A multi-exon deletion within WWOX is associated with a 46,XY disorder of sex development

Disorders of sex development (DSD) are congenital conditions where chromosomal, gonad or genital development is atypical. In a significant proportion of 46,XY DSD cases it is not possible to identify a causative mutation, making genetic counseling difficult and potentially hindering optimal treatment. Here, we describe the analysis of a 46,XY DSD patient that presented at birth with ambiguous genitalia. Histological analysis of the surgically removed gonads showed bilateral undifferentiated gonadal tissue and immature testis, both containing malignant germ cells. We screened genomic DNA from this patient for deletions and duplications using an Illumina whole-genome SNP microarray. This analysis revealed a heterozygous deletion within the WWOX gene on chromosome 16, removing exons 6-8. Analysis of parental DNA showed that the deletion was inherited from the mother. cDNA analysis confirmed that the deletion maintained the reading frame, with exon 5 being spliced directly onto exon 9. This deletion is the first description of a germline rearrangement affecting the coding sequence of WWOX in humans. Previously described Wwox knockout mouse models showed gonadal abnormalities, supporting a role for WWOX in human gonad development

Epistemic and Ontic Quantum Realities

Quantum theory has provoked intense discussions about its interpretation since its pioneer days. One of the few scientists who have been continuously engaged in this development from both physical and philosophical perspectives is Carl Friedrich von Weizsaecker. The questions he posed were and are inspiring for many, including the authors of this contribution. Weizsaecker developed Bohr's view of quantum theory as a theory of knowledge. We show that such an epistemic perspective can be consistently complemented by Einstein's ontically oriented position

Diagnosis and neurosurgical treatment of glossopharyngeal neuralgia: clinical findings and 3-D visualization of neurovascular compression in 19 consecutive patients

Glossopharyngeal neuralgia is a rare condition with neuralgic sharp pain in the pharyngeal and auricular region. Classical glossopharyngeal neuralgia is caused by neurovascular compression at the root entry zone of the nerve. Regarding the rare occurrence of glossopharyngeal neuralgia, we report clinical data and magnetic resonance imaging (MRI) findings in a case series of 19 patients, of whom 18 underwent surgery. Two patients additionally suffered from trigeminal neuralgia and three from additional symptomatic vagal nerve compression. In all patients, ipsilateral neurovascular compression syndrome of the IX cranial nerve could be shown by high-resolution MRI and image processing, which was confirmed intraoperatively. Additional neurovascular compression of the V cranial nerve was shown in patients suffering from trigeminal neuralgia. Vagal nerve neurovascular compression could be seen in all patients during surgery. Sixteen patients were completely pain free after surgery without need of anticonvulsant treatment. As a consequence of the operation, two patients suffered from transient cerebrospinal fluid hypersecretion as a reaction to Teflon implants. One patient suffered postoperatively from deep vein thrombosis and pulmonary embolism. Six patients showed transient cranial nerve dysfunctions (difficulties in swallowing, vocal cord paresis), but all recovered within 1 week. One patient complained of a gnawing and burning pain in the cervical area. Microvascular decompression is a second-line treatment after failure of standard medical treatment with high success in glossopharyngeal neuralgia. High-resolution MRI and 3D visualization of the brainstem and accompanying vessels as well as the cranial nerves is helpful in identifying neurovascular compression before microvascular decompression procedure

Dental management considerations for the patient with an acquired coagulopathy. Part 1: Coagulopathies from systemic disease

Current teaching suggests that many patients are at risk for prolonged bleeding during and following invasive dental procedures, due to an acquired coagulopathy from systemic disease and/or from medications. However, treatment standards for these patients often are the result of long-standing dogma with little or no scientific basis. The medical history is critical for the identification of patients potentially at risk for prolonged bleeding from dental treatment. Some time-honoured laboratory tests have little or no use in community dental practice. Loss of functioning hepatic, renal, or bone marrow tissue predisposes to acquired coagulopathies through different mechanisms, but the relationship to oral haemostasis is poorly understood. Given the lack of established, science-based standards, proper dental management requires an understanding of certain principles of pathophysiology for these medical conditions and a few standard laboratory tests. Making changes in anticoagulant drug regimens are often unwarranted and/or expensive, and can put patients at far greater risk for morbidity and mortality than the unlikely outcome of postoperative bleeding. It should be recognised that prolonged bleeding is a rare event following invasive dental procedures, and therefore the vast majority of patients with suspected acquired coagulopathies are best managed in the community practice setting

Longitudinal assessment of PCBs and chlorinated pesticides in pregnant women from Western Canada

BACKGROUND: Maternal exposures to organochlorines prior to pregnancy are considered a risk to neonatal welfare, specifically in relation to neurocognitive functions. There is growing interest in the evaluation of maternal blood testing as a marker for fetal exposure as well as the variable geographic distribution of these priority chemicals. METHODS: Three hundred and twenty-three women in the second trimester of pregnancy entered the study at a prenatal clinic providing genetic counselling information. Subjects who had an indication for genetic amniocentesis based on late maternal age were eligible to participate. Two hundred and thirty-eight completed an environmental questionnaire. A sample of amniotic fluid was taken for karyotype analysis in 323 women and blood samples during pregnancy (209), at birth (105) and from the umbilical cord (97) and breast milk (47) were also collected. These samples were tested for 29 PCB congeners and organochlorine pesticides. RESULTS: The concentrations of PCB 153 in these media were relatively low in relation to other studies. Σ PCBs measurements in samples taken during the second trimester of pregnancy, at birth and in the umbilical cord were strongly correlated. Specific measurements of PCB 153 and PCB 180 among those subjects with completed sampling of blood samples from mothers and cord samples were significantly correlated. The concentrations of PCBs and pesticides did not differ in relation to prior spontaneous abortion history. There were no organochlorines present in the amniotic fluid at the current level of quantification. CONCLUSION: Pregnant women from the Western Canada region of Calgary, Alberta are exposed to relatively low concentrations of organochlorines. Measurement of maternal blood during the second trimester of pregnancy can reliably estimate the fetal exposure to PCBs. This estimate is reliable for Group 2 and 3 PCBs as well as PCB 153 and PCB 180. The amniotic fluid does not contain measurable concentrations of pesticides and PCBs under the conditions of the levels of quantification

A mechanistic model of infection: why duration and intensity of contacts should be included in models of disease spread

<p>Abstract</p> <p>Background</p> <p>Mathematical models and simulations of disease spread often assume a constant per-contact transmission probability. This assumption ignores the heterogeneity in transmission probabilities, e.g. due to the varying intensity and duration of potentially contagious contacts. Ignoring such heterogeneities might lead to erroneous conclusions from simulation results. In this paper, we show how a mechanistic model of disease transmission differs from this commonly used assumption of a constant per-contact transmission probability.</p> <p>Methods</p> <p>We present an exposure-based, mechanistic model of disease transmission that reflects heterogeneities in contact duration and intensity. Based on empirical contact data, we calculate the expected number of secondary cases induced by an infector (i) for the mechanistic model and (ii) under the classical assumption of a constant per-contact transmission probability. The results of both approaches are compared for different basic reproduction numbers <it>R</it>₀.</p> <p>Results</p> <p>The outcomes of the mechanistic model differ significantly from those of the assumption of a constant per-contact transmission probability. In particular, cases with many different contacts have much lower expected numbers of secondary cases when using the mechanistic model instead of the common assumption. This is due to the fact that the proportion of long, intensive contacts decreases in the contact dataset with an increasing total number of contacts.</p> <p>Conclusion</p> <p>The importance of highly connected individuals, so-called super-spreaders, for disease spread seems to be overestimated when a constant per-contact transmission probability is assumed. This holds particularly for diseases with low basic reproduction numbers. Simulations of disease spread should weight contacts by duration and intensity.</p

Lower extremity joint kinetics and lumbar curvature during squat and stoop lifting

<p>Abstract</p> <p>Background</p> <p>In this study, kinematics and kinetics of the lower extremity joint and the lumbar lordosis during two different symmetrical lifting techniques(squat and stoop) were examined using the three-dimensional motion analysis.</p> <p>Methods</p> <p>Twenty-six young male volunteers were selected for the subjects in this study. While they lifted boxes weighing 5, 10 and 15 kg by both squat and stoop lifting techniques, their motions were captured and analyzed using the 3D motion analysis system which was synchronized with two forceplates and the electromyographic system. Joint kinematics was determined by the forty-three reflective markers which were attached on the anatomical locations based on the VICON Plug-in-Gait marker placement protocol. Joint kinetics was analyzed by using the inverse dynamics. Paired t-test and Kruskal-Wallis test was used to compare the differences of variables between two techniques, and among three different weights. Correlation coefficient was calculated to explain the role of lower limb joint motion in relation to the lumbar lordosis.</p> <p>Results</p> <p>There were not significant differences in maximum lumbar joint moments between two techniques. The hip and ankle contributed the most part of the support moment during squat lifting, and the knee flexion moment played an important role in stoop lifting. The hip, ankle and lumbar joints generated power and only the knee joint absorbed power in the squat lifting. The knee and ankle joints absorbed power, the hip and lumbar joints generated power in the stoop lifting. The bi-articular antagonist muscles' co-contraction around the knee joint during the squat lifting and the eccentric co-contraction of the gastrocnemius and the biceps femoris were found important for maintaining the straight leg during the stoop lifting. At the time of lordotic curvature appearance in the squat lifting, there were significant correlations in all three lower extremity joint moments with the lumbar joint. Differently, only the hip moment had significant correlation with the lumbar joint in the stoop lifting.</p> <p>Conclusion</p> <p>In conclusion, the knee extension which is prominent kinematics during the squat lifting was produced by the contributions of the kinetic factors from the hip and ankle joints(extensor moment and power generation) and the lumbar extension which is prominent kinematics during the stoop lifting could be produced by the contributions of the knee joint kinetic factors(flexor moment, power absorption, bi-articular muscle function).</p

Lower extremity joint kinetics and lumbar curvature during squat and stoop lifting

<p>Abstract</p> <p>Background</p> <p>In this study, kinematics and kinetics of the lower extremity joint and the lumbar lordosis during two different symmetrical lifting techniques(squat and stoop) were examined using the three-dimensional motion analysis.</p> <p>Methods</p> <p>Twenty-six young male volunteers were selected for the subjects in this study. While they lifted boxes weighing 5, 10 and 15 kg by both squat and stoop lifting techniques, their motions were captured and analyzed using the 3D motion analysis system which was synchronized with two forceplates and the electromyographic system. Joint kinematics was determined by the forty-three reflective markers which were attached on the anatomical locations based on the VICON Plug-in-Gait marker placement protocol. Joint kinetics was analyzed by using the inverse dynamics. Paired t-test and Kruskal-Wallis test was used to compare the differences of variables between two techniques, and among three different weights. Correlation coefficient was calculated to explain the role of lower limb joint motion in relation to the lumbar lordosis.</p> <p>Results</p> <p>There were not significant differences in maximum lumbar joint moments between two techniques. The hip and ankle contributed the most part of the support moment during squat lifting, and the knee flexion moment played an important role in stoop lifting. The hip, ankle and lumbar joints generated power and only the knee joint absorbed power in the squat lifting. The knee and ankle joints absorbed power, the hip and lumbar joints generated power in the stoop lifting. The bi-articular antagonist muscles' co-contraction around the knee joint during the squat lifting and the eccentric co-contraction of the gastrocnemius and the biceps femoris were found important for maintaining the straight leg during the stoop lifting. At the time of lordotic curvature appearance in the squat lifting, there were significant correlations in all three lower extremity joint moments with the lumbar joint. Differently, only the hip moment had significant correlation with the lumbar joint in the stoop lifting.</p> <p>Conclusion</p> <p>In conclusion, the knee extension which is prominent kinematics during the squat lifting was produced by the contributions of the kinetic factors from the hip and ankle joints(extensor moment and power generation) and the lumbar extension which is prominent kinematics during the stoop lifting could be produced by the contributions of the knee joint kinetic factors(flexor moment, power absorption, bi-articular muscle function).</p

Prevalence and risk factors of major depressive disorder in HIV/AIDS as seen in semi-urban Entebbe district, Uganda

BACKGROUND: Not much is known about the risk factors of major depressive disorder (MDD) in HIV/AIDS in the African socio-cultural context. Therefore a study was undertaken to examine the prevalence and risk factors of MDD in HIV/AIDS in semi-urban Uganda. METHODS: A cross-sectional study was undertaken among 618 respondents attending two HIV clinics in Uganda. RESULTS: Prevalence of MDD was 8.1%. Factors associated with MDD at univariate analysis only were female gender, family history of mental illness, negative coping style, alcohol dependency disorder, food insecurity and stress; not associated with MDD were social support, neurocognitive impairment, CD4 counts and BMI. Factors independently associated with MDD were psychosocial impairment, adverse life events, post traumatic stress disorder, generalised anxiety disorder and life-time attempted suicide. CONCLUSION: Psychological and social factors were the main risk factors of MDD among ambulatory HIV positive persons with no evidence for the role of the neurotoxic effects of HIV. Treatment approaches for MDD in this patient group should be modeled on those used among non-HIV groups

Sry delivery to the adrenal medulla increases blood pressure and adrenal medullary tyrosine hydroxylase of normotensive WKY rats

BACKGROUND: Our laboratory has shown that a locus on the SHR Y chromosome increases blood pressure (BP) in the SHR rat and in WKY rats that had the SHR Y chromosome locus crossed into their genome (SHR/y rat). A potential candidate for this Y chromosome hypertension locus is Sry, a gene that encodes a transcription factor that is responsible for testes development and the Sry protein may affect other target genes. METHODS: The following study examined if exogenous Sry would elevate adrenal Th, adrenal catecholamines, plasma catecholamines and blood pressure. We delivered 10 μg of either the expression construct, Sry1/pcDNA 3.1, or control vector into the adrenal medulla of WKY rats by electroporation. Blood pressure was measured by the tail cuff technique and Th and catecholamines by HPLC with electrochemical detection. RESULTS: In the animals receiving Sry there were significant increases after 3 weeks in resting plasma NE (57%) and adrenal Th content (49%) compared to vector controls. BP was 30 mmHg higher in Sry injected animals (160 mmHg, p < .05) compared to vector controls (130 mmHg) after 2–3 weeks. Histological analysis showed that the electroporation procedure did not produce morphological damage. CONCLUSION: These results provide continued support that Sry is a candidate gene for hypertension. Also, these results are consistent with a role for Sry in increasing BP by directly or indirectly activating sympathetic nervous system activity