A challenge. A synergistic augmentation of CSA production was noted with coincubation of sorted lymphocytes and autologous monocytes in the presence of mitogen. Finally, our results suggest that the ability of T lymphocytes to make CSA is not exclusively limited to either the OKT4+ or OKT8+ defined subsets.

Cyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B.

PubMed

Morohashi, Kengo; Sahara, Hiroeki; Watashi, Koichi; Iwabata, Kazuki; Sunoki, Takashi; Kuramochi, Kouji; Takakusagi, Kaori; Miyashita, Hiroki; Sato, Noriyuki; Tanabe, Atsushi; Shimotohno, Kunitada; Kobayashi, Susumu; Sakaguchi, Kengo; Sugawara, Fumio

2011-04-29

Cyclosporin A (CsA) is well known as an immunosuppressive drug useful for allogeneic transplantation. It has been reported that CsA inhibits hepatitis C virus (HCV) genome replication, which indicates that cellular targets of CsA regulate the viral replication. However, the regulation mechanisms of HCV replication governed by CsA target proteins have not been fully understood. Here we show a chemical biology approach that elucidates a novel mechanism of HCV replication. We developed a phage display screening to investigate compound-peptide interaction and identified a novel cellular target molecule of CsA. This protein, named CsA associated helicase-like protein (CAHL), possessed RNA-dependent ATPase activity that was negated by treatment with CsA. The downregulation of CAHL in the cells resulted in a decrease of HCV genome replication. CAHL formed a complex with HCV-derived RNA polymerase NS5B and host-derived cyclophilin B (CyPB), known as a cellular cofactor for HCV replication, to regulate NS5B-CyPB interaction. We found a cellular factor, CAHL, as CsA associated helicase-like protein, which would form trimer complex with CyPB and NS5B of HCV. The strategy using a chemical compound and identifying its target molecule by our phage display analysis is useful to reveal a novel mechanism underlying cellular and viral physiology.

Childhood Sexual Abuse Is Highly Associated With HIV Risk–Taking Behavior and Infection Among MSM in the EXPLORE Study

PubMed Central

Mimiaga, Matthew J.; Noonan, Elizabeth; Donnell, Deborah; Safren, Steven A.; Koenen, Karestan C.; Gortmaker, Steven; O’Cleirigh, Conall; Chesney, Margaret A.; Coates, Thomas J.; Koblin, Beryl A.; Mayer, Kenneth H.

2012-01-01

Background Previous studies have found high rates of childhood sexual abuse (CSA) among US men who have sex with men (MSM). CSA history has been associated with a variety of negative effects later in life including behaviors that place MSM at greater risk for HIV acquisition and transmission. The present analysis is the first to examine the longitudinal association between CSA and HIV infection, unprotected anal sex, and serodiscordant unprotected anal sex, as well as mediators of these relationships among a large sample of HIV-uninfected MSM. Methods The EXPLORE Study was a behavioral intervention trial conducted in 6 US cities over 48 months with HIV infection as the primary efficacy outcome. Behavioral assessments were done every 6 months via confidential computerized assessments. Longitudinal regression models were constructed, adjusting for randomization arm, geographical location of study site, age at enrollment, education, and race/ethnicity. Results Of the 4295 participants enrolled, 39.7% had a history of CSA. Participants with a history of CSA [adjusted hazards ratio = 1.30, 95% confidence interval (CI): 1.02 to 1.69] were at increased risk for HIV infection over study follow-up. A significant association was seen between history of CSA and unprotected anal sex (adjusted odds ratio = 1.24, 95% CI: 1.12 to 1.36) and serodiscordant unprotected anal sex (adjusted odds ratio = 1.30, 95% CI: 1.18 to 1.43). Among participants reporting CSA, the EXPLORE intervention had no effect in reducing HIV infection rates. Participants reporting CSA were significantly more likely to have symptoms of depression and use nonprescription drugs. Conclusions A predictive relationship between a history of CSA and subsequent HIV infection was observed among this large sample of HIV-uninfected MSM. Findings indicate that HIV-uninfected MSM with CSA histories are at greater risk for HIV infection, report higher rates of HIV sexual risk behavior, and may derive less benefit from prevention programs. Future HIV prevention interventions should address the specific mental health concerns of MSM with a history of CSA. PMID:19367173

Childhood sexual abuse and the development of recurrent major depression in Chinese women.

PubMed

Chen, Jing; Cai, Yiyun; Cong, Enzhao; Liu, Ying; Gao, Jingfang; Li, Youhui; Tao, Ming; Zhang, Kerang; Wang, Xumei; Gao, Chengge; Yang, Lijun; Li, Kan; Shi, Jianguo; Wang, Gang; Liu, Lanfen; Zhang, Jinbei; Du, Bo; Jiang, Guoqing; Shen, Jianhua; Zhang, Zhen; Liang, Wei; Sun, Jing; Hu, Jian; Liu, Tiebang; Wang, Xueyi; Miao, Guodong; Meng, Huaqing; Li, Yi; Hu, Chunmei; Li, Yi; Huang, Guoping; Li, Gongying; Ha, Baowei; Deng, Hong; Mei, Qiyi; Zhong, Hui; Gao, Shugui; Sang, Hong; Zhang, Yutang; Fang, Xiang; Yu, Fengyu; Yang, Donglin; Liu, Tieqiao; Chen, Yunchun; Hong, Xiaohong; Wu, Wenyuan; Chen, Guibing; Cai, Min; Song, Yan; Pan, Jiyang; Dong, Jicheng; Pan, Runde; Zhang, Wei; Shen, Zhenming; Liu, Zhengrong; Gu, Danhua; Wang, Xiaoping; Liu, Xiaojuan; Zhang, Qiwen; Li, Yihan; Chen, Yiping; Kendler, Kenneth S; Shi, Shenxun; Flint, Jonathan

2014-01-01

Our prior study in Han Chinese women has shown that women with a history of childhood sexual abuse (CSA) are at increased risk for developing major depression (MD). Would this relationship be found in our whole data set? Three levels of CSA (non-genital, genital, and intercourse) were assessed by self-report in two groups of Han Chinese women: 6017 clinically ascertained with recurrent MD and 5983 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression. We confirmed earlier results by replicating prior analyses in 3,950 new recurrent MD cases. There were no significant differences between the two data sets. Any form of CSA was significantly associated with recurrent MD (OR 4.06, 95% confidence interval (CI) [3.19-5.24]). This association strengthened with increasing CSA severity: non-genital (OR 2.21, 95% CI 1.58-3.15), genital (OR 5.24, 95% CI 3.52-8.15) and intercourse (OR 10.65, 95% CI 5.56-23.71). Among the depressed women, those with CSA had an earlier age of onset, longer depressive episodes. Recurrent MD patients those with CSA had an increased risk for dysthymia (OR 1.60, 95%CI 1.11-2.27) and phobia (OR 1.41, 95%CI 1.09-1.80). Any form of CSA was significantly associated with suicidal ideation or attempt (OR 1.50, 95% CI 1.20-1.89) and feelings of worthlessness or guilt (OR 1.41, 95% CI 1.02-2.02). Intercourse (OR 3.47, 95%CI 1.66-8.22), use of force and threats (OR 1.95, 95%CI 1.05-3.82) and how strongly the victims were affected at the time (OR 1.39, 95%CI 1.20-1.64) were significantly associated with recurrent MD. In Chinese women CSA is strongly associated with recurrent MD and this association increases with greater severity of CSA. Depressed women with CSA have some specific clinical traits. Some features of CSA were associated with greater likelihood of developing recurrent MD.

Cyclosporine A regulate oxidative stress-induced apoptosis in cardiomyocytes: mechanisms via ROS generation, iNOS and Hsp70

PubMed Central

Chen, Huei-Wen; Chien, Chiang-Ting; Yu, Sung-Liang; Lee, Yuan-Teh; Chen, Wen-Jone

2002-01-01

Previous study suggested that cyclosporine A (CsA) could partially reduce ischaemia/reperfusion-induced injury in isolated heart, but the mechanism was still unclear. In this study, the possible mechanisms of cyclosporine A in regulating oxidative stress-induced cardiomyocyte apoptosis were examined. Morphological (cell shrinkage, apoptotic body formation, and DNA fragmentation) and biochemical (annexin-V staining for exposed phosphatidylserine residues) evidences showed that both hydrogen peroxide (H2O2) and hypoxia/reoxygenation could induce apoptotic change in the embryonal rat heart myoblast-derived cells (H9c2). These effects were inhibited by pre-treatment with CsA at concentration of 0.01–1.0 μM for 24 h, but were increased with 10.0 μM CsA. While examining the mechanisms of CsA in protecting cardiomyocyte apoptosis, we found that the collapse of mitochondria membrane potential (ΔΨm) induced by oxidative stress was partially reversed by CsA (0.01–1.0 μM). Compared to the control, CSA at the concentration of 0.1 and 10.0 μM significantly increased the level of intracellular reactive oxygen species (ROS) to 117.2±12.4% and 234.4±9.3%, respectively. Co-incubating with the antioxidant, ascorbic acid (10.0 μM), could partially reduce the protective effect of CsA (0.01–1.0 μM) and the toxic effect of 10.0 μM CsA. Pre-treatment with CsA at concentration of 0.01–1.0 μM for 24 h produced up-regulation of heat shock protein 70 (Hsp 70), inducible nitric oxide synthase (iNOS) and also induced NO production, indicating that these factors might be associated with the cell protective effects of CsA. These results suggest that CsA could protect the oxidative stress-induced cardiomyocyte apoptosis not only by preventing the loss of ΔΨm in mitochondria, but also through ROS generation, Hsp70, and iNOS up-regulation. PMID:12411407

Up-converted 1/f PM and AM noise in linear HBT amplifiers.

PubMed

Ferre-Pikal, Eva S; Savage, Frederick H

2008-08-01

In this paper we describe a technique to predict the 1/f phase modulation (PM) and 1/f amplitude modulation (AM) noise due to up-conversion of 1/f baseband current noise in microwave heterojunction bipolar transistor (HBT) amplifiers. We obtain an accurate model for the amplifier and find the expression for voltage gain in terms of DC bias, transistor parameters, and circuit components. Theoretical 1/f PM and AM noise sensitivities to 1/f baseband current noise are then found by applying the definitions of PM and AM noise to the gain expression of the amplifier. Measurements of PM and AM sensitivities at 500 MHz and 1 GHz were in good agreement with the values predicted by theory, verifying the validity of this technique. This method can be used to optimize amplifier design for low PM and AM noise. We show that the amplifier PM noise can be reduced by 9 dB by adjusting the value of the input coupling capacitor.

Enhancement of High-Speed Infrared Array Electronics (Center Director's Discretionary Fund)

NASA Technical Reports Server (NTRS)

Sutherland, W. T.

1996-01-01

A state-of-the-art infrared detector was to be used as the sensor in a new spectrometer-camera for astronomical observations. The sensitivity of the detector required the use of low-noise, high-speed electronics in the system design. The key component in the electronic system was the pre-amplifier that amplified the low voltage signal coming from the detector. The system was designed based on the selection of the amplifier and that was driven by the maximum noise level, which would yield the desired sensitivity for the telescope system.

Childhood sexual abuse and two stages of cigarette smoking in African-American and European-American young women.

PubMed

Sartor, Carolyn E; Grant, Julia D; Duncan, Alexis E; McCutcheon, Vivia V; Nelson, Elliot C; Calvert, Wilma J; Madden, Pamela A F; Heath, Andrew C; Bucholz, Kathleen K

2016-09-01

The aim of the current study was to determine whether the higher rates of childhood sexual abuse (CSA) but lower rates of cigarette smoking in African-American vs. European-American women can be explained in part by a lower magnitude of association between CSA and smoking in African-American women. Data were drawn from a same-sex female twin study of substance use (n=3521; 14.3% African-American). Cox proportional hazards regression analyses using CSA to predict smoking initiation and progression to regular smoking were conducted separately by race/ethnicity. Co-twin status on the smoking outcome was used to adjust for familial influences on smoking (which may overlap with family-level influences on CSA exposure). After adjusting for co-twin status, CSA was associated with smoking initiation in European Americans (hazard ratio (HR)=1.43, 95% confidence intervals (CI): 1.26-1.62) and with smoking initiation ≤16 in African Americans (HR=1.70, CI: 1.26-2.29). CSA was associated with regular smoking onset ≤15 in European Americans (HR=1.63, CI: 1.21-2.18), with no change in HR after adjusting for co-twin status. In the African-American subsample, the HR for CSA was reduced to non-significance after adjusting for co-twin status (from HR=3.30, CI: 1.23-8.89 to HR=1.16, CI: 0.71-1.92 for regular smoking ≤15). CSA is associated with moderate elevation in risk for initiating smoking among African-American and European-American women. By contrast, CSA is associated with elevated risk for (adolescent onset) regular smoking only in European-American women. Furthermore, there is significant overlap between risk conferred by CSA and familial influences on regular smoking in African-American but not European-American women. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mediators of sexual functioning and marital quality in chronically depressed adults with and without a history of childhood sexual abuse.

PubMed

Dunlop, Boadie W; Hill, Eric; Johnson, Benjamin N; Klein, Daniel N; Gelenberg, Alan J; Rothbaum, Barbara O; Thase, Michael E; Kocsis, James H

2015-03-01

Sexual dysfunction is common among depressed adults. Childhood sexual abuse (CSA) and depressive symptomology are among the risk factors for sexual dysfunction, and these factors may interact to predict adult relationship functioning. Several models have been developed postulating interactions between these variables. We tested models of the effects of CSA and elucidate the associations between CSA, sexual dysfunction, depression severity, anxiety, and relationship quality in chronically depressed adults. Baseline data from 808 chronically depressed outpatients enrolled in the Research Evaluating the Value of Augmenting Medication with Psychotherapy study were evaluated using structural equation modeling. The Inventory of Depressive Symptomology, self-report version (IDS-SR) assessed depression severity, and the Mood and Anxiety Symptom Questionnaire Anxious Arousal subscale assessed anxiety. Sexual function was assessed with the Arizona Sexual Experiences Scale (ASEX), and the Quality of Marriage Index (QMI) assessed relationship quality for patients in stable relationships. CSA scores predicted depression severity on the IDS-SR, as well as lower relationship quality and sexual satisfaction. ASEX scores were significantly associated with depression severity but were not correlated with the QMI. Two models were evaluated to elucidate these associations, revealing that (i) depression severity and anxious arousal mediated the relationship between CSA and adult sexual function, (ii) anxious arousal and sexual functioning mediated the association between CSA and depression symptoms, and (iii) when these models were combined, anxious arousal emerged as the most important mediator of CSA on depression which, in turn, mediated associations with adult sexual satisfaction and relationship quality. Although CSA predicts lower relationship and sexual satisfaction among depressed adults, the long-term effects of CSA appear to be mediated by depressive and anxious symptoms. It is important to address depression and anxiety symptoms when treating patients with CSA who present with sexual dysfunction or marital concerns. © 2014 International Society for Sexual Medicine.

Disrupted Reinforcement Learning and Maladaptive Behavior in Women with a History of Childhood Sexual Abuse: A High-Density Event-Related Potential Study

PubMed Central

Pechtel, Pia; Pizzagalli, Diego A.

2013-01-01

Context Childhood sexual abuse (CSA) has been associated with psychopathology, particularly major depressive disorder (MDD), and high-risk behaviors. Despite grave epidemiological data, the mechanisms underlying these maladaptive outcomes remain poorly understood. Objective We examined whether CSA history, particularly in conjunction with past MDD, is associated with behavioral and neural dysfunction in reinforcement learning, and whether such dysfunction is linked to maladaptive behavior. Design Participants completed a clinical evaluation and a probabilistic reinforcement task while 128-channel event-related potentials were recorded. Setting Academic setting; participants recruited from the community. Participants Fifteen remitted depressed females with CSA history (CSA+rMDD), 16 remitted depressed females without CSA history (rMDD), and 18 healthy females. Main Outcome Measures Participants’ preference for choosing the most rewarded stimulus and avoiding the most punished stimulus was evaluated. The feedback-related negativity (FRN) and error-related negativity (ERN)–hypothesized to reflect activation in the anterior cingulate cortex–were used as electrophysiological indices of reinforcement learning. Results No group differences emerged in the acquisition of reinforcement contingencies. In trials requiring to rely partially or exclusively on previously rewarded information, the CSA+rMDD group showed (1) lower accuracy (relative to both controls and rMDD), (2) blunted electrophysiological differentiation between correct and incorrect responses (relative to controls), and (3) increased activation in the subgenual anterior cingulate cortex (relative to rMDD). CSA history was not associated with impairments in avoiding the most punished stimulus. Self-harm and suicidal behaviors correlated with poorer performance of previously rewarded–but not previously punished–trials. Conclusions Irrespective of past MDD, women with CSA histories showed neural and behavioral deficits in utilizing previous reinforcement to optimize decision-making in the absence of feedback (blunted “Go learning”). While the current study provides initial evidence for reward-specific deficits associated with CSA, future research is warranted to determine if disrupted positive reinforcement learning predicts high-risk behavior following CSA. PMID:23487253

Association between vertebral cross-sectional area and lumbar lordosis angle in adolescents.

PubMed

Wren, Tishya A L; Aggabao, Patricia C; Poorghasamians, Ervin; Chavez, Thomas A; Ponrartana, Skorn; Gilsanz, Vicente

2017-01-01

Lumbar lordosis (LL) is more prominent in women than in men, but the mechanisms responsible for this discrepancy are poorly defined. A recent study indicates that newborn girls have smaller vertebral cross-sectional area (CSA) when compared to boys-a difference that persists throughout life and is independent of body size. We determined the relations between vertebral cross-sectional area (CSA) and LL angle and whether sex differences in lumbar lordosis are related to sex differences in vertebral CSA. Using multi-planar magnetic resonance imaging (MRI), we measured vertebral cross-sectional area (CSA) and vertebral height of the spine of 40 healthy boys and 40 girls, ages 9-13 years. Measures of the CSA of the lumbar vertebrae significantly differed between sexes (9.38 ± 1.46 vs. 7.93 ± 0.69 in boys and girls, respectively; P < 0.0001), while the degree of LL was significantly greater in girls than in boys (23.7 ± 6.1 vs. 27.6 ± 8.0 in boys and girls, respectively; P = 0.02). When all subjects were analyzed together, values for LL angle were negatively correlated to vertebral CSA (r = -0.47; P < 0.0001); this was also true when boys and girls were analyzed separately. Multivariate regression analysis indicated that vertebral CSA was independently associated with LL, even after accounting for sex, age, height or vertebral height, and weight. Similar negative relations were present when thoracic vertebrae were analyzed (Model P < 0.0001, R2 = 0.37, thoracic vertebral CSA slope P < 0.0001), suggesting that deficient vertebral cross-sectional dimensions are not merely the consequence of the anterior lumbar curvature. We conclude that vertebral CSA is negatively associated with LL, and that the greater degree of LL in females could, at least in part, be due to smaller vertebral cross-sectional dimensions. Studies are needed to examine the potential relations between vertebral CSA and spinal conditions known to be associated with increased LL, such as spondylolysis and spondylolisthesis.

Substance use, childhood sexual abuse, and sexual risk behavior among women in methadone treatment.

PubMed

Cohen, Lisa R; Tross, Susan; Pavlicova, Martina; Hu, Mei-Chen; Campbell, Aimee N; Nunes, Edward V

2009-01-01

Substance use and a history of childhood sexual abuse (CSA) are risk factors for unprotected sex among women, yet questions remain as to how their combined influence may differentially affect sexual risk. The current study investigated how complex relationships among drug use and CSA may contribute to unprotected sexual occasions (USO). A Generalized Linear Mixed Model was used to examine the interaction between current cocaine/stimulants and opioid use and CSA on number of USOs in a sample of 214 sexually active women in outpatient methadone maintenance treatment. For women with CSA, an increase in days of cocaine/stimulant use was associated with a significant increase in USOs. In contrast, an increase in days of opiate use was associated with a significant decrease in USOs. For the group of women who did not report CSA, there was a significant increase in USOs with increased opiate use. Findings indicate that CSA is related to unprotected sexual occasions depending on drug type and severity of use. Women with CSA using cocaine are at particularly high risk for having unprotected sex and should be specifically targeted for HIV prevention interventions.

Dynamic CO₂ inhalation: a novel treatment for CSR-CSA associated with CHF.

PubMed

Wan, Zhi Hui; Wen, Fang Jing; Hu, Ke

2013-05-01

Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) is very common in patients with chronic congestive heart failure (CHF). A current concept of the key pathophysiological mechanism leading to CSR-CSA is a fluctuation of PaCO2 below and above the apneic threshold. A number of therapeutic approaches for CSR-CSA have been proposed-all with varying success, some of which include various modes of positive airway pressure among other strategies. However, CO2 oscillations seen in CSR-CSA have yet to be looked at as a specific therapeutic target by current treatments. Previous studies have shown that delivery of constant CO2 is efficacious in eliminating CSR-CSA by raising PaCO2, but there are serious concerns about the potential side effects, such as unwanted elevations in ventilation, work of breathing, and sympathetic nerve activity (SNA), and consequently CO2 inhalation therapy has not been recommended as a routine option for therapy. However, recent new studies into CO2 inhalation therapy have been made that may reshape its role as therapeutic. In this review, we will focus on the recent developments of administration of dynamic CO2 in the management of CSR-CSA in CHF patients.

Dissociative Experiences during Sexual Behavior among a Sample of Adults Living with HIV Infection and a History of Childhood Sexual Abuse

PubMed Central

Hansen, Nathan B.; Brown, Lauren J.; Tsatkin, Elizabeth; Zelgowski, Brittany; Nightingale, Vienna

2012-01-01

Little attention has been given to the occurrence of dissociative symptoms during sexual behavior in adults who have experienced childhood sexual abuse (CSA). For this study, 57 adults living with HIV infection who had experienced CSA and were entering a treatment study for traumatic stress completed study assessments and clinical interviews, including a 15-item scale of Dissociative Experiences during Sexual Behavior. Predictor variables included DSM-IV-TR diagnoses of PTSD and Dissociative Disorders, Rape by an Intimate Partner, Duration of CSA, Number of Perpetrators of CSA, and Current Sexual Satisfaction. A multiple regression analysis was conducted to identify significant associations between predictors and dissociation during sex. Mean differences by clinical diagnosis were also examined. Results indicated that PTSD, Dissociative Disorders, Rape by an Intimate Partner, Duration of CSA, and Number of Perpetrators of CSA were associated with increased dissociation during sexual behavior. Dissociation during sex likely increases vulnerability to sexual revictimization and risky sexual behavior. Standard behavioral prevention interventions may be ineffective for sexual situations when dissociation occurs, and prevention efforts should be integrated with mental health care for those who have experienced CSA. PMID:22545567

Effects of cyclosporin A on a kidney epithelial cell line (LLC-PK1).

PubMed

Becker, G M; Gandolfi, A J; Nagle, R B

1987-05-01

Cyclosporin A (CSA), a potent immunosuppressant with the adverse side effect of nephrotoxicity, inhibited cell growth of pig kidney tubule cells (LLC-PK1) in culture. CSA (10(-5) M) also induced intense cytoplasmic vacuolation and the formation of dense granules. At the same concentration an analogue of CSA, cyclosporin G, had much less effect. This cell line may prove useful for revealing the mechanism of CSA-nephrotoxicity and testing the nephrotoxic potential of new analogues of cyclosporine.

Anti-Inflammatory Effects of Cajaninstilbene Acid and Its Derivatives.

PubMed

Huang, Mei-Yan; Lin, Jing; Lu, Kuo; Xu, Hong-Gui; Geng, Zhi-Zhong; Sun, Ping-Hua; Chen, Wei-Min

2016-04-13

Cajaninstilbene acid (CSA) is one of the active components isolated from pigeon pea leaves. In this study, anti-inflammatory effects of CSA and its synthesized derivatives were fully valued with regard to their activities on the production of nitric oxide (NO) and pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in vitro cell model, as well as their impacts on the migration of neutrophils and macrophages in fluorescent protein labeled zebrafish larvae model by live image analysis. Furthermore, the anti-inflammatory mechanism of this type of compounds was clarified by western-blot and reverse transcription-polymerase chain reaction (RT-PCR). The results showed that CSA, as well as its synthesized derivatives 5c, 5e and 5h, exhibited strong inhibition activity on the release of NO and inflammatory factor TNF-α and IL-6 in lipopolysaccharides (LPS)-stimulated murine macrophages. CSA and 5c greatly inhibited the migration of neutrophils and macrophages in injury zebrafish larvae. CSA and 5c treatment greatly inhibited the phosphorylation of proteins involved in nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Moreover, we found that peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662 could reverse partly the roles of CSA and 5c, and CSA and 5c treatment greatly resist the decrease of PPARγ mRNA and protein induced by LPS stimulation. Our results identified the promising anti-inflammatory effects of CSA and its derivatives, which may serve as valuable anti-inflammatory lead compound. Additionally, the mechanism studies demonstrated that the anti-inflammatory activity of CSA and its derivative is associated with the inhibition of NF-κB and MAPK pathways, relying partly on resisting the LPS-induced decrease of PPARγ through improving its expression.

The effect of ketoconazole on whole blood and skin ciclosporin concentrations in dogs.

PubMed

Gray, Laura L; Hillier, Andrew; Cole, Lynette K; Rajala-Schultz, Päivi J

2013-02-01

Ciclosporin (CSA) is approved for the treatment of canine atopic dermatitis. Ciclosporin is metabolized by liver cytochrome P450 enzymes, a process inhibited by ketoconazole (KTZ). The aims of this study were to determine skin and blood CSA concentrations when CSA was administered alone at 5.0 (Treatment 1) or 2.5 mg/kg (Treatment 2) and when CSA was administered at 2.5 mg/kg concurrently with KTZ at 5 (Treatment 3) or 2.5 mg/kg (Treatment 4). We hypothesized that skin and blood CSA concentrations in Treatment 1 would not differ from those obtained with T3 or T4. In a randomized cross-over study, six healthy research dogs received each of the treatments (Treatment 1, 2, 3 and 4) once daily for 7 days. After the first, fourth and seventh dose for each treatment, a peak and trough skin punch biopsy sample and whole blood sample were collected and analysed with high-performance liquid chromatography-tandem mass spectrometry. Data were analysed using a repeated measures approach with PROC MIXED in SAS. Pairwise comparisons were performed with least squares means and Tukey-Kramer adjustment for multiple comparisons. Mean blood CSA concentrations in Treatment 1 were not different from those in Treatment 2 or 4, but were less than in Treatment 3. Mean skin CSA concentrations in Treatment 1 were greater than in Treatment 2, not different from those in Treatment 4, and less than those in Treatment 3. Administration of CSA and KTZ concurrently at 2.5 mg/kg each may be as effective as CSA alone at 5.0 mg/kg for treatment of canine atopic dermatitis. © 2013 The Authors. Veterinary Dermatology © 2013 ESVD and ACVD.

Sexual self-schemas of female child sexual abuse survivors: relationships with risky sexual behavior and sexual assault in adolescence.

PubMed

Niehaus, Ashley F; Jackson, Joan; Davies, Stephanie

2010-12-01

Childhood sexual trauma has been demonstrated to increase survivors' risk for engaging in unrestricted sexual behaviors and experiencing adolescent sexual assault. The current study used the sexual self-schema construct to examine cognitive representations of sexuality that might drive these behavioral patterns. In Study 1 (N = 774), we attempted to improve the content validity of the Sexual Self Schema Scale for child sexual abuse (CSA) survivors, introducing a fourth sexual self-schema factor titled the "immoral/irresponsible" factor. In Study 2 (N = 1150), the potential differences in sexual self-views, as assessed by the four sexual self-schema factors, between CSA survivors and non-victims were explored. In addition, Study 2 evaluated how these sexual self-schema differences may contribute to participation in unrestricted sexual behaviors and risk for sexual assault in adolescence. Results indicated that a history of CSA impacted the way women viewed themselves as a sexual person on each of the four factors. CSA survivors were found to view themselves as more open and possessing more immoral/irresponsible cognitions about sexuality as compared to women who did not have a CSA history. In addition, the CSA survivors endorsed less embarrassment and passionate/romantic views of their sexual selves. The interaction of CSA severity and the sexual self-schemas explained variance in adolescent sexual assault experiences above and beyond the severity of CSA history and participation in risky sexual behaviors. The findings suggest that sexual self-views may serve to moderate the relationship between CSA and adolescent sexual assault. Implications of these findings and directions for future research are discussed.

Cardiac resynchronization therapy and atrial overdrive pacing for the treatment of central sleep apnoea

PubMed Central

Lüthje, Lars; Renner, Bernd; Kessels, Roger; Vollmann, Dirk; Raupach, Tobias; Gerritse, Bart; Tasci, Selcuk; Schwab, Jörg O.; Zabel, Markus; Zenker, Dieter; Schott, Peter; Hasenfuss, Gerd; Unterberg-Buchwald, Christina; Andreas, Stefan

2009-01-01

Aims The combined therapeutic impact of atrial overdrive pacing (AOP) and cardiac resynchronization therapy (CRT) on central sleep apnoea (CSA) in chronic heart failure (CHF) so far has not been investigated. We aimed to evaluate the effect of CRT alone and CRT + AOP on CSA in CHF patients and to compare the influence of CRT on CHF between CSA positive and CSA negative patients. Methods and results Thirty patients with CRT indication underwent full night polysomnography, echocardiography, exercise testing, and neurohumoral evaluation before and 3 months after CRT implantation. In CSA positive patients (60%), two additional sleep studies were conducted after 3 months of CRT, with CRT alone or CRT + AOP, in random order. Cardiac resynchronization therapy resulted in significant improvements of NYHA class, left ventricular ejection fraction, N-terminal pro-brain natriuretic peptide, VO2max, and quality of life irrespective of the presence of CSA. Cardiac resynchronization therapy also reduced the central apnoea–hypopnoea index (AHI) (33.6 ± 14.3 vs. 23.8 ± 16.9 h−1; P < 0.01) and central apnoea index (17.3 ± 14.1 vs. 10.9 ± 13.9 h−1; P < 0.01) without altering sleep stages. Cardiac resynchronization therapy with atrial overdrive pacing resulted in a small but significant additional decrease of the central AHI (23.8 ± 16.9 vs. 21.5 ± 16.9 h−1; P < 0.01). Conclusion In this study, CRT significantly improved CSA without altering sleep stages. Cardiac resynchronization therapy with atrial overdrive pacing resulted in a significant but minor additional improvement of CSA. Positive effects of CRT were irrespective of the presence of CSA. PMID:19147446

The Cycle of Abuse: When Victims Become Offenders.

PubMed

Plummer, Malory; Cossins, Annie

2016-07-19

Various psychological theories exist in the literature to explain the behavior of men who commit child sex offences, including the belief that child sexual abuse (CSA) is a predisposing factor for the transition from victim to offender. These theories are, however, unable to explain the fact that while most victims of CSA are female, most perpetrators of CSA are male. The sex specificity of CSA in terms of victims and offenders suggests that the experience of CSA and its psychosocial effects may be different for boys, compared to girls. We hypothesize that CSA experiences may involve risk factors that affect the development of sexually abusive behavior for boys, rather than girls. Our aim was to determine whether the literature provides evidence of a cycle of abuse from victim to offender, and, if so, to document its characteristics. We undertook a comprehensive literature review of studies on both victims and offenders, including studies which revealed the following: age of onset of CSA, duration of abuse, gender of the abuser, the relationship between victim and abuser, grooming behaviors, the types and severity of abuse, and disclosure of abuse. While we found no evidence for the existence of a cycle of abuse for female CSA victims, we discovered evidence to support the existence of a cycle of abuse for male CSA victims who had experienced particular abuse characteristics. As an original contribution to the literature, we identified four factors that may be associated with a boy's transition from victim to offender as well as the methodological issues to be addressed in future research. Based on criminological theories, we argue that these four factors share a common theme, that is, that they represent experiences of power (for the abuser) and powerlessness (for the victim). © The Author(s) 2016.

Incidence and Progression of Cardiac Surgery-associated Acute Kidney Injury and its Relationship with Bypass and Cross Clamp Time

PubMed Central

Karim, Habib Md Reazaul; Yunus, Mohd; Saikia, Manuj Kumar; Kalita, Jyoti Prasad; Mandal, Mrinal

2017-01-01

Introduction: Cardiac surgery-associated kidney injury (CSA-AKI) is common but relatively less is known about its progression. The present study is aimed at evaluating the incidence and course of CSA-AKI and its relationship with the different durations of cardiopulmonary bypass (CPB) and cross clamp times. Materials and Methods: Occurrences of CSA-AKI are evaluated as per the Akin Kidney Injury Network (AKIN) criteria over the course of 5 postoperative day (POD) in 100 patients. The relationship of different durations of CPB and aortic cross clamp time with CSA-AKI is analyzed by Chi-squared test for trend and other appropriate tests using INSTAT software. Results: One hundred (43 male, 57 female; mean age of 37.01 ± 12.28 years, and baseline mean serum creatinine 0.99 ± 0.20 mg %) patients undergone mostly valve replacement, and congenital heart disease correction was evaluated. Nearly 49% suffered CSA-AKI (81.63% AKIN Class I) with maximum numbers on 2nd POD. Serum creatinine followed a falling trend 3rd POD onward except in 8.16% cases of CSA-AKI. Oliguria was absent even in AKIN Class II. The CPB time >70 min and cross clamp time >60 min increase CSA-AKI risk by an OR of 4.76 and 2.84, respectively (P < 0.05). Conclusion: CSA-AKI is very prevalent; mostly of AKIN Class I and increases with increasing CPB and cross clamp time. Urine output is not a reliable indicator of CSA-AKI. The AKIN Class II on the very 1st POD or increasing trend of serum creatinine beyond 3rd POD should alert for early intervention. PMID:28074790

Investigating the protective effects of aged garlic extract on cyclosporin-induced nephrotoxicity in rats.

PubMed

Wongmekiat, Orawan; Thamprasert, Kamthorn

2005-10-01

Cyclosporin A (CsA) nephrotoxicity has been described in solid organ recipients and in the patients who were treated for autoimmune diseases. Reactive oxygen species-induced oxidative stress and lipid peroxidations are implicated in the pathophysiology of CsA-induced renal injury. Aged garlic extract (AGE) has been reported to exhibit potent antioxidative and free radical scavenging abilities in various disease conditions. The present study was designed to investigate whether AGE could possibly have a protective effect against nephrotoxicity induced by CsA. Male Wistar rats were treated orally with CsA (50 mg/kg/day), CsA + AGE (0.25, 0.5, 1, and 2 g/kg/day started 3 days before the first dose of CsA), or the vehicle of CsA for a period of 10 days. Blood urea nitrogen, serum creatinine, creatinine clearance, and renal histopathological changes were evaluated after 24 h of the last treatment. CsA caused an increase in blood urea nitrogen and serum creatinine by 117 and 100%, respectively, whereas it decreased creatinine clearance by 78% compared with the vehicle-treated rats (all P < 0.001). AGE treatment (0.5, 1 and 2 g/kg) significantly protected animals against CsA-induced biochemical changes, albeit blood urea nitrogen and creatinine clearance in the 0.5 g/kg AGE treated-animals were only partially restored. Kidney sections taken from CsA-treated rats showed severe vacuolations and tubular necrosis. These histopathological changes were markedly improved by pretreatment of rats with AGE at the dose of 0.5--2 g/kg. The results indicate that AGE ameliorates renal dysfunction and morphological changes induced by CsA, and imply that it could be a beneficial remedy for attenuating the CsA nephrotoxicity.

The economic burden of child sexual abuse in the United States.

PubMed

Letourneau, Elizabeth J; Brown, Derek S; Fang, Xiangming; Hassan, Ahmed; Mercy, James A

2018-05-01

The present study provides an estimate of the U.S. economic impact of child sexual abuse (CSA). Costs of CSA were measured from the societal perspective and include health care costs, productivity losses, child welfare costs, violence/crime costs, special education costs, and suicide death costs. We separately estimated quality-adjusted life year (QALY) losses. For each category, we used the best available secondary data to develop cost per case estimates. All costs were estimated in U.S. dollars and adjusted to the reference year 2015. Estimating 20 new cases of fatal and 40,387 new substantiated cases of nonfatal CSA that occurred in 2015, the lifetime economic burden of CSA is approximately $9.3 billion, the lifetime cost for victims of fatal CSA per female and male victim is on average $1,128,334 and $1,482,933, respectively, and the average lifetime cost for victims of nonfatal CSA is of $282,734 per female victim. For male victims of nonfatal CSA, there was insufficient information on productivity losses, contributing to a lower average estimated lifetime cost of $74,691 per male victim. If we included QALYs, these costs would increase by approximately $40,000 per victim. With the exception of male productivity losses, all estimates were based on robust, replicable incidence-based costing methods. The availability of accurate, up-to-date estimates should contribute to policy analysis, facilitate comparisons with other public health problems, and support future economic evaluations of CSA-specific policy and practice. In particular, we hope the availability of credible and contemporary estimates will support increased attention to primary prevention of CSA. Copyright © 2018. Published by Elsevier Ltd.

Pulmonary Hypertension and Computed Tomography Measurement of Small Pulmonary Vessels in Severe Emphysema

PubMed Central

Matsuoka, Shin; Washko, George R.; Yamashiro, Tsuneo; Estepar, Raul San Jose; Diaz, Alejandro; Silverman, Edwin K.; Hoffman, Eric; Fessler, Henry E.; Criner, Gerard J.; Marchetti, Nathaniel; Scharf, Steven M.; Martinez, Fernando J.; Reilly, John J.; Hatabu, Hiroto

2010-01-01

Rationale: Vascular alteration of small pulmonary vessels is one of the characteristic features of pulmonary hypertension in chronic obstructive pulmonary disease. The in vivo relationship between pulmonary hypertension and morphological alteration of the small pulmonary vessels has not been assessed in patients with severe emphysema. Objectives: We evaluated the correlation of total cross-sectional area of small pulmonary vessels (CSA) assessed on computed tomography (CT) scans with the degree of pulmonary hypertension estimated by right heart catheterization. Methods: In 79 patients with severe emphysema enrolled in the National Emphysema Treatment Trial (NETT), we measured CSA less than 5 mm2 (CSA<5) and 5 to 10 mm2 (CSA5−10), and calculated the percentage of total CSA for the lung area (%CSA<5 and %CSA5–10, respectively). The correlations of %CSA<5 and %CSA5–10 with pulmonary arterial mean pressure (\\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}\\overline{Ppa}\\end{equation*}\\end{document}) obtained by right heart catheterization were evaluated. Multiple linear regression analysis using \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}\\overline{Ppa}\\end{equation*}\\end{document} as the dependent outcome was also performed. Measurements and Main Results: The %CSA<5 had a significant negative correlation with \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}\\overline{Ppa}\\end{equation*}\\end{document} (r = −0.512, P < 0.0001), whereas the correlation between %CSA5–10 and \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}\\overline{Ppa}\\end{equation*}\\end{document} did not reach statistical significance (r = −0.196, P = 0.083). Multiple linear regression analysis showed that %CSA<5 and diffusing capacity of carbon monoxide (DlCO) % predicted were independent predictors of \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}\\overline{Ppa}\\end{equation*}\\end{document} (r2 = 0.541): %CSA <5 (P < 0.0001), and DlCO % predicted (P = 0.022). Conclusions: The %CSA<5 measured on CT images is significantly correlated to \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}\\overline{Ppa}\\end{equation*}\\end{document} in severe emphysema and can estimate the degree of pulmonary hypertension. PMID:19875683

Single blinded, randomized, placebo-controlled study on the effects of ciclosporin on cutaneous barrier function and immunological response in atopic beagles.

PubMed

White, Amelia G; Santoro, Domenico; Ahrens, Kim; Marsella, Rosanna

2018-03-01

Ciclosporin (CsA) is a common treatment for canine atopic dermatitis (cAD). cAD is a very common skin disease with a multifactorial pathogenesis due to complex interactions between the host and the environment. The purpose of this study was to describe the physical and immunological effects of CsA in cAD using a canine model of AD. Fourteen beagles were enrolled; seven received CsA orally every 24 h for 28 days, and seven received placebo. All dogs were exposed to relevant allergens, house dust mite solution, one day prior to treatment and once weekly thereafter for 28 consecutive days. Canine atopic dermatitis extent and severity index-03 (CADESI-03) and skin biopsies were performed on day 0, 14, and 28. Quantitative RT-PCR was used to determine levels of cutaneous cytokines and barrier function markers. Indirect immunofluorescence was used to determine protein expression and distribution of nuclear messengers, barrier function and inflammatory [thymic stromal lymphopoietin (TSLP)] markers. The data were tested for normality and then the upaired two samples Student's t-test and the repeated measurements ANOVA, followed by the Dunnett's Multiple Comparison Test as post-hoc analysis, were performed. A P value of <0.05 was considered statistically significant. A significant decrease in CADESI-03 occurred for the treatment group compared to placebo (p = 0.023) on day 28. On day 14, a significant increase in TSLP protein expression [p = 0.019 (placebo); p = 0.02 (CsA)] and a significant decrease in Transforming Growth Factor (TGF)-β mRNA [p = 0.01 (placebo); p = 0.015 (CsA)] were noted in both groups compared to baseline. On day 28, a significant increase in canine beta defensin (cBD)103 [p = 0.012 (placebo)] and cBD3-like mRNAs [p = 0.044 (placebo)], and filaggrin [p = 0.035 (CsA)] and TSLP protein expressions [p = 0.0092 (CsA)] were seen compared to baseline. In contrast, a significant decrease in mRNA of Tumor Necrosis factor (TNF)-α [p = 0.013 (CsA)], Interleukin (IL)-10 [p = 0.038 (CsA)], TGF-β [p = 0.017 (CsA)], and caspase 14 [p = 0.014 (CsA)] was seen on day 28 compared to baseline. Comparison of the groups revealed no significant effect on skin immunologic milieu or barrier markers despite evident improvement of physical signs in the treatment group. Although this study confirmed the usefulness of CsA for the treatment of cAD, a clear involvement of CsA on some of the currently known immunological alterations present in cAD was not determined. However, it is important to note that there was no measurable exacerbation of skin barrier dysfunction secondary to CsA administration in this model. Copyright © 2018 Elsevier B.V. All rights reserved.

Design of a lock-amplifier circuit

NASA Astrophysics Data System (ADS)

Liu, H.; Huang, W. J.; Song, X.; Zhang, W. Y.; Sa, L. B.

2017-01-01

The lock-in amplifier is recovered by phase sensitive detection technique for the weak signal submerged in the noise background. This design is based on the TI ultra low power LM358, INA129, OPA227, OP07 and other chips as the core design and production of the lock-in amplifier. Signal generator by 10m ohms /1K ohm resistance points pressure network 10 mu V 1mV adjustable sine wave signal s (T). The concomitant interference signal together through the AC amplifier and band-pass filter signal x (T), on the other hand reference signal R (T) driven by square wave phase shift etc. steps to get the signal R (T), two signals and by phase sensitive detector are a DC full wave, again through its low pass filter and a DC amplifier to be measured signal more accurate detection, the final circuit through the AD conversion and the use of single-chip will display the output.

Dynamic Compression of the Signal in a Charge Sensitive Amplifier: From Concept to Design

NASA Astrophysics Data System (ADS)

Manghisoni, Massimo; Comotti, Daniele; Gaioni, Luigi; Ratti, Lodovico; Re, Valerio

2015-10-01

This work is concerned with the design of a low-noise Charge Sensitive Amplifier featuring a dynamic signal compression based on the non-linear features of an inversion-mode MOS capacitor. These features make the device suitable for applications where a non-linear characteristic of the front-end is required, such as in imaging instrumentation for free electron laser experiments. The aim of the paper is to discuss a methodology for the proper design of the feedback network enabling the dynamic signal compression. Starting from this compression solution, the design of a low-noise Charge Sensitive Amplifier is also discussed. The study has been carried out by referring to a 65 nm CMOS technology.

Child sexual abuse as a risk factor for teen dating violence: Findings from a representative sample of Quebec youth

PubMed Central

Hébert, Martine; Moreau, Catherine; Blais, Martin; Lavoie, Francine; Guerrier, Mireille

2016-01-01

Child sexual abuse (CSA) is identified as a significant risk factor for later victimization in the context of adult intimate relationships, but less is known about the risk associated with CSA in early romantic relationships. This paper aims to document the association between CSA and teen dating victimization in a large representative sample of Quebec high-school students. As part of the Youths’ Romantic Relationships Project, 8,194 teens completed measures on CSA and psychological, physical and sexual dating violence. After controlling for other interpersonal traumas, results show that CSA contributed to all three forms of dating victimization among both boys and girls. The heightened risk of revictimization appears to be stronger for male victims of CSA. Intervention and prevention efforts are clearly needed to reduce the vulnerability of male and female victims of sexual abuse who are entering the crucial phase of adolescence and first romantic relationships. PMID:29308104

Hypomagnesemia and mild rhabdomyolysis in living related donor renal transplant recipient treated with cyclosporine A.

PubMed

Cavdar, C; Sifil, A; Sanli, E; Gülay, H; Camsari, T

1998-12-01

Since cyclosporine A (CsA) had been used in renal transplant recipients, important improvements in short-term and long-term graft survivals have been detected. In spite of these improvements CsA seems to have several adverse effects. First, CsA leads to nephrotoxicity. Moreover, CsA affects the other organs and systems (skin, liver, nervous system, etc.) and causes, increased risks of infections and malignancies. Hypomagnesemia is one of the side effects of CsA therapy, but it is a rare condition in living related donor renal transplant recipients. It may also cause multi-system dysfunction, especially hypocalcemia and hypokalemia, which cannot be corrected without magnesium therapy. In addition, rhabdomyolysis was detected in animals, but it has not been reported in living related donor renal transplant recipients. In this case report, a living related donor renal transplant recipient who suffered from hypomagnesemia and mild rhabdomyolysis due to CsA therapy will be described and discussed.

Testing a model of the relationship between childhood sexual abuse and psychosis in a first-episode psychosis group: the role of hallucinations and delusions, posttraumatic intrusions, and selective attention.

PubMed

Bendall, Sarah; Hulbert, Carol Anne; Alvarez-Jimenez, Mario; Allott, Kelly; McGorry, Patrick D; Jackson, Henry James

2013-11-01

Several theories suggest that posttraumatic intrusive symptoms are central to the relationship between childhood trauma (CT) and hallucinations and delusions in psychosis. Biased selective attention has been implicated as a cognitive process underlying posttraumatic intrusions. The current study sought to test theories of the relationship between childhood sexual abuse (CSA), hallucinations and delusions, posttraumatic intrusions, and selective attention in first-episode psychosis (FEP). Twenty-eight people with FEP and 21 nonclinical controls were assessed for CT and psychotic and posttraumatic stress symptoms and completed an emotional Stroop test using CSA-related and other words. Those with FEP and CSA had more severe hallucinations and delusions than those with FEP and without CSA. They also reported posttraumatic intrusions at clinical levels and showed selective attention to CSA-related words. The results are consistent with the posttraumatic intrusions account of hallucinations and delusions in those with CSA and psychosis.

Debating the Controlled Substances Act.

PubMed

Spillane, Joseph F

2004-10-05

In the United States, the basis of modern drug regulation is the Controlled Substances Act (CSA) of 1970. The CSA laid out the authority of the federal government and provided a framework within which all existing and new substances could be regulated on their abuse potential, safety, and medical utility. The debates over the CSA centered on several critical issues: where to place the authority to make scheduling designations, the impact of scheduling on drug research, and defining what constituted drug "abuse" for purposes of scheduling. Passage of the CSA was aided by broad language that provided a kind of "big tent" which could accommodate diverse points of view. A retrospective assessment of the CSA shows it to have greatly expanded federal administrative authority over the nation's drug supply, much as its authors intended. Other impacts of the CSA, however, are much less certain. This article concludes by highlighting the issues and questions that should guide future retrospective research on the efficacy of drug control regimes.

The childhood sexual abuse among youth in three Asian cities: Taipei, Shanghai, and Hanoi.

PubMed

Li, Nan; Zabin, Laurie S; Ahmed, Saifuddin

2015-03-01

The article describes the prevalence and risk factors of childhood sexual abuse (CSA) among youth in Hanoi, Shanghai, and Taipei. Data used in this study are from the Three-City Asian Study of Adolescents and Youth, 2006-2007. Descriptive analysis and logistic regression models were used. The self-reported lifetime prevalence of CSA was 5.2% in Taipei, 1.3% in Shanghai, and 0.5% in Hanoi. The overall prevalence was 2.2% for females and 1.7% for males. The average age of first CSA was 10.5 years. Household instability, migration before age 14, and low maternal warmth were found to be positively associated with CSA, whereas discussing problems with father and being close to mother were negatively associated with CSA, after adjusting for sociodemographic characteristics. Our findings suggested the importance of prevention programs for preteen aged children, public education to raise awareness, and further prospective studies to identify various risk markers for CSA in Asia. © 2013 APJPH.

HIV-infected men who have sex with men and histories of childhood sexual abuse: implications for health and prevention.

PubMed

Schafer, Katherine R; Gupta, Shruti; Dillingham, Rebecca

2013-01-01

A personal history of childhood sexual abuse (CSA) is prevalent and deleterious to health for people living with HIV (PLWH), and current statistics likely underrepresent the frequency of these experiences. In the general population, the prevalence of CSA appears to be higher in men who have sex with men (MSM) than heterosexual men, but there are limited data available for HIV-infected MSM. CSA is associated with poor mental and physical health and may contribute to high rates of HIV risk behaviors, including unprotected sex and substance abuse. CSA exposure is also associated with low engagement in care for PLWH. More information is needed regarding CSA experiences of HIV-infected MSM to optimize health and wellbeing for this population and to prevent HIV transmission. This article reviews the epidemiology, implications, and interventions for MSM who have a history of CSA. Copyright © 2013 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Preparation and characterization of chondroitin-sulfate-A-coated magnetite nanoparticles for biomedical applications

NASA Astrophysics Data System (ADS)

Tóth, Ildikó Y.; Illés, Erzsébet; Szekeres, Márta; Tombácz, Etelka

2015-04-01

Polysaccharides are promising candidates for manufacturing biocompatible core-shell nanoparticles with potential in vivo use. Superparamagnetic magnetite nanoparticles (MNPs) have prospective application in both diagnosis and therapy, and so developing a novel polysaccharide shell on MNP core is of great challenge. MNPs were prepared by co-precipitation, then the surface of purified MNPs was coated with chondroitin-sulfate-A (CSA) to obtain core-shell structured magnetite nanoparticles (CSA@MNP). The effect of the added amount of CSA on the surface charging and the aggregation state of MNPs at various pHs and 10 mM NaCl was measured by electrophoresis and dynamic light scattering. The amphoteric behavior of MNPs was fundamentally modified by adsorption of CSA polyanions. A very low CSA-loading induces the aggregation of MNPs, while four times more stabilizes the dispersions over the whole pH-range studied. The coagulation kinetics experiments measured at pH=6.3±0.3 showed that salt tolerance of CSA@MNPs rises up to ~150 mM NaCl.

In vitro antioxidant properties, DNA damage protective activity, and xanthine oxidase inhibitory effect of cajaninstilbene acid, a stilbene compound derived from pigeon pea [Cajanus cajan (L.) Millsp.] leaves.

PubMed

Wu, Nan; Kong, Yu; Fu, Yujie; Zu, Yuangang; Yang, Zhiwei; Yang, Mei; Peng, Xiao; Efferth, Thomas

2011-01-12

The antioxidant properties, DNA damage protective activities, and xanthine oxidase (XOD) inhibitory effect of cajaninstilbene acid (CSA) derived from pigeon pea leaves were studied in the present work. Compared with resveratrol, CSA showed stronger antioxidant properties, DNA damage protective activity, and XOD inhibition activity. The IC(50) values of CSA for superoxide radical scavenging, hydroxyl radical scavenging, nitric oxide scavenging, reducing power, lipid peroxidation, and XOD inhibition were 19.03, 6.36, 39.65, 20.41, 20.58, and 3.62 μM, respectively. CSA possessed good protective activity from oxidative DNA damage. Furthermore, molecular docking indicated that CSA was more potent than resveratrol or allopurinol to interact with the active site of XOD (calculated free binding energy: -229.71 kcal mol(-1)). On the basis of the results, we conclude that CSA represents a valuable natural antioxidant source and may potentially be applicable in health food industry.

Identification of a Major Dimorphic Region in the Functionally Critical N-Terminal ID1 Domain of VAR2CSA

PubMed Central

Doritchamou, Justin; Sabbagh, Audrey; Jespersen, Jakob S.; Renard, Emmanuelle; Salanti, Ali; Nielsen, Morten A.; Deloron, Philippe; Tuikue Ndam, Nicaise

2015-01-01

The VAR2CSA protein of Plasmodium falciparum is transported to and expressed on the infected erythrocyte surface where it plays a key role in placental malaria (PM). It is the current leading candidate for a vaccine to prevent PM. However, the antigenic polymorphism integral to VAR2CSA poses a challenge for vaccine development. Based on detailed analysis of polymorphisms in the sequence of its ligand-binding N-terminal region, currently the main focus for vaccine development, we assessed var2csa from parasite isolates infecting pregnant women. The results reveal for the first time the presence of a major dimorphic region in the functionally critical N-terminal ID1 domain. Parasite isolates expressing VAR2CSA with particular motifs present within this domain are associated with gravidity- and parasite density-related effects. These observations are of particular interest in guiding efforts with respect to optimization of the VAR2CSA-based vaccines currently under development. PMID:26393516

Targeted cutaneous delivery of ciclosporin A using micellar nanocarriers and the possible role of inter-cluster regions as molecular transport pathways.

PubMed

Lapteva, Maria; Santer, Verena; Mondon, Karine; Patmanidis, Ilias; Chiriano, Gianpaolo; Scapozza, Leonardo; Gurny, Robert; Möller, Michael; Kalia, Yogeshvar N

2014-12-28

Oral administration of ciclosporin A (CsA) is indicated in the treatment of severe recalcitrant plaque psoriasis. However, CsA is both nephro- and hepatotoxic and its systemic administration also exposes the patient to other severe side effects. Although topical delivery of CsA, targeted directly to psoriatic skin, would offer significant advantages, there are no topical formulations approved for dermatological use. The aim of this work was to formulate CsA loaded polymeric micelles using the biodegradable and biocompatible MPEG-dihexPLA diblock copolymer and to evaluate their potential for delivering the drug selectively into the skin without concomitant transdermal permeation. Micelle formulations were characterised with respect to drug content, size and morphology. Micelle and drug penetration pathways were subsequently visualised with confocal laser scanning microscopy (CLSM) using fluorescein labelled CsA (Fluo-CsA) and Nile-Red (NR) labelled copolymer. Visualisation studies typically use fluorescent dyes as "model drugs"; however, these may have different physicochemical properties to the drug molecule under investigation. Therefore, in this study it was decided to chemically modify CsA and to use this structurally similar fluorescent analogue to visualise molecular distribution and transport pathways. Molecular modelling techniques and experimental determination of log D served as molecular scale and macroscopic methods to compare the lipophilicity of CsA and Fluo-CsA. The spherical, homogeneous and nanometre-scale micelles (with Zav from 25 to 52 nm) increased the aqueous solubility of CsA by 518-fold. Supra-therapeutic amounts of CsA were delivered to human skin (1.4±0.6 μg/cm2, cf. a statistically equivalent 1.1±0.5 μg/cm2 for porcine skin) after application of the formulation with the lowest CsA and copolymer content (1.67±0.03 mg/ml of CsA and 5mg/ml of copolymer) for only 1h without concomitant transdermal permeation. Fluo-CsA was successfully synthesised, characterised and incorporated into fluorescent NR-MPEG-dihexPLA micelles; its conformation was not modified by the addition of fluorescein and its log D, measured from pH4 to 8, was equivalent to that of CsA. Fluo-CsA and NR-MPEG-dihexPLA copolymer were subsequently visualised in skin by CLSM. The images indicated that micelles were preferentially deposited between corneocytes and in the inter-cluster regions (i.e. between the clusters of corneocytes). Fluo-CsA skin penetration was deeper in these structures, suggesting that inter-cluster penetration is probably the preferred transport pathway responsible for the increased cutaneous delivery of CsA. Copyright © 2014 Elsevier B.V. All rights reserved.

The relationship between childhood sexual abuse and alcohol abuse in women--a case-control study.

PubMed

Fleming, J; Mullen, P E; Sibthorpe, B; Attewell, R; Bammer, G

1998-12-01

The aim of this paper was to examine the association between reporting childhood sexual abuse (CSA) and alcohol abuse in a community sample of women using multivariate analysis which took into account a range of potential confounding variables (such as a family history of alcoholism) and effect modifiers (such as having an alcoholic partner). A two-stage retrospective case-control study was used to investigate the relationship between reporting CSA and alcohol abuse in women. Seven hundred and ten women randomly selected from the Australian federal electoral rolls. The Alcohol Use Disorders Identification Test (AUDIT) was used to measure alcohol abuse. A series of questions based on those developed by Wyatt (1985) were used to ascertain the prevalence of CSA. The final model showed that the relationship between a history of CSA and alcohol abuse reflected a complex interaction between CSA and a range of other factors in a woman's background. CSA was not by itself a significant predictor of alcohol abuse (OR = 0.61; 95% CI = 0.31-1.20). However, a history of CSA became significant in combination with co-factors which included: having a mother who was perceived as cold and uncaring; having an alcoholic partner; and believing that alcohol is a sexual disinhibitor. This study indicates that CSA alone is not a causative factor in the development of alcohol abuse among women and highlights the importance of examining the family background of women with alcohol problems.

Utilizing nanobody technology to target non-immunodominant domains of VAR2CSA.

PubMed

Ditlev, Sisse B; Florea, Raluca; Nielsen, Morten A; Theander, Thor G; Magez, Stefan; Boeuf, Philippe; Salanti, Ali

2014-01-01

Placental malaria is a major health problem for both pregnant women and their fetuses in malaria endemic regions. It is triggered by the accumulation of Plasmodium falciparum-infected erythrocytes (IE) in the intervillous spaces of the placenta and is associated with foetal growth restriction and maternal anemia. IE accumulation is supported by the binding of the parasite-expressed protein VAR2CSA to placental chondroitin sulfate A (CSA). Defining specific CSA-binding epitopes of VAR2CSA, against which to target the immune response, is essential for the development of a vaccine aimed at blocking IE adhesion. However, the development of a VAR2CSA adhesion-blocking vaccine remains challenging due to (i) the large size of VAR2CSA and (ii) the extensive immune selection for polymorphisms and thereby non-neutralizing B-cell epitopes. Camelid heavy-chain-only antibodies (HcAbs) are known to target epitopes that are less immunogenic to classical IgG and, due to their small size and protruding antigen-binding loop, able to reach and recognize cryptic, conformational epitopes which are inaccessible to conventional antibodies. The variable heavy chain (VHH) domain is the antigen-binding site of camelid HcAbs, the so called Nanobody, which represents the smallest known (15 kDa) intact, native antigen-binding fragment. In this study, we have used the Nanobody technology, an approach new to malaria research, to generate small and functional antibody fragments recognizing unique epitopes broadly distributed on VAR2CSA.

Incremental change in cross sectional area in small endotracheal tubes: A call for more size options.

PubMed

Mortelliti, Caroline L; Mortelliti, Anthony J

2016-08-01

To elucidate the relatively large incremental percent change (IPC) in cross sectional area (CSA) in currently available small endotracheal tubes (ETTs), and to make recommendation for lesser incremental change in CSA in these smaller ETTs, in order to minimize iatrogenic airway injury. The CSAs of a commercially available line of ETTs were calculated, and the IPC of the CSA between consecutive size ETTs was calculated and graphed. The average IPC in CSA with large ETTs was applied to calculate identical IPC in the CSA for a theoretical, smaller ETT series, and the dimensions of a new theoretical series of proposed small ETTs were defined. The IPC of CSA in the larger (5.0-8.0 mm inner diameter (ID)) ETTs was 17.07%, and the IPC of CSA in the smaller ETTs (2.0-4.0 mm ID) is remarkably larger (38.08%). Applying the relatively smaller IPC of CSA from larger ETTs to a theoretical sequence of small ETTs, starting with the 2.5 mm ID ETT, suggests that intermediate sizes of small ETTs (ID 2.745 mm, 3.254 mm, and 3.859 mm) should exist. We recommend manufacturers produce additional small ETT size options at the intuitive intermediate sizes of 2.75 mm, 3.25 mm, and 3.75 mm ID in order to improve airway management for infants and small children. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Conformational Space Annealing explained: A general optimization algorithm, with diverse applications

NASA Astrophysics Data System (ADS)

Joung, InSuk; Kim, Jong Yun; Gross, Steven P.; Joo, Keehyoung; Lee, Jooyoung

2018-02-01

Many problems in science and engineering can be formulated as optimization problems. One way to solve these problems is to develop tailored problem-specific approaches. As such development is challenging, an alternative is to develop good generally-applicable algorithms. Such algorithms are easy to apply, typically function robustly, and reduce development time. Here we provide a description for one such algorithm called Conformational Space Annealing (CSA) along with its python version, PyCSA. We previously applied it to many optimization problems including protein structure prediction and graph community detection. To demonstrate its utility, we have applied PyCSA to two continuous test functions, namely Ackley and Eggholder functions. In addition, in order to provide complete generality of PyCSA to any types of an objective function, we demonstrate the way PyCSA can be applied to a discrete objective function, namely a parameter optimization problem. Based on the benchmarking results of the three problems, the performance of CSA is shown to be better than or similar to the most popular optimization method, simulated annealing. For continuous objective functions, we found that, L-BFGS-B was the best performing local optimization method, while for a discrete objective function Nelder-Mead was the best. The current version of PyCSA can be run in parallel at the coarse grained level by calculating multiple independent local optimizations separately. The source code of PyCSA is available from http://lee.kias.re.kr.

Cyclosporin A Associated Helicase-Like Protein Facilitates the Association of Hepatitis C Virus RNA Polymerase with Its Cellular Cyclophilin B

PubMed Central

Sahara, Hiroeki; Iwabata, Kazuki; Sunoki, Takashi; Kuramochi, Kouji; Takakusagi, Kaori; Miyashita, Hiroki; Sato, Noriyuki; Tanabe, Atsushi; Shimotohno, Kunitada; Kobayashi, Susumu; Sakaguchi, Kengo; Sugawara, Fumio

2011-01-01

Background Cyclosporin A (CsA) is well known as an immunosuppressive drug useful for allogeneic transplantation. It has been reported that CsA inhibits hepatitis C virus (HCV) genome replication, which indicates that cellular targets of CsA regulate the viral replication. However, the regulation mechanisms of HCV replication governed by CsA target proteins have not been fully understood. Principal Findings Here we show a chemical biology approach that elucidates a novel mechanism of HCV replication. We developed a phage display screening to investigate compound-peptide interaction and identified a novel cellular target molecule of CsA. This protein, named CsA associated helicase-like protein (CAHL), possessed RNA-dependent ATPase activity that was negated by treatment with CsA. The downregulation of CAHL in the cells resulted in a decrease of HCV genome replication. CAHL formed a complex with HCV-derived RNA polymerase NS5B and host-derived cyclophilin B (CyPB), known as a cellular cofactor for HCV replication, to regulate NS5B-CyPB interaction. Conclusions We found a cellular factor, CAHL, as CsA associated helicase-like protein, which would form trimer complex with CyPB and NS5B of HCV. The strategy using a chemical compound and identifying its target molecule by our phage display analysis is useful to reveal a novel mechanism underlying cellular and viral physiology. PMID:21559518

The role of substance use coping in the relation between childhood sexual abuse and depression among methamphetamine users in South Africa.

PubMed

Berg, Martha K; Hobkirk, Andréa L; Joska, John A; Meade, Christina S

2017-07-01

Childhood sexual abuse (CSA) is a critical global health issue associated with poor psychosocial outcomes. Individuals with CSA histories are at risk for drug use, which is a growing problem in the Western Cape of South Africa. The present study of methamphetamine users in this region examined whether substance use coping, a contextually relevant type of avoidance-based coping, mediates the relation between CSA and depressive symptoms. Participants included 161 men and 108 women seeking treatment for methamphetamine use. Participants completed a computer-assisted survey and a face-to-face interview with clinic staff to evaluate history of CSA, current substance use severity and coping, and current depressive symptoms. Nearly a third of participants reported a history of CSA, and the average methamphetamine use severity score exceeded the threshold of high risk. A history of CSA was significantly associated with higher substance use coping and more depression symptoms. Substance use coping was a significant mediator of the association between CSA and depression symptoms. In this study of high-risk methamphetamine users, substance use coping emerged as a common means of managing stress, especially for those with a history of CSA, which was further linked to depressive symptoms. These findings underscore the potential benefit of integrating coping interventions and mental health treatment into substance abuse treatment programs, particularly for those with a history of childhood abuse and violence. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Adverse childhood experiences and sexual victimization in adulthood.

PubMed

Ports, Katie A; Ford, Derek C; Merrick, Melissa T

2016-01-01

Understanding the link between adverse childhood experiences (ACEs) and sexual victimization (SV) in adulthood may provide important information about the level of risk for adult SV and sexual re-victimization among childhood sexual abuse (CSA) survivors. In the present paper, we explore the relationship between ACEs, including CSA, and SV in adulthood. Data from the CDC-Kaiser ACE Study were used to examine the effect of experiences of early adversity on adult SV. Adult HMO members (n=7,272) undergoing a routine health exam provided detailed information about ACEs that occurred at age 18 or younger and their experiences of SV in adulthood. Analyses revealed that as ACE score increased, so did risk of experiencing SV in adulthood. Each of the ACE variables was significantly associated with adult SV, with CSA being the strongest predictor of adult SV. In addition, for those who reported CSA, there was a cumulative increase in adult SV risk with each additional ACE experienced. As such, early adversity is a risk factor for adult SV. In particular, CSA is a significant risk factor for sexual re-victimization in adulthood, and additional early adversities experienced by CSA survivors may heighten adult SV risk above and beyond the risk associated with CSA alone. Given the interconnectedness among various experiences of early adversity, adult SV prevention actions must consider how other violence-related and non-violence-related traumatic experiences may exacerbate the risk conferred by CSA on subsequent victimization. Published by Elsevier Ltd.

Victimization and Violence: An Exploration of the Relationship Between Child Sexual Abuse, Violence, and Delinquency.

PubMed

Kozak, Rebecca Shoaf; Gushwa, Melinda; Cadet, Tamara J

2018-05-24

Child sexual abuse (CSA) continues to be a major public health issue with significant short- and long-term consequences. However, little contemporary research has examined the relationship between CSA and delinquent and violent behavior in adolescence. Children who have been sexually abused experience a unique form of victimization compared to children who have endured other forms of maltreatment, as CSA can result in feelings of shame, powerlessness and boundary violations. The purpose of this study was to examine the effect of CSA on delinquent and violent behavior in adolescence. We examined self-report data at the age 18 interview from the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN) on measures of sexual abuse experience, and engagement in delinquent and violent behavior in the past year. All participants reported either a history of maltreatment or were identified at-risk based on demographic risk factors. Participants included 368 males and 445 females who self-reported experiences of CSA and delinquent and violent behavior (N = 813). Findings indicated that, when controlling for gender and race, the odds of engagement in delinquent and violent behavior for those who have experienced CSA are 1.7 times higher than for those who have not. Additionally, female victims of CSA were .52 times less likely to engage in violent and delinquent behavior compared to their male counterparts. Further efforts are needed to examine the effects of CSA on violent and delinquent behavior to better guide treatment efforts that prevent juvenile justice involvement.

A novel regio‑specific cyclosporin hydroxylase gene revealed through the genome mining of Pseudonocardia autotrophica.

PubMed

Ban, Jun-Gyu; Woo, Min-Woo; Lee, Bo-Ram; Lee, Mi-Jin; Choi, Si-Sun; Kim, Eung-Soo

2014-05-01

The regio-specific hydroxylation at the 4th N-methyl leucine of the immunosuppressive agent cyclosporin A (CsA) was previously proposed to be mediated by a unique cytochrome P450 hydroxylase (CYP), CYP-sb21 from the rare actinomycetes Sebekia benihana. Interestingly, a different rare actinomycetes species, Pseudonocardia autotrophica, was found to possess a different regio-selectivity, the preferential hydroxylation at the 9th N-methyl leucine of CsA. Through an in silico analysis of the whole genome of P. autotrophica, we describe here the classification of 31 total CYPs in P. autotrophica. Three putative CsA CYP genes, showing the highest sequence homologies with CYPsb21, were successfully inactivated using PCR-targeted gene disruption. Only one knock-out mutant, ΔCYP-pa1, failed to convert CsA to its hydroxylated forms. The hydroxylation activity of CsA by CYP-pa1 was confirmed by CYP-pa1 gene complementation as well as heterologous expression in the CsA non-hydroxylating Streptomyces coelicolor. Moreover, the cyclosporine regio-selectivity of CYP-pa1 expressed in the ΔCYP-sb21 S. benihana mutant strain was also confirmed unchanged through cross complementation. These results show that preferential regio-specific hydroxylation at the 9th N-methyl leucine of CsA is carried out by a specific P450 hydroxylase gene in P. autotrophica, CYP-pa1, setting the stage for the biotechnological application of CsA regioselective hydroxylation.

First demonstration of high-order QAM signal amplification in PPLN-based phase sensitive amplifier.

PubMed

Umeki, T; Tadanaga, O; Asobe, M; Miyamoto, Y; Takenouchi, H

2014-02-10

We demonstrate the phase sensitive amplification of a high-order quadrature amplitude modulation (QAM) signal using non-degenerate parametric amplification in a periodically poled lithium niobate (PPLN) waveguide. The interaction between the pump, signal, and phase-conjugated idler enables us to amplify arbitrary phase components of the signal. The 16QAM signals are amplified without distortion because of the high gain linearity of the PPLN-based phase sensitive amplifier (PSA). Both the phase and amplitude noise reduction capabilities of the PSA are ensured. Phase noise cancellation is achieved by using the interaction with the phase-conjugated idler. A degraded signal-to-noise ratio (SNR) is restored by using the gain difference between a phase-correlated signal-idler pair and uncorrelated excess noise. The applicability of the simultaneous amplification of multi-carrier signals and the amplification of two independent polarization signals are also confirmed with a view to realizing ultra-high spectrally efficient signal amplification.

A low-noise current-sensitive amplifier-discriminator system for beta particle counting.

PubMed

Sephton, J P; Johansson, L C; Williams, J M

2008-01-01

NPL has developed a low-noise current amplifier/discriminator system for radionuclides that emit low-energy electrons and X-rays. The new beta amplifier is based on the low-noise Amptek A-250 operational amplifier. The design has been configured for optimum signal to noise ratio. The new amplifier is described and results obtained using primarily electron-capture decaying radionuclides are presented. The new amplifier gives rise to higher particle detection efficiency than the previously used Atomic Energy of Canada Limited-designed amplifier. This is shown by measurements of (54)Mn and (65)Zn. The counting plateaux are significantly longer and have reduced gradients.

Contempt and defensiveness in couple relationships related to childhood sexual abuse histories for self and partner.

PubMed

Walker, Eric C; Sheffield, Rachel; Larson, Jeffry H; Holman, Thomas B

2011-01-01

This study examined the relationship between a history of childhood sexual abuse (CSA) for one or both members of a romantic couple and perceptions of contempt and defensiveness for self and partner. Data from the Relationship Evaluation (RELATE) were analyzed for 10,061 couples. The findings suggest that when either or both partner(s) has a history of CSA, contempt and defensiveness in the couple relationship are greater than when neither reports a history of CSA. Furthermore, the males' experience of CSA had a greater impact on their perceptions of self and partner's contempt and defensiveness than females' experience of CSA. Explanations of gender differences are offered and implications for future research and practice are suggested. © 2011 American Association for Marriage and Family Therapy.

Dissociative experiences during sexual behavior among a sample of adults living with HIV infection and a history of childhood sexual abuse.

PubMed

Hansen, Nathan B; Brown, Lauren J; Tsatkin, Elizabeth; Zelgowski, Brittany; Nightingale, Vienna

2012-01-01

Little attention has been given to the occurrence of dissociative symptoms during sexual behavior in adults who have experienced childhood sexual abuse (CSA). For this study, 57 adults living with HIV infection who had experienced CSA and were entering a treatment study for traumatic stress completed study assessments and clinical interviews, including a 15-item scale of dissociative experiences during sexual behavior. Predictor variables included Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnoses of posttraumatic stress disorder (PTSD) and dissociative disorders, rape by an intimate partner, duration of CSA, number of perpetrators of CSA, and current sexual satisfaction. A multiple regression analysis was conducted to identify significant associations between predictors and dissociation during sex. Mean differences by clinical diagnosis were also examined. Results indicated that PTSD, dissociative disorders, rape by an intimate partner, duration of CSA, and number of perpetrators of CSA were associated with increased dissociation during sexual behavior. Dissociation during sex likely increases vulnerability to sexual revictimization and risky sexual behavior. Standard behavioral prevention interventions may be ineffective for sexual situations when dissociation occurs, and prevention efforts should be integrated with mental health care for those who have experienced CSA.

Bilateral pharmacokinetic interaction between cyclosporine A and atorvastatin in renal transplant recipients.

PubMed

Asberg, A; Hartmann, A; Fjeldså, E; Bergan, S; Holdaas, H

2001-11-01

Atorvastatin is increasingly used as a cholesterol-lowering agent in solid organ transplant recipients receiving cyclosporine A (CsA). However, the potential bilateral pharmacokinetic interaction between atorvastatin and CsA in renal transplant recipients has not previously been examined. Baseline 12-h CsA pharmacokinetic investigation was performed in 21 renal transplant recipients and repeated after 4 weeks of atorvastatin treatment (10 mg/ d). At week 4, 24-h pharmacokinetics of atorvastatin was also performed. All patients received basiliximab induction followed by CsA and prednisolone immunosuppression. Compared with historic controls, CsA-treated patients showed, on average, sixfold higher plasma HMG-CoA reductase inhibitory activity after 4 weeks of atorvastatin treatment (p < 0.05). Atorvastatin had a moderate effect on the pharmacokinetics of CsA and reduced the AUC0-12 (area under curve, 0-12h) by 9.5 +/- 18% (p = 0.013) and Cmax (maximal concentration) by 13.5 +/- 24% (p =0.009), while C12 (trough level) was unchanged (p =0.42). Total and LDL cholesterol decreased by 26.8 +/- 8.4% (p < 0.0001) and 41.5 +/- 11.0% (p < 0.0001), respectively. Bilateral pharmacokinetic interaction between atorvastatin and CsA resulted in sixfold higher plasma HMG-CoA reductase inhibitory activity, but only a moderate decrease in systemic exposure of CsA.

Screaming Body and Silent Healthcare Providers: A Case Study with a Childhood Sexual Abuse (CSA) Survivor

PubMed Central

Sigurdardottir, Sigrun; Halldorsdottir, Sigridur

2018-01-01

Stressful early life experiences cause immune dysregulation across the lifespan. Despite the fact that studies have identified childhood sexual abuse (CSA) survivors as a particularly vulnerable group, only a few attempts have been made to study their lived-experience of the physical health consequences of CSA. The aim of this study was to explore a female CSA survivor’s lived-experience of the physical health consequences of CSA and how she experienced the reactions of healthcare providers. Seven interviews were conducted with this 40-year-old woman, Anne, using a phenomenological research approach. Anne was still a young child (two to three years old) when her father started to rape her. Since her childhood, she has experienced complex and widespread physical health consequences such as repeated vaginal and abdominal infections, widespread and chronic pain, sleeping problems, digestive problems, chronic back problems, fibromyalgia, musculoskeletal problems, repeated urinary tract infections, cervical dysplasia, inflammation of the Fallopian tubes, menorrhagia, endometrial hyperplasia, chlamydia, ovarian cysts, ectopic pregnancies, uterus problems, severe adhesions, and ovarian cancer. Anne disclosed her CSA experience to several healthcare providers but they were silent and failed to provide trauma-informed care. Anne’s situation, albeit unique, might reflect similar problems in other female CSA survivors. PMID:29316709

Differential recognition of terminal extracellular Plasmodium falciparum VAR2CSA domains by sera from multigravid, malaria-exposed Malian women.

PubMed

Travassos, Mark A; Coulibaly, Drissa; Bailey, Jason A; Niangaly, Amadou; Adams, Matthew; Nyunt, Myaing M; Ouattara, Amed; Lyke, Kirsten E; Laurens, Matthew B; Pablo, Jozelyn; Jasinskas, Algis; Nakajima, Rie; Berry, Andrea A; Takala-Harrison, Shannon; Kone, Abdoulaye K; Kouriba, Bourema; Rowe, J Alexandra; Doumbo, Ogobara K; Thera, Mahamadou A; Laufer, Miriam K; Felgner, Philip L; Plowe, Christopher V

2015-06-01

The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family mediates parasite sequestration in small capillaries through tissue-specific cytoadherence. The best characterized of these proteins is VAR2CSA, which is expressed on the surface of infected erythrocytes that bind to chondroitin sulfate in the placental matrix. Antibodies to VAR2CSA prevent placental cytoadherence and protect against placental malaria. The size and complexity of the VAR2CSA protein pose challenges for vaccine development, but smaller constitutive domains may be suitable for subunit vaccine development. A protein microarray was printed to include five overlapping fragments of the 3D7 VAR2CSA extracellular region. Malian women with a history of at least one pregnancy had antibody recognition of four of these fragments and had stronger reactivity against the two distal fragments than did nulliparous women, children, and men from Mali, suggesting that the C-terminal extracellular VAR2CSA domains are a potential focus of protective immunity. With carefully chosen sera from longitudinal studies of pregnant women, this approach has the potential to identify seroreactive VAR2CSA domains associated with protective immunity against pregnancy-associated malaria. © The American Society of Tropical Medicine and Hygiene.

Identification and characterization of B-cell epitopes in the DBL4ε domain of VAR2CSA.

PubMed

Ditlev, Sisse B; Nielsen, Morten A; Resende, Mafalda; Agerbæk, Mette Ø; Pinto, Vera V; Andersen, Pernille H; Magistrado, Pamela; Lusingu, John; Dahlbäck, Madeleine; Theander, Thor G; Salanti, Ali

2012-01-01

Malaria during pregnancy in Plasmodium falciparum endemic regions is a major cause of mortality and severe morbidity. VAR2CSA is the parasite ligand responsible for sequestration of Plasmodium falciparum infected erythrocytes to the receptor chondroitin sulfate A (CSA) in the placenta and is the leading candidate for a placental malaria vaccine. Antibodies induced in rats against the recombinant DBL4ε domain of VAR2CSA inhibit the binding of a number of laboratory and field parasite isolates to CSA. In this study, we used a DBL4ε peptide-array to identify epitopes targeted by DBL4ε-specific antibodies that inhibit CSA-binding of infected erythrocytes. We identified three regions of overlapping peptides which were highly antigenic. One peptide region distinguished itself particularly by showing a clear difference in the binding profile of highly parasite blocking IgG compared to the IgG with low capacity to inhibit parasite adhesion to CSA. This region was further characterized and together these results suggest that even though antibodies against the synthetic peptides which cover this region did not recognize native protein, the results using the mutant domain suggest that this linear epitope might be involved in the induction of inhibitory antibodies induced by the recombinant DBL4ε domain.

Cyclosporin A treatment induces overexpression of P-glycoprotein in the kidney and other tissues.

PubMed

Jetté, L; Beaulieu, E; Leclerc, J M; Béliveau, R

1996-05-01

To see whether P-glycoprotein (PGP) expressed in renal brush-border membranes (BBM) could interact with compounds known as modulators of multidrug resistance (MDR), photoaffinity-labeling experiments were performed. A 145k-Da protein was photolabeled with [125I] iodoarylazidoprazosin, and this labeling was reduced in the presence of cyclosporin A (CsA) and PSC-833 (PSC). Interaction of CsA with PGP was further investigated by treating rats with daily subcutaneous injections of CsA (10 mg.kg-1.day-1). After this treatment, PGP expression levels were dramatically increased in renal BBM, intestine, liver, and many other tissues except the brain. This induction was a reversible process, since after cessation of CsA administration PGP levels declined to reach values similar to those of the control groups. The increase in PGP expression in the kidney was also detected in photolabeling experiments, suggesting the induction of a functional PGP. A higher dose of CsA (50 mg/kg) given as a bolus injection did not modify PGP expression] in renal BBM. These results demonstrate that CsA induces reversible overexpression of PGP in the rat. This may present significant relevance in the design of clinical trials using CsA as a chemosensitizing agent.

The prevalence of child sexual abuse in out-of-home care: a comparison between abuse in residential and in foster care.

PubMed

Euser, Saskia; Alink, Lenneke R A; Tharner, Anne; van Ijzendoorn, Marinus H; Bakermans-Kranenburg, Marian J

2013-11-01

We investigated the 2010 year prevalence of child sexual abuse (CSA) in residential and foster care and compared it with prevalence rates in the general population. We used two approaches to estimate the prevalence of CSA. First, 264 professionals working in residential or foster care (sentinels) reported CSA for the children they worked with (N = 6,281). Second, 329 adolescents staying in residential or foster care reported on their own experiences with CSA. Sentinels and adolescents were randomly selected from 82 Dutch out-of-home care facilities. We found that 3.5 per 1,000 children had been victims of CSA based on sentinel reports. In addition, 58 per 1,000 adolescents reported having experienced CSA. Results based on both sentinel report and self-report revealed higher prevalence rates in out-of-home care than in the general population, with the highest prevalence in residential care. Prevalence rates in foster care did not differ from the general population. According to our findings, children and adolescents in residential care are at increased risk of CSA compared to children in foster care. Unfortunately, foster care does not fully protect children against sexual abuse either, and thus its quality needs to be further improved.

Chitosan Ascorbate Nanoparticles for the Vaginal Delivery of Antibiotic Drugs in Atrophic Vaginitis

PubMed Central

Vigani, Barbara; Puccio, Antonella; Ferrari, Franca

2017-01-01

The aim of the present work was the development of chitosan ascorbate nanoparticles (CSA NPs) loaded into a fast-dissolving matrix for the delivery of antibiotic drugs in the treatment of atrophic vaginitis. CSA NPs loaded with amoxicillin trihydrate (AX) were obtained by ionotropic gelation in the presence of pentasodium tripolyphosphate (TPP). Different CSA:TPP and CSA:AX weight ratios were considered and their influence on the particle size, polydispersion index and production yield were investigated. CSA NPs were characterized for mucoadhesive, wound healing and antimicrobial properties. Subsequently, CSA NPs were loaded in polymeric matrices, whose composition was optimized using a DoE (Design of Experiments) approach (simplex centroid design). Matrices were obtained by freeze-drying aqueous solutions of three hydrophilic excipients, polyvinylpirrolidone, mannitol and glycin. They should possess a mechanical resistance suitable for the administration into the vaginal cavity and should readily dissolve in the vaginal fluid. In addition to antioxidant properties, due to the presence of ascorbic acid, CSA NPs showed in vitro mucoadhesive, wound healing and antimicrobial properties. In particular, nanoparticles were characterized by an improved antimicrobial activity with respect to a chitosan solution, prepared at the same concentration. The optimized matrix was characterized by mechanical resistance and by the fast release in simulated vaginal fluid of nanoparticles characterized by unchanged size. PMID:29048359

Self-assembling colloidal system for the ocular administration of cyclosporine A.

PubMed

Luschmann, Christoph; Tessmar, Joerg; Schoeberl, Simon; Strauß, Olaf; Luschmann, Karl; Goepferich, Achim

2014-01-01

In this study, we developed a self-assembling micellar system to deliver cyclosporine A (CsA) in an aqueous solution to the cornea. Two nonionic surfactants of the poly(ethylene glycol)-fatty alcohol ether type (Sympatens AS and Sympatens ACS) were characterized in terms of micelle size, shape, and charge, and their encapsulation efficiency for CsA. In an in situ single dose bioavailability study, the corneal CsA levels were determined in an enucleated porcine eye model. A commercial formulation and a 2% CsA olive oil solution served as references. Both surfactants formed spherical micelles with a size of 9 to 12 nm in water. A concentration as low as 0.3% (wt/vol) Sympatens AS was sufficient to entrap therapeutic levels of at least 0.1% (wt/vol) CsA. In the porcine in situ model, exceptionally high drug levels in the cornea were obtained for the micellar CsA solution (1557 ± 407 ngCsA/gcornea). They were significantly higher than those of Restasis (545 ± 137 ngCsA/gcornea) or the olive oil solution (452 ± 142 ngCsA/gcornea). In conclusion, we have shown a promising simple and efficient approach for the application of CsA in an aqueous solution to the cornea to treat inflammatory corneal diseases.

Cyclosporine: A Historical Perspective on Its Role in the Treatment of Noninfectious Uveitis.

PubMed

Smith, Wendy M

2017-05-01

The history of cyclosporine and uveitis is intertwined with the development of experimental autoimmune uveitis (EAU) animal models and the understanding that T lymphocytes play a major role in the pathogenesis of uveitis. The early studies of CsA in uveitis also demonstrated the power of collaborative efforts in translational research. Dr. Robert Nussenblatt and his colleagues were the first to show that CsA can inhibit EAU. Over many years after the initial CsA experiments, Dr. Nussenblatt's group as well as others continued to study CsA under experimental conditions as well as in clinical trials with human patients. The data and observations from these studies significantly advanced our knowledge of uveitis pathophysiology and demonstrated the value of well-designed masked, controlled treatment trials in uveitis. Dr. Nussenblatt and his collaborators delved into the most significant adverse effect of CsA, renal toxicity, and helped elucidate the pathophysiology of renal injury. They explored adjunctive treatments to improve the efficacy and decrease the toxicity of CsA and also studied other members of the cyclosporine family. Among the immunosuppressives used to treat ocular inflammation, CsA was the first, and remains the only medication comprehensively studied under both experimental and clinical conditions.

Childhood Sexual Abuse and the Development of Recurrent Major Depression in Chinese Women

PubMed Central

Chen, Jing; Cai, Yiyun; Cong, Enzhao; Liu, Ying; Gao, Jingfang; Li, Youhui; Tao, Ming; Zhang, Kerang; Wang, Xumei; Gao, Chengge; Yang, Lijun; Li, Kan; Shi, Jianguo; Wang, Gang; Liu, Lanfen; Zhang, Jinbei; Du, Bo; Jiang, Guoqing; Shen, Jianhua; Zhang, Zhen; Liang, Wei; Sun, Jing; Hu, Jian; Liu, Tiebang; Wang, Xueyi; Miao, Guodong; Meng, Huaqing; Li, Yi; Hu, Chunmei; Li, Yi; Huang, Guoping; Li, Gongying; Ha, Baowei; Deng, Hong; Mei, Qiyi; Zhong, Hui; Gao, Shugui; Sang, Hong; Zhang, Yutang; Fang, Xiang; Yu, Fengyu; Yang, Donglin; Liu, Tieqiao; Chen, Yunchun; Hong, Xiaohong; Wu, Wenyuan; Chen, Guibing; Cai, Min; Song, Yan; Pan, Jiyang; Dong, Jicheng; Pan, Runde; Zhang, Wei; Shen, Zhenming; Liu, Zhengrong; Gu, Danhua; Wang, Xiaoping; Liu, Xiaojuan; Zhang, Qiwen; Li, Yihan; Chen, Yiping; Kendler, Kenneth S.; Shi, Shenxun; Flint, Jonathan

2014-01-01

Background Our prior study in Han Chinese women has shown that women with a history of childhood sexual abuse (CSA) are at increased risk for developing major depression (MD). Would this relationship be found in our whole data set? Method Three levels of CSA (non-genital, genital, and intercourse) were assessed by self-report in two groups of Han Chinese women: 6017 clinically ascertained with recurrent MD and 5983 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression. Results We confirmed earlier results by replicating prior analyses in 3,950 new recurrent MD cases. There were no significant differences between the two data sets. Any form of CSA was significantly associated with recurrent MD (OR 4.06, 95% confidence interval (CI) [3.19–5.24]). This association strengthened with increasing CSA severity: non-genital (OR 2.21, 95% CI 1.58–3.15), genital (OR 5.24, 95% CI 3.52–8.15) and intercourse (OR 10.65, 95% CI 5.56–23.71). Among the depressed women, those with CSA had an earlier age of onset, longer depressive episodes. Recurrent MD patients those with CSA had an increased risk for dysthymia (OR 1.60, 95%CI 1.11–2.27) and phobia (OR 1.41, 95%CI 1.09–1.80). Any form of CSA was significantly associated with suicidal ideation or attempt (OR 1.50, 95% CI 1.20–1.89) and feelings of worthlessness or guilt (OR 1.41, 95% CI 1.02–2.02). Intercourse (OR 3.47, 95%CI 1.66–8.22), use of force and threats (OR 1.95, 95%CI 1.05–3.82) and how strongly the victims were affected at the time (OR 1.39, 95%CI 1.20–1.64) were significantly associated with recurrent MD. Conclusions In Chinese women CSA is strongly associated with recurrent MD and this association increases with greater severity of CSA. Depressed women with CSA have some specific clinical traits. Some features of CSA were associated with greater likelihood of developing recurrent MD. PMID:24489940

Implementation of a Portable Personal EKG Signal Monitoring System

NASA Astrophysics Data System (ADS)

Tan, Tan-Hsu; Chang, Ching-Su; Chen, Yung-Fu; Lee, Cheng

This research develops a portable personal EKG signal monitoring system to help patients monitor their EKG signals instantly to avoid the occurrence of tragedies. This system is built with two main units: signal pro-cessing unit and monitoring and evaluation unit. The first unit consists of EKG signal sensor, signal amplifier, digitalization circuit, and related control circuits. The second unit is a software tool developed on an embedded Linux platform (called CSA). Experimental result indicates that the proposed system has the practical potential for users in health monitoring. It is demonstrated to be more convenient and with greater portability than the conventional PC-based EKG signal monitoring systems. Furthermore, all the application units embedded in the system are built with open source codes, no licensed fee is required for operating systems and authorized applications. Thus, the building cost is much lower than the traditional systems.

Amplifiers of free-space terahertz radiation

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

Kao, Tsung -Yu; Reno, John L.; Hu, Qing

Here, amplifiers of free-space radiation are quite useful, especially in spectral ranges where the radiation is weak and sensitive detectors are hard to come by. A preamplification of the said weak radiation signal will significantly boost the S/N ratio in remote sensing and imaging applications. This is especially true in the terahertz (THz) range where the radiation signal is often weak and sensitive detectors require the cooling of liquid helium. Although quantum cascade structures are promising for providing amplification in the terahertz band from 2 to 5 THz, a THz amplifier has been demonstrated in an integrated form, in whichmore » the source is in close proximity to the amplifier, which will not be suitable for the aforementioned applications. Here we demonstrate what we believe is a novel approach to achieve significant amplification of free-space THz radiation using an array of short-cavity, surface-emitting THz quantum cascade lasers operating marginally below the lasing threshold as a Fabry–Perot amplifier. This free-space “slow light” amplifier provides 7.5 dB(×5.6) overall gain at ~3.1 THz. The proposed devices are suitable for low-noise pre-amplifiers in heterodyne detection systems and for THz imaging systems. With the sub-wavelength pixel size of the array, the reflective amplifier can also be categorized as active metasurface, with the ability to amplify or absorb specific frequency components of the input THz signal.« less

Amplifiers of free-space terahertz radiation

DOE PAGES

Kao, Tsung -Yu; Reno, John L.; Hu, Qing

2017-07-20

Here, amplifiers of free-space radiation are quite useful, especially in spectral ranges where the radiation is weak and sensitive detectors are hard to come by. A preamplification of the said weak radiation signal will significantly boost the S/N ratio in remote sensing and imaging applications. This is especially true in the terahertz (THz) range where the radiation signal is often weak and sensitive detectors require the cooling of liquid helium. Although quantum cascade structures are promising for providing amplification in the terahertz band from 2 to 5 THz, a THz amplifier has been demonstrated in an integrated form, in whichmore » the source is in close proximity to the amplifier, which will not be suitable for the aforementioned applications. Here we demonstrate what we believe is a novel approach to achieve significant amplification of free-space THz radiation using an array of short-cavity, surface-emitting THz quantum cascade lasers operating marginally below the lasing threshold as a Fabry–Perot amplifier. This free-space “slow light” amplifier provides 7.5 dB(×5.6) overall gain at ~3.1 THz. The proposed devices are suitable for low-noise pre-amplifiers in heterodyne detection systems and for THz imaging systems. With the sub-wavelength pixel size of the array, the reflective amplifier can also be categorized as active metasurface, with the ability to amplify or absorb specific frequency components of the input THz signal.« less

Sensitive enhancement of vessel wall imaging with an endoesophageal Wireless Amplified NMR Detector (WAND).

PubMed

Zeng, Xianchun; Barbic, Mladen; Chen, Liangliang; Qian, Chunqi

2017-11-01

To improve the imaging quality of vessel walls with an endoesophageal Wireless Amplified NMR Detector (WAND). A cylindrically shaped double-frequency resonator has been constructed with a single metal wire that is self-connected by a pair of nonlinear capacitors. The double-frequency resonator can convert wirelessly provided pumping power into amplified MR signals. This compact design makes the detector easily insertable into a rodent esophagus. The detector has good longitudinal and axial symmetry. Compared to an external surface coil, the WAND can enhance detection sensitivity by at least 5 times, even when the distance separation between the region of interest and the detector's cylindrical surface is twice the detector's own radius. Such detection capability enables us to observe vessel walls near the aortic arch and carotid bifurcation with elevated sensitivity. A cylindrical MRI detector integrated with a wireless-powered amplifier has been developed as an endoesophageal detector to enhance detection sensitivity of vessel walls. This detector can greatly improve the imaging quality for vessel regions that are susceptible to atherosclerotic lesions. Magn Reson Med 78:2048-2054, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Multi-informant assessment of anxiety regarding ano-genital examinations for suspected child sexual abuse (CSA).

PubMed

Scribano, Philip V; Hornor, Gail; Rhoda, Dale; Curran, Sherry; Stevens, Jack

2010-08-01

Given the commonly held belief that physical examinations for child sexual abuse (CSA) are very distressing, our primary objective was to evaluate anxiety during these assessments using the Multidimensional Anxiety Score for Children (MASC-10). A second objective was to compare self-reported anxiety to parental report using the MASC-10 and to medical provider's rating of emotional distress using the Genital Examination Distress Scale (GEDS). Child/parent dyads completed the MASC-10 prior to the evaluation and were retested at the completion of the medical exam. GEDS assessment occurred during the medical exam. One hundred seventy-five subject dyads were enrolled and were predominantly female (77%), Caucasian (66%), accompanied by mother (90%), and receiving Medicaid (57%). A significant subgroup of children reported clinically significant levels of anxiety at the pre-examination assessment (17.1%) and post-examination assessment (15.4%). However, most subjects reported low anxiety at both pre- and post-examination assessments. Both child and parent report demonstrated less anxiety, on average, post-examination compared to pre-examination scores. Reduced anxiety was measured with a mean pre-T-score=55.8 versus mean post-T-score=53.1 (p<.001). Correlation coefficients for pre-T-scores and post-T-scores of child/parent dyad were 0.3257 (p<.0001) and 0.3403 (p<.0001). A small correlation was noted between child reported anxiety and medical provider observation using the GEDS for pre-exam (0.1904, p=.01), and post-exam (0.2090, p=.02). Our research indicates that the majority of children are not severely anxious during medical evaluations for CSA. In addition, the MASC-10 shows promise as an instrument to assess anxiety from the ano-genital examination in CSA because it could be quickly completed by most patients and their parents, indicated a wide range of anxiety levels, and demonstrated some sensitivity to change. While parent report may identify some child anxiety, parent and provider report should not be substitutes for the self-report of children's anxiety during this medical evaluation. A practical, quick, validated measure of anxiety can be used in the setting of CSA evaluations to identify anxiety in this population. 2010 Elsevier Ltd. All rights reserved.

Integrating multi-omics analyses of Nonomuraea dietziae to reveal the role of soybean oil in [(4'-OH)MeLeu]4-CsA overproduction.

PubMed

Liu, Huanhuan; Huang, Di; Jin, Lina; Wang, Cheng; Liang, Shaoxiong; Wen, Jianping

2017-07-14

Nonomuraea dietziae is a promising microorganism to mediate the region-specific monooxygenation reaction of cyclosporine A (CsA). The main product [(4'-OH)MeLeu] 4 -CsA possesses high anti-HIV/HCV and hair growth-stimulating activities while avoiding the immunosuppressive effect of CsA. However, the low conversion efficiency restricts the clinical application. In this study, the production of [(4'-OH)MeLeu] 4 -CsA was greatly improved by 55.6% from 182.8 to 284.4 mg/L when supplementing soybean oil into the production medium, which represented the highest production of [(4'-OH)MeLeu] 4 -CsA so far. To investigate the effect of soybean oil on CsA conversion, some other plant oils (corn oil and peanut oil) and the major hydrolysates of soybean oil were fed into the production medium, respectively. The results demonstrated that the plant oils, rather than the hydrolysates, could significantly improve the [(4'-OH)MeLeu] 4 -CsA production, suggesting that soybean oil might not play its role in the lipid metabolic pathway. To further unveil the mechanism of [(4'-OH)MeLeu] 4 -CsA overproduction under the soybean oil condition, a proteomic analysis based on the two-dimensional gel electrophoresis coupled with MALDI TOF/TOF mass spectrometry was implemented. The results showed that central carbon metabolism, genetic information processing and energy metabolism were significantly up-regulated under the soybean oil condition. Moreover, the gas chromatography-mass spectrometry-based metabolomic analysis indicated that soybean oil had a great effect on amino acid metabolism and tricarboxylic acid cycle. In addition, the transcription levels of cytochrome P450 hydroxylase (CYP) genes for CsA conversion were determined by RT-qPCR and the results showed that most of the CYP genes were up-regulated under the soybean oil condition. These findings indicate that soybean oil could strengthen the primary metabolism and the CYP system to enhance the mycelium growth and the monooxygenation reaction, respectively, and it will be a guidance for the further metabolic engineering of this strain.

Proton chemical shift tensors determined by 3D ultrafast MAS double-quantum NMR spectroscopy

NASA Astrophysics Data System (ADS)

Zhang, Rongchun; Mroue, Kamal H.; Ramamoorthy, Ayyalusamy

2015-10-01

Proton NMR spectroscopy in the solid state has recently attracted much attention owing to the significant enhancement in spectral resolution afforded by the remarkable advances in ultrafast magic angle spinning (MAS) capabilities. In particular, proton chemical shift anisotropy (CSA) has become an important tool for obtaining specific insights into inter/intra-molecular hydrogen bonding. However, even at the highest currently feasible spinning frequencies (110-120 kHz), 1H MAS NMR spectra of rigid solids still suffer from poor resolution and severe peak overlap caused by the strong 1H-1H homonuclear dipolar couplings and narrow 1H chemical shift (CS) ranges, which render it difficult to determine the CSA of specific proton sites in the standard CSA/single-quantum (SQ) chemical shift correlation experiment. Herein, we propose a three-dimensional (3D) 1H double-quantum (DQ) chemical shift/CSA/SQ chemical shift correlation experiment to extract the CS tensors of proton sites whose signals are not well resolved along the single-quantum chemical shift dimension. As extracted from the 3D spectrum, the F1/F3 (DQ/SQ) projection provides valuable information about 1H-1H proximities, which might also reveal the hydrogen-bonding connectivities. In addition, the F2/F3 (CSA/SQ) correlation spectrum, which is similar to the regular 2D CSA/SQ correlation experiment, yields chemical shift anisotropic line shapes at different isotropic chemical shifts. More importantly, since the F2/F1 (CSA/DQ) spectrum correlates the CSA with the DQ signal induced by two neighboring proton sites, the CSA spectrum sliced at a specific DQ chemical shift position contains the CSA information of two neighboring spins indicated by the DQ chemical shift. If these two spins have different CS tensors, both tensors can be extracted by numerical fitting. We believe that this robust and elegant single-channel proton-based 3D experiment provides useful atomistic-level structural and dynamical information for a variety of solid systems that possess high proton density.

Clinical Utility of Ultrasound Measurements of Plantar Fascia Width and Cross-Sectional AreaA Novel Technique.

PubMed

Bisi-Balogun, Adebisi; Rector, Michael

2017-09-01

We sought to develop a standardized protocol for ultrasound (US) measurements of plantar fascia (PF) width and cross-sectional area (CSA), which may serve as additional outcome variables during US examinations of both healthy asymptomatic PF and in plantar fasciopathy and determine its interrater and intrarater reliability. Ten healthy individuals (20 feet) were enrolled. Participants were assessed twice by two raters each to determine intrarater and interrater reliability. For each foot, three transverse scans of the central bundle of the PF were taken at its insertion at the medial calcaneal tubercle, identified in real time on the plantar surface of the foot, using a fine wire technique. Reliability was determined using intraclass correlation coefficients (ICC), standard errors of measurement (SEM), and limits of agreement (LOA) expressed as percentages of the mean. Reliability of PF width and CSA measurements was determined using PF width and CSA measurements from one sonogram measured once and the mean of three measurements from three sonograms each measured once. Ultrasound measurements of PF width and CSA showed a mean of 18.6 ± 2.0 mm and 69.20 ± 13.6 mm 2 respectively. Intra-reliability within both raters showed an ICC > 0.84 for width and ICC > 0.92 for CSA as well as a SEM% and LOA% < 10% for both width and CSA. Inter-rater reliability showed an ICC of 0.82 for width and 0.87 for CSA as well as a SEM% and LOA% < 10% for width and a SEM% < 10% and LOA% < 20% for CSA. Relative and absolute reliability within and between raters were higher when using the mean of three sonographs compared to one sonograph. Using this novel technique, PF CSA and width may be determined reliably using measurements from one sonogram or the mean of three sonograms. Measurement of PF CSA and width in addition to already established thickness and echogenicity measurements provides additional information on structural properties of the PF for clinicians and researchers in healthy and pathologic PF.

Correlates and Consequences Central Sleep Apnea in a National Sample of U.S. Veterans.

PubMed

Ratz, David; Wiitala, Wyndy; Badr, M S; Burns, Jennifer; Chowdhuri, Susmita

2018-03-28

The prevalence and consequences of central sleep apnea (CSA) in adults are not well- described. By utilizing the large Veterans Health Administration (VHA) national administrative databases, we sought to determine the incidence, clinical correlates and impact of CSA on healthcare utilization in Veterans. Analysis of a retrospective cohort of patients with sleep disorders was performed from outpatient visits and inpatient admissions from fiscal years 2006 through 2012. The CSA group, defined by International Classification of Diseases-9, was compared to a non-CSA group. The number of newly diagnosed CSA cases increased 5-fold during this timeframe; however, the prevalence was highly variable depending on the VHA site. The important predictors of CSA were male gender (Odds Ratio(OR)=2.31, 95% C.I.:1.94-2.76, p<0.0001), heart failure(HF) (OR=1.78, 95% C.I.:1.64-1.92, p<0.0001), atrial fibrillation (OR=1.83, 95% C.I.: 1.69-2.00, p<0.0001), pulmonary hypertension (OR=1.38, 95% C.I.:1.19-1.59, p<0.0001), stroke (OR=1.65, 95% C.I.:1.50-1.82, p<0.0001), and chronic prescription opioid use (OR=1.99, 95% C.I.:1.87-2.13, p<0.0001). Veterans with CSA were at an increased risk for hospital admissions related to cardiovascular disorders compared to the control group (Incidence Rate Ratio(IRR)=1.50, 95% C.I.:1.16-1.95, p=0.002). Additionally, the effect of prior HF on future admissions was greater in the CSA group (IRR: 4.78,95% C.I.: 3.87-5.91, p<0.0001) compared to the comparison group (IRR=3.32, 95% C.I.: 3.18-3.47, P<0.0001). Thus, CSA in Veterans is associated with cardiovascular disorders, chronic prescription opioid use and increased admissions related to the comorbid cardiovascular disorders. Furthermore, there is a need for standardization of diagnostics methods across the VHA to accurately diagnose CSA in high-risk populations.

Association between vertebral cross-sectional area and lumbar lordosis angle in adolescents

PubMed Central

Aggabao, Patricia C.; Poorghasamians, Ervin; Chavez, Thomas A.

2017-01-01

Lumbar lordosis (LL) is more prominent in women than in men, but the mechanisms responsible for this discrepancy are poorly defined. A recent study indicates that newborn girls have smaller vertebral cross-sectional area (CSA) when compared to boys—a difference that persists throughout life and is independent of body size. We determined the relations between vertebral cross-sectional area (CSA) and LL angle and whether sex differences in lumbar lordosis are related to sex differences in vertebral CSA. Using multi-planar magnetic resonance imaging (MRI), we measured vertebral cross-sectional area (CSA) and vertebral height of the spine of 40 healthy boys and 40 girls, ages 9–13 years. Measures of the CSA of the lumbar vertebrae significantly differed between sexes (9.38 ± 1.46 vs. 7.93 ± 0.69 in boys and girls, respectively; P < 0.0001), while the degree of LL was significantly greater in girls than in boys (23.7 ± 6.1 vs. 27.6 ± 8.0 in boys and girls, respectively; P = 0.02). When all subjects were analyzed together, values for LL angle were negatively correlated to vertebral CSA (r = -0.47; P < 0.0001); this was also true when boys and girls were analyzed separately. Multivariate regression analysis indicated that vertebral CSA was independently associated with LL, even after accounting for sex, age, height or vertebral height, and weight. Similar negative relations were present when thoracic vertebrae were analyzed (Model P < 0.0001, R2 = 0.37, thoracic vertebral CSA slope P < 0.0001), suggesting that deficient vertebral cross-sectional dimensions are not merely the consequence of the anterior lumbar curvature. We conclude that vertebral CSA is negatively associated with LL, and that the greater degree of LL in females could, at least in part, be due to smaller vertebral cross-sectional dimensions. Studies are needed to examine the potential relations between vertebral CSA and spinal conditions known to be associated with increased LL, such as spondylolysis and spondylolisthesis. PMID:28245271

Proton chemical shift tensors determined by 3D ultrafast MAS double-quantum NMR spectroscopy

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

Zhang, Rongchun; Mroue, Kamal H.; Ramamoorthy, Ayyalusamy, E-mail: ramamoor@umich.edu

2015-10-14

Proton NMR spectroscopy in the solid state has recently attracted much attention owing to the significant enhancement in spectral resolution afforded by the remarkable advances in ultrafast magic angle spinning (MAS) capabilities. In particular, proton chemical shift anisotropy (CSA) has become an important tool for obtaining specific insights into inter/intra-molecular hydrogen bonding. However, even at the highest currently feasible spinning frequencies (110–120 kHz), {sup 1}H MAS NMR spectra of rigid solids still suffer from poor resolution and severe peak overlap caused by the strong {sup 1}H–{sup 1}H homonuclear dipolar couplings and narrow {sup 1}H chemical shift (CS) ranges, which rendermore » it difficult to determine the CSA of specific proton sites in the standard CSA/single-quantum (SQ) chemical shift correlation experiment. Herein, we propose a three-dimensional (3D) {sup 1}H double-quantum (DQ) chemical shift/CSA/SQ chemical shift correlation experiment to extract the CS tensors of proton sites whose signals are not well resolved along the single-quantum chemical shift dimension. As extracted from the 3D spectrum, the F1/F3 (DQ/SQ) projection provides valuable information about {sup 1}H–{sup 1}H proximities, which might also reveal the hydrogen-bonding connectivities. In addition, the F2/F3 (CSA/SQ) correlation spectrum, which is similar to the regular 2D CSA/SQ correlation experiment, yields chemical shift anisotropic line shapes at different isotropic chemical shifts. More importantly, since the F2/F1 (CSA/DQ) spectrum correlates the CSA with the DQ signal induced by two neighboring proton sites, the CSA spectrum sliced at a specific DQ chemical shift position contains the CSA information of two neighboring spins indicated by the DQ chemical shift. If these two spins have different CS tensors, both tensors can be extracted by numerical fitting. We believe that this robust and elegant single-channel proton-based 3D experiment provides useful atomistic-level structural and dynamical information for a variety of solid systems that possess high proton density.« less

Optically pre-amplified lidar-radar

NASA Astrophysics Data System (ADS)

Morvan, Loic; Dolfi, Daniel; Huignard, Jean-Pierre

2001-09-01

We present the concept of an optically pre-amplified intensity modulated lidar, where the modulation frequency is in the microwave domain (1-10 GHz). Such a system permits to combine directivity of laser beams with mature radar processing. As an intensity modulated or dual-frequency laser beam is directed on a target, the backscattered intensity is collected by an optical system, pass through an optical preamplifier, and is detected on a high speed photodiode in a direct detection scheme. A radar type processing permits then to extract range, speed and identification information. The association of spatially multimode amplifier and direct detection allows low sensitivity to atmospheric turbulence and large field of view. We demonstrated theoretically that optical pre-amplification can greatly enhance sensitivity, even in spatially multimode amplifiers, such as free-space amplifier or multimode doped fiber. Computed range estimates based on this concept are presented. Laboratory demonstrations using 1 to 3 GHz modulated laser sources and >20 dB gain in multimode amplifiers are detailed. Preliminary experimental results on range and speed measurements and possible use for large amplitude vibrometry will be presented.

Resistance exercise-induced fluid shifts: change in active muscle size and plasma volume

NASA Technical Reports Server (NTRS)

Ploutz-Snyder, L. L.; Convertino, V. A.; Dudley, G. A.

1995-01-01

The purpose of this study was to test the hypothesis that the reduction in plasma volume (PV) induced by resistance exercise reflects fluid loss to the extravascular space and subsequently selective increase in cross-sectional area (CSA) of active but not inactive skeletal muscle. We compared changes in active and inactive muscle CSA and PV after barbell squat exercise. Magnetic resonance imaging (MRI) was used to quantify muscle involvement in exercise and to determine CSA of muscle groups or individual muscles [vasti (VS), adductor (Add), hamstring (Ham), and rectus femoris (RF)]. Muscle involvement in exercise was determined using exercise-induced contrast shift in spin-spin relaxation time (T2)-weighted MR images immediately postexercise. Alterations in muscle size were based on the mean CSA of individual slices. Hematocrit, hemoglobin, and Evans blue dye were used to estimate changes in PV. Muscle CSA and PV data were obtained preexercise and immediately postexercise and 15 and 45 min thereafter. A hierarchy of muscle involvement in exercise was found such that VS > Add > Ham > RF, with the Ham and RF showing essentially no involvement. CSA of the VS and Add muscle groups were increased 10 and 5%, respectively, immediately after exercise in each thigh with no changes in Ham and RF CSA. PV was decreased 22% immediately following exercise. The absolute loss of PV was correlated (r2 = 0.75) with absolute increase in muscle CSA immediately postexercise, supporting the notion that increased muscle size after resistance exercise reflects primarily fluid movement from the vascular space into active but not inactive muscle.

Highly sensitive lidar with a thumb-sized sensor-head built using an optical fiber preamplifier

NASA Astrophysics Data System (ADS)

Inoue, Daisuke; Ichikawa, Tadashi; Matsubara, Hiroyuki; Mao, Xueon; Maeda, Mitsutoshi; Nagashima, Chie; Kagami, Manabu

2011-06-01

We developed a LIDAR system with a sensor head as small as 22 cc, in spite of the inclusion of a scanning mechanism. This LIDAR system not only has a small body, but is also highly sensitive. Our LIDAR system is based on time-of-flight measurements, and it incorporates an optical fiber. The main feature of our system is the utilization of optical amplifiers for both the transmitter and the receiver, and the optical amplifiers enabled us to exceed the detection limit of thermal noise. In conventional LIDAR systems the detection limit is determined by thermal noise, because the avalanche photo-diodes (APD) and trans-impedance amplifiers (TIA) that they use detect the received signals directly. In the case of our LIDAR system, received signal is amplified by an optical fiber amplifier in front of the photo diode and the TIA. Therefore, our LIDAR system can boost the signal level before the weak incoming signal is depleted by thermal noise. There are conditions under which the noise figure for the combination of an optical fiber amplifier and a photo diode is superior to the noise figure for an avalanche photo diode. We optimized the gain of the optical fiber amplifier and TIA in our LIDAR system such that it is capable of detecting a single photon. As a result, the detection limit of our LIDAR system is determined by shot noise. This small and highly sensitive measurement technology shows great potential for use in LIDAR with an optical preamplifier.

Growing Opportunities: CSA Members, CSA Farmers, and Informal Learning in the USA

ERIC Educational Resources Information Center

Everson, Connie

2015-01-01

Community-supported agriculture (CSA) began as a loosely formalised, vaguely socialistic agreement between consumers and farmers through which the consumers were provided with fresh produce from the farms. When the institution became more structured, education gained a near-equal footing with the nutritional offerings. My research indicated that…

Associations among childhood sexual abuse, language use and adult sexual functioning and satisfaction

PubMed Central

Lorenz, Tierney Ahrold; Meston, Cindy May

2012-01-01

To better understand the link between childhood sexual abuse (CSA) and adult sexual functioning and satisfaction, we examined cognitive differences between women with (N = 128) and without (NSA, N = 99) CSA histories. We used the Linguistic Inquiry Word Count, a computerized text analysis program, to investigate language differences between women with and without CSA histories when writing about their daily life (neutral essay) and their beliefs about sexuality and their sexual experiences (sexual essay). Compared to NSA women, women with CSA histories used fewer first person pronouns in the neutral essay but more in the sexual essay, suggesting women with CSA histories have greater self-focus when thinking about sexuality. Women who reported CSA used more intimacy words and more language consistent with psychological distancing in the sexual essay than did NSA women. Use of positive emotion words in the sexual essay predicted sexual functioning and satisfaction in both groups. These findings support the view that language use differs in significant ways between women with and without sexual abuse histories, and that these differences relate to sexual functioning and satisfaction. PMID:22387124

Mediators of the relationship between childhood sexual abuse and suicidal behavior in borderline personality disorder.

PubMed

Soloff, Paul H; Feske, Ulrike; Fabio, Anthony

2008-06-01

A history of childhood sexual abuse (CSA) increases the risk of suicidal behavior and the lifetime number of suicide attempts in adults with BPD. Despite a strong association, specific variables mediating the relationship between CSA and adult suicidal behavior in BPD have not been identified. This study examined risk factors for suicidal behavior as potential mediators of the relationship between CSA and suicide attempts in 151 men and women with BPD. Diagnostic, clinical, and psychosocial risk factors, as well as CSA, and suicidal behaviors, were assessed by standardized interviews or self-rated measures. Psychotic and schizotypal symptoms, and poor social adjustment, were associated with both CSA and suicidal behavior, and partially mediated the relationship between CSA and attempter status. Psychotic and schizotypal symptoms in BPD define a vulnerability to cognitive and perceptual distortions under stress. They increase the likelihood of suicidal behavior in BPD, especially in the absence of mitigating social support. A theoretical model for suicidal behavior in BPD is presented which integrates direct, mediated, and moderated pathways between childhood sexual abuse and temperament, adolescent and adult risk factors, and suicidal behavior.

Parental reflective functioning as a moderator of child internalizing difficulties in the context of child sexual abuse.

PubMed

Ensink, Karin; Bégin, Michaël; Normandin, Lina; Fonagy, Peter

2017-11-01

The objective was to examine pathways from child sexual abuse (CSA) and maternal mentalizing to child internalizing and externalizing difficulties and to test a model of MRF as a moderator of the relationships between CSA and child difficulties. The sample was comprised of 154 mothers and children aged 2-12 where 64 children had experienced CSA. To assess parental mentalizing the Parental Development Interview was rated with the Parental Reflective Functioning Scale. Child internalizing and externalizing difficulties were assessed with the Child Behavior Checklist (CBCL). Results indicate that there were significant inverse relationships between maternal mentalizing and child internalizing and externalizing difficulties. When maternal mentalizing was considered together with CSA, only maternal mentalizing was a significant predictor of child difficulties. Furthermore, maternal mentalizing moderated the relationship between CSA and child internalizing difficulties. These findings provide evidence of the importance of the parents' mentalizing stance for psychiatric symptoms of children aged 2-12, as well as children's recovery from CSA. The clinical implications of the findings are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Childhood Sexual Abuse Moderates the Association between Sexual Functioning and Sexual Distress in Women

PubMed Central

Stephenson, Kyle R.; Hughan, Corey P.; Meston, Cindy M.

2012-01-01

Objective To assess the degree to which a history of CSA moderates the association between sexual functioning and sexual distress in women. Method Women with (n = 105, M age = 33.71, 66.1% Caucasian) and without (n = 71, M age = 32.63, 74.7% Caucasian) a history of CSA taking part in a larger clinical trial completed self-report questionnaires at intake including the Sexual Satisfaction Scale for Women (SSS-W), the Female Sexual Function Index (FSFI), and the Trauma History Questionnaire (THQ). Results Desire, arousal, lubrication, and orgasm interacted with sexual abuse status in predicting sexual distress such that sexual functioning was more weakly associated with distress for women with a history of CSA. This disconnect was more pronounced for women who were abused by a family member. Conclusion CSA status serves as an important moderator of the association between sexual functioning and sexual distress in women. Specifically, women with a history of CSA show higher levels of distress in the context of good sexual functioning as compared to women without a history of CSA. Possible explanations and clinical implications are discussed. PMID:22391416

Characterization of five fungal endophytes producing Cajaninstilbene acid isolated from pigeon pea [Cajanus cajan (L.) Millsp].

PubMed

Gao, Yuan; Zhao, Jin Tong; Zu, Yuan Gang; Fu, Yu Jie; Wang, Wei; Luo, Meng; Efferth, Thomas

2011-01-01

Five fungal endophytes (K4, K5, K6, K9, K14) producing Cajaninstilbene acid (CSA, 3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid) were isolated from the roots of pigeon pea [Cajanus cajan (L.) Millsp.]. CSA is responsible for the prominent pharmacological activities in pigeon pea. The amount of CSA in culture solution varied among the five fungal endophytes. K4 produced the highest levels of CSA (1037.13 µg/L) among the endophytes tested after incubation for five days. Both morphological characteristics and molecular methods were used for species identification of fungal endophytes. The five endophytic isolates were characterized by analyzing the internal transcribed spacer (ITS) rRNA and β-tubulin genes. The K4, K5, K9 and K14 strains isolated from pigeon pea roots were found to be closely related to the species Fusarium oxysporum. K6 was identified as Neonectria macrodidym. The present study is the first report on the isolation and identification of fungal endophytes producing CSA in pigeon pea. The study also provides a scientific base for large scale production of CSA.

The distinct proteome of placental malaria parasites.

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

Fried, Michal; Hixson, Kim K.; Anderson, Lori

Malaria proteins expressed on the surface of Plasmodium falciparum infected erythrocytes (IE) mediate adhesion and are targeted by protective immune responses. During pregnancy, IE sequester in the placenta. Placental IE bind to the molecule chondroitin sulfate A (CSA) and preferentially transcribe the gene that encodes VAR2CSA, a member of the PfEMP1 variant surface antigen family. Over successive pregnancies women develop specific immunity to CSA-binding IE and antibodies to VAR2CSA. We used tandem mass spectrometry together with accurate mass and time tag technology to study IE membrane fractions of placental parasites. VAR2CSA peptides were detected in placental IE and in IEmore » from children, but the MC variant of VAR2CSA was specifically associated with placental IE. We identified six conserved hypothetical proteins with putative TM or signal peptides that were exclusively expressed by the placental IE, and 11 such proteins that were significantly more abundant in placental IE. One of these hypothetical proteins, PFI1785w, is a 42kDa molecule detected by Western blot in parasites infecting pregnant women but not those infecting children.« less

Impact of adenosine nucleotide translocase (ANT) proline isomerization on Ca2+-induced cysteine relative mobility/mitochondrial permeability transition pore.

PubMed

Pestana, Cezar R; Silva, Carlos H T P; Uyemura, Sérgio A; Santos, Antonio C; Curti, Carlos

2010-08-01

Mitochondrial membrane carriers containing proline and cysteine, such as adenine nucleotide translocase (ANT), are potential targets of cyclophilin D (CyP-D) and potential Ca(2+)-induced permeability transition pore (PTP) components or regulators; CyP-D, a mitochondrial peptidyl-prolyl cis-trans isomerase, is the probable target of the PTP inhibitor cyclosporine A (CsA). In the present study, the impact of proline isomerization (from trans to cis) on the mitochondrial membrane carriers containing proline and cysteine was addressed using ANT as model. For this purpose, two different approaches were used: (i) Molecular dynamic (MD) analysis of ANT-Cys(56) relative mobility and (ii) light scattering techniques employing rat liver isolated mitochondria to assess both Ca(2+)-induced ANT conformational change and mitochondrial swelling. ANT-Pro(61) isomerization increased ANT-Cys(56) relative mobility and, moreover, desensitized ANT to the prevention of this effect by ADP. In addition, Ca(2+) induced ANT "c" conformation and opened PTP; while the first effect was fully inhibited, the second was only attenuated by CsA or ADP. Atractyloside (ATR), in turn, stabilized Ca(2+)-induced ANT "c" conformation, rendering the ANT conformational change and PTP opening less sensitive to the inhibition by CsA or ADP. These results suggest that Ca(2+) induces the ANT "c" conformation, apparently associated with PTP opening, but requires the CyP-D peptidyl-prolyl cis-trans isomerase activity for sustaining both effects.

Child Sexual Abuse and Negative Affect as Shared Risk Factors for Sexual Aggression and Sexual HIV Risk Behavior in Heterosexual Men.

PubMed

Peterson, Zoё D; Janssen, Erick; Goodrich, David; Fortenberry, J Dennis; Hensel, Devon J; Heiman, Julia R

2018-02-01

Previous research has suggested that sexually aggressive behavior and sexual HIV risk behavior are associated. Childhood sexual abuse (CSA) is a well-established risk factor for both types of problematic sexual behavior. Negative affect (i.e., anxiety, depression, and anger) is a less well-studied risk factor, but it has been theorized to relate to both sexual aggression and HIV risk behavior. Thus, this study sought to (1) confirm the relationship between sexual aggression and HIV risk behavior, (2) establish CSA and negative affect as shared risk factors for sexual aggression and HIV risk behavior, and (3) evaluate whether negative affect mediates the relationship between CSA and sexual aggression and between CSA and HIV sexual risk in a sample of heterosexual men. We recruited 18- to 30-year-old heterosexual men (N = 377) from urban sexually transmitted infection clinics. Men completed measures of sexual HIV risk history (number of partners and condom use), sexual aggression history, CSA history, and trait negative affect (anger, anxiety, and depression). Structural equation modeling was used to examine hypothesized direct and indirect relationships. In the final SEM model, sexual aggression history and sexual HIV risk behavior were correlated. CSA was associated with both types of problematic sexual behavior. Anxiety significantly mediated the relationship between CSA and sexual aggression and between CSA and sexual HIV risk behavior (χ 2 [1300] = 2121.79, p < .001; CFI = 0.905; RMSEA [90% CI] = .044 [.041-.047]). Sexual aggression appears to be part of a constellation of sexual risk behaviors; thus, it may be possible to develop prevention programs that target both sexual HIV risk and sexual aggression. CSA is a shared risk factor for sexual aggression and HIV risk behavior through the pathway of anxiety. Thus, anxiety might be one promising target for intervention.

[Local cyclosporin A therapy of nummuli after epidemic keratoconjunctivitis--case report].

PubMed

Reinhard, T; Sundmacher, R

1997-03-01

Steroid therapy for persistent or recurrent nummular adenoviral keratoconjunctivitis (AK) has little benefit because of the frequent recurrences, and mostly "offers" only serious steroid side effects. Since January 1995, we have treated different patients with nummuli after AK with topical Ciclosporin A (CSA) in an attempt to achieve at least the same symptomatic effect as with steroids, however, without side effects. Here, we report about our experiences in a very severe case with longterm treatment. The patient was sent to our clinic 4 months after AK with confluent nummuli and Descemet folds, more severe in the right than in the left eye. Best corrected visual acuity was 0.05 in the right and 0.5 in the left eye. Topical CSA 2% 4 times daily was first administered only in the right eye. When after 6 weeks a reduction of nummuli was noted in the right eye, the left eye, which had not improved, was started on the same regime. Therapy was tapered and finally stopped after 12 months in the right and 10 months in the left eye, when only minor changes were left in the corneae. A prompt recurrence of nummuli in both eyes within 4 weeks forced us to resume CSA therapy. At present, both corneae are clear with full vision, and this result is stable with 1 drop of CSA daily. No side effects of CSA therapy have been noted. The disappearance of nummuli with topical CSA and even more the reappearance of nummuli after cessation of CSA therapy show that topical CSA is about as effective as topical steroids in the symptomatic treatment of non-scarred nummuli after KE without the serious steroid side effects. Topical CSA treatment of nummuli after KE is, therefore, a very recommendable alternative for the potentially dangerous steroid therapy. Generally valid data on risk of recurrences, dosage and general effectiveness could only be learned from prospective studies with large numbers of AK patients, which, however, are not available outside epidemics.

Reported child sexual abuse in Bahrain: 2000-2009.

PubMed

Al-Mahroos, Fadheela; Al-Amer, Eshraq

2011-01-01

Child sexual abuse (CSA) is a common problem with severe short and long-term consequences to the abused child, the family and to society. The aim of this study was to evaluate the extent of CSA, and demographic and other characteristics of the abused and their families. Retrospective and descriptive study based on a review of medical records of CSA cases from 2000-2009 at Sulmaniya Medical Complex, the main secondary and tertiary medical care facility in Bahrain. The review included demographic data, child and family characteristics, manifestations and interventions. The 440 children diagnosed with CSA had a mean age of 8 years (range, 9 months to 17 years); 222 were males (50.5%) and 218 were females (49.5%). There was a steady increase in cases from 31 per year in 2000 to 77 cases in 2009. Children disclosed abuse in 26% of cases, while health sector professionals recognized 53% of the cases. Genital touching and fondling (62.5%) were the most common form of CSA, followed by sodomy in 39%. Gonorrhea was documented in 2% of the cases and pregnancy in 4% of the females. The illiteracy rate among the fathers and mothers was 9% and 12%, respectively, which is higher than the rate among the adult general population. Children came from all socio-economic classes. There was referral to police in 56%, public prosecution in 31% of the cases, but only 8% reached the court. During ten years there has been a 2.5% increase in reported cases of CSA. Improving the skill of professionals in identifying CSA indicators and a mandatory reporting law might be needed to improve the rate of recognition and referral of CSA cases. Further general population-based surveys are needed to determine more accurately the scope of CSA and the risk and protective factors in the family and community.

Reported child sexual abuse in Bahrain: 2000-2009

PubMed Central

Al-Mahroos, Fadheela; Al-Amer, Eshraq

2011-01-01

BACKGROUND AND OBJECTIVE: Child sexual abuse (CSA) is a common problem with severe short and long-term consequences to the abused child, the family and to society. The aim of this study was to evaluate the extent of CSA, and demographic and other characteristics of the abused and their families. DESIGN AND SETTING: Retrospective and descriptive study based on a review of medical records of CSA cases from 2000-2009 at Sulmaniya Medical Complex, the main secondary and tertiary medical care facility in Bahrain. PATIENTS AND METHODS: The review included demographic data, child and family characteristics, manifestations and interventions. RESULTS: The 440 children diagnosed with CSA had a mean age of 8 years (range, 9 months to 17 years); 222 were males (50.5%) and 218 were females (49.5%). There was a steady increase in cases from 31 per year in 2000 to 77 cases in 2009. Children disclosed abuse in 26% of cases, while health sector professionals recognized 53% of the cases. Genital touching and fondling (62.5%) were the most common form of CSA, followed by sodomy in 39%. Gonorrhea was documented in 2% of the cases and pregnancy in 4% of the females. The illiteracy rate among the fathers and mothers was 9% and 12%, respectively, which is higher than the rate among the adult general population. Children came from all socio-economic classes. There was referral to police in 56%, public prosecution in 31% of the cases, but only 8% reached the court. CONCLUSION: During ten years there has been a 2.5% increase in reported cases of CSA. Improving the skill of professionals in identifying CSA indicators and a mandatory reporting law might be needed to improve the rate of recognition and referral of CSA cases. Further general population-based surveys are needed to determine more accurately the scope of CSA and the risk and protective factors in the family and community. PMID:21808114

Phenotyping of Sleep-Disordered Breathing in Patients With Chronic Heart Failure With Reduced Ejection Fraction-the SchlaHF Registry.

PubMed

Arzt, Michael; Oldenburg, Olaf; Graml, Andrea; Erdmann, Erland; Teschler, Helmut; Wegscheider, Karl; Suling, Anna; Woehrle, Holger

2017-11-29

Different sleep-disordered breathing (SDB) phenotypes, including coexisting obstructive and central sleep apnea (OSA-CSA), have not yet been characterized in a large sample of patients with heart failure and reduced ejection fraction (HFrEF) receiving guideline-based therapies. Therefore, the aim of the present study was to determine the proportion of OSA, CSA, and OSA-CSA, as well as periodic breathing, in HFrEF patients with SDB. The German SchlaHF registry enrolled patients with HFrEF receiving guideline-based therapies, who underwent portable SDB monitoring. Polysomnography (n=2365) was performed in patients with suspected SDB. Type of SDB (OSA, CSA, or OSA-CSA), the occurrence of periodic breathing (proportion of Cheyne-Stokes respiration ≥20%), and blood gases were determined in 1557 HFrEF patients with confirmed SDB. OSA, OSA-CSA, and CSA were found in 29%, 40%, and 31% of patients, respectively; 41% showed periodic breathing. Characteristics differed significantly among SDB groups and in those with versus without periodic breathing. There was a relationship between greater proportions of CSA and the presence of periodic breathing. Risk factors for having CSA rather than OSA were male sex, older age, presence of atrial fibrillation, lower ejection fraction, and lower awake carbon dioxide pressure (pco 2 ). Periodic breathing was more likely in men, patients with atrial fibrillation, older patients, and as left ventricular ejection fraction and awake pco 2 decreased, and less likely as body mass index increased and minimum oxygen saturation decreased. SchlaHF data show that there is wide interindividual variability in the SDB phenotype of HFrEF patients, suggesting that individualized management is appropriate. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01500759. © 2017 The Authors and ResMed Germany Inc. Published on behalf of the American Heart Association, Inc., by Wiley.

Non suicidal self-injury, emotional eating and insomnia after child sexual abuse: Are those symptoms related to emotion regulation?

PubMed

Demirci, Esra

2018-01-01

The aim of this article was to assess the effects of child sexual abuse (CSA) on emotion regulation (ER) in adolescents and to evaluate the relationships between non suicidal self-injury (NSSI), emotional eating, insomnia and emotion disregulation (ED). Fifty two adolescents, aged 10-18 years, without who weren't diagnosed a psychiatric disease before abuse and completed 6-months of follow-up after abuse included the study. Control group consisted of 33 healthy voluntary participants without any known psychiatric disorders. Patients and volunteers who participated in the study were assessed with the Inventory of Statements About Self-injury (ISAS), Dutch Eating Behavior Questionnaire (DEBQ), Pittsburgh Sleep Quality Index (PSQI), Insomnia severity index (ISI), and the Difficulties in Emotion Regulation Scale (DERS). In our study, PSQI scores, DERS total scores and DEBQ emotional eating subscores were significantly higher in the CSA victims (In orderly; p = 0,034, p < 0.001, p = 0,023). 55.7% of the CSA victims reported self-injurious behavior, while 15.5% of healthy voluntary participants reporting self-injurious behavior. The CSA victims reporting NSSI had higher DERS scores than CSA victims without NSSI. (p = 0.024). The CSA victims with post-traumatic stress disorder (PTSD) and CSA victims without PTSD had a positive correlation between DEBQ emotional eating subscores and DERS total scores (In orderly: r = 0.762, p = 0.031; r = 0.872, p < 0.001). There was a positive correlation between the PSQI scores and DERS scores in the CSA victims with PTSD (r = 0.827, p = 0.023). Further studies are needed to assess the relationship between self-injury, emotional eating, insomnia and ED, and to determine how sexual abuse effect the ER in a clinical sample of CSA. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Ultrasound assessment of hamstring muscle size using posterior thigh muscle thickness.

PubMed

Abe, Takashi; Loenneke, Jeremy P; Thiebaud, Robert S

2016-05-01

Several studies have investigated the relationship between ultrasound-measured muscle thickness (MT) and individual muscle cross-sectional area (CSA) and muscle volume (MV) in extremity and trunk muscles; however, the hamstring muscle has not been studied. The purpose of this study was to examine the relationship between posterior thigh MT by ultrasound and the muscle CSA and MV of the hamstring obtained by magnetic resonance imaging (MRI). Ten young women aged 20-31 had MT measured by ultrasound at three sites on the medial anterior (50% of thigh length; TL) and posterior (50% and 70% of TL) aspects of the thigh. On the same day, a series of continuous muscle CSA along the thigh was measured by MRI. In each slice, the anatomical CSA of the hamstring (biceps femoris, semitendinosus and semimembranosus) and quadriceps muscle was analysed, and the CSAs at 50% and 70% of TL and maximal CSA of the hamstring (CSAmax ) were determined. MV was calculated by multiplying CSA by slice thickness. A significant correlation was observed between posterior 50% MT and 50% hamstring CSA (r = 0·848, P = 0·002) and between posterior 70% MT and 70% hamstring CSA (r = 0·679, P = 0·031). Posterior 50% MT (r = 0·732, P = 0·016) and 50% MTxTL (r = 0·873, P = 0·001) were also correlated to hamstring MV. Anterior:posterior 50% thigh MT ratio was correlated to MV ratio of quadriceps and hamstring muscles (r = 0·803, P = 0·005). Our results suggest that posterior thigh MT reflects hamstring muscle CSA and MV. The anterior:posterior MT ratio may serve as a surrogate for MV ratio of quadriceps and hamstring. © 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Muscle Torque Relative to Cross-Sectional Area and the Functional Muscle-Bone Unit in Children and Adolescents with Chronic Disease

PubMed Central

Lee, Dale Y.; Wetzsteon, Rachel J.; Zemel, Babette S.; Shults, Justine; Organ, Jason M.; Foster, Bethany J.; Herskovitz, Rita M.; Foerster, Debbie L.; Leonard, Mary B.

2015-01-01

Measures of muscle mass or size are often used as surrogates of forces acting on bone. However, chronic diseases may be associated with abnormal muscle force relative to muscle size. The muscle-bone unit was examined in 64 children and adolescents with new-onset Crohn’s disease (CD), 54 with chronic kidney disease (CKD), 51 treated with glucocorticoids for nephrotic syndrome (NS), and 264 healthy controls. Muscle torque was assessed by isometric ankle dynamometry. Calf muscle cross-sectional area (CSA) and tibia cortical section modulus (Zp) were assessed by quantitative CT. Log-linear regression was used to determine the relations among muscle CSA, muscle torque, and Zp, adjusted for tibia length, age, Tanner stage, sex, and race. Muscle CSA and muscle torque-relative-to-muscle CSA were significantly lower than controls in advanced CKD (CSA −8.7%, p = 0.01; torque −22.9%, p < 0.001) and moderate-to-severe CD (CSA −14.1%, p < 0.001; torque −7.6%, p = 0.05), but not in NS. Zp was 11.5% lower in advanced CKD (p = 0.005) compared to controls, and this deficit was attenuated to 6.7% (p = 0.05) with adjustment for muscle CSA. With additional adjustment for muscle torque and body weight, Zp was 5.9% lower and the difference with controls was no longer significant (p = 0.09). In participants with moderate-to-severe CD, Zp was 6.8% greater than predicted (p = 0.01) given muscle CSA and torque deficits (R2=0.92), likely due to acute muscle loss in newly diagnosed patients. Zp did not differ in NS, compared with controls. In conclusion, muscle torque relative to muscle CSA was significantly lower in CKD and CD, compared with controls, and was independently associated with Zp. Future studies are needed to determine if abnormal muscle strength contributes to progressive bone deficits in chronic disease, independent of muscle area. PMID:25264231

[The impact of childhood sexual abuse on the development of AIDS related high risk behaviors and psychological appearances among men who have sex with men].

PubMed

Yu, Zeng-Zhao; Zhang, Bei-Chuan; Li, Xiu-Fang; Wang, Ning; Shi, Tong-Xin; Chu, Quan-Sheng

2009-01-01

To study the AIDS related high risk behaviors and psychological appearances among men who have sex with men (MSM) who ever experienced childhood sexual abuse (CSA). Target sampling for a cross-sectional study was developed and valid anonymous questionnaires were adopted to compare the differences of high risk behaviors related to AIDS and psychological appearances between those with or without CSA experiences among 2147 MSM from nine cities. Compared to corresponding ones without CSA experience, CSA group had a significant larger numbers in the following events: total sexual partners, anal sex episodes with same sex, female sexual partners and anal sex in the previous six months, with the figures of median as 20.0, 10.0, 3.0, 3.0 respectively. In the previous year, 30.8% of them had ever participated in 'group sex', 19.2% ever exchanged money for sex, 36.7% bled while having sexual intercourse, 37.3% had sex with male partners away from his own region. All the above said figures were higher than non-CSA group, with significant differences. It also appeared that CSA experience had an impact on significant lower rate of condom use (67.3%) in the last anal sex. Those with CSA experience had more psychological problems which appeared as: 75.6% considered they would suffer from serious discrimination if their sexual orientation ever disclosed, 34.7% had a strong intention of suicide and 24.3% ever having had suicidal attempts. The differences of the two groups showed statistical significance. CSA experience not only increased the number of AIDS related high risk behaviors in adulthood, but also had negative impact on their psychological appearances. It is of urgent need to carry out psychological intervention approaches to target on MSM with CSA experiences while childhood sexual education and rights assurance towards juvenile population should also not be neglected.

[Treatment of transfusion-dependent nonsevere aplastic anemia with cyclosporine A plus ATG/ALG versus cyclosporine A plus androgens: a retrospective single center study].

PubMed

Song, L; Peng, G X; Wu, Z J; Zhang, L; Jing, L P; Zhou, K; Li, Y; Li, Y; Ye, L; Li, J P; Fan, H H; Zhao, X; Yang, W R; Yang, Y; Zhang, F K

2016-11-14

Objective: To determine whether cyclosporine A (CsA) plus androgens was as effective as the current standard immunosuppressive therapy (IST) for transfusion-dependent nonsevere aplastic anemia (TD-NSAA). Methods: The records of 125 consecutive TD-NSAA patients who were treated between Aug. 2007 and Sept. 2014, with either CsA plus androgen or ALG/ATG plus CsA regimen were reviewed. The 3-month and 6-month hematologic responses and survival were evaluated. Results: There were 125 TD-NSAA patients (70 were male and 55 female, 1.25∶1). Median age was 27 (6-66) years. There was no significant difference in early mortality between 48 treated by ATG/ALG plus CsA and 77 by CsA plus androgen patients (1/48 vs 0/77, P =0.384). Both the total hematologic response and the better hematological response rates at 3-month (70.8% vs 45.5%, P =0.006 and 27.1% vs 10.4%, P =0.015, respectively) and 6-month (75.0% vs 55.8%, P =0.031 and 41.7% vs 22.1% P =0.020, respectively) after treatment were much higher in the standard IST group than that in CsA plus androgen group. The median time to transfusion independent of 36.5 (0-149) days in the standard IST group was significantly shorter than 98 (14-180) days in CsA plus androgen group ( P <0.001). Survival was comparable between the two groups (97.9% vs 100.0%, P =0.227). It was superior (71.2% vs 59.5%) but not significantly ( P =0.227) in event-free survival in standard IST group. Conclusions: CsA plus androgen was inferior to the standard IST of ATG/ALG and CsA regimen in treating TD-NSAA in terms of the hematologic response and the quality of response, despite of comparable short-term survival.

Improvement of highly sensitive lidar with a thumb-sized sensor-head built using an optical fiber preamplifier

NASA Astrophysics Data System (ADS)

Inoue, Daisuke; Ichikawa, Tadashi; Matsubara, Hiroyuki; Mao, Xueon; Maeda, Mitsutoshi; Nagashima, Chie; Kagami, Manabu

2012-06-01

We have developed a LIDAR system with a sensor head which, although it includes a scanning mechanism, is less than 20 cc in size. The system is not only small, but is also highly sensitive. Our LIDAR system is based on time-of-flight measurements, and incorporates an optical fiber. The main feature of our system is the utilization of optical amplifiers for both the transmitter and the receiver, and the optical amplifiers enable us to exceed the detection limit set by thermal noise. In conventional LIDAR systems the detection limit is determined by the thermal noise, because the avalanche photo-diodes (APD) and trans-impedance amplifiers (TIA) that they use detect the received signals directly. In the case of our LIDAR system, the received signal is amplified by an optical fiber amplifier before reaching the photo diode and the TIA. Therefore, our LIDAR system boosts the signal level before the weak incoming signal is depleted by thermal noise. There are conditions under which the noise figure for the combination of an optical fiber amplifier and a photo diode is superior to the noise figure for an avalanche photo diode. We optimized the gains of the optical fiber amplifier and the TIA in our LIDAR system such that it would be capable of detecting a single photon. As a result, the detection limit of our system is determined by shot noise. We have previously demonstrated optical pre-amplified LIDAR with a perfect co-axial optical system[1]. For this we used a variable optical attenuator to remove internal reflection from the transmission and receiving lenses. However, the optical attenuator had an insertion loss of 6dB which reduced the sensitivity of the LIDAR. We re-designed the optical system such that it was semi-co-axial and removed the variable optical attenuator. As a result, we succeeded in scanning up to a range of 80 m. This small and highly sensitive measurement technology shows great potential for use in LIDAR.

Clinical Evaluation of the Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test for Rapid Diagnosis of Tuberculosis Lymphadenitis

PubMed Central

Kerleguer, A.; Fabre, M.; Bernatas, J. J.; Gerome, P.; Nicand, E.; Herve, V.; Koeck, J. L.

2004-01-01

This prospective study evaluated the performance of the Amplified Mycobacterium Tuberculosis Direct Test (MTD) for the diagnosis of lymph node tuberculosis in Djibouti, Republic of Djibouti. Of 197 specimens sampled from 153 patients, 123 were from 95 tuberculous patients. The sensitivity and specificity of MTD were 93 and 100%, respectively. The sensitivity of culture was 89%. PMID:15583341

Prevalence of childhood sexual abuse and timing of disclosure in a representative sample of adults from Quebec.

PubMed

Hébert, Martine; Tourigny, Marc; Cyr, Mireille; McDuff, Pierre; Joly, Jacques

2009-09-01

Our study sought to explore patterns of disclosure of child sexual abuse (CSA) in a sample of adult men and women. A telephone survey conducted with a representative sample of adults (n = 804) from Quebec assessed the prevalence of CSA and disclosure patterns. Analyses were carried out to determine whether disclosure groups differed in terms of psychological distress and symptoms of posttraumatic stress, and a logistic regression was used to examine factors associated with prompt disclosure. Prevalence of CSA was 22.1% for women and 9.7% for men. About 1 survivor out of 5 had never disclosed the abuse, with men more likely not to have told anyone, than women. Only 21.2% of adults reported prompt disclosure (within a month of the first abusive event), while 57.5% delayed disclosure (more than 5 years after the first episode). CSA victims who never disclosed the abuse and those who delayed disclosure were more likely to obtain scores of psychological distress and posttraumatic stress achieving clinical levels, compared with adults without a history of CSA. In the multivariate analysis, experiencing CSA involving a perpetrator outside the immediate family and being female were factors independently associated with prompt disclosure. A significant number of adult women and men reported experiencing CSA, and most victims attested to either not disclosing or significantly delaying abuse disclosure.

Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models

PubMed Central

Shen, Xiujin; Jiang, Hong; Ying, Meike; Xie, Zhoutao; Li, Xiayu; Wang, Haibing; Zhao, Jie; Lin, Chuan; Wang, Yucheng; Feng, Shi; Shen, Jia; Weng, Chunhua; Lin, Weiqiang; Wang, Huiping; Zhou, Qin; Bi, Yan; Li, Meng; Wang, Lingyan; Zhu, Tongyu; Huang, Xiaoru; Lan, Hui-Yao; Zhou, Jing; Chen, Jianghua

2016-01-01

Podocyte injury and the appearance of proteinuria are features of minimal-change disease (MCD). Cyclosporin A (CsA) and tacrolimus (FK506) has been reported to reduce proteinuria in patients with nephrotic syndrome, but mechanisms remain unknown. We, therefore, investigated the protective mechanisms of CsA and FK506 on proteinuria in a rat model of MCD induced by puromycin aminonucleoside (PAN) and in vitro cultured mouse podocytes. Our results showed that CsA and FK506 treatment decreased proteinuria via a mechanism associated to a reduction in the foot-process fusion and desmin, and a recovery of synaptopodin and podocin. In PAN-treated mouse podocytes, pre-incubation with CsA and FK506 restored the distribution of the actin cytoskeleton, increased the expression of synaptopodin and podocin, improved podocyte viability, and reduced the migrating activities of podocytes. Treatment with CsA and FK506 also inhibited PAN-induced podocytes apoptosis, which was associated with the induction of Bcl-xL and inhibition of Bax, cleaved caspase 3, and cleaved PARP expression. Further studies revealed that CsA and FK506 inhibited PAN-induced p38 and JNK signaling, thereby protecting podocytes from PAN-induced injury. In conclusion, CsA and FK506 inhibit proteinuria by protecting against PAN-induced podocyte injury, which may be associated with inhibition of the MAPK signaling pathway. PMID:27580845

Adaptive servo-ventilation as treatment of persistent central sleep apnea in post-acute ischemic stroke patients.

PubMed

Brill, Anne-Kathrin; Rösti, Regula; Hefti, Jacqueline Pichler; Bassetti, Claudio; Gugger, Matthias; Ott, Sebastian R

2014-11-01

Adaptive servo-ventilation (ASV) is a well-established treatment of central sleep apnea (CSA) related to congestive heart failure (CHF). Few studies have evaluated the effectiveness and adherence in patients with CSA of other etiologies, and even less is known about treatment of CSA in patients of post ischemic stroke. A single-centre retrospective analysis of ASV treatment for CSA in post-acute ischemic stroke patients without concomitant CHF was performed. Demographics, clinical data, sleep studies, ventilator settings, and adherence data were evaluated. Out of 154 patients on ASV, 15 patients had CSA related to ischemic stroke and were started on ASV a median of 11 months after the acute cerebrovascular event. Thirteen out of the 15 patients were initially treated with continuous positive airway pressure (11/15) and bilevel positive airway pressure (2/15) therapy with unsatisfactory control of CSA. ASV significantly improved AHI (46.7 ± 24.3 vs 8.5 ± 12/h, P = 0.001) and reduced ESS (8.7 ± 5.7 vs 5.6 ± 2.5, P = 0.08) with a mean nightly use of ASV of 5.4 ± 2.4 h at 3 months after the initiation of treatment. Results were maintained at 6 months. ASV was well tolerated and clinically effective in this group of patients with persistent CSA after ischemic stroke. Copyright © 2014 Elsevier B.V. All rights reserved.

Adults and Children in Low-Income Households that Participate in Cost-Offset Community Supported Agriculture Have High Fruit and Vegetable Consumption.

PubMed

Hanson, Karla L; Kolodinsky, Jane; Wang, Weiwei; Morgan, Emily H; Pitts, Stephanie B Jilcott; Ammerman, Alice S; Sitaker, Marilyn; Seguin, Rebecca A

2017-07-08

This paper examines fruit and vegetable intake (FVI) in low-income households that participated in a cost-offset (CO), or 50% subsidized, community-supported agriculture (CSA) program. CSA customers paid farms upfront for a share of the harvest, and received produce weekly throughout the growing season. A cohort of adults and children 2-12 y in a summer CO-CSA were surveyed online twice: August 2015 ( n = 41) and February 2016 ( n = 23). FVI was measured by the National Cancer Institute's (NCI) Fruit and Vegetable Screener (FVS) and an inventory of locally grown fruits and vegetables. FVI relative to United States (US) recommendations and averages, and across seasons, were tested with non-parametric tests and paired t -tests ( p < 0.05). Both adults and children in the CO-CSA had higher FVI than the US averages, and more often met recommendations for vegetables. Some summer fruits and vegetables were more often eaten when locally in-season. The CO-CSA model warrants further examination as an avenue for improving vegetable consumption among adults and children in low-income households. However, causality between CO-CSA participation and FVI cannot be inferred, as CO-CSA participants may be positive deviants with respect to FVI. A multi-state randomized controlled trial is currently underway to evaluate impacts of CO-CSAs on FVI and related outcomes.

Use of commercial soil amendments in initial soils (II) - Impact on soil respiratory and carbon isotopic characteristics

NASA Astrophysics Data System (ADS)

Nii-Annang, S.; Rodionov, A.; Dilly, O.; Bens, O.; Raab, T.; Hüttl, R. F.

2009-04-01

The search for viable re-cultivation techniques for the reclamation of large scale soil disturbances induced by mining of mineral resources has increasingly received attention in recent times. These techniques should favour plant growth under dry conditions and under nutrient-poor substrates; a problem in the lignite mining district in Lusatia, Germany. Substrates with basal respiration around 0.04 µg CO2 g-1 h-1, which is relatively low compared to mature soils, were amended with two nutrient rich commercial soil additives (CSA 1 and CSA 2). The CSA 1 is a synthetic-mineral mixture and CSA 2 an organo-mineral mixture. The amendment stimulated basal respiration based on both carbon dioxide evolution and oxygen uptake by 150 and 125 % for SCA 1 and CSA 2, respectively when 1 % of each additive was thoroughly mixed with substrate in a laboratory study. The stimulating effect was evident after glucose addition to CSA 2. The CSA 1 application in the field at lower rates still showed apparent stimulation of soil respiratory activities after one year. Similarly, the organo-mineral-mixture has prominent effects on basal respiration and substrate-induced respiration when glucose was added. We concluded that the commercial additives used as long-term amelioration techniques increased both nutrient preservation and, to some extent, soil microbial activity.

The influence of critical shoulder angle on secondary rotator cuff insufficiency following shoulder arthroplasty.

PubMed

Cerciello, Simone; Monk, Andrew Paul; Visonà, Enrico; Carbone, Stefano; Edwards, Thomas Bradley; Maffulli, Nicola; Walch, Gilles

2017-07-01

Secondary cuff failure after shoulder replacement is disabling and often requires additional surgery. Increased critical shoulder angle (CSA) has been found in patients with cuff tear compared to normal subjects. The interobserver reliability of the CSA and the relationship between CSA and symptomatic secondary cuff failure after shoulder replacement were investigated. Nineteen patients with symptomatic cuff failure after anatomic shoulder replacement (mean FU 45 months) were compared to a control group of 29 patients showing no signs of symptomatic cuff failure (mean FU 105.7 months). The CSA was measured by two blinded surgeons at a mean follow-up of 45 and 105.7 months, respectively. Inter-observer reliability was calculated. The mean CSA in the study group in neutral, internal and external rotations were 33°, 34° and 34°, respectively. Corresponding values in the control group were 32°, 32° and 32°. The interclass correlation coefficient for the whole population between the two examiners were 0.956 (P < 0.01), 0.964 (P < 0.01) and 0.955 (P < 0.01), respectively. There were no significant differences of CSA values between patients who had undergone shoulder replacement and experienced late cuff failure and those in whom the same procedure had been successful. A good inter-observer reliability was found for the CSA method.

Clinical efficacy and safety following dose tapering of ciclosporin in cats with hypersensitivity dermatitis.

PubMed

Roberts, Elizabeth S; Tapp, Tiffany; Trimmer, Ann; Roycroft, Linda; King, Stephen

2016-11-01

Objectives This study was designed to evaluate the efficacy and safety of reducing ciclosporin (CsA) dosing frequency from daily to every other day (EOD) or twice a week (TW) according to clinical response in cats with hypersensitivity dermatitis (HD) and treated with CsA. Methods One hundred and ninety-one cats with HD were given 7 mg/kg CsA daily for at least 4 weeks. Depending on clinical response, the dosing frequency was tapered from daily to EOD over the next 4 weeks and further to TW for an additional 4 weeks. Safety was evaluated through physical examinations, clinical pathology and the monitoring of adverse events (AEs). Results The majority of cats were able to have their dose of CsA tapered to either EOD (15.5%) or TW (62.9%) according to the clinical response. Observed AEs were most frequently mild and self-limiting vomiting and diarrhea. A higher percentage of AEs occurred with daily administration (73%) compared with other dosing regimens (27%). Conclusions and relevance Following 4 weeks of daily dosing at 7 mg/kg, CsA may be tapered to EOD or TW while maintaining the desired therapeutic response in cats with HD. Additionally, CsA appears to be well tolerated with fewer AEs at EOD or TW dosing. Establishing the lowest effective dosing frequency of CsA improves the drug's safety profile.

Myeloid-Derived Suppressor Cells Ameliorate Cyclosporine A-Induced Hypertension in Mice.

PubMed

Chiasson, Valorie L; Bounds, Kelsey R; Chatterjee, Piyali; Manandhar, Lochana; Pakanati, Abhinandan R; Hernandez, Marcos; Aziz, Bilal; Mitchell, Brett M

2018-01-01

The calcineurin inhibitor cyclosporine A (CsA) suppresses the immune system but promotes hypertension, vascular dysfunction, and renal damage. CsA decreases regulatory T cells and this contributes to the development of hypertension. However, CsA's effects on another important regulatory immune cell subset, myeloid-derived suppressor cells (MDSCs), is unknown. We hypothesized that augmenting MDSCs would ameliorate the CsA-induced hypertension and vascular and renal injury and dysfunction and that CsA reduces MDSCs in mice. Daily interleukin-33 treatment, which increased MDSC levels, completely prevented CsA-induced hypertension and vascular and renal toxicity. Adoptive transfer of MDSCs from control mice into CsA-treated mice after hypertension was established dose-dependently reduced blood pressure and vascular and glomerular injury. CsA treatment of aortas and kidneys isolated from control mice for 24 hours decreased relaxation responses and increased inflammation, respectively, and these effects were prevented by the presence of MDSCs. MDSCs also prevented the CsA-induced increase in fibronectin in microvascular and glomerular endothelial cells. Last, CsA dose-dependently reduced the number of MDSCs by inhibiting calcineurin and preventing cell proliferation, as other direct calcineurin signaling pathway inhibitors had the same dose-dependent effect. These data suggest that augmenting MDSCs can reduce the cardiovascular and renal toxicity and hypertension caused by CsA. © 2017 American Heart Association, Inc.

Adults and Children in Low-Income Households That Participate in Cost-Offset Community Supported Agriculture Have High Fruit and Vegetable Consumption

PubMed Central

Hanson, Karla L.; Kolodinsky, Jane; Wang, Weiwei; Morgan, Emily H.; Jilcott Pitts, Stephanie B.; Ammerman, Alice S.; Sitaker, Marilyn; Seguin, Rebecca A.

2017-01-01

This paper examines fruit and vegetable intake (FVI) in low-income households that participated in a cost-offset (CO), or 50% subsidized, community-supported agriculture (CSA) program. CSA customers paid farms upfront for a share of the harvest, and received produce weekly throughout the growing season. A cohort of adults and children 2–12 y in a summer CO-CSA were surveyed online twice: August 2015 (n = 41) and February 2016 (n = 23). FVI was measured by the National Cancer Institute’s (NCI) Fruit and Vegetable Screener (FVS) and an inventory of locally grown fruits and vegetables. FVI relative to United States (US) recommendations and averages, and across seasons, were tested with non-parametric tests and paired t-tests (p < 0.05). Both adults and children in the CO-CSA had higher FVI than the US averages, and more often met recommendations for vegetables. Some summer fruits and vegetables were more often eaten when locally in-season. The CO-CSA model warrants further examination as an avenue for improving vegetable consumption among adults and children in low-income households. However, causality between CO-CSA participation and FVI cannot be inferred, as CO-CSA participants may be positive deviants with respect to FVI. A multi-state randomized controlled trial is currently underway to evaluate impacts of CO-CSAs on FVI and related outcomes. PMID:28698460

Curriculum Development around Parenting Strategies to Prevent and Respond to Child Sexual Abuse in Sub-Saharan Africa: A Program Collaboration Between Families Matter! and Global Dialogues

PubMed Central

Miller, Kim S.; Winskell, Kate; Pruitt, Kaitlyn L.; Saul, Janet

2016-01-01

Despite widespread recognition of child sexual abuse (CSA) as a serious problem in sub-Saharan Africa (SSA), few far-reaching programmatic interventions addressing CSA in this setting are currently available, and those interventions that do exist tend to focus on response rather than prevention. Parents are in a unique position to engage their children in dialogues about sexuality-related issues and thereby both help prevent CSA and take swift action to stop CSA, address trauma, and minimize harm, in the event CSA does occur. The Families Matter! Program (FMP) is an evidence-based intervention for parents and caregivers of 9-12 year-olds in sub-Saharan African countries that promotes positive parenting practices and effective parent-child communication about sex-related issues and sexual risk reduction. This paper describes the enhancement of a new FMP session on CSA, drawing on authentic narratives contributed by young people to the Global Dialogues/Scenarios from Africa (GD/SfA) youth scriptwriting competition. The GD/SfA data permitted incorporation of young Africans’ voices and resulted in an interactive curriculum that is grounded in contextually-relevant and emotionally-compelling scenarios and adapted to the needs of low-literacy adult learners in SSA. Experiences are shared with a view to informing the development of interventions addressing CSA in SSA. PMID:26701277

Note: A high dynamic range, linear response transimpedance amplifier.

PubMed

Eckel, S; Sushkov, A O; Lamoreaux, S K

2012-02-01

We have built a high dynamic range (nine decade) transimpedance amplifier with a linear response. The amplifier uses junction-gate field effect transistors (JFETs) to switch between three different resistors in the feedback of a low input bias current operational amplifier. This allows for the creation of multiple outputs, each with a linear response and a different transimpedance gain. The overall bandwidth of the transimpedance amplifier is set by the bandwidth of the most sensitive range. For our application, we demonstrate a three-stage amplifier with transimpedance gains of approximately 10(9)Ω, 3 × 10(7)Ω, and 10(4)Ω with a bandwidth of 100 Hz.

Interactive Computer Simulation and Animation for Improving Student Learning of Particle Kinetics

ERIC Educational Resources Information Center

Fang, N.; Guo, Y.

2016-01-01

Computer simulation and animation (CSA) has been receiving growing attention and wide application in engineering education in recent years. A new interactive CSA module was developed in the present study to improve student learning of particle kinetics in an undergraduate engineering dynamics course. The unique feature of this CSA module is that…

Prevention of Child Sexual Abuse in China: Knowledge, Attitudes, and Communication Practices of Parents of Elementary School Children

ERIC Educational Resources Information Center

Chen, JingQi; Dunne, Michael P.; Han, Ping

2007-01-01

Objective: Active involvement by parents may contribute substantially to the success of school-based programs to prevent child sexual abuse (CSA). In China, little is known about parental understanding of CSA. This study investigated Chinese parents' knowledge, attitudes, and communication practices with their children about CSA. Method: Six…

Factors Related to Childhood Sexual Abuse among Gay/Bisexual Male Internet Escorts

ERIC Educational Resources Information Center

Parsons, Jeffrey T.; Bimbi, David S.; Koken, Juline A.; Halkitis, Perry N.

2005-01-01

This exploratory investigation examined the relationship between childhood sexual abuse (CSA) and related psychosocial characteristics and sexual behaviors among 46 gay/bisexual male escorts who advertise via the Internet. More than a quarter of men (28.3%) reported some history of CSA. Men reporting CSA were more likely to be from an ethnic…

Coping with child sexual abuse among college students and post-traumatic stress disorder: the role of continuity of abuse and relationship with the perpetrator.

PubMed

Cantón-Cortés, David; Cantón, José

2010-07-01

The purpose of this study was to examine the effects of child sexual abuse (CSA) on the use of coping strategies and post-traumatic stress disorder (PTSD) scores in young adults, as well as the role of avoidance and approach coping strategies in those PTSD scores in CSA victims. The role of coping strategies was studied by considering their possible interactive effect with the continuity of abuse and the relationship with the perpetrator; the effect of coping strategies on PTSD was also compared between CSA victim and non-CSA victim participants. The sample was comprised of 138 victims of CSA and another 138 participants selected as a comparison group. Data about child sexual abuse were obtained from a questionnaire developed for this purpose. Coping strategies were assessed with the How I Deal with Things Scale (Burt & Katz, 1987), while PTSD scores were assessed with the "Escala de Gravedad de Síntomas del Trastorno de Estrés Postraumático" (Severity of Symptoms of PTSD Scale; Echeburúa et al., 1997). Participants who had been victims of CSA showed significantly higher PTSD scores and lower approach coping strategies scores. However, differences in avoidance coping strategies between groups were not consistent and did not always follow the expected direction. Only the use of avoidance coping strategies was related to PTSD, participants who used these showing higher scores. The effects of avoidance strategies were stronger in continued than in isolated abuse, in intrafamilial than in extrafamilial abuse and in CSA victims than in non-victims. These results confirm the idea of CSA as a high-risk experience that can affect the victim's coping strategies and lead to PTSD to a lesser or greater extent depending on the coping strategy used. Moreover, the role of these strategies varies depending on whether or not the participant is a victim of CSA and on the characteristics of abuse (continuity and relationship with the perpetrator). In terms of intervention, a reduction of avoidance-type strategies appears to have a beneficial effect, especially in the case of intrafamilial and/or continued CSA victims. The encouragement of "spontaneous" approach strategies (devised by the victim herself, without counseling) would probably not lead to more positive outcomes in terms of PTSD symptomatology. However, encouraging CSA survivors to engage in therapy aimed at developing effective approach strategies, as other studies have suggested, may help reduce PTSD symptoms. Copyright © 2010 Elsevier Ltd. All rights reserved.

Quantitative In Situ Analysis of the Anterior Cruciate Ligament: Length, Midsubstance Cross-sectional Area, and Insertion Site Areas.

PubMed

Fujimaki, Yoshimasa; Thorhauer, Eric; Sasaki, Yusuke; Smolinski, Patrick; Tashman, Scott; Fu, Freddie H

2016-01-01

Quantification of the cross-sectional area (CSA) of the anterior cruciate ligament (ACL) in different loading conditions is important for understanding the native anatomy and thus achieving anatomic reconstruction. The ACL insertion sites are larger than the ACL midsubstance, and the isthmus (region of the smallest CSA) location may vary with the load or flexion angle. To (1) quantify the CSA along the entire ACL, (2) describe the location of the ACL isthmus, (3) explore the relationship between ACL length and CSA, and (4) validate magnetic resonance imaging (MRI) for assessing the CSA of the midsubstance ACL. Descriptive laboratory study. Eight cadaveric knees were dissected to expose the ACL and its attachments. Knees were positioned using a robotic loading system through a range of flexion angles in 3 loading states: (1) unloaded, (2) anterior tibial translation, and (3) combined rotational load of valgus and internal torque. Laser scanning quantified the shape of the ACL and its insertion site boundaries. The CSA of the ACL was measured, and the location of the isthmus was determined; the CSA of the ACL was also estimated from MRI and compared with the laser-scanned data. The CSA of the ACL varied along the ligament, and the isthmus existed at an average (±SD) of 53.8% ± 5.5% of the distance from the tibial insertion center to the femoral insertion center. The average CSA at the isthmus was smallest in extension (39.9 ± 13.7 mm(2)) and increased with flexion (43.9 ± 12.1 mm(2) at 90°). The ACL length was shortest at 90° of flexion and increased by 18.8% ± 10.1% in unloaded extension. Application of an anterior load increased the ACL length by 5.0% ± 3.3% in extension, and application of a combined rotational load increased its length by 4.1% ± 3.0% in extension. The ACL isthmus is located almost half of the distance between the insertion sites. The CSA of the ACL at the isthmus is largest with the knee unloaded and at 90° of flexion, and the area decreases with extension and applied loads. The CSA at the isthmus represents less than half the area of the insertion sites. These results may aid surgical planning, specifically for choosing a graft size and fixation angle that most closely matches the native anatomy and function across the entire range of knee motion. © 2015 The Author(s).

Childhood sexual abuse and HIV-related risks among men who have sex with men in Washington, DC.

PubMed

Phillips, Gregory; Magnus, Manya; Kuo, Irene; Rawls, Anthony; Peterson, James; Montanez, Luz; West-Ojo, Tiffany; Jia, Yujiang; Opoku, Jenevieve; Greenberg, Alan E

2014-05-01

Childhood sexual abuse (CSA) has been reported to be disproportionately higher among men who have sex with men (MSM) than among heterosexual men; it has also been found to be significantly positively associated with HIV status and HIV risk factors, including unprotected anal intercourse. The purpose of this study was to assess the correlates of CSA in a sample of community-recruited MSM, investigate race as a potential effect modifier, and describe the independent association between CSA and HIV infection in Washington, DC. A total of 500 MSM were recruited by venue-based sampling in 2008 as part of the National HIV Behavioral Surveillance. More than one-half of MSM identified as White, while one-third identified as Black. CSA was reported by 17.5 % of the 451 MSM, with the first instance of abuse occurring at a median age of 8.3 (interquartile range = 5.0, 11.0). In multivariable analysis, HIV-positive men were significantly more likely to report a history of CSA compared to HIV-negative men after adjusting for intimate partner violence in the last 12 months, having been arrested in the last 12 months, and depressive symptoms. HIV-positive MSM had more than four times the odds of reporting CSA after controlling for other correlates (aOR = 4.19; 95 % CI 2.26, 7.75). Despite hypothesizing that race modified the effect of CSA on HIV infection we found this was not the case in this sample. More research is needed to investigate the potential pathway between a history of CSA and HIV infection, and how this contributes to driving the HIV epidemic among MSM in Washington, DC.

Gendered pathways from child sexual abuse to sexual aggression victimization and perpetration in adolescence and young adulthood.

PubMed

Krahé, Barbara; Berger, Anja

2017-01-01

This study aimed to examine the pathways from child sexual abuse to sexual assault victimization and perpetration in adolescence and early adulthood, considering risky sexual behavior and lowered sexual self-esteem as mediator variables. In a two-wave longitudinal study with 2251 college students in Germany, male and female participants provided reports of sexual aggression victimization and perpetration since age 14 (T1) and again a year later (T2), covering the last 12 months. In addition, child sexual abuse (CSA; before the age of 14), risky sexual behavior, and sexual self-esteem were assessed at T1, and risky sexual behavior and sexual-self-esteem were assessed again at T2. Experience of CSA was significantly associated with greater likelihood of sexual aggression victimization and perpetration, lower sexual self-esteem, and more risky sexual behavior in both gender groups at T1 and was directly related to victimization at T2 among male participants. In both gender groups, CSA indirectly contributed to a higher probability of sexual victimization at T2 via its impact on victimization T1. In males, the indirect path from CSA to T2 perpetration via T1 perpetration was also significant. Through its negative impact on sexual self-esteem, CSA indirectly increased the probability of sexual victimization among women and the probability of sexual aggression perpetration among men. Risky sexual behavior mediated the pathway from CSA to sexual victimization at T2 for men and women and the pathway from CSA to sexual aggression perpetration for women. The findings contribute to the understanding of gendered effects of CSA on revictimization and the victim-to-perpetrator cycle. Copyright © 2016 Elsevier Ltd. All rights reserved.

Endothelin ETA receptor/lipid peroxides/COX-2/TGF-β1 signalling underlies aggravated nephrotoxicity caused by cyclosporine plus indomethacin in rats.

PubMed

Helmy, Maged W; El-Gowelli, Hanan M; Ali, Rabab M; El-Mas, Mahmoud M

2015-09-01

Cyclosporine (CSA) and non-steroidal anti-inflammatory drugs (NSAIDs) are co-prescribed for some arthritic conditions. We tested the hypothesis that this combined regimen elicits exaggerated nephrotoxicity in rats via the up-regulation of endothelin (ET) receptor signalling. The effects of a 10 day treatment with CSA (20 mg · kg(-1) · day(-1)), indomethacin (5 mg · kg(-1) · day(-1)) or their combination on renal biochemical, inflammatory, oxidative and structural profiles were assessed. The roles of ETA receptor and COX-2 pathways in the interaction were evaluated. Oral treatment with CSA or indomethacin elevated serum urea and creatinine, caused renal tubular atrophy and interstitial fibrosis, increased renal TGF-β1, and reduced immunohistochemical expressions of ETA receptors and COX-2. CSA, but not indomethacin, increased renal ET-1, the lipid peroxidation product malondialdehyde (MDA) and GSH activity. Compared with individual treatments, simultaneous CSA/indomethacin exposure caused: (i) greater elevations in serum creatinine and renal MDA; (ii) loss of the compensatory increase in GSH; (iii) renal infiltration of inflammatory cells and worsening of fibrotic and necrotic profiles; and (iv) increased renal ET-1 and decreased ETA receptor and COX-2 expressions. Blockade of ETA receptors by atrasentan ameliorated the biochemical, structural, inflammatory and oxidative abnormalities caused by the CSA/indomethacin regimen. Furthermore, atrasentan partly reversed the CSA/indomethacin-evoked reductions in the expression of ETA receptor and COX-2 protein. The exaggerated oxidative insult and associated dysregulation of the ETA receptor/COX-2/TGF-β1 signalling might account for the aggravated nephrotoxicity caused by the CSA/indomethacin regimen. The potential renoprotective effect of ETA receptor antagonism might be exploited therapeutically. © 2015 The British Pharmacological Society.

In vitro evaluation of the potential for resistance development to ceragenin CSA-13

PubMed Central

Pollard, Jake E.; Snarr, Jason; Chaudhary, Vinod; Jennings, Jacob D.; Shaw, Hannah; Christiansen, Bobbie; Wright, Jonathan; Jia, Wenyi; Bishop, Russell E.; Savage, Paul B.

2012-01-01

Objectives Though most bacteria remain susceptible to endogenous antimicrobial peptides, specific resistance mechanisms are known. As mimics of antimicrobial peptides, ceragenins were expected to retain antibacterial activity against Gram-positive and -negative bacteria, even after prolonged exposure. Serial passaging of bacteria to a lead ceragenin, CSA-13, was performed with representative pathogenic bacteria. Ciprofloxacin, vancomycin and colistin were used as comparators. The mechanisms of resistance in Gram-negative bacteria were elucidated. Methods Susceptible strains of Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii were serially exposed to CSA-13 and comparators for 30 passages. MIC values were monitored. Alterations in the Gram-negative bacterial membrane composition were characterized via mass spectrometry and the susceptibility of antimicrobial-peptide-resistant mutants to CSA-13 was evaluated. Results S. aureus became highly resistant to ciprofloxacin after <20 passages. After 30 passages, the MIC values of vancomycin and CSA-13 for S. aureus increased 9- and 3-fold, respectively. The Gram-negative organisms became highly resistant to ciprofloxacin after <20 passages. MIC values of colistin for P. aeruginosa and A. baumannii increased to ≥100 mg/L after 20 passages. MIC values of CSA-13 increased to ∼20–30 mg/L and plateaued over the course of the experiment. Bacteria resistant to CSA-13 displayed lipid A modifications that are found in organisms resistant to antimicrobial peptides. Conclusions CSA-13 retained potent antibacterial activity against S. aureus over the course of 30 serial passages. Resistance generated in Gram-negative bacteria correlates with modifications to the outer membranes of these organisms and was not stable outside of the presence of the antimicrobial. PMID:22899801

Child sexual abuse in Lebanon during war and peace.

PubMed

Usta, J; Farver, J

2010-05-01

Child sexual abuse (CSA) is rarely addressed in the Arab world. This study examined the prevalence, risk factors and consequences associated with CSA in Lebanese children before, during and after the 2006 Hezbollah-Israeli war. A total of 1028 Lebanese children (556 boys; 472 girls) were administered an interview questionnaire that included the International Child Abuse Screening Tool, the Trauma Symptom Checklist and the Family Functioning in Adolescence Questionnaire. In total, 249 (24%) children reported at least one incident of CSA; 110 (11%) occurred before the war, 90 (8%) took place in the 1-year period after the war to the time of the data collection and 49 (5%) occurred during the 33-day war. There were no gender differences in CSA reports before or after the war, but boys reported more incidents during the war than did girls. Girls who reported CSA had higher trauma-related symptoms for sleep disturbance, somatization, Post Traumatic Stress Disorder (PTSD) and anxiety than did boys. There were geographic differences in the reports of abuse that may be associated with poverty and living standards. Logistic regression analyses correctly classified 89.9% of the cases and indicated that children's age, family size, fathers' education level and family functioning significantly predicted CSA during the period following the war. The prevalence of CSA in the current study is within the reported international range. Given the increase in the incidents of CSA during the war and the significant findings for family-related risk factors, there is an urgent need to provide multi-component culturally appropriate interventions that target the child and the family system in times of peace and conflict.

Changes in cross-sectional area of pulmonary vessels on chest computed tomography after chemotherapy in patients with advanced non-squamous non-small-cell lung cancer.

PubMed

Karayama, Masato; Inui, Naoki; Kusagaya, Hideki; Suzuki, Seiichiro; Inoue, Yusuke; Enomoto, Noriyuki; Fujisawa, Tomoyuki; Nakamura, Yutaro; Suda, Takafumi

2016-05-01

Chemotherapy is associated with a risk of vascular damage. Novel anti-angiogenic agents, which can directly affect tumor angiogenesis, are increasingly being used. However, the effects of these agents on normal vasculature are not well understood. Here, we evaluated the effects of chemotherapy in general, and the anti-angiogenic agent bevacizumab, more specifically, on the pulmonary vasculature in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). For this, we used the cross-sectional area of pulmonary vessels (CSA), which is an easily measurable indicator of small pulmonary vasculature on non-contrast chest computed tomography (CT). We retrospectively reviewed CT scans of the lungs of 75 chemo-naïve patients with advanced non-squamous NSCLC, for measurement of CSA, before and after first-line platinum-based chemotherapy, using a semi-automatic image-processing program. Measured vessels were classified in two groups: small vessels with CSA <5 mm(2) and large vessels with CSA between 5 and 10 mm(2). The CSAs for each group of vessels were calculated and summed separately, and expressed as a percentage of the total lung area (%CSA<5 and %CSA5-10). Chemotherapy was associated with a selective decrease in small-diameter vessels, with a significant decrease in %CSA<5, but not %CSA5-10. When comparing chemotherapy with bevacizumab (n = 38) and without bevacizumab (n = 37), there was no significant difference in the reduction of %CSA<5. Platinum-based chemotherapy might induce small pulmonary vascular damage. Use of bevacizumab does not enhance the reduction in area of pulmonary vessels.

Attenuation of cyclosporine A toxicity by sublethal heat shock. Role of catalase.

PubMed

Andrés, David; Bautista, Mirandeli; Cascales, María

2005-02-01

Cyclosporine A (CsA) is the immunosuppressor most frequently used in transplant surgery and in the treatment of autoimmune diseases because of its specific inhibiting effect on signal transduction pathways of cell T receptor. It has been shown that CsA is able to generate reactive oxygen species and lipid peroxidation, which are directly involved in the CsA hepatotoxicity. In the present study, we investigated the effect of a sublethal heat pre-treatment (43 degrees C for 30 min) on the hepatoma cell line HepG2 exposed to cytotoxic concentrations of CsA (10 and 25 microM) for 3 and 24 h. Parameters of cytotoxicity were assayed by measuring LDH (lactate dehydrogenase) leakage into the medium. Peroxide concentration was tested by flow cytometry by measuring the fluorescence intensity of DCF (dichlorofluorescein). Gene expression of catalase was detected by measuring the respective mRNA and proteins, as well as protein level of HSP70. The enzymatic activity of catalase was also determined. Heat pre-treatment significantly reduced CsA cytotoxicity as well as the level of peroxide generation. The protective effect of the previous heat treatment (corroborated by the irreversible catalase inhibitor 3-aminotriazole) against the CsA cytotoxicity was due to an increased expression and activity of catalase that was significantly reduced by the effect of CsA. We conclude that heat pre-treatment strongly protects against CsA injury, and the mechanism of this protection is by means of inducing not only the expression of HSP70 but also the expression and activity of catalase, the main enzyme system involved in H(2)O(2) elimination.

A Comparison of Ultrasound and MRI Measurements of the Cross-Sectional Area of the Median Nerve at the Wrist.

PubMed

Hersh, Beverly; D'Auria, Jennifer; Scott, Michael; Fowler, John R

2018-05-01

Ultrasound (US) measurement of cross-sectional area (CSA) of the median nerve has emerged as a viable alternative to electromyography/nerve conduction studies (EMG/NCS) for diagnosis of carpal tunnel syndrome (CTS). The purpose of this study is to compare CSA of the median nerve between US and MRI using current MRI and US technology. The null hypothesis is there is no difference between US and MRI CSA measurements. The study design was an observational cohort, enrolling patients presenting to clinic with MRI of the wrist. Participants with clinical signs and symptoms of CTS were excluded. The CSA measurements of the median nerve on MRI T1-weighted axial images were performed by a hand fellow blinded to results of US measurements, and US measurement of median nerve CSA was performed by a hand fellowship trained surgeon blinded to results of the MRI measurements. Results were analyzed via percent error, Pearson correlation, and t tests. Twenty participants were enrolled with mean age of 29.4 years. Four left wrists and 16 right wrists were measured. The US mean CSA of the median nerve was 6.8 mm 2 (±2.330 mm 2 ). The MRI mean CSA of the median nerve was 6.8 mm 2 (±2.153 mm 2 ), P = .442. Pearson correlation between modalities was 0.93, suggesting near-perfect correlation. Mean percent error was 8.8%. Results of this study suggest that US is an accurate method to measure CSA of the median nerve at the carpal tunnel inlet. The mean difference between US and MRI was unlikely to be clinically significant.

Post-Traumatic Symptomatology and Compulsions as Potential Mediators of the Relation Between Child Sexual Abuse and Auditory Verbal Hallucinations.

PubMed

McCarthy-Jones, Simon

2018-05-01

Whilst evidence is mounting that childhood sexual abuse (CSA) can be a cause of auditory verbal hallucinations (AVH), it is unclear what factors mediate this relation. Recent evidence suggests that post-traumatic symptomatology may mediate the CSA-AVH relation in clinical populations, although this hypothesis has not yet been tested in the general population. There is also reason to believe that obsessive ideation could mediate the CSA-AVH relation. To test for evidence to falsify the hypotheses that post-traumatic symptomatology, obsessions, compulsions, anxiety and depression mediate the relation between CSA and AVH in a general population sample. Indirect effects of CSA on AVH via potential mediators were tested for, using a regression-based approach employing data from the 2007 Adult Psychiatric Morbidity Survey (n = 5788). After controlling for demographics, IQ and child physical abuse, it was found that CSA, IQ, post-traumatic symptomatology and compulsions predicted lifetime experience of AVH. Mediation analyses found significant indirect effects of CSA on AVH via post-traumatic symptomatology [odds ratio (OR): 1.11; 95% confidence interval (CI):1.00-1.29] and compulsions (OR: 1.10, 95% CI: 1.01-1.28). These findings offer further support for the hypothesis that post-traumatic symptomatology is a mediator of the CSA-AVH relation. Although no evidence was found for obsessional thoughts as a mediating variable, a potential mediating role for compulsions is theoretically intriguing. This study's findings reiterate the need to ask about experiences of childhood adversity and post-traumatic symptomology in people with AVH, as well as the likely therapeutic importance of trauma-informed and trauma-based interventions for this population.

VAR2CSA signatures of high Plasmodium falciparum parasitemia in the placenta.

PubMed

Rovira-Vallbona, Eduard; Monteiro, Isadora; Bardají, Azucena; Serra-Casas, Elisa; Neafsey, Daniel E; Quelhas, Diana; Valim, Clarissa; Alonso, Pedro; Dobaño, Carlota; Ordi, Jaume; Menéndez, Clara; Mayor, Alfredo

2013-01-01

Plasmodium falciparum infected erythrocytes (IE) accumulate in the placenta through the interaction between Duffy-binding like (DBL) domains of parasite-encoded ligand VAR2CSA and chondroitin sulphate-A (CSA) receptor. Polymorphisms in these domains, including DBL2X and DBL3X, may affect their antigenicity or CSA-binding affinity, eventually increasing parasitemia and its adverse effects on pregnancy outcomes. A total of 373 DBL2X and 328 DBL3X sequences were obtained from transcripts of 20 placental isolates infecting Mozambican women, resulting in 176 DBL2X and 191 DBL3X unique sequences at the protein level. Sequence alignments were divided in segments containing combinations of correlated polymorphisms and the association of segment sequences with placental parasite density was tested using Bonferroni corrected regression models, taking into consideration the weight of each sequence in the infection. Three DBL2X and three DBL3X segments contained signatures of high parasite density (P<0.003) that were highly prevalent in the parasite population (49-91%). Identified regions included a flexible loop that contributes to DBL3X-CSA interaction and two DBL3X motifs with evidence of positive natural selection. Limited antibody responses against signatures of high parasite density among malaria-exposed pregnant women could not explain the increased placental parasitemia. These results suggest that a higher binding efficiency to CSA rather than reduced antigenicity might provide a biological advantage to parasites with high parasite density signatures in VAR2CSA. Sequences contributing to high parasitemia may be critical for the functional characterization of VAR2CSA and the development of tools against placental malaria.

Limited value of cyclosporine A for the treatment of patients with uveitis associated with juvenile idiopathic arthritis.

PubMed

Tappeiner, C; Roesel, M; Heinz, C; Michels, H; Ganser, G; Heiligenhaus, A

2009-05-01

Juvenile idiopathic arthritis (JIA) is often associated with severe chronic anterior uveitis (CAU), and immunosuppressive therapy may be required. In this study, the value of cyclosporine A (CsA) as monotherapy or as combination therapy for treating uveitis was studied in a large cohort of JIA children. Multicentre retrospective study including 82 JIA children (girls n=60) suffering from unilateral or bilateral (n=55) CAU. The indication for CsA was active uveitis, although patients were on topical or systemic corticosteroids, MTX, or other immunosuppressive drugs. Inactivity of uveitis during the entire treatment period (mean 3.9 years) was obtained with CsA monotherapy in 6 of 25 (24%) patients, but more often when CsA was combined with the immunosuppressives (35/72 patients; 48.6%, P=0.037), or MTX (18/37 patients, 48.6%, P=0.065), which had already been given. With CsA (mean dosage 2.9 mg/kg), systemic immunosuppressive drugs and steroids could be reduced by >or=50% (n=19) or topical steroids reduced to

The process of coping with domestic violence in adult survivors of childhood sexual abuse.

PubMed

Griffing, Sascha; Lewis, Carla S; Jospitre, Tania; Chu, Melissa; Sage, Robert; Primm, Beny J; Madry, Lorraine

2006-01-01

Research suggests that the use of disengaged or avoidant strategies to cope with interpersonal violence contributes to the development of depressive symptoms and other psychological difficulties. Survivors of childhood sexual abuse (CSA) who are exposed to subsequent episodes of abuse may be more likely to rely on disengaged coping strategies, placing them at elevated risk of psychological symptomatology. In this study, we explored the interrelationships between coping, depression, and self-esteem in an ethnically diverse sample of domestic violence survivors (N = 219) with and without a history of CSA. As predicted, CSA survivors (n = 86) reported significantly greater use of disengaged coping strategies (wishful thinking, self-criticism, and social withdrawal) than non-CSA survivors (n = 133). As hypothesized, both a CSA history and the use of disengaged coping significantly predicted higher levels of depression and lower self- esteem. Clinical implications of the findings are discussed.

Voltage stability index based optimal placement of static VAR compensator and sizing using Cuckoo search algorithm

NASA Astrophysics Data System (ADS)

Venkateswara Rao, B.; Kumar, G. V. Nagesh; Chowdary, D. Deepak; Bharathi, M. Aruna; Patra, Stutee

2017-07-01

This paper furnish the new Metaheuristic algorithm called Cuckoo Search Algorithm (CSA) for solving optimal power flow (OPF) problem with minimization of real power generation cost. The CSA is found to be the most efficient algorithm for solving single objective optimal power flow problems. The CSA performance is tested on IEEE 57 bus test system with real power generation cost minimization as objective function. Static VAR Compensator (SVC) is one of the best shunt connected device in the Flexible Alternating Current Transmission System (FACTS) family. It has capable of controlling the voltage magnitudes of buses by injecting the reactive power to system. In this paper SVC is integrated in CSA based Optimal Power Flow to optimize the real power generation cost. SVC is used to improve the voltage profile of the system. CSA gives better results as compared to genetic algorithm (GA) in both without and with SVC conditions.

Autobiographical Memory Specificity in Child Sexual Abuse Victims

PubMed Central

Ogle, Christin M.; Block, Stephanie D.; Harris, LaTonya S.; Goodman, Gail S.; Pineda, Annarheen; Timmer, Susan; Urquiza, Anthony; Saywitz, Karen J.

2013-01-01

The present study examined the specificity of autobiographical memory in adolescents and adults with versus without child sexual abuse (CSA) histories. Eighty-five participants, approximately half of whom per age group had experienced CSA, were tested on the Autobiographical Memory Interview. Individual difference measures, including for trauma-related psychopathology, were also administered. Findings revealed developmental differences in the relation between autobiographical memory specificity and CSA. Even with depression statistically controlled, reduced memory specificity in CSA victims relative to controls was observed among adolescents but not among adults. A higher number of Posttraumatic Stress Disorder criteria met predicted more specific childhood memories in participants who reported CSA as their most traumatic life event. These findings contribute to the scientific understanding of childhood trauma and autobiographical memory functioning and underscore the importance of considering the role of age and degree of traumatization within the study of autobiographical memory. PMID:23627947

Prevention of child sexual abuse: evaluation of a community media campaign.

PubMed

Rheingold, Alyssa A; Campbell, Carole; Self-Brown, Shannon; de Arellano, Michael; Resnick, Heidi; Kilpatrick, Dean

2007-11-01

Given that mass media techniques have been an effective tool within the public health field for affecting behavioral change, these strategies may prove successful for the primary prevention of child sexual abuse (CSA). This study was an independent evaluation of a CSA media campaign. Two hundred parents were recruited from eight sites across the United States. Results indicated that the combined mass media campaign affected knowledge about CSA at the time of intervention compared to no intervention. No significant differences were found in regards to CSA attitudes. A significant positive impact on primary prevention response behaviors assessed using hypothetical vignettes was found; however, no significant findings were noted for several other behavioral responses. Knowledge and behavioral gains were not maintained at the one-month follow-up. Small sample size at follow-up may have affected findings. Results of this study imply that media campaigns alone may not significantly affect primary prevention of CSA.

Cyclosporin a inhibits T cell-mediated augmentation of mouse natural killer activity.

PubMed

Yanagihara, R H; Adler, W H

1982-06-01

Cyclosporin A (CSA) in vitro inhibited the spontaneous cytotoxic activity of mouse spleen cells against YAC target cells in a 4 hr 51Cr release assay. While natural killer (NK) cells were inhibited directly by CSA, these suppressive effects were largely reversible by coculture of effector cells for an optimal period with polyinosinic-polycytidylic acid (Poly I:C) or lipopolysaccharide (LPS). In contrast concanavalin A (Con A), in the presence of CSA, was unable to augment NK activity. The supernatant, however, of mouse spleen cells cultured with Con A was fully able to augment the NK the activity by freshly cultured spleen cells in the presence of CSA. The results indicate that CSA inhibits NK activity by two distinct mechanisms: a) a direct inactivation of NK cells and b) a suppression of production or release of an NK-activating factor from T cells, but not B cells or macrophages.

Sensitivity Enhancement of an Inductively Coupled Local Detector Using a HEMT-based Current Amplifier

PubMed Central

Qian, Chunqi; Duan, Qi; Dodd, Steve; Koretsky, Alan; Murphy-Boesch, Joe

2015-01-01

Purpose To improve the signal transmission efficiency and sensitivity of a local detection coil that is weakly inductively coupled to a larger receive coil. Methods The resonant detection coil is connected in parallel with the gate of a HEMT transistor without impedance matching. When the drain of the transistor is capacitively shunted to ground, current amplification occurs in the resonator by feedback that transforms a capacitive impedance on the transistor’s source to a negative resistance on its gate. Results High resolution images were obtained from a mouse brain using a small, 11 mm diameter surface coil that was inductively coupled to a commercial, phased array chest coil. Although the power consumption of the amplifier was only 88 µW, 14 dB gain was obtained with excellent noise performance. Conclusion An integrated current amplifier based on a High Electron Mobility Transistor (HEMT) can enhance the sensitivity of inductively coupled local detectors when weakly coupled. This amplifier enables efficient signal transmission between customized user coils and commercial clinical coils, without the need for a specialized signal interface. PMID:26192998

A High Sensitivity Preamplifier for Quartz Tuning Forks in QEPAS (Quartz Enhanced PhotoAcoustic Spectroscopy) Applications

PubMed Central

Starecki, Tomasz

2017-01-01

All the preamplifiers dedicated for Quartz Enhanced PhotoAcoustic Spectroscopy (QEPAS) applications that have so far been reported in the literature have been based on operational amplifiers working in transimpedance configurations. Taking into consideration that QEPAS sensors are based on quartz tuning forks, and that quartz has a relatively high voltage constant and relatively low charge constant, it seems that a transimpedance amplifier is not an optimal solution. This paper describes the design of a quartz QEPAS sensor preamplifier, implemented with voltage amplifier configuration. Discussion of an electrical model of the circuit and preliminary measurements are presented. Both theoretical analysis and experiments show that use of the voltage configuration allows for a substantial increase of the output signal in comparison to the transimpedance circuit with the same tuning fork working in identical conditions. Assuming that the sensitivity of the QEPAS technique depends directly on the properties of the preamplifier, use of the voltage amplifier configuration should result in an increase of QEPAS sensitivity by one to two orders of magnitude. PMID:29099765

A High Sensitivity Preamplifier for Quartz Tuning Forks in QEPAS (Quartz Enhanced PhotoAcoustic Spectroscopy) Applications.

PubMed

Starecki, Tomasz; Wieczorek, Piotr Z

2017-11-03

All the preamplifiers dedicated for Quartz Enhanced PhotoAcoustic Spectroscopy (QEPAS) applications that have so far been reported in the literature have been based on operational amplifiers working in transimpedance configurations. Taking into consideration that QEPAS sensors are based on quartz tuning forks, and that quartz has a relatively high voltage constant and relatively low charge constant, it seems that a transimpedance amplifier is not an optimal solution. This paper describes the design of a quartz QEPAS sensor preamplifier, implemented with voltage amplifier configuration. Discussion of an electrical model of the circuit and preliminary measurements are presented. Both theoretical analysis and experiments show that use of the voltage configuration allows for a substantial increase of the output signal in comparison to the transimpedance circuit with the same tuning fork working in identical conditions. Assuming that the sensitivity of the QEPAS technique depends directly on the properties of the preamplifier, use of the voltage amplifier configuration should result in an increase of QEPAS sensitivity by one to two orders of magnitude.

Endogenous Catalytic Generation of O2 Bubbles for In Situ Ultrasound-Guided High Intensity Focused Ultrasound Ablation.

PubMed

Liu, Tianzhi; Zhang, Nan; Wang, Zhigang; Wu, Meiying; Chen, Yu; Ma, Ming; Chen, Hangrong; Shi, Jianlin

2017-09-26

High intensity focused ultrasound (HIFU) surgery generally suffers from poor precision and low efficiency in clinical application, especially for cancer therapy. Herein, a multiscale hybrid catalytic nanoreactor (catalase@MONs, abbreviated as C@M) has been developed as a tumor-sensitive contrast and synergistic agent (C&SA) for ultrasound-guided HIFU cancer surgery, by integrating dendritic-structured mesoporous organosilica nanoparticles (MONs) and catalase immobilized in the large open pore channels of MONs. Such a hybrid nanoreactor exhibited sensitive catalytic activity toward H 2 O 2 , facilitating the continuous O 2 gas generation in a relatively mild manner even if incubated with 10 μM H 2 O 2 , which finally led to enhanced ablation in the tissue-mimicking PAA gel model after HIFU exposure mainly resulting from intensified cavitation effect. The C@M nanoparticles could be accumulated within the H 2 O 2 -enriched tumor region through enhanced permeability and retention effect, enabling durable contrast enhancement of ultrasound imaging, and highly efficient tumor ablation under relatively low power of HIFU exposure in vivo. Very different from the traditional perfluorocarbon-based C&SA, such an on-demand catalytic nanoreactor could realize the accurate positioning of tumor without HIFU prestimulation and efficient HIFU ablation with a much safer power output, which is highly desired in clinical HIFU application.

Relationship between sensitizer concentration and resist performance of chemically amplified extreme ultraviolet resists in sub-10 nm half-pitch resolution region

NASA Astrophysics Data System (ADS)

Kozawa, Takahiro; Santillan, Julius Joseph; Itani, Toshiro

2017-01-01

The development of lithography processes with sub-10 nm resolution is challenging. Stochastic phenomena such as line width roughness (LWR) are significant problems. In this study, the feasibility of sub-10 nm fabrication using chemically amplified extreme ultraviolet resists with photodecomposable quenchers was investigated from the viewpoint of the suppression of LWR. The relationship between sensitizer concentration (the sum of acid generator and photodecomposable quencher concentrations) and resist performance was clarified, using the simulation based on the sensitization and reaction mechanisms of chemically amplified resists. For the total sensitizer concentration of 0.5 nm-3 and the effective reaction radius for the deprotection of 0.1 nm, the reachable half-pitch while maintaining 10% critical dimension (CD) LWR was 11 nm. The reachable half-pitch was 7 nm for 20% CD LWR. The increase in the effective reaction radius is required to realize the sub-10 nm fabrication with 10% CD LWR.

Child Sexual Abuse, Coping Responses, Self-Blame, Posttraumatic Stress Disorder, and Adult Sexual Revictimization

ERIC Educational Resources Information Center

Filipas, Henrietta H.; Ullman, Sarah E

2006-01-01

The present study examined the psychological sequelae of child sexual abuse (CSA) and the factors that contributed to revictimization in the form of adult sexual assault (ASA) using a survey of 577 female college students. CSA characteristics, maladaptive coping in response to CSA, degree of self-blame at the time of the abuse and currently, and…

Further Understanding the Systemic Effects of Childhood Sexual Abuse: A Comparison of Two Groups of Clinical Couples.

ERIC Educational Resources Information Center

Nelson, Briana S.; Wampler, Karen S.

2002-01-01

Study compared female childhood sexual abuse (CSA) survivors and their male partners with a group of couples reporting no CSA. Both female CSA survivors and their partners reported higher symptoms of stress, suggesting support for the theory of secondary traumatic stress. Relationship impairment results did not support the hypothesis that CSA…

Relationship between diminution of small pulmonary vessels and emphysema in chronic obstructive pulmonary disease.

PubMed

Mashimo, Shuko; Chubachi, Shotaro; Tsutsumi, Akihiro; Kameyama, Naofumi; Sasaki, Mamoru; Jinzaki, Masahiro; Nakamura, Hidetoshi; Asano, Koichiro; Reilly, John J; Betsuyaku, Tomoko

To investigate the relationship between small pulmonary vessels and extent of emphysema on CT in individual lungs with chronic obstructive pulmonary disease (COPD). Forty-nine patients were included. The percentage of cross-sectional area of vessels <5mm 2 (%CSA <5) and extent of emphysema were assessed. Less than half of the COPD patients demonstrated an inverse correlation between %CSA <5 and percentage of low attenuation area (LAA%). In the remaining patients, %CSA <5 was homogeneously distributed. Not all patients with COPD demonstrated an inverse correlation of the distributions between %CSA <5 and LAA% in individual lungs. Copyright © 2017 Elsevier Inc. All rights reserved.

Investigation of Tribological Behavior of a Novel Hybrid Composite Prepared with Al-Coconut Shell Ash Mixed with Graphite

NASA Astrophysics Data System (ADS)

Siva Sankara Raju, R.; Panigrahi, M. K.; Ganguly, R. I.; Srinivasa Rao, G.

2017-08-01

The present investigation develops a next-generation hybrid Al metal matrix composite using coconut shell ash (CSA) and graphite (Gr) reinforcement. Stir-casting is adapted to prepare an Al-1100-based composite. Three other composites of Al-Al2O3, Al-Al2O3-Gr, and Al-CSA are prepared that contain equivalent volume fractions of Al2O3, CSA, and Gr. These assist in comparisons among the three composites and the developed hybrid Al-CSA-Gr composite. The study reveals that the addition of 3 pct Gr improves the specific strength, toughness, and tribological properties. The Al-CSA composite shows better mechanical properties, such as tensile strength and hardness, than the other three composites. Gr addition helps the hybrid Al-CSA-Gr composite to attain better tribological properties with a slightly lower specific strength. Scanning electron microscopy studies of the worn material surfaces corroborate the findings of the abrasion testing. Elemental analyses by energy-dispersive X-ray spectroscopy of the debris from the counter-face of the tribo surface confirm the presence of Al, O, Si, Fe, Mn, and C.

Simulating Memory Impairment for Child Sexual Abuse.

PubMed

Newton, Jeremy W; Hobbs, Sue D

2015-08-01

The current study investigated effects of simulated memory impairment on recall of child sexual abuse (CSA) information. A total of 144 adults were tested for memory of a written CSA scenario in which they role-played as the victim. There were four experimental groups and two testing sessions. During Session 1, participants read a CSA story and recalled it truthfully (Genuine group), omitted CSA information (Omission group), exaggerated CSA information (Commission group), or did not recall the story at all (No Rehearsal group). One week later, at Session 2, all participants were told to recount the scenario truthfully, and their memory was then tested using free recall and cued recall questions. The Session 1 manipulation affected memory accuracy during Session 2. Specifically, compared with the Genuine group's performance, the Omission, Commission, or No Rehearsal groups' performance was characterized by increased omission and commission errors and decreased reporting of correct details. Victim blame ratings (i.e., victim responsibility and provocativeness) and participant gender predicted increased error and decreased accuracy, whereas perpetrator blame ratings predicted decreased error and increased accuracy. Findings are discussed in relation to factors that may affect memory for CSA information. Copyright © 2015 John Wiley & Sons, Ltd.

Characterization of Five Fungal Endophytes Producing Cajaninstilbene Acid Isolated from Pigeon Pea [Cajanus cajan (L.) Millsp.

PubMed Central

Zu, Yuan Gang; Fu, Yu Jie; Wang, Wei; Luo, Meng; Efferth, Thomas

2011-01-01

Five fungal endophytes (K4, K5, K6, K9, K14) producing Cajaninstilbene acid (CSA, 3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid) were isolated from the roots of pigeon pea [Cajanus cajan (L.) Millsp.]. CSA is responsible for the prominent pharmacological activities in pigeon pea. The amount of CSA in culture solution varied among the five fungal endophytes. K4 produced the highest levels of CSA (1037.13 µg/L) among the endophytes tested after incubation for five days. Both morphological characteristics and molecular methods were used for species identification of fungal endophytes. The five endophytic isolates were characterized by analyzing the internal transcribed spacer (ITS) rRNA and β-tubulin genes. The K4, K5, K9 and K14 strains isolated from pigeon pea roots were found to be closely related to the species Fusarium oxysporum. K6 was identified as Neonectria macrodidym. The present study is the first report on the isolation and identification of fungal endophytes producing CSA in pigeon pea. The study also provides a scientific base for large scale production of CSA. PMID:22102911

Incidence of male childhood sexual abuse and psychological sequelae in disaster workers exposed to a terrorist attack.

PubMed

Leck, Pam; Difede, JoAnn; Patt, Ivy; Giosan, Cezar; Szkodny, Lauren

2006-01-01

This study documents the prevalence of male childhood sexual abuse (CSA) and psychological sequelae in a sample of disaster workers deployed to the World Trade Center (WTC) site following the September 11, 2001 terrorist attack. There are limited data on male CSA and its psychological impact, especially on a large non-treatment seeking sample. As part of a mandatory medical screening program, workers were assessed with well-validated and widely used clinician interview and self-report measures following their involvement in the restoration of services to Ground Zero and surrounding areas of lower Manhattan. Frequency of CSA measured by the Traumatic Events Interview (TEI) was 4.3% (n = 92). Clinician interview and self-report data were analyzed using t-tests, revealing statistically significant relationships (but not clinically meaningful scores) between CSA and scores on the CAPS, PCL, BDI, STAXI, and SDS. Further analyses revealed that individuals endorsing CSA were three-times more likely to score high (vs. low) on the BDI and CAPS. Since disaster workers traditionally summon images of strength and mastery, professionals may overlook CSA and symptoms of depression and PTSD in this population.

Cyclosporin A reduces matrix metalloproteinases and collagen expression in dermal fibroblasts from regenerative FOXN1 deficient (nude) mice

PubMed Central

2013-01-01

Background Cyclosporin A (CsA), an immunosuppressive agent modifies the wound healing process through an influence on extracellular matrix metabolism. We have compared the effects of CsA on dermal fibroblasts from nude (FOXN1 deficient) mice, a genetic model of skin scarless healing, and from control (C57BL/6 J (B6) mice to evaluate metabolic pathways that appear to have important roles in the process of scarless healing/regeneration. Results High levels of matrix metalloproteinases (MMPs) and collagen III expression in dermal fibroblasts from nude (regenerative) mice were down-regulated by CsA treatment to the levels observed in dermal fibroblasts from B6 (non-regenerative) mice. In contrast, dermal fibroblasts from control mice respond to CsA treatment with a minor reduction of Mmps mRNA and 2.5-fold increase expression of collagen I mRNA. An in vitro migratory assay revealed that CsA treatment profoundly delayed the migratory behavior of dermal fibroblasts from both nude and control mice. Conclusion The data suggest that by alternation of the accumulation of extracellular matrix components CsA treatment stimulates the transition from a scarless to a scar healing. PMID:23547542

Teachers' knowledge, attitudes and experience in sexual abuse prevention education in El Salvador.

PubMed

Hurtado, Alicia; Katz, Craig; Ciro, Dianne; Guttfreund, Daniel

2013-01-01

Research on how to prevent child sexual abuse (CSA) in developing nations is practically non-existent. We sought to determine Salvadoran teachers' knowledge, attitudes, experience and barriers to CSA detection and reporting to assess the need for a CSA prevention programme and to assess barriers in conducting such a programme. One hundred teachers completed a questionnaire while they visited the Tin Marin Children's Museum in San Salvador. Nineteen of these teachers also participated in a focus group. We found that 89% of teachers reported at least two signs and symptoms of child abuse. One hundred per cent of teachers agreed that it is their responsibility to teach students about sexual abuse. Unusual for a study of this kind, parental migration was mentioned as making children vulnerable to CSA, and fear of gang violence and retribution was identified as interfering with teachers' ability to protect children. We conclude that Salvadoran teachers were knowledgeable about CSA detection and reporting and would support a programme in which they are trained to speak to their students about this topic. Barriers to reporting child abuse, such as teachers' safety and fear, need to be addressed in future CSA prevention programmes.

Differential effects of immunosuppressive drugs on T-cell motility.

PubMed

Datta, A; David, R; Glennie, S; Scott, D; Cernuda-Morollon, E; Lechler, R I; Ridley, A J; Marelli-Berg, F M

2006-12-01

The best-characterized mechanism of the action of immunosuppressive drugs is to prevent T-cell clonal expansion, thus containing the magnitude of the ensuing immune response. As T-cell recruitment to the inflammatory site is another key step in the development of T-cell-mediated inflammation, we analyzed and compared the effects of two commonly used immunosuppressants, cyclosporin A (CsA) and the rapamycin-related compound SDZ-RAD, on the motility of human CD4+ T cells. We show that CsA, but not SDZ-RAD, inhibits T-cell transendothelial migration in vitro. CsA selectively impaired chemokine-induced T-cell chemotaxis while integrin-mediated migration was unaffected. The inhibition of T-cell chemotaxis correlated with reduced AKT/PKB but not ERK activation following exposure to the chemokine CXCL-12/SDF-1. In addition, CsA, but not SDZ-RAD, prevents some T-cell receptor-mediated effects on T-cell motility. Finally, we show that CsA, but not SDZ-RAD inhibits tissue infiltration by T cells in vivo. Our data suggest a prominent antiinflammatory role for CsA in T-cell-mediated tissue damage, by inhibiting T-cell trafficking into tissues in addition to containing clonal expansion.

Disrupted reinforcement learning and maladaptive behavior in women with a history of childhood sexual abuse: a high-density event-related potential study.

PubMed

Pechtel, Pia; Pizzagalli, Diego A

2013-05-01

Childhood sexual abuse (CSA) has been associated with psychopathology, particularly major depressive disorder (MDD), and high-risk behaviors. Despite the epidemiological data available, the mechanisms underlying these maladaptive outcomes remain poorly understood. We examined whether a history of CSA, particularly in conjunction with a past episode of MDD, is associated with behavioral and neural dysfunction in reinforcement learning, and whether such dysfunction is linked to maladaptive behavior. Participants completed a clinical evaluation and a probabilistic reinforcement task while 128-channel event-related potentials were recorded. Academic setting; participants recruited from the community. Fifteen women with a history of CSA and remitted MDD (CSA + rMDD), 16 women with remitted MDD with no history of CSA (rMDD), and 18 healthy women (controls). Three or more episodes of coerced sexual contact (mean [SD] duration, 3.00 [2.20] years) between the ages of 7 and 12 years by at least 1 male perpetrator. Participants' preference for choosing the most rewarded stimulus and avoiding the most punished stimulus was evaluated. The feedback-related negativity and error-related negativity-hypothesized to reflect activation in the anterior cingulate cortex-were used as electrophysiological indices of reinforcement learning. No group differences emerged in the acquisition of reinforcement contingencies. In trials requiring participants to rely partially or exclusively on previously rewarded information, the CSA + rMDD group showed (1) lower accuracy (relative to both controls and the rMDD group), (2) blunted electrophysiological differentiation between correct and incorrect responses (relative to controls), and (3) increased activation in the subgenual anterior cingulate cortex (relative to the rMDD group). A history of CSA was not associated with impairments in avoiding the most punished stimulus. Self-harm and suicidal behaviors correlated with poorer performance of previously rewarded, but not previously punished, trials. Irrespective of past MDD episodes, women with a history of CSA showed neural and behavioral deficits in utilizing previous reinforcement to optimize decision making in the absence of feedback (blunted "Go learning"). Although our study provides initial evidence for reward-specific deficits associated with CSA, future research is warranted to determine if disrupted positive reinforcement learning predicts high-risk behavior following CSA.

A fast, low power and low noise charge sensitive amplifier ASIC for a UV imaging single photon detector

NASA Astrophysics Data System (ADS)

Seljak, A.; Cumming, H. S.; Varner, G.; Vallerga, J.; Raffanti, R.; Virta, V.

2017-04-01

NASA has funded, through their Strategic Astrophysics Technology (SAT) program, the development of a cross strip (XS) microchannel plate (MCP) detector with the intention to increase its technology readiness level (TRL), enabling prototyping for future NASA missions. One aspect of the development is to convert the large and high powered laboratory Parallel Cross Strip (PXS) readout electronics into application specific integrated circuits (ASICs) to decrease their mass, volume, and power consumption (all limited resources in space) and to make them more robust to the environments of rocket launch and space. The redesign also foresees to increase the overall readout event rate, and decrease the noise contribution of the readout system. This work presents the design and verification of the first stage for the new readout system, the 16 channel charge sensitive amplifier ASIC, called the CSAv3. The single channel amplifier is composed of a charge sensitive amplifier (pre-amplifier), a pole zero cancellation circuit and a shaping amplifier. An additional output stage buffer allows polarity selection of the output analog signal. The operation of the amplifier is programmable via serial bus. It provides an equivalent noise charge (ENC) of around 600 e^- and a baseline gain of 10 mV/fC. The full scale pulse shaped output signal is confined within 100 ns, without long recovery tails, enabling up to 10 MHz periodic event rates without signal pile up. This ASIC was designed and fabricated in 130 nm, TSMC CMOS 1.2 V technology. In addition, we briefly discuss the construction of the readout system and plans for the future work.

Afatinib demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro and in vivo.

PubMed

Schwab, C L; Bellone, S; English, D P; Roque, D M; Lopez, S; Cocco, E; Nicoletti, R; Bortolomai, I; Bonazzoli, E; Ratner, E; Silasi, D-A; Azodi, M; Schwartz, P E; Rutherford, T J; Santin, A D

2014-10-28

Uterine serous carcinomas (USCs) are an aggressive form of uterine cancer that may rely on HER2/neu amplification as a driver of proliferation. The objective of this paper is to assess the sensitivity of USC cell lines with and without HER2/neu gene amplification to afatinib, an irreversible ErbB tyrosine kinase inhibitor, and to test the efficacy of afatinib in the treatment of HER2-amplified USC xenografts. Eight of fifteen primary USC cell lines (four with HER2 amplification and four without) demonstrating similar in vitro growth rates were treated with scalar concentrations of afatinib. Effects on cell growth, signalling and cell cycle distribution were determined by flow cytometry assays. Mice harbouring xenografts of HER2/neu-amplified USC were treated with afatinib by gavage to determine the effect on tumour growth and overall survival. Primary chemotherapy-resistant USC cell lines harbouring HER2/neu gene amplification were exquisitely sensitive to afatinib exposure (mean ± s.e.m. IC50=0.0056 ± 0.0006 μM) and significantly more sensitive than HER2/neu-non-amplified USC cell lines (mean ± s.e.m. IC50=0.563 ± 0.092 μM, P<0.0001). Afatinib exposure resulted in abrogation of cell survival, inhibition of HER2/neu autophosphorylation and S6 transcription factor phosphorylation in HER2/neu overexpressing USC and inhibited the growth of HER2-amplified tumour xenografts improving overall survival (P=0.0017). Afatinib may be highly effective against HER2/neu-amplified chemotherapy-resistant USC. The investigation of afatinib in patients harbouring HER2/neu-amplified USC is warranted.

Analysis of DNA Cytosine Methylation Patterns Using Methylation-Sensitive Amplification Polymorphism (MSAP).

PubMed

Guevara, María Ángeles; de María, Nuria; Sáez-Laguna, Enrique; Vélez, María Dolores; Cervera, María Teresa; Cabezas, José Antonio

2017-01-01

Different molecular techniques have been developed to study either the global level of methylated cytosines or methylation at specific gene sequences. One of them is the methylation-sensitive amplified polymorphism technique (MSAP) which is a modification of amplified fragment length polymorphism (AFLP). It has been used to study methylation of anonymous CCGG sequences in different fungi, plants, and animal species. The main variation of this technique resides on the use of isoschizomers with different methylation sensitivity (such as HpaII and MspI) as a frequent-cutter restriction enzyme. For each sample, MSAP analysis is performed using both EcoRI/HpaII- and EcoRI/MspI-digested samples. A comparative analysis between EcoRI/HpaII and EcoRI/MspI fragment patterns allows the identification of two types of polymorphisms: (1) methylation-insensitive polymorphisms that show common EcoRI/HpaII and EcoRI/MspI patterns but are detected as polymorphic amplified fragments among samples and (2) methylation-sensitive polymorphisms which are associated with the amplified fragments that differ in their presence or absence or in their intensity between EcoRI/HpaII and EcoRI/MspI patterns. This chapter describes a detailed protocol of this technique and discusses the modifications that can be applied to adjust the technology to different species of interest.

A search for the production of direct leptons in nucleon-nucleus and nucleus-nucleus collisions

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

Kirk, P.N.

1990-12-01

This report discusses the following topics: subthreshold production experiment; testing and selection of PCOS amplifiers; transverse energy detector; development of a sensitive new amplifiers; single-lepton experiment. (LSP)

Prevalence of childhood sexual abuse in a community sample of Australian women.

PubMed

Fleming, J M

1997-01-20

To ascertain the prevalence of childhood sexual abuse (CSA) in a community sample of Australian women. Retrospective study, done in 1994, of cross-sectional data on the prevalence of CSA, collected as part of a larger two-stage case-control study of the possible relationship between CSA and alcohol abuse. Data were appropriately weighted to adjust for the different selection probabilities of cases and controls. 710 Women randomly selected from Australian federal electoral rolls. One hundred and forty-four women (20%) had experienced CSA. In 14 of these 144 women (10%), the abuse involved either vaginal or anal intercourse (i.e., 2% of the sample population experienced such abuse). The mean age at first episode of CSA was 10 years, and most (71%) of the women were aged under 12 years at the time. Perpetrators of the abuse were usually male (98%) and usually known to the child; 41% were relatives. The mean age of abusers was 34 years, with a median age difference of 24 years from that of the abused individual. Only 10% of CSA experiences were ever reported to the police, a doctor or a helping agency (e.g., community organisations, such as sexual assault services). The high rates of CSA (estimated to be 20% of all women) and low rates of reporting (10%) indicate the need for general practitioners and other health professionals to be aware that a history of such abuse may be common in women in the general population.

A novel dietary improvement strategy: examining the potential impact of community-supported agriculture membership.

PubMed

Vasquez, Angie; Sherwood, Nancy E; Larson, Nicole; Story, Mary

2016-10-01

To investigate the use of community-supported agriculture (CSA) as an employer-based health promotion intervention. Quasi-experimental study using a convenience sample of employees at three employers. Participants and controls from three Minnesota employers completed baseline and follow-up health assessments and surveys about their experiences with CSA. A total of 324 participants purchased a CSA share and were eligible for study inclusion. Study participants were matched by age, sex, employer and occupation to a non-randomized control group of individuals who did not purchase a CSA share but completed health assessments during the same time frame as the study participants. The majority of participants were female, white, middle-aged and highly educated. The most common reason for purchasing a CSA share was a desire for fresh food, and the majority of participants were satisfied with their experience. Participants reported a significant increase in the number of vegetables present in the household and the frequency of family meals. The frequency of eating out decreased significantly, especially at fast-food restaurants. Participants also reported an increase in the amount and variety of produce consumed. However, health assessment data did not show significant changes in dietary intake, health status or BMI. CSA participation was associated with improvement in some aspects of the household environment and dietary behaviours. Further research is needed to determine whether employer-based CSA interventions may also lead to improvements in dietary intake and health.

Sirolimus and tacrolimus rather than cyclosporine A cause bone loss in healthy adult male rats.

PubMed

Rubert, Mercedes; Montero, Mercedes; Guede, David; Caeiro, Jose-Ramón; Martín-Fernández, Marta; Díaz-Curiel, Manuel; de la Piedra, Concepción

2015-06-01

The aim of this work was to study the effects of cyclosporine (CsA), tacrolimus (FK-506), and rapamycin (RAPA) on bone mass, femoral microstructure, femoral biomechanical properties, and bone remodeling in healthy adult male rats. Forty-eight 5-month-old male Wistar rats were used. CsA (2 mg/kg/day), FK-506 (3 mg/kg/day), RAPA (1.25 mg/kg/day), or water (0.5 ml/rat/day, control group) were administered orally for 3 months. After sacrifice, mean values of immunosuppressants in blood were: CsA (670.4 ng/ml), FK-506 (19.2 ng/ml), and RAPA (4.8 ng/ml). Levels of biochemical parameters were normal in all groups. Femoral BMD was decreased in FK-506 and RAPA groups and lumbar BMD in FK-506 group. Trabecular volume fraction (BV/TV) decreased only in FK-506 group. RAPA and CsA affected femoral cortical structure, but FK-506 did not. FK-506 produced an increase in bone remodeling, and CsA a decrease. FK-506 group showed a decrease in biomechanical parameters relative to all groups. RAPA group showed a decrease in ultimate stress vs control group, and CsA group presented an increase in biomechanical parameters versus control group. We found that administration of both RAPA and FK-506 as monotherapy for healthy rats produced osteopenia. CsA treatment only produces slight damages in the cortical zone of the femur.

Psychological counseling and accuracy of memory for child sexual abuse.

PubMed

Goodman, Gail S; Goldfarb, Deborah; Quas, Jodi A; Lyon, Alexandra

2017-12-01

Tens of thousands of child sexual abuse (CSA) cases are reported to authorities annually. Although some of the child victims obtain psychological counseling or therapy, controversy exists about the potential consequences for the accuracy of victims' memory of CSA, both in childhood and adulthood. Yet, delaying needed therapeutic intervention may have detrimental effects on the victims' well-being and recovery. To address this controversy, this study examined whether psychological counseling during a CSA prosecution predicts accuracy or inaccuracy of long-term memory for CSA. Participants (N = 71) were CSA victims who took part in a longitudinal study of memory and legal involvement. Data regarding participants' counseling attendance during the prosecution and details of their CSA cases were gathered throughout legal involvement and shortly thereafter (Time 1). Ten to 16 years later (Time 2), participants were questioned about a range of topics, including the alleged abuse. Time 1 counseling attendance significantly predicted more correct answers to abuse-related questions and (for corroborated cases) fewer overreporting responses at Time 2. Counseling was unrelated to underreporting responses. These results held even with other potential influences, such as abuse severity, victim-defendant relationship, posttraumatic stress disorder criteria met, testifying in the case, and delay, were statistically controlled. Although further research is needed, this study provides evidence that psychological counseling received by CSA victims during or shortly after prosecutions may improve later memory for abuse-related information. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Structure of the DBL3X-DBL4ε region of the VAR2CSA placental malaria vaccine candidate: insight into DBL domain interactions

PubMed Central

Gangnard, Stéphane; Lewit-Bentley, Anita; Dechavanne, Sébastien; Srivastava, Anand; Amirat, Faroudja; Bentley, Graham A.; Gamain, Benoît

2015-01-01

The human malaria parasite, Plasmodium falciparum, is able to evade spleen-mediated clearing from blood stream by sequestering in peripheral organs. This is due to the adhesive properties conferred by the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family exported by the parasite to the surface of infected erythrocytes. Expression of the VAR2CSA variant of PfEMP1 leads to pregnancy-associated malaria, which occurs when infected erythrocytes massively sequester in the placenta by binding to low-sulfated Chondroitin Sulfate A (CSA) present in the intervillous spaces. VAR2CSA is a 350 kDa protein that carries six Duffy-Binding Like (DBL) domains, one Cysteine-rich Inter-Domain Regions (CIDR) and several inter-domain regions. In the present paper, we report for the first time the crystal structure at 2.9 Å of a VAR2CSA double domain, DBL3X-DBL4ε, from the FCR3 strain. DBL3X and DBL4ε share a large contact interface formed by residues that are invariant or highly conserved in VAR2CSA variants, which suggests that these two central DBL domains (DBL3X-DBL4ε) contribute significantly to the structuring of the functional VAR2CSA extracellular region. We have also examined the antigenicity of peptides corresponding to exposed loop regions of the DBL4ε structure. PMID:26450557

Role of Body Esteem in the Sexual Excitation and Inhibition Responses of Women With and Without a History of Childhood Sexual Abuse

PubMed Central

Kiminik, Chelsea D.; Meston, Cindy M.

2016-01-01

Introduction Women’s sexuality is influenced by their perceptions of their bodies. Negative body appraisals have been implicated in the development and maintenance of sexual concerns in women with a history of childhood sexual abuse (CSA). The sexuality of these women is often expressed in extremes of approach and avoidant sexual tendencies, which have been related to the sexual inhibition and sexual excitation pathways of the dual control model. Aim To test the influence of body esteem on the sexual excitation and inhibition responses of women with and without a history of CSA. Methods One hundred thirty-nine women with CSA and 83 non-abused women reported on their abuse history, depressive symptomology, sexual response, and affective appraisals of their body. Main Outcome Measures Validated self-report measurements of sexual excitation and inhibition responses (Sexual Excitation/Sexual Inhibition Inventory for Women) and body esteem (Body Esteem Scale) were administered. Results Body esteem was significantly associated with sexual inhibition responses of women regardless of CSA history status but was significantly related only to the sexual excitation responses of women with a CSA history. Perceived sexual attractiveness was a unique predictor of sexual excitation in women with a history of CSA. Conclusion Women with a history of CSA have lower body esteem than non-abused women, particularly in self-perceived sexual attractiveness, and these perceptions appear to influence their sexual responses by acting on the sexual excitation and inhibition response pathways. PMID:27692843

Therapeutic Strategies Against Cyclin E1 Amplified Ovarian Cancers

DTIC Science & Technology

2017-10-01

interaction will lead to enhancement of RB/E2F interaction and suppression of E2F- dependent oncogenic activity resulting in activity against CCNE1-amplified...relevant for CCNE1-amplified ovarian tumors which are dependent on hyperactive HR and are sensitive to suppression of BRCA1. 15. SUBJECT TERMS Ovarian...enhancement of RB/E2F interaction and suppression of E2F- dependent oncogenic activity resulting in activity against CCNE1-amplified cells. In the third

On the matter of building high-frequency amplifiers minimally influenced by interstage stray reactances

NASA Astrophysics Data System (ADS)

A, Volkov Y.

2017-01-01

The expedience of building wideband multistage amplifiers, the stages of which are connected with each other so, that the “modes of impedance mismatch” are realized, is justified. Those modes allow us to reduce considerably the sensitivity of amplifier transfer factors to the stray (constructional) capacitances and inductances of interstage circuits. The procedure of synthesizing the schematics of such amplifiers is proposed, the efficiency and clarity of which are provided by using the method of signal graphs.

Highly sensitive LIDAR with a thumb-sized sensor-head built using an optical fiber preamplifier (3)

NASA Astrophysics Data System (ADS)

Inoue, Daisuke; Ichikawa, Tadashi; Matsubara, Hiroyuki; Kagami, Manabu

2013-05-01

We have developed a LIDAR system with a sensor head which, although it includes a scanning mechanism, is less than 20 cc in size. The system is not only small, but is also highly sensitive. Our LIDAR system is based on time-of-flight measurements, and incorporates an optical fiber. The main feature of our system is the utilization of optical amplifiers for both the transmitter and the receiver, and the optical amplifiers enable us to exceed the detection limit set by thermal noise. In conventional LIDAR systems the detection limit is determined by the thermal noise, because the avalanche photo-diodes (APD) and trans-impedance amplifiers (TIA) that they use detect the received signals directly. In the case of our LIDAR system, the received signal is amplified by an optical fiber amplifier before reaching the photo diode and the TIA. Therefore, our LIDAR system boosts the signal level before the weak incoming signal is depleted by thermal noise. There are conditions under which the noise figure for the combination of an optical fiber amplifier and a photo diode is superior to the noise figure for an avalanche photo diode. We optimized the gains of the optical fiber amplifier and the TIA in our LIDAR system such that it would be capable of detecting a single photon. As a result, the detection limit of our system is determined by shot noise. We have previously demonstrated scanning up to a range of 80 m with this LIDAR system with a 2 mm diameter of receiving lens. We improved the optical amplifier and the peak output power of LIDAR was over 10KW. We redesigned the sensor-head and improved coupling efficiency. As a result, we succeeded in scanning over a range of 100 m. This small and highly sensitive measurement technology shows great potential for use in LIDAR.

10 CFR 431.444 - Test procedures for the measurement of energy efficiency.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the following test methods: (1) Single-phase small electric motors: Either IEEE Std 114-2010 or CSA... to 1 horsepower (0.75 kW): Either IEEE Std 112-2004 Test Method A or CSA C747 (incorporated by...): Either IEEE Std 112-2004 Test Method B or CSA C390-10 (incorporated by reference, see § 431.443). [74 FR...

10 CFR 431.444 - Test procedures for the measurement of energy efficiency.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the following test methods: (1) Single-phase small electric motors: Either IEEE Std 114-2010 or CSA... to 1 horsepower (0.75 kW): Either IEEE Std 112-2004 Test Method A or CSA C747 (incorporated by...): Either IEEE Std 112-2004 Test Method B or CSA C390-10 (incorporated by reference, see § 431.443). [74 FR...

Childhood Sexual Abuse and Sexual Risk Behavior among Men and Women Attending a Sexually Transmitted Disease Clinic

ERIC Educational Resources Information Center

Senn, Theresa E.; Carey, Michael P.; Vanable, Peter A.; Coury-Doniger, Patricia; Urban, Marguerite A.

2006-01-01

Childhood sexual abuse (CSA) is associated with a wide range of negative outcomes. The authors investigated the relation between CSA and sexual risk behavior in 827 patients recruited from a sexually transmitted disease (STD) clinic. Overall, CSA was reported by 53% of women and 49% of men and was associated with greater sexual risk behavior,…

Mediators of Childhood Sexual Abuse and High-Risk Sex among Men-Who-Have-Sex-with-Men

ERIC Educational Resources Information Center

Catania, Joseph A.; Paul, Jay; Osmond, Dennis; Folkman, Susan; Pollack, Lance; Canchola, Jesse; Chang, Jason; Neilands, Torsten

2008-01-01

Objective: Mediators of childhood sexual abuse (CSA) and HIV risk behavior were examined for men-who-have-sex-with-men (MSM). Method: Data from a dual frame survey of urban MSM (N = 1078) provided prevalence estimates of CSA, and a test of two latent variable models (defined by partner type) of CSA-risk behavior mediators. Results: A 20%…

Continuous In Situ Measurements of Near Bottom Chemistry and Sediment-Water Fluxes with the Chimney Sampler Array (CSA)

NASA Astrophysics Data System (ADS)

Martens, C. S.; Mendlovitz, H. P.; White, B. L.; Hoer, D.; Sleeper, K.; Chanton, J.; Wilson, R.; Lapham, L.

2011-12-01

The Chimney Sampler Array (CSA) was designed to measure in situ chemical and physical parameters within the benthic boundary layer plus methane and oxygen sediment-water chemical fluxes at upper slope sites in the northern Gulf of Mexico. The CSA can monitor temporal changes plus help to evaluate oceanographic and sub-seafloor processes that can influence the formation and stability of gas hydrates in underlying sediments. The CSA consists of vertical cylinders (chimneys) equipped with internal chemical sensors and with laboratory flume-calibrated washout rates. Chimney washout rates multiplied by chimney mean versus ambient concentrations allow calculation of net O2 and methane sediment-water fluxes. The CSA is emplaced on the seafloor by a ROVARD lander using a ROV for chimney deployments. The CSA presently includes two 30 cm diameter by 90 cm length cylinders that seal against the sediment with lead pellet beanbags; within each chimney cylinder are optode, conductivity and methane sensors. The CSA's data logger platform also includes pressure and turbidity sensors external to the chimneys along with an acoustic Doppler current meter to measure temporal variation in ambient current velocity and direction. The CSA was deployed aboard a ROVARD lander on 9/13/2010 in the northern Gulf of Mexico (Lat. 28 51.28440, Long. 088 29.39421) on biogeochemically active sediments within Block MC-118. A ROV was utilized for chimney deployment away from the ROVARD lander. The CSA monitored temporal changes in water column physical parameters, obtained near-bottom chemical data to compare with pore fluid and sediment core measurements and measured temporal variability in oxygen and methane sediment-water fluxes at two closely spaced stations at MC-118. A continuous, three-week data set was obtained that revealed daily cycles in chemical parameters and episodic flux events. Lower than ambient chimney dissolved O2 concentrations controlled by temporal variability in washout rates were used to calculate sediment O2 demand. Episodic events yielding turbidity spikes produced episodic spikes in chimney methane concentrations and sediment-water fluxes. The robust data set reveals new capabilities for long-term monitoring of near-bottom processes in biogeochemically active, continental margin environments.

Profiles of musculoskeletal development in limbs of college Olympic weightlifters and wrestlers.

PubMed

Kanehisa, H; Fukunaga, T

1999-04-01

To investigate the event-related profiles of musculoskeletal development in weight-categorized athletes, we measured the cross-sectional areas (CSA) of bone and muscle in the forearm, upper arm, lower leg and thigh, using a B-mode ultrasound apparatus, in college Olympic weightlifters (OWL, n = 19) and wrestlers (WR, n = 17) and untrained men (UM, n = 24), whose body masses were within the range from 55 kg to 78 kg. Both bone and muscle CSA at all sites were significantly correlated to the two-thirds power of fat-free mass (FFM(2/3)) with correlation coefficients of 0.430-40.741 (P < 0.05) and 0.608-0.718 (P < 0.05), respectively. Moreover, there were significant correlations between bone and muscle CSA at all sites (r = 0.664-0.829, P < 0.05). Even when bone and muscle CSA were expressed relative value to FFM(2/3), both OWL and WR showed significantly greater values than UM at all sites except for the lower leg. Furthermore, the comparison of the lean (bone + muscle) CSA ratio from site to site indicated a higher distribution of lean tissues in the upper extremities in OWL and WR compared to UM. While there was no significant difference between the two athlete groups in FFM(2/3), OWL showed significantly larger values than WR in the bone CSA of the upper arm and thigh and in the muscle CSA of the lower leg and thigh. However, lean CSA ratios of the upper extremities to the lower ones were significantly higher in WR than in OWL. Thus, the present results indicated that, compared to UM, OWL and WR had a greater lean tissue CSA in limbs, especially in the upper extremities, even when the difference in FFM was normalized. Moreover, the relative distribution of lean tissues in limbs differed between the two weight-categorized athletes in spite of there being no difference in FFM, which may be attributable to their own training regimens and/or competition style.

Investigation of the intestinal permeability of ciclosporin using the in situ technique in rats and the relevance of P-glycoprotein.

PubMed

Zakeri-Milani, Parvin; Valizadeh, Hadi; Islambulchilar, Ziba; Damani, Sanaz; Mehtari, Maryam

2008-01-01

The primary endpoint of this study was to determine the intestinal permeability of ciclosporin (cyclosporine A, CsA, CAS 59865-13-3) using the single-pass intestinal perfusion technique (SPIP) and a range of concentrations in rats. The second objective was to assess the quantitative contribution of P-glycoprotein (P-gp)-mediated efflux in limiting the oral bioavailability of CsA using erythromycin (Ery, CAS 114-07-8) as an inhibitor of P-gp efflux transporter. A solution containing CsA and phenol red either in the presence or in the absence of Ery as a P-gp inhibitor was perfused through a cannulated jejunal segment in rats. Outlet samples were collected every 10 min in micro tubes up to 90 min. Samples were analyzed using a modified reverse phase HPLC method. The mean effective permeability coefficients (Peff) of CsA in concentrations of 5, 10, 15 and 20 micromol/L in the perfusion solution were found to be 2.21 (+/- 0.26) x 10(-4) cm/s, 3.34 (+/- 1.29) x 10(-4) cm/s, 3.12 (+/- 0.23) x 10(-4) cm/s and 2.73 (+/- 0.28) x 10(-4) cm/s, respectively. The corresponding values in the presence of Ery were found to be 3.96 (+/- 1.04) x 10(-4) cm/s, 5.34 (+/- 1.29) x 10(-4) cm/s, 3.72 (+/- 0.21) x 10(-4) cm/s and 4.41 (+/- 0.89) x 10(-4) cm/s, respectively. The two-tailed Student's t-test showed that the intestinal permeability of CsA was significantly increased by Ery in all four CsA concentrations used (P < 0.05). However, there was no significant difference between the Peff values of CsA in different concentrations, indicating that the CsA permeation was independent of the concentration. Therefore it is concluded that at least some part of the observed clinical interaction between Ery and CsA is due to the interaction in absorption level.

LOW-LEVEL DIRECT CURRENT AMPLIFIER

DOEpatents

Kerns, Q.A.

1959-05-01

A d-c amplifier is described. Modulation is provided between a d-c signal and an alternating current to give an output signal proportional to the d- c signal. The circuit has high sensitivity and accuracy. (T.R.H.)

CSA-90 Promotes Bone Formation and Mitigates Methicillin-resistant Staphylococcus aureus Infection in a Rat Open Fracture Model.

PubMed

Mills, Rebecca; Cheng, Tegan L; Mikulec, Kathy; Peacock, Lauren; Isaacs, David; Genberg, Carl; Savage, Paul B; Little, David G; Schindeler, Aaron

2018-06-01

Infection of open fractures remains a significant cause of morbidity and mortality to patients worldwide. Early administration of prophylactic antibiotics is known to improve outcomes; however, increasing concern regarding antimicrobial resistance makes finding new compounds for use in such cases a pressing area for further research. CSA-90, a synthetic peptidomimetic compound, has previously demonstrated promising antimicrobial action against Staphylococcus aureus in rat open fractures. However, its efficacy against antibiotic-resistant microorganisms, its potential as a therapeutic agent in addition to its prophylactic effects, and its proosteogenic properties all require further investigation. (1) Does prophylactic treatment with CSA-90 reduce infection rates in a rat open fracture model inoculated with S aureus, methicillin-resistant S aureus (MRSA), and methicillin-resistant Staphylococcus epidermidis (MRSE) as measured by survival, radiographic union, and deep tissue swab cultures? (2) Does CSA-90 reduce infection rates when administered later in the management of an open fracture as measured by survival, radiographic union, and deep tissue swab cultures? (3) Does CSA-90 demonstrate a synergistic proosteogenic effect with bone morphogenetic protein 2 (BMP-2) in a noninfected rat ectopic bone formation assay as assessed by micro-CT bone volume measurement? (4) Can CSA-90 elute and retain its antimicrobial efficacy in vitro when delivered using clinically relevant agents measured using a Kirby-Bauer disc diffusion assay? All in vivo studies were approved by the local animal ethics committee. In the open fracture studies, 12-week-old male Wistar rats underwent open midshaft femoral fractures stabilized with a 1.1-mm Kirschner wire and 10 µg BMP-2 ± 500 µg CSA-90 was applied to the fracture site using a collagen sponge along with 1 x 10 colony-forming units of bacteria (S aureus/MRSA/MRSE; n = 10 per group). In the delayed treatment study, débridement and treatment with 500 µg CSA-90 were performed at Day 1 and Day 5 after injury and bacterial insult (S aureus). All animals were reviewed daily for signs of local infection and/or sepsis. An independent, blinded veterinarian reviewed twice-weekly radiographs, and rats showing osteolysis and/or declining overall health were culled at his instruction. The primary outcome of both fracture studies was fracture infection, incorporating survival, radiographic union, and deep tissue swab cultures. For the ectopic bone formation assay, 0 to 10 µg BMP-2 and 0 to 500 µg CSA-90 were delivered on a collagen sponge into bilateral quadriceps muscle pouches of 8-week-old rats (n = 10 per group). Micro-CT quantification of bone volume and descriptive histologic analysis were performed for all in vivo studies. Modified Kirby-Bauer disc diffusion assays were used to quantify antimicrobial activity in vitro using four different delivery methods, including bone cement. Infection was observed in none of the MRSA inoculated open fractures treated with CSA-90 with 10 of 10 deep tissue swab cultures negative at the time of cull. Median survival was 43 days (range, 11-43 days) in the treated group versus 11 days (range, 8-11 days) in the untreated MRSA inoculated group (p < 0.001). However, delayed débridement and treatment of open fractures with CSA-90 at either Day 1 or Day 5 did not prevent infection, resulting in early culls by Day 21 with positive swab cultures (10 of 10 for each time point). Maximal ectopic bone formation was achieved with 500 μg CSA-90 and 10 μg BMP-2 (mean volume, 9.58 mm; SD, 7.83), creating larger bone nodules than formed with 250 μg CSA-90 and 10 μg BMP-2 (mean volume, 1.7 mm; SD, 1.07; p < 0.001). Disc diffusion assays showed that CSA-90 could successfully elute from four potential delivery agents including calcium sulphate (mean zone of inhibition, 11.35 mm; SD, 0.957) and bone cement (mean, 4.67 mm; SD, 0.516). CSA-90 shows antimicrobial action against antibiotic-resistant Staphylococcal strains in vitro and in an in vivo model of open fracture infection. The antimicrobial properties of CSA-90 combined with further evidence of its proosteogenic potential make it a promising compound to develop further for orthopaedic applications.

Assessment of renal dopaminergic system activity during cyclosporine A administration in the rat.

PubMed Central

Pestana, M.; Vieira-Coelho, M. A.; Pinto-do-O, P. C.; Fernandes, M. H.; Soares-da-Silva, P.

1995-01-01

1. Administration of cyclosporine A (CsA; 50 mg kg-1 day-1, s.c.) for 14 days produced an increase in both systolic (SBP) and diastolic (DBP) blood pressure by 60 and 25 mmHg, respectively. The urinary excretion of dopamine, DOPAC and HVA was reduced from day 5-6 of CsA administration onwards (dopamine from 19 to 46%, DOPAC from 16 to 48%; HVA from 18 to 42%). In vehicle-treated rats, the urinary excretion of dopamine and DOPAC increased (from 7 to 60%) from day 5 onwards; by contrast, the urinary excretion of HVA was reduced (from 27 to 60%) during the second week. 2. No significant difference was observed between the Vmax and Km values of renal aromatic L-amino acid decarboxylase (AAAD) in rats treated with CsA for 7 and 14 days or with vehicle. 3. Km and Vmax of monoamine oxidase types A and B did not differ significantly between rats treated with CsA for 7 and 14 days or with vehicle. 4. Maximal catechol-O-methyltransferase activity (Vmax) in homogenates of renal tissues obtained from rats treated with CsA for 7 or 14 days was significantly higher than that in vehicle-treated rats; Km (22.3 +/- 1.5 microM) values for COMT did not differ between the three groups of rats. 5. The accumulation of newly-formed dopamine and DOPAC in cortical tissues of rats treated with CsA for 14 days was three to four times higher than in controls. The outflow of both dopamine and DOPAC declined progressively with time and reflected the amine and amine metabolite tissue contents. No significant difference was observed between the DOPAC/dopamine ratios in the perifusate of renal tissues obtained from CsA- and vehicle-treated rats. In addition, no significant differences were observed in k values or in the slope of decline of both DA and DOPAC between experiments performed with CsA and vehicle-treated animals. 6. The Vmax for the saturable component of L-3,4-dihydroxyphenylalanine (L-DOPA) uptake in renal tubules from rats treated with CsA was twice that of vehicle-treated animals. Km in CsA- and vehicle-treated rats did not differ. 7. The decrease in the urinary excretion of sodium and an increase in blood pressure during CsA treatment was accompanied by a reduction in daily urinary excretion of dopamine. This appears to result from a reduction in the amount of L-DOPA made available to the kidney and does not involve changes in tubular AAAD, the availability of dopamine to leave the renal cells and dopamine metabolism.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8564191

Optimal packing for cascaded regenerative transmission based on phase sensitive amplifiers.

PubMed

Sorokina, Mariia; Sygletos, Stylianos; Ellis, Andrew D; Turitsyn, Sergei

2013-12-16

We investigate the transmission performance of advanced modulation formats in nonlinear regenerative channels based on cascaded phase sensitive amplifiers. We identify the impact of amplitude and phase noise dynamics along the transmission line and show that after a cascade of regenerators, densely packed single ring PSK constellations outperform multi-ring constellations. The results of this study will greatly simplify the design of future nonlinear regenerative channels for ultra-high capacity transmission.

Research on the ϕ-OTDR fiber sensor sensitive for all of the distance

NASA Astrophysics Data System (ADS)

Kong, Yong; Liu, Yang; Shi, Yi; Ansari, Farhad; Taylor, Todd

2018-01-01

In this paper, a modified construction for the traditional ϕ-OTDR fiber sensor sensitive for all of distance is presented, the related numerical simulation and experiment analysis results show that this construction can reduce the gain imbalance for all of the distance along the fiber caused by the Rayleigh scattering loss of the fiber and the gain imbalance of Raman fiber amplifier in this fiber sensor system. In order to improve further the vibration sensitivity of this system, the possible methods to restrain the influences of modulation instability effect, Stimulated Brillouin effect, reduce the amplified spontaneous emission (ASE) noises of Raman laser (RL) and Erbium3+-doped fiber amplifiers (EDFA), double Rayleigh backscattering noise in this system are discussed, which will offer a great reference value for the science research and engineering application in the field of fiber sensor as we believe.

A Review of Some Superconducting Technologies for AtLAST: Parametric Amplifiers, Kinetic Inductance Detectors, and On-Chip Spectrometers

NASA Astrophysics Data System (ADS)

Noroozian, Omid

2018-01-01

The current state of the art for some superconducting technologies will be reviewed in the context of a future single-dish submillimeter telescope called AtLAST. The technologies reviews include: 1) Kinetic Inductance Detectors (KIDs), which have now been demonstrated in large-format kilo-pixel arrays with photon background-limited sensitivity suitable for large field of view cameras for wide-field imaging. 2) Parametric amplifiers - specifically the Traveling-Wave Kinetic Inductance (TKIP) amplifier - which has enormous potential to increase sensitivity, bandwidth, and mapping speed of heterodyne receivers, and 3) On-chip spectrometers, which combined with sensitive direct detectors such as KIDs or TESs could be used as Multi-Object Spectrometers on the AtLAST focal plane, and could provide low-medium resolution spectroscopy of 100 objects at a time in each field of view.

Cyclosporine A delivery to the eye: A comprehensive review of academic and industrial efforts.

PubMed

Lallemand, Frédéric; Schmitt, Mathieu; Bourges, Jean-Louis; Gurny, Robert; Benita, Simon; Garrigue, Jean-Sébastien

2017-08-01

Local ocular delivery of cyclosporine A (CsA) is the preferred method for CsA delivery as a treatment for ocular inflammatory diseases such as uveitis, corneal healing, vernal keratoconjunctivitis and dry eye disease. However, due to the large molecular weight and hydrophobic nature of CsA and the natural protective mechanisms of the eye, achieving therapeutic levels of CsA in ocular tissues can be difficult. This review gives a comprehensive overview of the current products available to clinicians as well as emerging drug delivery solutions that have been developed at both the academic and industry levels. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Lack of gender-specific antibody recognition of products from domains of a var gene implicated in pregnancy-associated Plasmodium falciparum malaria.

PubMed

Jensen, Anja T R; Zornig, Hanne D; Buhmann, Caecilie; Salanti, Ali; Koram, Kwadwo A; Riley, Eleanor M; Theander, Thor G; Hviid, Lars; Staalsoe, Trine

2003-07-01

Gender-specific and parity-dependent acquired antibody recognition is characteristic of variant surface antigens (VSA) expressed by chondroitin sulfate A (CSA)-adherent Plasmodium falciparum involved in pregnancy-associated malaria (PAM). However, antibody recognition of recombinant products of a specific VSA gene (2O2var1) implicated in PAM and transcribed by a CSA-adhering parasite line did not have these characteristics. Furthermore, we could not demonstrate preferential transcription of 2O2var1 in the CSA-adhering line versus the unselected, parental isolate. Our data call for circumspection regarding the molecular identity of the parasite ligand mediating adhesion to CSA in PAM.

LOGARITHMIC AMPLIFIER

DOEpatents

De Shong, J.A. Jr.

1957-12-31

A logarithmic current amplifier circuit having a high sensitivity and fast response is described. The inventor discovered the time constant of the input circuit of a system utilizing a feedback amplifier, ionization chamber, and a diode, is inversely proportional to the input current, and that the amplifier becomes unstable in amplifying signals in the upper frequency range when the amplifier's forward gain time constant equals the input circuit time constant. The described device incorporates impedance networks having low frequency response characteristic at various points in the circuit to change the forward gain of the amplifler at a rate of 0.7 of the gain magnitude for every two times increased in frequency. As a result of this improvement, the time constant of the input circuit is greatly reduced at high frequencies, and the amplifier response is increased.

Sensitizers in EUV chemically amplified resist: mechanism of sensitivity improvement

NASA Astrophysics Data System (ADS)

Vesters, Yannick; Jiang, Jing; Yamamoto, Hiroki; De Simone, Danilo; Kozawa, Takahiro; De Gendt, Stefan; Vandenberghe, Geert

2018-03-01

EUV lithography utilizes photons with 91.6 eV energy to ionize resists, generate secondary electrons, and enable electron driven reactions that produce acid in chemically amplified photoresist. Efficiently using the available photons is of key importance. Unlike DUV lithography, where photons are selectively utilized by photoactive compounds, photons at 13.5nm wavelength ionize almost all materials. Nevertheless, specific elements have a significantly higher atomic photon-absorption cross section at 91.6 eV. To increase photon absorption, sensitizer molecules, containing highly absorbing elements, can be added to photoresist formulations. These sensitizers have gained growing attention in recent years, showing significant sensitivity improvement. But there are few experimental evidences that the sensitivity improvement is due to the higher absorption only, as adding metals salts into the resist formulation can induce other mechanisms, like modification of the dissolution rate, potentially affecting patterning performance. In this work, we used different sensitizers in chemically amplified resist. We measured experimentally the absorption of EUV light, the acid yield, the dissolution rate and the patterning performance of the resists. Surprisingly, the absorption of EUV resist was decreased with addition of metal salt sensitizers. Nevertheless, the resist with sensitizer showed a higher acid yield. Sensitizer helps achieving higher PAG conversion to acid, notably due to an increase of the secondary electron generation. Patterning data confirm a significant sensitivity improvement, but at the cost of roughness degradation at high sensitizer loading. This can be explained by the chemical distribution of the sensitizer in the resist combined with a modification of the dissolution contrast, as observed by Dissolution Rate Monitor.

Pain relief for women undergoing oocyte retrieval for assisted reproduction.

PubMed

Kwan, Irene; Wang, Rui; Pearce, Emily; Bhattacharya, Siladitya

2018-05-15

Various methods of conscious sedation and analgesia (CSA) have been used during oocyte retrieval for assisted reproduction. The choice of agent has been influenced by the quality of sedation and analgesia and by concerns about possible detrimental effects on reproductive outcomes. To assess the effectiveness and safety of different methods of conscious sedation and analgesia for pain relief and pregnancy outcomes in women undergoing transvaginal oocyte retrieval. We searched; the Cochrane Gynaecology and Fertility specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL, and trials registers in November 2017. We also checked references, and contacted study authors for additional studies. We included randomised controlled trials (RCTs) comparing different methods and administrative protocols for conscious sedation and analgesia during oocyte retrieval. We used standard methodological procedures expected by Cochrane. Our primary outcomes were intraoperative and postoperative pain. Secondary outcomes included clinical pregnancy, patient satisfaction, analgesic side effects, and postoperative complications. We included 24 RCTs (3160 women) in five comparisons. We report the main comparisons below. Evidence quality was generally low or very low, mainly owing to poor reporting and imprecision.1. CSA versus other active interventions.All evidence for this comparison was of very low quality.CSA versus CSA plus acupuncture or electroacupunctureData show more effective intraoperative pain relief on a 0 to 10 visual analogue scale (VAS) with CSA plus acupuncture (mean difference (MD) 1.00, 95% confidence interval (CI) 0.18 to 1.82, 62 women) or electroacupuncture (MD 3.00, 95% CI 2.23 to 3.77, 62 women).Data also show more effective postoperative pain relief (0 to 10 VAS) with CSA plus acupuncture (MD 0.60, 95% CI -0.10 to 1.30, 61 women) or electroacupuncture (MD 2.10, 95% CI 1.40 to 2.80, 61 women).Evidence was insufficient to show whether clinical pregnancy rates were different between CSA and CSA plus acupuncture (odds ratio (OR) 0.61, 95% CI 0.20 to 1.86, 61 women). CSA alone may be associated with fewer pregnancies than CSA plus electroacupuncture (OR 0.22, 95% CI 0.07 to 0.66, 61 women).Evidence was insufficient to show whether rates of vomiting were different between CSA and CSA plus acupuncture (OR 1.64, 95% CI 0.46 to 5.88, 62 women) or electroacupuncture (OR 1.09, 95% CI 0.33 to 3.58, 62 women).Trialists provided no usable data for other outcomes of interest.CSA versus general anaesthesia Postoperative pain relief was greater in the CSA group (0 to 3 Likert: mean difference (MD) 1.9, 95% CI 2.24 to 1.56, one RCT, 50 women).Evidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 1.00, 95% CI 0.43 to 2.35, two RCTs, 108 women, I 2 = 0%).Evidence was insufficient to show whether groups differed in rates of vomiting (OR 0.46, 95% CI 0.08 to 2.75, one RCT, 50 women) or airway obstruction (OR 0.14, 95% CI 0.02 to 1.22, one RCT, 58 women). Fewer women needed mask ventilation in the CSA group (OR 0.05, 95% CI 0.01 to 0.20, one RCT, 58 women).Evidence was also insufficient to show whether groups differed in satisfaction rates (OR 0.66, 95% CI 0.11 to 4.04, two RCTs, 108 women, I 2 = 34%; very low-quality evidence).Trialists provided no usable data for outcomes of interest.2. CSA + paracervical block (PCB) versus other interventions.CSA + PCB versus electroacupuncture + PCB Intraoperative pain scores were lower in the CSA + PCB group (0 to 10 VAS: MD -0.66, 95% CI -0.93 to -0.39, 781 women, I 2 = 76%; low-quality evidence).Evidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 0.96, 95% CI 0.72 to 1.29, 783 women, I 2 = 9%; low-quality evidence).Trialists provided no usable data for other outcomes of interest.CSA + PCB versus general anaesthesiaEvidence was insufficient to show whether groups differed in postoperative pain scores (0 to 10 VAS: MD 0.49, 95% CI -0.13 to 1.11, 50 women; very low-quality evidence).Evidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 0.70, 95% CI 0.22 to 2.26, 51 women; very low-quality evidence).Trialists provided no usable data for other outcomes of interest.CSA + PCB versus spinal anaesthesiaPostoperative pain scores were higher in the CSA + PCB group (0 to 10 VAS: MD 1.02, 95% CI 0.48 to 1.56, 36 women; very low-quality evidence).Evidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 0.93, 95% CI 0.24 to 3.65, 38 women; very low-quality evidence).Trialists provided no usable data for other outcomes of interest.CSA + PCB versus PCBEvidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 0.93, 95% CI 0.44 to 1.96, 150 women; low-quality evidence) or satisfaction (OR 1.63, 95% CI 0.68 to 3.89, 150 women, low-quality evidence).Trialists provided no usable data for other outcomes of interest.CSA + PCB versus CSA only Evidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 0.62, 95% CI 0.28 to 1.36, one RCT, 100 women; very low-quality evidence). Rates of postoperative nausea and vomiting were lower in the CS + PCB group (OR 0.42, 95% CI 0.18 to 0.97, two RCTs, 140 women, I 2 = 40%; very low-quality evidence).Trialists provided no usable data for other outcomes of interest. The evidence does not support one particular method or technique over another in providing effective conscious sedation and analgesia for pain relief during and after oocyte retrieval. Simultaneous use of sedation combined with analgesia such as the opiates, further enhanced by paracervical block or acupuncture techniques, resulted in better pain relief than occurred with one modality alone. Evidence was insufficient to show conclusively whether any of the interventions influenced pregnancy rates. All techniques reviewed were associated with a high degree of patient satisfaction. Women's preferences and resource availability for choice of pain relief merit consideration in practice.

Assessment of physical activity with the Computer Science and Applications, Inc., accelerometer: laboratory versus field validation.

PubMed

Nichols, J F; Morgan, C G; Chabot, L E; Sallis, J F; Calfas, K J

2000-03-01

Our purpose was to compare the validity of the Computer Science and Applications, (CSA) Inc., accelerometer in laboratory and field settings and establish CSA count ranges for light, moderate, and vigorous physical activity. Validity was determined in 60 adults during treadmill exercise, using oxygen consumption (VO2) as the criterion measure, while 30 adults walked and jogged outdoors on a 400-m track. The relationship between CSA counts and VO2 was linear (R2 = .89 SEE = 3.72 ml.kg-1.min-1), as was the relationship between velocity and counts in the field (R2 = .89, SEE = 0.89 mi.hr-1). However, significant differences were found (p < .05) between laboratory and field measures of CSA counts for light and vigorous intensity. We conclude that the CSA can be used to quantify walking and jogging outdoors on level ground; however, laboratory equations may not be appropriate for use in field settings, particularly for light and vigorous activity.

Resilience Moderates the Association Between Childhood Sexual Abuse and Depressive Symptoms Among Women with and At-Risk for HIV.

PubMed

Dale, Sannisha K; Weber, Kathleen M; Cohen, Mardge H; Kelso, Gwendolyn A; Cruise, Ruth C; Brody, Leslie R

2015-08-01

Childhood sexual abuse (CSA) places women at risk for HIV infection and once infected, for poor mental health outcomes, including lower quality of life and depressive symptoms. Among HIV-positive and demographically matched HIV-negative women, we investigated whether resilience and HIV status moderated the relationships between CSA and health indices as well as the relationships among CSA, depressive symptoms, and health-related quality of life (HRQOL). Participants included 202 women (138 HIV+, 64 HIV-, 87 % African American) from the Women's Interagency HIV Study Chicago CORE Center site. Results indicated that in both HIV-positive and HIV-negative women, higher resilience significantly related to lower depressive symptoms and higher HRQOL. CSA related to higher depressive symptoms only for women scoring low in resilience. Interventions to promote resilience, especially in women with a CSA history, might minimize depressive symptoms and poor HRQOL among HIV-positive and HIV-negative women.

Resilience Moderates the Association between Childhood Sexual Abuse and Depressive Symptoms Among Women with and At-Risk for HIV

PubMed Central

Dale, Sannisha K.; Weber, Kathleen M.; Cohen, Mardge H.; Kelso, Gwendolyn A.; Cruise, Ruth C.; Brody, Leslie R.

2014-01-01

Childhood sexual abuse (CSA) places women at risk for HIV infection and once infected, for poor mental health outcomes, including lower quality of life and depressive symptoms. Among HIV-positive and demographically matched HIV-negative women, we investigated whether resilience and HIV status moderated the relationships between CSA and health indices as well as the relationships among CSA, depressive symptoms, and health-related quality of life (HRQOL). Participants included 202 women (138 HIV+, 64 HIV−, 87% African American) from the Women’s Interagency HIV Study (WIHS) Chicago CORE Center site. Results indicated that in both HIV-positive and HIV-negative women, higher resilience significantly related to lower depressive symptoms and higher HRQOL. CSA related to higher depressive symptoms only for women scoring low in resilience. Interventions to promote resilience, especially in women with a CSA history, might minimize depressive symptoms and poor HRQOL among HIV-positive and HIV-negative women. PMID:25085079

Family Violence and Child Sexual Abuse Among South Asians in the US.

PubMed

Robertson, Hillary A; Chaudhary Nagaraj, Nitasha; Vyas, Amita N

2016-08-01

Family violence, including child sexual abuse (CSA), is a significant public health problem in the United States. It is particularly difficult to assess family violence and CSA among South Asians because it is often hidden due to cultural and familial stigma. A web-based survey was administered to a convenience sample (n = 368) of South Asian adults in the US. One-fourth (25.2 %) of the sample reported CSA; 13.8 % reported abuse involving exposure; 21.5 % reported abuse involving touching; 4.5 % reported attempted sexual intercourse; and 3.5 % reported forced sexual intercourse. Adjusted odds ratios found that participants who reported any relationship violence were significantly more likely to have experienced CSA (OR 2.28; 95 % CI 1.26-4.13); and suicide attempt was significantly associated with CSA (OR 3.96; 95 % CI 1.27-12.3). The findings presented in this formative study will assist in guiding future studies and interventions for South Asians in the United States.

Trajectories of Childhood Sexual Abuse and Early Adolescent HIV/AIDS Risk Behaviors: The Role of Other Maltreatment, Witnessed Violence, and Child Gender

PubMed Central

Jones, Deborah J.; Runyan, Desmond K.; Lewis, Terri; Litrownik, Alan J.; Black, Maureen M.; Wiley, Tisha; English, Diana E.; Proctor, Laura J.; Jones, Bobby L.; Nagin, Daniel S.

2013-01-01

Childhood sexual abuse (CSA) has been associated with HIV/AIDS risk behavior; however, much of this work is retrospective and focuses on women. The current study used semiparametric mixture modeling with youth (n = 844; 48.8% boys) from the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN) to examine the link between trajectories of CSA (2 to 12 y.o.) and HIV/AIDS risk behavior at age 14 (i.e., sexual intercourse & alcohol use). Trajectory analyses revealed a link between a history of CSA and the development of risky behavior. In addition, trajectories for physical and emotional abuse, but not neglect or witnessed violence, contributed to risky behavior over and above the role of CSA. Child gender did not moderate the findings. Findings highlight the signficance of CSA histories, as well as the broader context of maltreatment, for better understanding the development of risk behaviors in both girls and boys. PMID:20706919

Memory of childhood sexual abuse among clinicians: characteristics, outcomes, and current therapy attitudes.

PubMed

Little, L; Hamby, S L

2001-10-01

This paper reports preliminary data on a sample of therapists with memory of childhood sexual abuse. Therapists who reported experiencing childhood sexual abuse (CSA, n = 131) were compared with therapists who suspected sexual abuse but had no memories (n = 24) on variables related to abuse characteristics, outcomes, and perceived difficulties working with clients with a CSA history. Therapists who suspected abuse, in contrast to those who made definite reports, were more likely to report that the perpetrator was a family member, that their CSA did not involve physical contact, that there was alcoholism in their families of origin, and that the CSA had negative effects on their relationships with their own children, ability to trust others, sexual satisfaction, and work life. Therapists who suspected abuse also reported more difficulty treating CSA clients because of interpersonal pulls during sessions, arousal without memories of abuse, and some countertransferential behaviors. These findings indicate that issues related to personal trauma should be addressed during training and practice.

Childhood sexual abuse severity and disclosure as predictors of depression among adult African American and Latina women

PubMed Central

Sciolla, Andres; Glover, Dorie A.; Loeb, Tamra B.; Zhang, Muyu; Myers, Hector F.; Wyatt, Gail E.

2011-01-01

A history of childhood sexual abuse (CSA) has been associated with adult depression, but data on abuse severity and disclosure are scant, particularly among low income ethnic minorities. CSA often co-occurs with other adversities, which also increase the risk of depression. This study examined the peri-trauma variable of abuse severity and the post-trauma variables of disclosure and self-blame as predictors of current depression symptoms in 94 low-income African American and Latina women with histories of CSA. After controlling for non-sexual childhood adversity and adult burden (i.e., chronic stress), severe CSA overall was associated with higher depression scores, especially among Latinas who disclosed their abuse. Depression symptoms among African American women were highest in those who disclosed and reported high levels of self-blame at the time of the incident. The link between depression and specific peri- and post-CSA factors in minority women may help guide future interventions. PMID:21716061

PUCA pump and IABP comparison: analysis of hemodynamic and energetic effects using a digital computer model of the circulation.

PubMed

Fresiello, Libera; Gu, Y John; Ferrari, Gianfranco; Di Molfetta, Arianna; Rakhorst, Gerhard

2011-05-01

The pulsatile catheter pump (PUCA pump) is a left ventricular assist device that provides additional flow to the left ventricle. It is usually run in order to ensure a counterpulsation effect, as in the case of the intra-aortic balloon pump (IABP). Because of this similarity, a comparison between the PUCA pump and the IABP was conducted from both the hemodynamic and energetic points of view. Numerical models of the two devices were created and connected to the CARDIOSIM cardiovascular simulator. The PUCA and IABP models were then verified using in vivo experimental data and literature data, respectively. Numerical experiments were conducted for different values of left ventricular end systolic elastance (Els) and systemic arterial compliance (Csa). The energetic comparison was conducted taking into account the diastolic pressure time index and the endocardial viability ratio. Hemodynamic results expressed as cardiac output (CO) and mean coronary blood flow (CBF) show that both the IABP and the PUCA pump efficacy decrease with higher values of Els and Csa. The IABP especially shows higher sensitivity to these parameters, to the extent that in some cases CO actually drops and CBF does not increase. On the other hand, for lower values of Csa, IABP performance improves so much that the PUCA pump flow needs to be increased in order to ensure a hemodynamic effect comparable to that of the IABP. Energetic results show a trend similar to the hemodynamic ones. The study will be continued by investigating other energetic variables and the autonomic response of the cardiovascular system.

The Surface Layer Homology Domain-Containing Proteins of Alkaliphilic Bacillus pseudofirmus OF4 Play an Important Role in Alkaline Adaptation via Peptidoglycan Synthesis.

PubMed

Fujinami, Shun; Ito, Masahiro

2018-01-01

It is well known that the Na + cycle and the cell wall are essential for alkaline adaptation of Na + -dependent alkaliphilic Bacillus species. In Bacillus pseudofirmus OF4, surface layer protein A (SlpA), the most abundant protein in the surface layer (S-layer) of the cell wall, is involved in alkaline adaptation, especially under low Na + concentrations. The presence of a large number of genes that encode S-layer homology (SLH) domain-containing proteins has been suggested from the genome sequence of B. pseudofirmus OF4. However, other than SlpA, the functions of SLH domain-containing proteins are not well known. Therefore, a deletion mutant of the csaB gene, required for the retention of SLH domain-containing proteins on the cell wall, was constructed to investigate its physiological properties. The csaB mutant strain of B. pseudofirmus OF4 had a chained morphology and alkaline sensitivity even under a 230 mM Na + concentration at which there is no growth difference between the parental strain and the slpA mutant strain. Ultra-thin section transmission electron microscopy showed that a csaB mutant strain lacked an S-layer part, and its peptidoglycan (PG) layer was disturbed. The slpA mutant strain also lacked an S-layer part, although its PG layer was not disturbed. These results suggested that the surface layer homology domain-containing proteins of B. pseudofirmus OF4 play an important role in alkaline adaptation via peptidoglycan synthesis.

Models relating stem growth to crown length dynamics: application to loblolly pine and Norway spruce

Treesearch

Harry T. Valentine; Annikki Makela; Edward J. Green; Ralph L. Amateis; Harri Makinen; Mark J. Ducey

2012-01-01

We derive and analyze a model that relates the growth rate of cross-sectional area ('csa') at any height on the central stem of a tree to crown-length dynamics. The derivation is based, in part, on assumptions that (a) active csa on the central stem relates allometrically to the length of crown above the cross section, and (b) inactive csa is proportional to...

Childhood Sexual Abuse Patterns, Psychosocial Correlates, and Treatment Outcomes among Adults in Drug Abuse Treatment

ERIC Educational Resources Information Center

Boles, Sharon M.; Joshi, Vandana; Grella, Christine; Wellisch, Jean

2005-01-01

This study reports on the effects of having a history of childhood sexual abuse (CSA) on treatment outcomes among substance abusing men and women (N = 2,434) in a national, multisite study of drug treatment outcomes. A history of CSA was reported by 27.2% of the women and 9.2% of the men. Controlling for gender, compared to patients without CSA,…

DESIGN OF MEDICAL RADIOMETER FRONT-END FOR IMPROVED PERFORMANCE

PubMed Central

Klemetsen, Ø.; Birkelund, Y.; Jacobsen, S. K.; Maccarini, P. F.; Stauffer, P. R.

2011-01-01

We have investigated the possibility of building a singleband Dicke radiometer that is inexpensive, small-sized, stable, highly sensitive, and which consists of readily available microwave components. The selected frequency band is at 3.25–3.75 GHz which provides a reasonable compromise between spatial resolution (antenna size) and sensing depth for radiometry applications in lossy tissue. Foreseen applications of the instrument are non-invasive temperature monitoring for breast cancer detection and temperature monitoring during heating. We have found off-the-shelf microwave components that are sufficiently small (< 5 mm × 5 mm) and which offer satisfactory overall sensitivity. Two different Dicke radiometers have been realized: one is a conventional design with the Dicke switch at the front-end to select either the antenna or noise reference channels for amplification. The second design places a matched pair of low noise amplifiers in front of the Dicke switch to reduce system noise figure. Numerical simulations were performed to test the design concepts before building prototype PCB front-end layouts of the radiometer. Both designs provide an overall power gain of approximately 50 dB over a 500 MHz bandwidth centered at 3.5 GHz. No stability problems were observed despite using triple-cascaded amplifier configurations to boost the thermal signals. The prototypes were tested for sensitivity after calibration in two different water baths. Experiments showed superior sensitivity (36% higher) when implementing the low noise amplifier before the Dicke switch (close to the antenna) compared to the other design with the Dicke switch in front. Radiometer performance was also tested in a multilayered phantom during alternating heating and radiometric reading. Empirical tests showed that for the configuration with Dicke switch first, the switch had to be locked in the reference position during application of microwave heating to avoid damage to the active components (amplifiers and power meter). For the configuration with a low noise amplifier up front, damage would occur to the active components of the radiometer if used in presence of the microwave heating antenna. Nevertheless, this design showed significantly improved sensitivity of measured temperatures and merits further investigation to determine methods of protecting the radiometer for amplifier first front ends. PMID:21779411

Cardiorenal benefits of early versus late cyclosporine to sirolimus conversion in a rat model

PubMed Central

Sereno, José; Romão, Ana M.; Parada, Belmiro; Lopes, Patrícia; Carvalho, Eugénia; Teixeira, Frederico; Reis, Flávio

2012-01-01

Objective: To compare the cardiorenal effects of early versus late cyclosporine (CsA) to sirolimus (SRL) conversion, using a novel animal model that mimics these protocols used in the clinical practice, and focusing on blood pressure, heart rate (HR), biochemical data and heart and kidney lipid peroxidation. Materials and Methods: The study had five groups. Six male Wistar rats in each group were used during a 9-week study protocol: control, CsA (5 mg/kg/day), SRL (1 mg/kg/day); early conversion and late conversion. Cardiorenal evaluation was assessed by biochemical data, blood pressure, HR, and heart and kidney lipid peroxidation. Results: As expected, CsA promoted cardiorenal impairment, viewed by development of hypertension, tachycardia, increased urea, creatine kinase, and glucose levels, as well as heart and kidney oxidative stress. SRL, as expected, promoted less cardiorenal side effects, namely those related with nephrotoxicity. In agreement, both early and late conversions from CsA to SRL produced less side-effects, namely those related to the CsA-induced nephrotoxicity. Conclusions: In our model, both early and late CsA to SRL conversion promoted amelioration of the CsA -induced cardiorenal damage. However, early substitution seems to produce more benefits, in particular due to higher improvement of the cardiac profile. PMID:22629089

[Comparison of the determination of cyclosporin-A in blood samples collected on filter paper and by the ordinary technique].

PubMed

Azevedo, L S; Manrique, R; Sabbaga, E

1995-01-01

Monitoring cyclosporin-A (CsA) blood levels is of utmost importance for the rational use of this drug. Although many centers perform transplants, in Brazil there are few laboratories able to measure CsA blood levels. Therefore making blood samples reach the laboratory emerged as a problem. Collection of blood on filter paper has been a technique used for a long time in special cases. PURPOSE--To confirm the usefulness of measuring CsA blood levels in blood samples collected on filter paper and in the usual way. METHOD--We studied twenty renal cadaver kidney recipients who were receiving CsA, azathioprine and prednisone. Ninety five blood samples were collected and divided into two aliquots. One of them was sent routinely to one laboratory to perform whole blood CsA measurements. From the other aliquot, 20 microliters were pipetted on filter paper. When dried they were mailed to the other laboratory, where, after elution, CsA was measured. In both cases radioimmunoassay with polyclonal antibody was used. RESULTS--Linear correlation between both measurements revealed r = 0.81 with no statistical difference. CONCLUSION--The technique showed to be useful in clinical practice. In countries with continental size, as Brazil, it may be very helpful.

Crime Prevention Through Environmental Design (CPTED) Characteristics Associated With Violence and Safety in Middle Schools.

PubMed

Vagi, Kevin J; Stevens, Mark R; Simon, Thomas R; Basile, Kathleen C; Carter, Sherry P; Carter, Stanley L

2018-04-01

This study used a new Crime Prevention Through Environmental Design (CPTED) assessment tool to test the associations between physical attributes of schools and violence-related behaviors and perceptions of students. Data were collected from 4717 students from 50 middle schools. Student perceptions of risk and safety, and violence were assessed. Evaluators used the CPTED School Assessment (CSA) to quantify how well the physical elements of each school correspond to ideal CPTED principles. Generalized linear mixed models were used to adjust for school- and student-level characteristics. Higher CSA scores were generally associated with higher perceptions of safety and lower levels of violence perpetration and perceived risk in unadjusted models. Higher CSA scores were also associated with lower odds of missing school because of safety concerns in most adjusted models, with significant adjusted odds ratios (AORs) ranging from 0.32 to 0.63. CSA scores for parking and bus loading areas also remained associated with higher perceived safety (AORs = 1.28 and 1.32, respectively) and lower perceived risk (AORs = 0.73 and 0.66, respectively) in adjusted models. The CSA is useful for assessing school environments that are associated with violence-related behaviors and perceptions. The CSA might help guide school environmental modifications to reduce violence. © 2018, American School Health Association.

Sleep-disordered breathing in patients with atrial fibrillation and normal systolic left ventricular function.

PubMed

Bitter, Thomas; Langer, Christoph; Vogt, Jürgen; Lange, Mathias; Horstkotte, Dieter; Oldenburg, Olaf

2009-03-01

Obstructive sleep apnea (OSA) is more common in patients with atrial fibrillation (AFib). Recently, an additional association between central sleep apnea/Cheyne-Stokes respiration (CSA/CSR) and AFib has been described. The aim of this study was to investigate the prevalence and type of sleep-disordered breathing in patients with AFib and normal systolic left ventricular function. 150 patients (110 men and 40 women, aged 66.1 +/- 1.7 years) underwent cardiorespiratory polygraphy, capillary blood gas analysis, measurement of NT-proBNP, and echocardiography to determine the diameter of the left atrium (LAD) and the peak systolic pulmonary artery pressure (PAP). Sleep-disordered breathing was documented in 74% of all patients with AFib (43% had OSA and 31% had CSA/CSR). Patients with CSA/CSR had a higher PAP, a higher apnea-hypopnea index, a greater LAD, and a lower capillary blood pCO(2) than patients with OSA. Patients with AFib were found to have not only a high prevalence of obstructive sleep apnea, as has been described previously, but also a high prevalence of CSA/CSR. It remains unknown whether CSA/CSR is more common in AFib because of diastolic dysfunction or whether phenomena associated with CSA/CSR predispose to AFib. Further research on this question is needed.

Adult Coping with Childhood Sexual Abuse: A Theoretical and Empirical Review

PubMed Central

Walsh, Kate; Fortier, Michelle A.; DiLillo, David

2009-01-01

Coping has been suggested as an important element in understanding the long-term functioning of individuals with a history of child sexual abuse (CSA). The present review synthesizes the literature on coping with CSA, first by examining theories of coping with trauma, and, second by examining how these theories have been applied to studies of coping in samples of CSA victims. Thirty-nine studies were reviewed, including eleven descriptive studies of the coping strategies employed by individuals with a history of CSA, eighteen correlational studies of the relationship between coping strategies and long-term functioning of CSA victims, and ten investigations in which coping was examined as a mediational factor in relation to long-term outcomes. These studies provide initial information regarding early sexual abuse and subsequent coping processes. However, this literature is limited by several theoretical and methodological issues, including a failure to specify the process of coping as it occurs, a disparity between theory and research, and limited applicability to clinical practice. Future directions of research are discussed and include the need to understand coping as a process, identification of coping in relation to adaptive outcomes, and considerations of more complex mediational and moderational processes in the study of coping with CSA. PMID:20161502

De Novo Design of Skin-Penetrating Peptides for Enhanced Transdermal Delivery of Peptide Drugs.

PubMed

Menegatti, Stefano; Zakrewsky, Michael; Kumar, Sunny; De Oliveira, Joshua Sanchez; Muraski, John A; Mitragotri, Samir

2016-03-09

Skin-penetrating peptides (SPPs) are attracting increasing attention as a non-invasive strategy for transdermal delivery of therapeutics. The identification of SPP sequences, however, currently performed by experimental screening of peptide libraries, is very laborious. Recent studies have shown that, to be effective enhancers, SPPs must possess affinity for both skin keratin and the drug of interest. We therefore developed a computational process for generating and screening virtual libraries of disulfide-cyclic peptides against keratin and cyclosporine A (CsA) to identify SPPs capable of enhancing transdermal CsA delivery. The selected sequences were experimentally tested and found to bind both CsA and keratin, as determined by mass spectrometry and affinity chromatography, and enhance transdermal permeation of CsA. Four heptameric sequences that emerged as leading candidates (ACSATLQHSCG, ACSLTVNWNCG, ACTSTGRNACG, and ACSASTNHNCG) were tested and yielded CsA permeation on par with previously identified SPP SPACE (TM) . An octameric peptide (ACNAHQARSTCG) yielded significantly higher delivery of CsA compared to heptameric SPPs. The safety profile of the selected sequences was also validated by incubation with skin keratinocytes. This method thus represents an effective procedure for the de novo design of skin-penetrating peptides for the delivery of desired therapeutic or cosmetic agents. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

What prevents Chinese parents from reporting possible cases of child sexual abuse to authority? A holistic-interactionistic approach.

PubMed

Xie, Qian Wen; Sun, Xiaoyue; Chen, Mengtong; Qiao, Dong Ping; Chan, Ko Ling

2017-02-01

The reporting of suspected CSA cases to authorities in a timely manner is important in preventing continued abuse and protecting abused children at early ages. The current study seeks to explore parents' intentions of reporting their own children's CSA experiences to authorities as well as their reporting willingness when they become aware of possible CSA cases happening to children in other families. Two rounds of semi-structured interviews were conducted among a sample of 26 parents in Beijing; these parents were purposefully selected so as to be diverse in terms of gender, age, and socioeconomic status. The data were analyzed thematically. The findings showed that the reporting of suspected CSA to authorities was a choice made by only a few Chinese parents; it was often even a last resort. By using a holistic-interactionistic approach, the interaction between Chinese parents' intentions of reporting CSA and the Chinese socio-cultural context was analyzed as a dynamic and continuously ongoing process. The impacts of the definition and perceptions of CSA on reporting, the balance of children's rights and parents' power, and the double effect of informal social control are discussed. The implications, both locally and globally, are also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Alcohol Myopia and Sexual Abdication among Women: Examining the Moderating Effect of Child Sexual Abuse

PubMed Central

Staples, Jennifer M.; George, William H.; Stappenbeck, Cynthia A.; Davis, Kelly Cue; Norris, Jeanette; Heiman, Julia

2014-01-01

HIV and other STIs are major public health concerns for women, and risky sexual behaviors increase the risk of transmission. Risky sexual behaviors include sexual abdication, that is, willingness to let a partner decide how far to go sexually. Alcohol intoxication is a risk factor for risky sexual behavior, and the Inhibition Conflict Model of Alcohol Myopia may help explain this relationship (Steele et al., 1985). This model suggests that in order for intoxication to influence behavior there must be high conflict, meaning the strength of the instigatory cues and inhibitory cues are both high. Recent research indicates that the degree to which cues are experienced as high in instigation or inhibition is subject to individual difference factors. One individual difference factor associated with alcohol-related sexual risk taking is child sexual abuse (CSA) history. The current study examined the influence of acute alcohol intoxication, CSA, and inhibition conflict on sexual abdication with 131 women (mean age 25) randomized into a 2 (alcohol, control) x 2 (high conflict, low conflict) experimental design. Regression analyses yielded a significant 3-way interaction, F (1,122) = 8.15, R2 = .14, p <.01. When there was high conflict, intoxicated CSA women were more likely to abdicate than sober CSA women, however, sober CSA women were less likely to abdicate than sober NSA women. When there was low conflict, CSA history and alcohol intoxication had no influence on abdication. These results may help explain the association between alcohol and risky sexual decision making among women with CSA. PMID:25310825

Alcohol myopia and sexual abdication among women: examining the moderating effect of child sexual abuse.

PubMed

Staples, Jennifer M; George, William H; Stappenbeck, Cynthia A; Davis, Kelly Cue; Norris, Jeanette; Heiman, Julia R

2015-02-01

HIV and other STIs are major public health concerns for women, and risky sexual behaviors increase the risk of transmission. Risky sexual behaviors include sexual abdication, that is, willingness to let a partner decide how far to go sexually. Alcohol intoxication is a risk factor for risky sexual behavior, and the Inhibition Conflict Model of Alcohol Myopia may help explain this relationship. This model suggests that in order for intoxication to influence behavior there must be high conflict, meaning the strength of the instigatory cues and inhibitory cues are both high. Recent research indicates that the degree to which cues are experienced as high in instigation or inhibition is subject to individual difference factors. One individual difference factor associated with alcohol-related sexual risk taking is child sexual abuse (CSA) history. The current study examined the influence of acute alcohol intoxication, CSA, and inhibition conflict on sexual abdication with 131 women (mean age 25) randomized into a 2 (alcohol, control)×2 (high conflict, low conflict) experimental design. Regression analyses yielded a significant 3-way interaction, F (1,122)=8.15, R(2)=.14, p<.01. When there was high conflict, intoxicated CSA women were more likely to abdicate than sober CSA women, however, sober CSA women were less likely to abdicate than sober NSA women, when there was low conflict, CSA history and alcohol intoxication had no influence on abdication. These results may help explain the association between alcohol and risky sexual decision making among women with CSA. Copyright © 2014 Elsevier Ltd. All rights reserved.

Association between childhood sexual abuse and adverse psychological outcomes among youth in Taipei.

PubMed

Li, Nan; Ahmed, Saifuddin; Zabin, Laurie S

2012-03-01

The objective of this study was to examine the relationship between a history of childhood sexual abuse (CSA) and negative psychological consequences in adulthood, controlling for family environments and Confucian values. The data used in this study were collected from Taipei. The final analysis sample comprised 4,084 participants aged 15-24 years. Three sets of logistic regression models were fitted to verify the association between CSA and negative psychological outcomes. Sociodemographic variables, household instability, and parenting variables, as well as Confucian value variables were controlled in models step by step. The overall prevalence of CSA in our analysis sample was 5.2%. The overall prevalence of depression, anxiety, and suicidal ideation among Taipei respondents was 11.8%, 16.4%, and 16.7%, respectively, but young people who experienced CSA had significantly higher rates of all three than young adults who had not experienced CSA. After controlling for other covariates, the odds ratios of depression, anxiety, and suicidal ideation associated with a history of CSA were 1.78 (95% confidence intervals [CI]: 1.25-2.54), 1.77 (95% CI: 1.28-2.44), and 2.56 (95% CI: 1.56-4.29), respectively. Our findings suggested that CSA was an independent predictor of negative psychological consequences in adulthood. In our analysis, we controlled for household, parenting, and Confucian culture factors, which provides a better understanding of how they work together to affect adult psychological status. Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Experiences of Mothers Who Are Child Sexual Abuse Survivors: A Qualitative Exploration

PubMed Central

Cavanaugh, Courtenay E.; Harper, Bianca; Classen, Catherine C.; Palesh, Oxana; Koopman, Cheryl; Spiegel, David

2018-01-01

Child sexual abuse (CSA) has been associated with a number of problems affecting women over their lifespan, including difficulties with parenting. However, there is a modest number of qualitative studies examining the impact of CSA on survivors who are mothers. There is a particular need for qualitative investigations that ask survivors who are mothers general questions about the impact of CSA on their lives rather than those that specifically ask about the impact of CSA on parenting. The former approach would allow survivors to describe effects that may impact parenting, but which survivors do not consciously link to affecting their parenting. Such information may inform interventions to assist this population of survivors. This secondary data analysis examined themes revealed in interviews with 44 survivors of CSA who were mothers. Participants were seeking treatment for their CSA and completed an in-person interview where they were asked open-ended questions about the sexual abuse they experienced as a child and how their abuse affects them now as adults. The interviews were recorded, transcribed, and coded using thematic analysis. The following six themes emerged from the narratives: 1) being a parent, 2) family of origin dysfunction, 3) the impact of abuse, 4) the abuse history and response to abuse, 5) coping, and 6) hopes and desires for the future. This study highlights several ways in which CSA impacts survivors who are mothers, areas for further study, and the need for interventions to assist this population in meeting the challenges they face as mothers. PMID:26301437

Immunophilin ligands demonstrate common features of signal transduction leading to exocytosis or transcription.

PubMed Central

Hultsch, T; Albers, M W; Schreiber, S L; Hohman, R J

1991-01-01

Investigations of the actions and interactions of the immunophilin ligands FK506, cyclosporin A (CsA), rapamycin, and 506BD suggest that complexes of FK506 with an FK506-binding protein or of CsA with a cyclophilin (CsA-binding protein) inhibit the T-cell receptor-mediated signal transduction that results in the transcription of interleukin 2. Now we report an identical spectrum of activities of FK506, CsA, rapamycin, and 506BD on IgE receptor-mediated signal transduction that results in exocytosis of secretory granules from the rat basophilic leukemia cell line RBL-2H3, a mast cell model. Both FK506 and CsA inhibit receptor-mediated exocytosis (CsA IC50 = 200 nM; FK506 IC50 = 2 nM) without affecting early receptor-associated events (hydrolysis of phosphatidylinositol, synthesis and release of eicosanoids, uptake of Ca2+). In contrast, rapamycin and 506BD, which share common structural elements with FK506, by themselves have no effect on IgE receptor-mediated exocytosis. Both compounds, however, prevent inhibition by FK506 but not by CsA. Affinity chromatography with FK506, CsA, and rapamycin matrices indicates that the same set of immunophilins present in RBL-2H3 cells have been found in Jurkat T cells and calf thymus; however, the relative amounts of these proteins differ in the two cell types. These results suggest the existence of a common step in cytoplasmic signaling in T cells and mast cells that may be part of a general signaling mechanism. Images PMID:1712484

Early Stigmatization, PTSD, and Perceived Negative Reactions of Others Predict Subsequent Strategies for Processing Child Sexual Abuse

PubMed Central

Simon, Valerie A.; Feiring, Candice; Cleland, Charles M.

2017-01-01

Objective Trauma processing is central to healthy recovery, but few studies examine how youth process experiences of child sexual abuse (CSA). The current study builds on our prior work identifying individual differences in CSA processing strategies (i.e., Constructive, Absorbed, Avoidant) to examine whether abuse stigmatization, PTSD symptoms, and negative reactions from others experienced during the year after abuse discovery were associated with subsequent CSA processing strategies. Method Participants included 160 ethnically diverse youth (8−15 years, 73% female) with confirmed cases of CSA. Predictors were measured at abuse discovery (T1) and 1 year later (T2). Individual differences in CSA processing strategies were assessed 6 years after discovery (T3) from participants’ abuse narratives. Results The persistence of abuse stigmatization from T1 to T2 significantly increased the odds of using either an Avoidant or Absorbed (vs. Constructive) strategy at T3. Higher levels of PTSD symptoms at T1 as well as their persistence from T1 to T2 each significantly increased the odds of having an Absorbed versus Constructive strategy. The persistence of perceived negative reactions from others from T1 to T2 increased the odds of an Absorbed versus Avoidant strategy. Effect sizes ranged from medium to large (M d = 0.636). Conclusions Results further validate prior work identifying distinct CSA processing strategies and suggest the persistence of abuse-specific disruptions over the year after abuse discovery may be associated with subsequent problems processing CSA experiences. PMID:28936363

Association of visceral fat area with abdominal skeletal muscle distribution in overweight Japanese adults.

PubMed

Tanaka, Noriko I; Murakami, Haruka; Ohmori, Yumi; Aiba, Naomi; Morita, Akemi; Watanabe, Shaw; Miyachi, Motohiko

2016-07-20

Quantitative evaluation of visceral fat mass and skeletal muscle mass is important for health promotion. Recently, some studies suggested the existence of adipocyte-myocyte negative crosstalk. If so, abdominal skeletal muscles may easily and negatively affected not only by the age but also the visceral fat because age-related reduction in abdominal region is greater compared with limbs. We cross-sectionally examined the existence of quantitative associations between visceral fat area and abdominal skeletal muscle distribution in overweight people. A total of 230 Japanese males and females who aged 40-64 years and whose body mass index (BMI) was 28.0-44.8kg/m 2 participated in this study. The cross-sectional area (CSA) of the visceral fat, subcutaneous fat, and abdominal skeletal muscles, namely, the rectus abdominis, abdominal oblique, erector spinae, and iliopsoas muscles were measured by the computed tomography images. Stepwise regression analyses revealed the existence of sex difference in the relation between visceral fat CSA and other morphological variables. In males, BMI was a positive, and the iliopsoas muscle group CSA was a negative contributor of the visceral fat CSA. In females, both age and BMI were selected as positive contributors. These data suggested that the visceral fat CSA may negatively associated with iliopsoas muscle group CSA in males. In females, the visceral fat CSA was not significantly related to the distribution of the abdominal skeletal muscle groups. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Comparison of continuous spinal anaesthesia using a 32-gauge catheter with anaesthesia using a single-dose 24-gauge atraumatic needle in young patients.

PubMed

de Andrés, J; Bellver, J; Bolinches, R

1994-12-01

One hundred and twenty-eight ASA I-III patients less than 40 yr of age, undergoing orthopaedic or trauma lower limb surgery, were allocated randomly to receive either continuous spinal anaesthesia (CSA) using a 32-gauge polyimide microcatheter with a permanent stylet (Rusch/TFX Medical, Duluth, GA, USA) or single-dose spinal anaesthesia (SDSA) with a 24-gauge x 103-mm Sprotte spinal needle (Pajunk, Germany). Plain bupivacaine (0.5%) was used as the local anaesthetic. The initial doses were 1 ml (5 mg) of CSA and 3 ml (15 mg) of SDSA, while the re-injection doses were 1 ml (5 mg) in the CSA group. SDSA was quicker to perform: mean 4.4 (SD 1.6) min compared with 6.2 (2.6) min for CSA (P < 0.01). Times to onset and surgical anaesthesia were also significantly greater in the CSA group (P < 0.01). The quality of the block was better in the SDSA group (P < 0.05), but was associated with greater haemodynamic instability (P < 0.05). The segmental level of analgesia was significantly lower in the CSA group (median T10 (range T12-T8)) than in the SDSA group (T9 (T11-T5)) (P < 0.05). There were no significant differences in the incidence of postoperative complications, with two mild spinal headaches in both groups. We conclude that CSA using a microcatheter in young patients is difficult to perform and affords no advantages over SDSA with a small gauge atraumatic needle.

Detection of contaminated pixels based on the short-term continuity of NDVI and correction using spatio-temporal continuity

NASA Astrophysics Data System (ADS)

Cho, A.-Ra; Suh, Myoung-Seok

2013-08-01

The present study developed and assessed a correction technique (CSaTC: Correction based on Spatial and Temporal Continuity) for the detection and correction of contaminated Normalized Difference Vegetation Index (NDVI) time series data. Global Inventory Modeling and Mapping Studies (GIMMS) NDVI data from 1982 to 2006 with a 15-day period and an 8-km spatial resolution was used. CSaTC utilizes short-term continuity of vegetation to detect contaminated pixels, and then, corrects the detected pixels using the spatio-temporal continuity of vegetation. CSaTC was applied to the NDVI data over the East Asian region, which exhibits diverse seasonal and interannual variations in vegetation activities. The correction skill of CSaTC was compared to two previously applied methods, IDR (iterative Interpolation for Data Reconstruction) and Park et al. (2011) using GIMMS NDVI data. CSaTC reasonably resolved the overcorrection and spreading phenomenon caused by excessive correction of Park et al. (2011). The validation using the simulated NDVI time series data showed that CSaTC shows a systematically better correction skill in bias and RMSE irrespective of phenology types of vegetation and noise levels. In general, CSaTC showed a good recovery of the contaminated data appearing over the short-term period on a level similar to that obtained using the IDR technique. In addition, it captured the multi-peak of NDVI, and the germination and defoliating patterns more accurately than that by IDR, which overly compensates for seasons with a high temporal variation and where NDVI data exhibit multi-peaks.

Induction of synapse associated protein 102 expression in cyclosporin A-stimulated hair growth.

PubMed

Kim, Chang Deok; Lee, Min-Ho; Sohn, Kyung-Cheol; Kim, Jin-Man; Li, Sheng Jin; Rang, Moon-Jeong; Roh, Seok-Seon; Oh, Young-Seon; Yoon, Tae-Jin; Im, Myung; Seo, Young-Joon; Lee, Jeung-Hoon; Park, Jang-Kyu

2008-08-01

Cyclosporin A (CsA) has been used as a potent immunosuppressive agent for inhibiting the graft rejection after organ transplantation. However, CsA provokes lots of side effects including hirsutism, the phenomenon of abnormal hair growth in the body. In the present study, we investigated the hair growth stimulating effect of CsA using in vivo and in vitro test models. When topically applied on the back skin of mice, CsA induced fast telogen to anagen transition. In contrast, CsA had no effect on the growth of human hair follicle tissues cultured in vitro, indicating that it might not have the mitogenic effect on hair follicles. To identify the genes related with CsA-induced hair growth, we performed differential display RT-PCR. Among the genes obtained, the expression of synapse associated protein 102 (SAP102) was verified using competitive RT-PCR. The result showed that the expression of SAP102 was significantly induced by CsA treatment in the back skin of C57BL/6 mice. However, the increase of SAP102 mRNA was also seen in spontaneous anagen mice, suggesting that induction of SAP102 is one event of the anagen hair growth response regardless of how the growth state was induced. SAP102 was not expressed in cultured human hair outer root sheath and dermal papilla cells. Immunohistochemistry analysis showed that CsA induced the expression of SAP102 in perifollicular region of mouse anagen hair. Together, these results suggest that SAP102 is one of hair-cycle-dependent genes, whose expression is related with the anagen progression.

Role of Body Esteem in the Sexual Excitation and Inhibition Responses of Women With and Without a History of Childhood Sexual Abuse.

PubMed

Kilimnik, Chelsea D; Meston, Cindy M

2016-11-01

Women's sexuality is influenced by their perceptions of their bodies. Negative body appraisals have been implicated in the development and maintenance of sexual concerns in women with a history of childhood sexual abuse (CSA). The sexuality of these women is often expressed in extremes of approach and avoidant sexual tendencies, which have been related to the sexual inhibition and sexual excitation pathways of the dual control model. To test the influence of body esteem on the sexual excitation and inhibition responses of women with and without a history of CSA. One hundred thirty-nine women with CSA and 83 non-abused women reported on their abuse history, depressive symptomology, sexual response, and affective appraisals of their body. Validated self-report measurements of sexual excitation and inhibition responses (Sexual Excitation/Sexual Inhibition Inventory for Women) and body esteem (Body Esteem Scale) were administered. Body esteem was significantly associated with sexual inhibition responses of women regardless of CSA history status but was significantly related only to the sexual excitation responses of women with a CSA history. Perceived sexual attractiveness was a unique predictor of sexual excitation in women with a history of CSA. Women with a history of CSA have lower body esteem than non-abused women, particularly in self-perceived sexual attractiveness, and these perceptions appear to influence their sexual responses by acting on the sexual excitation and inhibition response pathways. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Birth experiences in adult women with a history of childhood sexual abuse.

PubMed

Leeners, Brigitte; Görres, Gisela; Block, Emina; Hengartner, Michael Pascal

2016-04-01

Although childhood sexual abuse (CSA) may seriously impair childbirth experiences, few systematic evaluations on associations, mediating influences, risk and protective factors are available. As such information is mandatory to improve obstetric care, the present study aimed to provide such data. The study compared childbirth experiences from 85 women after CSA and at least one pregnancy resulting in a life birth with those from 170 control women matched for nationality, personal age and children's age. Trained specialists from support centers investigated CSA. Obstetrical data were collected from the official personal clinical record of each pregnancy (Mutterpass) and data on CSA as well as childbirth experiences were examined by questionnaires. Childbirth was more often highly frightening (24.7 vs. 5.3%; p<0.01) and a negative experience (40.7 vs. 19.6%, p<0.01) in women with a history of CSA than in controls. Multivariate regression models support the hypothesis that at least part of this association was mediated by covariates (specifically, birth preparation classes, presence of a trusted person, participation in medical decision-making, pain relief, emergency during labor and extreme duration of labor), which represent important resources in improving obstetric care. In 41% of women with CSA, memories of traumatic experiences intruded during childbirth, whereas about 58% experienced dissociation. While dissociation may result in loss of contact with obstetric staff, it was also used to reduce labor pain. Childbirth following a history of CSA is associated with particular challenges. Creating a trusting environment by evaluating and integrating individual needs could ameliorate birth experiences. Copyright © 2016 Elsevier Inc. All rights reserved.

Central Sleep Apnoea Is Related to the Severity and Short-Term Prognosis of Acute Coronary Syndrome.

PubMed

Florés, Marina; de Batlle, Jordi; Sánchez-de-la-Torre, Alicia; Sánchez-de-la-Torre, Manuel; Aldomá, Albina; Worner, Fernando; Galera, Estefanía; Seminario, Asunción; Torres, Gerard; Dalmases, Mireia; Montserrat, Josep M; Garmendia, Onintza; Barbé, Ferran

2016-01-01

To evaluate the relation of central sleep apnoea (CSA) to the severity and short-term prognosis of patients who experience acute coronary syndrome (ACS). Observational study with cross-sectional and longitudinal analyses. Patients acutely admitted to participating hospitals because of ACS underwent respiratory polygraphy during the first 24 to 72 h. CSA was defined as an apnoea-hypopnoea index (AHI) >15 events•h-1 (>50% of central apnoeas). ACS severity (Killip class, ejection fraction, number of diseased vessels and peak plasma troponin) was evaluated at baseline, and short-term prognosis (length of hospitalization, complications and mortality) was evaluated at discharge. A total of 68 CSA patients (AHI 31±18 events•h-1, 64±12 years, 87% males) and 92 controls (AHI 7±5 events•h-1, 62±12 years, 84% males) were included in the analyses. After adjusting for age, body mass index, hypertension and smoking status, patients diagnosed with CSA spent more days in the coronary unit compared with controls (3.7±2.9 vs. 1.5±1.7; p<0.001) and had a worse Killip class (Killip I: 16% vs. 96%; p<0.001). No differences were observed in ejection fraction estimates. CSA patients exhibited increased ACS severity as indicated by their Killip classification. These patients had a worse prognosis, with longer lengths of stay in the coronary care units. Our results highlight the relevance of CSA in patients suffering ACS episodes and suggest that diagnosing CSA may be a useful strategy to improve the management of certain ACS patients.

Evaluation of hepatitis B virus replication and proteomic analysis of HepG2.2.15 cell line after cyclosporine A treatment.

PubMed

Xie, Hai-Yang; Xia, Wei-Liang; Zhang, Chun-Chao; Wu, Li-Ming; Ji, Hao-Feng; Cheng, Yu; Zheng, Shu-Sen

2007-07-01

The effect of cyclosporine A (CsA) on hepatitis B virus (HBV) replication was investigated, and proteomics expression differentiation after CsA treatment was studied in order to provide clues to explore the effect of CsA on HBV replication. Methyl thiazolyl tetrazolium (MTT) assay was used to evaluate the cytotoxicity of CsA. The HBV replication level in the HBV genomic DNA transfected HepG2.2.15 cell line was determined by an ELISA analysis of hepatitis B surface antigens (HBsAg) and Hepatitis B e antigens (HBeAg) in culture supernatant, while the intracellular HBV DNA replication level was analyzed by slot blot hybridization. Two-dimensional electrophoresis was used to investigate the alteration of protein expression in HepG2.2.15 after CsA treatment in vitro. The differentially-expressed proteins were identified by Matrix-assisted laser desorption/ionization-time of flight mass spectrometry combined with an online database search. CsA was able to inhibit the expression of HBsAg, HBeAg, and HBV DNA replication in vitro in a dose-dependent manner. A proteomics analysis indicated that the expression of 17 proteins changed significantly in the CsA treatment group compared to the control group. Eleven of the 17 proteins were identified, including the overexpression of eukaryotic translation initiation factors (eIF) 3k, otubain 1, 14.3.3 protein, eIF2-1 alpha, eIF5A, and the tyrosine 3/tryptophan 5-mono-oxygenase activation protein in CsA-treated HepG2.2.15 cells. The downregulation of the ferritin light subunit, erythrocyte cytosolic protein of 51 kDa (ECP-51), stathmin 1/oncoprotein, adenine phosphoribosyl-transferase, and the position of a tumor protein, translationally controlled 1, was shifted, suggesting it had undergone posttranslational modifications. Our study identified the inhibitory effect of CsA on HBV replication, and found that a group of proteins may be responsible for this inhibitory effect.

Compressed spectral arrays of patients with fulminant hepatic failure in hepatic coma undergoing liver transplantation.

PubMed

Takeichi, Takayuki; Asonuma, Katsuhiro; Kim, Ildeok; Inomata, Yukihiro; Kasahara, Mureo; Ohwada, Susumu; Morishita, Yasuo; Tanaka, Koichi

2002-08-01

Assessing the coma status of patients with fulminant hepatic failure (FHF) is important for determining the reversibility of brain damage and for properly timing liver transplantation. The compressed spectral array (CSA) method is a frequency analysis technique that processes electroencephalogram signals by computer to facilitate on-line interpretation. This method has been used to monitor the consciousness levels of neurointensive care unit patients. In this study, we determined whether CSA could be used to assess the coma status of patients with FHF, and whether CSA provided information that was useful in deciding when to proceed with liver transplantation. CSA recording was carried out in 17 FHF patients with encephalopathy (coma grade III-IV) who underwent living-related liver transplantation between August 1997 and May 1999. Recording was performed with a Neuromonitor OEE-72044 (NIHON KOHDEN, Osaka, Japan) every 24 h before and after transplantation, until the patients regained consciousness. The CSAs of healthy controls were distributed almost equally between 0 and 16 Hz. The CSAs of FHF patients in hepatic coma were classified into three patterns. Eight of the 17 patients showed very prominent slow waves of about 2 Hz (group A), and seven patients showed strongly suppressed rapid waves between 8 and 16 Hz (group B). The remaining two patients showed CSA patterns that were similar to those of healthy controls, even though these patients were comatose (group C). Abnormal CSA patterns were observed in 15 of the 17 patients (88%). Group B patients seemed to have higher coma grades than did group A patients. Sixteen patients underwent liver transplantation, completely recovered from hepatic encephalopathy, and subsequently showed CSA patterns similar to those of healthy controls. One patient died without regaining consciousness. These results suggest that CSA is useful in assessing the coma status of FHF patients and in evaluating electrophysiological recovery from hepatic coma after liver transplantation.

A new laser reflectance system capable of measuring changing cross-sectional area of soft tissues during tensile testing.

PubMed

Pokhai, Gabriel G; Oliver, Michele L; Gordon, Karen D

2009-09-01

Determination of the biomechanical properties of soft tissues such as tendons and ligaments is dependent on the accurate measurement of their cross-sectional area (CSA). Measurement methods, which involve contact with the specimen, are problematic because soft tissues are easily deformed. Noncontact measurement methods are preferable in this regard, but may experience difficulty in dealing with the complex cross-sectional shapes and glistening surfaces seen in soft tissues. Additionally, existing CSA measurement systems are separated from the materials testing machine, resulting in the inability to measure CSA during testing. Furthermore, CSA measurements are usually made in a different orientation, and with a different preload, prior to testing. To overcome these problems, a noncontact laser reflectance system (LRS) was developed. Designed to fit in an Instron 8872 servohydraulic test machine, the system measures CSA by orbiting a laser transducer in a circular path around a soft tissue specimen held by tissue clamps. CSA measurements can be conducted before and during tensile testing. The system was validated using machined metallic specimens of various shapes and sizes, as well as different sizes of bovine tendons. The metallic specimens could be measured to within 4% accuracy, and the tendons to within an average error of 4.3%. Statistical analyses showed no significant differences between the measurements of the LRS and those of the casting method, an established measurement technique. The LRS was successfully used to measure the changing CSA of bovine tendons during uniaxial tensile testing. The LRS developed in this work represents a simple, quick, and accurate way of reconstructing complex cross-sectional profiles and calculating cross-sectional areas. In addition, the LRS represents the first system capable of automatically measuring changing CSA of soft tissues during tensile testing, facilitating the calculation of more accurate biomechanical properties.

Is There an Association Between the “Critical Shoulder Angle” and Clinical Outcome After Rotator Cuff Repair?

PubMed Central

Kirsch, Jacob M.; Nathani, Amit; Robbins, Christopher B.; Gagnier, Joel J.; Bedi, Asheesh; Miller, Bruce S.

2017-01-01

Background: Variations in scapular morphology have been associated with the development of atraumatic rotator cuff tears (RCTs). The critical shoulder angle (CSA) accounts for both glenoid inclination and lateral extension of the acromion. The impact of the CSA on outcomes after rotator cuff repair (RCR) has not been investigated previously. Hypothesis: Our hypothesis was that individuals with smaller CSAs will have better patient-reported outcome scores over time compared with those with larger CSAs. Theoretically, a smaller CSA minimizes the biomechanical forces favoring superior translation of the humeral head, which may be advantageous after RCR. This is the first study to examine the relationship between the CSA and clinical outcomes after RCR. Study Design: Cohort study; Level of evidence, 2. Methods: Fifty-three patients (mean age, 61 years) with atraumatic full-thickness RCTs who underwent arthroscopic RCR were prospectively evaluated. Demographic data as well as the Western Ontario Rotator Cuff Index (WORC) score, American Shoulder and Elbow Surgeons (ASES) score, and a visual analog scale (VAS) for pain were prospectively collected at various time points up to 24 months postoperatively. Statistical analysis included longitudinal multilevel regression modeling to investigate the association between the CSA and the WORC, ASES, and VAS scores. Results: The overall clinical outcome, as measured by the WORC, ASES, and VAS, improved significantly (P < .0001). Controlling for demographic and clinical characteristics, a multilevel regression analysis demonstrated that the CSA was not a significant independent predictor for change in WORC (P = .581), ASES (P = .458), or VAS (P = .859) scores at 24 months after arthroscopic RCR. Interobserver and intraobserver reliability for CSA measurements resulted in interclass correlation coefficients of 0.986 and 0.982, respectively (P < .001), indicating excellent agreement. Conclusion: The CSA did not appear to be a significant predictor of patient-reported outcomes after arthroscopic repair of atraumatic full-thickness RCTs. PMID:28451621

Effects of Gallic Acid and Cyclosporine A on Antioxidant Capacity and Cardiac Markers of Rat Isolated Heart After Ischemia/Reperfusion

PubMed Central

Badavi, Mohammad; Sadeghi, Najmeh; Dianat, Mahin; Samarbafzadeh, Alireza

2014-01-01

Background: Myocardial infarction is one of the important causes of death during old ages. Gallic acid as an antioxidant or cyclosporine A (CsA) as inhibitor of mitochondrial permeability transition pore (mPTP) alone could prevent these complications to some extent, but their combination effect has not been investigated. Objectives: The aim of this study was to determine the combined effect of gallic acid and CsA on antioxidant capacity of isolated heart tissues during ischemia reperfusion. Materials and Methods: Eighty male Wistar rats were randomly assigned to different groups: sham, control (Ca, received saline, 1 mL/kg); 3 groups were pretreated with gallic acid (G1a: 7.5, G2a: 15, G3a: 30 mg/kg) for 10 days, and the other 3 groups were pretreated with gallic acid and received CsA (0.2 µM) for 10 minutes before induction of ischemia and during the first 10 minutes of reperfusion (G1b, G2b and G3b) and the last group received CsA alone (Cb). After 10 days of pretreatment, the heart was isolated and transferred to the Langendorff apparatus and exposed to 30 minutes ischemia followed by 60 minutes of reperfusion. After that cardiac markers and antioxidant enzymes were assessed in cardiac tissues. Results: Lactate dehydrogenase (LDH), Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activity increased and malondialdehyde (MDA) decreased in animals pretreated with gallic acid significantly. However, pretreatment with gallic acid followed by CsA during reperfusion improved the antioxidant capacity and cardiac marker enzymes and restored the lipid peroxidation more effective than gallic acid or CsA alone. Nevertheless, CsA did not change the cardiac marker enzymes significantly. Conclusions: Gallic acid and CsA combination improved antioxidant capacity and cell membrane integrity more than each one alone. Therefore, it can be a therapeutic approach to reduce the I/R injury. PMID:25068044

Murine Model for Preclinical Studies of Var2CSA-Mediated Pathology Associated with Malaria in Pregnancy

PubMed Central

Dechavanne, Sebastien; Sousa, Patrícia M.; Barateiro, André; Cunha, Sónia F.; Nunes-Silva, Sofia; Lima, Flávia A.; Murillo, Oscar; Marinho, Claudio R. F.; Gangnard, Stephane; Srivastava, Anand; Braks, Joanna A.; Janse, Chris J.; Gamain, Benoit; Penha-Gonçalves, Carlos

2016-01-01

Plasmodium falciparum infection during pregnancy leads to abortions, stillbirth, low birth weight, and maternal mortality. Infected erythrocytes (IEs) accumulate in the placenta by adhering to chondroitin sulfate A (CSA) via var2CSA protein exposed on the P. falciparum IE membrane. Plasmodium berghei IE infection in pregnant BALB/c mice is a model for severe placental malaria (PM). Here, we describe a transgenic P. berghei parasite expressing the full-length var2CSA extracellular region (domains DBL1X to DBL6ε) fused to a P. berghei exported protein (EMAP1) and characterize a var2CSA-based mouse model of PM. BALB/c mice were infected at midgestation with different doses of P. berghei-var2CSA (P. berghei-VAR) or P. berghei wild-type IEs. Infection with 104 P. berghei-VAR IEs induced a higher incidence of stillbirth and lower fetal weight than P. berghei. At doses of 105 and 106 IEs, P. berghei-VAR-infected mice showed increased maternal mortality during pregnancy and fetal loss, respectively. Parasite loads in infected placentas were similar between parasite lines despite differences in maternal outcomes. Fetal weight loss normalized for parasitemia was higher in P. berghei-VAR-infected mice than in P. berghei-infected mice. In vitro assays showed that higher numbers of P. berghei-VAR IEs than P. berghei IEs adhered to placental tissue. Immunization of mice with P. berghei-VAR elicited IgG antibodies reactive to DBL1-6 recombinant protein, indicating that the topology of immunogenic epitopes is maintained between DBL1-6–EMAP1 on P. berghei-VAR and recombinant DBL1-6 (recDBL1-6). Our data suggested that impairments in pregnancy caused by P. berghei-VAR infection were attributable to var2CSA expression. This model provides a tool for preclinical evaluation of protection against PM induced by approaches that target var2CSA. PMID:27045035

Green Tea Polyphenols Stimulate Mitochondrial Biogenesis and Improve Renal Function after Chronic Cyclosporin A Treatment in Rats

PubMed Central

Rehman, Hasibur; Krishnasamy, Yasodha; Haque, Khujista; Lemasters, John J.; Schnellmann, Rick G.; Zhong, Zhi

2013-01-01

Our previous studies showed that an extract from Camellia sinenesis (green tea), which contains several polyphenols, attenuates nephrotoxicity caused by cyclosporine A (CsA). Since polyphenols are stimulators of mitochondrial biogenesis (MB), this study investigated whether stimulation of MB plays a role in green tea polyphenol protection against CsA renal toxicity. Rats were fed a powdered diet containing green tea polyphenolic extract (0.1%) starting 3 days prior to CsA treatment (25 mg/kg, i.g. daily for 3 weeks). CsA alone decreased renal nuclear DNA-encoded oxidative phosphorylation (OXPHOS) protein ATP synthase-β (AS-β) by 42%, mitochondrial DNA (mtDNA)-encoded OXPHOS protein NADH dehydrogenase-3 (ND3) by 87% and their associated mRNAs. Mitochondrial DNA copy number was also decreased by 78% by CsA. Immunohistochemical analysis showed decreased cytochrome c oxidase subunit IV (COX-IV), an OXPHOS protein, in tubular cells. Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, the master regulator of MB, and mitochondrial transcription factor-A (Tfam), the transcription factor that regulates mtDNA replication and transcription, were 42% and 90% lower, respectively, in the kidneys of CsA-treated than in untreated rats. These results indicate suppression of MB by chronic CsA treatment. Green tea polyphenols alone and following CsA increased AS-β, ND3, COX-IV, mtDNA copy number, PGC-1α mRNA and protein, decreased acetylated PGC-1α, and increased Tfam mRNA and protein. In association with suppressed MB, CsA increased serum creatinine, caused loss of brush border and dilatation of proximal tubules, tubular atrophy, vacuolization, apoptosis, calcification, and increased neutrophil gelatinase-associated lipocalin expression, leukocyte infiltration, and renal fibrosis. Green tea polyphenols markedly attenuated CsA-induced renal injury and improved renal function. Together, these results demonstrate that green tea polyphenols attenuate CsA-induced kidney injury, at least in part, through the stimulation of MB. PMID:23755172

Stable bioavailability of cyclosporin A, regardless of food intake, from soft gelatin capsules containing a new self-nanoemulsifying formulation.

PubMed

Yang, S G; Kim, D D; Chung, S J; Shim, C K

2006-05-01

We recently succeeded in preparing soft gelatin capsules containing a new self-nanoemulsifying formulation consisting of cyclosporin A (CsA), triacetin, polyoxyl 40 hydrogenated castor oil, polysorbate 20, medium chain triglycerides and medium chain mono- and diglycerides. The soft capsules containing the new formulation exhibited a significantly improved physical stability in terms of the appearance of the gelatin capsule shells and the composition of the fill mass during long-term storage, compared to commercially available soft capsules containing CsA, in which ethanol was employed as a cosolvent of CsA. In the present study, the influence of a fat-rich meal on the bioavailability of CsA from the soft capsule containing the new formulation (test drug) was evaluated and the results compared to those obtained with a representative soft capsule of CsA. A randomized, open-label, 3-way crossover study was performed in the test capsules and reference soft capsules, in a fasted state or after a fat-rich breakfast. 18 healthy male volunteers received a single dose of the reference formulation (Neoral, Novartis AG, Basel, Switzerland) or test formulation (2 capsules each, 200 mg as CsA) with 240 ml of water with a 1-week washout period between the treatments, after a fat-rich (670 kcal, 45 g fat) breakfast (for the test drug, Treatment A; for the reference drug, Treatment B) or a 12-h fasting (for the test drug, Treatment C). Serial blood samples, collected over a 24-h period after the administration, were assayed for blood CsA concentrations using a specific monoclonal radioimmunoassay. The differences in bioavailability parameters (i.e., AUC(0-24h), AUC(0-infinity) and C(max)) between the treatments were within the range of 80-125% of the reference treatment. An analysis of variance (ANOVA) revealed no significant differences (p > 0.05) between subjects, formulations or periods. The 90% confidence intervals (CI) indicated that the differences between the treatments (Treatments A and B, Treatments A and C) were also within the criteria. These results indicate that the bioavailability of CsA from the test drug is equivalent to reference in the fed state, and is likely to be less influenced by a fat-rich meal. Therefore, the new formulation of CsA using triacetin appears to have an advantage over the commercial soft capsules of CsA using a volatile cosolvent such as ethanol.

Novel micelle carriers for cyclosporin A topical ocular delivery: in vivo cornea penetration, ocular distribution and efficacy studies.

PubMed

Di Tommaso, Claudia; Bourges, Jean-Louis; Valamanesh, Fatemeh; Trubitsyn, Gregory; Torriglia, Alicia; Jeanny, Jean-Claude; Behar-Cohen, Francine; Gurny, Robert; Möller, Michael

2012-06-01

Cornea transplantation is one of the most performed graft procedures worldwide with an impressive success rate of 90%. However, for "high-risk" patients with particular ocular diseases in addition to the required surgery, the success rate is drastically reduced to 50%. In these cases, cyclosporin A (CsA) is frequently used to prevent the cornea rejection by a systemic treatment with possible systemic side effects for the patients. To overcome these problems, it is a challenge to prepare well-tolerated topical CsA formulations. Normally high amounts of oils or surfactants are needed for the solubilization of the very hydrophobic CsA. Furthermore, it is in general difficult to obtain ocular therapeutic drug levels with topical instillations due to the corneal barriers that efficiently protect the intraocular structures from foreign substances thus also from drugs. The aim of this study was to investigate in vivo the effects of a novel CsA topical aqueous formulation. This formulation was based on nanosized polymeric micelles as drug carriers. An established rat model for the prevention of cornea graft rejection after a keratoplasty procedure was used. After instillation of the novel formulation with fluorescent labeled micelles, confocal analysis of flat-mounted corneas clearly showed that the nanosized carriers were able to penetrate into all corneal layers. The efficacy of a 0.5% CsA micelle formulation was tested and compared to a physiological saline solution and to a systemic administration of CsA. In our studies, the topical CsA treatment was carried out for 14 days, and the three parameters (a) cornea transparency, (b) edema, and (c) neovascularization were evaluated by clinical observation and scoring. Compared to the control group, the treated group showed a significant higher cornea transparency and significant lower edema after 7 and 13 days of the surgery. At the end point of the study, the neovascularization was reduced by 50% in the CsA-micelle treated animals. The success rate of cornea graft transplantation was 73% in treated animals against 25% for the control group. This result was as good as observed for a systemic CsA treatment in the same animal model. This new formulation has the same efficacy like a systemic treatment but without the serious CsA systemic side effects. Ocular drug levels of transplanted and healthy rat eyes were dosed by UPLC/MS and showed a high CsA value in the cornea (11710 ± 7530 ng(CsA)/g(tissue) and 6470 ± 1730 ng(CsA)/g(tissue), respectively). In conclusion, the applied formulation has the capacity to overcome the ocular surface barriers, the micelles formed a drug reservoir in the cornea from, where a sustained release of CsA can take place. This novel formulation for topical application of CsA is clearly an effective and well-tolerated alternative to the systemic treatment for the prevention of corneal graft rejection. Copyright © 2012 Elsevier B.V. All rights reserved.

The clinical pattern of nephrotic syndrome in children has no effect on the concentration of soluble urokinase receptor (suPAR) in serum and urine.

PubMed

Ochocińska, Agnieszka; Jarmużek, Wioletta; Janas, Roman

2018-04-23

Concentration of soluble urokinase receptor (suPAR) was regarded as viable marker to differentiate the focal segmental glomerulosclerosis (FSGS) from other glomerulopathies and also as predictive parameter for progression of renal disease. The aim of this study was to evaluate serum and urine (s)(u)suPAR concentration in steroid-sensitive and steroid-resistant nephrotic children treated with different (double and triple-drug) regimens. Overall 43 children were evaluated including 14 patients with steroid-resistant nephrotic syndrome (SRNS) aged 9±6 years and 29 with steroid-sensitive nephrotic syndrome (SSNS) aged 9±5 years, as well as control group (n=59). The concentration of suPAR was measured with ELISA kit (R∧D Systems Inc.). There was no difference in serum suPAR level between SRNS (6404, range: 4613-9575 pg/mL) and SSNS (5745, range: 4666-8246 pg/mL) patients, and also in urinary suPAR: SRNS (2877, range: 847- 19121 pg/mL) and SSNS (2854, range: 328-7434 pg/mL), respectively. There was no statistically significant difference in serum biomarker concentrations between patients with severe course of the disease, in combination therapy, with three drugs: CsA + MMF + Pred (5968, range: 4613-9575 pg/mL) in comparison with patients receiving double therapy: CsA + Pred or MMF + Pred (5449, range: 4666-6623 pg/mL, 5905, range: 5102-6730 pg/mL, respectively). SuPAR concentration in the urine of patients treated with Pred + MMF was lower (1493, range: 328-4444 pg/mL) than in patients receiving Pred + CsA (3193, range: 629-7434 pg/mL), as well as lower than in patients with triple combination of drugs (3318, range: 448-5570 pg/mL), however the difference was not statistically significant. Serum and urine concentration of suPAR did not different between different clinical patterns of nephrotic syndrome in children, regardless the immunosuppressive treatment used. © 2018 MEDPRESS.

Method and apparatus for detection of charge on ions and particles

DOEpatents

Fuerstenau, Stephen Douglas; Soli, George Arthur

2002-01-01

The present invention provides a tessellated array detector with charge collecting plate (or cup) electrode pixels and amplifying circuitry integrated into each pixel making it sensitive to external electrostatic charge; a micro collector/amplifier pixel design possessing a small capacitance to ensure a high charge to voltage signal conversion for low noise/high sensitivity operation; a micro-fabricated array of such pixels to create a useful macroscopic target area for ion and charged particle collection.

One Week of Bed Rest Leads to Substantial Muscle Atrophy and Induces Whole-Body Insulin Resistance in the Absence of Skeletal Muscle Lipid Accumulation.

PubMed

Dirks, Marlou L; Wall, Benjamin T; van de Valk, Bas; Holloway, Tanya M; Holloway, Graham P; Chabowski, Adrian; Goossens, Gijs H; van Loon, Luc J C

2016-10-01

Short (<10 days) periods of muscle disuse, often necessary for recovery from illness or injury, lead to various negative health consequences. The current study investigated mechanisms underlying disuse-induced insulin resistance, taking into account muscle atrophy. Ten healthy, young males (age: 23 ± 1 years; BMI: 23.0 ± 0.9 kg · m(-2)) were subjected to 1 week of strict bed rest. Prior to and after bed rest, lean body mass (dual-energy X-ray absorptiometry) and quadriceps cross-sectional area (CSA; computed tomography) were assessed, and peak oxygen uptake (VO2peak) and leg strength were determined. Whole-body insulin sensitivity was measured using a hyperinsulinemic-euglycemic clamp. Additionally, muscle biopsies were collected to assess muscle lipid (fraction) content and various markers of mitochondrial and vascular content. Bed rest resulted in 1.4 ± 0.2 kg lean tissue loss and a 3.2 ± 0.9% decline in quadriceps CSA (both P < 0.01). VO2peak and one-repetition maximum declined by 6.4 ± 2.3 (P < 0.05) and 6.9 ± 1.4% (P < 0.01), respectively. Bed rest induced a 29 ± 5% decrease in whole-body insulin sensitivity (P < 0.01). This was accompanied by a decline in muscle oxidative capacity, without alterations in skeletal muscle lipid content or saturation level, markers of oxidative stress, or capillary density. In conclusion, 1 week of bed rest substantially reduces skeletal muscle mass and lowers whole-body insulin sensitivity, without affecting mechanisms implicated in high-fat diet-induced insulin resistance. © 2016 by the American Diabetes Association.

Mental Health Among Help-Seeking Urban Women: The Relationships Between Adverse Childhood Experiences, Sexual Abuse, and Suicidality.

PubMed

Hamdullahpur, Kevin; Jacobs, Kahá Wi J; Gill, Kathryn J

2018-03-01

Adverse childhood experiences (ACEs) and adult mental health were explored in a sample of urban Aboriginal ( n = 83) and non-Aboriginal ( n = 89) women. Childhood sexual abuse (CSA) was associated with negative home environments, teenage pregnancy, lifetime suicide attempts, and treatment seeking. Aboriginal women with CSA witnessed higher levels of physical/sexual abuse of family members. The severity of current psychological distress was associated with a history of childhood neglect. The results indicate that CSA rarely occurs in isolation, and that multiple ACEs are strongly associated with suicide attempts and treatment seeking in adulthood. Future studies should focus on the role of CSA in suicidality, as well as familial, community, and cultural protective factors.

Overgeneral autobiographical memory and age of onset of childhood sexual abuse in patients with recurrent suicidal behaviour.

PubMed

Crane, Catherine; Duggan, Danielle S

2009-03-01

To explore the association between age of onset of childhood sexual abuse (CSA) and overgeneral memory (OGM) in a clinical sample. Presence and age of onset of CSA and levels of OGM were assessed in 49 patients attending hospital following a recurrence of suicidal behaviour. Twenty six participants reported CSA. Earlier age of onset of CSA was associated with greater OGM, indexed by fewer specific and more categoric memories. The association was not accounted for either by elevated levels of depression in those reporting earlier abuse, nor by levels of general verbal fluency. The findings are consistent with previous work and support the hypothesis that abuse occurring earlier in development results in more pronounced OGM.

Mass amplifying probe for sensitive fluorescence anisotropy detection of small molecules in complex biological samples.

PubMed

Cui, Liang; Zou, Yuan; Lin, Ninghang; Zhu, Zhi; Jenkins, Gareth; Yang, Chaoyong James

2012-07-03

Fluorescence anisotropy (FA) is a reliable and excellent choice for fluorescence sensing. One of the key factors influencing the FA value for any molecule is the molar mass of the molecule being measured. As a result, the FA method with functional nucleic acid aptamers has been limited to macromolecules such as proteins and is generally not applicable for the analysis of small molecules because their molecular masses are relatively too small to produce observable FA value changes. We report here a molecular mass amplifying strategy to construct anisotropy aptamer probes for small molecules. The probe is designed in such a way that only when a target molecule binds to the probe does it activate its binding ability to an anisotropy amplifier (a high molecular mass molecule such as protein), thus significantly increasing the molecular mass and FA value of the probe/target complex. Specifically, a mass amplifying probe (MAP) consists of a targeting aptamer domain against a target molecule and molecular mass amplifying aptamer domain for the amplifier protein. The probe is initially rendered inactive by a small blocking strand partially complementary to both target aptamer and amplifier protein aptamer so that the mass amplifying aptamer domain would not bind to the amplifier protein unless the probe has been activated by the target. In this way, we prepared two probes that constitute a target (ATP and cocaine respectively) aptamer, a thrombin (as the mass amplifier) aptamer, and a fluorophore. Both probes worked well against their corresponding small molecule targets, and the detection limits for ATP and cocaine were 0.5 μM and 0.8 μM, respectively. More importantly, because FA is less affected by environmental interferences, ATP in cell media and cocaine in urine were directly detected without any tedious sample pretreatment. Our results established that our molecular mass amplifying strategy can be used to design aptamer probes for rapid, sensitive, and selective detection of small molecules by means of FA in complex biological samples.

Current pulse amplifier transmits detector signals with minimum distortion and attenuation

NASA Technical Reports Server (NTRS)

Bush, N. E.

1967-01-01

Amplifier translates the square pulses generated by a boron-trifluoride neutron sensitive detector located adjacent to a nuclear reactor to slower, long exponential decay pulses. These pulses are transmitted over long coaxial cables with minimum distortion and loss of frequency.

Mouse forepaw lumbrical muscles are resistant to age-related declines in force production.

PubMed

Russell, Katelyn A; Ng, Rainer; Faulkner, John A; Claflin, Dennis R; Mendias, Christopher L

2015-05-01

A progressive loss of skeletal muscle mass and force generating capacity occurs with aging. Mice are commonly used in the study of aging-associated changes in muscle size and strength, with most models of aging demonstrating 15-35% reductions in muscle mass, cross-sectional area (CSA), maximum isometric force production (Po) and specific force (sPo), which is Po/CSA. The lumbrical muscle of the mouse forepaw is exceptionally small, with corresponding short diffusion distances that make it ideal for in vitro pharmacological studies and measurements of contractile properties. However, the aging-associated changes in lumbrical function have not previously been reported. To address this, we tested the hypothesis that compared to adult (12month old) mice, the forepaw lumbrical muscles of old (30month old) mice exhibit aging-related declines in size and force production similar to those observed in larger limb muscles. We found that the forepaw lumbricals were composed exclusively of fibers with type II myosin heavy chain isoforms, and that the muscles accumulated connective tissue with aging. There were no differences in the number of fibers per whole-muscle cross-section or in muscle fiber CSA. The whole muscle CSA in old mice was increased by 17%, but the total CSA of all muscle fibers in a whole-muscle cross-section was not different. No difference in Po was observed, and while sPo normalized to total muscle CSA was decreased in old mice by 22%, normalizing Po by the total muscle fiber CSA resulted in no difference in sPo. Combined, these results indicate that forepaw lumbrical muscles from 30month old mice are largely protected from the aging-associated declines in size and force production that are typically observed in larger limb muscles. Copyright © 2015 Elsevier Inc. All rights reserved.

Mechanical characteristics of distension-evoked peristaltic contractions in the esophagus of systemic sclerosis patients.

PubMed

Gregersen, Hans; Villadsen, Gerda E; Liao, Donghua

2011-12-01

Systemic sclerosis (SS) patients with severe esophageal affection have impaired peristalsis. However, motor function evaluated in vivo by manometry and fluoroscopy does not provide detailed information about the individual contraction cycles. To apply, for the first time in gastrointestinal (GI) patients, a method and principles modified from cardiac research to study esophageal muscle behavior in SS patients. Muscle contraction cycles were analyzed using pressure-cross-sectional area (P-CSA) loops during distension pressure up to 5 kPa. The probe with bag and electrodes for CSA measurements was positioned 7 and 15 cm above the lower esophageal sphincter (LES) in eleven healthy volunteers and eleven SS patients. The P-CSA, the wall tension, Δtension (afterload tension - preload tension), contraction velocity, work output (area of the tension-CSA loops), and power output (preload tension × CSA rate) were analyzed. The P-CSA loops consisted of phases with relaxation and contraction behavior. The tension-stretch ratio loops in patients were shifted to the left at both distension sites, indicative of a stiffer wall in patients. Lower contraction amplitudes and smaller P-CSA loops were observed for the SS patients. The work output, power output, Δtension, and contraction velocity were lower in patients (P < 0.001). Association was found between disease duration and the work output, Δtension, and velocity at pressure steps higher than 3 kPa (P < 0.05). Distension-evoked esophageal contraction can be studied in vivo and analyzed with advanced methods. Increased esophageal stiffness and impaired muscle function that depended on disease duration were observed for SS patients. The analysis may be useful for characterization of other diseases affecting GI function.

Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats

PubMed Central

Caires, A.; Fernandes, G.S.; Leme, A.M.; Castino, B.; Pessoa, E.A.; Fernandes, S.M.; Fonseca, C.D.; Vattimo, M.F.; Schor, N.; Borges, F.T.

2017-01-01

Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects. PMID:29267497

Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats.

PubMed

Caires, A; Fernandes, G S; Leme, A M; Castino, B; Pessoa, E A; Fernandes, S M; Fonseca, C D; Vattimo, M F; Schor, N; Borges, F T

2017-12-11

Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

Molecular dissection of placental malaria protein VAR2CSA interaction with a chemo-enzymatically synthesized chondroitin sulfate library.

PubMed

Sugiura, Nobuo; Clausen, Thomas Mandel; Shioiri, Tatsumasa; Gustavsson, Tobias; Watanabe, Hideto; Salanti, Ali

2016-12-01

Placental malaria, a serious infection caused by the parasite Plasmodium falciparum, is characterized by the selective accumulation of infected erythrocytes (IEs) in the placentas of the pregnant women. Placental adherence is mediated by the malarial VAR2CSA protein, which interacts with chondroitin sulfate (CS) proteoglycans present in the placental tissue. CS is a linear acidic polysaccharide composed of repeating disaccharide units of D-glucuronic acid and N-acetyl-D-galactosamine that are modified by sulfate groups at different positions. Previous reports have shown that placental-adhering IEs were associated with an unusually low sulfated form of chondroitin sulfate A (CSA) and that a partially sulfated dodecasaccharide is the minimal motif for the interaction. However, the fine molecular structure of this CS chain remains unclear. In this study, we have characterized the CS chain that interacts with a recombinant minimal CS-binding region of VAR2CSA (rVAR2) using a CS library of various defined lengths and sulfate compositions. The CS library was chemo-enzymatically synthesized with bacterial chondroitin polymerase and recombinant CS sulfotransferases. We found that C-4 sulfation of the N-acetyl-D-galactosamine residue is critical for supporting rVAR2 binding, whereas no other sulfate modifications showed effects. Interaction of rVAR2 with CS is highly correlated with the degree of C-4 sulfation and CS chain length. We confirmed that the minimum structure binding to rVAR2 is a tri-sulfated CSA dodecasaccharide, and found that a highly sulfated CSA eicosasaccharide is a more potent inhibitor of rVAR2 binding than the dodecasaccharides. These results suggest that CSA derivatives may potentially serve as targets in therapeutic strategies against placental malaria.

Electrical Stimulation During Gait Promotes Increase of Muscle Cross-sectional Area in Quadriplegics: A Preliminary Study

PubMed Central

Cliquet, Alberto; Rondina, Jane Maryan; Cendes, Fernando

2008-01-01

Increases in muscular cross-sectional area (CSA) occur in quadriplegics after training, but the effects of neuromuscular electrical stimulation (NMES) along with training are unknown. Thus, we addressed two questions: (1) Does NMES during treadmill gait training increase the quadriceps CSA in complete quadriplegics?; and (2) Is treadmill gait training alone enough to observe an increase in CSA? Fifteen quadriplegics were divided into gait (n = 8) and control (n = 7) groups. The gait group performed training with NMES for 6 months twice a week for 20 minutes each time. After 6 months of traditional therapy, the control group received the same gait training protocol but without NMES for an additional 6 months. Axial images of the thigh were acquired at the beginning of the study, at 6 months (for both groups), and at 12 months for the control group to determine the average quadriceps CSA. After 6 months, there was an increase of CSA in the gait group (from 49.8 ± 9.4 cm2 to 57.3 ± 10.3 cm2), but not in the control group (from 43.6 ± 7.6 cm2 to 41.8 ± 8.4 cm2). After another 6 months of gait without NMES in the control group, the CSA did not change (from 41.8 ± 8.4 cm2 to 41.7 ± 7.9 cm2). The increase in quadriceps CSA after gait training in patients with chronic complete quadriplegia appears associated with NMES. PMID:18791775

Measurement of esophago-gastric junction cross-sectional area and distensibility by an endolumenal functional lumen imaging probe for the diagnosis of gastro-esophageal reflux disease.

PubMed

Tucker, E; Sweis, R; Anggiansah, A; Wong, T; Telakis, E; Knowles, K; Wright, J; Fox, M

2013-11-01

Measurement of esophago-gastric junction (EGJ) cross-sectional area (CSA) and distensibility by an Endolumenal Functional Lumen Imaging Probe (EndoFLIP®) may distinguish between gastro-esophageal reflux disease (GERD) patients and healthy volunteers (HV). We aimed to assess the agreement of EndoFLIP® measurements with clinical and physiologic diagnosis of GERD. Twenty-one HV and 18 patients with typical GERD symptoms were studied. After gastroscopy, EGJ CSA, and distensibility were measured by EndoFLIP®. Forty-eight hour esophageal pH monitoring was then performed by a wireless system. The ability of EndoFLIP® to discriminate GERD patient and HVs was assessed. Planned secondary analysis then assessed whether EGJ CSA and distensibility were increased in individuals with pathologic acid exposure. Healthy volunteers were younger and had lower body mass index (BMI; both p < 0.001). Pathologic acid exposure was present in 3/21 (14%) HVs and 9/18 (50%) patients (p = 0.126). At 30 mL EndoFLIP® bag volume, EGJ CSA was higher (p = 0.058) and EGJ distensibility was lower (p = 0.020) in HVs than patients. Secondary analysis showed that EGJ measurements were similar in participants with and without pathologic acid exposure (CSA 98 mm² vs 107 mm²; p = 0.789, distensibility; p = 0.704). An inverse association between BMI and CSA (R² = 0.2758, p = 0.001) and distensibility (R² = 0.2005, p = 0.005) was present. Endolumenal Functional Lumen Imaging Probe is not useful for GERD diagnosis because EGJ CSA and distensibility do not distinguish between HVs and GERD patients defined by clinical presentation or pH measurement. This unexpected result may be due to an important, confounding interaction of obesity. © 2013 John Wiley & Sons Ltd.

The effect of cyclosporin-A on peri-operative myocardial injury in adult patients undergoing coronary artery bypass graft surgery: a randomised controlled clinical trial

PubMed Central

Hausenloy, DJ; Kunst, G; Boston-Griffiths, E; Kolvekar, S; Chaubey, S; John, L; Desai, J; Yellon, DM

2014-01-01

Objective Cyclosporin-A (CsA) has been reported to reduce myocardial infarct size in both the experimental and clinical settings. This protective effect is dependent on its ability to prevent the opening of the mitochondrial permeability transition pore, a critical determinant of cell death in the setting of acute ischaemia-reperfusion injury. Whether CsA can reduce the extent of peri-operative myocardial injury (PMI) in patients undergoing coronary artery bypass graft (CABG) surgery is unknown, and is investigated in this randomised controlled clinical trial. Methods 78 adult patients undergoing elective CABG surgery were randomised to receive either an intravenous bolus of CsA (2.5 mg/kg) or placebo administered after induction of anaesthesia and prior to sternotomy. PMI was assessed by measuring serum cardiac enzymes, troponin T (cTnT) and CK-MB at 0, 6, 12, 24, 48 and 72 h after surgery. Results There was no significant difference in mean peak cTnT levels between control (n=43) and CsA treatment (n=40) patients (0.56±0.06 ng/mL with control vs 0.35±0.05 ng/mL with CsA; p=0.07). However, in higher-risk patients with longer cardiopulmonary bypass times, there was a significant reduction in PMI with CsA therapy (p=0.049), with a reduced postoperative cTnT rise by 0.03 ng/mL for every 10 min, when compared with control. Conclusions In patients with longer cardiopulmonary bypass times, a single intravenous bolus of CsA administered prior to CABG surgery reduced the extent of PMI. PMID:24488610

Acute non-contact anterior cruciate ligament tears are associated with relatively increased vastus medialis to semimembranosus cross-sectional area ratio: a case-control retrospective MR study.

PubMed

Wieschhoff, Ged G; Mandell, Jacob C; Czuczman, Gregory J; Nikac, Violeta; Shah, Nehal; Smith, Stacy E

2017-11-01

Hamstring muscle deficiency is increasingly recognized as a risk factor for anterior cruciate ligament (ACL) tears. The purpose of this study is to evaluate the vastus medialis to semimembranosus cross-sectional area (VM:SM CSA) ratio on magnetic resonance imaging (MRI) in patients with ACL tears compared to controls. One hundred knee MRIs of acute ACL tear patients and 100 age-, sex-, and side-matched controls were included. Mechanism of injury, contact versus non-contact, was determined for each ACL tear subject. The VM:SM CSA was measured on individual axial slices with a novel method using image-processing software. One reader measured all 200 knees and the second reader measured 50 knees at random to assess inter-reader variability. The intraclass correlation coefficient (ICC) was calculated to evaluate for correlation between readers. T-tests were performed to evaluate for differences in VM:SM CSA ratios between the ACL tear group and control group. The ICC for agreement between the two readers was 0.991 (95% confidence interval 0.984-0.995). Acute ACL tear patients have an increased VM:SM CSA ratio compared to controls (1.44 vs. 1.28; p = 0.005). Non-contact acute ACL tear patients have an increased VM:SM CSA ratio compared to controls (1.48 vs. 1.20; p = 0.003), whereas contact acute ACL tear patients do not (1.23 vs. 1.26; p = 0.762). Acute non-contact ACL tears are associated with increased VM:SM CSA ratios, which may imply a relative deficiency in hamstring strength. This study also demonstrates a novel method of measuring the relative CSA of muscles on MRI.

Amygdala habituation to emotional faces in adolescents with internalizing disorders, adolescents with childhood sexual abuse related PTSD and healthy adolescents.

PubMed

van den Bulk, Bianca G; Somerville, Leah H; van Hoof, Marie-José; van Lang, Natasja D J; van der Wee, Nic J A; Crone, Eveline A; Vermeiren, Robert R J M

2016-10-01

Adolescents with internalizing disorders and adolescents with childhood sexual abuse related post-traumatic stress disorder (CSA-related PTSD) show a large overlap in symptomatology. In addition, brain research indicated hyper-responsiveness and sustained activation instead of habituation of amygdala activation to emotional faces in both groups. Little is known, however, about whether the same patterns of amygdala habituation are present in these two groups. The current study examined habituation patterns of amygdala activity to emotional faces (fearful, happy and neutral) in adolescents with a DSM-IV depressive and/or anxiety disorder (N=25), adolescents with CSA-related PTSD (N=19) and healthy controls (N=26). Behaviourally, the adolescents from the internalizing and CSA-related PTSD group reported more anxiety to fearful and neutral faces than adolescents from the control group and adolescents from the CSA-related PTSD group reacted slower compared to the internalizing group. At the whole brain level, there was a significant interaction between time and group within the left amygdala. Follow-up ROI analysis showed elevated initial activity in the amygdala and rapid habituation in the CSA-related PTSD group compared to the internalizing group. These findings suggest that habituation patterns of amygdala activation provide additional information on problems with emotional face processing. Furthermore, the results suggest there are differences in the underlying neurobiological mechanisms related to emotional face processing for adolescents with internalizing disorders and adolescents with CSA-related PTSD. Possibly CSA-related PTSD is characterized by a stronger primary emotional response driven by the amygdala. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Developing an in situ nanosuspension: a novel approach towards the efficient administration of poorly soluble drugs at the anterior eye.

PubMed

Luschmann, Christoph; Tessmar, Joerg; Schoeberl, Simon; Strauss, Olaf; Framme, Carsten; Luschmann, Karl; Goepferich, Achim

2013-11-20

With about 50-60 million cases in the US alone, dry eye disease represents a severe health care problem. Cyclosporin A (CsA) would be a potent candidate for a causal therapy. However, CsA is not sufficiently water soluble to be administrated via simple eye drops. We developed an in situ nanosuspension (INS) as a novel approach towards the administration of CsA to the cornea. It precipitates upon contact with the tear fluid and creates CsA nanoparticles that enter the cornea and release the drug by dissolution. We selected two liquid poly(ethylene glycols) (PEG) that dissolve CsA and create nanoparticles by precipitation of CsA upon water contact. Aqueous solutions of PEG and Solutol, a non-ionic surfactant, were well tolerated by primary human epithelial cells in vitro. To determine the critical water content needed for a precipitation, the solubility of CsA was investigated in quaternary systems of drug, solvent, surfactant and water. The best INS formulation showed a particle size of 505 ± 5 nm, a polydispersity index (PdI) of 0.23 ± 0.03 and a neutral zeta potential of -0.07 ± 0.05 mV. After single administration to porcine eyes in vitro, 3165 ± 597 ng(CsA)/g(cornea) were detected in corneal tissue, while the levels of Restasis a commercial formulation were, with 545 ± 137 ng(CsA)/g(cornea), significantly lower (P<0.01). These results demonstrate that an INS is a promising, novel approach towards the causal treatment of inflammatory diseases at the anterior eye. Copyright © 2013 Elsevier B.V. All rights reserved.

Confirmatory field study for the evaluation of ciclosporin at a target dose of 7.0 mg/kg (3.2 mg/lb) in the control of feline hypersensitivity dermatitis.

PubMed

Roberts, Elizabeth S; Speranza, Cindy; Friberg, Cecilia; Griffin, Craig; Steffan, Jean; Roycroft, Linda; King, Stephen

2016-11-01

Objectives This study was designed to confirm the efficacy and tolerability of a daily dose of 7.0 mg/kg (3.2 mg/lb) ciclosporin (CsA) in the treatment of feline hypersensitivity dermatitis (HD), as this includes some of the most frequently suspected skin diseases in cats and recent publications have reported the successful use of CsA in the treatment of feline HD. Methods In total, 217 cats with feline HD were treated daily for 42 days with a target dose of 7 mg/kg CsA (n = 144) or a placebo control (n = 73) administered either in the food or directly in the mouth following feeding. Clinical and dermatological evaluations were conducted on days 0, 21 and 42, or study exit. Safety was evaluated through physical examinations, clinical pathology and the monitoring of adverse events (AEs). Results Administration of CsA at 7.0 mg/kg produced a significant improvement in the total lesion score ( P <0.0001). The average reduction from visit 1 to visit 3 was 65.1% in the CsA group (9.2% for the placebo). In addition, owners assessed 78.3% of the cases in the CsA group as a success. Statistically significant recoveries were also seen in extent of lesions, investigator assessment of overall improvement, and mean improvement in both the investigators' and owners' assessment of pruritus. Mild gastrointestinal disorders were the most common AEs but did not require cessation of therapy. Conclusions and relevance Results confirm that 7.0 mg/kg CsA dosed daily in food or orally for up to 6 weeks is effective and well tolerated by cats with feline HD.

Repeatability of diagnostic ultrasonography in the assessment of the equine superficial digital flexor tendon.

PubMed

Pickersgill, C H; Marr, C M; Reid, S W

2001-01-01

A quantitative investigation of the variation that can occur during the course of ultrasonography of the equine superficial digital flexor tendons (SDFT) was undertaken. The aim of this investigation was to use an objective measure, namely the measurement of CSA, to quantify the variability occurring during the course of the ultrasonographic assessment of the equine SDFT. The effects of 3 variables on the CSA measurements were determined. 1) Image acquisition operator (IAc): two different operators undertaking the ultrasonographic examination; 2) image analysis operator (IAn): two different operators undertaking the calculation of CSA values from previously stored images; and 3) analytical equipment (used during CSA measurement) (IEq): the use of 2 different sets of equipment during calculation of CSA values. Tendon cross-sectional area (CSA) measurements were used as the comparative variable of 3 potential sources: interoperator, during image acquisition; interoperator, during CSA measurement; and intraoperator, when using different analytical equipment. Two operators obtained transverse ultrasonographic images from the forelimb SDFTs of 16 National Hunt (NH) Thoroughbred (TB) racehorses, each undertaking analysis of their own and the other operator's images. One operator undertook analysis of their images using 2 sets of equipment. There was no statistically significant difference in the results obtained when different operators undertook image acquisition (P>0.05). At all but the most distal level, there was no significant difference when different equipment was used during analysis (P>0.05). A significant difference (P<0.01) was reported when different operators undertook image analysis, one operator consistently returning larger measurements. Different operators undertaking different stages of an examination can result in significant variability. To reduce confounding during ultrasonographic investigations involving multiple persons, one operator should undertake image analysis, although different operators may undertake image acquisition.

Willingness to disclose child maltreatment: CSA vs other forms of child abuse in relation to gender.

PubMed

Lev-Wiesel, Rachel; First, Maya

2018-05-01

The aim of the study was to examine the role of gender in willingness to disclose childhood sexual abuse (CSA) compared to other forms of abuse (physical, emotional and neglect) in young adolescents. Willingness was examined through two terms: reluctance- the level of unwillingness or disinclination to disclose, and urge-the need to share in order to get rid of unbearable feelings. The sample consisted of 3,156 boys (n = 1,544) and girls (n = 1,612) between the ages of 11-16 who reported having been abused at least once during their life. Participants were divided into three groups: experiencing other than CSA, sexual abuse with no physical contact, and sexual abuse with physical contact. Regarding measures, a self-report questionnaire incorporating the following instruments was administered: Demographics, the Juvenile Victimization Questionnaire (JVQ), and the Disclosure of Trauma Questionnaire (DTQ). Study results indicated that CSA victims were more reluctant to disclose than victims of other than CSA forms of abuse. The more severe the CSA (physical contact) the lower was the willingness to disclose. Boys were more reluctant than girls to disclose sexual abuse whether or not it involved physical contact. Reluctance to disclose was positively associated with emotional reactions to disclosure while urge to talk was negatively correlated with emotional reactions to disclosure. Copyright © 2018. Published by Elsevier Ltd.

Childhood Sexual Abuse and Acute Alcohol Effects on Men’s Sexual Aggression Intentions

PubMed Central

Davis, Kelly Cue; Schraufnagel, Trevor J.; Jacques-Tiura, Angela J.; Norris, Jeanette; George, William H.; Kiekel, Preston A.

2012-01-01

Objective Although research has established childhood sexual abuse (CSA) as a risk factor for men’s perpetration of sexual aggression, there has been little investigation of the factors undergirding this association. This study represents one of the first to use a laboratory-based sexual aggression analogue coupled with an alcohol administration protocol to investigate the pathways through which CSA and alcohol influence men’s self-reported sexual aggression intentions. Method After completing background questionnaires, male social drinkers (N = 220) were randomly assigned to a control, placebo, low alcohol dose or high alcohol dose condition. Following beverage consumption, participants read a sexual scenario in which the female partner refused to have unprotected sexual intercourse, after which they completed dependent measures. Results Path analysis indicated that men with a CSA history and intoxicated men perceived the female character as more sexually aroused and reported stronger sexual entitlement cognitions, both of which were in turn associated with greater condom use resistance and higher sexual aggression intentions. Exploratory analyses revealed that intoxication moderated the effects of CSA history on sexual entitlement cognitions, such that sexual entitlement cognitions were highest for men who had a CSA history and consumed alcohol. Conclusions Findings suggest that CSA history may facilitate sexual assault perpetration through its effects on in-the-moment cognitions, and that these effects may be exacerbated by alcohol intoxication. PMID:22754720

Black grape and garlic extracts protect against cyclosporine a nephrotoxicity.

PubMed

Durak, Ilker; Cetin, Recep; Candir, Ozden; Devrim, Erdinç; Kiliçoğlu, Bülent; Avci, Aslihan

2007-01-01

The aim of this study was to determine if the natural antioxidant foods, dried black grape and garlic, protect against cyclosporine nephrotoxicity. Forty-two Sprague-Dawley rats were given Cyclosporine A (CsA) orally for 10 days, with the antioxidant food supplementation begun 3 days before CsA treatment and continued during the study period (totaling 13 days). In each group (control, CsA alone, CsA plus black grape, CsA plus aqueous garlic extract, aqueous garlic extract alone and black grape alone), there were 7 animals. At the end of the study period, the animals were sacrificed; their kidneys were removed and prepared for biochemical and histopathological investigations. Oxidant (xanthine oxidase enzyme and malondialdehyde) and antioxidant (superoxide dismutase, glutathione peroxidase and catalase enzymes) parameters were measured in the kidney tissues of the groups. Histopathological examinations of the tissues were also performed. It has been found that CsA creates oxidant load to the kidneys through both xanthine oxidase activation and impaired antioxidant defense system, which accelerates oxidation reactions in the kidney tissue. Supplementation with either dried black grape or aqueous garlic extract led to reduced malondialdehyde level in the kidney tissue possibly, by preventing oxidant reactions. In conclusion, the results suggest that impaired oxidant/antioxidant balance may play part in the CsA-induced nephrotoxicity, and some foods with high antioxidant power may ameliorate this toxicity, in agreement with studies with antioxidant vitamins.

Functional Antibodies against VAR2CSA in Nonpregnant Populations from Colombia Exposed to Plasmodium falciparum and Plasmodium vivax

PubMed Central

Doritchamou, Justin; Arango, Eliana M.; Cabrera, Ana; Arroyo, Maria Isabel; Kain, Kevin C.; Ndam, Nicaise Tuikue; Maestre, Amanda

2014-01-01

In pregnancy, parity-dependent immunity is observed in response to placental infection with Plasmodium falciparum. Antibodies recognize the surface antigen, VAR2CSA, expressed on infected red blood cells and inhibit cytoadherence to the placental tissue. In most settings of malaria endemicity, antibodies against VAR2CSA are predominantly observed in multigravid women and infrequently in men, children, and nulligravid women. However, in Colombia, we detected antibodies against multiple constructs of VAR2CSA among men and children with acute P. falciparum and Plasmodium vivax infection. The majority of men and children (>60%) had high levels of IgGs against three recombinant domains of VAR2CSA: DBL5ε, DBL3X, and ID1-ID2. Surprisingly, these antibodies were observed only in pregnant women, men, and children exposed either to P. falciparum or to P. vivax. Moreover, the anti-VAR2CSA antibodies are of high avidity and efficiently inhibit adherence of infected red blood cells to chondroitin sulfate A in vitro, suggesting that they are specific and functional. These unexpected results suggest that there may be genotypic or phenotypic differences in the parasites of this region or in the host response to either P. falciparum or P. vivax infection outside pregnancy. These findings may hold significant clinical relevance to the pathophysiology and outcome of malaria infections in this region. PMID:24686068

Conversion to Sirolimus Ameliorates Cyclosporine-Induced Nephropathy in the Rat: Focus on Serum, Urine, Gene, and Protein Renal Expression Biomarkers

PubMed Central

Sereno, José; Nunes, Sara; Rodrigues-Santos, Paulo; Rocha-Pereira, Petronila; Fernandes, João; Teixeira, Frederico; Reis, Flávio

2014-01-01

Protocols of conversion from cyclosporin A (CsA) to sirolimus (SRL) have been widely used in immunotherapy after transplantation to prevent CsA-induced nephropathy, but the molecular mechanisms underlying these protocols remain nuclear. This study aimed to identify the molecular pathways and putative biomarkers of CsA-to-SRL conversion in a rat model. Four animal groups (n = 6) were tested during 9 weeks: control, CsA, SRL, and conversion (CsA for 3 weeks followed by SRL for 6 weeks). Classical and emergent serum, urinary, and kidney tissue (gene and protein expression) markers were assessed. Renal lesions were analyzed in hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome stains. SRL-treated rats presented proteinuria and NGAL (serum and urinary) as the best markers of renal impairment. Short CsA treatment presented slight or even absent kidney lesions and TGF-β, NF-κ β, mTOR, PCNA, TP53, KIM-1, and CTGF as relevant gene and protein changes. Prolonged CsA exposure aggravated renal damage, without clear changes on the traditional markers, but with changes in serums TGF-β and IL-7, TBARs clearance, and kidney TGF-β and mTOR. Conversion to SRL prevented CsA-induced renal damage evolution (absent/mild grade lesions), while NGAL (serum versus urine) seems to be a feasible biomarker of CsA replacement to SRL. PMID:24971338

Rehabilitative ultrasound imaging of the supraspinatus muscle: Intra- and interrater reliability of thickness and cross-sectional area.

PubMed

Schneebeli, Alessandro; Egloff, Michele; Giampietro, Amelia; Clijsen, Ron; Barbero, Marco

2014-04-01

To examine intra- and interrater reliability of thickness and cross-sectional area (CSA) measurements of the supraspinatus muscle using rehabilitative ultrasound imaging (RUSI). Two physical therapists acquired b-mode images of the supraspinatus muscles in twenty-five healthy subjects. Thickness and CSA were measured. Intra- and interrater reliability were examined. Intrarater reliability for thickness was high, (ICC1.1 0.91) for rater 1 and (ICC1.1 0.92) for rater 2. Intrarater reliability for CSA was also high, (ICC1.1 0.90) for rater 1 and (ICC1.1 0.85) for rater 2. Interrater reliability for the thickness was high, (ICC3.1 0.86). For CSA, interrater reliability was moderate, (ICC3.1 0.70). Supraspinatus muscle thickness and CSA can be reliably measured by physical therapists in healthy subjects. These findings confirm that RUSI has an interesting potential for physiotherapy clinical practice, especially to assess morphometric changes in skeletal muscles. Further research is needed in subjects with shoulder disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

A comparison of nickel-titanium rotary instruments manufactured using different methods and cross-sectional areas: ability to resist cyclic fatigue.

PubMed

Oh, So-Ram; Chang, Seok-Woo; Lee, Yoon; Gu, Yu; Son, Won-Jun; Lee, Woocheol; Baek, Seung-Ho; Bae, Kwang-Shik; Choi, Gi-Woon; Lim, Sang-Min; Kum, Kee-Yeon

2010-04-01

This study examined the effect of the manufacturing methods (ground, electropolished, and twisted) and the cross-sectional area (CSA) of nickel-titanium (NiTi) rotary instruments on their cyclic fatigue resistance. A total of 80 NiTi rotary instruments (ISO 25/.06 taper) from 4 brands (K3, ProFile, RaCe, and TF) were rotated in a simulated root canal with pecking motion until fracture. The number of cycles to failure (NCF) was calculated. The CSA at 3 mm from the tip of new instruments of each brand was calculated. The correlation between the CSA and NCF was evaluated. All fractured surfaces were analyzed using a scanning electron microscope to determine the fracture mode. The TF instruments were the most resistant to fatigue failure. The resistance to cyclic failure increased with decreasing CSA. All fractured surfaces showed the coexistence of ductile and brittle properties. The CSA had a significant effect on the fatigue resistance of NiTi rotary instruments. Copyright 2010 Mosby, Inc. All rights reserved.

Childhood Sexual Abuse and Fear of Abandonment Moderate the Relation of Intimate Partner Violence to Severity of Dissociation.

PubMed

Zerubavel, Noga; Messman-Moore, Terri L; DiLillo, David; Gratz, Kim L

2018-01-01

Betrayal trauma theory proposes a relation between intimate partner violence (IPV) and dissociation, suggesting that dissociation among victims of IPV may function to restrict awareness of abuse in order to preserve attachments perceived as vital. We investigated two factors that may moderate the relation between IPV and dissociation-childhood sexual abuse (CSA) severity and fear of abandonment-among 348 women currently in a relationship. The relation between frequency of IPV (sexual and physical) and dissociation (amnesia and depersonalization) was moderated by CSA severity and fear of abandonment. Specifically, among women with clinically relevant fear of abandonment, the strength of the relation between IPV and dissociation became stronger as CSA severity increased. This study is the first to demonstrate the moderating roles of fear of abandonment and CSA history in the relation between IPV and dissociation among women. Findings suggest that it may be important to target fear of abandonment in interventions with IPV victims who have a CSA history. Results suggest that fear of abandonment warrants greater attention in research on IPV revictimization.

Cyclosporin A-induced new cementum formation: a morphometric evaluation in the periapical region of rats.

PubMed

Spolidorio, Luis Carlos; Spolidorio, Denise Madalena Palomari; Holzhausen, Marinella; Nassar, Carlos Augusto; Nassar, Patricia Oehlmeyer

2007-01-01

Cyclosporin A (CsA) is a potent immunosuppressor used in organ transplantation and in the management of various autoimmune diseases. Recent studies have shown that CsA stimulates deposition of cementum on root surfaces. The aim of this study was to evaluate the periapical cementum thickness and the apical foramen width in CsA-treated rats. Rats weighing 50 g were treated with a daily injection of 10 mg/kg body weight of CsA in the chow for 60 days. The cementum of the mandibular 1st molars was histologically and morphometricaly examined by analysis of 5-microm-thick serial buccolingual paraffin sections stained with hematoxylin and eosin. Histometric and stereologic analyses revealed the presence of large amounts of cementum in all root surfaces, particularly abundant in the periapical region and obliterating the foramen. The volume density of cementoblasts did not increase. Five to 90 days after the termination of CsA therapy, there was no reduction of cementum thickness. These results suggest that cementum deposition is not reversible after cessation of CsA treatment.

Hydration studies of calcium sulfoaluminate cements blended with fly ash

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

García-Maté, M.; De la Torre, A.G.; León-Reina, L.

The main objective of this work is to study the hydration and properties of calcium sulfoaluminate cement pastes blended with fly ash (FA) and the corresponding mortars at different hydration ages. Laboratory X-ray powder diffraction, rheological studies, thermal analysis, porosimetry and compressive strength measurements were performed. The analysis of the diffraction data by Rietveld method allowed quantifying crystalline phases and overall amorphous contents. The studied parameters were: i) FA content, 0, 15 and 30 wt.%; and ii) water addition, water-to-CSA mass ratio (w/CSA = 0.50 and 0.65), and water-to-binder mass ratio (w/b = 0.50). Finally, compressive strengths after 6 monthsmore » of 0 and 15 wt.% FA [w/CSA = 0.50] mortars were similar: 73 ± 2 and 72 ± 3 MPa, respectively. This is justified by the filler effect of the FA as no strong evidences of reactivity of FA with CSA were observed. These results support the partial substitution of CSA cements with FA with the economic and environmental benefits.« less

Cell cycle arrest and induction of apoptosis by cajanin stilbene acid from Cajanus cajan in breast cancer cells.

PubMed

Fu, Yujie; Kadioglu, Onat; Wiench, Benjamin; Wei, Zuofu; Gao, Chang; Luo, Meng; Gu, Chengbo; Zu, Yuangang; Efferth, Thomas

2015-04-15

The low abundant cajanin stilbene acid (CSA) from Pigeon Pea (Cajanus cajan) has been shown to kill estrogen receptor α positive cancer cells in vitro and in vivo. Downstream effects such as cell cycle and apoptosis-related mechanisms have not been analyzed yet. We analyzed the activity of CSA by means of flow cytometry (cell cycle distribution, mitochondrial membrane potential, MMP), confocal laser scanning microscopy (MMP), DNA fragmentation assay (apoptosis), Western blotting (Bax and Bcl-2 expression, caspase-3 activation) as well as mRNA microarray hybridization and Ingenuity pathway analysis. CSA induced G2/M arrest and apoptosis in a concentration-dependent manner from 8.88 to 14.79 µM. The MMP broke down, Bax was upregulated, Bcl-2 downregulated and caspase-3 activated. Microarray profiling revealed that CSA affected BRCA-related DNA damage response and cell cycle-regulated chromosomal replication pathways. CSA inhibited breast cancer cells by DNA damage and cell cycle-related signaling pathways leading to cell cycle arrest and apoptosis. Copyright © 2015 Elsevier GmbH. All rights reserved.

Cyclosporine A alleviated matrix metalloproteinase 9 associated blood-brain barrier disruption after subarachnoid hemorrhage in mice.

PubMed

Pan, Pengyu; Zhang, Xuan; Li, Qiang; Zhao, Hengli; Qu, Jie; Zhang, John H; Liu, Xin; Feng, Hua; Chen, Yujie

2017-05-10

The aim of this study was to investigate whether Cyclosporine A (CsA) attenuates early brain injury by alleviating matrix metalloproteinase 9 (MMP-9) associated blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH). A standard intravascular perforation model was used to produce the experimental SAH in C57B6J mice. Dosages of 5mg/kg, 10mg/kg and 15mg/kg CsA were evaluated for effects on neurological score, brain water content, Evans blue extravasation and fluorescence, P-p65, MMP-9 and BBB components' alterations after SAH. We found that CsA 15mg/kg is effective in attenuating BBB disruption, lowering edema, and improving neurological outcomes. In addition, Collagen IV, ZO-1, Occludin and Claudin 5 expressions in ipsilateral/left hemisphere were downregulated after SAH, but increased after CsA treatment. Our results suggest that CsA exert a neuroprotective role in SAH pathophysiology, possibly by alleviating MMP-9 associated BBB disruption. Copyright © 2017 Elsevier B.V. All rights reserved.

The Prevalence of Child Sexual Abuse in Out-of-home Care: Increased Risk for Children with a Mild Intellectual Disability.

PubMed

Euser, Saskia; Alink, Lenneke R A; Tharner, Anne; van IJzendoorn, Marinus H; Bakermans-Kranenburg, Marian J

2016-01-01

Children without disabilities in out-of-home care have a higher risk of child sexual abuse [CSA (Euser et al. 2013)]. In this study, we examined the year prevalence of CSA in out-of-home care for children with a mild intellectual disability, and compared it with the prevalence in out-of-home care for non-disabled children and children in the general population. Professionals (N = 104) from out-of-home care facilities reported cases of CSA that occurred in 2010 for the children they worked with (N = 1650). In out-of-home care for children with a mild intellectual disability, 9.8 per 1000 children were victims of CSA. This prevalence was significantly higher than in regular out-of-home care and in the general population. Children with a mild intellectual disability in out-of-home care have an increased risk of CSA. Adequate education and support for both children and caregivers is necessary to recognize and prevent further sexual abuse. © 2015 John Wiley & Sons Ltd.

Disorders of Sex Development: Pediatric Psychology and the Genital Exam.

PubMed

Tishelman, Amy C; Shumer, Daniel E; Nahata, Leena

2017-06-01

To provide suggestions for clinical care of youth with disorders of sex development (DSD) and their families, by drawing on preexisting pediatric psychology literature with a particular focus on child sexual abuse (CSA) genital exams. Relevant peer-reviewed papers published since 1990 in the CSA literature were systematically reviewed, as well as an illustrative sample of general pediatric psychology papers. Empirical research from the CSA literature provided information on prevalence of distress and the impact of provider behavior, the importance of preparation, and proposed interventions. Expert recommendations from CSA literature and general findings gleaned from pediatric psychology also address these issues. Psychological findings in the CSA pediatric population suggest that fears and anxieties are not universal and can be linked to a number of variables. Based on this review, we make a number of recommendations for potential interventions for youth with DSD and their families, emphasizing the need for further clinical research. © The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Research and development of a high-performance differential-hybrid charge sensitive preamplifier.

PubMed

Zeng, Guoqiang; Hu, Chuanhao; Wei, Shilong; Yang, Jian; Li, Qiang; Ge, Liangquan; Tan, Chengjun

2017-02-01

A differential-hybrid charge sensitive preamplifier (CSP) was designed by taking a monolithic dual N-Channel Junction Field-effect Transistor (JFET) and a high-speed, low-noise, operational amplifier as the core parts. Input-stage of the circuit employs low-noise differential dual JFET, which ensures high input impedance and low noise. The differential dual transistor makes the quiescent point of the first-stage differential output stable, which is convenient for connecting with the post stage high-speed operational amplifier. Broadband could be amplified by connecting to the double differential dual transistors through the folded cascode-bootstrap. The amplifying circuit which replaces the interstage and post stage discrete components of a traditional CSP with integrated operational amplifier is simpler and more reliable. It simplifies the design of the quiescent point, gives full play to advantages of releasing large open-loop gain, and improves charge-voltage conversion gain stability. Particularly, the charge-voltage conversion gain is larger under a smaller feedback capacitor, thus enabling to gain better signal-noise ratio. The designed CSP was tested, reporting 3.3×10 13 V/C charge sensitivity, about 90ns rise time of signals, 35:1 signal-noise ratio to gamma-rays of 137 Cs (662keV) and a 0.023 fC/pF noise slope. Gamma-rays of 241 Am (59.5keV) were measured by the BPX66 detector and the designed CSP under room temperature, providing 1.97% energy resolution. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preparation of melt-spun antimicrobially modified LDH/polyolefin nanocomposite fibers.

PubMed

Kutlu, Burak; Schröttner, Percy; Leuteritz, Andreas; Boldt, Regine; Jacobs, Enno; Heinrich, Gert

2014-08-01

Layered double hydroxide (LDH) was synthesized and organically modified with camphorsulfonic acid (CSA) and ciprofloxacin. The thermal stability of CSA was improved remarkably under LDH shielding. A minimal inhibitory concentration of free CSA against tested bacteria was determined in order to define the essential quantity in LDH modification. The modified LDHs were melt-compounded with high density polyethylene and the prepared nanocomposites were further melt-spun using a piston-type spinning device. The melt-spun fibers were tested for their antimicrobial activity against Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa, Enterobacter cloacae, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes. CSA integrated fibers show susceptibility against Gram-positive bacteria and ciprofloxacin integrated fibers showed activity against both Gram-positive and Gram-negative bacteria. Copyright © 2014 Elsevier B.V. All rights reserved.

[Effect of glutamate on membrane potential and volume of the skeletal muscle fibers in rats following NO-synthase inhibition in vivo].

PubMed

Khairova, P A; Malomuzh, A I; Naumenko, N V; Urazaev, A Kh

2002-11-01

Cross-sectional area (CSA) of muscle fibers incubated in culture medium 199 for 3 hours dramatically increases, whereas resting membrane potential (RMP) decreases compared to "freshly-isolated" muscles. Both glutamate and sodium nitroprusside prevent these changes. MK-801, a specific inhibitor of NMDA-receptors, eliminates protective effects of glutamate on both CSA and RMP. NO-synthase inhibition in vivo promotes an increase of initial CSA and decrease of mean RMP. Under these conditions, effects of glutamate and sodium nitroprusside on CSA and RMP of denervated muscles are less obvious. It has been concluded that synaptic glutamate is able to participate in regulation of RMP and cell volume in muscle fibers through the activation of postsynaptic NMDA-receptors and muscle NO-synthase.

Analysis of ploidy and the patterns of amplified fragment length polymorphism and methylation sensitive amplified polymorphism in strawberry plants recovered from cryopreservation.

PubMed

Hao, Yu-Jin; You, Chun-Xiang; Deng, Xui-Xin

2002-01-01

Shoot-tips of 10 strawberry genotypes were successfully cryopreserved using a modified encapsulation-dehydration method. All genotypes survived cryopreservation with high survival and regeneration rates. Eight Joho single-bud sibling lines were established as a model system for genetic analysis. Although cytological examination found chromosomal variation in both non-cryopreserved and cryopreserved samples, the ploidy constitution remained relatively stable after cryopreservation. DNA samples digested with MseI and PstI were used for amplified fragmentation length polymorphism (AFLP) assay. In 16 primer combinations, only one, namely, PCCA-MCAG, detected one site where band pattern changed after cryopreservation, which might be contributed to the change in DNA methylation status at PstI recognition site. Methylation sensitive amplified polymorphism (MSAP) assay was carried out for further investigation on the influence of cryopreservation on DNA methylation status. It was found that cryopreservation induced a significant change in DNA methylation status.

[Absorption spectrum of Quasi-continuous laser modulation demodulation method].

PubMed

Shao, Xin; Liu, Fu-Gui; Du, Zhen-Hui; Wang, Wei

2014-05-01

A software phase-locked amplifier demodulation method is proposed in order to demodulate the second harmonic (2f) signal of quasi-continuous laser wavelength modulation spectroscopy (WMS) properly, based on the analysis of its signal characteristics. By judging the effectiveness of the measurement data, filter, phase-sensitive detection, digital filtering and other processing, the method can achieve the sensitive detection of quasi-continuous signal The method was verified by using carbon dioxide detection experiments. The WMS-2f signal obtained by the software phase-locked amplifier and the high-performance phase-locked amplifier (SR844) were compared simultaneously. The results show that the Allan variance of WMS-2f signal demodulated by the software phase-locked amplifier is one order of magnitude smaller than that demodulated by SR844, corresponding two order of magnitude lower of detection limit. And it is able to solve the unlocked problem caused by the small duty cycle of quasi-continuous modulation signal, with a small signal waveform distortion.

SQUID amplifiers for axion search experiments

NASA Astrophysics Data System (ADS)

Matlashov, Andrei; Schmelz, Matthias; Zakosarenko, Vyacheslav; Stolz, Ronny; Semertzidis, Yannis K.

2018-04-01

In the experiments for dark-matter QCD-axion searches, very weak microwave signals from a low-temperature High-Q resonant cavity should be detected using the highest sensitivity. The best commercial low-noise cryogenic semiconductor amplifiers based on high electron mobility transistors have a lowest noise temperature above 1.0 K, even if they are cooled well below 1 K. Superconducting quantum interference devices can work as microwave amplifiers with temperature noise close to the standard quantum limit. Previous SQUID-based RF amplifiers designed for axion search experiments have a microstrip resonant input coil and are thus called micro-strip SQUID amplifiers or MSAs. Due to the resonant input coupling they usually have narrow bandwidth. In this paper we report on a SQUID-based wideband microwave amplifier fabricated using sub-micron size Josephson junctions with very low capacitance. A single amplifier can be used in a frequency range of approximately 1-5 GHz.

32 CFR 2004.5 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... organizational entity delegated by the Head of a CSA to administer industrial security on behalf of the CSA. (c... States. (e) “Proscribed information” means Top Secret; Communications Security, except classified keys...

csa2sac—A program for computing discharge from continuous slope-area stage data

USGS Publications Warehouse

Wiele, Stephen M.

2015-12-17

In addition to csa2sac, the SAC7 program is required. It is the same as the original SAC program, except that it is compiled for 64-bit Windows operating systems and has a slightly different command line input. It is available online (http://water.usgs.gov/software/SAC/) as part of the SACGUI installation program. The program name, “SAC7.exe,” is coded into csa2sac, and must not be changed.

Diode amplifier of modulated optical beam power

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

D'yachkov, N V; Bogatov, A P; Gushchik, T I

2014-11-30

Analytical relations are obtained between characteristics of modulated light at the output and input of an optical diode power amplifier operating in the highly saturated gain regime. It is shown that a diode amplifier may act as an amplitude-to-phase modulation converter with a rather large bandwidth (∼10 GHz). The low sensitivity of the output power of the amplifier to the input beam power and its high energy efficiency allow it to be used as a building block of a high-power multielement laser system with coherent summation of a large number of optical beams. (lasers)

Analysis of the osseointegrative force of a hyperhydrophilic and nanostructured surface refinement for TPS surfaces in a gap healing model with the Göttingen minipig.

PubMed

Seidling, Roland; Lehmann, Lars J; Lingner, Manuel; Mauermann, Eckhard; Obertacke, Udo; Schwarz, Markus L R

2016-10-17

A lot of advantages can result in a high wettability as well as a nanostructure at a titanium surface on bone implants. Thus, the aim of this study was to evaluate the osseointegrative potential of a titan plasma-sprayed (TPS) surface refinement by acid-etching with chromosulfuric acid. This results in a hyperhydrophilic surface with a nanostructure and an extreme high wetting rate. In total, 72 dumbbell shape titan implants were inserted in the spongy bone of the femora of 18 Göttingen minipigs in a conservative gap model. Thirty-six titan implants were coated with a standard TPS surface and 36 with the hyperhydrophilic chromosulfuric acid (CSA) surface. After a healing period of 4, 8, and 12 weeks, the animals were killed. The chronological healing process was histomorphometrically analyzed. The de novo bone formation, represented by the bone area (BA), is increased by approximately 1.5 times after 12 weeks with little additional benefit by use of the CSA surface. The bone-to-implant contact (BIC), which represents osseoconductive forces, shows results with a highly increased osteoid production in the CSA implants beginning at 8 and 12 weeks compared to TPS. This culminates in a 17-fold increase in BIC after a healing period of 12 weeks. After 4 weeks, significantly more osteoid was seen in the gap as de novo formation in the CSA group (p = 0.0062). Osteoid was also found more frequently after 12 weeks at the CSA-treated surface (p = 0.0355). The site of implantation, intertrochanteric or intercondylar, may influence on the de novo bone formation in the gap. There is a benefit by the CSA surface treatment of the TPS layer for osseointegration over an observation time up to 12 weeks. Significant differences were able to be shown in two direct comparisons between the CSA and the TPS surface for osteoid formation in the gap model. Further trials may reveal the benefit of the CSA treatment of the TPS layer involving mechanical tests if possible.

Continuous spinal anaesthesia versus ultrasound-guided combined psoas compartment-sciatic nerve block for hip replacement surgery in elderly high-risk patients: a prospective randomised study.

PubMed

Aksoy, Mehmet; Dostbil, Aysenur; Ince, Ilker; Ahiskalioglu, Ali; Alici, Hacı Ahmet; Aydin, Ali; Kilinc, Osman Ozgur

2014-01-01

Our aim is to compare the hemodynamic effects of combined psoas compartment-sciatic nerve block (PCSNB) with continuous spinal anaesthesia (CSA) in elderly high-risk patients undergoing hip replacement surgery. Seventy patients over the age of 60 with ASA III or IV physical status were randomly allocated to two groups: In the PCSNB group, ultrasound-guided psoas compartment block was performed with modified Winnie technique using 30 mL of 0.25% bupivacaine with 1:200.000 epinephrine (5 μgr/mL) and iliac crest block was performed using the same local anaesthetic solution (5 mL). All patients in the PCSNB group needed continuing infusion of propofol (2 mg/kg/h) during operation. In the CSA group, CSA was performed in the L3-L4 interspaced with the patient in lateral decubitus position using 2.5 mg of isobaric bupivacaine 0.5%. When sensory block was not reached to the level of T12 within 10 minutes in the CSA group, additional 2.5 mg of isobaric bupivacaine 0.5% was administered through the catheter at 5-min intervals by limiting the total dose of 15 mg until a T12 level of the sensory block was achieved. The PCSNB group had significantly higher mean arterial blood pressure values at the beginning of surgery and at 5(th), 10(th) and 20(th) minutes of surgery compared to the CSA group (P = 0.038, P = 0.029, P = 0.012, P = 0.009 respectively). There were no significant differences between groups in terms of heart rate and peripheral oxygen saturation values during surgery and the postoperative period (P >0.05). Arterial hypotension required ephedrine was observed in 13 patients in the CSA and 4 patients in the PCSNB group (P =0.012). CSA and PCSNB produce satisfactory quality of anaesthesia in elderly high-risk patients with fewer hemodynamic changes in PCSNB cases compared with CSA cases. Australian New Zealand Clinical Trials Registry: ACTRN12614000658617, Registered 24 June 2014.

Cyclosporine A-induced nephrotoxicity is ameliorated by dose reduction and conversion to sirolimus in the rat.

PubMed

Sereno, J; Vala, H; Nunes, S; Rocha-Pereira, P; Carvalho, E; Alves, R; Teixeira, F; Reis, F

2015-04-01

Side-effect minimization strategies to avoid serious side-effects of cyclosporine A (CsA), such as nephrotoxicity, have been mainly based on dose reduction and conversion to other putatively less nephrotoxic drugs, such as sirolimus (SRL), an inhibitor of the mammalian target of rapamycin. This study intended to evaluate the impact of protocols based on CsA dose reduction and further conversion to SRL on kidney function and lesions, based on serum, urine and renal tissue markers. The following 3 groups (n=6) were tested during a 9-week protocol: control (vehicle); CsA (5 mg/kg/day) and Red + Conv (CsA 30 mg/kg/day during 3 weeks + 3 weeks with CsA 5 mg/kg/day + SRL 1 mg/kg/day during the last 3 weeks). The following parameters were analysed: blood pressure, heart rate and biochemical data; serum and urine contents and clearances of creatinine, urea and neutrophil gelatinase-associated lipocalin (NGAL), as well as, glomerular filtration rate; kidney lipid peroxidation and clearance; kidney lesions were evaluated and protein expression was performed by immunohistochemistry. After the first 3 weeks of CsA (30 mg/kg/day) treatment animals showed body weight loss, hypertension, tachycardia, as well as, increased serum levels of non-HDL cholesterol, glucose, triglycerides, creatinine and urea, accompanied by decreased GFR and insulin levels. In addition, a significant increase in the expression of connective tissue growth factor, kidney injury molecule-1 (KIM-1), mammalian target of rapamycin, nuclear factor-κβ1 and transforming growth factor-β was found in the kidney, accompanied by extensive renal damage. The following 3 weeks with CsA dose reduction revealed amelioration of vascular and glomerular lesions, but without significant tubular improvement. The last 3 weeks with the conversion to sirolimus revealed high serum and urine NGAL contents but the CsA-evoked renal damage was substantially ameliorated, by reduced of connective tissue growth factor, mammalian target of rapamycin, nuclear factor-κβ1 protein expression. In conclusion, CsA nephrotoxicity is dose dependent and moderate dysfunction could be ameliorated/prevented by SRL conversion, which could be pivotal for the preservation of kidney function and structure.

Analog pulse processor

DOEpatents

Wessendorf, Kurt O.; Kemper, Dale A.

2003-06-03

A very low power analog pulse processing system implemented as an ASIC useful for processing signals from radiation detectors, among other things. The system incorporates the functions of a charge sensitive amplifier, a shaping amplifier, a peak sample and hold circuit, and, optionally, an analog to digital converter and associated drivers.

Sensitivity Enhancement of an Inductively Coupled Local Detector Using a HEMT-Based Current Amplifier.

PubMed

Qian, Chunqi; Duan, Qi; Dodd, Steve; Koretsky, Alan; Murphy-Boesch, Joe

2016-06-01

To improve the signal transmission efficiency and sensitivity of a local detection coil that is weakly inductively coupled to a larger receive coil. The resonant detection coil is connected in parallel with the gate of a high electron mobility transistor (HEMT) transistor without impedance matching. When the drain of the transistor is capacitively shunted to ground, current amplification occurs in the resonator by feedback that transforms a capacitive impedance on the transistor's source to a negative resistance on its gate. High resolution images were obtained from a mouse brain using a small, 11 mm diameter surface coil that was inductively coupled to a commercial, phased array chest coil. Although the power consumption of the amplifier was only 88 μW, 14 dB gain was obtained with excellent noise performance. An integrated current amplifier based on a HEMT can enhance the sensitivity of inductively coupled local detectors when weakly coupled. This amplifier enables efficient signal transmission between customized user coils and commercial clinical coils, without the need for a specialized signal interface. Magn Reson Med 75:2573-2578, 2016. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. Published 2015 This article is a U.S. Government work and is in the public domain in the USA.

Uncoupling of oxidative phosphorylation and Smac/DIABLO release are not sufficient to account for induction of apoptosis by sulindac sulfide in human colorectal cancer cells.

PubMed

Daouphars, Mikael; Koufany, Meriem; Benani, Alexandre; Marchal, Sophie; Merlin, Jean-Louis; Netter, Patrick; Jouzeau, Jean-Yves

2005-04-01

Non-steroidal anti-inflammatory drugs (NSAIDs) have shown chemopreventive properties in colorectal cancer, involving both cyclooxygenase (COX)-dependent and -independent mechanisms. Apart from their selectivity for COX isoenzymes, NSAIDs differ in their acidic character which supports ability to uncouple oxidative phosphorylation. To assess the possible contribution of uncoupling to their antineoplastic properties, we compared the effect of sulindac sulfide (SS), an acidic NSAID and NS-398, a non-acidic tricyclic, on mitochondrial function and apoptosis in colorectal cancer cell lines (HT29, Caco-2, HCT15 and HCT116). Although cell lines displayed a different COX status, SS and NS-398 caused growth arrest in a dose-related manner. High dose (10(-4)M) of SS but not of NS-398, increased the percentage of subG1 cell population while reducing mitochondrial transmembrane potential (DeltaPsim). Cyclosporin A (CsA, 1 microM) prevented collapse of DeltaPsim induced by 10(-4)M SS but not by 7.5 microM FCCP used as a protonophoric control. SS and FCCP increased the cytosolic release of Smac/DIABLO which was differently affected by CsA pretreatment depending on the uncoupler. Finally, 7.5 microM FCCP failed to induce apoptosis whereas CsA prevented apoptosis induced by SS from 16% in HCT15 to 41% in HCT116. The present study shows that despite the ability of sulindac sulfide to behave as a protonophoric uncoupler, CsA-sensitive opening of mitochondrial permeability transition pore contributes little to its pro-apoptotic effect in colorectal cancer cells.

Bax-mediated mitochondrial outer membrane permeabilization (MOMP), distinct from the mitochondrial permeability transition, is a key mechanism in diclofenac-induced hepatocyte injury: Multiple protective roles of cyclosporin A

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

Siu, W.P.; Pun, Pamela Boon Li; Latchoumycandane, Calivarathan

2008-03-15

Diclofenac, a widely used nonsteroidal anti-inflammatory drug, has been associated with rare but severe cases of clinical hepatotoxicity. Diclofenac causes concentration-dependent cell death in human hepatocytes (after 24-48 h) by mitochondrial permeabilization via poorly defined mechanisms. To explore whether the cyclophilin D (CyD)-dependent mitochondrial permeability transition (mPT) and/or the mitochondrial outer membrane permeabilization (MOMP) was primarily involved in mediating cell death, we exposed immortalized human hepatocytes (HC-04) to apoptogenic concentrations of diclofenac (> 500 {mu}M) in the presence or absence of inhibitors of upstream mediators. The CyD inhibitor, cyclosporin A (CsA, 2 {mu}M) fully inhibited diclofenac-induced cell injury, suggesting thatmore » mPT was involved. However, CyD gene silencing using siRNA left the cells susceptible to diclofenac toxicity, and CsA still protected the CyD-negative cells from lethal injury. Diclofenac induced early (9 h) activation of Bax and Bak and caused mitochondrial translocation of Bax, indicating that MOMP was involved in cell death. Inhibition of Bax protein expression by using siRNA significantly protected HC-04 from diclofenac-induced cell injury. Diclofenac also induced early Bid activation (tBid formation, 6 h), which is an upstream mechanism that initiates Bax activation and mitochondrial translocation. Bid activation was sensitive to the Ca{sup 2+} chelator, BAPTA. In conclusion, we found that Bax/Bak-mediated MOMP is a key mechanism of diclofenac-induced lethal cell injury in human hepatocytes, and that CsA can prevent MOMP through inhibition of Bax activation. These data support our concept that the Ca{sup 2+}-Bid-Bax-MOMP axis is a critical pathway in diclofenac (metabolite)-induced hepatocyte injury.« less

Risk Reduction for HIV-Positive African American and Latino Men with Histories of Childhood Sexual Abuse

PubMed Central

Wyatt, Gail E.; Rivkin, Inna; Ramamurthi, Hema Codathi; Li, Xiaomin; Liu, Honghu

2014-01-01

While the HIV epidemic has disproportionately affected African American and Latino men who have sex with men (MSM), few HIV prevention interventions have focused on African American and Latino men who have sex with both men and women (MSMW). Even fewer interventions target HIV-positive African American and Latino MSM and MSMW with histories of childhood sexual abuse (CSA), a population that may be vulnerable to high-risk sexual behaviors, having multiple sexual partners, and depression. The Men’s Health Project, a small randomized clinical trial, compared the effects of two 6-session interventions, the Sexual Health Intervention for Men (S-HIM), guided by social learning theory and aimed at decreasing high-risk sexual behaviors, number of sexual partners, and depressive symptoms, and a standard health promotion control (SHP).A community sample of 137 HIV-positive gay and non-gay identifying African American and Latino MSM and MSMW with histories of CSA was recruited. Results were based on an “intent to treat” analyses of baseline to post, 3 and 6 month follow-ups. The sample as a whole reported reductions in sexual risk behaviors and number of sexual partners from baseline to post-test, and from the 3 to 6 month follow-ups, although the decrease in sexual risk behavior from baseline to post-test was significant only for S-HIM participants. No significant differences between conditions were reported for depressive symptoms, but the total sample reported a significant decrease at 6 months. These findings highlight the importance of addressing sexual decision-making and psychological adjustment for ethnic men, while being sensitive to CSA histories and sexual minority status, and suggest the need to develop additional strategies to heighten HIV risk reduction over time. PMID:18506611

Therapeutic Strategies Against Cyclin E1 Amplified Ovarian Cancers

DTIC Science & Technology

2017-10-01

interaction and suppression of E2F- dependent oncogenic activity resulting in activity against CCNE1-amplified cells. In the third aim, we hypothesize...tumors which are dependent on hyperactive HR and are sensitive to suppression of BRCA1. 15. SUBJECT TERMS Ovarian Cancer, CCNE1 amplification...suppression of E2F- dependent oncogenic activity resulting in activity against CCNE1-amplified cells. In the third aim, we hypothesize that miR-1255b, miR

Contractile properties are disrupted in Becker muscular dystrophy, but not in limb girdle type 2I.

PubMed

Løkken, Nicoline; Hedermann, Gitte; Thomsen, Carsten; Vissing, John

2016-09-01

We investigated whether a linear relationship between muscle strength and cross-sectional area (CSA) is preserved in calf muscles of patients with Becker muscular dystrophy (BMD, n = 14) and limb-girdle type 2I muscular dystrophy (LGMD2I, n = 11), before and after correcting for muscle fat infiltration. The Dixon magnetic resonance imaging technique was used to quantify fat and calculate a fat-free contractile CSA. Strength was assessed by dynamometry. Muscle strength/CSA relationships were significantly lower in patients versus controls. The strength/contractile-CSA relationship was still severely lowered in BMD, but was almost normalized in LGMD2I. Our findings suggest close to intact contractile properties in LGMD2I, which are severely disrupted in BMD. Ann Neurol 2016;80:466-471. © 2016 American Neurological Association.

Cyclosporin A and intravenous immunoglobulin treatment in polymyositis/dermatomyositis

PubMed Central

Danieli, M; Malcangi, G; Palmieri, C; Logullo, F; Salvi, A; Piani, M; Danieli, G

2002-01-01

Objective: To describe the treatment of polymyositis (PM) and dermatomyositis (DM) with prednisone (PRED) and cyclosporin A (CSA) alone or associated with intravenous immunoglobulin (IVIg) and plasmapheresis (PEX). Methods: Between 1992 and 1999 CSA and PRED were used to treat 20 patients with idiopathic myositis (12 with DM, eight with PM), diagnosed according to the Bohan and Peter criteria. In patients with refractory or relapsed disease, IVIg was added alone (seven cases) or synchronised with PEX (six cases). A standardised protocol was used to evaluate the patients, and assess disease activity and treatment response. Results: Despite a transient response to PRED and CSA in 16/20 cases, this combination did not induce full remission in 13/20 cases, which led to the IVIg trial with or without PEX. Patients receiving PRED and CSA plus IVIg had a significantly higher probability of maintaining complete remission at the end of the four year follow up period than those treated with PRED and CSA alone (p<0.001). No further benefit was added by the PEX. The presence of arthritis significantly correlated with a poorer response to treatment (p<0.05). Adverse effects were gingival hyperplasia (one patient) and transient renal dysfunction (one). Conclusions: This open study suggests that combined treatment with PRED, CSA, and IVIg is useful in patients with myositis, even those with refractory or relapsed disease; no increase in the number or type of side effects is seen. PMID:11779756

The effect of cyclosporin A on the primary immune response to allogeneic red cells in rabbits.

PubMed Central

Smith, G N

1982-01-01

Cyclosporin A (CSA) has been used in an attempt to suppress the primary immune response of HgA(A)-negative rabbits to A-positive red cells. The immune response was assessed by measuring the survival of a small intravenous (i.v.) dose of 51Cr-labelled A-positive cells and by testing the serum of the immunized rabbits for anti-A. In one experiment, eight A-negative rabbits were given a first i.v. injection of A-positive red cells, and CSA (25 mg/kg/day) in olive oil was given by mouth for 17-34 days. There was no evidence of impaired alloimmunization compared with the responses in control animals treated with olive oil alone. In a second experiment, eight A-negative rabbits were given a first injection of A-positive muscularly (i.m.), and CSA (25 mg/kg/day) in miglyol was given by im.m. injection for 10 days. Six of these rabbits were rendered unresponsive, and the remaining two, who showed impaired survival of the monitoring red cells, produced only low anit-A titres. Seven out of eight controls given i.m. miglyol without CSA responded with good anti-A production. Rabbits that were unresponsive to A-positive red cells responded normally to sheep red blood cells 15 weeks after CSA treatment. Higher serum levels of CSA were found following i.m. administration of the drug but treatment by this route as associated with severe toxicity in some rabbits. PMID:7056563

Anti-schistosomal activity of cyclosporin A: studies on murine spleen cells and the influence of a cyclosporin antagonist on resistance to infection.

PubMed Central

Brannan, L R; Chappell, L H; Woo, J; Thomson, A W

1989-01-01

Mice were treated with 5-day courses of cyclosporin A (CsA) around the time of infection with Schistosoma mansoni. Recovery of lung-stage worms 4-8 days post-infection (p.i.) was substantially reduced (80%) and no sexually mature adults were recovered from the hepatic portal system at 7 weeks p.i. Flow cytometric analysis of spleen cells from CsA-treated animals during the period of maximal parasite attrition revealed transient reductions in CD3+ and CD4+ cells and in the CD4+: CD8+ ratio compared with drug vehicle-treated, infected controls. No significant numerical changes in B cells, macrophages or eosinophils were detected relative to vehicle-treated infected mice. Transfer of spleen cells from CsA-treated donors 8 days after infection failed to confer increased resistance to S. mansoni infection on untreated recipients. Moreover, concomitant administration of CsA and an inducer of interleukin-2 production (ADA-202-718) did not interfere with the anti-schistosomal effect of CsA. Despite our incomplete understanding of the in vivo properties of CsA and reports of its paradoxical effects on immune responses, these new data indicate that the influence of CsA in schistosomiasis is unlikely to be mediated by modulation of host cell mediated immunity. This contrasts with certain other anti-parasitic effects of CsA which appear to be mediated by an action on T cells. PMID:2503438

Cyclosporine treatment of severe Hidradenitis suppurativa--A case series.

PubMed

Anderson, Marianne D; Zauli, Stefania; Bettoli, Vincenzo; Boer, Jurr; Jemec, Gregor B E

2016-01-01

Hidradenitis suppurativa (HS) is an overlooked but common disease severely affecting both genders. HS is generally perceived as difficult to treat and although a number of treatments are available, the need for more effective treatment is apparent. Cyclosporine A (CsA) has been suggested as an effective treatment in four smaller case series. It was therefore decided to review a larger series of cases, reporting all outcomes in order to provide a less biased base for evaluating the potential of CsA for use in HS. An exploratory retrospective review of case notes was performed at three departments of dermatology with a special interest in HS, where HS had been treated with CsA in the period 2009-2012. In total, 18 HS patients treated with CsA were identified and analysed and 50% reported some benefit. All patients had previously been treated with multiple various other modalities. This is an exploratory retrospective review with a limited number of patients. This retrospective review found some effect of CsA in the recalcitrant cases studied, mainly reported as "slight improvement". This may be due to a number of factors which may have overestimated (e.g., concommitant therapy) or underestimated (e.g., case selection of recalcitrant cases) the effect, and indicates the need for prospective evaluation of the claims. The present data provide a basis for power calculations in future studies investigating the potential for treating HS with CsA in a randomised controlled trial.

Valency-Controlled Framework Nucleic Acid Signal Amplifiers.

PubMed

Liu, Qi; Ge, Zhilei; Mao, Xiuhai; Zhou, Guobao; Zuo, Xiaolei; Shen, Juwen; Shi, Jiye; Li, Jiang; Wang, Lihua; Chen, Xiaoqing; Fan, Chunhai

2018-06-11

Weak ligand-receptor recognition events are often amplified by recruiting multiple regulatory biomolecules to the action site in biological systems. However, signal amplification in in vitro biomimetic systems generally lack the spatiotemporal regulation in vivo. Herein we report a framework nucleic acid (FNA)-programmed strategy to develop valence-controlled signal amplifiers with high modularity for ultrasensitive biosensing. We demonstrated that the FNA-programmed signal amplifiers could recruit nucleic acids, proteins, and inorganic nanoparticles in a stoichiometric manner. The valence-controlled signal amplifier enhanced the quantification ability of electrochemical biosensors, and enabled ultrasensitive detection of tumor-relevant circulating free DNA (cfDNA) with sensitivity enhancement of 3-5 orders of magnitude and improved dynamic range. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence of the rate of infusion on cyclosporine nephrotoxicity in the rat.

PubMed

Finn, W F; McCormack, A J; Sullivan, B A; Hak, L J; Clark, R L

1989-01-01

The effect of the rate of infusion of single and multiple doses of cyclosporine (CsA) on renal function was evaluated in Sprague-Dawley rats. CsA was dissolved in cremophore (Crem) or Tween 80 (Tween) and infused over consecutive 10-min periods at doses of 10, 20, 30 and 40 mg/kg. CsA-Crem and CsA-Tween produced similar and progressive changes in MAP, RBF, and RVR. By the end of the infusion, the mean values (% of control) of MAP (122 +/- 16% and 131 +/- 22%), RBF (56 +/- 11% and 66 +/- 20%), and RVR (222 +/- 38% and 232 +/- 134%) were significantly different from their respective preinfusion values. Infusion of Crem alone resulted in renal vasodilation at low doses and renal vasoconstriction at high doses. Vasoconstriction was not produced by infusion of Tween alone. In addition, animals were treated with vehicle alone (Gp 1), CsA 10 mg/kg/day by injection (Gp 2), or CsA 20 mg/kg/day by i.v. infusion over 4 hr (Gp 3), and were studied at 1 week. Systemic toxicity was greater with the 4-hr infusion as judged by an increase in MAP. The mean values of MAP were 107 +/- 8 (Gp 1), 101 +/- 13 (Gp 2), and 135 +/- 5 mm Hg (Gp 3; p less than 0.05). However, renal function was less severely affected with the 4-hr infusion. The mean values of CIn were 434 +/- 99 (Gp 1), 298 +/- 101 (Gp 2; p less than 0.05), and 425 +/- 114 microL/min/100 g BW (Gp 3); and the mean values for RBF were 2.72 +/- 0.74 (Gp 1), 2.08 +/- 0.17 (Gp 2; p less than 0.05), and 3.35 +/- 0.61 mL/min/100 g BW (Gp 3), respectively. Microangiograms showed marked abnormalities in the intrarenal perfusion pattern in the rats injected with CsA, 10 mg/kg BW. In rats infused over 4 hr with CsA, 20 mg/kg BW, the microangiographic pattern was normal. These studies demonstrate that the acute hemodynamic effects of CsA are directly related to the rate of infusion. Furthermore, the renal toxicity which follows repetitive injection of CsA can be minimized or avoided by administering CsA as a slow infusion. In addition to the total dose administered, the rate of infusion is an important determinant of nephrotoxicity.

Putting the past behind us: Social stress-induced urinary retention can be overcome.

PubMed

Weiss, Dana A; Butler, Stephan J; Fesi, Joanna; Long, Christopher J; Valentino, Rita J; Canning, Douglas A; Zderic, Stephen A

2015-08-01

To study the pathophysiology of dysfunctional voiding, we have previously developed a model of stress-induced voiding dysfunction. We have shown that cyclosporine A (CsA), an inhibitor of the Ca(2+)-calmodulin complex, can prevent social stress-induced urinary retention. However, treatment with cyclosporine has not had an effect on the increase in the stress peptide corticotrophin-releasing factor (CRF) in Barrington's nucleus, which is involved in the micturition pathway. We now investigate whether cyclosporine administered after stress can reverse the abnormal voiding phenotype, and whether it has effects on the bladder wall itself, or on the stress response within Barrington's nucleus. Six-week old Swiss-Webster mice were exposed to aggressor males for 1 h a day, followed by 23 h of barrier separation. In a long-term trial, 1 month of stress was followed by single-cage housing for 6 months. In a separate CsA reversal trial, mice either received CsA in drinking water or had plain drinking water during 1 month of single-cage housing during recovery. Bladder contractile function was examined on a Guth myograph. Nuclear translocation of myocyte enhancing factor (MEF)-2 and NFAT (nuclear factor of activated T cells) in the bladder was assessed using electrophoretic mobility shift assays (EMSAs). The expression of CRF was determined in Barrington's nucleus using in situ hybridization. Voiding dysfunction persisted for up to 6 months after stress exposure while mice recovered in single-cage housing. In the CsA reversal trial, voiding patterns improved when they received CsA in water during single-cage housing following stress, whereas those that underwent single-cage housing alone had persistent abnormal voiding (Fig. A). There was no difference between CRF levels in Barrington's nucleus between reversal groups (p = 0.42) (Fig. B), possibly indicating a direct effect on the bladder rather than a persistent stress effect. There were no differences in the contractility of bladder wall muscle. CsA decreased the nuclear translocation of MEF-2 and NFAT induced by stress (Fig. C,D). CsA reverses stress-induced urinary retention, but does not change the stress-induced CRF increase in Barrington's nucleus. Furthermore, bladder smooth muscle contractility is unchanged by CsA; however, there are changes in the levels of the downstream transcription factors MEF-2 and NFAT. We suspect that additional CsA responsive neural changes play a pivotal role in the abnormal voiding phenotype following social stress. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Pilot Test of an Integrated Sexual Risk Reduction Intervention for Women with a History of Childhood Sexual Abuse.

PubMed

Senn, Theresa E; Braksmajer, Amy; Urban, Marguerite A; Coury-Doniger, Patricia; Carey, Michael P

2017-11-01

HIV and childhood sexual abuse (CSA) are intersecting public health problems for women. We pilot tested an integrated sexual risk reduction intervention for women with a history of CSA that addressed both the consequences of CSA [based on the Traumagenic Dynamics (TD) framework] and the antecedents of sexual risk behavior (based on the Information-Motivation-Behavioral Skills [IMB] model). Women with a history of CSA who were attending a public STI clinic (n = 84) were randomly assigned to a five-session integrated TD/IMB (experimental) group intervention or to a time-matched IMB-guided sexual risk reduction (control) group intervention. Preliminary findings indicated that women in the integrated TD/IMB intervention reduced their average number of episodes of unprotected sex with a primary partner, their alcohol use, and their likelihood of being in a violent relationship, relative to women in the IMB-only group. Our findings suggest that sexual risk reduction interventions that address both the consequences of CSA and the antecedents of sexual risk behavior may be efficacious in reducing sexual risk behavior among women who were sexually abused.

Effects of expressive writing on sexual dysfunction, depression, and PTSD in women with a history of childhood sexual abuse: Results from a randomized clinical trial

PubMed Central

Meston, Cindy M.; Lorenz, Tierney A.; Stephenson, Kyle R.

2013-01-01

Introduction Women with a history of childhood sexual abuse (CSA) have high rates of depression, post-traumatic stress disorder, and sexual problems in adulthood. Aim We tested an expressive writing based intervention for its effects on psychopathology, sexual function, satisfaction and distress in women who have a history of CSA. Main Outcome measures Validated self-report measures of psychopathology and sexual function were conducted at post-treatment, 2 weeks, one month, and six months. Methods Seventy women with CSA histories completed five 30-minute sessions of expressive writing, either with a trauma focus or a sexual schema focus. Results Women in both writing interventions exhibited improved symptoms of depression and posttraumatic stress disorder (PTSD). Women who were instructed to write about the impact of the abuse on their sexual schema were significantly more likely to recover from sexual dysfunction. Conclusions Expressive writing may improve depressive and PTSD symptoms in women with CSA histories. Sexual schema-focused expressive writing in particular appears to improve sexual problems, especially for depressed women with CSA histories. Both treatments are accessible, cost-effective, and acceptable to patients. PMID:23875721

Effects of expressive writing on sexual dysfunction, depression, and PTSD in women with a history of childhood sexual abuse: results from a randomized clinical trial.

PubMed

Meston, Cindy M; Lorenz, Tierney A; Stephenson, Kyle R

2013-09-01

Women with a history of childhood sexual abuse (CSA) have high rates of depression, posttraumatic stress disorder, and sexual problems in adulthood. We tested an expressive writing-based intervention for its effects on psychopathology, sexual function, satisfaction, and distress in women who have a history of CSA. Seventy women with CSA histories completed five 30-minute sessions of expressive writing, either with a trauma focus or a sexual schema focus. Validated self-report measures of psychopathology and sexual function were conducted at posttreatment: 2 weeks, 1 month, and 6 months. Women in both writing interventions exhibited improved symptoms of depression and posttraumatic stress disorder (PTSD). Women who were instructed to write about the impact of the abuse on their sexual schema were significantly more likely to recover from sexual dysfunction. Expressive writing may improve depressive and PTSD symptoms in women with CSA histories. Sexual schema-focused expressive writing in particular appears to improve sexual problems, especially for depressed women with CSA histories. Both treatments are accessible, cost-effective, and acceptable to patients. © 2013 International Society for Sexual Medicine.

A Novel Hybrid Clonal Selection Algorithm with Combinatorial Recombination and Modified Hypermutation Operators for Global Optimization

PubMed Central

Lin, Jingjing; Jing, Honglei

2016-01-01

Artificial immune system is one of the most recently introduced intelligence methods which was inspired by biological immune system. Most immune system inspired algorithms are based on the clonal selection principle, known as clonal selection algorithms (CSAs). When coping with complex optimization problems with the characteristics of multimodality, high dimension, rotation, and composition, the traditional CSAs often suffer from the premature convergence and unsatisfied accuracy. To address these concerning issues, a recombination operator inspired by the biological combinatorial recombination is proposed at first. The recombination operator could generate the promising candidate solution to enhance search ability of the CSA by fusing the information from random chosen parents. Furthermore, a modified hypermutation operator is introduced to construct more promising and efficient candidate solutions. A set of 16 common used benchmark functions are adopted to test the effectiveness and efficiency of the recombination and hypermutation operators. The comparisons with classic CSA, CSA with recombination operator (RCSA), and CSA with recombination and modified hypermutation operator (RHCSA) demonstrate that the proposed algorithm significantly improves the performance of classic CSA. Moreover, comparison with the state-of-the-art algorithms shows that the proposed algorithm is quite competitive. PMID:27698662