In India, the Trans-Himalayan zone lies in the rain shadow of the main Himalayan region and is usually described as a "high-altitude cold desert". These regions are represented by sparse but unique vegetation composition. The present study is an attempt to investigate the vegetation composition in the alpine ecosystem of the cold desert landscape of the Nelang Valley in Western Himalayas (Uttarakhand), India.
View Article and Find Full Text PDFThe International Staging System for multiple myeloma recently underwent a second revision (R2-ISS) to include gain/amplification of 1q21 and account for the additive prognostic significance of multiple high-risk features. The phase 3 ICARIA-MM (isatuximab-pomalidomide-dexamethasone vs. pomalidomide-dexamethasone) and IKEMA (isatuximab-carfilzomib-dexamethasone vs.
View Article and Find Full Text PDFBackground: An eschar is not always present in all scrub typhus patients. Furthermore, such patients may present to tertiary care hospitals after administration of doxycycline. The present study aimed to determine the usefulness of using the swab from eschar sites in the diagnosis of scrub typhus in patients who present post-doxycycline therapy.
View Article and Find Full Text PDFBackground: In the intricate landscape of healthcare amid the COVID-19 pandemic, the emergence of mucormycosis as a severe complication posed a significant challenge to primary healthcare. This study delved into the complexities of adverse drug reactions (ADRs) in COVID-19 patients with mucormycosis undergoing treatment with conventional amphotericin B.
Methods: Ethically approved and meticulously conducted, the study scrutinized 154 ADRs in depth, shedding light on their classification, outcomes, and interventions in COVID patients with mucormycosis.
Influenza A virus (IAV) RNA synthesis produces full-length and deletion-containing RNA molecules, which include defective viral genomes (DVG) and mini viral RNAs (mvRNA). Sequencing approaches have shown that DVG and mvRNA species may be present during infection, and that they can vary in size, segment origin, and sequence. Moreover, a subset of aberrant RNA molecules can bind and activate host-pathogen receptor retinoic acid-inducible gene I (RIG-I), leading to innate immune signaling and the expression of type I and III interferons.
View Article and Find Full Text PDFThe heterocyclic 2-aminothiazoles scaffolds are used in a wide range of therapeutic applications against various diseases for its antioxidant, anti-inflammatory, antimicrobial and anticancer actions. In this study, we synthesized novel aniline aromatic ring-substituted 2-aminothiazole derivatives. Molecular docking was performed using Glide module of the Schrödinger Suite to fit compounds JG-49, JG-62, and KBA-18 against the Nicotinamide phosphoribosyl transferase (Nampt) enzyme, an intracellular regulator of nicotinamide adenine dinucleotide (NAD) redox cofactor involved in energy metabolism and epigenetics and are implicated in aging and metabolic diseases.
View Article and Find Full Text PDFα-Synuclein, a key player in Parkinson's disease and other synucleinopathies, possesses an inherently disordered structure that allows for versatile structural changes during aggregation. Microglia, the brain immune cells, respond differently to various α-synuclein strains, influencing their activation and release of harmful molecules, leading to neuronal death. Post-translational modifications, such as glycation in α-synuclein, add a layer of complexity to microglial activation.
View Article and Find Full Text PDFVersatility in carbon source utilization is a major contributor to niche adaptation in . Malonate is among the abundant carbon sources in the lung airways, yet it is understudied. Recently, we characterized how malonate impacts quorum sensing regulation, antibiotic resistance, and virulence factor production in .
View Article and Find Full Text PDFThere is accumulating evidence of BCMA and GPRC5D loss after treatment with T-cell redirecting therapies in patients with relapsed/refractory multiple myeloma (RRMM). While complete CD38 loss is not observed upon relapses after treatment with anti-CD38 monoclonal antibodies (mAb), there is downregulation of surface CD38 expression and decreased number and function of NK cells, which renders these patients resistant to retreatment with anti-CD38 mAb. Here, we provide preclinical evidence that RRMM patients previously exposed to anti-CD38 mAb could benefit from T-cell-based immunotherapy that depend less on CD38 antigen density and NK-cell activity, such as the novel CD38/CD3xCD28 trispecific T-cell engager, SAR442257.
View Article and Find Full Text PDFPurpose: To describe the construction and diagnostic accuracy of a modularized, virtual reality (VR)-based, pupillometer for detecting relative afferent pupillary defect (RAPD) in unilateral optic neuropathies, vis-à-vis, clinical grading by experienced neuro-ophthalmologists.
Methods: Protocols for the swinging flashlight test and pupillary light response analysis used in a previous stand-alone pupillometer was integrated into the hardware of a Pico Neo 2 Eye VR headset with built-in eye tracker. Each eye of 77 cases (mean ± 1SD age: 39.
Current treatment strategies for multiple myeloma (MM) are highly effective, but most patients develop relapsed/refractory disease (RRMM). The anti-CD38/CD3xCD28 trispecific antibody SAR442257 targets CD38 and CD28 on MM cells and co-stimulates CD3 and CD28 on T cells (TCs). We evaluated different key aspects such as MM cells and T cells avidity interaction, tumor killing, and biomarkers for drug potency in three distinct cohorts of RRMM patients.
View Article and Find Full Text PDFStatins are drugs for preventing cardiac events in the elderly population. Statins are well tolerated with a lower reported incidence of serious side effects (<0.15%) like myopathy and elevated transaminases [>3× upper limit of normal (ULN)].
View Article and Find Full Text PDFDrug-induced bullous pemphigoid (DBP) may present identical to an idiopathic type of illness. Thus, DBP should be considered as a differential diagnosis when evaluating the cause of bullous pemphigoid (BP) in elderly individuals with diabetes. We present the case of a 65-year-old "young-elderly" female who developed bullous lesions after initiation of medication.
View Article and Find Full Text PDFUnlabelled: Versatility in carbon source utilization assists in its adaptation to various niches. Recently, we characterized the role of malonate, an understudied carbon source, in quorum sensing regulation, antibiotic resistance, and virulence factor production in . These results indicate that global responses to malonate metabolism remain to be uncovered.
View Article and Find Full Text PDFPhospholamban (PLB) is a transmembrane micropeptide that regulates the sarcoplasmic reticulum Ca-ATPase (SERCA) in cardiac muscle, but the physical mechanism of this regulation remains poorly understood. PLB reduces the Ca sensitivity of active SERCA, increasing the Ca concentration required for pump cycling. However, PLB does not decrease Ca binding to SERCA when ATP is absent, suggesting PLB does not inhibit SERCA Ca affinity.
View Article and Find Full Text PDFIntroduction: Medication errors are inherent in a healthcare system. This results in both time and cost burdens for both the patient and the health system. The aim of this study was to conduct a root-cause analysis of medication errors in elderly patients with methotrexate toxicity, analyze associated factors, and propose solutions.
View Article and Find Full Text PDFBackground: Arglabin is a plant alkaloid (sesquiterpene lactone) that is used as an anticancer drug. It has potential anti-diabetic and anti-atherogenic effects.
Purpose: Arglabin has drawn particular attention because of its therapeutic effects as an anti-inflammatory agent in multiple diseases.
Foot-and-mouth disease (FMD) is a contagious viral disease of cloven-footed animals. Immunization with inactivated virus vaccine is effective to control the disease. Six-monthly vaccination regimen in endemic regions has proven to be effective.
View Article and Find Full Text PDFUnlabelled: T cell-engaging antibodies (TCEs) are showing promising efficacy in relapsed/refractory multiple myeloma, even in patients that relapsed after B-cell maturation antigen (BCMA)-targeted therapy. Patients with multiple myeloma may have compromised T-cell health unaccounted for by preclinical models. Here, we use Myeloma Drug Sensitivity Testing (My-DST) for ex vivo measurement of anti-multiple myeloma cytotoxicity for the trispecific CD38/CD28xCD3 TCE SAR442257 through activation of the patients' own endogenous T cells to inform clinical development of the compound in multiple myeloma.
View Article and Find Full Text PDFGain/amplification of 1q21 (≥3 copies), a chromosomal abnormality frequently observed in multiple myeloma, can negatively affect prognosis, due to its involvement in resistance to anti-myeloma therapy and disease progression. In this updated subgroup analysis of the randomized, Phase 3 IKEMA study (NCT03275285) in relapsed/refractory multiple myeloma (RRMM), we evaluated progression-free survival (PFS) and depth of response with the anti-CD38 antibody isatuximab plus carfilzomib-dexamethasone (Isa-Kd) versus Kd, in 1q21+ patients and related subgroups, at long-term follow-up (44.2 months).
View Article and Find Full Text PDFMembrane voltage plays a vital role in the behavior and functions of the lipid bilayer membrane. For instance, it regulates the exchange of molecules across the membrane through transmembrane proteins such as ion channels. In this paper, we study the membrane voltage-sensing mechanism, which entails the reorientation of α-helices with a change in the membrane voltage.
View Article and Find Full Text PDF