Efficacy and Safety of Triple Fixed Dose Combination of Dapagliflozin + Sitagliptin + Metformin IR in Indian Patients with Type 2 Diabetes Mellitus: A Randomized, Phase 3 Study in Comparison with Dual FDC Sitagliptin + Metformin IR.

Introduction: This study aims to evaluate the efficacy and safety of a triple fixed-dose combination (FDC) of dapagliflozin, sitagliptin, and immediate-release metformin (DAPA + SITA + MET IR) compared to dual FDCs in patients with type 2 diabetes mellitus (T2DM).

Methods: This Phase 3, randomized, open-label study included eligible patients with T2DM who were randomly assigned in a 1:1 ratio to receive either a triple FDC of DAPA + SITA + MET IR (5 + 50 + 500/1000 mg) or a dual FDC of sitagliptin and MET IR (SITA + MET IR; 50 + 500/1000 mg), administered twice daily for 16 weeks. The primary endpoint was the mean change in glycated haemoglobin (HbA1c) from baseline to Week 16.

Oat bran fiber protects against radiation-induced disruption of gut barrier dynamics and mucosal damage.

Dietary fibers are recognized for their health benefits, yet cancer patients undergoing pelvic radiotherapy are often advised to reduce fiber intake. This may negatively impact their bowel health. To evaluate the effects of dietary fibers on bowel health post-irradiation, male C57BL/6 mice were fed diets containing either 0 or 15% fiber with varying proportions of readily fermentable bioprocessed oat bran fiber and/or poorly fermentable microcrystalline cellulose, and either irradiated or sham-irradiated.

Exploring the O-glycomic Degradome Using Natural Mucin Libraries.

The interactions between intestinal mucins and the gut microbiota significantly influence digestive processes, metabolic activities, and pathogen resistance in the gastrointestinal tract. To explore this dynamic relationship, this chapter describes a workflow for studying the degradation of mucin oligosaccharides from isolated mucins. The approach involves purifying mucins from intestinal tissues and then subjecting them to a mixture of fecal glycosidases originating from commensal bacteria.

Inhalation safety and tolerability of a novel fixed-dose combination of glycopyrronium-vilanterol powder in Wistar rats.

Fixed-dose combinations (FDCs) offer therapeutic benefits like enhanced efficacy, reduced adverse effects, and better patient compliance, making them cost-effective. They are particularly effective in managing chronic obstructive pulmonary disease (COPD). Combining a long-acting muscarinic antagonist with a long-acting beta-agonist improves lung function, reduces the need for rescue bronchodilators, alleviates respiratory symptoms, and enhances the overall quality of life in COPD patients.

Real-World Evaluation of the Safety and Efficacy of Surgi-ORC® in Orthopedic Surgeries: A Multicenter Prospective Study.

Aim Achieving adequate hemostasis is a critical aspect of surgical practice, especially in orthopedics, where bleeding can impact visibility and patient outcomes. Surgi-ORC® (Aegis Lifesciences Pvt. Ltd.

Fixed dose combination of dapagliflozin, glimepiride and extended-release metformin tablets in patients with type 2 diabetes poorly controlled by metformin and glimepiride: A phase III, open label, randomized clinical study in India.

Aim: To evaluate the efficacy and safety of a triple fixed-dose combination (FDC) therapy of dapagliflozin + glimepiride + metformin hydrochloride extended-release (DAPA + GLIM + MET ER) tablets in Indian patients with type 2 diabetes mellitus (T2DM) inadequately controlled by combination of GLIM + MET.

Materials And Methods: A phase III, randomized, open-label, active-controlled study was conducted for a maximum 30 weeks (primary treatment [16 weeks]; uptitration [12 weeks] and follow-up [2 weeks]). Eligible patients were randomized in a 1:1 ratio to receive either the FDC of DAPA + GLIM + MET ER or the FDC of GLIM + MET prolonged-release (PR) once-daily.

Salutary impact of spontaneous oxidation in CHNHSnI on CZTS-based solar cell.

From the time of discovery, CHNHSnI has been a promising candidate in photovoltaics due to its outstanding optoelectronic properties. However, stabilization was not easy to achieve in CHNHSnI-based solar cells. Because CHNHSnI was used as an absorber, its naturally-occurring self-doping property spontaneously modified band alignment, which increased carrier recombination and decreased the efficiency of solar cell gradually.

BPP43_05035 is a cell surface adhesin that weakens the integrity of the epithelial barrier during infection.

The anaerobic spirochete causes intestinal spirochetosis, characterized by the intimate attachment of bacterial cells to the colonic mucosa, potentially leading to symptoms such as diarrhea, abdominal pain, and weight loss. Despite the clinical significance of infections, the mechanism of the interaction between and the colon epithelium is not known. We characterized the molecular mechanism of the -epithelium interaction and its impact on the epithelial barrier during infection.

Discovery of TYRA-300: First Oral Selective FGFR3 Inhibitor for the Treatment of Urothelial Cancers and Achondroplasia.

Activating FGFR3 alterations have been identified in up to 15-20% of muscle-invasive bladder cancer and metastatic urothelial carcinoma (mUC), and as high as 80% in nonmuscle invasive bladder cancers. FGFR3 germline mutations have also been associated with a variety of skeletal dysplasias. Achondroplasia, the most common form of dwarfism in humans, results from a G380R mutation in FGFR3.

Efficacy, Safety and Immunogenicity of Sun's Ranibizumab Biosimilar in Neovascular Age-Related Macular Degeneration: A Phase 3, Double-Blind Comparative Study.

Introduction: The study aimed to evaluate comparability in terms of efficacy, safety and immunogenicity of Sun's ranibizumab biosimilar with reference ranibizumab in patients with neovascular age-related macular degeneration (nAMD).

Methods: This prospective, randomised, double-blind, two-group, parallel-arm, multicentre, phase 3 comparative study included patients with nAMD ≥ 50 years, randomised (in a 2:1 ratio) in a double-blind manner to receive 0.5 mg (0.

Understanding non-stationarity of hydroclimatic extremes and resilience in Peninsular catchments, India.

Climate change significantly impacts the global hydrological cycle, leading to pronounced shifts in hydroclimatic extremes such as increased duration, occurrence, and intensity. Despite these significant changes, our understanding of hydroclimatic risks and hydrological resilience remains limited, particularly at the catchment scale in peninsular India. This study aims to address this gap by examining hydroclimatic extremes and resilience in 54 peninsular catchments from 1988 to 2011.

Fixed-Dose Combination of Dapagliflozin + Sitagliptin + Metformin in Patients with Type 2 Diabetes Poorly Controlled with Metformin: Phase 3, Randomized Comparison with Dual Combinations.

Introduction: This study compared efficacy and safety of triple drug fixed-dose combination (FDC) of dapagliflozin (DAPA) + sitagliptin (SITA) + metformin (MET) extended release (ER) with SITA + MET sustained release (SR) and DAPA + MET ER in patients with type 2 diabetes poorly controlled with metformin.

Methods: This phase 3, randomized, open-label, active-controlled study included adult patients with glycated hemoglobin (HbA1c) ≥ 8% (64 mmol/mol) and ≤ 11% (97 mmol/mol), randomized in 1:1:1 ratio to receive either FDC of DAPA + SITA + MET ER (10 mg + 100 mg + 1000 mg) tablets once daily (n = 137) or co-administration of SITA + MET SR (100 mg + 1000 mg) tablets once daily (n = 139) or FDC of DAPA + MET ER (10 mg + 1000 mg) tablets once daily (n = 139). Primary endpoint was mean change in HbA1c from baseline to week 16.

Phase I randomized, observer-blinded, placebo-controlled study of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B.

Access to vaccines against SARS-CoV-2 virus was limited in poor countries during the COVID-19 pandemic. Therefore, a low-cost mRNA vaccine, PTX-COVID19-B, was produced and evaluated in a Phase 1 trial. PTX-COVID19-B encodes Spike protein D614G variant without the proline-proline (986-987) mutation present in other COVID-19 vaccines.

Subpial delivery of adeno-associated virus 9-synapsin-caveolin-1 () preserves motor neuron and neuromuscular junction morphology, motor function, delays disease onset, and extends survival in hSOD1 mice.

Elevating neuroprotective proteins using adeno-associated virus (AAV)-mediated gene delivery shows great promise in combating devastating neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is one such disease resulting from loss of upper and lower motor neurons (MNs) with 90-95% of cases sporadic (SALS) in nature. Due to the unknown etiology of SALS, interventions that afford neuronal protection and preservation are urgently needed.

Seasonal Patterns of Oestrus and Reproduction in Street Dogs of Indian Cities.

Understanding seasonal breeding dynamics is essential for maximizing efficiency and welfare in the application of street dog management programs. Humane Society International (HSI) has conducted many animal birth control programmes concerning the street dog populations in urban India. This paper analyses the data on reproductive indicators-oestrus, pregnancy, and pups-collected by HSI sterilization clinics in the cities of Jamshedpur, Dehradun, and Vadodara over a period of 3, 5, and 4 years, respectively.

Cyclosporine release and distribution in ophthalmic emulsions determined by pulsatile microdialysis.

An in vitro release test based on pulsatile microdialysis (PMD) is presented for the purpose of measuring the release of cyclosporine from ophthalmic emulsions, along with a method to determine the drug distribution within the oil-rich globule, surfactant-rich micelle and aqueous phases of the emulsion formulation. Compositionally equivalent formulations containing 0.05% cyclosporine were prepared with similar physical parameters (globule size, viscosity, surface tension zeta potential, osmolality, pH) but made with different manufacturing conditions.

A Fiber-Rich Diet and Radiation-Induced Injury in the Murine Intestinal Mucosa.

Dietary fiber is considered a strong intestinal protector, but we do not know whether dietary fiber protects against the long-lasting mucosal damage caused by ionizing radiation. To evaluate whether a fiber-rich diet can ameliorate the long-lasting pathophysiological hallmarks of the irradiated mucosa, C57BL/6J mice on a fiber-rich bioprocessed oat bran diet or a fiber-free diet received 32 Gray in four fractions to the distal colorectum using a linear accelerator and continued on the diets for one, six or 18 weeks. We quantified degenerating crypts, crypt fission, cell proliferation, crypt survival, macrophage density and bacterial infiltration.

The Effects of Human Milk Oligosaccharides on Gut Microbiota, Metabolite Profiles and Host Mucosal Response in Patients with Irritable Bowel Syndrome.

Background: Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2'-O-fucosyllactose and lacto-N-neotetraose (2'FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients.

Methods: Biological samples were collected from IBS patients ( = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2'FL/LNnT.

Fixed dose combination of capecitabine and cyclophosphamide in metastatic breast cancer: Results from THE ENCLOSE phase 2/3 randomized multicenter study.

Aim: To evaluate pharmacokinetics, efficacy and safety of fixed-dose combination (FDC) of oral capecitabine + cyclophosphamide in metastatic breast cancer (MBC) patients progressing after anthracycline and/or taxane chemotherapy.

Methods: In this prospective, adaptive, phase-2/3, open-label study (CTRI/2014/12/005234), patients were randomized (1:1:1) to three FDC doses (doses/day: D1, capecitabine + cyclophosphamide 1400 mg + 60 mg; D2, 1800 mg + 80 mg; D3, 2200 mg + 100 mg) for 14 days, in 21-day cycles. In Part-I, multiple-dose pharmacokinetics and optimal dose(s) were evaluated with futility analysis.

Dietary Fiber and the Hippocampal Neurogenic Niche in a Model of Pelvic Radiotherapy.

We sought to determine whether radiation to the colorectum had an impact on parameters of hippocampal neurogenesis and, if so, whether it could be modulated by a fiber-rich diet. Male C57BL/6J mice were fed a diet containing bioprocessed oat bran or a fiber-free diet, starting two weeks before colorectal irradiation with 4 fractions of 8 Gray or sham-irradiation. Diets were then continued for 1, 6 or 18 weeks, whereafter parameters of hippocampal neurogenesis were analyzed and correlated to serum cytokine levels.

Synthesis and Cytotoxicity Evaluation of Spirocyclic Bromotyrosine Clavatadine C Analogs.

Marine-originated spirocyclic bromotyrosines are considered as promising scaffolds for new anticancer drugs. In a continuation of our research to develop potent and more selective anticancer compounds, we synthesized a library of 32 spirocyclic clavatadine analogs by replacing the agmatine, i.e.

Technical standards in allergen exposure chambers worldwide - an EAACI Task Force Report.

Allergen exposure chambers (AECs) can be used for controlled exposure to allergenic and non-allergenic airborne particles in an enclosed environment, in order to (i) characterize the pathological features of respiratory diseases and (ii) contribute to and accelerate the clinical development of pharmacological treatments and allergen immunotherapy for allergic disease of the respiratory tract (such as allergic rhinitis, allergic rhinoconjunctivitis, and allergic asthma). In the guidelines of the European Medicines Agency for the clinical development of products for allergen immunotherapy (AIT), the role of AECs in determining primary endpoints in dose-finding Phase II trials is emphasized. Although methodologically insulated from the variability of natural pollen exposure, chamber models remain confined to supporting secondary, rather than primary, endpoints in Phase III registration trials.

Synapsin-caveolin-1 gene therapy preserves neuronal and synaptic morphology and prevents neurodegeneration in a mouse model of AD.

Alzheimer's disease (AD) is the most common form of neurodegeneration and cognitive dysfunction in the elderly. Identifying molecular signals that mitigate and reverse neurodegeneration in AD may be exploited therapeutically. Transgenic AD mice (PSAPP) exhibit learning and memory deficits at 9 and 11 months, respectively, with associated decreased expression of caveolin-1 (Cav-1), a membrane/lipid raft (MLR) scaffolding protein necessary for synaptic and neuroplasticity.