Gujarat Vidyapith

Present study involves synthesis of derivatives of (5‐chloro‐2‐methoxyphenyl) (5‐alkyl‐3‐(substituted) (phenyl/alkyl)‐1 H ‐pyrazol‐1‐yl) methanones. Structural elucidation of the synthesized compounds was depicted by the data of ¹ H and ¹³ C NMR, IR, and Mass spectral analysis. The newly synthesized compounds 1a–1d and 2a–2i were screened in vitro against Mycobacterium tuberculosis H37Ra using an established XRMA protocol. Among the screened compounds, 2d, 2f, and 2h showed good percent inhibition against the active stage of M. tuberculosis H37Ra 80.77, 55.70, and 79.54, respectively, at 30 μg/mL of inhibitor concentration. Further in secondary screening, compound 2d exhibited significant antitubercular activity on the active stage of M. tuberculosis H37Ra with IC 50 of 0.208 μg/mL. The synthesized compounds were also screened for antibacterial activity and found no significant activity against Gram‐positive Bacteria Bacillus subtitles and Staphylococcus aureus and Gram negative bacteria Pseudomonas aeruginosa and Escherichia coli at 30 μg/mL, which confirms the specificity of inhibitory activity against M. tuberculosis and more selectively against the active stage. The present study will be helpful for the further development of these molecules into antitubercular lead candidates.

The ancient science of life known as Ayurveda offers countless potential to uncover many unexplored manuscripts that lead to effective medications. Understanding traditional medicinal plants can open up a wealth of significant bioactive phytoconstituents with numerous significant pharmacological functions. This treasure must be located based on the understanding of old Ayurveda and other traditional references. Sapindaceae family member Cardiospermum halicacabum Linn. is a rich source of phytochemicals, including tannins, saponins, phenols, flavonoids, terpenoids, alkaloids, and sterols. Many of these phytochemicals exhibit antioxidant, anxiolytic, antiinflammatory, anti-ulcer, anti-cancer, anti-microbial, antifungal, anti-bacterial, anti-diabetic, immunomodulatory, antiviral, cardioprotective, mainly neuroprotective properties according to Ayurveda. The plants' aerial parts are rich in phenolic acids, glycosidic compounds, tannins, and sterols. Researchers and academicians are examining the pharmacognosy, phytochemistry, and other pharmacological effects of the traditional medicinal plant known as Karnasphota (Cardiospermum halicacabum Linn.), which is cited in Ayurveda as one of the neuroprotective agents. Karnasphota (Cardiospermum halicacabum Linn.) is shown to have promising therapeutic potential by the scientific evidence offered by researchers and academics, and it can be further assessed as a novel candidate for drug discovery. The current review aims to examine the potential of the underexplored herb from Ayurveda "Karnasphota" for developing and designing future medications by reviewing the existence of medicinally significant secondary metabolites, potential pharmacological importance, and its role in neuroprotection in neurodegenerative diseases.

Background Tenecteplase has been approved for acute ischemic stroke at a dose of 0.2 mg/kg by the Indian licensing authority. A registry to evaluate the safety of tenecteplase was mandated by the licensing authority. The research aim was to use the Indian Registry in Ischemic Stroke‐Tenecteplase (IRIS‐TNK) to assess the safety and clinical outcomes in patients treated with tenecteplase in routine clinical practice. Methods and Results In this prospective, registry‐based observational, cohort study, the primary outcome was proportion of symptomatic intracerebral hemorrhages at 36±6 hours after treatment. Secondary outcomes included improvement in National Institutes of Health Stroke Scale (NIHSS) score by either ≥4 or 8 points or an NIHSS score of 0, assessment of excellent outcome (modified Rankin Scale score 0 or 1), functional independence (modified Rankin Scale score 0–2), and Barthel Index score. From October 2017 to May 2023, 1015 patients with a median age of 62 years (interquartile range [IQR, 52–71 years]) were recruited across India. The median baseline NIHSS score was 9 (IQR, 6–13). The proportion of patients with symptomatic intracerebral hemorrhage was 0.6% (95% CI, 0.2–1.3%), and 10 patients (1% [95% CI, 0.5–1.9%]) died within 3 months. Improvement in NIHSS score by ≥4 points or an NIHSS score of 0 at 24 hours was observed in 34.4% (95% CI, 31.5–37.4%) of patients. An excellent outcome (modified Rankin Scale score 0 or 1) at 3 months was achieved in 55.4% (95% CI, 52.3–58.5%) of patients. Conclusions These results confirm that tenecteplase at a dose of 0.2 mg/kg is safe in routine clinical practice, when administered within 4.5 hours of symptom onset. Registration https://ctri.nic.in/Clinicaltrials/ . Identifier: CTRI/2017/11/010380.

Industrial microbiology and advancements in biotechnology have revolutionized the agriculture sector by increasing the use of living microbes as biopesticides and biofertilizers which ultimately function as alternatives to chemical pesticides and fertilizers. These biopesticides and biofertilizers have gained significant attention due to their potential benefits for plants and are also commercially as well as environmentally sustainable. Many procedures are currently employed for the development of these biopesticides/biofertilizers but still need more attention to increase the shelf life of these bio-products. Apart from that, many microbes have been reported as a valuable tool for the bioremediation of persistent pollutants of soil and water using various strategies for the removal of recalcitrant compounds. As individual organisms, biopesticides and biofertilizers have shown reliable results on the crop yield, but there will be other consequences, while one is adding foreign microbes into the soil. Microbial ecology plays a vital role. It is the complex intricate relationships between microorganisms and their roles in shaping agricultural ecosystems. From soil microbial communities to interactions with plants, it affects agricultural productivity. This chapter emphasizes on the reliance on microorganisms used in sustainable agriculture and waste management sectors.

Industrial microbiology deals with desired organisms that produce various industrially important products. It includes various aspects: growth of microorganisms and media formulation and optimization. Advancement in techniques resulted into production of a wide range of natural and non-natural products. Recently, researchers are developing techniques for strain improvements which enhance products and their characteristics. This chapter focuses on various aspects of growth of organisms including kinetics and product yields. As the media provides an environment for better growth, the development in media formulation and optimization with various methods is needed for enhancing the products. To increase product yields and to ensure consistent product quality, key issues of industrial fermentations, process optimization, and scale up are aimed at maintaining optimum and homogeneous reaction conditions minimizing microbial stress exposure and enhancing metabolic accuracy. Metabolic engineering and recombinant DNA technology are applied to generate engineered microbial strains to produce economically better products.

The scholarship on sustainability transitions has surprisingly few studies on agriculture and food systems, especially from emerging economies such as India. The role of firms and businesses, especially cooperatives and producer organisations in agri-food systems transitions, has not been explored as much. Over the past decade, many Farmer Producer Organisations (FPOs) have been formed, primarily focused on facilitating the supply of agro-chemical inputs, while offering limited support to farmers in transitioning towards ecologically sustainable agricultural practices. This study looks at four case studies FPOs from across geographies in India, providing an opportunity to look at these FPOs as intermediaries of sustainable transitions and how they situate themselves in the agricultural ecosystem that has mainstream market actors as well as FPOs that are not engaged in sustainable agriculture. Additionally, to understand the intermediary role of FPOs, it is essential to examine how key actors—such as civil society organizations, financial institutions, marketing partners, and government agencies—contribute to and influence the intermediary role of FPOs in sustainable transition. These FPOs that are engaged in and promote sustainable agricultural practices bring out their strong potential transition intermediaries of the future

The in vitro activity of two novel antibiotics with different modes of action, (i) siderophore cefiderocol and (ii) β-lactam-enhancer mechanism-based cefepime/zidebactam, was tested against New Delhi Metallo-β-lactamase (NDM)-producing Enterobacterales and Pseudomonas aeruginosa collected in India. Minimum inhibitory concentrations of antibiotics against multicentric NDM-producing Escherichia coli (n = 117), Klebsiella pneumoniae (n = 103), and P. aeruginosa (n = 72) were determined by the reference broth microdilution method. Among E. coli, 111 isolates were NDM-alone, and six were NDM + OXA-48-like producers. Among K. pneumoniae, 47 and 56 isolates were NDM-alone and NDM + OXA-48-like producers, respectively. All E. coli isolates harbored four amino acid inserts in their penicillin-binding protein 3. Using the highest susceptible breakpoint among CLSI, FDA, and EUCAST interpretive criteria, cefiderocol susceptibility was 39.3%, ≤80%, and 57%, for NDM ± OXA-48-like-producing E. coli, NDM ± OXA-48-like-producing K. pneumoniae, and NDM-producing P. aeruginosa, respectively. At a cefepime break point of ≤8 mg/L, 100% of Enterobacterales and ≥90% of P. aeruginosa isolates were cefepime/zidebactam-susceptible. NDM being a dominant carbapenemase among Enterobacterales and P. aeruginosa in India, the variable activity of cefiderocol against NDM producers is a concern. Post approval, cefepime/zidebactam could offer a promising treatment option against NDM producers. IMPORTANCE Metallo-β-lactamases are therapeutically challenging due to the limited treatment options. Against such isolates, currently approved newer β-lactam/β-lactamase inhibitor combinations are ineffective. In this study, we tested siderophore cephalosporin, cefiderocol, which utilizes an unconventional iron uptake pathway for efficient cellular penetration, and cefepime/zidebactam that utilizes novel β-lactam enhancer mechanisms for overcoming diverse carbapenemases. Cefiderocol showed limited activity against Escherichia coli isolates co-harboring New Delhi metallo-β-lactamase (NDM) with PBP3 insert, dual carbapenemase (NDM with OXA-48 like)-producing Klebsiella pneumoniae, and NDM-producing Pseudomonas aeruginosa isolates, while cefepime/zidebactam potently inhibited NDM-producing Enterobacterales and P. aeruginosa isolates. NDM being a dominant carbapenemase among Enterobacterales and P. aeruginosa in India, the variable activity of cefiderocol against NDM producers is a concern. Post approval, cefepime/zidebactam could offer a promising treatment option against NDM producers.

Mutations in doublecortin domain‐containing protein 2 ( DCDC2 ) lead to neonatal sclerosing cholangitis (NSC), and portal hypertension (PHTN). The objective of the study was to systematically evaluate PHTN, variceal bleeding, and outcomes of patients with DCDC2 ‐related NSC. The study included children with homozygous or compound heterozygous variants in DCDC2 . All 14 children with DCDC2 ‐related NSC had PHTN. Eight (57.1%) developed variceal bleed at a median age of 3 years (range: 1.9–5 years). Eleven (78.6%) children with high‐risk varices underwent endotherapy. Varices were completely eradicated in three, downstaged to low‐risk in five, and there was no response with endotherapy in three. All three children with failure to eradicate/downstage varices had rebleed, and required listing for liver transplantation (LT). The study shows that children with variants in DCDC2 have a high incidence of variceal bleed at a very young age. Variceal eradication may often be difficult and rebleed rates are high; often necessitating LT.

Objective Brivaracetam (BRV), a third‐generation anti‐seizure medication (ASM) offers strong conformational receptor domain binding, faster blood brain barrier (BBB) permeability and better tolerability making it potential therapeutic option as an initial line or initial line add‐on strategy for focal onset seizure (FoS). The following study was planned to further understand the role and relevance of BRV in the real world settings of India. Method This was a multicentric, cross‐sectional, and non‐interventional study conducted in patients with FoS across India. The study was approved by central independent ethics committee. Descriptive and analytical statistics employed using SPSS version 29.0.1.0. Results Per protocol (PP) analysis included 8479 eligible patients from 1069 sites, gender; 5771 (68.06%) male and 2708 (31.94%) female with mean age 41.21 ± 12.74 years. Total 8019 (94.57%) patients had FoS and 460 (5.43%) patients had focal to bilateral tonic–clonic seizures (FBTCs). In FoS, 4105 (51.19%) patients switched from LEV to BRV whereas 3914 (48.81%) switched from other ASMs to BRV. BAEs accounted for 2059 (50.16%) patients in LEV to BRV switch versus 133 (3.39%) in other ASM to BRV switch. Post switch, LEV‐associated BAEs reduced irrespective of being used as monotherapy 85.65% (p < 0.001) or as an adjuvant therapy 83.71% (p < 0.001) at BRV dosage of 50 to 100 mg BID. This RWE showed the utility of BRV as mono component as an initial add‐on strategy in FoS cases. Significance BRV remains a pertinent therapeutic choice for FoS for the treatment naïve and/or BAE cases. Exposure of LEV leads to considerable BAEs compared to patients without LEV exposure. Patients who switched to BRV due to LEV‐induced BAEs significantly improved tolerability with BRV irrespective being used as monotherapy or as adjuvant therapy. Plain Language Summary Current study was planned to understand the clinical role and relevance of third‐generation anti‐seizure medication (ASM), brivaracetam (BRV) in the real world settings of India. Outcome of the study highlighted that BRV is an emerging, potential and safe ASM treatment option for epilepsy in Indian context. Many patients with epilepsy who are not able to tolerate the other ASM including levetiracetam (LEV) primarily due to behavioral side effects improves tolerability post switch to BRV, additionally results are consistent either BRV being used as an adjuvant therapy or as monotherapy therapy.

Despite the pervasiveness of Artificial intelligence (AI) and its widespread adoption in the marketplace, its impact on consumer emotions has remained understudied. To fill the gap, our study examines the impact of AI on consumer emotions in the service industry by identifying and mitigating its dark sides. We identified 12 dark side categories using a systematic literature review and probed using a modified total interpretive structural modelling (TISM) approach and MICMAC analysis. Therefore, we follow an exploratory qualitative approach based on in‐depth personal interviews with users of short‐term technology‐based platform Airbnb in the hospitality sector. The findings reveal six significant issues impacting consumer perception and responses toward AI‐enabled services, that is, authenticity, affective challenges, deployment problems, ethical dilemmas, discrimination in service, and adoption barriers. Our study advances the ongoing debate around AI and human entrapment. The present investigation contributes to the AI literature with a structured framework for understanding the dark side of AI on consumer emotions and the strategies to reduce those effects. The findings have significant practical implications for the hospitality industry, enabling it to prepare for a human‐centric approach to designing and applying AI, ethical concerns with privacy issues, and cultural expectations of the consumer. Finally, we lay out an agenda for exciting AI‐dark side‐related future research.

A bstract Lissencephaly or smooth brain can be classified based on the site of predominant cortical involvement. Identification of “gene-imaging pattern” associations facilitates specific analysis in some genes. KIF5C , a motor kinesin has been implicated in cortical dysplasia with eight reported cases to date. The Glu237 residue represents a hotspot being substituted in six out of seven patients. A uniform pattern of neuroimaging with a predominant frontal and mesio-frontal pachygyria has been observed in patients with mutations in the hotspot residue. Two different de novo disease-causing variants (nonhotspot mutations) were detected to be causative in the remaining two patients, resulting in posterior predominant pachygyria. This has led to the hypothesis of a mutation-specific imaging pattern, in KIF5C-associated lissencephaly. We hereby present a female with a novel nonhotspot mutation in the KIF5C gene. Using whole exome sequencing, a novel de novo missense mutation c.265T>C (p.Ser89Pro) of KIF5C was identified. Neuroimaging revealed a predominant frontal pachygyria, which is akin to the pattern observed with the Glu237 hotspot residue of KIF5C . We also compared the phenotype between patients with and without involvement of the hotspot residue and were able to show that no major differences exist between both groups. We expand the currently known narrow KIF5C mutation spectrum and challenge the notion of a typical pattern of “mutation-specific” imaging abnormality.

Injectable polymeric hydrogels delivered via endoscopic catheter have emerged as promising submucosal agents, offering durable, long‐lasting cushions to enhance the efficacy of endoscopic submucosal dissection (ESD) for the removal of small, flat polyps from the gastrointestinal tract (GIT). However, polymer‐based injections do not meet the easy‐injectability criteria via catheter because their high viscosity tends to clog the catheter needle. To the best of knowledge, for the first time, report the fabrication of an amphiphile‐based small molecule hydrogel of diglycerol monostearate (DGMS) that self‐assembles to form hydrogel (DGMSH) for delivery via an endoscopic catheter. Physicochemical characterization of the hydrogel reveals its fibrous morphology, shear‐thinning behaviour, and easy injectability, along with its scalability and long shelf‐life (6 months). Ex vivo studies on the goat's stomach and intestine demonstrate the ease of injectability through the catheters and the development of visible submucosal cushion depots with the desired height. Moreover, the hydrogel can encapsulate both hydrophobic and hydrophilic drugs/dyes. In vivo studies in small animals have found that the hydrogel depot is durable, biocompatible, non‐immunogenic, and has a hemostatic effect. Endoscopic studies in the porcine model demonstrate a safe injection and endoscopic excision of GI polyps acting as a suitable agent for ESD.

People with diabetes are at increased risk for infections, and vaccine-preventable diseases such as pneumococcal and influenza infections pose serious complications, including increased mortality rates. Despite the benefits of vaccinations in preventing such infections and their complications, vaccine uptake among individuals with diabetes remains suboptimal, particularly in countries like India. This article aims to address the importance of vaccinations in people with diabetes, discuss various vaccine-preventable diseases, and present harmonized vaccine recommendations tailored to the Indian context. A review of current guidelines from international health organizations such as the American Diabetes Association (ADA), Centers for Disease Control and Prevention (CDC), and Advisory Committee on Immunization Practices (ACIP) was conducted. Vaccination recommendations for pneumococcal, influenza, hepatitis B, Tdap, shingles, and respiratory syncytial virus (RSV) were evaluated, with a focus on their applicability to people with diabetes in India. Vaccines including pneumococcal polysaccharide vaccine (PPSV23) and pneumococcal conjugate vaccine (PCV13) have proven efficacy in preventing pneumococcal infections among people with diabetes. Influenza vaccines are shown to reduce all-cause mortality and prevent cardiovascular events during flu seasons. Hepatitis B, Tdap, and shingles vaccines are recommended for adults with diabetes. However, evidence reveals low vaccination coverage, particularly in India, where awareness and education regarding vaccination are lacking. The article provides harmonized vaccination recommendations specifically for the Indian context, aiming to address gaps in vaccine coverage and accessibility. The need for culturally sensitive education campaigns and healthcare provider engagement to improve vaccination rates is emphasized. Vaccinations play a key role in preventing serious infections in people with diabetes, yet hesitancy and limited awareness persist, especially in India. By providing clear, country-specific guidelines and increasing education efforts, vaccine uptake can be improved, ultimately reducing the burden of preventable diseases.

Objective Pelvic floor dysfunctions (pfds) such as urinary incontinence, pelvic organ prolapse, and vaginismus are very common and are affecting the quality of life of the female suffering through it. The pelvic floor muscles can be in spasm, thus resulting in the inability to relax or the pelvic floor muscles can be extremely weak or loose, resulting in the inability to contract strongly and completely. The spasmodic pelvic floor can result in vaginismus, dyspareunia, chronic pelvic pain, constipation, etc., Moreover, a weak pelvic floor can lead to issues such as urinary incontinence, pelvic organ prolapse, and sexual dysfunction. There is a scarcity of a valid and reliable scale that assesses both the components of pfd. Subjects and Methods The present study was conducted on 1349 participants which were divided into three groups on the basis of their symptoms. Group A – No symptoms ( n = 439), Group B – Hypotonus pfd ( n = 658), and Group C – Hypertonus pfd (n = 252). Examination: Vaginal examination to assess the pelvic floor muscles relaxation and contraction was done by Het’s Manual Muscle Testing (MMT). Inter rater reliability was assessed by comparing the data of two independent examiners on the same day. The intra rater reliability was assessed by comparing the data of test and retest at an interval of 1 week. Results The intra rater reliability at 95% confidence interval (CI) was 0.92 – Normal pelvic floor function, 0.96 – Hypotonus pfd, and 0.97 – Hypertonus pfd. Moreover, inter rater reliability at 95% CI was 0.93 – normal pelvic floor function, 0.95 for hypotonus pfd, and 0.98 – hypertonus pfd. Conclusions This study concludes Het’s MMT is a highly reliable manual muscle testing tool to assess the pelvic floor muscles.

Background The management of cardiovascular diseases often includes the use of statins, which, while reducing cardiovascular risk, can interact with other medications leading to significant adverse effects. This case report explores the complex interactions between atorvastatin, clopidogrel, and repaglinide, which precipitated severe hypoglycemia and myopathy in a patient with multiple comorbidities. Case Presentation We describe a 68-year-old female with a history of type 2 diabetes mellitus, hypertension, and ischemic heart disease, who developed severe hypoglycemia and myopathy following the adjustment of her statin therapy post-cardiac diagnosis. Her treatment regimen was modified to include an increased dose of atorvastatin and the introduction of clopidogrel, shortly after which she presented with hypoglycemia and symptoms of myopathy. Investigations revealed significantly elevated muscle injury markers and magnetic resonance imaging findings consistent with myositis. Discussion The pharmacokinetic interactions between clopidogrel with repaglinide and repaglinide with atorvastatin exacerbated by the increased dose of atorvastatin, likely led to the observed clinical manifestations. This case highlights the critical need for careful monitoring of drug interactions, especially in patients with polypharmacy. Adjustments in drug dosages and consideration of alternative medications with fewer interaction risks are essential components of managing similar cases. Conclusion This case underscores the importance of vigilant therapeutic management and individualized patient care in the context of complex drug regimens. Understanding and anticipating drug interactions can prevent significant adverse effects and improve patient outcomes in a population at high risk of polypharmacy complications.

The hygroscopic nature of chlorides gives them the potential to provide a harbor for microbes to adapt and survive in extreme conditions, which is pertinent to Mars, given its evolution of climatic conditions. Moreover, observations of secondary hydrous minerals in chloride‐rich regions have opened the case for a diverse geological environment on the Martian surface. Therefore, through comprehensive analysis, we aim to reconstruct the geological evolution of a chloride‐rich basin within Terra Sirenum. We conducted morphological, morphometric, and mineralogical analyses of the basin and its surrounding area to determine its geological evolution, longevity, and environmental condi5tions during its activity. Subsequently, we carried out a discharge analysis of the surrounding valley networks and determined the water activity using ionic forms of the associated mineralogy. We observed bright‐toned polygonal cracks within the basin as well as its surrounding terrain, suggesting that the basin extended beyond its present boundary. Mineralogical diversity and age dating of the basin and the surrounding area indicated different geochemical environments and cycles of wetting and drying until the late Hesperian. Whereas, sediment transport modeling suggests that the basin was hydrologically active for more than ten thousand years. Our results show a tell‐tale signature of a large sedimentary basin and a large‐scale geological process within the Terra Sirenum. The water activity modeling show that the geochemical composition of the basin was favorable to support the origin of life forms and/or sustain them and suggest promising aspects of the basin for future landing missions.

Ubiquitin‐specific protease 53 (USP53) is essential for formation of cellular tight junctions and variations in this gene disrupt the tight junctions, resulting in cholestasis. We describe the clinical manifestations and outcomes of patients with USP53 mutations from the Indian progressive familial intrahepatic cholestasis registry. All 29 patients who harbored mutations in the USP53 gene either in the homozygous, compound heterozygous, or heterozygous state and presented with cholestasis were included. USP53 variants related to cholestasis had good outcomes, with native liver survival in 82.7%, whereas 17.3% required liver transplantation. Jaundice developed in 93% and within 3 months of age in 48.8%. Jaundice resolved in 21 (72.4%). Pruritus 76% at a median age of 7 months (severe in 10/22, 45% and refractory to medical therapy in 4, 18.1%). Majority of them (82.7%) had biallelic mutations. Protein‐truncating mutations were present in 20 (69%) and missense mutations in 9 (31%). No correlation was found between the genotype and the outcome.