Salicylate Poisoning and Rebound Toxicity.

Salicylate exposure and toxicity are associated with a myriad of symptoms and signs, and a comprehensive knowledge of diagnosing and treating salicylate poisoning is needed. Here, we present a case of a 29-year-old female with a past medical history of schizoaffective disorder and bipolar disorder with multiple suicide attempts brought to our hospital, Nassau University Medical Center, East Meadow, by the Emergency Medical Service (EMS) due to an intentional overdose of 300 pills of acetylsalicylic acid. She had mixed acid-base disturbance with respiratory alkalosis and metabolic acidosis. She was started on bicarbonate infusion in the emergency department to maintain a blood pH of 7.5 and to maintain a urine pH of more than 7.5. As her salicylate levels were 98.2 at admission with altered mental status, she was started on slow, low-efficiency hemodialysis. A few hours later, she developed a rebound increase in salicylate levels to 129, associated with a change in mental status and the patient was more confused. She was started on regular hemodialysis with improvement in mental status and elimination of salicylate steadily. Given the extensive nature of toxic effects, a patient with severe salicylate toxicity can deteriorate rapidly and can be challenging to manage. As there is no specific antidote for aspirin, the goals of therapy depend primarily on limiting the absorption of salicylate, enhancing elimination, and providing supportive care. Monitoring the acid-base status and serum salicylate levels closely and monitoring for rebound increase in salicylate levels is of paramount importance. Aggressive hydration to maintain euvolemia, alkalinization, aggressive replenishment of potassium and magnesium, activated charcoal to decrease absorption, and hemodialysis remain the cornerstones of treatment.

[3+3] Annulation of Diazoenals and α-Mercapto Ketones via Protic Sulfonium Ylides: Direct Synthesis of 2H-Thiopyrans, Innovative Progenitors for Unstudied 2H-Thiopyran-2-ones and 4H-Thiopyran-4-ones.

Herein, we report a new Rh(II)/Sc(III)-catalyzed [3+3] annulation between diazoenals and α-mercapto ketones for the direct synthesis of 4-formyl-2H-thiopyrans. The reaction proceeds via protic sulfonium ylides derived from highly electrophilic Rh-enalcarbenoids, followed by regioselective intramolecular aldol condensation. Further studies revealed that 4-formyl-2H-thiopyrans are novel precursors for unstudied 2H-thiopyran-2-ones and 4H-thiopyran-4-ones. The 4H-thiopyran-4-ones were obtained via a novel O2/Et3N-mediated oxidative deformylation. This methodology was applied to the short synthesis of structurally complex pyrimidine-fused 2H-thiopyran via cascade Schmidt, Ritter, and intramolecular cyclization reactions.

A clinical alert: Oral glucose tolerance test triggering diabetic ketoacidosis in pregnancy.

Gestational diabetes mellitus is a common medical disorder of pregnancy. Diabetic ketoacidosis is a complication that may affect both maternal and perinatal wellbeing adversely. It is rare, most often involving women with type 1 or type 2 diabetes, but occasionally can be seen in gestational diabetes mellitus. Here are two cases of ketoacidosis seemingly triggered by glucose ingestion for the oral glucose tolerance test in previously normoglycemic women, posing a diagnostic and therapeutic challenge. Prevention of such complications must be considered when treating high-risk pregnant women> 40 years of age, pregnant as a result of assisted reproductive techniques. Fasting blood glucose checked before ingestion of the glucose in a selected group of women may be one way of avoiding this complication. This suggestion may put women at risk of prolonged fasting and stretching services. Glucose tolerance test is a diagnostic test, and these cases demonstrate a rare complication.

Retron Library Recombineering: Next Powerful Tool for Genome Editing after CRISPR/Cas.

Retron library recombineering (RLR) is a powerful tool in the field of genome editing that exceeds the scope and specificity of the CRISPR/Cas technique. In RLR, single-stranded DNA produced in vivo by harnessing the in-built potential of bacterial retrons is used for replication-dependent genome editing. RLR introduces several genomic variations at once, resulting in pooled and barcoded variant libraries, thus permitting multiplexed applications. Retron-generated RT-DNA has already shown promise for use in genome editing. Thus, this new tool will result in fresh, intriguing, and surprising developments in molecular biology and its juncture with other disciplines of research, including medicine, agriculture, and microbiology. In this review, we discuss the current state of this brand-new tool that could eventually boost genome editing research.

Air pollution status and attributable health effects across the state of West Bengal, India, during 2016-2021.

Air pollution is one of the most significant threats to human safety due to its detrimental health consequences worldwide. This study examines the air pollution levels in 22 districts of West Bengal from 2016 to 2021, using data from 81 stations operated by the West Bengal Pollution Control Board (WBPCB). The study assesses the short- and long-term impacts of particulate matter (PM) on human health. The highest annual variation of PM10 was noted in 2016 (106.99 ± 34.17 µg/m3), and the lowest was reported in 2020 (88.02 ± 13.61 µg/m3), whereas the highest annual variations of NO2 (µg/m3) were found in 2016 (35.17 ± 13.55 µg/m3), and lowest in 2019 (29.72 ± 13.08 µg/m3). Similarly, the SO2 level was lower (5.35 µg/m3) in 2017 and higher in 2020 (7.78 µg/m3). In the state, Bardhaman, Bankura, Kolkata, and Howrah recorded the highest PM10 concentrations. The monthly and seasonal variations of pollution showed higher in December, January, and February (winter season) and lowest observed in June, July, and August (rainy season). The southern part of West Bengal state has recorded higher pollution levels than the northern part. The short- and long-term health impact assessment due to particulate matter shows that the estimated number of attributable cases (ENACs) for incidence of chronic bronchitis in adults and prevalence of bronchitis in children were 305,234 and 14,652 respectively. The long-term impact of PM2.5 on human health ENACs for mortality due to chronic obstructive pulmonary disease for adults, acute lower respiratory infections in children aged 0-5, lung cancer, and stroke for adults were 21,303, 12,477, 25,064, 94,406, and 86,272 respectively. This outcome assists decision-makers and stakeholders in effectively addressing the air pollution and health risk concerns within the specified area.

Rh-Catalyzed Chemodivergent [3+3] Annulations of Diazoenals and α-Aminoketones: Direct Synthesis of Functionalized 1,2-Dihydropyridines and Fused 1,4-Oxazines.

Novel rhodium-catalyzed [3+3] annulations of diazoenals and α-amino ketones has been disclosed here. The reactivity of diazoenals has been switched from carbenoid to vinylogous NH-insertion by altering acyclic to cyclic α-amino ketones. In this direction, we report an efficient strategy to synthesize 1,2-dihydropyridines (DHPs) and fused 1,4-oxazines. Mechanistic investigation revealed that the formyl group is necessary for carbenoid [3+3] annulation and the cyclohexyl group is the dictating factor for vinylogous NH- insertion. The synthetic utility of 1,2-dihydropyridines was demonstrated by synthesizing piperidine, pyrido[1,2-a]indole, and 2-pyridone scaffolds. Further, structural diversification of fused 1,4-oxazines resulted in the short synthesis of hexahydroquinolin-2(1H)-ones, hexahydro quinolines and tetrahydroquinolinones via ring opening rearrangement and a new oxidative deformylation, respectively.

Schematic-portfolio of potent anti-microbial scaffolds targeting DNA gyrase: Unlocking ways to overcome resistance.

Drug development process demands validation of specific drug target impeding the Multi Drug Resistance (MDR). DNA gyrase, as a bacterial target has been in trend for developing newer antibacterial candidates due to its absence in higher eukaryotes. The fluoroquinolones are the leading molecules in the drug discovery pipeline for gyrase inhibition due to its diversity. The fluoroquinolones like levofloxacin and moxifloxacin have been listed in class A drugs for treating MDR. Gatifloxacin and ciprofloxacin also proved its efficacy against MDR TB and MDR enteric fever in adults, whereas nemonoxacin can induce anti-MDR activity of other antibiotics already suggested by studies. Though fluoroquinolones already proved its effectiveness against gyrase, other molecules viz., benzothiazinone, phenyl pyrrolamide, substituted oxadiazoles, triazolopyrimidine, arylbenzothiazole, coumarinyl amino alcohols and ciprofloxacin uracil, can inhibit the target more precisely. The structure-activity-relationships of the different scaffolds along with their synthetic strategies have been deciphered in the current review. Also, the naturally occurring compounds along with their extraction procedure have also been highlighted as potent DNA gyrase inhibitors. In addition to fluoroquinolone, the natural compounds novobiocin and simocyclinone could also inhibit the gyrase, impressively which has been designed with the gyrase structure for better understanding. Herein, ongoing clinical development of some novel drugs possessing triazaacenaphthylenes, spiropyrimidinetriones, and oxazolidinone-quinolone hybrids have been highlighted which could further assist the future generation antibiotic development corroborating gyrase as a potential target against MDR pathogens.

Phytomolecules from conventional to nano form: Next-generation approach for Parkinson's disease.

The incidence of neurodegenerative diseases is increasing exponentially worldwide. Parkinson's disease (PD) is a neurodegenerative disease caused by factors like oxidative stress, gene mutation, mitochondrial dysfunction, neurotoxins, activation of microglial inflammatory mediators, deposition of Lewy's bodies, and α- synuclein proteins in the neurons leading to neuroinflammation and neurodegeneration in the substantia nigra. Hence the development of efficacious neuro-therapy is in demand which can prevent neurodegeneration and protect the nigrostriatal pathway. One of the approaches for managing PD is reducing oxidative stress due to aging and other co-morbid diseased conditions. The phytomolecules are reported as safe and efficacious antioxidants as they contain different secondary metabolites. However, the limitations of low solubility restricted permeability through the blood-brain barrier, and low bioavailability limits their clinical evaluation and application. This review discusses the therapeutic efficacy of phytomolecules in PD and different nanotechnological approaches to improve their brain permeability.

Clinical and Immunological Features, Genetic Variants, and Outcomes of Patients with CD40 Deficiency.

PURPOSE: Inherited deficiencies of CD40 and CD40 ligand (CD40L) reflect the crucial immunological functions of CD40-CD40L interaction/signaling. Although numerous studies have provided a detailed description of CD40L deficiency, reports of CD40 deficiency are scarce. Herein, we describe the characteristics of all reported patients with CD40 deficiency. METHODS: The PubMed, Embase and Web of Science databases were searched for relevant literature published till 7th August 2023. Study deduplication and identification of relevant reports was performed using the online PICO Portal. The data were extracted using a pre-designed data extraction form and the SPSS software was used for analysis. RESULTS: Systematic literature review revealed 40 unique patients with CD40 deficiency. Respiratory tract and gastrointestinal infections were the predominant clinical manifestations (observed in 93% and 57% patients, respectively). Sclerosing cholangitis has been reported in nearly one-third of patients. Cryptosporidium sp. (29%) and Pneumocystis jirovecii (21%) were the most common microbes identified. Very low to undetectable IgG levels and severely reduced/absent switch memory B cells were observed in all patients tested/reported. Elevated IgM levels were observed in 69% patients. Overall, splice-site and missense variants were the most common (36% and 32%, respectively) molecular defects identified. All patients were managed with immunoglobulin replacement therapy and antimicrobial prophylaxis was utilized in a subset. Hematopoietic stem cell transplantation (HSCT) has been performed in 45% patients (curative outcome observed in 73% of these patients). Overall, a fatal outcome was reported in 21% patients. CONCLUSIONS: We provide a comprehensive description of all important aspects of CD40 deficiency. HSCT is a promising curative treatment option for CD40 deficiency.

Laparoscopic Management of Median Arcuate Ligament Syndrome: A Case Report.

Median arcuate ligament syndrome (MALS) is an uncommon disorder characterized by postprandial abdominal pain, vomiting, anorexia, and weight loss. The symptoms are due to the MAL compressing the celiac artery and irritating the celiac plexus/ganglion. We report the case of one patient who presented with chronic abdominal pain, bloating, vomiting, and weight loss. Computed tomography angiography led to the diagnosis of MALS. The patient was treated surgically by laparoscopic division of the MLA and excision of the celiac plexus. He was discharged on day two without complications. On one-month follow-up, he was symptom-free, eating well, and had gained weight. He is on regular follow-up.

Automatic selection of IMFs to denoise the sEMG signals using EMD.

Surface Electromyography (sEMG) signals are muscle activation signals, which has applications in muscle diagnosis, rehabilitation, prosthetics, and speech etc. However, they are known to be affected by noises such as Power Line Interference (PLI), motion artifacts etc. Currently, Empirical Mode Decomposition (EMD) and its modifications such as Ensemble EMD (EEMD), and Complementary EEMD (CEEMD) are used to decompose EMG into a series of Intrinsic Mode Functions (IMFs). The denoised EMG can be obtained from the selected IMFs. Statistical methods are used to select the signal dominant IMFs to reconstruct the denoised signal. In this work, a novel procedure is proposed to automatically separate noisy IMFs from the original sEMG signal. For this purpose, Permutation Entropy (PE) is employed in EEMD sifting process called Partly EEMD (PEEMD), to separate the noisy IMFs from the original sEMG signal according to the preset PE threshold. PEEMD decomposes the original signal into various modes according to a preset PE threshold and the denoised signal is reconstructed from resultant IMFs. The PEEMD denoising procedure is applied on the experimental sEMG data collected from eight subjects, that include six various upper limb movement classes. The proposed denoising procedure achieved an improved denoising performance in comparison with EMD, EEMD, and CEEMD. An alternate measure called Sample Entropy (SE) is also used in place of PE, for the automated sifting process as a comparison. Signal to Noise Ratio (SNR), Root Mean Square Error (RMSE), and Reconstruction Error (RE) parameters are used to evaluate the denoising performance. The results, averaged across eight subjects, demonstrate that the proposed denoising procedure outperforms the state-of-the-art EMD techniques in terms of these performance measures on the experimentally collected sEMG data samples.

CD40 gene polymorphism and its expression in children with Kawasaki disease from North India: a preliminary case-control study and meta-analysis.

Introduction: CD40 gene single-nucleotide polymorphisms (SNPs) have been associated with susceptibility and development of coronary artery abnormalities (CAAs) in children with Kawasaki disease (KD) in Japanese, Chinese, and Taiwanese populations. However, data on SNPs of the CD40 gene in patients with KD from the Indian subcontinent are not available. We studied the CD40 gene polymorphisms and its expression in children with KD from North India. Methods: SNPs of the CD40 gene (rs4810485, rs1535045) were studied using Sanger sequencing. CD40 expression was studied by flow cytometry. Meta-analysis was carried out to assess the role of both SNPs of the CD40 gene in KD. GRADEpro GDT software (v.3.2) was used to assess the "certainty of evidence." Results: Forty-one patients with KD and 41 age-, sex-matched febrile controls were enrolled. However, none of the alleles and genotypes of the CD40 gene were found to be associated with KD. CD40 expression was higher in KD and in KD with CAAs compared to controls, but it failed to reach statistical significance. In a meta-analysis, the T allele of rs153045 was found to be significantly associated with KD (OR = 1.28; 95% confidence interval (: 1.09-1.50; p = 0.002). The GRADE of evidence for this outcome, however, is of " very low certainty." Conclusion: The present study found no association between SNPs (rs4810485 and rs153045) and susceptibility to KD. This could be a reflection of a modest sample size. CD40 expression was higher in KD and in KD with CAAs. In the meta-analysis, the T allele of rs153045 was significantly associated with KD. Our study confirms a significant genetic heterogeneity in KD among different ethnicities.

Performance evaluation of ZnSnN2 solar cells with Si back surface field using SCAPS-1D: A theoretical study.

The earth-abundant semiconductor zinc tin nitride (ZnSnN2) has garnered significant attention as a prospective material in photovoltaic and lighting applications, primarily due to its tunable narrow bandgap and high absorption coefficient. This study focuses on a numerical investigation of ZnSnN2 solar cell structures using the SCAPS 1-D software. The objective is to analyze the influence of various physical and geometrical parameters on solar cell performance. These parameters include the thicknesses of the ZnO window layer, CdS buffer layer, ZnSnN2 absorber layer, and Si back surface field layer (BSF), as well as operating temperature, series and shunt resistances (RS and Rsh), absorber layer defect density, interface defects, and the generation-recombination profile of the n-ZnO:Al/n-CdS/p-ZnSnN2/p-Si/Mo structure. We have evaluated the capabilities of this novel material absorber by investigating its performance across a range of thicknesses. We have started with ultrathin absorber thicknesses and gradually increased them to thicker levels to determine the optimal thickness for achieving high efficiency. Under optimal conditions, a thin solar cell with a thickness (wp) of 1 µm achieved an efficiency (η) of 23.9%. In a practical solar cell operating at room temperature, optimal parameters were observed with a thicker absorber layer (wp = 8 µm) and a BSF width of 0.3 µm. The cell exhibited resistances of Rsh = 106 Ω cm2 and Rs = 1 Ω cm2, along with a low defect density (Nt = 1010 cm-3) in the ZnSnN2 semiconductor. These factors combined to yield an impressive efficiency of 29.5%. Numerous studies on emerging ternary nitride semiconductors (Zn-IV-N2) have highlighted ZnSnN2 as a promising material for thin-film photovoltaics. This compound is appealing due to its abundance, non-toxicity, and cost-effectiveness. Unlike conventional solar cells that depend on rare, toxic, and costly elements, these components are still essential for today's solar cell technology.

Metal Nanoparticles in Alzheimer's Disease.

Nanotechnology has emerged in different fields of biomedical application, including lifestyle diseases like diabetes, hypertension, and chronic kidney disease, neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease, and different types of cancers. Metal nanoparticles are one of the most used drug delivery systems due to the benefits of their enhanced physicochemical properties as compared to bulk metals. Neurodegenerative diseases are the second most cause affecting mortality worldwide after cancer. Hence, they require the most specific and targeted drug delivery systems for maximum therapeutic benefits. Metal nanoparticles are the preferred drug delivery system, possessing greater blood-brain barrier permeability, biocompatibility, and enhanced bioavailability. But some metal nanoparticles exhibit neurotoxic activity owing to their shape, size, surface charge, or surface modification. This review article has discussed the pathophysiology of AD. The neuroprotective mechanism of gold, silver, selenium, ruthenium, cerium oxide, zinc oxide, and iron oxide nanoparticles are discussed. Again, the neurotoxic mechanisms of gold, iron oxide, titanium dioxide, and cobalt oxide are also included. The neuroprotective and neurotoxic effects of nanoparticles targeted for treating AD are discussed elaborately. The review also focusses on the biocompatibility of metal nanoparticles for targeting the brain in treating AD. The clinical trials and the requirement to develop new drug delivery systems are critically analyzed. This review can show a path for the researchers involved in the brain-targeted drug delivery for AD.

Basic Investigations in Pediatric Rheumatology.

The spectrum of pediatric rheumatological disorders is diverse and they are important differential diagnoses in a variety of clinical scenarios. Basic investigations not only provide supporting evidence for the diagnosis of a rheumatological illness but also help in exclusion of other diseases as well as for monitoring the activity of disease. Among these, complete blood count, biochemical assays including tests for inflammatory response, urine analysis, and various autoantibodies are often used. In addition, depending on the clinical features, imaging and tissue biopsies are used to confirm the diagnosis.

Preliminary assessment of the water quality of Rushikulya estuary based on the abundance of pathogenic bacteria.

Estuaries are among the most dynamic ecosystems in coastal regions and are facing serious threats due to increasing anthropogenic activities. The aim of the present study is to evaluate the water quality of the Rushikulya estuary by analyzing the abundance of pathogenic bacteria in both its water and sediment. Water and sediment samples were collected from five different stations at the mouth of the Rushikulya estuary during the monsoon and post-monsoon seasons. These samples were analyzed to assess the abundance of pathogenic bacteria and environmental parameters. The results revealed that bacterial abundance is significantly higher in the sediment than in the water, possibly due to a longer residence time of pathogenic bacteria in the sediment. Seasonal observations indicated an increase in pathogenic bacterial abundance during the monsoon season, suggesting an impact from monsoonal discharge. Escherichia coli-like organism, faecal coliforms, Shigella-like organisms, and Vibrio cholera-like organisms were the dominant pathogenic bacteria in both the water and sediment of the Rushikulya estuary. The higher abundance of these pathogens and the results of statistical analysis, which showed a strong correlation between Total Streptococci and BOD (r = 0.79), indicate the influence of human settlement and the mixing of untreated sewage in the Rushikulya estuary. The elevated levels of E. coli, faecal coliforms, and Shigella-like organisms in the Rushikulya estuary raise significant concerns that require immediate attention.

Assistive technology usage, unmet needs and barriers to access: a sub-population-based study in India.

Background: Assistive technology (AT) is essential to minimize functional limitations. The current study aimed to estimate the prevalence of needs, met and unmet needs for AT, and barriers to accessing AT among a subnational population in India. Methods: This cross-sectional study was conducted in eight districts, representing four zones of India, using the WHO Rapid Assistive Technology Assessment (rATA) tool. The tool was administered by trained staff using read aloud technique. Multi-stage cluster random sampling was used, as well as the probability proportional to size, to select smaller administrative units from the larger ones. Findings: In total, 8486 participants were surveyed out of 8964 individuals enumerated with a response rate of 94.6%. The sample prevalence of at least one difficulty was 31.8% (2700), with 6.3% (532) having severe or total difficulties. The sample prevalence for AT need was 27.8% (2357) with an estimated population prevalence of 24.5% (95% CI: 23.5-25.4). Similarly, the sample prevalence of unmet needs was 9.7% (823) with an estimated population unmet needs of 8.0% (95% CI: 7.43-8.60). The unmet needs among persons with severe or total difficulties was 52.3% (278/532), and was higher among females, rural residents, and older persons. Spectacles were the most used products, followed by canes/sticks, tripods, and quadripods. Nearly two-thirds of AT users purchased assistive products at their own expense, particularly from the private sector. The inability to afford AT (36.9%) was the most common barrier. Interpretation: The results show that the need for AT was substantial in the study population, the highest being for seeing difficulties. The unmet needs are higher in females, older population, rural residents, and persons having serious difficulties. While the majority of users have to make out-of-pocket payments to obtain AT, inability to afford and limited availability were the common barriers among those with unmet needs. Funding: This research is non-commercial, and was conducted in the interest of public health. The authors have not declared any specific grant for this research.

Ameliorative and Neuroprotective Effect of Core-Shell Type Se@Au Conjugated Hesperidin Nanoparticles in Diabetes-Induced Cognitive Impairment.

Diabetes mellitus is the most chronic metabolic ailment characterized by insulin deficiency leading to aberrant cognitive dysfunction in later stages. Hesperidin is a bioflavonoid, having different pharmacological activities, but its poor water solubility and short plasma half-life restrict its applications in the clinical field. So, the hesperidin was conjugated with gold, selenium, and core-shell bimetallic nanoparticles of gold and selenium. Different spectroscopic methods characterized the synthesized monometallic and bimetallic nanoparticles. The rats were injected with streptozotocin to induce cognitive dysfunction, followed by administering HSP, HSP-Au NPs, HSP-Se NPs, and Se@Au-HSP NPs daily for 21 days. Then, the neurobehavioral studies, oxidative stress parameters, AChE and nitrite levels, the content of amyloid-ß42, and inflammatory mediators were accessed to evaluate the effect of the nanoparticles against the STZ rat model. The results showed a significant increase in oxidative stress, AChE activity, amyloid-ß42, nitrite levels, and neuroinflammation by upregulating the inflammatory cytokines in the streptozotocin-administered rat brain. The HSP, HSP-Au NPs, HSP-Se NPs, and Se@Au-HSP NPs effectively reversed all these effects of streptozotocin. However, the bimetallic nanoparticle Se@Au-HSP NPs revealed better neuroprotective action than HSP-Au NPs and HSP-Se NPs. Hesperidin-conjugated bimetallic nanoparticles improved learning and memory in the STZ rat model and may be an alternative approach for neurodegenerative diseases, including Alzheimer's disease.