Mandatory fortification of rice in the public distribution system in India: An ethics perspective.

In response to the continuing high prevalence of anaemia recorded in the National Family Health Survey-5, the Indian government launched a policy for mandatory iron fortification of the rice provided through public nutrition programmes in India. This was done even though a rigorous evidence analysis had already concluded that rice fortification was not effective in preventing anaemia or iron deficiency at the population level. Fortification also poses a potential risk of iron toxicity over time, but there is no stated time period for the policy's implementation. The risk is particularly high in segments of the population who already have a high habitual iron intake, and who could be exposed to simultaneous fortification in different staples and food commodities along with the ongoing weekly Iron and Folic Acid tablets supplementation programme. Finally, this fortification policy also requires significant additional funding and resources to implement. It is crucial to examine such mandatory health actions, and to weigh the benefits and risks of harm, using the principles of public health ethics.

Immunoglobulin A Deposits In Renal Allografts: A Prospective Longitudinal Single-Center Study.

AIMS AND BACKGROUND: To describe the prevalence of IgA deposits (IgAD) in renal allografts in a cohort of renal transplant recipients and to analyze their management strategies and histopathology. To assess graft function and proteinuria after 1 year of follow-up. MATERIALS AND METHODS: A prospective longitudinal follow-up study was carried out in VPS Lakeshore Hospital and Research Centre, Kochi, Kerala, over a period of 5 years (July 2015 to June 2020). Kidney transplant recipients with allograft biopsies that reported IgAD on immunofluorescence were included in the study. Light microscopy and immunofluorescence studies were performed. Mesangial hypercellularity (M); segmental glomerulosclerosis (S); endocapillary hypercellularity (E); tubular atrophy/interstitial fibrosis (T); crescents (C) (MEST-C) Scoring was done in patients with pathogenic IgAD. Treatment strategies included increased baseline steroid dosage, rituximab administration, and plasma exchange. Clinical details and management strategies were analyzed, and patients were followed up for 1 year after diagnosis. Changes in graft function (S. Creatinine) and proteinuria (Urine Protein/Creatinine ratio) were analyzed. Clinico-pathologic correlation with the MEST-C scores was also done. RESULTS: Out of 1036 kidney transplants done in the study period, 760 graft biopsies were performed. Sixty-four cases had post-transplant deposition of IgA (8%). The mean age was 45 ± 11.25SD years. The study had 51 men and 13 women. Induction immunosuppression comprised rabbit antithymocyte globulin in 29 (45%) patients and basiliximab in 35 (54%). Maintenance immunosuppression in all comprised tacrolimus, mycophenolate mofetil, and steroids. There were 2 groups: group A (pathogenic IgAD) and group B (incidental IgAD). Group A had 46 cases (71.9%), out of which 8 had "active" IgA nephropathy (endocapillary proliferation, crescents, and IgA vasculitis), and 38 had "inactive" IgAD. In patients with active deposits, 3 had cellular crescents (18%, 30%, and 23%), all 8 had endocapillary proliferation, and 2 had vasculitis. Group B had 18 cases (28.1%), comprising T cell-mediated rejections (5), antibody-mediated rejection (8), BK virus nephropathy (1), and interstitial fibrosis and tubular atrophy (4). In group A, 22 (47.8%) presented with graft dysfunction, 8 (17.3%) with isolated proteinuria, and 14 (30.4%) patients presented with a combination. Two (4.3%) patients had neither. Fourteen (30.4%) patients presented within 1 month of renal transplant. In patients of group A, at the end of 1 year of treatment, the mean S. Creatinine reduced to 1.68 mg/dL from 1.84 mg/dL, and the mean protein/creatinine ratio reduced from 1.2 to 0.5 (±1.17). In patients with "active IgA" lesions, at the end of 1 year of treatment, the mean S. Creatinine increased slightly to 1.68 mg/dL (±0.47SD) from 1.48 mg/dL (±0.52SD), and the mean protein/creatinine ratio reduced from 2.32 (±1.56SD) to 1.05 (±1.70SD). In the 16 patients with IgAD and proteinuria, at the end of 1 year of treatment, the mean S. Creatinine decreased to 1.41 ± 0.32 SD mg/dL from 1.47±0.37SD mg/dL and the mean protein/creatinine ratio reduced from 1.12 ± 1.31 SD to 0.39±0.75 SD. In the remaining 22 patients with acute tubular injury, at the end of 1 year, the mean S. Creatinine decreased to 1.920.32 SD mg/dL from 2.10.8SD mg/dL, and the mean protein/creatinine ratio reduced from 1.1 ± 1.31 SD to 0.66 ± 1.45 SD. In the MEST-C scoring analysis, all scores were 0 in 20 (43.4%) biopsies, only M1 score in 11 (23.9%) biopsies, only E1 score in 10 biopsies (21.7%), S1 in 13 (28.2%) cases. CONCLUSION: Immunoglobulin A deposits occur commonly after transplant; these may represent recurrence, de novo IgA, or donor-derived IgAD. Although commonly benign, some may cause significant graft dysfunction and graft loss. IgAD can present as varying combinations of graft dysfunction and proteinuria. Active IgA pathologies may occur early in the post-transplant course, may have significant graft dysfunction, and need proactive management. There is a correlation between segmental sclerosis and proteinuria. Evidence for the efficacy of Rituximab, plasma exchange, and prolonged courses of steroids is wanting; however, some benefits are possible. Long-term follow-up is essential.

Transcriptional profiles of pulmonary artery endothelial cells in pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is characterized by endothelial cell (EC) dysfunction. There are no data from living patients to inform whether differential gene expression of pulmonary artery ECs (PAECs) can discern disease subtypes, progression and pathogenesis. We aimed to further validate our previously described method to propagate ECs from right heart catheter (RHC) balloon tips and to perform additional PAEC phenotyping. We performed bulk RNA sequencing of PAECs from RHC balloons. Using unsupervised dimensionality reduction and clustering we compared transcriptional signatures from PAH to controls and other forms of pulmonary hypertension. Select PAEC samples underwent single cell and population growth characterization and anoikis quantification. Fifty-four specimens were analyzed from 49 subjects. The transcriptome appeared stable over limited passages. Six genes involved in sex steroid signaling, metabolism, and oncogenesis were significantly upregulated in PAH subjects as compared to controls. Genes regulating BMP and Wnt signaling, oxidative stress and cellular metabolism were differentially expressed in PAH subjects. Changes in gene expression tracked with clinical events in PAH subjects with serial samples over time. Functional assays demonstrated enhanced replication competency and anoikis resistance. Our findings recapitulate fundamental biological processes of PAH and provide new evidence of a cancer-like phenotype in ECs from the central vasculature of PAH patients. This "cell biopsy" method may provide insight into patient and lung EC heterogeneity to advance precision medicine approaches in PAH.

Optimization studies on batch extraction of phenolic compounds from Azadirachta indica using genetic algorithm and machine learning techniques.

Phenolic compounds play a crucial role as secondary metabolites due to their substantial biological activity and medicinal value. These compounds are present in various parts of plant species. This study focused on solid-liquid batch extraction to recover total phenolic compounds from Azadirachta indica leaves. The experimental design was based on the Taguchi L16 array, considering four independent factors: extraction time, temperature, particle size, and solid-to-solvent ratio. Among these factors, the particle size exerted the maximum influence. Particle size inversely affects the yield of total phenolic content (TPC), while temperature, time, and solid-to-liquid ratio have a direct impact. The process factors concerned were investigated both experimentally and through machine learning techniques. Support vector regression (SVR) and random forest method (RFM) algorithms were utilized for predicting TPC, while a genetic algorithm (GA) was employed to derive optimal process parameters. The GA predicts the optimal extraction factors, yielding the maximum TPC. During this study, these factors were the following: particle size of 0.15 mm, extraction time of 40 min, solid-to-liquid ratio of 1:25 g/mL, and a temperature of 55 °C, with a predicted value of 23.039 mg GAE/g of plant material. Notably, in this study, the SVR values of TPC yield closely matched the experimental values for the training and test data set when compared with the random forest method values.

Human YRNA 4 (HY4) plasma levels are a prognostic indicator of SARS-CoV-2 infection clinical severity.

SARS-CoV-2 infection can result in a range of outcomes from asymptomatic/mild disease to severe COVID-19/fatality. In this study, we investigated the differential expression of small noncoding RNAs (sncRNAs) between patient cohorts defined by disease severity. We collected plasma samples, stratified these based on clinical outcomes, and sequenced their circulating sncRNAs. Excitingly, we found YRNA HY4 displays significant differential expression (p=0.025) between patients experiencing mild and severe disease. In agreement with recent reports identifying plasma YRNAs as indicators of influenza infection severity, our results strongly suggest that circulating HY4 levels represent a powerful prognostic indicator of likely SARS-CoV-2 patient infection outcome.

Comparison of Hysterosalpingography and Laparoscopy in the Evaluation of Infertility: A Prospective Study.

Background: Worldwide one of the major problems of human reproduction that haunts men and women is infertility. Hysterosalpingography (HSG) and laparoscopy (LS) are the two most important modalities to evaluate infertility. Our aim is to compare the efficacy of both. Methodology: This is a prospective study. One hundred and five females of both primary and secondary infertility together were included. Detailed history, examination and routine investigations were carried out. Tuberculosis polymerase chain reaction (TBPCR) was made from endometrial biopsy sample for all patients. Ovulation study was done by transvaginal ultrasonography. Hysterosalpingography and diagnostic laparoscopy were done. Results: Out of 105 infertile patients, 51.42% were in 26-30 years group. 52.3% were from lower economic group. 55.23% presented between 1 to 5 years of infertility. Twelve patients had used contraception in the past. Sixteen patients were serologically positive. Twenty-nine patients were with positive TBPCR among 105 females. Fifty-four and fifty-six patients had patent tubes by HSG and laparoscopy, respectively. Uterine filling defects and congenital anomalies could be detected four times more by HSG than by laparoscopy. TO mass was detected only by laparoscopy. Bilateral spill was present in 66.6% by HSG and 67.6% by laparoscopy and unilateral spillage in 22.8% and 21.9%, respectively. The sensitivity, specificity and accuracy of HSG in predicting unilateral block taking laparoscopy as gold standard are 85%, 96.4% and 94.2%, respectively, and sensitivity and specificity of bilateral tubal block are 81.8% and 98%, respectively. Conclusions: HSG and laparoscopy are not alternative, but complimentary in diagnosing tubal pathologies. HSG remains as primary screening procedure, but laparoscopy is gold standard.

Combined hyperspectral imaging, monolayer stress microscopy, and S8 image analysis approaches for simultaneously interrogating cellular signals and biomechanics.

Second messenger signals, e.g., Ca2+ and cyclic nucleotides, orchestrate a wide range of cellular events. The methods by which second messenger signals determine specific physiological responses are complex. Recent studies point to the importance of temporal and spatial encoding in determining signal specificity. Studies also indicate the importance of mechanical stimuli, substrate stiffness, and mechanical responses - the "mechanosome" - in regulating physiology. Hence, approaches that probe both chemical and mechanical signals are needed. Here, we report preliminary efforts to combine hyperspectral imaging for second messenger signal measurements, monolayer stress microscopy for mechanical force measurements, and S8 analysis software for quantifying localized signals - specifically, Ca2+ dynamics and mechanical forces in human airway smooth muscle cells (HASMCs). HASMCs were prepared as confluent monolayers on 11 kPa gels with embedded fluorescent microparticles that serve as fiducial markers as well as smaller microparticles to measure deformation (strain). Imaging was performed using a custom excitation-scanning hyperspectral microscope. Hyperspectral images were unmixed to identify signals from cellular fluorescent labels (e.g., CAL 590-AM) and fluorescent microparticles. Images were analyzed to quantify localized force dynamics through monolayer stress microscopy. S8 software was used to identify, track, and quantify spatially-localized Ca2+ activity. Results indicate that localized and transient cellular signals and forces can be quantified and mapped within cell populations. Importantly, these results establish a method for simultaneous interrogation of cellular signals and mechanical forces that may play synergistic roles in regulating downstream cellular physiology in confluent monolayers. This work was supported by NIH P01HL066299, R01HL137030, R01HL058506, and NSF MRI1725937. Drs. Leavesley and Rich disclose financial interest in a university start-up company, SpectraCyte LLC, to commercialize spectral imaging technologies.

Rescuing the Hidden Canine: A Case Report of Successful Surgical Exposure and Orthodontic Management.

Canine impaction, a recognized dental condition, particularly in the maxillary region, poses both functional and esthetic challenges. This case report explores the management of impacted maxillary canines coexisting with missing upper third molars in the same patient, showcasing the complexity of dental anomalies. Its multifaceted etiology includes complex eruption pathways and potential genetic factors. Addressing the impacted canine (upper left), particularly in the anterior region, is essential for oral health and aesthetics. Surgical-orthodontic techniques, guided eruption, and interdisciplinary collaboration have revolutionized management. This report emphasizes early diagnosis, personalized treatment, and the transformative potential of surgical exposure and orthodontic intervention in enhancing oral health, function, and aesthetics.

Primary hepatic lymphoma- A diagnostic dilemma.

Primary non-Hodgkin lymphoma of liver is a very rare malignancy. Here we report the case of a 50 year old female who presented with dull ache in the right hypochondrium and decreased appetite since 1 month. CT scan of abdomen and pelvis showed an enlarged liver with an ill- defined soft tissue lesion arising from left lobe measuring 13 × 9 cm suggestive of primary hepatic neoplasm. CT scan of chest, abdomen, and pelvis and whole body positron emission tomography showed no involvement of bone marrow, lymph nodes, spleen, or any other organ. Her liver function tests, alpha fetoprotein and carcinoembryonic antigen levels were normal. Serology was negative for viruses. Pathological examination favored diagnosis of Burkitt's lymphoma. Cytogenetic studies for MYC translocation t (8;14) is suggested for confirming the diagnosis since Ki 67 index is > 70% and not nearly 100% which is characteristic of Burkitt's lymphoma.

Population-based repeat cross-sectional seroprevalence survey of SARS-CoV-2 IgG antibodies in Pimpri Chinchwad Municipal Corporation Area, Maharashtra, India.

Context: Population-based seroepidemiological studies are recommended to measure the extent of spread of coronavirus disease of 2019 (COVID-19) infection in an area. The present seroprevalence survey was planned with the aim to estimate the cumulative burden of the COVID-19 disease in the Pimpri Chinchwad corporation area. Aims: To estimate the cumulative burden of the COVID-19 disease in the Pimpri Chinchwad corporation area. Settings and Design: The study was carried out in Pimpri Chinchwad Municipal Corporation (PCMC) city area. It was a descriptive cross-sectional survey. Materials and Methods: A population-based seroprevalence study for immunoglobulin G (IgG) antibodies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was carried out among 10082 residents in the age group of 6 years and above selected by cluster random sampling. Thirty-five clusters were in slums, 45 clusters in tenements and 120 clusters from housing societies. The fieldwork for the collection of samples was carried out from 16 June to 17 June 2021. For antibody testing, a kit from Abbott (SARS-CoV-2 IgG) was used which employs chemiluminescent microparticle immunoassay (CMIA) technology. Statistical Analysis Used: Frequency analysis was done for sociodemographic variables, the cumulative incidence of COVID-19, age-stratified infection rate, risk factors and COVID symptomatic versus asymptomatic cases. Chi-square test of association was applied to test the association between seropositivity and sociodemographic and clinical profile of participants. Results: The overall seropositivity for IgG antibodies was 81.34%. Those living in the Gaothan area (tenements) had a positivity rate of 84.5%. The age group between 45 and 60 years had a seropositivity of 91%. Conclusions: The study indicates that a considerable proportion of the population had encountered the novel coronavirus approaching herd immunity.

Carbonic anhydrase IX proteoglycan-like and intracellular domains mediate pulmonary microvascular endothelial cell repair and angiogenesis.

The lungs of patients with acute respiratory distress syndrome (ARDS) have hyperpermeable capillaries that must undergo repair in an acidic microenvironment. Pulmonary microvascular endothelial cells (PMVECs) have an acid-resistant phenotype, in part due to carbonic anhydrase IX (CA IX). CA IX also facilitates PMVEC repair by promoting aerobic glycolysis, migration, and network formation. Molecular mechanisms of how CA IX performs such a wide range of functions are unknown. CA IX is composed of four domains known as the proteoglycan-like (PG), catalytic (CA), transmembrane (TM), and intracellular (IC) domains. We hypothesized that the PG and CA domains mediate PMVEC pH homeostasis and repair, and the IC domain regulates aerobic glycolysis and PI3k/Akt signaling. The functions of each CA IX domain were investigated using PMVEC cell lines that express either a full-length CA IX protein or a CA IX protein harboring a domain deletion. We found that the PG domain promotes intracellular pH homeostasis, migration, and network formation. The CA and IC domains mediate Akt activation but negatively regulate aerobic glycolysis. The IC domain also supports migration while inhibiting network formation. Finally, we show that exposure to acidosis suppresses aerobic glycolysis and migration, even though intracellular pH is maintained in PMVECs. Thus, we report that 1) the PG and IC domains mediate PMVEC migration and network formation, 2) the CA and IC domains support PI3K/Akt signaling, and 3) acidosis impairs PMVEC metabolism and migration independent of intracellular pH homeostasis.

Study on prevalence of obesity using different scales and its association with hypertension among the elderly in a district of Gujarat.

Introduction: In older adults, excess weight is associated with a higher prevalence of cardiovascular disease, metabolic disease, several important cancers, and numerous other medical conditions. Several indices such as body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) are used to classify general. Some studies also reported that WC and WHR is a better indicator of cardiovascular disease (CVD) risk than BMI and WHR. Aims and Objective: 1. To estimate the prevalence of obesity among the elderly using three scale viz. BMI, WHR, and WHtR 2. To compare the results of these three-scale used for assessment of obesity 3. To determine the presence of association between obesity and hypertension if any. Material and Methods: For selection of the area, in both the urban and rural areas, the sampling units were enumerated and samples were collected from them. The estimated geriatric population combined in both Urban and Rural areas amounted to 12,220 (7% of geriatric population as per Census 2001), out of which 5% was selected as sample. This came out to be 611 elderly subjects which were selected equally from both urban and rural areas. For assessment of obesity BMI, WHR, and WHtR were measured. Assessment of hypertension was as per JNC classification. Result: Prevalence of obesity as per BMI in the urban area was found to be 40%, whereas that in rural areas was found to be 47.4%. WHR and WHtR showed higher prevalence in rural areas (70%) and also in urban areas (60%). BMI and WHR were significantly associated with hypertensive status of elderly. Conclusion: Anthropometric assessments of obesity like WHR and WHTR are more sensitive indicators of obesity among the elderly. BMI is found to be significantly associated with hypertension as well in the present study. Logistic regression showed that the association of BMI with hypertension was higher than other obesity assessments.

Integrative Toolkit to Analyze Cellular Signals: Forces, Motion, Morphology, and Fluorescence.

Quantitative assessment of cellular forces and motion advanced considerably over the last four decades. These advancements provided the framework to examine insightful mechanical signaling processes in cell culture systems. However, the field currently faces three problems: lack of quality standardization of the acquired data, technical errors in data analysis and visualization, and perhaps most importantly, the technology remains largely out of reach for common cell biology laboratories. To overcome these limitations, we developed a new experimental platform - Integrative Toolkit to Analyze Cellular Signals (iTACS). iTACS consists of two components: Acquisition and Training Module (AcTrM) and Analysis and Visualization Module (AnViM). AcTrM is based on µManager - an NIH-ImageJ-based microscope control software - and facilitates user self-training and automation of common image acquisition protocols. AnViM is based on NIH-ImageJ and facilitates user-friendly automation of data analysis and insightful visualization of results. These experiments involve culturing adherent cells on hydrogels, imaging fiducial markers embedded in the hydrogel, and finally extracting from these images a comprehensive mechanical characterization of the cells. Currently, iTACS enables the user to analyze and track a wide array of properties, including morphology, motion, cytoskeletal forces, and fluorescence of individual cells and their neighboring region. The quality standardization issue was addressed in AcTrM with, a reference image-guided refocusing technique. The technical issues in data analysis were addressed in AnViM with a multi-pronged image segmentation procedure, a user-friendly approach to identify boundary conditions, and a novel cellular property-based data visualization. AcTrM is designed to facilitate the straightforward transformation of basic fluorescence microscopes into experimental cell mechanics rigs, and AnViM is equipped to enable users to measure cellular mechanical signals without requiring an engineering background. iTACS will be available to the research community as an open-source suite with community-driven development capabilities.

Cognition in middle aged adults: A comparison between hypertensives and normotensives / Cognición en adultos de mediana edad: una comparación entre hipertensos y normotensos

Objective: The American Heart association in December 2016 published a position paper concluding that there was insufficient data to make evidence-based recommendations on the relationship between hypertension and cognition of a person. The aim of the study was to study the effect of increased blood pressure on cognitive function. Methods: A cross sectional study of hypertensives (cases) and normotensive (controls) was done between January 2018 and December 2019. Subjects were recruited by convenience sampling. Subjects who were known cases of hypertension and had been on antihypertensive drug therapy for at least more than six months were considered as cases. Controls were those subjects who were having normal blood pressure and not suffering from any disease known to affect cognition. Out of 413 subjects, data from 388 subjects was used in the study (200 cases, 188 controls). The subjects were allowed to rest for 5min before measuring their blood pressure. Blood pressure was measured with a mercury sphygmomanometer in the right arm with the subject in seated position. Neuropsychological battery consisted of tests for domains of memory (auditory, visual, spatial), learning ability, attention, visuo-spatial construction, working memory. Results: On the neuropsychological tests, patients with hypertension had lower scores in the different domains. Age, hypertension duration, and educational level were the best predictors of cognitive impairment in patients with hypertension. Conclusion: Middle aged adults with hypertension have reduced cognitive functions as compared to normotensives. (AU)

Objetivo: En diciembre de 2016 la American Heart Association publicó un documento expositivo concluyendo que existían datos suficientes para emitir recomendaciones basadas en la evidencia sobre la relación entre la hipertensión y la cognición de una persona. El objetivo de este trabajo fue estudiar el efecto del incremento de la presión arterial en la función cognitiva. Métodos: Se realizó un estudio transversal de sujetos hipertensos (casos) y normotensos (controles) entre enero de 2018 y diciembre de 2019. Dichos sujetos fueron reclutados de una muestra de conveniencia. Se consideró como casos a aquellos sujetos que fueran casos conocidos de hipertensión y siguieran una terapia antihipertensiva durante al menos 6 meses. Los controles fueron aquellos sujetos con presión arterial normal y que no padecieran ninguna enfermedad conocida que afectara a la cognición. De los 413 sujetos se utilizaron en el estudio los datos procedentes de 388 (200 casos y 188 controles). Se permitió a los sujetos que descansaran durante 5minutos antes de medir su presión arterial, utilizando un esfigmomanómetro de mercurio en el brazo derecho, estando el sujeto en posición sentada. La batería neuropsicológica consistió en pruebas de los dominios de memoria (auditiva, visual, espacial), capacidad de aprendizaje, atención, construcción visoespacial y memoria funcional. Resultados: En las pruebas neuropsicológicas los pacientes hipertensos tuvieron menores puntuaciones en los diferentes dominios. Edad, duración de la hipertensión y nivel educativo fueron los mejores factores predictivos del deterioro cognitivo en los pacientes hipertensos. Conclusión: Los adultos hipertensos de mediana edad muestran una reducción de sus funciones cognitivas en comparación con los sujetos normotensos. (AU)

A novel bicistronic DNA vaccine with enhanced protective immune response against Bacillus anthracis through DNA prime-protein boost vaccination approach.

Anthrax, by Bacillus anthracis, remains a dreadful fatal hazard worldwide. The currently used anthrax vaccines are plagued by numerous issues that limit their widespread use. As an immunization approach targeting both extracellular antigens and toxins of B. anthracis may achieve better sterile immunity, the present investigation designed a bicistronic secretory anti-anthrax DNA vaccine targeting immune response against toxin and cells. The efficacy of the vaccine was compared with monocistronic DNA vaccines and the currently used anthrax vaccine. For this, mice were immunized with the developed vaccine containing pag (encoding protective antigen to block toxin) and eag genes (encoding EA1 to target cells) of B. anthracis through DNA-prime/Protein-boost (D/P) and DNA prime/DNA-boost (D/D) approaches. There was a >2 and > 5 fold increase in specific antibody level by D/D and D/P approaches respectively, on 42nd days post-immunization (dpi). Serum cytokine profiling showed that both Th1 and Th2 immune responses were elicited, with more Th2 responses in D/P strategy. More importantly, challenge with 100 times LD50 of B. anthracis at 42nd dpi exhibited maximum cumulative survival (83.33 %) by bicistronic D/P approach. Remarkably, immunization with EA1 delayed mortality onset in infection. The study forms the first report on complement-dependent bactericidal activity of antiEA1 antibodies. In short, co-immunization of PA and EA1 through the developed bicistronic DNA vaccine would be an effective immunization approach in anthrax vaccination. Further, D/P strategy could enhance vaccine-induced immunity against B. anthracis. Altogether, the study generates certain critical insights having direct applications in next-generation vaccine development against anthrax.

Endothelial metabolism in pulmonary vascular homeostasis and acute respiratory distress syndrome.

Capillary endothelial cells possess a specialized metabolism necessary to adapt to the unique alveolar-capillary environment. Here, we highlight how endothelial metabolism preserves the integrity of the pulmonary circulation by controlling vascular permeability, defending against oxidative stress, facilitating rapid migration and angiogenesis in response to injury, and regulating the epigenetic landscape of endothelial cells. Recent reports on single-cell RNA-sequencing reveal subpopulations of pulmonary capillary endothelial cells with distinctive reparative capacities, which potentially offer new insight into their metabolic signature. Lastly, we discuss broad implications of pulmonary vascular metabolism on acute respiratory distress syndrome, touching on emerging findings of endotheliitis in coronavirus disease 2019 (COVID-19) lungs.

Empowering the visually impaired by customized Braille prescription and thus reducing medication errors.

Purpose: To assess the use of routine Braille prescription in reducing medication errors in visually impaired patients. Methods: This observational, questionnaire-based study was conducted in 100 blind or visually impaired patients who were Braille literate (aged ≥18 years). We initiated our Braille prescription from January 2017 to March 2018. The questionnaire consisted of 8 items that captured patient details on the medication management process in addition to a face-to-face interview with them. It was administered twice to each patient at baseline and at the end. Braille prescription included details regarding all medicines, their dosages, instructions, expiry dates, and major side effects. The prescription was developed easily and quickly with an average turnaround time of 1 hour. Results: It was seen that most of the study patients aged between 30-40 years (n = 80) and majority were men (78%). At baseline, 73% of our respondents faced challenges when self-administering medications as compared to 17.5% at endline. After using Braille prescription, only 5% reported of taking a wrong dosage compared to 46.2% at baseline. Patients missing a dosage significantly reduced after using routine Braille prescription (43.7% vs. 7.5% respectively, P < 0.05). Conclusion: Our study successfully has rolled out Braille prescription as an efficacious method in addressing the key issues to medication safety with the visually impaired.

Synthesis and Evaluation of Cytotoxicity of Novel Coumarin Peptide Alcohol Derivatives.

BACKGROUND: Coumarins are naturally occurring biologically active heterocyclic molecules endowed with a wide range of biological properties, including antibacterial, antifungal, and antitumor activities. OBJECTIVE: The present work was aimed to synthesize new coumarin-containing compounds and to investigate their cytotoxic activity. METHODS: Coumarin peptide and coumarin amino alcohols were prepared by treating epoxidecontaining coumarin derivatives with suitable aromatic amines and peptides in trifluoroethanol as a solvent at 50°C. These derivatives were evaluated for their cytotoxic activity on three different cell lines: HeLa, MDA-MB-231 and L-132. Cell viability was determined by MTT (3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. RESULTS: A new protocol was developed for the synthesis of thirteen novel coumarin peptide and coumarin amino alcohol derivatives. Among the tested compounds, three derivatives showed significant activity against all the tested cell lines. Docking studies indicated favorable interactions of the disubstituted peptide coumarin derivatives with the Asp 351 and Thr 347 amino acids at the active site of the human estrogen receptor. CONCLUSIONS: The results suggest that the synthesized compounds may be promising candidates in the research of new antitumor compounds.

Comparative Evaluation of Cytotoxic and Genotoxic Effects of Three Resin-Based Sealers by 3,(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide Assay and Comet Assay - An In Vitro Study.

BACKGROUND AND AIM: The complete sealing of the pulpal space contributes to the better healing potential after an root canal treatment, and root canal sealers are an integral part of this treatment which comes in contact with the periodontal tissue. Biocompatibility of an endodontic sealer plays an important role in the root canal treatment procedure. Hence, the aim of the study was to compare and evaluate the cytotoxicity and genotoxicity effect of three resin-based sealers on human periodontal fibroblast cells. SETTINGS AND DESIGN: This in vitro study was conducted in Dr. Prabhakar Kore's Basic Science and Research Center and K. L. E V. K. Institute of Dental Sciences, Belagavi. MATERIALS AND METHODS: Human periodontal fibroblasts were incubated with 15 specimens of Group 1 - AH Plus Group 2 - MTA Fillapex, and Group 3 - GuttaFlow 2, respectively. Cytotoxicity was assessed by 3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and genotoxicity was assessed by Comet assay at time intervals at 24 h and 48 h. STATISTICAL ANALYSIS: Data were analyzed by the Kruskal-Wallis and Mann-Whitney U-test. RESULTS: AH Plus and GuttaFlow 2 did not show any cytotoxicity or genotoxicity. MTA Fillapex was slightly cytotoxic throughout the time interval, and it also showed low genotoxicity throughout the time periods for which it was tested. CONCLUSION: AH Plus and GuttaFlow 2 did not show any cytotoxic and genotoxic effect; however, MTA Fillapex showed cytotoxic and genotoxic effect throughout the time interval.