Fragment-Based Design and Synthesis of Symmetrical bis-Peptidotriazoles Using Alkylidene bis-Amide Formations and Subsequent Triazole Ligation with ß-Acetamido Carbonyl Scaffolds.

A novel and efficient fragment-based assembly of symmetrical bis-peptidotraizoles has been developed based on double Sharpless azide-alkyne click chemistry. A new Cu(II) catalyzed protocol with a wide substrate scope was developed for accessing the symmetrical alkylidene bis-azidoamide fragment that yields the products in very good yields at room temperature without employing column purifications. The propargylated ß-acetamido ketone fragment was accessed using another Cu(II) catalyzed room temperature MCR protocol. A fast double-click reaction (2 h) of symmetrical alkylidene bis-azidoamides with propargylated ß-acetamido ketone fragments leads to the formation of unusual symmetrical bis-peptidotriazoles.

Enhancement of dielectric permittivity and Havriliak-Negami relaxation mechanism in MnFe2O4through Dy substitution.

Pristine and Dy substituted MnFe2O4,MnFe2-xDyxO4(x= 0.00, 0.02, 0.04, 0.06, 0.08 & 0.10) were successfully synthesized by sol-gel method to investigate the dielectric properties of the system. MnFe2O4exhibits a high dielectric permittivity of order 104which is further augmented by 60% through Dy substitution. This is owing to the rise in interfacial polarization resulting from localized states, dipolar polarization arising from the multiple valence states of Fe and Mn ions, atomic polarization due to structural distortion induced by strain, and electronic polarization stemming from the concentration of free charge carriers. The enhancement of induced strain, mixed valence ratio of Fe2+/Fe3+and Mn4+/Mn2+, localized states, and free charge carrier concentration are confirmed from the XRD, XPS, and optical studies, respectively. The dielectric relaxation mechanism of MnFe2-xDyxO4follows a modified Havriliak-Negami relaxation model with conductivity contribution. Complex impedance analyses further validate the contribution of grain-grain boundary mechanisms to the dielectric properties confirmed through Nyquist plots. A comprehensive analysis of conductivity reveals the significant impact of Dy substitution on the electrical conductivity of MnFe2O4. This influence is strongly related to the variations in the concentration of free charge carriers within the MnFe2-xDyxO4system. The understanding of the underlying physics governing the dielectric properties of Dy-substituted MnFe2O4not only enhances the fundamental knowledge of material behavior but also opens new avenues for the design and optimization of advanced electronic and communication devices.

Anterior pituitary hormone dysfunction among individuals with complete heart block requiring pacemaker.

Background & objectives Neuronal hypoxia associated with conditions like traumatic brain injury and cardiac tachyarrhythmia has been implicated in causing hypopituitarism. Individuals with complete heart block (CHB) may be predisposed to develop anterior pituitary hormone dysfunction in the long term. The objective of this study was to investigate anterior pituitary hormone functions in individuals after CHB. Methods This prospective cohort study included 30 individuals (21 men and 9 women) with CHB requiring pacemaker implantation, who were evaluated at admission and then at a mean follow up of 12.4 ± 2.2 months to look for development of any degree of hypopituitarism. In addition to the measurement of hormones like follicle-stimulating hormone (FSH), luteinising hormone (LH), thyroid stimulating hormone (TSH), total tetra iodothyronines (TT4), free tetraiodothyronines (FT4), cortisol, insulin-like growth factor-1 (IGF-1), testosterone and estradiol, a fixed-dose glucagon stimulation test (GST) was performed to assess growth hormone (GH) and adrenocorticotrophic hormone (ACTH) axis. Results The mean age of the participants was 64.9 ± 11.3 yr. At follow up evaluation, 17 (56.7%) had low serum IGF-1, and among them, seven (23%) had growth hormone deficiency (GHD) (peak GH <1.0 ng/ml after GST). Six participants (20%) had ACTH deficiency (peak cortisol <9 ug/dl after GST) and one had TSH deficiency. None had prolactin (PRL) or gonadotropin deficiency. Overall, hormone deficiencies were observed in nine patients (30%). Interpretation & conclusions This pilot study detected loss of anterior pituitary hormones in a significant number of individuals of CHB at 12 months follow up. Unrecognised hypopituitarism may have resulted in significant morbidity and mortality in these individuals.

In search of universalities in the dissociative photoionization of PANHs via isomerizations.

In search of the cause behind the similarities often seen in the fragmentation of PANHs, vacuum ultraviolet (VUV) photodissociation of two pairs of isomers quinoline-isoquinoline and 2-naphthylamine-3-methyl-quinoline are studied using the velocity map imaging technique. The internal energy dependence of all primary fragmentation channels is obtained for all four target molecules. The decay dynamics of the four molecules is studied by comparing their various experimental signatures. The dominant channel for the first pair of isomers is found to be hydrogen cyanide (HCN) neutral loss, while the second pair of isomers lose HCNH neutral as its dominant channel. Despite this difference in their primary decay products and the differences in the structures of the four targets, various similarities in their experimental signatures are found, which could be explained by isomerization mechanisms to common structures. The fundamental role of these isomerization in controlling different dissociative channels is explored via a detailed analysis of the experimental photoelectron-photoion coincidences and the investigation of the theoretical potential energy surface. These results add to the notion of a universal PANH fragmentation mechanism and suggests the seven member isomerization as a key candidate for this universal mechanism. The balance between isomerization, dissociation, and other key mechanistic processes in the reaction pathways, such as hydrogen migrations, is also highlighted for the four molecules.

Rainfall-Runoff modelling using SWAT and eight artificial intelligence models in the Murredu Watershed, India.

The growing concerns surrounding water supply, driven by factors such as population growth and industrialization, have highlighted the need for accurate estimation of streamflow at the river basin level. To achieve this, rainfall-runoff models are widely employed as valuable tools in watershed management. For this specific study, two modelling approaches were employed: the Soil and Water Assessment Tool (SWAT) model and a set of eight artificial intelligence (AI) models. The AI models consisted of seven data-driven approaches, namely k-nearest neighbour regression, support vector regression, linear regression, artificial neural networks, random forest regression, XGBoost, and Histogram-based Gradient Boost regression. Additionally, a deep learning model known as Long Short-Term Memory (LSTM) was also utilized. The study focused on monthly streamflow modelling in the Murredu River basin, with a calibration period from 1999 to 2003 and a validation period from 2004 to 2005, spanning a total of 7 years from 1999 to 2005. The results indicated that all nine models were generally suitable for simulating the rainfall-runoff process, with the LSTM model demonstrating exceptional performance in both the calibration (R2 is 0.97 and NSE is 0.96) and validation (R2 is 0.97 and NSE is 0.92) periods. Its high coefficient of determination (R2) and Nash-Sutcliffe efficiency (NSE) values indicated its superior ability to accurately model the rainfall-runoff relationship. While the other models also produced satisfactory results, the findings suggest that selecting the most efficient model, such as the LSTM model, could significantly contribute to the effective management and planning of sustainable water resources in the Murredu watershed.

Photodissociation of quinoline cation: Mapping the potential energy surface.

A detailed exploration of the potential energy surface of quinoline cation (C9H7N·+) is carried out to extend the present understanding of its fragmentation mechanisms. Density functional theory calculations have been performed to explore new fragmentation schemes, giving special attention to previously unexplored pathways, such as isomerization and elimination of HNC. The isomerization mechanisms producing five- to seven-membered ring intermediates are described and are found to be a dominant channel both energetically and kinetically. Energetically competing pathways are established for the astrochemically important HNC-loss channel, which has hitherto never been considered in the context of the loss of a 27 amu fragment from the parent ions. Elimination of acetylene was also studied in great detail. Overall, the computational results are found to complement the experimental observations from the concurrently conducted PEPICO investigation. These could potentially open the doors for rich and interesting vacuum ultraviolet radiation-driven chemistry on planetary atmospheres, meteorites, and comets.

Comprehensive survey of dissociative photoionization of quinoline by PEPICO experiments.

Dissociative photoionization of quinoline induced by vacuum ultraviolet radiation is investigated using photoelectron-photoion coincidence spectroscopy. Branching ratios of all the detectable fragment ions are measured as a function of internal energy ranging from 2 to 30 eV. A specific generation hierarchy is observed in the breakdown curves of a set of dissociation channels. Moreover, a careful comparison of the breakdown curves of fragments among the successive generations allowed to establish a decay sequence in the fragmentation of quinoline cation. This enabled us to revisit and refine the understanding of the first generation decay and reassign the origin of a few of the higher generation decay products of quinoline cation. With the help of the accompanying computational work (reported concurrently), we have demonstrated the dominance of two different HCN elimination pathways over previously interpreted mechanisms. For the first time, a specific pathway for acetylene elimination is identified in quinoline+ and the role of isomerization in both acetylene as well as hydrogen cyanide loss is also demonstrated. The experiment also established that the acetylene elimination exclusively occurs from the non-nitrogen containing rings of quinoline cation. The formation of a few astronomically important species is also discussed.

Antibiotic-resistant Enterobacteriaceae from diseased freshwater goldfish.

Goldfish farming gained more attention among the ornamental fishes in aquaculture industry. The occurrence of bacterial infections and further antimicrobial treatment lead to the major crisis of antibiotic resistance in aquaculture. We have isolated diverse enterobacteriaceae groups which affect the goldfish and identified their response towards 46 antimicrobials of 15 different classes. Thirteen significant bacterial isolates such as Edwardsiella tarda, Serratia marcescens, Klebsiella aerogenes, Proteus penneri, P. hauseri, Enterobacter cloacae, E. cancerogenus, E. ludwigii, Citrobacter freundii, E. coli, Kluyvera cryocrescens, Plesiomonas shigelloides and Providencia vermicola were recovered from the infected fish with the Shannon-wiener diversity index of 2.556. Multiple antibiotic resistance (MAR) index was found to be maximum for P. penneri (0.87) and minimum for C. freundii and E. cloacae (0.22), highlighting the hyper antibiotic selection pressure in the farm. The minimum concentration of antibiotics required to inhibit most of the resistant isolates was found to be > 256 mcg/ml. All the isolates were susceptible towards ciprofloxacin. Plasmid curing and further AMR tests could reveal the location of antibiotic resistance genes mainly as plasmids which determine the large extent of AMR spread through horizontal gene transfer. This study is the first of its kind to investigate the antimicrobial resistance profile of enterobacteriaceae recovered from goldfish, before and after plasmid curing.

Prevalence, pattern & correlates of hypertension among tribal population of Kashmir, India: A cross-sectional study.

Background & objectives: The prevalence of hypertension is increasing among all ethnic groups across the globe with only a handful of studies from India addressing the prevalence of hypertension among tribal population. In view of paucity of data, this study was aimed at estimating the prevalence of hypertension and associated risk factors among tribal population of Kashmir, India. Methods: This cross-sectional survey included 6808 tribals aged >20 yr (5695 Gujjars and 1113 Bakarwals) from five randomly selected districts of Kashmir. Modified WHO-STEPS surveillance questionnaire was used to collect relevant data. Hypertension was defined by Joint National Committee on Prevention, Detection, Evaluation and Treatment of Hypertension (JNC 8) criteria. Results: The mean age of our study participants was 43.12 ± 15.69 years. Overall prevalence of hypertension [95% confidence interval (CI)] was 41.4% (39.9-42.9%) [men=46.7% (44.1-49.1%); women=37.9% (35.9-39.9%)]. The prevalence of prehypertension (95% CI) in our study was 35 per cent (33.7-36.6%). Higher age [adjusted odds ratio (OR) (95% CI): >70 yr-2.2 (1.9-2.4)], passive smoking [OR-1.3 (1.1-1.5)], family history of hypertension [OR-1.6 (1.4-1.7)] and obesity [OR-1.3 (1.1-1.6)] were significantly associated with hypertension. A weak positive correlation was observed between BP (systolic/diastolic) with haemoglobin, red blood cell count and haematocrit (P<0.05). Interpretation & conclusions: Gujjar and Bakarwal tribes of Jammu and Kashmir showed high prevalence of hypertension. Hence, urgent policies and reforms are needed to tackle this silent epidemic and further studies focusing on community-based interventions are required.

Establishment and cryopreservation of a cell line derived from caudal fin of endangered catfish Clarias dussumieri Valenciennes, 1840.

We describe a new cell line, Clarias dussumieri fin (ClDuF), from the caudal fin of C. dussumieri using the explant technique followed by cryopreservation. The cryopreserved CiDuF cells were validated for quality and other characteristics. They showed typical epithelial morphology in vitro and epithelial cells outgrew their fibroblast cells after the fifth passage. ClDuF cells had a characteristic sigmoid curve with population doubling in 24 h. Immunotyping of the ClDuF cells against cytokeratin suggested the epithelial lineage. Chromosome analysis showed normal diploid (2n = 50) numbers and the cells did not contain any contamination, including Mycoplasma and other microbes. Partial sequencing of fragments of mitochondrial 16s rRNA and COI genes of ClDuF confirmed that the cell line was initiated from C. dussumieri. Cells at the 10th and 25th passages had more than 80% and 70% viability in the culture, respectively, after 6 months of storage at LN2 . These ClDuF cells were morphologically identical to the cells before freezing and the genetic resource of C. dussumieri was preserved. The species-specific cells can serve as a valuable source for virus isolation, conservation and cloning of somatic cells.

Comparison of equiosmolar dose of hyperosmolar agents in reducing intracranial pressure-a randomized control study in pediatric traumatic brain injury.

INTRODUCTION: There are no comparative studies available for hyperosmolar therapy in children. The present study is a prospective open label randomized control trial to compare the effect of equiosmolar doses of mannitol and hypertonic saline in reducing intracranial pressure in children who sustained severe traumatic brain injury. METHODS: This is a prospective open-label randomized controlled trial. Thirty children aged less than or equal to 16 years with severe traumatic brain injury and raised intracranial pressure as measured by ventricular catheter insertion were enrolled. Sixteen children received 20% mannitol, and 14 children received 3% saline as 2.5 ml/kg bolus for episodes of intracranial pressure above cutoff value for age. The mean reduction in intracranial pressure and Glasgow outcome scale at 6 months after injury was measured. RESULTS: The mean reduction in intracranial pressure in mannitol group was 7.13 mmHg and in hypertonic saline group was 5.67 mmHg, and the difference was not statistically significant, p = 0.33. The incidence of death or survival in vegetative state was 23.07% in mannitol group and 16.66% in hypertonic saline group, and the difference was not statistically significant, p = 0.69. CONCLUSION: Both mannitol and hypertonic saline were equally effective for treatment of raised intracranial pressure in children with severe traumatic brain injury.

Morphometric analysis of talus and calcaneus.

PURPOSE: The variations in the subtalar joint regarding its morphology and articulation of bones are common worldwide. This study aimed to analyze the morphometric variations in articulating facets of talus and calcaneum in South Indian population. METHODS: For this study, the morphometric parameters of 92 dry tali and 49 dry calcanei of unknown gender were analyzed. The pattern of articulating facets was classified based on Boyan et al. as Type A (A1-A4), Type B (B1 and B2), and Type C. RESULTS: Type B was found to be the most common pattern in the study population (talus-97.8%; calcaneus-80.2%). The morphometric parameters were expressed as mean ± 2 SD. The anteroposterior length of the left talus was more than right talus, while the transverse width of right and left talus is almost equal. The length of right sulcus tali appears to be more than left sulcus tali, whereas the width and depth of right and left sulcus tali was almost equal. The transverse width of the right calcaneus was greater than left calcaneus. Width and depth of right and left sulcus calcanei were almost equal, but the length of right sulcus calcanei was more than the left sulcus calcanei (p value - 0.036). CONCLUSION: Analysis of the pattern of articulating facets of talus and calcaneum and establishing the common types and their morphometric parameters will be helpful as an important tool for reconstruction surgeries of hind-foot deformities and foot rehabilitation procedures.

Self-Assembly of a Guanosine Derivative To Form Nanostructures and Transmembrane Channels.

We herein report the self-assembly of a lipophilic bromoguanosine derivative (G1) in homogeneous solution, in the solid state and in planar bilayer membranes. The self-assembly of G1, driven by H-bonding and π-π stacking interactions can form different nano-structures depending on incubation time. The G1 nanostructure is able to bind a bioactive dye like Rose Bengal. In crystal state, it shows ribbon type H-bonding pattern and exhibits birefringence in polarized light. And further, the self-assembled nanostructure of G1 can form discrete transmembrane ion channels in lipid bilayer membranes, enabling passage of potassium ions.

Fever, thrombocytopenia, and AKI-A profile of malaria, dengue, and leptospirosis with renal failure in a South Indian tertiary-care hospital.

INTRODUCTION: In the tropics, the triad of fever, thrombocytopenia, and AKI portends a grim prognosis with high mortality and a severe strain on already-stretched resources. Malaria, dengue, and leptospirosis account for most cases. We undertook a review of cases to determine factors accounting for adverse prognosis. METHODS: All patients presenting to the emergency room (ER) with a history of fever, thrombocytopenia, and renal failure were included in the study. Patients were followed until discharge or death, and end points looked at were 1-week and 30-day mortality, and renal function upon discharge. Parameters like liver function test (LFT), renal function, and platelet count upon discharge were also documented. RESULTS: A total of 43 patients was included in the study. Mean age was 42.5 years with 86% males. Mean APACHE and SOFA scores on admission were 23.89 and 15.42, respectively. Mean admission platelet counts were 41,000. Mean serum creatinine was 4.1, and bilirubin was 9.94. A platelet count of < 34,000, serum creatinine of > 4, albumin of > 2.3, SOFA score of > 20, and APACHE score of > 32.2 were significantly predictive of 1 week mortality. Need for mechanical ventilation, oliguria on admission, and need for dialysis all were highly predictive of 30-day mortality. In addition, a serum bicarbonate of < 12, INR of > 1.5, hemoglobin of < 9.5 were highly predictive of higher 30 day mortality. Overall, 1-week mortality was 16.3%, of which 48% was accounted for by patients with leptospirosis. CONCLUSIONS: Factors like low platelet count, oliguria, need for dialysis, high APACHE and SOFA scores on admission, need for mechanical ventilation, and low serum albumin portend a grave prognosis. There is need for randomized control trials (RCT) to further determine adverse prognostic factors in this subsect of patients.

Controllable pulse width of bright similaritons in a tapered graded index diffraction decreasing waveguide.

We obtain the bright similariton solutions for generalized inhomogeneous nonlinear Schrödinger equation (GINLSE) which governs the pulse propagation in a tapered graded index diffraction decreasing waveguide (DDW). The exact solutions have been worked out by employing similarity transformations which involve the mapping of the GINLSE to standard NLSE for the certain conditions of the parameters. By making use of the exact analytical solutions, we have investigated the dynamical behavior of optical similariton pairs and have suggested the methods to control them as they propagate through DDW. Moreover, pulse width of similariton is controlled through various profiles. These results are helpful to understand the similaritons in DDW and can be potentially useful for future experiments in optical communications which involve optical amplifiers and long-haul telecommunication networks.

Aerobic biodegradation of azo dye Acid Black-24 by Bacillus halodurans.

Bacillus halodurans MTCC 865 was employed for decolorization of textile azo dye, Acid Black-24 (AB-24). Thousand mgl⁻¹ of AB-24 was decolorized with 90% efficiency by the strain within 6 hrs at pH 9 and 37 °C with 5% NaCl under static conditions in screening medium. Decolorization was evaluated by measuring the periodic decrease in absorbance at 557 nm (λ(max)). Biodegradation of Acid Black-24 was determined by FTIR and HPLC. The FTIR spectrum of the AB-24 dye suggests the presence of azo bond (-N = N-) peak at 1618.28 cm⁻¹. Absence of the azo bond in the degraded sample spectrum indicates biodegradation of the dye. Formation of metabolites with different retention times in HPLC analysis further confirmed degradation of the azo dye, Acid Black-24 by Bacillus halodurans.

Improving sepsis classification performance with artificial intelligence algorithms: A comprehensive overview of healthcare applications.

PURPOSE: This study investigates the potential of machine learning (ML) algorithms in improving sepsis diagnosis and prediction, focusing on their relevance in healthcare decision-making. The primary objective is to contribute to healthcare decision-making by evaluating the performance of various supervised and unsupervised models. MATERIALS AND METHODS: Through an extensive literature review, optimal ML models used in sepsis research were identified. Diverse datasets from relevant sources were employed, and rigorous evaluation metrics, including accuracy, specificity, and sensitivity, were applied. Innovative techniques were introduced, such as a Stacked Blended Ensemble Model and Skopt Optimization with Blended Ensemble, incorporating Bayesian optimization for hyperparameter tuning. RESULTS: ML algorithms demonstrate efficacy in sepsis diagnosis, presenting an improved balance between specificity and sensitivity, critical for effective clinical decision-making. Classifier ensemble models show enhanced accuracy and efficiency, with novel optimization techniques contributing to improved adaptability. CONCLUSION: The study emphasizes the potential benefits of ML algorithms in sepsis management, advocating for ongoing research to optimize performance and ensure ethical utilization in healthcare decision-making. Ethical considerations, interpretability, and transparency are crucial factors in implementing these algorithms in clinical practice.

Nintedanib-induced osteomyelitis of the jaw against the background of COVID-19 infection.

PURPOSE: Various medications are administered to treat Coronavirus Disease 2019 (COVID-19) infection and prevent its complications. Some medicines have complications and long-term effects, which may mimic other conditions, making precise diagnosis difficult. This report aims to bring to light one such complication, medication-related osteonecrosis of the jaw (MRONJ), secondary to a commonly prescribed medication for preventing lung fibrosis post-COVID-19 infection. METHOD: A 33-year-old male reported to our department with the typical clinical and radiological features of Mucormycosis of the upper jaw post-COVID-19 infection. However, on detailed evaluation of his history (controlled diabetic and short duration of steroid therapy) and review of the mycology staining, bacteriology, culture, and histopathological reports, we came to a negative diagnosis for Mucormycosis. The patient was, however, on treatment for the prevention of lung fibrosis with Nintedanib (tyrosine kinase inhibitor) 150 mg twice a day for one month. RESULT: In the absence of predisposing factors and negative laboratory findings for mucormycosis, we arrived at a diagnosis of MRONJ, attributable to Nintedanib therapy given to prevent lung fibrosis post-COVID-19 infection. CONCLUSION: The use of Nintedanib has recently increased due to the high incidence of lung fibrosis post-COVID-19 infection. However, Nintedanib should be considered a causative agent for osteonecrosis of the jaw in the absence of other obvious predisposing factors. Therefore, Nintedanib must be administered after a thorough consideration of risk factors.

Thoracic Continuous Spinal Anesthesia in Patients With Destroyed Lung Resulted in Favorable Perioperative Outcome.

Among patients needing open abdominal surgery, those with high-risk medical conditions impose significant challenges from an anesthesia point of view. Thoracic continuous spinal anesthesia (TCSA) is an evolving technique that may be beneficial for a subset of patients with underlying high-risk medical conditions where general anesthesia (GA) becomes a relative contraindication. TCSA, as a primary anesthesia technique, is gaining favor for its advantages over GA in open abdominal surgery as it avoids airway intervention and mechanical ventilation. The current article focuses on TCSA in 2 patients at high risk for GA, which resulted in favorable perioperative outcomes.

Occupational Injuries and Health Status Among Rural Tribal Non-Traditional Fishing Communities in the Coastal Region of Tamil Nadu, India.

OBJECTIVES: This study evaluated the occupational injuries and health hazards associated with fishing as an occupation among non-traditional rural tribal fishing communities in the coastal region of Tamil Nadu, India. METHODS: This cross-sectional study included a total of 170 individuals belonging to a fishing community, comprising both male (n = 82) and female (n = 88) participants. The demographic details including occupational history, lifestyle characteristics, socio-economic status, personal habits, and health status were assessed through the questionnaire survey. RESULTS: The fishing community has a low socioeconomic status and poor literacy, lifestyle, and personal habits. The mean age of the participants was 38.8 yrs (male 34.8; female 39.9 yrs). Only 10% reported usage of personal protective equipment (PPE), and the work duration varied from 8 to 24 hrs in a day. While male subjects reported smoking habits (12%) and alcohol consumption (23%), none of the females reported alcohol consumption and smoking habits. The major occupational injuries that occurred were due to catfish (72%) and oysters (48%). A large number of female subjects reported musculoskeletal pains. The body mass index of about 28% of fishermen was above the normal range. Abnormal blood sugar, blood pressure, and respiratory and neurological symptoms were the other major health complaints. The major environmental hazards reported were salinity, solar radiation, tides, and high wind. CONCLUSION: Injuries from handling fish and oysters were observed to be the major occupational burden. Additonally, a high prevalence of musculoskeletal pain and chronic health illness was commonly observed among the fishers. Adequate training and awareness programs are required for effective management of occupational health hazards and health promotion.