POU6F2 mutation in humans with pubertal failure alters GnRH transcript expression.

Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by the absence of pubertal development and subsequent impaired fertility often due to gonadotropin-releasing hormone (GnRH) deficits. Exome sequencing of two independent cohorts of IHH patients identified 12 rare missense variants in POU6F2 in 15 patients. POU6F2 encodes two distinct isoforms. In the adult mouse, expression of both isoform1 and isoform2 was detected in the brain, pituitary, and gonads. However, only isoform1 was detected in mouse primary GnRH cells and three immortalized GnRH cell lines, two mouse and one human. To date, the function of isoform2 has been verified as a transcription factor, while the function of isoform1 has been unknown. In the present report, bioinformatics and cell assays on a human-derived GnRH cell line reveal a novel function for isoform1, demonstrating it can act as a transcriptional regulator, decreasing GNRH1 expression. In addition, the impact of the two most prevalent POU6F2 variants, identified in five IHH patients, that were located at/or close to the DNA-binding domain was examined. Notably, one of these mutations prevented the repression of GnRH transcripts by isoform1. Normally, GnRH transcription increases as GnRH cells mature as they near migrate into the brain. Augmentation earlier during development can disrupt normal GnRH cell migration, consistent with some POU6F2 variants contributing to the IHH pathogenesis.

Cellulose Nanocrystals Crosslinked with Sulfosuccinic Acid as Sustainable Proton Exchange Membranes for Electrochemical Energy Applications.

Nanocellulose is a sustainable material which holds promise for many energy-related applications. Here, nanocrystalline cellulose is used to prepare proton exchange membranes (PEMs). Normally, this nanomaterial is highly dispersible in water, preventing its use as an ionomer in many electrochemical applications. To solve this, we utilized a sulfonic acid crosslinker to simultaneously improve the mechanical robustness, water-stability, and proton conductivity (by introducing -SO3-H+ functional groups). The optimization of the proportion of crosslinker used and the crosslinking reaction time resulted in enhanced proton conductivity up to 15 mS/cm (in the fully hydrated state, at 120 °C). Considering the many advantages, we believe that nanocellulose can act as a sustainable and low-cost alternative to conventional, ecologically problematic, perfluorosulfonic acid ionomers for applications in, e. fuel cells and electrolyzers.

PLXNB1 mutations in the etiology of idiopathic hypogonadotropic hypogonadism.

Idiopathic hypogonadotropic hypogonadism (IHH) comprises a group of rare genetic disorders characterized by pubertal failure caused by gonadotropin-releasing hormone (GnRH) deficiency. Genetic factors involved in semaphorin/plexin signaling have been identified in patients with IHH. PlexinB1, a member of the plexin family receptors, serves as the receptor for semaphorin 4D (Sema4D). In mice, perturbations in Sema4D/PlexinB1 signaling leads to improper GnRH development, highlighting the importance of investigating PlexinB1 mutations in IHH families. In total, 336 IHH patients (normosmic IHH, n = 293 and Kallmann syndrome, n = 43) from 290 independent families were included in the present study. Six PLXNB1 rare sequence variants (p.N361S, p.V608A, p.R636C, p.V672A, p.R1031H, and p.C1318R) are described in eight normosmic IHH patients from seven independent families. These variants were examined using bioinformatic modeling and compared to mutants reported in PLXNA1. Based on these analyses, the variant p.R1031H was assayed for alterations in cell morphology, PlexinB1 expression, and migration using a GnRH cell line and Boyden chambers. Experiments showed reduced membrane expression and impaired migration in cells expressing this variant compared to the wild-type. Our results provide clinical, genetic, molecular/cellular, and modeling evidence to implicate variants in PLXNB1 in the etiology of IHH.

Use of a Motorized Intramedullary Bone Transport Nail for Trauma: Tips, Tricks, Corticotomy Techniques, and Rate and Rhythm.

SUMMARY: The introduction of internal magnetic nails (IMNs) for bone lengthening and bone transport has given us exciting new tools with which to treat segmental bone loss. Distraction osteogenesis has a long record of success in recreating even large segments of bone, but the availability of IMNs now offers the possibility of performing distraction osteogenesis without the drawbacks of external fixation. However, there are aspects of treatment with IMNs that are critical to understand to achieve success and minimize complications. These include assessment of feasibility in relation to available bone stock and segment configuration, the condition of the soft tissue envelope, and the presence of contamination or infection. They also include execution aspects such as bone end preparation, nail placement, need for and positioning of adjuvant fixation, corticotomy techniques, rate and rhythm of distraction, staged screw exchange, docking site preparation, and nail extraction. We discuss these issues in detail and introduce some novel techniques not previously described including the comminuted wedge osteotomy, testing of the nail with initial compression, and retention plug application for nail extraction to assist in optimizing success in certain clinical situations.

Prevalence and predictors of gestational diabetes mellitus among pregnant women attending antenatal clinic in Dodoma region, Tanzania: an analytical cross-sectional study.

INTRODUCTION: Gestational diabetes mellitus (GDM) is rapidly increasing worldwide. Globally, 18.4 million pregnancies are complicated by GDM. Despite its known effect, GDM screening is not part of routine antenatal services in Tanzania. There is paucity of data on the magnitude and risk factors for GDM. Therefore, this study sought to determine prevalence and predictors of GDM among pregnant women in Dodoma region, Tanzania from March to August 2018. RESEARCH DESIGN AND METHODS: A cross-sectional study was carried out in Dodoma region, Tanzania between April and August of 2018. A total of 582 pregnant women were recruited from four local health facilities, where purposive sampling procedure was used to select the region, districts and health facilities. Simple random sampling was used to select study participants. Screening and diagnosis of GDM were performed using the 2013 WHO criteria. Descriptive and inferential analyses were performed using SPSS V.23 to determine prevalence and independent predictors of GDM. RESULTS: Among 582 participants, 160 (27.5%) participants were diagnosed with GDM. GDM was more prevalent in urban areas than rural areas, among overweight participants, among participants with a history of a large for gestational age baby, among participants with a history of caesarean section, and among participants with college or university education. Multiple logistic regression analysis showed that maternal age above 35 years (adjusted OR (AOR) 3.115 (95% CI: 1.165 to 8.359)), pre-eclampsia (AOR 3.684 (95% CI: 1.202 to 5.293)), low physical activity level (AOR 4.758 (95% CI: 2.232 to 10.143)), lack of awareness of GDM (AOR 6.371 (95% CI: 1.944 to 13.919)), alcohol use (AOR 4.477 (95% CI: 1.642 to 12.202)) and family history of diabetes (AOR 2.344 (95% CI: 1.239 to 4.434)) were significantly associated with GDM. CONCLUSIONS: Prevalence of GDM is relatively high in Dodoma region. Most pregnant women are unaware of the condition such that it leads to a high-risk lifestyle. Besides, GDM significantly contributes to the number of high-risk pregnancies that go undetected and suboptimally managed. The antenatal care centres offer an optimum platform for screening, preventing and treating GDM by prioritising high-risk women.

Drebrin regulates cytoskeleton dynamics in migrating neurons through interaction with CXCR4.

Stromal cell-derived factor-1 (SDF-1) and chemokine receptor type 4 (CXCR4) are regulators of neuronal migration (e.g., GnRH neurons, cortical neurons, and hippocampal granule cells). However, how SDF-1/CXCR4 alters cytoskeletal components remains unclear. Developmentally regulated brain protein (drebrin) stabilizes actin polymerization, interacts with microtubule plus ends, and has been proposed to directly interact with CXCR4 in T cells. The current study examined, in mice, whether CXCR4 under SDF-1 stimulation interacts with drebrin to facilitate neuronal migration. Bioinformatic prediction of protein-protein interaction highlighted binding sites between drebrin and crystallized CXCR4. In migrating GnRH neurons, drebrin, CXCR4, and the microtubule plus-end binding protein EB1 were localized close to the cell membrane. Coimmunoprecipitation (co-IP) confirmed a direct interaction between drebrin and CXCR4 using wild-type E14.5 whole head and a GnRH cell line. Analysis of drebrin knockout (DBN1 KO) mice showed delayed migration of GnRH cells into the brain. A decrease in hippocampal granule cells was also detected, and co-IP confirmed a direct interaction between drebrin and CXCR4 in PN4 hippocampi. Migration assays on primary neurons established that inhibiting drebrin (either pharmacologically or using cells from DBN1 KO mice) prevented the effects of SDF-1 on neuronal movement. Bioinformatic prediction then identified binding sites between drebrin and the microtubule plus end protein, EB1, and super-resolution microscopy revealed decreased EB1 and drebrin coexpression after drebrin inhibition. Together, these data show a mechanism by which a chemokine, via a membrane receptor, communicates with the intracellular cytoskeleton in migrating neurons during central nervous system development.

Hepatic Cystadenocarcinoma presenting as an ovarian new growth in a 65‐year‐old female: Case report

@#Biliary cystic tumors (BCT), which include the subgroups biliary cystadenoma (BCA) and biliary cystadenocarcinoma (BCAC), affect 5 to 10% of the global population. BCTs are solitary, multiloculated cysts that are usually intrahepatic in location. BCACs are rare tumors that arise from the malignant transformation of BCA. The presentation of BCT often mimics simple hepatic cysts and other hepatic cystic lesions making diagnosis difficult. With the recent advances in medical imaging, BCTs have been diagnosed more often. Patients with BCT are often asymptomatic. When symptoms are present, however, patients usually manifest with abdominal pain and distention. Given the high risk of recurrence, complete surgical resection by formal hepatic resection or enucleation is the best treatment of choice for patients. We present a case of a 65-year-old female who came in due to a four-year history of an enlarging abdomen. She was initially treated, preoperatively, as a case of ovarian new growth but was later managed as hepatic cystadenocarcinoma.

Tunable Anion-Selective Transport through Monolayer Graphene and Hexagonal Boron Nitride.

Membranes that selectively filter for both anions and cations are central to technological applications from clean energy generation to desalination devices. 2D materials have immense potential as these ion-selective membranes due to their thinness, mechanical strength, and tunable surface chemistry; however, currently, only cation-selective membranes have been reported. Here we demonstrate the controllable cation and anion selectivity of both monolayer graphene and hexagonal boron nitride. In particular, we measure the ionic current through membranes grown by chemical vapor deposition containing well-known defects inherent to scalably produced and wet-transferred 2D materials. We observe a striking change from cation selectivity with monovalent ions to anion selectivity by controlling the concentration of multivalent ions and inducing charge inversion on the 2D membrane. Furthermore, we find good agreement between our experimental data and theoretical predictions from the Goldman-Hodgkin-Katz equation and use this model to extract selectivity ratios. These tunable selective membranes conduct up to 500 anions for each cation and thus show potential for osmotic power generation.

Turner syndrome and autosomal dominant polycystic kidney disease.

Turner syndrome is a chromosomal disorder that involves multiple organ systems and is typically associated with short stature. A multidisciplinary approach with regular screening and surveillance is key to managing this condition's multiple comorbidities. We present a case of a young girl with Turner syndrome and associated short stature on growth hormone treatment who presented with cystic renal disease found to be autosomal dominant kidney disease. We propose reevaluation of renal screening guidelines in this population due to the potential association of growth hormone and cyst proliferation.

Metachronous occurrence of anal melanoma and papillary thyroid carcinoma in a 72-year-old female: Case in images

@#Anal melanoma is a rare melanocytic malignancy, which roughly comprises 2% of all anorectal malignancies.1 2 The anal area is the most common site for primary gastrointestinal melanomas.2 Patients with anal melanomas commonly complain of bleeding, anal pain and mass, tenesmus, and changes in bowel habits. In cases with metastases, symptoms such as weight loss, anemia, fatigue and bowel obstruction could be present.2 Risk factors of anal melanoma include old age, multiple sexual partners, anal sex, smoking, history of other malignancies (i.e., cervical, vulvar, or vaginal cancer), activation of the receptor tyrosine kinase c-Kit, and family history of malignancies.3 4 The diagnosis of anal melanoma is established through biopsy—usually done with colonoscopy—and immunological staining.5 HMB-45 is the immunological stain commonly used for the detection of both primary and metastatic melanomas.6 Endoscopic ultrasonography also helps to characterize lesions and assess the depth of infiltration.7

DEPOT TRIAMCINOLONE INJECTION CONTRIBUTING TO ADRENAL SUPPRESSION AND CUSHING SYNDROME: CASE REPORT AND LITERATURE REVIEW.

OBJECTIVE: To present an unusual case of Cushing syndrome in a pediatric patient caused by a single depot triamcinolone injection. METHODS: A case report followed by a literature review are presented. RESULTS: A 13-year-old male presented with rapid weight gain, elevated blood pressure, headaches, and diffuse purplish striae. Lab results revealed a low 24-hour urinary free cortisol of <3 µg (reference range is 4.0 to 56 µg/24 hours), a low midnight salivary cortisol of <50 ng/dL (reference range is <100 ng/dL), a low adrenocorticotropic hormone of <5 pg/mL (reference range is 6 to 55 pg/mL), and a lower than expected testosterone of 86 ng/dL. The values were not consistent, and upon further questioning the family admitted the patient had received a "Jesus shot" from a practitioner which was sold as a cure all. Upon further investigation, it was determined that this injection contained both dexamethasone and depot triamcinolone. The triamcinolone in this injection was quantified and remained measureable for over 4 months following injection. CONCLUSION: The cause of Cushing syndrome symptoms with adrenal suppression was exogenous glucocorticoid, specifically depot triamcinolone. Exogenous glucocorticoids can create adrenal suppression, contributing to life-threatening adrenal crises with illness or stress. Recovery of our patient's adrenal axis was demonstrable within a few months. This case highlights the potentially devastating effects of glucocorticoid treatment for unclear medical indications. Further, it raises concerns about the potential unintended consequences of such therapies and the importance for providers to raise additional questions whenever the clinical presentation and laboratory investigation are inconsistent.

Invasive ductal carcinoma in a 51-year-old male: Case report

@#Male breast cancer (MBC), which constitutes only 1% of all breast cancer cases worldwide, is associated with mutations in the BRCA1 and BRCA2 genes, Klinefelter’s syndrome and a positive family history of breast or ovarian malignancy. Patients with MBC typically present with a palpable subareolar mass, with or without nipple involvement. MBC can be identified by mammography and/or ultrasonography. The definitive diagnosis is made through core needle biopsy and cytology. Breast cancer in men are typically low-grade, and usually estrogen- and progesterone-receptor positive. The surgical treatment of choice is usually a modified radical mastectomy. Hormone therapy, can be used as first-line treatment for hormone-receptor positive MBC, and as adjuvant or palliative therapy for advanced cases. The use of adjuvant cytotoxic chemotherapy has been shown to reduce cancer recurrence and improve overall survival. We present the case of a 51-year-old male who came in due to an enlarging right breast mass that had been removed twice in the past eight years. We were able to establish that the patient had MBC, for which he subsequently underwent a modified radical mastectomy

Prevalence and Factors Influencing Alcohol Use in Pregnancy among Women Attending Antenatal Care in Dodoma Region, Tanzania: A Cross-Sectional Study.

BACKGROUND: Alcohol use during pregnancy is high despite the well-established evidence on its adverse pregnancy outcomes and poor child development. Early identification and behavioural modification are of great significance. This study aimed to determine the prevalence and associated factors of alcohol use during pregnancy among women in Dodoma region. METHODS: 365 randomly selected pregnant women attending antenatal care services in Dodoma region were included. Structured questionnaires were used to assess sociodemographic characteristic and alcohol use. Both descriptive and inferential analyses were used to estimate the prevalence and independent relationships of factors associated with alcohol use in pregnancy, respectively. RESULTS: Results showed a prevalence of 15.1% out of the 365 women attending antenatal services in Dodoma region. Prepregnancy alcohol use and having relatives who use alcohol were associated with alcohol use (AOR= 5.19; 95% CI: 4.791-34.867 and AOR=1.57; 95% CI: 1.393-6.248), respectively. Moreover, other associated factors included low education status (AOR=10.636; 95% CI: 1.89-19.844), making local brews as a source of income (AOR=11.44; 95% CI: 1.008-19.86), and not having had complications in previous pregnancies (AOR=4.93; 95% CI: 1.031-23.59). CONCLUSION: There is a significantly high prevalence of alcohol use during pregnancy in Dodoma. Social networks and low social, economic status were associated with alcohol use in pregnancy. There is a need for public health interventions to address alcohol use particularly targeting women of reproductive age with low socioeconomic status.

Factors Associated with HIV Status Disclosure and Its Effect on Treatment Adherence and Quality of Life among Children 6-17 Years on Antiretroviral Therapy in Southern Highlands Zone, Tanzania: Unmatched Case Control Study.

BACKGROUND: The World Health Organization (WHO) recommends that children should be informed of their HIV status at ages 6 to 12 years and full disclosure of HIV and AIDS be offered in a caring and supportive manner at about 8 to 10 years. The objective of this study was to determine factors associated with HIV status disclosure and its effect on treatment adherence and health-related quality of life among children between 6 and 17 years of age living with HIV/AIDS in the Southern Highlands Zone, Tanzania, 2017. METHODS: A hospital based unmatched case control study was conducted between April and September 2017. A total of 309 children between 6 and 17 years on ART for at least six months were enrolled in this study. Simple random sampling was employed in selecting the children from existing treatment registers. Data were collected using a structured questionnaire which included the WHO Quality of Life standard tool (WHOQOL-BREF 2012 tool) and treatment adherence manual. Multiple logistic regression was used to test for the independent effect of HIV status disclosure on treatment adherence and quality of life at p value less than 0.05. RESULTS: Out of 309 children, only 102 (33%) had their HIV status disclosed to them. The mean age at HIV status disclosure was 12.39 (SD=3.015). HIV status disclosure was high among girls (51%), children aged 10-13 years (48.3%), and those living with their biological parents (59.8%). After adjusting for confounders, being aged between 10-13 and 14-17 years was associated with HIV status disclosure (AOR 19.178, p<0.05 and AOR=65.755, p<0.001, respectively). HIV status disclosure was associated with ART adherence (AOR=8.173, p<0.05) and increased the odds of having good quality of life (AOR=3.283, p<0.001). CONCLUSIONS: HIV status disclosure significantly improved adherence to treatment and quality of life among children living with HIV/AIDS.

Association between HIV status and depressive symptoms among children and adolescents in the Southern Highlands Zone, Tanzania: A case-control study.

BACKGROUND: Children and adolescents continue to have HIV/AIDS in southern Saharan Africa. Scaling up of HIV services has significantly improved access to ARV and consequently improved on morbidity and mortality related to HIV/AIDS including opportunistic infection. Despite the above efforts, non-communicable conditions including mental disorders such as depression have been observed to contribute to the burden of disabilities about which little is documented. This study, therefore, aimed to determine the magnitude of depressive symptoms and the associated factors among HIV-infected children and adolescents. METHODS: The study was a matched case-control design involving 300 cases of HIV-infected children matched by age and sex against 600 uninfected controls. Systematic sampling technique was used to select the cases while multistage sampling technique was employed to identify villages/ streets purposive and sampling technique was employed to obtain participants from households. RESULTS: The overall prevalence of depressive symptoms among the cohort of 900 participants was found to be 12.9%, with 27% of HIV-infected and 5.8% of HIV-uninfected children and adolescents screened positive for depressive symptoms. Multiple logistic regression revealed that being HIV-infected (AOR 1.96(1.11-3.45)), residing in a rural setting (AOR 0.61(0.39-0.96)) and history of childhood deprivation (AOR 4.76 (2.79-8.13)) were significantly associated with depressive symptoms. CONCLUSION: HIV infected adolescents are more affected by depression compared to non-infected counterparts. Childhood deprivation was significantly associated with presence of depressive symptoms. Integration of mental health evaluation and treatment into the HIV care provided for adolescents can be beneficial. More studies to delineate factors associated with depressed adolescents with HIV may add value to the body of knowledge and overall improvement of care.

Prevalence and Factors Associated with Diarrhoea among Children between 6 and 59 Months of Age in Mwanza City Tanzania.

Background: Childhood diarrhoea is a global public health problem especially in unplanned settlements of low- and middle-income countries. Different studies have associated household settlement and childhood diarrhoea, but the prevalence and risk factors associated with childhood diarrhoea at the community level are not clearly known. Method: A community-based cross-sectional study was performed to determine the prevalence and risk factors associated with diarrhoea in among 480 children between 6 and 59 months of age in Mwanza city from June to August 2016. Risk factors associated with childhood diarrhoea in Mwanza city were determined using univariate, bivariate and multivariate analysis. Results: The study showed a prevalence of diarrhoea of 20.4% and an association between type of settlement and childhood diarrhoea (p < 0.001) in a chi-square analysis. During bivariate analysis, and logistic regression, after controlling for other factors, unplanned settlement was significantly associated with childhood diarrhoea (odds ratio=3.475, p < 0.001 and AOR=3.469, p < 0.001). Other factors associated with childhood diarrhoea were behaviour of mother washing hands before preparing food (AOR = 0, 193, p < 0.001), mother washing hands after changing child's napkins (AOR = 0.544, p < 0.036) and the behaviour of the child washing hands after toilet (AOR = 0.447, p < 0.006). Conclusion: Risk factors associated with childhood diarrhoea in Mwanza city are unplanned settlement and behaviour of mother and child washing hands during critical time; hence, continuous community health promotion insisting on washing hands with soap and water during critically time is the best method for fighting childhood diarrhoea in Mwanza city.

Anterior insular thickness predicts speech sound learning ability in bilinguals.

A previous fMRI study of novel speech sound learning, tied to the methods and results presented here, identified groups of advanced and novice learners and related their classification to neural activity. To complement those results and better elucidate the role of the entire neural system in speech learning, the current study analyzed the neuroanatomical data with the goals of 1) uncovering the regions of interest (ROIs) that predicted speech learning performance in a sample of monolingual and bilingual adults, and 2) examining if the relationship between cortical thickness from selected ROIs and individual learning ability depends on language group. The ROIs selected were brain regions well-established in the literature as areas associated with language and speech processing (i.e., Transverse Superior Temporal Gyrus, anterior insula and posterior insula, all bilaterally). High-resolution brain scans (T1-weighted) were acquired from 23 Spanish-English bilinguals and 20 English monolingual adults. The thickness of the left anterior insula significantly predicted speech sound learning ability in bilinguals but not monolinguals. These results suggest that aptitude for learning a new language is associated with variations in the cortical thickness of the left anterior insula in bilinguals. These findings may provide insight into the higher order mechanisms involved in speech perception and advance our understanding of the unique strategies employed by the bilingual brain during language learning.

Optimizing Bone Defect Reconstruction-Balanced Cable Transport With Circular External Fixation.

Distraction osteogenesis has proven effective in the management of tibial bone loss from severe trauma and infection. Unfortunately, pain and scarring from wires and half pins dragging through the skin and the required prolonged time in the external fixator make treatment difficult. Cable bone transport has been shown to improve cosmesis and decrease pain during transport. However, the published methods have limitations in that they have poor control of transport segment alignment, do not allow for lengthening of the limb, and do not permit weight bearing during the treatment process. We describe a novel method of cable bone transport that addresses each of these limitations with excellent control of alignment including the transport segment, easy conversion to allow limb lengthening, and full weight bearing throughout the treatment process. In addition, the method facilitates multifocal transport and safe conversion to intramedullary nail fixation, both of which can be used to substantially shorten the time of reconstruction.