Knowledge and attitudes toward the COVID-19 vaccine among India's general rural population.

Introduction: Even after the enforcement of the lockdown, the government was unable to control the spread of the COVID-19 infection. Vaccination is the only remaining hope for preventing and controlling COVID-19 infections. The knowledge and attitude of the recipients can influence vaccine acceptance. In this study, we aim to assess the knowledge and attitude toward the COVID-19 vaccine among the general rural population of India. Methodology: A community-based, prospective, cross-sectional study was conducted from May 2021 to October 2021 in the rural part of the Mandya district of Karnataka, India. Individuals over the age of 18 who met the Ministry of Health and Family Welfare's vaccination eligibility criteria were included in the study. Demographic details of participants and assessment of knowledge and attitude towards the COVID-19 vaccine were done in a designed and validated data collection form. Results: The study included 596 participants, with females dominating males by 54.9 % (327). The average age of the participants was 31 years. Among them, 81.71% (487) had adequate knowledge, and 81.5% (486) had a positive attitude towards the COVID-19 vaccine. Females (85.3%, 279) tend to have a more positive attitude than males (77%, 207). Positive attitude participants (86.86 %, 423) have a higher level of knowledge about the COVID-19 vaccine than negative attitude participants (57.79 %, 63). Conclusion: In the study, we found that 81.71% had adequate knowledge and 81.5% had a positive attitude toward the COVID-19 vaccine.

Introducción: Incluso tras la obligatoriedad del confinamiento el gobierno fue incapaz de controlar la propagación de la infección por COVID-19. La vacuna es la única esperanza que queda para prevenir y controlar las infecciones por COVID-19. El conocimiento y la actitud de los receptores pueden influir en la aceptación de la vacuna. En este estudio, nuestro objetivo fue evaluar el conocimiento y la actitud hacia la vacuna contra la COVID-19 entre la población rural general de India. Metodología: Se realizó un estudio transversal, prospectivo y con base comunitaria de mayo a octubre de 2021 en la zona rural del distrito Mandya de Karnataka, India. Se incluyó en el estudio a los individuos mayores de 18 años que cumplieron los criterios de elegibilidad del Ministerio de Sanidad y Bienestar Familiar. Los datos demográficos de los participantes y la evaluación del conocimiento y la actitud hacia la vacuna contra la COVID-19 se incluyeron en un formulario de recopilación de datos diseñado y validado. Resultados: El estudio incluyó a 596 participantes, siendo más numerosas las mujeres que los hombres en un 54,9 % (327). La edad media de los participantes fue de 31 años. Entre ellos, el 81,71% (487) tenía un conocimiento adecuado, y el 81,5% (486) una actitud positiva hacia la vacuna contra la COVID-19. Las mujeres (85,3%, 279) tendieron a tener una actitud más positiva que los hombres (77%, 207). Los participantes con actitud positiva (86,86 %, 423) tuvieron un mayor nivel de conocimiento sobre la vacuna contra la COVID-19 que los participantes con actitud negativa (57,79 %, 63). Conclusión: En el estudio, encontramos que el 81,71% tuvo un conocimiento adecuado, y el 81,5% una actitud positiva hacia la vacuna contra la COVID-19.

The prevalence of inverse health consequences of COVID-19 vaccines: A post-vaccination study.

Background: COVID-19 vaccinations are intended to help produce neutralizing antibodies which target surface spike protein to combat the SARS-Cov-2 virus. Similarly, COVID-19 recovered patients exhibit high levels of SARS-CoV-2 neutralizing antibodies, which predominantly target the surface spike protein and are associated with the occurrence of health consequences in survivors. Objective: The aim of the study is to explore the long-term health consequences of the COVID-19 vaccines. Methodology: A prospective, exploratory observational study conducted both online and offline using various questionnaires with all immunized individuals who had been inoculated for at least a month following their last COVID-19 vaccine either AZD1222® or BBV152® vaccines. Results: We evaluated 258 individuals who had taken the COVID vaccine and found that females made up the majority (54.3%) and that the mean age was 24 years. Post-vaccination long-term health issues were reported by 36.05% (93) of the participants, with 37.86% (53) of females and 33.9% (40) of males (p = 0.292). Myalgia was reported by 20.15% (52), fatigue was 13.95% (36), paresthesia was 1.16% (3), ageusia was 0.77% (2), sadness/irritability was 2.31% (6), and lack of concentration/excessive worry was 3.1% (8). Conclusions: Myalgia, fatigue, paresthesia, ageusia, coughs and colds, dyspnea, sadness/irritability, and lack of concentration/excessive worry are health consequences related to the COVID-19 vaccination which follow a similar pattern of post-COVID syndrome.

Antecedentes: El objetivo de las vacunas frente a la COVID-19 es el de ayudar a producir anticuerpos neutralizantes dirigidos a la proteína de la espícula para combatir el virus SARS-Cov-2. De igual modo, los pacientes que se recuperan de la COVID-19 exhiben grandes niveles de anticuerpos neutralizantes de SARS-CoV-2, que se dirigen predominantemente a la superficie de la proteína de la espícula, y están asociados a la incidencia de consecuencias para la salud de los sobrevivientes. Objetivo: El objetivo del estudio es explorar las consecuencias para la salud a largo plazo de las vacunas frente a la COVID-19. Metodología: Estudio prospectivo, exploratorio y observacional realizado tanto online como offline, utilizando diversos cuestionarios con todos los individuos vacunados a quienes se había inoculado en el plazo de al menos un mes, tras la última vacuna frente a la COVID-19, bien fueran las vacunas AZD1222® o BBV152®. Resultados: Evaluamos a 258 individuos que habían recibido la vacuna frente a la COVID, y encontramos que la mayoría eran mujeres (54,3%) con una edad media de 24 años. Las cuestiones de salud a largo plazo, tras la vacuna, fueron reportadas por un 36,05% (93) de los participantes, con un 37,86% (53) de mujeres y un 33.9% (40) de varones (p = 0,292). Se reportó mialgia en el 20,15% (52) de los casos, fatiga en el 13,95% (36), parestesia en el 1,16% (3), ageusia en el 0,77% (2), tristeza/irritabilidad en el 2,31% (6), y falta de concentración/preocupación excesiva en el 3,1% (8). Conclusiones: Mialgia, fatiga, parestesia, ageusia, tos y resfriado, disnea, tristeza/irritabilidad, y falta de concentración/preocupación excesiva son las consecuencias de salud relacionadas con la vacuna frente a la COVID-19, y siguen un patrón similar al del síndrome post-COVID.

The rise in antimicrobial resistance: An obscure issue in COVID-19 treatment.

A saturated health care system with a lack of evidence-based antiviral medicine and ignorance of antimicrobial stewardship during pandemics has prompted clinicians to prescribe a broad-spectrum antibiotic more often. A prospective, cross-sectional study of COVID-infected patients was conducted to gain insight into antibiotic prescribing practices and their impact on antimicrobial resistance. The antibiotic susceptibility test was performed using the disc diffusion method. 318 patients met the study's inclusion criteria, with a mean age of 46 years and 55% (175) of them being males. Antibiotics were prescribed for 93.72% (209) of mild cases, 92.45% (49) of moderate cases, 96.15% (25) of severe cases, and 100% (16) of critical cases of COVID-19. A total of 95 samples were sent in for culture and antibiotic sensitivity testing, with 58.95% (56) confirming growth. The majority of the growth was found to contain E. coli (14). In 54.9% of cases, antibiotics with less than 50% sensitivity to curing bacterial infection were detected. In the study, we found that antibiotics were being used unnecessarily in excessive quantities and that more than half of the antibiotics were less sensitive to isolated bacteria.

Hypermagnesemia in critically ill patients with cancer: A case report.

Hypermagnesemia is often an under reported finding in critically ill patients with cancer. Hypomagnesemia is a commonly encountered electrolyte abnormality in patients with cancer that is primarily caused by a reduced intake, secondary to chemotherapeutic drugs and malnutrition. Hypermagnesemia is rarely observed in patients with normal renal function, as excess intake can be compensated by renal excretion. However, in critically ill patients with reduced renal function, hypermagnesemia can add further to complications and increase mortality. Drugs such as lactulose, antacids, fentanyl and peptide hormones, including vasopressin, can further increase chances of hypermagnesemia, particularly when patients demonstrate decreased renal function and multiple organ failure. Prudence and caution must therefore be exercised while using these agents in critically ill patients with cancer to avoid increased complications and mortality. Herein, the current study reports three cases of critically ill patients with cancer admitted into intensive care who had refractory hypermagnesemia.

Gsα deficiency in the dorsomedial hypothalamus leads to obesity, hyperphagia, and reduced thermogenesis associated with impaired leptin signaling.

OBJECTIVE: Gsα couples multiple receptors, including the melanocortin 4 receptor (MC4R), to intracellular cAMP generation. Germline inactivating Gsα mutations lead to obesity in humans and mice. Mice with brain-specific Gsα deficiency also develop obesity with reduced energy expenditure and locomotor activity, and impaired adaptive thermogenesis, but the underlying mechanisms remain unclear. METHODS: We created mice (DMHGsKO) with Gsα deficiency limited to the dorsomedial hypothalamus (DMH) and examined the effects on energy balance and thermogenesis. RESULTS: DMHGsKO mice developed severe, early-onset obesity associated with hyperphagia and reduced energy expenditure and locomotor activity, along with impaired brown adipose tissue thermogenesis. Studies in mice with loss of MC4R in the DMH suggest that defective DMH MC4R/Gsα signaling contributes to abnormal energy balance but not to abnormal locomotor activity or cold-induced thermogenesis. Instead, DMHGsKO mice had impaired leptin signaling along with increased expression of the leptin signaling inhibitor protein tyrosine phosphatase 1B in the DMH, which likely contributes to the observed hyperphagia and reductions in energy expenditure, locomotor activity, and cold-induced thermogenesis. CONCLUSIONS: DMH Gsα signaling is critical for energy balance, thermogenesis, and leptin signaling. This study provides insight into how distinct signaling pathways can interact to regulate energy homeostasis and temperature regulation.

Gsα deficiency in the dorsomedial hypothalamus underlies obesity associated with Gsα mutations.

Gsα, encoded by Gnas, mediates hormone and neurotransmitter receptor-stimulated cAMP generation. Heterozygous Gsα-inactivating mutations lead to obesity in Albright hereditary osteodystrophy (AHO) patients, but only when the mutations occur on the maternal allele. This parent-of-origin effect is due to Gsα imprinting in the CNS, although the relevant CNS regions are unknown. We have now shown that mice with a Gnas gene deletion disrupting Gsα expression on the maternal allele, but not the paternal allele, in the dorsomedial nucleus of the hypothalamus (DMH) developed obesity and reduced energy expenditure without hyperphagia. Although maternal Gnas deletion impaired activation of brown adipose tissue (BAT) in mice, their responses to cold environment remained intact. Similar findings were observed in mice with DMH-specific deficiency of melanocortin MC4R receptors, which are known to activate Gsα. Our results show that Gsα imprinting in the DMH underlies the parent-of-origin metabolic phenotype that results from Gsα mutations and that DMH MC4R/Gsα signaling is important for regulation of energy expenditure and BAT activation, but not the metabolic response to cold.

G(q/11)α and G(s)α mediate distinct physiological responses to central melanocortins.

Activation of brain melanocortin 4 receptors (MC4Rs) leads to reduced food intake, increased energy expenditure, increased insulin sensitivity, and reduced linear growth. MC4R effects on energy expenditure and glucose metabolism are primarily mediated by the G protein G(s)α in brain regions outside of the paraventricular nucleus of the hypothalamus (PVN). However, the G protein(s) that is involved in MC4R-mediated suppression of food intake and linear growth, which are believed to be regulated primarily though action in the PVN, is unknown. Here, we show that PVN-specific loss of G(q)α and G11α, which stimulate PLC, leads to severe hyperphagic obesity, increased linear growth, and inactivation of the hypothalamic-pituitary-adrenal axis, without affecting energy expenditure or glucose metabolism. Moreover, we demonstrate that the ability of an MC4R agonist delivered to PVN to inhibit food intake is lost in mice lacking G(q/11)α in the PVN but not in animals deficient for G(s)α. The blood pressure response to the same MC4R agonist was only lost in animals lacking G(s)α specifically in the PVN. Together, our results exemplify how different physiological effects of GPCRs may be mediated by different G proteins and identify a pathway for appetite regulation that could be selectively targeted by G(q/11)α-biased MC4R agonists as a potential treatment for obesity.

Gsα deficiency in adipose tissue improves glucose metabolism and insulin sensitivity without an effect on body weight.

Gsα, the G protein that transduces receptor-stimulated cAMP generation, mediates sympathetic nervous system stimulation of brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT), which are both potential targets for treating obesity, as well as lipolysis. We generated a mouse line with Gsα deficiency in mature BAT and WAT adipocytes (Ad-GsKO). Ad-GsKO mice had impaired BAT function, absent browning of WAT, and reduced lipolysis, and were therefore cold-intolerant. Despite the presence of these abnormalities, Ad-GsKO mice maintained normal energy balance on both standard and high-fat diets, associated with decreases in both lipolysis and lipid synthesis. In addition, Ad-GsKO mice maintained at thermoneutrality on a standard diet also had normal energy balance. Ad-GsKO mice had improved insulin sensitivity and glucose metabolism, possibly secondary to the effects of reduced lipolysis and lower circulating fatty acid binding protein 4 levels. Gsα signaling in adipose tissues may therefore affect whole-body glucose metabolism in the absence of an effect on body weight.

Neural innervation of white adipose tissue and the control of lipolysis.

White adipose tissue (WAT) is innervated by the sympathetic nervous system (SNS) and its activation is necessary for lipolysis. WAT parasympathetic innervation is not supported. Fully-executed SNS-norepinephrine (NE)-mediated WAT lipolysis is dependent on ß-adrenoceptor stimulation ultimately hinging on hormone sensitive lipase and perilipin A phosphorylation. WAT sympathetic drive is appropriately measured electrophysiologically and neurochemically (NE turnover) in non-human animals and this drive is fat pad-specific preventing generalizations among WAT depots and non-WAT organs. Leptin-triggered SNS-mediated lipolysis is weakly supported, whereas insulin or adenosine inhibition of SNS/NE-mediated lipolysis is strongly supported. In addition to lipolysis control, increases or decreases in WAT SNS drive/NE inhibit and stimulate white adipocyte proliferation, respectively. WAT sensory nerves are of spinal-origin and sensitive to local leptin and increases in sympathetic drive, the latter implicating lipolysis. Transsynaptic viral tract tracers revealed WAT central sympathetic and sensory circuits including SNS-sensory feedback loops that may control lipolysis.

Pmch-deficiency in rats is associated with normal adipocyte differentiation and lower sympathetic adipose drive.

The orexigenic neuropeptide melanin-concentrating hormone (MCH), a product of Pmch, is an important mediator of energy homeostasis. Pmch-deficient rodents are lean and smaller, characterized by lower food intake, body-, and fat mass. Pmch is expressed in hypothalamic neurons that ultimately are components in the sympathetic nervous system (SNS) drive to white and interscapular brown adipose tissue (WAT, iBAT, respectively). MCH binds to MCH receptor 1 (MCH1R), which is present on adipocytes. Currently it is unknown if Pmch-ablation changes adipocyte differentiation or sympathetic adipose drive. Using Pmch-deficient and wild-type rats on a standard low-fat diet, we analyzed dorsal subcutaneous and perirenal WAT mass and adipocyte morphology (size and number) throughout development, and indices of sympathetic activation in WAT and iBAT during adulthood. Moreover, using an in vitro approach we investigated the ability of MCH to modulate 3T3-L1 adipocyte differentiation. Pmch-deficiency decreased dorsal subcutaneous and perirenal WAT mass by reducing adipocyte size, but not number. In line with this, in vitro 3T3-L1 adipocyte differentiation was unaffected by MCH. Finally, adult Pmch-deficient rats had lower norepinephrine turnover (an index of sympathetic adipose drive) in WAT and iBAT than wild-type rats. Collectively, our data indicate that MCH/MCH1R-pathway does not modify adipocyte differentiation, whereas Pmch-deficiency in laboratory rats lowers adiposity throughout development and sympathetic adipose drive during adulthood.

Effect of reducing hypothalamic ghrelin receptor gene expression on energy balance.

Central and peripheral injections of fghrelin potently stimulates food intake via its receptor, GHSR1a expressed in the brain. In this study, we explored the role of GHSR1a in the paraventricular nucleus of the hypothalamus (PVN) by reducing their gene expression using the RNA interference (RNAi). pSUPER plasmids inserted with sh (short hairpin)-GHSR1a were injected into the PVN to reduce its expression. The transfected rats were monitored daily for their food intake and body weight throughout the experimental period lasting 8 days. We found that knockdown of GHSR1a did not affect daily food intake but significantly reduced body weight and blood ghrelin levels. This suggests that the central ghrelin system could selectively regulate body weight without affecting energy intake.

Direct effects of nutrients, acetylcholine, CCK, and insulin on ghrelin release from the isolated stomachs of rats.

Ghrelin is a powerful orexigenic peptide predominantly secreted by the stomach. Blood concentration of ghrelin increases before meals and fall postprandial. Its regulation appears to be influenced by the type of macronutrient ingested, the vagus nerve stimulation and by other post-meal stimulated hormonal factors. However, the direct role of nutrients (amino acids or lipids), neuronal (vagal neurotransmitter acetylcholine) and satiety-inducing factor such as CCK are not known. To study this we applied amino acids, lipids, acetylcholine and CCK via vascular perfusion to the isolated stomachs and found that amino acids significantly reduced ghrelin release from the isolated stomach by approximately approximately 30% vs. the control while lipids (10% intralipid) had no affect. Acetylcholine (1 microM) increased ghrelin release from the stomach by approximately 37% whereas insulin (10nM) decreased it by approximately 30% vs. the control. Interestingly, CCK (100 nM) potently increased ghrelin release by approximately 200% vs. the control. Therefore it appears that ghrelin secretion from the stomach is under direct influence of amino acids, neurotransmitter acetylcholine and hormones such as insulin and CCK.

Role of AgRP on Ghrelin-induced feeding in the hypothalamic paraventricular nucleus.

MT II, agonist for MC3/4-Rs, inhibited Ghrelin's orexigenic effect in the paraventricular nucleus of the hypothalamus (PVN). To further investigate the role of the melanocortin system as mediator of ghrelin's orexigenic actions, we explored the involvement of AgRP in Ghrelin's orexigenic effect by testing the effect on food intake after their co-administration in the PVN, during the light and dark phases of feeding in rats. During both the phases of feeding, co-administration of Ghrelin with either AgRP 50 or AgRP 100 pmol into the PVN did not produce a synergistic effect on the food intake, suggesting that ghrelin induction of feeding occurs by recruiting Agrp as one of the obligatory mediators of its orexigenic effect.

Action of MT-II on ghrelin-induced feeding in the paraventricular nucleus of the hypothalamus.

Ghrelin is a 28 amino-acid peptide that has been shown to induce positive energy balance when administered both peripherally and centrally. This effect appears to occur by increasing food intake and by reducing fat utilization. Ghrelin injected into the PVN increases food intake dose-dependently. The NPY receptor has been implicated in the orexigenic effect of ghrelin, but until now, the role of melanocortins on the effect of ghrelin in the PVN has not been reported. Sprague-Dawley rats were stimulated to eat by PVN ghrelin. Pre-injection of 10 pmol of MT II into the PVN caused a significant decrease in ghrelin-induced feeding in both 0-1 h and 0-4 h food intake studies. This finding indicates that MC 3/4-R signaling appears to be recruited by ghrelin, in the PVN, in its role to induce feeding.

The role of ghrelin and growth hormone secretagogues receptor on rat adipogenesis.

Recent research progress indicates a close link between ghrelin, a natural ligand of GH secretagogues receptor (GHS-R), and both the metabolic balance and body composition. To clarify the involvement of ghrelin and GHS-R in the process of adipogenesis, we measured the expression of GHS-R and peroxisome proliferator-activated receptor gamma 2 (PPAR-gamma 2) mRNA in rat adipocytes using semiquantitative RT-PCR methods. The levels of GHS-R mRNA increased by up to 4-fold in adipose tissue from epididymal and parametrial regions as the rat aged from 4-20 wk and were significantly elevated during the differentiation of preadipocytes in vitro. Ghrelin (10(-8) M for 10 d) stimulated the activity of glycerol-3-phosphate dehydrogenase and the differentiation of rat preadipocytes in vitro. Ghrelin treatment also significantly increased the levels of PPAR-gamma 2 mRNA in primary cultured rat differentiated adipocytes. In addition, isoproterenol (10(-8) M, 40 min)-stimulated lipolysis was significantly reduced by simultaneous ghrelin treatment in a dose-dependent manner in vitro. In conclusion, the expression of GHS-R in rat adipocytes increases with the age and during adipogenesis. Ghrelin in vitro stimulates the differentiation of preadipocytes and antagonizes lipolysis. Ghrelin may therefore play an important role in the process of adipogenesis in rats.

Is GHRH receptor essential to GHRP-2-induced GH secretion in primary cultured rat pituitary cells?

It is still controversial in rat whether the stimulation of GH secretion by GH-releasing peptides (GHRP) requires both GHRP receptor (GHRP-R) and GH-releasing hormone receptor (GHRH-R). To clarify this issue, we have postulated that inhibition of GHS-R or GHRH-R gene transcription should block GHRP-2-induced GH secretion. Rat pituitary cells were incubated for 3 days in the presence or absence of antisense 18-mer phosphorothiate oligonucleotides (ONs) complementary to the codon region of GHS-R or GHRH-R mRNAs. A significant decrease in GHRH-R and GHS-R mRNA levels was found in corresponding antisense-treated cells compared with the control cells treated with sense ON. Treatment with antisense GHS-R ON reduced (but not abolished) GHRP-2-induced GH secretion although GHRH-induced GH secretion was not altered. GHRH-stimulated GH secretion was totally abolished by the treatment with antisense GHRH-R ON, whereas GHRP-2 induced GH secretion was not affected. Treatment of cells with both GHS-R and GHRH-2 ONs however completely inhibited GHRH and GHRP-2-stimulated GH secretion. These results suggest that GHRH-R is vital for GHRH-induced GH secretion but only partially involved in GHRP-2-stimulated GH secretion under the condition of down-regulation of GHS-R gene transcription.