Factors Associated with Hospital Length of Stay among VTE Cases: Insights from the i-RegVed Registry.

INTRODUCTION: Venous thromboembolism (VTE) is a multifactorial condition and one of the leading causes of mortality and disability. The present study explores the factors associated with hospitalization duration among different types of venous thromboembolism diagnoses, such as deep vein thrombosis (DVT), pulmonary embolism (PE), and other forms of thrombosis. METHODS: The data included participants with VTE admitted to 13 hospitals within pan-India from June 2022 to December 2023 to the i-RegVed registry, where socio-demographic data, clinical history, and various factors associated with hospital length of stay (LOS) were included for analyses. Multilinear regression was performed to explore the factors associated with hospital LOS among VTE conditions such as DVT, PE, forms of thrombosis other than PE and DVT, and all VTE diagnoses. RESULTS: A total of 633 participants were included in the study, with 55% being males, and 28.9% being homemakers. Longer hospital LOS was significantly associated with age (ß = -.09, P < .05), sex (ß = 3.21, P < .05), and non-communicable diseases (ß = 3.51, P < .05) among participants with DVT and among participants with at least one of the VTE diagnoses, age (ß = -.12, P < .001) and anticoagulant use (ß = -2.49, P < .05) was significantly associated. CONCLUSION: The findings provide insights into the factors influencing hospital outcomes among participants with different types of VTE, highlighting the importance of age and comorbidities in predicting the hospital LOS.

Valsartan: An Angiotensin Receptor Blocker Modulates BDNF Expression and Provides Neuroprotection Against Cerebral Ischemic Reperfusion Injury.

AT1 receptor blockers (ARBs) are commonly used drugs to treat cardiovascular disease and hypertension, but research on their impact on brain disorders is unattainable. Valsartan (VAL) is a drug that specifically blocks AT1 receptor. Despite the previous evidence for VAL to provide neuroprotection in case of ischemic reperfusion injury, evaluation of their potential in mitigating mitochondrial dysfunction that causes neuronal cell death and neurobehavioral impairment remains unknown. The aim of this study was to evaluate the therapeutic effect of repurposed drug VAL against ischemic reperfusion injury-induced neuronal alternation. tMCAO surgery was performed to induce focal cerebral ischemic reperfusion injury. Following ischemic reperfusion injury, we analyzed the therapeutic efficacy of VAL by measuring the infarct volume, brain water content, mitochondrial oxidative stress, mitochondrial membrane potential, histopathological architecture, and apoptotic marker protein. Our results showed that VAL administrations (5 and 10 mg/kg b.wt.) mitigated the brain damage, enhanced neurobehavioral outcomes, and alleviated mitochondrial-mediated oxidative damage. In addition to this, our findings demonstrated that VAL administration inhibits neuronal apoptosis by restoring the mitochondrial membrane potential. A follow-up investigation demonstrated that VAL induces BDNF expression and promoted ischemic tolerance via modulating the Akt/p-Creb signaling pathway. In summary, our results suggested that VAL administration provided neuroprotection, ameliorated mitochondrial dysfunction, preserved the integrity of neurons, and lead to functional improvement after ischemic reperfusion injury.

Dantrolene alleviates mitochondrial dysfunction and neuroinflammation in traumatic brain injury by modulating the NF-ĸß/Akt pathway.

Traumatic brain injury (TBI) triggers a bevy of changes including mitochondrial dysfunction, apoptosis, oxidative stress, neurobehavioural impairment, and neuroinflammation, among others. Dantrolene (DNT), a muscle relaxant which inhibits intracellular Ca2+ signaling from the ER, has been repurposed as a potential neuroprotective agent in various neurological diseases. However, there have been limited studies on whether it can mitigate TBI-induced deficits and restore impaired mitochondrial dynamics. This study sought to evaluate whether Dantrolene can potentially provide neuroprotection in an in vivo model of TBI. Male wistar rats subjected to TBI were treated with DNT (10 mg/kg) 1 h and 12 h post surgery. Animals were assessed 24 h post-TBI to evaluate neurobehavioural deficits and cerebral edema. We evaluated the protein expressions of apoptotic, autophagic, and neuroinflammatory markers by immunoblotting, as well as Mitochondrial Membrane Potential (MMP) and Reactive Oxygen Species (ROS) via Flow Cytometry to ascertain the effects of DNT on TBI. We further analysed immunofluorescence staining with Glial Fibrillary Acidic Protein (GFAP) and immunohistochemistry with NF-κß to investigate neuroinflammation. H&E staining was also performed post-TBI. Our findings revealed DNT administration inhibits mitochondria-mediated apoptotis and reduces heightened oxidative stress. DNT treatment was also found to reverse neurobehavioural impairments and offer neuroprotection by preserving neuronal architechture. We also demonstrated that DNT inhibits neuronal autophagy and alleviates neuroinflammation following TBI by modulating the NF-κß/Akt signaling pathway. Thus, our results suggest a novel application of DNT in ameliorating the multitude of deficits induced by TBI, thereby conferring neuroprotection.

Campesterol and dithymoquinone as a potent inhibitors of SARS cov-2 main proteases-promising drug candidates for targeting its novel variants.

The sudden outbreak of the COVID-19 pandemic has currently taken approximately 2.4 million lives, with no specific medication and fast-tracked tested vaccines for prevention. These vaccines have their own adverse effects, which have severely affected the global healthcare system. The discovery of the main protease structure of coronavirus (Mpro/Clpro) has resulted in the identification of compounds having antiviral potential, especially from the herbal system. In this study, the computer-associated drug design tools were utilised to analyze the reported phytoconstituents of Nigella sativa for their antiviral activity against the main protease. Fifty-eight compounds were subjected to pharmacological parameter analysis to determine their lead likeness in comparison to the standard drugs (chloroquine and nirmatrelvir) used in the treatment of SARS-CoV-2. Nearly 31 compounds were docked against five different SARS-CoV-2 main proteases, and all compounds showed better binding affinity and inhibition constant against the proteases. However, dithymoquinone and campesterol displayed the best binding scores and hence were further subjected to dynamics and MMPBSA study for 100 ns. The stability analysis shows that dithymoquinone and campesterol show less variation in fluctuation in residues compared to standard complexes. Moreover, dithymoquinone exhibited higher binding affinity and favorable interaction followed by campesterol as compared to the standard drug. The in silico computational analysis provides a promising hit for regulating the main proteases activity.Communicated by Ramaswamy H. Sarma.