Elevated level of metabotropic glutamate receptor 2/3 in the prefrontal cortex in major depression

Clinical, postmortem and preclinical research strongly implicates dysregulation of glutamatergic neurotransmission in major depressive disorder (MDD). Recently, metabotropic glutamate receptors (mGluRs) have been proposed as attractive targets for the discovery of novel therapeutic approaches against depression. The aim of this study was to examine mGluR2/3 protein levels in the prefrontal cortex (PFC) from depressed subjects. In addition, to test whether antidepressants influence mGluR2/3 expression we also studied levels of mGluR2/3 in fluoxetine-treated monkeys. Postmortem human prefrontal samples containing Brodmann's area 10 (BA10) were obtained from 11 depressed and 11 psychiatrically healthy controls. Male rhesus monkeys were treated chronically with fluoxetine (dose escalated to 3 mg/kg, p.o.; n = 7) or placebo (n = 6) for 39 weeks. The mGluR2/3 immunoreactivity was investigated using Western blot method. There was a robust (+ 67%) increase in the expression of the mGlu2/3 protein in the PFC of depressed subjects relative to healthy controls. The expression of mGlu2/3 was unchanged in the PFC of monkeys treated with fluoxetine. Our findings provide the first evidence that mGluR2/3 is elevated in the PFC in MDD. This observation is consistent with reports showing that mGluR2/3 antagonists exhibit antidepressant-like activity in animal models and demonstrates that these receptors are promising targets for the discovery of novel antidepressants.     

The evolution into personalized therapies in pancreatic ductal adenocarcinoma: challenges and opportunities

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is projected to be the second leading cause of cancer related mortality in the United States in 2030, with a 5-year overall survival of less than 10% despite decades of extensive research. Pancreatic cancer is marked by the accumulation of complex molecular changes, complex tumor-stroma interaction, and an immunosuppressive tumor microenvironment. PDAC has proven to be resistant to many cytotoxic, targeted and immunologic treatment approaches.

Areas covered: In this paper, we review the major areas of research in PDAC, with highlights on the challenges and areas of opportunity for personalized treatment approaches.

Expert commentary: The focus of research in pancreatic cancer has moved away from developing conventional cytotoxic combinations. The marked advances in understanding the molecular biology of this disease especially in the areas of the microenvironment, metabolism, and DNA repair have opened new opportunities for developing novel treatment strategies. Improved understanding of molecular abnormalities allows the development of personalized treatment approaches.     

Thyrotoxic hypokalemic periodic paralysis in an African male: a case report

Thyrotoxic hypokalemic periodic paralysis is a rare manifestation of thyrotoxicosis and is rarely reported in non‐Asian populations. A 26‐year‐old Ethiopian male who presented with recurrent flaccid tetraparesis, hypokalemia, and hyperthyroidism is reported here. Thyroid function should be routinely checked in patients with acute or recurrent hypokalemic paralysis.     

A review of the neuropharmacological properties of khat

BACKGROUND: The psychostimulant khat (Catha edulis Forsk), is a herbal drug cultivated and chewed as a recreational and socializing drug in East Africa and the Arabian Peninsula for centuries. Due to increasing air transportation and the loosening of customs restrictions, it is now readily available in the Western Countries mainly used by immigrants from khat growing areas causing a concern to policy-makers. OBJECTIVE: We conducted this review to further gain an insight to the neuropharmacological effects of khat. METHODOLOGY: PubMed search engine with key terms 'khat' or 'qat' or 'mirra' or'qaad/jaad' or 'cathinone' was used to obtain articles relevant to khat chewing. In total 284 English written articles published from 1959 to 2007 were screened. RESULTS: Most of the studies focused on cathinone, the postulated active psychostimulant alkaloid in khat. There were few studies which investigated the entire plant extract in either in vitro or animal studies. In the majority of the studies it was reported that both cathinone and cathine, another psychoactive constituent, have actions that are similar to those of amphetamine. CONCLUSIONS: It seems that the well investigated khat alkaloids have many features similar to amphetamines; however there is a need for a more thorough examination of khat itself in well designed in vitro, animal and human studies with a range of comparator drugs before confirming the claim that khat is a "natural amphetamine".     

Optimized Ni1−xAlxO hole transport layer for silicon solar cells

NiO alloyed with aluminum, Ni_1−xAl_xO, is analyzed in terms of its stoichiometry, electronic and transport properties, as well as interfacial band alignment with Si to evaluate its potential use as a hole transport layer (HTL) in p–i–n type solar cells. The analysis is based on component material and slab structural simulations, as well as simulated and measured angle-resolved valence-band photoemission spectroscopy (PES) data, in order to reveal the best suitable stoichiometry. It is concluded that the ionization energy from the highest occupied states tends to increase with Al content as the simulated work function grows from 4.1 eV for pure NiO to 4.7 eV for heavily alloyed Al_0.50Ni_0.50O. The electronic structure as a function of the interface design between crystalline silicon and the transport layer is used to assess the band lineup and its correlation with the discontinuity of the affinities. The affinity rule is tested by evaluating the workfunctions of the component layers and justified best for a particular Ni-enriched interface design. Technology Computer-Aided Design (TCAD) device simulations show, that the band offset between oxide and crystalline silicon remains within the range of values to sustain a staggering alignment – a condition suitable for effective charge separation, similar to a situation in a tunneling diode. The self-energy of the hole carriers is estimated by contrasting simulated and measured photoemission data, which in the case of non-annealed Al-rich samples is shown to be an order of magnitude higher due to the disorder effects. The work functions derived from the measured PES data for the epitaxially grown oxide films with nearly identical alloy stoichiometry correlate well with the simulated values. The findings suggest that the optimal HTL is formed by starting with a pure Ni layer, followed by a graded doping Al_xNi_1−xO, with x high at contact/oxide interface and low at the oxide/semiconductor.

NiO alloyed with aluminum, Ni_1−xAl_xO, is analyzed in terms of its stoichiometry, electronic and transport properties, as well as interfacial band alignment with Si to evaluate its potential use as a hole transport layer (HTL) in p–i–n type solar cells.     

Prevalence and associated factors of treatment failure among HIV/AIDS patients on HAART attending University of Gondar Referral Hospital Northwest Ethiopia

Background

The initiation of highly active antiretroviral therapy (HAART) plays a significant role in the clinical management of HIV infected people by preventing morbidity and mortality. This benefit becomes, the most terrible when treatment failure develops. Thus, this research aims to assess the prevalence and associated factors of treatment failure among HIV/AIDS patients on HAART attending University of Gondar Referral Hospital Northwest Ethiopia.

Results

Patients on ART with a minimum of 6?months and up to 12?years of treatment were being enrolled. The prevalence of treatment failure, immunological failure and virological failure among people living with HIV/AIDS attending University of Gondar referral hospital were 20.3, 13.2, and 14.7%, respectively. Patients who had no formal education (Adjusted odds ratio (AOR): 3.8; 95% CI, 1.05–13.77), primary level education (AOR: 4.2; 95% CI, 1.16–15.01) and duration on ART <?6?years (AOR: 2.1; 95%CI, 1.12–3.81) were a significant risk factor. However, initial adult regimen D4T?+? 3TC+ EFV (AOR: 0.025; 95% CI, 0.002–0.36), AZT +3TC?+?NVP (AOR: 0.07; 95% CI, 0.01–0.71), AZT?+? 3TC?+?EFV (AOR: 0.046; 95% CI, 0.004–0.57) andTDF+3TC?+?EFV (AOR: 0.04; 95% CI, 0.004–0.46) were significantly protective for treatment failure.

Conclusions

Timely and early identification of associated factors and monitoring antiretroviral therapy treatment failure should be done to enhance the benefit and to prevent further complication of the patients. It is preferable to initiate ART using any one of the following ART regimens: AZT +3TC?+?NVP, AZT?+?3TC?+?EFV and TDF?+?3TC?+?EFV to prevent treatment failure. Since the prevalence of this treatment failure and its associated factor may be different from other ART centers and community in Ethiopia, further national representative institutional based cross-sectional researches are needed across all ART centers of Ethiopia in order to determine the prevalence of treatment failure and its associated factors.

     

Intersections of girl child marriage and family planning beliefs and use: qualitative findings from Ethiopia and India

Child marriage and subsequent early first birth is a considerable social, economic and health concern, and a pervasive practice in sub-Saharan Africa and South Asia. This study explores barriers and facilitators to family planning among women and girls, and their marital decision-makers subsequent to receipt of child marriage prevention programmes in Ethiopia and India. In-depth interviews with 128 women and girls who were married as minors or who cancelled or postponed marriage as minors and their marital decision-makers were analysed using content analysis. Respondents identified social norms, including child marriage and pressure to have children, and lack of information as barriers to family planning. Benefits included delayed first birth and increased birth spacing, improved maternal and child health and girls’ educational attainment. Respondents associated family planning use with delayed pregnancy and increased educational attainment, particularly in Ethiopia. Child marriage prevention programmes were identified as important sources of family planning information. Ethiopia’s school-based programme strengthened access to health workers and contraception more so than India’s community-based programme. Findings highlight young wives’ vulnerability with regard to reproductive control, and support the need for multi-sector approaches across communities, schools and community health workers to improve family planning among young wives.     

GAD65 antibody‐associated autoimmune epilepsy with unique independent bitemporal‐onset ictal asystole

Antibodies against the 65‐kDa isoform of the intracellular enzyme, glutamate decarboxylase (GAD65), have been found in patients with limbic encephalitis and drug‐resistant autoimmune epilepsy. We report a 22‐year‐old female who presented with new‐onset seizures and neuropsychiatric symptoms. Video‐EEG captured unique, independent bitemporal‐onset focal seizures with impaired awareness and ictal asystole. An autoimmune epilepsy panel revealed elevated GAD65 antibodies in the serum (225 nmol/l) and CSF (2.78 nmol/l), while [¹⁸F]‐fluoro‐deoxy‐glucose positron emission tomography showed bitemporal hypometabolism (left > right). The patient was diagnosed with GAD65 antibody‐associated autoimmune epilepsy. Our observation adds to the spectrum of neurocardiac syndromes associated with autoimmune epilepsy.