Combatting Antibiotic Resistance: Identifying Gaps in Knowledge, Attitude, and Practice Among Medical Interns.

INTRODUCTION: Antibiotic resistance presents a significant global health threat to modern medicine. The awareness and attitude of future doctors undergoing training may play a crucial role in addressing this important issue, influencing the control of resistance and promoting responsible antibiotic stewardship. This study aimed to estimate knowledge, attitudes, and practices regarding antibiotic usage and antimicrobial resistance among tertiary care teaching hospital medical interns. METHODOLOGY: The questionnaire-based cross-sectional study was conducted on 123 MBBS interns from multiple medical institutions. Intern's knowledge, attitudes, and self-reported practices regarding antibiotic use were recorded. RESULTS: Based on survey responses from 123 participants, 116 (94.31%) were aware of the adverse effects of indiscriminate antibiotic use, recognizing the risks of ineffective treatment, increased adverse effects, prolonged illness, bacterial resistance, and higher medical costs. Most (106, 86.18%) acknowledged the challenges of treating antibiotic-resistant infections, and 69 (56.10%) correctly identified that bacteria are not a cause of the common cold and flu. Most (115, 93.5%) recognized antibiotic resistance as a significant global health problem. In attitude, 90 (73%) believed antibiotics should be avoided for colds, but 80 (65%) thought they hastened fever recovery. Only 48 (39%) recognized that antibiotics contribute to resistance, while 102 (83%) agreed skipping doses fosters resistance. Most support hospital policies (118, 96%) and curriculum courses (112, 91%) for rational antibiotic use. Regarding practice, 12 (9.76%) interns admitted to overusing antibiotics, 68 (55.28%) consulted a doctor before starting antibiotics, and 87 (70.73%) checked expiry dates. Additionally, 62 (50.41%) preferred antibiotics for cough and sore throat symptoms. CONCLUSIONS: The study highlights that while interns have a good knowledge and awareness of the harms of antibiotic misuse, they are not translating this knowledge into practice. This indicates a disconnect between understanding and application. Therefore, there is a need to add a rational antibiotic prescription and stewardship module to the medical curriculum to ensure that knowledge is effectively translated into changing beliefs and practices.

Expedient, regioselective C-H chalcogenation of 3,4-dihydro-1,4-benzoxazines using a palladium-copper catalyst.

The palladium-catalysed regioselective C-H chalcogenation of benzoxazines with disulfides and diselenides in air has been described. In this protocol, palladium acetate serves as the catalyst in conjunction with copper as an oxidizing agent. Through this approach, a wide array of sulfenylation and selenylation reactions of benzomorpholines have been effected, yielding results ranging from good to excellent. Thus, the established procedure demonstrates superb regioselectivity and a strong tolerance towards various functional groups and is suitable for gram-scale synthesis. Additionally, this synthetic approach offers a practical and convenient pathway for late-stage functionalization leading to the Rosenmund-von Braun reaction.

Dual fluid silhouette in X-ray of the abdomen: a diagnostic flag for neurogenic bladder with urinary ascites.

A neonate presented with abdominal distension and decreased urinary output. X-ray revealed dual abdominal fluid condition-ascites with a distended bladder, along with vertebral anomalies. The possibility of urinary ascites and neurogenic bladder was kept, which was further confirmed on evaluation. Here, we emphasise the crucial role of abdominal X-ray as a diagnostic tool in uncovering this intricate medical puzzle. By detailing the clinical presentation, diagnostic approach and treatment strategy, the report contributes insights into the rare and complex abdominal condition.

Comparison of Three Methods of Umbilical Cord Management in Late Preterm and Term Newborns on Hemoglobin and Ferritin Levels at Six Weeks of Age: A Randomized Controlled Trial.

BACKGROUND: Umbilical cord milking (UCM) and delayed cord clamping (DCC) are strategies that improve the hemodynamic condition of the newborn and also increase the storage of iron. This study aimed to compare the effects of DCC with or without milking in late preterm and term neonates at different time intervals after birth (60, 120, and 180 seconds) on hematological and hemodynamic parameters in neonates at six weeks of age. MATERIALS AND METHODS: In this double-arm, parallel-group, triple-blind, and active-controlled trial, all 150 eligible neonates were randomized with allocation concealment into three groups: Group A (DCC with UCM at 60 seconds), Group B (DCC with UCM at 120 seconds), and Group C (only DCC for 180 seconds). Hemodynamic parameters were recorded and compared during the first 48 hours, and hematological parameters were compared at six weeks of age. RESULTS: At six weeks, a significant difference in hemoglobin levels was noted between Groups A, B, and C (p<0.001). The difference in serum ferritin values at six weeks was also statistically significant in comparisons across all three groups (p=0.003). Regarding secondary outcomes examined, hemodynamic parameters and the incidence of neonatal hyperbilirubinemia were found to be comparable at 48 hours after birth. CONCLUSION: DCC followed by UCM at 120 seconds and DCC till 180 seconds proves superior to DCC with UCM at 60 seconds in preserving elevated hemoglobin levels and iron stores in neonates at six weeks of age. DCC for 180 seconds yielded comparable results, followed by UCM at 120 seconds. All three methods are considered safe and effective without compromising the neonate's hemodynamics.

Advances in chromone-based copper(ii) Schiff base complexes: synthesis, characterization, and versatile applications in pharmacology and biomimetic catalysis.

Chromones are well known as fundamental structural elements found in numerous natural compounds and medicinal substances. The Schiff bases of chromones have a much wider range of pharmacological applications such as antitumor, antioxidant, anti-HIV, antifungal, anti-inflammatory, and antimicrobial properties. A lot of research has been carried out on chromone-based copper(ii) Schiff-base complexes owing to their role in the organometallic domain and promise as potential bioactive cores. This review article is centered on copper(ii) Schiff-base complexes derived from chromones, highlighting their diverse range of pharmacological applications documented in the past decade, as well as the future research opportunities they offer.

Synthesis, characterization and photophysical studies of dual-emissive base-modified fluorescent nucleosides.

A straightforward and efficient methodology has been employed for the synthesis of a diverse set of base-modified fluorescent nucleoside conjugates via Cu(I)-catalysed cycloaddition reaction of 5-ethynyl-2',3',5'-tri-O-acetyluridine/3',5'-di-O-acetyl-2'-deoxyuridine with 4-(azidomethyl)-N9-(4'-aryl)-9,10-dihydro-2H,8H-chromeno[8,7-e][1,3]oxazin-2-ones in tBuOH to afford the desired 1,2,3-triazoles in 92-95% yields. Treatment with NaOMe/MeOH resulted in the final deprotected nucleoside analogues. The synthesized 1,2,3-triazoles demonstrated a significant emission spectrum, featuring two robust bands in the region from 350-500 nm (with excitation at 300 nm) in fluorescence studies. Photophysical investigations revealed a dual-emissive band with high fluorescence intensity, excellent Stokes shift (140-164 nm) and superior quantum yields (0.068-0.350). Furthermore, the electronic structures of the synthesized triazoles have been further verified by DFT studies. Structural characterization of all synthesized compounds was carried out using various analytical techniques, including IR, 1H-NMR, 13C-NMR, 1H-1H COSY, 1H-13C HETCOR experiments, and HRMS measurements. The dual-emissive nature of these nucleosides would be a significant contribution to nucleoside chemistry as there are limited literature reports on the same.

Natural product inspired diastereoselective synthesis of sugar-derived pyrano[3,2-c]quinolones and their in-silico studies.

Herein, we report the development of a diastereoselective and efficient route to construct sugar-derived pyrano[3,2-c]quinolones utilizing 1-C-formyl glycal and 4-hydroxy quinolone annulation. This methodology will open a route to synthesize nature inspired pyrano[3,2-c]quinolones. This is the first report for the stereoselective synthesis of sugar-derived pyrano[3,2-c]quinolones, where 100% stereoselectivity was observed. A total of sixteen compounds have been synthesized in excellent yields with 100% stereoselectivity. The molecular docking of the synthesized novel natural product analogues demonstrated their binding modes within the active site of type II topoisomerase. The results of the in-silico studies displayed more negative binding energies for the all the synthesized compounds in comparison to the natural product huajiosimuline A, indicating their affinity for the active pocket. Ten out of the sixteen novel synthesized compounds were found to have comparative or relatively more negative binding energy in comparison to the standard anti-cancer drug, doxorubicin. Additionally, the scalability and viability of this protocol was illustrated by the gram scale synthesis.

Phenyliodine bis(trifluoroacetate) as a sustainable reagent: exploring its significance in organic synthesis.

Iodine-containing molecules, especially hypervalent iodine compounds, have gained significant attention in organic synthesis. They are valuable and sustainable reagents, leading to a remarkable surge in their use for chemical transformations. One such hypervalent iodine compound, phenyliodine bis(trifluoroacetate)/bis(trifluoroacetoxy)iodobenzene, commonly referred to as PIFA, has emerged as a prominent candidate due to its attributes of facile manipulation, moderate reactivity, low toxicity, and ready availability. PIFA presents an auspicious prospect as a substitute for costly organometallic catalysts and environmentally hazardous oxidants containing heavy metals. PIFA exhibits remarkable catalytic activity, facilitating an array of consequential organic reactions, including sulfenylation, alkylarylation, oxidative coupling, cascade reactions, amination, amidation, ring-rearrangement, carboxylation, and numerous others. Over the past decade, the application of PIFA in synthetic chemistry has witnessed substantial growth, necessitating an updated exploration of this field. In this discourse, we present a concise overview of PIFA's applications as a 'green' reagent in the domain of synthetic organic chemistry. A primary objective of this article is to bring to the forefront the scientific community's awareness of the merits associated with adopting PIFA as an environmentally conscientious alternative to heavy metals.

Visible-Light-Driven Regioselective Decarboxylative Acylation of N-Methyl-3-phenylquinoxalin-2(1H)-one by Dual Palladium-Photoredox Catalysis Through C-H Activation.

We report herein an efficient visible-light-promoted approach for the regioselective decarboxylative C-H acylation of N-methyl-3-phenylquinoxalin-2(1H)-ones using α-oxo-2-phenylacetic acids via dual palladium-photoredox catalysis. The reactions were carried out at room temperature in the presence of 24 W blue LEDs. The established protocol tolerated a wide range of functional groups and enabled the synthesis of several acylated N-methyl-3-phenylquinoxalin-2(1H)-ones in good to excellent yields. The proposed mechanism for this transformation was supported by control experiments.

Recent advances in the synthesis and utility of thiazoline and its derivatives.

Thiazolines and their derivatives hold significant importance in the field of medicinal chemistry due to their promising potential as pharmaceutical agents. These molecular entities serve as critical scaffolds within numerous natural products, including curacin A, thiangazole, and mirabazole, and play a vital role in a wide array of physiological reactions. Their pharmacological versatility encompasses anti-HIV, neurological, anti-cancer, and antibiotic activities. Over the course of recent decades, researchers have extensively explored and developed analogs of these compounds, uncovering compelling therapeutic properties such as antioxidant, anti-tumor, anti-microbial, and anti-inflammatory effects. Consequently, thiazoline-based compounds have emerged as noteworthy targets for synthetic endeavors. In this review, we provide a comprehensive summary of recent advancements in the synthesis of thiazolines and thiazoline-based derivatives, along with an exploration of their diverse potential applications across various scientific domains.

Transition-Metal Catalyzed Synthesis of Pyrimidines: Recent Advances, Mechanism, Scope and Future Perspectives.

Pyrimidine is a pharmacologically important moiety that exhibits diverse biological activities. This review reflects the growing significance of transition metal-catalyzed reactions for the synthesis of pyrimidines (with no discussion being made on the transition metal-catalyzed functionalization of pyrimidines). The effect of different catalysts on the selectivity/yields of pyrimidines and catalyst recyclability (wherever applicable) are described, together with attempts to illustrate the role of the catalyst through mechanisms. Although several methods have been researched for synthesizing this privileged scaffold, there has been a considerable push to expand transition metal-catalyzed, sustainable, efficient and selective synthetic strategies leading to pyrimidines. The aim of the authors with this update (2017-2023) is to drive the designing of new transition metal-mediated protocols for pyrimidine synthesis.

Solvent-free synthesis and in-silico molecular docking study of (E)-3-(ß-C-glycosylmethylidene)-N-aryl/alkyl succinimides.

Globally, human papillomavirus (HPV) infection is the leading cause of mortality associated with cervical cancer, oral cancer (oropharyngeal), and head and neck squamous cell carcinoma (HNSCC). It is essential to explore anti-cancer drugs against life-threatening HPV infections. Aiming to search for potentially better anticancer agents, a small library of ß-C-glycosylated methylidene succinimides have been synthesized under bulk and mechanical grinding conditions using the Wittig olefination reaction. Thus, the reaction of different 2,3,4,6-tetra-O-benzyl-C-glycosyl aldehydes with N-aryl/alkyl maleimides in the presence of PPh3 at 25 °C under bulk and mechanical grinding conditions results in the formation of stereochemically defined (E)-3-(2,3,4,6-tetra-O-benzyl-C-glycosylmethylidene)-N-alkyl/phenyl succinimides, which upon debenzylation with 1 M BCl3 in DCM at -78 °C lead to the synthesis of (E)-3-(C-glycosylmethylidene)-N-alkyl/phenyl succinimides in good to excellent yields. The developed methodology is efficient and environmentally benign because there is no use of organic solvents, and the products are obtained in a stereochemically defined form and in high yields. The aqueous solubility of all synthesized ß-C-glycosylated methylidene succinimides makes them potential candidates for the evaluation of their different biological activities. In the present work, the synthesized glycosylated alkylidine succinimides were subjected to an in-silico molecular docking study against the E6 oncoprotein of high-risk type HPV16, which is responsible for the inactivation of the tumor suppressor p53 protein. Analysis of the molecular docking data revealed that the synthesized compounds are effective inhibitors of HPV infection, which is the cause of oral, head and neck, and cervical cancer. In comparison with the positive control 5-FU, an anti-cancer drug used in chemotherapy, more than fifteen compounds were found to be better E6 protein inhibitors.

Efficient synthesis of glycosylated imidazo[1,2-a]pyridines via solvent catalysed Groebke-Blackburn-Bienayme reaction.

A solvent catalysed and metal catalyst-free Groebke-Blackburn-Bienayame three component reaction (GBB-3CR) has been developed for the synthesis of 2-(ß-D-glycal-1-yl)-3-N-alkylamino-1-azaindolizines and 2-alkyl/aryl/heteroaryl-3-N-alkylamino-1-azaindolizines. The modified GBB reaction protocol is highly efficient, versatile, atom economic and has been performed in hexafluoroisopropanol (HFIP) without any added catalyst. The GBB-3CR showed high tolerance for a large no of substrates in term of aldehydes, differently substituted 2-aminopyridines and isocyanides without being affected by the presence of electron donating and electron withdrawing substituents at either aldehydes or 2-aminopyridines.

Efficient and stereoselective synthesis of sugar fused pyrano[3,2-c]pyranones as anticancer agents.

A highly stereoselective, efficient and facile route was achieved for the synthesis of novel and biochemically potent sugar fused pyrano[3,2-c]pyranone derivatives starting from inexpensive, naturally occurring d-galactose and d-glucose. First, ß-C-glycopyranosyl aldehydes were synthesized from these d-hexose sugars in six steps, with overall yields 41-55%. Next, two different 1-C-formyl glycals were synthesized from these ß-C-glycopyranosyl aldehydes by treatment in basic conditions. The optimization of reaction conditions was carried out following reactions between 1-C-formyl galactal and 4-hydroxycoumarin. Next, 1-C-formyl galactal and 1-C-formyl glucal were treated with nine substituted 4-hydroxy coumarins at room temperature (25 °C) in ethyl acetate for ∼1-2 h in the presence of l-proline to obtain exclusively single diastereomers of pyrano[3,2-c]pyranone derivatives in excellent yields. Four compounds were found to be active for the MCF-7 cancer cell line. The MTT assay, apoptosis assay and migration analysis showed significant death of the cancer cells induced by the synthesized compounds.

Recent advances in synthesis of sugar and nucleoside coumarin conjugates and their biological impact.

Naturally occurring coumarin and sugar molecules have a diverse range of applications along with superior biocompatibility. Coumarin, a member of the benzopyrone family, exhibits a wide spectrum of medicinal properties, such as anti-coagulant, anti-bacterial, anti-tumor, anti-oxidant, anti-cancer, anti-inflammatory and anti-viral activities. The sugar moiety functions as the central scaffold for the synthesis of complex molecules, attributing to their excellent biocompatibility, well-defined stereochemistry, benign nature and outstanding aqueous solubility. When the coumarin moiety is conjugated with the sugar or nucleoside molecule, the resulting conjugates exhibit significant biological properties. Due to the remarkable growth of such bioconjugates in the field of science over the last decade, owing to their future prospect as a potential bioactive core, an update to this area is very much needed. The present review focusses on the synthesis, characterization and the various therapeutic applications of coumarin conjugates, i.e., sugar and nucleoside coumarin conjugates along with their perspective for future research.

Microwave assisted regioselective halogenation of benzo[b][1,4]oxazin-2-ones via sp2 C-H functionalization.

A microwave assisted, palladium-catalyzed regioselective halogenation of 3-phenyl-2H-benzo[b][1,4]oxazin-2-ones has been demonstrated using inexpensive and readily available N-halosuccinimide. The reaction utilizes the nitrogen atom present in the heterocyclic ring as the directing group to afford regioselective halogenated products in good to moderate yields. The established protocol provides wide substrate scope, high functional group tolerance, and high atom and step economy. The reaction proved to be cost-effective and time-saving as it required only a few minutes for completion and is amenable to gram scale. The halogen atoms present in synthesized products provide further scope for post-functionalization. Several post-functionalized products have also been synthesised to demonstrate the high utility of the reaction in the field of drug discovery and late-stage functionalization.

Rhodium-catalyzed selenylation and sulfenylation of quinoxalinones 'on water'.

A rhodium-catalysed, regioselective synthetic methodology for selenylation and sulfenylation of 3-phenyl quinoxolinones has been developed through N-directed C-H activation in the presence of silver triflimide, and silver carbonate using dichalcogenides 'on water'. The methodology has been proven to be efficient, regioselective and green. Using this method, a range of selenylations and sulfenylations of the substrates has been carried out in good to excellent yields. Further, late-stage functionalisation produced potential anti-tumour, anti-fungal and anti-bacterial agents making these compounds potential drug candidates.

Sustainable C-H activation approach for palladium-catalyzed, regioselective functionalization of 1-methyl-3-phenyl quinoxaline-2(1H)-ones in water.

A sustainable and environment-friendly approach for the regioselective acylation of 1-methyl-3-phenyl quinoxaline-2(1H)-ones has been developed in water. The present protocol requires palladium acetate as a catalyst and exhibits a wide substrate scope by employing commercially available, non-toxic aldehydes, benzyl alcohols and toluenes as acyl surrogates. The mechanistic studies demonstrated the adoption of a free radical pathway for this transformation. Furthermore, the established protocol exhibits excellent regioselectivity and high functional group tolerance and is amenable to the gram scale. The established synthetic method also provides a practical and convenient route for the late-stage functionalization of some potential drug candidates.

De-escalation of asymptomatic testing and potential of future COVID-19 outbreaks in US nursing homes amidst rising community vaccination coverage: A modeling study.

As of 2 September 2021, United States nursing homes have reported >675,000 COVID-19 cases and >134,000 deaths according to the Centers for Medicare & Medicaid Services (CMS). More than 205,000,000 persons in the United States had received at least one dose of a COVID-19 vaccine (62% of total population) as of 2 September 2021. We investigate the role of vaccination in controlling future COVID-19 outbreaks. We developed a stochastic, compartmental model of SARS-CoV-2 transmission in a 100-bed nursing home with a staff of 99 healthcare personnel (HCP) in a community of 20,000 people. We parameterized admission and discharge of residents in the model with CMS data, for a within-facility basic reproduction number (R0) of 3.5 and a community R0 of 2.5. The model also included: importation of COVID-19 from the community, isolation of SARS-CoV-2 positive residents, facility-wide adherence to personal protective equipment (PPE) use by HCP, and testing. We systematically varied coverage of mRNA vaccine among residents, HCP, and the community. Simulations were run for 6 months after the second dose in the facility, with results summarized over 1,000 simulations. Expected resident cases decreased as community vaccination increased, with large reductions at high HCP coverage. The probability of a COVID-19 outbreak was lower as well: at HCP vaccination coverage of 60%, probability of an outbreak was below 20% for community coverage of 50% or above. At high coverage, stopping asymptomatic screening and facility-wide testing yielded similar results. Results suggest that high coverage among HCP and in the community can prevent infections in residents. When vaccination is high in nursing homes, but not in their surrounding communities, asymptomatic and facility-wide testing remains necessary to prevent the spread of COVID-19. High adherence to PPE may increase the likelihood of containing future COVID-19 outbreaks if they occur.