Enhanced cardiovascular disease prediction through self-improved Aquila optimized feature selection in quantum neural network & LSTM model.

Introduction: Cardiovascular disease (CVD) stands as a pervasive catalyst for illness and mortality on a global scale, underscoring the imperative for sophisticated prediction methodologies within the ambit of healthcare data analysis. The vast volume of medical data available necessitates effective data mining techniques to extract valuable insights for decision-making and prediction. While machine learning algorithms are commonly employed for CVD diagnosis and prediction, the high dimensionality of datasets poses a performance challenge. Methods: This research paper presents a novel hybrid model for predicting CVD, focusing on an optimal feature set. The proposed model encompasses four main stages namely: preprocessing, feature extraction, feature selection (FS), and classification. Initially, data preprocessing eliminates missing and duplicate values. Subsequently, feature extraction is performed to address dimensionality issues, utilizing measures such as central tendency, qualitative variation, degree of dispersion, and symmetrical uncertainty. FS is optimized using the self-improved Aquila optimization approach. Finally, a hybridized model combining long short-term memory and a quantum neural network is trained using the selected features. An algorithm is devised to optimize the LSTM model's weights. Performance evaluation of the proposed approach is conducted against existing models using specific performance measures. Results: Far dataset-1, accuracy-96.69%, sensitivity-96.62%, specifity-96.77%, precision-96.03%, recall-97.86%, F1-score-96.84%, MCC-96.37%, NPV-96.25%, FPR-3.2%, FNR-3.37% and for dataset-2, accuracy-95.54%, sensitivity-95.86%, specifity-94.51%, precision-96.03%, F1-score-96.94%, MCC-93.03%, NPV-94.66%, FPR-5.4%, FNR-4.1%. The findings of this study contribute to improved CVD prediction by utilizing an efficient hybrid model with an optimized feature set. Discussion: We have proven that our method accurately predicts cardiovascular disease (CVD) with unmatched precision by conducting extensive experiments and validating our methodology on a large dataset of patient demographics and clinical factors. QNN and LSTM frameworks with Aquila feature tuning increase forecast accuracy and reveal cardiovascular risk-related physiological pathways. Our research shows how advanced computational tools may alter sickness prediction and management, contributing to the emerging field of machine learning in healthcare. Our research used a revolutionary methodology and produced significant advances in cardiovascular disease prediction.

Antioxidants of commercial interest from Homalium tomentosum attenuates hepatocellular necrosis: Insights from experimental and computational studies.

Homalium tomentosum (Vent.) Benth, is a valuable agroforestry species and has industrial importance high-quality wood is used for malas, the manufacture of matches, and is suitable for making a wide range of articles. Nevertheless, leaves and bark are relatively rich in phenols and flavonoids, used for medicinal purposes. In this study, phenols and flavonoids rich in bio-privileged antioxidants in ethyl-acetate extracted fractions of bark (HTEB), and leaves (HTEL) at 300, and 400 mg/kg were examined in carbon tetrachloride (CCl4)-induced hepatotoxicity in experimental rats. HTEB and HTEL (400) showed improvement in liver structural integrity, but, HTEB400 significantly improved serum (total protein, TP; alkaline phosphatase, ALP; total bilirubin, TB; serum glutamate oxaloacetate transaminase, SGOT, and serum glutamate pyruvate transaminase, SGPT), and hepatic oxidative (catalase, CAT; thiobarbituric acid reactive species, TBARS; reduced glutathione, GSH; superoxide dismutase, SOD), and inflammatory (transforming growth factor, TGF-ß; ineterleukin-6, IL-6) biomarkers accompanied by histopathological improvements of the liver. GC-MS analysis of HTEB and HTEL identified 14 and 18 compounds, but physicochemical properties of 3-major antioxidants of HTEB (levoglucosenone, (+)-borneol, α-N-normethadol), and HTEL (2-coumaranone, salicyl alcohol, D-allose) were satisfied for the parameters molecular weight, no. of H-acceptor and H-donor, partition co-efficient (clogP), and topological polar surface area (tPSA) of Lipinski's rule. ADME-Tox properties were directly related to the biological activities of HTEB and HTEL. Molecular docking investigation of α-N-normethadol showed the highest binding energy against TGF-ß and IL-6 than other antioxidants. HTEB and HTEL were powerful antioxidant potential, but levoglucosenone, (+)-borneol, and α-N-normethadol of HTEB demonstrated better activities in neutralizing reactive oxygen species (ROS) to preserve cellular membrane integrity in liver cirrhosis as found evidence in restoring the liver inflammatory cytokines. This study confirmed the economic interest of H. tomentosum bark as crude material for the preparation of biobased materials for the pharmaceutical and food industries.

"Purple-Xed" by a baffling bleed - A clinical care conundrum.

Human retro-viral disease and the myriad opportunistic infections associated with it continue to pose a diagnostic challenge to clinicians. Disseminated Kaposi sarcoma (KS) and KS-associated immune reconstitution inflammatory syndrome (IRIS) are entities that can be associated with adverse clinical outcomes unless recognized early by the treating physician. We present the case of a 36-year-old homosexual HIV-positive male who presented with unusual symptoms of KS and KS IRIS with lower gastrointestinal bleeding and respiratory distress devoid of any cutaneous manifestations.

Nickel complexes bearing quinoline derived NNS donor ligands as catalytic activators for N-alkylation of anilines with alcohols.

Herein, we have reported a new series of NNS-donor ligands coordinated Ni(II) complexes and utilized them as catalytic activator to synthesize N-alkylated aminesand 1,2-disubstituted benzimidazoles. The separate reaction of  [C9H6N-NH-C(O)-CH2-S-Ar] [Ar = C6H5 (L1); C6H4Cl-4 (L2);C6H4Me-4 (L3) and C6H4-OMe-4 (L4)] with Ni(OAc)2 in methanol at 80°C for 3 hours resulted in octahedral nickel complexes [(L1-H)2Ni] (C1), [(L2-H)2Ni] (C2), [(L3-H)2Ni] (C3), and [(L4-H)2Ni] (C4), respectively. All compounds have been characterized by micro and spectroscopic analysis. The molecular structure of complexes C1-C3 has also been determined by single crystal X-ray diffraction data. The utility of complexes C1-C4 were evaluated for the N-alkylation of aniline with benzyl alcohols, and for 1,2-disubstituted benzimidazoles synthesis. The obtained results indicate that complex C1 showed better catalytic activity in both N-alkylation of amines with benzyl alcohols [catalyst loading: 2.0 mol%; Yield up to 92%], and for 1,2-disubstituted benzimidazoles derivatives [catalyst loading: 2.0 mol%; Yield up to 94%)]. The mechanistic studies suggested that the reaction works through hydrogen borrowing from benzyl alcohol and its subsequent utilization for in situ reduction of imine. The experimentally observed catalytic reactivity patterns of complexes C1-C4 have found in good agreement with the HOMO-LUMO energy gaps obtained by DFT analysis of corresponding complexes.

In vivo single-cell CRISPR uncovers distinct TNF programmes in tumour evolution.

The tumour evolution model posits that malignant transformation is preceded by randomly distributed driver mutations in cancer genes, which cause clonal expansions in phenotypically normal tissues. Although clonal expansions can remodel entire tissues1-3, the mechanisms that result in only a small number of clones transforming into malignant tumours remain unknown. Here we develop an in vivo single-cell CRISPR strategy to systematically investigate tissue-wide clonal dynamics of the 150 most frequently mutated squamous cell carcinoma genes. We couple ultrasound-guided in utero lentiviral microinjections, single-cell RNA sequencing and guide capture to longitudinally monitor clonal expansions and document their underlying gene programmes at single-cell transcriptomic resolution. We uncover a tumour necrosis factor (TNF) signalling module, which is dependent on TNF receptor 1 and involving macrophages, that acts as a generalizable driver of clonal expansions in epithelial tissues. Conversely, during tumorigenesis, the TNF signalling module is downregulated. Instead, we identify a subpopulation of invasive cancer cells that switch to an autocrine TNF gene programme associated with epithelial-mesenchymal transition. Finally, we provide in vivo evidence that the autocrine TNF gene programme is sufficient to mediate invasive properties and show that the TNF signature correlates with shorter overall survival of patients with squamous cell carcinoma. Collectively, our study demonstrates the power of applying in vivo single-cell CRISPR screening to mammalian tissues, unveils distinct TNF programmes in tumour evolution and highlights the importance of understanding the relationship between clonal expansions in epithelia and tumorigenesis.

Observation of multiple attractors and diffusive transport in a periodically driven Klein-Gordon chain.

We consider a Klein-Gordon chain that is periodically driven at one end and has dissipation at one or both boundaries. An interesting numerical observation in a recent study [Prem et al., Phys. Rev. B 107, 104304 (2023)2469-995010.1103/PhysRevB.107.104304] was that for driving frequency in the phonon band, there is a range of values of the driving amplitude F_{d}∈(F_{1},F_{2}) over which the energy current remains constant. In this range the system exhibits a traveling wave solution termed a "resonant nonlinear wave" (RNW). It was noted that the RNW mode occurs over a range (F_{1},F_{2}) and shrinks with increasing system size, N. Remarkably, we find that the RNW mode is in fact a stable solution even for F_{d}>F_{2}, and that in this regime there exist two attractors, both with finite basins of attraction. We improve the perturbative treatment for the RNW mode, presented in the earlier work, by including the contributions of third harmonics. We also consider the effect of thermal noise at the boundaries and find that the RNW mode is stable for small temperatures. Corresponding to the two attractors for large F_{d} at zero temperature, the system can now be in two nonequilibrium steady states. Finally, we present results for a different driving protocol [Komorowski et al., Commun. Math. Phys. 400, 2181 (2023)10.1007/s00220-023-04654-4] where F_{d} is taken to scale with system size as N^{-1/2} and dissipation is only at the nondriven end. We find that the steady state for this case can be characterized by Fourier's law. We point out interesting differences that occur because of our dynamics being nonlinear and Hamiltonian. Our results suggest the intriguing possibility of observing the high-current-carrying RNW phase in experiments by careful preparation of initial conditions.

Expanding Arsenal against Ocular Diseases through Nanoemulsion: Success So Far and the Road Ahead.

The eye is a most delicate organ protected by several complex biological barriers that are static and dynamic. The presence of these ocular barriers retards drug absorption from topically applied dosage forms at the conjunctival sac. The efficient topical delivery of the drug into the globe is more difficult to achieve and there is a need to develop a topical formulation that may reduce the use of injections and increase patient compliance with decreased frequency of administration. In the advancements of research in nanotechnology, nanoemulsions can be used as biocompatible carriers to deliver the drug to the ocular cavity. The lipophilic globules can increase the solubility of hydrophobic cargos which provides increased permeation ability and ocular bioavailability which can sustain drug release and corneal retention. Because of their small size, these formulations do not cause blurring of vision. Nanoemulsions (NEs) over the past decade have been used to treat several ocular diseases in the anterior eye segment. This review summarizes the economic burden, pathology of ocular diseases, formulation considerations for ocular formulations, and recent advances of these NEs as effective carriers for ocular drug delivery highlighting their performance in pre-clinical studies.

Isolation, purification, and physio-chemical characterization of melanin pigment from nigerseed hulls (Guizotia abysinica).

Plant melanin, a natural pigment, has gained significant attention recently due to its potential therapeutic and industrial applications. In this study, melanin pigments were extracted from Nigerseed hulls (NH) via alkali and acid extraction methods, followed by acid hydrolysis, organic solvent treatment, and repeated precipitation. The solubility of NH melanin was assessed, revealing solubility in alkali and dimethyl sulfoxide (DMSO) but insolubility in other common organic solvents. High-performance liquid chromatography (HPLC) was employed to measure the purity of NH melanin in comparison to standard melanin, while elemental analysis indicated a similarity between melanin extracted from nigerseed hulls and the standard counterpart. LC-MS data revealed a molecular weight of NH melanin. Furthermore, the stability of melanin was evaluated under varying conditions including temperature, oxidants, reducing agents, light exposure, and metal ion presence. Results demonstrated significant effects of Mg2+, Cu2+, and Fe2+ metal ions on melanin stability, with a minor effect observed for Ca2+, while sodium hyposulfite was found to destabilize the pigments. Our findings suggest that nigerseed hulls hold promise as a novel source for efficient melanin production, with potential applications in the food sector, food packaging, and biomedical fields.

Dr. Dilip Mahalanabis (1934-2022): Trailblazer in Diarrheal Disease Management.

Dilip Mahalanabis, an esteemed Indian pediatrician, revolutionized global health through his pioneering work in combatting diarrheal diseases, particularly during the Bangladesh War of Independence in 1971. His development of oral rehydration therapy (ORT) provided a simple, cost-effective solution that significantly reduced mortality rates among cholera patients. Mahalanabis' dedication to equitable healthcare, evidenced by his leadership roles in organizations such as the World Health Organization (WHO), underscores his legacy as a champion for vulnerable populations. ORT's widespread adoption has democratized treatment, empowering communities and drastically reducing mortality rates associated with diarrheal diseases.

Defining genomic landscape for identification of potential candidate resistance genes associated with major rice diseases through MetaQTL analysis.

Rice production is severely affected by various diseases such as bacterial leaf blight (BLB), brown spot (BS), false smut (FS), foot rot (FR), rice blast (RB), and sheath blight (SB). In recent years, several quantitative trait loci (QTLs) studies involving different populations have been carried out, resulting in the identification of hundreds of resistance QTLs for each disease. These QTLs can be integrated and analyzed using meta-QTL (MQTL) analysis for better understanding of the genetic architecture underlying multiple disease resistance (MDR). This study involved an MQTL analysis on 661 QTLs (378, 161, 21, 41, 44, and 16 QTLs for SB, RB, BLB, BS, FS, and FR, respectively) retrieved from 50 individual studies published from 1995 to 2021. Of these, 503 QTLs were projected finally onto the consensus map saturated with 6,275 markers, resulting in 73 MQTLs, including 27 MDR-MQTLs conferring resistance to three or more diseases. Forty-seven MQTLs were validated using marker-trait associations identified in published genome-wide association studies. A total of 3,310 genes, including both R and defense genes, were also identified within some selected high-confidence MQTL regions that were investigated further for the syntenic relationship with barley, wheat, and maize genomes. Thirty-nine high-confidence candidate genes were selected based on their expression patterns and recommended for future studies involving functional validation, genetic engineering, and gene editing. Nineteen MQTLs were co-localized with 39 known R genes for BLB and RB diseases. These results could pave the way to utilize candidate genes in a marker-assisted breeding program for MDR in rice.

Stability of extemporaneously prepared hydroxyurea solutions.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To evaluate the stability of a new, more convenient (<30 minutes for preparation), extemporaneously prepared hydroxyurea solution over 78 days. METHODS: A high-performance liquid chromatography (HPLC) method using a hydrophilic interaction chromatography (HILIC) column was developed and validated to accurately measure the concentration of hydroxyurea directly from solution without the need for chemical derivatization. Hydroxyurea was dissolved in sterile water in less than 5 minutes to yield a 100-mg/mL solution, which was then diluted by an equal volume of ORA-sweet vehicle to yield a 50-mg/mL extemporaneously prepared solution of hydroxyurea. The solution samples were kept at refrigeration (4 °C), room temperature (26 °C), and elevated temperature (40 °C) for 78 days. RESULTS: The 50-mg/mL solutions of hydroxyurea in a 1:1 mixture of water and ORA-sweet kept at 4 °C and 26 °C showed no significant loss of potency (<2%) after 78 days. The solutions kept at 40 °C showed greater than 10% loss of potency after 28 days. CONCLUSION: Extemporaneously compounded hydroxyurea 50-mg/mL solutions prepared in a 1:1 mixture of water and ORA-Sweet and stored in amber polypropylene plastic bottles were stable for at least 78 days at room temperature and under refrigeration.

Intratumoral Escherichia Is Associated With Improved Survival to Single-Agent Immune Checkpoint Inhibition in Patients With Advanced Non-Small-Cell Lung Cancer.

PURPOSE: The impact of the intratumoral microbiome on immune checkpoint inhibitor (ICI) efficacy in patients with non-small-cell lung cancer (NSCLC) is unknown. Preclinically, intratumoral Escherichia is associated with a proinflammatory tumor microenvironment and decreased metastases. We sought to determine whether intratumoral Escherichia is associated with outcome to ICI in patients with NSCLC. PATIENTS AND METHODS: We examined the intratumoral microbiome in 958 patients with advanced NSCLC treated with ICI by querying unmapped next-generation sequencing reads against a bacterial genome database. Putative environmental contaminants were filtered using no-template controls (n = 2,378). The impact of intratumoral Escherichia detection on overall survival (OS) was assessed using univariable and multivariable analyses. The findings were further validated in an external independent cohort of 772 patients. Escherichia fluorescence in situ hybridization (FISH) and transcriptomic profiling were performed. RESULTS: In the discovery cohort, read mapping to intratumoral Escherichia was associated with significantly longer OS (16 v 11 months; hazard ratio, 0.73 [95% CI, 0.59 to 0.92]; P = .0065) in patients treated with single-agent ICI, but not combination chemoimmunotherapy. The association with OS in the single-agent ICI cohort remained statistically significant in multivariable analysis adjusting for prognostic features including PD-L1 expression (P = .023). Analysis of an external validation cohort confirmed the association with improved OS in univariable and multivariable analyses of patients treated with single-agent ICI, and not in patients treated with chemoimmunotherapy. Escherichia localization within tumor cells was supported by coregistration of FISH staining and serial hematoxylin and eosin sections. Transcriptomic analysis correlated Escherichia-positive samples with expression signatures of immune cell infiltration. CONCLUSION: Read mapping to potential intratumoral Escherichia was associated with survival to single-agent ICI in two independent cohorts of patients with NSCLC.

What do people with intellectual disabilities, their family members and paid carers understand about psychotropic medication? A rapid review.

BACKGROUND: People with intellectual disabilities are more likely to be prescribed psychotropic medication than the general population and are frequently prescribed multiple medications. Understanding people with intellectual disabilities and carer perspectives is essential to improving the quality of psychotropic medication prescribing and usage. METHOD: A rapid review explored people with intellectual disabilities' understanding of psychotropic medications, as well as family members and paid carers, and how this understanding can be improved. RESULTS: Twenty-one journal articles were included. Lack of understanding of medication was universal, with participants often unaware of adverse effects, alternatives, and rights around medication. There was also a lack of involvement in decision making for all participants. Some interventions aimed at people with intellectual disabilities or paid carers helped to improve knowledge. CONCLUSION: Evaluating how best to improve psychotropic medication understanding for people with intellectual disabilities, family members and paid carers should be a focus for future research.

Are we making progress in curing advanced cervical cancer-again?

Major improvements in radiotherapy over the past two decades in the definitive treatment of locally advanced cervical cancer have significantly improved loco-regional control and survival, whereas little progress has been made with chemotherapy since the implementation of concomitant cisplatin 25 years ago. However, the randomized study INTERLACE (A phase III multicenter trial of weekly induction chemotherapy followed by standard chemoradiation versus standard chemoradiation alone in patients with locally advanced cervical cancer) of neoadjuvant chemotherapy presented recently, has shown significant improvement in survival with the use of six cycles of weekly carboplatin and paclitaxel. Although INTERLACE is yet to be published, neoadjuvant chemotherapy is already being advocated as the new standard, and studies are being designed with neoadjuvant chemotherapy followed by chemoradiation and brachytherapy as the standard arm. It is noteworthy that INTERLACE was initiated before the improvements in radiotherapy mentioned above were broadly implemented. The survival rate in the standard arm of INTERLACE was therefore inferior to the results obtained with the latest state-of-the-art external beam radiotherapy and image guided adaptive brachytherapy (EMBRACE, Magnetic Resonance Imaging (MRI)-Guided Brachytherapy in Locally Advanced Cervical Cancer). Moreover, patient selection impedes the comparison of INTERLACE with other studies as the patients included in INTERLACE were younger, had better performance status, and had less advanced disease than in other studies. Notably patients with involved para-aortic nodes were excluded. In this review, we discuss neoadjuvant chemotherapy in the frame of the EMBRACE studies and show how the impact of modern radiotherapy and patient selection affects the interpretation of the results of INTERLACE. This has led us to conclude that neoadjuvant chemotherapy is not needed for the majority of patients with cervical cancer treated with definitive modern radiotherapy, and may cause harm. However, it is possible that short course neoadjuvant chemotherapy may benefit a minor subgroup of patients who need to be identified. Comprehensive understanding, including cost utility analyses, are needed to draw conclusions regarding the potential benefit of neoadjuvant chemotherapy in low and middle income countries with limited access to modern radiotherapy.

Efficacy of dexamethasone implant in the management of chronic central serous chorioretinopathy without choroidal neovascularization.

PURPOSE: To demonstrate the treatment efficacy of intravitreal dexamethasone (DEX) implant in chronic recurrent/persistent central serous chorioretinopathy (CSC). DESIGN: Prospective, non-randomized, open-label study. METHODS: In this study, subjects with chronic CSC without signs of choroidal neovascularization (CNV) received intravitreal DEX implant therapy. The primary outcome measure was the change in visual acuity. Changes in central macular thickness (CMT) and change in subfoveal choroidal thickness (SFCT) on optical coherence tomography (OCT), incidence of recurrent fluid, and safety of DEX implant were secondary outcome measures. Subjects were followed up for a minimum of 3 months after DEX implantation. RESULTS: In total, 20 eyes of 20 subjects (mean age: 47 ± 9 years) with a median disease duration of 23.5 months were enrolled. With a single injection of DEX implant, a reduction in CMT was noted in 90% of eyes. Complete resolution of subretinal and intraretinal fluid was noted in 55% of eyes within 3 months of injection. A significant improvement in vision (mean Log MAR visual acuity 0.66 ± 0.49 vs. 0.54 ± 0.45; P = 0.020), mean CMT (338 ± 110 microns to 238 ± 73 microns; P < 0.001) and SFCT (514 ± 95 microns to 445 ± 111 microns; P < 0.001) was noted over 3 months. Recurrent fluid was noted in 50% of eyes after a mean follow-up duration of 7 ± 4 months. Elevated intraocular pressure, managed by topical therapy, was noted in six eyes. CONCLUSION: The consistent improvement in visual acuity, fluid resolution, and reduction in choroidal thickness suggests a possible role for DEX implants in managing chronic CSC. A larger randomized trial is warranted.

Prevalence and patient risk factors for pneumothorax in COVID-19 and in influenza pneumonia: a nationwide comparative analysis.

Background: Pneumothorax is a rare but deadly complication in patients who require mechanical ventilation. As with any condition associated with acute respiratory distress syndrome (ARDS), coronavirus disease 2019 (COVID-19) is known to be associated with pneumothorax. However, in the literature, comparative data on the risk factors for pneumothorax in COVID-19 and other diseases like influenza are limited. The aim of this study is to determine the prevalence and risk factors for pneumothorax in hospitalized COVID-19 patients and compare them with influenza pneumonia patients. Methods: This study is a retrospective analysis of the National Inpatient Sample (NIS) 2020 database cohort. Univariate and multivariate logistic regression were used to identify the prevalence and risk factors for pneumothorax in COVID-19 patients and compared with the risk of pneumothorax in influenza patients. Results: The NIS 2020 database includes 1,608,980 hospitalizations of COVID-19 patients, of which 22,545 [95% confidence interval (CI): 21,491-23,598] (1.4%) developed pneumothorax. On multivariate analysis, factors associated with pneumothorax in COVID-19 included patient age of 41-64 years; male sex; Hispanics, Native Americans, and other races; hospitals with large-bed size; privately owned hospitals; urban teaching hospitals; hospitals in the southern United States (US); stroke; malnutrition; chronic obstructive pulmonary disease (COPD); bronchiectasis; pulmonary fibrosis; liver disease; non-invasive and invasive ventilation; and extracorporeal membrane oxygenation (ECMO). Of 184,980 influenza patients, 1,630 (95% CI: 1,448-1,811) (0.88%) developed pneumothorax. The prevalence of pneumothorax was higher (1.4%) in COVID-19 patients compared to patients with influenza pneumonia (0.88%). Conclusions: COVID-19 patients who develop pneumothorax have a poor prognosis. Several risk factors for the development of pneumothorax were identified. Patients with these risk factors should be prioritized in applying evidence-based guidelines to prevent pneumothorax.

Dr. Himmatrao Bawaskar: Transforming Rural Healthcare Through Scientific Inquiry and Advocacy.

Dr. Himmatrao Bawaskar, a distinguished figure in Indian healthcare, has made significant contributions to medical research and public health, particularly in rural areas. Born in 1951 in Maharashtra, his journey from a rural upbringing to receiving one of the highest civilian awards of the Government of India, the Padma Shri, reflects his dedication to the field of medicine and public health. Dr. Bawaskar's groundbreaking research on scorpion stings, notably the use of prazosin, has revolutionized treatment protocols, significantly reducing mortality rates. Beyond scorpion stings, his work spans diverse medical areas, including snake bites and cardiovascular diseases. Moreover, Dr. Bawaskar's advocacy for ethical practices and healthcare reform underscores his commitment to improving healthcare outcomes. His legacy serves as an inspiration for future generations of healthcare professionals and policymakers, emphasizing the transformative power of dedication, compassion, and scientific inquiry in addressing critical healthcare challenges.

Biocompatibility of polymethyl methacrylate heat-polymerizing denture base resin copolymerized with antimicrobial monomers.

STATEMENT OF PROBLEM: Quaternary ammonium (QA)-based monomers such as dimethyl-hexadecyl-methacryloxyethyl-ammonium iodide (DHMAI) and 2-dimethyl-2-dodecyl-1-methacryloxyethyl ammonium iodine (DDMAI) have been investigated as copolymerizable monomers to impart antimicrobial activity to dental restorative and prosthetic materials. However, the biocompatibility of these antimicrobial monomers needs to be investigated in vivo before their clinical use. PURPOSE: The purpose of this study was to assess the in vivo biocompatibility of polymethyl methacrylate (PMMA) heat-polymerizing denture base resin copolymerized with varying concentrations of DHMAI and DDMAI. MATERIAL AND METHODS: The toxicity and genotoxicity of the antimicrobial monomers (DHMAI 5 µg/mL and DDMAI 20 µg/mL) at 1 to 100 µg/mL concentrations were investigated against zebrafish embryos (Danio rerio, n=10) using a zebrafish embryotoxicity test (ZET) or fish embryotoxicity test (FET) and comet assay, respectively. Further, DHMAI 5 µg/mL and DDMAI 20 µg/mL were incorporated into a conventional PMMA denture base system and a similar test was done on specimens of modified PMMA resin. For the evaluation of in vivo biocompatibility, modified PMMA specimens were subcutaneously implanted into Wistar rats (n=6) and biochemical, hematological, and histopathological parameters were investigated. Results were analyzed and compared using ANOVA and the Tukey post hoc test (α=.05). RESULTS: Toxicity and genotoxicity studies using zebrafish embryos revealed that the incorporation of monomer to PMMA did not increase the toxicity, as confirmed by post-hour fertilization. Modified PMMA did not affect the hematological parameters, such as red blood cell (RBC) and white blood cell (WBC) except for the platelet count, which was significantly increased (P<.001), and the biochemical parameter, such as total protein (TP), blood urea nitrogen (BUN), serum glutamic-oxaloacetic transaminase (SGOT), triglyceride (TG), creatinine (Crea), total cholesterol, and serum glutamic pyruvic transaminase (SGPT), except for high-density lipoprotein (HDL) cholesterol, which was significantly decreased (P<.01). Histopathologically, no changes were observed in the sections of the liver, kidney, spleen, and subcutaneous tissues in the modified PMMA implanted rats. Additionally, no significant variation was found in the expression of immunohistochemical marker tumor necrosis factor alpha (TNF-α), confirming the noninflammatory response exerted by the modified PMMA on experimental rats. CONCLUSIONS: Zebrafish embryos treated with modified PMMA specimens demonstrated favorable biological properties and did not exhibit significant cytotoxicity and genotoxicity. Subcutaneously implanted modified PMMA did not cause any major hematological, biochemical, and histopathological alterations in Wistar albino rats, thus confirming the biocompatibility of PMMA heat-polymerizing denture base resin incorporated with DHMAI and DDMAI for dental applications.

Synthesis and Reactivity of Masked Organic Sulfates.

Nature offers a variety of structurally unique, sulfated endobiotics including sulfated glycosaminoglycans, sulfated tyrosine peptides, sulfated steroids/bile acids/catecholamines. Sulfated molecules display a large number of biological activities including antithrombotic, antimicrobial, anticancer, anti-inflammatory, and others, which arise from modulation of intracellular signaling and enhanced in vivo retention of certain hormones. These characteristics position sulfated molecules very favorably as drug-like agents. However, few have reached the clinic. Major hurdles exist in realizing sulfated molecules as drugs. This state-of-the-art has been transformed through recent works on the development of sulfate masking technologies for both alkyl (sulfated carbohydrates, sulfated steroids) and aryl (sTyr-bearing peptides/proteins, sulfated flavonoids) sulfates. This review compiles the literature on different strategies implemented for different types of sulfate groups. Starting from early efforts in protection of sulfate groups to the design of newer SuFEx, trichloroethyl, and gem-dimethyl-based protection technologies, this review presents the evolution and application of concepts in realizing highly diverse, sulfated molecules as candidate drugs and/or prodrugs. Overall, the newer strategies for sulfate masking and demasking are likely to greatly enhance the design and development of sulfated molecules as non-toxic drugs of the future.

Incidence of and risk factors for small vulnerable newborns in north India: a secondary analysis of a prospective pregnancy cohort.

BACKGROUND: Globally, recent estimates have shown there have been 3·6 million stillbirths and neonatal deaths in 2022, with nearly 60% occurring in low-income and middle-income countries. The Small Vulnerable Newborn Consortium has proposed a framework combining preterm birth (<37 weeks of gestation), small for gestational age (SGA) by INTERGROWTH-21st standard, and low birthweight (<2500 g) under the category small vulnerable newborns (SVN). Reliable data on SVN from sub-Saharan Africa, central Asia, and south Asia are sparse. We aimed to estimate the incidence of SVN and its types, and quantify risk factors, both overall and trimester-specific, from a pregnancy cohort in north India. METHODS: In the GARBH-Ini (Interdisciplinary Group for Advanced Research on Birth Outcomes-DBT India Initiative) pregnancy cohort, 8000 participants were enrolled with less than 20 weeks' gestation between May 11, 2015, and Aug 8, 2020, at a secondary-care hospital in north India. The cohort was followed up across the antenatal period for a detailed study on preterm birth. We conducted a secondary analysis of cohort data for the outcome of SVN, classified into its types: preterm-SGA, preterm-nonSGA, and term-SGA. We estimated the relative risk and population attributable fraction of candidate risk factors for SVN (modified Poisson regression) and its types (multinomial regression). FINDINGS: 7183 (89·9%) of 7990 participants completed the study. Among 6206 newborns included for analysis, the incidence of SVN was 48·4% (35·1% term-SGA newborns [n=2179], 9·7% preterm-nonSGA newborns [n=605], and 3·6% preterm-SGA newborns [n=222]). Compared with term-nonSGA newborns, proportions of stillbirths and neonatal deaths within 72 h of birth among SVN were three times and 2·5 times higher, respectively. Preterm-SGA newborns had the highest incidence of stillbirth (15 [6·8%] of 222) and neonatal deaths (six [4·2%] of 142). Low body-mass index (BMI <18·5 kg/m2) of participants at the start of pregnancy was associated with higher risk for preterm-SGA (adjusted relative risk [RR] 1·61 [95% CI 1·17-2·22]), preterm-nonSGA (1·35 [1·09-1·68]), and term-SGA (1·44 [1·27- 1·64]), with population attributable fraction ranging from 8·7% to 13·8%. Pre-eclampsia (adjusted RR 1·48 [95% CI 1·30-1·71]), short cervical length (1·15 [1·04-1·26]), and bacterial vaginosis (1·13 [0·88-1·45]) were other important antenatal risk factors. INTERPRETATION: In a comprehensive analysis of SVN and its types from north India, we identified risk factors to guide prioritisation of interventions. Complemented with risk-stratification tools, this focused approach will enhance antenatal care, and accelerate achievement of Sustainable Development Goals-namely, to end preventable deaths of newborns and children younger than 5 years by 2030 (target 3·2). FUNDING: Department of Biotechnology, Government of India and Grand Challenges India-Biotechnology Industry Research Assistance Council, Government of India. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.