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Background Many studies have been conducted on heart, liver, and endocrine abnormalities in thalassemia; however, studies on pulmonary dysfunction (PD) have been limited. Previous studies on the prevalence of restrictive lung disease (RLD) and obstructive lung disease (OLD) in β-thalassemia major patients have lacked agreement. Objective To assess the prevalence of PD in β-thalassemia major patients by systematic review of the literature and meta-analysis. Methods We searched Cochrane library, PubMed, Web of Science, MEDLINE, Scopus, and Embase for relevant articles. Articles were selected according to the inclusion criteria and data were extracted. The primary outcome was prevalence of pulmonary dysfunction in β-thalassemia major with 95% confidence interval (95%CI). Subgroup analyses were applied to explore the prevalence in different age groups, regions, and serum ferritin levels. Sensitivity analysis and publication bias assessment were also conducted. Results A total of 37 studies comprising 1,467 cases were included in this analysis. Pulmonary dysfunction was present in 64.7% (95%CI 57.6 to 71.1) of cases. The pooled prevalence of RLD (44.9%) was higher than that of OLD (7.6%) and diffusion impairment (DI) (35.6%). Subgroup analysis revealed that the region with the highest pooled prevalence of PD was the Americas (75.2%). The highest prevalence of RLD and DI was found in Asia (48.2% and 44.6%, respectively) and that of OLD in Europe (9.7%). Sensitivity analysis showed that the pooled results were robust. Conclusion A high prevalence of pulmonary dysfunction, mainly RLD rather than OLD, was detected in β-thalassemia major patients.

Background& Objective: Ever changing dynamic field of science, technology and health care had made it essential for a health care professional to keep abreast of the latest development. Continuous Professional Development (CPD) can be considered as a process in which individual practitioners identify their own learning needs, makes plan to meet those objectives and finally evaluates the effectiveness of the plan .Perceived barriers to CPD vary significantly by individual's personal characteristics, job position, and organizational factors. Present study was done to explore the faculty views of CPD in terms of its need, methods, impact and barriers. Objectives: 1.To assess the perceptions of healthcare faculty about Continuous Professional Development 2. To identify the barriers perceived by health care faculty for Continuous Professional Development. Methodology: A Cross Sectional study was conducted among 32 faculty, enrolled for Foundation for Advancement in International Medical Education and Research (FAIMER) Fellowship programme at one of the regional institutes of India. A self-administered structured and modified questionnaire was given to participants as a part of Mentoring and Learning (ML) web sessions through 'Survey Monkey". Results: In the study, 16 (50%) out of 32 faculty members participated, where majority of participants considered attending conferences, reading journals and E-learning Modules as a CPD activity undertaken in the past one year. Nearly all participants agreed that CPD can make positive change in terms of diagnostic and treatment practices (81.25%), knowledge acquisition (100%) as well as attitude (93.75%) towards patients. Availability of study leave (56.25%) and work-life balance (75%) were significant barriers to participation. Participants strongly believed that CPD helps to recognize knowledge gaps, promoted self-reflection and focused endeavours. Conclusion: Present study reported good knowledge, favourable attitudes and practices towards Continuous Professional Development activities among health care faculty members. The study also revealed combination of responses among faculty about their own CPD activities. [ABSTRACT FROM AUTHOR]

Background and Purpose: Agmatine, a multifaceted neurotransmitter, is abundantly expressed in the hypothalamic paraventricular nucleus (PVN). Our aim was to assess (i) the effect of agmatine on feeding behaviour and (ii) its association, if any, with neuropeptide Y (NPY).Experimental Approach: Satiated rats fitted with intra-PVN cannulae were administered agmatine, alone or jointly with (i) α₂-adrenoceptor agonist, clonidine, or antagonist, yohimbine; (ii) NPY, NPY Y₁ receptor agonist, [Leu³¹, Pro³⁴]-NPY, or antagonist, BIBP3226; or (iii) yohimbine and NPY. Cumulative food intake was monitored at different post-injection time points. Furthermore, the expression of hypothalamic NPY following i.p. treatment with agmatine, alone or in combination with yohimbine (i.p.), was evaluated by immunocytochemistry.Key Results: Agmatine robustly increased feeding in a dose-dependent manner. While pretreatment with clonidine augmented, yohimbine attenuated the orexigenic response to agmatine. Similarly, NPY and [Leu³¹, Pro³⁴]-NPY potentiated the agmatine-induced hyperphagia, whereas BIBP3226 inhibited it. Moreover, yohimbine attenuated the synergistic orexigenic effect induced by the combination of NPY and agmatine. Agmatine increased NPY immunoreactivity in the PVN fibres and in the cells of the hypothalamic arcuate nucleus (ARC) and this effect was prevented by pretreatment with yohimbine. NPY immunoreactivity in the fibres of the ARC, dorsomedial, ventromedial and lateral nuclei of the hypothalamus was not affected by any of the above treatments.Conclusions and Implications: The orexigenic effect of agmatine is coupled to increased NPY activity mediated by stimulation of α₂-adrenoceptors within the PVN. This signifies the importance of agmatine or α₂-adrenoceptor modulators in the development of novel therapeutic agents to treat feeding-related disorders. [ABSTRACT FROM AUTHOR]

An autosomal dominant neurodegenerative disease called Huntington's disease (HD) is characterized by motor dysfunction, cognitive decline, and a variety of psychiatric symptoms due to the expansion of polyglutamine in the Huntingtin gene. The disease primarily affects the striatal neurons within the basal ganglia, leading to significant neuronal loss and associated symptoms such as chorea and dystonia. Current therapeutic approaches focus on symptom management without altering the disease's progression, highlighting a pressing need for novel treatment strategies. Recent studies have identified imidazoline receptors (IRs) as promising targets for neuroprotective and disease-modifying interventions in HD. IRs, particularly the I1 and I2 subtypes, are involved in critical physiological processes such as neurotransmission, neuronal excitability, and cell survival. Activation of these receptors has been shown to modulate neurotransmitter release and provide neuroprotective effects in preclinical models of neurodegeneration. This review discusses the potential of IR-targeted therapies to not only alleviate multiple symptoms of HD but also possibly slow the progression of the disease. We emphasize the necessity for ongoing research to further elucidate the role of IRs in HD and develop selective ligands that could lead to effective and safe treatments, thereby significantly improving patient outcomes and quality of life., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Depression is a global health concern affecting nearly 280 million individuals. It not only imposes a significant burden on economies and healthcare systems but also manifests complex physiological connections and consequences. Agmatine, a putative neuromodulator derived primarily from beneficial gut microbes specially Lactobacillus, has emerged as a potential therapeutic agent for mental health. The microbiota-gut-brain axis is involved in the development of depression through the peripheral nervous system, endocrine system, and immune system and may be a key factor in the effect of agmatine. Therefore, this study aimed to investigate the potential mechanism of agmatine in antibiotic-induced dysbiosis and depression-like behavior in rats, focusing on its modulation of the gut-brain axis. Depression-like behavior associated with dysbiosis was induced through a seven-day regimen of the broad-spectrum antibiotic, comprising ampicillin and metronidazole and validated through microbial, biochemical, and behavioral alterations. On day 8, antibiotic-treated rats exhibited loose fecal consistency, altered fecal microbiota, and depression-like behavior in forced swim test. Pro-inflammatory cytokines were elevated, while agmatine and monoamine levels decreased in the hippocampus and prefrontal cortex. Antibiotic administration disrupted tight junction proteins in the ileum, affecting gut architecture. Oral administration of agmatine alone or combined with probiotics significantly reversed antibiotic-induced dysbiosis, restoring gut microbiota and mitigating depression-like behaviors. This intervention also restored neuro-inflammatory markers, increased agmatine and monoamine levels, and preserved gut integrity. The study highlights the regulatory role of endogenous agmatine in the gut-brain axis in broad-spectrum antibiotic induced dysbiosis and associated depression-like behavior., Competing Interests: Declaration of competing interest Authors declare that there are no conflicts of any interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Huntington's disease (HD) is a progressive neurodegenerative condition characterized by a severe motor incoordination, cognitive decline, and psychiatric complications. However, a definitive cure for this devastating disorder remains elusive. Agmatine, a biogenic amine, has gain attention for its reported neuromodulatory and neuroprotective properties. The present study was designed to examine the influence of agmatine on the behavioral, biochemical, and molecular aspects of HD in an animal model. A mitochondrial toxin, 3-nitro propionic acid (3-NP), was used to induce HD phenotype and similar symptoms such as motor incoordination, memory impairment, neuro-inflammation, and depressive-like behavior in rats. Rats were pre-treated with 3-NP (10 mg/kg, i.p.) on days 1, 3, 5, 7, and 9 and then continued on agmatine treatment (5 - 20 µg/rat, i.c.v.) from day-8 to day-27 of the treatment protocol. 3-NP-induced cognitive impairment was associated with declined in agmatine levels within prefrontal cortex, striatum, and hippocampus. Further, the 3-NP-treated rats showed an increase in IL-6 and TNF-α and a reduction in BDNF immunocontent within these brain areas. Agmatine treatment not only improved the 3-NP-induced motor incoordination, depression-like behavior, rota-rod performance, and learning and memory impairment but also normalized the GABA/glutamate, BDNF, IL-6, and TNF-α levels in discrete brain areas. Similarly, various agmatine modulators, which increase the endogenous agmatine levels in the brain, such as L-arginine (biosynthetic precursor), aminoguanidine (diamine oxidase inhibitor), and arcaine (agmatinase inhibitor) also demonstrated similar effects exhibiting the importance of endogenous agmatinergic pathway in the pathogenesis of 3-NP-induced HD like symptoms. The present study proposed the possible role of agmatine in the pathogenesis and treatment of HD associated motor incoordination, and psychiatric and cognitive complications., Competing Interests: Declaration of Competing Interest Authors declare that there are no conflicts of any interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder characterized by abnormal accumulation of extracellular β-amyloid (Aβ) plaques and neuronal damage. Although AD is typically considered a cognitive neurodegenerative disorder, almost all people diagnosed with AD develop neuropsychiatric complications at some stage in their life span. The present study investigated the effect of chronic Nattokinase (NK) administration on β-Amyloid peptide (Aβ 1-42 ) induced neuropsychiatric conditions (depression-like behaviour, anxiety, and memory impairment) in mice. Aβ 1-42 peptide injected mice demonstrated depression, anxiety, and impairment of cognitive abilities evaluated as increased immobility time in forced swim test (FST), decreased open arm time/entries in elevated plus maze (EPM) and reference and working memory error in radial arm maze (RAM) respectively with elevation in Interleukin-6 (IL-6), Tumour necrosis factor-α (TNF-α), reduction in Interleukin-10 (IL-10) and Brain-derived neurotrophic factor (BDNF) immunocontent within the hippocampus. Chronic administration of NK (50-100 mg/kg, i.p.) from day 8-27, prevented depression-like behaviour, anxiety, and memory impairment and normalized the neurochemical alteration within the hippocampus of mice injected with Aβ 1-42 peptide. The effect of NK on psychiatric complications, learning, and memory was comparable to peripheral donepezil treatment. This study suggests that NK improves learning, memory impairment, and neuropsychiatric complications possibly through the downregulation of neuroinflammatory pathways and restoring BDNF signalling in AD., Competing Interests: Declaration of competing interest Authors hereby declare that there are no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Premenstrual dysphoric disorder (PMDD) is characterized by various physical and affective symptoms, including anxiety, irritability, anhedonia, social withdrawal, and depression. The present study investigated the role of the agmatinergic system in animal model of progesterone withdrawal in female rats. Chronic progesterone exposure of female rats for 21 days and its abrupt withdrawal showed enhanced marble burying, increased immobility time, and reduced no. of entries in open arm as compared to control animals. The progesterone withdrawal-induced enhanced marble burying anxiety and immobility time was significantly attenuated by agmatine (5-20 mg/kg, i.p.), and its endogenous modulators like L-arginine (100 mg/kg, i.p.), amino-guanidine (25 mg/kg, i.p.) and arcaine (50 mg/kg, i.p.) by their once-daily administration from day 14-day 21 of the protocol. We have also analysed the levels of agmatine, progesterone, and inflammatory cytokines in the hippocampal region of progesterone withdrawn rats. There was a significant decline in agmatine and progesterone levels and an elevation in cytokine levels in the hippocampal region of progesterone withdrawn rats compared to the control animals. In conclusion, the present studies suggest the importance of the endogenous agmatinergic system in progesterone withdrawal-induced anxiety-like and depression-like behaviour. The data also projects agmatine as a potential therapeutic target for the premenstrual dysphoric disorder., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Reactive oxygen species are found to be having a wide range of biological effects ranging from regulating functions in normal physiology to alteration and damaging various processes and cell components causing a number of diseases. Mitochondria are an important organelle responsible for energy production and in many signalling mechanisms. The electron transport chain in mitochondria, where oxidative phosphorylation takes place, is also coupled with the generation of reactive oxygen species (ROS). Changes in normal homeostasis and overproduction of reactive oxygen species by various sources are found to be involved in multiple neurological and major neurodegenerative diseases. This review summarises the role of reactive oxygen species and the mechanism of neuronal loss in major neuronal disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, depression, and schizophrenia., (Copyright © 2021 Académie Nationale de Pharmacie. All rights reserved.)

Background and Aim: Achyranthes aspera Linn. ( A. aspera ) (family: Amaranthaceae) is highly recognized in ethnomedicine and traditional systems of Indian medicine as a nervine restorative for several psychiatric disorders. Study presented here was designed to appraise the antidepressant-like effects of A. aspera in murine model of chronic unpredictable mild stress (CUMS) induced depression., Experimental Procedures: Rodents were exposed to different stressor in unpredictive manner during CUMS protocol once a day for 4 weeks. Mice were intraperitoneally injected with A. aspera extract (2.5, 5 and 10 mg/kg) or fluoxetine (10 mg/kg) or betaine (20 mg/kg) once daily during day 15-28 of the CUMS protocol. Sucrose preference, motivation and self-care, immobility latency and plasma corticosterone were evaluated after 24 h of last stressor. After behavioral assessments TNF-α, Il-6 and BDNF immunocontent was determined in hippocampus and prefrontal cortex., Results and Conclusion: A. aspera extract as well as betaine improved sucrose preference, increased grooming frequency and latency in splash test and ameliorated depression-like condition in CUMS mice in Porsolt test. A. aspera treatment decreased the elevated plasma corticosterone and reversed the effect of CUMS on TNF-α, Il-6 and BDNF immunocontent in mice. The results of the present study suggest A. aspera as a promising indigenous medicine for stress associated neurobehavioral and comorbid complications., Competing Interests: Authors declare that there are no actual or potential conflicts of interests including any financial, personal or other relationships., (© 2022 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

Drug tolerance is directly correlated with drug abuse and physical dependence. The development of tolerance is manifested as the decline in pharmacological responses of drugs following repeated administration of the constant dose. The present study evaluated the effect of agmatine in ethanol-induced anti-nociception and tolerance in the tail-flick assay in mice. In an acute protocol, ethanol (1 and 2 g/kg, i.p. [intraperitoneally]) and agmatine (20 and 40 μg/mouse, i.c.v. [intracerebroventricularly]) produced significant analgesic effects in mice, as was evident from the increased baseline tail-flick latency when tested 20 minutes after their administration. Agmatine in a per se non-effective dose (5 μg/mouse, i.c.v.), L-arginine (40 μg/mouse, i.c.v.), and arcaine (25 μg/mouse, i.c.v.) significantly potentiated the anti-nociceptive effect of ethanol. Blood ethanol analysis showed no significant differences in blood ethanol concentration between ethanol/saline- and ethanol/agmatine-treated mice, suggesting that the effects of agmatine were not due to any possible effects on the pharmacokinetics of ethanol. In a separate study, mice were injected with ethanol (2 g/kg, i.p., 12%) or saline (1 mL/kg, i.p.) once daily for 9 days. On days 1, 3, 5, 7, and 9 of the experiment, they were subjected to the tail-flick test. Agmatine (5-20 μg/mouse, i.c.v.), L-arginine (40 μg/mouse, i.c.v.), arcaine (25 μg/mouse, i.c.v.), aCSF (2 μL/mouse, i.c.v.), or saline (1 mL/kg, i.p.) was administered daily prior to the first daily ethanol or saline injections, and reaction latencies were determined in the tail-flick assay. Injections of agmatine, L-arginine, and arcaine prevented the development of tolerance to ethanol-induced analgesia. Given that agmatine and its endogenous modulation can prevent tolerance to the anti-nociceptive effects of ethanol, these data suggest it as a possible new therapeutic strategy for the treatment of alcohol use disorder and associated complications., Competing Interests: Declaration of competing interest The author declares that there is no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Pulmonary hypertension (PH) has serious short- and long-term consequences. PH is gaining increasing importance in high risk groups such as Down syndrome (DS) as it influences their overall survival and prognosis. Hence, there is a dire need to collate the prevalence rates of PH in order to undertake definitive measures for early diagnosis and management., Aim: To determine the prevalence of PH in children with DS., Methods: The authors individually conducted a search of electronic databases manually (Cochrane library, PubMed, EMBASE, Scopus, Web of Science). Data extraction and quality control were independently performed by two reviewers and a third reviewer resolved any conflicts of opinion. The words used in the literature search were "pulmonary hypertension" and "pulmonary arterial hypertension"; "Down syndrome" and "trisomy 21" and "prevalence". The data were analyzed by Comprehensive Meta-Analysis Software Version 2. Risk of bias assessment and STROBE checklist were used for quality assessment., Results: Of 1578 articles identified, 17 were selected for final analysis. The pooled prevalence of PH in these studies was 25.5%. Subgroup analysis was carried out for age, gender, region, year of publication, risk of bias and etiology of PH., Conclusion: This review highlights the increasing prevalence of PH in children with DS. It is crucial for pediatricians to be aware of this morbid disease and channel their efforts towards earlier diagnosis and successful management. Community-based studies with a larger sample size of children with DS should be carried out to better characterize the epidemiology and underlying etiology of PH in DS., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no competing interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

The risk of psychiatric and neurological disorders is significantly higher in patients with diabetes mellitus. Diabetic patients are more susceptible to depression, anxiety and memory impairment as compared with non-diabetic individuals. Metformin, a biguanide used for the management of type 2 diabetes mellitus (T2DM), promotes neurogenesis, enhances spatial memory function and protects the brain against oxidative imbalance beyond its effect on glucose metabolism. However, the exact mechanism of its neuropharmacological actions in T2DM is not known. We investigated the role of the agmatinergic system in neuropharmacological actions of metformin in diabetic mice. Diabetes was induced by the streptozotocin (STZ) injection and confirmed by high blood glucose levels. After 28 days, STZ treated mice exhibited memory impairment in radial arm maze, depression-like behavior in forced swim test and anxiety-like behavior in elevated plus maze along with increased expression of pro-inflammatory cytokines like TNF-α, IL-1β, IL-6, IL-10 also, reduced agmatine and BDNF levels in the hippocampus and prefrontal cortex compared to the control animals. Metformin and agmatine alone or in combination, by once-daily administration during 14-27 day of the protocol significantly reversed the STZ induced high blood glucose levels, memory impairment, depression and anxiety-like behaviors. It also reduced neuro-inflammatory markers and increased agmatine and BDNF levels in the hippocampus and prefrontal cortex. The present study suggests the importance of endogenous agmatine in the neuropharmacological action of metformin in diabetic mice. The data projects agmatine and metformin combination as a potential therapeutic strategy for diabetes associated memory impairment, depression, anxiety, and other comorbidities., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Red reflex test (RRT) screening is yet to be a part of the neonate's normal examination before discharge from hospital in a majority of low- and middle-income countries. The purpose was this review was to systematically evaluate the diagnostic accuracy of RRT for the detection of ocular abnormalities in newborns. PubMed, EMBASE, Scopus, Web of Science, and Cochrane database of systematic reviews were the data sources. Quality of Diagnostic Accuracy Studies-2 (QUADAS-2) was utilized for quality assessment of bias and applicability. Random effects models were used to summarize sensitivities, specificities, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and respective confidence intervals (CI). The pooled sensitivity, calculated from the meta analysis of 11 studies, was 23% (95% CI: 21-24%) and pooled specificity was 98% (95% CI: 98-98%). The PLR was 32.52 (95% CI: 7.89-134.15), NLR was less than 1 (0.69 [95% CI: 0.55-0.88]), and DOR calculated was 138.48 (95% CI: 23.85-803.97). The area under the curve (AUC) and Q* index for RRT were 0.98 ± 0.02 and 0.95 ± 0.045, respectively. The results of our study justify the conclusion that RRT is a highly sensitive and specific test for the detection of anterior segment abnormalities.

Introduction: the spectrum of pulmonary complications in sickle cell anemia (SCA) comprises mainly of acute chest syndrome (ACS), pulmonary hypertension (PH) and airway hyper-responsiveness (AHR). This study was conducted to examine the abnormalities in pulmonary function tests (PFTs) seen in children with SCA., Methods: electronic databases (Cochrane library, PubMed, EMBASE, Scopus, Web of Science) were used as data sources. Two authors independently reviewed studies. All case-control studies with PFT performed in patients with SCA and normal controls were reviewed. Pulmonary functions were assessed with the help of spirometry, lung volume and gas diffusion findings., Results: nine studies with 788 SCA children and 1101 controls were analyzed. For all studies, the pooled mean difference for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, peak expiratory flow rate (PEFR), total lung capacity (TLC) and carbon mono-oxide diffusing capacity (DLCO) were -12.67, (95% CI: -15.41,-9.94), -11.69, (95% CI: -14.24, -9.14), -1.90, (95% CI: -4.32, 0.52), -3.36 (95% CI: -6.69, -0.02), -7.35, (95% CI: -14.97, -0.27) and -4.68, (95% CI -20.64, -11.29) respectively. FEV1 and FVC and were the only parameters found to be significantly decreased., Conclusion: sickle cell anemia was associated with lower FEV1 and FVC, thus, supporting the role of routine monitoring for the progression of lung function decline in children with SCA with ACS. We recommend routine screening and lung function monitoring for early recognition of pulmonary function decline., Competing Interests: The authors declare no competing interests., (Copyright: Amar Taksande et al.)

3-Hydroxy-3-methyl-glutaryl-co-enzyme-A (HMG-CoA) reductase inhibitors (statins) are popularly used for the treatment of obesity and hypercholesterolemia with established safety profile. Statins exhibits a wide range of neurobehavioral effects in addition to their peripheral actions, and may be beneficial in treatment of psychiatric conditions. Present study investigated the role of agmatine and imidazoline receptors in antidepressant-like effect of statins in mouse forced swimming test (FST). The antidepressant-like effect of atorvastatin (5 mg/kg, p.o.) and simvastatin (10 mg/kg, p.o.) was potentiated by pretreatment with agmatine (5 mg/kg, i.p.) as well as the drugs known to increase endogenous agmatine levels in brain viz., L-arginine (40 μg/mouse, i.c.v.), an agmatine biosynthetic precursor; arcaine (50 μg/mouse, i.c.v), agmatinase inhibitor; and aminoguanidine (6.5 μg/mouse, i.c.v.), a diamine oxidase inhibitor. Further, both the statins increased agmatine levels within hippocampus and prefrontal cortex. Conversely, prior administration of I 1 receptor antagonist, efaroxan (1 mg/kg, i.p.) and I 2 receptor antagonist, idazoxan (0.25 mg/kg, i.p.) blocked the antidepressant-like effect of statins and their synergistic combination with agmatine. These results demonstrate the involvement of agmatine and imidazoline receptors in antidepressant-like effect of statins and suggest as a potential therapeutic target for the treatment of depressive disorders., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Epidemiological studies indicated that mood disorders like depression and anxiety are highly prevalent in type-II diabetes mellitus (T2DM). However, the neurobiological mechanisms underlying the relationship between T2DM and depression have yet to be identified. Thus, understanding the neural mechanisms that mediate the co-morbidity of depression and type-II diabetes mellitus may unlock new pharmacological treatments for this condition. The present study investigated the role of the agmatinergic system in T2DM induced depression using forced swim test (FST) and anxiety in the elevated plus-maze (EPM)in rats. T2DM was induced by the combination of high-fat diet (HFD) and streptozotocin (STZ) injection and confirmed by high blood glucose levels. After 12 weeks, HFD fed and STZ injected rats exhibited depression-like behaviors and anxiety. It was associated with increased expression of pro-inflammatory cytokines like IL-6 and TNF-α, and reduced BDNF immunocontent in the hippocampal tissues. The T2DM-induced depression, anxiety, and neuroinflammatory markers were significantly inhibited by agmatine (10-20 mg/kg, i.p.), by once-daily administration during 9th to 12th week of the protocol. Agmatine levels were significantly reduced in the hippocampus of T2DM rats as compared to the normal fed (NF) control animals. In conclusion, the present study suggests the importance of endogenous agmatine in T2DM induced anxiety and depressive-like behavior in rats. The data projects agmatine as a potential therapeutic target for T2DM-associated depression, anxiety, and comorbidities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Agmatine is a biogenic amine synthesized following decarboxylation of L-arginine by the enzyme arginine decarboxylase and exhibits favourable outcome in neurodegenerative disorders. Present study was designed to examine the relationship between agmatine and the imidazoline receptors in memory deficits induced by Aβ 1 - 42 peptide in mice. Mice were treated with single intracerebroventricular (i.c.v.) injection of Aβ 1 - 42 peptide (3 μg) and evaluated for learning and memory in Morris water maze (MWM) and subjected to Aβ 1 - 42, TNF-α and IL-6 and BDNF immunocontent analysis within the hippocampus. While the learning and memory impairment was evident in the mice subjected to MWM test following Aβ 1 - 42 peptide administration, there was a significant increase in Aβ 1 - 42, TNF-α and IL-6 and reduction in BDNF immunocontent within the hippocampus. Daily intraperitoneal (i.p.) treatment with agmatine (10 and 20 mg/kg); imidazoline I 1 receptor agonist, moxonidine and imidazoline I 2 receptor agonist, 2-BFI starting from day 8 to 27 post-Aβ 1 - 42 injection, significantly prevented the cognitive deficits and normalized the Aβ 1 - 42 peptide, IL-6, TNF-α and BDNF immunocontent in hippocampus. On the other hand, pre-treatment with imidazoline I 1 receptor antagonist, efaroxan and imidazoline I 2 receptor antagonist, BU 224 attenuated the effects of agmatine on learning and memory in MWM, IL-6, TNF-α and BDNF content. In conclusion, the present study provides functional evidence for the involvement of the imidazoline receptors in agmatine induced reversal of Aβ 1 - 42 induced memory deficits in mice. The data projects agmatine and imidazoline receptor agonists as a potential therapeutic target for the treatment of AD., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder characterized by abnormal accumulation of extracellular β-amyloid (Aβ) plaques and neuronal damage. The present study investigated the effect of chronic intra-hippocampal agmatine administration on β-Amyloid (Aβ) induced memory impairment in mice. Aβ 1-42 peptide injected mice demonstrated impairment of cognitive abilities evaluated as reference memory error and working memory error in radial arm maze (RAM) and decreased exploration time for novel object as well as recognition index in novel object recognition (NOR) test along with elevation in Aβ 1-42 peptide, β-Site APP cleaving enzyme 1 (BACE 1), microtubule-associated protein tau (MAPt), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and reduction in neprilysin and brain derived neurotrophic factor (BDNF) immunocontent within hippocampus and prefrontal cortex. Importantly, this was associated with a reduction in the agmatine levels following Aβ 1-42 peptide administration. Chronic administration of agmatine from day 8-27, prevented the memory impairment in mice and normalized the neurochemical alteration within prefrontal cortex and hippocampus induced by Aβ 1-42 peptide administration. However, it did not modulate the amyloid precursor protein and BACE expression. This study suggests that agmatine improves learning and memory impairment possibly through the down regulation of neuroinflammatory pathways in AD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Extensive clinical and experimental studies established that depression and mood disorders are highly prevalent neuropsychiatric conditions in Alzheimer's disease (AD). However, its neurochemical basis is not clearly understood. Thus, understanding the neural mechanisms involved in mediating the co-morbidity of depression and AD may be crucial in exploring new pharmacological treatments for this condition. The present study investigated the role of the agmatinergic system in β-amyloid (Aβ β1-42 ) peptide-induced depression using forced swim test (FST) in mice. Following the 28th days of its administration, Aβ 1-42 peptide produced depression-like behavior in mice as evidenced by increased immobility time in FST and increased expression of pro-inflammatory cytokines like IL-6 and TNF-α compared to the control animals. The Aβ 1-42 peptide-induced depression and neuroinflammatory markers were significantly inhibited by agmatine -, moxonidine, 2-BFI and l-arginine by once-daily administration during day 8-27 of the protocol. The antidepressant-like effect of agmatine in Aβ 1-42 peptide in mice was potentiated by imidazoline receptor I 1 agonist, moxonidine and imidazoline receptor I 2 agonist 2-BFI at their sub-effective doses. On the other hand, it was completely blocked by imidazoline receptor I 1 antagonist, efaroxan and imidazoline receptor I 2 antagonist, idazoxan Also, agmatine levels were significantly reduced in brain samples of β-amyloid injected mice as compared to the control animals. In conclusion, the present study suggests the importance of endogenous agmatinergic system and imidazoline receptors system in β-amyloid induced a depressive-like behavior in mice. The data projects agmatine as a potential therapeutic target for the AD-associated depression and comorbidities., (Copyright © 2020 Elsevier Inc. All rights reserved.)

India being a land of farmer, the pesticides are freely and easily available and therefore organophosphorous poisoning is one of the major health issues. Suicidal poisoning is more common than accidental poisoning. Cardiac manifestations of organophosphorous poisoning are well known. It results in various electrocardiographic changes from sinus tachycardia to ST elevation. We hereby present a rare ECG finding of ventricular bigeminy in a case of acute organophosphorous poisoning.

Background: Cardiovascular diseases (CVD) are a leading cause of mortality among adults in India, and their risk factors (tobacco, hypertension, diabetes, overweight, and obesity) are common. Most risk-factor surveys have focused on young and middle aged adults. We measured the prevalence of risk factors for CVD among elderly (age 60 years or more) in rural India., Methods and Results: In a door-to-door cross-sectional survey we did a non-laboratory based assessment of risk factors (smoking or tobacco use in any form, diabetes mellitus, either known or newly detected hypertension, abnormal waist-hip-ratio, or a high body mass index) among elderly living in 23 villages in rural central India. Laboratory based assessment of risk factors was done in those who had two or more of the five measured conventional risk factors. We compared the distribution of risk factors between men and women. Among 2424 elderly included in the study (51% women, mean age 67), the prevalence of smokeless tobacco use was 50.8% (95% CI 48.1-52.8; smoking 10.5% (95% CI 9.3-11.8); and hypertension46.3% (95% CI 44.3-48.4). Only 10.2% participants were previously known to have had hypertension, and remaining 36.1% were detected to be hypertensive during the survey. A total of 8.2%(95% CI 7.0-9.5) participants were overweight and 4.1% (95% CI 3.3-4.9) had central obesity. The prevalence of dyslipidemia in those who underwent blood based tests was 40.6% (95% CI 36.5-44.9); and hyperglycemia 4.9% (95% CI 3.2-7.1)., Conclusions: Strategies to reduce the risk of cardiovascular disorders among elderly should be focused on reducing tobacco use and early detection and optimal control of hypertension.

Rural India has an undetected load of HIV-positive individuals. Few rural adults present for HIV testing and counseling due to stigma, discrimination, and fear of social ostracization. In this rural hospital clinic-based study, we document profiles of rural adults seeking voluntary testing and counseling, and analyze correlates of HIV seropositivity. This cross-sectional study was conducted in 450 participants presenting to the outpatient clinics of Mahatma Gandhi Institute of Medical Sciences, Sevagram, Central India. After informed consent, pre- and post-test counseling, HIV testing, and face-to-face interviews were conducted. Data were collected using a structured questionnaire. The median age of the 450 study participants was 34 years (range 18-88 years); the majority (74%) was married. The overall proportion of HIV seropositivity was 32% [95% CI 28%, 37%]. The proportions of HIV seropositivity in married women, married men, and single men were 41%, 37%, 18%, respectively. No single woman was found seropositive in the study. Very few married women were aware of their husbands' HIV status. In a multivariate analysis, correlates of HIV seropositivity in men were: age 30-39 years, being married, having sex with multiple partners, use of alcohol before sex, and testing positive for HIV in the past. In married women, the only predictor of seropositivity was being married. Although limited by the non-random nature of the sampling method, this pilot study is unique in that it is the first from this rural region of Central India. It provides baseline data on marginalized, largely unstudied populations that may aid in designing probabilistic community-based surveys in this neglected population.

Background: Oral fluid-based rapid tests are promising for improving HIV diagnosis and screening. However, recent reports from the United States of false-positive results with the oral OraQuick ADVANCE HIV1/2 test have raised concerns about their performance in routine practice. We report a field evaluation of the diagnostic accuracy, client preference, and feasibility for the oral fluid-based OraQuick Rapid HIV1/2 test in a rural hospital in India., Methodology/principal Findings: A cross-sectional, hospital-based study was conducted in 450 consenting participants with suspected HIV infection in rural India. The objectives were to evaluate performance, client preference and feasibility of the OraQuick Rapid HIV-1/2 tests. Two Oraquick Rapid HIV1/2 tests (oral fluid and finger stick) were administered in parallel with confirmatory ELISA/Western Blot (reference standard). Pre- and post-test counseling and face to face interviews were conducted to determine client preference. Of the 450 participants, 146 were deemed to be HIV sero-positive using the reference standard (seropositivity rate of 32% (95% confidence interval [CI] 28%, 37%)). The OraQuick test on oral fluid specimens had better performance with a sensitivity of 100% (95% CI 98, 100) and a specificity of 100% (95% CI 99, 100), as compared to the OraQuick test on finger stick specimens with a sensitivity of 100% (95% CI 98, 100), and a specificity of 99.7% (95% CI 98.4, 99.9). The OraQuick oral fluid-based test was preferred by 87% of the participants for first time testing and 60% of the participants for repeat testing., Conclusion/significance: In a rural Indian hospital setting, the OraQuick Rapid- HIV1/2 test was found to be highly accurate. The oral fluid-based test performed marginally better than the finger stick test. The oral OraQuick test was highly preferred by participants. In the context of global efforts to scale-up HIV testing, our data suggest that oral fluid-based rapid HIV testing may work well in rural, resource-limited settings.