Publications by authors named "Vikram Joshi"

Piezo2 is a mechanically gated ion channel most commonly expressed by specialized mechanoreceptors, such as the enteroendocrine cells (EECs) of the gastrointestinal epithelium. A subpopulation of EECs expresses Piezo2 and functionally resembles the skin's touch sensors, called Merkel cells. Low-magnitude mechanical stimuli delivered to the mucosal layer are primarily sensed by mechanosensitive EECs in a process we term "gut touch.

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Invited for the cover of this issue are Mubarak Almehairbi, Vikram C. Joshi, Changquan Calvin Sun and Sharmarke Mohamed. The image depicts the digital exploration of the mechanical properties of crystals on specific facets that may be of interest for materials applications by "dialing-in" their stress response.

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Dynamic molecular crystals are an emerging class of crystalline materials that can respond to mechanical stress by dissipating internal strain in a number of ways. Given the serendipitous nature of the discovery of such crystals, progress in the field requires advances in computational methods for the accurate and high-throughput computation of the nanomechanical properties of crystals on specific facets which are exposed to mechanical stress. Here, we develop and apply a new atomistic model for computing the surface elastic moduli of crystals on any set of facets of interest using dispersion-corrected density functional theory (DFT-D) methods.

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Gastrointestinal (GI) motility is a key component of digestive health, and it is complex, involving a multitude of cell types and mechanisms to drive both rhythmic and arrhythmic activity. Tracking GI motility in organ and tissue cultures across multiple temporal (seconds, minutes, hours, days) scales can provide valuable information regarding dysmotility and to evaluate treatment options. Here, the chapter describes a simple method to monitor GI motility in organotypic cultures, using a single video camera is placed perpendicularly to the surface of the tissue.

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Background: Frailty is a complex, multi-dimensional syndrome commonly observed in patients with heart failure (HF). The presence of frailty in patients living with HF is strongly associated with increased vulnerability to adverse events, including falls, hospitalisation, and increased mortality. Several scoring systems have been developed to assess the presence of frailty in patients with HF.

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Radioiodine is one of the long-lived fission products and also an important radionuclide released during nuclear accidents, which generates interest in its environmental fate. Its sorption has been studied in a wide range of materials, but no equivalent study exists for microplastics, an emerging environmental vector. Weathering and biofilm formation on microplastics can enhance radioiodine sorption.

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Supersaturating drug delivery systems (SDDS) enhance the oral absorption of poorly water-soluble drugs by achieving a supersaturated state in the gastrointestinal tract. The maintenance of a supersaturated state is decided by the complex interplay among inherent properties of drug, excipients and physiological conditions of gastrointestinal tract. The biopharmaceutical advantage through SDDS can be mechanistically investigated by coupling biopredictive dissolution testing with physiologically based absorption modeling (PBAM).

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Co-amorphous (CAM) systems are promising drug-delivery systems in the arena of therapeutic drug delivery, addressing the poor aqueous solubility of drugs by enhancing solubility and thereby improving the oral bioavailability and therapeutic effect of the drug. A CAM system is a single-phase homogeneous blend of two or more low molecular weight molecules that can be drug-drug or drug-co-former, stabilized via intermolecular interactions, adding the benefit of thermodynamic stability. This review covers the fundamentals of CAM systems and recent advances in formulation development.

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Mechanosensation, the ability to properly sense mechanical stimuli and transduce them into physiologic responses, is an essential determinant of gastrointestinal (GI) function. Abnormalities in this process result in highly prevalent GI functional and motility disorders. In the GI tract, several cell types sense mechanical forces and transduce them into electrical signals, which elicit specific cellular responses.

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Background: Alcohol consumption during pregnancy is widespread and contributes to pediatric neurological defects, including hippocampal and neocortex dysfunction, causing cognitive deficits termed fetal alcohol spectrum disorders. However, the critical mechanisms underlying these brain abnormalities remain poorly described.

Methods: Using a postnatal ethanol exposure (PEE) animal model and pharmacological, epigenetic, synaptic plasticity-related and behavioral approaches, we discovered a novel persistent epigenetic mechanism of neurodegeneration in neonatal hippocampus and neocortex brain regions and of cognitive decline in adult animals.

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Objective: This study was designed to evaluate the roles of microRNAs (miRNAs) in slow transit constipation (STC).

Design: All human tissue samples were from the of the colon. Expression of 372 miRNAs was examined in a discovery cohort of four patients with STC versus three age/sex-matched controls by a quantitative PCR array.

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Background: Vaccine-preventable viral infections are associated with increased risk of morbidity and mortality in immunocompromised patients. Current guidelines recommend routine screening and vaccination of all patients before solid organ transplantation. We studied rates of immunity against vaccine-preventable viruses in liver transplantation (LT) recipients.

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Δ -tetrahydrocannabinol, the principal active component in Cannabis sativa extracts such as marijuana, participates in cell signalling by binding to cannabinoid CB and CB receptors on the cell surface. The CB receptors are present in both inhibitory and excitatory presynaptic terminals and the CB receptors are found in neuronal subpopulations in addition to microglial cells and astrocytes and are present in both presynaptic and postsynaptic terminals. Subsequent to the discovery of the endocannabinoid (eCB) system, studies have suggested that alcohol alters the eCB system and that this system plays a major role in the motivation to abuse alcohol.

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Fetal alcohol spectrum disorders (FASD) represent a wide array of defects that arise from ethanol exposure during development. However, the underlying molecular mechanisms are limited. In the current report, we aimed to further evaluate the cannabinoid receptor type 1 (CB1R)-mediated mechanisms in a postnatal ethanol-exposed animal model.

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Postnatal ethanol exposure has been shown to cause persistent defects in hippocampal synaptic plasticity and disrupt learning and memory processes. However, the mechanisms responsible for these abnormalities are less well studied. We evaluated the influence of postnatal ethanol exposure on several signaling and epigenetic changes and on expression of the activity-regulated cytoskeletal (Arc) protein in the hippocampus of adult offspring under baseline conditions and after a Y-maze spatial memory (SP) behavior (activity).

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Alcohol exposure can affect brain development, leading to long-lasting behavioral problems, including cognitive impairment, which together is defined as fetal alcohol spectrum disorder (FASD). However, the fundamental mechanisms through which this occurs are largely unknown. In this study, we report that the exposure of postnatal day 7 (P7) mice to ethanol activates caspase-3 via cannabinoid receptor type-1 (CB1R) in neonatal mice and causes a reduction in methylated DNA binding protein (MeCP2) levels.

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Aim: To determine the prevalence, characteristics and clinical course of pancreatic cystic neoplasms (PCNs) in liver transplantation (LT) recipients.

Methods: We retrospectively studied consecutive patients who underwent LT between January 1998 to April 2016. Clinical and laboratory data were obtained from patient medical records.

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Snake venom Kunitz-type proteins are well known to inhibit serine proteases but a few studies have also shown matrix metalloproteases (MMPs) inhibition. In view of the fact that MMPs and snake venom metalloproteases (SVMPs) have similar catalytic site, inhibition of SVMP activity by Kunitz-type proteins remains to be studied. Recent proteomic studies of Naja naja (N.

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Most neurodegenerative disorders (NDDs) are characterized by cognitive impairment and other neurological defects. The definite cause of and pathways underlying the progression of these NDDs are not well-defined. Several mechanisms have been proposed to contribute to the development of NDDs.

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Elevated production of arachidonic acid (AA)-derived pro-inflammatory eicosanoids due to the concerted action of secretory phospholipase A group IIA (sPLAIIA), 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) is a common feature of many inflammatory disorders. Hence, modulation of the bioactivity of these 3 enzymes is an important strategy to control inflammation. However, the failure of drugs specific for an individual enzyme (sPLAIIA-, 5-LOX- or COX-2) and the success of 5-LOX/COX-2 dual inhibitors in effectively controlling inflammation in clinical trials prompted us to evaluate a common inhibitor for sPLAIIA, 5-LOX and COX-2 enzymes.

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Background: Routine data collections are used increasingly to examine outcomes of real-world cancer drug use. These datasets lack clinical details about important endpoints such as disease progression.

Aim: To validate a proxy for disease progression in metastatic cancer patients using prescribing and dispensing claims.

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Background And Aim: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with roux-en-Y anastomosis (REYA) is challenging. Use of double balloon enteroscope-assisted ERCP (DBE-ERCP) has been successful. We aim to determine predictors of successful biliary cannulation with DBE-ERCP in patients with REYA.

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Context And Objective: Viperid venom-induced chronic local-toxicity continues even after anti-snake venom treatment. Therefore, traditional antidote Albizia lebbeck L. (Fabaceae) seed extract was tested against Echis carinatus S.

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