[Charcot, Freud and the unconscious].

PubMed

Lellouch, Alain

2004-01-01

The aim of this work is to assess, on an historical and critical point of view, the new psychological perspective, introduced by Charcot (1825-1893), during the ten last years (1882-1892) of his life to explain hysteria symptomas. From clinical examples (hypnosis and hypnotherapy, "hystero-traumatism", "psychological theory of hysteria", "faith healing"), the paper shows how psychological dimension went back into the Parisian Hospital Medicine. This occurred on the late XIXth century, just one century after Mesmer, when Freud was Charcot's intern, at La Salpêtrière hospital, during years 1885-1886. The return of a non-rational thought into hospital medicine upset the organicist concepts of the Parisian "Ecole anatomo-clinique".

Charcot-Marie-Tooth Disease

MedlinePlus

Charcot-Marie-Tooth disease (CMT) is a group of genetic nerve disorders. It is named after the three doctors who first identified it. ... a nerve biopsy. There is no cure. The disease can be so mild you don't realize ...

Charcot's famous secretaries.

PubMed

Teive, Hélio Afonso Ghizoni; Germiniani, Francisco Manoel Branco; Munhoz, Renato Puppi; Walusinski, Olivier

2017-05-01

At the pinnacle of his career, Professor Charcot had four secretaries: Charles Féré, Pierre Marie, Georges Gilles de la Tourette and Georges Guinon. They helped the great founder of neurology with his activities at La Salpêtrière Hospital and his private clinic, examining patients before he made the final diagnosis.

Freud with Charcot: Freud's discovery and the question of diagnosis.

PubMed

Lepoutre, Thomas; Villa, François

2015-04-01

Although Charcot's seminal role in influencing Freud is widely stated, although Freud's trip to Paris to study with Charcot is well recognized as pivotal in his shift from neurological to psychopathological work, a key fact of the Freudian heuristic remains largely underestimated: namely, that Freud's psychopathological breakthrough, which gave birth to psychoanalysis, cannot be separated from his 'diagnostic preoccupation', which is a crucial and at times the first organizing principle of his earliest writings. The purpose of this article is therefore to reopen the question of diagnosis by following its development along the path leading from Charcot to Freud. The authors demonstrate that Freud's careful attention to diagnostic distinctions follows strictly in the direction of Charcot's 'nosological method'. More importantly, the article intends to identify the precise way in which his ideas operate in Freud's own work, in order to understand how Freud reinvests them to forge his own nosological system. If the authors trace the destiny of Charcot's lessons as they reach Freud's hands, it is the importance granted to mixed neuroses in Freud's psychopathology that allows them to pinpoint the role played by the diagnostic process in the rationality of psychoanalysis. Copyright © 2014 Institute of Psychoanalysis.

High levels of anxiety and depression in diabetic patients with Charcot foot.

PubMed

Chapman, Zahra; Shuttleworth, Charles Matthew James; Huber, Jörg Wolfgang

2014-01-01

Charcot foot is a rare but devastating complication of diabetes. Little research is available on the mental health impact of Charcot foot. Aim of the study is to assess mental health in diabetes patients with Charcot foot and to investigate the moderating effects of socio-demographic factors. The severity of the problem will be statistically evaluated with the help of a reference data set. Cross-sectional questionnaire data using the Hospital Anxiety and Depression Scale (HADS) and demographic background were collected from 50 patients with diabetes and Charcot complications (males 62%; mean age 62.2 ± 8.5 years). Statistical comparisons with a large data set of general diabetes patients acting as a point of reference were carried out. Anxiety and depression levels were high, (anxiety and depression scores 6.4 ± 4 and 6.3 ± 3.6 respectively). Females reported more severe anxiety and depression. Ethnic minorities and patients out of work reported more severe anxiety. Comparisons with published HADS data indicate that diabetes patients with Charcot foot experience more serious levels of anxiety and depression. The high levels of mental health problems which were found in this study in diabetes patients with Charcot foot require recognition by researchers and clinicians. The findings imply the need to screen for mental health problems in diabetes patients with Charcot foot.

High levels of anxiety and depression in diabetic patients with Charcot foot

PubMed Central

2014-01-01

Background/aims Charcot foot is a rare but devastating complication of diabetes. Little research is available on the mental health impact of Charcot foot. Aim of the study is to assess mental health in diabetes patients with Charcot foot and to investigate the moderating effects of socio-demographic factors. The severity of the problem will be statistically evaluated with the help of a reference data set. Methods Cross-sectional questionnaire data using the Hospital Anxiety and Depression Scale (HADS) and demographic background were collected from 50 patients with diabetes and Charcot complications (males 62%; mean age 62.2 ± 8.5 years). Statistical comparisons with a large data set of general diabetes patients acting as a point of reference were carried out. Results Anxiety and depression levels were high, (anxiety and depression scores 6.4 ± 4 and 6.3 ± 3.6 respectively). Females reported more severe anxiety and depression. Ethnic minorities and patients out of work reported more severe anxiety. Comparisons with published HADS data indicate that diabetes patients with Charcot foot experience more serious levels of anxiety and depression. Conclusions The high levels of mental health problems which were found in this study in diabetes patients with Charcot foot require recognition by researchers and clinicians. The findings imply the need to screen for mental health problems in diabetes patients with Charcot foot. PMID:24650435

Jean-Martin Charcot's Role in the 19th Century Study of Music Aphasia

ERIC Educational Resources Information Center

Johnson, Julene K.; Lorch, Marjorie; Nicolas, Serge; Graziano, Amy

2013-01-01

Jean-Martin Charcot (1825-93) was a well-known French neurologist. Although he is widely recognized for his discovery of several neurological disorders and his research into aphasia, Charcot's ideas about how the brain processes music are less well known. Charcot discussed the music abilities of several patients in the context of his "Friday…

The effectiveness of non-surgical interventions in the treatment of Charcot foot.

PubMed

Smith, Caroline; Kumar, Saravana; Causby, Ryan

2007-12-01

Background  Charcot neuropathic osteoarthropathy is commonly known as 'Charcot foot'. It is a serious foot complication of diabetes mellitus that can frequently lead to foot ulceration, gangrene, hospital admission and foot amputation. A multidisciplinary approach to the management of Charcot foot is taken involving medical and allied health professionals. The management approach may also differ between different countries. To date, there is no systematic review of the literature undertaken to identify the clinical effectiveness of non-operative interventions in the treatment of acute Charcot foot. Objective  The objective of this review was to identify the effectiveness of non-surgical interventions with reducing lesions, ulceration, the rate of surgical intervention, reducing hospital admissions and improve the quality of life of subjects with Charcot foot. Search strategy  A comprehensive search strategy was undertaken on databases available from University of South Australia from their inception to November 2006. Selection criteria  Randomised controlled trials or clinical controlled trials were primarily sought. Critical appraisal of study quality and data extraction was undertaken using Joanna Briggs Institute instruments. Review Manager software was used to calculate comparative statistics. Results  This review identified 11 trials and five trials were included in the review. Three trials involved the use of bisphosphonate, a pharmacological agent. Two experimental treatments were also included, evaluating palliative radiology and magnetic fields. No trials were found using immobilisation and off-loading interventions for acute Charcot foot. The overall methodological quality score of the five studies was moderate. Owing to heterogeneous data, meta-analysis could not be performed. The trials did not report on reducing lesions, ulceration, rate of surgical intervention, hospital admissions and the quality of life of subjects with Charcot foot. The

X-linked Charcot-Marie-Tooth disease predominates in a cohort of multiethnic Malaysian patients.

PubMed

Shahrizaila, Nortina; Samulong, Sarimah; Tey, Shelisa; Suan, Liaw Chiew; Meng, Lao Kah; Goh, Khean Jin; Ahmad-Annuar, Azlina

2014-02-01

Data regarding Charcot-Marie-Tooth disease is lacking in Southeast Asian populations. We investigated the frequency of the common genetic mutations in a multiethnic Malaysian cohort. Patients with features of Charcot-Marie-Tooth disease or hereditary liability to pressure palsies were investigated for PMP22 duplication, deletion, and point mutations and GJB1, MPZ, and MFN2 point mutations. Over a period of 3 years, we identified 25 index patients. A genetic diagnosis was reached in 60%. The most common were point mutations in GJB1, accounting for X-linked Charcot-Marie-Tooth disease (24% of the total patient population), followed by PMP22 duplication causing Charcot-Marie-Tooth disease type 1A (20%). We also discovered 2 novel GJB1 mutations, c.521C>T (Proline174Leucine) and c.220G>A (Valine74Methionine). X-linked Charcot-Marie-Tooth disease was found to predominate in our patient cohort. We also found a better phenotype/genotype correlation when applying a more recently recommended genetic approach to Charcot-Marie-Tooth disease. Copyright © 2013 Wiley Periodicals, Inc.

George Sigerson: Charcot's translator.

PubMed

Lyons, J B

1997-04-01

Senator George Sigerson (1836-1925), Dublin's first neurologist, was also a significant contributor to Anglo-Irish literature. His medical career and literary accomplishments are outlined, the focus of the article being Sigerson's friendly relationship with Charcot (with whom he corresponded), and whose Leçons sur les maladies du système nerveux he translated.

Charcot, la salpêtrière, and hysteria as represented in European literature.

PubMed

Koehler, Peter J

2013-01-01

In this chapter, I describe the influence of Jean-Martin Charcot (1825-1893), his neurological school at the Salpêtrière (Paris), and his teaching of hysteria on European literature. Many references to Charcot and descriptions of hysterical attacks are found not only in French naturalistic literature but also subsequently in naturalistic novels from other European countries (the Netherlands, Russia, Scandinavian countries, Spain, Italy, and Germany) and furthermore in novels written in new literary movements that followed naturalism. At first, objective descriptions were presented, but in the periods that followed, in particular during the past decades, criticism, rather than objective descriptions, became the motivation for continuing to use Charcot and his teaching of hysteria as inspiration for novels and plays, although Charcot as an admired founder of neurology did not quite disappear, even in recent novels. It is quite impressive to observe how Charcot and his demonstrations of hysterical attacks still resound throughout European literature, even after more than a century. © 2013 Elsevier B.V. All rights reserved.

Etiology, pathophysiology and classifications of the diabetic Charcot foot

PubMed Central

Papanas, Nikolaos; Maltezos, Efstratios

2013-01-01

In people with diabetes mellitus, the Charcot foot is a specific manifestation of peripheral neuropathy that may involve autonomic neuropathy with high blood flow to the foot, leading to increased bone resorption. It may also involve peripheral somatic polyneuropathy with loss of protective sensation and high risk of unrecognized acute or chronic minor trauma. In both cases, there is excess local inflammatory response to foot injury, resulting in local osteoporosis. In the Charcot foot, the acute and chronic phases have been described. The former is characterized by local erythema, edema, and marked temperature elevation, while pain is not a prominent symptom. In the latter, signs of inflammation gradually recede and deformities may develop, increasing the risk of foot ulceration. The most common anatomical classification describes five patterns, according to the localization of bone and joint pathology. This review article aims to provide a brief overview of the diabetic Charcot foot in terms of etiology, pathophysiology, and classification. PMID:23705058

Jean-Martin Charcot and art: relationship of the "founder of neurology" with various aspects of art.

PubMed

Bogousslavsky, Julien; Boller, François

2013-01-01

Jean-Martin Charcot (1825-1893), the "father of neurology" in France and much beyond, was also the man who established academic psychiatry in Paris, differentiating it from clinical alienism. In his teaching, he used artistic representations from previous centuries to illustrate the historical developments of hysteria, mainly with the help of his pupil Paul Richer. Charcot liked to draw portraits (in particular, sketches of colleagues during boring faculty meetings and students' examinations), caricatures of himself and others, church sculptures, landscapes, soldiers, etc. He also used this skill in his clinical and scientific work; he drew histological or anatomic specimens, as well as patients' features and demeanor. His most daring artistic experiments were drawing under the influence of hashish. Charcot's tastes in art were conservative; he displayed no affinity for the avant-gardes of his time, including impressionism, or for contemporary musicians, such as César Franck or Hector Berlioz. Léon Daudet, son of Charcot's former friend and famous writer Alphonse Daudet, described Charcot's home as a pseudo-gothic kitsch accumulation of heteroclite pieces of furniture and materials. However, as Henry Meige wrote a few years after his mentor's death, Charcot the artist remains "inseparable from Charcot the physician." © 2013 Elsevier B.V. All rights reserved.

Hybrid Fixation for Ankle Fusion in Diabetic Charcot Arthropathy.

PubMed

El-Mowafi, Hani; Abulsaad, Mazen; Kandil, Yasser; El-Hawary, Ahmed; Ali, Samer

2018-01-01

Ankle fusion is difficult to achieve in the diabetic Charcot ankle Brodsky type 3a because of the poor quality of the bone and the inability to achieve a stable biomechanical construct. The aim of this study was to report the outcome of ankle fusion using a combination of an intramedullary nail and a circular external fixator in patients with diabetic Charcot arthropathy. We prospectively studied 24 patients with diabetic Charcot arthropathy of the ankle who were treated by fusion of the tibiotalar joint using a combined retrograde intramedullary nail and Ilizarov external fixator. Their mean age was 50.7 ± 6.9 (range, 43-62) years. The mean follow-up after surgery was 36.4 ± 5.8 (range, 24-98) months. Twenty-two patients (92%) achieved clinical and radiographic solid bony fusion. No patients in this series needed amputation. All the patients were pain free, and the mean American Orthopaedic Foot & Ankle Society Score (AOFAS) improved significantly from 34.6 ± 6.8 to 66.4 ± 4.5 at the last follow-up. Two patients developed an ulcer over the heel due to a prominent nail. The ulcer healed after nail removal. Eight patients developed pin tract infection. We report a successful outcomes of ankle fusions using combined intramedullary nail locked only proximally and ring external fixator (hybrid fixation) in patients with diabetic Charcot arthropathy. Level IV, case series.

The DenA/DEN1 Interacting Phosphatase DipA Controls Septa Positioning and Phosphorylation-Dependent Stability of Cytoplasmatic DenA/DEN1 during Fungal Development

PubMed Central

Schinke, Josua; Kolog Gulko, Miriam; Christmann, Martin; Valerius, Oliver; Stumpf, Sina Kristin; Stirz, Margarita; Braus, Gerhard H.

2016-01-01

DenA/DEN1 and the COP9 signalosome (CSN) represent two deneddylases which remove the ubiquitin-like Nedd8 from modified target proteins and are required for distinct fungal developmental programmes. The cellular DenA/DEN1 population is divided into a nuclear and a cytoplasmatic subpopulation which is especially enriched at septa. DenA/DEN1 stability control mechanisms are different for the two cellular subpopulations and depend on different physical interacting proteins and the C-terminal DenA/DEN1 phosphorylation pattern. Nuclear DenA/DEN1 is destabilized during fungal development by five of the eight CSN subunits which target nuclear DenA/DEN1 for degradation. DenA/DEN1 becomes stabilized as a phosphoprotein at S243/S245 during vegetative growth, which is necessary to support further asexual development. After the initial phase of development, the newly identified cytoplasmatic DenA/DEN1 interacting phosphatase DipA and an additional developmental specific C-terminal phosphorylation site at serine S253 destabilize DenA/DEN1. Outside of the nucleus, DipA is co-transported with DenA/DEN1 in the cytoplasm between septa and nuclei. Deletion of dipA resulted in increased DenA/DEN1 stability in a strain which is unresponsive to illumination. The mutant strain is dysregulated in cytokinesis and impaired in asexual development. Our results suggest a dual phosphorylation-dependent DenA/DEN1 stability control with stabilizing and destabilizing modifications and physical interaction partner proteins which function as control points in the nucleus and the cytoplasm. PMID:27010942

Combined Internal and External Fixation for Diabetic Charcot Reconstruction: A Retrospective Case Series.

PubMed

Hegewald, Kenneth W; Wilder, Megan L; Chappell, Todd M; Hutchinson, Byron L

2016-01-01

Diabetic Charcot neuroarthropathy is a complex, limb-threatening disease process with major lifestyle-altering repercussions for patients. When Charcot neuroarthropathy leads to unstable deformity, ulceration, and potential infection despite conservative therapies, foot and ankle surgeons often consider reconstructive limb salvage procedures to restore function. The purpose of the present study was to evaluate the clinical and radiographic outcomes of diabetic Charcot reconstruction using combined internal and external fixation. A total of 22 patients were reviewed; 16 (72.73%) midfoot and 6 (27.27%) tibiotalocalcaneal arthrodesis procedures were consecutively performed from March 2009 to May 2013. All surgical procedures were performed in nonacute phases of the Charcot process in patients with diagnosed diabetes mellitus and documented peripheral neuropathy. Patients were excluded from the study if they were not diabetic despite having undergone Charcot reconstruction, regardless of the fixation method, or if they did not complete radiographic imaging. During a mean follow-up period of 58.60 ± 42.37 (range 16 to 164) weeks, limb salvage was achieved in 20 patients (90.91%), and 2 (9.09%) required below-the-knee amputation at a mean of 42 ± 14.14 weeks. Wound dehiscence occurred in 8 (36.36%), pin tract infection in 10 (45.45%), and superficial wound infection in 9 (40.91%) and peaked in bimodal fashion at 4 and 8 weeks postoperatively. Radiographic analysis of the pre- versus postoperative alignment showed statistically significant changes in the lateral talo-first metatarsal angle (p = .02) and lateral talar declination angle (p = .01). The limb salvage rates with diabetic Charcot reconstruction are improving in part because of the continued development of increasingly superior modalities for both internal and external fixation. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Angiographic assessment of atherosclerotic load at the lower extremity in patients with diabetic foot and charcot neuro-arthropathy.

PubMed

Çildağ, Mehmet B; Ertuğrul, Bülent M; Köseoğlu, Ömer Fk; Çildağ, Songül; Armstrong, David G

2018-06-01

The aim of this study was to investigate atherosclerotic load at the lower extremity in patients with diabetic foot and charcot neuro-arthropathy and compare them with patients with diabetic foot without charcot neuro-arthropathy. This retrospective study consists of 78 patients with diabetic foot who had lower extremity angiography with antegrade approach. All patients were classified into two groups; neuro ischemic wounds with charcot neuro-arthropathy (30/78) and without charcot neuro-arthropathy (48/78).Atherosclerotic load at the side of diabetic foot was determined by using the Bollinger angiogram scoring method. Comparison of atherosclerotic load between the two groups was performed. The mean of total and infrapopliteal level angiogram scoring of all patients was 33.3 (standard deviation, sd:±17.2) and 29.3 (sd:±15.6), respectively. The mean of total and infrapopliteal level angiogram scoring of neuroischemic wounds with charcot neuro-arthropathy group was 18.1 (sd:±11.6) and 15.7 (sd:±10.4), respectively. The mean of total and infrapopliteal level angiogram scoring of neuroischemic wounds without charcot neuro-arthropathy group was 42.8 (sd:±12.7) and 37.7 (sd:±12.0), respectively. There was a statistically significant difference between the two groups of mean total and infrapopliteal angiogram scoring (p < 0.01). This angiographic study confirms that the atherosclerotic load in patients with diabetic foot and chronic charcot neuro-arthropathy is significantly less than in patients with neuroischemic diabetic foot wounds without chronic charcot neuro-arthropathy. Copyright © 2017. Published by Elsevier Taiwan LLC.

Charcot Neuroarthropathy of the Foot and Ankle.

PubMed

Burson, Lisa K; Schank, Christopher H

2016-03-01

Charcot neuropathy is a painless, progressive, degeneration most notably of the ankle or midfoot joints, seen in patients with diabetes and neuropathy. This article will describe the etiology, diagnosis, and treatment of this potentially debilitating joint disease and provide implications for home care clinicians.

Circular External Fixation as a Primary or Adjunctive Therapy for the Podoplastic Approach of the Diabetic Charcot Foot.

PubMed

Short, Daniel J; Zgonis, Thomas

2017-01-01

Numerous techniques have been described for surgical management of the diabetic Charcot foot. External fixation has become a main surgical tool for the reconstructive foot and ankle surgeon when dealing with the ulcerated diabetic Charcot foot. In the presence of an open wound and/or osteomyelitis, staged reconstruction with circular external fixation becomes ideal for salvage of the diabetic lower extremity. Also, circular external fixation can provide simultaneous compression and stabilization, correct the underlying osseous or soft tissue deformities, and surgically offload the diabetic Charcot foot. This article describes a variety of circular external fixation applications for the diabetic Charcot foot. Copyright © 2016 Elsevier Inc. All rights reserved.

What lessons can history teach us about the Charcot foot?

PubMed

Sanders, Lee J

2008-01-01

Regrettably, physicians today receive very little instruction in the history of medicine. Most health care providers have a very limited, contemporary knowledge of the condition that we know of as the Charcot foot. Yet, historical concepts of the pathogenesis and natural history of this condition provide us with important lessons that enhance our understanding, recognition, and management of this rare but debilitating neurogenic arthropathy. It is my belief that knowledge of the history of medicine provides us with a better understanding of present-day issues and clearer vision as we look to the future. This article describes some of the important lessons learned from the history of the Charcot foot.

Surgical versus accommodative treatment for Charcot arthropathy of the midfoot.

PubMed

Pinzur, Michael

2004-08-01

The treatment of Charcot foot arthropathy is one of the most controversial issues facing orthopaedic foot and ankle surgeons. Although current orthopaedic textbooks are in almost universal agreement that treatment should be nonoperative, accommodating the deformity with orthotic methods, most peer-reviewed clinical studies recommend early surgical correction of the deformity. In a university health system orthopaedic foot and ankle clinic with a special interest in diabetic foot disorders, a moderate approach evolved for management of this difficult patient population. Patients with Charcot arthropathy and plantigrade feet were treated with accommodative orthotic methods. Those with nonplantigrade feet were treated with surgical correction of the deformity, followed by long-term management with commercial therapeutic footwear. The desired outcome for both groups was long-term management with standard, commercially available, therapeutic depth-inlay shoes and custom-fabricated accommodative foot orthoses. During a 6-year period, 198 patients (201 feet) were treated for diabetes-associated Charcot foot arthropathy. The location of the deformity was in the midfoot in 147 feet, in the ankle in 50, and in the forefoot in four. At a minimum 1-year follow-up, 87 of the 147 feet with midfoot disease (59.2%) achieved the desired endpoint without surgical intervention. Sixty (40.8%) required surgery. Corrective osteotomy with or without arthrodesis was attempted in 42, while debridement or simple exostectomy was attempted in 18 feet. Three patients had initial amputation (one partial foot amputation, one Syme ankle disarticulation, and one transtibial amputation), and five had amputation (two Syme ankle disarticulations and three transtibial amputations) after attempted salvage failed. Using a simple treatment protocol with the desired endpoint being long-term management with commercially available, therapeutic footwear and custom foot orthoses, more than half of patients

Charcot joint-like changes following ankle fracture in a patient with no underlying disease: report of a rare case.

PubMed

Kumagai, Masaru; Yokota, Kiyoshi; Endoh, Toshiya; Takemoto, Hitoshi; Nagata, Kensei

2002-01-01

Charcot joint is a disease that often occurs in patients with diabetes mellitus, tabes dorsalis, syringomyelia, chronic alcoholism, leprosy, trauma, or infection after fractures and dislocations. The treatment for Charcot joint has various complications, such as skin lesions, infections, and delayed union. We present our experience with a male patient who developed Charcot joint-like changes without diabetes mellitus or any other disease after an ankle fracture due to minor trauma.

ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.

PubMed

Montecchiani, Celeste; Pedace, Lucia; Lo Giudice, Temistocle; Casella, Antonella; Mearini, Marzia; Gaudiello, Fabrizio; Pedroso, José L; Terracciano, Chiara; Caltagirone, Carlo; Massa, Roberto; St George-Hyslop, Peter H; Barsottini, Orlando G P; Kawarai, Toshitaka; Orlacchio, Antonio

2016-01-01

Charcot-Marie-Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼ 40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot-Marie-Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot-Marie-Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot-Marie-Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot-Marie-Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot-Marie-Tooth disease (CMT2A2/HMSN2A2/MFN2, CMT2B1/LMNA, CMT2B2/MED25, CMT2B5/NEFL, ARCMT2F/dHMN2B/HSPB1, CMT2K/GDAP1, CMT2P/LRSAM1, CMT2R/TRIM2, CMT2S/IGHMBP2, CMT2T/HSJ1, CMTRID/COX6A1, ARAN-NM/HINT and GAN/GAN), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/PGN, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG46/GBA2, SPG55/C12orf65 and SPG56/CYP2U1), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum (SLC12A6). Mitochondrial disorders related to Charcot-Marie-Tooth disease type 2 were also excluded by sequencing POLG and TYMP genes. An additional locus for autosomal recessive Charcot

Serial casting for reconstruction of a deformed Charcot foot: a case report.

PubMed

Rosenblum, Jonathan I; Weiss, Shmuel; Gazes, Michael; Amit-Kohn, Michal

2015-05-01

Charcot neuroarthropathy may occur in patients with peripheral neuropathy who do not notice pain while their bones and joints collapse or breakdown under the constant pressure of body weight. This can lead to ulcerations from severe deformity and potentially limb-threatening and life-threatening infections. Current treatments vary from immobilization to extensive reconstructive surgical interventions. Serial casting, used to correct many pediatric deformities while bones are often more pliable, was used with a 63-year-old male patient who presented with an active phase of Charcot foot with ulceration. The patient previously underwent foot reconstruction and had all hardware removed prior to serial casting. Due to the potential pliability of the bones, serial casting was attempted to reform the shape and position of the foot in a reverse Ponseti-type serial casting to create a more stable structure with less deformity that could lead to epithelial breakdown. The patient regained full ambulation with a plantargrade foot and no wounds, and was followed without complications for 36 months. Serial weekly casting was an effective modality for treatment of this patient's Charcot foot deformity.

About medicine and the arts. Charcot and French literature at the fin-de-siècle.

PubMed

Koehler, P

2001-03-01

The relationship between medicine and the arts, literature in particular, has many aspects. One of the most obvious relations is the use of literature as a source for historical studies. Jean-Martin Charcot and his school often appear in French literature at the end of the 19th century. Several aspects will be highlighted in this study, including (1) the ideas about degenerative diseases in the work of Emile Zola, the main author of the naturalistic movement; (2) decadence and spiritism in two "transitional" novels by Joris Karl Huysmans, who, once supporter of the naturalistic movement, changed his ideas following observations of disease and cure that could not be explained in a scientific way. Charcot's work on hysteria and hypnosis, as well as Brown-Séquard's rejuvenation experiments with testicular extracts played an important role with this respect; (3) Charcot's relationship with the Daudets, in particular his treatment of Alphonse's tabes dorsalis and the ambivalent attitude of his son Léon Daudet towards Charcot; (4) the influence of the lectures at the Salpêtrière on the work of Guy de Maupassant, who attended the lessons in the mid-1880s. The reading of novels and biographies of these authors provides a part of the social context and the cultural atmosphere in Paris at the "fin-de-siècle" when Charcot and his school played an important role in medicine. Moreover, it shows the influence of medicine and science on society as recorded by writers.

Surgical Correction of the Achilles Tendon for Diabetic Foot Ulcerations and Charcot Neuroarthropathy.

PubMed

Ramanujam, Crystal L; Zgonis, Thomas

2017-04-01

Achilles tendon pathologic conditions are implicated in contributing to the development of many diabetic foot complications including diabetic foot ulceration and Charcot neuroarthropathy. Surgical correction of the diabetic equinus deformity has been studied as an isolated or adjunctive treatment when dealing with difficult-to-close diabetic foot ulcerations or when surgically addressing the diabetic Charcot neuroarthropathy foot or ankle. This article reviews the most common indications, complications, and surgical procedures for equinus correction by either a tendo-Achilles lengthening or gastrocnemius recession for the management of diabetic foot conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-term effects on the progress of neuropathy after diabetic Charcot foot: an 8.5-year prospective case-control study.

PubMed

Jansen, Rasmus Bo; Møller Christensen, Tomas; Bülow, Jens; Rørdam, Lene; Holstein, Per E; Lander Svendsen, Ole

2018-02-20

Charcot foot is a severe complication to diabetes mellitus, associated with diabetic neuropathy. Any long-term effects of a Charcot foot on the progress of neuropathy are still largely unexplored. The objective was to investigate whether a previous Charcot foot had any long-term effects on the progress of neuropathy. An 8.5-year follow-up case-control study of 49 individuals with diabetes mellitus, 24 of whom also had Charcot foot at baseline visit in 2005-2007. Neuropathy was assessed with a questionnaire, biothesiometry, heart rate variability and venous occlusion plethysmography. Of the 49 baseline participants, 22 were able to participate in the follow-up. Twelve had passed away in the meantime. Heart rate variability was unchanged in both groups; from 9.7 to 7.2 beats/min (p = 0.053) in the Charcot group, and 14.3 to 12.6 beats/min (p = 0.762) in the control group. Somato-sensoric neuropathy showed no difference between baseline and follow-up in the Charcot group (from 39.1 to 38.5 V) (p = 0.946), but a significantly worsened sensitivity in the control group (from 25.1 to 38.9 V) (p = 0.002). In conclusion, we found that any differences in somatic or cardial autonomic neuropathy present at baseline had disappeared at follow-up after 8.5 years.

Targeting the colony stimulating factor 1 receptor alleviates two forms of Charcot-Marie-Tooth disease in mice.

PubMed

Klein, Dennis; Patzkó, Ágnes; Schreiber, David; van Hauwermeiren, Anemoon; Baier, Michaela; Groh, Janos; West, Brian L; Martini, Rudolf

2015-11-01

See Scherer (doi:10.1093/awv279) for a scientific commentary on this article.Charcot-Marie-Tooth type 1 neuropathies are inherited disorders of the peripheral nervous system caused by mutations in Schwann cell-related genes. Typically, no causative cure is presently available. Previous preclinical data of our group highlight the low grade, secondary inflammation common to distinct Charcot-Marie-Tooth type 1 neuropathies as a disease amplifier. In the current study, we have tested one of several available clinical agents targeting macrophages through its inhibition of the colony stimulating factor 1 receptor (CSF1R). We here show that in two distinct mouse models of Charcot-Marie-Tooth type 1 neuropathies, the systemic short- and long-term inhibition of CSF1R by oral administration leads to a robust decline in nerve macrophage numbers by ∼70% and substantial reduction of the typical histopathological and functional alterations. Interestingly, in a model for the dominant X-linked form of Charcot-Marie-Tooth type 1 neuropathy, the second most common form of the inherited neuropathies, macrophage ablation favours maintenance of axonal integrity and axonal resprouting, leading to preserved muscle innervation, increased muscle action potential amplitudes and muscle strengths in the range of wild-type mice. In another model mimicking a mild, demyelination-related Charcot-Marie-Tooth type 1 neuropathy caused by reduced P0 (MPZ) gene dosage, macrophage blockade causes an improved preservation of myelin, increased muscle action potential amplitudes, improved nerve conduction velocities and ameliorated muscle strength. These observations suggest that disease-amplifying macrophages can produce multiple adverse effects in the affected nerves which likely funnel down to common clinical features. Surprisingly, treatment of mouse models mimicking Charcot-Marie-Tooth type 1A neuropathy also caused macrophage blockade, but did not result in neuropathic or clinical improvements

Bone mineral density and markers of bone turnover and inflammation in diabetes patients with or without a Charcot foot: An 8.5-year prospective case-control study.

PubMed

Jansen, Rasmus Bo; Christensen, Tomas Møller; Bülow, Jens; Rørdam, Lene; Holstein, Per E; Jørgensen, Niklas Rye; Svendsen, Ole Lander

2018-02-01

Charcot foot is a rare but severe complication to diabetes and peripheral neuropathy. It is still unclear if an acute Charcot foot has long-term effects on the bone metabolism. To investigate this, we conducted a follow-up study to examine if a previously acute Charcot foot has any long-term effects on bone mineral density (BMD) or local or systemic bone metabolism. An 8.5-year follow-up case-control study of 44 individuals with diabetes mellitus, 24 of whom also had acute or chronic Charcot foot at the baseline visit in 2005-2007, who were followed up in 2015 with DXA scans and blood samples. 21 of the 44 baseline participants participated in the follow-up. There were no difference in the change in total hip BMD from baseline to follow-up in either the Charcot or the control group (p = 0.402 and 0.517), and no increased risk of osteoporosis in the previous Charcot feet either. From baseline to follow-up, there was a significant difference in the change in levels of fsRANK-L in the Charcot group, but not in the control group (p = 0.002 and 0.232, respectively). At follow-up, there were no differences in fsRANK-L between the groups. The fsRANK-L/OPG ratio also significantly decreased from baseline to follow-up in the Charcot group (3.4 versus 0.5) (p = 0.009), but not in the control group (1.3 versus 1.1) (p = 0.302). We found that diabetes patients with an acute Charcot foot have an elevated fsRANK-L/OPG ratio, and that the level decreased from baseline to follow-up to be comparable to the level in diabetes patients without previous or current Charcot foot. We found no permanent effect of an acute Charcot foot on hip or foot BMD. Copyright © 2017 Elsevier Inc. All rights reserved.

De Novo duplication in Charcot-Marie-Tooth Type 1A

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

Mandich, P.; Bellone, E.; Ajmar, F.

1996-09-01

We read with interest the paper on {open_quotes}Prevalence and Origin of De Novo Duplications in Charcot-Marie-Tooth Disease Type 1A: First Report of a De Novo Duplication with a Maternal Origin,{close_quotes}. They reported their experience with 10 sporadic cases of Charcot-Marie-Tooth type 1A (CMT1A) in which it was demonstrated that the disease had arisen as the result of a de novo duplication. They analyzed the de novo-duplication families by using microsatellite markers and identified the parental origin of the duplication in eight cases. In one family the duplication was of maternal origin, whereas in the remaining seven cases it was ofmore » paternal origin. The authors concluded that their report was the first evidence of a de novo duplication of maternal origin, suggesting that this is not a phenomenon associated solely with male meiosis. 7 refs.« less

Novel use of a Dektak 150 surface profiler unmasks differences in resorption pit profiles between control and Charcot patient osteoclasts.

PubMed

Petrova, Nina L; Petrov, Peter K; Edmonds, Michael E; Shanahan, Catherine M

2014-04-01

We hypothesized that newly formed osteoclasts from patients with acute Charcot osteoarthropathy can resorb surfaces of bone more extensively compared with controls. Peripheral blood monocytes, isolated from eight Charcot patients and nine controls, were cultured in vitro on 24-well plates and bovine bone discs in duplicate with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κβ ligand (RANKL). Osteoclast formation was assessed by tartrate-resistant acid phosphatase staining (TRAcP) at day 17. Resorption was measured at day 21 after toluidine blue staining by two methods: (1) area of resorption at the surface by image analysis (%) and (2) area of resorption under the surface (μm(2)) measured by a Dektak 150 Surface Profiler. Ten 1,000 μm-long scans were performed per disc. Pits were classified as unidented, bidented, and multidented according to their shape. Although the number of newly formed TRAcP positive multinucleated cells (>3 nuclei) was similar in M-CSF + RANKL-treated cultures between controls and Charcot patients, the latter exhibited increased resorbing activity. The area of resorption on the surface by image analysis was significantly greater in Charcot patients compared with controls (21.1 % [14.5-26.2] vs. 40.8 % [35.4-46.0], median [25-75th percentile], p < 0.01), as was the area of resorption under the surface (2.7 x 10(3) μm(2) [1.6 x 10(3)- 3.9 x 10(3)] vs. 8.3 x 10(3) μm (2) [5.6 x 10(3)- 10.6 x 10(3), [corrected] p < 0.01) after profilometry. In Charcot patients pits were deeper and wider and more frequently presented as multidented pits. This application of the Dektak 150 Surface Profiler revealed novel differences in resorption pit profile from osteoclasts derived from Charcot patients compared with controls. Resorption in Charcot patients was mediated by highly aggressive newly formed osteoclasts from monocytes eroding large and deep areas of bone.

Cost comparison: limb salvage versus amputation in diabetic patients with charcot foot.

PubMed

Gil, Joseph; Schiff, Adam P; Pinzur, Michael S

2013-08-01

The negative impact on health-related quality of life in patients with Charcot foot has prompted operative correction of the acquired deformity. Comparative effectiveness financial models are being introduced to provide valuable information to assist clinical decision making. Seventy-six patients with Charcot foot underwent operative correction with the use of circular external fixation. Thirty-eight (50%) had osteomyelitis. A control group was created from 17 diabetic patients who successfully underwent transtibial amputation and prosthetic fitting during the same period. Cost of care during the 12 months following surgery was derived from inpatient hospitalization, placement in a rehabilitation unit or skilled nursing facility, home health care including parenteral antibiotic therapy, physical therapy, and purchase of prosthetic devices or footwear. Fifty-three of the patients with limb salvage (69.7%) did not require inpatient rehabilitation. Their average cost of care was $56,712. Fourteen of the patients with amputation (82.4%) required inpatient rehabilitation, with an average cost of $49,251. Many surgeons now favor operative correction of Charcot foot deformity. This investigation provides preliminary data on the relative cost of transtibial amputation and prosthetic limb fitting compared with limb salvage. The use of comparative effectiveness models such as this simple attempt may provide valuable information in planning resource allocation for similar complex groups of patients. Level III, economic and decision analysis.

The motor function measure to study limitation of activity in children and adults with Charcot-Marie-Tooth disease.

PubMed

Allard, L; Rode, G; Jacquin-Courtois, S; Pouget, M C; Rippert, P; Hamroun, D; Poirot, I; Bérard, C; Vuillerot, C

2014-12-01

To study the applicability and responsiveness of the motor function measure (total score and sub-scores D1, D2 and D3) in patients with Charcot-Marie-Tooth disease. Two hundred and thirty-three patients aged 4-86 years were included in the descriptive study. Scores and sub-scores were analyzed by age and by disease subtypes. Sensitivity to change (responsiveness) was estimated in patients having had at least two evaluations with at least six months between the first and the second. Motor function measure scores decrease with age, especially sub-scores D1 and D3. There were no significant differences between the scores according to type of Charcot-Marie-Tooth disease. The scores were significantly higher for ambulatory than for non-ambulatory patients. Significant responsiveness was demonstrated only in type 2 Charcot-Marie-Tooth disease. Our results suggest that, especially for D1 and D3 sub-scores, the motor function measure is a reliable and valid outcome measure that can be usefully applied in longitudinal follow-up. Studies of longer duration could demonstrate its responsiveness in other Charcot-Marie-Tooth disease subtypes. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

[Hindfoot fusion for Charcot osteoarthropathy with a curved retrograde nail].

PubMed

Pyrc, J; Fuchs, A; Zwipp, H; Rammelt, S

2015-01-01

Charcot osteoarthropathy of the hindfoot with considerable dislocation and instability represents a therapeutic dilemma. The treatment goal is a plantigrade, stable foot that is free of infection and ulceration with the ability to ambulate in special footwear. Over a period of 6 years, we performed 23 hindfoot fusions in 21 patients with manifest Charcot arthropathy with the help of a curved retrograde nail (HAN). All patients suffered from insulin-dependent diabetes mellitus with polyneuropathy; 12 patients had additional peripheral vasculopathy. An average of 3.5 previous surgeries had been performed prior to hindfoot fusion. Complete tibiotalocalcaneal fusion was obtained in 16 of 21 patients (76 %). Of these 21 patients, 18 (86 %) were followed clinically and radiologically for an average of 2 years. Overall, 16 patients (89 %) reported a substantial subjective improvement compared to the preoperative state. Hardware failure occurred in 7 cases (30 %) that could be brought to consolidation with exchange of the locking bolts or the complete nail. In 5 cases (22 %), a postoperative hematoma had to be removed and in 8 cases (35 %) wound edge necrosis was treated with local wound care. In 2 cases (9 %), a secondary or reactivated osteitis occurred that finally required below knee amputation. Tibiotalocalcaneal fusion with a curved retrograde intramedullary nail (HAN) is an effective treatment option in highly unstable and deforming Charcot osteoarthropathy of the hindfoot. It is an alternative to external or other internal fixation methods and helps to avoid below knee amputation in more than 90 % of cases.

Autosomal recessive Charcot-Marie-Tooth neuropathy.

PubMed

Espinós, Carmen; Calpena, Eduardo; Martínez-Rubio, Dolores; Lupo, Vincenzo

2012-01-01

Charcot-Marie-Tooth (CMT) disease, a hereditary motor and sensory neuropathy that comprises a complex group of more than 50 diseases, is the most common inherited neuropathy. CMT is generally divided into demyelinating forms, axonal forms and intermediate forms. CMT is also characterized by a wide genetic heterogeneity with 29 genes and more than 30 loci involved. The most common pattern of inheritance is autosomal dominant (AD), although autosomal recessive (AR) forms are more frequent in Mediterranean countries. In this chapter we give an overview of the associated genes, mechanisms and epidemiology of AR-CMT forms and their associated phenotypes.

Jules Bernard Luys in Charcot's penumbra.

PubMed

Parent, Martin; Parent, André

2011-01-01

Jules Bernard Luys (1828-1897) is a relatively unknown figure in 19th century French neuropsychiatry. Although greatly influenced by Jean-Martin Charcot (1825-1893), Luys worked in the shadow of the 'master of La Salpêtrière' for about a quarter of a century. When he arrived at this institution in 1862, he used microscopy and photomicrography to identify pathological lesions underlying locomotor ataxia and progressive muscular atrophy. He later made substantial contributions to our knowledge of normal human brain anatomy, including the elucidation of thalamic organization and the discovery of the subthalamic nucleus. Luys's name has long been attached to the latter structure (corps de Luys), which is at the center of our current thinking about the functional organization of basal ganglia and the physiopathology of Parkinson's disease. As head of the Maison de santé d'Ivry, Luys developed a highly original view of the functional organization of the normal human brain, while improving our understanding of the neuropathological and clinical aspects of mental illnesses. In 1886, Luys left La Salpêtrière and became chief physician at La Charité hospital. Following Charcot, whom he considered as the father of scientific hypnotism, Luys devoted the last part of his career to hysteria and hypnosis. However, Luys ventured too deeply into the minefield of hysteria. He initiated experiments as unconventional as the distant action of medication, and became one of the most highly caricatured examples of the fascination that hysteria exerted upon neurologists as well as laypersons at the end of the 19th century. Copyright © 2011 S. Karger AG, Basel.

An anterior ankle-foot orthosis improves walking economy in Charcot-Marie-Tooth type 1A patients.

PubMed

Menotti, Federica; Laudani, Luca; Damiani, Antonello; Mignogna, Teresa; Macaluso, Andrea

2014-10-01

Ankle-foot orthoses are commonly prescribed in Charcot-Marie-Tooth type 1A disease to improve quality of walking and reduce the risk of falling due to the foot drop. This study aimed at assessing the effect of an anterior ankle-foot orthosis on walking economy in a group of Charcot-Marie-Tooth type 1A patients. Within-group comparisons. 7 Charcot-Marie-Tooth type 1A patients (four women and three men; 37 ± 11 years; age range = 22-53 years) were asked to walk on a circuit at their self-selected speeds ('slow', 'comfortable' and 'fast') in two walking conditions: (1) with shoes only and (2) with Taloelast(®) anterior elastic ankle-foot orthoses. Speed of walking and metabolic cost of walking energy cost per unit of distance were assessed at the three self-selected speeds of walking for both walking conditions. Speed of walking at the three self-selected speeds did not differ between shoes only and anterior elastic ankle-foot orthoses, whereas walking energy cost per unit of distance at comfortable speed was lower in patients using anterior elastic ankle-foot orthoses with respect to shoes only (2.39 ± 0.22 vs 2.70 ± 0.19 J kg(-1) m(-1); P < 0.05). In Charcot-Marie-Tooth type 1A patients, the use of anterior elastic ankle-foot orthoses improved walking economy by reducing the energy cost of walking per unit of distance, thus reflecting a lower level of metabolic effort and improved mechanical efficiency in comparison with shoes only. From a practical perspective, Charcot-Marie-Tooth type 1A patients with anterior elastic ankle-foot orthoses can walk for a longer duration with a lower level of physical effort. Improvements in walking economy due to ankle-foot orthoses are likely a consequence of the reduction in steppage gait. © The International Society for Prosthetics and Orthotics 2013.

An Analysis of the Symptomatic Domains Most Relevant to Charcot Marie Tooth Neuropathy (CMT) Patients

ClinicalTrials.gov

2017-06-09

Charcot Marie Tooth Disease (CMT); Hereditary Sensory and Motor Neuropathy; Nerve Compression Syndromes; Tooth Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System

Pierre Janet, Sigmund Freud and Charcot's psychological and psychiatric legacy.

PubMed

Pérez-Rincón, Héctor

2011-01-01

A key moment in the history of psychiatry occurred during Charcot's time at La Salpêtriere. Though his studies on hysteria and hypnotism, the founder of neurology inspired the work of two of his alumni: a Viennese Nervenartz and a French philosopher interested in the dissociation of personality. Even though neither of them was originally an alienist, their respective work allowed the field of neurosis--then belonging to internal medicine--to pass to psychiatry. The parallel lives of these frères enemis, both of whom were treated differently by fame, developed inside a very complex cultural and scientific milieu. Therefore, it is necessary to consider them together with other physicians, some of whom are much less well-known nowadays, who one way or another carried Charcot's influence into psychiatry, psychology and psychotherapy. The fates of the Dioscuri have been reversed--the fame and success of Freudian psychoanalysis ran parallel to Janet's oblivion and his long 'purgatory', but now the 'renaissance' of his work coincides with the decline of psychoanalysis as a theoretical explanation for mental pathology. Copyright © 2011 S. Karger AG, Basel.

Nerve Excitability Properties in Charcot-Marie-Tooth Disease Type 1A

ERIC Educational Resources Information Center

Nodera, Hiroyuki; Bostock, Hugh; Kuwabara, Satoshi; Sakamoto, Takashi; Asanuma, Kotaro; Jia-Ying, Sung; Ogawara, Kazue; Hattori, Naoki; Hirayama, Masaaki; Kaji, Ryuji

2004-01-01

Charcot-Marie-Tooth disease type 1A (CMT1A) is commonly considered a prototype of a hereditary demyelinating polyneuropathy. Apart from the myelin involvement, there has been little information on axonal membrane properties in this condition. Taking advantage of the uniform nature of the disease process, we undertook the "in vivo" assessment of…

[Charcot, working and 'Male Hysteria': A new approach to the Leçons du mardi (Tuesday Lessons) from the standpoint of psychodynamics of work].

PubMed

Molinier, Pascale

2015-01-01

This paper examines the role of work in Charcot's clinical teaching focusing on cases of male hysteria in The Tuesday's Lessons from 1887 to 1889. Today, we read the work of Charcot in a retrospective way as having ended in a failure: He would have missed the discovery of the sexual unconscious. From the perspective of psychodynamics of work, it appears an alternative way which was present in Charcot, though unfinished, opening on a possible development of a relationship between psychic and body. The role of work in traumatic hysteria has been forgotten by Freud's posterity and this obliteration continues today.

Neuromuscular Hip Dysplasia in Charcot-Marie-Tooth Disease Type 1A

ERIC Educational Resources Information Center

Bamford, Nigel S.; White, Klane K.; Robinett, Stephanie A.; Otto, Randolph K.; Gospe, Sidney M., Jr.

2009-01-01

Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological disorders, affecting 36 in 100,000 people. CMT type 1A (hereditary motor and sensory neuropathy) is the most frequent form of this disease, affecting 60 to 80% of the CMT population, but its diagnosis may be delayed because of inconsistent clinical signs and…

Functional pedal construct achieved by combined operative treatment in peritalar complex Charcot arthropathy: A prospective study of 38 feet.

PubMed

El-Mowafi, Hani; El-Hawary, Ahmed; Kandil, Yasser

2017-03-06

Charcot arthropathy of the peritalar complex carries a high risk of amputation if not properly managed. Our aim is to assess the functional outcome of severe Charcot arthropathy of the peritalar complex following enblock resection of the ulcer, massive debridement and stabilizing all the elements of the peritalar complex. We prospectively studied 38 feet in 35 patients with peritalar complex Charcot arthropathy. All Feet underwent intense debridement and fusion using a combination of (Ilizarov) external fixation, and (plate and locked nail) internal fixation. Thirty two feet were graded as Eichenholtz 2, and six feet were graded as Eichenholtz 3. The mean follow up was 35.9months. The mean AOFAS score was significantly elevated from 25.4±9.1 preoperatively to 67.6±5.7 at the most recent follow-up (p<0.001). Complete bony fusion was achieved in 28 feet. Unsound bony fusion occurred in 8 feet. Two feet required below knee amputation. Peritalar complex Charcot arthropathy is not uncommon variety. Such cases carry high risk of complications and amputation is not excluded. The proper timing of surgery is crucial. Massive debridement and rigid fixation with strict follow up is mandatory to achieve the ultimate goal of obtaining a plantigrade, stable, mechanically sound, painless and infection free pedal construct. Copyright © 2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Refined genetic mapping of X-linked Charcot-Marie-Tooth neuropathy

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

Fain, P.R.; Barker, D.F.; Chance, P.F.

1994-02-01

Genetic linkage studies were conducted in four multigenerational families with X-linked Charcot-Marie-Tooth disease (CMTX), using 12 highly polymorphic short-tandem-repeat markers for the pericentromeric region of the X Chromosome. Pairwise linkage analysis with individual markers confirmed tight linkage of CMTX to the pericentromeric region in each family. Multipoint analyses strongly support the order DXS337-CMTX-DXS441-(DXS56, PGK1). 38 refs., 2 figs., 1 tab.

Pain in Charcot-Marie-Tooth disease: an update.

PubMed

Azevedo, Helen; Pupe, Camila; Pereira, Rouse; Nascimento, Osvaldo J M

2018-04-01

Charcot-Marie-Tooth (CMT) disease, the most common inherited peripheral neuropathy, has pain as one of its clinical features, yet it remains underdiagnosed and undertreated. This literature review assessed data related to pain from CMT to determine its prevalence, type and importance as a symptom, which, unlike other symptoms, is likely to be treated. The research encompassed 2007 to 2017 and included five articles that addressed pain from CMT. All of the papers concurred that pain is frequently present in CMT patients, yet its classification remains undefined as there has been no consensus in the literature about the mechanisms that cause it.

Polar bear maternity denning in the Beaufort Sea

USGS Publications Warehouse

Amstrup, Steven C.; Gardner, Craig L.

1994-01-01

The distribution of polar bears (Ursus maritimus) is circumpolar in the NOrthern Hemisphere, but known locations of maternal dens are concentrated in relatively few, widely scattered locations. Denning is either uncommon or unknown within gaps. To understand effects of industrial development and propose increases in hunting, the temporal and spatial distribution of denning in the Beaufort Sea must be known. We caputred and radiocollared polar bears between 1981 and 1991 and determined tht denning in the Beaufort Sea region was sufficient to account for the estimated population there. Of 90 dend, 48 were on drifting pack ice, 38 on land, and 4 on land-fast ice. The portions of dens on land was higher (P= 0.029) in later compared with earlier years of the study. Bears denning on pack ice drifting as far as 997 km (x=385km) while in dens. there was no difference in cun production by bears denning on land and pack ice (P =0.66). Mean entry and exit dates were 11 November and 5 April for land dens and 22 November and 26 March for pack-ice dens. Female polar bears captured in the Beaufort Sea appeared to be isolated from those caught eat of Cape Bathurst in Canada. Of 35 polar bears that denned along the mainland coast of Alaska and Canada 80% denned between 137 00'W snf 146 59'W. Bears followed to >1 den did not reuse sites and consecutive dens were 20-1,304 km apart. However radio-collared bears are largely faithful to substrate (pack-ice, land, and land-fast ice) and the general geographic area of previous dens. Bears denning on land may be vunerable to human activities such as hunting and industrial development. However, predictable denning chronology and alck of site fidelity indicate that many potential impacts on denning polar bears could be mitigated.

Acellular fetal bovine dermal matrix for treatment of chronic ulcerations of the midfoot associated with Charcot neuroarthropathy.

PubMed

Kavros, Steven J

2012-08-01

Gross deformity of the foot in Charcot neuroarthropathy can lead to collapse and subsequent ulceration, infection, amputation, or premature death. This study evaluated healing of midfoot ulcerations of Charcot neuroarthropathy using PriMatrix, a novel acellular fetal bovine dermal matrix. In this retrospective analysis, 20 patients with ulcerations of the midfoot associated with Charcot neuroarthropathy were treated with either PriMatrix in addition to standard wound care (PriMatrix group,n = 12) or standard wound care alone (control group, n = 8). All patients had chronic, nonhealing foot ulcerations of at least 2250 mm(3) for a minimum of 30 days duration. All foot ulcerations were full thickness with subcutaneous involvement. Ankle brachial index ≥0.90 and/or transcutaneous oximetry (TcPo(2)) ≥40 mm Hg at the periulcer site was necessary for inclusion. Patients were excluded if they had acute or chronic osteomyelitis of the foot. Demography, risk factors, baseline severity of Charcot neuroarthropathy, and wound volume (control 4078 mm(3), PriMatrix 3737.5 mm(3), P = nonsignificant) were similar between treatment groups. Mean time to healing in the PriMatrix group (116 days, 95% CI = 109-123) was significantly shorter than in the control group (180 days, 95% confidence interval [CI] = 171-188); P < .0001. A significantly faster rate of healing was observed with PriMatrix (87.9 mm(3)/wk, 95% CI = 115.2% to 60.6%) compared with control (59.0 mm(3)/wk, 95% CI = 72.8% to 45.3%); P < .0001). The significantly faster rate of healing and steeper slope of volume reduction in the PriMatrix group warrants further investigation into its effects on healing of neuropathic ulcerations and potential limb salvage.

Characteristics of American marten den sites in Wyoming

Treesearch

Leonard F. Ruggiero; Dean E. Pearson; Stephen E. Henry

1998-01-01

We examined characteristics of den structures and den sites used by female American marten (Martes americana) for natal and maternal dens in the Sierra Madre Range, Wyoming. During 1988-95, we located 18 natal dens (parturition sites) and 97 maternal dens (sites where kits were present exclusive of parturition) used by 10 female marten. Important den structures...

Clinical Results of Total Hip Arthroplasty in Two Patients with Charcot Hip Joints due to Congenital Insensivity to Pain with Anhydrosis

PubMed Central

Inoue, Daisuke; Kajino, Yoshitomo; Taga, Tadashi; Yamamoto, Takashi; Takagi, Tomoharu

2018-01-01

Traditionally, Charcot arthropathy has been considered an absolute contraindication for total hip arthroplasty (THA). However, some recent reports have shown that good short- to mid-term results can be achieved by improving the durability of the implant. This paper reports the mid- to long-term results of THA in two patients with Charcot hip joints caused by congenital insensivity to pain with anhydrosis. Both patients suffered multiple posterior dislocations in the six months immediately following surgery. However, with the continuous use of a hard abduction brace, one patient was eventually able to walk with a lofstrand cane and the other with the use of one crutch. Although one patient experienced a dislocation five years after surgery, X-rays taken after nine years and five years, respectively, revealed no clinical signs of implant loosening. We conclude that, with careful planning and appropriate precautions, THA may be a viable treatment option for Charcot hip joints caused by congenital insensivity to pain with anhydrosis. PMID:29666733

The central nervous system phenotype of X-linked Charcot-Marie-Tooth disease: a transient disorder of children and young adults.

PubMed

Al-Mateen, Majeed; Craig, Alexa Kanwit; Chance, Phillip F

2014-03-01

We describe 2 patients with X-linked Charcot-Marie-Tooth disease, type 1 (CMTX1) disease and central nervous system manifestations and review 19 cases from the literature. Our first case had not been previously diagnosed with Charcot-Marie-Tooth disease, and the second case, although known to have Charcot-Marie-Tooth disease, was suspected of having CMTX1 after presentation with central nervous system manifestations. The most common central nervous system manifestations were transient and included dysarthria, ataxia, hemiparesis, and tetraparesis resembling periodic paralysis. Of the 21 patients, 19 presented at 21 years of age or younger, implicating CMTX1 with transient central nervous system manifestations as a disorder that predominantly affects children and adolescents. CMTX1 should be included in the differential diagnosis of patients who present with transient central nervous system phenomena, including stroke-like episodes, tetraparesis suggestive of periodic paralysis, dysarthria, ataxia, or combinations of these deficits. Reversible, bilateral, nonenhancing white matter lesions and restricted diffusion on magnetic resonance imaging are characteristic features of the central nervous system phenotype of CMTX1.

A Factor Increasing Venous Contamination on Bolus Chase Three-dimensional Magnetic Resonance Imaging: Charcot Neuroarthropathy.

PubMed

Çildağ, Mehmet B; Ertuğrul, Mustafa B; Köseoğlu, Ömer Fk; Armstrong, David G

2018-01-01

The study aimed to evaluate the ratio of venous contamination in diabetic cases without foot lesion, with foot lesion and with Charcot neuroarthropathy (CN). Bolus-chase three-dimensional magnetic resonance (MR) of 396 extremities of patients with diabetes mellitus was analyzed, retrospectively. Extremities were divided into three groups as follows: diabetic patients without foot ulcer or Charcot arthropathy (Group A), patients with diabetic foot ulcers (Group B) and patients with CN accompanying diabetic foot ulcers (Group C). Furthermore, amount of venous contamination classified as no venous contamination, mild venous contamination, and severe venous contamination. The relationship between venous contamination and extremity groups was investigated. Severe venous contamination was seen in Group A, Group B, and Group C, 5.6%, 15.2%, and 34.1%, respectively. Statistically significant difference was seen between groups with regard to venous contamination. Venous contamination following bolus chase MR was higher in patients with CN.

Genetic epidemiology of Charcot-Marie-Tooth disease.

PubMed

Braathen, G J

2012-01-01

Charcot-Marie-Tooth disease (CMT) is the most common inherited disorder of the peripheral nervous system. The frequency of different CMT genotypes has been estimated in clinic populations, but prevalence data from the general population is lacking. Point mutations in the mitofusin 2 (MFN2) gene has been identified exclusively in Charcot-Marie-Tooth disease type 2 (CMT2), and in a single family with intermediate CMT. MFN2 point mutations are probably the most common cause of CMT2. The CMT phenotype caused by mutation in the myelin protein zero (MPZ) gene varies considerably, from early onset and severe forms to late onset and milder forms. The mechanism is not well understood. The myelin protein zero (P(0) ) mediates adhesion in the spiral wraps of the Schwann cell's myelin sheath. X-linked Charcot-Marie Tooth disease (CMTX) is caused by mutations in the connexin32 (cx32) gene that encodes a polypeptide which is arranged in hexameric array and form gap junctions. Estimate prevalence of CMT. Estimate frequency of Peripheral Myelin Protein 22 (PMP22) duplication and point mutations, insertions and deletions in Cx32, Early growth response 2 (EGR2), MFN2, MPZ, PMP22 and Small integral membrane protein of lysosome/late endosome (SIMPLE) genes. Description of novel mutations in Cx32, MFN2 and MPZ. Description of de novo mutations in MFN2. Our population based genetic epidemiological survey included persons with CMT residing in eastern Akershus County, Norway. The participants were interviewed and examined by one geneticist/neurologist, and classified clinically, neurophysiologically and genetically. Two-hundred and thirty-two consecutive unselected and unrelated CMT families with available DNA from all regions in Norway were included in the MFN2 study. We screened for point mutations in the MFN2 gene. We describe four novel mutations, two in the connexin32 gene and two in the MPZ gene. A total of 245 affected from 116 CMT families from the general population of eastern

Hierarchical den selection of Canada lynx in western Montana

Treesearch

John R. Squires; Nicholas J. Decesare; Jay A. Kolbe; Leonard F. Ruggiero

2008-01-01

We studied den selection of Canada lynx (Lynx canadensis; hereafter lynx) at multiple ecological scales based on 57 dens from 19 females located in western Montana, USA, between 1999 and 2006. We considered 3 spatial scales in this analysis, including den site (11-m-radius circle surrounding dens), den area (100-m-radius circle), and den environ (1-...

Novel Use of Active Leptospermum Honey for Ringed Fixator Pin Site Care in Diabetic Charcot Deformity Patients.

PubMed

Lazarides, Alexander L; Hamid, Kamran S; Kerzner, Michael S

2018-04-01

Open reduction with external fixation (OREF) utilizing fine wire ringed fixators for correction of Charcot deformity has gained popularity over the past decade. Pin site infections are a well-documented complication of external fixation as well as a driver of escalating health care costs. We aimed to demonstrate the safety and efficacy of a novel method of pin site care utilizing active Leptospermum honey-impregnated dressings (MediHoney) in diabetic patients undergoing deformity correction with OREF. Twenty-one diabetic patients with Charcot deformities of the lower extremity were prospectively enrolled and followed for pin site complications following OREF for deformity correction. Active Leptospermum honey dressings were applied at metal-cutaneous interfaces at the end of the OREF procedure and replaced weekly for a total of 8 weeks. Patients were monitored for pin site infections from the time of surgery until external fixator removal. Sixteen consecutive patients receiving standard OREF for Charcot deformities were evaluated retrospectively to serve as a control group. Of the 21 enrolled patients, 19 underwent OREF and followed up throughout the study period. Treated patients had a mean age of 58.5 years and mean body mass index measuring 33.3 kg/m 2 as documented prior to surgery. The 15 patients with hemoglobin A1c labs drawn in the 3 months preceding surgery averaged 7.5. Fixators were removed at an average of 12.1 weeks after adequate bony healing. Of the 244 pin sites in 19 patients, 3 pin sites (1.2% of pins) in 2 patients (10.5% of patients) showed evidence of superficial infection. All infections resolved with oral antibiotics. Infection rates were significantly reduced when compared to the standard care control group. Pilot data in a prospectively collected case series demonstrate safety and efficacy of active Leptospermum honey-impregnated dressings when used for fine wire ringed fixator pin site care in diabetic Charcot deformity patients. Further

A neurological bias in the history of hysteria: from the womb to the nervous system and Charcot.

PubMed

Mota Gomes, Marleide da; Engelhardt, Eliasz

2014-12-01

Hysteria conceptions, from ancient Egypt until the 19th century Parisian hospital based studies, are presented from gynaecological and demonological theories to neurological ones. The hysteria protean behavioral disorders based on nervous origin was proposed at the beginning, mainly in Great Britain, by the "enlightenment nerve doctors". The following personages are highlighted: Galen, William, Sydenham, Cullen, Briquet, and Charcot with his School. Charcot who had hysteria and hypnotism probably as his most important long term work, developed his conceptions, initially, based on the same methodology he applied to studies of other neurological disorder. Some of his associates followed him in his hysteria theories, mainly Paul Richer and Gilles de La Tourette who produced, with the master's support, expressive books on Salpêtrière School view on hysteria.

Persistent inflammation with pedal osteolysis 1 Year after Charcot neuropathic osteoarthropathy

PubMed Central

Sinacore, David R.; Bohnert, Kathryn L.; Smith, Kirk E.; Hastings, Mary K.; Commean, Paul K.; Gutekunst, David J.; Johnson, Jeffrey E.; Prior, Fred W.

2017-01-01

Structured Abstract Aims To determine local and systemic markers of inflammation and bone mineral density (BMD) in the foot and central sites in participants with diabetes mellitus and peripheral neuropathy (DMPN) with and without acute Charcot neuropathic osteoarthropathy (CN). Methods Eighteen participants with DMPN and CN and 19 participants without CN had foot temperature assessments, serum markers of inflammation [C-reactive protein, (CRP) and erythrocyte sedimentation rate, (ESR)] and BMD of the foot, hip and lumbar spine at baseline and 1 year follow-up. Results CN foot temperature difference was higher compared to DMPN controls at baseline (4.2 ± 1.9 °F vs. 1.2 ± 0.9 °F, P < 0.01) and after 1 year (2.9 ± 3.2 °F vs. 0.9 ± 1.1 °F, P < 0.01). Serum inflammatory markers in the CN group were greater at baseline and remained elevated 1 year later compared to DMPN controls (CRP, P =0.02, ESR, P = 0.03). All pedal bones’ BMD decreased an average of 3% in the CN foot with no changes in hip or lumbar spine. DMPN controls’ foot, hip and lumbar spine BMD remained unchanged. Conclusions Local and systemic inflammation persists1 year after CN with an accompanying pedal osteolysis that may contribute to mid foot deformity which is the hallmark of the chronic Charcot foot. PMID:28254346

Mid-term follow-up of patients with hindfoot arthrodesis with retrograde compression intramedullary nail in Charcot neuroarthropathy of the hindfoot.

PubMed

Chraim, M; Krenn, S; Alrabai, H M; Trnka, H-J; Bock, P

2018-02-01

Hindfoot arthrodesis with retrograde intramedullary nailing has been described as a surgical strategy to reconstruct deformities of the ankle and hindfoot in patients with Charcot arthropathy. This study presents case series of Charcot arthropathy patients treated with two different retrograde intramedullary straight compression nails in order to reconstruct the hindfoot and assess the results over a mid-term follow-up. We performed a retrospective analysis of 18 consecutive patients and 19 operated feet with Charcot arthropathy who underwent a hindfoot arthrodesis using a retrograde intramedullary compression nail. Patients were ten men and eight women with a mean age of 63.43 years (38.5 to 79.8). We report the rate of limb salvage, complications requiring additional surgery, and fusion rate in both groups. The mean duration of follow-up was 46.36 months (37 to 70). The limb salvage rate was 16 of 19 limbs. Three patients had to undergo below-knee amputation due to persistent infection followed by osteomyelitis resistant to parenteral antibiotic therapy and repeated debridement. Complications including infection, hardware removal, nonunion, and persistent ulcers requiring further intervention were also observed. Postoperative functional scores revealed significant improvement compared with preoperative scores on American Orthopaedic Foot and Ankle Society (AOFAS) - Hindfoot scale, Foot Function Index (FFI), visual analogue scale (VAS), and Foot and Ankle Outcome Score (FAOS). The use of retrograde intramedullary compression nail results in good rates of limb salvage when used for hindfoot reconstruction in patients with Charcot arthropathy. Cite this article: Bone Joint J 2018;100-B:190-6. ©2018 The British Editorial Society of Bone & Joint Surgery.

A study of physical activity comparing people with Charcot-Marie-Tooth disease to normal control subjects.

PubMed

Ramdharry, Gita M; Pollard, Alexander J; Grant, Robert; Dewar, Elizabeth L; Laurá, Matilde; Moore, Sarah A; Hallsworth, Kate; Ploetz, Thomas; Trenell, Michael I; Reilly, Mary M

2017-08-01

Charcot Marie Tooth disease (CMT) describes a group of hereditary neuropathies that present with distal weakness, wasting and sensory loss. Small studies indicate that people with CMT have reduced daily activity levels. This raises concerns as physical inactivity increases the risk of a range of co- morbidities, an important consideration in the long-term management of this disease. This study aimed to compare physical activity, patterns of sedentary behavior and overall energy expenditure of people with CMT and healthy matched controls. We compared 20 people with CMT and 20 matched controls in a comparison of physical activity measurement over seven days, using an activity monitor. Patterns of sedentary behavior were explored through a power law analysis. Results showed a decrease in daily steps taken in the CMT group, but somewhat paradoxically, they demonstrate shorter bouts of sedentary activity and more frequent transitions from sedentary to active behaviors. No differences were seen in energy expenditure or time spent in sedentary, moderate or vigorous activity. The discrepancy between energy expenditure and number of steps could be due to higher energy requirements for walking, but also may be due to an over-estimation of energy expenditure by the activity monitor in the presence of muscle wasting. Alternatively, this finding may indicate that people with CMT engage more in activities or movement not related to walking. Implications for Rehabilitation Charcot-Marie-Tooth disease: • People with Charcot-Marie-Tooth disease did not show a difference in energy expenditure over seven days compared to healthy controls, but this may be due to higher energy costs of walking, and/or an over estimation of energy expenditure by the activity monitor in a population where there is muscle wasting. This needs to be considered when interpreting activity monitor data in people with neuromuscular diseases. • Compared to healthy controls, people with Charcot

Denning of grizzly bears in the Yellowstone National Park area

USGS Publications Warehouse

Judd, Steven L.; Knight, Richard R.; Blanchard, Bonnie M.

1986-01-01

Radiotelemetry was used to locate 101 grizzly bear (Ursus arctos) dens from 1975 to 1980; 35 dens were examined on the ground. Pregnant females denned in late October, and most other bears denned by mid-November. Duration of denning average 113, 132, and 170 days for males, females, and females with new cubs, respectively. Males emerged from mid-February to late March, followed by single females and females with yearlings and 2-year-olds. Females with new cubs emerged from early mid-April. Den sites were associated with moderate tree cover (26%-75% canopy cover) on 30°-60° slopes. Dens occurred on all aspects, although northerly exposures were most common. Grizzly bears usually dug new dens but occasionally used natural cavities or a den from a previous year. Males usually dug larger dens than females with young. Eight excavated and 2 natural dens of the 35 examined dens were used for more than 1 year.

Treatment for Charcot-Marie-Tooth disease.

PubMed

Young, P; De Jonghe, P; Stögbauer, F; Butterfass-Bahloul, T

2008-01-23

Charcot-Marie-Tooth disease (CMT) comprises a large variety of different forms of motor and sensory neuropathies. The most frequent are demyelinating forms (CMT1) and axonal forms (CMT2). The molecular basis of several CMT forms has been clarified during the last 15 years. Since muscle wasting and sensory disturbance are the main features of these syndromes, treatments aim to improve motor impairment and sensory disturbances. Specific treatment trials are rare. The objective was to review systematically all randomised and quasi-randomised studies of any treatment for CMT. We searched the Cochrane Neuromuscular Disease Group Trials Register, MEDLINE (January 1966 to August 2007), EMBASE (January 1980 to August 2007), LILACS (January 1982 to August 2007) for randomised controlled trials of treatment for CMT. We included randomised and quasi-randomised trials of any treatment for people with CMT. Where a study aimed to evaluate the treatment of general neuromuscular symptoms of people with peripheral neuropathy including CMT, we included the study if we were able to identify the effect of treatment in the CMT group. Observational studies and case reports on the treatment of people with CMT were not included. Two review authors (PY and TBB) extracted the data, assessed study quality and performed data extraction independently. Only one trial with only eight participants met all the inclusion criteria and provided the primary outcome measure for this review. In this trial, four participants treated with neurotrophin-3 had more improvement after six months on the Neuropathy Impairment Score, mean difference -9.50 (95% CI -13.77 to -5.23), than those four treated with placebo. Small trials of exercise training, creatine monohydrate, orthoses and purified bovine brain ganglioside injections (Cronassial) showed no significant benefit in people with genetically undefined CMT1 or CMT2. Small trials of exercise, creatine, purified brain gangliosides, and orthoses have been

Diabetic charcot neuroarthropathy of the foot and ankle with osteomyelitis.

PubMed

Ramanujam, Crystal L; Stapleton, John J; Zgonis, Thomas

2014-10-01

One of the most devastating foot and/or ankle complications in the diabetic population with peripheral neuropathy is the presence of Charcot neuroarthropathy (CN). In recent years, diabetic limb salvage has been attempted more frequently as opposed to major lower extremity amputation for CN of the foot and ankle with ulceration and/or deep infection. Treatment strategies for osteomyelitis in the diabetic population have evolved. This article reviews some of the most common surgical strategies recommended for the diabetic patient with CN of the foot and/or ankle and concomitant osteomyelitis. Copyright © 2014 Elsevier Inc. All rights reserved.

Detecting denning polar bears with Forward-Looking Infrared (FLIR) imagery

USGS Publications Warehouse

Amstrup, Steven C.; York, G.; McDonald, T.L.; Nielson, R.; Simac, K.

2004-01-01

Polar bears give birth in snow dens in midwinter and remain in dens until early spring. The survival and development of cubs is dependent on a stable environment within the maternal den. To mitigate potential disruption of polar bear denning by existing and proposed petroleum activities, we used forward-looking infrared (FLIR) viewing to try to detect heat rising from dens.We flew transects over dens of radio-collared females with FLIR imager-equipped aircraft, recorded weather conditions at each observation, and noted whether the den was detected.We surveyed 23 dens on 67 occasions (1 to 7 times each). Nine dens were always detected, and 10 dens visited more than once were detected on some flights but not on others. Four dens were never detected (17 percent), but three of those were visited only under marginal conditions. The odds of detecting a den were 4.8 times greater when airborne moisture (snow, blowing snow, fog, etc.) was absent than when it was present, and they increased 3-fold for every 1?C increase in temperature-dew point spread. The estimated probability of detecting dens in sunlight was 0. Data suggested that FLIR surveys conducted during optimal conditions for detection can produce detection rates approaching 90 percent and thus can be an important management and mitigation tool. polar bear, infrared imagery, maternal denning, human impacts, management

American black bear denning behavior: Observations and applications using remote photography

USGS Publications Warehouse

Bridges, A.S.; Fox, J.A.; Olfenbuttel, C.; Vaughan, M.B.

2004-01-01

Researchers examining American black bear (Ursus americanus) denning behavior have relied primarily on den-site visitation and radiotelemetry to gather data. Repeated den-site visits are time-intensive and may disturb denning bears, possibly causing den abandonment, whereas radiotelemetry is sufficient only to provide gross data on den emergence. We used remote cameras to examine black bear denning behavior in the Allegheny Mountains of western Virginia during March-May 2003. We deployed cameras at 10 den sites and used 137 pictures of black bears. Adult female black bears exhibited greater extra-den activity than we expected prior to final den emergence, which occurred between April 12 and May 6, 2003. Our technique provided more accurate den-emergence estimation than previously published methodologies. Additionally, we observed seldom-documented behaviors associated with den exits and estimated cub age at den emergence. Remote cameras can provide unique insights into denning ecology, and we describe their potential application to reproductive, survival, and behavioral research.

Internal Versus External Fixation of Charcot Midfoot Deformity Realignment.

PubMed

Lee, Daniel J; Schaffer, Joseph; Chen, Tien; Oh, Irvin

2016-07-01

Internal and external fixation techniques have been described for realignment and arthrodesis of Charcot midfoot deformity. There currently is no consensus on the optimal method of surgical reconstruction. This systematic review compared the clinical results of surgical realignment with internal and external fixation, specifically in regard to return to functional ambulation, ulcer occurrence, nonunion, extremity amputation, unplanned further surgery, deep infection, wound healing problems, peri- or intraoperative fractures, and total cases with any complication. A search of multiple databases for all relevant articles published from January 1, 1990, to March 22, 2014, was performed. A logistic regression model evaluated each of the outcomes and its association with the type of fixation method. The odds of returning to functional ambulation were 25% higher for internal fixation (odds ratio [OR], 1.259). Internal fixation had a 42% reduced rate of ulcer occurrence (OR, 0.578). External fixation was 8 times more likely to develop radiographic nonunion than internal fixation (OR, 8.2). Internal fixation resulted in a 1.5-fold increase in extremity amputation (OR, 1.488), a 2-fold increase in deep infection (OR, 2.068), a 3.4-fold increase in wound healing complications (OR, 3.405), and a 1.5-fold increase in the total number of cases experiencing any complication (OR, 1.525). This was associated with a 20% increase in the need for unplanned further surgery with internal fixation (OR, 1.221). Although internal fixation may decrease the risk of nonunion and increase return to functional ambulation, it had a higher rate of overall complications than external fixation for realignment and arthrodesis of Charcot midfoot deformity. [Orthopedics. 2016; 39(4):e595-e601.]. Copyright 2016, SLACK Incorporated.

Assignment of a second Charcot-Marie-Tooth type II locus to chromosome 3q

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

Kwon, J.M.; Elliott, J.L.; Yee, W.C.

1995-10-01

Charcot-Marie-Tooth disease (CMT) is the most common inherited motor and sensory neuropathy. The neuronal form of this disorder is referred to as Charcot-Marie-Tooth type II disease (CMT2). CMT2 is usually inherited as an autosomal dominant trait with a variable age at onset of symptoms associated with progressive axonal neuropathy. In some families, the locus that predisposes to CMT2 has been demonstrated to map to the distal portion of the short arm of chromosome 1. Other families with CMT2 do not show linkage with 1p markers, suggesting genetic heterogeneity in CMT2. We investigated linkage in a single large kindred with autosomalmore » dominant CMT2. The gene responsible for CMT2 in this kindred (CMT2B) was mapped to the interval between the microsatellite markers D3S1769 and D3S1744 in the 3q13-22 region. Study of additional CMT2 kindreds should serve to further refine the disease gene region and may ultimately lead to the identification of a gene defect that underlies the CMT2 phenotype. 21 refs., 3 figs., 1 tab.« less

Intramedullary compressive nail fixation for the treatment of severe Charcot deformity of the ankle and rear foot.

PubMed

Caravaggi, Carlo; Cimmino, Marzio; Caruso, Sebastiano; Dalla Noce, Sergio

2006-01-01

Involvement of the ankle joint in Charcot osteoarthropathy may be associated with severe instability and fracture or collapse of the talus. Recalcitrant ulceration may result over the lateral malleolus, increasing the risk of major amputation. This study evaluated ankle arthrodesis with a compressive intramedullary nail in 14 patients with diabetes affected by Charcot of the ankle. The mean patient age was 58 +/- 12 years, and the mean duration of diabetes was 17 +/- 5 years. Transcutaneous oxygen pressures were > or = 50 mm Hg in all patients, indicating a good distal blood supply. A below-knee amputation had previously been suggested because of severe ankle joint instability. None of the patients were able to walk without a brace. Four patients had an ulceration that had healed before the index procedure. All procedures were performed in the quiescent phase of the disease. After a mean follow-up of 18 +/- 4 months, 10 patients (71.4%) achieved a solid arthrodesis, returning to walking with protective shoes. Three patients (21.4%) developed breakage of the calcaneus screws, necessitating removal of the screws in 2 cases and removal of the entire nail in 2 cases. These 3 patients went on to fibrous union that allowed walking with a brace. One patient (7.2%) required a below-knee amputation because of postoperative osteomyelitis of the distal tibia. The data from our study demonstrate a high rate of limb salvage (92.8%), suggesting that this device is safe and effective in the treatment of Charcot arthropathy of the ankle.

MCM3AP in recessive Charcot-Marie-Tooth neuropathy and mild intellectual disability.

PubMed

Ylikallio, Emil; Woldegebriel, Rosa; Tumiati, Manuela; Isohanni, Pirjo; Ryan, Monique M; Stark, Zornitza; Walsh, Maie; Sawyer, Sarah L; Bell, Katrina M; Oshlack, Alicia; Lockhart, Paul J; Shcherbii, Mariia; Estrada-Cuzcano, Alejandro; Atkinson, Derek; Hartley, Taila; Tetreault, Martine; Cuppen, Inge; van der Pol, W Ludo; Candayan, Ayse; Battaloglu, Esra; Parman, Yesim; van Gassen, Koen L I; van den Boogaard, Marie-José H; Boycott, Kym M; Kauppi, Liisa; Jordanova, Albena; Lönnqvist, Tuula; Tyynismaa, Henna

2017-08-01

Defects in mRNA export from the nucleus have been linked to various neurodegenerative disorders. We report mutations in the gene MCM3AP, encoding the germinal center associated nuclear protein (GANP), in nine affected individuals from five unrelated families. The variants were associated with severe childhood onset primarily axonal (four families) or demyelinating (one family) Charcot-Marie-Tooth neuropathy. Mild to moderate intellectual disability was present in seven of nine affected individuals. The affected individuals were either compound heterozygous or homozygous for different MCM3AP variants, which were predicted to cause depletion of GANP or affect conserved amino acids with likely importance for its function. Accordingly, fibroblasts of affected individuals from one family demonstrated severe depletion of GANP. GANP has been described to function as an mRNA export factor, and to suppress TDP-43-mediated motor neuron degeneration in flies. Thus our results suggest defective mRNA export from nucleus as a potential pathogenic mechanism of axonal degeneration in these patients. The identification of MCM3AP variants in affected individuals from multiple centres establishes it as a disease gene for childhood-onset recessively inherited Charcot-Marie-Tooth neuropathy with intellectual disability. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Grizzly bear denning chronology and movements in the Greater Yellowstone Ecosystem

USGS Publications Warehouse

Haroldson, Mark A.; Ternent, Mark A.; Gunther, Kerry A.; Schwartz, Charles C.

2002-01-01

Den entrance and emergence dates of grizzly bears (Ursus arctos) in the Greater Yellowstone Ecosystem are important to management agencies that wish to minimize impacts of human activities on bears. Current estimates for grizzly bear denning events use data that were collected from 1975–80. We update these estimates by including data obtained from 1981–99. We used aerial telemetry data to estimate week of den entry and emergence by determining the midpoint between the last known active date and the first known date denned, as well as the last known date denned and the first known active date. We also investigated post emergence movement patterns relative to den locations. Mean earliest and latest week of den entry and emergence were also determined. Den entry for females began during the fourth week in September, with 90% denned by the fourth week of November. Earliest den entry for males occurred during the second week of October, with 90% denned by the second week of December. Mean week of den entry for known pregnant females was earlier than males. Earliest week of den entry for known pregnant females was earlier than other females and males. Earliest den emergence for males occurred during the first week of February, with 90% of males out of dens by the fourth week of April. Earliest den emergence for females occurred during the third week of March; by the first week of May, 90% of females had emerged. Male bears emerged from dens earlier than females. Denning period differed among classes and averaged 171 days for females that emerged from dens with cubs, 151 days for other females, and 131 days for males. Known pregnant females tended to den at higher elevations and, following emergence, remained at higher elevation until late May. Females with cubs remained relatively close (<3 km) to den sites until the last 2 weeks in May. Timing of denning events was similar to previous estimates for this and other grizzly bear populations in the southern Rocky

Connexin mutations in X-linked Charcot-Marie-Tooth disease

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

Bergoffen, J.; Scherer, S.S.; Wang, S.

1993-12-24

X-linked Charcot-Marie-Tooth disease (CMTX) is a form of hereditary neuropathy with demyelination. Recently, this disorder was mapped to chromosome Xq13.1. The gene for the gap junction protein connexin32 is located in the same chromosomal segment, which led to its consideration as a candidate gene for CMTX. With the use of Northern (RNA) blot and immunohistochemistry techniques, it was found that connexin32 is normally expressed in myelinated peripheral nerve. Direct sequencing of the connexin32 gene showed seven different mutations in affected persons from eight CMTX families. These findings, a demonstration of inherited defects in a gap junction protein, suggest that connexin32more » plays an important role in peripheral nerve.« less

Follow up of MRI bone marrow edema in the treated diabetic Charcot foot – a review of patient charts

PubMed Central

Chantelau, Ernst-A.; Zweck, Brigitte; Haage, Patrick

2018-01-01

ABSTRACT Background: Ill-defined areas of water-like signal on bone magnetic resonance imaging (MRI), characterized as bone marrow edema or edema-equivalent signal-changes (EESC), is a hallmark of active-stage pedal neuro-osteoarthropathy (Charcot foot) in painless diabetic neuropathy, and is accompanied by local soft-tissue edema and hyperthermia. The longitudinal effects on EESC of treating the foot in a walking cast were elucidated by reviewing consecutive cases of a diabetic foot clinic. Study design: Retrospective observational study, chart review Material and methods: Cases with active-stage Charcot foot were considered, in whom written reports on baseline and follow-up MRI studies were available for assessment. Only cases without concomitant infection or skin ulcer were chosen, in whom both was documented, onset of symptomatic foot swelling and patient compliance with cast treatment. Results: From 1994 to 2017, 45 consecutive cases in 37 patients were retrieved, with 95 MRI follow-up studies (1–6 per case, average interval between studies 13 weeks). Decreasing EESC was documented in 66/95 (69%) follow-up studies. However, 29/95 (31%) studies revealed temporarily increasing, migrating or stagnating EESC. Conclusion: EESC on MRI disappear in response to prolonged offloading and immobilizing treatment; however, physiologic as well as pathologic fluctuations of posttraumatic EESC have to be considered when interpreting the MR images. Conventional MRI is useful for surveillance of active-stage Charcot foot recovery. PMID:29713425

Crime, hysteria and belle époque hypnotism: the path traced by Jean-Martin Charcot and Georges Gilles de la Tourette.

PubMed

Bogousslavsky, Julien; Walusinski, Olivier; Veyrunes, Denis

2009-01-01

Hysteria and hypnotism became a favorite topic of studies in the fin de siècle neurology that emerged from the school organized at La Salpêtrière by Jean-Martin Charcot, where he had arrived in 1861. Georges Gilles de la Tourette started working with Charcot in 1884 and probably remained his most faithful student, even after his mentor's death in 1893. This collaboration was particularly intense on 'criminal hypnotism', an issue on which Hippolyte Bernheim and his colleagues from the Nancy School challenged the positions taken by the Salpêtrière School. Bernheim claimed that hypnotism was not a diagnostic feature of hysteria and that there were real-life examples of murders suggested under hypnosis, while hypnosis susceptibility was identified with hysteria by Charcot and Gilles de la Tourette, who saw rape as the only crime associated with hypnotism. The quarrel was particularly virulent during a series of famous criminal cases which took place between 1888 and 1890. At the time, it was considered that La Salpêtrière had succeeded over Nancy, since the role of hypnotism was discarded during these famous trials. However, the theories of Charcot and Gilles de la Tourette were also damaged by the fight, which probably triggered the conceptual evolution leading to Joseph Babinski's revision of hysteria in 1901. Gilles de la Tourette's strong and public interest in hypnotism nearly cost him his life, when a young woman who claimed to have been hypnotized against her will shot him in the head at his own home in 1893. It was subsequently shown that hypnotism had nothing to do with it. The delusional woman was interned at Sainte-Anne for mental disturbance, thus escaping trial. Ironically, Gilles de la Tourette may have been partly responsible, since he had been one of the strongest proponents of placing mentally-ill criminals in asylums instead of prisons. 2009 S. Karger AG, Basel

Remote identification of polar bear maternal den habitat in northern Alaska

USGS Publications Warehouse

Durner, George M.; Amstrup, Steven C.; Ambrosius, Ken J.

2001-01-01

Polar bears (Ursus maritimus) give birth in dens of ice and snow to protect their altricial young. During the snow-free season, we visited 25 den sites located previously by radiotelemetry and characterized the den site physiognomy. Seven dens occurred in habitats with minimal relief. Eighteen dens (72%) were in coastal and river banks. These "banks" were identifiable on aerial photographs. We then searched high-resolution aerial photographs (n = 3000) for habitats similar to those of the 18 dens. On aerial photos, we mapped 1782 km of bank habitats suitable for denning. Bank habitats comprised 0.18% of our study area between the Colville River and the Tamayariak River in northern Alaska. The final map, which correctly identified 88% of bank denning habitat in this region, will help minimize the potential for disruptions of maternal dens by winter petroleum exploration activities.

Overlapping molecular pathological themes link Charcot-Marie-Tooth neuropathies and hereditary spastic paraplegias.

PubMed

Timmerman, Vincent; Clowes, Virginia E; Reid, Evan

2013-08-01

In this review we focus on Charcot-Marie-Tooth (CMT) neuropathies and hereditary spastic paraplegias (HSPs). Although these diseases differ in whether they primarily affect the peripheral or central nervous system, both are genetically determined, progressive, long axonopathies that affect motor and sensory pathways. This commonality suggests that there might be similarities in the molecular pathology underlying these conditions, and here we compare the molecular genetics and cellular pathology of the two groups. Copyright © 2012 Elsevier Inc. All rights reserved.

Malignant melanoma and Charcot-Marie-Tooth disease: A further case

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

Manoukian, S.; Briscioli, V.; Lalatta, F.

1997-01-20

In a previous issue of this journal, Greene et al. described 2 patients with Charcot-Marie-Tooth (CMT) disease who later developed cutaneous malignant melanoma. Although the development of the two diseases in the same patient may have occurred by chance, the authors raised the possibility of a shared neural crest defect or a genetic linkage. Among the patients reported by Greene et al., one had a dominant form of CMT. The patient`s mother and brother were similarly affected. A paternal aunt died of melanoma. The second patient had a neuronal type of CMT. His brother showed the same disease, but themore » parents were not examined. 7 refs.« less

Denning behaviour of non-gravid wolves, Canis lupus

USGS Publications Warehouse

Mech, L.D.; Phillips, M.K.; Smith, D.W.; Kreeger, T.J.

1996-01-01

Wild wolves (Canis lupus) that had produced pups in earlier years but were not currently pregnant, and ovariectomized captive wolves, dug dens during and after the whelping season even though they produced no pups. These observations suggest that den digging is not a function of pregnancy or of ovarian estrogen or progesterone. We hypothesize that increasing prolactin in spring elicits or mediates den-digging behavior.

Selection of den sites by black bears in the southern Appalachians

USGS Publications Warehouse

Reynolds-Hogland, M. J.; Mitchell, M.S.; Powell, R.A.; Brown, D.C.

2007-01-01

We evaluated selection of den sites by American black bears (Ursus americanus) in the Pisgah Bear Sanctuary, western North Carolina, by comparing characteristics of dens at 53 den sites with availability of habitat characteristics in annual home ranges of bears and in the study area. We also tested whether den-site selection differed by sex, age, and reproductive status of bears. In addition, we evaluated whether the den component of an existing habitat model for black bears predicted where bears would select den sites. We found bears selected den sites far from gravel roads, on steep slopes, and at high elevations relative to what was available in both annual home ranges and in the study area. Den-site selection did not differ by sex or age, but it differed by reproductive status. Adult females with cubs preferred to den in areas that were relatively far from gravel roads, but adult females without cubs did not. The habitat model overestimated the value of areas near gravel roads, underestimated the value of moderately steep areas, and did not include elevation as a predictor variable. Our results highlight the importance of evaluating den selection in terms of both use and availability of den characteristics. ?? 2007 American Society of Mammalogists.

Entropy and time: A search for Denning's resting place

NASA Astrophysics Data System (ADS)

Beech, Martin

2013-04-01

The interminable scientific literature reveals William Frederick Denning (1848-1931) as one of the great practitioners of meteor astronomy: he wrote widely on the subject and dedicated innumerable hours to his observations. But who was Denning? What can we learn of his life, living and death. Glimpses of Denning the man do exist, but he is largely a man of translucency and unknowns. The journey recounted here reflects upon a recent search for Denning's final resting place, but, once again, it is found that time and circumstance have erased virtually all of the physical history.

[The clinical and pathologic features of Charcot-Marie-Tooth disease].

PubMed

Xiao, Bo; Xie, Jusheng; Yang, Xiaosu; Wu, Zhiguo; Xiao, Jianfeng; Li, Jing

2002-11-01

To study the clinical and pathological features of Charcot-Marie-Tooth disease (CMT). The general clinical data, the changes of neuroelectrophysiology and the pathological features of neural and muscular biopsy of 20 CMT patients were comprehensively analyzed. The clinical manifestations in the two types of CMT were nearly the same, but the changes of neuroelectrophysiology and the pathological characteristics of the neural and muscular biopsy in the two types were obviously different. 16 cases of CMT type 1 were characterized by decreased sensory nerve conduction velocity (SNCV < 30 m/s) and are associated with demyelinating hypertrophic neuropathy. 4 cases of CMT tylpe 2 were characterized by normal SNCV and associated with axonopathy. Neuroelectrophysiology and neural and muscular biopsy are important for the diagnosis of CMT.

Habitat characteristics of polar bear terrestrial maternal den sites in northern Alaska

USGS Publications Warehouse

Durner, George M.; Amstrup, Steven C.; Fischbach, Anthony S.

2003-01-01

Polar bears (Ursus maritimus) give birth to and nurture their young in dens of ice and snow. During 1999-2001, we measured the structure of 22 dens on the coastal plain of northern Alaska after polar bear families had evacuated their dens in the spring. During the summers of 2001 and 2002, we revisited the sites of 42 maternal and autumn exploratory dens and recorded characteristics of the under-snow habitat. The structure of polar bear snow dens was highly variable. Most were simple chambers with a single entrance/egress tunnel. Others had multiple chambers and additional tunnels. Thickness of snow above and below dens was highly variable, but most dens were overlain by less than 1 m of snow. Dens were located on, or associated with, pronounced landscape features (primarily coastal and river banks, but also a lake shore and an abandoned oil field gravel pad) that are readily distinguished from the surrounding terrain in summer and catch snow in early winter. Although easily identified, den landforms in northern Alaska were more subtle than den habitats in many other parts of the Arctic. The structure of polar bear dens in Alaska was strikingly similar to that of dens elsewhere and has remained largely unchanged in northern Alaska for more than 25 years. Knowledge of den structure and site characteristics will allow resource managers to identify habitats with the greatest probability of holding dens. This information may assist resource managers in preventing negative impacts of mineral exploration and extraction on polar bears.

Limb salvage in Charcot foot and ankle osteomyelitis: combined use single stage/double stage of arthrodesis and external fixation.

PubMed

Dalla Paola, Luca; Brocco, Enrico; Ceccacci, Tanja; Ninkovic, Sasa; Sorgentone, Sara; Marinescu, Maria Grazia; Volpe, Antonio

2009-11-01

Charcot neuroarthropathy of the foot/ankle is a devastating complication of diabetes. Along with neuroarthropathy, osteomyelitis can occur which can result in amputation. This prospective study evaluated a limb salvage procedure as an alternative to amputation through surgical treatment of osteomyelitis of the midfoot or the ankle and stabilization with external fixation. Forty-five patients with Charcot arthropathy and osteomyelitis underwent debridement and attempted fusion with an external fixator. Chart and radiograph review was performed to assess the success of the fusion and eradication of infection. Out of 45 patients, 39 patients healed using emergent surgery to drain an acute manifestation of the infection while maintaining the fixation for an average of 25.7 weeks. Two patients were treated with intramedullary nail in a subsequent surgical procedure. In four patients, the infection could not be controlled, therefore a major amputation was carried out. For select patients, external fixation proved to be a reasonable alternative to below-knee amputation.

A female black bear denning habitat model using a geographic information system

USGS Publications Warehouse

Clark, J.D.; Hayes, S.G.; Pledger, J.M.

1998-01-01

We used the Mahalanobis distance statistic and a raster geographic information system (GIS) to model potential black bear (Ursus americanus) denning habitat in the Ouachita Mountains of Arkansas. The Mahalanobis distance statistic was used to represent the standard squared distance between sample variates in the GIS database (forest cover type, elevation, slope, aspect, distance to streams, distance to roads, and forest cover richness) and variates at known bear dens. Two models were developed: a generalized model for all den locations and another specific to dens in rock cavities. Differences between habitat at den sites and habitat across the study area were represented in 2 new GIS themes as Mahalanobis distance values. Cells similar to the mean vector derived from the known dens had low Mahalanobis distance values, and dissimilar cells had high values. The reliability of the predictive model was tested by overlaying den locations collected subsequent to original model development on the resultant den habitat themes. Although the generalized model demonstrated poor reliability, the model specific to rock dens had good reliability. Bears were more likely to choose rock den locations with low Mahalanobis distance values and less likely to choose those with high values. The model can be used to plan the timing and extent of management actions (e.g., road building, prescribed fire, timber harvest) most appropriate for those sites with high or low denning potential. 

Den-site characteristics of black bears in Rocky Mountain National Park, Colorado

USGS Publications Warehouse

Baldwin, R.A.; Bender, L.C.

2008-01-01

We compared historic (1985-1992) and contemporary (2003-2006) black bear (Ursus americanus) den locations in Rocky Mountain National Park (RMNP), Colorado, USA, for habitat and physiographic attributes of den sites and used maximum entropy modeling to determine which factors were most influential in predicting den-site locations. We observed variability in the relationship between den locations and distance to trails and elevation over rime. Locations of historic den sites were most associated with slope, elevation, and covertype, whereas contemporary sites were associated with slope, distance to roads, aspect, and canopy height. Although relationships to covariates differed between historic and contemporary periods, preferred den-site characteristics consistently included steep slopes and factors associated with greater snow depth. Distribution of den locations shifted toward areas closer to human developments, indicating little negative influence of this factor on den-site selection by black bears in RMNP.

Vector competence of Aedes albopictus and Aedes aegypti (Diptera: Culicidae) for the DEN2-FJ10 and DEN2-FJ11 strains of the dengue 2 virus in Fujian, China.

PubMed

Guo, Xiao-Xia; Li, Chun-Xiao; Zhang, Ying-Mei; Xing, Dan; Dong, Yan-De; Zhang, Heng-Duan; Qin, Cheng-Feng; Zhao, Tong-Yan

2016-09-01

Dengue is an acute, emerging, infectious disease transmitted by Aedes mosquitoes that has become a serious global public health problem. The DEN2-FJ10 and DEN2-FJ11 strains of the dengue 2 virus were originally isolated from the serum of a patient with dengue fever in Fujian Province, China, in 1999. Our data provide the first assessment of the vector competence of Aedes mosquitoes with respect to the DEN2-FJ10 and DEN2-FJ11 strains of the dengue virus. There were significant differences in the replication rates of these two viral strains in Aedes albopictus and Aedes aegypti (P<0.05); replication of the DEN2-FJ10 strain was greater in Ae. aegypti than in Ae. albopictus 5 days post infection whereas replication of the DEN2-FJ11 was greater in Ae. albopictus than in Ae. aegypti 7 days post infection. The replicative ability of the DEN2-FJ11 strain was greater than that of the DEN2-FJ10 strain in infected Ae. albopictus. In infected Ae. aegypti, rapid proliferation of the DEN2-FJ10 strain occurred earlier than in the DEN2-FJ11 strain. There were no significant differences in the midgut and salivary gland infection rates of Ae. albopictus and Ae. aegypti with respect to either viral strain. Although the DEN2-FJ10 and DEN2-FJ11 strains differ in their virulence to neonatal rats, there was no significant difference in the ability of either Ae. albopictus or Ae. aegypti to transmit the DEN2-FJ10 and DEN2-FJ10 strains of the dengue 2 virus (P>0.05). In summary, our results indicate that Ae. albopictus and Ae. aegypti mosquitoes are moderately competent vectors of the DEN2-FJ10 and DEN2-FJ11 strains of the dengue virus and provide the first evidence of the effect of these two viral strains on the vector competence of mosquitoes in China. Copyright © 2016 Elsevier B.V. All rights reserved.

Post-den emergence behavior of polar bears (Ursus maritimus) in Northern Alaska

USGS Publications Warehouse

Smith, T.S.; Partridge, Steven T.; Amstrup, Steven C.; Schliebe, S.

2007-01-01

We observed polar bear (Ursus maritimus) maternity den sites on Alaska’s North Slope in March 2002 and 2003 in an effort to describe bears’ post-den emergence behavior. During 40 sessions spanning 459 h, we observed 8 adults and 14 dependent cubs outside dens for 37.5 h (8.2% of total observation time). There was no significant difference between den emergence dates in 2002 (mean = 15 Mar ± 4.1 d) and 2003 (mean = 21 Mar ± 2.1 d). Following initial den breakout, polar bears remained at their den sites for 1.5 to 14 days (mean = 8.1 ± 5.1 d). The average length of stay in dens between emergent periods was significantly shorter in 2002 (1.79 h) than in 2003 (4.82 h). While outside, adult bears were inactive 49.5% of the time, whereas cubs were inactive 13.4% of the time. We found no significant relationships between den emergence activity and weather. Adult polar bears at den sites subjected to industrial activity exhibited significantly fewer bouts of vigilance than denned bears in undisturbed areas (t = -5.5164, df = 4, p= 0.00). However, the duration of vigilance behaviors at sites near industrial activity was not significantly shorter than at the other sites studied (t = -1.8902, df = 4, p = 0.07). Results for these bears were within the range of findings in other studies of denned polar bears.

[Identification of Dens Draconis and Os Draconis by XRD method].

PubMed

Chen, Guang-Yun; Wu, Qi-Nan; Shen, Bei; Chen, Rong

2012-04-01

To establish an XRD method for evaluating the quality of Os Draconis and Dens Draconis and applying in judgement of the counterfeit. Dens Draconis, Os Draconis and the counterfeit of Os Draconis were analyzed by XRD. Their diffraction patterns were clustered analysis and evaluated their similarity degree. Established the analytical method of Dens Draconis and Os Draconis basing the features fingerprint information of the 10 common peaks by XRD pattern. Obtained the XRD pattern of the counterfeit of Os Draconis. The similarity degree of separate sources of Dens Draconis was high,while the similarity degree of separate sources of Os Draconis was significant different from each other. This method can be used for identification and evaluation of Os Draconis and Dens Draconis. It also can be used for identification the counterfeit of Os Draconis effectively.

Den use by arctic foxes (Alopex lagopus) in a subarctic region of western Alaska

USGS Publications Warehouse

Anthony, R. Michael

1996-01-01

Distribution, abundance, and use of arctic fox dens located in coastal tundra communities of the Yukon–Kuskokwim delta were determined in studies from 1985 to 1990. Dens were denser and less complex than those described in studies conducted above the Arctic Circle. Eighty-three dens of varying complexity were found in the 52-km2 study area. Nineteen dens were used by arctic foxes for whelping or rearing pups. Three females relocated litters to multiple dens; a maximum of four dens were used concurrently by pups from one litter. Although red foxes (Vulpes vulpes) were common in the region, their use of dens in the study area was minimal. Differences in vegetation at den sites and nearby unoccupied sites were minimal. Furthermore, den sites could not be distinguished from non-den sites during aerial surveys.

Despotism and risk of infanticide influence grizzly bear den-site selection.

PubMed

Libal, Nathan S; Belant, Jerrold L; Leopold, Bruce D; Wang, Guiming; Owen, Patricia A

2011-01-01

Given documented social dominance and intraspecific predation in bear populations, the ideal despotic distribution model and sex hypothesis of sexual segregation predict adult female grizzly bears (Ursus arctos) will avoid areas occupied by adult males to reduce risk of infanticide. Under ideal despotic distribution, juveniles should similarly avoid adult males to reduce predation risk. Den-site selection and use is an important component of grizzly bear ecology and may be influenced by multiple factors, including risk from conspecifics. To test the role of predation risk and the sex hypothesis of sexual segregation, we compared adult female (n = 142), adult male (n = 36), and juvenile (n = 35) den locations in Denali National Park and Preserve, Alaska, USA. We measured elevation, aspect, slope, and dominant land cover for each den site, and used maximum entropy modeling to determine which variables best predicted den sites. We identified the global model as the best-fitting model for adult female (area under curve (AUC) = 0.926) and elevation as the best predictive variable for adult male (AUC = 0.880) den sites. The model containing land cover and elevation best-predicted juvenile (AUC = 0.841) den sites. Adult females spatially segregated from adult males, with dens characterized by higher elevations (mean= 1,412 m, SE = 52) and steeper slopes (mean = 21.9°, SE = 1.1) than adult male (elevation: mean = 1,209 m, SE = 76; slope: mean = 15.6°, SE = 1.9) den sites. Juveniles used a broad range of landscape attributes but did not avoid adult male denning areas. Observed spatial segregation by adult females supports the sex hypothesis of sexual segregation and we suggest is a mechanism to reduce risk of infanticide. Den site selection of adult males is likely related to distribution of food resources during spring.

The enduring mark left by Jean-Martin Charcot on rheumatology.

PubMed

Lagier, R

1997-12-01

Although Charcot is remembered above all as an outstanding neurologist, he also left a lasting imprint on the study of rheumatic diseases, primarily in two fields. a) He performed a pathologic-nosographic confrontation based on principles that remain relevant in today's era of imaging techniques. His vision as a pathologist allowed him to establish links between nonspecific lesions, which led him to develop a unified concept of chronic rheumatism. At the same time however, his experience as a clinician gave him a sense of the nosologic distinctions that are widely accepted today. b) He analyzed osteoarticular dystrophies associated with neurologic disorders, most notably tabetic arthropathies with epiphyseal fragmentation and in some instances spontaneous fractures. In addition, a constellation of alterations of the synovial membrane, ligaments, and muscles identified in those analyses foreshadowed today's concept of reflex sympathetic dystrophy syndrome.

Polar bear maternal den habitat in the Arctic National Wildlife Refuge, Alaska

USGS Publications Warehouse

Durner, George M.; Amstrup, Steven C.; Ambrosius, Ken J.

2006-01-01

Polar bears (Ursus maritimus) give birth during mid-winter in dens of ice and snow. Denning polar bears subjected to human disturbances may abandon dens before their altricial young can survive the rigors of the Arctic winter. Because the Arctic coastal plain of Alaska is an area of high petroleum potential and contains existing and planned oil field developments, the distribution of polar bear dens on the plain is of interest to land managers. Therefore, as part of a study of denning habitats along the entire Arctic coast of Alaska, we examined high-resolution aerial photographs (n = 1655) of the 7994 km2 coastal plain included in the Arctic National Wildlife Refuge (ANWR) and mapped 3621 km of bank habitat suitable for denning by polar bears. Such habitats were distributed uniformly and comprised 0.29% (23.2 km2) of the coastal plain between the Canning River and the Canadian border. Ground-truth sampling suggested that we had correctly identified 91.5% of bank denning habitats on the ANWR coastal plain. Knowledge of the distribution of these habitats will help facilitate informed management of human activities and minimize disruption of polar bears in maternal dens.

Denning chronology and design of effective bear management units

USGS Publications Warehouse

Inman, R.M.; Costello, C.M.; Jones, D.E.; Inman, K.H.; Thompson, B.C.; Quigley, H.B.

2007-01-01

Reports on the effectiveness of using late fall hunting seasons to reduce the proportion of female black bears (Ursus americanus) in the harvest are limited, and the geographic scale over which the technique functions as intended has not been examined. During 1992-2000, we radio-equipped black bears in New Mexico, USA, obtained estimates of 175 den entry and 137 den emergence dates, and used New Mexico Department of Game and Fish harvest data (1985-2000) to test for differences in proportion of females in the harvest relative to denning chronology. Bears in northern New Mexico entered dens earlier and emerged later than bears in southern New Mexico (P ??? 0.001). In northern New Mexico bears displayed the typical pattern of earlier entry and later emergence by reproductive females, proportion of females in the harvest varied over time as expected, and late fall seasons were effective (P ??? 0.10). In contrast, denning chronology did not differ by sex in southern New Mexico, proportion of females in the harvest did not change over time, and late fall seasons were not effective (P ??? 0.18). Manipulation of hunting season dates to influence female mortality can be an effective tool, however our study provides an example of an area where denning chronology did not differ by sex and late seasons were not effective. We also observed regional differences in timing of entrance and emergence, which suggest that scale of application may be key. In management jurisdictions that encompass ecologically distinct areas, cover a wide range of latitudes, or are mountainous, successful use of the technique may depend on knowledge of denning chronology at multiple locations and appropriate designation of hunting unit boundaries, season dates, and data analysis units.

Den use and selection by northern flying squirrels in fragmented landscapes

Treesearch

Sanjay Pyare; Winston P. Smith; Colin S. Shanley

2010-01-01

We studied den use and den-habitat selection by the Prince of Wales Island flying squirrel (Glaucomys sabrinus griseifrons) at multiple spatial scales in fragmented temperate rain-forest habitats because of the role dens play in the distribution, reproduction, and population density of this endemic subspecies. We observed differences in spatial...

Biological and epistemological models of localization in the nineteenth century: from Gall to Charcot.

PubMed

Kaitaro, T

2001-12-01

In the latter half of the nineteenth century, the localizationist doctrines became closely associated with the memory trace paradigm. The analysis of the texts dealing with the localization and the nature of 'the loss of articulated speech' (motor aphasia) by Bouillaud, Lordat, Dax, Broca, Trousseau, Baillarger, Charcot and Wernicke shows how the biological paradigm of localization presented by Gall and based on the notion of organ-function correspondence was transformed into a model based on localizable memory traces. This change resulted in the theoretical unification of the mechanisms of motor and non-motor forms of aphasia. These forms, which the earlier authors tended to separate in their analyses of the underlying mechanisms, were now regarded as involving similar mechanisms related to the loss of mnestic images. The crucial step in this development was taken by Broca who presented the hypothesis that the faculty of coordination of speech movements, which according to his predecessors was the faculty lost in motor aphasia, was actually an intellectual faculty and a specific form of memory, and motor aphasia consequently a selective kind of amnesia. Theorists like Charcot and Wernicke generalized this idea into a comprehensive theory of the nature of localization based on the notion of memory traces. Thus, the localization of function was reduced to the localization of representations. Instead of biological paradigms, this model of localization is rooted in the epistemological tradition of psychology represented by Locke and Condillac, who were primarily interested in the problem of representation. In physiology, this approach usually resulted in attempts at localizing representations instead of functions.

Patterns of den occupation by the spotted hyaena (Crocuta crocuta)

USGS Publications Warehouse

Boydston, E.E.; Kapheim, K.M.; Holekamp, K.E.

2006-01-01

Spotted hyaenas utilize isolated natal dens (NDs) and communal dens (CDs) for rearing their cubs. Here we describe patterns of natal and CD occupation by hyaenas belonging to one well-studied clan in the Maasai Mara National Reserve during a 10-year period. Locations of 98 den sites that were used as natal or CDs by hyaenas in the study clan were digitized in a Geographic Information System, and the duration of use of each den site, frequency of re-use, and distances involved in den moves were quantified. Hyaenas moved their CD monthly on average. Most CD sites were occupied only once during the study, but several sites were used repeatedly. On rare occasions, the movement of hyaenas to a new den site could be attributed to a disturbance event at the CD, but factors regularly prompting hyaenas to move to new CD sites were unclear. High-ranking female hyaenas were more likely to rear their cubs from birth in a CD than low-ranking females. Low-ranking females almost always utilized isolated NDs for the first few weeks of a litter's development, and low-ranking females transferred their cubs over longer distances than did high-ranking females. ?? 2006 East African Wild Life Society.

Raccoon (Procyon lotor) diurnal den use within an intensively managed forest in central West Virginia

USGS Publications Warehouse

Owen, Sheldon F.; Berl, Jacob L.; Edwards, John W.; Ford, W. Mark; Wood, Petra Bohall

2015-01-01

Intensive forest management may influence the availability of suitable den sites for large den-seeking species, such as Procyon lotor (Raccoon). As part of a Raccoon ecology study on an industrial forest in the Allegheny Mountains of central West Virginia, we radio-tracked 32 Raccoons to 175 diurnal den sites to determine relative use of dens that included cavity trees, rock dens, log piles, slash piles, and exposed limbs. Patterns of den use significantly differed between sexes and among seasons. Overall, we recorded 58 cavity dens in 12 tree species with 7 maternal dens found in 5 tree species. Raccoons selected larger-diameter den trees than available cavity trees and non-cavity trees. Because the abundance of suitable tree cavities is known to influence Raccoon densities and recruitment at fine spatial scales and female Raccoons in this study used tree cavities as maternal den sites, the continued harvest of large-diameter trees (i.e., those capable of developing den cavities) without replacement may impact Raccoon recruitment within intensively managed forests throughout the central Appalachians.

Late Corrective Arthrodesis in Nonplantigrade Diabetic Charcot Midfoot Disease Is Associated with High Complication and Reoperation Rates

PubMed Central

Wussow, Annekatrin

2015-01-01

Introduction. Charcot arthropathy may lead to a loss of osteoligamentous foot architecture and consequently loss of the plantigrade alignment. In this series of patients a technique of internal corrective arthrodesis with maximum fixation strength was provided in order to lower complication rates. Materials/Methods. 21 feet with severe nonplantigrade diabetic Charcot deformity Eichenholtz stages II/III (Sanders/Frykberg II/III/IV) and reconstructive arthrodesis with medial and additional lateral column support were retrospectively enrolled. Follow-up averaged 4.0 years and included a clinical (AOFAS score/PSS), radiological, and complication analysis. Results. A mean of 2.4 complications/foot occurred, of which 1.5/foot had to be solved surgically. 76% of feet suffered from soft tissue complications; 43% suffered hardware-associated complications. Feet with only 2 out of 5 high risk criteria according to Pinzur showed significantly lower complication counts. Radiographs revealed a correct restoration of all foot axes postoperatively with superior fixation strength medially. Conclusion. Late corrective arthrodesis with medial and lateral column stabilization in the nonplantigrade stages of neuroosteoarthropathy can provide reasonable reconstruction of the foot alignment. Nonetheless, overall complication/reoperation rates were high. With separation into low/high risk criteria a helpful guide in treatment choice is provided. This trial is registered with German Clinical Trials Register (DRKS) under number DRKS00007537. PMID:26000309

Linkage localization of X-linked Charcot-Marie-Tooth disease

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

Bergoffen, J.; Trofatter, J.; Haines, J.L.

1993-02-01

Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy, is a heterogeneous group of slowly progressive, degenerative disorders of peripheral nerve. X-linked CMT (CMTX) (McKusick 302800), a subdivision of type I, or demyelinating, CMT is an X-linked dominant condition with variable penetrance. Previous linkage analysis using RFLPs demonstrated linkage to markers on the proximal long and short arms of the X chromosome, with the more likely localization on the proximal long arm of the X chromosome. Available variable simple-sequence repeats (VSSRs) broaden the possibilities for linkage analysis. This paper presents new linkage data and recombination analysis derived frommore » work with four VSSR markers - AR, PGKP1, DXS453, and DXYS1X - in addition to analysis using RFLP markers described elsewhere. These studies localize the CMTX gene to the proximal Xq segment between PGKP1 (Xq11.2-12) and DXS72 (Xq21.1), with a combined maximum multipoint lod score of 15.3 at DXS453 ([theta] = 0). 32 refs., 3 figs., 2 tabs.« less

Challenge of handling a Charcot spinal arthropathy with a novel hybrid fibular autograft and expandable cage.

PubMed

Ohana, Nissim; Benharroch, Daniel; Sheinis, Dimitri

2018-04-13

A 26-year-old man, who was paraplegic for 6 years due to a motor vehicle accident, presented to the authors' clinic following his incapacity to withstand a sitting posture, the frequent sensation of "clicks" in his back, and a complaint of back pain while in his wheelchair. On imaging, his dorsal spine showed a complete arthrodesis of the primarily fused vertebrae. However, distal to this segment, a Charcot spinal arthropathy with subluxation of T12-L1 was evident. Repair of this complex, uncommon, late complication of his paraplegia by the frequently used fusion techniques was shown to be inappropriate. A novel and elaborate surgical procedure is presented by which a complete fusion of the affected spine was secured. A left retrodiaphragmatic approach was used. Complete corpectomy of both the T-12 and L-1 vertebrae to the preserved endplates was performed. Most of the patient's fibula was resected and shaped for engrafting. The segment of the fibula was introduced into a mesh cage, before its intramedullary implantation into the T-12 and L-1 vertebrae. This 2-step procedure combined the hybrid use of a fibular autograft and an expandable mesh cage, incorporated one into the other, in an innovative intramedullary position. This intervention allowed the patient to resume his former condition as an extremely physically active patient with paraplegia. Nine years later, an asymptomatic early-stage Charcot spine was found at L5-S1, but no treatment is planned at this point.

Psychometrics evaluation of Charcot-Marie-Tooth Neuropathy Score (CMTNSv2) second version, using Rasch analysis.

PubMed

Sadjadi, Reza; Reilly, Mary M; Shy, Michael E; Pareyson, Davide; Laura, Matilde; Murphy, Sinead; Feely, Shawna M E; Grider, Tiffany; Bacon, Chelsea; Piscosquito, Giuseppe; Calabrese, Daniela; Burns, Ted M

2014-09-01

Charcot-Marie-Tooth Neuropathy Score second version (CMTNSv2) is a validated clinical outcome measure developed for use in clinical trials to monitor disease impairment and progression in affected CMT patients. Currently, all items of CMTNSv2 have identical contribution to the total score. We used Rasch analysis to further explore psychometric properties of CMTNSv2, and in particular, category response functioning, and their weight on the overall disease progression. Weighted category responses represent a more accurate estimate of actual values measuring disease severity and therefore could potentially be used in improving the current version. © 2014 Peripheral Nerve Society.

Identification of polar bear den habitat in northern Alaska

USGS Publications Warehouse

Amstrup, Steven C.; Garner, Gerald W.; Derocher, Andrew E.; Garner, Gerald W.; Lunn, Nicholas J.; Wiig, Øystein; Derocher, Andrew E.; Garner, Gerald W.; Lunn, Nicholas J.; Wiig, Øystein

1998-01-01

The goal of this project is to refine the information collected previously on maternal denning, into digital maps that show where polar bears are likely to create future dens in northern Alaska. Such maps will allow a priori recommendations regarding timing and geographic locations of proposed human developments; and hence provide managers with an important mitigation and management tool.

Biomechanics of halo-vest and dens screw fixation for type II odontoid fracture.

PubMed

Ivancic, Paul C; Beauchman, Naseem N; Mo, Fred; Lawrence, Brandon D

2009-03-01

An in vitro biomechanical study of halo-vest and odontoid screw fixation of Type II dens fracture. The objective were to determine upper cervical spine instability due to simulated dens fracture and investigate stability provided by the halo-vest and odontoid screw, applied individually and combined. Previous studies have evaluated posterior fixation techniques for stabilizing dens fracture. No previous biomechanical study has investigated the halo-vest and odontoid screw for stabilizing dens fracture. A biofidelic skull-neck-thorax model was used with 5 osteoligamentous whole cervical spine specimens. Three-dimensional flexibility tests were performed on the specimens while intact, following simulated dens fracture, and following application of the halo-vest alone, odontoid screw alone, and halo-vest and screw combined. Average total neutral zone and total ranges of motion at C0/1 and C1/2 were computed for each experimental condition and statistically compared with physiologic motion limits, obtained from the intact flexibility test. Significance was set at P < 0.05 with a trend toward significance at P < 0.1. Type II dens fracture caused trends toward increased sagittal neutral zone and lateral bending range of motion at C1/2. Spinal motions with the dens screw alone could not be differentiated from physiologic limits. Significant reductions in motion were observed at C0/1 and C1/2 in flexion-extension and axial rotation due to the halo-vest, applied individually or combined with the dens screw. At C1/2, the halo-vest combined with the dens screw generally allowed the smallest average percentages of intact motion: 3% in axial rotation, 17% in flexion-extension, and 18% in lateral bending. The present reduction in C1/2 motion observed, due to the halo-vest and dens screw combined is similar to previously reported immobilization provided by the polyaxial screw/rod system and transarticular screw fixation combined with wiring. The present biomechanical data may be

Landward and eastward shift of Alaskan polar bear denning associated with recent sea ice changes

USGS Publications Warehouse

Fischbach, Anthony S.; Amstrup, Steven C.; Douglas, David C.

2007-01-01

Polar bears (Ursus maritimus) in the northern Alaska region den in coastal areas and on offshore drifting ice. We evaluated changes in the distribution of polar bear maternal dens between 1985 and 2005, using satellite telemetry. We determined the distribution of maternal dens occupied by 89 satellite collared female polar bears between 137°W and 167°W longitude. The proportion of dens on pack ice declined from 62% in 1985–1994 to 37% in 1998–2004 (P = 0.044) and among pack ice dens fewer occurred in the western Beaufort Sea after 1998. We evaluated whether hunting, attraction to bowhead whale remains, or changes in sea ice could explain changes in den distribution. We concluded that denning distribution changed in response to reductions in stable old ice, increases in unconsolidated ice, and lengthening of the melt season. In consort, these changes have likely reduced the availability and quality of pack ice denning habitat. Further declines in sea ice availability are predicted. Therefore, we expect the proportion of polar bears denning in coastal areas will continue to increase, until such time as the autumn ice retreats far enough from shore that it precludes offshore pregnant females from reaching the Alaska coast in advance of denning.

Fox Den Disease: An Interesting Case Following Delayed Diagnosis.

PubMed

Stehr, Ryan C; Kim, Nicholas; LoGiudice, John A; Ludwig, Kirk

2015-06-01

Pyoderma fistulans sinifica, also known as fox den disease, is a rare and poorly understood inflammatory disorder of the skin and subcutaneous tissues. This disorder is often mistaken for other inflammatory skin disorders and treated inappropriately. The authors describe the case of a 53-year-old male who presented to the colorectal surgery service with a longstanding diagnosis of perirectal Crohn's disease. Despite aggressive immunosuppression and numerous surgical procedures, the patient continued to have unrelenting purulent drainage from the skin of his buttocks. Following wide excision of the affected skin and subcutaneous tissues by the colorectal surgeon, the plastic surgery team reconstructed the 30 cm x 55 cm wound using a combination of local flaps and skin grafts. The initial pathology report of the excised specimen confirmed the presence of nonspecific abscesses and inflammation. Upon special request by the plastic surgery team, the sample was resectioned with the specific intent of establishing a diagnosis of fox den disease. The additional slides met the criteria for an unequivocal diagnosis of fox den disease. Immunosuppression was discontinued and the patient healed his wounds without complication. Fox den disease is often overlooked because of the obscurity of the disease and the special histological sectioning needed to establish a diagnosis. In this case, the patient was unnecessarily treated with immunosuppressive drugs for more than 3 decades because of a misdiagnosis. With increased awareness of fox den disease, perhaps its pathophysiology can be better elucidated as more patients are appropriately diagnosed and treated.

Endodontic, surgical and periodontal treatment of dens invaginatus. Case report.

PubMed

Castellarin, M; Demitri, V; Politi, M

2001-01-01

The aim of this paper is to propose a single stage global treatment of endodontic, periapical and periodontal lesions in a lateral maxillary incisor with dens invaginatus. A 24 year-old woman presenting a lateral maxillary incisor with dens invaginatus in association with periapica1 and periodontal lesions underwent simultaneous surgical, endodontic and periodontal regenerative procedures. At 2, 6, 12, 18 months follow-up the radiographic healing appeared to be improved and the periapical lesion healed completely 1 year after surgical intervention. Surgery in association with endodontic and periodontal procedures represents the treatment of choice to maximize long term prognosis in cases of dens invaginatus with chronic periapical and periodontal lesions.

An Overview of Internal and External Fixation Methods for the Diabetic Charcot Foot and Ankle.

PubMed

Ramanujam, Crystal L; Zgonis, Thomas

2017-01-01

Diabetic Charcot neuroarthropathy (DCN) of the foot and ankle is a challenging disease with regard to clinical presentation, pathogenesis, and prognosis. Its surgical management is equally difficult to interpret based on the wide array of options available. In the presence of an ulceration or concomitant osteomyelitis, internal fixation by means of screws, plates, or intramedullary nailing needs to be avoided when feasible. External fixation becomes a great surgical tool when managing DCN with concomitant osteomyelitis. This article describes internal and external fixation methods along with available literature to enlighten surgeons faced with treating this complex condition. Copyright © 2016 Elsevier Inc. All rights reserved.

Vegetative characteristics of swift fox denning and foraging sites in southwestern South Dakota

Treesearch

Daniel W. Uresk; Kieth E. Severson; Jody Javersak

2003-01-01

Vegetative characteristics of swift fox (Vulpes velox) denning and foraging habitats were studied in southwestern South Dakota. We followed 14 radio-collared foxes over a two-year period and identified 17 den sites and 82 foraging sites. Height-density of vegetation (visual obstruction reading, VOR) was determined on each den and foraging site and on...

Dragons' Den: promoting healthcare research and innovation.

PubMed

Mazhindu, Deborah; Gregory, Siobhan

2015-07-01

The changing health and social care landscape, and, in particular, the financial challenges affecting the NHS, can present difficulties for staff looking for funding to support innovation and new ways of working. One method of competitive tendering that is becoming more accepted as a way of allocating funds, encouraging staff engagement and developing innovation for research is a format based the BBC television series, Dragons' Den. This article describes how Hounslow and Richmond Community Healthcare NHS Trust, London, has developed a 'Dragons' Den initiative' of annual competitive research funding allocation to ensure that some of the most dynamic practice in the trust is captured.

Anesthetic and Surgical Management of a Bilateral Mandible Fracture in a Patient With Charcot-Marie-Tooth Disease: A Case Report.

PubMed

Smith, Jeffrey D; Minkin, Patton; Lindsey, Sean; Bovino, Brian

2015-10-01

This report describes the case of a 74-year-old man who had been diagnosed with Charcot-Marie-Tooth disease as a child. Because the patient had serious motor and sensory neuropathy associated with his disease, special anesthetic and surgical recommendations had to be considered before he underwent general anesthesia to repair his mandibular fracture. Repair of the mandible was performed under general anesthesia with a nasal endotracheal tube and the use of the nondepolarizing muscle relaxant rocuronium. Open reduction and internal fixation through extraoral approaches were used to fixate the displaced right subcondylar and symphyseal fractures. A closed reduction approach using maxillary fixation screws and a mandibular arch bar with light elastic guidance was used to treat a nondisplaced fracture of the left mandibular ramus. Rigid fixation allowed for avoidance of a period of intermaxillary fixation. General anesthesia and muscle relaxant were administered without complication. Treatment of bilateral mandibular fractures with combined open and closed approaches resulted in restoration of premorbid occlusion and masticatory function. Repair of mandibular fractures under general anesthesia appears to be a safe procedure in patients with Charcot-Marie-Tooth disease when appropriate anesthetic and surgical methods are used. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Differentially expressed circulating microRNAs in the development of acute diabetic Charcot foot.

PubMed

Pasquier, Jennifer; Ramachandran, Vimal; Abu-Qaoud, Moh'd Rasheed; Thomas, Binitha; Benurwar, Manasi J; Chidiac, Omar; Hoarau-Véchot, Jessica; Robay, Amal; Fakhro, Khalid; Menzies, Robert A; Jayyousi, Amin; Zirie, Mahmoud; Al Suwaidi, Jassim; Malik, Rayaz A; Talal, Talal K; Najafi-Shoushtari, Seyed Hani; Rafii, Arash; Abi Khalil, Charbel

2018-06-05

Charcot foot (CF) is a rare complication of Type 2 diabetes (T2D). We assessed circulating miRNAs in 17 patients with T2D and acute CF (G1), 17 patients with T2D (G2) and equivalent neuropathy and 17 patients with T2D without neuropathy (G3) using the high-throughput miRNA expression profiling. 51 significantly deregulated miRNAs were identified in G1 versus G2, 37 in G1 versus G3 and 64 in G2 versus G3. Furthermore, we demonstrated that 16 miRNAs differentially expressed between G1 versus G2 could be involved in osteoclastic differentiation. Among them, eight are key factors involved in CF pathophysiology. Our data reveal that CF patients exhibit an altered expression profile of circulating miRNAs.

Dens invaginatus in primary maxillary molar: a rare case report and review of literature.

PubMed

Bansal, Arpana V; Bansal, Abhinav; Kulkarni, Vinaya Kumar; Dhar, Reema Sharma

2012-05-01

Dens invaginatus is a rare developmental anomaly. It is unusual to find this anomaly in primary dentition. Diagnosis of this dens invaginatus is important due to possible pulpal involvement. Not only that, simultaneous presence of other dental anomaly may require long-term treatment planning. Dens invaginatus can be detected clinically in the tooth presenting unusual crown morphology or radiographically as radiopacity within tooth. This article describes one of the first case reports of dens invaginatus in primary maxillary second molar in a 5-year-old female patient. How to cite this article: Bansal AV, Bansal A, Kulkarni VK, Dhar RS. Dens Invaginatus in Primary Maxillary Molar: A Rare Case Report and Review of Literature. Int J Clin Pediatr Dent 2012;5(2):139-141.

Central motor and sensory pathway involvement in an X-linked Charcot-Marie-Tooth family.

PubMed

Zambelis, T; Panas, M; Kokotis, P; Karadima, G; Kararizou, E; Karandreas, N

2008-06-01

The aim of the present study was to investigate the subclinical involvement of the central nervous system (CNS) in an X-linked Charcot-Marie-Toth (CMTX) family. Seven subjects, all members of one family with a C.462T > G connexin 32 (Cx32) mutation were investigated by Blink reflex, Somatosensory evoked potentials (SEP) and Transcranial magnetic stimulation (TMS). There were five clinically symptomatic for CMT neuropathy (four male and one female) and two asymptomatic (female) subjects. Subclinical CNS involvement was observed in all, symptomatic and asymptomatic subjects. This is the largest CMTX neuropathy family investigated for CNS involvement. Electrophysiological involvement of the CNS in every examined member of this family was observed, raising the question of a more systematic involvement of the CNS in CMTX disease.

Critical Limb Ischemia in Association with Charcot Neuroarthropathy: Complex Endovascular Therapy for Limb Salvage

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

Palena, Luis Mariano, E-mail: marianopalena@hotmail.com; Brocco, Enrico; Manzi, Marco

2013-05-09

Charcot neuroarthropathy is a low-incidence complication of diabetic foot and is associated with ankle and hind foot deformity. Patients who have not developed deep ulcers are managed with offloading and supportive bracing or orthopedic arthrodesis. In patients who have developed ulcers and severe ankle instability and deformity, below-the-knee amputation is often indicated, especially when deformity and cutaneous involvement result in osteomyelitis. Ischemic association has not been described but can be present as a part of peripheral arterial disease in the diabetic population. In this extreme and advanced stage of combined neuroischemic diabetic foot disease, revascularization strategies can support surgical andmore » orthopedic therapy, thus preventing osteomyelitis and leading to limb and foot salvage.« less

View east along Wolf Den Road showing residences on the ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View east along Wolf Den Road showing residences on the north side of the road - Brooklyn Green, North Green, South Green, & West Green, parts of Brown Road, Canterbury Road (Route 169), Hartford Road (Route 6), Hyde Road, Pomfret Road (Route 169), Prince Hill Road, Providence Road (Route 6), Wauregan Road (Routes 169 & 205), & Wolf Den Road, Brooklyn, Windham County, CT

View northwest along Wolf Den Road showing residences on the ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View northwest along Wolf Den Road showing residences on the north side of the road - Brooklyn Green, North Green, South Green, & West Green, parts of Brown Road, Canterbury Road (Route 169), Hartford Road (Route 6), Hyde Road, Pomfret Road (Route 169), Prince Hill Road, Providence Road (Route 6), Wauregan Road (Routes 169 & 205), & Wolf Den Road, Brooklyn, Windham County, CT

ACQUIRED PES CAVUS IN CHARCOT-MARIE-TOOTH DISEASE.

PubMed

Maranho, Daniel Augusto; Volpon, José Batista

2009-01-01

Hereditary motor and sensory neuropathies, especially Charcot-Marie-Tooth disease, are frequently expressed with an acquired cavusvarus foot which is characterized by a fixed increase of the plantar arch and hindfoot inversion. Diagnosis of the underlying condition achieved through careful patient assessment and local evaluations is the keystone for decision-making about the adequate treatment. The cavus may present as an isolated deformity of the forefoot, hindfoot or it may be a combination of both locations. Related deformities, mainly the varus and toe clawing require appropriate evaluation; clinical characteristics such as severity of the deformity, impairment of the muscular power, flexibility and patient's age are important characteristics in the treatment decision. Conservative treatment of the cavusvarus foot with physiotherapy, insoles and shoe modifications are reserved to young patients and mild deformities. However, there is a tendency of the deformity to become more severe over time because of the progressive feature of the underlying neurological condition. So, the surgical treatment by using classical techniques is performed in early stages. Most importantly is the identification of the primary and main components of each deformity to properly correct them, if possible. Muscular transfers are used to treat the dynamic unbalance, retracted structures should be either divided or lengthened and localized osteotomies should be preferred over arthrodeses, which are reserved for stiff and severely deformed feet in adults.

Den site activity patterns of adult male and female swift foxes, Vulpes velox, in Northwestern Texas

USGS Publications Warehouse

Lemons, P.R.; Ballard, W.B.; Sullivan, R.M.; Sovada, M.A.

2003-01-01

Activity of Swift Foxes (Vulpes velox) at den sites was studied in northwestern Texas during pup rearing seasons in 2000 and 2001 to determine role of males in parental care. Twenty-four percent of radio-collared females with a potential to breed successfully raised pups to eight weeks of age. We intensively monitored presence and absence of male and female Swift Foxes at two den sites each year. Females were present >2.6 times more at den sites than males during the pup rearing season. Female and male Swift Foxes largely stayed at dens during diurnal hours and were active away from dens during nocturnal and crepuscular hours. Females and males spent 12.4% and 3.0% more time at dens before pups emerged, than after pups emerged, respectively. Following depredation of one male parent, the female spent 29% less time at the den site. Decrease in time spent at the den by the female following loss of her mate suggested that loss of one parent might severely impact recruitment of Swift Foxes. Our observations indicated that intense Coyote (Canis latrans) depredation may severely impact pup-rearing success as well as the parental care within Swift Fox family groups.

[Dens invaginatus. Review of the literature and diagnostic and therapeutic guidelines].

PubMed

Baumgart, Manuela; Hänni, Stefan; Suter, Beat; Schaffner, Markus; Lussi, Adrian

2009-01-01

Dens invaginatus is a clinically relevant malformation of teeth resulting from an infolding of enamel and dentine into the dental structure during tooth formation, hence the former denomination "dens in dente". The dens invaginatus shows multiple morphological variations of crown and root formation. This frequently leads to caries, pulpal and periodontal involvement with necrosis and loss of attachment. Therefore, early diagnosis and prevention are of utmost importance. Due to the complexity of the malformation, treatment options in former days were limited. This article presents a profound review of the literature regarding etiology, epidemiology and histology. It discusses clinical appearance and diagnosis and it provides guidelines for decision-making and treatment of invaginated teeth.

Hand involvement in children with Charcot-Marie-Tooth disease type 1A.

PubMed

Burns, Joshua; Bray, Paula; Cross, Lauren A; North, Kathryn N; Ryan, Monique M; Ouvrier, Robert A

2008-12-01

Charcot-Marie-Tooth disease type 1A (CMT1A), a demyelinating neuropathy characterised by progressive length-dependent muscle weakness and atrophy, is thought to affect the foot and leg first followed some time later by hand weakness and dysfunction. We aimed to characterise hand strength, function and disease-related symptoms in children with CMT1A. Intrinsic and extrinsic hand strength was measured by hand-held dynamometry, function by nine-hole peg test, and disease-related symptoms by interview and examination in 84 affected children aged 2-16 years. Hand weakness and dysfunction was present from the earliest stages of the disease. While hand strength and function measures tended to increase with age throughout childhood, at no point did they reach normal values. Day-to-day hand problems such as poor handwriting, weakness, pain and sensory symptoms also worsened with age. The hand is affected at all ages in children with CMT1A, but may be under-recognised in its early stages, potentially delaying therapy.

Exercise training improves autonomic profiles in patients with Charcot-Marie-Tooth disease.

PubMed

El Mhandi, Lhassan; Pichot, Vincent; Calmels, Paul; Gautheron, Vincent; Roche, Frédéric; Féasson, Léonard

2011-11-01

The effect of an interval exercise training (ITE) program on heart rate variability (HRV) was studied in 8 patients with Charcot-Marie-Tooth (CMT) disease and 8 healthy controls. At baseline, all subjects underwent ambulatory 24-hour Holter electrocardiographic (ECG) monitoring to evaluate HRV. HRV analysis was repeated on CMT patients after they completed a 24-week ITE program on a cycle ergometer. Before exercise, all HRV indices were lower in patients compared with controls, and the difference reached statistical significance for pNN50 (percent of differences between adjacent R-R intervals exceeding 50 ms). After ITE, time- and frequency-domain indices were significantly improved, particularly at night (+8% mean R-R interval, +95% pNN50, 52% reduction in low/high-frequency ratio). We observed significant increases in some of the time and frequency parameters, and values sometimes exceeded those of controls at baseline. Our results suggest that ITE improves HRV modulation in CMT patients by enhancing parasympathetic activity. Copyright © 2011 Wiley Periodicals, Inc.

Atypical den use of Carolina Northern Flying Squirrels (Glaucomys sabrinus coloratus) in the southern Appalachian Mountains

USGS Publications Warehouse

Diggins, Corinne A.; Kelly, Christine A.; Ford, W. Mark

2015-01-01

Glaucomys sabrinus coloratus (Carolina Northern Flying Squirrel) is a federally endangered subspecies that occurs in high elevation forests of the southern Appalachian Mountains. Denning sites may be a limiting factor for this subspecies in areas where cavity trees are not abundant or where interspecific competition from other tree squirrels occurs. This shortage can result in use of unusual denning sites, such as subterranean dens. Herein, we report atypical denning habits of radio-collared Carolina Northern Flying Squirrels in southwestern Virginia and western North Carolina from 2008 to 2011 and 2014. Increased knowledge of denning habitats may be beneficial for conservation and habitat management of this subspecies, particularly in sub-optimal or degraded habitats.

A family with autosomal dominant mutilating neuropathy not linked to either Charcot-Marie-Tooth disease type 2B (CMT2B) or hereditary sensory neuropathy type I (HSN I) loci.

PubMed

Bellone, Emilia; Rodolico, Carmelo; Toscano, Antonio; Di Maria, Emilio; Cassandrini, Denise; Pizzuti, Antonio; Pigullo, Simona; Mazzeo, Anna; Macaione, Vincenzo; Girlanda, Paolo; Vita, Giuseppe; Ajmar, Franco; Mandich, Paola

2002-03-01

Sensory loss and ulcero-mutilating features have been observed in hereditary sensory neuropathy type I and in hereditary motor and sensory neuropathy type IIB, also referred as Charcot-Marie-Tooth disease type 2B. To date two loci associated with ulcero-mutilating neuropathy have been described: CMT2B at 3q13-q22 and HSN I at 9q22.1-q22.3. We performed linkage analysis with chromosomal markers representing the hereditary sensory neuropathy type I and Charcot-Marie-Tooth disease type 2B loci on an Italian family with a severe distal sensory loss leading to an ulcero-mutilating peripheral neuropathy. Negative likelihood-of-odds scores excluded any evidence of linkage to both chromosome 3q13 and chromosome 9q22 markers, confirming the genetic heterogeneity of this clinical entity and the presence of a third locus responsible for ulcero-mutilating neuropathies.

On the centenary of Charcot: hysteria, suggestibility and hypnosis.

PubMed

Chertok, L

1984-06-01

In studying hysteria by means of hypnosis, Charcot placed emphasis on the psychological aetiology of the neuroses. Among his pupils, Freud alone grasped this epistemological turning-point, from which he made his great discoveries. But hysteria and hypnosis still remain today largely unknown. We have not yet elucidated the 'mysterious leap' between the psychological and the somatic for the former, and between the relational and the instrumental for the latter. While psychoanalysts have constantly concerned themselves with hysteria, they have shown a lack of interest in hypnosis after Freud abandoned its practice. According to Freud, thanks to transference, affect would be controlled by cognition, a viewpoint eminently suited to satisfy his rationalistic outlook. Affect, however, remains an unknown realm. The affective relationship has, at all events, acquired an ever-increasing importance in psychoanalysis during the last few years, with the emphasis on the early mother-child relationship. The 'affective locus' remains the basic, as well as the most obscure, element in the hypno-suggestive relationship. The behaviourist approach, which quantifies the 'vertical' dimension in depth, is a limited one. The study of the 'horizontal' dimension of subjective experience represents a new line of research, which may make it possible to distinguish different forms of hypnosis. The understanding of hypno-suggestion may throw light on psychoanalysis, psychotherapy, and the human sciences in general.

Hibernacula and summer den sites of pine snakes (Pituophis melanoleucus) in the New Jersey pine barrens

USGS Publications Warehouse

Burger, J.; Zappalorti, R.T.; Gochfeld, M.; Boarman, W.I.; Caffrey, M.; Doig, V.; Garber, S.D.; Lauro, B.; Mikovsky, M.; Safina, C.; Saliva, Jorge

1988-01-01

We examined eight summer dens (used only in summer) and seven hibernacula (occupied both in winter and summer) of the snake Pituophis melanoleucus in the New Jersey Pine Barrens, comparing above ground characteristics of hibernacula and summer dens with characteristics at nearby random points. Temperatures at the soil surface and at 10 cm depth were significantly warmer, and there was less leaf cover around the random points compared to the entrances of the hibernacula and summer dens. Hibernacula had significantly more vegetation cover within 5 m, more leaf cover over the burrow entrance, and were closer to trees than were summer dens. Most hibernacula and summer dens were beside old fallen logs (73%), the entrance tunnels following decaying roots into the soil. Excavation of the hibernacula and summer dens indicated that most hibernacula appeared to be dug by the snakes and had an average of eight side chambers and 642 cm of tunnels, compared to less than one side chamber and 122 cm of tunnels for summer dens. Except for hatchlings, most snakes in hibernacula were located in individual chambers off the main tunnel; all snakes were at depths of 50-111 cm (X̄ = 79 cm). Pine snakes may select optimum hibernation sites which reduce winter mortality.

Mutational studies in X-linked Charcot-Marie-Tooth disease (CMTX)

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

Cherryson, A.K.; Yeung, L.; Kennerson, M.L.

1994-09-01

Charcot-Marie-Tooth disease, also known as hereditary motor and sensory neuropathy (HMSN), is a heterogeneous group of slowly progressive disorders of the peripheral nerve. X-linked CMT (CMTX) is characterized by slow motor nerve conduction velocities in affected males and the presence of mildly affected or normal carrier females with intermediate or normal nerve conduction velocities. CMTX, which has an incidence of 3.1 per 100,000 and accounts for approximately 10% of CMT cases, has been mapped to Xq13. One of the genes lying in this region, connexin 32, has been found to contain alterations in individuals affected with X-linked CMT. We havemore » identified our X-linked families from dominant type 1 CMT families using the clinical criteria given above. These families were screened for point mutations in connexin 32. We have identified three missense mutations, a G{r_arrow}A transition at amino acid 35 (valine to methionine), a C{r_arrow}G transition at amino acid 158 (proline to alanine) and a T{r_arrow}A transition at amino acid 182 (serine to threonine). Another family showed a 18 bp deletion, which removed the amino acid 111 to 116 inclusive (histidine, glycine, aspartic acid, proline, leucine, histidine).« less

Collar temperature sensor data reveal long-term patterns in southern Beaufort Sea polar bear den distribution on pack ice and land

USGS Publications Warehouse

Olson, Jay W; Rode, Karyn D.; Eggett, Dennis L.; Smith, T.S.; Wilson, R. R.; Durner, George M.; Fischbach, Anthony S.; Atwood, Todd C.; Douglas, David C.

2017-01-01

In response to a changing climate, many species alter habitat use. Polar bears Ursus maritimus in the southern Beaufort Sea have increasingly used land for maternal denning. To aid in detecting denning behavior, we developed an objective method to identify polar bear denning events using temperature sensor data collected by satellite-linked transmitters deployed on adult females between 1985 and 2013. We then applied this method to determine whether southern Beaufort Sea polar bears have continued to increase land denning with recent sea-ice loss and examined whether sea-ice conditions affect the distribution of dens between pack-ice and coastal substrates. Because land use in summer and autumn has also increased, we examined potential associations between summering substrate and denning substrate. Statistical process control methods applied to temperature-sensor data identified denning events with 94.5% accuracy in comparison to direct observations (n = 73) and 95.7% accuracy relative to subjective classifications based on temperature, location, and activity sensor data (n = 116). We found an increase in land-based denning during the study period. The frequency of land denning was directly related to the distance that sea ice retreated from the coast. Among females that denned, all 14 that summered on land subsequently denned there, whereas 29% of the 69 bears summering on ice denned on land. These results suggest that denning on land may continue to increase with further loss of sea ice. While the effects that den substrate have on nutrition, energetics, and reproduction are unclear, more polar bears denning onshore will likely increase human-bear interactions.

Relapsing remitting multiple sclerosis in x-linked charcot-marie-tooth disease with central nervous system involvement.

PubMed

Koutsis, Georgios; Karadima, Georgia; Floroskoufi, Paraskewi; Raftopoulou, Maria; Panas, Marios

2015-01-01

We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars). Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

PubMed Central

Karadima, Georgia; Floroskoufi, Paraskewi; Raftopoulou, Maria; Panas, Marios

2015-01-01

We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars). Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis. PMID:25883816

Remote identification of maternal polar bear (Ursus maritimus) denning habitat on the Colville River Delta, Alaska

NASA Astrophysics Data System (ADS)

Blank, Justin J.

High resolution digital aerial photographs (1 foot pixel size) of the Colville River Delta, Alaska were examined in 3D, with the use of a digital photogrammetric workstation. Topographic features meeting the criteria required for adequate snow accumulation, and subsequent construction of terrestrial polar bear maternal dens, were identified and digitized into an ArcGIS line shapefile. Effectiveness, efficiency, and accuracy were improved when compared to previous polar bear denning habitat efforts which utilized contact photo prints and a pocket stereoscope in other geographic areas of northern Alaska. Accuracy of photograph interpretation was systematically evaluated visually from the air with the use of a helicopter and physically on the ground. Results show that the mapping efforts were successful in identifying den habitat 91.3% of the time. Knowledge denning habitat can improve and inform decision making by managers and regulators when considering travel and development in the study area. An understanding of polar bear denning habitat extent and location will be a crucial tool for planning activities within the study area in a way that minimizes conflicts with maternal dens.

A mid-holocene fauna from Bear Den Cave, Sequoia National Park, California

USGS Publications Warehouse

Mead, Jim I.; McGinnis, Thomas W.; Keeley, Jon E.

2006-01-01

Test excavation of floor fill deposits in the first room in Bear Den Cave, Sequoia National Park, produced fossiliferous sediments down to at least 40 cm depth. Radiocarbon analysis of charcoal from this layer indicates an early-middle Holocene age of 7220 CAL BP. The fossil accumulation represents prey recovered from generations of ringtail (Bassariscus astutus) dung. Microvertebrate remains include salamanders, lizards, snakes, and mammals. The recovery of Aneides ferreus/vagransfrom early-middle Holocene deposits in Bear Den Cave is a first for this species group. Equally interesting is the recovery of Plethodon sp. Neither taxa live in the Sierra Nevada today. The fossil-rich deposits of Bear Den Cave indicate that future paleoecological studies will be productive in Sequoia National Park.

Heading for the Hills: Risk Avoidance Drives Den Site Selection in African Wild Dogs

PubMed Central

Jackson, Craig R.; Power, R. John; Groom, Rosemary J.; Masenga, Emmanuel H.; Mjingo, Ernest E.; Fyumagwa, Robert D.; Røskaft, Eivin; Davies-Mostert, Harriet

2014-01-01

Compared to their main competitors, African wild dogs (Lycaon pictus) have inferior competitive abilities and interspecific competition is a serious fitness-limiting factor. Lions (Panthera leo) are the dominant large carnivore in African savannah ecosystems and wild dogs avoid them both spatially and temporally. Wild dog young are particularly vulnerable and suffer high rates of mortality from lions. Since lions do not utilize all parts of the landscape with an equal intensity, spatial variation in lion densities can be exploited by wild dogs both during their general ranging behaviour, but more specifically when they are confined to a den with vulnerable young. Since patches of rugged terrain are associated with lower lion densities, we hypothesized that these comparatively safe habitats should be selected by wild dogs for denning. We investigated the relationship between the distribution of 100 wild dog den sites and the occurrence of rugged terrain in four wild dog populations located in Tanzania, Zimbabwe and South Africa. A terrain ruggedness index was derived from a 90 m digital elevation model and used to map terrain ruggedness at each site. We compared characteristics of actual and potential (random) den sites to determine how wild dogs select den sites. The distributions of wild dog dens were strongly associated with rugged terrain and wild dogs actively selected terrain that was more rugged than that available on average. The likelihood of encountering lions is reduced in these habitats, minimizing the risk to both adults and pups. Our findings have important implications for the conservation management of the species, especially when assessing habitat suitability for potential reintroductions. The simple technique used to assess terrain ruggedness may be useful to investigate habitat suitability, and even predict highly suitable denning areas, across large landscapes. PMID:24918935

Heading for the hills: risk avoidance drives den site selection in African wild dogs.

PubMed

Jackson, Craig R; Power, R John; Groom, Rosemary J; Masenga, Emmanuel H; Mjingo, Ernest E; Fyumagwa, Robert D; Røskaft, Eivin; Davies-Mostert, Harriet

2014-01-01

Compared to their main competitors, African wild dogs (Lycaon pictus) have inferior competitive abilities and interspecific competition is a serious fitness-limiting factor. Lions (Panthera leo) are the dominant large carnivore in African savannah ecosystems and wild dogs avoid them both spatially and temporally. Wild dog young are particularly vulnerable and suffer high rates of mortality from lions. Since lions do not utilize all parts of the landscape with an equal intensity, spatial variation in lion densities can be exploited by wild dogs both during their general ranging behaviour, but more specifically when they are confined to a den with vulnerable young. Since patches of rugged terrain are associated with lower lion densities, we hypothesized that these comparatively safe habitats should be selected by wild dogs for denning. We investigated the relationship between the distribution of 100 wild dog den sites and the occurrence of rugged terrain in four wild dog populations located in Tanzania, Zimbabwe and South Africa. A terrain ruggedness index was derived from a 90 m digital elevation model and used to map terrain ruggedness at each site. We compared characteristics of actual and potential (random) den sites to determine how wild dogs select den sites. The distributions of wild dog dens were strongly associated with rugged terrain and wild dogs actively selected terrain that was more rugged than that available on average. The likelihood of encountering lions is reduced in these habitats, minimizing the risk to both adults and pups. Our findings have important implications for the conservation management of the species, especially when assessing habitat suitability for potential reintroductions. The simple technique used to assess terrain ruggedness may be useful to investigate habitat suitability, and even predict highly suitable denning areas, across large landscapes.

Mapping polar bear maternal denning habitat in the National Petroleum Reserve -- Alaska with an IfSAR digital terrain model

USGS Publications Warehouse

Durner, George M.; Simac, Kristin S.; Amstrup, Steven C.

2013-01-01

The National Petroleum Reserve–Alaska (NPR-A) in northeastern Alaska provides winter maternal denning habitat for polar bears (Ursus maritimus) and also has high potential for recoverable hydrocarbons. Denning polar bears exposed to human activities may abandon their dens before their young are able to survive the severity of Arctic winter weather. To ensure that wintertime petroleum activities do not threaten polar bears, managers need to know the distribution of landscape features in which maternal dens are likely to occur. Here, we present a map of potential denning habitat within the NPR-A. We used a fine-grain digital elevation model derived from Interferometric Synthetic Aperture Radar (IfSAR) to generate a map of putative denning habitat. We then tested the map’s ability to identify polar bear denning habitat on the landscape. Our final map correctly identified 82% of denning habitat estimated to be within the NPR-A. Mapped denning habitat comprised 19.7 km2 (0.1% of the study area) and was widely dispersed. Though mapping denning habitat with IfSAR data was as effective as mapping with the photogrammetric methods used for other regions of the Alaskan Arctic coastal plain, the use of GIS to analyze IfSAR data allowed greater objectivity and flexibility with less manual labor. Analytical advantages and performance equivalent to that of manual cartographic methods suggest that the use of IfSAR data to identify polar bear maternal denning habitat is a better management tool in the NPR-A and wherever such data may be available.

Potential skin involvement in ALS: revisiting Charcot's observation - a review of skin abnormalities in ALS.

PubMed

Paré, Bastien; Gros-Louis, François

2017-07-26

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons of the brain and spinal cord, leading to progressive paralysis and death. Interestingly, many skin changes have been reported in ALS patients, but never as yet fully explained. These observations could be due to the common embryonic origin of the skin and neural tissue known as the ectodermal germ layer. Following the first observation in ALS patients' skin by Dr Charcot in the 19th century, in the absence of bedsores unlike other bedridden patients, other morphological and molecular changes have been observed. Thus, the skin could be of interest in the study of ALS and other neurodegenerative diseases. This review summarizes skin changes reported in the literature over the years and discusses about a novel in vitro ALS tissue-engineered skin model, derived from patients, for the study of ALS.

A novel mouse model carrying a human cytoplasmic dynein mutation shows motor behavior deficits consistent with Charcot-Marie-Tooth type 2O disease.

PubMed

Sabblah, Thywill T; Nandini, Swaran; Ledray, Aaron P; Pasos, Julio; Calderon, Jami L Conley; Love, Rachal; King, Linda E; King, Stephen J

2018-01-29

Charcot-Marie-Tooth disease (CMT) is a peripheral neuromuscular disorder in which axonal degeneration causes progressive loss of motor and sensory nerve function. The loss of motor nerve function leads to distal muscle weakness and atrophy, resulting in gait problems and difficulties with walking, running, and balance. A mutation in the cytoplasmic dynein heavy chain (DHC) gene was discovered to cause an autosomal dominant form of the disease designated Charcot-Marie-Tooth type 2 O disease (CMT2O) in 2011. The mutation is a single amino acid change of histidine into arginine at amino acid 306 (H306R) in DHC. In order to understand the onset and progression of CMT2, we generated a knock-in mouse carrying the corresponding CMT2O mutation (H304R/+). We examined H304R/+ mouse cohorts in a 12-month longitudinal study of grip strength, tail suspension, and rotarod assays. H304R/+ mice displayed distal muscle weakness and loss of motor coordination phenotypes consistent with those of individuals with CMT2. Analysis of the gastrocnemius of H304R/+ male mice showed prominent defects in neuromuscular junction (NMJ) morphology including reduced size, branching, and complexity. Based on these results, the H304R/+ mouse will be an important model for uncovering functions of dynein in complex organisms, especially related to CMT onset and progression.

Arctic foxes as ecosystem engineers: increased soil nutrients lead to increased plant productivity on fox dens

NASA Astrophysics Data System (ADS)

Gharajehdaghipour, Tazarve; Roth, James D.; Fafard, Paul M.; Markham, John H.

2016-04-01

Top predators can provide fundamental ecosystem services such as nutrient cycling, and their impact can be even greater in environments with low nutrients and productivity, such as Arctic tundra. We estimated the effects of Arctic fox (Vulpes lagopus) denning on soil nutrient dynamics and vegetation production near Churchill, Manitoba in June and August 2014. Soils from fox dens contained higher nutrient levels in June (71% more inorganic nitrogen, 1195% more extractable phosphorous) and in August (242% more inorganic nitrogen, 191% more extractable phosphorous) than adjacent control sites. Inorganic nitrogen levels decreased from June to August on both dens and controls, whereas extractable phosphorous increased. Pup production the previous year, which should enhance nutrient deposition (from urine, feces, and decomposing prey), did not affect soil nutrient concentrations, suggesting the impact of Arctic foxes persists >1 year. Dens supported 2.8 times greater vegetation biomass in August, but δ15N values in sea lyme grass (Leymus mollis) were unaffected by denning. By concentrating nutrients on dens Arctic foxes enhance nutrient cycling as an ecosystem service and thus engineer Arctic ecosystems on local scales. The enhanced productivity in patches on the landscape could subsequently affect plant diversity and the dispersion of herbivores on the tundra.

Arctic foxes as ecosystem engineers: increased soil nutrients lead to increased plant productivity on fox dens

PubMed Central

Gharajehdaghipour, Tazarve; Roth, James D.; Fafard, Paul M.; Markham, John H.

2016-01-01

Top predators can provide fundamental ecosystem services such as nutrient cycling, and their impact can be even greater in environments with low nutrients and productivity, such as Arctic tundra. We estimated the effects of Arctic fox (Vulpes lagopus) denning on soil nutrient dynamics and vegetation production near Churchill, Manitoba in June and August 2014. Soils from fox dens contained higher nutrient levels in June (71% more inorganic nitrogen, 1195% more extractable phosphorous) and in August (242% more inorganic nitrogen, 191% more extractable phosphorous) than adjacent control sites. Inorganic nitrogen levels decreased from June to August on both dens and controls, whereas extractable phosphorous increased. Pup production the previous year, which should enhance nutrient deposition (from urine, feces, and decomposing prey), did not affect soil nutrient concentrations, suggesting the impact of Arctic foxes persists >1 year. Dens supported 2.8 times greater vegetation biomass in August, but δ15N values in sea lyme grass (Leymus mollis) were unaffected by denning. By concentrating nutrients on dens Arctic foxes enhance nutrient cycling as an ecosystem service and thus engineer Arctic ecosystems on local scales. The enhanced productivity in patches on the landscape could subsequently affect plant diversity and the dispersion of herbivores on the tundra. PMID:27045973

Arctic foxes as ecosystem engineers: increased soil nutrients lead to increased plant productivity on fox dens.

PubMed

Gharajehdaghipour, Tazarve; Roth, James D; Fafard, Paul M; Markham, John H

2016-04-05

Top predators can provide fundamental ecosystem services such as nutrient cycling, and their impact can be even greater in environments with low nutrients and productivity, such as Arctic tundra. We estimated the effects of Arctic fox (Vulpes lagopus) denning on soil nutrient dynamics and vegetation production near Churchill, Manitoba in June and August 2014. Soils from fox dens contained higher nutrient levels in June (71% more inorganic nitrogen, 1195% more extractable phosphorous) and in August (242% more inorganic nitrogen, 191% more extractable phosphorous) than adjacent control sites. Inorganic nitrogen levels decreased from June to August on both dens and controls, whereas extractable phosphorous increased. Pup production the previous year, which should enhance nutrient deposition (from urine, feces, and decomposing prey), did not affect soil nutrient concentrations, suggesting the impact of Arctic foxes persists >1 year. Dens supported 2.8 times greater vegetation biomass in August, but δ(15)N values in sea lyme grass (Leymus mollis) were unaffected by denning. By concentrating nutrients on dens Arctic foxes enhance nutrient cycling as an ecosystem service and thus engineer Arctic ecosystems on local scales. The enhanced productivity in patches on the landscape could subsequently affect plant diversity and the dispersion of herbivores on the tundra.

Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice.

PubMed

D'Antonio, Maurizio; Musner, Nicolò; Scapin, Cristina; Ungaro, Daniela; Del Carro, Ubaldo; Ron, David; Feltri, M Laura; Wrabetz, Lawrence

2013-04-08

P0 glycoprotein is an abundant product of terminal differentiation in myelinating Schwann cells. The mutant P0S63del causes Charcot-Marie-Tooth 1B neuropathy in humans, and a very similar demyelinating neuropathy in transgenic mice. P0S63del is retained in the endoplasmic reticulum of Schwann cells, where it promotes unfolded protein stress and elicits an unfolded protein response (UPR) associated with translational attenuation. Ablation of Chop, a UPR mediator, from S63del mice completely rescues their motor deficit and reduces active demyelination by half. Here, we show that Gadd34 is a detrimental effector of CHOP that reactivates translation too aggressively in myelinating Schwann cells. Genetic or pharmacological limitation of Gadd34 function moderates translational reactivation, improves myelination in S63del nerves, and reduces accumulation of P0S63del in the ER. Resetting translational homeostasis may provide a therapeutic strategy in tissues impaired by misfolded proteins that are synthesized during terminal differentiation.

Franz Xaver Eder (1914 - 2009) Wanderer zwischen den Welten

NASA Astrophysics Data System (ADS)

Lindner, Sigrid; Hoffmann, Dieter

In seinem Essay "Die Struktur des historischen Universums" vergleicht Siegfried Kracauer die Mikrogeschichte mit den Großaufnahmen etwa von der Hand einer Figur, wie sie in Spielfilmen zwischengeschnitten werden.

Novel Semiquantitative Bone Marrow Oedema Score and Fracture Score for the Magnetic Resonance Imaging Assessment of the Active Charcot Foot in Diabetes

PubMed Central

Meacock, L.; Donaldson, Ana; Isaac, A.; Briody, A.; Ramnarine, R.; Edmonds, M. E.; Elias, D. A.

2017-01-01

There are no accepted methods to grade bone marrow oedema (BMO) and fracture on magnetic resonance imaging (MRI) scans in Charcot osteoarthropathy. The aim was to devise semiquantitative BMO and fracture scores on foot and ankle MRI scans in diabetic patients with active osteoarthropathy and to assess the agreement in using these scores. Three radiologists assessed 45 scans (Siemens Avanto 1.5T, dedicated foot and ankle coil) and scored independently twenty-two bones (proximal phalanges, medial and lateral sesamoids, metatarsals, tarsals, distal tibial plafond, and medial and lateral malleoli) for BMO (0—no oedema, 1—oedema < 50% of bone volume, and 2—oedema > 50% of bone volume) and fracture (0—no fracture, 1—fracture, and 2—collapse/fragmentation). Interobserver agreement and intraobserver agreement were measured using multilevel modelling and intraclass correlation (ICC). The interobserver agreement for the total BMO and fracture scores was very good (ICC = 0.83, 95% confidence intervals (CI) 0.76, 0.91) and good (ICC = 0.62; 95% CI 0.48, 0.76), respectively. The intraobserver agreement for the total BMO and fracture scores was good (ICC = 0.78, 95% CI 0.6, 0.95) and fair to moderate (ICC = 0.44; 95% CI 0.14, 0.74), respectively. The proposed BMO and fracture scores are reliable and can be used to grade the extent of bone damage in the active Charcot foot. PMID:29230422

HyDEn: A Hybrid Steganocryptographic Approach for Data Encryption Using Randomized Error-Correcting DNA Codes

PubMed Central

Regoui, Chaouki; Durand, Guillaume; Belliveau, Luc; Léger, Serge

2013-01-01

This paper presents a novel hybrid DNA encryption (HyDEn) approach that uses randomized assignments of unique error-correcting DNA Hamming code words for single characters in the extended ASCII set. HyDEn relies on custom-built quaternary codes and a private key used in the randomized assignment of code words and the cyclic permutations applied on the encoded message. Along with its ability to detect and correct errors, HyDEn equals or outperforms existing cryptographic methods and represents a promising in silico DNA steganographic approach. PMID:23984392

Crowned dens syndrome diagnosed on ¹⁸F-FDG PET/CT.

PubMed

Monet, Antoine; Massonnat, Richard; Merino, Bertrand; Riviere, Annalisa; Richez, Christophe

2014-12-01

An 87-year-old woman with corticosteroid-resistant polymyalgia rheumatica underwent ¹⁸F-FDG PET/CT for suspected giant cell arteritis or neoplastic disease. FDG uptake in the immediate vicinity of the odontoid process, with a crownlike calcification, was identified on the CT scan on the posterior side of the dens, thus confirming the diagnosis of crowned dens syndrome. Because this rare syndrome is frequently misdiagnosed, nuclear physicians should be aware of the signs and symptoms of this condition, which may call for the use of PET/CT imagery.

XVI European Charcot Foundation Lecture: Nutrition and environment, can MS be prevented?

PubMed Central

Simon, Kelly Claire; Munger, Kassandra L; Ascherio, Alberto

2012-01-01

Multiple sclerosis is a relatively common debilitating neurologic disease that affects people in early adulthood. While the characteristic pathology of MS has been well described, the etiology of the disease is not well understood, despite decades of research and the identification of strong genetic and environmental candidates for susceptibility. A question central to all diseases, but posed specifically for MS at the XVI European Charcot Foundation Lecture, was ‘Can MS be prevented?’ To address this question, we have evaluated the available data regarding nutritional and environmental factors that may be related to MS susceptibility and suggest the extent to which a potential intervention may reduce disease burden. It is our opinion that intervention, particularly supplementation with vitamin D, could have a dramatic impact on disease prevalence. Understanding that any intervention or behavioral modification will surely act in the context of genetic susceptibility and unidentified stochastic events, it is likely that not all MS is ‘preventable’. Epidemiologic observation has provided key insights into environmental and nutritional factors that may alter one’s susceptibility to MS, however, there are still many questions in unraveling the etiology of this complex disease. PMID:21975017

Habitat characteristics at den sites of the Point Arena mountain beaver (Aplodontia rufa nigra)

Treesearch

William J. Zielinski; John E. Hunter; Robin Hamlin; Keith M. Slauson; M. J. Mazurek

2010-01-01

The Point Arena mountain beaver (Aplodontia rufa nigra) is a federally listed endangered species, but has been the subject of few studies. Mountain beavers use burrows that include a single subterranean den. Foremost among the information needs for this subspecies is a description of the above-ground habitat features associated with dens. Using...

Successful Ultra-Conservative Management of a Mandibular Premolar with Dens Invaginatus.

PubMed

Abazarpour, Ramin; Parirokh, Masoud; Farhadi, Aida; Jalali, Zahra; Kheirabadi, Nasir

2017-01-01

Dens invaginatus is one of the most common anomalies of tooth structure. It is caused by the invagination of the crown surface during odontogenesis that enters the pulp chamber of the affected tooth. Depending on the complexity of invagination, the tooth might present with pulp necrosis, open apex and a complicated root canal system. This case report presents an Oehlers' type 2 dens-invaginatus in a mandibular premolar with chronic apical abscess. In most cases, dens invaginatus is removed during treatment. However, in this case report, based on cone-beam computed tomography (CBCT) evaluation, non-surgical treatment and maintenance of the invaginated segment was chosen in order to prevent compromising the tooth structure and its susceptibility to future root fracture. This is a new treatment approach and has not been performed in previous reports. Calcium-enriched mixture (CEM) cement was used as an apical plug followed by gutta-percha in warm vertical compaction for root canal obturation. The case was followed up for 36 months after treatment. This report highlights the importance of selecting the appropriate treatment approach based on CBCT evaluation.

Lack of gp130 expression in hepatocytes attenuates tumor progression in the DEN model.

PubMed

Hatting, M; Spannbauer, M; Peng, J; Al Masaoudi, M; Sellge, G; Nevzorova, Y A; Gassler, N; Liedtke, C; Cubero, F J; Trautwein, C

2015-03-05

Chronic liver inflammation is a crucial event in the development and growth of hepatocellular carcinoma (HCC). Compelling evidence has shown that interleukin-6 (IL-6)/gp130-dependent signaling has a fundamental role in liver carcinogenesis. Thus, in the present study we aimed to investigate the role of gp130 in hepatocytes for the initiation and progression of HCC. Hepatocyte-specific gp130 knockout mice (gp130(Δhepa)) and control animals (gp130(f/f)) were treated with diethylnitrosamine (DEN). The role of gp130 for acute injury (0-144 h post treatment), tumor initiation (24 weeks) and progression (40 weeks) was analyzed. After acute DEN-induced liver injury we observed a reduction in the inflammatory response in gp130(Δhepa) animals as reflected by decreased levels of IL-6 and oncostatin M. The loss of gp130 slightly attenuated the initiation of HCC 24 weeks after DEN treatment. In contrast, 40 weeks after DEN treatment, male and female gp130(Δhepa) mice showed smaller tumors and reduced tumor burden, indicating a role for hepatocyte-specific gp130 expression during HCC progression. Oxidative stress and DNA damage were substantially and similarly increased by DEN in both gp130(f/f) and gp130(Δhepa) animals. However, gp130(Δhepa) livers revealed aberrant STAT5 activation and decreased levels of transforming growth factor-β (TGFβ), pSMAD2/3 and SMAD2, whereas phosphorylation of STAT3 at Tyr705 and Ser727 was absent. Our results indicate that gp130 deletion in hepatocytes reduces progression, but not HCC initiation in the DEN model. Gp130 deletion resulted in STAT3 inhibition but increased STAT5 activation and diminished TGF-dependent signaling. Hence, blocking gp130 in hepatocytes might be an interesting therapeutic target to inhibit the growth of HCC.

Painful Charcot-Marie-Tooth neuropathy type 2E/1F due to a novel NEFL mutation.

PubMed

Doppler, Kathrin; Kunstmann, Erdmute; Krüger, Stefan; Sommer, Claudia

2017-05-01

Charcot-Marie-Tooth neuropathy (CMT) 2E/1F is caused by mutations in the neurofilament light-chain polypeptide (NEFL) gene. Giant axons are a histological hallmark frequently seen in nerves of patients with CMT2E. We describe the case of a 43-year-old patient with a painful, predominantly sensory neuropathy. The patient's sural nerve biopsy showed multiple giant axons. Genetic sequencing of the NEFL gene revealed that the patient was heterozygous for an altered sequence of the gene, c.816C>G, p.Asn272Lys, which has not yet been described in CMT2E/1F. In contrast to other cases of CMT2E/1F, where motor symptoms are predominant, pain was the most disabling symptom in this patient. Muscle Nerve 55: 752-755, 2017. © 2016 Wiley Periodicals, Inc.

Severe vincristine-induced polyneuropathy in a teenager with anaplastic medulloblastoma and undiagnosed Charcot-Marie-Tooth disease.

PubMed

Aghajan, Yasmin; Yoon, Janet M; Crawford, John Ross

2017-04-24

Severe neuropathy is a known adverse effect of vincristine in patients with Charcot-Marie-Tooth disease (CMT). We present the case of a 16-year-old girl with anaplastic medulloblastoma treated with gross total resection and high-dose craniospinal radiation with adjuvant vincristine chemotherapy who developed acute-onset severe quadriplegia and vocal cord paralysis. Vincristine and radiation therapy were discontinued. Although her neuropathy slowly improved over several weeks, she developed metastatic extraneural medulloblastoma and died 5 months after diagnosis. Subsequent genetic testing revealed previously asymptomatic and undiagnosed CMT1A. Our case highlights the importance of early recognition of acute vincristine neurotoxicity that should raise suspicion of an underlying hereditary neuropathy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

DenTimol as A Dendrimeric Timolol Analogue for Glaucoma Therapy: Synthesis and Preliminary Efficacy and Safety Assessment.

PubMed

Lancina, Michael G; Wang, Juan; Williamson, Geoffrey S; Yang, Hu

2018-05-30

In this work, we report the synthesis and characterization of DenTimol, a dendrimer-based polymeric timolol analog, as a glaucoma medication. A timolol precursor ( S)-4-[4-(oxiranylmethoxy)-1,2,5-thiadiazol-3-yl]morpholine (OTM) was reacted with the heterobifunctional amine polyethylene glycol acetic acid (amine-PEG-acetic acid, M n = 2000 g/mol) via a ring opening reaction of an epoxide by an amine to form the OTM-PEG conjugate. OTM-PEG was then coupled to an ethylenediamine (EDA) core polyamidoamine (PAMAM) dendrimer G3 to generate DenTimol using the N-(3-(dimethylamino)propyl)- N'-ethylcarbodiimide hydrochloride (EDC)/ N-hydroxysuccinimide (NHS) coupling reaction. MALDI mass spectrometry, 1 H NMR spectroscopy, and HPLC were applied to characterize the intermediate and final products. Ex vivo corneal permeation of DenTimol was assessed using the Franz diffusion cell system mounted with freshly extracted rabbit cornea. The cytotoxicity of DenTimol was assessed using the WST-1 assay. Our results show that DenTimol is nontoxic up to an OTM equivalent concentration of 100 μM. DenTimol is efficient at crossing the cornea. About 8% of the dendrimeric drug permeated through the cornea in 4 h. Its IOP-lowering effect was observed in normotensive adult Brown Norway male rats. Compared to the undosed eye, an IOP reduction by an average of 7.3 mmHg (∼30% reduction from baseline) was observed in the eye topically treated with DenTimol (2 × 5 μL, 0.5% w/v timolol equivalent) in less than 30 min. Daily dosing of DenTimol for a week did not cause any irritation or toxicity as confirmed by the histological examination of ocular tissues, including the cornea, ciliary body, and retina.

Catalogue of polar bear (Ursus maritimus) maternal den locations in the Beaufort Sea and neighboring regions, Alaska, 1910-2010

USGS Publications Warehouse

Durner, George M.; Fischbach, Anthony S.; Amstrup, Steven C.; Douglas, David C.

2010-01-01

This report presents data on the approximate locations and methods of discovery of 392 polar bear (Ursus maritimus) maternal dens found in the Beaufort Sea and neighboring regions between 1910 and 2010 that are archived by the U.S. Geological Survey, Alaska Science Center, Anchorage, Alaska. A description of data collection methods, biases associated with collection method, primary time periods, and spatial resolution are provided. Polar bears in the Beaufort Sea and nearby regions den on both the sea ice and on land. Standardized VHF surveys and satellite radio telemetry data provide a general understanding of where polar bears have denned in this region over the past 3 decades. Den observations made during other research activities and anecdotal reports from other government agencies, coastal residents, and industry personnel also are reported. Data on past polar bear maternal den locations are provided to inform the public and to provide information for natural resource agencies in planning activities to avoid or minimize interference with polar bear maternity dens.

Long-Term Effective Thalamic Deep Brain Stimulation for Neuropathic Tremor in Two Patients with Charcot-Marie-Tooth Disease.

PubMed

Cabañes-Martínez, Lidia; Del Álamo de Pedro, Marta; de Blas Beorlegui, Gema; Bailly-Bailliere, Ignacio Regidor

2017-01-01

It has been described that many Charcot-Marie-Tooth syndrome type 2 patients are affected by a very disabling type of tremor syndrome, the pathophysiology of which remains unclear. Deep brain stimulation (DBS) has been successfully applied to treat most types of tremors by implanting electrodes in the ventral intermediate nucleus of the thalamus (Vim). We used DBS applied to the Vim in 2 patients with severe axonal inherited polyneuropathies who developed a disabling tremor. Both patients responded positively to stimulation, with a marked reduction of the tremor and with an improvement of their quality of life. We report 2 cases of tremor associated with a hereditary neuropathy with a good response to DBS. © 2017 S. Karger AG, Basel.

Remote identification of potential polar bear maternal denning habitat in northern Alaska using airborne LiDAR

NASA Astrophysics Data System (ADS)

Jones, B. M.; Durner, G. M.; Stoker, J.; Shideler, R.; Perham, C.; Liston, G. E.

2013-12-01

Polar bear (Ursus maritimus) populations throughout the Arctic are being threatened by reductions in critical sea ice habitat. Throughout much of their range, polar bears give birth to their young in winter dens that are excavated in snowdrifts. New-born cubs, which are unable to survive exposure to Arctic winter weather, require 2-3 months of the relatively warm, stable, and undisturbed environment of the den for their growth. In the southern Beaufort Sea (BS), polar bears may den on the Alaskan Arctic Coastal Plain (ACP).The proportion of dens occurring on land has increased because of reductions in stable multi-year ice, increases in unconsolidated ice, and lengthening of the fall open-water period. Large portions of the ACP are currently being used for oil and gas activities and proposed projects will likely expand this footprint in the near future. Since petroleum exploration and development activities increase during winter there is the potential for human activities to disturb polar bears in maternal dens. Thus, maps showing the potential distribution of terrestrial denning habitat can help to mitigate negative interactions. Prior remote sensing efforts have consisted of manual interpretation of vertical aerial photography and automated classification of Interferometric Synthetic Aperture (IfSAR) derived digital terrain models (DTM) (5-m spatial resolution) focused on the identification of snowdrift forming landscape features. In this study, we assess the feasibility of airborne Light Detection and Ranging (LiDAR) data (2-m spatial resolution) for the automated classification of potential polar bear maternal denning habitat in a 1,400 km2 area on the central portion of the ACP. The study region spans the BS coast from the Prudhoe Bay oilfield in the west to near Point Thompson in the east and extends inland from 10 to 30 km. Approximately 800 km2 of the study area contains 19 known den locations, 51 field survey sites with information on bank height and

DenHunt - A Comprehensive Database of the Intricate Network of Dengue-Human Interactions

PubMed Central

Arjunan, Selvam; Sastri, Narayan P.; Chandra, Nagasuma

2016-01-01

Dengue virus (DENV) is a human pathogen and its etiology has been widely established. There are many interactions between DENV and human proteins that have been reported in literature. However, no publicly accessible resource for efficiently retrieving the information is yet available. In this study, we mined all publicly available dengue–human interactions that have been reported in the literature into a database called DenHunt. We retrieved 682 direct interactions of human proteins with dengue viral components, 382 indirect interactions and 4120 differentially expressed human genes in dengue infected cell lines and patients. We have illustrated the importance of DenHunt by mapping the dengue–human interactions on to the host interactome and observed that the virus targets multiple host functional complexes of important cellular processes such as metabolism, immune system and signaling pathways suggesting a potential role of these interactions in viral pathogenesis. We also observed that 7 percent of the dengue virus interacting human proteins are also associated with other infectious and non-infectious diseases. Finally, the understanding that comes from such analyses could be used to design better strategies to counteract the diseases caused by dengue virus. The whole dataset has been catalogued in a searchable database, called DenHunt (http://proline.biochem.iisc.ernet.in/DenHunt/). PMID:27618709

DenHunt - A Comprehensive Database of the Intricate Network of Dengue-Human Interactions.

PubMed

Karyala, Prashanthi; Metri, Rahul; Bathula, Christopher; Yelamanchi, Syam K; Sahoo, Lipika; Arjunan, Selvam; Sastri, Narayan P; Chandra, Nagasuma

2016-09-01

Dengue virus (DENV) is a human pathogen and its etiology has been widely established. There are many interactions between DENV and human proteins that have been reported in literature. However, no publicly accessible resource for efficiently retrieving the information is yet available. In this study, we mined all publicly available dengue-human interactions that have been reported in the literature into a database called DenHunt. We retrieved 682 direct interactions of human proteins with dengue viral components, 382 indirect interactions and 4120 differentially expressed human genes in dengue infected cell lines and patients. We have illustrated the importance of DenHunt by mapping the dengue-human interactions on to the host interactome and observed that the virus targets multiple host functional complexes of important cellular processes such as metabolism, immune system and signaling pathways suggesting a potential role of these interactions in viral pathogenesis. We also observed that 7 percent of the dengue virus interacting human proteins are also associated with other infectious and non-infectious diseases. Finally, the understanding that comes from such analyses could be used to design better strategies to counteract the diseases caused by dengue virus. The whole dataset has been catalogued in a searchable database, called DenHunt (http://proline.biochem.iisc.ernet.in/DenHunt/).

Technische Systeme für den Herzersatz und die Herzunterstützung

NASA Astrophysics Data System (ADS)

Schöb, Reto; Loree, Howard M.

Herzkrankheiten verursachen allein in den Vereinigten Staaten jährlich mehr als 700’000 Todesfälle. Ungefähr 3 Millionen Patienten in den U.S.A. leiden gemäss der American Heart Association (AHA) und dem National Heart, Lung and Blood Institute (NHLBI) an kongestivem Herzversagen (Congestive Heart Failure, CHF), welches eine chronische, sehr entkräftende und degenerative Krankheit ist: Das Herz ist dabei unfähig, hinreichend Blut zu den Organen des Körpers zu pumpen. Über 400’000 Fälle von CHF werden jedes Jahr diagnostiziert. Ähnliche Zahlen werden für Europa und Japan zusammen geschätzt. Basierend auf Daten vom AHA und NHLBI beträgt die fünfjährige Überlebensrate für CHF-Patienten lediglich etwa 50% [1]. 70’000-120’000 dieser Patienten könnten von einer Herzverpflanzung profitieren. 1999 wurden in den USA aber nur 2185 Herztransplantationen durchgeführt während die Warteliste über 4000 Patienten beträgt [2]. Ein akuter Mangel an Spenderherzen und die enormen Kosten (250’000-400’000 USD pro Patient) sind die begrenzenden Faktoren für Herztransplantationen [3]. Dies bedeutet, dass eine riesige Anzahl von Patienten durch ein zuverlässiges und verschleissfreies, nichtthrombotisches, total implantierbares, künstliches Herz gerettet werden könnten. Bis heute jedoch kein derartiges Implantat kommerziell verfügbar.

Successful Ultra-Conservative Management of a Mandibular Premolar with Dens Invaginatus

PubMed Central

Abazarpour, Ramin; Parirokh, Masoud; Farhadi, Aida; Jalali, Zahra; Kheirabadi, Nasir

2017-01-01

Dens invaginatus is one of the most common anomalies of tooth structure. It is caused by the invagination of the crown surface during odontogenesis that enters the pulp chamber of the affected tooth. Depending on the complexity of invagination, the tooth might present with pulp necrosis, open apex and a complicated root canal system. This case report presents an Oehlers’ type 2 dens-invaginatus in a mandibular premolar with chronic apical abscess. In most cases, dens invaginatus is removed during treatment. However, in this case report, based on cone-beam computed tomography (CBCT) evaluation, non-surgical treatment and maintenance of the invaginated segment was chosen in order to prevent compromising the tooth structure and its susceptibility to future root fracture. This is a new treatment approach and has not been performed in previous reports. Calcium-enriched mixture (CEM) cement was used as an apical plug followed by gutta-percha in warm vertical compaction for root canal obturation. The case was followed up for 36 months after treatment. This report highlights the importance of selecting the appropriate treatment approach based on CBCT evaluation. PMID:28808472

Hyperactivation of HUSH complex function by Charcot-Marie-Tooth disease mutation in MORC2.

PubMed

Tchasovnikarova, Iva A; Timms, Richard T; Douse, Christopher H; Roberts, Rhys C; Dougan, Gordon; Kingston, Robert E; Modis, Yorgo; Lehner, Paul J

2017-07-01

Dominant mutations in the MORC2 gene have recently been shown to cause axonal Charcot-Marie-Tooth (CMT) disease, but the cellular function of MORC2 is poorly understood. Here, through a genome-wide CRISPR-Cas9-mediated forward genetic screen, we identified MORC2 as an essential gene required for epigenetic silencing by the HUSH complex. HUSH recruits MORC2 to target sites in heterochromatin. We exploited a new method, differential viral accessibility (DIVA), to show that loss of MORC2 results in chromatin decompaction at these target loci, which is concomitant with a loss of H3K9me3 deposition and transcriptional derepression. The ATPase activity of MORC2 is critical for HUSH-mediated silencing, and the most common alteration affecting the ATPase domain in CMT patients (p.Arg252Trp) hyperactivates HUSH-mediated repression in neuronal cells. These data define a critical role for MORC2 in epigenetic silencing by the HUSH complex and provide a mechanistic basis underpinning the role of MORC2 mutations in CMT disease.

Sleep disorders in Charcot-Marie-Tooth disease type 1.

PubMed

Boentert, Matthias; Knop, Katharina; Schuhmacher, Christine; Gess, Burkhard; Okegwo, Angelika; Young, Peter

2014-03-01

Obstructive sleep apnoea (OSA) and restless legs syndrome (RLS) have been reported in Charcot-Marie-Tooth disease (CMT) type 1A and axonal subtypes of CMT, respectively. The aim of this case-control study was to investigate both prevalence and severity of OSA, RLS and periodic limb movements in sleep (PLMS) in adult patients with genetically proven CMT1. 61 patients with CMT1 and 61 insomnic control subjects were matched for age, sex, and Body Mass Index. Neurological disability in patients with CMT was assessed using the Functional Disability Scale (FDS). RLS diagnosis was based on a screening questionnaire and structured clinical interviews. All participants underwent overnight polysomnography. OSA was present in 37.7% of patients with CMT1 and 4.9% of controls (p<0.0001). The mean Apnoea Hypoponea Index (AHI) was significantly higher in patients with CMT1 than in control individuals (9.1/h vs 1.2/h). RLS was present in 40.9% of patients with CMT1 and in 16.4% of controls (p<0.001). In the CMT1 group, OSA was significantly more common in men and RLS in women. The AHI correlated with both age and the FDS score, the latter being a significant independent predictor of OSA. PLMS were found in 41.0% of patients with CMT1, but were not correlated with measures of sleep quality. In addition to known risk factors, CMT may predispose to OSA. RLS is highly prevalent not only in axonal subtypes of CMT but also in primarily demyelinating subforms of CMT. PLMS are common in CMT1, but do not significantly impair sleep quality.

Effects of Self-Selected Exercise on Strength in Charcot-Marie-Tooth Disease Subtypes.

PubMed

Djordjevic, Djurdja; Fell, Sabrina; Baker, Steven

2017-09-01

Preliminary studies have supported the utility of exercise as a treatment for Charcot-Marie-Tooth disease (CMT) patients. Despite being the most common inherited neuropathy, there remains a paucity of guidelines for CMT management. A retrospective chart review was performed on 297 CMT patients. Self-reported exercise and strength results from standardized dynamometer testing were obtained from adult patients' first visits. Values were converted and analyzed based on previously reported age- and sex-matched normative values. Participants with CMT2 had greater strength values than those with CMT1 in hand grip, elbow flexion, and dorsiflexion (p<0.05). Participants with CMT1 and CMT2 who exercised were statistically significantly stronger in elbow flexion and dorsiflexion than those who did not exercise. These preliminary results suggest that self-directed exercise is associated with greater strength in CMT patients of both CMT1 and CMT2 subtypes. Self-directed exercise may be a convenient, sustainable, and effective method of improving strength and decreasing disability in this population. Future research should explore the type of exercise prescription that best addresses the needs of the CMT population.

Aerobic anti-gravity exercise in patients with Charcot-Marie-Tooth disease types 1A and X: A pilot study.

PubMed

Knak, Kirsten L; Andersen, Linda K; Vissing, John

2017-12-01

Charcot-Marie-Tooth (CMT) disease is a hereditary neuropathy associated with impaired walking capacity. Some patients are too weak in the lower extremity muscles to walk at gravity with sufficient intensity or duration to gain benefit. The aim was to investigate the effect of aerobic anti-gravity exercise in weak patients with CMT 1A and X. Five adult patients performed moderate-intensity aerobic anti-gravity exercise 3/week for 10 weeks. There was a significant positive difference in Berg balance scale and postural stability test between test occasions, and walking distance in the 6-min walk test trended to increase. The study indicates that the anti-gravity treadmill training of patients with CMT should be pursued in larger CMT cohorts.

Dens of northern flying squirrels in the Pacific Northwest.

Treesearch

A.B. Carey; T.M. Wilson; C.C. Maguire; B.L. Biswell

1997-01-01

Silvicultural prescriptions to enhance northern flying squirrel (Glaucoinys sabrinus) habitat have been suggested as an aid for recovery of the threatened northern spotted owl (Strix occidentalis caurina). Flying squirrels are hypothesized to be limited by den sites (cavities in trees) and by food (truffles). However, no...

Correlation between connexin 32 gene mutations and clinical phenotype in X-linked dominant Charcot-Marie-Tooth neuropathy

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

Ionasescu, V.; Ionasescu, R.; Searby, C.

1996-06-14

We studied the relationship between the genotype and clinical phenotype in 27 families with dominant X-linked Charcot-Marie-Tooth (CMTX1) neuropathy. Twenty-two families showed mutations in the coding region of the connexin32 (cx32) gene. The mutations include four nonsense mutations, eight missense mutations, two medium size deletions, and one insertion. Most missense mutations showed a mild clinical phenotype (five out of eight), whereas all nonsense mutations, the larger of the two deletions, and the insertion that produced frameshifts showed severe phenotypes. Five CMTX1 families with mild clinical phenotype showed no point mutations of the cx32 gene coding region. Three of these familiesmore » showed positive genetic linkage with the markers of the Xq13.1 region. The genetic linkage of the remaining two families could not be evaluated because of their small size. 25 refs., 1 fig., 1 tab.« less

Surgical orthodontic treatment of an impacted canine in the presence of dens invaginatus and follicular cyst.

PubMed

Spallarossa, Marialuce; Canevello, Carola; Silvestrini Biavati, Francesca; Laffi, Nicola

2014-01-01

Introduction. "Dens invaginatus" is a dental anomaly which originates from the invagination of the ameloblastic epithelium into the lingual surface of the dental crown during the odontogenesis. It can cause early pulpal necrosis, abscesses, retention or dislocation of contiguous elements, cysts, and internal resorptions. It normally affects the upper lateral incisors. In the following study the authors will discuss the etiology, the physiopathology, and the surgical-orthodontic management of a rare case of impacted canine associated with dens invaginatus and follicular cyst, with the aim of highlighting the importance of taking any therapeutic decision based on the data available in the literature. Case Report. The present study describes a combined surgical-orthodontic treatment of an impacted canine associated with a lateral incisor (2.2) suffering from type III dens invaginatus with radicular cyst, in a 15-year-old patient. Discussion. When treating a dens invaginatus there are different therapeutic solutions: they depend on the gravity of the anomaly and on the association with the retention of a permanent tooth. The aesthetic and functional restoration becomes extremely important when performing a surgical-orthodontic repositioning.

Intermittent fasting alleviates the neuropathic phenotype in a mouse model of Charcot-Marie-Tooth disease

PubMed Central

Madorsky, Irina; Opalach, Katherine; Waber, Amanda; Verrier, Jonathan D.; Solmo, Chelsea; Foster, Thomas; Dunn, William A; Notterpek, Lucia

2009-01-01

Charcot-Marie-Tooth type 1A (CMT1A) neuropathies linked to the misexpression of peripheral myelin protein 22 (PMP22) are progressive demyelinating disorders of the peripheral nervous system. In this study we asked whether dietary restriction by intermittent fasting (IF) could alleviate the neuropathic phenotype in the Trembler J (TrJ) mouse model of CMT1A. Our results show that neuropathic mice kept on a five month long IF regimen had improved locomotor performance compared to ad libitum (AL) fed littermates. The functional benefits of this dietary intervention are associated with an increased expression of myelin proteins combined with a thicker myelin sheath, less redundant basal lamina, and a reduction in aberrant Schwann cell proliferation. These morphological improvements are accompanied by a decrease in PMP22 protein aggregates, and enhanced expression of cytosolic chaperones and constituents of the autophagy-lysosomal pathway. These results indicate that dietary restriction is beneficial for peripheral nerve function in TrJ neuropathic mice, as it promotes the maintenance of locomotor performance. PMID:19320048

Hyper-activation of HUSH complex function by Charcot-Marie-Tooth disease mutation in MORC2

PubMed Central

Douse, Christopher H.; Roberts, Rhys C.; Dougan, Gordon; Kingston, Robert E.; Modis, Yorgo; Lehner, Paul J.

2017-01-01

Dominant mutations in the MORC2 gene have recently been shown to cause axonal Charcot-Marie-Tooth (CMT) disease, but the cellular function of MORC2 is poorly understood. Here, through a genome-wide CRISPR/Cas9-mediated forward genetic screen, we identify MORC2 as an essential gene required for epigenetic silencing by the HUSH complex. HUSH recruits MORC2 to target sites in heterochromatin. We exploit a new method – Differential Viral Accessibility (DIVA) – to show that loss of MORC2 results in chromatin decompaction at these target loci, which is concomitant with a loss of H3K9me3 deposition and transcriptional derepression. The ATPase activity of MORC2 is critical for HUSH-mediated silencing, and the most common mutation affecting the ATPase domain found in CMT patients (R252W) hyper-activates HUSH-mediated repression in neuronal cells. These data define a critical role for MORC2 in epigenetic silencing by the HUSH complex and provide a mechanistic basis underpinning the role of MORC2 mutations in CMT disease. PMID:28581500

Clinical and neurophysiological investigation of a large family with dominant Charcot-Marie-Tooth type 2 disease with pyramidal signs.

PubMed

Neves, Eduardo Luis de Aquino; Kok, Fernando

2011-06-01

Charcot-Marie-Tooth (CMT) disease is a hereditary neuropathy of motor and sensory impairment with distal predominance. Atrophy and weakness of lower limbs are the first signs of the disease. It can be classified, with the aid of electromyography and nerve conduction studies, as demyelinating (CMT1) or axonal (CMT2). Clinical and neurophysiological investigation of a large multigenerational family with CMT2 with autosomal dominant mode of transmission. Fifty individuals were evaluated and neurophysiological studies performed in 22 patients. Thirty individuals had clinical signs of motor-sensory neuropathy. Babinski sign was present in 14 individuals. Neurophysiological study showed motor-sensory axonal polyneuropathy. The clinical and neurophysiological characteristics of this family does not differ from those observed with other forms of CMT, except for the high prevalence of Babinski sign.

DEVILS DEN ROADLESS AREA, VERMONT.

USGS Publications Warehouse

Slack, John F.; Sabin, Andrew E.

1984-01-01

A mineral-resource survey was made of the Devils Den Roadless Area, Vermont, Geochemical sampling found traces of gold, copper, barium, lead, molybdenum, silver, tin, and thorium in rocks, stream sediments, and panned concentrates, but not in sufficient quantities to identify any resource potential. The only apparent resources are nonmetallic commodities including abundant rock suitable for crushihg, and very small deposits of sand and gravel and marble; these also occur outside the roadless area. The area was also evaluated for bedrock uranium and thorium deposits, but not anomalously high radioactive bedrock was found. A potential may exist for oil or natural gas at great depth, but this cannot be evaluated by the present study.

Exacerbation of Charcot-Marie-Tooth type 2E neuropathy following traumatic nerve injury

PubMed Central

Villalon, Eric; Dale, Jeffrey M.; Jones, Maria; Shen, Hailian; Garcia, Michael L.

2018-01-01

Charcot-Marie-Tooth disease (CMT) is the most commonly inherited peripheral neuropathy. CMT disease signs include distal limb neuropathy, abnormal gait, sensory defects, and deafness. We generated a novel line of CMT2E mice expressing hNF-LE397K, which displayed muscle atrophy of the lower limbs without denervation, proximal reduction in large caliber axons, and decreased nerve conduction velocity. In this study, we challenged wild type, hNF-L, and hNF-LE397K mice with crush injury to the sciatic nerve. We analyzed functional recovery by measuring toe spread and analyzed gaitusing the Catwalk system. hNF-LE397K mice demonstrated reduced recovery from nerve injury consistent with increased susceptibility to neuropathy observed in CMT patients. In addition, hNF-LE397K developed a permanent reduction in their ability to weight bear, increased mechanical allodynia, and premature gait shift in the injured limb, which led to increasingly disrupted interlimb coordination in hNF-LE397K. Exacerbation of neuropathy after injury and identification of gait alterations in combination with previously described pathology suggests that hNF-LE397K mice recapitulate many of clinical signs associated with CMT2. Therefore, hNF-LE397K mice provide a model for determining the efficacy of novel therapies. PMID:26423936

Lower urinary tract functions in a series of Charcot-Marie-Tooth neuropathy patients.

PubMed

Krhut, J; Mazanec, R; Seeman, P; Mann-Gow, T; Zvara, P

2014-05-01

To evaluate lower urinary tract (LUT), bowel, and sexual dysfunctions in a series of patients with Charcot-Marie-Tooth disease (CMT). A cohort of 58 patients and 54 healthy controls filled out the International Prostate Symptoms Score (IPSS) and the International Consultation on Incontinence Modular (ICIQ) Questionnaires to assess their symptoms and their impact on the patient's quality of life. On the IPSS questionnaire, CMT patients reported a significantly higher score compared with the healthy controls in 7 of 8 questions. The ICIQ-male LUT symptoms questionnaire revealed a significantly higher score in 7 of 26 questions. In the ICIQ-female LUT questionnaire, a significantly higher score was observed in 13 of 24 questions. When assessing the bowel function in CMT patients using the ICIQ-bowel questionnaire, a significantly higher score in 30 of 40 questions was noted. No differences in sexual function were found in either group. The occurrence of the LUT symptoms and bowel dysfunctions in CMT patients was significantly higher when compared with an age-matched control group. The symptoms were more frequent in female patients. The findings suggest that autonomic dysfunction should be evaluated and included in the diagnostic approach and care of CMT patients. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Myelin protein zero gene mutated in Charcot-Marie-Tooth type 1B patients

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

Su, Ying; Li, Lanying; Lepercq, J.

1993-11-15

The autosomal dominant of Charcot-Marie-Tooth disease (CMT), whose gene is type 1B (CMT1B), has slow nerve conduction with demyelinated Schwann cells. In this study the abundant peripheral myelin protein zero (MPZ) gene, MPZ, was mapped 130 kb centromeric to the Fc receptor immunoglobulin gene cluster in band 1q22, and a major MPZ point mutation was found to cosegregate with CMT1B in one large CMT1B family. The MPZ point mutation in 18 of 18 related CMT1B pedigree 1 patients converts a positively charged lysine in codon 96 to a negatively charged glutamate. The same MPZ locus cosegregates with the CMT1B diseasemore » gene in a second CMT1B family [total multipoint logarithm of odds (lod) = 11.4 at [theta] = 0.00] with a splice junction mutation. Both mutations occur in MPZ protein regions otherwise conserved identically in human, rat, and cow since these species diverged 100 million years ago. MPZ protein, expressed exclusively in myelinated peripheral nerve Schwann cells, constitutes >50% of myelin protein. These mutations are anticipated to disrupt homophilic MPZ binding and result in CMT1B peripheral nerve demyelination.« less

First evidence of gregarious denning in opossums (Didelphimorphia, Didelphidae), with notes on their social behaviour

PubMed Central

Astúa, Diego; Carvalho, Rafael A.; Maia, Paula F.; Magalhães, Arthur R.; Loretto, Diogo

2015-01-01

The Didelphidae are considered solitary opossums with few social interactions, usually limited to mating-related or mother–pouch young interactions. Anecdotal reports suggest that additional interactions occur, including den sharing by a few individuals, usually siblings. Here, we report novel observations that indicate opossums are more social than previously thought. These include nest sharing by males and females of Marmosa paraguayana, Gracilinanus microtarsus and Marmosops incanus prior to the onset of the breeding season and without signs of sexual activity; this is taken to indicate early pair-bonding matching and cooperative nest building. We also recorded den sharing among recently weaned siblings of Didelphis aurita and Caluromys philander. In addition, we observed 13 individuals of Didelphis albiventris representing three age classes resting without agonistic interactions in a communal den. These are the first reports of gregarious behaviour involving so many individuals, which are either unrelated or represent siblings from at least two litters, already weaned, sharing the same den with three adults. Sociality in opossums is probably more complex than previously established, and field experimental designs combining the use of artificial nests with camera traps or telemetry may help to gauge the frequency and extent of these phenomena. PMID:26085500

24. Typical 1bedroom apartment, from entry hall, den (right) bedroom ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

24. Typical 1-bedroom apartment, from entry hall, den (right) bedroom (left), and kitchen (not shown) on left. - Techwood Homes, Building No. 5, 467 Techwood Drive & 114-120 Pine Street, Atlanta, Fulton County, GA

Balance and muscle power of children with Charcot-Marie-Tooth.

PubMed

Silva, Tais R; Testa, Amanda; Baptista, Cyntia R J A; Marques, Wilson; Mattiello-Sverzut, Ana C

2014-01-01

In certain diseases, functional constraints establish a greater relationship with muscle power than muscle strength. However, in hereditary peripheral polyneuropathies, no such relationship was found in the literature. In children with Charcot-Marie-Tooth (CMT), to identify the impact of muscle strength and range of movement on the static/dynamic balance and standing long jump based on quantitative and functional variables. The study analyzed 19 participants aged between 6 and 16 years, of both genders and with clinical diagnoses of CMT of different subtypes. Anthropometric data, muscle strength of the lower limbs (hand-held dynamometer), ankle and knee range of movement, balance (Pediatric Balance Scale) and standing long jump distance were obtained by standardized procedures. For the statistical analysis, Pearson and Spearman correlation coefficients were used. There was a strong positive correlation between balance and the muscle strength of the right plantar flexors (r=0.61) and dorsiflexors (r=0.59) and a moderate correlation between balance and the muscle strength of inversion (r=0.41) and eversion of the right foot (r=0.44). For the long jump and range of movement, there was a weak positive correlation with right and left plantar flexion (r=0.20 and r=0.12, respectively) and left popliteal angle (r=0.25), and a poor negative correlation with left dorsiflexion (r=-0.15). The data on the patients analyzed suggests that the maintenance of distal muscle strength favors performance during balance tasks, while limitations in the range of movement of the legs seem not to be enough to influence the performance of the horizontal long jump.

21. Typical 2bedroom apartment with entry into den, hallway with ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

21. Typical 2-bedroom apartment with entry into den, hallway with bathroom and bedrooms (right). Entry to kitchen (left). - Techwood Homes, Building No. 5, 467 Techwood Drive & 114-120 Pine Street, Atlanta, Fulton County, GA

27. Typical 2bedroom apartment with entry into den, hallway with ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

27. Typical 2-bedroom apartment with entry into den, hallway with bathroom and bedrooms (left), entry to kitchen (right) - Techwood Homes, Building No. 6, 465 Techwood Drive & 119-125 Hunnicutt Street, Atlanta, Fulton County, GA

Surgical Orthodontic Treatment of an Impacted Canine in the Presence of Dens Invaginatus and Follicular Cyst

PubMed Central

Canevello, Carola; Laffi, Nicola

2014-01-01

Introduction. “Dens invaginatus” is a dental anomaly which originates from the invagination of the ameloblastic epithelium into the lingual surface of the dental crown during the odontogenesis. It can cause early pulpal necrosis, abscesses, retention or dislocation of contiguous elements, cysts, and internal resorptions. It normally affects the upper lateral incisors. In the following study the authors will discuss the etiology, the physiopathology, and the surgical-orthodontic management of a rare case of impacted canine associated with dens invaginatus and follicular cyst, with the aim of highlighting the importance of taking any therapeutic decision based on the data available in the literature. Case Report. The present study describes a combined surgical-orthodontic treatment of an impacted canine associated with a lateral incisor (2.2) suffering from type III dens invaginatus with radicular cyst, in a 15-year-old patient. Discussion. When treating a dens invaginatus there are different therapeutic solutions: they depend on the gravity of the anomaly and on the association with the retention of a permanent tooth. The aesthetic and functional restoration becomes extremely important when performing a surgical-orthodontic repositioning. PMID:24963421

Different nerve ultrasound patterns in charcot-marie-tooth types and hereditary neuropathy with liability to pressure palsies.

PubMed

Padua, Luca; Coraci, Daniele; Lucchetta, Marta; Paolasso, Ilaria; Pazzaglia, Costanza; Granata, Giuseppe; Cacciavillani, Mario; Luigetti, Marco; Manganelli, Fiore; Pisciotta, Chiara; Piscosquito, Giuseppe; Pareyson, Davide; Briani, Chiara

2018-01-01

Nerve ultrasound in Charcot-Marie-Tooth (CMT) disease has focused mostly on the upper limbs. We performed an evaluation of a large cohort of CMT patients in which we sonographically characterized nerve abnormalities in different disease types, ages, and nerves. Seventy patients affected by different CMT types and hereditary neuropathy with liability to pressure palsies (HNPP) were evaluated, assessing median, ulnar, fibular, tibial, and sural nerves bilaterally. Data were correlated with age. Nerve dimensions were correlated with CMT type, age, and nerve site. Nerves were larger in demyelinating than in axonal neuropathies. Nerve involvement was symmetric. CMT1 patients had larger nerves than did patients with other CMT types. Patients with HNPP showed enlargement at entrapment sites. Our study confirms the general symmetry of ultrasound nerve patterns in CMT. When compared with ultrasound studies of nerves of the upper limbs, evaluation of the lower limbs did not provide additional information. Muscle Nerve 57: E18-E23, 2018. © 2017 Wiley Periodicals, Inc.

The first de novo mutation of the connexin 32 gene associated with X linked Charcot-Marie-Tooth disease.

PubMed Central

Meggouh, F; Benomar, A; Rouger, H; Tardieu, S; Birouk, N; Tassin, J; Barhoumi, C; Yahyaoui, M; Chkili, T; Brice, A; LeGuern, E

1998-01-01

X linked Charcot-Marie-Tooth disease (CMTX) is a hereditary motor and sensory neuropathy caused by mutations in the connexin 32 gene (Cx32). Using the SSCP technique and direct sequencing of PCR amplified genomic DNA fragments of the Cx32 gene from a Moroccan patient and her relatives, we identified the first de novo mutation of the Cx32 gene, consisting of a deletion of a G residue at position 499 in the Cx32 open reading frame. This previously unreported mutation produces a frameshift at position 147 in the protein and introduces a premature stop codon (TAG) at nucleotide 643, which results in the production of a truncated Cx32 molecule. This mutation illustrates the risk of an erroneous diagnosis of autosomal recessive CMT, especially in populations where consanguineous unions are frequent, and its consequences for genetic counselling, which can be avoided by molecular analysis. Images PMID:9541114

Four novel connexin 32 mutations in X-linked Charcot-Marie-Tooth disease. Phenotypic variability and central nervous system involvement.

PubMed

Karadima, Georgia; Koutsis, Georgios; Raftopoulou, Maria; Floroskufi, Paraskewi; Karletidi, Karolina-Maria; Panas, Marios

2014-06-15

Charcot-Marie-Tooth (CMT) disease, the most common hereditary neuropathy, is clinically and genetically heterogeneous. X-linked CMT (CMTX) is usually caused by mutations in the gap junction protein b 1 gene (GJB1) coding for connexin 32 (Cx32). The clinical manifestations of CMTX are characterized by significant variability, with some patients exhibiting central nervous system (CNS) involvement. We report four novel mutations in GJB1, c.191G>A (p.Cys64Tyr), c.508G>T (p.Val170Phe), c.778A>G (p.Lys260Glu) and c.300C>G (p.His100Gln) identified in four unrelated Greek families. These mutations were characterized by variable phenotypic expression, including a family with the Roussy-Lévy syndrome, and three of them were associated with mild clinical CNS manifestations. Copyright © 2014. Published by Elsevier B.V.

Hereditary motor and sensory neuropathies or Charcot-Marie-Tooth diseases: an update.

PubMed

Tazir, Meriem; Hamadouche, Tarik; Nouioua, Sonia; Mathis, Stephane; Vallat, Jean-Michel

2014-12-15

Hereditary motor and sensory neuropathies (HMSN) or Charcot-Marie-Tooth (CMT) diseases are the most common degenerative disorders of the peripheral nervous system. However, the frequency of the different subtypes varies within distinct populations. Although more than seventy clinical and genetic forms are known to date, more than 80% of CMT patients in Western countries have genetic abnormalities associated with PMP22, MPZ, MFN2 and GJB1. Given the considerable genetic heterogeneity of CMT, we emphasize the interest of both clinical and pathological specific features such that focused genetic testing could be performed. In this regard, peripheral nerve lesions in GDAP1 mutations (AR CMT1A), such as mitochondrial abnormalities, have been newly demonstrated. Otherwise, while demyelinating autosomal recessive CMT used to be classified as CMT4 (A, B, C …), we propose a simplified classification such as AR CMT1 (A, B, C …), and AR CMT2 for axonal forms. Also, we stress that next generation sequencing techniques, now considered to be the most efficient methods of genetic testing in CMT, will be helpful in molecular diagnosis and research of new genes involved. Finally, while no effective therapy is known to date, ongoing new therapeutic trials such as PXT3003 (a low dose combination of the three already approved drugs baclofen, naltrexone, and D-sorbitol) give hopes for potential curative treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Exploratory study of physical activity in persons with Charcot-Marie-Tooth disease.

PubMed

Anens, Elisabeth; Emtner, Margareta; Hellström, Karin

2015-02-01

To explore and describe the perceived facilitators and barriers to physical activity, and to examine the physical activity correlates in people with Charcot-Marie-Tooth (CMT) disease. Cross-sectional survey study. Community-living subjects. Swedish people with CMT disease (N=44; men, 54.5%; median age, 59.5 y [interquartile range, 45.3-64.8 y]). Not applicable. The survey included open-ended questions and standardized self-reported scales measuring physical activity, fatigue, activity limitation, self-efficacy for physical activity, fall-related self-efficacy, social support, and enjoyment of physical activity. Physical activity was measured by the Physical Activity Disability Survey-Revised. Qualitative content analysis revealed that personal factors such as fatigue, poor balance, muscle weakness, and pain were important barriers for physical activity behavior. Facilitators of physical activity were self-efficacy for physical activity, activity-related factors, and assistive devices. Multiple regression analysis showed that self-efficacy for physical activity (β=.41) and fatigue (β=-.30) explained 31.8% of the variation in physical activity (F2,40=10.78, P=.000). Despite the well-known benefits of physical activity, physical activity in people with CMT disease is very sparsely studied. These new results contribute to the understanding of factors important for physical activity behavior in people with CMT disease and can guide health professionals to facilitate physical activity behavior in this group of patients. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Biomarkers predict outcome in Charcot-Marie-Tooth disease 1A.

PubMed

Fledrich, Robert; Mannil, Manoj; Leha, Andreas; Ehbrecht, Caroline; Solari, Alessandra; Pelayo-Negro, Ana L; Berciano, José; Schlotter-Weigel, Beate; Schnizer, Tuuli J; Prukop, Thomas; Garcia-Angarita, Natalia; Czesnik, Dirk; Haberlová, Jana; Mazanec, Radim; Paulus, Walter; Beissbarth, Tim; Walter, Maggie C; Triaal, Cmt-; Hogrel, Jean-Yves; Dubourg, Odile; Schenone, Angelo; Baets, Jonathan; De Jonghe, Peter; Shy, Michael E; Horvath, Rita; Pareyson, Davide; Seeman, Pavel; Young, Peter; Sereda, Michael W

2017-11-01

Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited neuropathy, a debilitating disease without known cure. Among patients with CMT1A, disease manifestation, progression and severity are strikingly variable, which poses major challenges for the development of new therapies. Hence, there is a strong need for sensitive outcome measures such as disease and progression biomarkers, which would add powerful tools to monitor therapeutic effects in CMT1A. We established a pan-European and American consortium comprising nine clinical centres including 311 patients with CMT1A in total. From all patients, the CMT neuropathy score and secondary outcome measures were obtained and a skin biopsy collected. In order to assess and validate disease severity and progression biomarkers, we performed qPCR on a set of 16 animal model-derived potential biomarkers in skin biopsy mRNA extracts. In 266 patients with CMT1A, a cluster of eight cutaneous transcripts differentiates disease severity with a sensitivity and specificity of 90% and 76.1%, respectively. In an additional cohort of 45 patients with CMT1A, from whom a second skin biopsy was taken after 2-3 years, the cutaneous mRNA expression of GSTT2, CTSA, PPARG, CDA, ENPP1 and NRG1-Iis changing over time and correlates with disease progression. In summary, we provide evidence that cutaneous transcripts in patients with CMT1A serve as disease severity and progression biomarkers and, if implemented into clinical trials, they could markedly accelerate the development of a therapy for CMT1A. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

DHTKD1 Deficiency Causes Charcot-Marie-Tooth Disease in Mice.

PubMed

Xu, Wang-Yang; Zhu, Houbao; Shen, Yan; Wan, Ying-Han; Tu, Xiao-Die; Wu, Wen-Ting; Tang, Lingyun; Zhang, Hong-Xin; Lu, Shun-Yuan; Jin, Xiao-Long; Fei, Jian; Wang, Zhu-Gang

2018-07-01

DHTKD1, a part of 2-ketoadipic acid dehydrogenase complex, is involved in lysine and tryptophan catabolism. Mutations in DHTKD1 block the metabolic pathway and cause 2-aminoadipic and 2-oxoadipic aciduria (AMOXAD), an autosomal recessive inborn metabolic disorder. In addition, a nonsense mutation in DHTKD1 that we identified previously causes Charcot-Marie-Tooth disease (CMT) type 2Q, one of the most common inherited neurological disorders affecting the peripheral nerves in the musculature. However, the comprehensive molecular mechanism underlying CMT2Q remains elusive. Here, we show that Dhtkd1 -/- mice mimic the major aspects of CMT2 phenotypes, characterized by progressive weakness and atrophy in the distal parts of limbs with motor and sensory dysfunctions, which are accompanied with decreased nerve conduction velocity. Moreover, DHTKD1 deficiency causes severe metabolic abnormalities and dramatically increased levels of 2-ketoadipic acid (2-KAA) and 2-aminoadipic acid (2-AAA) in urine. Further studies revealed that both 2-KAA and 2-AAA could stimulate insulin biosynthesis and secretion. Subsequently, elevated insulin regulates myelin protein zero ( Mpz ) transcription in Schwann cells via upregulating the expression of early growth response 2 (Egr2), leading to myelin structure damage and axonal degeneration. Finally, 2-AAA-fed mice do reproduce phenotypes similar to CMT2Q phenotypes. In conclusion, we have demonstrated that loss of DHTKD1 causes CMT2Q-like phenotypes through dysregulation of Mpz mRNA and protein zero (P 0 ) which are closely associated with elevated DHTKD1 substrate and insulin levels. These findings further indicate an important role of metabolic disorders in addition to mitochondrial insufficiency in the pathogenesis of peripheral neuropathies. Copyright © 2018 American Society for Microbiology.

Exacerbation of Charcot-Marie-Tooth type 2E neuropathy following traumatic nerve injury.

PubMed

Villalón, Eric; Dale, Jeffrey M; Jones, Maria; Shen, Hailian; Garcia, Michael L

2015-11-19

Charcot-Marie-Tooth disease (CMT) is the most commonly inherited peripheral neuropathy. CMT disease signs include distal limb neuropathy, abnormal gait, sensory defects, and deafness. We generated a novel line of CMT2E mice expressing hNF-L(E397K), which displayed muscle atrophy of the lower limbs without denervation, proximal reduction in large caliber axons, and decreased nerve conduction velocity. In this study, we challenged wild type, hNF-L and hNF-L(E397K) mice with crush injury to the sciatic nerve. We analyzed functional recovery by measuring toe spread and analyzed gait using the Catwalk system. hNF-L(E397K) mice demonstrated reduced recovery from nerve injury consistent with increased susceptibility to neuropathy observed in CMT patients. In addition, hNF-L(E397K) developed a permanent reduction in their ability to weight bear, increased mechanical allodynia, and premature gait shift in the injured limb, which led to increasingly disrupted interlimb coordination in hNF-L(E397K). Exacerbation of neuropathy after injury and identification of gait alterations in combination with previously described pathology suggests that hNF-L(E397K) mice recapitulate many of clinical signs associated with CMT2. Therefore, hNF-L(E397K) mice provide a model for determining the efficacy of novel therapies. Copyright © 2015 Elsevier B.V. All rights reserved.

Cerebral involvement in axonal Charcot-Marie-Tooth neuropathy caused by mitofusin2 mutations.

PubMed

Brockmann, Knut; Dreha-Kulaczewski, Steffi; Dechent, Peter; Bönnemann, Carsten; Helms, Gunther; Kyllerman, Marten; Brück, Wolfgang; Frahm, Jens; Huehne, Kathrin; Gärtner, Jutta; Rautenstrauss, Bernd

2008-07-01

Mutations in the mitofusin 2 (MFN2) gene are a major cause of primary axonal Charcot- Marie-Tooth (CMT) neuropathy. This study aims at further characterization of cerebral white matter alterations observed in patients with MFN2 mutations. Molecular genetic, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) investigations were performed in four unrelated patients aged 7 to 38 years with early onset axonal CMT neuropathy. Three distinct and so far undescribed MFN2 mutations were detected. Two patients had secondary macrocephaly and mild diffuse predominantly periventricular white matter alterations on MRI. In addition, one boy had symmetrical T2-hyperintensities in both thalami. Two patients had optic atrophy, one of them with normal MRI. In three patients proton MRS revealed elevated concentrations of total N-acetyl compounds (neuronal marker), total creatine (found in all cells) and myo-inositol (astrocytic marker) in cerebral white and gray matter though with regional variation. These alterations were most pronounced in the two patients with abnormal MRI. DTI of these patients revealed mild reductions of fractional anisotropy and mild increase of mean diffusivity in white matter. The present findings indicate an enhanced cellular density in cerebral white matter of MFN2 neuropathy which is primarily due to a reactive gliosis without axonal damage and possibly accompanied by mild demyelination.

Astronauts Lodewijk van den Berg observes growth of crystals in VCGS

NASA Image and Video Library

1985-04-30

51B-06-010 (29 April-6 May 1985) --- Lodewijk van den Berg, 51-B payload specialist, observes the growth of mercuric iodide crystal in the vapor crystal growth system (VCGS) on the Spacelab 3 science module aboard the Space Shuttle Challenger.

Dysregulation of ErbB Receptor Trafficking and Signaling in Demyelinating Charcot-Marie-Tooth Disease

PubMed Central

Lee, Samuel M.; Chin, Lih-Shen; Li, Lian

2016-01-01

Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy with the majority of cases involving demyelination of peripheral nerves. The pathogenic mechanisms of demyelinating CMT remain unclear, and no effective therapy currently exists for this disease. The discovery that mutations in different genes can cause a similar phenotype of demyelinating peripheral neuropathy raises the possibility that there may be convergent mechanisms leading to demyelinating CMT pathogenesis. Increasing evidence indicates that ErbB receptor-mediated signaling plays a major role in the control of Schwann cell-axon communication and myelination in the peripheral nervous system. Recent studies reveal that several demyelinating CMT-linked proteins are novel regulators of endocytic trafficking and/or phosphoinositide metabolism that may affect ErbB receptor signaling. Emerging data have begun to suggest that dysregulation of ErbB receptor trafficking and signaling in Schwann cells may represent a common pathogenic mechanism in multiple subtypes of demyelinating CMT. In this review, we focus on the roles of ErbB receptor trafficking and signaling in regulation of peripheral nerve myelination and discuss the emerging evidence supporting the potential involvement of altered ErbB receptor trafficking and signaling in demyelinating CMT pathogenesis and the possibility of modulating these trafficking and signaling processes for treating demyelinating peripheral neuropathy. PMID:26732592

Dysregulation of ErbB Receptor Trafficking and Signaling in Demyelinating Charcot-Marie-Tooth Disease.

PubMed

Lee, Samuel M; Chin, Lih-Shen; Li, Lian

2017-01-01

Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy with the majority of cases involving demyelination of peripheral nerves. The pathogenic mechanisms of demyelinating CMT remain unclear, and no effective therapy currently exists for this disease. The discovery that mutations in different genes can cause a similar phenotype of demyelinating peripheral neuropathy raises the possibility that there may be convergent mechanisms leading to demyelinating CMT pathogenesis. Increasing evidence indicates that ErbB receptor-mediated signaling plays a major role in the control of Schwann cell-axon communication and myelination in the peripheral nervous system. Recent studies reveal that several demyelinating CMT-linked proteins are novel regulators of endocytic trafficking and/or phosphoinositide metabolism that may affect ErbB receptor signaling. Emerging data have begun to suggest that dysregulation of ErbB receptor trafficking and signaling in Schwann cells may represent a common pathogenic mechanism in multiple subtypes of demyelinating CMT. In this review, we focus on the roles of ErbB receptor trafficking and signaling in regulation of peripheral nerve myelination and discuss the emerging evidence supporting the potential involvement of altered ErbB receptor trafficking and signaling in demyelinating CMT pathogenesis and the possibility of modulating these trafficking and signaling processes for treating demyelinating peripheral neuropathy.

The Advantages of Hybrid 4DEnVar in the Context of the Forecast Sensitivity to Initial Conditions

NASA Astrophysics Data System (ADS)

Song, Hyo-Jong; Shin, Seoleun; Ha, Ji-Hyun; Lim, Sujeong

2017-11-01

Hybrid four-dimensional ensemble variational data assimilation (hybrid 4DEnVar) is a prospective successor to three-dimensional variational data assimilation (3DVar) in operational weather prediction centers currently developing a new weather prediction model and those that do not operate adjoint models. In experiments using real observations, hybrid 4DEnVar improved Northern Hemisphere (NH; 20°N-90°N) 500 hPa geopotential height forecasts up to 5 days in a NH summer month compared to 3DVar, with statistical significance. This result is verified against ERA-Interim through a Monte Carlo test. By a regression analysis, the sensitivity of 5 day forecast is associated with the quality of the initial condition. The increased analysis skill for midtropospheric midlatitude temperature and subtropical moisture has the most apparent effect on forecast skill in the NH including a typhoon prediction case. Through attributing the analysis improvements by hybrid 4DEnVar separately to the ensemble background error covariance (BEC), its four-dimensional (4-D) extension, and climatological BEC, it is revealed that the ensemble BEC contributes to the subtropical moisture analysis, whereas the 4-D extension does to the midtropospheric midlatitude temperature. This result implies that hourly wind-mass correlation in 6 h analysis window is required to extract the potential of hybrid 4DEnVar for the midlatitude temperature analysis to the maximum. However, the temporal ensemble correlation, in hourly time scale, between moisture and another variable is invalid so that it could not work for improving the hybrid 4DEnVar analysis.

Sustained Expression of Negative Regulators of Myelination Protects Schwann Cells from Dysmyelination in a Charcot-Marie-Tooth 1B Mouse Model.

PubMed

Florio, Francesca; Ferri, Cinzia; Scapin, Cristina; Feltri, M Laura; Wrabetz, Lawrence; D'Antonio, Maurizio

2018-05-02

Schwann cell differentiation and myelination in the PNS are the result of fine-tuning of positive and negative transcriptional regulators. As myelination starts, negative regulators are downregulated, whereas positive ones are upregulated. Fully differentiated Schwann cells maintain an extraordinary plasticity and can transdifferentiate into "repair" Schwann cells after nerve injury. Reactivation of negative regulators of myelination is essential to generate repair Schwann cells. Negative regulators have also been implicated in demyelinating neuropathies, although their role in disease remains elusive. Here, we used a mouse model of Charcot-Marie-Tooth neuropathy type 1B (CMT1B), the P0S63del mouse characterized by ER stress and the activation of the unfolded protein response, to show that adult Schwann cells are in a partial differentiation state because they overexpress transcription factors that are normally expressed only before myelination. We provide evidence that two of these factors, Sox2 and Id2, act as negative regulators of myelination in vivo However, their sustained expression in neuropathy is protective because ablation of Sox2 or/and Id2 from S63del mice of both sexes results in worsening of the dysmyelinating phenotype. This is accompanied by increased levels of mutant P0 expression and exacerbation of ER stress, suggesting that limited differentiation may represent a novel adaptive mechanism through which Schwann cells counter the toxic effect of a mutant terminal differentiation protein. SIGNIFICANCE STATEMENT In many neuropathies, Schwann cells express high levels of early differentiation genes, but the significance of these altered expression remained unclear. Because many of these factors may act as negative regulators of myelination, it was suggested that their misexpression could contribute to dysmyelination. Here, we show that the transcription factors Sox2 and Id2 act as negative regulators of myelination in vivo , but that their sustained

Foot drop splints improve proximal as well as distal leg control during gait in Charcot-Marie-Tooth disease.

PubMed

Ramdharry, Gita M; Day, Brian L; Reilly, Mary M; Marsden, Jonathan F

2012-10-01

During walking, people with Charcot-Marie-Tooth (CMT) disease may compensate for distal weakness by using proximal muscles. We investigated the effect of different AFOs on distal leg control and proximal compensatory actions. Fourteen people with CMT were tested while wearing 3 types of ankle-foot orthosis (AFO) bilaterally compared with shoes alone. Walking was assessed using three-dimensional gait analysis. Stiffness of the splints was measured by applying controlled 5-degree ankle stretches using a motor. The results showed that each AFO significantly stiffened the ankle and increased ankle dorsiflexion at foot clearance compared with shoes alone. At push off, peak ankle power generation was reduced, but only with 1 type of AFO. A significant decrease in hip flexion amplitude during the swing phase was observed with all 3 AFOs. These results indicate that AFOs reduce foot drop and remove the need for some proximal compensatory action. Copyright © 2012 Wiley Periodicals, Inc.

Activity rhythms and distribution of natal dens for red foxes

USGS Publications Warehouse

Wenyang, Zhou; Wanhong, Wei; Biggins, Dean E.

1995-01-01

The red fox, Vulpes vulpes, was investigated with snow tracking, radiotracking and directive observation at the Haibei Research Station of Alpine Meadow Ecosystem, Academia Sinica, from March to September 1994. The objectives of this study were to determine the distribution and use of natal dens, activity rhythms, and home range sizes for the foxes.

Enhancement of DEN-induced liver tumorigenesis in heme oxygenase-1 G143H mutant transgenic mice

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

Jin, Jianfeng; Wang, Dayong; Xiao, Haifeng

Heme oxygenase (HO) is the rate-limiting enzyme in heme metabolism. HO-1 exhibits anti-oxidative and anti-inflammatory function via the actions of its metabolite, respectively. A growing body of evidence demonstrates that HO-1 is implicated in the pathogenesis and progression of several types of cancer. However, whether HO-1 takes part in healthy-premalignant-malignant transformation is still undefined. In this study, we took advantage of transgenic mice which over-expressed HO-1 dominant negative mutant (HO-1 G143H) and observed its susceptibility to DEN-induced hepatocarcinogenesis. Our results indicate that HO-1 G143H mutant accelerates the progression of tumorigenesis and tumor growth. The mechanism is closely related to enhancementmore » of ROS production which induce more hepatocytes death and secretion of inflammatory cytokines, proliferation of surviving hepatocytes. Our result provides the direct evidence that HO-1 plays an important protective role in liver carcinogenesis. Alternatively, we suggest the possible explanation on effect of HO-1 promoter polymorphism which involved in tumorigenesis. - Highlights: • Enhancement of DEN-induced hepatocarcinogenesis in HO-1 G143H Tg mice. • HO-1G143H mutant enhanced DEN-induced ROS production and liver injury. • HO-1G143H mutant aggravated DEN-induced changes of inflammatory factors and cell proliferation.« less

Is the Charcot and Bernard case (1883) of loss of visual imagery really based on neurological impairment?

PubMed

Zago, Stefano; Allegri, Nicola; Cristoffanini, Marta; Ferrucci, Roberta; Porta, Mauro; Priori, Alberto

2011-11-01

INTRODUCTION. The Charcot and Bernard case of visual imagery, Monsieur X, is a classic case in the history of neuropsychology. Published in 1883, it has been considered the first case of visual imagery loss due to brain injury. Also in recent times a neurological valence has been given to it. However, the presence of analogous cases of loss of visual imagery in the psychiatric field have led us to hypothesise functional origins rather than organic. METHODS. In order to assess the validity of such an inference, we have compared the symptomatology of Monsieur X with that found in cases of loss of visual mental images, both psychiatric and neurological, presented in literature. RESULTS. The clinical findings show strong assonances of the Monsieur X case with the symptoms manifested over time by the patients with functionally based loss of visual imagery. CONCLUSION. Although Monsieur X's damage was initially interpreted as neurological, reports of similar symptoms in the psychiatric field lead us to postulate a functional cause for his impairment as well.

Psychometric properties of DAPonDEN: definitions, attitudes and practices in relation to diarrhea during enteral nutrition questionnaire.

PubMed

Majid, Hazreen A; Bin Sidek, Muhamad Adam; Chinna, Karuthan

2013-01-01

To investigate the psychometric properties of the developed 21 item questionnaire to measure definitions, attitudes and management practices in relation to diarrhea during enteral nutrition (DAPonDEN). Data were analyzed using exploratory factor analysis from a cross sectional study of 102 nurses aged 18 and over, conducted from December 2011 to February 2012 in Malaysia. Face and content validity of DAPonDEN were first evaluated by few expert panels and patients. For this study, adult nurses were recruited from the adult wards. In the final model, three items in DAPonDEN were dropped. In the exploratory factor analysis, five factors were extracted that explained a total of 55% of the variation in the remaining 18 items. The Kaiser-Meyer-Olkin (KMO) value was 0.723. For definition, there were two underlying factors: 'Key items in defining diarrhea' and 'non-key items in defining diarrhea'. For attitude there was a single factor. For practice, there were two underlying factors: 'enteral nutrition (EN) related' and 'awareness related'. The items in each of the underlying dimensions seem to measure the respective concepts for definition, attitude and practices adequately. The 18-items DAPonDEN instrument can be a suitable education tool to be used in relation to diarrhea during EN. Copyright © 2013 Elsevier Inc. All rights reserved.

Rückwärtsintegration - Zu den Verhältnissen Gymnasium, Hochschule und Arbeitswelt

NASA Astrophysics Data System (ADS)

Schmid, Gerhard; Heppner, Winfried; Focht, Eva

In seiner 2007 erschienen Sammlung von Vorträgen und Essays beschäftigt sich Wolfgang Frühwald, mit der Frage "Wieviel Wissen brauchen wir?“ [1] Die Kernproblematik moderner Wissenschaft und Forschung sieht der Autor, emeritierter Ordinarius für Neuere Deutsche Literaturwissenschaft und von 1992 bis 1997 Präsident der Deutschen Forschungsgemeinschaft, einerseits in der zunehmenden Spezialisierung der Wissenschaftsbereiche, andererseits in der Gefahr der Abkoppelung der Naturwissenschaften von den Geisteswissenschaften. Wiederholt plädiert er dafür, über der rasanten Entwicklung beispielsweise in der Biologie und Physik, die historische, gesellschaftliche und besonders die ethische Dimension der Forschung nicht zu übersehen und fordert eine übergeordnete Theorie der Wissenschaft, die nur im Dialog zwischen den einzelnen Fachgebieten zu entwickeln sei.

CheckDen, a program to compute quantum molecular properties on spatial grids.

PubMed

Pacios, Luis F; Fernandez, Alberto

2009-09-01

CheckDen, a program to compute quantum molecular properties on a variety of spatial grids is presented. The program reads as unique input wavefunction files written by standard quantum packages and calculates the electron density rho(r), promolecule and density difference function, gradient of rho(r), Laplacian of rho(r), information entropy, electrostatic potential, kinetic energy densities G(r) and K(r), electron localization function (ELF), and localized orbital locator (LOL) function. These properties can be calculated on a wide range of one-, two-, and three-dimensional grids that can be processed by widely used graphics programs to render high-resolution images. CheckDen offers also other options as extracting separate atom contributions to the property computed, converting grid output data into CUBE and OpenDX volumetric data formats, and perform arithmetic combinations with grid files in all the recognized formats.

Endodontic retreatment of dens invaginatus presenting with gutta-percha overfilling at the attached gingiva and chronic apical periodontitis: unusual clinical report.

PubMed

Robazza, Carlos Roberto Colombo; Alves e Motta, Julio Cesar; de Carli, Marina Lara; de Oliveira Pedreira, Fernanda Rafaelly; Hanemann, Joao Adolfo Costa

2013-05-01

This work describes the retreatment of an unusual case of dens invaginatus with gutta-percha overfilling at the gingival mucosa and chronic apical periodontitis in a 34-year-old woman. Initial periapical radiograph showed the presence of type II dens invaginatus with poor quality obturation, root perforation and chronic apical periodontitis of tooth 22. Dens invaginatus is a tooth malformation caused by infolding of the dental papilla during tooth development. This anomaly has been associated with increased prevalence of pulpal and periapical diseases. Conventional endodontic retreatment was performed using rotary files and calcium hydroxide paste as intracanal dressing. After 7 days, root canal was filled with guttapercha points and Sealapex® sealer. Obturation was radiographically followed and, after 3 years, absence of fistula and periapical radiolucency was observed, thus conventional endodontic therapy proved to be successful. Conventional endodontic retreatment of type II dens invaginatus has been successful for a 3-year period, showing a better treatment alternative. Conservative endodontic retreatment of dens invaginatus should be considered to promote periapical healing with complete reconstitution of bone and periodontal ligament regeneration without signs of recurrence over a period of 3 years. Moreover, it preserves the entire tooth.

Raccoon Use of Den Trees and Plant Associations in Western Mesophytic Forests: Tree Attributes and Availability or Landscape Heterogeneity?

Treesearch

Winston P. Smith; Keith M. Endres

2012-01-01

We monitored 15 radio-collared raccoons (Procyon lotor) on Davies Island in March 1987 - May 1988 to determine the extent to which individual tree attributes or spatial configuration of plant associations (habitat types) across the land-scape influenced den use. Of 1091 verified den sites, 428 were in tree cavities. Raccoon occurrence among 4 cover...

Handwriting difficulties of children with Charcot-Marie-Tooth disease type 1A.

PubMed

Kunovsky, Daniel; Cordier, Reinie; Bray, Paula; Burns, Joshua

2017-03-01

Hand weakness and impaired manual dexterity have been reported in children with Charcot-Marie-Tooth disease type 1A (CMT1A). This early onset of upper limb involvement might explain frequent clinical referrals for assessment and treatment of impaired handwriting performance. The aim of this study was to examine the impact of CMT1A on handwriting speed and legibility, and identify demographic, anthropometric, and physical measures that might relate to handwriting performance. Handwriting speed (Handwriting Speed Test), handwriting legibility (Evaluation Tool of Children's Handwriting-Cursive), and hand strength (hand-held dynamometry of tip pinch, lateral pinch and grip) were assessed in 30 children with CMT1A (aged 8-17 years) and 30 age- and sex-matched controls. Children with CMT1A exhibited 34% slower handwriting speed (p < 0.0001) with 4% reduced legibility (p = 0.001) and 37-48% lower hand strength (p < 0.0001). All measures of strength, age, height, and weight were positively associated with handwriting speed (r = 0.39-0.79, p < 0.01). None of these factors related to handwriting legibility (p > 0.05). Regression modelling identified a diagnosis of CMT1A, lateral pinch weakness and younger age as significant independent predictors of slower handwriting speed, explaining 78% of the variance. Children with CMT1A have considerable handwriting difficulties, primarily with speed, and substantial associated hand and finger weakness. Understanding the cause-effect relationship between strength and function might provide modifiable targets for upper limb intervention. © 2016 Peripheral Nerve Society.

‘Neanderthal bone flutes’: simply products of Ice Age spotted hyena scavenging activities on cave bear cubs in European cave bear dens

PubMed Central

Diedrich, Cajus G.

2015-01-01

Punctured extinct cave bear femora were misidentified in southeastern Europe (Hungary/Slovenia) as ‘Palaeolithic bone flutes’ and the ‘oldest Neanderthal instruments’. These are not instruments, nor human made, but products of the most important cave bear scavengers of Europe, hyenas. Late Middle to Late Pleistocene (Mousterian to Gravettian) Ice Age spotted hyenas of Europe occupied mainly cave entrances as dens (communal/cub raising den types), but went deeper for scavenging into cave bear dens, or used in a few cases branches/diagonal shafts (i.e. prey storage den type). In most of those dens, about 20% of adult to 80% of bear cub remains have large carnivore damage. Hyenas left bones in repeating similar tooth mark and crush damage stages, demonstrating a butchering/bone cracking strategy. The femora of subadult cave bears are intermediate in damage patterns, compared to the adult ones, which were fully crushed to pieces. Hyenas produced round–oval puncture marks in cub femora only by the bone-crushing premolar teeth of both upper and lower jaw. The punctures/tooth impact marks are often present on both sides of the shaft of cave bear cub femora and are simply a result of non-breakage of the slightly calcified shaft compacta. All stages of femur puncturing to crushing are demonstrated herein, especially on a large cave bear population from a German cave bear den. PMID:26064624

Mechanism, Prevalence, and More Severe Neuropathy Phenotype of the Charcot-Marie-Tooth Type 1A Triplication

PubMed Central

Liu, Pengfei; Gelowani, Violet; Zhang, Feng; Drory, Vivian E.; Ben-Shachar, Shay; Roney, Erin; Medeiros, Adam C.; Moore, Rebecca J.; DiVincenzo, Christina; Burnette, William B.; Higgins, Joseph J.; Li, Jun; Orr-Urtreger, Avi; Lupski, James R.

2014-01-01

Copy-number variations cause genomic disorders. Triplications, unlike deletions and duplications, are poorly understood because of challenges in molecular identification, the choice of a proper model system for study, and awareness of their phenotypic consequences. We investigated the genomic disorder Charcot-Marie-Tooth disease type 1A (CMT1A), a dominant peripheral neuropathy caused by a 1.4 Mb recurrent duplication occurring by nonallelic homologous recombination. We identified CMT1A triplications in families in which the duplication segregates. The triplications arose de novo from maternally transmitted duplications and caused a more severe distal symmetric polyneuropathy phenotype. The recombination that generated the triplication occurred between sister chromatids on the duplication-bearing chromosome and could accompany gene conversions with the homologous chromosome. Diagnostic testing for CMT1A (n = 20,661 individuals) identified 13% (n = 2,752 individuals) with duplication and 0.024% (n = 5 individuals) with segmental tetrasomy, suggesting that triplications emerge from duplications at a rate as high as ∼1:550, which is more frequent than the rate of de novo duplication. We propose that individuals with duplications are predisposed to acquiring triplications and that the population prevalence of triplication is underascertained. PMID:24530202

Histopathological features of a patient with Charcot-Marie-Tooth disease type 2U/AD-CMTax-MARS.

PubMed

Hirano, Makito; Oka, Nobuyuki; Hashiguchi, Akihiro; Ueno, Shuichi; Sakamoto, Hikaru; Takashima, Hiroshi; Higuchi, Yujiro; Kusunoki, Susumu; Nakamura, Yusaku

2016-12-01

Charcot-Marie-Tooth (CMT) disease is a complex of peripheral nervous system disorders. CMT type 2U (CMT2U) is an autosomal dominant (AD) disease caused by mutations in the MARS gene encoding methionyl-tRNA synthetase; this disease has thus been newly called AD-CMTax-MARS. A few families with mutations in the MARS gene have been reported, without detailed histopathological findings. We describe a 70-year-old woman who had bilateral dysesthesia of the soles since the age of 66 years. Sural nerve biopsy showed a decrease in the density of large myelinated nerve fibers. Increased clusters of regenerating myelinated nerve fibers were noted. Electron microscopic analyses revealed degeneration of unmyelinated nerves. There was no vasculitis or inflammatory cell infiltration. Genetic analysis identified a heterozygous p.P800T mutation, a reported mutation in the MARS gene. We report the detailed histopathological findings in a patient with CMT2U/AD-CMTax-MARS. The findings are similar to those found in CMT2D caused by mutations in the GARS gene, encoding glycyl-tRNA synthetase. © 2016 Peripheral Nerve Society.

Charcot Marie Tooth 2B Peripheral Sensory Neuropathy: How Rab7 Mutations Impact NGF Signaling?

PubMed

Liu, Harry; Wu, Chengbiao

2017-02-04

Charcot-Marie-Tooth 2B peripheral sensory neuropathy (CMT2B) is a debilitating autosomal dominant hereditary sensory neuropathy. Patients with this disease lose pain sensation and frequently need amputation. Axonal dysfunction and degeneration of peripheral sensory neurons is a major clinical manifestation of CMT2B. However, the cellular and molecular pathogenic mechanisms remain undefined. CMT2B is caused by missense point mutations (L129F, K157N, N161T/I, V162M) in Rab7 GTPase. Strong evidence suggests that the Rab7 mutation(s) enhances the cellular levels of activated Rab7 proteins, thus resulting in increased lysosomal activity and autophagy. As a consequence, trafficking and signaling of neurotrophic factors such as nerve growth factor (NGF) in the long axons of peripheral sensory neurons are particularly vulnerable to premature degradation. A "gain of toxicity" model has, thus, been proposed based on these observations. However, studies of fly photo-sensory neurons indicate that the Rab7 mutation(s) causes a "loss of function", resulting in haploinsufficiency. In the review, we summarize experimental evidence for both hypotheses. We argue that better models (rodent animals and human neurons) of CMT2B are needed to precisely define the disease mechanisms.

Oral Health, Temporomandibular Disorder, and Masticatory Performance in Patients with Charcot-Marie-Tooth Type 2

PubMed Central

Rezende, Rejane L. S.; Bonjardim, Leonardo R.; Neves, Eduardo L. A.; Santos, Lidiane C. L.; Nunes, Paula S.; Garcez, Catarina A.; Souza, Cynthia C.; Araújo, Adriano A. S.

2013-01-01

Background. The aim of this study was to evaluate the oral health status of temporomandibular disorders (TMD) and bruxism, as well as to measure masticatory performance of subjects with Charcot-Marie-Tooth type 2 (CMT2). Methods and Results. The average number of decayed, missing, and filled teeth (DMFT) for both groups, control (CG) and CMT2, was considered low (CG = 2.46; CMT2 = 1.85, P = 0.227). The OHIP-14 score was considered low (CG = 2.86, CMT2 = 5.83, P = 0.899). The prevalence of self-reported TMD was 33.3% and 38.9% (P = 0.718) in CG and CMT2 respectively and for self-reported bruxism was 4.8% (CG) and 22.2% (CMT2), without significant difference between groups (P = 0.162). The most common clinical sign of TMD was masseter (CG = 38.1%; CMT2 = 66.7%) and temporalis (CG = 19.0%; GCMT2 = 33.3%) muscle pain. The geometric mean diameter (GMD) was not significantly different between groups (CG = 4369; CMT2 = 4627, P = 0.157). Conclusion. We conclude that the CMT2 disease did not negatively have influence either on oral health status in the presence and severity of TMD and bruxism or on masticatory performance. PMID:24391462

A Novel Missense Mutation in Peripheral Myelin Protein-22 Causes Charcot-Marie-Tooth Disease.

PubMed

Li, Li-Xi; Dong, Hai-Lin; Xiao, Bao-Guo; Wu, Zhi-Ying

2017-08-05

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. A great number of causative genes have been described in CMT, and among them, the heterozygous duplication of peripheral myelin protein-22 (PMP22) is the major cause. Although the missense mutation in PMP22 is rarely reported, it has been demonstrated to be associated with CMT. This study described a novel missense mutation of PMP22 in a Chinese family with CMT phenotype. Targeted next-generation sequencing (NGS) was used to screen the causative genes in a family featured with an autosomal dominant demyelinating form of CMT. The potential variants identified by targeted NGS were verified by Sanger sequencing and classified according to the American College of Medical Genetics and Genomics standards and guidelines. Further cell transfection studies were performed to characterize the function of the novel variant. Using targeted NGS, a novel heterozygous missense variant in PMP22 (c.320G>A, p.G107D) was identified. In vitro cell functional studies revealed that mutant PMP22 protein carrying p.G107D mutation lost the ability to reach the plasma membrane, was mainly retained in the endoplasmic reticulum, and induced cell apoptosis. This study supported the notion that missense mutations in PMP22 give rise to a CMT phenotype, possibly through a toxic gain-of-function mechanism.

Einsteins Spuren in den Archiven der Wissenschaft: Physikgeschichte

NASA Astrophysics Data System (ADS)

Marx, Werner

2005-07-01

Die Erwähnungen und Zitierungen von Einsteins Arbeiten dokumentieren lediglich den quantifizierbaren Anteil von Einsteins Beitrag zur Physik. Gleichwohl belegen sie die außergewöhnliche Resonanz und Langzeitwirkung seiner Arbeiten. Die Häufigkeit der Zitierungen entspricht nicht der allgemeinen Einschätzung ihrer Bedeutung. Insbesondere die Pionierarbeiten werden inzwischen als bekannt vorausgesetzt und nicht mehr explizit zitiert. Interessanterweise ist seine nach 1945 meist zitierte Arbeit nicht eine der Pionierarbeiten zur Quantenphysik oder Relativitätstheorie, sondern jene aus dem Jahr 1935 zum berühmten Einstein-Podolsky-Rosen-Paradoxon.

Home range, den selection and habitat use of Carolina northern flying squirrels (Glaucomys sabrinus coloratus)

USGS Publications Warehouse

Diggins, Corinne A.; Silvis, Alexander; Kelly, Christine A.; Ford, W. Mark

2017-01-01

Context: Understanding habitat selection is important for determining conservation and management strategies for endangered species. The Carolina northern flying squirrel (CNFS; Glaucomys sabrinus coloratus) is an endangered subspecies found in the high-elevation montane forests of the southern Appalachians, USA. The primary use of nest boxes to monitor CNFS has provided biased information on habitat use for this subspecies, as nest boxes are typically placed in suitable denning habitat.Aims: We conducted a radio-telemetry study on CNFS to determine home range, den site selection and habitat use at multiple spatial scales.Methods: We radio-collared 21 CNFS in 2012 and 2014–15. We tracked squirrels to diurnal den sites and during night-time activity.Key results: The MCP (minimum convex polygon) home range at 95% for males was 5.2 ± 1.2 ha and for females was 4.0 ± 0.7. The BRB (biased random bridge) home range at 95% for males was 10.8 ± 3.8 ha and for females was 8.3 ± 2.1. Den site (n = 81) selection occurred more frequently in montane conifer dominate forests (81.4%) vs northern hardwood forests or conifer–northern hardwood forests (9.9% and 8.7%, respectively). We assessed habitat selection using Euclidean distance-based analysis at the 2nd order and 3rd order scale. We found that squirrels were non-randomly selecting for habitat at both 2nd and 3rd order scales.Conclusions: At both spatial scales, CNFS preferentially selected for montane conifer forests more than expected based on availability on the landscape. Squirrels selected neither for nor against northern hardwood forests, regardless of availability on the landscape. Additionally, CNFS denned in montane conifer forests more than other habitat types.Implications: Our results highlight the importance of montane conifer to CNFS in the southern Appalachians. Management and restoration activities that increase the quality, connectivity and extent of this naturally rare forest type may be

Nonsurgical Management of an Immature Maxillary Central Incisor with Type III Dens Invaginatus Using MTA Plug: A Case Report

PubMed Central

Norouzi, Negar; Kazem, Majid; Gohari, Atefeh

2017-01-01

Dens invaginatus is a developmental anomaly, caused by deepening of the enamel organ into the dental papilla before calcification of the dental tissues. Teeth with dens invagination are susceptible to early caries and pulp necrosis within a few years of eruption or even before root end closure. This article reports two immature maxillary central incisors with type I and III dens invaginatus which had necrotic pulp and a large periradicular lesion, that were treated successfully by nonsurgical root canal treatment. After apical plug placement, the remaining space was backfilled using warm vertical gutta-percha technique and the crowns were restored by composite restoration. At 6 months of follow up the patient was asymptomatic and probing depths were less than 3 mm. In addition, the reduction in the size of apical radiolucencies was observed by radiographic examinations. This case report revealed that even type III des invaginatus with an open apex and large periapical lesion, can be treated non-surgically using MTA as an apical plug. Although this case report presents a favorable result, further studies with long term follow-up periods are encouraged to support the use of nonsurgical endodontic treatment for type III dens invaginatus. PMID:29225653

A comparison of photograph-interpreted and IfSAR-derived maps of polar bear denning habitat for the 1002 Area of the Arctic National Wildlife Refuge, Alaska

USGS Publications Warehouse

Durner, George M.; Atwood, Todd C.

2018-05-11

Polar bears (Ursus maritimus) in Alaska use the Arctic National Wildlife Refuge (ANWR) for maternal denning. Pregnant bears den in snow banks for more than 3 months in winter during which they give birth to and nurture young. Denning is one of the most vulnerable times in polar bear life history as the family group cannot simply walk away from a disturbance without jeopardizing survival of newly born cubs. The ANWR includes the “1002 Area”, a region recently opened for oil and gas exploration by the U.S. Department of the Interior (DOI). As a part of its mission, the DOI “… protects and manages the Nation's natural resources …” and is therefore responsible for conserving polar bears and encouraging development of energy potential. Because future industrial activities could overlap habitats used by denning polar bears, identifying these habitats can inform the decisions of resource managers tasked to develop resources and protect polar bears. To help inform these efforts, we qualitatively compared the distribution of denning habitat identified by two different methods: previously published habitat from manual interpretation of aerial photographs, and habitat derived by computer interrogation of interferometric synthetic aperture radar (IfSAR) digital terrain models (DTM). Because photograph-interpreted methods depicted denning habitat as a line and IfSAR-derived methods depicted habitat as a polygon, we assessed agreement between the two methods with distance measurements. We found that 77.5 percent of IfSAR-derived denning habitat (79.6 km2 ; 1.2 percent of the 6,837.0 km2 1002 Area) was within 600 m of photograph-interpreted habitat (3,026.9 km), including 53.9 percent within 200 m. This distribution differed from that of randomly distributed points, as only 49.4 percent of these occurred within 600 m of photograph-interpreted habitat, including 18.3 percent within 200 m. Both methods appear to identify the major physiographic features that polar bears

Multicolor in situ hybridization and linkage analysis order Charcot-Marie-Tooth type I (CMTIA) gene-region markers

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

Lebo, R.V.; Lynch, E.D.; Golbus, M.S.

1992-01-01

This study demonstrates a clear and current role for multicolor in situ hybridization in expediting positional cloning studies of unknown disease genes. Nine polymorphic DNA cosmids have been mapped to eight ordered locations spanning the Charcot-Marie-Tooth type 1 (CMT1A) disease gene region in distal band 17p11.2, by multicolor in situ hybridization. When used with linkage analysis, these methods have generated a fine physical map and have firmly assigned the CMT1A gene to distal band 17p11.2. Linkage analysis with four CMT1A pedigrees mapped the CMT1A gene with respect to two flanking markers. Additional loci were physically mapped and ordered by inmore » situ hybridization and analysis of phase-known recombinants in CMT1A pedigrees. These data demonstrate the ability of in situ hybridization to resolve loci within 0.5 Mb on early-metaphase chromosomes. Multicolor in situ hybridization also excluded the possibility of pericentric inversions in two unrelated patients with CMT1 and neurofibromatosis type 1. When used with pulsed-field gel electrophoresis, multicolor in situ hybridization can establish physical location, order, and distance in closely spaced chromosome loci.« less

Relationship between physical performance and quality of life in Charcot-Marie-Tooth disease: a pilot study.

PubMed

Roberts-Clarke, Daniel; Fornusek, Che; Saigal, Nidhi; Halaki, Mark; Burns, Joshua; Nicholson, Garth; Fiatarone Singh, Maria; Hackett, Daniel

2016-12-01

Charcot-Marie-Tooth (CMT) is a rare inherited peripheral neuropathy in which quality of life (QoL) is reduced compared with the general population. This paper investigates the relationship between QoL and physical performance in people with CMT with the aim of identifying avenues for future research into rehabilitation strategies. Cross-sectional data was obtained from 10 participants (5 men, 5 women, age 46 ± 13 years, height 1.7 ± 0.1 m, body mass 77 ± 17 kg) with CMT (CMT1A n = 5; CMT-X n = 3; unknown genetic origin n = 2). Participants were evaluated for QoL, falls efficacy (FES), balance, mobility, muscle strength, and power. Physical component score (PCS) of the Short Form-36 (SF-36) was significantly and directly related to higher leg press power (r = 0.75, p = 0.02). Better FES scores were significantly related to faster habitual gait speed (r = -0.70, p = 0.02), left hip abduction, and seated row strength (r = -0.68, p = 0.03; r = -0.73, p = 0.03, respectively). Future research should aim to substantiate these preliminary findings in a larger cohort and investigate whether interventions targeting muscle strength and power can improve QoL and mobility outcomes in people with CMT. © 2016 Peripheral Nerve Society.

Benefits of interval-training on fatigue and functional capacities in Charcot-Marie-Tooth disease.

PubMed

El Mhandi, Lhassan; Millet, Guillaume Y; Calmels, Paul; Richard, Antoine; Oullion, Roger; Gautheron, Vincent; Féasson, Léonard

2008-05-01

Exercise intolerance and undue fatigue are common complaints in patients with Charcot-Marie-Tooth (CMT) disease. Reduced physical ability is due directly to the disease, but it is also due to physical deconditioning. The aim of this study was to test whether 24 weeks of interval-training exercise (ITE) cycling can significantly improve physiological, neuromuscular, and functional capacities and alleviate fatigue in CMT patients. Eight CMT patients (4 CMT1A and 4 CMT2) participated in ITE for 3 nonconsecutive days per week. Cardiovascular fitness, muscle strength, fatigue resistance, and functional capacities were measured before and after 12 weeks of supervised hospital training and again after another 12 weeks of unsupervised home training. Training was well tolerated. There were significant improvements in cardiorespiratory capacities, isokinetic concentric strength, and functional ability measurements. All patients experienced an improvement in their self-reported visual analogic scale for fatigue and pain during training. However, there was no significant change in their isometric force production and indices of fatigue resistance after training. Although the improvement in exercise tolerance may be due in part to reversal of the deconditioning effect of their related sedentary lifestyle, this clinical trial suggests that ITE can benefit CMT patients especially in their functional performance and subjective perception of pain and fatigue. Moreover, the improvement observed at the end of the first supervised period ITE was maintained after the second unsupervised home period, although there was no further improvement in performance and tolerance.

Absence of NEFL in patient-specific neurons in early-onset Charcot-Marie-Tooth neuropathy.

PubMed

Sainio, Markus T; Ylikallio, Emil; Mäenpää, Laura; Lahtela, Jenni; Mattila, Pirkko; Auranen, Mari; Palmio, Johanna; Tyynismaa, Henna

2018-06-01

We used patient-specific neuronal cultures to characterize the molecular genetic mechanism of recessive nonsense mutations in neurofilament light ( NEFL ) underlying early-onset Charcot-Marie-Tooth (CMT) disease. Motor neurons were differentiated from induced pluripotent stem cells of a patient with early-onset CMT carrying a novel homozygous nonsense mutation in NEFL . Quantitative PCR, protein analytics, immunocytochemistry, electron microscopy, and single-cell transcriptomics were used to investigate patient and control neurons. We show that the recessive nonsense mutation causes a nearly total loss of NEFL messenger RNA (mRNA), leading to the complete absence of NEFL protein in patient's cultured neurons. Yet the cultured neurons were able to differentiate and form neuronal networks and neurofilaments. Single-neuron gene expression fingerprinting pinpointed NEFL as the most downregulated gene in the patient neurons and provided data of intermediate filament transcript abundancy and dynamics in cultured neurons. Blocking of nonsense-mediated decay partially rescued the loss of NEFL mRNA. The strict neuronal specificity of neurofilament has hindered the mechanistic studies of recessive NEFL nonsense mutations. Here, we show that such mutation leads to the absence of NEFL, causing childhood-onset neuropathy through a loss-of-function mechanism. We propose that the neurofilament accumulation, a common feature of many neurodegenerative diseases, mimics the absence of NEFL seen in recessive CMT if aggregation prevents the proper localization of wild-type NEFL in neurons. Our results suggest that the removal of NEFL as a proposed treatment option is harmful in humans.

Coexistence of true talon cusp and double dens invaginatus in a single tooth: a rare case report and review of the literature.

PubMed

Nu Nu Lwin, Hnin; Phyo Kyaw, Pyae; Wai Yan Myint Thu, Sai

2017-12-01

Co-occurrence of a talon cusp and double dens invaginatus is an extremely rare developmental dental anomaly. This case report represents a talon cusp with two dens invaginatus on a maxillary right lateral incisor. Early identification is needed for prevention of potential problems on the affected or opposing tooth.

Where to deliver baits for deworming urban red foxes for Echinococcus multilocularis control: new protocol for micro-habitat modeling of fox denning requirements.

PubMed

Ikeda, Takako; Yoshimura, Masashi; Onoyama, Keiichi; Oku, Yuzaburo; Nonaka, Nariaki; Katakura, Ken

2014-08-06

Deworming wild foxes by baiting with the anthelmintic praziquantel is being established as a preventive technique against environmental contamination with Echinococcus multilocularis eggs. Improvement of the cost-benefit performance of baiting treatment is required urgently to raise and maintain the efficacy of deworming. We established a spatial model of den site selection by urban red foxes, the definitive host, to specify the optimal micro-habitats for delivering baits in a new modeling approach modified for urban fox populations. The model was established for two cities (Obihiro and Sapporo) in Hokkaido, Japan, in which a sylvatic cycle of E. multilocularis is maintained. The two cities have different degrees of urbanization. The modeling process was designed to detect the best combination of key environmental factors and spatial scale that foxes pay attention to most (here named 'heeding range') when they select den sites. All possible models were generated using logistic regression analysis, with "presence" or "absence" of fox den as the objective variable, and nine landscape categories customized for urban environments as predictor variables to detect the best subset of predictors. This procedure was conducted for each of ten sizes of concentric circles from dens and control points to detect the best circle size. Out of all models generated, the most parsimonious model was selected using Akaike's Information Criterion (AIC) inspection. Our models suggest that fox dens in Obihiro are located at the center of a circle with 500 m radius including low percentages of wide roads, narrow roads, and occupied buildings, but high percentages of green covered areas; the dens in Sapporo within 300 m radius with low percentages of wide roads, occupied buildings, but high percentages of riverbeds and green covered areas. The variation of the models suggests the necessity of accumulating models for various types of cities in order to reveal the patterns of the model. Our

A Rare Bilateral Presentation of Multiple Dens Invaginatus, Shovel-Shaped Incisor and Talon Cusp With Mesiodens.

PubMed

Hegde, S; Jain, M; Shubha, A B

2014-01-01

The aim of this paper is to describe a unique and unusual case of concomitant appearance of morphological dental anomalies in the maxillary anterior region, along with its management in a patient with no systemic abnormality. This case report describes the clinical and radiographic features of talon cusp, dens invaginatus, shovel-shaped incisors and a supernumerary tooth occurring in a single patient, which is a rare presentation. All 4 permanent maxillary incisors had dens invaginatus, the permanent maxillary canines showed the presence of talon cusps, the permanent maxillary central incisors were shovel-shaped and an erupted mesiodens was also observed. Treatment included restorative, surgical and orthodontic approaches.

The Influence of the Outdoor Environment: Den-Making in Three Different Contexts

ERIC Educational Resources Information Center

Canning, Natalie

2010-01-01

This small-scale research examined den-making in three different settings in the UK. The research consisted of non-participant, narrative observations of children aged between 3- and 5-years and early years practitioners involved in supporting them in their play. Content analysis revealed common themes: the impact of the environment on the way…

SensInDenT-Noncontact Sensors Integrated Into Dental Treatment Units.

PubMed

Teichmann, Daniel; Teichmann, Maren; Weitz, Philippe; Wolfart, Stefan; Leonhardt, Steffen; Walter, Marian

2017-02-01

This paper presents the first system design (SensInDenT) for noncontact cardiorespiratory monitoring during dental treatment. The system is integrated into a dental treatment unit, and combines sensors based on electromagnetic, optical, and mechanical coupling at different sensor locations. The measurement principles and circuits are described and a system overview is presented. Furthermore, a first proof of concept is provided by taking measurements in healthy volunteers under laboratory conditions.

Long-Range Structural Effects of a Charcot-Marie-Tooth Disease-Causing Mutation in Human Glycyl-TRNA Synthetase

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

Xie, W.; Nangle, L.A.; Zhang, W.

2009-06-04

Functional expansion of specific tRNA synthetases in higher organisms is well documented. These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease, the most common heritable disease of the peripheral nervous system. At least 10 disease-causing mutant alleles of GlyRS have been annotated. These mutations scatter broadly across the primary sequence and have no apparent unifying connection. Here we report the structure of wild type and a CMT-causing mutant (G526R) of homodimeric human GlyRS. The mutation is at the site for synthesis of glycyl-adenylate, but the rest of the two structuresmore » are closely similar. Significantly, the mutant form diffracts to a higher resolution and has a greater dimer interface. The extra dimer interactions are located {approx}30 {angstrom} away from the G526R mutation. Direct experiments confirm the tighter dimer interaction of the G526R protein. The results suggest the possible importance of subtle, long-range structural effects of CMT-causing mutations at the dimer interface. From analysis of a third crystal, an appended motif, found in higher eukaryote GlyRSs, seems not to have a role in these long-range effects.« less

The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein

PubMed Central

Qin, Wenxia; Wunderley, Lydia; Barrett, Anne L.; High, Stephen; Woodman, Philip G.

2016-01-01

LITAF (LPS-induced TNF-activating factor) is an endosome-associated integral membrane protein important for multivesicular body sorting. Several mutations in LITAF cause autosomal-dominant Charcot Marie Tooth disease type 1C. These mutations map to a highly conserved C-terminal region, termed the LITAF domain, which includes a 22 residue hydrophobic sequence and flanking cysteine-rich regions that contain peptide motifs found in zinc fingers. Although the LITAF domain is thought to be responsible for membrane integration, the membrane topology of LITAF has not been established. Here, we have investigated whether LITAF is a tail-anchored (TA) membrane-spanning protein or monotopic membrane protein. When translated in vitro, LITAF integrates poorly into ER-derived microsomes compared with Sec61β, a bona fide TA protein. Furthermore, introduction of N-linked glycosylation reporters shows that neither the N-terminal nor C-terminal domains of LITAF translocate into the ER lumen. Expression in cells of an LITAF construct containing C-terminal glycosylation sites confirms that LITAF is not a TA protein in cells. Finally, an immunofluorescence-based latency assay showed that both the N- and C-termini of LITAF are exposed to the cytoplasm. Recombinant LITAF contains 1 mol/mol zinc, while mutation of predicted zinc-binding residues disrupts LITAF membrane association. Hence, we conclude that LITAF is a monotopic membrane protein whose membrane integration is stabilised by a zinc finger. The related human protein, CDIP1 (cell death involved p53 target 1), displays identical membrane topology, suggesting that this mode of membrane integration is conserved in LITAF family proteins. PMID:27582497

Evaluation Studies of the DEN-2/S-1 Vaccine.

DTIC Science & Technology

1981-08-01

1.0 3.0, L o 1 .0 I11 125 11111 1.4 n .6_t _ MICROCOPY RESOLUTION TEST CHART NATIONAL WII ALI 0 MF S’ANDAkLT, ,’I, A ;40- AD EVALUATION STUDIES OF THE...monkeys Vaccination DEN-2/S-l Vaccine /AE TlhACT ( i - ,ewr e e1 If .,ceweu7 amd Iderdtlfy by block number) A dengue-2 live virus vaccine was tested in...viremia was detected in control animals. Serological tests were pi.r- formed on sera taken on post infection days 30,56 and 90. HI tests revealed sero

A cost-effective traffic data collection system based on the iDEN mobile telecommunication network.

DOT National Transportation Integrated Search

2008-10-01

This report describes a cost-effective data collection system for Caltrans 170 traffic signal : controller. The data collection system is based on TCP/IP communication over existing : low-cost mobile communication networks and Motorola iDEN1 mobile...

Wie verstehen Schülerinnen und Schüler den Begriff der Unendlichkeit?

NASA Astrophysics Data System (ADS)

Schimmöller, Tabea

Wie Hilbert bereits feststellte, wirkt die Idee der Unendlichkeit, wie keine andere, schon seit Zeiten sehr anregend und fruchtbar auf den Verstand und bewegt das Gemüt der Menschen. Der Begriff der Unendlichkeit bedarf aber auch, wie kein anderer, der Aufklärung, denn mit ihm eröffnet sich ein weites Feld, welches nicht nur aus vielen verschiedenen Definitionen besteht, sondern auch aus völlig unterschiedlichen Disziplinen. Physiker suchen immer dringender nach einer "Theorie für Alles" oder einer "Weltformel", Kosmologen beschäftigen sich unter anderem mit der Ewigkeit des Universums, Theologen interessiert eher die Unendlichkeit Gottes, Philosophen diskutieren unter anderem Grenzfragen zwischen Naturwissenschaft und Philosophie und die Mathematiker versuchen den Paradoxien des Unendlichen einen Sinn zu geben. Und so wird ersichtlich, dass nichts abstrakter ist als das Unendliche: Obwohl die Unendlichkeit für die unterschiedlichsten Wissenschaften von großer Bedeutung ist, "[ist] in der Wirklichkeit das Unendliche nirgends zu finden, [egal] was für Erfahrungen und Beobachtungen und welcherlei Wissenschaft wir auch heranziehen".

The genomic structure of the human Charcot-Leyden crystal protein gene is analogous to those of the galectin genes

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

Dyer, K.D.; Handen, J.S.; Rosenberg, H.F.

The Charcot-Leyden crystal (CLC) protein, or eosinophil lysophospholipase, is a characteristic protein of human eosinophils and basophils; recent work has demonstrated that the CLC protein is both structurally and functionally related to the galectin family of {beta}-galactoside binding proteins. The galectins as a group share a number of features in common, including a linear ligand binding site encoded on a single exon. In this work, we demonstrate that the intron-exon structure of the gene encoding CLC is analogous to those encoding the galectins. The coding sequence of the CLC gene is divided into four exons, with the entire {beta}-galactoside bindingmore » site encoded by exon III. We have isolated CLC {beta}-galactoside binding sites from both orangutan (Pongo pygmaeus) and murine (Mus musculus) genomic DNAs, both encoded on single exons, and noted conservation of the amino acids shown to interact directly with the {beta}-galactoside ligand. The most likely interpretation of these results suggests the occurrence of one or more exon duplication and insertion events, resulting in the distribution of this lectin domain to CLC as well as to the multiple galectin genes. 35 refs., 3 figs.« less

Partial complementation of the UV sensitivity of E. coli and yeast excision repair mutants by the cloned denV gene of bacteriophage T4.

PubMed

Chenevert, J M; Naumovski, L; Schultz, R A; Friedberg, E C

1986-04-01

The denV gene of bacteriophage T4 was reconstituted from two overlapping DNA fragments cloned in M13 vectors. The coding region of the intact gene was tailored into a series of plasmid vectors containing different promoters suitable for expression of the gene in E. coli and in yeast. Induction of the TAC promoter with IPTG resulted in overexpression of the gene, which was lethal to E. coli. Expression of the TACdenV gene in the absence of IPTG, or the use of the yeast GAL1 or ADH promoters resulted in partial complementation of the UV sensitivity of uvrA, uvrB, uvrC and recA mutants of E. coli and rad1, rad2, rad3, rad4 and rad10 mutants of S. cerevisiae. The extent of denV-mediated reactivation of excision-defective mutants was approximately equal to that of photoreactivation of such strains. Excision proficient E. coli cells transformed with a plasmid containing the denV gene were slightly more resistant to ultraviolet (UV) radiation than control cells without the denV gene. On the other hand, excision proficient yeast cells were slightly more sensitive to killing by UV radiation following transformation with a plasmid containing the denV gene. This effect was more pronounced in yeast mutants of the RAD52 epistasis group.

Reconnaissance study of late quaternary faulting along cerro GoDen fault zone, western Puerto Rico

USGS Publications Warehouse

Mann, P.; Prentice, C.S.; Hippolyte, J.-C.; Grindlay, N.R.; Abrams, L.J.; Lao-Davila, D.

2005-01-01

The Cerro GoDen fault zone is associated with a curvilinear, continuous, and prominent topographic lineament in western Puerto Rico. The fault varies in strike from northwest to west. In its westernmost section, the fault is ???500 m south of an abrupt, curvilinear mountain front separating the 270- to 361-m-high La CaDena De San Francisco range from the Rio A??asco alluvial valley. The Quaternary fault of the A??asco Valley is in alignment with the bedrock fault mapped by D. McIntyre (1971) in the Central La Plata quadrangle sheet east of A??asco Valley. Previous workers have postulated that the Cerro GoDen fault zone continues southeast from the A??asco Valley and merges with the Great Southern Puerto Rico fault zone of south-central Puerto Rico. West of the A??asco Valley, the fault continues offshore into the Mona Passage (Caribbean Sea) where it is characterized by offsets of seafloor sediments estimated to be of late Quaternary age. Using both 1:18,500 scale air photographs taken in 1936 and 1:40,000 scale photographs taken by the U.S. Department of Agriculture in 1986, we iDentified geomorphic features suggestive of Quaternary fault movement in the A??asco Valley, including aligned and Deflected drainages, apparently offset terrace risers, and mountain-facing scarps. Many of these features suggest right-lateral displacement. Mapping of Paleogene bedrock units in the uplifted La CaDena range adjacent to the Cerro GoDen fault zone reveals the main tectonic events that have culminated in late Quaternary normal-oblique displacement across the Cerro GoDen fault. Cretaceous to Eocene rocks of the La CaDena range exhibit large folds with wavelengths of several kms. The orientation of folds and analysis of fault striations within the folds indicate that the folds formed by northeast-southwest shorTening in present-day geographic coordinates. The age of Deformation is well constrained as late Eocene-early Oligocene by an angular unconformity separating folDed, Deep

Myelin protein zero gene sequencing diagnoses Charcot-Marie-Tooth Type 1B disease

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

Su, Y.; Zhang, H.; Madrid, R.

1994-09-01

Charcot-Marie-Tooth disease (CMT), the most common genetic neuropathy, affects about 1 in 2600 people in Norway and is found worldwide. CMT Type 1 (CMT1) has slow nerve conduction with demyelinated Schwann cells. Autosomal dominant CMT Type 1B (CMT1B) results from mutations in the myelin protein zero gene which directs the synthesis of more than half of all Schwann cell protein. This gene was mapped to the chromosome 1q22-1q23.1 borderline by fluorescence in situ hybridization. The first 7 of 7 reported CMT1B mutations are unique. Thus the most effective means to identify CMT1B mutations in at-risk family members and fetuses ismore » to sequence the entire coding sequence in dominant or sporadic CMT patients without the CMT1A duplication. Of the 19 primers used in 16 pars to uniquely amplify the entire MPZ coding sequence, 6 primer pairs were used to amplify and sequence the 6 exons. The DyeDeoxy Terminator cycle sequencing method used with four different color fluorescent lables was superior to manual sequencing because it sequences more bases unambiguously from extracted genomic DNA samples within 24 hours. This protocol was used to test 28 CMT and Dejerine-Sottas patients without CMT1A gene duplication. Sequencing MPZ gene-specific amplified fragments identified 9 polymorphic sites within the 6 exons that encode the 248 amino acid MPZ protein. The large number of major CMT1B mutations identified by single strand sequencing are being verified by reverse strand sequencing and when possible, by restriction enzyme analysis. This protocol can be used to distringuish CMT1B patients from othre CMT phenotypes and to determine the CMT1B status of relatives both presymptomatically and prenatally.« less

Whole Genome Sequencing Identifies a 78 kb Insertion from Chromosome 8 as the Cause of Charcot-Marie-Tooth Neuropathy CMTX3

PubMed Central

Brewer, Megan H.; Chaudhry, Rabia; Qi, Jessica; Kidambi, Aditi; Drew, Alexander P.; Ryan, Monique M.; Subramanian, Gopinath M.; Young, Helen K.; Zuchner, Stephan; Reddel, Stephen W.; Nicholson, Garth A.; Kennerson, Marina L.

2016-01-01

With the advent of whole exome sequencing, cases where no pathogenic coding mutations can be found are increasingly being observed in many diseases. In two large, distantly-related families that mapped to the Charcot-Marie-Tooth neuropathy CMTX3 locus at chromosome Xq26.3-q27.3, all coding mutations were excluded. Using whole genome sequencing we found a large DNA interchromosomal insertion within the CMTX3 locus. The 78 kb insertion originates from chromosome 8q24.3, segregates fully with the disease in the two families, and is absent from the general population as well as 627 neurologically normal chromosomes from in-house controls. Large insertions into chromosome Xq27.1 are known to cause a range of diseases and this is the first neuropathy phenotype caused by an interchromosomal insertion at this locus. The CMTX3 insertion represents an understudied pathogenic structural variation mechanism for inherited peripheral neuropathies. Our finding highlights the importance of considering all structural variation types when studying unsolved inherited peripheral neuropathy cases with no pathogenic coding mutations. PMID:27438001

Charcot-Marie-Tooth disease type 2 caused by homozygous MME gene mutation superimposed by chronic inflammatory demyelinating polyneuropathy.

PubMed

Fujisawa, Miwako; Sano, Yasuteru; Omoto, Masatoshi; Ogasawara, Jyun-Ichi; Koga, Michiaki; Takashima, Hiroshi; Kanda, Takashi

2017-09-30

We report a 59-year-old Japanese male who developed gradually worsening weakness and numbness of distal four extremities since age 50. His parents were first cousins, and blood and cerebral spinal examinations were unremarkable. Homozygous mutation of MME gene was detected and thus he was diagnosed as autosomal-recessive Charcot-Marie-Tooth disease 2T (AR-CMT2T); however, electrophysiological examinations revealed scattered demyelinative changes including elongated terminal latency in several peripheral nerve trunks. Sural nerve biopsy showed endoneurial edema and a lot of thinly myelinated nerve fibers with uneven distribution of remnant myelinated fibers within and between fascicles. Immunoglobulin treatment was initiated considering the possibility of superimposed inflammation and demyelination, and immediate clinical as well as electrophysiological improvements were noted. Our findings indicate that AR-CMT2T caused by MME mutation predisposes to a superimposed inflammatory demyelinating neuropathy. This is the first report which documented the co-existence of CMT2 and chronic inflammatory demyelinating polyneuropathy (CIDP); however, in the peripheral nervous system, neprilysin, a product of MME gene, is more abundant in myelin sheath than in axonal component. The fragility of myelin sheath due to mutated neprilysin may trigger the detrimental immune response against peripheral myelin in this patient.

Clinical, neurophysiological and morphological study of dominant intermediate Charcot-Marie-Tooth type C neuropathy.

PubMed

Thomas, Florian P; Guergueltcheva, Velina; Gondim, Francisco A A; Tournev, Ivailo; Rao, Chitharanjan V; Ishpekova, Boryana; Kinsella, Laurence J; Pan, Yi; Geller, Thomas J; Litvinenko, Ivan; De Jonghe, Peter; Scherer, Steven S; Jordanova, Albena

2016-03-01

Dominant intermediate Charcot-Marie-Tooth neuropathy subtype C (DI-CMTC) was associated with mutations in the YARS gene, encoding tyrosyl-tRNA synthetase, in two large unrelated Bulgarian and US pedigrees and one sporadic case. Here for the first time we describe the clinical, neurophysiological and histopathological features, and phenotypic differences between these two DI-CMTC families. Twenty-one affected individuals from the US family and 27 from the Bulgarian family were evaluated. The mean age of onset in US subjects was 10.7 years in men and 7.3 years in women, while in the Bulgarian participants it was 18.2 years in men and 33.7 years in women. The course was slowly progressive. Extensor digitorum brevis atrophy was uniform. Atrophy and/or weakness of upper and lower limb muscles were found in over 50 % of the subjects. Nerve conduction studies (NCS) were abnormal in all US adults and five of six children and all Bulgarian patients except one asymptomatic 25-year-old man. Median motor NCS were in the range of 29.5-45.6 m/s in the US family and 24.7-57.8 m/s in the Bulgarian family. Sural sensory nerve action potentials were absent in 14/21 and 4/12 NCS from adult US and Bulgarian participants, respectively. Analysis of sural nerve biopsies from US patients revealed age-dependent morphological changes of axonal degeneration, absence of onion bulbs, and <10 % fibers with segmental remyelination. Our findings provide further insights into the diagnosis and pathology of intermediate CMT. They also extend the phenotypic spectrum of peripheral neuropathies associated with aminoacyl-tRNA synthetase mutations.

MARS variant associated with both recessive interstitial lung and liver disease and dominant Charcot-Marie-Tooth disease.

PubMed

Rips, Jonathan; Meyer-Schuman, Rebecca; Breuer, Oded; Tsabari, Reuven; Shaag, Avraham; Revel-Vilk, Shoshana; Reif, Shimon; Elpeleg, Orly; Antonellis, Anthony; Harel, Tamar

2018-04-12

Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed enzymes responsible for charging tRNA with cognate amino acids during protein translation. Non-canonical functions are increasingly recognized, and include transcription and translation control and extracellular signaling. Monoallelic mutations in genes encoding several ARSs have been identified in axonal Charcot-Marie-Tooth (CMT2) disease, whereas biallelic mutations in ARS loci have been associated with multi-tissue syndromes, variably involving the central nervous system, lung, and liver. We report a male infant of non-consanguineous origin, presenting with successive onset of transfusion-dependent anemia, hypothyroidism, cholestasis, interstitial lung disease, and developmental delay. Whole-exome sequencing (WES) revealed compound heterozygosity for two variants (p.Tyr307Cys and p.Arg618Cys) in MARS, encoding methionyl-tRNA synthetase. Biallelic MARS mutations are associated with interstitial lung and liver disease (ILLD). Interestingly, the p.Arg618Cys variant, inherited from an unaffected father, was previously reported in a family with autosomal dominant late-onset CMT2. Yeast complementation assays confirmed pathogenicity of p.Arg618Cys, yet suggested retained function of p.Tyr307Cys. Our findings underscore the phenotypic variability associated with ARS mutations, and suggest genetic or environmental modifying factors in the onset of monoallelic MARS-associated CMT2. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Two Novel Mutations in the GDAP1 and PRX Genes in Early Onset Charcot-Marie-Tooth Syndrome

PubMed Central

Auer-Grumbach, M.; Fischer, C.; Papić, L.; John, E.; Plecko, B.; Bittner, R. E.; Bernert, G.; Pieber, T. R.; Miltenberger, G.; Schwarz, R.; Windpassinger, C.; Grill, F.; Timmerman, V.; Speicher, M. R.; Janecke, A. R.

2011-01-01

Autosomal recessive Charcot-Marie-Tooth syndrome (AR-CMT) is often characterised by an infantile disease onset and a severe phenotype. Mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene are thought to be a common cause of AR-CMT. Mutations in the periaxin (PRX) gene are rare. They are associated with severe demyelination of the peripheral nerves and sometimes lead to prominent sensory disturbances. To evaluate the frequency of GDAP1 and PRX mutations in early onset CMT, we examined seven AR-CMT families and 12 sporadic CMT patients, all presenting with progressive distal muscle weakness and wasting. In one family also prominent sensory abnormalities and sensory ataxia were apparent from early childhood. In three families we detected four GDAP1 mutations (L58LfsX4, R191X, L239F and P153L), one of which is novel and is predicted to cause a loss of protein function. In one additional family with prominent sensory abnormalities a novel homozygous PRX mutation was found (A700PfsX17). No mutations were identified in 12 sporadic cases. This study suggests that mutations in the GDAP1 gene are a common cause of early-onset AR-CMT. In patients with early-onset demyelinating AR-CMT and severe sensory loss PRX is one of the genes to be tested. PMID:18504680

DensToolKit: A comprehensive open-source package for analyzing the electron density and its derivative scalar and vector fields

NASA Astrophysics Data System (ADS)

Solano-Altamirano, J. M.; Hernández-Pérez, Julio M.

2015-11-01

DensToolKit is a suite of cross-platform, optionally parallelized, programs for analyzing the molecular electron density (ρ) and several fields derived from it. Scalar and vector fields, such as the gradient of the electron density (∇ρ), electron localization function (ELF) and its gradient, localized orbital locator (LOL), region of slow electrons (RoSE), reduced density gradient, localized electrons detector (LED), information entropy, molecular electrostatic potential, kinetic energy densities K and G, among others, can be evaluated on zero, one, two, and three dimensional grids. The suite includes a program for searching critical points and bond paths of the electron density, under the framework of Quantum Theory of Atoms in Molecules. DensToolKit also evaluates the momentum space electron density on spatial grids, and the reduced density matrix of order one along lines joining two arbitrary atoms of a molecule. The source code is distributed under the GNU-GPLv3 license, and we release the code with the intent of establishing an open-source collaborative project. The style of DensToolKit's code follows some of the guidelines of an object-oriented program. This allows us to supply the user with a simple manner for easily implement new scalar or vector fields, provided they are derived from any of the fields already implemented in the code. In this paper, we present some of the most salient features of the programs contained in the suite, some examples of how to run them, and the mathematical definitions of the implemented fields along with hints of how we optimized their evaluation. We benchmarked our suite against both a freely-available program and a commercial package. Speed-ups of ˜2×, and up to 12× were obtained using a non-parallel compilation of DensToolKit for the evaluation of fields. DensToolKit takes similar times for finding critical points, compared to a commercial package. Finally, we present some perspectives for the future development and

Muscle spindle alterations precede onset of sensorimotor deficits in Charcot-Marie-Tooth type 2E.

PubMed

Villalón, E; Jones, M R; Sibigtroth, C; Zino, S J; Dale, J M; Landayan, D S; Shen, H; Cornelison, D D W; Garcia, M L

2017-02-01

Charcot-Marie-Tooth (CMT) is the most common inherited peripheral neuropathy, affecting approximately 2.8 million people. The CMT leads to distal neuropathy that is characterized by reduced motor nerve conduction velocity, ataxia, muscle atrophy and sensory loss. We generated a mouse model of CMT type 2E (CMT2E) expressing human neurofilament light E396K (hNF-L E396K ), which develops decreased motor nerve conduction velocity, ataxia and muscle atrophy by 4 months of age. Symptomatic hNF-L E396K mice developed phenotypes that were consistent with proprioceptive sensory defects as well as reduced sensitivity to mechanical stimulation, while thermal sensitivity and auditory brainstem responses were unaltered. Progression from presymptomatic to symptomatic included a 50% loss of large diameter sensory axons within the fifth lumbar dorsal root of hNF-L E396K mice. Owing to proprioceptive deficits and loss of large diameter sensory axons, we analyzed muscle spindle morphology in presymptomatic and symptomatic hNF-L E396K and hNF-L control mice. Muscle spindle cross-sectional area and volume were reduced in all hNF-L E396K mice analyzed, suggesting that alterations in muscle spindle morphology occurred prior to the onset of typical CMT pathology. These data suggested that CMT2E pathology initiated in the muscle spindles altering the proprioceptive sensory system. Early sensory pathology in CMT2E could provide a unifying hypothesis for the convergence of pathology observed in CMT. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Analysis of neural crest cells from Charcot-Marie-Tooth disease patients demonstrates disease-relevant molecular signature.

PubMed

Kitani-Morii, Fukiko; Imamura, Keiko; Kondo, Takayuki; Ohara, Ryo; Enami, Takako; Shibukawa, Ran; Yamamoto, Takuya; Sekiguchi, Kazuya; Toguchida, Junya; Mizuno, Toshiki; Nakagawa, Masanori; Inoue, Haruhisa

2017-09-06

Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy. The majority of CMT is demyelinating type (demyelinating CMT) caused by Schwann cell involvement. Although a large number of genes responsible for demyelinating CMT have been found, the common molecular target of the pathophysiology caused by these different genes in demyelinating CMT is still unknown. We generated induced pluripotent stem cells (iPSCs) from healthy controls and patients with demyelinating CMT caused by duplication in peripheral myelin protein 22 kDa (PMP22) or point mutations in myelin protein zero (MPZ) or early growth response 2 (EGR2). iPSCs were differentiated into neural crest cells, progenitors of Schwann cells, followed by purification using the neural crest cell markers p75 and human natural killer-1. To identify a disease-relevant molecular signature at the early stage of demyelinating CMT, we conducted global gene expression analysis of iPSC-derived neural crest cells and found that a glutathione-mediated detoxification pathway was one of the related pathways in demyelinating CMT. mRNA expression of glutathione S-transferase theta 2 (GSTT2), encoding an important enzyme for glutathione-mediated detoxification, and production of reactive oxygen species were increased in demyelinating CMT. Our study suggested that patient-iPSC-derived neural crest cells could be a cellular model for investigating genetically heterogeneous disease CMT and might provide a therapeutic target for the disease.

Modes of thermal protection in polar bear cubs--at birth and on emergence from the den.

PubMed

Blix, A S; Lentfer, J W

1979-01-01

At birth in late December the polar bear is small (700 g), uninsulated, and helpless. It probably has a modest capacity for metabolic heat production and depends on the female and a snow den in which it is born for thermal protection. The microclimate of an artificial polar bear den was investigated at Point Barrow, AK, and the temperature therein found to stay around 0 degrees C provided a heat source (200 W) equivalent to an adult polar bear was introduced. When the bears desert the den in early April the cub has grown to about 10 kg and has a well-developed fur insulation, but almost no subcutaneous fat. The cub has a high resting metabolic rate (4.6 W.kg-1), which is supported by the fat polar bear milk. Its lower critical temperature is about -30 degrees C, and an ambient temperature of -45 degrees C results in only a 33% increase in metabolism. The cub can tolerate a wind chill of 2.3 kW.m2 without apparent stress of drop in rectal temperature. If the cub is immersed in ice water rectal temperature drops 11 degrees C in 30 min. It is concluded that the cub can tolerate extremely low temperatures in air due to fur insulation and high metabolic heat production, but is unable to cope with the chill of ice water for any prolonged period of time.

DenInv3D: a geophysical software for three-dimensional density inversion of gravity field data

NASA Astrophysics Data System (ADS)

Tian, Yu; Ke, Xiaoping; Wang, Yong

2018-04-01

This paper presents a three-dimensional density inversion software called DenInv3D that operates on gravity and gravity gradient data. The software performs inversion modelling, kernel function calculation, and inversion calculations using the improved preconditioned conjugate gradient (PCG) algorithm. In the PCG algorithm, due to the uncertainty of empirical parameters, such as the Lagrange multiplier, we use the inflection point of the L-curve as the regularisation parameter. The software can construct unequally spaced grids and perform inversions using such grids, which enables changing the resolution of the inversion results at different depths. Through inversion of airborne gradiometry data on the Australian Kauring test site, we discovered that anomalous blocks of different sizes are present within the study area in addition to the central anomalies. The software of DenInv3D can be downloaded from http://159.226.162.30.

Conservative Management of Dens Evaginatus: Report of Two Unusual Cases

PubMed Central

Vijaykumar, S; Tenny, J; Ravi, GR

2010-01-01

ABSTRACT Dens evaginatus (DE) is a rare developmental anomaly characterized by presence of an extra cusp arising from occlusal or lingual surfaces. Isolated occurrence or concomitant presence of DE with other dental anomalies has been reported. DE commonly affects permanent teeth and is rarely seen in primary dentition. Treatment may be conservative or radical. This article presents two unusual cases of concomitant occurrence of a supernumerary tooth and DE affecting maxillary deciduous lateral incisor and conservative management of DE occurring concurrently with a possible Oehler’s type I invagination in maxillary permanent lateral incisor. PMID:27507925

Steppe lion remains imported by Ice Age spotted hyenas into the Late Pleistocene Perick Caves hyena den in northern Germany

NASA Astrophysics Data System (ADS)

Diedrich, Cajus G.

2009-05-01

Upper Pleistocene remains of the Ice Age steppe lion Panthera leo spelaea (Goldfuss, 1810) have been found in the Perick Caves, Sauerland Karst, NW Germany. Bones from many hyenas and their imported prey dating from the Lower to Middle Weichselian have also been recovered from the Perick Cave hyena den. These are commonly cracked or exhibit deep chew marks. The absence of lion cub bones, in contrast to hyena and cave bear cub remains in the Perick Caves, and other caves of northern Germany, excludes the possibility that P. leo spelaea used the cave for raising cubs. Only in the Wilhelms Cave was a single skeleton of a cub found in a hyena den. Evidence of the chewing, nibbling and cracking of lion bones and crania must have resulted from the importation and destruction of lion carcasses (4% of the prey fauna). Similar evidence was preserved at other hyena den caves and open air sites in Germany. The bone material from the Perick and other Central European caves points to antagonistic hyena and lion conflicts, similar to clashes of their modern African relatives.

Protective Effect of Ethanolic Extract of Tabernaemontana divaricata (L.) R. Br. against DEN and Fe NTA Induced Liver Necrosis in Wistar Albino Rats

PubMed Central

2014-01-01

This study is an attempt to evaluate the hepatoprotective activity of Tabernaemontana divaricata against DEN and Fe NTA induced liver necrosis in rats. Ethanolic extract of the whole plant of Tabernaemontana divaricata at doses of 200 and 400 mg/kg body weight and 5-fluorouracil (standard drug) was orally administered to male Wistar Albino rats once daily for 24 weeks, simultaneously treated with the carcinogen DEN and Fe NTA. In simultaneously treated animals, the plant extract significantly decreased the levels of uric acid, bilirubin, AST, ALT, and ALP in serum and increased the levels of liver marker enzymes in liver. Treatment with the extracts resulted in a significant increase in the levels of antioxidants accompanied by a marked reduction in the levels of malondialdehyde when compared to DEN and Fe NTA treated group. When compared with 200 mg/kg bw rats, 400 mg/kg bw rats and 5-fluorouracil treated rats showed better results in all the parameters. The histopathological studies confirmed the protective effects of extract against DEN and Fe NTA induced liver necrosis. Thus, it could be concluded that the use of Tabernaemontana divaricata extract in the treatment of carcinogen induced hepatic necrosis. PMID:25136566

Joint DEnKF-albedo assimilation scheme that considers the common land model subgrid heterogeneity and a snow density-based observation operator for improving snow depth simulations

NASA Astrophysics Data System (ADS)

Xu, Jianhui; Zhang, Feifei; Zhao, Yi; Shu, Hong; Zhong, Kaiwen

2016-07-01

For the large-area snow depth (SD) data sets with high spatial resolution in the Altay region of Northern Xinjiang, China, we present a deterministic ensemble Kalman filter (DEnKF)-albedo assimilation scheme that considers the common land model (CoLM) subgrid heterogeneity. In the albedo assimilation of DEnKF-albedo, the assimilated albedos over each subgrid tile are estimated with the MCD43C1 bidirectional reflectance distribution function (BRDF) parameters product and CoLM calculated solar zenith angle. The BRDF parameters are hypothesized to be consistent over all subgrid tiles within a specified grid. In the SCF assimilation of DEnKF-albedo, a DEnKF combining a snow density-based observation operator considers the effects of the CoLM subgrid heterogeneity and is employed to assimilate MODIS SCF to update SD states over all subgrid tiles. The MODIS SCF over a grid is compared with the area-weighted sum of model predicted SCF over all the subgrid tiles within the grid. The results are validated with in situ SD measurements and AMSR-E product. Compared with the simulations, the DEnKF-albedo scheme can reduce errors of SD simulations and accurately simulate the seasonal variability of SD. Furthermore, it can improve simulations of SD spatiotemporal distribution in the Altay region, which is more accurate and shows more detail than the AMSR-E product.

PFN2 and GAMT as common molecular determinants of axonal Charcot-Marie-Tooth disease.

PubMed

Juneja, Manisha; Azmi, Abdelkrim; Baets, Jonathan; Roos, Andreas; Jennings, Matthew J; Saveri, Paola; Pisciotta, Chiara; Bernard-Marissal, Nathalie; Schneider, Bernard L; Verfaillie, Catherine; Chrast, Roman; Seeman, Pavel; Hahn, Angelika F; de Jonghe, Peter; Maudsley, Stuart; Horvath, Rita; Pareyson, Davide; Timmerman, Vincent

2018-02-15

Charcot-Marie-Tooth type 2 (CMT2) neuropathy is characterised by a vast clinical and genetic heterogeneity complicating its diagnosis and therapeutic intervention. Identification of molecular signatures that are common to multiple CMT2 subtypes can aid in developing therapeutic strategies and measuring disease outcomes. A proteomics-based approach was performed on lymphoblasts from CMT2 patients genetically diagnosed with different gene mutations to identify differentially regulated proteins. The candidate proteins were validated through real-time quantitative PCR and western blotting on lymphoblast samples of patients and controls, motor neurons differentiated from patient-derived induced pluripotent stem cells (iPSCs) and sciatic nerves of CMT2 mouse models. Proteomic profiling of patient lymphoblasts resulted in the identification of profilin 2 (PFN2) and guanidinoacetate methyltransferase (GAMT) as commonly downregulated proteins in different genotypes compared with healthy controls. This decrease was also observed at the transcriptional level on screening 43 CMT2 patients and 22 controls, respectively. A progressive decrease in PFN2 expression with age was observed in patients, while in healthy controls its expression increased with age. Reduced PFN2 expression was also observed in motor neurons differentiated from CMT2 patient-derived iPSCs and sciatic nerves of CMT2 mice when compared with controls. However, no change in GAMT levels was observed in motor neurons and CMT2 mouse-derived sciatic nerves. We unveil PFN2 and GAMT as molecular determinants of CMT2 with possible indications of the role of PFN2 in the pathogenesis and disease progression. This is the first study describing biomarkers that can boost the development of therapeutic strategies targeting a wider spectrum of CMT2 patients. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise

Bicyclic-Capped Histone Deacetylase 6 Inhibitors with Improved Activity in a Model of Axonal Charcot-Marie-Tooth Disease.

PubMed

Shen, Sida; Benoy, Veronick; Bergman, Joel A; Kalin, Jay H; Frojuello, Mariana; Vistoli, Giulio; Haeck, Wanda; Van Den Bosch, Ludo; Kozikowski, Alan P

2016-02-17

Charcot-Marie-Tooth (CMT) disease is a disorder of the peripheral nervous system where progressive degeneration of motor and sensory nerves leads to motor problems and sensory loss and for which no pharmacological treatment is available. Recently, it has been shown in a model for the axonal form of CMT that histone deacetylase 6 (HDAC6) can serve as a target for the development of a pharmacological therapy. Therefore, we aimed at developing new selective and activity-specific HDAC6 inhibitors with improved biochemical properties. By utilizing a bicyclic cap as the structural scaffold from which to build upon, we developed several analogues that showed improved potency compared to tubastatin A while maintaining excellent selectivity compared to HDAC1. Further screening in N2a cells examining both the acetylation of α-tubulin and histones narrowed down the library of compounds to three potent and selective HDAC6 inhibitors. In mutant HSPB1-expressing DRG neurons, serving as an in vitro model for CMT2, these inhibitors were able to restore the mitochondrial axonal transport deficits. Combining structure-based development of HDAC6 inhibitors, screening in N2a cells and in a neuronal model for CMT2F, and preliminary ADMET and pharmacokinetic profiles, resulted in the selection of compound 23d that possesses improved biochemical, functional, and druglike properties compared to tubastatin A.

Conspecific scent trailing by garter snakes (Thamnophis sirtalis) during autumn Further evidence for use of pheromones in den location.

PubMed

Costanzo, J P

1989-11-01

Adult garter snakes (Thamnophis sirtalis), collected in October near a traditional, communal hibernaculum in central Wisconsin, were acclimated to autumnal conditions and subjected to laboratory tests to determine whether they could follow scent trails of a conspecific. Graded responses were obtained, but 75% of the sample showed at least some inclination to follow scent trails. The results suggest that pheromone cues may be used by male and female garter snakes to locate traditional dens during autumnal migrations. Evidence from this and other studies suggests that pheromones are probably used in conjunction with other homing mechanisms and that the role of pheromones in den location may be more important in younger snakes and in populations inhabiting northern latitudes.

Bacoside A downregulates matrix metalloproteinases 2 and 9 in DEN-induced hepatocellular carcinoma.

PubMed

Janani, Panneerselvam; Sivakumari, Kanakarajan; Geetha, Arumugam; Yuvaraj, Sambandam; Parthasarathy, Chandrakesan

2010-03-01

Cancer metastasis is a complex multi-step process, responsible for a majority of cancer-related deaths by affecting the critical organs and causing complications in therapies. Hepatocellular carcinoma is a multi-factorial disease and is the third most common cause of cancer related mortality worldwide. Clinical and experimental studies have shown that MMP-2 and MMP-9 are involved in tumor invasion and metastases and their elevated expression has been associated with poor prognosis. Our recent studies showed a strong anti-oxidant and hepatoprotective effects of bacoside A (BA) against carcinogen. Nevertheless the effect of BA on the activities and expression of MMP-2 and MMP-9 during hepatocellular carcinoma is not yet recognized. Therefore, the present study was designed to assess the same. Results of gelatin zymography study showed that BA co-treatment significantly decreased the activities of MMP-2 and MMP-9, which is increased during hepatocellular carcinoma. Further immunoblot analysis showed decreased expression of MMP-2 and MMP-9 in rats co-treated with BA compared to DEN-induced hepatocellular carcinoma. Our results reveal that BA exerts its anti-metastatic effect against DEN-induced hepatocellular carcinoma by inhibiting the activities and expressions of MMP-2 and MMP-9. 2010 John Wiley & Sons, Ltd.

Diagnosis of Van den Ende-Gupta syndrome: Approach to the Marden-Walker-like spectrum of disorders.

PubMed

Niederhoffer, Karen Y; Fahiminiya, Somayyeh; Eydoux, Patrice; Mawson, John; Nishimura, Gen; Jerome-Majewska, Loydie A; Patel, Millan S

2016-09-01

Marden-Walker syndrome is challenging to diagnose, as there is significant overlap with other multi-system congenital contracture syndromes including Beals congenital contractural arachnodactyly, D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome), Schwartz-Jampel syndrome, Freeman-Sheldon syndrome, Cerebro-oculo-facio-skeletal syndrome, and Van den Ende-Gupta syndrome. We discuss this differential diagnosis in the context of a boy from a consanguineous union with Van den Ende-Gupta syndrome, a diagnosis initially confused by the atypical presence of intellectual disability. SNP microarray and whole exome sequencing identified a homozygous frameshift mutation (p.L870V) in SCARF2 and predicted damaging mutations in several genes, most notably DGCR2 (p.P75L) and NCAM2 (p.S147G), both possible candidates for this child's intellectual disability. We review distinguishing features for each Marden-Walker-like syndrome and propose a clinical algorithm for diagnosis among this spectrum of disorders. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Surgical management of lateral incisor with type II dens invaginatus and a periapical pathosis: A case report with 1-year follow-up.

PubMed

Lakshmi, V Naga; Varma, K Madhu; Sajjan, Girija S; Rambabu, Tanikonda

2017-01-01

Dens invaginatus is a relatively common dental malformation resulting from an infolding of enamel organ into the dental papilla varying in depth into the tooth tissues. Complex morphological anatomy associated with the pulpal pathology presents inaccessibility to completely remove the necrotic pulp tissues and hence poses challenges in rendering endodontic treatment. A combination of nonsurgical and surgical management in treating such cases is advisable depending on the presented variations. The present case reports the surgical endodontic treatment of an immature maxillary lateral incisor with type II dens invaginatus and periapical pathology.

Surgical management of lateral incisor with type II dens invaginatus and a periapical pathosis: A case report with 1-year follow-up

PubMed Central

Lakshmi, V. Naga; Varma, K. Madhu; Sajjan, Girija S.; Rambabu, Tanikonda

2017-01-01

Dens invaginatus is a relatively common dental malformation resulting from an infolding of enamel organ into the dental papilla varying in depth into the tooth tissues. Complex morphological anatomy associated with the pulpal pathology presents inaccessibility to completely remove the necrotic pulp tissues and hence poses challenges in rendering endodontic treatment. A combination of nonsurgical and surgical management in treating such cases is advisable depending on the presented variations. The present case reports the surgical endodontic treatment of an immature maxillary lateral incisor with type II dens invaginatus and periapical pathology. PMID:28761255

Abnormal neurofilament inclusions and segregations in dorsal root ganglia of a Charcot-Marie-Tooth type 2E mouse model.

PubMed

Zhao, Jian; Brown, Kristy; Liem, Ronald K H

2017-01-01

Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy is the most prevalent inherited peripheral neuropathy and is associated with over 90 causative genes. Mutations in neurofilament light polypeptide gene, NEFL cause CMT2E, an axonal form of CMT that results in abnormal structures and/or functions of peripheral axons in spinal cord motor neurons and dorsal root ganglion neurons. We have previously generated and characterized a knock-in mouse model of CMT2E with the N98S mutation in Nefl that presented with multiple inclusions in spinal cord neurons. In this report, we conduct immunofluorescence studies of cultured dorsal root ganglia (DRG) from NeflN98S/+ mice, and show that inclusions found in DRG neurites can occur in embryonic stages. Ultrastructural analyses reveal that the inclusions are disordered neurofilaments packed in high density, segregated from other organelles. Immunochemical studies show decreased NFL protein levels in DRG, cerebellum and spinal cord in NeflN98S/+ mice, and total NFL protein pool is shifted toward the triton-insoluble fraction. Our findings reveal the nature of the inclusions in NeflN98S/+ mice, provide useful information to understand mechanisms of CMT2E disease, and identify DRG from NeflN98S/+ mice as a useful cell line model for therapeutic discoveries.

Misclassification and linkage of hereditary sensory and autonomic neuropathy type 1 as Charcot-Marie-Tooth disease, Type 2B

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

Vance, J.M.; Speer, M.C.; Stajich, J.M.

1996-07-01

Recently Kwon et al. published in the Journal their work describing linkage of a single large family with an inherited axonal neuropathy to chromosome 3, which they suggest is a second locus for Charcot-Marie-Tooth (CMT) type 2 and subsequently named {open_quotes}CMT2B.{close_quotes} We think that the diagnostic classification of this family as CMT2 is incorrect, since the subjects have a severe sensory neuropathy that fits within the hereditary sensory and autonomic neuropathy (HSAN) type 1 classification of Dyck (1993). Abnormal sensory findings in CMT2 separate it from distal spinal muscular atrophy but are a minor component of clinical symptoms in mostmore » CMT patients, as CMT is primarily a motor neuropathy. When Kwon et al. state that {open_quotes}all [patients] had characteristic findings in their physical examinations, including... evidence of foot sores that were slow to heal, or amputated limbs related to the poorly healing foot ulcers,{close_quotes} it suggests that a different diagnosis is more appropriate. In our experience collecting data on >950 individuals in >60 CMT1, CMT2, CMTX and CMT4 families, we have not seen foot ulcers, osteomyelitis, or amputations. Ulcerations leading to osteomyelitis and amputations are usually associated with severe sensory neuropathies. 16 refs., 1 tab.« less

Novel mutations in the connexin 32 gene associated with X-linked Charcot-Marie-Tooth disease

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

Tan, C.; Ainsworth, P.

1994-09-01

Charcot-Marie-Tooth disease is a pathologically and genetically hetergenous group of disorders that cause a progressive neuropathy, defined pathologically by degeneration of the myelin (CMT 1) of the axon (CMT 2) of the peripheral nerves. An X-linked type of the demyelinating form of this disorder (CMT X) has recently been linked to mutations in the connexin 32 (Cx32) gene, which codes for a 284 amino acid gap junction protein found in myelinated peripheral nerve. To date some 7 different mutations in this gene have been identified as being responsible for CMT X. The majority of these predict nonconservative amino acid substitutions,more » while one is a frameshift mutation which predicts a premature stop at codon 21. We report the results of molecular studies on three further local CMT X kindreds. The Cx32 gene was amplified by PCR in three overlapping fragments 300-450 bp in length using leukocyte-derived DNA as template. These were either sequenced directly using a deaza dGTP sequencing protocol, or were cloned and sequenced using a TA vector. In two of the kindreds the affected members carried a point mutation which was predicted to effect a non-conservative amino acid change within the first transmembrane domain. Both of these mutations caused a restriction site alteration (the loss of an Nla III and the creation of a Pvu II, respectively), and the former mutation was observed to segregate with the clinicial phenotype in affected family members. Affected members of the third kindred, which was a very large multigenerational family that had been extensively studied previously, were shown to carry a point mutation predicted to cause a premature truncation of the Cx32 gene product in the intracellular carboxy terminus. This mutation obliterated an Rsa I site which allowed a rapid screen of several other family members.« less

Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy

PubMed Central

Sames, Lori; Moore, Allison; Arnold, Renee; Ekins, Sean

2014-01-01

Approximately 1 in 2500 Americans suffer from Charcot-Marie-Tooth (CMT) disease. The underlying disease mechanisms are unique in most forms of CMT, with many point mutations on various genes causing a toxic accumulation of misfolded proteins. Symptoms of the disease often present within the first two decades of life, with CMT1A patients having reduced compound muscle and sensory action potentials, slow nerve conduction velocities, sensory loss, progressive distal weakness, foot and hand deformities, decreased reflexes, bilateral foot drop and about 5% become wheelchair bound. In contrast, the ultra-rare disease Giant Axonal Neuropathy (GAN) is frequently described as a recessively inherited condition that results in progressive nerve death. GAN usually appears in early childhood and progresses slowly as neuronal injury becomes more severe and leads to death in the second or third decade. There are currently no treatments for any of the forms of CMTs or GAN. We suggest that further clinical studies should analyse electrical impedance myography as an outcome measure for CMT. Further, additional quality of life (QoL) assessments for these CMTs are required, and we need to identify GAN biomarkers as well as develop new genetic testing panels for both diseases. We propose that using the Global Registry of Inherited Neuropathy (GRIN) could be useful for many of these studies. Patient advocacy groups and professional organizations (such as the Hereditary Neuropathy Foundation (HNF), Hannah's Hope Fund (HHF), The Neuropathy Association (TNA) and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) can play a central role in educating clinicians and patients. Undertaking these studies will assist in the correct diagnosis of disease recruiting patients for clinical studies, and will ultimately improve the endpoints for clinical trials. By addressing obstacles that prevent industry investment in various forms of inherited neuropathies, we can

Den use and activity patterns in female Canada lynx (Lynx Canadensis) in the northern Rocky Mountains

Treesearch

Lucretia E. Olson; John R. Squires; Nicholas J. DeCesare; Jay A. Kolbe

2011-01-01

Knowledge of female behavior while rearing young can have important implications for species conservation. We located dens and analyzed activity (defined as movement between consecutive GPS locations) for nine female lynx with kittens in the northcentral Rocky Mountains in 2005 and 2007. We used GPS tracking collars to quantify the percentage of time a female spent...

Patterns of Cellular Immunity Associated with Experimental Infection with rDEN2Δ30 (Tonga/74) Support Its Suitability as a Human Dengue Virus Challenge Strain

PubMed Central

Grifoni, Alba; Angelo, Michael; Sidney, John; Paul, Sinu; Peters, Bjoern; de Silva, Aruna D.; Phillips, Elizabeth; Mallal, Simon; Diehl, Sean A.; Botten, Jason; Boyson, Jonathan; Kirkpatrick, Beth D.; Whitehead, Stephen S.; Durbin, Anna P.; Sette, Alessandro

2017-01-01

ABSTRACT A deletion variant of the dengue virus (DENV) serotype 2 (DENV2) Tonga/74 strain lacking 30 nucleotides from its 3′ untranslated region (rDEN2Δ30) has previously been established for use in a controlled human DENV challenge model. To evaluate if this model is appropriate for the derivation of correlates of protection for DENV vaccines on the basis of cellular immunity, we wanted to compare the cellular immune response to this challenge strain to the response induced by natural infection. To achieve this, we predicted HLA class I- and class II-restricted peptides from rDEN2Δ30 and used them in a gamma interferon enzyme-linked immunosorbent spot assay to interrogate CD8+ and CD4+ T cell responses in healthy volunteers infected with rDEN2Δ30. At the level of CD8 responses, vigorous ex vivo responses were detected in approximately 80% of donors. These responses were similar in terms of the magnitude and the numbers of epitopes recognized to the responses previously observed in peripheral blood mononuclear cells from donors from regions where DENV is hyperendemic. The similarity extended to the immunodominance hierarchy of the DENV nonstructural proteins, with NS3, NS5, and NS1 being dominant in both donor cohorts. At the CD4 level, the responses to rDEN2Δ30 vaccination were less vigorous than those to natural DENV infection and were more focused on nonstructural proteins. The epitopes recognized following rDEN2Δ30 infection and natural infection were largely overlapping for both the CD8 (100%) and CD4 (85%) responses. Finally, rDEN2Δ30 induced stronger CD8 responses than other, more attenuated DENV isolates. IMPORTANCE The lack of a known correlate of protection and the failure of a neutralizing antibody to correlate with protection against dengue virus have highlighted the need for a human DENV challenge model to better evaluate the candidate live attenuated dengue vaccines. In this study, we sought to characterize the immune profiles of rDEN2Δ30

Honors and Theater: Spinoza's Pedagogical Experience and His Relation to F. Van Den Enden

ERIC Educational Resources Information Center

Rovere, Maxime

2018-01-01

Franciscus Van den Enden (1602-1674) is commonly considered as the man who taught Latin to B. de Spinoza (1632-1677). It is unknown if he actually taught him something else, but we do know he used a pedagogy of his own and made the young philosopher aware of the importance of pedagogical issues. The present article helps to document their…

A Mutation of COX6A1 Causes a Recessive Axonal or Mixed Form of Charcot-Marie-Tooth Disease

PubMed Central

Tamiya, Gen; Makino, Satoshi; Hayashi, Makiko; Abe, Akiko; Numakura, Chikahiko; Ueki, Masao; Tanaka, Atsushi; Ito, Chizuru; Toshimori, Kiyotaka; Ogawa, Nobuhiro; Terashima, Tomoya; Maegawa, Hiroshi; Yanagisawa, Daijiro; Tooyama, Ikuo; Tada, Masayoshi; Onodera, Osamu; Hayasaka, Kiyoshi

2014-01-01

Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy characterized by clinical and genetic heterogeneity. Although more than 30 loci harboring CMT-causing mutations have been identified, many other genes still remain to be discovered for many affected individuals. For two consanguineous families with CMT (axonal and mixed phenotypes), a parametric linkage analysis using genome-wide SNP chip identified a 4.3 Mb region on 12q24 showing a maximum multipoint LOD score of 4.23. Subsequent whole-genome sequencing study in one of the probands, followed by mutation screening in the two families, revealed a disease-specific 5 bp deletion (c.247−10_247−6delCACTC) in a splicing element (pyrimidine tract) of intron 2 adjacent to the third exon of cytochrome c oxidase subunit VIa polypeptide 1 (COX6A1), which is a component of mitochondrial respiratory complex IV (cytochrome c oxidase [COX]), within the autozygous linkage region. Functional analysis showed that expression of COX6A1 in peripheral white blood cells from the affected individuals and COX activity in their EB-virus-transformed lymphoblastoid cell lines were significantly reduced. In addition, Cox6a1-null mice showed significantly reduced COX activity and neurogenic muscular atrophy leading to a difficulty in walking. Those data indicated that COX6A1 mutation causes the autosomal-recessive axonal or mixed CMT. PMID:25152455

Assurance of neuroattenuation of a live vaccine against West Nile virus: A comprehensive study of neuropathogenesis after infection with chimeric WN/DEN4Δ30 vaccine in comparison to two parental viruses and a surrogate flavivirus reference vaccine

PubMed Central

Maximova, Olga A.; Speicher, James M.; Skinner, Jeff R.; Murphy, Brian R.; St Claire, Marisa C.; Ragland, Danny R.; Herbert, Richard L.; Pare, Dan R.; Moore, Rashida M.; Pletnev, Alexander G.

2014-01-01

The upsurge of West Nile virus (WNV) human infections in 2012 suggests that the US can expect periodic WNV outbreaks in the future. Availability of safe and effective vaccines against WNV in endemic areas, particularly for aging populations that are at high risk of West Nile neuroinvasive disease (WNND), could be beneficial. WN/DEN4Δ30 is a live, attenuated chimeric vaccine against WNV produced by replacement of the genes encoding the pre-membrane and envelope protein genes of the vaccine virus against dengue virus type 4 (DEN4Δ30) with corresponding sequences derived from a wild type WNV. Following intrathalamic inoculation of nonhuman primates (NHPs), a comprehensive neuropathogenesis study was performed and neurovirulence of WN/DEN4Δ30 vaccine candidate was compared to that of two parental viruses (i.e., WNV and DEN4Δ30), as well as to that of an attenuated flavivirus surrogate reference (i.e., yellow fever YF 17D). Clinical and virological data, as well as results of a semi-quantitative histopathological analysis, demonstrated that WN/DEN4Δ30 vaccine is highly attenuated for the central nervous system (CNS) of NHPs in comparison to a wild type WNV. Importantly, based on the virus replicative ability in the CNS of NHPs and the degree of induced histopathological changes, the level of neuroattenuation of WN/DEN4Δ30 vaccine was similar to that of YF 17D, and therefore within an acceptable range. In addition, we show that the DEN4Δ30 vaccine tested in this study also has a low neurovirulence profile. In summary, our results demonstrate a high level of neuroattenuation of two vaccine candidates, WN/DEN4Δ30 and DEN4Δ30. We also show here a remarkable sensitivity of our WNV-NY99 NHP model, as well as striking resemblance of the observed neuropathology to that seen in human WNND. These results support the use of this NHP model for translational studies of WNV neuropathogenesis and/or testing the effectiveness of vaccines and therapeutic approaches. PMID

Pheromonally mediated sexual isolation among denning populations of red-sided garter snakes, Thamnophis sirtalis parietalis.

PubMed

Lemaster, Michael P; Mason, Robert T

2003-04-01

Utilizing behavioral experiments and chemical analyses, we examined whether pheromonally mediated sexual isolation exists between denning populations of red-sided garter snakes (Thamtnophis sirtalis parietalis) in Manitoba, Canada. Simultaneous choice tests conducted during the breeding season revealed that adult males from a hibernaculum in central Manitoba displayed a strong courtship preference for females from their own population over females from a hibernaculum in western Manitoba, whereas males from the western Manitoba hibernaculum showed no such preference. In addition. trailing experiments testing the response of males from the two hibernacula to familiar and unfamiliar female trails showed similar results, demonstrating that the observed male preference is mediated through chemical cues. Subsequent chemical analysis of the female sexual attractiveness pheromone. a homologous series of long-chain saturated and (omega-9 cis-unsaturated methyl ketones responsible for eliciting male courtship behavior and trailing behavior in garter snakes, showed significant variation in the composition of the pheromone between the two populations. Specifically, the two populations varied in the relative concentrations of individual unsaturated methyl ketones expressed by females. These results suggest that sexual isolation exists to a degree among denning populations of red-sided garter snakes due to variation in the expression of the female sexual attractiveness pheromone.

Mapping of the chromosome 1p36 region surrounding the Charcot-Marie-Tooth disease type 2A locus

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

Denton, P.; Gere, S.; Wolpert, C.

1994-09-01

Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy. Although CMT2 is clinically indistinguishable from CMT1, the two forms can be differentiated by pathological and neurophysiological methods. We have established one locus, CMT2A on chromosome 1p36, and have established genetic heterogeneity. This locus maps to the region of the deletions associated with neuroblastoma. We have now identified an additional 11 CMT2 families. Three families are linked to chromosome 1p36 while six families are excluded from this region. Another six families are currently under analysis and collection. To date the CMT2A families represent one third of those CMT2 families examined.more » We have established a microdissection library of the 1p36 region which is currently being characterized for microsatellite repeats and STSs using standard hybridization techniques and a modified degenerate primer method. In addition, new markers (D1S253, D1S450, D1S489, D1S503, GATA27E04, and GATA4H04) placed in this region are being mapped using critical recombinants in the CEPH reference pedigrees. Fluorescent in situ hybridization (FISH) has been used to confirm mapping. A YAC contig is being assembled from the CEPH megabase library using STSs to isolate key YACs which are extended by vectorette end clone and Alu-PCR. These findings suggest that the CMT2 phenotype is secondary to at least two different genes and demonstrates further heterogeneity in the CMT phenotype.« less

Dietary plasticity in a nutrient-rich system does not influence brown bear (Ursus arctos) body condition or denning

USGS Publications Warehouse

Mangipane, Lindsey S.; Belant, Jerrold L.; Lafferty, Diana J. R.; Gustine, David D.; Hiller, Tim L.; Colvin, Michael E.; Mangipane, Buck A.; Hilderbrand, Grant V.

2018-01-01

Behavioral differences within a population can allow use of a greater range of resources among individuals. The brown bear (Ursus arctos) is a generalist omnivore that occupies diverse habitats and displays considerable plasticity in food use. We evaluated whether brown bear foraging that resulted in deviations from a proposed optimal diet influenced body condition and, in turn, denning duration in Lake Clark National Park and Preserve, Alaska. To assess assimilated diet, we used sectioned guard hair samples (n = 23) collected in autumn to determine stable carbon and nitrogen isotope ratios. To index proportional contributions of meat and vegetation to assimilated diets, we compared the carbon (δ13C) and nitrogen (δ15N) values of hair samples with the values identified for major food categories. We then compared percentage body fat and body mass in relation to the proportion of assimilated meat in the diet using linear models. We also examined the influence of autumn percentage body fat and mass on denning duration. Percentage body fat was not influenced by the proportion of assimilated meat in the diet. Additionally, percentage body fat and body mass did not influence denning duration. However, body mass of bears assimilating proportionately more meat was greater than bears assimilating less meat. Our results provide support for previous findings that larger bears consume higher amounts of protein to maintain their body size and therefore forage further from the proposed optimal diet. Additionally, our results demonstrate that individuals can achieve similar biological outcomes (e.g., percentage body fat) despite variable foraging strategies, suggesting that individuals within generalist populations may confer an adaptive advantage through behavioral plasticity.

Recombination hot spot in 3.2-kb region of the Charcot-Marie Tooth type 1A repeat sequences: New tools for molecular diagnosis of hereditary neuropathy with liability to pressure palsies and of Charcot-Marie-Tooth type 1A

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

Lopes, J.; LeGuern, E.; Gouider, R.

1996-06-01

Charcot-Marie-Tooth type 1A (CMT1A) disease and hereditary neuropathy with liability to pressure palsies (HNPP) are autosomal dominant neuropathies, associated, respectively, with duplications and deletions of the same 1.5-Mb region on 17p11.2-p12. These two rearrangements are the reciprocal products of an unequal meiotic crossover between the two chromosome 17 homologues, caused by the misalignment of the CMT1A repeat sequences (CMT1A-REPs), the homologous sequences flanking the 1.5-Mb CMT1A/HNPP monomer unit. In order to map recombination breakpoints within the CMT1A-REPs, a 12.9-kb restriction map was constructed from cloned EcoRI fragments of the proximal and distal CMT1A-REPs. Only 3 of the 17 tested restrictionmore » sites were present in the proximal CMT1A-REP but absent in the distal CMT1A-REP, indicating a high degree of homology between these sequences. The rearrangements were mapped in four regions of the CMT1A-REPs by analysis of 76 CMT1A index cases and 38 HNPP patients, who were unrelated. A hot spot of crossover breakpoints located in a 3.2-kb region accounted for three-quarters of the rearrangements, detected after EcoRI/SacI digestion, by the presence of 3.2-kb and 7.8-kb junction fragments in CMT1A and HNPP patients, respectively. These junction fragments, which can be detected on classical Southern blots, permit molecular diagnosis. Other rearrangements can also be detected by gene dosage on the same Southern blots. 25 refs., 4 figs., 2 tabs.« less

Injury biomechanics of C2 dens fractures.

PubMed

Yoganandan, Narayan; Pintar, Frank; Baisden, Jamie; Gennarelli, Thomas; Maiman, Dennis

2004-01-01

The objective of this study is to analyze the biomechanics of dens fractures of the second cervical vertebra in the adult population due to motor vehicle crashes. Case-by-case records from the Crash Injury Research and Engineering Network (CIREN) and National Automotive Sampling System (NASS) databases were used. Variables such as change in velocity, impact direction and body habitus were extracted. Results indicated that similarities exist in the two databases despite differences in sampling methods between the two sources (e.g., CIREN is not population based). Trauma is predominantly associated with the frontal mode of impact. Majority of injuries occur with change in velocities below current federal guideline thresholds. No specific bias exists with respect to variables such as age, height, weight, and gender. Because similar conclusions can be drawn with regard to vehicle model years, design changes during these years may have had little effect on this injury. To ameliorate trauma, emphasis should be placed on the frontal impact mode and entire adult population. Because of clinical implications in the fracture type (II being most critical) and lack of specific coding, CIREN data demonstrates the need to improve injury coding in the AIS and application in the NASS to enhance occupant safety and treatment in the field of automotive medicine.

Circulating microparticles in acute diabetic Charcot foot exhibit a high content of inflammatory cytokines, and support monocyte-to-osteoclast cell induction.

PubMed

Pasquier, Jennifer; Thomas, Binitha; Hoarau-Véchot, Jessica; Odeh, Tala; Robay, Amal; Chidiac, Omar; Dargham, Soha R; Turjoman, Rebal; Halama, Anna; Fakhro, Khalid; Menzies, Robert; Jayyousi, Amin; Zirie, Mahmoud; Al Suwaidi, Jassim; Rafii, Arash; Malik, Rayaz A; Talal, Talal; Abi Khalil, Charbel

2017-11-27

Circulating microparticles (MPs) are major mediators in cardiovascular complications of type 2 diabetes (T2D); however, their contribution to Charcot foot (CF) disease is not known. Here, we purified and assessed the origin, concentration and content of circulating MPs from 33 individuals: 11 with T2D and acute CF, 11 T2D patients with equivalent neuropathy and 11 non-diabetic controls. First, we demonstrated that there were no differences in the distribution of MPs of endothelial, platelet origin among the 3 groups. However, MPs from leukocytes and monocytes origin were increased in CF patients. Moreover, we demonstrated that monocytes-derived MPs originated more frequently from intermediate and non-classical monocytes in CF patients. Five cytokines (G-CSF, GM-CSF, IL-1-ra, IL-2 and IL-16) were significantly increased in MPs from acute CF patients. Applying ingenuity pathways analysis, we found that those cytokines interacted well and induced the activation of pathways that are involved in osteoclast formation. Further, we treated THP-1 monocytes and monocytes sorted from healthy patients with CF-derived MPs during their differentiation into osteoclasts, which increased their differentiation into multinucleated osteoclast-like cells. Altogether, our study suggests that circulating MPs in CF disease have a high content of inflammatory cytokines and could increase osteoclast differentiation in vitro.

Genetics of the Charcot-Marie-Tooth disease in the Spanish Gypsy population: the hereditary motor and sensory neuropathy-Russe in depth.

PubMed

Sevilla, T; Martínez-Rubio, D; Márquez, C; Paradas, C; Colomer, J; Jaijo, T; Millán, J M; Palau, F; Espinós, C

2013-06-01

Four private mutations responsible for three forms demyelinating of Charcot-Marie-Tooth (CMT) or hereditary motor and sensory neuropathy (HMSN) have been associated with the Gypsy population: the NDRG1 p.R148X in CMT type 4D (CMT4D/HMSN-Lom); p.C737_P738delinsX and p.R1109X mutations in the SH3TC2 gene (CMT4C); and a G>C change in a novel alternative untranslated exon in the HK1 gene causative of CMT4G (CMT4G/HMSN-Russe). Here we address the findings of a genetic study of 29 Gypsy Spanish families with autosomal recessive demyelinating CMT. The most frequent form is CMT4C (57.14%), followed by HMSN-Russe (25%) and HMSN-Lom (17.86%). The relevant frequency of HMSN-Russe has allowed us to investigate in depth the genetics and the associated clinical symptoms of this CMT form. HMSN-Russe probands share the same haplotype confirming that the HK1 g.9712G>C is a founder mutation, which arrived in Spain around the end of the 18th century. The clinical picture of HMSN-Russe is a progressive CMT disorder leading to severe weakness of the lower limbs and prominent distal sensory loss. Motor nerve conduction velocity was in the demyelinating or intermediate range. © 2012 John Wiley & Sons A/S.

Geochemical survey of the Devil's Den Roadless Area, Rutland and Windsor counties, Vermont

USGS Publications Warehouse

Slack, J.F.; Atelsek, P.J.; Grosz, A.E.

1985-01-01

The Devils Den area is named for a large undercut cliff (Dale, 1915, p. 21) developed in Precambrian basement rocks. This undercut cliff forms a broad natural cave immediately west of and below Forest Service Road 10, at the head of Mt. Tabor Brook. Another much smaller cave is present in dolomite of probable Paleozoic (Early Cambrian) age on the east side of the same road. This smaller cave apparently is of artificial origin, having been made during early mining of the dolomite (Dale, 1915, p. 21). This man-made cave is the only evidence of previous mining activity within the study area.

Assurance of neuroattenuation of a live vaccine against West Nile virus: a comprehensive study of neuropathogenesis after infection with chimeric WN/DEN4Δ30 vaccine in comparison to two parental viruses and a surrogate flavivirus reference vaccine.

PubMed

Maximova, Olga A; Speicher, James M; Skinner, Jeff R; Murphy, Brian R; St Claire, Marisa C; Ragland, Danny R; Herbert, Richard L; Pare, Dan R; Moore, Rashida M; Pletnev, Alexander G

2014-05-30

The upsurge of West Nile virus (WNV) human infections in 2012 suggests that the US can expect periodic WNV outbreaks in the future. Availability of safe and effective vaccines against WNV in endemic areas, particularly for aging populations that are at high risk of West Nile neuroinvasive disease (WNND), could be beneficial. WN/DEN4Δ30 is a live, attenuated chimeric vaccine against WNV produced by replacement of the genes encoding the pre-membrane and envelope protein genes of the vaccine virus against dengue virus type 4 (DEN4Δ30) with corresponding sequences derived from a wild type WNV. Following intrathalamic inoculation of nonhuman primates (NHPs), a comprehensive neuropathogenesis study was performed and neurovirulence of WN/DEN4Δ30 vaccine candidate was compared to that of two parental viruses (i.e., WNV and DEN4Δ30), as well as to that of an attenuated flavivirus surrogate reference (i.e., yellow fever YF 17D). Clinical and virological data, as well as results of a semi-quantitative histopathological analysis, demonstrated that WN/DEN4Δ30 vaccine is highly attenuated for the central nervous system (CNS) of NHPs in comparison to a wild type WNV. Importantly, based on the virus replicative ability in the CNS of NHPs and the degree of induced histopathological changes, the level of neuroattenuation of WN/DEN4Δ30 vaccine was similar to that of YF 17D, and therefore within an acceptable range. In addition, we show that the DEN4Δ30 vaccine tested in this study also has a low neurovirulence profile. In summary, our results demonstrate a high level of neuroattenuation of two vaccine candidates, WN/DEN4Δ30 and DEN4Δ30. We also show here a remarkable sensitivity of our WNV-NY99 NHP model, as well as striking resemblance of the observed neuropathology to that seen in human WNND. These results support the use of this NHP model for translational studies of WNV neuropathogenesis and/or testing the effectiveness of vaccines and therapeutic approaches. Published

Long-term follow-up of the surgical management of neuropathic arthropathy of the spine.

PubMed

Haus, Brian M; Hsu, Andrew R; Yim, Eugene S; Meter, Jeffrey J; Rinsky, Lawrence A

2010-06-01

No studies have discussed the long-term surgical management and outcomes of Charcot arthropathy of the spine. This case series presents nine patients treated over 30 years. The study hypothesis was that surgery would reduce instability, pain, recurrence, and the need for revision surgery in the long-term, given previous study findings of successful fusion of Charcot spine in the short-term. To evaluate the long-term outcomes of surgery for Charcot spine. Retrospective case series. Cases took place at Stanford University Medical Center and Santa Clara Valley Medical Center. All patients had either complete paraplegia or dense paraparesis with both major motor and sensory deficits. Seven patients developed Charcot spine after spinal instrumentation for trauma, one after scoliosis repair for meningomyelocele, and one after spinal instrumentation for neuromuscular scoliosis caused by birth injury resulting in C6-C7 quadraplegia. Average time between initial instrumentation and development of Charcot spine was 7.6 years. Two patients underwent posterior fusion alone, six had anterior-posterior fusion, and one was managed with thoracolumbar orthosis. Average follow-up was 14.3 years. Revisions were necessary in 75% (6 of 8) of patients for complications including nonunion, new Charcot joints, recurrent hardware failure, and osteomyelitis. Achieving fusion often required multiple operations, and there were no deaths or neurologic complications. Long-term follow-up showed a high rate of revision surgery. Solid fusions often resulted in late breakdown or new junctional Charcot arthropathies. Patients initially fused to the lumbar spine instead of the sacrum or pelvis had a higher rate of developing another Charcot joint. Fusion was often difficult with persistent nonunions and functional deficits because of decreased mobility. We recommend that Charcot spine well tolerated without skin, seating problems, or dysreflexia should be cautiously observed with conservative

Loss of the E3 ubiquitin ligase LRSAM1 sensitizes peripheral axons to degeneration in a mouse model of Charcot-Marie-Tooth disease.

PubMed

Bogdanik, Laurent P; Sleigh, James N; Tian, Cong; Samuels, Mark E; Bedard, Karen; Seburn, Kevin L; Burgess, Robert W

2013-05-01

Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous condition characterized by peripheral axon degeneration with subsequent motor and sensory deficits. Several CMT gene products function in endosomal sorting and trafficking to the lysosome, suggesting that defects in this cellular pathway might present a common pathogenic mechanism for these conditions. LRSAM1 is an E3 ubiquitin ligase that is implicated in this process, and mutations in LRSAM1 have recently been shown to cause CMT. We have generated mouse mutations in Lrsam1 to create an animal model of this form of CMT (CMT2P). Mouse Lrsam1 is abundantly expressed in the motor and sensory neurons of the peripheral nervous system. Both homozygous and heterozygous mice have largely normal neuromuscular performance and only a very mild neuropathy phenotype with age. However, Lrsam1 mutant mice are more sensitive to challenge with acrylamide, a neurotoxic agent that causes axon degeneration, indicating that the axons in the mutant mice are indeed compromised. In transfected cells, LRSAM1 primarily localizes in a perinuclear compartment immediately beyond the Golgi and shows little colocalization with components of the endosome to lysosome trafficking pathway, suggesting that other cellular mechanisms also merit consideration.

An 8-generation family with X-linked Charcot-Marie-Tooth: Confirmation Of the pathogenicity Of a 3' untranslated region mutation in GJB1 and its clinical features.

PubMed

Chen, Dong-Hui; Ma, Maxwell; Scavina, Mena; Blue, Elizabeth; Wolff, John; Karna, Prasanthi; Dorschner, Michael O; Raskind, Wendy H; Bird, Thomas D

2018-05-01

Mutations in gap junction protein beta 1 (GJB1) on the X chromosome represent one of the most common causes of hereditary neuropathy. We assessed manifestations associated with a rare 3' untranslated region mutation (UTR) of GJB1 in a large family with X-linked Charcot-Marie-Tooth disease (CMTX). Clinical, electrophysiological, and molecular genetic analyses were performed on an 8-generation family with CMTX. There were 22 affected males and 19 symptomatic females, including an 83-year-old woman followed for 40 years. Electrophysiological studies showed a primarily axonal neuropathy. The c.*15C>T mutation in the GJB1 3' UTR was identified in 4 branches of the family with a log of odds (LOD) of 4.91. This created a BstE II enzyme recognition site that enabled detection by restriction digestion. The c.*15C>T mutation in the GJB1 3' UTR segregates with CMTX1 in 8 generations. Penetrance in males and females is essentially complete. A straightforward genetic method to detect this mutation is described. Muscle Nerve 57: 859-862, 2018. © 2017 Wiley Periodicals, Inc.

Regenerative Endodontic Treatment with Orthodontic Treatment in a Tooth with Dens Evaginatus: A Case Report with a 4-year Follow-up.

PubMed

Natera, Marianella; Mukherjee, Padma M

2018-06-01

Dens evaginatus is a developmental tooth anomaly in which an extra cusp or tubercle protrudes on the occlusal surface of the tooth along with some pulpal tissue. Because of the fragile nature of the protrusion, these teeth are often at risk of pulpal exposure. When this occurs in an immature tooth, regenerative endodontic treatment may be a good treatment approach to promote root formation. There is limited literature that documents the occurrence of orthodontic treatment in teeth that have undergone regenerative endodontic therapy using triple antibiotic paste. Here we present a case of an immature premolar tooth with dens evaginatus that was diagnosed with pulp necrosis and chronic apical abscess. The tooth was treated with regenerative endodontic treatment; after which, the patient received orthodontic treatment with fixed appliances for 2 years. The tooth responded favorably to the regenerative endodontic treatment and orthodontic tooth movement. Clinically and radiographically, all the follow-up examinations revealed an asymptomatic tooth with evidence of periapical healing with stunted root development. The tooth remained asymptomatic even after 4 years. The regenerative endodontic procedure (REP) was successful in treating an immature permanent premolar with pulp necrosis and apical periodontitis with dens evaginatus. In this case, the tooth treated with an REP responded to orthodontic treatment similar to the nonendodontically treated teeth. Further studies are recommended to clarify the precise effects of orthodontic treatment on teeth treated with an REP. Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies.

PubMed

van Paassen, Barbara W; van der Kooi, Anneke J; van Spaendonck-Zwarts, Karin Y; Verhamme, Camiel; Baas, Frank; de Visser, Marianne

2014-03-19

PMP22 related neuropathies comprise (1) PMP22 duplications leading to Charcot-Marie-Tooth disease type 1A (CMT1A), (2) PMP22 deletions, leading to Hereditary Neuropathy with liability to Pressure Palsies (HNPP), and (3) PMP22 point mutations, causing both phenotypes. Overall prevalence of CMT is usually reported as 1:2,500, epidemiological studies show that 20-64% of CMT patients carry the PMP22 duplication. The prevalence of HNPP is not well known. CMT1A usually presents in the first two decades with difficulty walking or running. Distal symmetrical muscle weakness and wasting and sensory loss is present, legs more frequently and more severely affected than arms. HNPP typically leads to episodic, painless, recurrent, focal motor and sensory peripheral neuropathy, preceded by minor compression on the affected nerve. Electrophysiological evaluation is needed to determine whether the polyneuropathy is demyelinating. Sonography of the nerves can be useful. Diagnosis is confirmed by finding respectively a PMP22 duplication, deletion or point mutation. Differential diagnosis includes other inherited neuropathies, and acquired polyneuropathies. The mode of inheritance is autosomal dominant and de novo mutations occur. Offspring of patients have a chance of 50% to inherit the mutation from their affected parent. Prenatal testing is possible; requests for prenatal testing are not common. Treatment is currently symptomatic and may include management by a rehabilitation physician, physiotherapist, occupational therapist and orthopaedic surgeon. Adult CMT1A patients show slow clinical progression of disease, which seems to reflect a process of normal ageing. Life expectancy is normal.

Correction of ankle and hind foot deformity in Charcot neuroarthropathy using a retrograde hind foot nail-The Kings' Experience.

PubMed

Vasukutty, N; Jawalkar, H; Anugraha, A; Chekuri, R; Ahluwalia, R; Kavarthapu, V

2017-04-28

Corrective fusion for the unstable deformed hind foot and mid foot in Charcot Neuroarthropathy (CN) is quite challenging and is best done in tertiary centres under the supervision of multidisciplinary teams. We present a follow up to our initial report with a series of 42 hind foot corrections in 40 patients from a tertiary level teaching hospital in the United Kingdom. The mean patient age was 59 (33-82). 17 patients had type1diabetes mellitus, 23 had type 2. 23 feet in 22 patients had chronic ulceration despite offloading. 17 patients were ASA 2 and 23 were ASA grade 3. All patients had hind foot nail fusion performed through a standard technique by the senior author and managed perioperatively by the multidisciplinary team. At a mean follow up of 42 months (12-99) we achieved 100% limb salvage initially and a 97% fusion rate. One patient with persisting non-union of ankle and subtalar joint with difficulty in bracing has been offered below-knee amputation. We achieved deformity correction in 100% and ulcer healing in 83%. 83% patients are able to mobilize and manage independent activities of daily living. There were 11 patients with one or more complications including metal work failure, infection and ulcer reactivation. There have been nine repeat procedures including one revision fixation and one vascular procedure. Single stage corrective fusion for hind foot deformity in CN is an effective procedure when delivered by a skilled multidisciplinary team. Copyright © 2017. Published by Elsevier Ltd.

PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies

PubMed Central

2014-01-01

PMP22 related neuropathies comprise (1) PMP22 duplications leading to Charcot-Marie-Tooth disease type 1A (CMT1A), (2) PMP22 deletions, leading to Hereditary Neuropathy with liability to Pressure Palsies (HNPP), and (3) PMP22 point mutations, causing both phenotypes. Overall prevalence of CMT is usually reported as 1:2,500, epidemiological studies show that 20-64% of CMT patients carry the PMP22 duplication. The prevalence of HNPP is not well known. CMT1A usually presents in the first two decades with difficulty walking or running. Distal symmetrical muscle weakness and wasting and sensory loss is present, legs more frequently and more severely affected than arms. HNPP typically leads to episodic, painless, recurrent, focal motor and sensory peripheral neuropathy, preceded by minor compression on the affected nerve. Electrophysiological evaluation is needed to determine whether the polyneuropathy is demyelinating. Sonography of the nerves can be useful. Diagnosis is confirmed by finding respectively a PMP22 duplication, deletion or point mutation. Differential diagnosis includes other inherited neuropathies, and acquired polyneuropathies. The mode of inheritance is autosomal dominant and de novo mutations occur. Offspring of patients have a chance of 50% to inherit the mutation from their affected parent. Prenatal testing is possible; requests for prenatal testing are not common. Treatment is currently symptomatic and may include management by a rehabilitation physician, physiotherapist, occupational therapist and orthopaedic surgeon. Adult CMT1A patients show slow clinical progression of disease, which seems to reflect a process of normal ageing. Life expectancy is normal. PMID:24646194

Radiographic and functional results in the treatment of early stages of Charcot neuroarthropathy with a walker boot and immediate weight bearing.

PubMed

Parisi, Maria Candida Ribeiro; Godoy-Santos, Alexandre Leme; Ortiz, Rafael Trevisan; Sposeto, Rafael Barban; Sakaki, Marcos Hideyo; Nery, Marcia; Fernandes, Tulio Diniz

2013-01-01

One of the most common gold standards for the treatment of Charcot neuroarthropathy (CN) in the early Eichenholtz stages I and II is immobilization with the total contact casting and lower limb offloading. However, the total amount of offloading is still debatable. This study evaluates the clinical and radiographic findings in the treatment of early stages of CN (Eichenholtz stages I and II) with a walker boot and immediate total weight-bearing status. Twenty-two patients with type 2 diabetes mellitus (DM) and CN of Eichenholtz stages I and II were selected for non-operative treatment. All patients were educated about their condition, and full weight bearing was allowed as tolerated. Patients were monitored on a fortnightly basis in the earlier stages, with clinical examination, temperature measurement, and standardized weight-bearing radiographs. Their American Orthopedic Foot and Ankle Society (AOFAS) scores were determined before and after the treatment protocol. No cutaneous ulcerations or infections were observed in the evaluated cases. The mean measured angles at the beginning and end of the study, although showing relative increase, did not present a statistically significant difference (p > 0.05). Mean AOFAS scores showed a statistically significant improvement by the end of the study (p < 0.005). The treatment of early stages of CN (Eichenholtz stages I and II) with emphasis on walker boot and immediate weight bearing has shown a good functional outcome, non-progressive deformity on radiographic assessment, and promising results as a safe treatment option.

Complication assessment and prevention strategies using midfoot fusion bolt for medial column stabilization in Charcot's osteoarthropathy.

PubMed

Mehlhorn, Alexander T; Walther, Markus; Iblher, Niklas; Südkamp, Norbert P; Schmal, Hagen

2016-12-01

In Charcot's osteoarthropathy stabilization of the medial column of the foot was introduced in order to establish a stable foot and reduce the risk for amputation. This study was performed to analyze postoperative complications, define risk factors for those and develop strategies for prevention. Since bolt dislocation takes place frequently, it was aimed to predict an appropriate time point for bolt removal under the condition that osseous healing has occurred. Fourteen consecutive patients with neuroosteoarthropathy of the foot and arch collapse were treated with open reduction and stabilization using midfoot fusion bolt and lateral lag screws. Age, gender, presence of preoperative osteomyelitis or ulcer, number of complications and operative revisions, Hba1c value, consolidation of arthrodesis, presence of a load-bearing foot and period to bolt dislocation was assessed. The mean follow-up was 21.4±14.6 (mean±SDM) months, 64% of patients suffered from diabetes with a preoperative Hba1c of 8.5±2.4. The mean number of revisions per foot was 3.6±4.1. Bolt dislocation was seen in 57% of the patients following 11.3±8.5 months; in 75% of these patients bony healing occurred before dislocation. There was a significant association between preoperative increased Hba1c value, presence of preoperative ulcer and wound infection. Healing of arthrodesis was demonstrated in 57% and a permanent weight-bearing foot without recurrent ulcer was achieved in 79%. The early and late postoperative complications could be controlled in general. A fully load-bearing and stable foot was obtained, despite osseous consolidation was not detected in all of these cases. Once a stable foot has established early removal of fusion bolt should be considered. To decrease the risk of infection Hba1c should be adjusted and ulcers should be treated before the operation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ankle foot orthoses for people with Charcot Marie Tooth disease--views of users and orthotists on important aspects of use.

PubMed

Phillips, Margaret; Radford, Kathryn; Wills, Adrian

2011-01-01

To explore important aspects of the benefits, important characteristics, barriers to use and disadvantages of using ankle foot orthoses (AFOs) as seen by people with Charcot Marie Tooth disease (CMT) and the orthotists who will fit and supply them. This qualitative study used the nominal group technique and individual semi-structured interviews, according to participant preference and ability to travel. Propositions were put to 15 participants (eight females) with CMT regarding benefits, disadvantages, barriers to use and important characteristics of ankle foot orthoses AFOs and regarding benefits and disadvantages to seven orthotists. Priorities in these areas were ranked and a thematic analysis of the free text was made separately by two observers and a joint decision made of final themes. Fifteen people (eight females) with CMT and seven orthotists participated. Users' themes concerned functional mobility walking, pain/discomfort, choice of AFOs and associated footwear, custom made design, use in practical situations and support for foot and ankle. They noted that AFOs improved walking, but practical aspects of use and provision, as well as consideration of cosmetic aspects, were frequently problematic. Orthotists had similar themes, but with a difference in emphasis, that included prevention of future complications, education regarding device limitations and craftsmanship as a further theme. Users understood the potential benefits of AFOs and could identify disadvantages which might be remedied, but were frustrated by the difficulties in translating this into practice. Further refinement of current orthoses and delivery of orthotic services may assist in addressing these issues. © 2011 Informa UK, Ltd.

Molecular analyses of unrelated Charcot-Marie-Tooth (CMT) disease patients suggest a high frequency of the CMT1A duplication

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

Wise, C.A.; Davis, S.N.; Heju, Z.

1993-10-01

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. One form of CMT, CMT type 1A, is characterized by uniformly decreased nerve conduction velocities, usually shows autosomal dominant inheritance, and is associated with a large submicroscopic duplication of the p11.2-p12 region of chromosome 17. A cohort of 75 unrelated patients diagnosed clinically with CMT and evaluated by electrophysiological methods were analyzed molecularly for the presence of the CMT1A DNA duplication. Three methodologies were used to assess the duplication: Measurement of dosage differences between RFLP alleles, analysis of polymorphic (GT)[sub n] repeats, and detection of a junction fragment by pulsed-fieldmore » gel electrophoresis. The CMT1A duplication was found in 68% of the 63 unrelated CMT patients with electrophysiological studies consistent with CMT type 1 (CMT1). The CMT1A duplication was detected as a de novo event in two CMT1 families. Twelve CMT patients who did not have decreased nerve conduction velocities consistent with a diagnosis of CMT type 2 (CMT2) were found not to have the CMT1A duplication. The most informative molecular method was the detection of the CMT1A duplication-specific junction fragment. Given the high frequency of the CMT1A duplication in CMT patients and the high frequency of new mutations, the authors conclude that a molecular test for the CMT1A DNA duplication is very useful in the differential diagnosis of patients with peripheral neuropathies. 61 refs., 4 figs.« less

Implantate für den Bandscheibenersatz (Stand 1993)

NASA Astrophysics Data System (ADS)

Mathey, Michael; Wintermantel, Erich

Die Bandscheiben sind besonders betroffen von Fehlhaltungen und -stellungen der Wirbelsäule. Sie unterliegen als grösstes zusammenhängendes, nicht vaskularisiertes Gewebe im Menschen, statisch und dynamisch extrem belastet, besonders der Alterung. Um die teilweise sehr starken Schmerzen bei Bandscheibenschädigungen zu lindern, ist eine Operation vielfach die einzige Hilfe. Bei dieser Operation (Nukleotomie) entfernt man das aus der Bandscheibe ausgetretene Gewebe des Gallertkerns (nucleus pulposus), welches durch Druck auf die Nervenstränge im Bereich der Wirbelsäule die Beschwerden (Ischias-Schmerz) verursacht hat. Nach der Entfernung des Gallertkerns werden die auftretenden Kräfte bei veränderter Biomechanik übertragen. Dabei erhalten die Zwischenwirbelgelenke (Facettengelenke) eine erheblich grössere Flächenpressung als dies bei intakter Bandscheibe der Fall war. Die höhere Flächenpressung kommt durch die Verringerung des Abstandes zwischen den oberen und unteren Deckplatten der benachbarten Wirbelkörper zustande, zwischen denen sich der Gallertkern befand. Durch geeignetes Training der Rückenmuskulatur kann eine Stabilisierung des operierten Bandscheibensegmentes erreicht werden, jedoch ist es eine klinische Erfahrung, dass die meisten Patienten, die momentan durch die Operation schmerzfrei geworden sind, keine adäquate zusätzliche sportliche Betätigung auf sich nehmen.

Coronary artery disease as an independent predictor of survival in patients with type 2 diabetes and Charcot neuro-osteoarthropathy.

PubMed

Bergis, Dominik; Bergis, Pia Maria; Hermanns, Norbert; Zink, Karl; Haak, Thomas

2014-12-01

Charcot neuro-osteoarthropathy (CN) is a rare complication of diabetic foot syndrome associated with chronic inflammation of the foot and severe, limb-threatening musculoskeletal deformities. Aim of this study was to investigate patients with CN for comorbidities, amputations, ulcers, secondary diseases and mortality. The study was conducted at a specialized German hospital for patients with diabetes. One-hundred and eleven patients were enrolled, and their course was followed over a period of 15 years. Association of CN with comorbidity, foot ulcers, amputations and mortality was assessed. Clinical course of patients was followed using two standardized questionnaires. Presence of CN was significantly associated with diabetic retinopathy (p = 0.047), plantar (p < 0.001), tarsal (p = 0.032) and middle-foot ulcers (p = 0.01). A significant correlation between the presence of CN and a history of amputations was seen (p = 0.022). Patients were at increased risk to suffer from subsequent amputations during follow-up when micro- and macrovascular comorbidities such as retinopathy (p = 0.01) and peripheral artery disease (p < 0.001) were present. Additionally, coronary artery disease (CHD) was identified as an independent predictor of mortality in the cohort of this study (OR 6.192, 95 % CI 1.155-33.208, p = 0.033). Median overall survival of patients with CN and CHD was significantly shorter than OS of patients without CHD (7.8 vs. 13.1 years, p = 0.0045, HR 2.8437, 95 % CI 0.9818-8.2364). In our study, CHD was the most important factor of survival in CN patients. For optimal management of CN, adequate diagnostics and treatment of CHD according to current guidelines should be considered.

Gait and footwear in children and adolescents with Charcot-Marie-Tooth disease: A cross-sectional, case-controlled study.

PubMed

Kennedy, Rachel A; McGinley, Jennifer L; Paterson, Kade L; Ryan, Monique M; Carroll, Kate

2018-05-01

Children with Charcot-Marie-Tooth disease (CMT) report problems with gait and footwear. We evaluated differences in spatio-temporal gait variables and gait variability between children with CMT and typically developing (TD) children, and investigated the effect of footwear upon gait. A cross-sectional study of 30 children with CMT and 30 age- and gender-matched TD children aged 4-18 years. Gait was assessed at self-selected speed on an electronic walkway while barefoot and in two types of the child's own footwear; optimal (e.g., athletic-type runners) and suboptimal (e.g., flip-flops). Children with CMT walked more slowly (mean (SD) -13.81 (3.61) cm/s), with shorter steps (-6.28 (1.37) cm), wider base of support (+2.47 (0.66) cm; all p < 0.001) and greater base of support variability (0.48 (0.15) cm, p = 0.002) compared to TD children. Gait was faster in optimal footwear than suboptimal (-7.55 (1.31) cm/s) and barefoot (-7.42 (1.07) cm/sec; both p < 0.001) in the combined group of children. Gait in suboptimal footwear was more variable compared to barefoot and optimal footwear. Greater base of support variability and reduced balance was moderately correlated for both groups (CMT and TD). Gait is slower with shorter, wider steps and greater base of support variability in children with CMT. Poor balance is associated with greater base of support gait variability. Suboptimal footwear negatively affects gait in all children (CMT and TD), which has clinical implications for children and adolescents with CMT who have weaker feet and ankles, and poor balance. Copyright © 2018 Elsevier B.V. All rights reserved.

Electromyographic and biomechanical analysis of step negotiation in Charcot Marie Tooth subjects whose level walk is not impaired.

PubMed

Lencioni, Tiziana; Piscosquito, Giuseppe; Rabuffetti, Marco; Sipio, Enrica Di; Diverio, Manuela; Moroni, Isabella; Padua, Luca; Pagliano, Emanuela; Schenone, Angelo; Pareyson, Davide; Ferrarin, Maurizio

2018-05-01

Charcot-Marie-Tooth (CMT) is a slowly progressive disease characterized by muscular weakness and wasting with a length-dependent pattern. Mildly affected CMT subjects showed slight alteration of walking compared to healthy subjects (HS). To investigate the biomechanics of step negotiation, a task that requires greater muscle strength and balance control compared to level walking, in CMT subjects without primary locomotor deficits (foot drop and push off deficit) during walking. We collected data (kinematic, kinetic, and surface electromyographic) during walking on level ground and step negotiation, from 98 CMT subjects with mild-to-moderate impairment. Twenty-one CMT subjects (CMT-NLW, normal-like-walkers) were selected for analysis, as they showed values of normalized ROM during swing and produced work at push-off at ankle joint comparable to those of 31 HS. Step negotiation tasks consisted in climbing and descending a two-step stair. Only the first step provided the ground reaction force data. To assess muscle activity, each EMG profile was integrated over 100% of task duration and the activation percentage was computed in four phases that constitute the step negotiation tasks. In both tasks, CMT-NLW showed distal muscle hypoactivation. In addition, during step-ascending CMT-NLW subjects had relevant lower activities of vastus medialis and rectus femoris than HS in weight-acceptance, and, on the opposite, a greater activation as compared to HS in forward-continuance. During step-descending, CMT-NLW showed a reduced activity of tibialis anterior during controlled-lowering phase. Step negotiation revealed adaptive motor strategies related to muscle weakness due to disease in CMT subjects without any clinically apparent locomotor deficit during level walking. In addition, this study provided results useful for tailored rehabilitation of CMT patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Hypoxia causes IL-8 secretion, Charcot Leyden crystal formation, and suppression of corticosteroid-induced apoptosis in human eosinophils.

PubMed

Porter, L M; Cowburn, A S; Farahi, N; Deighton, J; Farrow, S N; Fiddler, C A; Juss, J K; Condliffe, A M; Chilvers, E R

2017-06-01

Inflamed environments are typically hypercellular, rich in pro-inflammatory cytokines, and profoundly hypoxic. While the effects of hypoxia on neutrophil longevity and function have been widely studied, little is known about the consequences of this stimulus on eosinophils. We sought to investigate the effects of hypoxia on several key aspects of eosinophil biology, namely secretion, survival, and their sensitivity to glucocorticosteroids (GCS), agents that normally induce eosinophil apoptosis. Eosinophils derived from patients with asthma/atopy or healthy controls were incubated under normoxia and hypoxia, with or without glucocorticoids. Activation was measured by flow cytometry, ELISA of cultured supernatants, and F-actin staining; apoptosis and efferocytosis by morphology and flow cytometry; and GCS efficacy by apoptosis assays and qPCR. Hypoxic incubation (3 kPa) caused (i) stabilization of HIF-2α and up-regulation of hypoxia-regulated genes including BNIP3 (BCL2/adenovirus E1B 19-kDa protein-interacting protein 3) and GLUT1 (glucose transporter 1); (ii) secretion of pre-formed IL-8, and Charcot Leyden crystal (CLC) formation, which was most evident in eosinophils derived from atopic and asthmatic donors; (iii) enhanced F-actin formation; (iv) marked prolongation of eosinophil lifespan (via a NF-κB and Class I PI3-kinase-dependent mechanism); and (v) complete abrogation of the normal pro-apoptotic effect of dexamethasone and fluticasone furoate. This latter effect was evident despite preservation of GCS-mediated gene transactivation under hypoxia. These data indicate that hypoxia promotes an eosinophil pro-inflammatory phenotype by enhancing eosinophil secretory function, delaying constitutive apoptosis, and importantly, antagonizing the normal pro-apoptotic effect of GCS. As eosinophils typically accumulate at sites that are relatively hypoxic, particularly during periods of inflammation, these findings may have important implications to understanding the

WES homozygosity mapping in a recessive form of Charcot-Marie-Tooth neuropathy reveals intronic GDAP1 variant leading to a premature stop codon.

PubMed

Masingue, Marion; Perrot, Jimmy; Carlier, Robert-Yves; Piguet-Lacroix, Guenaelle; Latour, Philippe; Stojkovic, Tanya

2018-05-01

Charcot-Marie-Tooth disease (CMT) refers to a group of clinically and genetically heterogeneous inherited neuropathies. Ganglioside-induced differentiation-associated protein 1 GDAP1-related CMT has been reported in an autosomal dominant or recessive form in patients presenting either axonal or demyelinating neuropathy. We report two Sri Lankan sisters born to consanguineous parents and presenting with a severe axonal sensorimotor neuropathy. The early onset of the disease, the distal and proximal weakness and atrophy leading to major disability, along with areflexia, and, most notably, vocal cord and diaphragm paralysis were highly evocative of a GDAP1-related CMT. However, sequencing of the coding regions of the gene was normal. Whole-exome sequencing (WES) was performed and revealed that the largest region of homozygosity was around GDAP1 with several variants, mostly in non-coding regions. In view of the high clinical suspicion of GDAP1 gene involvement, we examined the variants in this gene and this, along with functional studies, allowed us to identify an alternative splicing site revealing a cryptic in-frame stop codon in intron 4 responsible for a severe loss of wild-type GDAP1. This work is the first to describe a deleterious mutation in GDAP1 gene outside of coding sequences or intronic junctions and emphasizes the importance of interpreting molecular analysis, and in particular WES results, in light of the clinical and electrophysiological phenotype.

Rater Biases in Genetically Informative Research Designs: Comment on Bartels, Boomsma, Hudziak, van Beijsterveldt, and van den Oord (2007)

ERIC Educational Resources Information Center

Hoyt, William T.

2007-01-01

Rater biases are of interest to behavior genetic researchers, who often use ratings data as a basis for studying heritability. Inclusion of multiple raters for each sibling pair (M. Bartels, D. I. Boomsma, J. J. Hudziak, T. C. E. M. van Beijsterveldt, & E. J. C. G. van den Oord, 2007) is a promising strategy for controlling bias variance and may…

Novel homozygous missense mutation in GAN associated with Charcot-Marie-Tooth disease type 2 in a large consanguineous family from Israel.

PubMed

Aharoni, Sharon; Barwick, Katy E S; Straussberg, Rachel; Harlalka, Gaurav V; Nevo, Yoram; Chioza, Barry A; McEntagart, Meriel M; Mimouni-Bloch, Aviva; Weedon, Michael; Crosby, Andrew H

2016-11-16

CMT-2 is a clinically and genetically heterogeneous group of peripheral axonal neuropathies characterized by slowly progressive weakness and atrophy of distal limb muscles resulting from length-dependent motor and sensory neurodegeneration. Classical giant axonal neuropathy (GAN) is an autosomal recessively inherited progressive neurodegenerative disorder of the peripheral and central nervous systems, typically diagnosed in early childhood and resulting in death by the end of the third decade. Distinctive phenotypic features are the presence of "kinky" hair and long eyelashes. The genetic basis of the disease has been well established, with over 40 associated mutations identified in the gene GAN, encoding the BTB-KELCH protein gigaxonin, involved in intermediate filament regulation. An Illumina Human CytoSNP-12 array followed by whole exome sequence analysis was used to identify the disease associated gene mutation in a large consanguineous family diagnosed with Charcot-Marie-Tooth disease type 2 (CMT-2) from which all but one affected member had straight hair. Here we report the identification of a novel GAN missense mutation underlying the CMT-2 phenotype observed in this family. Although milder forms of GAN, with and without the presence of kinky hair have been reported previously, a phenotype distinct from that was investigated in this study. All family members lacked common features of GAN, including ataxia, nystagmus, intellectual disability, seizures, and central nervous system involvement. Our findings broaden the spectrum of phenotypes associated with GAN mutations and emphasize a need to proceed with caution when providing families with diagnostic or prognostic information based on either clinical or genetic findings alone.

Polar bear mother-offspring interactions in maternity dens in captivity.

PubMed

van Gessel, Chad

2015-01-01

Two female polar bears at Dierenrijk Zoo in the Netherlands were monitored at their maternity den one day before the birth of their cubs and three days postpartum. Each bear was monitored for 96 hr to document behaviour and vocalisations. The goal was to obtain insight into the differences between the mother that lost her litter and the other that successfully reared her cubs. Six groups of cub vocalisations were identified: Comfort, Discomfort, Distress, Nursing Attempts, Nursing, and No Vocalisation. Maternal vocalisations were split into three groups: Calm, Grooming, and Stress. Maternal behaviours were also split into three groups: Active, Rest, and Stress. The unsuccessful mother produced more stress vocalisations before and during the birth of her cub, whereas the successful mother appeared less stressed. Vocalisations indicate that the cub that died tried to nurse but was unsuccessful. The unsuccessful mother showed less stress as her cub got weaker and vocalised less. From this I suggest that maternal stress was a factor in cub mortality. © 2015 Wiley Periodicals, Inc.

Three-phase bone scintigraphy for diagnosis of Charcot neuropathic osteoarthropathy in the diabetic foot - does quantitative data improve diagnostic value?

PubMed

Fosbøl, M; Reving, S; Petersen, E H; Rossing, P; Lajer, M; Zerahn, B

2017-01-01

To investigate whether inclusion of quantitative data on blood flow distribution compared with visual qualitative evaluation improve the reliability and diagnostic performance of 99 m Tc-hydroxymethylene diphosphate three-phase bone scintigraphy (TPBS) in patients suspected for charcot neuropathic osteoarthropathy (CNO) of the foot. A retrospective cohort study of TPBS performed on 148 patients with suspected acute CNO referred from a single specialized diabetes care centre. The quantitative blood flow distribution was calculated based on the method described by Deutsch et al. All scintigraphies were re-evaluated by independent, blinded observers twice with and without quantitative data on blood flow distribution at ankle and focus level, respectively. The diagnostic validity of TPBS was determined by subsequent review of clinical data and radiological examinations. A total of 90 patients (61%) had confirmed diagnosis of CNO. The sensitivity, specificity and accuracy of three-phase bone scintigraphy without/with quantitative data were 89%/88%, 58%/62% and 77%/78%, respectively. The intra-observer agreement improved significantly by adding quantitative data in the evaluation (Kappa value 0·79/0·94). The interobserver agreement was not significantly improved. Adding quantitative data on blood flow distribution in the interpretation of TBPS improves intra-observer variation, whereas no difference in interobserver variation was observed. The sensitivity of TPBS in the diagnosis of CNO is high, but holds limited specificity. Diagnostic performance does not improve using quantitative data in the evaluation. This may be due to the reference intervals applied in the study or the absence of a proper gold standard diagnostic procedure for comparison. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Bumpus in the snake den: effects of sex, size, and body condition on mortality of red-sided garter snakes.

PubMed

Shine, R; LeMaster, M P; Moore, I T; Olsson, M M; Mason, R T

2001-03-01

Huge breeding aggregations of red-sided garter snakes (Thamnophis sirtalis parietalis) at overwintering dens in Manitoba provide a unique opportunity to identify sources of mortality and to clarify factors that influence a snake's vulnerability to these factors. Comparisons of sexes, body sizes, and body condition of more than 1000 dead snakes versus live animals sampled at the same time reveal significant biases. Three primary sources of mortality were identified. Predation by crows, Corvus brachyrhynchos (590 snakes killed), was focussed mostly on small snakes of both sexes. Crows generally removed the snake's liver and left the carcass, but very small snakes were sometimes brought back to the nest. Suffocation beneath massive piles of other snakes within the den (301 dead animals) involved mostly small males and (to a lesser extent) large females; snakes in poor body condition were particularly vulnerable. Many emaciated snakes (n = 142, mostly females) also died without overt injuries, probably due to depleted energy reserves. These biases in vulnerability are readily interpretable from information on behavioral ecology of the snakes. For example, sex biases in mortality reflect differences in postemergence behavior and locomotor capacity, the greater attractiveness of larger females to males, and the high energy costs of reproduction for females.

Mutational analysis of the myelin protein zero (MPZ) gene associated with Charcot-Marie-Tooth neuropathy type 1B

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

Roa, B.B.; Warner, L.E.; Lupski, J.R.

1994-09-01

The MPZ gene that maps to chromosome 1q22q23 encodes myelin protein zero, which is the most abundant peripheral nerve myelin protein that functions as a homophilic adhesion molecule in myelin compaction. Association of the MPZ gene with the dysmyelinating peripheral neuropathies Charcot-Marie-Tooth disease type 1B (CMT1B) and the more severe Dejerine-Sottas syndrome (DSS) was previously demonstrated by MPZ mutations identified in CMT1B and in rare DSS patients. In this study, the coding region of the MPZ gene was screened for mutations in a cohort of 74 unrelated patients with either CMT type 1 or DSS who do not carry themore » most common CMT1-associated molecular lesion of a 1.5 Mb DNA duplication on 17p11.2-p12. Heteroduplex analysis detected base mismatches in ten patients that were distributed over three exons of MPZ. Direct sequencing of PCR-amplified genomic DNA identified a de novo MPZ mutation associated with CMT1B that predicts an Ile(135)Thr substitution. This finding further confirms the role of MPZ in the CMT1B disease process. In addition, two polymorphisms were identified within the Gly(200) and Ser(228) codons that do not alter the respective amino acid residues. A fourth base mismatch in MPZ exon 3 detected by heteroduplex analysis is currently being characterized by direct sequence determination. Previously, four unrelated patients in this same cohort were found to have unique point mutations in the coding region of the PMP22 gene. The collective findings on CMT1 point mutations could suggest that regulatory region mutations, and possibly mutations in CMT gene(s) apart from the MPZ, PMP22 and Cx32 genes identified thus far, may prove to be significant for a number of CMT1 cases that do not involve DNA duplication.« less

Management of 2 teeth diagnosed with dens invaginatus with regenerative endodontics and apexification in the same patient: a case report and review.

PubMed

Kumar, Harleen; Al-Ali, Muna; Parashos, Peter; Manton, David J

2014-05-01

This review and case report present the treatment of a 10-year-old boy with both permanent maxillary lateral incisors demonstrating Oehlers type II dens invaginatus and pulpal involvement. Treatment was complicated by dental anxiety, supraventricular tachycardia, immature tooth development, and facial cellulitis. An infected necrotic pulp of the permanent maxillary left lateral incisor was treated by apexification and endodontic treatment with mineral trioxide aggregate. The necrotic pulp of the permanent maxillary right lateral incisor was treated with canal debridement and dressing under general anesthesia. Periapical healing of both teeth occurred, with the right lateral incisor showing continued root growth, thickening of the dentinal root walls, and completed apex formation. This tooth responded normally to pulp testing. Twenty-eight months after initial treatment, the right lateral incisor displayed progressive sclerosis of the canal. This case demonstrates possible pulpal regeneration of an infected maxillary right lateral incisor with dens invaginatus and an immature apex after minimal canal debridement. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Homological dimensions and Van den Bergh isomorphisms for nuclear Fréchet algebras

NASA Astrophysics Data System (ADS)

Pirkovskii, Alexei Yu

2012-08-01

We prove the equation \\operatorname{w{.}dg} A=\\operatorname{w{.}db} A for every nuclear Fréchet-Arens-Michael algebra A of finite weak bidimension, where \\operatorname{w{.}dg} A is the weak global dimension and \\operatorname{w{.}db} A the weak bidimension of A. Assuming that A has a projective bimodule resolution of finite type, we establish the estimate \\operatorname{db}A\\le\\operatorname{dg}A+1, where \\operatorname{dg} A is the global dimension and \\operatorname{db} A the bidimension of A. We also prove that \\operatorname{dg}A=\\operatorname{db}A=\\operatorname{w{.}dg}A=\\operatorname{w{.}db} A=n for all nuclear Fréchet-Arens-Michael algebras satisfying the Van den Bergh conditions \\operatorname{VdB}(n). As an application, we calculate the homological dimensions of smooth and complex-analytic quantum tori.

[Hysteria 100 years later].

PubMed

Widlocher, D

1982-01-01

Is it true that hysteria we see today is no longer that described at the end of the last century? Is it true that Charcot's work on hysteria ended in failure? Contrary to currently accepted opinion, it can be demonstrated not only that Charcot truly laid the foundation for the psychological theory of hysteria but that his explanation of the mechanism of conversion forms the basis for one of the most effective therapies. Furthermore the major streams of thought in psychopathology have come to complete Charcot's point of view and in no way contradict it. A general view of neurosis can thus be distinguished, while not forgetting that these complementary points of view are based on logics of action irreducibles to each other. The interest shown by Charcot in cultural phenomena, such as ecstasy or demoniacal possession, even introduces to an anthropological point of view which situates the hysterical symptom within the more general framework of a universal modality of action.

A Live Attenuated Chimeric West Nile Virus Vaccine, rWN/DEN4Δ30, Is Well Tolerated and Immunogenic in Flavivirus-Naive Older Adult Volunteers.

PubMed

Pierce, Kristen K; Whitehead, Stephen S; Kirkpatrick, Beth D; Grier, Palmtama L; Jarvis, Adrienne; Kenney, Heather; Carmolli, Marya P; Reynolds, Cynthia; Tibery, Cecilia M; Lovchik, Janece; Janiak, Anna; Luke, Catherine J; Durbin, Anna P; Pletnev, Alexander G

2017-01-01

West Nile virus (WNV) is a major cause of mosquito-borne illness in the United States. Human disease ranges from mild febrile illness to severe fatal neurologic infection. Adults aged >60 years are more susceptible to neuroinvasive disease accompanied by a high mortality rate or long-lasting neurologic sequelae. A chimeric live attenuated West Nile virus vaccine, rWN/DEN4Δ30, was shown to be safe and immunogenic in healthy adults aged 18-50 years. This study evaluated rWN/DEN4Δ30 in flavivirus-naive adults aged 50-65 years and found it to be safe and immunogenic. Outbreaks of WNV infection tend to be unpredictable, and a safe and effective vaccine will be an important public health tool. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

"Das Konkrete ist das Abstrakte, an das man sich schließlich gewöhnt hat." (Laurent Schwartz) Über den Ablauf des mathematischen Verstehens

NASA Astrophysics Data System (ADS)

Lowsky, Martin

Die im Titel genannte Aussage findet sich in den Lebenserinnerungen von Laurent Schwartz (1915-2002), einem der fruchtbarsten Mathematiker, Mitglied der Gruppe Bourbaki. Im Original lautet die Aussage: "un objet concret est un objet abstrait auquel on a fini par s'habituer." Schwartz erläutert sie am Beispiel des Integrals über {e^{-1/2{x^2}}} , das den Wert Wurzel aus 2π hat und in dem sich also die Zahlen e und π verknüpfen. Was Schwartz aber vor allem ausdrücken will, ist dies: Das mathematische Verständnisd geht langsam vor sich und es bedarf der Anstrengung. "Es ist eine Frage der Zeit und der Energie", sagt Schwartz, und gerade dies mache es so schwer, die höhere Mathematik unter das Volk zu bringen. Das Lernen und Lehren von Mathematik laufe eben mühevoll und langsam ab.

[Babinski and hysteria].

PubMed

Allilaire, Jean-François

2007-10-01

Babinski made important contributions to both psychiatry and neurology. He disagreed with Charcot's theatrical interpretation of hysteria and made a subtle distinction between Suggestion and Persuasion, thereby differentiating Hysteria from Pithiatism. This paper examines Charcot's concepts and the way in which Babinski refined and honed his master's theories.

Quantitative fluorescence-polymerase chain reaction assay for the detection of the duplication of the Charcot Marie Tooth disease type 1A critical region.

PubMed

De Toffol, Simona; Bellone, Emilia; Dulcetti, Francesca; Ruggeri, Anna Maria; Maggio, Pietro Paolo; Pulimeno, Maria Rosaria; Mandich, Paola; Maggi, Federico; Simoni, Giuseppe; Grati, Francesca Romana

2010-04-01

Charcot Marie Tooth (CMT) syndrome is the most common hereditary peripheral neuropathy, with an incidence of about 1 in 2500. The subtype 1A (CMT1A) is caused by a tandem duplication of a 1.5-Mb region encompassing the PMP22 gene. Conventional short tandem repeat (STR) analysis can reveal this imbalance if a triallelic pattern, defining with certainty the presence of duplication, is present. In case of duplication with a biallelic pattern, it can only indicate a semiquantitative dosage of the fluorescence intensity ratio of the two fragments. In this study we developed a quantitative fluorescence-PCR using seven highly informative STRs within the CMT1A critical region that successfully disclosed or excluded the presence of the pathogenic imbalance in a cohort of 60 samples including 40 DNAs from samples with the CMT1A duplication previously characterized with two different molecular approaches, and 20 diagnostic samples from 10 members of a five-generation pedigree segregating CMT1A, 8 unrelated cases and 2 prenatal samples. The application of the quantitative fluorescence-PCR using STRs located in the critical region could be a reliable method to evaluate the presence of the PMP22 duplication for the diagnosis and classification of hereditary neuropathies in asymptomatic subjects with a family history of inherited neuropathy, in prenatal samples in cases with one affected parent, and in unrelated patients with a sporadic demyelinating neuropathy with clinical features resembling CMT (i.e., pes cavus with hammer toes) or with conduction velocities in the range of CMT1A.

Whole-exome sequencing reveals a novel missense mutation in the MARS gene related to a rare Charcot-Marie-Tooth neuropathy type 2U.

PubMed

Sagi-Dain, Lena; Shemer, Lilach; Zelnik, Nathanel; Zoabi, Yusri; Orit, Sadeh; Adir, Vardit; Schif, Aharon; Peleg, Amir

2018-06-01

Charcot-Marie-Tooth (CMT) is a heterogeneous group of progressive disorders, characterized by chronic motor and sensory polyneuropathy. This hereditary disorder is related to numerous genes and varying inheritance patterns. Thus, many patients do not reach a final genetic diagnosis. We describe a 13-year-old girl presenting with progressive bilateral leg weakness and gait instability. Extensive laboratory studies and spinal magnetic resonance imaging scan were normal. Nerve conduction studies revealed severe lower limb peripheral neuropathy with prominent demyelinative component. Following presumptive diagnosis of chronic inflammatory demyelinating polyneuropathy, the patient received treatment with steroids and intravenous immunoglobulins courses for several months, with no apparent improvement. Whole-exome sequencing revealed a novel heterozygous c.2209C>T (p.Arg737Trp) mutation in the MARS gene (OMIM 156560). This gene has recently been related to CMT type 2U. In-silico prediction programs classified this mutation as a probable cause for protein malfunction. Allele frequency data reported this variant in 0.003% of representative Caucasian population. Family segregation analysis study revealed that the patient had inherited the variant from her 60-years old mother, reported as healthy. Neurologic examination of the mother demonstrated decreased tendon reflexes, while nerve conduction studies were consistent with demyelinative and axonal sensory-motor polyneuropathy. Our report highlights the importance of next-generation sequencing approach to facilitate the proper molecular diagnosis of highly heterogeneous neurologic disorders. Amongst other numerous benefits, this approach might prevent unnecessary diagnostic testing and potentially harmful medical treatment. © 2018 Peripheral Nerve Society.

Magnetic nanoparticles are highly toxic to chloroquine-resistant Plasmodium falciparum, dengue virus (DEN-2), and their mosquito vectors.

PubMed

Murugan, Kadarkarai; Wei, Jiang; Alsalhi, Mohamad Saleh; Nicoletti, Marcello; Paulpandi, Manickam; Samidoss, Christina Mary; Dinesh, Devakumar; Chandramohan, Balamurugan; Paneerselvam, Chellasamy; Subramaniam, Jayapal; Vadivalagan, Chithravel; Wei, Hui; Amuthavalli, Pandiyan; Jaganathan, Anitha; Devanesan, Sandhanasamy; Higuchi, Akon; Kumar, Suresh; Aziz, Al Thabiani; Nataraj, Devaraj; Vaseeharan, Baskaralingam; Canale, Angelo; Benelli, Giovanni

2017-02-01

A main challenge in parasitology is the development of reliable tools to prevent or treat mosquito-borne diseases. We investigated the toxicity of magnetic nanoparticles (MNP) produced by Magnetospirillum gryphiswaldense (strain MSR-1) on chloroquine-resistant (CQ-r) and sensitive (CQ-s) Plasmodium falciparum, dengue virus (DEN-2), and two of their main vectors, Anopheles stephensi and Aedes aegypti, respectively. MNP were studied by Fourier-transform infrared spectroscopy and transmission electron microscopy. They were toxic to larvae and pupae of An. stephensi, LC 50 ranged from 2.563 ppm (1st instar larva) to 6.430 ppm (pupa), and Ae. aegypti, LC 50 ranged from 3.231 ppm (1st instar larva) to 7.545 ppm (pupa). MNP IC 50 on P. falciparum were 83.32 μg ml -1 (CQ-s) and 87.47 μg ml -1 (CQ-r). However, the in vivo efficacy of MNP on Plasmodium berghei was low if compared to CQ-based treatments. Moderate cytotoxicity was detected on Vero cells post-treatment with MNP doses lower than 4 μg ml -1 . MNP evaluated at 2-8 μg ml -1 inhibited DEN-2 replication inhibiting the expression of the envelope (E) protein. In conclusion, our findings represent the first report about the use of MNP in medical and veterinary entomology, proposing them as suitable materials to develop reliable tools to combat mosquito-borne diseases.

A Rare Case of Type III Dens Invaginatus in a Mandibular Second Premolar and Its Nonsurgical Endodontic Management by Using Cone-beam Computed Tomography: A Case Report.

PubMed

Agrawal, Pritesh Kisanlal; Wankhade, Jyoti; Warhadpande, Manjusha

2016-04-01

Invaginated teeth present technical difficulties in clinical management because of their abnormal anatomic configuration. Endodontic clinical management of type III dens invaginatus can be greatly enhanced by newer techniques and materials such as cone-beam computed tomography (CBCT), mineral trioxide aggregate, and platelet-rich fibrin. This case report presents a 13-year-old male patient with type III dens invaginatus (DI) in left mandibular second premolar with history of recurrent swelling. Pulp testing revealed no response with the tooth. Dens invaginatus type III with an immature apex and periapical lesion was seen on radiograph. The case was diagnosed as Oehlers type III DI with pulp necrosis and chronic apical abscess. The treatment was planned and performed by using CBCT imaging. CBCT was performed to see the canal anatomy and to know the size of periapical lesion. Root canal treatment was completed in 2 visits. Calcium hydroxide dressing was placed in the first visit. In the second visit MTA was used for apexification in the main canal, and warm vertical compaction technique with gutta-percha was used in the invaginated canal. At the 2-year reevaluation, the patient was asymptomatic, and his tooth had remained functional since the treatment was completed. Radiographic assessment of the tooth showed significant osseous healing of the preoperative lesion. Three-dimensional imaging is a valuable tool for endodontic management of teeth with complex internal anatomy. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Gait analysis in a patient with severe Charcot-Marie-Tooth disease: a case study with a new orthotic device for footdrop.

PubMed

Vinci, Paolo; Paoloni, M; Ioppolo, F; Gargiulo, P; Santilli, V

2010-09-01

Management of footdrop in severe Charcot-Marie-Tooth (CMT) patients is a challenge owing to the combination of quadriceps muscle weakness, distal muscular atrophy, sensory impairment and poor soft tissue resistance to the placement of an orthotic device. We present a case study of a patient who gradually became unable to use his ankle-foot orthoses because they hampered the compensative movements required to stabilize his knees passively and caused pain. The aim of this report is to describe orthotic management in such a severe CMT case and to present a new orthotic device that we devised for the footdrop in this patient. We provided him with 3 different footdrop devices, each of which was highly elastic to allow knee hyperextension, and left him free to decide which one to use: 1) the silicone-ankle-foot orthoses were rapidly discarded because of pain; 2) the Codivilla support was not used because of discomfort and poor aesthetic appearance; 3) a new device, called the "Soft Footdrop Insert" (SFI), consisting of a sheet of Veolform, a reticulated polyolephinic foam, stuck to the counter of midcalf boots, was found to be effective, comfortable, pain-free and aesthetically acceptable, and was consequently used the vast majority of the time. At a 3-year follow-up, an instrumental gait analysis, in which ordinary shoes were compared with the Codivilla support and the SFI, revealed that both the Codivilla support and the SFI controlled footdrop more effectively than ordinary shoes and increased swing and mean velocity; in addition, the SFI yielded the best gait performances. We think that a soft, invisible device, such as the SFI, may satisfy the needs of CMT patients and improve compliance with orthoses-wearing for footdrop.

Novel INF2 mutations in an Italian cohort of patients with focal segmental glomerulosclerosis, renal failure and Charcot-Marie-Tooth neuropathy.

PubMed

Caridi, Gianluca; Lugani, Francesca; Dagnino, Monica; Gigante, Maddalena; Iolascon, Achille; Falco, Mariateresa; Graziano, Claudio; Benetti, Elisa; Dugo, Mauro; Del Prete, Dorella; Granata, Antonio; Borracelli, Donella; Moggia, Elisabetta; Quaglia, Marco; Rinaldi, Rita; Gesualdo, Loreto; Ghiggeri, Gian Marco

2014-09-01

Mutations of INF2 represent the major cause of familial autosomal dominant (AD) focal segmental glomerulosclerosis (FSGS). A few patients present neurological symptoms of Charcot-Marie-Tooth (CMT) disease but the prevalence of the association has not been assessed yet. We screened 28 families with AD FSGS and identified 8 INF2 mutations in 9 families (32 patients overall), 3 of which were new. Mutations were in all cases localized in the diaphanous-inhibitory domain (DID) of the protein. Clinical features associated with INF2 mutations in our patient cohort included mild proteinuria (1.55 g/L; range 1-2.5) and haematuria as a unique symptom that was recognized at a median age of 21.75 years (range 8-30). Eighteen patients developed end-stage renal disease during their third decade of life; 12 patients presented a creatinine range between 1.2 and 1.5 mg/dL and 2 were healthy at 45 and 54 years of age. CMT was diagnosed in four cases (12.5%); one of these patients presented an already known mutation on exon 2 of INF2, whereas the other patients presented the same mutation on exon 4, a region that was not previously associated with CMT. We confirmed the high incidence of INF2 mutations in families with AD FSGS. The clinical phenotype was mild at the onset of the disease, but evolution to ESRD was frequent. The incidence of CMT has, for the first time, been calculated here to be 12.5% of mutation carriers. Our findings support INF2 gene analysis in families in which renal failure and/or neuro-sensorial defects are inherited following an AD model. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Dens invaginatus with necrotic pulp in a right maxillary lateral incisor with preserved vitality.

PubMed

Alessandro, Lanza; Fabrizio, Di Francesco; Gennaro, De Marco; Dario, Di Stasio; Eugenio, Guidetti; Letizia, Perillo; Luigi, Femiano; Felice, Femiano

2018-01-01

Dens invaginatus (DI) is a dental malformation occurring in several morphologic types. Consequently, treatment of teeth affected by DI can get complicated because of the complex root canal anatomy. The aim is to describe how to manage a rare report of a DI with necrotic pulp held within the vital pulp of a maxillary lateral incisor. Oral fistula was found on the buccal mucosa of the apex of the vital maxillary lateral incisor with a DI having necrotic pulp. Endodontic treatment of the maxillary lateral incisor and of the tract canal of DI was realized. Clinical disappearance of oral sinus tract was observed after 10 days. On the contrary, the disappearance of radiolucent area occurred after 6 months. A proper and prompt diagnosis is necessary to carry out effective prevention protocols or prevent consequences generating nonrecoverable endo-perio diseases.

Non-surgical root canal treatment of Dens invaginatus: reports of three cases.

PubMed

Cengiz, Sevi Burcak; Korasli, Deniz; Ziraman, Fatmagul; Orhan, Kaan

2006-02-01

Dens invaginatus is a rare developmental malformation of teeth showing a deep infolding of enamel and dentine which may extend deep into the root. To date, conventional root canal therapy, endodontic surgery and extraction have been reported as treatment modalities, when the pulpo-dentinal complex of such teeth is affected. In the present report, non-surgical endodontic treatment of three maxillary lateral incisors with invaginatus (DI) is discussed. The Tri Auto ZX rotary system was used for shaping the root canals of two affected teeth and the Profile system was used in the third. Teeth with periradicular lesions received calcium hydroxide as an interim therapy. Two teeth were obturated with gutta percha points and AH Plus sealer using cold lateral compaction. In the third case, obturation was accomplished using a coated carrier system (Thermafil) due to the specific shape of the root canal system. Twelve months postoperatively all teeth were asymptomatic with resolution of the periapical radiolucency on two affected teeth, as confirmed radiographically. Healing was achieved without any need for further surgical intervention.

Mitochondrial deficits and abnormal mitochondrial retrograde axonal transport play a role in the pathogenesis of mutant Hsp27-induced Charcot Marie Tooth Disease

PubMed Central

Innes, Amy; Wanisch, Klaus; Kolaszynska, Alicia Koyen; Pandraud, Amelie; Kelly, Gavin; Abramov, Andrey Y.; Reilly, Mary M.; Schiavo, Giampietro; Greensmith, Linda

2017-01-01

Abstract Mutations in the small heat shock protein Hsp27, encoded by the HSPB1 gene, have been shown to cause Charcot Marie Tooth Disease type 2 (CMT-2) or distal hereditary motor neuropathy (dHMN). Protein aggregation and axonal transport deficits have been implicated in the disease. In this study, we conducted analysis of bidirectional movements of mitochondria in primary motor neuron axons expressing wild type and mutant Hsp27. We found significantly slower retrograde transport of mitochondria in Ser135Phe, Pro39Leu and Arg140Gly mutant Hsp27 expressing motor neurons than in wild type Hsp27 neurons, although anterograde movement velocities remained normal. Retrograde transport of other important cargoes, such as the p75 neurotrophic factor receptor was minimally altered in mutant Hsp27 neurons, implicating that axonal transport deficits primarily affect mitochondria and the axonal transport machinery itself is less affected. Investigation of mitochondrial function revealed a decrease in mitochondrial membrane potential in mutant Hsp27 expressing motor axons, as well as a reduction in mitochondrial complex 1 activity, increased vulnerability of mitochondria to mitochondrial stressors, leading to elevated superoxide release and reduced mitochondrial glutathione (GSH) levels, although cytosolic GSH remained normal. This mitochondrial redox imbalance in mutant Hsp27 motor neurons is likely to cause low level of oxidative stress, which in turn will contribute to, and indeed may be the underlying cause of the deficits in mitochondrial axonal transport. Together, these findings suggest that the mitochondrial abnormalities in mutant Hsp27-induced neuropathies may be a primary cause of pathology, leading to further deficits in the mitochondrial axonal transport and onset of disease. PMID:28595321

The diagnosis and conservative treatment of a complex type 3 dens invaginatus using cone beam computed tomography (CBCT) and 3D plastic models.

PubMed

Kfir, A; Telishevsky-Strauss, Y; Leitner, A; Metzger, Z

2013-03-01

To investigate the use of 3D plastic models, printed from cone beam computed tomography (CBCT) data, for accurate diagnosis and conservative treatment of a complex case of dens invaginatus. A chronic apical abscess with a draining sinus tract was diagnosed during the treatment planning stage of orthodontic therapy. Radiographic examination revealed a large radiolucent area associated with an invaginated right maxillary central incisor, which was found to contain a vital pulp. The affected tooth was strategic in the dental arch. Conventional periapical radiographs provided only partial information about the invagination and its relationship with the main root canal and with the periapical tissues. A limited-volume CBCT scan of the maxilla did not show evidence of communication between the infected invagination and the pulp in the main root canal, which could explain the pulp vitality. A novel method was adopted to allow for instrumentation, disinfection and filling of the invagination, without compromising the vitality of the pulp in the complex root canal system. The CBCT data were used to produce precise 3D plastic models of the tooth. These models facilitated the treatment planning process and the trial of treatment approaches. This approach allowed the vitality of the pulp to be maintained in the complex root canal space of the main root canal whilst enabling the healing of the periapical tissues. Even when extensive periapical pathosis is associated with a tooth with type III dens invaginatus, pulp sensibility tests should be performed. CBCT is a diagnostic tool that may allow for the management of such teeth with complex anatomy. 3D printed plastic models may be a valuable aid in the process of assessing and planning effective treatment modalities and practicing them ex vivo before actually performing the clinical procedure. Unconventional technological approaches may be required for detailed treatment planning of complex cases of dens invaginatus. © 2012

Localization of a gene (CMT2A) for autosomal dominant Charcot-Marie-Tooth disease type 2 to chromosome 1p and evidence of genetic heterogeneity

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

Othmane, K.B.; Loprest, L.J.; Wilkinson, K.M.

1993-08-01

Charcot-Marie-Tooth (CMT) disease type 2 (CMT2) is an inherited peripheral neuropathy characterized by variable age of onset and normal or slightly diminished nerve conduction velocity. CMT2 is pathologically and genetically distinct from CMT type 1 (CMT1). While CMT1 has been shown to be genetically heterogeneous, no chromosomal localization has been established for CMT2. The authors have performed pedigree linkage analysis in six large autosomal dominant CMT2 families and have demonstrated linkage and heterogeneity to a series of microsatellites (D1S160, D1S170, D1S244, D1S228 and D1S199) in the distal region of the short arm of chromosome 1. Significant evidence for heterogeneity wasmore » found using admixture analyses and the two-point lod scores. Admixture analyses using the multipoint results for the markers D1S244, D1S228, and D1S199 supported the two-point findings. Three families, DUK662, DUK1241, and 1523 gave posterior probabilities of 1.0, 0.98, and 0.88 of being of the linked type. Multipoint analysis examining the [open quotes]linked[close quotes] families showed that the most favored location for the CMT2A gene is within the interval flanked by D1S244 and D1S228 (odds approximately 70:1 of lying within versus outside that interval). These findings suggest that the CMT2 phenotype is secondary to at least two different genes and demonstrate further heterogeneity in the CMT phenotype.« less

Mitochondrial deficits and abnormal mitochondrial retrograde axonal transport play a role in the pathogenesis of mutant Hsp27-induced Charcot Marie Tooth Disease.

PubMed

Kalmar, Bernadett; Innes, Amy; Wanisch, Klaus; Kolaszynska, Alicia Koyen; Pandraud, Amelie; Kelly, Gavin; Abramov, Andrey Y; Reilly, Mary M; Schiavo, Giampietro; Greensmith, Linda

2017-09-01

Mutations in the small heat shock protein Hsp27, encoded by the HSPB1 gene, have been shown to cause Charcot Marie Tooth Disease type 2 (CMT-2) or distal hereditary motor neuropathy (dHMN). Protein aggregation and axonal transport deficits have been implicated in the disease. In this study, we conducted analysis of bidirectional movements of mitochondria in primary motor neuron axons expressing wild type and mutant Hsp27. We found significantly slower retrograde transport of mitochondria in Ser135Phe, Pro39Leu and Arg140Gly mutant Hsp27 expressing motor neurons than in wild type Hsp27 neurons, although anterograde movement velocities remained normal. Retrograde transport of other important cargoes, such as the p75 neurotrophic factor receptor was minimally altered in mutant Hsp27 neurons, implicating that axonal transport deficits primarily affect mitochondria and the axonal transport machinery itself is less affected. Investigation of mitochondrial function revealed a decrease in mitochondrial membrane potential in mutant Hsp27 expressing motor axons, as well as a reduction in mitochondrial complex 1 activity, increased vulnerability of mitochondria to mitochondrial stressors, leading to elevated superoxide release and reduced mitochondrial glutathione (GSH) levels, although cytosolic GSH remained normal. This mitochondrial redox imbalance in mutant Hsp27 motor neurons is likely to cause low level of oxidative stress, which in turn will contribute to, and indeed may be the underlying cause of the deficits in mitochondrial axonal transport. Together, these findings suggest that the mitochondrial abnormalities in mutant Hsp27-induced neuropathies may be a primary cause of pathology, leading to further deficits in the mitochondrial axonal transport and onset of disease. © The Author 2017. Published by Oxford University Press.

Charcot Foot

MedlinePlus

... occur in people who have significant nerve damage (neuropathy). The bones are weakened enough to fracture, and ... living with diabetes—a disease often associated with neuropathy—take preventive measures and seek immediate care if ...

Application of DEN refinement and automated model building to a difficult case of molecular-replacement phasing: the structure of a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum.

PubMed

Brunger, Axel T; Das, Debanu; Deacon, Ashley M; Grant, Joanna; Terwilliger, Thomas C; Read, Randy J; Adams, Paul D; Levitt, Michael; Schröder, Gunnar F

2012-04-01

Phasing by molecular replacement remains difficult for targets that are far from the search model or in situations where the crystal diffracts only weakly or to low resolution. Here, the process of determining and refining the structure of Cgl1109, a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum, at ∼3 Å resolution is described using a combination of homology modeling with MODELLER, molecular-replacement phasing with Phaser, deformable elastic network (DEN) refinement and automated model building using AutoBuild in a semi-automated fashion, followed by final refinement cycles with phenix.refine and Coot. This difficult molecular-replacement case illustrates the power of including DEN restraints derived from a starting model to guide the movements of the model during refinement. The resulting improved model phases provide better starting points for automated model building and produce more significant difference peaks in anomalous difference Fourier maps to locate anomalous scatterers than does standard refinement. This example also illustrates a current limitation of automated procedures that require manual adjustment of local sequence misalignments between the homology model and the target sequence.

Application of DEN refinement and automated model building to a difficult case of molecular-replacement phasing: the structure of a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum

PubMed Central

Brunger, Axel T.; Das, Debanu; Deacon, Ashley M.; Grant, Joanna; Terwilliger, Thomas C.; Read, Randy J.; Adams, Paul D.; Levitt, Michael; Schröder, Gunnar F.

2012-01-01

Phasing by molecular replacement remains difficult for targets that are far from the search model or in situations where the crystal diffracts only weakly or to low resolution. Here, the process of determining and refining the structure of Cgl1109, a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum, at ∼3 Å resolution is described using a combination of homology modeling with MODELLER, molecular-replacement phasing with Phaser, deformable elastic network (DEN) refinement and automated model building using AutoBuild in a semi-automated fashion, followed by final refinement cycles with phenix.refine and Coot. This difficult molecular-replacement case illustrates the power of including DEN restraints derived from a starting model to guide the movements of the model during refinement. The resulting improved model phases provide better starting points for automated model building and produce more significant difference peaks in anomalous difference Fourier maps to locate anomalous scatterers than does standard refinement. This example also illustrates a current limitation of automated procedures that require manual adjustment of local sequence misalignments between the homology model and the target sequence. PMID:22505259

Upper Pleistocene Gulo gulo (Linne, 1758) remains from the Srbsko Chlum-Komin Hyena den cave in the Bohemian Karst, Czech Republic, with comparisons to contemporary wolverines

Treesearch

Cajus G. Diedrich; Jeffrey P. Copeland

2010-01-01

Wolverine bone material is described from the famous Upper Pleistocene cave Srbsko Chlum-Komin in the Bohemian Karst, Czech Republic, along with an overview of recently known Czech sites. The Gulo gulo Linne material was found in one of the largest Ice Age spotted-hyena dens in Europe. As a result of non-systematic excavations, the taphonomy is partly unclear. Lower-...

Neurofilament light polypeptide gene N98S mutation in mice leads to neurofilament network abnormalities and a Charcot-Marie-Tooth Type 2E phenotype.

PubMed

Adebola, Adijat A; Di Castri, Theo; He, Chui-Zhen; Salvatierra, Laura A; Zhao, Jian; Brown, Kristy; Lin, Chyuan-Sheng; Worman, Howard J; Liem, Ronald K H

2015-04-15

Charcot-Marie-Tooth disease (CMT) is the most commonly inherited neurological disorder with a prevalence of 1 in 2500 people worldwide. Patients suffer from degeneration of the peripheral nerves that control sensory information of the foot/leg and hand/arm. Multiple mutations in the neurofilament light polypeptide gene, NEFL, cause CMT2E. Previous studies in transfected cells showed that expression of disease-associated neurofilament light chain variants results in abnormal intermediate filament networks associated with defects in axonal transport. We have now generated knock-in mice with two different point mutations in Nefl: P8R that has been reported in multiple families with variable age of onset and N98S that has been described as an early-onset, sporadic mutation in multiple individuals. Nefl(P8R/+) and Nefl(P8R/P8R) mice were indistinguishable from Nefl(+/+) in terms of behavioral phenotype. In contrast, Nefl(N98S/+) mice had a noticeable tremor, and most animals showed a hindlimb clasping phenotype. Immunohistochemical analysis revealed multiple inclusions in the cell bodies and proximal axons of spinal cord neurons, disorganized processes in the cerebellum and abnormal processes in the cerebral cortex and pons. Abnormal processes were observed as early as post-natal day 7. Electron microscopic analysis of sciatic nerves showed a reduction in the number of neurofilaments, an increase in the number of microtubules and a decrease in the axonal diameters. The Nefl(N98S/+) mice provide an excellent model to study the pathogenesis of CMT2E and should prove useful for testing potential therapies. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Prevalence and origin of De Novo duplications in Charcot-Marie-Tooth disease type 1A: First report of a De Novo duplication with a maternal origin

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

Blair, I.P.; Nash, J.; Gordon, M.J.

1996-03-01

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. Sporadic cases of CMT have been described since the earliest reports of the disease. The most frequent form of the disorder, CMT1A, is associated with a 1.5-Mb DNA duplication on chromosome 17p11.2, which segregates with the disease. In order to investigate the prevalence of de novo CMT1A duplications, this study examined 118 duplication-positive CMT1A families. In 10 of these families it was demonstrated that the disease had arisen as the result of a de novo mutation. By taking into account the ascertainment of families, it can be estimated that {>=}10%more » of autosomal dominant CMT1 families are due to de novo duplications. The CMT1A duplication is thought to be the product of unequal crossing over between parental chromosome 17 homologues during meiosis. Polymorphic markers from within the duplicated region were used to determine the parental origin of these de novo duplications in eight informative families. Seven were of paternal and one of maternal origin. This study represents the first report of a de novo duplication with a maternal origin and indicates that it is not a phenomenon associated solely with male meioses. Recombination fractions for the region duplicated in CMT1A are larger in females than in males. That suggests that oogenesis may be afforded greater protection from misalignment during synapsis, and/or that there may be lower activity of those factors or mechanisms that lead to unequal crossing over at the CMT1A locus. 41 refs., 2 figs.« less

Clinical and quantitative analysis of patients with crowned dens syndrome.

PubMed

Takahashi, Teruyuki; Tamura, Masato; Takasu, Toshiaki; Kamei, Satoshi

2017-05-15

Crowned dens syndrome (CDS) is a radioclinical entity defined by calcium deposition on the transverse ligament of atlas (TLA). In this study, the novel semi-quantitative diagnostic criteria for CDS to evaluate the degree of calcification on TLA by cervical CT are proposed. From January 2010 to September 2014, 35 patients who were diagnosed with CDS by cervical CT were adopted as subjects in this study. Based on novel criteria, calcium deposition on TLA was classified into "Stage" and "Grade", to make a score, which was evaluated semi-quantitatively. The correlation between calcification score and CRP level or pain score, and the effects of treatments, such as NSAIDs and corticosteroids, were statistically analyzed. The total calcification score from added "Stage" and "Grade" scores demonstrated a significantly strong and linear correlation with CRP level (R 2 =0.823, **p<0.01). In the multiple comparison test for the treatment effects, significant improvement of the CRP level and pain score were demonstrated after corticosteroid therapy (**p<0.01) compared with NSAIDs. In the conditional logistic regression analysis, the rapid end of corticosteroid therapy was an independent risk factor for relapse of cervico-occipital pain [OR=50.761, *p=0.0419]. The degree of calcification on TLA evaluated by the novel semi-quantitative criteria significantly correlated with CRP level. In the treatment of CDS, it is recommended that a low dosage (15-30mg) of corticosteroids be used as first-line drugs rather than conventional NSAID therapy. Additionally, it is also recommended to gradually decrease the dosage of corticosteroids. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevalence of Charcot Arthropathy in Type 2 Diabetes Patients Aged over 50 Years with Severe Peripheral Neuropathy: A Retrospective Study in a Tertiary Care South Indian Hospital.

PubMed

Salini, Dharmadas; Harish, Kumar; Minnie, Pillay; Sundaram, Karimassery R; Arun, Bal; Sandya, Chirukandath J; Mangalanandan, Thacho S; Vivek, Lakshmanan; Praveen, Valiyaparambil P

2018-01-01

Available literature on the prevalence of Charcot arthropathy (CA) represents mainly Western population. No study has been reported from India so far. Hence we attempted to study the prevalence of CA in patients with type 2 diabetes mellitus and severe peripheral neuropathy (T2DMPN), belonging to Indian population amongst whom type 2 diabetes is on the rise in alarming proportions. Medical records of 3387 patients who performed an objective vibration perception threshold test during the year 2015 were screened for T2DMPN. Out of these, 1475 T2DMPN patients above 50 years were selected and analyzed in detail for CA. CA was diagnosed based on clinical features and/or radiological investigations. The anatomical localization of the disease distribution of the affected foot was done according to Brodsky's classification. The prevalence of CA in T2DMPN patients was found to be 9.8%. The mean age of patients diagnosed with CA was 63 ± 8.36 years, and mean duration of DM for CA to develop was 18.01 ± 8.23 years. About 62.5% of the patients were male and 37.5% female. Bilateral presentation of CA was observed in 20.8% of patients. Multiple sites of the foot were affected in 48.6% of patients and belonged to type 4 classification of Brodsky. A high prevalence of CA (9.8%) was observed in the present study conducted on T2DMPN patients who presented to the endocrinology department of a tertiary care South Indian hospital. In the majority of patients, the area of foot affected belonged to type 4 classification of Brodsky.

Prevalence of Charcot Arthropathy in Type 2 Diabetes Patients Aged over 50 Years with Severe Peripheral Neuropathy: A Retrospective Study in a Tertiary Care South Indian Hospital

PubMed Central

Salini, Dharmadas; Harish, Kumar; Minnie, Pillay; Sundaram, Karimassery R.; Arun, Bal; Sandya, Chirukandath J.; Mangalanandan, Thacho S.; Vivek, Lakshmanan; Praveen, Valiyaparambil P.

2018-01-01

Aims: Available literature on the prevalence of Charcot arthropathy (CA) represents mainly Western population. No study has been reported from India so far. Hence we attempted to study the prevalence of CA in patients with type 2 diabetes mellitus and severe peripheral neuropathy (T2DMPN), belonging to Indian population amongst whom type 2 diabetes is on the rise in alarming proportions. Materials and Methods: Medical records of 3387 patients who performed an objective vibration perception threshold test during the year 2015 were screened for T2DMPN. Out of these, 1475 T2DMPN patients above 50 years were selected and analyzed in detail for CA. CA was diagnosed based on clinical features and/or radiological investigations. The anatomical localization of the disease distribution of the affected foot was done according to Brodsky's classification. Results: The prevalence of CA in T2DMPN patients was found to be 9.8%. The mean age of patients diagnosed with CA was 63 ± 8.36 years, and mean duration of DM for CA to develop was 18.01 ± 8.23 years. About 62.5% of the patients were male and 37.5% female. Bilateral presentation of CA was observed in 20.8% of patients. Multiple sites of the foot were affected in 48.6% of patients and belonged to type 4 classification of Brodsky. Conclusions: A high prevalence of CA (9.8%) was observed in the present study conducted on T2DMPN patients who presented to the endocrinology department of a tertiary care South Indian hospital. In the majority of patients, the area of foot affected belonged to type 4 classification of Brodsky. PMID:29535947

Factors affecting date of implantation, parturition, and den entry estimated from activity and body temperature in free-ranging brown bears.

PubMed

Friebe, Andrea; Evans, Alina L; Arnemo, Jon M; Blanc, Stéphane; Brunberg, Sven; Fleissner, Günther; Swenson, Jon E; Zedrosser, Andreas

2014-01-01

Knowledge of factors influencing the timing of reproduction is important for animal conservation and management. Brown bears (Ursus arctos) are able to vary the birth date of their cubs in response to their fat stores, but little information is available about the timing of implantation and parturition in free-ranging brown bears. Body temperature and activity of pregnant brown bears is higher during the gestation period than during the rest of hibernation and drops at parturition. We compared mean daily body temperature and activity levels of pregnant and nonpregnant females during preimplantation, gestation, and lactation. Additionally we tested whether age, litter size, primiparity, environmental conditions, and the start of hibernation influence the timing of parturition. The mean date of implantation was 1 December (SD = 12), the mean date of parturition was 26 January (SD = 12), and the mean duration of the gestation period was 56 days (SD = 2). The body temperature of pregnant females was higher during the gestation and lactation periods than that of nonpregnant bears. The body temperature of pregnant females decreased during the gestation period. Activity recordings were also used to determine the date of parturition. The parturition dates calculated with activity and body temperature data did not differ significantly and were the same in 50% of the females. Older females started hibernation earlier. The start of hibernation was earlier during years with favorable environmental conditions. Dates of parturition were later during years with good environmental conditions which was unexpected. We suggest that free-ranging pregnant brown bears in areas with high levels of human activities at the beginning of the denning period, as in our study area, might prioritize investing energy in early denning than in early parturition during years with favorable environmental conditions, as a strategy to prevent disturbances caused by human.

Factors Affecting Date of Implantation, Parturition, and Den Entry Estimated from Activity and Body Temperature in Free-Ranging Brown Bears

PubMed Central

Friebe, Andrea; Evans, Alina L.; Arnemo, Jon M.; Blanc, Stéphane; Brunberg, Sven; Fleissner, Günther; Swenson, Jon E.; Zedrosser, Andreas

2014-01-01

Knowledge of factors influencing the timing of reproduction is important for animal conservation and management. Brown bears (Ursus arctos) are able to vary the birth date of their cubs in response to their fat stores, but little information is available about the timing of implantation and parturition in free-ranging brown bears. Body temperature and activity of pregnant brown bears is higher during the gestation period than during the rest of hibernation and drops at parturition. We compared mean daily body temperature and activity levels of pregnant and nonpregnant females during preimplantation, gestation, and lactation. Additionally we tested whether age, litter size, primiparity, environmental conditions, and the start of hibernation influence the timing of parturition. The mean date of implantation was 1 December (SD = 12), the mean date of parturition was 26 January (SD = 12), and the mean duration of the gestation period was 56 days (SD = 2). The body temperature of pregnant females was higher during the gestation and lactation periods than that of nonpregnant bears. The body temperature of pregnant females decreased during the gestation period. Activity recordings were also used to determine the date of parturition. The parturition dates calculated with activity and body temperature data did not differ significantly and were the same in 50% of the females. Older females started hibernation earlier. The start of hibernation was earlier during years with favorable environmental conditions. Dates of parturition were later during years with good environmental conditions which was unexpected. We suggest that free-ranging pregnant brown bears in areas with high levels of human activities at the beginning of the denning period, as in our study area, might prioritize investing energy in early denning than in early parturition during years with favorable environmental conditions, as a strategy to prevent disturbances caused by human. PMID:24988486

Hysteria: the history of an idea.

PubMed

Merskey, H

1983-10-01

Hysteria has long been recognized as a condition involving multiple somatic symptoms and resulting from a state of the emotions. By the time of Charcot, it became possible to attribute a hysterical symptom to an idea. It appears that the first detailed statement to this effect was made by Russell Reynolds (1) and it was adopted by Charcot (2), particularly because of his experience that hypnosis could be used to suggest hysterical symptoms. These concepts provided the starting point for Freud's theories.

KENNEDY SPACE CENTER, FLA. -- An alligator is spotted sunning on the muddy bank of a canal in KSC. Nearly 5,000 alligators can be found in canals, ponds, and waterways throughout the Center and the surrounding Merritt Island National Wildlife Refuge. American alligators feed and rest in the water, and lay their eggs in dens they dig into the banks. The young alligators spend their first several weeks in these dens. The Wildlife Refuge encompasses 92,000 acres that are a habitat for more than 331 species of birds, 31 mammals, 117 fishes, and 65 amphibians and reptiles.

NASA Image and Video Library

2004-01-08

KENNEDY SPACE CENTER, FLA. -- An alligator is spotted sunning on the muddy bank of a canal in KSC. Nearly 5,000 alligators can be found in canals, ponds, and waterways throughout the Center and the surrounding Merritt Island National Wildlife Refuge. American alligators feed and rest in the water, and lay their eggs in dens they dig into the banks. The young alligators spend their first several weeks in these dens. The Wildlife Refuge encompasses 92,000 acres that are a habitat for more than 331 species of birds, 31 mammals, 117 fishes, and 65 amphibians and reptiles.

Nerve-dependent changes in skeletal muscle myosin heavy chain after experimental denervation and cross-reinnervation and in a demyelinating mouse model of Charcot-Marie-Tooth disease type 1A.

PubMed

Maggs, Alison M; Huxley, Clare; Hughes, Simon M

2008-12-01

Innervation regulates the contractile properties of vertebrate muscle fibers, in part through the effect of electrical activity on expression of distinct myosins. Herein we analyze the role of innervation in regulating the accumulation of the general, maturational, and adult forms of rodent slow myosin heavy chain (MyHC) that are defined by the presence of distinct antigenic epitopes. Denervation increases the number of fibers that express general slow MyHC, but it decreases the adult slow MyHC epitope. Cross-reinnervation of slow muscle by a fast nerve leads to an increase in the number of fibers that express fast MyHC. In both cases, there is an increase in the number of fibers that express slow and fast IIA MyHCs, but without the adult slow MyHC epitope. The data suggest that innervation is required for maturation and maintenance of diversity of both slow and fast fibers. The sequence of slow MyHC epitope transitions is a useful biomarker, and it may play a significant role during nerve-dependent changes in muscle fiber function. We applied this detailed muscle analysis to a transgenic mouse model of human motor and sensory neuropathy IA, also known as Charcot-Marie-Tooth disease type 1A (CMT1A), in which electrical conduction in some motor nerves is poor due to demyelination. The mice display atrophy of some muscle fibers and changes in slow and fast MyHC epitope expression, suggestive of a progressive increase in innervation of muscle fibers by fast motor neurons, even at early stages. The potential role of these early changes in disease pathogenesis is assessed.

Mutations in SCARF2 Are Responsible for Van Den Ende-Gupta Syndrome

PubMed Central

Anastasio, Natascia; Ben-Omran, Tawfeg; Teebi, Ahmad; Ha, Kevin C.H.; Lalonde, Emilie; Ali, Rehab; Almureikhi, Mariam; Der Kaloustian, Vazken M.; Liu, Junhui; Rosenblatt, David S.; Majewski, Jacek; Jerome-Majewska, Loydie A.

2010-01-01

Van Den Ende-Gupta syndrome (VDEGS) is an extremely rare autosomal-recessive disorder characterized by distinctive craniofacial features, which include blepharophimosis, malar and/or maxillary hypoplasia, a narrow and beaked nose, and an everted lower lip. Other features are arachnodactyly, camptodactyly, peculiar skeletal abnormalities, and normal development and intelligence. We present molecular data on four VDEGS patients from three consanguineous Qatari families belonging to the same highly inbred Bedouin tribe. The patients were genotyped with SNP microarrays, and a 2.4 Mb homozygous region was found on chromosome 22q11 in an area overlapping the DiGeorge critical region. This region contained 44 genes, including SCARF2, a gene that is expressed during development in a number of mouse tissues relevant to the symptoms described above. Sanger sequencing identified a missense change, c.773G>A (p.C258Y), in exon 4 in the two closely related patients and a 2 bp deletion in exon 8, c.1328_1329delTG (p.V443DfsX83), in two unrelated individuals. In parallel with the candidate gene approach, complete exome sequencing was used to confirm that SCARF2 was the gene responsible for VDEGS. SCARF2 contains putative epidermal growth factor-like domains in its extracellular domain, along with a number of positively charged residues in its intracellular domain, indicating that it may be involved in intracellular signaling. However, the function of SCARF2 has not been characterized, and this study reports that phenotypic effects can be associated with defects in the scavenger receptor F family of genes. PMID:20887961

Ultrasonographic nerve enlargement of the median and ulnar nerves and the cervical nerve roots in patients with demyelinating Charcot-Marie-Tooth disease: distinction from patients with chronic inflammatory demyelinating polyneuropathy.

PubMed

Sugimoto, Takamichi; Ochi, Kazuhide; Hosomi, Naohisa; Takahashi, Tetsuya; Ueno, Hiroki; Nakamura, Takeshi; Nagano, Yoshito; Maruyama, Hirofumi; Kohriyama, Tatsuo; Matsumoto, Masayasu

2013-10-01

Demyelinating Charcot-Marie-Tooth disease (CMT) and chronic inflammatory demyelinating polyneuropathy (CIDP) are both demyelinating polyneuropathies. The differences in nerve enlargement degree and pattern at multiple evaluation sites/levels are not well known. We investigated the differences in nerve enlargement degree and the distribution pattern of nerve enlargement in patients with demyelinating CMT and CIDP, and verified the appropriate combination of sites/levels to differentiate between these diseases. Ten patients (aged 23-84 years, three females) with demyelinating CMT and 16 patients (aged 30-85 years, five females) with CIDP were evaluated in this study. The nerve sizes were measured at 24 predetermined sites/levels from the median and ulnar nerves and the cervical nerve roots (CNR) using ultrasonography. The evaluation sites/levels were classified into three regions: distal, intermediate and cervical. The number of sites/levels that exhibited nerve enlargement (enlargement site number, ESN) in each region was determined from the 24 sites/levels and from the selected eight screening sites/levels, respectively. The cross-sectional areas of the peripheral nerves were markedly larger at all evaluation sites in patients with demyelinating CMT than in patients with CIDP (p < 0.01). However, the nerve sizes of CNR were not significantly different between patients with either disease. When we evaluated ESN of four selected sites for screening from the intermediate region, the sensitivity and specificity to distinguish between demyelinating CMT and CIDP were 0.90 and 0.94, respectively, with the cut-off value set at four. Nerve ultrasonography is useful to detect nerve enlargement and can clarify morphological differences in nerves between patients with demyelinating CMT and CIDP.

A comprehensive photometric study of dynamically evolved small van den Bergh-Hagen open clusters

NASA Astrophysics Data System (ADS)

Piatti, Andrés E.

2016-12-01

We present results from Johnson UBV, Kron-Cousins RI and Washington CT1T2 photometries for seven van den Bergh-Hagen (vdBH) open clusters, namely, vdBH 1, 10, 31, 72, 87, 92, and 118. The high-quality, multiband photometric data sets were used to trace the cluster stellar density radial profiles and to build colour-magnitude diagrams and colour-colour diagrams from which we estimated their structural parameters and fundamental astrophysical properties. The clusters in our sample cover a wide age range, from ˜60 Myr up to 2.8 Gyr, are of relatively small size (˜1-6 pc) and are placed at distances from the Sun which vary between 1.8 and 6.3 kpc, respectively. We also estimated lower limits for the cluster present-day masses as well as half-mass relaxation times (tr). The resulting values in combination with the structural parameter values suggest that the studied clusters are in advanced stages of their internal dynamical evolution (age/tr ˜ 20-320), possibly in the typical phase of those tidally filled with mass segregation in their core regions. Compared to open clusters in the solar neighbourhood, the seven vdBH clusters are within more massive (˜80-380 M⊙), with higher concentration parameter values (c ˜ 0.75-1.15) and dynamically evolved ones.

Mutations in SCARF2 are responsible for Van Den Ende-Gupta syndrome.

PubMed

Anastasio, Natascia; Ben-Omran, Tawfeg; Teebi, Ahmad; Ha, Kevin C H; Lalonde, Emilie; Ali, Rehab; Almureikhi, Mariam; Der Kaloustian, Vazken M; Liu, Junhui; Rosenblatt, David S; Majewski, Jacek; Jerome-Majewska, Loydie A

2010-10-08

Van Den Ende-Gupta syndrome (VDEGS) is an extremely rare autosomal-recessive disorder characterized by distinctive craniofacial features, which include blepharophimosis, malar and/or maxillary hypoplasia, a narrow and beaked nose, and an everted lower lip. Other features are arachnodactyly, camptodactyly, peculiar skeletal abnormalities, and normal development and intelligence. We present molecular data on four VDEGS patients from three consanguineous Qatari families belonging to the same highly inbred Bedouin tribe. The patients were genotyped with SNP microarrays, and a 2.4 Mb homozygous region was found on chromosome 22q11 in an area overlapping the DiGeorge critical region. This region contained 44 genes, including SCARF2, a gene that is expressed during development in a number of mouse tissues relevant to the symptoms described above. Sanger sequencing identified a missense change, c.773G>A (p.C258Y), in exon 4 in the two closely related patients and a 2 bp deletion in exon 8, c.1328_1329delTG (p.V443DfsX83), in two unrelated individuals. In parallel with the candidate gene approach, complete exome sequencing was used to confirm that SCARF2 was the gene responsible for VDEGS. SCARF2 contains putative epidermal growth factor-like domains in its extracellular domain, along with a number of positively charged residues in its intracellular domain, indicating that it may be involved in intracellular signaling. However, the function of SCARF2 has not been characterized, and this study reports that phenotypic effects can be associated with defects in the scavenger receptor F family of genes. Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

A Probabilistic Wake Vortex Lateral Transport Model Using Data from SFO and DEN

NASA Technical Reports Server (NTRS)

Mellman, George R.; Delisi, Donald P.

2008-01-01

In a previous report, we considered the behavior of the lateral position of vortices as a function of time after vortex formation for Out of Ground Effects (OGE) data for aircraft landing at San Francisco International Airport (SFO). We quantified the spread in lateral position as a function of time and examined how predictable lateral position is under a variety of assumptions. The combination of spread and predictability allowed us to derive probability distribution functions (PDFs) for lateral position given observed crosswind (CW) velocities. In this study, we examine the portability of these PDFs with respect to other landing sites. To this end, we consider OGE data obtained by the Federal Aviation Administration for landings at Denver International Airport (DEN) between 04/05/2006 and 06/03/2006. We consider vortices from both B733 (Boeing 737 models 200-500) and B757 (Boeing 757) aircraft. The data set contains 635 B733 landings and 506 B757 landings. The glide slope altitude for these measurements was 280 m, determined by the average initial vortex observation adjusted for a 3-second delay in the initial observation. The comparable SFO altitude was 158 m. We note that the principal mechanism for lateral transport in the OGE regime is advection by the ambient wind. This implies that a simple crosswind correction may be effective in explaining much of the variation in the lateral transport data. In this study, we again consider the use of ASOS data and average Lidar crosswind data over the vortex altitude range to predict vortex location as a function of time.

Charcot-Marie-Tooth disease

MedlinePlus

... disorder. A nerve biopsy may confirm the diagnosis. Genetic testing is also available for most forms of the ... decreased sensation in the feet or legs. Prevention Genetic counseling and testing is advised if there is a strong family ...

Charcot-Marie-Tooth Disease

MedlinePlus

... with one X and one Y chromosome are male. In rare cases the gene mutation causing CMT ... involved in Schwann cell communication with the axon. Males who inherit one mutated gene from their mothers ...

Charcot-Marie-Tooth Disease

MedlinePlus

... can cause curvature of the spine and hip displacement. Most individuals with CMT have some amount of ... can cause curvature of the spine and hip displacement. Most individuals with CMT have some amount of ...

Use of multiple den sites by Eurasian badgers, Meles meles, in a Mediterranean habitat.

PubMed

Loureiro, Filipa; Rosalino, Luís Miguel; Macdonald, David W; Santos-Reis, Margarida

2007-10-01

Den sites are a conspicuous feature of Eurasian badgers, Meles meles, and in many environments include large communal burrows used by several group members. In Serra de Grândola, southwest Portugal, nine badgers from three social groups were captured and radio collared from 2000 to 2004. A total of 1,787 locations of badgers in their resting sites were registered along with a brief description of the type of site and weather conditions. Resting sites were grouped according to structure (burrows, shrubs, rocks, hollow trees and man-made structures) and function (main, secondary and occasional). Although main setts were the most frequently used shelter (62.25%), an average of 14 (SD 7.55) resting sites were used in each territory. The pattern of use varied seasonally, showing differences according to sex and social group. Overall, females used more than twice as many occasional resting sites as did males. Generally burrows, predominantly main setts, were most frequently used during winter and autumn, whilst non-burrow shelters were preferred during spring and summer, when the weather was hot, dry and not windy. Proximity to food patches had no apparent influence on the location of resting sites. Our results offered no support for the foraging-related hypotheses that multiple resting sites are a means of conserving energy or of maintaining proximity to rich food patches. We suggest that other factors such as thermoregulation needs, disturbance, and reproductive status, could be influencing the observed pattern of resting-site use by badgers in Serra de Grândola.

The epileptic singers of belle époque Paris.

PubMed

Baxendale, Sallie; Marshall, Fiona

2012-12-01

In late 19th century Paris, people with epilepsy were treated alongside those with hysteria in the now famous Salpêtrière Hospital, where both conditions were deemed to have a neurological basis. When Jean Martin Charcot became chief physician at the Salpêtrière Hospital in 1862, he described himself 'in possession of a kind of museum of living pathology whose holdings were virtually inexhaustible'. He opened the doors of his 'living museum' and exhibited his prize specimens to all of Paris. By putting his patients on display, Charcot introduced a vogue for pathology that permeated well beyond the world of medical enquiry and into the public psyche and vernacular. Not only did Charcot's demonstrations provide the inspiration for high culture in the form of operas, plays and novels, they also provided the inspiration for the 'gommeuses epileptiques' (epileptic singers), who entertained the masses at the café concerts. This paper explores the foundations of our current medical approaches to mental illness and epilepsy, with a particular focus on the boundaries that emerged between hysteria and epilepsy in 19th century Paris. These clinical boundaries were both shaped by and reflected in the popular entertainments in the city.

Metals and magnets in medicine: hysteria, hypnosis and medical culture in fin-de-siècle Paris.

PubMed

Harrington, A

1988-02-01

It is well known that the end of the nineteenth century represented a 'golden age' of hysteria and hypnosis research under Jean-Martin Charcot in Paris, but the extent to which metals and magnets figured in this strange and provocative world has been very incompletely told. This paper offers itself as a first corrective to this neglect. In 1876 a certain elderly physician and mesmerist, Victor Burq, asked the Parisian Société de Biologie formally to establish the validity of his so-called 'metallotherapy' (later 'metalloscopy') treatment for hysteria. The paper argues that Charcot's participation in the investigation of Burq's work--undertaken in conjunction with two other leading French neurologists, Amédée Dumontpallier and Jules Bernard Luys--served as a major catalyst in arousing the great neurologist's interest in hypnosis in the first place, and was subsequently responsible for several of his key beliefs about the underlying physiological link between hypnosis and hysteria. It is also shown how these early metalloscopy studies--and especially the discovery by Charcot and his colleagues of so-called metalloscopic 'transfer'--opened the door to the rise of a neo-mesmeric, and increasingly occult, branch of hypnosis research in French psychiatry, which has to date, in the secondary literature, gone almost wholly unremarked.

Endodontic Management of a Maxillary Lateral Incisor with 4 Root Canals and a Dens Invaginatus Tract.

PubMed

Nosrat, Ali; Schneider, S Craig

2015-07-01

Dens invaginatus (DI) is associated with complex internal anatomy. This article represents a maxillary lateral incisor with 5 root canals including DI. The treatment was planned and performed using cone-beam computed tomographic (CBCT) imaging. After clinical and radiographic evaluations, tooth #7 was diagnosed with DI and pulp necrosis with symptomatic apical periodontitis. Periapical radiographs of the tooth showed 2 roots and complex internal anatomy. CBCT evaluation revealed tooth #7 had 5 separate canals (4 root canals and 1 DI canal extending through the root to the periodontal ligament), communication between DI and the root canal system, and severe and multiple curvatures of the palatal canals. Root canal treatment was completed in 2 visits. Modified access openings were required to safely treat the dilacerated palatal canals. At the 6-month re-evaluation, the patient reported he had remained asymptomatic and his tooth had remained functional since the treatment was completed. Clinical examination showed tooth #7 had no sensitivity to percussion or palpation, probe depths within normal limits (≤3 mm), and no mobility. Radiographic assessment of the tooth showed significant osseous healing of the preoperative lesion. Three-dimensional imaging is a valuable tool for endodontic management of teeth with complex internal anatomy. Three-dimensional imaging is recommended for evaluating and treatment planning cases with DI. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Effekt einer ad libitum verzehrten fettreduzierten Kost, reich an Obst, Gemüse und Milchprodukten auf den Blutdruck bei Borderline-Hypertonikern

NASA Astrophysics Data System (ADS)

Möseneder, Jutta M.

2002-01-01

In der randomisierten, multizentrischen DASH-Studie (Dietary Approaches to Stop Hy-pertension), die unter kontrollierten Bedingungen stattfand, führte eine fettreduzierte Mischkost, reich an Obst, Gemüse und Milchprodukten, bei Borderline-Hypertonikern zu einer signifikanten Blutdrucksenkung. Während der Studienphase wurden Körpermasse, Natrium-Aufnahme sowie Alkoholzufuhr aufgrund der bekannten Einflussnahme auf den Blutdruck konstant gehalten. In der eigenen Pilot-Studie sollte untersucht werden, ob das Ergebnis der DASH-Studie (i) mit deutschen Hypertonikern und (ii) unter habituellen Ernährungs- und Lebensbedingungen mit regelmäßig durchgeführter Ernährungsberatung und ad libitum Verzehr anstelle des streng kontrollierten Studienansatzes bestätigt werden kann. Eine Konstanz der Körpermasse, der Natrium-Urinausscheidung (unter diesem Studienansatz valider als die Aufnahme) und des Alkoholkonsums wurde vorausgesetzt. Die Studienpopulation setzte sich aus 53 übergewichtigen Probanden mit einer nicht medikamentös therapierten Borderline-Hypertonie und ohne Stoffwechselerkrankungen zusammen. Die Studienteilnehmer wurden randomisiert entweder der Idealgruppe mit einer fettarmen Kost reich an Milchprodukten, Obst und Gemüse (ähnlich der DASH-Idealgruppe) oder der Kontrollgruppe mit habitueller Ernährungsweise zugeteilt. Über einen Zeitraum von fünf Wochen wurde den Probanden etwa 50% ihres täglichen Lebensmittelbedarfes entsprechend ihrer Gruppenzugehörigkeit kostenfrei zur Verfügung gestellt. Gelegenheitsblutdruckmessungen und 24h-Blutdruckmessungen, Ernährungs- und Aktivitätsprotokolle, Blut- und Urinproben sowie anthropometrische Messungen wurden vor, während und fünf Wochen nach der Interventionsphase durchgeführt. Die Ergebnisse zeigen, dass in der Idealgruppe keine signifikante Blutdrucksenkung beobachtet werden konnte. Dies lässt sich durch die Tatsache erklären, dass die Lebens-mittel- und Nährstoffaufnahme der deutschen

Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

ClinicalTrials.gov

2015-08-24

Spinal Muscular Atrophy; Charcot-Marie-Tooth Disease; Muscular Dystrophy; Spinal Muscular Atrophy With Respiratory Distress 1; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Disease; Peroneal Muscular Atrophy; Fragile X Syndrome

[Presence of the dinoflagellates Ceratium dens, C. fusus and C. furca (Gonyaulacales: Ceratiaceae) in Golfo de Nicoya, Costa Rica].

PubMed

Vargas-Montero, Maribelle; Freer, Enrique

2004-09-01

Harmful Algae Blooms (HAB) are a frequent phenomenon in the Gulf of Nicoya, Costa Rica, as in other parts of the world. The morphology and physiology of these microalgae are important because HAB species have adaptive characteristics. The production of high concentrations of paralytic toxins by Ceratium dinoflagellates has only been documented at the experimental level. However, this genus has been associated with the mortality of aquatic organisms, including oyster and shrimp larva, and fish, and with decreased water quality. Recently, fishermen reported massive mortality of encaged fish near Tortuga Island (Gulf of Nicoya). Samples were taken from an algal bloom that had produced an orange coloration and had a strong foul-smelling odor. Ultrastructural details were examined with scanning electron microscopy. The dinoflagellates Ceratium dens, C. furca and C. fusus were found in samples taken at the surface. The cell count revealed four million cells of this genus per liter. The morphological variability of these species is high; therefore electron microscopy is an useful tool in the ultrastructural study of these organisms. This is the first time that three Ceratium species are reported concurrently producing harmful blooms in Costa Rica.

Axonal neuropathy with neuromyotonia: there is a HINT.

PubMed

Peeters, Kristien; Chamova, Teodora; Tournev, Ivailo; Jordanova, Albena

2017-04-01

Recessive mutations in the gene encoding the histidine triad nucleotide binding protein 1 (HINT1) were recently shown to cause a motor-predominant Charcot-Marie-Tooth neuropathy. About 80% of the patients exhibit neuromyotonia, a striking clinical and electrophysiological hallmark that can help to distinguish this disease and to guide diagnostic screening. HINT1 neuropathy has worldwide distribution and is particularly prevalent in populations inhabiting central and south-eastern Europe. With 12 different mutations identified in more than 60 families, it ranks among the most common subtypes of axonal Charcot-Marie-Tooth neuropathy. This article provides an overview of the present knowledge on HINT1 neuropathy with the aim to increase awareness and spur interest among clinicians and researchers in the field. We propose diagnostic guidelines to recognize and differentiate this entity and suggest treatment strategies to manage common symptoms. As a recent player in the field of hereditary neuropathies, the role of HINT1 in peripheral nerves is unknown and the underlying disease mechanisms are unexplored. We provide a comprehensive overview of the structural and functional characteristics of the HINT1 protein that may guide further studies into the molecular aetiology and treatment strategies of this peculiar Charcot-Marie-Tooth subtype. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Medical Management

MedlinePlus

... org Close Charcot-Marie-Tooth Disease (CMT) Medical Management Although there’s no cure for CMT, there are ... individualized physical therapy program. For more on medical management of CMT, see Surgery Sometimes, Bracing Often, Caution ...

The use of differential scintigraphy in the clinical diagnosis of osseous and soft tissue changes affecting the diabetic foot

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

Visser, H.J.; Jacobs, A.M.; Oloff, L.

Prompt recognition of cellulitis, osteomyelitis, diabetic osteolysis, Charcot neuroarthropathy, septic synovitis, and deep plantar abscesses in the diabetic foot is essential because the therapy is drastically different. Differential diagnosis has been greatly facilitated by recently developed scanning techniques.

Computational Analysis Reveals the Association of Threonine 118 Methionine Mutation in PMP22 Resulting in CMT-1A

PubMed Central

Swetha, Rayapadi G.

2014-01-01

The T118M mutation in PMP22 gene is associated with Charcot Marie Tooth, type 1A (CMT1A). CMT1A is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Mutations in CMT related disorder are seen to increase the stability of the protein resulting in the diseased state. We performed SNP analysis for all the nsSNPs of PMP22 protein and carried out molecular dynamics simulation for T118M mutation to compare the stability difference between the wild type protein structure and the mutant protein structure. The mutation T118M resulted in the overall increase in the stability of the mutant protein. The superimposed structure shows marked structural variation between the wild type and the mutant protein structures. PMID:25400662

Auditory Neuropathy

MedlinePlus

... sound vibrations entering the inner ear from the middle ear. When hearing is working normally, the inner hair ... Examples of such disorders are Charcot-Marie-Tooth syndrome and Friedreich’s ... (ear, nose, and throat doctors), pediatricians, and audiologists —use ...

Assemblages of micronektonic fishes and invertebrates in a gradient of regional warming along the Western Antarctic Peninsula

NASA Astrophysics Data System (ADS)

Parker, Melanie L.; Fraser, William R.; Ashford, Julian; Patarnello, Tomaso; Zane, Lorenzo; Torres, Joseph J.

2015-12-01

Micronektonic fishes and invertebrates were sampled with 32 midwater trawls at nine sites along the Western Antarctic Peninsula (WAP) in the austral fall (March-April) of 2010. Study sites were located within four hypothesized hydrographic regions: near Joinville Island in Region I, at Croker Passage, near Anvers Island, and near Renaud Island in Region II, within Marguerite Bay and the Marguerite Trough in Region III, and near Charcot Island in Region IV. A total of 62 taxa representing 12 taxonomic groups of pelagic invertebrates and 9 families of fish were captured, but assemblages were dominated by only a few species. The most numerically abundant taxa were the euphausiids, Thysanoessa macrura, Euphausia superba, and E. crystallorophias, combining to contribute nearly 79% of the total catch. Biomass dominants included E. superba, which contributed more than 44% of the total catch, the notothenioid Pleuragramma antarctica, and the salp, Salpa thompsoni. A comparison of total catches among sites revealed that the largest volumetric abundances and biomasses were captured at the Marguerite Bay site. Cluster analysis of abundance data identified distinct multispecies assemblages at Joinville Island in Region I, Croker Passage in Region II, Marguerite Bay in Region III, and Charcot Island in Region IV. A fifth distinct assemblage included samples from sites near Anvers and Renaud Island in Region II, and from the Marguerite Trough in Region III. Assemblages at Joinville Island and Croker Passage were both dominated by E. superba and S. thompsoni, but hydrographic conditions at Joinville Island favored a neritic assemblage, underscored by substantial numbers of P. antarctica. The assemblage at Croker Passage was more oceanic in nature with major inputs from the myctophid, Electrona antarctica and the hyperiid amphipod, Themisto gaudichaudii. Marguerite Bay and Charcot Island were well-mixed assemblages with strong representation by both neritic and oceanic fauna. The

Unmasking of a Recessive SCARF2 Mutation by a 22q11.12 de novo Deletion in a Patient with Van den Ende-Gupta Syndrome.

PubMed

Bedeschi, M F; Colombo, L; Mari, F; Hofmann, K; Rauch, A; Gentilin, B; Renieri, A; Clerici, D

2010-01-01

Van den Ende-Gupta syndrome (VDEGS) is a congenital condition characterized by craniofacial and skeletal manifestations, specifically blepharophimosis, malar and maxillary hypoplasia, distinctive nose, arachnocamptodactyly, and long slender bones of the hands and feet. To date, only 24 patients have been described. It is generally thought that the syndrome is transmitted by an autosomal recessive mode of inheritance, although evidence for genetic heterogeneity has recently been presented. We report on a girl followed from birth up to 3 years of life with a set of peculiar minor anomalies, arachnocamptodactyly of hands and feet, characteristic of VDEGS in association with a 22q11.12 deletion. Recently, the VDEGS gene was mapped to the DiGeorge syndrome region on 22q11.2, and homozygous mutations in the SCARF2 gene were identified. We now report the first patient with VDEGS due to compound heterozygosity for the common 22q11.2 microdeletion and a hemizygous SCARF2 splice site mutation.

Georges Marinesco (1863-1938): neurologist, neurohistologist and neuropathologist.

PubMed

Catala, M; Poirier, J

2012-01-01

Gheorghe Marinescu (Georges Marinesco, in French) is a Romanian physician, founder of the School of Neurology in that country. He begins his medical studies in Bucharest, then has the opportunity to reach Paris and join the School of Neurology in La Salpêtrière Hospital, lead by Jean-Martin Charcot. This trip will forever imprint the mind of Marinescu, a great friend of France, a respectful student of Charcot and a friendly colleague of many Parisian neurologists. Marinescu's works are multiple and very important. He describes the succulent hand in syringomyelia and the palmar-jaw reflex. Marinescu is also one of the first to use the cinema for medical purposes. His work as an anatomo-clinician, a method developed by Charcot, is important. We denote the description of the locus niger affected by tuberculosis in a case of parkinsonism (this description paving Etienne Brissaud's way to highlight the anatomical origin of Parkinson's disease), the original clinical description of Marinesco-Sjögren syndrome, and that of medullomyoblastoma. Marinescu is also a famous neurocytologist as evidenced by his work, La Cellule Nerveuse, published in 1909. The first volume of the book is devoted to the aspects of the normal nervous tissue: the neurofibrillar network, the chromatophilic elements, and the paranucleolar corpuscles (now known as Marinescu's bodies). The second volume of the book is almost related to features revealed by experimental lesions: chromatolysis and neuronophagia. Furthermore, Marinescu describes with Oscar Blocq, small nodules than are now regarded as the first description of senile plaques.

Fish debris record the hydrothermal activity in the Atlantis II deep sediments (Red Sea)

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

Oudin, E.; Cocherie, A.

1988-01-01

The REE and U, Th, Zr, Hf, Sc have been analyzed in samples from Atlantis II and Shaban/Jean Charcot Deeps in the Red Sea. The high Zr/Hf ratio in some sediments indicates the presence of fish debris or of finely crystallized apatite. The positive ..sigma..REE vs P/sub 2/O/sub 5/ and ..sigma..REE vs Zr/Hf correlations show that fish debris and finely crystallized apatite are the main REE sink in Atlantis II Deep sediments as in other marine environments. The hydrothermal sediments and the fish debris concentrates have similar REE patterns, characterized by a LREE enrichment and a large positive Eu anomaly.more » This REE pattern is also observed in E.P.R. hydrothermal solutions. Fish debris from marine environments acquire their REE content and signature mostly from sea water during early diagenesis. The hydrothermal REE signature of Atlantis II Deep fish debris indicate that they probably record the REE signature of their hydrothermal sedimentation and diagenetic environment. The different REE signatures of the Shaban/Jean Charcot and Atlantis II Deep hydrothermal sediments suggest a sea water-dominated brine in the Shaban/Jean Charcot Deep as opposed to the predominantly hydrothermal brine in Atlantis II Deep. Atlantis II Deep fish debris are also characterized by their high U but low Th contents. Their low Th contents probably reflect the low Th content of the various possible sources (sea water, brine, sediments). Their U contents are probably controlled by the redox conditions of sedimentation.« less

Successful nonsurgical endodontic outcome of a severely affected permanent maxillary canine with dens invaginatus Oehlers type 3.

PubMed

Brooks, John K; Ribera, Michael J

2014-10-01

The morphogenic complexities of dens invaginatus (DI) Oehlers type 3 in maxillary canines offer significant endodontic challenges. A case report is provided of a 14-year-old female patient who presented with an anomalous-looking permanent maxillary canine associated with a sinus tract. Pulp testing revealed a normal response on the distal aspect of the tooth, whereas the mesial segment tested nonresponsive. A radiolucent lesion was seen on the mesiolateral radicular area adjacent to the severely distended pulp chamber. A gutta-percha point inserted into the sinus tract traced to this same region. The diagnosis was normal pulp coincident with DI Oehlers type 3 with pulp necrosis and chronic apical abscess. Despite a concerted effort to limit the root canal therapy to only the necrotic canal, its proximity to the normal canal obviated this possibility, entailing endodontic treatment of the entire root canal system. The necrotic pulp space was subjected to sustained irrigation with 5.25% sodium hypochlorite and then completed with 17% ethylenediaminetetraacetic acid. A bolus of gutta-percha was used to create an apical barrier, and then the remainder of the enlarged pulp space was obturated with injectable thermoplasticized gutta-percha. At a 4.5-year recall, there was no clinical and radiographic evidence of infection. Endodontic success was accomplished with meticulous efforts of disinfection. Thermoplasticized gutta-percha can offer utility for obturation of anatomically complicated pulp spaces. The use of the dental operating microscope is an invaluable aid for discernment of the intricacies of teeth affected with DI type 3 variant and can enhance clinical outcomes. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

[On "early pathologic anatomy" and "anatomy of medical structure": continuity or point of epistemological rupture?].

PubMed

Lellouch, Alain

2006-06-01

The aim of this paper is to analyse the technical, conceptual and institutional changes from which, through macroscopic pathology, a new medical science (microscopic pathology) emerged. The "early" pathology was mainly implemented by the Ecole de Paris, at the beginning of the 19th century. After 1850, histo-pathology emerged, in German university institutes (which were separate buildings from the wards and from the dissecting rooms of the hospitals). The birth of histo-pathology is also linked with technical improvements in mass manufactured microscopes, with better techniques for fixing and staining histological samples and lastly, in (1848) withVirchow's cellular theory. Among French doctors, only one, the very famous physician Jean-Martin Charcot (1825-1893) was aware of these dramatic changes. Charcot wrote many texts which are testimonies of an epistemological rupture between two very different types of medicine, the old French "médecine d'hôpital" and the new "lab medicine", developed in German speaking countries and based on the microscope.

Die Steuerung von den Multigenerationteams in den Industriebetrieben

NASA Astrophysics Data System (ADS)

Vraňaková, Natália; Chlpeková, Andrea; Koltnerová, Kristína; Pračková, Petra

2017-09-01

The current workforce in industrial enterprises is formed from four generational groups. These generational groups are called Baby boomers, Generation "X", Generation "Y" and Generation "Z". Each of generational groups is specific by own characteristics, positives and negatives. The aim of the article is to refer the features of individual generational groups, to analyze their representation on labor market and to specify recommendations for the management of multigenerational teams for the practice of industrial enterprises in order to achieve the satisfaction and synergy of employees in accordance with the objectives of enterprise.

Learning about Charcot-Marie-Tooth Disease

MedlinePlus

... Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for Teachers ... Education Kit Online Genetics Education Resources Smithsonian NHGRI Genome ... Subjects Research Informed Consent for Genomics Research Intellectual ...

Charcot-Marie-Tooth and Related Diseases

MedlinePlus

... acquired neu- ropathy, and thus might exacerbate CMT. Case studies have shown that the chemo- therapy drug vincristine ... respira- tory or speech therapy consultations • annual flu shots • support groups for those affected, spouses, parents or ...

Differential Predation by Age and Sex Classes in Blue Wildebeest in Serengeti: Study of a Modern Carnivore Den in Olduvai Gorge (Tanzania)

PubMed Central

Arriaza, Mari Carmen; Domínguez-Rodrigo, Manuel; Martínez-Maza, Cayetana; Mabulla, Audax; Baquedano, Enrique

2015-01-01

Age and sex selection of prey is an aspect of predator ecology which has been extensively studied in both temperate and African ecosystems. This dimension, along with fecundity, survival rates of prey and mortality factors other than predation are important in laying down the population dynamics of prey and have important implications in the management of species. A carnivore den located in the short-grassland ecological unit of the Serengeti was studied. Sex- and age- class (using five age categories) of the wildebeest remains recovered were analyzed through horn morphology, biometrics of the bones and tooth wear patterns. We compared our results with previous studies from lion and hyaena kills through multivariate analyses. Seasonality of the accumulation was analyzed through tooth histology. PCA and CVA results show that age class selection by predators depends on season, habitat-type, and growth rate of the wildebeest population. Female-biased predation was found to contradict classical hypotheses based on territorial male behaviour. The lion and spotted hyaena showed strong selection on age classes, contrary to previous studies. Migratory wildebeest sex ratio is regulated through differential predation by seasons and female deaths in the wet season are a trade-off for population stability. These data are crucial for an effective management of the species and the new method created may be useful for different carnivore species and their prey. PMID:26017363

CMT2C with vocal cord paresis associated with short stature and mutations in the TRPV4 gene

PubMed Central

Chen, D.-H.; Sul, Y.; Weiss, M.; Hillel, A.; Lipe, H.; Wolff, J.; Matsushita, M.; Raskind, W.; Bird, T.

2010-01-01

Background: Recently, mutations in the transient receptor potential cation channel, subfamily V, member 4 gene (TRPV4) have been reported in Charcot-Marie-Tooth Type 2C (CMT2C) with vocal cord paresis. Other mutations in this same gene have been described in separate families with various skeletal dysplasias. Further clarification is needed of the different phenotypes associated with this gene. Methods: We performed clinical evaluation, electrophysiology, and genetic analysis of the TRPV4 gene in 2 families with CMT2C. Results: Two multigenerational families had a motor greater than sensory axonal neuropathy associated with variable vocal cord paresis. The vocal cord paresis varied from absent to severe, requiring permanent tracheotomy in 2 subjects. One family with mild neuropathy also manifested pronounced short stature, more than 2 SD below the average height for white Americans. There was one instance of dolichocephaly. A novel S542Y mutation in the TRPV4 gene was identified in this family. The other family had a more severe, progressive, motor neuropathy with sensory loss, but less remarkable short stature and an R315W mutation in TRPV4. Third cranial nerve involvement and sleep apnea occurred in one subject in each family. Conclusion: CMT2C with axonal neuropathy, vocal cord paresis, and short stature is a unique syndrome associated with mutations in the TRPV4 gene. Mutations in TRPV4 can cause abnormalities in bone, peripheral nerve, or both and may result in highly variable orthopedic and neurologic phenotypes. GLOSSARY CMAP = compound muscle action potential; CMT = Charcot-Marie-Tooth; CMT2C = Charcot-Marie-Tooth Type 2C; HMSN = hereditary motor and sensory neuropathy; NCV = nerve conduction velocity; RFLP = restriction fragment length polymorphism; SMA = spinal muscular atrophy; SNAP = sensory nerve action potential; SPSMA = scapuloperoneal spinal muscular atrophy. PMID:21115951

Binaural speech processing in individuals with auditory neuropathy.

PubMed

Rance, G; Ryan, M M; Carew, P; Corben, L A; Yiu, E; Tan, J; Delatycki, M B

2012-12-13

Auditory neuropathy disrupts the neural representation of sound and may therefore impair processes contingent upon inter-aural integration. The aims of this study were to investigate binaural auditory processing in individuals with axonal (Friedreich ataxia) and demyelinating (Charcot-Marie-Tooth disease type 1A) auditory neuropathy and to evaluate the relationship between the degree of auditory deficit and overall clinical severity in patients with neuropathic disorders. Twenty-three subjects with genetically confirmed Friedreich ataxia and 12 subjects with Charcot-Marie-Tooth disease type 1A underwent psychophysical evaluation of basic auditory processing (intensity discrimination/temporal resolution) and binaural speech perception assessment using the Listening in Spatialized Noise test. Age, gender and hearing-level-matched controls were also tested. Speech perception in noise for individuals with auditory neuropathy was abnormal for each listening condition, but was particularly affected in circumstances where binaural processing might have improved perception through spatial segregation. Ability to use spatial cues was correlated with temporal resolution suggesting that the binaural-processing deficit was the result of disordered representation of timing cues in the left and right auditory nerves. Spatial processing was also related to overall disease severity (as measured by the Friedreich Ataxia Rating Scale and Charcot-Marie-Tooth Neuropathy Score) suggesting that the degree of neural dysfunction in the auditory system accurately reflects generalized neuropathic changes. Measures of binaural speech processing show promise for application in the neurology clinic. In individuals with auditory neuropathy due to both axonal and demyelinating mechanisms the assessment provides a measure of functional hearing ability, a biomarker capable of tracking the natural history of progressive disease and a potential means of evaluating the effectiveness of interventions

Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes.

PubMed

Hytönen, Marjo K; Arumilli, Meharji; Lappalainen, Anu K; Owczarek-Lipska, Marta; Jagannathan, Vidhya; Hundi, Sruthi; Salmela, Elina; Venta, Patrick; Sarkiala, Eva; Jokinen, Tarja; Gorgas, Daniela; Kere, Juha; Nieminen, Pekka; Drögemüller, Cord; Lohi, Hannes

2016-05-01

One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions.

Complications of ankle fracture in patients with diabetes.

PubMed

Chaudhary, Saad B; Liporace, Frank A; Gandhi, Ankur; Donley, Brian G; Pinzur, Michael S; Lin, Sheldon S

2008-03-01

Ankle fractures in patients with diabetes mellitus have long been recognized as a challenge to practicing clinicians. Complications of impaired wound healing, infection, malunion, delayed union, nonunion, and Charcot arthropathy are prevalent in this patient population. Controversy exists as to whether diabetic ankle fractures are best treated noninvasively or by open reduction and internal fixation. Patients with diabetes are at significant risk for soft-tissue complications. In addition, diabetic ankle fractures heal, but significant delays in bone healing exist. Also, Charcot ankle arthropathy occurs more commonly in patients who were initially undiagnosed and had a delay in immobilization and in patients treated nonsurgically for displaced ankle fractures. Several techniques have been described to minimize complications associated with diabetic ankle fractures (eg, rigid external fixation, use of Kirschner wires or Steinmann pins to increase rigidity). Regardless of the specifics of treatment, adherence to the basic principles of preoperative planning, meticulous soft-tissue management, and attention to stable, rigid fixation with prolonged, protected immobilization are paramount in minimizing problems and yielding good functional outcomes.

Sigmund Freud's evolution from neurology to psychiatry: evidence from his La Salpêtrière library.

PubMed

Bogousslavsky, Julien

2011-10-04

To analyze the parallel between the scientific evolution of Sigmund Freud and his French library during and after his stay with Jean-Martin Charcot at La Salpêtrière in 1885-1886. Systematic review of all identified volumes of Freud's personal library, and comparison with his life data and publications. The largest part of Freud's 125 French medical books up to 1900 (of 3,725 books overall) are devoted to hysteria and hypnotism, published mainly between 1885 and 1895. Over one-third (50) of the neurology (94) and alienism (22) books have Charcot or one of his direct pupils (Janet, Féré, Babinski, Gilles de la Tourette, Richer, Pitres, Sollier, Raymond, Marie, Binet, Ball, Bourneville, Blocq, Berbez, Guinon, and Souques) as author. During that period, Freud evolved from the clinical-anatomic method (after mainly experimental histologic studies) to theoretical neurology (using hysteria and aphasia models) and psychology, a process which subsequently led to the birth of psychoanalysis. The library of Freud gives an interesting account on his own evolving thinking, which led him to leave neurology for psychology and psychoanalysis.

Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes

PubMed Central

Hytönen, Marjo K.; Arumilli, Meharji; Lappalainen, Anu K.; Owczarek-Lipska, Marta; Jagannathan, Vidhya; Hundi, Sruthi; Salmela, Elina; Venta, Patrick; Sarkiala, Eva; Jokinen, Tarja; Gorgas, Daniela; Kere, Juha; Nieminen, Pekka

2016-01-01

One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions. PMID:27187611

Red fox spatial characteristics in relation to waterfowl predation

USGS Publications Warehouse

Sargeant, A.B.

1972-01-01

Radio-equipped red foxes (Vulpes vulpes) on the Cedar Creek area in Minnesota were spatially distributed, with individual families occupying well defined, nonoverlapping, contiguous territories. Territory boundaries often conformed to natural physical boundaries and appeared to be maintained through some nonaggressive behavior mechanism. Individual foxes traveled extensively throughout the family territory each night. Fox territories appeared to range from approximately 1 to 3 square miles in size, dependent largely on population density. Red foxes used a sequence of dens to rear their pups, and the amount and location of food remains at individual dens changed as the pups matured. The denning season was divided into pre-emergence, confined-use, and dispersed-use periods of 4 to 5 weeks each. Remains of adult waterfowl were collected at rearing dens on six townships in three ecologically different regions of eastern North Dakota. Remains of 172 adult dabbling ducks and 16 adult American coots (Fulica americana) were found at 35 dens. No remains from diving ducks were found. The number of adult ducks per den averaged 1.6, 5.9, and 10.2 for paired townships in regions with relatively low, moderate and high duck populations, respectively. Eighty-four percent of the ducks were females. The species and sex composition of ducks found at dens during early and late sampling periods reflected the nesting chronology of prairie dabbling ducks. Occupied rearing dens were focal points of red fox travel, and the locations of dens may have had considerable influence on predation. Thirty-five of 38 dens found on the six township study areas were on pastured or idle lands. The distribution of rearing dens on the Sand Lake and Arrowwood national wildlife refuges suggested that, on these areas, fox dens were concentrated because of the topography and land-use practices.

Phenotyping of peripheral blood mononuclear cells during acute dengue illness demonstrates infection and increased activation of monocytes in severe cases compared to classic dengue fever

PubMed Central

Durbin, Anna P.; Vargas, Maria José; Wanionek, Kimberli; Hammond, Samantha N.; Gordon, Aubree; Rocha, Crisanta; Balmaseda, Angel; Harris, Eva

2008-01-01

In vitro studies have attempted to identify dengue virus (DEN) target cells in peripheral blood; however, extensive phenotyping of peripheral blood mononuclear cells (PBMCs) from dengue patients has not been reported. PBMCs collected from hospitalized children suspected of acute dengue were analyzed for DEN prM, CD32, CD86, CD14, CD11c, CD16, CD209, CCR7, CD4, and CD8 by flow cytometry to detect DEN antigen in PBMCs and to phenotype DEN-positive cells. DEN prM was detected primarily in activated monocytes (CD14+, CD32+, CD86+, CD11c+). A subset of samples analyzed for DEN nonstructural protein 3 (NS3) confirmed that approximately half of DEN antigen-positive cells contained replicating virus. A higher percentage of PBMCs from DHF patients expressed prM, CD86, CD32, and CD11c than did those from DF patients. Increased activation of monocytes and greater numbers of DEN-infected cells were associated with more severe dengue, implicating a role for monocyte activation in dengue immunopathogenesis. PMID:18452966

Capture, anesthesia, and disturbance of free-ranging brown bears (Ursus arctos) during hibernation.

PubMed

Evans, Alina L; Sahlén, Veronica; Støen, Ole-Gunnar; Fahlman, Åsa; Brunberg, Sven; Madslien, Knut; Fröbert, Ole; Swenson, Jon E; Arnemo, Jon M

2012-01-01

We conducted thirteen immobilizations of previously collared hibernating two- to four-year-old brown bears (Ursus arctos) weighing 21-66 kg in central Sweden in winter 2010 and 2011 for comparative physiology research. Here we report, for the first time, an effective protocol for the capture and anesthesia of free-ranging brown bears during hibernation and an assessment of the disturbance the captures caused. Bears were darted in anthill, soil, or uprooted tree dens on eleven occasions, but two bears in rock dens fled and were darted outside the den. We used medetomidine at 0.02-0.06 mg/kg and zolazepam-tiletamine at 0.9-2.8 mg/kg for anesthesia. In addition, ketamine at 1.5 mg/kg was hand-injected intramuscularly in four bears and in six it was included in the dart at 1.1-3.0 mg/kg. Once anesthetized, bears were removed from the dens. In nine bears, arterial blood samples were analyzed immediately with a portable blood gas analyzer. We corrected hypoxemia in seven bears (PaO(2) 57-74 mmHg) with supplemental oxygen. We placed the bears back into the dens and antagonized the effect of medetomidine with atipamezole. Capturing bears in the den significantly increased the risk of den abandonment. One of twelve collared bears that were captured remained at the original den until spring, and eleven, left their dens (mean ± standard deviation) 3.2±3.6 (range 0.5-10.5) days after capture. They used 1.9±0.9 intermediate resting sites, during 6.2±7.8 days before entering a new permanent den. The eleven new permanent dens were located 730±589 m from the original dens. We documented that it was feasible and safe to capture hibernating brown bears, although they behaved differently than black bears. When doing so, researchers should use 25% of the doses used for helicopter darting during the active period and should consider increased energetic costs associated with den abandonment.

Friedreich's ataxia mimicking hereditary motor and sensory neuropathy.

PubMed

Panas, Marios; Kalfakis, Nikolaos; Karadima, Georgia; Davaki, Panagiota; Vassilopoulos, Demetris

2002-11-01

Four patients from three unrelated families, with clinical and electrophysiological findings compatible with the diagnosis of hereditary motor and sensory neuropathy, are presented. The molecular analysis showed that the affected individuals were homozygous for the mutation in the X25 gene, characteristic of Friedreich's ataxia. These patients seem to represent a form of Friedreich's ataxia mimicking Charcot-Marie-Tooth disease.

Causes of Charcot-Marie-Tooth Disease (CMT)

MedlinePlus

... t always easy to trace through a family tree: X-linked, autosomal dominant and autosomal recessive. X- ... can be easy to recognize in the family tree. In contrast, X-linked or autosomal recessive types ...

Genetics Home Reference: Charcot-Marie-Tooth disease

MedlinePlus

... located on the X chromosome . The inheritance is dominant if one copy of the altered gene is sufficient to cause the condition. In most cases, affected males, who have the alteration on their only copy ...

Temporal distribution of dengue virus serotypes in Colombian endemic area and dengue incidence. Re-introduction of dengue-3 associated to mild febrile illness and primary infection.

PubMed

Ocazionez, Raquel Elvira; Cortés, Fabián Mauricio; Villar, Luis Angel; Gómez, Sergio Yebrail

2006-11-01

We have investigated the temporal distribution of dengue (DEN) virus serotypes in the department (state) of Santander, Colombia, in relation to dengue incidence, infection pattern, and severity of disease. Viral isolation was attended on a total of 1452 acute serum samples collected each week from 1998 to 2004. The infection pattern was evaluated in 596 laboratory-positive dengue cases using an IgG ELISA, and PRNT test. The dengue incidence was documented by the local health authority. Predominance of DEN-1 in 1998 and DEN-3 re-introduction and predominance in 2001-2003 coincided with outbreaks. Predominance of DEN-2 in 2000-2001 coincided with more dengue hemorrhagic fever (DHF). DEN-4 was isolated in 2000-2001 and 2004 but was not predominant. There was an annual increase of primary dengue infections (from 13.7 to 81.4%) that correlated with frequency of DEN-3 (r = 0.83; P = 0.038). From the total number of primary dengue infections DEN-3 (81.3%) was the most frequent serotype. DHF was more frequent in DEN-2 infected patients than in DEN-3 infected patients: 27.5 vs 10.9% (P < 0.05). DEN-3 viruses belonged to subtype C (restriction site-specific-polymerase chain reaction) like viruses isolated in Sri-Lanka and other countries in the Americas. Our findings show the importance of continuous virological surveillance to identify the risk factors of dengue epidemics and severity.

The Scientific Illusion of Victor Burq (1822-1884).

PubMed

Walusinski, Olivier

2018-03-07

Victor Burq (1822-1884) is closely associated with a therapy named "burquism" by Jean-Martin Charcot, which was used in treating hysteria, especially hysteric anesthesia and paralysis, by applying metals, mainly copper, to affected zones. In 1876, Charcot, Luys, and Dumontpallier, commissioned by the Société de Biologie, issued 2 opinions validating the results obtained by Burq during the 25 years he dedicated to his research. From that point forward, the careers of these 3 famous physicians were lastingly reoriented toward the practice of hypnosis. This neo-mesmeric resurgence at the end of the nineteenth century can be considered the cause of an epistemological change that gave rise to "psychological medicine." During the repeated cholera epidemics in the mid-nineteenth century, Burq recommended preventive and corrective ingestion of copper, after observing that smelter workers were unaffected by the disease. The mechanisms of copper's anti-bacterial action have since been elucidated and legitimize Burq's anti-cholera campaign. Burq also advocated the ingestion of copper sulphate to treat diabetes. Current-day findings on intestinal microbiota and how these organisms influence blood sugar regulation support Burq's claims, considered far-fetched for many years. © 2018 S. Karger AG, Basel.

[Dengue hemorrhagic fever serotype and infection pattern in a Colombian endemic area].

PubMed

Ocazionez, Raquel E; Gómez, Sergio Y; Cortés, Fabián M

2007-01-01

Describing the relationship between viral serotypes, infection pattern and dengue hemorrhagic fever. 1,545 febrile patients were studied from 1998-2004 in the Santander department of Colombia. Dengue infection was confirmed by IgM ELISA and the virus was isolated in C6/36 cells. Infection pattern was established by detecting IgG antibodies in acute serum. Neutralising antibody titres were investigated in dengue cases occurring during years when less (1998) and more (2001) dengue hemorrhagic cases were reported by using PRNT. DEN-1 predominance in 1998 and the re-introduction of DEN-3 in 2001 coincided with an epidemic. DEN-2 infection caused more hemorrhagic cases than DEN-3 infection (24,5 % cf 11,2 %; p<0.05). DEN-2 was more associated with secondary infection than DEN-3 (56,8 % cf 15,7 %; p<0.001). An annual decrease of DHF was correlated with decreased DEN-2 dominance (r=0.95; p= 0.01), and secondary infection (r=0.9; p=0.03) and increased DEN-3 predominance (r=-0.91; p=0.03). There were no differences in neutralising antibody titres amongst analysed cases. DEN-1 neutralising antibodies presented the highest titres. Change in relative dengue virus serotype abundance was associated with changed infection pattern and DHF frequency. Continuing virological surveillance should become a priority for preventing dengue hemorrhagic fever in endemic areas.

A nonsurgical endodontic treatment in open-apex and immature teeth affected by dens invaginatus: using a collagen membrane as an apical barrier.

PubMed

Gharechahi, Maryam; Ghoddusi, Jamileh

2012-02-01

The authors' objective in this case report is to demonstrate an effective nonsurgical endodontic treatment in open-apex teeth affected by dens invaginatus (DI) by using a collagen membrane as an apical barrier and using a mineral trioxide aggregate (MTA) apical plug. . The authors present two cases of DI with open apexes in maxillary lateral incisors. In the first case, an adolescent had bilateral Oehlers type II DI and extensive periradicular radiolucency, internal root resorption and a vestibular fistula in the left maxillary lateral incisor. In the second case, an adult had Oehlers type II DI and an incomplete apex in the left maxillary lateral incisor. For both patients, the clinician placed a collagen membrane through the apexes of the left maxillary incisors to provide a resorbable extraradicular barrier against which MTA cement could be packed. The clinician obturated the adolescent's right lateral incisor. In the adolescent, the vestibular sinus tract was closed after one week. At subsequent follow-up examinations, the periradicular regions were completely healed, and postoperative radiographs revealed good bone healing in the lateral incisors. The teeth were asymptomatic and healing was achieved without any need for further endodontic surgical intervention. In the adult patient, the tooth was symptom free after one week, and radiography performed six months after the procedure showed complete healing. and Despite complex anatomy and diagnoses of DI and open apexes, both patients successfully underwent nonsurgical endodontic treatment involving the use of a collagen membrane and an MTA apical plug. Using an extraradicular barrier clinically can help improve the adaptation of MTA in the apexes of open-apex teeth to achieve a complete seal.

Modeling and experimental assessment of a buried Leu–Ile mutation in dengue envelope domain III

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

Kulkarni, Manjiri R.; Numoto, Nobutaka; Ito, Nobutoshi

Envelope protein domain III (ED3) of the dengue virus is important for both antibody binding and host cell interaction. Here, we focused on how a L387I mutation in the protein core could take place in DEN4 ED3, but cannot be accommodated in DEN3 ED3 without destabilizing its structure. To this end, we modeled a DEN4-L387I structure using the Penultimate Rotamer Library and taking the DEN4 ED3 main-chain as a fixed template. We found that three out of seven Ile{sup 387} conformers fit in DEN4 ED3 without introducing the severe atomic clashes that are observed when DEN3 serotype’s ED3 is usedmore » as a template. A more extensive search using 273 side-chain rotamers of the residues surrounding Ile{sup 387} confirmed this prediction. In order to assess the prediction, we determined the crystal structure of DEN4-L387I at 2 Å resolution. Ile{sup 387} indeed adopted one of the three predicted rotamers. Altogether, this study demonstrates that the effects of single mutations are to a large extent successfully predicted by systematically modeling the side-chain structures of the mutated as well as those of its surrounding residues using fixed main-chain structures and assessing inter-atomic steric clashes. More accurate and reliable predictions require considering sub-angstrom main-chain deformation, which remains a challenging task. - Highlights: • We mutated L387I of DEN4 ED3 and examined its effects on structure and stability. • We modeled the side-chain of Ile{sup 387} using DEN4 ED3's structure as a template. • We determined the crystal structure of DEN4-L387I and confirmed the modeling. • Side-chain repacking occurring around Ile{sup 387} involved >3 inter-connected residues. • These results explained why L387I mutation in DEN4 ED3 conserves thermostability.« less

Diethylnitrosamine initiation does not alter clofibric acid-induced hepatocarcinogenesis in the rat.

PubMed

Michel, Cecile; Desdouets, Chantal; Slaoui, Mohamed; Isaacs, Kevin Robert; Roberts, Ruth Angela; Boitier, Eric

2007-09-01

Clofibric acid (CLO) is a nongenotoxic hepatocarcinogen in rodents that causes altered hepatocellular foci and/or neoplasms. Initiation by DNA-damaging agents such as diethylnitrosamine (DEN) accelerates focus and tumor appearance and could therefore significantly contribute to shortening of the regulatory 2-year rodent carcinogenicity bioassays. However, it is crucial to evaluate the histological and molecular impact of initiation with DEN on hepatocarcinogenesis promoted by CLO. Male F344 rats were given a single nonnecrogenic injection of DEN (0 or 30 mg/kg) followed by Control diet or CLO (5000 ppm) in diet for up to 20 months. Histopathology and gene expression profiling were performed in liver tumors and surrounding nontumoral liver tissues. The molecular signature of DEN was characterized and its histopathological and immunohistopathological effects on focus and tumor types were also determined. Although foci and tumors appeared earlier in the DEN+CLO-treated group compared to the group treated with CLO alone, DEN had little impact on gene expression in nontumoral tissues since the gene expression profiles were highly similar between Control and DEN-treated rats, and DEN+CLO- and CLO-treated rats. Finally, tumors obtained from DEN+CLO and CLO-treated groups displayed highly correlated gene expression profiles (r>0.83, independently of the time-point). The pathways involved in tumor development revealed by Gene Ontology functional analysis are similar when driven either by spontaneous initiation or by a chemically induced initiation step. Our work described here may contribute to the design optimization of shorter preclinical tests for the evaluation of the nongenotoxic hepatocarcinogenic potential of drugs under development.

Expression of heat shock protein 72 in atrophied rat skeletal muscles

NASA Technical Reports Server (NTRS)

Oishi, Y.; Ishihara, A.; Talmadge, R. J.; Ohira, Y.; Taniguchi, K.; Matsumoto, H.; Roy, R. R.; Edgerton, V. R.

2001-01-01

Changes in the expression of heat shock protein 72 (HSP72) in response to atrophic-inducing perturbations of muscle involving chronic mechanical unloading and denervation were determined. Adult male Wistar rats were assigned randomly to a sedentary cage control (CON), hind limb unloading (HU, via tail suspension), HU plus tenotomy (HU + TEN), HU plus denervation (HU + DEN), or HU + TEN + DEN group. Tenotomy and DEN involved cutting the Achilles tendon and removing a segment of the sciatic nerve, respectively. After 5 days, HSP72 levels in the soleus of the HU + DEN and HU + TEN + DEN groups were 42 (P < 0.05) and 53% (P < 0.01) less than CON, respectively. Soleus weight decreased in both groups. Heat shock protein 72 levels in the plantaris of the HU + TEN, HU + DEN, and HU + TEN + DEN groups were 31, 25, and 30% lower than CON, respectively (P < 0.05). Plantaris weight decreased in the HU + DEN and HU + TEN + DEN, but not in the HU + TEN group. Hind limb unloading alone had little effect on the HSP72 level in either muscle. Reduced levels of HSP72 were associated with a decreased soleus (r=0.62, P < 0.01) and plantaris (r=0.78, P < 0.001) weight. These results indicate that the levels of HSP72 in both a slow and a fast rat plantarflexor are responsive to a chronic decrease in the levels of loading and/or activation and suggest that the neuromuscular activity level and the presence of innervation of a muscle are important factors that induce HSP72 expression.

Deep Seafloor Acoustic Backscattering Measurements Using Sea Beam

DTIC Science & Technology

1985-12-01

Am. Soc. Mech. Eng. Ocean engineering Symposium (submitted). C. de Moustier, "A Sea Beam acoustic data acquisition system" , MPL TM-379 Marine...paper submitted to the American Society of Mechanical Engineers for its symposium on Ocean Engineering. As such, it also reviews the approaches...seafloor down to maximum ocean depth (11 km). Since 1977 when the first system became operational aboard the French R/V Jean Charcot, nine other

Department of Clinical Investigation, Annual Research Progress Report, Fiscal Year 2006 (Madigan Army Medical Center)

DTIC Science & Technology

2006-09-30

45(4): p. 227-34, 2006. Roukis TS, Zgonis T. The management of acute Charcot fracture -dislocations with the Taylor’s spatial external fixation...Protocol No. S T Title Johnston GM #206028 C L Application of the Wells Criteria to determine Pretest Probability of Pulmonary Embolism ...Evaluation of Pulmonary Embolism - An Examination of Hospital-Wide Referral Practices Kwon HP #206087 O L Hemoptysis in Young Adults Kwon HP #206069

Systemübersicht Common Rail

NASA Astrophysics Data System (ADS)

Reif, Konrad

Die Anforderungen an die Einspritzsysteme des Dieselmotors steigen ständig. Höhere Drücke, schnellere Schaltzeiten und eine flexible Anpassung des Einspritzverlaufs an den Betriebszustand des Motors machen den Dieselmotor sparsam, sauber und leistungsstark. So haben Dieselmotoren auch den Einzug in die automobile Oberklasse gefunden.

Boden

NASA Astrophysics Data System (ADS)

Pfeiffer, Eva-Maria; Eschenbach, Annette; Munch, Jean Charles

Auch wenn die Risiken bisher kaum quantifizierbar sind, ist davon auszugehen, dass aufgrund der Einbindung des Bodens in die Energie-, Wasser- und Stoffkreisläufe die zu erwartenden Temperatur- und Niederschlagsänderungen die Funktionen dieser zentralen Lebensgrundlage auch in Deutschland gefährden. Nach einer Darstellung der Vielfältigkeit von Böden geht es in diesem Kapitel um mögliche Änderungen der Standortfunktion von Böden und der Leistungen im Ökosystem sowie um den Bodenwasserhaushalt. An herausgehobener Stelle diskutieren die Autoren die Klimafunktion von Böden und stellen mögliche Strategien zu ihrem Schutz vor. Eine große Rolle spielt die Verschränkung mit den anderen Themenbereichen von Teil III, etwa Landwirtschaft, Forstwirtschaft und Wasser.

Tertiary syphilis in the lumbar spine: a case report.

PubMed

Bai, Yang; Niu, Feng; Liu, Lidi; Sha, Hui; Wang, Yimei; Zhao, Song

2017-07-24

The incidence of tertiary syphilis involvement in the spinal column with destructive bone lesions is very rare. It is difficult to establish the correct diagnosis from radiographs and histological examination alone. Limited data are available on surgical treatment to tertiary syphilitic spinal lesions. In this article, we report a case of tertiary syphilis in the lumbar spine with osteolytic lesions causing cauda equina compression. A 44-year-old man who suffered with low back pain for 6 months and progressive radiating pain at lower extremity for 1 week. Radiologic findings showed osteolytic lesion and new bone formation in the parts of the bodies of L4 and L5. Serum treponema pallidum hemagglutination (TPHA) test was positive. A surgery of posterior debridement, interbody and posterolateral allograft bone fusion with instrumentation from L3 to S1 was performed. The low back pain and numbness abated after operation. But the follow-up radiographs showed absorption of the bone grafts and failure of instrumentation. A Charcot's arthropathy was formed between L4 and L5. It is challenging to diagnose the tertiary syphilis in the spine. Surgery is a reasonable auxiliary method to antibiotic therapy for patients who suffered with neuropathy. Charcot's arthropathy should be considered as an operative complication.

Foot ulcer risk and location in relation to prospective clinical assessment of foot shape and mobility among persons with diabetes.

PubMed

Cowley, Matthew S; Boyko, Edward J; Shofer, Jane B; Ahroni, Jessie H; Ledoux, William R

2008-11-01

We assessed baseline clinical foot shape for 2939 feet of diabetic subjects who were monitored prospectively for foot ulceration. Assessments included hammer/claw toes, hallux valgus, hallux limitus, prominent metatarsal heads, bony prominences, Charcot deformity, plantar callus, foot type, muscle atrophy, ankle and hallux mobility, and neuropathy. Risk factors were linked to ulcer occurrence and location via a Cox proportional hazards model. Hammer/claw toes (hazard ratio [HR] (95% confidence interval [CI])=1.43 (1.06, 1.94) p=0.02), marked hammer/claw toes (HR=1.77 (1.18, 2.66) p=0.006), bony prominences (HR=1.38 (1.02, 1.88), p=0.04), and foot type (Charcot or drop foot vs. neutrally aligned) (HR=2.34 (1.33, 4.10), p=0.003) were significant risk factors for ulceration adjusting for age, body mass index, insulin medication, ulcer history and amputation history. With adjustment for neuropathy only hammer/claw toes (HR=1.40 (1.03, 1.90), p=0.03) and foot type (HR=1.76 (1.04, 3.04), p=0.05) were significantly related to ulceration. However, there was no relationship between ulcer location and foot deformity. Certain foot deformities were predictive of ulceration, although there was no relationship between clinical foot deformity and ulcer location.

Diabetic Foot Complications Despite Successful Pancreas Transplantation.

PubMed

Seo, Dong-Kyo; Lee, Ho Seong; Park, Jungu; Ryu, Chang Hyun; Han, Duck Jong; Seo, Sang Gyo

2017-06-01

It is known that successful pancreas transplantation enables patients with diabetes to maintain a normal glucose level without insulin and reduces diabetes-related complications. However, we have little information about the foot-specific morbidity in patients who have undergone successful pancreas transplantation. The purpose of this study was to investigate the prevalence and predisposing factors for foot complications after successful pancreas transplantation. This retrospective study included 218 patients (91 males, 127 females) who had undergone pancreas transplantation for diabetes. The mean age was 40.7 (range, 15-76) years. Diabetes type, transplantation type, body mass index, and diabetes duration before transplantation were confirmed. After pancreas transplantation, the occurrence and duration of foot and ankle complications were assessed. Twenty-two patients (10.1%) had diabetic foot complications. Fifteen patients (6.9%) had diabetic foot ulcer and 7 patients (3.2%) had Charcot arthropathy. Three patients had both diabetic foot ulcer and Charcot arthropathy. Three insufficiency fractures (1.4%) were included. Mean time of complications after transplantation was 18.5 (range, 2-77) months. Creatinine level 1 year after surgery was higher in the complication group rather than the noncomplication group ( P = .02). Complications of the foot and ankle still occurred following pancreas transplantation in patients with diabetes. Level III, comparative study.

The origins of scientific cinematography and early medical applications.

PubMed

Barboi, Alexandru C; Goetz, Christopher G; Musetoiu, Radu

2004-06-08

To examine the neurologic cinematographic contributions of Gheorghe Marinescu. Near the end of the 19th century, cinematography developed and was immediately recognized as a new technique applicable to medical documentation. After studying with several prominent European neurologists and deeply influenced by Jean-Martin Charcot, Marinescu returned to Bucharest in 1897 and applied moving picture techniques to the study of neurologic patients. The Romanian State Archives were researched for original Marinescu films, and related publications were translated from Romanian and French. Between 1899 and 1902, Marinescu perfected the use of cinematography as a research method in neurosciences and published five articles based on cinematographic documents. He focused his studies particularly on organic gait disorders, locomotor ataxia, and hysteria. He adapted Charcot's method of lining up several patients with the same disorder and showing them together to permit appreciation of archetypes and formes frustes. He decomposed the moving pictures into sequential tracings for publication. He documented treatment results with cases filmed before and after therapy. Processed and digitized excerpts of these films accompany this manuscript. Marinescu's cinematographic studies led to several original contributions in clinical neurology. Remaining film archives include examples of many neurologic diseases, his examination techniques, and the working medical environment of the young founder of the Romanian school of neurology.

Mitofusin2 mutations disrupt axonal mitochondrial positioning and promote axon degeneration

PubMed Central

Misko, Albert; Sasaki, Yo; Tuck, Elizabeth; Milbrandt, Jeffrey; Baloh, Robert H.

2012-01-01

Summary Alterations in mitochondrial dynamics (fission, fusion and movement) are implicated in many neurodegenerative diseases, from rare genetic disorders such as Charcot-Marie-Tooth disease, to common conditions including Alzheimer’s disease. However, the relationship between altered mitochondrial dynamics and neurodegeneration is incompletely understood. Here we show that disease associated MFN2 proteins suppressed both mitochondrial fusion and transport, and produced classic features of segmental axonal degeneration without cell body death, including neurofilament filled swellings, loss of calcium homeostasis, and accumulation of reactive oxygen species. By contrast, depletion of Opa1 suppressed mitochondrial fusion while sparing transport, and did not induce axonal degeneration. Axon degeneration induced by mutant MFN2 proteins correlated with the disruption of the proper mitochondrial positioning within axons, rather than loss of overall mitochondrial movement, or global mitochondrial dysfunction. We also found that augmenting expression of MFN1 rescued the axonal degeneration caused by MFN2 mutants, suggesting a possible therapeutic strategy for Charcot-Marie-Tooth disease. These experiments provide evidence that the ability of mitochondria to sense energy requirements and localize properly within axons is key to maintaining axonal integrity, and may be a common pathway by which disruptions in axonal transport contribute to neurodegeneration. PMID:22442078

[Neurology of hysteria (conversion disorder)].

PubMed

Sonoo, Masahiro

2014-07-01

Hysteria has served as an important driving force in the development of both neurology and psychiatry. Jean Martin Charcot's devotion to mesmerism for treating hysterical patients evoked the invention of psychoanalysis by Sigmund Freud. Meanwhile, Joseph Babinski took over the challenge to discriminate between organic and hysterical patients from Charcot and found Babinski's sign, the greatest milestone in modern neurological symptomatology. Nowadays, the usage of the term hysteria is avoided. However, new terms and new classifications are complicated and inconsistent between the two representative taxonomies, the DSM-IV and ICD-10. In the ICD-10, even the alternative term conversion disorder, which was becoming familiar to neurologists, has also disappeared as a group name. The diagnosis of hysteria remains important in clinical neurology. Extensive exclusive diagnoses and over investigation, including various imaging studies, should be avoided because they may prolong the disease course and fix their symptoms. Psychological reasons that seem to explain the conversion are not considered reliable. Positive neurological signs suggesting nonorganic etiologies are the most reliable measures for diagnosing hysteria, as Babinski first argued. Hysterical paresis has several characteristics, such as giving-way weakness or peculiar distributions of weakness. Signs to uncover nonorganic paresis utilizing synergy include Hoover's test and the Sonoo abductor test.

Combined circular external fixation and open reduction internal fixation with pro-syndesmotic screws for repair of a diabetic ankle fracture

PubMed Central

Facaros, Zacharia; Ramanujam, Crystal L.; Stapleton, John J.

2010-01-01

The surgical management of ankle fractures among the diabetic population is associated with higher complication rates compared to the general population. Efforts toward development of better methods in prevention and treatment are continuously evolving for these injuries. The presence of peripheral neuropathy and the possible development of Charcot neuroarthropathy in this high risk patient population have stimulated much surgical interest to create more stable osseous constructs when open reduction of an ankle fracture/dislocation is required. The utilization of multiple syndesmotic screws (pro-syndesmotic screws) to further stabilize the ankle mortise has been reported by many foot and ankle surgeons. In addition, transarticular Steinmann pins have been described as an adjunct to traditional open reduction with internal fixation (ORIF) of the ankle to better stabilize the talus, thus minimizing risk of further displacement, malunion, and Charcot neuroarthropathy. The authors present a unique technique of ORIF with pro-syndesmotic screws and the application of a multi-plane circular external fixator for management of a neglected diabetic ankle fracture that prevented further deformity while allowing a weight-bearing status. This techniqu may be utilized for the management of complex diabetic ankle fractures that are prone to future complications and possible limb loss. PMID:22396812

Revision Tibiotalocalcaneal Arthrodesis With a Pseudoelastic Intramedullary Nail.

PubMed

Latt, L Daniel; Smith, Kathryn Elizabeth; Dupont, Kenneth Michael

2017-02-01

Hindfoot (tibiotalocalcaneal or TTC) arthrodesis is commonly used to treat concomitant arthritis of the ankle and subtalar joints. Simultaneous fusion of both joints can be difficult to achieve especially in patients with impaired healing due to smoking, diabetes mellitus, or Charcot neuroarthropathy. Conventional intramedullary fixation devices allow for compression to be applied at the time of surgery, but this compression can be lost due to bone resorption or settling, leading to impaired healing. In contrast, the novel pseudoelastic intramedullary nail is designed to maintain compression at the arthrodesis sites throughout the healing process by the use of an internal pseudoelastic element. We present 2 cases of revision TTC arthrodesis using the pseudoelastic intramedullary nail. In the first case, an 80-year-old diabetic man with previous ankle and failed subtalar fusion with screws underwent revision TTC arthrodesis. In the second case, a 66-year-old man with Charcot neuroarthropathy and a failed TTC arthrodesis with a static intramedullary nail underwent revision tibiotalar arthrodesis. In both cases, computed tomography scan demonstrated successful union and patients were allowed full weight bearing by 3 months after surgery. These cases provide early evidence that sustained compression via an intramedullary nail can lead to rapid successful hindfoot fusion when standard approaches have failed. Therapeutic, Level IV: Case study.

Individual variation in space use by female spotted hyenas

USGS Publications Warehouse

Boydston, Erin E.; Kapheim, Karen M.; Szykman, Micaela; Holekamp, Kay E.

2003-01-01

Large carnivores range more widely than many other terrestrial mammals, and this behavior tends to bring them into frequent conflict with humans. Within any carnivore population, individual variation in patterns of space use should be expected to make some animals more vulnerable than others to risks of mortality from humans and other sources. In this study, our goal was to document variation among individuals in space use by female spotted hyenas (Crocuta crocuta). We examined predictions of hypotheses suggesting that space use by female hyenas is affected by reproductive state, social rank, and local prey abundance. Home-range size, distance at which females were found from the current communal den, and distance at which they were found from the nearest territorial boundary all varied significantly with the 3 independent variables. Females with den-dwelling cubs had smaller home ranges, were found closer to the communal den, and were found farther from the territorial boundary than were females with no den-dwelling cubs. Neither social rank nor prey availability significantly influenced the space-use patterns of females with den-dwelling cubs. Among females with no den-dwelling cubs, high-ranking females had smaller home ranges, were closer to the communal den, and were farther from the territorial boundary than were low-ranking females. The females ranging most widely were low-ranking individuals with no den-dwelling cubs when they were observed during periods of prey scarcity.

Dual stimuli-sensitive dendrimers: Photothermogenic gold nanoparticle-loaded thermo-responsive elastin-mimetic dendrimers.

PubMed

Fukushima, Daichi; Sk, Ugir Hossain; Sakamoto, Yasuhiro; Nakase, Ikuhiko; Kojima, Chie

2015-08-01

Dendrimers are synthetic macromolecules with unique structures that can work as nanoplatforms for both photothermogenic gold nanoparticles (AuNPs) and thermosensitive elastin-like peptides (ELPs) with valine-proline-glycine-valine-glycine (VPGVG) repeats. In this study, photothermogenic AuNPs were loaded into thermo-responsive elastin-mimetic dendrimers (dendrimers conjugating ELPs at their periphery) to produce dual stimuli-sensitive nanoparticles. Polyamidoamine G4 dendrimers were modified with acetylated VPGVG and (VPGVG)2, and the resulting materials were named ELP1-den and ELP2-den, respectively. The AuNPs were prepared by the reduction of Au ions using a dendrimer-nanotemplated method. The AuNP-loaded elastin-mimetic dendrimers exhibited photothermal properties. ELP1-den and ELP2-den showed similar temperature-dependent changes in their conformations. Phase transitions were observed at around 55°C and 35°C for the AuNP-loaded ELP1-den and AuNP-loaded ELP2-den, respectively, but not for the corresponding PEGylated dendrimer. In contrast to the AuNP-loaded PEGylated dendrimer, AuNP-loaded ELP2-den readily associated with cells and induced efficient photocytotoxicity at 37°C. The cell association and the photocytotoxicity properties of AuNP-loaded ELP2-den could be controlled by temperature. These results therefore suggest that dual stimuli-sensitive dendrimer nanoparticles of this type could be used for photothermal therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

An adenovirus prime/plasmid boost strategy for induction of equipotent immune responses to two dengue virus serotypes.

PubMed

Khanam, Saima; Rajendra, Pilankatta; Khanna, Navin; Swaminathan, Sathyamangalam

2007-02-15

Dengue is a public health problem of global significance for which there is neither an effective antiviral therapy nor a preventive vaccine. It is a mosquito-borne viral disease, caused by dengue (DEN) viruses, which are members of the Flaviviridae family. There are four closely related serotypes, DEN-1, DEN-2, DEN-3 and DEN-4, each of which is capable of causing disease. As immunity to any one serotype can potentially sensitize an individual to severe disease during exposure to a heterologous serotype, the general consensus is that an effective vaccine should be tetravalent, that is, it must be capable of affording protection against all four serotypes. The current strategy of creating tetravalent vaccine formulations by mixing together four monovalent live attenuated vaccine viruses has revealed the phenomenon of viral interference leading to the manifestation of immune responses biased towards a single serotype. This work stems from the emergence of (i) the DEN virus envelope (E) domain III (EDIII) as the most important region of the molecule from a vaccine perspective and (ii) the adenovirus (Ad) as a promising vaccine vector platform. We describe the construction of a recombinant, replication-defective Ad (rAd) vector encoding a chimeric antigen made of in-frame linked EDIIIs of DEN virus serotypes 2 and 4. Using this rAd vector, in conjunction with a plasmid vector encoding the same chimeric bivalent antigen, in a prime-boost strategy, we show that it is possible to elicit equipotent neutralizing and T cell responses specific to both DEN serotypes 2 and 4. Our data support the hypothesis that a DEN vaccine targeting more than one serotype may be based on a single DNA-based vector to circumvent viral interference. This work lays the foundation for developing a single Ad vector encoding EDIIIs of all four DEN serotypes to evoke a balanced immune response against each one of them. Thus, this work has implications for the development of safe and effective

Safety and immunogenicity of different doses and schedules of a live attenuated tetravalent dengue vaccine (TDV) in healthy adults: A Phase 1b randomized study.

PubMed

Rupp, Richard; Luckasen, Gary Joseph; Kirstein, Judith Lee; Osorio, Jorge E; Santangelo, Joseph D; Raanan, Marsha; Smith, Mary Kathryn; Wallace, Derek; Gordon, Gilad S; Stinchcomb, Dan T

2015-11-17

A safe, effective dengue vaccine that can simultaneously induce immunity to all four dengue virus serotypes (DENV-1-4) is a public health priority. A chimeric tetravalent dengue vaccine (TDV) based on an attenuated DENV-2 serotype backbone was evaluated in healthy, flavivirus-seronegative adults. In this randomized, multicenter, Phase 1b study conducted in the United States, the safety and immunogenicity of TDV were evaluated in 140 participants aged 18-45 years in six dosing regimen study groups. Participants were injected subcutaneously on Days 0 and 90; placebo (saline) was injected where appropriate to maintain double blinding. Three different TDV dosages (TDV, a vaccine in which TDV-4 had been increased three-fold, and a one-tenth TDV dose), and single or double dosing were evaluated in one and/or both arms. Primary endpoints were solicited and unsolicited adverse events (AEs) and seroconversion rates to DENV-1-4 at Day 120. The severity of all AEs was generally mild. The most common unsolicited AEs were headache (52%), fatigue (43%) and myalgia (29%). The incidence of injection site pain ranged from 29 to 64% and 5 to 52% among study groups after the first and second doses, respectively. At Day 120, the ranges of seroconversion rates among the groups were DEN-1: 84-100%; DEN-2: 96-100%; DEN-3: 83-100%; and DEN-4: 33-77%. More than 80% of participants in each group seroconverted to at least three dengue serotypes. Substantial GMT increases from baseline were observed for DEN-1-3 at all time points from Day 30 onward; DEN-4 GMT increases were lower. Increasing TDV-4 slightly increased DEN-4 GMT, did not impact DEN-2 and DEN-3 GMT, but reduced DEN-1 GMT. Neither multiple dosing in both arms, nor one-tenth TDV dosing meaningfully impacted GMT increases relative to TDV. All TDV doses and dosing schedules were well tolerated and immunogenic in healthy flavivirus-naive adults (ClinicalTrials.gov NCT01511250). Copyright © 2015 The Authors. Published by Elsevier Ltd

Measurements and Predictions for a Distributed Exhaust Nozzle

NASA Technical Reports Server (NTRS)

Kinzie, Kevin W.; Brown, Martha C.; Schein, David B.; Solomon, W. David, Jr.

2001-01-01

The acoustic and aerodynamic performance characteristics of a distributed exhaust nozzle (DEN) design concept were evaluated experimentally and analytically with the purpose of developing a design methodology for developing future DEN technology. Aerodynamic and acoustic measurements were made to evaluate the DEN performance and the CFD design tool. While the CFD approach did provide an excellent prediction of the flowfield and aerodynamic performance characteristics of the DEN and 2D reference nozzle, the measured acoustic suppression potential of this particular DEN was low. The measurements and predictions indicated that the mini-exhaust jets comprising the distributed exhaust coalesced back into a single stream jet very shortly after leaving the nozzles. Even so, the database provided here will be useful for future distributed exhaust designs with greater noise reduction and aerodynamic performance potential.

Die Struktur von schlankem Materialfluss mit Lean Production Kanban und Innovationen

NASA Astrophysics Data System (ADS)

Scheid, Wolf-Michael

In der Literatur wird Materialfluss überwiegend in Spezialdisziplinen betrachtet, etwa der Steuerungslogik, der Logistiktechnik oder dem Supply Chain Management. Ein charakterisierendes Merkmal des Materialflusses ist jedoch, dass er sich aus vielfältigen Einzelbausteinen zusammensetzt, die alle harmonisch abgestimmt sein müssen. Die maximal erreichbare Effizienz wird nicht durch Höchstleistungen in dem einen oder anderen Spezialthema bestimmt, sondern durch das schwächste Glied im gesamten komplexen Netzwerk. Den Schnittstellen zwischen den betroffenen Fachbereichen in einem Unternehmen kommt hier eine ganz besondere Bedeutung zu: Erst ein harmonischer Einklang ermöglicht hohe Effektivität. Dies setzt umfassendes Verständnis für interdisziplinäre Notwendigkeiten, ein hohes Maß an Abstimmung mit den operativen Prozessen und letztlich einen einvernehmlichen Umgang und den Respekt vor den Problemstellungen des Anderen voraus.

Degradable Implantate: Entwicklungsbeispiele

NASA Astrophysics Data System (ADS)

Ruffieux, Kurt; Wintermantel, Erich

Resorbierbare Implantate werden seit mehreren Jahrzehnten in der Implantologie eingesetzt. Bekannt wurden diese Biomaterialien mit dem Aufkommen von sich selbst auflösenden Nahtfäden auf der Basis von synthetisch hergestellten Polylactiden und Polyglycoliden in den 70er Jahren. In einem nächsten Schritt wurden Implantate wie Platten und Schrauben zur Gewebefixation aus den gleichen Biomaterialien hergestellt.

Evaluation of the severe combined immunodeficient (SCID) mouse as an animal model for dengue viral infection.

PubMed

Wu, S J; Hayes, C G; Dubois, D R; Windheuser, M G; Kang, Y H; Watts, D M; Sieckmann, D G

1995-05-01

Severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood lymphocytes (hu-PBL) were evaluated as an animal model for demonstrating dengue (DEN) viral infection. Reconstituted mice (hu-PBL-SCID) that demonstrated successful engraftment by the presence of serum titers of human immunoglobulin (Ig) were inoculated intraperitoneally with DEN virus serotype 1 (DEN-1). Serial blood samples were taken postinoculation and assayed for virus in C6/36 cells. The identity of all viral isolates was confirmed by an immunofluorescence antibody assay using DEN-1 monoclonal antibody. A total of six experiments were performed using different procedures of reconstitution and infection, and in three of these experiments, DEN-1 virus was recovered from the hu-PBL-SCID mice. In the first successful experiment, DEN-1 virus was recovered on postinoculation day (PID) 24 from blood, spleen, thymus, and lung tissues of one of eight hu-PBL-SCID mice. A second group of eight hu-PBL-SCID mice were inoculated with human monocytes infected in vitro with DEN-1 virus. Virus was recovered from the blood of mice between PID 15 and 23, and from lung tissue of one of these mice. In a third experiment, seven SCID mice were treated initially with anti-asialo GM1 antibody to eliminate natural killer cells, and then were injected simultaneously with a mixture of hu-PBL and DEN-1 virus. Virus was demonstrated in the blood of one mouse on PID 38, and in another mouse on PID 8, 12, 20, 24, and 36.(ABSTRACT TRUNCATED AT 250 WORDS)

A spring aerial census of red foxes in North Dakota

USGS Publications Warehouse

Sargeant, A.B.; Pfeifer, W.K.; Allen, S.H.

1975-01-01

Systematic aerial searches were flown on transects to locate adult red foxes (Vulpes vulpes), pups, and rearing dens on 559.4 km2 (six townships) in eastern North Dakota during mid-May and mid-June each year from 1969 through 1973 and during mid-April 1969 and early May 1970. The combined sightings of foxes and fox dens from the mid-May and mid-June searches were used to identify individual fox families. The number of fox families was used as the measurement of density. Dens, highly visible during the mid-May searches, were the most reliable family indicator; 84 percent of 270 families identified during the study were represented by dens. Adult foxes second in importance, were most observable during the mid-May searches when 20 to 35 percent of those estimated to be available were sighted. Adult sightings during other search periods ranged from 4 to 17 percent of those available. Pup sightings were the most variable family indicator, but they led to the discovery of some dens. Sources of error for which adjustment factors were determined are: den moves exceeding criterion established for the spacing of dens in a single family, overestimation of the number of fox families living near township boundaries, and the percentage of fox families overlooked during the aerial searches. These adjustment factors appeared to be largely compensatory.

Pioneers of movement disorders: Georges Gilles de la Tourette.

PubMed

Krämer, H; Daniels, C

2004-06-01

Georges Albert Edouard Brutus Gilles de la Tourette (1857-1904), a French neurologist and pupil of Jean Martin Charcot at the Salpêtrière hospital in Paris, has gained common recognition through his description of the 'Maladie des Tics'. This complex neuropsychiatric disorder, later known as the 'Tourette's syndrome', nowadays is accepted as a specific entity of movement disorders. Gilles had started working under Charcot (1825-1893), the first physician to occupy a designated chair of neurology of neuropsychiatric history, in 1884. Then the Salpêtrière hospital was a centre of intensive research with an emphasis on hysteria and hypnosis. Tourette took an interest in hysteria, but also dedicated himself to various other neuropsychiatric disorders and to neuropathology. He published scientific works on epilepsia, neurasthenia and syphilitic myelitis. Although he devoted much time to his neuropsychiatric research and the publication of articles in medical journals, his career did not make significant progress, despite Charcot's unrestricted support. One reason was, that he disregarded questions, answers and problems, which were outside his interest fields. Hence, he was accused for having acquired an extremely filtered and one-sided knowledge. Also, his alienated and critical behaviour, which had not helped him to find many friends over the years, prevented him from professional promotion. In 1893 an assassination attempt on Gilles de la Tourette raised considerable public interest: Gilles was shot in his appartement in the Rue de l'Université 39 by a young woman, who had been his patient in the Salpêtrière and who claimed that she had been hypnotized without her agreement and thereby had lost her mental health. However, the patient was diagnosed with a disease nowadays called paranoid schizophrenia and therefore hypnosis was not attributed to any part of the disease. Due to episodes of melancholia and phases of delusions of grandeur and megalomania Gilles de

New mutation of the MPZ gene in a family with the Dejerine-Sottas disease phenotype.

PubMed

Floroskufi, Paraskewi; Panas, Marios; Karadima, Georgia; Vassilopoulos, Demetris

2007-05-01

Charcot-Marie-Tooth disease type 1B is associated with mutations in the myelin protein zero gene. In the present study a new myelin protein zero gene mutation (c.89T>C,Ile30Thr) was detected in a family with the Dejerine-Sottas disease phenotype. The results support the hypothesis that severe, early-onset neuropathy may be related to either an alteration of a conserved amino acid or a disruption of the tertiary structure of myelin protein zero.

Safety of direct endoscopic necrosectomy in patients with gastric varices

PubMed Central

Storm, Andrew C; Thompson, Christopher C

2016-01-01

AIM: To determine the feasibility and safety of transgastric direct endoscopic necrosectomy (DEN) in patients with walled-off necrosis (WON) and gastric varices. METHODS: A single center retrospective study of consecutive DEN for WON was performed from 2012 to 2015. All DEN cases with gastric fundal varices noted on endoscopy, computed tomography (CT) or magnetic resonance imaging (MRI) during the admission for DEN were collected for analysis. In all cases, external urethral sphincter (EUS) with doppler was used to exclude the presence of intervening gastric varices or other vascular structures prior to 19 gauge fine-needle aspiration (FNA) needle access into the cavity. The tract was serially dilated to 20 mm and was entered with an endoscope for DEN. Pigtail stents were placed to facilitate drainage of the cavity. Procedure details were recorded. Comprehensive chart review was performed to evaluate for complications and WON recurrence. RESULTS: Fifteen patients who underwent DEN for WON had gastric varices at the time of their procedure. All patients had an INR < 1.5 and platelets > 50. Of these patients, 11 had splenic vein thrombosis and 2 had portal vein thrombosis. Two patients had isolated gastric varices, type 1 and the remaining 13 had > 5 mm gastric submucosal varices on imaging by CT, MRI or EUS. No procedures were terminated without completing the DEN for any reason. One patient had self-limited intraprocedural bleeding related to balloon dilation of the tract. Two patients experienced delayed bleeding at 2 and 5 d post-op respectively. One required no therapy or intervention and the other received 1 unit transfusion and had an EGD which revealed no active bleeding. Resolution rate of WON was 100% (after up to 2 additional DEN in one patient) and no patients required interventional radiology or surgical interventions. CONCLUSION: In patients with WON and gastric varices, DEN using EUS and doppler guidance may be performed safely. Successful resolution

Taphonomic and zooarchaeological implications of spotted hyena (crocuta crocuta) bone accumulations in kenya: A modern behavioral ecological approach

USGS Publications Warehouse

Lansing, S.W.; Cooper, S.M.; Boydston, E.E.; Holekamp, K.E.

2009-01-01

The significant impact of extant carnivores, particularly spotted hyenas, on the depo-sitional history and physical characteristics of archaeofaunal and paleontological assemblages is well recognized. We focus on the behavioral ecology of extant spotted hyenas (Crocuta crocuta) in relation to bone accumulations produced by one East African clan at communal dens. Limbs and skulls of prey animals more frequently appear at dens than do other carcass portions. These items reflect the relative abundance of prey species near dens; carnivore remains are poorly represented. Comparative analysis reveals that bones are deposited far more slowly (<7 carcass portions per month) and accumulations tend to be smaller at Crocuta dens than at dens of either brown (Para-hyaena brunnea) or striped (Hyaena hyaena) hyenas. We propose that extant Crocuta bone accumu-lation rates and sizes are likely affected by prey species abundance, clan size, social interactions within the clan, and the type and availability of den sites. We also suggest that the potential for intraspecific behavioral variability in bone accumulation patterns is important when comparisons are made among spotted hyena populations and across hyena species. For example, accumulation patterns may be dramatically influenced by the temporal span, potentially ranging from days to hundreds or thousands of years, in which bones are collected, depending on the species-specific history of occupation at a given site. Understanding the behavioral and ecological variability likely to influence bone accumulation patterns at dens used by different hyaenids will allow taphonomists and zooarchaeologists to refine their knowledge of mechanisms underlying site formation pro-cesses and potential causes of variability in deeper-time den assemblages. ?? 2009 The Paleontological Society.

Physikgeschichte Das Rätsel bleibt

NASA Astrophysics Data System (ADS)

Hoffmann, Dieter

2002-05-01

Die jüngst erfolgte Veröffentlichung von Dokumenten aus dem Privatarchiv der Familie Bohr [1] über den geheimnisumwitterten Besuch von Werner Heisenberg in Kopenhagen im September 1941 hat in den deutschen Medien große Resonanz gefunden [2]. Tatsächlich verraten uns die jetzt veröffentlichten Dokumente sehr viel mehr über die Zeit ihres Entstehens als über den Besuch selbst.

Ebenen des Verstehens: Überlegungen zu einem Verfahren zum Wurzelziehen

NASA Astrophysics Data System (ADS)

Winter, Martin

Wir bemühen uns, insbesondere bei Kindern, den Lernprozess auch im Mathematikunterricht durch den Einsatz von Materialien zu unterstützen. Die Arbeitsschritte dienen dabei oft der Vorbereitung oder Herleitung von Verfahren - in der Hoffnung, dass durch die Veranschaulichung Zusammenhänge besser verstanden werden. Worin dann das Verstehen besteht, wenn im Ergebnis ein Verfahren von den Kindern erfolgreich abgearbeitet wird, ist nicht unmittelbar zu sehen.

Morphofunctional characteristics of the foot in patients with diabetes mellitus and diabetic neuropathy.

PubMed

García-Álvarez, Yolanda; Lázaro-Martínez, José Luis; García-Morales, Esther; Cecilia-Matilla, Almudena; Aragón-Sánchez, Javier; Carabantes-Alarcón, David

2013-01-01

To determine the structural and biomechanical characteristics associated with the conditions diabetes mellitus and diabetic neuropathy. Observational study of 788 patients conducted between February 2007 and February 2009, which included subjects with and without diabetes mellitus who had no active ulcer at enrollment. Demographic variables and the general and specific history of diabetes mellitus were recorded. The patient's foot type according to the Foot Posture Index, joint mobility and deformity were recorded. No associations were found between the different foot types (neutral, pronated and supinated) and the structural and demographic variables at a general level, except for the pronated foot that was associated with a higher body mass index, longer suffering from diabetes and the presence of neuropathy [p<0.001, OR (95% CI): 6.017 (4.198-8.624); p<0.001, OR (95% CI): 1.710 (1.266-2.309); p=0.010, OR (95% CI): 0.759 (0.615-0.937), respectively]. The confluence of risk factors such as neuropathy, body mass index, duration of diabetes and limited joint mobility in patients with diabetes mellitus and pronated foot may be a high-risk anthropometric pattern for developing associated complications such as Charcot foot. A prospective analysis of these patients is required to define the risk for developing Charcot neuroarthropathy. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Genetic heterogeneity of motor neuropathies

PubMed Central

Bansagi, Boglarka; Griffin, Helen; Whittaker, Roger G.; Antoniadi, Thalia; Evangelista, Teresinha; Miller, James; Greenslade, Mark; Forester, Natalie; Duff, Jennifer; Bradshaw, Anna; Kleinle, Stephanie; Boczonadi, Veronika; Steele, Hannah; Ramesh, Venkateswaran; Franko, Edit; Pyle, Angela; Lochmüller, Hanns; Chinnery, Patrick F.

2017-01-01

Objective: To study the prevalence, molecular cause, and clinical presentation of hereditary motor neuropathies in a large cohort of patients from the North of England. Methods: Detailed neurologic and electrophysiologic assessments and next-generation panel testing or whole exome sequencing were performed in 105 patients with clinical symptoms of distal hereditary motor neuropathy (dHMN, 64 patients), axonal motor neuropathy (motor Charcot-Marie-Tooth disease [CMT2], 16 patients), or complex neurologic disease predominantly affecting the motor nerves (hereditary motor neuropathy plus, 25 patients). Results: The prevalence of dHMN is 2.14 affected individuals per 100,000 inhabitants (95% confidence interval 1.62–2.66) in the North of England. Causative mutations were identified in 26 out of 73 index patients (35.6%). The diagnostic rate in the dHMN subgroup was 32.5%, which is higher than previously reported (20%). We detected a significant defect of neuromuscular transmission in 7 cases and identified potentially causative mutations in 4 patients with multifocal demyelinating motor neuropathy. Conclusions: Many of the genes were shared between dHMN and motor CMT2, indicating identical disease mechanisms; therefore, we suggest changing the classification and including dHMN also as a subcategory of Charcot-Marie-Tooth disease. Abnormal neuromuscular transmission in some genetic forms provides a treatable target to develop therapies. PMID:28251916

Figures and institutions of the neurological sciences in Paris from 1800 to 1950. Part III: neurology.

PubMed

Broussolle, E; Poirier, J; Clarac, F; Barbara, J-G

2012-04-01

We present a short historical review of the major figures, their administrative functions and their works that contributed to make Paris a renowned centre of physiology and neurology during the xixth and the first half of the xxth century. We purposely chose to focus on the period 1800-1950, as 1800 corresponds to the actual beginning of neurosciences, and 1950 marks their exponential rise. Our presentation is divided into four chapters, matching the main disciplines which have progressed and contributed the most to the knowledge we have of the brain sciences: anatomy, physiology, neurology, and psychiatry-psychology. The present article is the third of four parts of this review, and deals with neurology. A special credit should be given to Jean-Martin Charcot who founded the Salpêtrière School of neurology and became one of the world's most important neurologists of the xixth century. We provide below the biographical sketches of Armand Trousseau, Guillaume Benjamin Amand Duchenne, Jean-Martin Charcot, Alfred Vulpian, Désiré-Magloire Bourneville, Paul Richer, Henri Parinaud, Albert Pitres, Jules Joseph Dejerine, Mrs. Augusta Dejerine-Klumpke, Édouard Brissaud, Pierre Marie, Georges Édouard Brutus Gilles de la Tourette, Joseph Babinski, André Thomas, Georges Marinesco, Achille Alexandre Souques, Georges Guillain and Charles Foix. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Molecular studies with Aedes (Stegomyia) aegypti (Linnaeus, 1762), mosquito transmitting the dengue virus.

PubMed

Pereira, Luciana Patrícia Lima Alves; Brito, Maria Cristiane Aranha; Araruna, Felipe Bastos; de Andrade, Marcelo Souza; Moraes, Denise Fernandes Coutinho; Borges, Antônio Carlos Romão; do Rêgo Barros Pires Leal, Emygdia Rosa

2017-08-01

Dengue is an infectious viral disease, which can present a wide clinical picture, ranging from oligo or asymptomatic forms, to bleeding and shock, and can progress to death. The disease problem has increased in recent years, especially in urban and suburban areas of tropical and subtropical regions. There are five dengue viruses, called serotypes (DEN-1, DEN-2, DEN-3, DEN-4, and DEN-5), which belong to the Flaviviridae family and are transmitted to humans through infected mosquito bites, with the main vector the Aedes aegypti mosquito (Linnaeus, 1762). Studies performed with Ae. aegypti, aimed at their identification and analysis of their population structure, are fundamental to improve understanding of the epidemiology of dengue, as well for the definition of strategic actions that reduce the transmission of this disease. Therefore, considering the importance of such research to the development of programs to combat dengue, the present review considers the techniques used for the molecular identification, and evaluation of the genetic variability of Ae. aegypti.

A grid-enabled web service for low-resolution crystal structure refinement.

PubMed

O'Donovan, Daniel J; Stokes-Rees, Ian; Nam, Yunsun; Blacklow, Stephen C; Schröder, Gunnar F; Brunger, Axel T; Sliz, Piotr

2012-03-01

Deformable elastic network (DEN) restraints have proved to be a powerful tool for refining structures from low-resolution X-ray crystallographic data sets. Unfortunately, optimal refinement using DEN restraints requires extensive calculations and is often hindered by a lack of access to sufficient computational resources. The DEN web service presented here intends to provide structural biologists with access to resources for running computationally intensive DEN refinements in parallel on the Open Science Grid, the US cyberinfrastructure. Access to the grid is provided through a simple and intuitive web interface integrated into the SBGrid Science Portal. Using this portal, refinements combined with full parameter optimization that would take many thousands of hours on standard computational resources can now be completed in several hours. An example of the successful application of DEN restraints to the human Notch1 transcriptional complex using the grid resource, and summaries of all submitted refinements, are presented as justification.

Evolutionary Relationships of Endemic/Epidemic and Sylvatic Dengue Viruses

PubMed Central

Wang, Eryu; Ni, Haolin; Xu, Renling; Barrett, Alan D. T.; Watowich, Stanley J.; Gubler, Duane J.; Weaver, Scott C.

2000-01-01

Endemic/epidemic dengue viruses (DEN) that are transmitted among humans by the mosquito vectors Aedes aegypti and Aedes albopictus are hypothesized to have evolved from sylvatic DEN strains that are transmitted among nonhuman primates in West Africa and Malaysia by other Aedes mosquitoes. We tested this hypothesis with phylogenetic studies using envelope protein gene sequences of both endemic/epidemic and sylvatic strains. The basal position of sylvatic lineages of DEN-1, -2, and -4 suggested that the endemic/epidemic lineages of these three DEN serotypes evolved independently from sylvatic progenitors. Time estimates for evolution of the endemic/epidemic forms ranged from 100 to 1,500 years ago, and the evolution of endemic/epidemic forms represents relatively recent events in the history of DEN evolution. Analysis of envelope protein amino acid changes predicted to have accompanied endemic/epidemic emergence suggested a role for domain III in adaptation to new mosquito and/or human hosts. PMID:10708439

Wolfgang Pauli

NASA Astrophysics Data System (ADS)

Enz, Charles P.

2000-11-01

Wolfgang Pauli gehört zu den bedeutendsten Physikern des 20. Jahrhunderts. Erst das von ihm entdeckte Ausschließungsprinzip erklärt den Aufbau des Periodensystems der Elemente. Darüber hinaus legte er den Grundstein für die Quantenfeldtheorie. Privat zeigte sich Pauli als bissiger und humorvoller Mensc gleichermaßen, und sein Hang zur Psychoanalyse lässt ihn überdies als interessante Persönlichkeit erscheinen.

Rapid detection and differentiation of dengue virus serotypes by NS1 specific reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay in patients presenting to a tertiary care hospital in Hyderabad, India.

PubMed

Neeraja, M; Lakshmi, V; Lavanya, Vanjari; Priyanka, E N; Parida, M M; Dash, P K; Sharma, Shashi; Rao, P V Lakshmana; Reddy, Gopal

2015-01-01

Early and rapid detection of dengue virus (DENV) infection during the acute phase of illness is crucial for proper patient management and prevention of the spread of the infection. In the present study, the standardization and validation of a one step, four tube reverse transcription loop-mediated isothermal amplification assay (RT-LAMP) for rapid detection and serotyping of the DENV targeting NS1 gene using the Genie® II flourometer was carried out. The performance of the RT-LAMP was compared to RT-PCR, CDC 1-4 Real time PCR and the NS1 antigen ELISA, IgM and IgG anti DENV antibodies. Acute DENV infection was confirmed in 250/300 patients suspected clinically of DENV infection. RT- LAMP and CDC 1-4 Real time PCR assay was positive in 148/250 patients, while 92/250 patients were positive for anti- Dengue IgM and IgG antibodies. The RT-LAMP assay and the CDC real-time RT-PCR assay showed high concordance (k=1.0). The detection rate of acute DENV infection improved to 96% (240/250) when the results of RT-LAMP were combined with NS1 Ag, IgM and IgG ELISA. The RT-LAMP had a detection limit of 100 copies for DEN-1 and DEN-2, 10 copies for DEN-3 and DEN-4 compared to 1000 copies for DEN-1 and DEN-2, 100 copies for DEN-3 and DEN-4 by the conventional RT-PCR. The assay showed 100% specificity. The RT-LAMP assay developed in this study has potential use for early clinical diagnosis, serotyping and surveillance of DENV infection in endemic countries such as India. Copyright © 2014 Elsevier B.V. All rights reserved.

Development of a novel mouse model of hepatocellular carcinoma with nonalcoholic steatohepatitis using a high-fat, choline-deficient diet and intraperitoneal injection of diethylnitrosamine.

PubMed

Kishida, Norihiro; Matsuda, Sachiko; Itano, Osamu; Shinoda, Masahiro; Kitago, Minoru; Yagi, Hiroshi; Abe, Yuta; Hibi, Taizo; Masugi, Yohei; Aiura, Koichi; Sakamoto, Michiie; Kitagawa, Yuko

2016-06-13

The incidence of hepatocellular carcinoma with nonalcoholic steatohepatitis is increasing, and its clinicopathological features are well established. Several animal models of nonalcoholic steatohepatitis have been developed to facilitate its study; however, few fully recapitulate all its clinical features, which include insulin resistance, inflammation, fibrosis, and carcinogenesis. Moreover, these models require a relatively long time to produce hepatocellular carcinoma reliably. The aim of this study was to develop a mouse model of hepatocellular carcinoma with nonalcoholic steatohepatitis that develops quickly and reflects all clinically relevant features. Three-week-old C57BL/6J male mice were fed either a standard diet (MF) or a choline-deficient, high-fat diet (HFCD). The mice in the MF + diethylnitrosamine (DEN) and HFCD + DEN groups received a one-time intraperitoneal injection of DEN at the start of the respective feeding protocols. The mice in the HFCD and HFCD + DEN groups developed obesity early in the experiment and insulin resistance after 12 weeks. Triglyceride levels peaked at 8 weeks for all four groups and decreased thereafter. Alanine aminotransferase levels increased every 4 weeks, with the HFCD and HFCD + DEN groups showing remarkably high levels; the HFCD + DEN group presented the highest incidence of nonalcoholic steatohepatitis. The levels of fibrosis and steatosis varied, but they tended to increase every 4 weeks in the HFCD and HFCD + DEN groups. Computed tomography scans indicated that all the HFCD + DEN mice developed hepatic tumors from 20 weeks, some of which were glutamine synthetase-positive. The nonalcoholic steatohepatitis-hepatocellular carcinoma model we describe here is simple to establish, results in rapid tumor formation, and recapitulates most of the key features of nonalcoholic steatohepatitis. It could therefore facilitate further studies of the development, oncogenic potential, diagnosis

Acute recreational drug and new psychoactive substance toxicity in Europe: 12 months data collection from the European Drug Emergencies Network (Euro-DEN).

PubMed

Dines, Alison M; Wood, David M; Yates, Christopher; Heyerdahl, Fridtjof; Hovda, Knut Erik; Giraudon, Isabelle; Sedefov, Roumen; Dargan, Paul I

2015-11-01

Despite the potential for recreational drugs and new psychoactive substances (NPSs) to cause significant morbidity and mortality, there is limited collection of systematic data on acute drug/NPS toxicity in Europe. To report data on acute drug/NPS toxicity collected by a network of sentinel centres across Europe with a specialist clinical and research interest in the acute toxicity of recreational drugs and NPS to address this knowledge gap. Sixteen sentinel centres in 10 European countries (Denmark, Estonia, France, Germany, Ireland, Norway, Poland, Spain, Switzerland and the UK) collected data on all acute drug toxicity presentations to their Emergency Rooms (ERs) for 12 months (October 2013-September 2014); information on the drug(s) involved in the presentations was on the basis of patient self-reporting. Data were collected on a total of 5529 presentations involving 8709 drugs (median (interquartile range [IQR]): 1 (1-2) drugs per presentation), a median of 0.3% of all ER attendances. Classical recreational drugs were most common (64.6%) followed by prescription drugs (26.5%) and NPS (5.6%). The 'top five' drugs recorded were heroin (1345 reports), cocaine (957), cannabis (904), GHB/GBL (711) and amphetamine (593). 69.5% of individuals went to hospital by ambulance (peak time between 19:00 and 02:00 at weekends); the median (IQR) age was 31 (24-39) years and 75.4% were male. Although serious clinical features were not seen in most presentations and 56.9% were medically discharged from the ER (median length of stay: 4.6 hours), a significant number (26.5%) was agitated, in 10.5% the GCS was 8 or less and 35 presented in cardiac arrest. There were 27 fatalities with opioids implicated in 13. The Euro-DEN dataset provides a unique insight into the drugs involved in and clinical pattern of toxicity/outcome of acute recreational drug toxicity presentations to hospitals around Europe. This is complimentary to other indicators of drug-related harm and helps to build

Experiments and Analyses of Distributed Exhaust Nozzles

NASA Technical Reports Server (NTRS)

Kinzie, Kevin W.; Schein, David B.; Solomon, W. David, Jr.

2002-01-01

Experimental and analytical aeroacoustic properties of several distributed exhaust nozzle (DEN) designs are presented. Significant differences between the designs are observed and correlated back to Computational Fluid Dynamics (CFD) flowfield predictions. Up to 20 dB of noise reduction on a spectral basis and 10 dB on an overall sound pressure level basis are demonstrated from the DEN designs compared to a round reference nozzle. The most successful DEN designs acoustically show a predicted thrust loss of approximately 10% compared to the reference nozzle. Characteristics of the individual mini-jet nozzles that comprise the DEN such as jet-jet shielding and coalescence are shown to play a major role in the noise signature.

A rare case of idiopathic thumb CMC joint neuropathic arthropathy complicated by blunt trauma.

PubMed

Singh, Manavdeep; Butala, R R; Khedekar, R G; Tripati, Manish

2016-01-01

Neuropathic arthropathy (Charcot joints), which most frequently affects the weight-bearing joints of the body, is commonly associated with a variety of medical and neurological conditions, and is notoriously difficult to treat due to the nature of the underlying pathology. We present a case of idiopathic neuropathic arthropathy of the thumb CMC joint of an elderly female complicated by blunt trauma to the thumb. To our knowledge, this is the first reported case in the literature of this rare association.

Dose-related cell proliferation in medaka (Oryzias latipes) after N-nitrosodiethylamine exposure

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

Ortego, L.S.; Hawkins, W.E.; Walker, W.W.

1994-12-31

Cell proliferation is important in toxic and carcinogenic mechanisms. Carcinogens such as N-nitrosodiethylamine (DEN) that cause necrotizing injury stimulate cell proliferation as part of an injury-repair mechanism. A stimulus to cell division in an organ with a low rate of cell division, such as the liver, may initiate or enhance the carcinogenicity of a chemical. The authors examined the effect of DEN exposure on cell proliferation in the liver of medaka (Oryzias latipes). Two age groups (6 and 56 days post-hatch) were exposed to DEN continuously at 5 doses (0.0, 2.5, 5.0, 10.0, and 20.0 ppm) for 28 days. Cellmore » proliferation was measured using the proliferating cell nuclear antigen (PCNA) assay two months post-initiation of DEN exposure. The assay involves monoclonal antibody detection of PCNA, an auxiliary protein of DNA polymerase delta which is, expressed during cell division. Results suggested that cell proliferation paralleled the DEN dose and that age at initiation of exposure did not affect this relationship. The increase in cell proliferation appeared to be a sustained response from that initiated during DEN exposure. The study suggests that cell proliferation in medaka is an important component in carcinogenesis and is related to carcinogen exposure dose.« less

Walter Reed Army Institute of Research Annual Progress Report Fiscal Year 1982.

DTIC Science & Technology

1982-10-01

antibacterial activity . Fed. Proc. 4787, 1981. 11. Collins, H.H., D.F. Keren, P. Gemski, S.B. Formal, -.--| W.D. Zollinger, and G.H. Lowell...murlne myeloma cells. The fused cells will be subjected to specific selection by growth in selective media. The survivors from actively growing cell...prototype dengue virus strains. DEN-1 (Hawaiian), DEN-2 (New Guinea C), ÜEN-3 ( Philippines H-87), and DEN-4 ( Philippines H-241). Lymphocyte

Diethylnitrosamine-induced hepatocarcinogenesis is suppressed in lecithin:retinol acyltransferase-deficient mice primarily through retinoid actions immediately after carcinogen administration.

PubMed

Shirakami, Yohei; Gottesman, Max E; Blaner, William S

2012-02-01

Loss of retinoid-containing lipid droplets upon hepatic stellate cell (HSC) activation is one of the first events in the development of liver disease leading to hepatocellular carcinoma. Although retinoid stores are progressively lost from HSCs during the development of hepatic disease, how this affects hepatocarcinogenesis is unclear. To investigate this, we used diethylnitrosamine (DEN) to induce hepatic tumorigenesis in matched wild-type (WT) and lecithin:retinol acyltransferase (LRAT) knockout (KO) mice, which lack stored retinoid and HSC lipid droplets. Male 15-day-old WT or Lrat KO mice were given intraperitoneal injections of DEN (25 mg/kg body wt). Eight months later, Lrat KO mice showed significantly less liver tumor development compared with WT mice, characterized by less liver tumor incidence and smaller tumor size. Two days after DEN injection, lower serum levels of alanine aminotransferase and decreased hepatic levels of cyclin D1 were observed in Lrat KO mice. Lrat KO mice also exhibited increased levels of retinoic acid-responsive genes, including p21, lower levels of cytochrome P450 enzymes required for DEN bioactivation and higher levels of the DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT), both before and after DEN treatment. Our results indicate that Lrat KO mice are less susceptible to DEN-induced hepatocarcinogenesis due to increased retinoid signaling and higher expression of p21, which is accompanied by altered hepatic levels of DEN-activating enzymes and MGMT in Lrat KO mice also contribute to decreased cancer initiation and suppressed liver tumor development.

Auditory Function in Children with Charcot-Marie-Tooth Disease

ERIC Educational Resources Information Center

Rance, Gary; Ryan, Monique M.; Bayliss, Kristen; Gill, Kathryn; O'Sullivan, Caitlin; Whitechurch, Marny

2012-01-01

The peripheral manifestations of the inherited neuropathies are increasingly well characterized, but their effects upon cranial nerve function are not well understood. Hearing loss is recognized in a minority of children with this condition, but has not previously been systemically studied. A clear understanding of the prevalence and degree of…

Denitrification synergized with ANAMMOX for the anaerobic degradation of benzene: performance and microbial community structure.

PubMed

Peng, Shuchan; Zhang, Lilan; Zhang, DaiJun; Lu, Peili; Zhang, Xiaoting; He, Qiang

2017-05-01

To evaluate the effect of anaerobic ammonium oxidation (ANAMMOX) on benzene degradation under denitrification, a sequencing batch reactor (SBR) under denitrification synergized with ANAMMOX (SBR-DenAna) for benzene degradation was established by inoculating anaerobic ammonium-oxidizing bacteria (AnAOB) into a SBR under denitrification reactor (SBR-Den) for benzene degradation. The average rate of benzene degradation and the maximum first-order kinetic constant in SBR-DenAna were 2.34- and 1.41-fold those in SBR-Den, respectively, indicating that ANAMMOX improved the degradation of benzene under denitrification synergized with ANAMMOX. However, the average rate of benzene degradation decreased by 35% in the denitrification-ANAMMOX synergistic reactor when 10 mg N L -1 NO 2 - was added; the rate recovered once NO 2 - was depleted, indicating that ANAMMOX might detoxify NO 2 - . Results from high-throughput sequencing analysis revealed that Azoarcus within the family Rhodocyclaceae might be associated with benzene degradation in the two SBRs. AnAOB affiliated with the family Candidatus Brocadiaceae were just detected in SBR-DenAna.

Fluorescent, Plasmonic, and Radiotherapeutic Properties of the 177Lu–Dendrimer-AuNP–Folate–Bombesin Nanoprobe Located Inside Cancer Cells

PubMed Central

Mendoza-Nava, Héctor; Ramírez, Flor de María; Ocampo-García, Blanca; Santos-Cuevas, Clara; Azorín-Vega, Erika; Jiménez-Mancilla, Nallely; Luna-Gutiérrez, Myrna; Isaac-Olivé, Keila

2017-01-01

The integration of fluorescence and plasmonic properties into one molecule is of importance in developing multifunctional imaging and therapy nanoprobes. The aim of this research was to evaluate the fluorescent properties and the plasmonic–photothermal, therapeutic, and radiotherapeutic potential of 177Lu–dendrimer conjugated to folate and bombesin with gold nanoparticles in the dendritic cavity (177Lu–DenAuNP–folate–bombesin) when it is internalized in T47D breast cancer cells. The intense near-Infrared (NIR) fluorescence emitted at 825 nm from the conjugate inside cells corroborated the usefulness of DenAuNP–folate–bombesin for optical imaging. After laser irradiation, the presence of the nanosystem in cells caused a significant increase in the temperature of the medium (46.8°C, compared to 39.1°C without DenAuNP–folate–bombesin, P < 0.05), resulting in a significant decrease in cell viability (down to 16.51% ± 1.52%) due to the 177Lu–DenAuNP–folate–bombesin plasmonic properties. After treatment with 177Lu–DenAuNP–folate–bombesin, the T47D cell viability decreased 90% because of the radiation-absorbed dose (63.16 ± 4.20 Gy) delivered inside the cells. The 177Lu–DenAuNP–folate–bombesin nanoprobe internalized in cancer cells exhibited properties suitable for optical imaging, plasmonic–photothermal therapy, and targeted radiotherapy. PMID:28654384

Different induction of LPA receptors by chemical liver carcinogens regulates cellular functions of liver epithelial WB-F344 cells.

PubMed

Hirane, Miku; Ishii, Shuhei; Tomimatsu, Ayaka; Fukushima, Kaori; Takahashi, Kaede; Fukushima, Nobuyuki; Honoki, Kanya; Tsujiuchi, Toshifumi

2016-11-01

Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA 1 to LPA 6 ) mediates a variety of cellular functions, including cell motility. In the present study, we investigated the effects of LPA receptors on cell motile activity during multi-stage hepatocarcinogenesis in rat liver epithelial WB-F344 cells treated with chemical liver carcinogens. Cells were treated with a initiator (N-nitrosodiethylamine (DEN)) and three promoters (phenobarbital (PB), okadaic acid (OA) and clofibrate) every 24 h for 2 days. Cell motile activity was elevated by DEN, correlating with Lpar3 expression. PB, OA, and clofibrate elevated Lpar1 expression and inhibited cell motile activity. To evaluate the effects of long-term treatment on cell motility, cells were treated with DEN and/or PB for at least 6 months. Lpar3 expression and cell motile activity were significantly elevated by the long-term DEN treatment with or without further PB treatment. In contrast, long-term PB treatment with or without further DEN elevated Lpar1 expression and inhibited cell motility. When the synthesis of extracellular LPA was blocked by a potent ATX inhibitor S32826 before cell motility assay, the cell motility induced by DEN and PB was markedly suppressed. These results suggest that activation of the different LPA receptors may regulate the biological functions of cells treated with chemical carcinogens. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Direct endoscopic necrosectomy versus step-up approach for walled-off pancreatic necrosis: comparison of clinical outcome and health care utilization.

PubMed

Kumar, Nitin; Conwell, Darwin L; Thompson, Christopher C

2014-11-01

Infected walled-off pancreatic necrosis (WOPN) is a complication of acute pancreatitis requiring intervention. Surgery is associated with considerable morbidity. Percutaneous catheter drainage (PCD), initial therapy in the step-up approach, minimizes complications. Direct endoscopic necrosectomy (DEN) has demonstrated safety and efficacy. We compared outcome and health care utilization of DEN versus step-up approach. This was a matched cohort study using a prospective registry. Twelve consecutive DEN patients were matched with 12 step-up approach patients. Outcomes were clinical resolution after primary therapeutic modality, new organ failure, mortality, endocrine or exocrine insufficiency, length of stay, and health care utilization. Clinical resolution in 11 of 12 patients after DEN versus 3 of 12 step-up approach patients after PCD (P < 0.01). Nine step-up approach patients required surgery; 7 of these experienced complications. Direct endoscopic necrosectomy resulted in less new antibiotic use, pulmonary failure, endocrine insufficiency, and shorter length of stay (P < 0.05). Health care utilization was lower after DEN by 5.2:1 (P < 0.01). Direct endoscopic necrosectomy may be superior to step-up approach for WOPN with suspected or established infection. Primary PCD generally delayed definitive therapy. Given the higher efficacy, shorter length of stay, and lower health care utilization, DEN could be the first-line therapy for WOPN, with primary PCD for inaccessible or immature collections.

Die Grundlagen der Fernsehtechnik: Systemtheorie und Technik der Bildübertragung

NASA Astrophysics Data System (ADS)

Mahler, Gerhard

Umfassende Einführung in die Grundlagen der Bewegtbild-Übertragung von den Anfängen bis zum heutigen Stand des digitalen Fernsehens mit einer aus der Praxis entstandenen systemtheoretischen Analyse. Die kompakte und anschaulich bebilderte Darstellung mit elementaren mathematischen Beschreibungen macht es dem Leser leicht, sich in die Bildübertragungstechnik einzuarbeiten. Thematische Einheiten erweitern den Wissensstoff - u.a. zu den Themen visuelle Wahrnehmung, mehrdimensionale Signaldarstellung, Farbmetrik, Digitalisierung, Elektronenoptik - und zeigen deren Anwendung auf die elektronische Bildübertragung.

Smart Meter Rollout: Intelligente Messsysteme als Schnittstelle zum Kunden im Smart Grid und Smart Market

NASA Astrophysics Data System (ADS)

Vortanz, Karsten; Zayer, Peter

Das Gesetz zur Digitalisierung der Energiewende ist verabschiedet. Ab 2017 sind moderne Messeinrichtungen (mME) und intelligente Messsysteme (iMSys) zu verbauen und zu betreiben. Der "deutsche Weg" für die Einführung von Smart Metern sieht einen stufenweisen Rollout sowie ein Höchstmaß an Informations- und Datensicherheit vor. Dabei spielen iMSys und mME eine wichtige Rolle bei der Neugestaltung der intelligenten Netze (Smart Grids) und des neuen Marktmodells (Smart Market). Dieser Beitrag beschäftigt sich mit den neuen Gesetzen, den Marktrollen und ihren Aufgaben, Datenschutz und Datensicherheit, dem iMSys als sichere Lösung, dem sicheren Betrieb von Smart Meter Gateways, Smart Grid - Smart Market, dem Zusammenspiel zwischen reguliertem Bereich und Markt, den Einsatzbereichen der iMSys sowie den Auswirkungen auf Prozesse und Systeme und gibt Handlungsempfehlungen.

Red fox predation on breeding ducks in midcontinent North America

USGS Publications Warehouse

Sargeant, Alan B.; Allen, Stephen H.; Eberhardt, Robert T.

1984-01-01

Red fox (Vulpes vulpes) predation on nesting ducks was assessed by examining 1,857 adult duck remains found at 1,432 fox rearing dens from 1968 to 1973. Dabbling ducks were much more vulnerable to foxes than diving ducks. Dabbling ducks (1,798) found at dens consisted of 27% blue-winged teals (Anas discors), 23% mallards (A. platyrhynchos), 20% northern pintails (A. acuta), 9% northern shovelers (Spatula clypeata), 8% gadwalls (A. strepera), 3% green-winged teals (A. crecca), 2% American wigeons (A. americana), and 10% unidentified. Relative abundance of individual species and nesting chronology were the most important factors affecting composition of ducks taken by foxes. Seventy-six percent of 1,376 adult dabbling ducks and 40% of 30 adult diving ducks for which sex was determined were hens. In western North Dakota and western South Dakota, 65% of mallard and northern pintail remains found at dens were hens compared with 76% in eastern North Dakota and eastern South Dakota (P < 0.05). Percentage hens varied among the 5 most common dabbling ducks found at dens. In eastern North Dakota and eastern South Dakota, where predation on ducks was greatest, an average of 64% of gadwall, 73% of northern pintail, 81% of blue-winged teal, 81% of mallard, and 90% of northern shoveler remains found at dens were hens. Percentage hens among duck remains found at dens increased as the duck nesting season progressed. Numbers of adult ducks found at individual dens ranged from 0 to 67. The average number of ducks found in and around den entrances was used as an index of fox predation rates on ducks. Predation rate indices ranged from 0.01 duck/den in Iowa to 1.80 ducks/den in eastern North Dakota. Average annual predation rate indices for dabbling ducks in a 3-county intensive study area in eastern North Dakota were closely correlated with May pond numbers (r = 0.874, P < 0.10) and duck population size (r = 0.930, P < 0.05), but all species were not affected in the same manner or to

Genetic heterogeneity of motor neuropathies.

PubMed

Bansagi, Boglarka; Griffin, Helen; Whittaker, Roger G; Antoniadi, Thalia; Evangelista, Teresinha; Miller, James; Greenslade, Mark; Forester, Natalie; Duff, Jennifer; Bradshaw, Anna; Kleinle, Stephanie; Boczonadi, Veronika; Steele, Hannah; Ramesh, Venkateswaran; Franko, Edit; Pyle, Angela; Lochmüller, Hanns; Chinnery, Patrick F; Horvath, Rita

2017-03-28

To study the prevalence, molecular cause, and clinical presentation of hereditary motor neuropathies in a large cohort of patients from the North of England. Detailed neurologic and electrophysiologic assessments and next-generation panel testing or whole exome sequencing were performed in 105 patients with clinical symptoms of distal hereditary motor neuropathy (dHMN, 64 patients), axonal motor neuropathy (motor Charcot-Marie-Tooth disease [CMT2], 16 patients), or complex neurologic disease predominantly affecting the motor nerves (hereditary motor neuropathy plus, 25 patients). The prevalence of dHMN is 2.14 affected individuals per 100,000 inhabitants (95% confidence interval 1.62-2.66) in the North of England. Causative mutations were identified in 26 out of 73 index patients (35.6%). The diagnostic rate in the dHMN subgroup was 32.5%, which is higher than previously reported (20%). We detected a significant defect of neuromuscular transmission in 7 cases and identified potentially causative mutations in 4 patients with multifocal demyelinating motor neuropathy. Many of the genes were shared between dHMN and motor CMT2, indicating identical disease mechanisms; therefore, we suggest changing the classification and including dHMN also as a subcategory of Charcot-Marie-Tooth disease. Abnormal neuromuscular transmission in some genetic forms provides a treatable target to develop therapies. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Fragmentation alters stream fish community structure in dendritic ecological networks.

PubMed

Perkin, Joshuah S; Gido, Keith B

2012-12-01

Effects of fragmentation on the ecology of organisms occupying dendritic ecological networks (DENs) have recently been described through both conceptual and mathematical models, but few hypotheses have been tested in complex, real-world ecosystems. Stream fishes provide a model system for assessing effects of fragmentation on the structure of communities occurring within DENs, including how fragmentation alters metacommunity dynamics and biodiversity. A recently developed habitat-availability measure, the "dendritic connectivity index" (DCI), allows for assigning quantitative measures of connectivity in DENs regardless of network extent or complexity, and might be used to predict fish community response to fragmentation. We characterized stream fish community structure in 12 DENs in the Great Plains, USA, during periods of dynamic (summer) and muted (fall) discharge regimes to test the DCI as a predictive model of fish community response to fragmentation imposed by road crossings. Results indicated that fish communities in stream segments isolated by road crossings had reduced species richness (alpha diversity) relative to communities that maintained connectivity with the surrounding DEN during summer and fall. Furthermore, isolated communities had greater dissimilarity (beta diversity) to downstream sites notisolated by road crossings during summer and fall. Finally, dissimilarity among communities within DENs decreased as a function of increased habitat connectivity (measured using the DCI) for summer and fall, suggesting that communities within highly connected DENs tend to be more homogeneous. Our results indicate that the DCI is sensitive to community effects of fragmentation in riverscapes and might be used by managers to predict ecological responses to changes in habitat connectivity. Moreover, our findings illustrate that relating structural connectivity of riverscapes to functional connectivity among communities might aid in maintaining metacommunity

The Corona Dentis: Description of an Anatomic Variant with Technical Implications for Anterior Odontoid Screw Placement.

PubMed

Alonso, Fernando; Iwanaga, Joe; Chapman, Jens R; Oskouian, Rod J; Tubbs, R Shane

2017-08-01

Type 2 odontoid fractures are the most common cervical fractures among the elderly. Neurologic deficit is usually caused by myelopathy as a result of posterior dens migration. Direct anterior screw placement provides stabilization and can preserve C1-C2 movement. The presence of a bony excrescence on the anterior superior tip of the dens may lead to placement of a screw of incorrect length. Twenty C2 dry specimens were examined for the presence of a corona dentis, which is a bony excrescence in the coronal plane near the apex of the dens. When identified, measurements of the corona dentis were performed using calipers and a ruler. In addition, anteroposterior (AP) and lateral fluoroscopy was performed on all specimens found to have a corona dentis. A corona dentis was found on 20% of our C2 specimens and had an average width of 9 mm and an average height of 4.5 mm. The average width of the dens did not vary as the normal tip of the dens transitioned into the coronae. In no specimen did the corona dentis seem to be composed of trabecular bone and it was seen as a superior projection of cortical bone on fluoroscopy. On fluoroscopy, the corona dentis could be identified on a true AP projection. In angulated AP views, fluoroscopic images overestimated the length of the corona dentis. We describe a new entity termed the corona dentis because of its crownlike feature. It is a superior cortical bone protrusion and should be noted as a variant of the dens during anterior odontoid screw placement. Its propensity to increase the height of the dens markedly can lead to higher rates of neurologic deficits during type 2 odontoid fractures if not appreciated. A true AP view is critical for correct screw size placement. Copyright © 2017 Elsevier Inc. All rights reserved.

A Prototype Regional GSI-based EnKF-Variational Hybrid Data Assimilation System for the Rapid Refresh Forecasting System: Dual-Resolution Implementation and Testing Results

NASA Astrophysics Data System (ADS)

Pan, Yujie; Xue, Ming; Zhu, Kefeng; Wang, Mingjun

2018-05-01

A dual-resolution (DR) version of a regional ensemble Kalman filter (EnKF)-3D ensemble variational (3DEnVar) coupled hybrid data assimilation system is implemented as a prototype for the operational Rapid Refresh forecasting system. The DR 3DEnVar system combines a high-resolution (HR) deterministic background forecast with lower-resolution (LR) EnKF ensemble perturbations used for flow-dependent background error covariance to produce a HR analysis. The computational cost is substantially reduced by running the ensemble forecasts and EnKF analyses at LR. The DR 3DEnVar system is tested with 3-h cycles over a 9-day period using a 40/˜13-km grid spacing combination. The HR forecasts from the DR hybrid analyses are compared with forecasts launched from HR Gridpoint Statistical Interpolation (GSI) 3D variational (3DVar) analyses, and single LR hybrid analyses interpolated to the HR grid. With the DR 3DEnVar system, a 90% weight for the ensemble covariance yields the lowest forecast errors and the DR hybrid system clearly outperforms the HR GSI 3DVar. Humidity and wind forecasts are also better than those launched from interpolated LR hybrid analyses, but the temperature forecasts are slightly worse. The humidity forecasts are improved most. For precipitation forecasts, the DR 3DEnVar always outperforms HR GSI 3DVar. It also outperforms the LR 3DEnVar, except for the initial forecast period and lower thresholds.

Predicting cattle age from eye lens weight and nitrogen content, dentition, and United States Department of Agriculture maturity score.

PubMed

Raines, C R; Dikeman, M E; Unruh, J A; Hunt, M C; Knock, R C

2008-12-01

This research explores the relationship between generally accepted and alternative cattle age-prediction methods and chronological age. Cattle (n = 386) of documented ages ranging from 370 to 1,115 d of age were used. Dentition (DEN), USDA maturity score (MS), lens weight (LW), and lens total N (LN) content were used as possible predictors of age. Correlations with age were determined: LW (r = 0.77); DEN (r = 0.74); LN (r = 0.71); and MS (r = 0.64). Stepwise backward regression was used to generate an age prediction equation: Age (mo) = -21.79 + 17.23(LW, g) + 0.038(DEN). By this equation, 38% of cattle DEN (9.6%), and LN (8.7%). The DEN verified that 87.6% were verified as <30 mo old, and LW verified 81.6% of cattle as <30 mo old. A separate group of cattle (n = 18) ranging in age from 1 to 12 yr were evaluated for lens properties, for which LW (R(2) = 0.91) and LN (R(2) = 0.92) were highly correlated with age. The LW and DEN were the best predictors of age for cattle 13- to 37-mo-old and yielded the most accurate age prediction when used in combination (R(2) = 0.67).

Prolonged local retention of subcutaneously injected polymers monitored by noninvasive SPECT imaging.

PubMed

Kojima, Chie; Niki, Yuichiro; Ogawa, Mikako; Magata, Yasuhiro

2014-12-10

Polymers are widely applied to drug delivery systems because polymers are generally excreted from the body more slowly than small molecules. Subcutaneous injection is one plausible means of administration. In this study, the in vivo behaviors of subcutaneously injected polymers, linear poly(glutamic acid) (Poly-Glu), acetylated dendrimer (Ac-den) and collagen peptide-conjugated dendrimer (CP-den), were investigated. Single photon emission computed tomography (SPECT) imaging was used to noninvasively monitor the in vivo behaviors. Diethylenetriaminepentaacetic acid (DTPA) was conjugated to these polymers, which were labeled with radioactive (111)In. These (111)In-DTPA-bearing polymers (Poly-Glu-DTPA, Ac-den-DTPA and CP-den-DTPA) and unconjugated DTPA were subcutaneously injected into tumor-bearing mice, which were subjected to SPECT imaging. These (111)In-DTPA-bearing polymers were largely retained at the injection site for at least 1 day, whereas the unconjugated DTPA was rapidly cleared from the whole body through excretion. Poly-Glu-DTPA and Ac-den-DTPA were partly accumulated in the kidney (and the liver), but the CP-den-DTPA was not. However, these (111)In-DTPA-bearing polymers were accumulated in the liver and the kidney following intravenous administration. These results indicate that the subcutaneously injected polymers did not largely gain substantial access to the systemic circulation, which is useful for a depot of drug around the injection site. Copyright © 2014 Elsevier B.V. All rights reserved.

Unexpected storm-time nightside plasmaspheric density enhancement at low L shell

NASA Astrophysics Data System (ADS)

Chu, X.; Bortnik, J.; Denton, R. E.; Yue, C.

2017-12-01

We have developed a three-dimensional dynamic electron density (DEN3D) model in the inner magnetosphere using a neural network approach. The DEN3D model can provide spatiotemporal distribution of the electron density at any location and time that spacecraft observations are not available. Given DEN3D's good performance in predicting the structure and dynamic evolution of the plasma density, the salient features of the DEN3D model can be used to gain further insight into the physics. For instance, the DEN3D models can be used to find unusual phenomena that are difficult to detect in observations or simulations. We report, for the first time, an unexpected plasmaspheric density increase at low L shell regions on the nightside during the main phase of a moderate storm during 12-16 October 2004, as opposed to the expected density decrease due to storm-time plasmaspheric erosion. The unexpected density increase is first discovered in the modeled electron density distribution using the DEN3D model, and then validated using in-situ density measurements obtained from the IMAGE satellite. The density increase was likely caused by increased earthward transverse field plasma transport due to enhanced nightside ExB drift, which coincided with enhanced solar wind electric field and substorm activity. This is consistent with the results of physics-based simulation SAMI3 model which show earthward enhanced plasma transport and electron density increase at low L shells during storm main phase.

Off-loading neuropathic wounds associated with diabetes using an ankle-foot orthosis.

PubMed

Landsman, A S; Sage, R

1997-08-01

Patients with chronic diabetes have a broad spectrum of associated peripheral neurologic deficits that culminate in an increased susceptibility to ulcer formation. The authors focus on the use of the ankle-foot orthosis as both a treatment and a definitive solution for achieving ulcer closure and for minimizing the chance of ulcer recurrence in the ambulatory patient. An analysis of the pathologic forces encountered, and the solution achieved with the ankle-foot orthosis is presented. In addition, the results from a clinical pilot study in subjects with recalcitrant ulcers secondary to Charcot's neuroarthropathy are presented.

James Parkinson and his essay on "shaking palsy", two hundred years later.

PubMed

Palacios-Sánchez, Leonardo; Torres Nupan, Martha; Botero-Meneses, Juan Sebastián

2017-09-01

In 1817, British physician James Parkinson published a 66-page document entitled "Essay on the Shaking Palsy". This brief text became a classical and fundamental piece in the history of medicine and, in particular, of neurology. The authors of this article wish to pay tribute to this great pioneer of neurology, 200 years after the publication of his findings, which would, in turn, immortalize his name and give rise to the renaming on the entity in 1860 by Professor Jean Martin Charcot, father of neurology. It would be known, henceforth as Parkinson's disease.

Note on online books and articles about the history of dissociation.

PubMed

Alvarado, Carlos S

2008-01-01

Students of the history of dissociation will be interested in the materials on the subject available in the digital document database Google Book Search. This includes a variety of books and journals covering automatic writing, hypnosis, mediumship, multiple personality, trance, somnambulism, and other topics. Among the authors represented in the database are: Eugène Azam, Alfred Binet, James Braid, Jean-Martin Charcot, Pierre Janet, Frederic W.H. Myers, Morton Prince, and Boris Sidis, among others. The database includes examples of case reports, conceptual discussions, and psychiatric and psychological textbook literature.

The Biology of Bone and Ligament Healing.

PubMed

Cottrell, Jessica A; Turner, Jessica Cardenas; Arinzeh, Treena Livingston; O'Connor, J Patrick

2016-12-01

This review describes the normal healing process for bone, ligaments, and tendons, including primary and secondary healing as well as bone-to-bone fusion. It depicts the important mediators and cell types involved in the inflammatory, reparative, and remodeling stages of each healing process. It also describes the main challenges for clinicians when trying to repair bone, ligaments, and tendons with a specific emphasis on Charcot neuropathy, fifth metatarsal fractures, arthrodesis, and tendon sheath and adhesions. Current treatment options and research areas are also reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

Tourismus

NASA Astrophysics Data System (ADS)

Matzarakis, Andreas; Lohmann, Martin

Für den Tourismus haben Klima und Wetter eine große Relevanz: als Treiber des Verhaltens wie auch als Angebotsfaktor. Wetter und Klima sind demnach sowohl Bestandteil des touristischen Angebotes als auch limitierende Faktoren des Tourismus und Steuergrößen für die touristische Nachfrage. Insofern liegt es nahe, dass dieser Sektor vom Klimawandel betroffen sein wird. Der Tourismus ist aber auch ein Faktor, der seinerseits erheblich auf das Klima und den Klimawandel zurückwirkt. Dabei ist der Klimawandel aber nur einer von vielen voneinander abhängig erscheinenden Einflussfaktoren, denen der Sektor "Tourismus" ausgesetzt ist. Das heißt, es handelt sich um ein komplexes Wirkungsgefüge. Das Kapitel widmet sich den Klimawandelfolgen im Tourismus und macht diese beispielhaft an den Regionen "Küsten" sowie "Mittel- und Hochgebirge" fest, um Anpassungsmöglichkeiten anzufügen.

Mikrodaten und statistische Auswertungsmethoden

NASA Astrophysics Data System (ADS)

Hujer, Reinhard

Mit der zunehmenden Verfügbarkeit immer größerer Querschnitts- und Längschnittsdatensätze für Personen, Haushalte und Betriebe sowie deren Verknüpfungen hat sich die mikroökonometrische Forschung in den vergangenen Jahren rasant weiterentwickelt. Dies gilt sowohl aus methodischer als auch aus empirischer, anwendungsorientierter Sicht. Mikrodaten und mikroökonometrische Ansätze dienen dazu, aktuelle, politikrelevante Fragen aufzugreifen, sie zu analysieren und fundierte politische Empfehlungen zu geben, beispielsweise im Rahmen der Arbeitsmarkt- und Sozialpolitik, der Finanzanalyse und der Marketingforschung. Die Deutsche Statistische Gesellschaft (DStatG) und deren Mitglieder haben sich in den Ausschüssen und in Hauptversammlungen kontinuierlich mit den Weiterentwicklungen der mikroökonometrischen Methodik und den empirischen Anwendungen befasst. Zahlreiche Publikationen von Mitgliedern der DStatG haben entscheidend zum kritischen Diskurs und zum wissenschaftlichen Fortschritt in diesem Bereich beigetragen.

Symmetriebrechung und Emergenz in der Kosmologie.

NASA Astrophysics Data System (ADS)

Mainzer, K.

Seit der Antike wird der Aufbau des Universums mit einfachen und regulären (symmetrischen) Grundstrukturen verbunden. Diese Annahme liegt selbst noch den Standardmodellen der relativistischen Kosmologie zugrunde. Demgegenüber läßt sich die Emergenz neuer Strukturen von den Elementarteilchen über Moleküle bis zu den komplexen Systemen des Lebens als Symmetriebrechung verstehen. Symmetriebrechung und strukturelle Komplexität bestimmen die kosmische Evolution. Damit zeichnet sich ein fachübergreifendes Forschungsprogramm von Physik, Chemie und Biologie ab, in dem die Evolution des Universums untersucht werden kann.

Genetics Home Reference: Leber congenital amaurosis

MedlinePlus

... FP, van den Hurk JA, den Hollander AI. Molecular genetics of Leber congenital amaurosis. Hum Mol Genet. 2002 ... J. Leber congenital amaurosis: comprehensive survey of the genetic ... as a strategy for molecular diagnosis. Hum Mutat. 2004 Apr;23(4):306- ...

A Comprehensive Context for Mobile-Code Deployment

DTIC Science & Technology

2005-01-01

18 Gal, Probst, Franz, 2003 Freund, Mitchell, 1999 Sohr, 1999, 2001 Microsoft, 2000 LSDRG, 2002 Dean, Felten, Balfanz , Wallach, 2003 Govindavajhala...D. Balfanz . Java security: Web browsers and beyond. In D. E. Denning and P. J. Denning, editors, Internet Besieged: Countering Cyberspace Scofflaws

Biokompatible Implantate und Neuentwicklungen in der Gynäkologie

NASA Astrophysics Data System (ADS)

Jacobs, Volker R.; Kiechle, Marion

Für den Einsatz in der Gynäkologie stehen heute eine Vielzahl unterschiedlicher, biokompatibler Materialien und Implantate zur Verfügung. Auf eine Auswahl soll hier näher eingegangen werden, die die verschiedenen Materialien und Bauweisen repräsentieren. So sind Brustimplantate seit fast vier Jahrzehnten im Gebrauch für die Brustvergrösserung und den Brustwiederaufbau. Material, Bauweisen und medizinische Aspekte einschliesslich der kontroversen Diskussion um Silikon werden im folgenden erläutert. Neuere Entwicklungen von Verhütungstechniken für permanente Sterilisation wie den Filshie ClipTM für transabdominalen und den STOPTM für intraluminalen Verschluss der Eileiter oder die intrauterin plazierte Hormonspirale MirenaTM für zeitlich begrenzte Verhütung werden beschrieben. Eine neue Perspektive zur Verhinderung postoperativer intraabdominaler Adhäsionen stellt Spray-GelTM, ein Zweikomponenten Hydrogel aus Polyethylenglykol, dar.

BOK promotes chemical-induced hepatocarcinogenesis in mice.

PubMed

Rabachini, Tatiana; Fernandez-Marrero, Yuniel; Montani, Matteo; Loforese, Giulio; Sladky, Valentina; He, Zhaoyue; Bachmann, Daniel; Wicki, Simone; Villunger, Andreas; Stroka, Deborah; Kaufmann, Thomas

2018-03-01

BCL-2-related ovarian killer (BOK) is a conserved and widely expressed BCL-2 family member with sequence homology to pro-apoptotic BAX and BAK, but with poorly understood pathophysiological function. Since several members of the BCL-2 family are critically involved in the regulation of hepatocellular apoptosis and carcinogenesis we aimed to establish whether loss of BOK affects diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mice. Short-term exposure to DEN lead to upregulation of BOK mRNA and protein in the liver. Of note, induction of CHOP and the pro-apoptotic BH3-only proteins PUMA and BIM by DEN was strongly reduced in the absence of BOK. Accordingly, Bok -/- mice were significantly protected from DEN-induced acute hepatocellular apoptosis and associated inflammation. As a consequence, Bok -/- animals were partially protected against chemical-induced hepatocarcinogenesis showing fewer and, surprisingly, also smaller tumors than WT controls. Gene expression profiling revealed that downregulation of BOK results in upregulation of genes involved in cell cycle arrest. Bok -/- hepatocellular carcinoma (HCC) displayed higher expression levels of the cyclin kinase inhibitors p19 INK4d and p21 cip1 . Accordingly, hepatocellular carcinoma in Bok -/- animals, BOK-deficient human HCC cell lines, as well as non-transformed cells, showed significantly less proliferation than BOK-proficient controls. We conclude that BOK is induced by DEN, contributes to DEN-induced hepatocellular apoptosis and resulting hepatocarcinogenesis. In line with its previously reported predominant localization at the endoplasmic reticulum, our findings support a role of BOK that links the cell cycle and cell death machineries upstream of mitochondrial damage.

Zu einer inhaltsorientierten Theorie des Lernens und Lehrens der biologischen Evolution

NASA Astrophysics Data System (ADS)

Wallin, Anita

Der Zweck dieser Studie (zwecks Überblick siehe dazu Abb. 9.1) war zu untersuchen, wie die Schüler der Sekundarstufe II ein Verständnis von der Theorie der biologischen Evolution entwickeln. Vom Ausgangspunkt "Vorurteile der Schüler“ ausgehend wurden Unterrichtssequenzen entwickelt und drei verschiedene Lernexperimente in einem zyklischen Prozess durchgeführt. Das Wissen der Schüler wurde vor, während und nach den Unterrichtssequenzen mit Hilfe von schriftlichen Tests, Interviews und Diskussionsrunden in kleinen Gruppen abgefragt. Etwa 80 % der Schüler hatten vor dem Unterricht alternative Vorstellungen von Evolution, und in dem Nachfolgetest erreichten circa 75 % ein wissenschaftliches Niveau. Die Argumentation der Schüler in den verschiedenen Tests wurde sorgfältig unter Rücksichtnahme auf Vorurteile, der konzeptionellen Struktur der Theorie der Evolution und den Zielen des Unterrichts analysiert. Daraus konnten Einsichten in solche Anforderungen an Lehren und Lernen gewonnen werden, die Herausforderungen an Schüler und Lehrer darstellen, wenn sie anfangen, evolutionäre Biologie zu lernen oder zu lehren. Ein wichtiges Ergebnis war, dass das Verständnis existierender Variation in einer Population der Schlüssel zum Verständnis von natürlicher Selektion ist. Die Ergebnisse sind in einer inhaltsorientierten Theorie zusammengefasst, welche aus drei verschiedenen Aspekten besteht: 1) den inhaltsspezifischen Aspekten, die einzigartig für jedes wissenschaftliche Feld sind; 2) den Aspekten, die die Natur der Wissenschaft betreffen; und 3) den allgemeinen Aspekten. Diese Theorie kann in neuen Experimenten getestet und weiter entwickelt werden.

Legislative Environmental Impact Statement: Small Intercontinental Ballistic Missile Program.

DTIC Science & Technology

1986-11-01

beautiful shiner, and Apache trout) and four federal-candidate species (desert pupfish, Sonora chub, loach minnow, and flat-tailed horned lizard) occur...Archaeology. A Class I Inventory of Prehistoric Resources. Ethnoscience, Billings, Montana. 9-13 INV Den Beste, Ken and Lois Den Beste 1976 Backgrounded

Assessment of Forecast Sensitivity to Observation and Its Application to Satellite Radiances

NASA Astrophysics Data System (ADS)

Ide, K.

2017-12-01

The Forecast sensitivity to observation provides practical and useful metric for the assessment of observation impact without conducting computationally intensive data denial experiments. Quite often complex data assimilation systems use a simplified version of the forecast sensitivity formulation based on ensembles. In this talk, we first present the comparison of forecast sensitivity for 4DVar, Hybrid-4DEnVar, and 4DEnKF with or without such simplifications using a highly nonlinear model. We then present the results of ensemble forecast sensitivity to satellite radiance observations for Hybrid-4DEnVart using NOAA's Global Forecast System.

Protective Effect of Boiled and Freeze-dried Mature Silkworm Larval Powder Against Diethylnitrosamine-induced Hepatotoxicity in Mice.

PubMed

Cho, Jae-Min; Kim, Kee-Young; Ji, Sang-Deok; Kim, Eun-Hee

2016-09-01

Hepatocellular carcinoma (HCC) is a representative inflammation-associated cancer and known to be the most frequent tumors. HCC may also induce important pro- and anti-tumor immune reactions. However, the underlying mechanisms are unsatisfactorily identified. We investigated the protective effect of boiled and freeze-dried mature silkworm larval powder (BMSP) on diethylnitrosamine (DEN)-induced hepatotoxicity in mice. Mice were fed with diet containing BMSP (0.1, 1, and 10 g/kg) for two weeks and DEN (100 mg/kg, intraperitoneally) was injected 18 hours before the end of this experiment. Liver toxicity was determined in serum and histopathological examination was assessed in the liver tissues. Infiltration of immune cells and expressions of inflammatory cytokines and chemokines were also examined. Pretreatment with BMSP reduced necrotic and histopathological changes induced by DEN in the liver. Measurement of serum biochemical indicators, the levels of alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase, showed that pretreatment with BMSP also decreased DEN-induced hepatotoxicity. In addition, BMSP inhibited the macrophage and CD31 infiltration in a dose-dependent manner. The expressions of interleukin-1β, IFN-γ and chemokines for T cell activation were decreased in BMSP pretreatment groups. BMSP may have a protective effect against acute liver injury by inhibiting necrosis and inflammatory response in DEN-treated mice.

Characterization of dengue virus 2 growth in megakaryocyte–erythrocyte progenitor cells

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

Clark, Kristina B.; Hsiao, Hui-Mien; Bassit, Leda

Megakaryocyte–erythrocyte progenitor (MEP) cells are potential in vivo targets of dengue virus (DENV); the virus has been found associated with megakaryocytes ex vivo and platelets during DENV-induced thrombocytopenia. We report here that DENV serotype 2 (DENV2) propagates well in human nondifferentiated MEP cell lines (Meg01 and K562). In comparison to virus propagated in Vero cells, viruses from MEP cell lines had similar structure and buoyant density. However, differences in MEP-DENV2 stability and composition were suggested by distinct protein patterns in western blot analysis. Also, antibody neutralization of envelope domain I/II on MEP-DENV2 was reduced relative to that on Vero-DENV2. Infectiousmore » DENV2 was produced at comparable kinetics and magnitude in MEP and Vero cells. However, fewer virion structures appeared in electron micrographs of MEP cells. We propose that DENV2 infects and produces virus efficiently in megakaryocytes and that megakaryocyte impairment might contribute to dengue disease pathogenesis. - Highlights: • DenV replicates efficiently in undifferentiated megakaryocyte–erythrocyte progenitors. • MEP produced DenV differs in protein content from Vero produced DenV. • MEP produced DenV may be more difficult to neutralize relative to Vero DenV.« less

Epidemiology of dengue and dengue hemorrhagic fever in a cohort of adults living in Bandung, West Java, Indonesia.

PubMed

Porter, Kevin R; Beckett, Charmagne G; Kosasih, Herman; Tan, Ratna Irsiana; Alisjahbana, Bachti; Rudiman, Pandji Irani Fianza; Widjaja, Susana; Listiyaningsih, Erlin; Ma'Roef, Chairin Nisa; McArdle, James L; Parwati, Ida; Sudjana, Primal; Jusuf, Hadi; Yuwono, Djoko; Wuryadi, Suharyono

2005-01-01

A prospective study of dengue fever (DF) and dengue hemorrhagic fever (DHF) was conducted in a cohort of adult volunteers from two textile factories located in West Java, Indonesia. Volunteers in the cohort were bled every three months and were actively followed for the occurrence of dengue (DEN) disease. The first two years of the study showed an incidence of symptomatic DEN disease of 18 cases per 1,000 person-years and an estimated asymptomatic/ mild infection rate of 56 cases per 1,000 person-years in areas of high disease transmission. In areas where no symptomatic cases were detected, the incidence of asymptomatic or mild infection was 8 cases per 1,000 person-years. Dengue-2 virus was the predominant serotype identified, but all four serotypes were detected among the cohort. Four cases of DHF and one case of dengue shock syndrome (DSS) were identified. Three of the four DHF cases were due to DEN-3 virus. The one DSS case occurred in the setting of a prior DEN-2 virus infection, followed by a secondary infection with DEN-1 virus. To our knowledge, this is the first report of a longitudinal cohort study of naturally acquired DF and DHF in adults.

Validation of a preclinical model of diethylnitrosamine-induced hepatic neoplasia in Yucatan miniature pigs

PubMed Central

Mitchell, Jennifer; Tinkey, Peggy T.; Avritscher, Rony; Van Pelt, Carolyn; Eskandari, Ghazaleh; George, Suraj Konnath; Xiao, Lianchun; Cressman, Erik; Morris, Jeffrey S.; Rashid, Asif; Kaseb, Ahmed O.; Amin, Hesham M.; Uthamanthil, Rajesh

2016-01-01

Objective The purpose of this study was to reduce time to tumor onset in a diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) swine model via partial liver embolization (PLE) and to characterize the model for use in translational research. Methods Eight Yucatan miniature pigs were injected intraperitoneally with either saline (n=2) or DEN (n=6) solution weekly for 12 weeks. Three of the DEN-treated pigs underwent PLE. Animals underwent periodic radiological evaluation, liver biopsy, and blood sampling, and full necropsy was performed at study termination (~29 months). Results All DEN-treated pigs developed hepatic adenoma and HCC. PLE accelerated the time to adenoma development but not to HCC development. Biomarker analysis results showed that IGF1 levels decreased in all DEN-treated pigs, as functional liver capacity decreased with progression of HCC. VEGF and IL-6 levels were positively correlated with disease progression. Immunohistochemical probing of HCC tissues demonstrated the expression of several important survival-promoting proteins. Conclusion To our knowledge, we are the first to demonstrate accelerated development of hepatic neoplasia in Yucatan miniature pigs. Our HCC swine model closely mimics the human condition (i.e., progressive disease stages and expression of relevant molecular markers) and is a viable translational model. PMID:27305144

Assessing the spreading patterns of dengue infection and chikungunya fever outbreaks in lower southern Thailand using a geographic information system.

PubMed

Ditsuwan, Thanittha; Liabsuetrakul, Tippawan; Chongsuvivatwong, Virasakdi; Thammapalo, Suwich; McNeil, Edward

2011-04-01

The aims of this study were to assess the incidence of dengue infection (DEN) and chikungunya fever (CHIK) and determine the direction and speed of CHIK between August 2008 and June 2009 in lower southern Thailand. The National Communicable Disease Surveillance System database and a geographic information system containing data on case locations were combined. R and ArcView were used for identifying incidence, direction, and speed of disease outbreaks. A total of 27,166 patients were identified, of which 3319 and 23,847 had DEN and CHIK, with incidences of 73 and 521 per 100,000, respectively. The direction of the CHIK outbreak moved from south to north with a median speed of 7.5 km per week. CHIK cases increased after 6 weeks of increasing cumulative rainfall with variation of average daily temperatures (23.7-30.7 degrees C) per week. There was no clear association of DEN with climate variables. The combination of surveillance and geographic information system data of DEN and CHIK can be used to determine the speed and direction of disease spread. DEN is endemic, but CHIK is an emerging disease. Because of the rapid spread of CHIK, strict and timely integrated vector control programs after case notification must be implemented. Copyright © 2011 Elsevier Inc. All rights reserved.

Denning, William Frederick (1848-1931)

NASA Astrophysics Data System (ADS)

Murdin, P.

2000-11-01

Possibly a journalist and certainly an amateur astronomer. Born in Redpost, Somerset, England. The spectacular meteor storm of 1866, and a fireball in 1869, focused his interest on meteor astronomy. In 1877 he demonstrated a steady night by night movement in the Perseid meteor radiant, which proved that meteors came from showers of dust distributed along the path of a comet. Had the distinction t...

Nest Boxes Artificial Homes for Woodland Mammals.

ERIC Educational Resources Information Center

Decker, Daniel J.; Kelley, John W.

1983-01-01

Provides instructions for constructing artificial "homes" for squirrels, raccoons, and rabbits. These include squirrel dens constructed from discarded automobile tires and squirrel nest boxes, raccoon dens, and rabbit burrows constructed from wood. Includes a chart giving dimensions of materials needed and suggestions on where to place the…

Genetics Home Reference: bare lymphocyte syndrome type II

MedlinePlus

... 6. Citation on PubMed Gobin SJ, Peijnenburg A, van Eggermond M, van Zutphen M, van den Berg R, van den Elsen PJ. The RFX complex is crucial ... D, Szöllosi J, Jenei A. Bare lymphocyte syndrome: an opportunity to discover our immune system. Immunol Lett. ...

Energy as a Service

NASA Astrophysics Data System (ADS)

Pell, Wolfgang

Energie wird zum Gebrauchsgegenstand, zur Commodity und rückt doch in den Blickpunkt der Aufmerksamkeit. Volkswirtschaftliche, politische, gesellschaftliche und betriebswirtschaftliche Ansprüche lassen Services rund um die Energieversorgung (Energy-related Services) entstehen. Convenience Services, die den Ansprüchen der Konsumenten gerecht werden, wie Visualisierung von (dezentraler) Energieerzeugung und -verbrauch auf Basis digitaler Smart Meter, die den analogen Ferraris-Zähler ersetzen, sowie optimierter Energieeinsatz halten in Haushalten als digitalisierten Standorten (Smart Sites) Einzug. Energieoptimierung auf Basis des Paradigmas "Verbrauch folgt Erzeugung" stellt Nachfrageflexibilität industrieller Prozesse (Demand Response) als Energie-Effizienz-Faktor in den Vordergrund und lässt Services wie ihre Vermarktung als Regelenergie zur Stabilisierung der Netzfrequenz entstehen. Ein Innovation Action Plan liefert einen Ausblick, wohin die Integration neuer Technologien, die Steigerung der Kundennähe und die Entwicklung neuer Geschäftsmodelle die Energiewirtschaft führen kann. Mit Eco-Home und Power-Pool werden zwei konkrete Beispiele für Energy as a Service vorgestellt.

Corticosterone and the transition from courtship behavior to dispersal in male red-sided garter snakes (Thamnophis sirtalis parietalis).

PubMed

Cease, Arianne J; Lutterschmidt, Deborah I; Mason, Robert T

2007-01-01

Seasonal modulation of baseline glucocorticoid concentrations as well as the sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis plays an important role in supporting critical life-history events such as seasonal reproduction and migration. Despite numerous studies on adrenocortical modulation, little is known about the exact timing of this seasonal modulation with respect to critical life-history stages. We tested the hypothesis that seasonal modulation of the HPA axis during the spring mating season in male red-sided garter snakes (Thamnophis sirtalis parietalis) is temporally linked to the mechanisms regulating dispersal. We compared hormonal responses to capture stress in courting male red-sided garter snakes collected from the den site and den perimeter to those of dispersing snakes collected 0.6 km from the den. We also investigated possible changes in steroid hormones during the spring mating season. These studies support previous findings that plasma androgen and corticosterone concentrations significantly decline over the mating season. Our results demonstrate that males 0.6 km into a 15-20 km route to the feeding grounds have lower baseline corticosterone concentrations than male snakes actively courting at the den. Dispersing males also exhibit a typical stress response marked by a significant increase in corticosterone while actively courting males do not. Capture stress did not significantly influence androgen concentrations of either courting or dispersing male red-sided garter snakes. There were no significant differences in body composition indices among male snakes collected from the den, den perimeter, or 0.6 km away from the den. However, we did observe a significant negative correlation between baseline corticosterone levels and body composition indices. These data suggest that breeding is a distinct stage accompanied by specific physiological parameters that differ from those during dispersal to the feeding grounds. Our results

Japanese neuropathy patients with peripheral myelin protein-22 gene aneuploidy

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

Lebo, R.V.; Li, L.Y.; Flandermeyer, R.R.

1994-09-01

Peripheral myelin protein (PMP-22) gene aneuploidy results in Charcot-Marie-Tooth disease Type 1A (CMT1A) and the Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) in Japanese patients as well as Caucasian Americans. Charcot-Marie-Tooth disease (CMT), the most common genetic neuropathy, results when expression of one of at least seven genes is defective. CMT1A, about half of all CMT mutations, is usually associated with a duplication spanning the peripheral myelin protein-22 gene on distal chromosome band 17p11.2. Autosomal dominant HNPP (hereditary pressure and sensory neuropathy, HPSN) results from a deletion of the CMT1A gene region. Multicolor in situ hybridization with PMP-22 genemore » region probe characterized HNPP deletion reliably and detected all different size duplications reported previously. In summary, 72% of 28 Japanese CMT1 (HMSNI) patients tested had the CMT1A duplication, while none of the CMT2 (HMSNII) or CMT3 (HMSNIII) patients had a duplication. Three cases of HNPP were identified by deletion of the CMT1A gene region on chromosome 17p. HNPP and CMT1A have been reported to result simultaneously from the same unequal recombination event. The lower frequency of HNPP compared to CMT1A suggests that HNPP patients have a lower reproductive fitness than CMT1A patients. This result, along with a CMT1A duplication found in an Asian Indian family, demonstrates the broad geographic distribution and high frequency of PMP-22 gene aneuploidy.« less

Articulating Breath: Writing Charcot's Hysteric with "Performance Writing"

ERIC Educational Resources Information Center

Worden, Jessica

2014-01-01

The overlap between the visual and textual in practice research provides an opportunity to explore ways of presenting knowledge through "performance writin". The purpose of this paper is to demonstrate how a performance writing practice can be incorporated into and shape research writing. This text uses descriptions of Jean-Martin…

[Charcot foot treated by correction and arthrodesis of the hindfoot].

PubMed

Wagner, Andreas; Fuhrmann, Renée; Roth, Andreas

2005-10-01

First patient: neuropathic osteoarthropathy with severely deformed foot, plantar ulceration and recurrent purulent infections. Second patient: diabetic osteoarthropathy with pathologic fracture. First patient: 50-year-old man with hereditary sensory and motor neuropathy, plantar ulceration, equinus of the hindfoot, and extensive destruction of all bones of the foot. Recurrent infections necessitated repeated surgical interventions during the last 7 years. At the time of admission purulent infection of the foot. Healing after debridement including a resection of metatarsal bones and part of sequestrated bones of the foot. Patient was left with a severe equinus of the hindfoot. Orthopedic shoes with or without below-knee orthesis. Lengthening of the Achilles tendon and plantar alignment of the calcaneus. Arthrodesis of the hindfoot. Below-knee amputation, if necessary as a primary procedure to combat infection. Arthrodesis of the hindfoot after realignment; an amputation of the foot was refused. Two-stage procedure: treatment of infection followed by astragalectomy and tibiocalcaneal arthrodesis achieved with cancellous lag screws. Bridging of the area of resection with a segment of the fibula. Bony fusion and full load bearing in an orthopedic shoe after 3 months. Recurrence of ulcerations after 20 and 27 months due to wear of ill-fitting shoes. The accompanying purulent process forced the authors to resort to a below-knee amputation and fitting of a prosthesis. Second patient: of this patient only radiographs with a retrograde introduced intramedullary nail are shown.

Retrospektive Analyse von Zufallsbefunden, die bei Patienten mit kutanem malignen Malignom durch (18) F-Fluordeoxyglucose-PET/CT erhoben wurden.

PubMed

Conrad, Franziska; Winkens, Thomas; Kaatz, Martin; Goetze, Steven; Freesmeyer, Martin

2016-08-01

Bei der (18) F-Fluordeoxyglucose-Positronenemissionstomographie/Computertomographie (FDG-PET/CT) ergeben sich häufig Zufallsbefunde. In der vorliegenden Studie konzentrierten wir uns auf mittels FDG-PET/CT erhaltene Zufallsbefunde bei Patienten mit kutanem Melanom und überprüften deren Relevanz hinsichtlich weiterer diagnostischer Maßnahmen und Interventionen. Die Krankenakten von 181 konsekutiven Melanom-Patienten wurden retrospektiv ausgewertet, um das Management von Zufallsbefunden zu dokumentieren. Der Schwerpunkt lag dabei auf den histologischen Befunden. Bei 33 von 181 (18 %) Patienten lagen 39 relevante Zufallsbefunde vor, und zwar im Kolorektalbereich (n = 15 Patienten), in der Schilddrüse (n = 8), der Prostata (n = 2), dem Bewegungsapparat (n = 2), in Lymphknoten (n = 2), der Parotis (n = 1), den Mandeln (n = 1), den Nieren (n = 1) und der Gallenblase (n = 1). Bei 25 Patienten schlossen sich weitere diagnostische Verfahren an, wobei in 21 Fällen ein klinisches Korrelat nachgewiesen wurde. Bei 16 von 21 Patienten ergab sich eine Neoplasie, darunter fünf maligne Läsionen (vier Kolonkarzinome und ein Prostatakarzinom). Die Malignome wurden frühzeitig diagnostiziert und in der Mehrzahl der Fälle erfolgreich entfernt. Der Einsatz der FDG-PET/CT als Routine-Diagnostik wird in den Leitlinien empfohlen und ist indiziert bei malignem Melanom ab Stadium IIC. In dieser Studie wurden auf effektive Weise ansonsten nicht erkannte Krebserkrankungen, insbesondere Kolonkarzinome, detektiert. In den meisten Fällen war eine frühe Intervention möglich. Zufallsbefunde durch FDG-PET/CT sollten, unter Berücksichtigung des Zustands und der Wünsche des Patienten, mit den geeigneten diagnostischen Maßnahmen abgeklärt werden. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Hypertonic Saline Reduces Vascular Leakage in a Mouse Model of Severe Dengue

PubMed Central

Tan, Kar Wai; Angeli, Veronique; Moochhala, Shabbir; Ooi, Eng Eong; Alonso, Sylvie

2013-01-01

Dengue (DEN) is a mosquito-borne viral disease and represents a serious public health threat and an economical burden throughout the tropics. Dengue clinical manifestations range from mild acute febrile illness to severe DEN hemorrhagic fever/DEN shock syndrome (DHF/DSS). Currently, resuscitation with large volumes of isotonic fluid remains the gold standard of care for DEN patients who develop vascular leakage and shock. Here, we investigated the ability of small volume of hypertonic saline (HTS) suspensions to control vascular permeability in a mouse model of severe DEN associated with vascular leakage. Several HTS treatment regimens were considered and our results indicated that a single bolus of 7.5% NaCl at 4 mL per kg of body weight administered at the onset of detectable vascular leakage rapidly and significantly reduced vascular leak for several days after injection. This transient reduction of vascular leakage correlated with reduced intestine and liver damage with restoration of the hepatic functions, and resulted in delayed death of the infected animals. Mechanistically, we showed that HTS did not directly impact on the viral titers but resulted in lower immune cells counts and decreased systemic levels of soluble mediators involved in vascular permeability. In addition, we demonstrated that neutrophils do not play a critical role in DEN-associated vascular leakage and that the therapeutic effect of HTS is not mediated by its impact on the neutrophil counts. Together our data indicate that HTS treatment can transiently but rapidly reduce dengue-associated vascular leakage, and support the findings of a recent clinical trial which evaluated the efficacy of a hypertonic suspension to impact on vascular permeability in DSS children. PMID:23637867

Assimilating MODIS-based albedo and snow cover fraction into the Common Land Model to improve snow depth simulation with direct insertion and deterministic ensemble Kalman filter methods

NASA Astrophysics Data System (ADS)

Xu, Jianhui; Shu, Hong

2014-09-01

This study assesses the analysis performance of assimilating the Moderate Resolution Imaging Spectroradiometer (MODIS)-based albedo and snow cover fraction (SCF) separately or jointly into the physically based Common Land Model (CoLM). A direct insertion method (DI) is proposed to assimilate the black and white-sky albedos into the CoLM. The MODIS-based albedo is calculated with the MODIS bidirectional reflectance distribution function (BRDF) model parameters product (MCD43B1) and the solar zenith angle as estimated in the CoLM for each time step. Meanwhile, the MODIS SCF (MOD10A1) is assimilated into the CoLM using the deterministic ensemble Kalman filter (DEnKF) method. A new DEnKF-albedo assimilation scheme for integrating the DI and DEnKF assimilation schemes is proposed. Our assimilation results are validated against in situ snow depth observations from November 2008 to March 2009 at five sites in the Altay region of China. The experimental results show that all three data assimilation schemes can improve snow depth simulations. But overall, the DEnKF-albedo assimilation shows the best analysis performance as it significantly reduces the bias and root-mean-square error (RMSE) during the snow accumulation and ablation periods at all sites except for the Fuyun site. The SCF assimilation via DEnKF produces better results than the albedo assimilation via DI, implying that the albedo assimilation that indirectly updates the snow depth state variable is less efficient than the direct SCF assimilation. For the Fuyun site, the DEnKF-albedo scheme tends to overestimate the snow depth accumulation with the maximum bias and RMSE values because of the large positive innovation (observation minus forecast).

Cell expression patterns of CD147 in N-diethylnitrosamine/phenobarbital-induced mouse hepatocellular carcinoma.

PubMed

Lu, Meng; Wu, Jiao; He, Feng; Wang, Xi-Long; Li, Can; Chen, Zhi-Nan; Bian, Huijie

2015-02-01

Overexpression of CD147/basigin in hepatic cells promotes the progression of hepatocellular carcinoma (HCC). Whether CD147 also expressed in liver non-parenchymal cells and associated with HCC development was unknown. The aim of the study was to explore time-dependent cell expression patterns of CD147 in a widely accepted N-diethylnitrosamine/phenobarbital (DEN/PB)-induced HCC mouse model. Liver samples collected at month 1-12 of post-DEN/PB administration were assessed the localization of CD147 in hepatocytes, endothelial cells, hepatic stellate cells, and macrophages. Immunohistochemistry analysis showed that CD147 was upregulated in liver tumors during month 1-8 of DEN/PB induction. Expression of CD147 was positively correlated with cytokeratin 18, a hepatocyte marker (r = 0.7857, P = 0.0279), CD31 (r = 0.9048, P = 0.0046), an endothelial cell marker, and CD68, a macrophage marker (r = 0.7619, P = 0.0368). A significant correlation was also observed between CD147 and alpha-smooth muscle actin (r = 0.8857, P = 0.0333) at DEN/PB initiation and early stage of tumor formation. Immunofluorescence and fluorescence in situ hybridization showed that CD147 co-expressed with cytokeratin 18, CD31, alpha-smooth muscle actin, and CD68. Moreover, there existed positive correlations between CD147 and microvessel density (r = 0.7857, P = 0.0279), CD147 and Ki-67 (r = 0.9341, P = 0.0022) in the development of DEN/PB-induced HCC. In conclusion, our results demonstrated that CD147 was upregulated in the liver parenchymal and mesenchymal cells and involved in angiogenesis and tumor cell proliferation in the development of DEN/PB-induced HCC.

From subduction to collision: results of French POP2 program on Taiwan-Philippine festoon

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

Blanchet, R.; Stephan, J.F.; Rangin, C.

1986-07-01

A sea-beam, seismic, magnetic, and gravimetric survey was conducted with the R/V Jean-Charcot in three key regions off the Taiwan-Philippine festoon in the western Pacific: (1) Ryukyu active margin and its junction with Taiwan; (2) northern part of the Manila Trench and its junction with the Taiwan tectonic prism; and (3) southern termination of Manila Trench in front of Mindoro Island. Transitions between active subduction along the Manila Trench and collision of Taiwan and Mindoro, and relations between active subduction and extension in the Okinawa-Ryukyu and the northeastern Taiwan systems are particularly studied.

High resolution neurography of the lumbosacral plexus on 3T magneteic resonance imaging.

PubMed

Cejas, C; Escobar, I; Serra, M; Barroso, F

2015-01-01

Magnetic resonance neurography is a technique that complements clinical and electrophysiological study of the peripheral nerves and brachial and lumbosacral plexuses. Numerous focal processes (inflammatory, traumatic, primary tumors, secondary tumors) and diffuse processes (diabetic polyneuropathy, chronic idiopathic demyelinating polyneuropathy due to amyloidosis or Charcot-Marie-Tooth disease) can involve the lumbosacral plexus. This article reviews the anatomy of the lumbosacral plexus, describes the technique for neurography of the plexus at our institution, and shows the diverse diseases that affect it. Copyright © 2014 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

The expanding syndrome of amyotrophic lateral sclerosis: a clinical and molecular odyssey

PubMed Central

Turner, Martin R; Swash, Michael

2015-01-01

Recent advances in understanding amyotrophic lateral sclerosis (ALS) have delivered new questions. Disappointingly, the initial enthusiasm for transgenic mouse models of the disease has not been followed by rapid advances in therapy or prevention. Monogenic models may have inadvertently masked the true complexity of the human disease. ALS has evolved into a multisystem disorder, involving a final common pathway accessible via multiple upstream aetiological tributaries. Nonetheless, there is a common clinical core to ALS, as clear today as it was to Charcot and others. We stress the continuing relevance of clinical observations amid the increasing molecular complexity of ALS. PMID:25644224

Diabetic calcaneal fractures.

PubMed

Sagray, Bryan A; Stapleton, John J; Zgonis, Thomas

2013-01-01

Calcaneal fractures among the diabetic population are severe and complex injuries that warrant careful evaluation in an effort to carry out adequate conservative or surgical management. The complication rates associated with diabetic fracture management are increased and may include poor wound healing, deep infection, malunion, and Charcot neuroarthropathy, each of which can pose a risk for limb loss. The significant surgery-associated morbidity accompanying diabetic calcaneal fractures has led to improved methods of calcaneal fracture management. This article reviews the overall management of diabetic calcaneal fractures, complications, and outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

[The "aphasia" article in Villaret's Handwörterbuch].

PubMed

Menninger, Anneliese

2016-01-01

Freud's authorship is founded on three arguments: 1) the reasoning of the article is close to Charcot's lectures which Freud had just translated; 2) there is a specific Freudian core thesis, common to the article and his later writings, namely the notion of an associative speech area extending between the "motor fields of the cortex and those of the optic and auditory nerves" and touching them like "corners" of a continuous field; 3) general observations on the revision or non- revision of articles taken over from the 1st to the 2nd edition of Villaret.

Personen- und Güterverkehr

NASA Astrophysics Data System (ADS)

Flämig, Heike; Gertz, Carsten; Mühlhausen, Thorsten

Im Jahr 2010 war in Deutschland der Verkehrssektor für fast 20 % der energiebedingten Treibhausgase verantwortlich. Das Klima hat sich bereits so weit verändert, dass zur Sicherung der Funktion der Verkehrssysteme auch Anpassungsmaßnahmen notwendig sind. Diese Maßnahmen müssen durch verkehrsreduzierende bzw. -beeinflussende Maßnahmen ergänzt werden. Ausgehend von den Emissionen im Verkehrssektor und möglichen Minderungen schlägt das Kapitel den Bogen zu Optionen der Anpassung an den Klimawandel, die ausführlich und konkret dargestellt werden. Besonders betrachtet werden die mannigfaltigen Gefahren der Rückkopplung sowie die vielfältigen Wechselwirungen mit anderen Themengebieten und Sektoren.

Unfallaufnahme und Datenerhebung

NASA Astrophysics Data System (ADS)

Brösdorf, Klaus-Dieter; Moser, Andreas; Burg, Jürgen

Unfälle ereignen sich in unterschiedlichen Schweregraden. Man unterscheidet zwischen Unfälle mit nur Sachschaden und in Unfälle mit Personenschaden. Gemäß Statistik [1] machten in Deutschland im Jahr 2005 Unfälle mit Personenschaden (336.619) etwa 15 % der Gesamtanzahl der polizeilich erfassten Unfälle (2.253.992) aus. In den amtlichen Statistiken sind nur polizeilich erfasste Unfälle enthalten. Eine größere Zahl von Unfällen, insbesondere leichtere Unfälle, wird offensichtlich polizeilich nicht gemeldet. Mit den Daten der Versicherungswirtschaft wird die Anzahl der Kfz-Schäden pro Jahr in Deutschland mit 8.673.000 angegeben [2].

Effects of anisotropy in permeability on the two-phase flow and heat transfer in a porous cavity

NASA Astrophysics Data System (ADS)

Zhang, X. L.; Nguyen, T. Hung; Kahawita, R.

Zusammenfassung In der Arbeit wird über die Ergebnisse einer numerischen Studie, betreffend die stationäre Konvektionsströmung und den stationären Wärmeübergang in einer rechteckigen, mit einem porösen, phasenveränderlichen Medium (PCM) verfüllten Kavität, berichtet. Den zwei vertikalen Berandungen der Kavität sind zwei, den Schmelzpunkt des PCM einschließende Temperaturen aufgeprägt, während die beiden horizontalen Berandungen adiabat gehalten werden. Das poröse Medium ist durch einen anisotropen Permeabilitätstensor charakterisiert, dessen Hauptachsen bezüglich des Gravitationsvektors beliebig orientiert sein können. Das Problem ist durch das Seitenverhältnis A, die Rayleigh-Zahl Ra, das Anisotropienverhältnis R und den Orientierungswinkel Θ des Permeabilitätstensor bestimmt. Hauptaugenmerk gilt dem Einfluß der anisotropen Permeabilität auf das Strömungsverhalten und den Wärme-übergang beim Phasenwechselprozeß flüssig/fest. Die Lösungsmethode basiert auf dem Kontrollvolumenprinzip in Verbindung mit der Landau-Transformation über welche das irreguläre Strömungsgebiet in ein rechteckiges abgebildet wird. Ergebnisse bezüglich Strömungsfeld, Temperaturverteilung, Phasengrenzenort und Wärmeübergang werden fürA=2,5Ra=40 0<=Θ<=π 0,25<=R<=4 mitgeteilt. Es zeigte sich, daß der Gleichgewichtszustand des Phasenwechselsprozesses fest/flüssig sowohl durch das Anisotropieverhältnis R als auch durch den Orientierungswinkel Θ des Permeabilitätstensors wesentlich beeinflußt werden kann. Zum einen existiert bei festgehaltenen ParameternA, Ra undR eine optimale Orientierung Θmax, bei der die Stromstärke, das Flüssigkeitsvolumen und der Wärmestrom Maximalwerte erreichen, während für Θmin=Θmax+π/2 Minimalwerte resultieren. Ist das anisotrope Medium entlang der Optimalrichtung Θmax orientiert, so ergibt sich zum anderen, daß eine Vergrößerung der in diese Richtung fallenden Permeabilitätskomponente die Stromstärke und den W�

76 FR 13453 - Marine Mammals; Incidental Take During Specified Activities

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-11

... and interactions between polar bears, Pacific walruses, and Industry; recent studies of potential... activity and location. For example, an LOA issued in response to a request to conduct activities in areas with known, active bear dens or a history of polar bear denning, may be conditioned to require one or...

Rede und Gesinnung (Speech and Ways of Thinking)

ERIC Educational Resources Information Center

Kienzle, Bertram

1974-01-01

Analyzes some of the basic ideas in Georg Franklin's book "Versuch einer neuen Lehre von den vornehmsten Gegenstanden der deutschen Sprachlehre; nach den Regeln der Vernunftlehre in sechs Abhandlungen verfasst" (1778) and compares them to those of such modern linguists and philosophers a s Searle, Austin and Wunderlich. Concludes that…

Chikungunya and dengue virus infections during pregnancy: seroprevalence, seroincidence and maternal-fetal transmission, southern Thailand, 2009-2010.

PubMed

Laoprasopwattana, K; Suntharasaj, T; Petmanee, P; Suddeaugrai, O; Geater, A

2016-01-01

Limited information is available on the seroprevalence of chikungunya virus (CHIKV) infection and maternal-fetal transmission incidence of CHIKV and dengue virus (DENV) infections during the 2008-2009 CHIKV outbreak in southern Thailand. A community-based post-epidemic seroprevalence study was conducted in parturient women admitted to the Thepa District Hospital in Songkhla Province, Thailand, for delivery from November 2009 to May 2010. The women were tested for chikungunya (CHIK) IgM/IgG and dengue (DEN) IgM/IgG. Cord blood samples were also tested for CHIK IgM or DEN IgM in women who tested positive for CHIK IgM or DEN IgM, respectively. The seroprevalence of CHIKV infection (CHIK IgM or IgG positive) was 227/319 (71·2%) with pre-outbreak seroprevalence (IgM-/IgG+) of 43·6% and the seroprevalence of DENV infection was 288/319 (90·3%). Complications during pregnancy, newborn outcomes and congenital anomalies were not different in those who had recent, remote or no CHIKV infections. None of the newborns whose mothers were CHIK or DEN IgM positive had cord blood positive for both CHIK and DEN IgM. In conclusion, both CHIKV and DENV are endemic in southern Thailand; during the recent CHIKV outbreak CHIK seroprevalence increased from 43·6% to 71·2%.

Orally administered lycopene attenuates diethylnitrosamine-induced hepatocarcinogenesis in rats by modulating Nrf-2/HO-1 and Akt/mTOR pathways.

PubMed

Sahin, Kazim; Orhan, Cemal; Tuzcu, Mehmet; Sahin, Nurhan; Ali, Shakir; Bahcecioglu, Ibrahim H; Guler, Osman; Ozercan, Ibrahim; Ilhan, Necip; Kucuk, Omer

2014-01-01

Hepatocarcinogenesis is one of the most prevalent and lethal cancers. We studied the mechanisms underlying the inhibition of diethylnitrosamine (DEN)-induced hepatocarcinogenesis by lycopene in rats. Hepatocarcinogenesis was induced by an intraperitoneal injection of DEN followed by promotion with phenobarbital for 24 successive wk. The rats were given lycopene (20 mg/kg body weight) 3 times a week orally for 4 wk prior to initiation, and the treatment was continued for 24 consecutive wk. Lycopene reduced incidence, number, size, and volume of hepatic nodules. Serum alanine transaminase, aspartate aminotransferase, total bilirubin, and malondialdehyde (MDA) considerably increased and hepatic antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase) and glutathione decreased in DEN-treated rats when compared with the control group. Lycopene significantly reversed these biochemical changes and increased the expression of NF-E-2-related factor-2)/heme oxygenase-1, and it decreased NF-κB/cyclooxygenase-2, inhibiting the inflammatory cascade and activating antioxidant signaling (P < 0.05). Lycopene also decreased DEN-induced increases in phosphorylated mammalian target of rapamycin (p-mTOR), phosphorylated p70 ribosomal protein S6 kinase 1, phosphorylated 4E-binding protein 1, and protein kinase B (P < 0.05). Lycopene is an active chemopreventive agent that offers protection against DEN-induced hepatocarcinogenesis by inhibiting NF-κB and mTOR pathways.

Trophic cascades linking wolves (Canis lupus), coyotes (Canis latrans), and small mammals

USGS Publications Warehouse

Miller, B.J.; Harlow, H.J.; Harlow, T.S.; Biggins, D.; Ripple, W.J.

2012-01-01

When large carnivores are extirpated from ecosystems that evolved with apex predators, these systems can change at the herbivore and plant trophic levels. Such changes across trophic levels are called cascading effects and they are very important to conservation. Studies on the effects of reintroduced wolves in Yellowstone National Park have examined the interaction pathway of wolves (Canis lupus L., 1758) to ungulates to plants. This study examines the interaction effects of wolves to coyotes to rodents (reversing mesopredator release in the absence of wolves). Coyotes (Canis latrans Say, 1823) generally avoided areas near a wolf den. However, when in the proximity of a den, they used woody habitats (pine or sage) compared with herbaceous habitats (grass or forb or sedge)- when they were away from the wolf den. Our data suggested a significant increase in rodent numbers, particularly voles (genus Microtus Schrank, 1798), during the 3-year study on plots that were within 3 km of the wolf den, but we did not detect a significant change in rodent numbers over time for more distant plots. Predation by coyotes may have depressed numbers of small mammals in areas away from the wolf den. These factors indicate a top-down effect by wolves on coyotes and subsequently on the rodents of the area. Restoration of wolves could be a powerful tool for regulating predation at lower trophic levels.

Long-term Outcomes and Quality of Life of 186 Patients With Primary Parotid Carcinoma Treated With Surgery and Radiotherapy at the Daniel den Hoed Cancer Center

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

Al-Mamgani, Abrahim, E-mail: a.al-mamgani@erasmusmc.nl; Rooij, Peter van; Verduijn, Gerda M.

2012-09-01

Purpose: To assess the outcomes, toxicity, and quality of life (QOL) of patients with primary parotid carcinoma treated with surgery and postoperative radiotherapy at the Daniel den Hoed Cancer Center. Methods and Materials: Between 1995 and 2010, 186 patients with parotid carcinoma were treated with parotidectomy with or without neck dissection, followed by radiotherapy. Elective nodal irradiation (ENI) was applied to high-risk, node-negative disease. End points were locoregional control (LRC), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS), late toxicity, and QOL. Results: After a median follow-up of 58 months (range, 4-172 months), the 5-year Kaplan-Meier estimates formore » LRC, DFS, CSS, and OS were 89%, 83%, 80%, and 68%, respectively. Forty-five events were reported: 24 distant metastases (DM) and 21 locoregional failures (LRF). Event-free survival rates by histological types were 89%, 78%, 76%, 74%, and 70% for acinic cell, mucoepidermoid, adenoid cystic, adenocarcinoma, and squamous cell carcinoma, respectively. More LRF were reported in patients with squamous cell and high-grade mucoepidermoid carcinoma (21% and 19%, respectively) than in patients with other histological types (p = 0.04) and more DM in patients with adenoid cystic and adenocarcinoma (20% and 19%, respectively) than in patients with other types (p = 0.03). None of the high-risk node-negative patients who received ENI developed regional failure. On multivariate analysis, T stage, N stage, grade, and presence of perineural invasion and facial paralysis correlated significantly with DFS. The 5-year cumulative incidence of grade {>=}2 late toxicity was 8%. QOL scores deteriorate during and shortly after treatment but returned in almost all scales to baseline scores within 6 months. Conclusions: Of the entire group, surgery and postoperative radiotherapy resulted in excellent outcomes with minimal side effects and preservation of good QOL scores. However

Die physikalischen Umweltwissenschaften und das Militär Zur Erforschung Grönlands im Kalten Krieg

NASA Astrophysics Data System (ADS)

Heymann, Matthias

Die modernen Umweltwissenschaften stehen heute im Mittelpunkt von Forschungsförderung und öffentlicher Aufmerksamkeit. Im Zuge des seit den 1970er Jahren erwachten Interesses am globalen Wandel der Umwelt und den damit verknüpften Problemen, ist ihre Bedeutung rasch gestiegen. Viele Wurzeln der modernen Umweltwissenschaften liegen jedoch im Kalten Krieg.

Estimating Performance of Single Bus, Shared Memory Multiprocessors

DTIC Science & Technology

1987-05-01

Chandy78] K.M. Chandy, C.M. Sauer, "Approximate methods for analyzing queuing network models of computing systems," Computing Surveys, vol10 , no 3...Denning78] P. Denning, J. Buzen, "The operational analysis of queueing network models", Computing Sur- veys, vol10 , no 3, September 1978, pp 225-261

Earth Observations taken by the Expedition 15 Crew

NASA Image and Video Library

2007-04-30

ISS015-E-05977 (1 May 2007) --- Den Helder, Netherlands is featured in this image photographed by an Expedition 15 crewmember on the International Space Station. The city and harbor of Den Helder in the northern Netherlands has been the home port of the Dutch Royal Navy for over 175 years. Its favorable location provides access to the North Sea, and has made it an important commercial shipping port in addition to its strategic role. Bright red agricultural fields to the south of Den Helder indicate another noteworthy aspect of the region--commercial farming of tulips and hyacinth. This image is an oblique view--the camera is oriented at an angle relative to "straight down"--of the Den Helder region taken from the space station, which was located to the southeast, near Dulmen, Germany (approximately 225 kilometers away in terms of ground distance) when the image was acquired. In addition to the manmade structures of the Den Helder urban area (reddish gray to gray street grids) and dockyards to the east of the city, several striking geomorphic features are visible. The extensive gray mudflats, with their prominent branching pattern (top right), indicate that this image was acquired at low tide, and suggest the general low elevation of the region. Parallel wave patterns along the mudflats and in the Marsdiep strait are formed as water interacts with the sea bottom between Den Helder and Texel Island during tidal flow. Some ship wakes are also visible. According to scientists, the bright white-gray triangular region at the southern tip of Texel Island (bottom center) is a dune field, consisting mainly of eolian (windborne) sands deposited during the last Ice Age. Subsequent sea level rise and shoreline processes have mobilized and re-deposited these sands into their current configuration -- including a new dune field island to the southwest of Texel (bottom center).

Clock gene Per2 as a controller of liver carcinogenesis

PubMed Central

Mteyrek, Ali; Filipski, Elisabeth; Guettier, Catherine; Okyar, Alper; Lévi, Francis

2016-01-01

Environmental disruption of molecular clocks promoted liver carcinogenesis and accelerated cancer progression in rodents. We investigated the specific role of clock gene Period 2 (Per2) for liver carcinogenesis and clock-controlled cellular proliferation, genomic instability and inflammation. We assessed liver histopathology, and determined molecular and physiology circadian patterns in mice on chronic diethylnitrosamine (DEN) exposure according to constitutive Per2 mutation. First, we found that Per2m/m liver displayed profound alterations in proliferation gene expression, including c-Myc derepression, phase-advanced Wee1, and arrhythmic Ccnb1 and K-ras mRNA expressions, as well as deregulated inflammation, through arrhythmic liver IL-6 protein concentration, in the absence of any DEN exposure. These changes could then make Per2m/m mice more prone to subsequently develop liver cancers on DEN. Indeed, primary liver cancers were nearly fourfold as frequent in Per2m/m mice as compared to wild-type (WT), 4 months after DEN exposure. The liver molecular clock was severely disrupted throughout the whole carcinogenesis process, including the initiation stage, i.e. within the initial 17 days on DEN. Per2m/m further exhibited increased c-Myc and Ccnb1 mean 24h expressions, lack of P53 response, and arrhythmic ATM, Wee1 and Ccnb1 expressions. DEN-induced tumor related inflammation was further promoted through increased protein concentrations of liver IL-6 and TNF-α as compared to WT during carcinogenesis initiation. Per2 mutation severely deregulated liver gene or protein expressions related to three cancer hallmarks, including uncontrolled proliferation, genomic instability, and tumor promoting inflammation, and accelerated liver carcinogenesis several-fold. Clock gene Per2 acted here as a liver tumor suppressor from initiation to progression. PMID:27494874

Branched-Chain Amino Acids Ameliorate Fibrosis and Suppress Tumor Growth in a Rat Model of Hepatocellular Carcinoma with Liver Cirrhosis

PubMed Central

Cha, Jung Hoon; Bae, Si Hyun; Kim, Hye Lim; Park, Na Ri; Choi, Eun Suk; Jung, Eun Sun; Choi, Jong Young; Yoon, Seung Kew

2013-01-01

Purpose Recent studies have revealed that branched-chain amino acids (BCAA) reduce the development of hepatocellular carcinoma (HCC) in patients with obesity and hepatitis C virus infection by improving insulin resistance (IR). The aim of this study was to examine the anti-cancer and anti-fibrotic effects of BCAA on the development of diethylnitrosamine (DEN)-induced HCC and liver cirrhosis in a rat model. Methods Male SD rats received weekly intraperitoneal injections of DEN (50 mg/kg of body weight) for 16 weeks to induce HCC. They were fed a diet containing 3% casein, 3% or 6% BCAA for 13 weeks beginning 6 weeks after DEN administration. DEN was used to induce HCC through stepwise development from cirrhosis to HCC. The effect of BCAA was evaluated in tumor tissues by histopathologic analyses, reverse transcription-polymerase chain reaction, and Western blotting. Results The mean area and number of dysplastic nodules (DNs) and tumors in the casein group tended to be larger than those in the BCAA group 16 weeks after DEN administration. The mean fibrotic area in the BCAA group was smaller than that in the casein group. The BCAA group showed decreased mRNA levels for markers of fibrosis, angiogenesis, and apoptosis inhibition. Compared with the casein group, the BCAA group had lower levels of α-smooth muscle actin, vascular endothelial growth factor, p-β-catenin, p-p38 mitogen-activated protein kinase, proliferating cell nuclear antigen, and caspase-3 protein expression, as well as a higher level of cleaved caspase-3 protein expression. Conclusions BCAA supplementation of the diet ameliorated liver fibrosis and HCC development in a DEN-induced rat model of HCC with liver cirrhosis, but not in the IR model. These results provide a rationale for anti-fibrosis and chemoprevention using BCAA treatment for HCC with liver cirrhosis, as well as decreasing the ammonia level. PMID:24223741

Liver tumor promoting effect of etofenprox in rats and its possible mechanism of action.

PubMed

Hojo, Yuri; Shiraki, Ayako; Tsuchiya, Takuma; Shimamoto, Keisuke; Ishii, Yuji; Suzuki, Kazuhiko; Shibutani, Makoto; Mitsumori, Kunitoshi

2012-01-01

To investigate the liver tumor-promoting effects of etofenprox (ETF), a pyrethroid-like insecticide, 6 week-old male F344 rats were given an intraperitoneal injection of N-diethylnitrosamine (DEN). After 2 weeks from the DEN treatment, 12 rats per group received a powdered diet containing 0, 0.25, 0.50, or 1.0% ETF for 8 weeks. At the time of 2nd week of ETF administration, all animals were subjected to two-thirds partial hepatectomy (PH). One rat per group except for the 0.25% ETF group died due to surgical operation of PH. The number and area of glutathione S-transferase placental form (GST-P) positive foci significantly increased in the livers of DEN-initiated rats given 0.50% and 1.0% ETF compared with the DEN-alone group. Quantitative real-time RT-PCR analysis revealed that the mRNA expression of phase I enzymes Cyp2b1/2, phase II enzymes such as Akr7a3, Gsta5, Ugt1a6, Nqo1 significantly increased in the DEN+ETF groups. The immunohistochemistry showed the translocation of CAR from the cytoplasm to the nuclei of hepatocytes in the ETF-treated groups. Reactive oxygen species (ROS) production increased in microsomes isolated from the livers of ETF-treated rats, and thiobarbituric acid-reactive substances (TBARS) levels and 8- hydroxy-2-deoxyguanosine (8-OHdG) content significantly increased in all of the ETF-treated groups and DEN+1.0% ETF group, respectively. The results of the present study indicate that ETF has a liver tumor-promoting activity in rats, and suggest that ETF activates the constitutive active/androstane receptor (CAR) and enhances microsomal ROS production, resulting in the upregulation of Nrf2 gene batteries; such an oxidative stress subsequently induces liver tumor-promoting effects by increased cellular proliferation.

Integrating conservation management, species protection, and economic viability into sustainable land use practices for the Cerulean Warbler (Setophaga cerulea) in the Appalachian and Northern Andes Mountains

Treesearch

Brian W. Smith; Jorge Botero; Jeff L. Larkin; Amanda D. Rodewald; Petra B. Wood; Patrick N. Angel; Scott E. Eggerud

2012-01-01

We monitored 15 radio-collared raccoons (Procyon lotor) on Davies Island in March 1987 - May 1988 to determine the extent to which individual tree attributes or spatial configuration of plant associations (habitat types) across the land-scape influenced den use. Of 1091 verified den sites, 428 were in tree cavities. Raccoon occurrence among 4 cover...

Modelling dendritic ecological networks in space: An integrated network perspective

Treesearch

Erin E. Peterson; Jay M. Ver Hoef; Dan J. Isaak; Jeffrey A. Falke; Marie-Josee Fortin; Chris E. Jordan; Kristina McNyset; Pascal Monestiez; Aaron S. Ruesch; Aritra Sengupta; Nicholas Som; E. Ashley Steel; David M. Theobald; Christian E. Torgersen; Seth J. Wenger

2013-01-01

Dendritic ecological networks (DENs) are a unique form of ecological networks that exhibit a dendritic network topology (e.g. stream and cave networks or plant architecture). DENs have a dual spatial representation; as points within the network and as points in geographical space. Consequently, some analytical methods used to quantify relationships in other types of...