Sex-Dimorphic Effects of Hypoglycemia on Metabolic Sensor mRNA Expression in Ventromedial Hypothalamic Nucleus-Dorsomedial Division (VMNdm) Growth Hormone-Releasing Hormone Neurons.

Growth hormone-releasing hormone (Ghrh) neurons in the dorsomedial ventromedial hypothalamic nucleus (VMNdm) express the metabolic transcription factor steroidogenic factor-1 and hypoglycemia-sensitive neurochemicals of diverse chemical structures, transmission modes, and temporal signaling profiles. Ghrh imposes neuromodulatory control of coexpressed transmitters. Multiple metabolic sensory mechanisms are employed in the brain, including screening of the critical nutrient glucose or the energy currency ATP. Here, combinatory laser-catapult-microdissection/single-cell multiplex qPCR tools were used to investigate whether these neurons possess molecular machinery for monitoring cellular metabolic status and if these biomarkers exhibit sex-specific sensitivity to insulin-induced hypoglycemia. Data show that hypoglycemia up- (male) or downregulated (female) Ghrh neuron glucokinase (Gck) mRNA; Ghrh gene silencing decreased baseline and hypoglycemic patterns of Gck gene expression in each sex. Ghrh neuron glucokinase regulatory protein (Gckr) transcript levels were respectively diminished or augmented in hypoglycemic male vs female rats; this mRNA profile was decreased by Ghrh siRNA in both sexes. Gene transcripts encoding catalytic alpha subunits of the energy monitor 5-AMP-activated protein kinase (AMPK), i.e., Prkaa1 and 2, were increased by hypoglycemia in males, yet only the former mRNA was hypoglycemia-sensitive in females. Ghrh siRNA downregulated baseline and hypoglycemia-associated Prkaa subunit mRNAs in males but elicited divergent changes in Prkaa2 transcripts in eu- vs hypoglycemic females. Results provide unique evidence that VMNdm Ghrh neurons express the characterized metabolic sensor biomarkers glucokinase and AMPK and that the corresponding gene profiles exhibit distinctive sex-dimorphic transcriptional responses to hypoglycemia. Data further document Ghrh neuromodulation of baseline and hypoglycemic transcription patterns of these metabolic gene profiles.

Fostering effective and sustainable scientific collaboration and knowledge exchange: a workshop-based approach to establish a national ecological observatory network (NEON) domain-specific user group.

The decision to establish a network of researchers centers on identifying shared research goals. Ecologically specific regions, such as the USA's National Ecological Observatory Network's (NEON's) eco-climatic domains, are ideal locations by which to assemble researchers with a diverse range of expertise but focused on the same set of ecological challenges. The recently established Great Lakes User Group (GLUG) is NEON's first domain specific ensemble of researchers, whose goal is to address scientific and technical issues specific to the Great Lakes Domain 5 (D05) by using NEON data to enable advancement of ecosystem science. Here, we report on GLUG's kick off workshop, which comprised lightning talks, keynote presentations, breakout brainstorming sessions and field site visits. Together, these activities created an environment to foster and strengthen GLUG and NEON user engagement. The tangible outcomes of the workshop exceeded initial expectations and include plans for (i) two journal articles (in addition to this one), (ii) two potential funding proposals, (iii) an assignable assets request and (iv) development of classroom activities using NEON datasets. The success of this 2.5-day event was due to a combination of factors, including establishment of clear objectives, adopting engaging activities and providing opportunities for active participation and inclusive collaboration with diverse participants. Given the success of this approach we encourage others, wanting to organize similar groups of researchers, to adopt the workshop framework presented here which will strengthen existing collaborations and foster new ones, together with raising greater awareness and promotion of use of NEON datasets. Establishing domain specific user groups will help bridge the scale gap between site level data collection and addressing regional and larger ecological challenges.

Positive Bacterial Culture among Adults with Suspected Urinary Tract Infections Presenting to the Department of Medicine of a Tertiary Care Centre.

Introduction: Urinary tract infections are the most common infections encountered in clinical practice. Treatment needs to take into account the likely organism, comorbidities and local antibiotic sensitivity pattern. This study aimed to find the prevalence of positive bacterial culture among adults with suspected urinary tract infections presenting to the department of medicine of a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among adults with suspected urinary tract infections. Data was collected between 1 July 2022 to 31 December 2022 after obtaining ethical approval from the Institutional Review Committee. Individuals with symptomatic urinary tract infections were included in the study. The antibiotic susceptibility tests of the isolates were done. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: Among 355 patients, positive cultures were obtained in 148 (41.69%) (36.56-46.82, 95% Confidence Interval). Escherichia coli 120 (81.08%) was the predominant organism cultured among the positive bacterial culture cases. Conclusions: The prevalence of positive bacterial culture was found to be higher than other studies done in similar settings. Keywords: aminoglycosides; Escherichia coli; prevalence; urinary tract infections.

Diazepam Binding Inhibitor Control of Eu- and Hypoglycemic Patterns of Ventromedial Hypothalamic Nucleus Glucose-Regulatory Signaling.

Pharmacological stimulation/antagonism of astrocyte glio-peptide octadecaneuropeptide signaling alters ventromedial hypothalamic nucleus (VMN) counterregulatory γ-aminobutyric acid (GABA) and nitric oxide transmission. The current research used newly developed capillary zone electrophoresis-mass spectrometry methods to investigate hypoglycemia effects on VMN octadecaneuropeptide content, along with gene knockdown tools to determine if octadecaneuropeptide signaling regulates these transmitters during eu- and/or hypoglycemia. Hypoglycemia caused dissimilar adjustments in the octadecaneuropeptide precursor, i.e., diazepam-binding-inhibitor and octadecaneuropeptide levels in dorsomedial versus ventrolateral VMN. Intra-VMN diazepam-binding-inhibitor siRNA administration decreased baseline 67 and 65 kDa glutamate decarboxylase mRNA levels in GABAergic neurons laser-microdissected from each location, but only affected hypoglycemic transcript expression in ventrolateral VMN. This knockdown therapy imposed dissimilar effects on eu- and hypoglycemic glucokinase and 5'-AMP-activated protein kinase-alpha1 (AMPKα1) and -alpha2 (AMPKα2) gene profiles in dorsomedial versus ventrolateral GABAergic neurons. Diazepam-binding-inhibitor gene silencing up-regulated baseline (dorsomedial) or hypoglycemic (ventrolateral) nitrergic neuron neuronal nitric oxide synthase mRNA profiles. Baseline nitrergic cell glucokinase mRNA was up- (ventrolateral) or down- (dorsomedial) regulated by diazepam-binding-inhibitor siRNA, but knockdown enhanced hypoglycemic profiles in both sites. Nitrergic nerve cell AMPKα1 and -α2 transcripts exhibited division-specific responses to this genetic manipulation during eu- and hypoglycemia. Results document the utility of capillary zone electrophoresis-mass spectrometric tools for quantification of ODN in small-volume brain tissue samples. Data show that hypoglycemia has dissimilar effects on ODN signaling in the two major neuroanatomical divisions of the VMN and that this glio-peptide imposes differential control of glucose-regulatory neurotransmission in the VMNdm versus VMNvl during eu- and hypoglycemia.

GHRH Neurons from the Ventromedial Hypothalamic Nucleus Provide Dynamic and Sex-Specific Input to the Brain Glucose-Regulatory Network.

The ventromedial hypothalamic nucleus (VMN) controls glucose counter-regulation, including pituitary growth hormone (GH) secretion. VMN neurons that express the transcription factor steroidogenic factor-1/NR5A1 (SF-1) participate in glucose homeostasis. Research utilized in vivo gene knockdown tools to determine if VMN growth hormone-releasing hormone (Ghrh) regulates hypoglycemic patterns of glucagon, corticosterone, and GH outflow according to sex. Intra-VMN Ghrh siRNA administration blunted hypoglycemic hypercorticosteronemia in each sex, but abolished elevated GH release in males only. Single-cell multiplex qPCR showed that dorsomedial VMN (VMNdm) Ghrh neurons express mRNAs encoding Ghrh, SF-1, and protein markers for glucose-inhibitory (γ-aminobutyric acid) or -stimulatory (nitric oxide; glutamate) neurotransmitters. Hypoglycemia decreased glutamate decarboxylase67 (GAD67) transcripts in male, not female VMNdm Ghrh/SF-1 neurons, a response that was refractory to Ghrh siRNA. Ghrh gene knockdown prevented, in each sex, hypoglycemic down-regulation of Ghrh/SF-1 nerve cell GAD65 transcription. Ghrh siRNA amplified hypoglycemia-associated up-regulation of Ghrh/SF-1 neuron nitric oxide synthase mRNA in male and female, without affecting glutaminase gene expression. Ghrh gene knockdown altered Ghrh/SF-1 neuron estrogen receptor-alpha (ERα) and ER-beta transcripts in hypoglycemic male, not female rats, but up-regulated GPR81 lactate receptor mRNA in both sexes. Outcomes infer that VMNdm Ghrh/SF-1 neurons may be an effector of SF-1 control of counter-regulation, and document Ghrh modulation of hypoglycemic patterns of glucose-regulatory neurotransmitter along with estradiol and lactate receptor gene transcription in these cells. Co-transmission of glucose-inhibitory and -stimulatory neurochemicals of diverse chemical structure, spatial, and temporal profiles may enable VMNdm Ghrh neurons to provide complex dynamic, sex-specific input to the brain glucose-regulatory network.

Fusobacterium bacteremia presenting with inferior mesenteric vein thrombosis.

Isolated mesenteric vein thrombosis associated with Fusobacterium is rare. Physicians should be aware regarding the association of Fusobacterium with thrombosis at various sites.

The infectious salmon anemia virus esterase prunes erythrocyte surfaces in infected Atlantic salmon and exposes terminal sialic acids to lectin recognition.

Many sialic acid-binding viruses express a receptor-destroying enzyme (RDE) that removes the virus-targeted receptor and limits viral interactions with the host cell surface. Despite a growing appreciation of how the viral RDE promotes viral fitness, little is known about its direct effects on the host. Infectious salmon anemia virus (ISAV) attaches to 4-O-acetylated sialic acids on Atlantic salmon epithelial, endothelial, and red blood cell surfaces. ISAV receptor binding and destruction are effectuated by the same molecule, the haemagglutinin esterase (HE). We recently discovered a global loss of vascular 4-O-acetylated sialic acids in ISAV-infected fish. The loss correlated with the expression of viral proteins, giving rise to the hypothesis that it was mediated by the HE. Here, we report that the ISAV receptor is also progressively lost from circulating erythrocytes in infected fish. Furthermore, salmon erythrocytes exposed to ISAV ex vivo lost their capacity to bind new ISAV particles. The loss of ISAV binding was not associated with receptor saturation. Moreover, upon loss of the ISAV receptor, erythrocyte surfaces became more available to the lectin wheat germ agglutinin, suggesting a potential to alter interactions with endogenous lectins of similar specificity. The pruning of erythrocyte surfaces was inhibited by an antibody that prevented ISAV attachment. Furthermore, recombinant HE, but not an esterase-silenced mutant, was sufficient to induce the observed surface modulation. This links the ISAV-induced erythrocyte modulation to the hydrolytic activity of the HE and shows that the observed effects are not mediated by endogenous esterases. Our findings are the first to directly link a viral RDE to extensive cell surface modulation in infected individuals. This raises the questions of whether other sialic acid-binding viruses that express RDEs affect host cells to a similar extent, and if such RDE-mediated cell surface modulation influences host biological functions with relevance to viral disease.

Barraquer-Simons syndrome in systemic lupus erythematosus: A case report.

Barraquer-Simons syndrome is a rare entity characterized by progressive loss of subcutaneous tissue in the face and/or upper half of the body and can be associated with autoimmune conditions such as systemic lupus erythematosus. Close long-term follow-up is required to identify metabolic disturbances, potentially life-threatening renal problems, and other associated diseases.

Perception of Problem Based Learning by Undergraduate Dental Students in Basic Medical Science.

BACKGROUND: Problem based learning is self-directed form of learning. Problem of Diabetes Mellitus was chosen. The objective was to evaluate perception of students towards Problem based learning and test their understanding. METHODS: A descriptive study was conducted from November 2019 till October 2020. An online Problem based learning session of a week was conducted to second-year Bachelors of Dental Surgery students using online applications. Tutors facilitated students in a group of five to six each. Pre-post testing of evaluation questions was done. At end of session, feedback of students on Problem based learning and tutor of Problem based learning were received with 'Dolmans and Schmidt' and 'Dolmans and Ginns' questionnaire. RESULTS: There was increase in correct response in nine out of 12 evaluation questions. Most students agreed to influence of discussion, content tested, course objectives, lectures, tutor and reference literature. The students agreed that tutors facilitated active, self-directed, contextual and collaborative learning. CONCLUSIONS: The influence of discussion among participants, content tested, course objectives, reference literature during the Problem based learning session were agreed upon by majority of the students. The tutors' role was accepted by participants in terms of stimulation to self-directed, active, collaborative and contextual learning.

Cilnidipine for Amlodipine Induced Pedal Edema and its Anti-hypertensive Effect in a Tertiary Care Teaching Hospital of Western Nepal.

BACKGROUND: Hypertension is the most common cardiovascular disease. In Nepal, 27.3% populations are suffering from hypertension. Amlodipine is the most frequently prescribed anti-hypertensive drug. Up to 15% of patients develop pedal edema with amlodipine that may lead to discontinuation. Cilnidipine, a new calcium channel blocker, found equally effective and edema is uncommon in different studies from India. We aimed to study anti-hypertensive effect and to assess resolution of amlodipine induced Pedal edema with clinidipine. METHODS: This was a prospective, single centre observational study. Study was conducted in the department of cardiology, Manipal teaching hospital from 7th May to 6th November 2020. Hypertensive Patients who were on amlodipine for at least 6 months and presented with pedal edema were enrolled for the study. RESULTS: Total of 107 patients were enrolled for the study. The mean age of patients was 56.35 ± 12.84 years, ranged from 29 to 85 years and more than half(52.3 %) were male. Of the 107 patients, 90 (84.1%) patients received 10mg of clinidipine. On follow up, all patients except three (2.8%) had resolution of pedal edema. The blood pressure reduction with clinidipine was comparable with amlodipine (p: >0.05). Three patients who had persistent edema on follow up were on higher dose of clinidipine. CONCLUSIONS: The newer L and N type CCB, Clinidipine has comparable efficacy with amlodipine and well tolerated in our population. Though the incidence of pedal edema is low but can occur with clinidipine especially with higher doses.

Prevalence of wormian bones in dried adult human skulls: an osteo-morphometric study in Nepal.

The purpose of this study was to determine the incidence of wormian bones (WBs) in different head shapes of Nepalese skulls along with their distribution at various sites. This study was conducted on 70 Nepalese skulls obtained from the Department of Anatomy, Nepal Medical College, and the Institute of Medicine from September 2017 to January 2018. The skulls were examined for the presence and topographic distribution of WBs. The occurrence of WBs at various sites was correlated among different head shapes. The incidence of skulls showing WBs was 88.57%. The WBs were observed at the lambdoid (61.43%), parietomastoid (41.43%), occipitomastoid (27.14%), pterion (25.71%), asterion (24.29%), lambda (11.43%), sagittal (7.14%) and coronal sutures (4.28%). The dominant head type was dolichocephalic (44.29%) and the least dominant was brachycephalic (10%). The maximum number of WBs was shown on brachycephalic (mean 8.86 ± 7.13) then hyperdolichocephalic (mean 8.33 ± 9.15), mesaticephalic (mean 5.10 ± 4.45) and dolichocephalic heads (mean 4.16 ± 5.30). Brachycephalic heads frequently exhibited WBs at the pterion (57.14%) and at different sutures: lambdoid (71.42%), parietomastoid (57.14%), sagittal (28.57%) and squamous (14.28%). Hyperdolichocephalic heads displayed more lambda (33.33%) and coronal (8.33%) WBs. Similarly, dolichocephalic and mesaticephalic heads showed WBs at the occipitomastoid (35.48%) and asterion (30%), respectively. Inca bones were only identified in three dolichocephalic skulls. Neurosurgeons, radiologists and orthopedists should be careful when doing clinical and surgical procedures on different head shapes of the Nepalese population.

Correction to: Prevalence of wormian bones in dried adult human skulls: an osteo-morphometric study in Nepal.

In the original publication of the article, the affiliation of the coauthor Subash Sapkota and the formula of the cranial index were published incorrectly. The correct affiliation is provided in this correction.

Dengue and Scrub Typhus Coinfection in a Patient Presenting with Febrile Illness.

Dengue fever and scrub typhus are common causes of acute febrile illness of unclear origin in Asia. Though coinfections of many vector-borne diseases have been described, articles on dengue and scrub typhus coinfection are distinctly limited. In case of coinfection with dengue and scrub typhus, vigilant monitoring of vitals, platelets transfusion, and timely treatment with doxycycline are necessary. High degree of suspicion has to be made for coinfection in a patient presenting with febrile illness with thrombocytopenia and deranged laboratory parameters in postmonsoon season in endemic regions in Asia.

Etiology and adverse outcome predictors of upper gastrointestinal bleeding in 589 patients in Nepal.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a common clinical condition associated with significant morbidity and mortality. AIM: The purpose of this study was to determine the etiology of UGIB and predict the adverse outcome of variceal and non-variceal UGIB by using the parameters of validated scores. METHODS: This is a prospective observational study in which 589 UGIB patients underwent upper gastrointestinal endoscopy from May 2010 to April 2013 in Nepal. The variables of Glasgow-Blatchford score (GBS) and Rockall score (RS) were used to predict adverse outcomes, which were defined as transfusion, rebleeding, readmission, surgery and death within 30 days. RESULTS: Among UGIB patients, 33.1 % were variceal and 66.9 % were non-variceal bleeding (peptic ulcers 23.9 %, gastric erosion 16.5 % and others). The adverse outcomes of variceal and non-variceal UGIB were 77.9 % and 72.6 %, respectively. The significant predictors of adverse outcome were hemoglobin and systolic blood pressure in overall UGIB (p < 0.001), blood urea (p = 0.002), melena (p < 0.001) and syncope (p < 0.001) in variceal UGIB, and heart rate, melena, syncope and malignancy in non-variceal UGIB (p < 0.001). The area under receiver operating curve for adverse outcome in overall UGIB was 0.76, 0.80 and 0.94 using clinical RS, complete RS and GBS, respectively (p < 0.001). CONCLUSIONS: Variceal bleeding was the leading cause of UGIB in Nepal followed by peptic ulcers and gastric erosion. Those variables of GBS and RS, which were significant predictors of adverse outcome for UGIB, can be utilized in determining more aggressive endoscopic management during endoscopy, or more prolonged intravenous proton pump inhibitor use, or an additional day or two of hospitalization.