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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with an impairment of cognition and memory. Current research on connectomics have now related changes in the network organization in AD to the patterns of accumulation and spread of amyloid and tau, providing insights into the neurobiological mechanisms of the disease. In addition, network analysis and modeling focus on particular use of graphs to provide intuition into key organizational principles of brain structure, that stipulate how neural activity propagates along structural connections. The utility of connectome-based computational models aids in early predicting, tracking the progression of biomarker-directed AD neuropathology. In this article, we present a short review of tau trajectory, the connectome changes in tau pathology, and the dependent recent connectome-based computational modelling approaches for tau spreading, reproducing pragmatic findings, and developing significant novel tau targeted therapies.

Background: Social isolation (SI) and loneliness are major adult and adolescent health concerns, particularly in the coronavirus disease 2019 (COVID-19) era. Recent prospective cohort studies indicate that older women who experienced both SI and loneliness had a significantly higher risk of cardiovascular disease (CVD). Hypertension, a well-established risk factor for CVD, is more prevalent in elderly women than men. Furthermore, a lack of social relationships is strongly associated with an increased risk of hypertension in middle-aged and elderly women compared to men. Although this has not been extensively studied, adolescents and young adults who experience loneliness or SI may also be at risk for CVD and depression. The purpose of this study was to examine the effect of SI on blood pressure and depression-like behavior in young male and female mice. Methods: Weaned C57BL/6 mice were randomly assigned ( n = 6/group/sex) to either group housing (GH) or SI. Animals in the SI group were housed in individual cages for 8 weeks with no view of other animals. The cages were kept in ventilated racks to prevent pheromone exposure and socially isolated animals had no cage enrichment. Results: SI increased systolic, diastolic, and mean arterial blood pressure in females and elevated heart rate in both sexes. Body weight gain was dramatically increased in socially isolated females but tended to decrease in socially isolated males. In the forced swim test, which detects depression-like behavior, there was no difference between groups in total immobility time. The latency to immobility, however, was significantly decreased in socially isolated females. Serum concentrations of corticosterone and metanephrine did not differ between socially isolated and group-housed females, but corticosterone levels were significantly reduced in socially isolated males. Conclusions: Our results indicate that 8 weeks of SI leads to significant changes in blood pressure and heart rate and mild changes in depression-like behavior in young mice, with females affected more than males.

We recently showed that the post-ischemic induction of matrix metalloproteinase-12 (MMP-12) in the brain degrades tight junction proteins, increases MMP-9 and TNFα expression, and contributes to the blood-brain barrier (BBB) disruption, apoptosis, demyelination, and infarct volume development. The objectives of this study were to (1) determine the effect of MMP-12 suppression by shRNA-mediated gene silencing on neurological/functional recovery, (2) establish the optimal timing of MMP-12shRNA treatment that provides maximum therapeutic benefit, (3) compare the effectiveness of acute versus chronic MMP-12 suppression, and (4) evaluate potential sex-related differences in treatment outcomes. Young male and female Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion and reperfusion. Cohorts of rats were administered either MMP-12shRNA or scrambled shRNA sequence (control) expressing plasmids (1 mg/kg; i.v.) formulated as nanoparticles. At designated time points after reperfusion, rats from various groups were subjected to a battery of neurological tests to assess their reflex, balance, sensory, and motor functions. Suppression of MMP-12 promoted the neurological recovery of stroke-induced male and female rats, although the effect was less apparent in females. Immediate treatment after reperfusion resulted in a better recovery of sensory and motor function than delayed treatments. Chronic MMP-12 suppression neither enhanced nor diminished the therapeutic effects of acute MMP-12 suppression, indicating that a single dose of plasmid may be sufficient. We conclude that suppressing MMP-12 after an ischemic stroke is a promising therapeutic strategy for promoting the recovery of neurological function.

Introduction: The status report on the global burden of cancer worldwide by the International Agency for Research on Cancer using GLOBOCAN 2018 estimated 18.1 million newer cancer cases and 9.6 million cancer deaths in 2018. Particularly, breast cancer ranks second according to incidence of cancers in women in the world. There is growing evidence that anaemia has an impact on treatment outcome, prognosis and survival of cancer patients. Aim: To assess the prevalence of different types of cancers and frequency of pre-diagnosed haemoglobin levels in cancer patients. Materials and Methods: A cross-sectional study was carried out for two months period between September 2017 and October 2017 in a Tertiary cancer care hospital, A South Indian hospital based study. A total of 90 patients were recruited into the study based on inclusion criteria. The collected data was analysed by calculating the percentage frequency. Results: Breast cancer (n=45, 50%), gastrointestinal cancers (n=14, 16%), urogenital cancers (n=14, 16%), Hodgkin’s lymphoma (n=5, 6%), non-Hodgkin’s lymphoma (n=1, 1%), other advanced metastatic carcinomas (n=9, 10%), sarcomas (n=2, 2%) were reported. In our study population breast cancer patients were highly prevalent. In breast cancer patients, the maximum number of patients was diagnosed with Infiltrating Ductal Carcinoma (IDC). In IDC patients, majority of patients were diagnosed in Grade II IDC. Conclusion: Prevalence of breast cancer patients was high in our study population of cancer patients. Most of the patients diagnosed in Grade II were found to have less haemoglobin levels while it was not observed in Grade I. Our result implies that anaemia could be one of the poor prognostic factors for cancer progression.

Background: Soya supplements are used in the treatment of neuropathic pain. Previous reports reveal that consumption of soy diet before nerve injury prevents the development of neuropathic pain in rats. Biochanin-A, a soy isoflavone, has a naturally occurring inhibitor of fatty acid amide hydrolase (FAAH) that metabolized endocannabinoids. Objective: The objective was to evaluate efficacy of biochanin-A in streptozotocin (STZ) induced neuropathic pain in rat model. Materials and methods: Diabetes mellitus was induced by an injection of STZ at a dose of 45 mg/kg, i.v. into tail vein of male albino Wistar rats. Biochanin-A was dosed at 0.1, 1 and 5 mg/kg by intraperitoneal (i.p.) administration in diabetic neuropathic rats. Mechanical hyperalgesia and allodynia was measured using Randall–Selitto analgesymeter and manual von Frey filaments of increasing weights respectively. Paw withdrawal threshold (PWT) and percent PWT was determined with respect to both hyperalgesia and allodynia. Results: Treatment of biochanin-A at three different levels of 0.1, 1 and 5 mg/kg had not significantly altered serum glucose levels throughout the treatment period. In hyperalgesia study, acute treatment with higher dose exhibited 51.1% reversal of paw withdrawal threshold (PWT) while with chronic treatment, efficacy declined to 22.5% reversal of PWT. In allodynia study, acute treatment reversed PWT by 79.4% while with chronic treatment, efficacy was raised to 88.2% reversal of PWT. Conclusion: Biochanin-A demonstrated better efficacy in reversing mechanical allodynia than mechanical hyperalgesia. Biochanin-A could be a good drug candidate for further studies to establish the mechanism of attenuation of neuropathic pain.

Introduction: Education of the patients regarding KAP management has shown to improve patient outcomes in various health care settings across the world. Aim: To assess the impact of patient counselling by the pharmacist on KAP, Health related Quality of life and glycaemic control. Materials and Methods: A prospective observational study was conducted in hospitalised patients of various departments of the tertiary care hospital during the period of November 2016 to April 2017. Patient counselling was given by pharmacist at baseline visit and first follow-up (after three months). Patients were followed for six months with first follow-up at third month and with second follow-up at sixth month and KAP and HR-QoL were assessed using WHO-BREF QoL and KAP questionnaire respectively in all visits. Similarly, glycaemic control (HbA1C) values were noted at each visit. Results: A total of 50 patients were recruited in the study. KAP score at baseline visit, follow up-1 and follow up-2 were found to be 87.92±7.82, 117.47±6.98 and 119.9±5.30 respectively. Data analysis indicated that KAP score was improved at follow up-1 (p

Introduction: Several studies have demonstrated the efficacy and safety of switching from intravenous to oral antibiotics in clinically stable patients. Early switch from Intravenous (IV) to Per Oral (PO) could be one of the factors that influence the Length of Hospital Stay (LOHS). Aim: To evaluate the practice of switch from intravenous to oral antibiotics and its impact on the LOHS at a tertiary care hospital. Materials and Methods: A prospective observational study was conducted over a period of six months from November 2015 to April 2016. The practice of conversion from IV to PO antibiotic therapy was assessed according to predefined criteria for clinical stability. Clinical end points such as day of IV to PO switch, LOHS and duration of antibiotic therapy were assessed. Results: Results reveal that 43.68% of antibiotics were converted from IV to oral formulation while 56.32% of antibiotic courses were not converted from IV to oral. Out of all IV to oral conversions, sequential therapy was more commonly used than switch and step-down therapy. LOHS for patients had significantly (p

Objective: The study was aimed to assess the incidence and characteristics of drug-related problems (DRPs). Methods: A prospective, observational study was conducted among 133 patients with stroke disease who were aged 18 years or older and admitted to the general medicine ward. During the 6 months study period, the incidence of DRPs was identified using the Pharmaceutical Care Network Europe Foundation classification system, version 6.2. Findings: A total of 133 patients were screened for DRPs. Among them, 120 patients have at least one DRP. A total of 254 DRPs were identified (on average, 2.015 DRPs per each patient case). Conclusion: Increasing the evidence of the incidence of medication-related problems in tertiary care hospitals indicates the need for the establishment of a clinical pharmacist in hospital settings.

The study is aimed to assess the incidence of drug-related problems (DRPs) and provide pharmacist interventions for identified DRPs. A prospective, observational study was conducted among 189 patients with cardiovascular disease who were aged 18 years or older and admitted to the general medicine in-patient ward. During the 6 months study period, the incidence of DRPs was identified using Pharmaceutical Care Network Europe Foundation classification system version 6.2. A total of 189 patients were screened for DRPs. Among them, 130 patients have at least one DRP. A total of 416 DRPs were identified (on average, 2.2 DRPs per each patient). Of the 416 DRPs, 125 (30.04%) interventions were accepted, 7 (1.68%) interventions were not accepted, while remaining (68.26%) accepted but no action taken. The results of the study indicate that incidence of DRPs is substantial and pharmacist-led interventions resulted in resolution of DRPs. This represents the need for the active role of the clinical pharmacist in the developing countries like India.

Diabetic cardiomyopathy is a distinct clinical entity that produces asymptomatic heart failure in diabetic patients without evidence of coronary artery disease and hypertension. Abnormalities in diabetic cardiomyopathy include: myocardial hypertrophy, impairment of contractile proteins, accumulation of extracellular matrix proteins, formation of advanced glycation end products, and decreased left ventricular compliance. These abnormalities lead to the most common clinical presentation of diabetic cardiomyopathy in the form of diastolic dysfunction. We evaluated the role of various proteins that are likely to be involved in diabetic cardiomyopathy by employing multiple sequence alignment using ClustalW tool and constructed a Phylogenetic tree using functional protein sequences extracted from NCBI. Phylogenetic tree was constructed using Neighbour—Joining Algorithm in bioinformatics approach. These results suggest a causal relationship between altered calcium homeostasis and diabetic cardiomyopathy that implies that efforts directed to normalize calcium homeostasis could form a novel therapeutic approach.

Background and purpose The therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.Methods Transient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.Results The infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).Conclusions Despite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.

Aim: The aim of the study is to evaluate the oxidant and antioxidant balance in experimentally induced testicular injury by ischemia reperfusion in rats with different time intervals of torsion/detorsion of the spermatic cord. Method: Male rats were divided into thirteen groups and each group containing six rats. All rats were subjected to right spermatic cord torsion followed by detorsion for different time intervals except the sham control group. Result: Malondialdehyde, super oxide dismutase, catalase levels were estimated in testicular tissue of each rat. Spermatic cord torsion/detorsion induced a significant increase in testicular malondialdehyde contents and significant decrease in SOD, catalase levels when compared to sham control group in a time dependent manner. Conclusion: Our findings clearly represents that torsion for 4 hours followed by detorsion for 4 hours induces the highest oxidative stress with a great extent of lipid peroxidation and drastic reduction of SOD and catalase levels of the testis and is, therefore, a valid model for studying the oxidative antioxidant effects of the ischemia/reperfusion injury in rat testis. [ABSTRACT FROM AUTHOR]

Aim: The combined hepatoprotective effect of Bi-herbal ethanolic extract (BHEE) was evaluated against paracetamol induced hepatic damage in albino rats., Materials and Methods: Liver function tests and biochemical parameters were estimated using standard kits. Livers were quickly removed and fixed in 10% formalin and subjected to histopathological studies., Results: Ethanolic extract from the leaves of Aerva lanata and leaves of Achyranthes aspera at a dose level of 200 mg/kg, 400mg/kg body weight was administered orally once for 3 days. Substantially elevated serum marker enzymes such as SGOT, SGPT, ALP, due to paracetamol treatment were restored towards normal. Biochemical parameters like total protein, total bilirubin, total cholesterol, triglycerides, and urea were also restored towards normal levels. In addition, BHEE significantly decreased the liver weight of paracetamol intoxicated rats. Silymarin at a dose level of 25 mg/kg used as a standard reference also exhibited significant hepatoprotective activity against paracetamol induced hepatotoxicity., Conclusion: The results of this study strongly indicate that BHEE has got a potent hepatoprotective action against paracetamol induced hepatic damage in rats.