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A 11-year-old boy with acute myeloid leukemia was brought for treatment of severe acute respiratory infection in the National Capital Region, New Delhi, India. Avian influenza A(H5N1) infection was laboratory confirmed. Complete genome analysis indicated hemagglutinin gene clade 2.3.2.1a. We found the strain to be susceptible to amantadine and neuraminidase inhibitors.

Summary: Background: Cardiovascular diseases (CVDs) are the leading cause of death in most low- and middle-income countries (LMICs). CVDs and their metabolic risk factors have historically been concentrated among urban residents with higher socioeconomic status (SES) in LMICs such as India. However, as India develops, it is unclear whether these socioeconomic and geographic gradients will persist or change. Understanding these social dynamics in CVD risk is essential for mitigating the rising burden of CVDs and to reach those with the greatest needs. Methods: Using nationally representative data with biomarker measurements from the fourth (2015–16) and fifth (2019–21) Indian National Family and Health Surveys, we investigated trends in the prevalence of four CVD risk factors: smoking (self-reported), unhealthy weight (BMI ≥25 kgm2), diabetes (random plasma glucose concentration ≥200 mg/dL or self-reported diabetes), and hypertension (one of: average systolic blood pressure ≥140 mmHg, average diastolic blood pressure ≥90 mmHg, self-reported past diagnosis, or self-reported current antihypertensive medication use) among adults aged 15–49 years. We first described changes at the national level and then trends stratified by place of residence (urban versus rural), geographic region (northern, northeastern, central, eastern, western, southern), regional level of development (Empowered Action Group member state or not), and two measures of socioeconomic status: level of education (no education, primary incomplete, primary complete, secondary incomplete, secondary complete, higher) and wealth (quintiles). Findings: Unhealthy weight increased among all social and geographic groups but both the absolute and the relative changes were substantially higher among people with low SES (as measured by education or wealth) and in rural areas. For diabetes and hypertension, the prevalence increased for those from disadvantaged groups while staying constant or even decreasing among the wealthier and more educated. In contrast, smoking consumption declined for all social and geographic groups. Interpretation: In 2015–16, CVD risk factors were higher among more advantaged subpopulations in India. However, between 2015–16 and 2019–21, the prevalence of these risk factors grew more rapidly for less wealthy and less educated subpopulations and those living in rural areas. These trends have resulted in CVD risk becoming far more widespread throughout the population; CVD can no longer be characterized as a wealthy urban phenomenon. Funding: This work was supported by the Alexander von Humboldt Foundation (grant received by NS); the Stanford Diabetes Research Center [grant received by PG] and the Chan Zuckerberg Biohub [grant received by PG].

Cannon ball metastases refer to large, well circumscribed, round pulmonary nodules like cannon balls that are scattered over both lungs, being a classical presentation of haematogenous tumour spread.Cannon ball pulmonary metastases are typically seen in the patients with choriocarcinoma or renal cell carcinoma. Rarely, pulmonary metastases with the same appearance may be secondary from prostate cancer, synovial sarcoma, endometrial carcinoma or haepatocellular carcinoma.The present case series is about six patients diagnosed with cannon ball metastases which occurred from primary lung carcinoma. Out of these six cases, three were of small cell carcinoma, two of squamous cell carcinoma and one of adenocarcinoma.The histopathology of all the cases was established by biopsy from the tumour site and appropriate treatment was started in the form of chemotherapy and radiotherapy as needed. Clinicians must investigate thoroughly for primary origin of cannon ball metastasis, though rare but lung cancer can present as this kind of metastasis.

Background: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is a helpful adjunct in the management of hemorrhagic shock due to bleeding in the abdomen or pelvis. Ischemia distal to the occlusion is a concern; intermittent aortic balloon inflation (i-REBOA) is a novel way to achieve decreased ischemia time. Methods: This study was conducted using data from the multinational ABO Trauma Registry. All patients entered between January 2016 and December 2019 were included. Results: The sample consisted of 157 patients. There were 57 patients in the i-REBOA group (36%) and 100 in the REBOA group (64%). The groups were similar in gender (P = 0.50), age (P = 0.17), mechanism of injury (P = 0.42), and injury severity score (P = 0.13). The levels of international normalized ratio (INR) (P < 0.01), activated partial thromboplastin time (aPTT) (P < 0.01) and lactate (P = 0.02) were higher in the i-REBOA group. Total balloon inflation times were longer in the i-REBOA group (P < 0.01). Major complication rates did not differ between groups. Mortality rates between groups were similar in the Emergency Department (ED) (3.8% for i-REBOA vs 10.1%; P = 0.17), within 24 hours (43.4% for i-REBOA vs 38.2%; P = 0.54), and at 30 days (63.6% for i-REBOA vs 48.4%; P = 0.07). Conclusions: The data from this registry show that i-REBOA is currently being used and may allow for longer total balloon inflation times without higher morbidity or mortality rates.

Abstract Sustainable and precision agriculture practices are essential to meet the global food demand with minimal impact on soil, air and water. In the present study, nanofertilizers of nitrogen and zinc was used with the organic farming practice under field condition for the cereal i.e. wheat, pearl millet, and oil seed crops i.e. mustard, sesame. The field trial was compared with chemical fertilizer based agricultural settings. A total of 160 field demonstrations were conducted at two locations: Khaliyawas (28.19° N, 76.76° E) and Khatawali (28.22° N, 76.76° E) of Haryana, India with a total area of 1225 acre and randomized block design. It was found that an average yield was recorded 5.35% higher in wheat, 24.24% higher yield in sesame, 4.2% higher in pearl millet and 8.4% higher yield in mustard by applying nanofertilizers of nitrogen and zinc along with the organic farming practice. The increased yield corroborated with the development parameters of plants such as wheat tillers, ear head length of pearl millet, capsule number per plant in sesame and siliquae number per plant in mustard. The trial observation suggests that the fields with applied organic manure, bio-fertilizer and nanofertilizers in combination resulted in higher yield and better plant growth performances when compared to the fields under conventional chemical fertilizer practice. The results suggest that the intervention of nanotechnology along with organic farming practice can help in minimizing the mass volume requirement of conventional chemical fertilizer while improving crop production.

Neurotoxin-related optic neuritis (ON) after snake bite is uncommon. Here, we present a case of a 70-year-old female who developed bilateral painless loss of vision after she received treatment with anti-snake venom (ASV). She had only perception of light on assessment of visual acuity on admission which then improved drastically after administration of intravenous methylprednisolone (MP) after making the provisional diagnosis of ON on the basis of history and clinical findings of the patient. Imaging and visual-evoked potential could not be done initially, and they were done after the administration of intravenous MP which had normal findings. ASV, though being a lifesaving treatment, has been sometimes associated with ON.

Compact inductor-capacitor (LC) resonators, in contrast to coplanar waveguide (CPW) resonators, have a simple lumped-element circuit representation but usually call for sophisticated finite-element method (FEM) simulations for an accurate modeling. Here we present a simple analytical model for a family of coplanar LC resonators where the electrical properties are directly obtained from the circuit geometry with a satisfying accuracy. Our experimental results on ten high-internal-quality-factor resonators (Q_{i}≳2×10^{5}), with frequencies ranging from 300MHz to 1GHz, show an excellent consistency with both the derived analytical model and detailed FEM simulations. These results showcase the ability to design sub-gigahertz resonators with less than 2% deviation in the resonance frequency, which has immediate applications, for example, in the implementation of ultrasensitive cryogenic detectors. The achieved compact resonator size of the order of a square millimeter indicates a feasible way to integrate hundreds of microwave resonators on a single chip for realizing photonic lattices.

Accurate quantification of immunoglobulin G (IgG) levels is vital for understanding immune status and diagnosing various medical conditions. Lateral flow assays (LFAs) offer rapid and convenient diagnostic tools, but their sensitivity has been a limitation. Our research introduces a refined method incorporating europium nanoparticles, enhancing both sensitivity and accuracy of LFAs in human IgG measurement. Utilizing a unique sandwich format, carboxylate-modified polystyrene Eu (III) chelate microparticles (CM-EUs) acted as the primary reporters. The concentrations of both detection and capture antibodies on the strip were optimized to bolster the LFA’s quantitative performance. The subsequent calibration curve between the IgG concentration and the measured intensity ratio (VR) established the linearity and analytical sensitivity of our method with a high correlation coefficient (r = 0.99) and an impressively low limit of detection (LoD = 0.04 ng/mL). Our precision assessment, segmented into intra-assay and inter-assay evaluations, showcases the method’s consistency and reproducibility. The LFA assay’s stability was established by demonstrating its resistance to degradation and affirming its potential for extended storage without a dip in performance. The study’s findings underscore the potential of this method to contribute to diagnostic medicine and improve patient care.

Single-qubit sensing protocols can be used to measure qubit-bath coupling parameters. However, for sufficiently large coupling, the sensing protocol itself perturbs the bath, which is predicted to result in a characteristic response in the sensing measurements. Here, we observe this bath perturbation, also known as a quantum quench, by preparing the nuclear spin bath of a nitrogen-vacancy (NV) center in polarized initial states and performing phase-resolved spin-echo measurements on the NV electron spin. These measurements reveal a time-dependent phase determined by the initial state of the bath. We derive the relationship between the sensor phase and the Gaussian spin-bath polarization and apply it to reconstruct both the axial and transverse polarization components. Using this insight, we optimize the transfer efficiency of our dynamic nuclear polarization sequence. This technique for directly measuring bath polarization may assist in preparing high-fidelity quantum memory states, improving nanoscale NMR methods, and investigating non-Gaussian quantum baths.

Molecular tests for infectious diseases and genetic anomalies, which account for significant global morbidity and mortality, are central to nucleic acid analysis. In this study, we present a digital droplet LAMP (ddLAMP) platform that offers a cost-effective and portable solution for such assays. Our approach integrates disposable 3D-printed droplet generator chips with a consumer smartphone equipped with a custom image analysis application for conducting ddLAMP assays, thereby eliminating the necessity for expensive and complicated photolithographic techniques, optical microscopes, or flow cytometers. Our 3D printing technique for microfluidic chips facilitates rapid chip fabrication in under 2 h, without the complications of photolithography or chip bonding. The platform’s heating mechanism incorporates low-powered miniature heating blocks with dual resistive cartridges, ensuring rapid and accurate temperature modulation in a compact form. Instrumentation is further simplified by integrating miniaturized magnification and fluorescence optics with a smartphone camera. The fluorescence quantification benefits from our previously established RGB to CIE-xyY transformation, enhancing signal dynamic range. Performance assessment of our ddLAMP system revealed a limit of detection at 10 copies/μL, spanning a dynamic range up to 104 copies/μL. Notably, experimentally determined values of the fraction of positive droplets for varying DNA concentrations aligned with the anticipated exponential trend per Poisson statistics. Our holistic ddLAMP platform, inclusive of chip production, heating, and smartphone-based droplet evaluation, provides a refined method compatible with standard laboratory environments, alleviating the challenges of traditional photolithographic methods and intricate droplet microfluidics expertise.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), poses a global health challenge and is responsible for over a million deaths each year. Current treatment is lengthy and complex, and new, abbreviated regimens are urgently needed. Mtb adapts to nutrient starvation, a condition experienced during host infection, by shifting its metabolism and becoming tolerant to the killing activity of bactericidal antibiotics. An improved understanding of the mechanisms mediating antibiotic tolerance in Mtb can serve as the basis for developing more effective therapies. We performed a forward genetic screen to identify candidate Mtb genes involved in tolerance to the two key first-line antibiotics, rifampin and isoniazid, under nutrient-rich and nutrient-starved conditions. In nutrient-rich conditions, we found 220 mutants with differential antibiotic susceptibility (218 in the rifampin screen and 2 in the isoniazid screen). Following Mtb adaptation to nutrient starvation, 82 mutants showed differential antibiotic susceptibility (80 in the rifampin screen and 2 in the isoniazid screen). Using targeted mutagenesis, we validated the rifampin-hypersusceptible phenotype under nutrient starvation in Mtb mutants lacking the following genes: ercc3, moeA1, rv0049, and rv2179c. These findings shed light on potential therapeutic targets, which could help shorten the duration and complexity of antitubercular regimens.

The ability to simultaneously heat and image samples using transmitted light is crucial for several biological applications. However, existing techniques such as heated stage microscopes, thermal cyclers equipped with imaging capabilities, or non-contact heating systems are often bulky, expensive, and complex. This work presents the development and characterization of a Miniaturized Optically-clear Thermal Enclosure (MOTE) system—an open-source, inexpensive, and low-powered modular system—capable of convectively heating samples while simultaneously imaging them with transmitted light. We develop and validate a computational fluid dynamics (CFD) model to design and optimize the heating chamber. The model simulates velocity and temperature profiles within the heating chamber for various chamber materials and sizes. The computational model yielded an optimal chamber dimension capable of achieving a stable temperature ranging from ambient to 95 °C with a spatial discrepancy of less than 1.5 °C, utilizing less than 8.5 W of power. The dual-functionality of the MOTE system, enabling synchronous heating and transmitted light imaging, was demonstrated through the successful execution of paper-based LAMP reactions to detect λ DNA samples in real-time down to 10 copies/µL of the target concentration. The MOTE system offers a promising and flexible platform for various applications, from molecular diagnostics to biochemical analyses, cell biology, genomics, and education.

In this work, the viability of Friction Stir Processing (FSP) was explored as a potential method to enhance the tribological properties of aerospace alloy AA2219-T87. The dry sliding wear properties of FSP, and as-received AA2219 alloy in mild and severe wear regimes were studied using a vertical- interaction tribometer by varying contact pressures and sliding speeds. The results show that, FSP samples exhibited an enhanced wear resistance in the severe wear regime and can be attributed to the propensity of FSP aluminium alloy to undergo friction-induced strain hardening in-situ during dry sliding. This recurrent ‘sliding-friction induced strain hardening’ facilitated for an increased hardness towards the sliding-interface, thereby enhancing the wear resistance and this was confirmed through cross sectional nano-indentation studies.

INTRODUCTION: Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. Various triggers, lack of knowledge about the disease, and unawareness about the correct inhalation techniques lead to poor control of the disease. This study aimed to study the factors responsible for uncontrolled asthma using the asthma control test (ACT) and explore other ways to improve asthma control. MATERIALS AND METHODS: One hundred and eighty diagnosed cases of bronchial asthma according to Global Initiative for Asthma (GINA) guidelines, >18 years were enrolled for the study in an outpatient setting. The level of asthma control was assessed using the self-administered ACT. Factors responsible for uncontrolled asthma were evaluated using a questionnaire based on GINA guidelines. RESULTS: Our study noted that in the majority (66.11%) of patients, asthma was poorly controlled followed by well-controlled (24.44%). Asthma was perfectly controlled in only 9.44% of patients. The mean value of the ACT score of study subjects was 17.5 ± 4.16 with a median (25th–75th percentile) of 17 (15–20) within the range of 7–25. Smoking (P < 0.0001), poor education about asthma (P < 0.0001), social stigma regarding inhaler use (P < 0.0001), wrong inhalation techniques (P < 0.0001), environmental triggers (P < 0.0001), associated comorbidities (P = 0.005), poor adherence to treatment (P < 0.0001), inappropriate therapy (P < 0.0001), and frequent hospitalizations (P = 0.006) were the factors responsible for uncontrolled asthma. CONCLUSION: The present study identified various factors responsible for the high prevalence of asthma in an outpatient clinical setting. Common risk factors that contribute to poor asthma control were assessed in a comprehensive manner.

Purpose: To analyze intraoperative difficulties and visual and surgical outcomes following pediatric cataract surgery. Methods: This five-year retrospective study (2014–2019) included 138 eyes (85 children) with cataract aged between 12 months and 18 years (either sex). All children had undergone best-corrected visual acuity (BCVA), anterior and posterior segment evaluation, intraocular lens (IOL) power calculation, superior manual-small-incision cataract surgery (MSICS) with or without posterior capsulotomy/anterior vitrectomy and IOL implantation under general or local anesthesia, visual rehabilitation, and had been followed up for a minimum period of 12 months. Results: The mean age was 111.27 ± 4.84 months. Preoperative BCVA distance: 113 (81.88%)eyes had BCVA < 6/60; near BCVA: 114 (82.6%) eyes had ≤N36. At last postoperative follow-up (mean: 20.98 ± 13.08 months): distant BCVA- ≥6/60 had been recorded in 120 (86.96%) eyes; near BCVA- >N36 in 123 (89.13%) eyes. Improvement in BCVA was statistically significant. Intraoperative scleral tunnel difficulties were seen in three eyes (thin flap in two, and buttonhole in one eye); in the majority of the eyes 113 (81.88%), IOL was placed in the bag. Twenty eyes had early postoperative inflammation. At last follow-up: posterior capsular opacity was recorded in six eyes, IOL decenteration in two eyes, secondary glaucoma in six eyes, and severe amblyopia in 36 (26.09%) eyes. The mean myopic shift was − 1.11 ± 0.89 D and was statistically significant. Conclusion: Superior MSICS as a treatment for pediatric cataract has minimal intraoperative complications and satisfactory visual and surgical outcomes.

BACKGROUND: The Sysmex XN-series hematology analyzers provide newer parameters including high fluorescence lymphocyte cell percentage (HFLC%) which correlates with the presence of atypical lymphocytes in peripheral blood. We aimed to analyze the sensitivity and specificity of HFLC% as a diagnostic tool and its association with serological status in diagnosed dengue patients and thereby establish a cutoff of HFLC% based on serology. Besides, we also wish to correlate HFLC% with thrombocytopenia in these patients. MATERIALS AND METHODS: A total of 1500 serum samples were subjected to serological evaluation for dengue. After excluding hematological malignancies and autoimmune disorders, the same day complete blood count parameters including HFLC% and platelet counts were collected retrospectively for 292 serologically positive dengue cases and 76 seronegative controls. RESULTS: Our result shows that in nonstructural 1 antigen-positive cases, a cutoff of >5.2% HFLC can have a sensitivity of 79.5% and specificity of 98.6%. We found a different cut off of HFLC% >3.2% (sensitivity 83.4%, specificity 98.6%) for the cases with only immunoglobulin M positivity and a cut off of HFLC% >2.6% (sensitivity 86.1%, specificity 96%) in the dual positive cases (immunoglobulin M with nonstructural 1 antigen). Besides, high HFLC% also shows a strong correlation with platelet count with a Spearman correlation coefficient of −0.6. CONCLUSIONS: The result of our study shows that a specific cutoff of HFLC% can not only help us to suspect dengue fever but also predict the risk of thrombocytopenia in already diagnosed dengue patients. The sensitivity and specificity of HFLC% varied with the serological status of the patients which depend on the days of fever on presentation.

Abstract Complete or improving civil registration systems in sub-national areas in low- and middle-income countries provide several opportunities to better understand population health and its determinants. In this article, we provide an assessment of vital statistics in Kerala, India. Kerala is home to more than 33 million people and is a comparatively low-mortality context. We use individual-level vital registration data on more than 2.8 million deaths between 2006 and 2017 from the Kerala MARANAM (Mortality and Registration Assessment and Monitoring) Study. Comparing age-specific mortality rates from the Civil Registration System (CRS) to those from the Sample Registration System (SRS), we do not find evidence that the CRS underestimates mortality. Instead, CRS rates are smoother across ages and less variable across periods. In particular, the CRS records higher death rates than the SRS for ages, where mortality is usually low and for women. Using these data, we provide the first set of annual sex-specific life tables for any state in India. We find that life expectancy at birth was 77.9 years for women in 2017 and 71.4 years for men. Although Kerala is unique in many ways, our findings strengthen the case for more careful attention to mortality records within low- and middle-income countries, and for their better dissemination by government agencies.

Background: Rotator cuff injuries have traditionally been managed by either single-row or double-row arthroscopic repair techniques. Complex single-row techniques have recently been proposed as a biomechanically stronger alternative treatment option. However, no rigorous meta-analysis has evaluated the effectiveness of complex single-row against double-row repair. This meta-analysis aims to evaluate clinical outcomes in patients with full-thickness rotator cuff injuries treated with both simple and complex single-row, as well as transosseous-equivalent (TOE) double-row procedures. Methods: An up-to-date literature search was performed using the predefined search strategy. All studies that met the inclusion criteria were assessed for methodological quality and included in the meta-analysis. Pain, functional scores, range of motion, and retear rate were all considered in the study. Conclusion: The results of our meta-analysis suggest that there is no significant difference between complex single-row and TOE double-row procedures in any of the observed outcomes. At this point in time, the available comparative data between simple single-row and TOE double-row repair techniques are limited. Further high-quality studies are required to assess the clinical outcomes and cost-effectiveness of these different techniques.

Introduction: Respiratory syncytial virus (RSV) is a common cause of morbidity among hematopoietic stem cell transplant (HSCT) recipients, with RSV-associated lower respiratory tract infection carrying high mortality rates. There have been no large studies till date, describing the incidence, clinical features, and outcomes of RSV infection among adult HSCT recipients in India. Methods: A prospective cohort of 100 adults who underwent HSCT was followed up for a maximum period of 18 months starting from the date of transplantation for any episode of respiratory tract infectious disease (RTID). Respiratory samples were collected for laboratory confirmation of the presence and subtyping of RSV by real-time reverse transcriptase-polymerase chain reaction. Results: The study population comprised of 66% (66/100) males and 34% (34/100) females. Autologous HSCT recipients constituted 78% (78/100) and allogeneic HSCT recipients constituted 22% (22/100) of the study population. The incidence of RSV-RTID among adults after HSCT was 0.82/100 patient months. Most cases occurred during the winter season and the predominant subtype was RSV-A (9/11, 81.8%). Lower RTID was the most common clinical diagnosis made at presentation (9/11, 81.8%). Female gender was predictive of RSV-RTID (log rank P = 0.002). All the RSV-RTID episodes recovered completely without targeted therapy. Conclusion: RSV is a significant cause of morbidity among adult HSCT recipients in India. Prophylaxis and treatment measures need to be instituted after a proper risk-benefit assessment. Longitudinal studies with larger sample sizes are needed to confirm these results.

Background: Patients undergoing elective cardiac surgery often experience pre-operative anxiety. Preoperative anxiety influences surgical outcome. There are very few studies which have assessed the impact of clonidine and Gabapentin in the treatment of anxiety especially in Indian populations and its implications on major adverse cardiac events (MACE) and 30 days mortality. Materials and Methods: Adult patients aged 18 to 80 years old who were scheduled to have an elective coronary artery by-pass graft (CABG) were included in the study. Those who satisfied the inclusion criteria were given either Gabapentin (800 mg) or Clonidine (300 mcg) 90-120 minutes before the induction. State trait anxiety inventory (STAI) was used to assess anxiety in baseline and taking just before operating room. The primary endpoint was a reduction in the STAI associated with the study drug, while the secondary endpoint was the incidence of MACE in the perioperative period (30 days), which included composite episodes of non-fatal cardiac arrest, chaotic rhythm, acute myocardial infarction, congestive heart failure, cardiac arrhythmia, angina, and death. Results: A total of 75 patients were considered for the statistical analysis. The demographic and clinical features of the study participants were similar in both groups. Nearly 75-80% of participants had severe anxiety in the preoperative period while 10-20% had moderate anxiety. While both the drugs showed a reduction in the anxiety levels, the clonidine group fared better (statistically insignificant). The incidence of MACE was similar in both groups. Conclusion: The preoperative anxiety levels were high among cardiac surgery patients. Both clonidine and gabapentin were equally effective in reducing the levels of preoperative anxiety. Preoperative STAI scores in the range of 32-53 is not associated with MACE and 30-day mortality among cardiac surgery patients.

The operation of power systems needs uninterrupted and precise wide-area real-time monitoring for secure and automated control of power networks, therefore, there is a requirement of robust state estimation (SE) by the smart control centre. An iterative free static state estimation (IFSSE) scheme is developed using the linear measurement model (LMM) in this paper for microgrids (MGs) integrating distributed generation energy resources (DGERs). The developed scheme of IFSSE utilizes M-estimator (ME) concept, which is combined with the linear static state estimation (SSE) approach in order to provide robust estimation. The developed IFSSE scheme is iteration-free due to the implementation LMM that is achieved from placing the microphasor measurement units (μPMUs) and separate bad data processing (BDP) is not required for this proposed scheme. The proposed scheme's performance has been verified by employing it on modified IEEE-14 bus test systems (BTS) integrating DGERs and modified IEEE 30 BTS integrating DGERs then comparison has been done by taking two cases, i.e., linear SSE without BDP and linear SSE with BDP.

Picrorhiza kurroa Royle ex Benth, Kutki (P.kurroa) is an important medicinal plant, traditionally recommended and used in Ayurveda for millennia, with certain cautions. There has been a significant revival of keen interest in its pharmacology, pharmacognosy, and phytochemistry for the last few decades. The evidence of its hepatoprotective activity, in experimental and clinical studies, accelerated the correlation of the specific phytochemical constituents of P.kurroa with precise pharmacological activities. Iridoid glycosides, particularly picrosides, emerged as the active molecules. For effective translation of traditional remedies into modern therapy, value addition by mechanistic understanding of molecular actions, drug targets, the degrees of efficacy and safety as well as convenient dosage forms is needed. Reverse pharmacology approach and phytopharmaceutical drug category facilitate such a translation. The present review illustrates how a potential translation of traditional practices of using P.kurroa into a phytochemically standardized, clinically targeted natural product for global unmet medical needs viz. Fatty liver disease can be attained.

Objective. Epilepsy is one of the most prevalent neurological illnesses defined by periodic seizures with or without loss of consciousness caused by aberrant neural activity. There are many allopathic medications available for the treatment of epilepsy such as phenytoin (PHY), but the side effects are a major concern. Therefore, the present study involved the evaluation of the pharmacological significance of Amaranthus viridis L. extract (EAV) in the management of strychnine (STR)-induced epilepsy. Method. STR (3.5 mg/kg, i.p.) was injected into male rats 30 minutes after the pre-treatment of a standard drug (PHY: 20 mg/kg) and the two doses of EAV (EAV-200 and EAV-400 mg/kg, p.o.) to the respective groups to cause the convulsions. The anti-convulsant effect of EAV-200 and EAV-400 against STR-induced convulsion in rats was investigated in terms of convulsion onset, duration of convulsions, number of convulsions, and convulsion score. Furthermore, the mitochondrial function and integrity in the brain’s prefrontal cortex (PFC) were also estimated. Results. EAV-400 significantly increased the onset of convulsion from 61.67±3.051 to 119.2±2.738 and reduced the STR-induced duration of convulsions from 144.8±3.582 to 69.17±3.736, number of convulsions from 4.000±0.1592 to 1.533±0.1542, and convulsion score from 5.000±0.3651 to 2.833±0.3073 in rats. EAV-400 significantly attenuated the STR-induced decrease in the mitochondrial function and integrity of the rat PFC. In rats, EAV-400 significantly accelerated the onset of convulsions while decreasing the STR-induced duration, frequency, and score. Conclusion. Based on investigational findings, EAV-400 could be inferred to be a possible anti-epileptic option for the treatment of epilepsy of this plan in preclinical research.

A large proportion of the global tuberculosis (TB) burden is asymptomatic and not detectable by symptom-based screening, driving the TB epidemic through continued M. tuberculosis transmission. Currently, no validated tools exist to diagnose incipient and subclinical TB. Nested within a large prospective study in household contacts of pulmonary TB cases in Southern India, we assessed 35 incipient TB and 12 subclinical TB cases, along with corresponding household active TB cases (n=11), and household controls (n=39) using high throughput methods for transcriptional and protein profiling. We split the data into training and test sets and applied a support vector machine classifier followed by a Lasso regression model to identify signatures. The Lasso regression model identified an 11-gene signature (ABLIM2, C20orf197, CTC-543D15.3, CTD-2503O16.3, HLADRB3, METRNL, RAB11B-AS1, RP4-614C10.2, RNA5SP345, RSU1P1, and UACA) that distinguished subclinical TB from incipient TB with a very good discriminatory power by AUCs in both training and test sets. Further, we identified an 8-protein signature comprising b-FGF, IFNγ, IL1RA, IL7, IL12p70, IL13, PDGF-BB, and VEGF that differentiated subclinical TB from incipient TB with good and moderate discriminatory power by AUCs in the training and test sets, respectively. The identified 11-gene signature discriminated well between the distinct stages of the TB disease spectrum, with very good discriminatory power, suggesting it could be useful for predicting TB progression in household contacts. However, the high discriminatory power could partly be due to over-fitting, and validation in other studies is warranted to confirm the potential of the immune biosignatures for identifying subclinical TB.

Background: Radiation-induced hypothyroidism is a common toxicity of head and neck radiation. Our re-planning study aimed to reduce thyroid dose while maintaining target coverage with IMRT. Methods: We retrospectively identified patients with oral-cavity (n = 5) and oropharyngeal cancer (n = 5). Treatment plans were re-optimized with 45 Gy thyroid mean dose constraint, then we cropped the thyroid out of PTVs and further reduced thyroid dose. Target coverage was delivering 100% dose to ≥ 93% of PTV and 95% of dose to > 99% of PTV. Results: Originally, average mean dose to thyroid was 5580 cGy. In model I, this dropped to 4325 cGy (p

Every year, more than 200 million surgeries are performed around the world, and recent statistics show that adverse event rates for surgical pathologies remain unacceptably high, despite several national and global patient safety initiatives over the last decade. Patient safety is diverse and highly complicated in nature, with several critical components. Although concern for patient safety is fundamental in health care practice, its transition into knowledge is comparatively recent, and hence patient safety may be deemed a "new" field. Current surgical safety guidelines and checklists are generic and not adapted to specific patient concerns and risk factors in surgical subspecialties. All surgical practitioners and health care organizations must therefore become better aware of the fundamental context of patient safety, actively participate in endeavors to integrate patient safety measures in daily practice, and foster a patient safety culture. The purpose of this review article is to outline patient safety in surgical techniques that should be adopted and implemented.

COVID-19 imposed significant limitations upon the 2021 U.S. National Resident Matching Program (NRMP), most important of which is the replacement of traditional in-person interviews with a virtual format. To determine the strengths, limitations, and overall utility of virtual interviews (VIs) for residency applicant selection, a 14-question electronic survey was administered to programme directors (PDs) of all American Council for Graduate Medical Education (ACGME)-accredited residency programmes, from December 2020 through March 2021. PDs were asked about their experience with VIs and the ability to assess residency applicants using the virtual format. A total of 1123 PDs (30% response rate) representing 30 different specialities responded to our survey. Compared to in-person interviews, VIs made it more challenging to assess applicants’ fit with the programme, emotional intelligence, commitment to speciality, and ability to function as a resident physician. Overall, only 15% of PDs believed that VIs were better than in-person interviews. Once travel restrictions are lifted and in-person interviews are possible, 67% of PDs plan on hosting dual-format residency interviews, while 26% and 5% of PDs will exclusively host in-person interviews and VIs, respectively. This result was significantly different between surgical and non-surgical programmes [35% of surgical PDs suggested they would offer in-person interviews exclusively, compared to 21% of non-surgical PDs, p

When trying to characterise a bath coupled to a sensor qubit, one should consider that quantum environments change their properties in response to external perturbations. Here, the authors show how back-action of the qubit on the bath leads to a quench, which can be used to infer the bath spectral function.

Abstract Conservation of large carnivores such as leopards requires large and interconnected habitats. Despite the wide geographic range of the leopard globally, only 17% of their habitat is within protected areas. Leopards are widely distributed in Nepal, but their population status and occupancy are poorly understood. We carried out the sign‐based leopard occupancy survey across the entire Chure range (~19,000 km2) to understand the habitat occupancy along with the covariates affecting their occupancy. Leopard signs were obtained from in 70 out of 223 grids surveyed, with a naïve leopard occupancy of 0.31. The model‐averaged leopard occupancy was estimated to be 0.5732 (SE 0.0082) with a replication‐level detection probability of 0.2554 (SE 0.1142). The top model shows the additive effect of wild boar, ruggedness, presence of livestock, and human population density positively affecting the leopard occupancy. The detection probability of leopard was higher outside the protected areas, less in the high NDVI (normalized difference vegetation index) areas, and higher in the areas with livestock presence. The presence of wild boar was strong predictor of leopard occupancy followed by the presence of livestock, ruggedness, and human population density. Leopard occupancy was higher in west Chure (0.70 ± SE 0.047) having five protected areas compared with east Chure (0.46 ± SE 0.043) with no protected areas. Protected areas and prey species had positive influence on leopard occupancy in west Chure range. Similarly in the east Chure, the leopard occupancy increased with prey, NDVI, and terrain ruggedness. Enhanced law enforcement and mass awareness activities are necessary to reduce poaching/killing of wild ungulates and leopards in the Chure range to increase leopard occupancy. In addition, maintaining the sufficient natural prey base can contribute to minimize the livestock depredation and hence decrease the human–leopard conflict in the Chure range.

Abstract Background Coronary artery disease (CAD) is increasing day by day in young Indian population with increase in risk factors such as obesity, hypertension etc. Although in early age, these risk factors are clinically asymptomatic but physiologically they are symptomatic. These symptoms can be best assessed by assessing the response of autonomic nervous system Therefore the purpose of this study was to compare the autonomic response of gradient exercise testing protocol in normotensive, overweight, and pre-hypertensive subjects in the form of chronotropic response to exercise, inotropic reponse, heart rate recovery, blood pressure recovery, BRPE, and heart rate variability so that the physiological abnormalities can be corrected. Results There were significant differences (p < 0.05) found in gradient exercise testing protocol in diastolic blood pressure in normotensive, in heart rate variability in overweight and in both systolic as well as diastolic blood pressure in pre-hypertensive subjects. Conclusion Gradient exercise testing protocol can be best utilized as a clinical tool in normotensive, overweight, and pre-hypertensive subjects for the assessment of autonomic nervous system which provides diagnostic and prognostic information regarding cardiovascular disease or abnormalities.

AIM: To evaluate the effect of vitamin B12 deficiency anemia (BDA) on peripapillary retinal nerve fiber layer thickness (RNFLT) using spectral domain optical coherence tomography (SD-OCT), and to determine any correlation arising thereof. METHODS: In this cross-sectional observational study, 99 eyes of 50 BDA patients of age 18-65y were compared with 100 eyes of 50 healthy control subjects. All subjects underwent comprehensive clinical, ophthalmic, and hematological evaluation, followed by peripapillary RNFLT assessment using SD-OCT. RESULTS: The mean total, inferior, nasal, and temporal RNFLT were significantly lower in BDA group as compared to control group (P

Cytomegalovirus (CMV) infection is asymptomatic in the majority of immunocompetent patients. However, it can cause severe presentations, particularly in patients who are immunocompromised. We are reporting a rare association between respiratory failure secondary to cavitary pneumonia and a large pericardial effusion due to CMV infection in a patient with human immunodeficiency virus. The patient presented with hypoxic respiratory failure and a large pericardial effusion at risk of tamponade. After extensive investigation, the sole pathogen identified in the patient’s bronchoalveolar lavage and pericardial fluid was CMV.

Size of wallet (SOW) estimation is an important problem to solve from a company's perspective. The total business volume conducted by the customer for a product category across firms is generally unobservable, while the volume of transactions conducted by the customer with the company is mostly accessible. This paper focuses on the estimation of SOW and the estimation of opportunity, which is the difference between the SOW and the actual transactional value of the business that a customer does with a company. K-nearest neighbour (KNN) and quantile regression (QR) are applied here to arrive at the estimations, and their performance is compared. Based on the SOW and opportunity estimates, a company can decide its target segment and design specific marketing strategies accordingly, thereby improving its profitability.

Objective Describe the population of babies who do and do not receive postnatal corticosteroids for prevention or treatment of bronchopulmonary dysplasia (BPD).Design Retrospective cohort study using data held in the National Neonatal Research Database.Setting National Health Service neonatal units in England and Wales.Patients Babies born less than 32 weeks gestation and admitted to neonatal units from 1 January 2012 to 31 December 2019.Main outcomes Proportion of babies given postnatal corticosteroid; type of corticosteroid; age at initiation and duration, trends over time.Secondary outcomes Survival to discharge, treatment for retinopathy of prematurity, BPD, brain injury, severe necrotising enterocolitis, gastrointestinal perforation.Results 8% (4713/62019) of babies born

Quantum transduction is an essential ingredient in scaling up distributed quantum architecture and is actively pursued based on various physical platforms. However, demonstrating a transducer with positive quantum capacity is still practically challenging. In this Letter, we discuss a new approach to relax the impedance matching condition to half impedance matching condition, achieved by introducing two-photon drive in the electro-optic transducer. We show the quantum transduction capacity can be enhanced and can be understood in a simple interference picture with the help of the Bloch-Messiah decomposition. The parameter regimes with positive quantum capacity is identified and compared with and without the drive, indicating that the parametric drive-induced enhancement is promising in demonstrating quantum state conversion and is expected to boost the performance of transduction with various physical platforms.

β-Arrestins are master regulators of cellular signaling that operate by desensitizing ligand-activated G-protein-coupled receptors (GPCRs) at the plasma membrane and promoting their subsequent endocytosis. The endocytic activity of β-arrestins is ligand dependent, triggered by GPCR binding, and increasingly recognized to have a multitude of downstream signaling and trafficking consequences that are specifically programmed by the bound GPCR. However, only one biochemical ‘mode’ for GPCR-mediated triggering of the endocytic activity is presently known – displacement of the β-arrestin C-terminus (CT) to expose clathrin-coated pit-binding determinants that are masked in the inactive state. Here, we revise this view by uncovering a second mode of GPCR-triggered endocytic activity that is independent of the β-arrestin CT and, instead, requires the cytosolic base of the β-arrestin C-lobe (CLB). We further show each of the discrete endocytic modes is triggered in a receptor-specific manner, with GPCRs that bind β-arrestin transiently (‘class A’) primarily triggering the CLB-dependent mode and GPCRs that bind more stably (‘class B’) triggering both the CT and CLB-dependent modes in combination. Moreover, we show that different modes have opposing effects on the net signaling output of receptors – with the CLB-dependent mode promoting rapid signal desensitization and the CT-dependent mode enabling prolonged signaling. Together, these results fundamentally revise understanding of how β-arrestins operate as efficient endocytic adaptors while facilitating diversity and flexibility in the control of cell signaling.

Graphical Abstract

Climate change is causing pronounced shifts during winter in the US, including shortening the snow season, reducing snowpack, and altering the timing and volume of snowmelt-related runoff. These changes in winter precipitation patterns affect in-stream freeze-thaw cycles, including ice and snow cover, and can trigger direct and indirect effects on in-stream physical, chemical, and biological processes in ~60% of river basins in the Northern Hemisphere. We used high-resolution, multi-parameter data collected in a headwater stream and its local environment (climate and soil) to determine interannual variability in physical, chemical, and biological signals in a montane stream during the winter of an El Niño and a La Niña year. We observed ~77% greater snow accumulation during the El Niño year, which caused the formation of an ice dam that shifted the system from a primarily lotic to a lentic environment. Water chemistry and stream metabolism parameters varied widely between years. They featured anoxic conditions lasting over a month, with no observable gross primary production (GPP) occurring under the ice and snow cover in the El Niño year. In contrast, dissolved oxygen and GPP remained relatively high during the winter months of the La Niña year. These redox and metabolic changes driven by changes in winter precipitation have significant implications for water chemistry and biological functioning beyond the winter. Our study suggests that as snow accumulation and hydrologic conditions shift during the winter due to climate change, hot-spots and hot-moments for biogeochemical processing may be reduced, with implications for the downstream movement of nutrients and transported materials.

BackgroundIn India, leprosy clusters at hamlet level but detailed information is lacking. We aim to identify high-incidence hamlets to be targeted for active screening and post-exposure prophylaxis.MethodologyWe paid home visits to a cohort of leprosy patients registered between April 1st, 2020, and March 31st, 2022. Patients were interviewed and household members were screened for leprosy. We used an open-source app(ODK) to collect data on patients' mobility, screening results of household members, and geographic coordinates of their households. Clustering was analysed with Kulldorff's spatial scan statistic(SaTScan). Outlines of hamlets and population estimates were obtained through an open-source high-resolution population density map(https://data.humdata.org), using kernel density estimation in QGIS, an open-source software.ResultsWe enrolled 169 patients and screened 1,044 household contacts in Bisfi and Benipatti blocks of Bihar. Median number of years of residing in the village was 17, interquartile range(IQR)12-30. There were 11 new leprosy cases among 658 household contacts examined(167 per 10,000), of which seven had paucibacillary leprosy, one was a child under 14 years, and none had visible disabilities. We identified 739 hamlets with a total population of 802,788(median 163, IQR 65-774). There were five high incidence clusters including 12% of the population and 46%(78/169) of the leprosy cases. One highly significant cluster with a relative risk (RR) of 4.7(pConclusionsWe found a high yield of active household contact screening. Our tools for identifying high-incidence hamlets appear effective. Focusing labour-intensive interventions such as door-to-door screening on such hamlets could increase efficiency.

BackgroundRegulated breathing facilitates ventilation and reduces breathlessness. However, the effect of Yogic breathing on patients with COVID remains unclear. We aimed to evaluate the efficacy of two breathing protocols, i.e., short breathing technique (SBT) and long duration breathing technique (LBDT).MethodsThree groups including COVID-positive patients, COVID-recovered patients, and healthcare workers (HCWs) were included in the study and segregated into Yoga and control groups. SBT was administered to COVID-positive patients. Both SBT and LBDT were administered to COVID-recovered patients and HCWs. A total of 18 biochemical parameters, a 6-min walk test (6MWT), and a 1-min sit-stand test (1MSST) were assessed on 0th, 7th, and 15th days, where biochemical parameters were the primary outcome. Pre-post estimation of neuropsychological parameters (nine questionnaires) and heart rate variability (HRV) were carried out. The paired t-test or Wilcoxon rank test was applied for pre-post comparison and the Student's t-test or Mann–Whitney U test was used for group comparison. Repeated measures test was applied for data recorded at three time points.ResultsA significant elevation in white blood cell (WBC) count was observed in COVID-positive intervention (p < 0.001) and control groups (p = 0.003), indicating no role of intervention on change in WBC number. WBC count (p = 0.002) and D-dimer (p = 0.002) significantly decreased in the COVID-recovered intervention group. D-dimer was also reduced in HCWs practicing Yogic breathing as compared to controls (p = 0.01). D-dimer was the primary outcome, which remained below 0.50 μg/ml (a cutoff value to define severity) in the COVID-positive yoga group (CYG) and decreased in the COVID-recovered yoga group (RYG) and the HCW yoga group (HYG) after intervention. A 6-min walk test (6MWT) showed an increase in distance covered among the COVID-positive patients (p = 0.01) and HCWs (p = 0.002) after intervention. The high-frequency power (p = 0.01) was found to be reduced in the COVID-positive intervention group. No significant change in neuropsychological parameters was observed.ConclusionYogic breathing lowered D-dimer, which is helpful in reducing thrombosis and venous thromboembolism in patients with COVID-19 besides lowering the chances of vaccine-induced thrombotic thrombocytopenia in vaccinated individuals. The breathing intervention improved exercise capacity in mild to moderate cases of COVID-19. Further studies can show if such breathing techniques can influence immunity-related genes, as reported recently in a study. We suggest that Yogic breathing may be considered an integrative approach for the management of patients with COVID.Trial registrationhttp://ctri.nic.in/Clinicaltrials/login.php, identifier: CTRI/2020/10/028195.

The connections between standard theoretical tools used to study open quantum systems can sometimes seem opaque. Whether it is a Lindblad master equation, the equation of motion for the Wigner function, or a dissipative Keldysh action, features evident in one formalism are often masked in another. Here, we reformulate the technique of third quantization in a way that explicitly connects all three methods. We first show that our formulation reveals a fundamental dissipative symmetry present in all quadratic bosonic or fermionic Lindbladians. This symmetry can then be used to easily diagonalize these models, and it provides an intuitive way to demonstrate the separation of dissipation and fluctuations in linear systems. For bosons, we then show that the Wigner function and the characteristic function can be thought of as “wave functions” of the density matrix in the eigenbasis of the third-quantized superoperators we introduce. The field-theory representation of the time-evolution operator in this basis is then the Keldysh path integral. To highlight the utility of our approach, we apply our version of third quantization to a dissipative nonlinear oscillator, and we use it to obtain new exact results.

Alt-EJ is an error-prone DNA double-strand break (DSBs) repair pathway coming to the fore when first-line repair pathways, c-NHEJ and HR, are defective or fail. It is thought to benefit from DNA end-resection—a process whereby 3′ single-stranded DNA-tails are generated—initiated by the CtIP/MRE11-RAD50-NBS1 (MRN) complex and extended by EXO1 or the BLM/DNA2 complex. The connection between alt-EJ and resection remains incompletely characterized. Alt-EJ depends on the cell cycle phase, is at maximum in G2-phase, substantially reduced in G1-phase and almost undetectable in quiescent, G0-phase cells. The mechanism underpinning this regulation remains uncharacterized. Here, we compare alt-EJ in G1- and G0-phase cells exposed to ionizing radiation (IR) and identify CtIP-dependent resection as the key regulator. Low levels of CtIP in G1-phase cells allow modest resection and alt-EJ, as compared to G2-phase cells. Strikingly, CtIP is undetectable in G0-phase cells owing to APC/C-mediated degradation. The suppression of CtIP degradation with bortezomib or CDH1-depletion rescues CtIP and alt-EJ in G0-phase cells. CtIP activation in G0-phase cells also requires CDK-dependent phosphorylation by any available CDK but is restricted to CDK4/6 at the early stages of the normal cell cycle. We suggest that suppression of mutagenic alt-EJ in G0-phase is a mechanism by which cells of higher eukaryotes maintain genomic stability in a large fraction of non-cycling cells in their organisms.

Introduction: Most rhinologic procedures, particularly endoscopic sinonasal procedures, are liable to produce aerosols. The severe acute respiratory syndrome coronavirus 2 (SARS-Co V-2) transmits via respiratory droplets, but the degree of its spread through airborne routes by aerosol is unclear. Objective: The aim of this article is to counsel rhinologists on how to modify their conventional practice during the COVID-19 pandemic by prioritising the need of procedures, identifying aerosol- generating procedures and using precise personal protection equipment for various endonasal procedures. Methods: We did a review of articles indexed for MEDLINE on PubMed, ENT Cochrane, DOAJ and Web of Science databases using the keywords nasal endoscopy, SARS‐CoV‐2, COVID‐19, aerosol generating medical procedures and rhinology to formulate guidelines for the safety of healthcare workers. Results: The review included evidence from 28 articles from the otorhinolaryngology, surgery, infectious disease, head and neck surgery and cancer biology literature. We have provided recommendations and relevant information for rhinologists during the COVID-19 pandemic, based on the available studies and data, to warrant high-quality patient care and requisite levels of infection prevention during rhinology procedures. Conclusion: In rhinology, marked care is advised during nasal packing, electrocauterisation and use of high-speed rotating devices in potentially infected tissue as they are considerable aerosol- producing procedures. The choice of personal protective equipment is based on the risk of exposure and possible modes of aerosol generation.