Rejected

Sirtuin1 deficiency or reduced activity comprises one of the hallmarks of diseases as diverse as chronic cardiovascular, renal, and metabolic, some malignancies, and infections, as well as aging-associated diseases. In a mouse model of endothelium-limited defect in sirtuin 1 deacetylase activity, we found a dramatic reduction in the volume of endothelial glycocalyx. This was associated with the surge in the levels of one of key scaffolding heparan sulfate proteoglycans of endothelial glycocalyx, syndecan-4, and specifically, its extracellular domain (ectodomain). We found that the defect in endothelial sirtuin 1 deacetylase activity is associated with (a) elevated basal and stimulated levels of superoxide generation (via the FoxO1 over-acetylation mechanism) and (b) increased nuclear translocation of NF-kB (via p65 over-acetylation mechanism). These findings laid the foundation for the proposed novel function of sirtuin 1, namely, the maintenance of endothelial glycocalyx, particularly manifest in conditions associated with sirtuin 1 depletion. In the forthcoming review, we summarize the emerging conceptual framework of the enhanced glycocalyx degradation in the states of defective endothelial sirtuin 1 function, thus explaining a broad footprint of the syndrome of endothelial dysfunction, from impaired flow-induced nitric oxide production, deterrent leukocytes infiltration, increased endothelial permeability, coagulation, and pro-inflammatory changes to development of microvascular rarefaction and progression of an underlying disease.

Canonical transient receptor potential-5 (TRPC5), which belongs to the subfamily of transient receptor potential (TRP) channels, is a non-selective cation channel mainly expressed in the central nervous system and shows more restricted expression in the periphery. TRPC5 plays a crucial role in human physiology and pathology, for instance, anxiety, depression, epilepsy, pain, memory and chronic kidney disease (CKD). However, due to lack of the effective and selective inhibitors, its physiological and pathological mechanism remains so far unknown. It is therefore pivotal to identify potential TRPC5 inhibitors. We have applied ligand-based virtual screening (LBVS) and structure-based virtual screening (SBVS) methods. The pharmacophore models of TRPC5 antagonists generated by using the HypoGen and HipHop algorithms were used as a query model for the screening of potential inhibitors against the Specs database. The resultant hits from LBVS were further screened by SBVS. SBVS was carried out based on the homology model generation of human TRPC5, binding site identification, molecular dynamics optimization and molecular docking studies. In our systematic screening approaches, we have identified 7 hits compounds with comparable dock score after Lipinski and Veber rules, ADMET, PAINS analysis, cluster analysis, and similarity analysis. In conclusion, the current research provides novel backbones for the new-generation of TRPC5 inhibitors.

To evaluate the effect of music therapy on the chronic pain and midterm quality of life of patients after mechanical valve replacement.

We aimed to compare the outcomes of a second voiding trial (VT) performed 2-4 days (earlier group) versus 7 days (later group) post-operatively in women with incomplete bladder emptying following vaginal prolapse surgery. Secondary aims included post-operative urinary tract infection (UTI) rates, total days with a catheter, and patient reported catheter bother between groups.

Chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus spread by the species of mosquito. Chikungunya virus causes a condition characterized by high fever, headache, rash, and joint pain. Recent investigations reveal the presence of bone lesions and erosive arthritis in the joints of CHIKV-infected patients, indicating an association of bone pathology with CHIKV infection. However, the molecular mechanism underlying CHIKV-induced bone pathology remains poorly defined. Bone marrow-derived mesenchymal stem cells (BMSCs) contribute to bone homeostasis by differentiating into osteogenic cells which later mature to form the bone. Disruption of osteogenic differentiation and function of BMSCs leads to bone pathologies. Studies show that virus infections can alter the properties and function of BMSCs. However, to date, pathogenesis of CHIKV infection in this context has not been studied. In the current study, we investigated the susceptibility of BMSCs and osteogenic cells to CHIKV and studied the effect of infection on these cells. For the first time to our knowledge, we report that CHIKV can productively infect BMSCs and osteogenic cells. We also observed decreased gene expression of the major regulator of osteogenic differentiation, RUNX2, in CHIKV-infected osteogenic cells. Furthermore, impaired functional properties of osteogenic cells, i.e., decreased production and activity of alkaline phosphatase (ALP) and matrix mineralization, were observed in the presence of CHIKV infection. Thus, we conclude that CHIKV likely impairs osteogenic differentiation of BMSCs, indicating a possible role of BMSCs in altering bone homeostasis during CHIKV infection. Presently, no vaccines or treatment options are available for CHIKV infection. Joint pain is one of the major concerns. Although studies have shown an association between bone pathology and infection, the molecular pathogenesis in the context of bone pathology is poorly defined. Here, we demonstrate for the first time that BMSCs and BMSC-derived osteogenic cells are susceptible to CHIKV infection, and that infection likely alters the function of osteogenic cells. This study highlights altered osteogenic differentiation as a possible mechanism for causing the bone pathology observed in CHIKV pathogenesis.

Although previous studies have reported nephrotoxicity associated with hydroxyethyl starch (HES), the long-term effect of HES on renal function after nephrectomy has rarely been reported. We evaluated the association between intraoperative HES administration and short- and long-term renal function after nephrectomy.

We will investigate the effectiveness of Interferon Beta 1a, compared to Interferon Beta 1b and the usual therapeutic regimen in COVID-19 in patients that have tested positive and are moderately to severely ill.

Globally, non-steroidal anti-inflammatory drugs (NSAIDs) are highly used to treat pain. With the rise of the COVID-19 pandemic, the safety of NSAIDs use has been called into question. These concerns are worthy of review. At present, there is no compelling data showing that NSAIDs worsen the severity of COVID-19 symptoms or increase one's likelihood of contracting the illness. For patients in pain and without symptoms that could potentially be attributed to COVID-19 (cough, fevers/chills, lethargy, myalgias, anosmia and so on), NSAIDs should continue to remain a viable option to provide analgesia to patients in need.

Occipital neuralgia is one of the main causes of occipital pain. This systematic review aims to assess the level of evidence in randomized controlled trials (RCTs) on the effects of acupuncture on occipital neuralgia.

Neurofibromatosis type 1 (NF1, Von Recklinghausen disease) is an autosomal dominant disease with a birth incidence of 1/2500-3000. The most common presentations of NF1 are cutaneous presentations like café-au-lait spots and neurofibromas. 5%-25% of patients with NF1 have gastrointestinal manifestations of the disease. Appendiceal neurofibroma are extremely rare and only a few cases are described in literature. An appendectomy is indicated because of high risk of appendicitis and malignant transformation. We report the case of a 74-year-old male patient with a history of NF1 with chronic right lower quadrant pain. Successive imaging scans showed suspicion of chronic appendicitis. A diagnostic laparoscopy, resulting in a laparoscopic appendectomy was performed without complications. Histopathology showed appendiceal neurofibroma and diverticula. The postoperative course was uneventful. In patients with NF1 with right lower quadrant pain benign appendiceal neurofibroma should be included in the differential diagnosis. A diagnostic laparoscopy should be performed followed by an appendectomy.