Knowledge, attitude, and practice regarding COVID-19 pandemic among medical students of Ernakulam, India

Background: COVID – 19 infection is a serious pandemic the world is now facing. This study aimed to assess the knowledge, attitude, and practice regarding COVID-19 infection among medical students at a private medical college in central Kerala.  Methods: A cross-sectional web-based study was conducted during April-May 2020 in a private medical college in Ernakulam District using the Universal sampling technique. The study tool was a semi-structured validated questionnaire containing sociodemographic details and questions on knowledge, attitude, and practice (KAP) regarding COVID-19 infection. Data were analyzed using SPSS version 20 software. Results: A total of 288 students were included in the study, with a mean age of 21±1.4. The male-to-female ratio was 2.75:1. Medical students showed adequate knowledge (81.6%), attitude (91.3%), and practice (84.7%) towards the COVID-19 pandemic, respectively. The main symptoms of COVID-19 infection were known to at least 83% of the participants. The majority (85.4%) were aware that there is no specific treatment for COVID-19 infection and 90% were aware of the main modes of the disease transmission. The majority (99%) of the medical students believed that COVID-19 infection could be prevented through social distancing, wearing masks, and the practice of self-hygiene. About 75.6% believed that government measures for prevention are adequate. Steam inhalation, saline gargling, and consumption of vitamin C-rich foodstuffs were the main specific measures adopted. Older age and female gender were found to be associated with better knowledge. Conclusion: Adequate KAP levels among medical students in this study are attributable to the current lockdown and the strict government measures to contain the infection

Prevalence and correlates of geriatric depression in a rural community in Kerala, India

Background: Elderly constitutes a vulnerable group for depression, as they are especially prone to suffer adverse consequences of a depressive episode and have greater rates of completed suicides. This study aims to estimate the prevalence and determinants of geriatric depression.  Methods: A cross-sectional study was done among 250 elderlies from 1st January 2019 to 1st January 2020 in the different rural blocks of Ernakulam district, India. The multistage sampling technique and the Geriatric Depression Scale (GDS-30) were used to collect the data. A score of 0 9 is considered "normal", 10 19 is labeled as "mildly depressed", and 20 30 as "severely depressed". Statistical analysis was performed using the IBM SPSS software. The Chi-square test /Fisher's exact test was used to study the association between the socio-demographic and behavioral variables with depression. Results: The mean age was 69.33 ± 7.41years and male: female ratio was 0.55: 1.The overall prevalence of depression was 52.4%. Advanced age over 70years [OR=2.04;95% CI, 1.227 – 3.394; P=0.006], female gender[OR=2.844;95% CI,1.663-4.865; P =<0.001], lack of gainful employment [OR=3.504; 95% CI, 1.833–6.699; P =<0.001], physical dependence [OR=0.365;95% CI,0.162–0.821; P =0.012], financial dependence [OR=0.388; 95% CI, 0.219–0.687; P =<0.001], presence of medical co morbidities [OR=0.428; 95% CI, 0.212–0.866; P =0.016],poor lifestyle including the lack of regular exercise [OR =2.020; 95% CI,1.174–3.473; P =0.010], addiction to alcohol [OR=4.932;95%CI,1.600-15.208; P =0.004] and addiction to tobacco smoking [OR=2.905;95%CI,1.273-6.628; P =0.009] and poor family support [OR= 5.180;95% CI,716–15.636; P = 0.002] were found to be significantly associated with depression. Conclusion: The prevalence of depression among the elderlies was high, and hence early diagnosis and prompt treatment are essential to reduce its burden in the community

Genetic background modifies vulnerability to glaucoma related phenotypes in Lmx1b mutant mice

Variants in the LIM homeobox transcription factor 1-beta (LMX1B) gene predispose individuals to elevated intraocular pressure (IOP), a key risk factor for glaucoma. However, the effect of LMX1Bmutations varies widely between individuals. To better understand the mechanisms underlying LMX1B-related phenotypes and individual differences, we backcrossed the Lmx1bV265D (also known as Lmx1bIcst ) allele onto the C57BL/6J (B6), 129/Sj (129), C3A/BLiA-Pde6b+ /J (C3H) and DBA/2J-Gpnmb+ (D2-G) mouse strain backgrounds. Strain background had a significant effect on the onset and severity of ocular phenotypes in Lmx1bV265D/+ mutant mice. Mice of the B6 background were the most susceptible to developing abnormal IOP distribution, severe anterior segment developmental anomalies (including malformed eccentric pupils, iridocorneal strands and corneal abnormalities) and glaucomatous nerve damage. By contrast, Lmx1bV265D mice of the 129 background were the most resistant to developing anterior segment abnormalities, had less severe IOP elevation than B6 mutants at young ages and showed no detectable nerve damage. To identify genetic modifiers of susceptibility to Lmx1bV265D -induced glaucoma-associated phenotypes, we performed a mapping cross between mice of the B6 (susceptible) and 129 (resistant) backgrounds. We identified a modifier locus on Chromosome 18, with the 129 allele(s) substantially lessening severity of ocular phenotypes, as confirmed by congenic analysis. By demonstrating a clear effect of genetic background in modulating Lmx1b-induced phenotypes, providing a panel of strains with different phenotypic severities and identifying a modifier locus, this study lays a foundation for better understanding the roles of LMX1B in glaucoma with the goal of developing new treatments

Inhibition of monocyte-like cell extravasation protects from neurodegeneration in DBA/2J glaucoma.

BACKGROUND: Glaucoma is characterized by the progressive dysfunction and loss of retinal ganglion cells. Recent work in animal models suggests that a critical neuroinflammatory event damages retinal ganglion cell axons in the optic nerve head during ocular hypertensive injury. We previously demonstrated that monocyte-like cells enter the optic nerve head in an ocular hypertensive mouse model of glaucoma (DBA/2 J), but their roles, if any, in mediating axon damage remain unclear. METHODS: To understand the function of these infiltrating monocyte-like cells, we used RNA-sequencing to profile their transcriptomes. Based on their pro-inflammatory molecular signatures, we hypothesized and confirmed that monocyte-platelet interactions occur in glaucomatous tissue. Furthermore, to test monocyte function we used two approaches to inhibit their entry into the optic nerve head: (1) treatment with DS-SILY, a peptidoglycan that acts as a barrier to platelet adhesion to the vessel wall and to monocytes, and (2) genetic targeting of Itgam (CD11b, an immune cell receptor that enables immune cell extravasation). RESULTS: Monocyte specific RNA-sequencing identified novel neuroinflammatory pathways early in glaucoma pathogenesis. Targeting these processes pharmacologically (DS-SILY) or genetically (Itgam / CD11b knockout) reduced monocyte entry and provided neuroprotection in DBA/2 J eyes. CONCLUSIONS: These data demonstrate a key role of monocyte-like cell extravasation in glaucoma and demonstrate that modulating neuroinflammatory processes can significantly lessen optic nerve injury

Tropomodulin1 is required for membrane skeleton organization and hexagonal geometry of fiber cells in the mouse lens

The spectrin–actin network is disrupted in Tmod1 mutants, disturbing fiber cell morphology, and disordering lens cell organization

The Drosophila Anion Exchanger (DAE) lacks a detectable interaction with the spectrin cytoskeleton

<p>Abstract</p> <p>Background</p> <p>Current models suggest that the spectrin cytoskeleton stabilizes interacting ion transport proteins at the plasma membrane. The human erythrocyte anion exchanger (AE1) was the first membrane transport protein found to be associated with the spectrin cytoskeleton. Here we evaluated a conserved anion exchanger from Drosophila (DAE) as a marker for studies of the downstream effects of spectrin cytoskeleton mutations.</p> <p>Results</p> <p>Sequence comparisons established that DAE belongs to the SLC4A1-3 subfamily of anion exchangers that includes human AE1. Striking sequence conservation was observed in the C-terminal membrane transport domain and parts of the N-terminal cytoplasmic domain, but not in the proposed ankyrin-binding site. Using an antibody raised against DAE and a recombinant transgene expressed in <it>Drosophila </it>S2 cells DAE was shown to be a 136 kd plasma membrane protein. A major site of expression was found in the stomach acid-secreting region of the larval midgut. DAE codistributed with an infolded subcompartment of the basal plasma membrane of interstitial cells. However, spectrin did not codistribute with DAE at this site or in anterior midgut cells that abundantly expressed both spectrin and DAE. Ubiquitous knockdown of DAE with dsRNA eliminated antibody staining and was lethal, indicating that DAE is an essential gene product in <it>Drosophila</it>.</p> <p>Conclusions</p> <p>Based on the lack of colocalization and the lack of sequence conservation at the ankyrin-binding site, it appears that the well-characterized interaction between AE1 and the spectrin cytoskeleton in erythrocytes is not conserved in <it>Drosophila</it>. The results establish a pattern in which most of the known interactions between the spectrin cytoskeleton and the plasma membrane in mammals do not appear to be conserved in <it>Drosophila</it>.</p

Anchoring skeletal muscle development and disease: the role of ankyrin repeat domain containing proteins in muscle physiology

The ankyrin repeat is a protein module with high affinity for other ankyrin repeats based on strong Van der Waals forces. The resulting dimerization is unusually resistant to both mechanical forces and alkanization, making this module exceedingly useful for meeting the extraordinary demands of muscle physiology. Many aspects of muscle function are controlled by the superfamily ankyrin repeat domain containing proteins, including structural fixation of the contractile apparatus to the muscle membrane by ankyrins, the archetypical member of the family. Additionally, other ankyrin repeat domain containing proteins critically control the various differentiation steps during muscle development, with Notch and developmental stage-specific expression of the members of the Ankyrin repeat and SOCS box (ASB) containing family of proteins controlling compartment size and guiding the various steps of muscle specification. Also, adaptive responses in fully formed muscle require ankyrin repeat containing proteins, with Myotrophin/V-1 ankyrin repeat containing proteins controlling the induction of hypertrophic responses following excessive mechanical load, and muscle ankyrin repeat proteins (MARPs) acting as protective mechanisms of last resort following extreme demands on muscle tissue. Knowledge on mechanisms governing the ordered expression of the various members of superfamily of ankyrin repeat domain containing proteins may prove exceedingly useful for developing novel rational therapy for cardiac disease and muscle dystrophies

Host-Toxin Interactions Involving EspC and Pet, Two Serine Protease Autotransporters of the Enterobacteriaceae

EspC and Pet are toxins secreted by the diarrheagenic enteropathogenic and enteroaggregative Escherichia coli pathotypes, respectively. Both toxins have a molecular mass around 110 kDa and belong to the same protein family called Serine Protease Autotransporters of the Enterobacteriaceae (SPATE). Furthermore, both toxins act within the cytosol of intoxicated epithelial cells to disrupt the architecture of the actin cytoskeleton. This cytopathic and enterotoxic effect results from toxin cleavage of the actin-binding protein fodrin, although the two toxins recognize different cleavage sites on fodrin. EspC and Pet also have dramatically different mechanisms of entering the target cell which appear dependent upon the E. coli pathotype. In this review, we compare/contrast EspC and Pet in regards to their mode of delivery into the target cell, their effects on fodrin and the actin cytoskeleton, and their possible effects on the physiology of the intestinal epithelial cell

GLIS1 regulates trabecular meshwork function and intraocular pressure and is associated with glaucoma in humans.

Chronically elevated intraocular pressure (IOP) is the major risk factor of primary open-angle glaucoma, a leading cause of blindness. Dysfunction of the trabecular meshwork (TM), which controls the outflow of aqueous humor (AqH) from the anterior chamber, is the major cause of elevated IOP. Here, we demonstrate that mice deficient in the Krüppel-like zinc finger transcriptional factor GLI-similar-1 (GLIS1) develop chronically elevated IOP. Magnetic resonance imaging and histopathological analysis reveal that deficiency in GLIS1 expression induces progressive degeneration of the TM, leading to inefficient AqH drainage from the anterior chamber and elevated IOP. Transcriptome and cistrome analyses identified several glaucoma- and extracellular matrix-associated genes as direct transcriptional targets of GLIS1. We also identified a significant association between GLIS1 variant rs941125 and glaucoma in humans (P = 4.73 × 1

Is Ankyrin a genetic risk factor for psychiatric phenotypes?

Background Genome wide association studies reported two single nucleotide polymorphisms in ANK3 (rs9804190 and rs10994336) as independent genetic risk factors for bipolar disorder. Another SNP in ANK3 (rs10761482) was associated with schizophrenia in a large European sample. Within the debate on common susceptibility genes for schizophrenia and bipolar disorder, we tried to investigate common findings by analyzing association of ANK3 with schizophrenia, bipolar disorder and unipolar depression. Methods We genotyped three single nucleotide polymorphisms (SNPs) in ANK3 (rs9804190, rs10994336, and rs10761482) in a case-control sample of German descent including 920 patients with schizophrenia, 400 with bipolar affective disorder, 220 patients with unipolar depression according to ICD 10 and 480 healthy controls. Sample was further differentiated according to Leonhard's classification featuring disease entities with specific combination of bipolar and psychotic syndromes. Results We found no association of rs9804190 and rs10994336 with bipolar disorder, unipolar depression or schizophrenia. In contrast to previous findings rs10761482 was associated with bipolar disorder (p = 0.015) but not with schizophrenia or unipolar depression. We observed no association with disease entities according to Leonhard's classification. Conclusion Our results support a specific genetic contribution of ANK3 to bipolar disorder though we failed to replicate findings for schizophrenia. We cannot confirm ANK3 as a common risk factor for different diseases