Prognostic Nutritional Index Prior to Rectal Cancer Resection Predicts Overall Survival.

Prognostic nutritional index (PNI) correlates with postoperative complications and survival in colorectal cancers. Separate studies for rectal cancers are not available where the majority have preoperative radiation, operated by minimally invasive approaches and have diverting ostomies.Consecutive rectal resections between October 2014 and December 2017 from a single center were included. PNI was calculated as 10 x (serum Albumin) + 0.005 x TLC (per mm3) before operation. Multivariate cox regression was used with overall survival (OS) as the dependent variable. Interaction terms of PNI with neoadjuvant therapy, surgical approach and postoperative complications were used to assess specific subgroups.Three-hundred forty elective rectal resections were included with a mean PNI of 46.711 (SD - 6.692), and a median follow up of 44 mo. In multivariable regression, PNI predicted OS (HR - 0.943; p-0.001). Interaction of PNI with preoperative radiation or surgical approach (open, laparoscopic, or robotic) did not change its influence on survival. PNI predicted survival with similar hazard even in patients without major postoperative complicationsDespite routine diversion after rectal resections, PNI predicted OS with an absolute survival benefit of 1.2% at 3-year for every unit increase in PNI irrespective of preoperative therapy or surgical approach.

Personal and household PM2.5 and black carbon exposure measures and respiratory symptoms in 8 low- and middle-income countries.

BACKGROUND: Household air pollution (HAP) from cooking with solid fuels has been associated with adverse respiratory effects, but most studies use surveys of fuel use to define HAP exposure, rather than on actual air pollution exposure measurements. OBJECTIVE: To examine associations between household and personal fine particulate matter (PM2.5) and black carbon (BC) measures and respiratory symptoms. METHODS: As part of the Prospective Urban and Rural Epidemiology Air Pollution study, we analyzed 48-h household and personal PM2.5 and BC measurements for 870 individuals using different cooking fuels from 62 communities in 8 countries (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Self-reported respiratory symptoms were collected after monitoring. Associations between PM2.5 and BC exposures and respiratory symptoms were examined using logistic regression models, controlling for individual, household, and community covariates. RESULTS: The median (interquartile range) of household and personal PM2.5 was 73.5 (119.1) and 65.3 (91.5) µg/m3, and for household and personal BC was 3.4 (8.3) and 2.5 (4.9) x10-5 m-1, respectively. We observed associations between household PM2.5 and wheeze (OR: 1.25; 95%CI: 1.07, 1.46), cough (OR: 1.22; 95%CI: 1.06, 1.39), and sputum (OR: 1.26; 95%CI: 1.10, 1.44), as well as exposure to household BC and wheeze (OR: 1.20; 95%CI: 1.03, 1.39) and sputum (OR: 1.20; 95%CI: 1.05, 1.36), per IQR increase. We observed associations between personal PM2.5 and wheeze (OR: 1.23; 95%CI: 1.00, 1.50) and sputum (OR: 1.19; 95%CI: 1.00, 1.41). For household PM2.5 and BC, associations were generally stronger for females compared to males. Models using an indicator variable of solid versus clean fuels resulted in larger OR estimates with less precision. CONCLUSIONS: We used measurements of household and personal air pollution for individuals using different cooking fuels and documented strong associations with respiratory symptoms.

Design, synthesis and SAR of antitubercular benzylpiperazine ureas.

N-furfuryl piperazine ureas disclosed by scientists at GSK Tres Cantos were chosen as antimycobacterial hits from a phenotypic whole-cell screen. Bioisosteric replacement of the furan ring in the GSK Tres Cantos molecules with a phenyl ring led to molecule (I) with an MIC of 1 µM against Mtb H37Rv, low cellular toxicity (HepG2 IC50 ~ 80 µM), good DMPK properties and specificity for Mtb. With the aim of delineating the SAR associated with (I), fifty-five analogs were synthesized and screened against Mtb. The SAR suggests that the piperazine ring, benzyl urea and piperonyl moieties are essential signatures of this series. Active compounds in this series are metabolically stable, have low cellular toxicity and are valuable leads for optimization. Molecular docking suggests these molecules occupy the Q0 site of QcrB like Q203. Bioisosteric replacement of N-furfuryl piperazine-1-carboxamides yielded molecule (I) a novel lead with satisfactory PD, metabolism, and toxicity profiles.

Next Generation Sequencing and Cytogenetic Based Evaluation of Indian Pierre Robin Sequence Families Reveals CNV Regions of Modest Effect and a Novel LOXL3 Mutation.

BACKGROUND: Pierre Robin Sequence (PRS) affects approximately 1 per 8500 to 14000 new-borns worldwide. Although the clinical entity is well defined, the pathogenesis of PRS is debated. The present study aims to understand the contribution of genomic imbalances and genetic variants in patients clinically diagnosed of PRS. METHODOLOGY: A total of 7 independent patients with nonsyndromic PRS thoroughly evaluated by a medical geneticist at a tertiary care hospital, were included in the study. Blood samples were collected from these patients and their family members. Array CGH was performed on all 7 patients and their respective family members for detection of underlying cytogenetic defects. Whole exome sequencing (WES) was performed for 5 families to capture single nucleotide variants or small indels. RESULTS: Cytogenetic analyses did not detect any previously reported gross chromosomal aberrations for PRS in the patient cohort. However, copy number variations (CNVs) of size <1 Mb were detected in patients which may have implications in PRS. The present study provided evidence for the occurrence of de novo deletions at 7p14.1 locus in PRS patients: further validating the candidate loci susceptibility in oral clefts. WES data identified LOXL3 as candidate gene, carrying novel deleterious variant, which is suggestive of the role of point mutations in the pathogenesis of PRS. CONCLUSION: The present study offered considerable insight into the contribution of cytogenetic defects and novel point mutation in the etiology of nonsyndromic PRS. Studies comprising large number of cases are required to fully elucidate the genetic mechanisms underlying the PRS phenotype.

Clinical Spectrum of Neurological Manifestations in Pediatric COVID-19 Illness: A Case Series.

We describe a cohort of three patients with variable neurological presentations by SARS-COV-2 infection. It includes one case each of acute cerebellitis, acute encephalomyelitis and arterial ischemic stroke. To the best of our knowledge, we report the first pediatric case of acute cerebellitis due to SARS-CoV-2 infection. All critically ill patients were treated with methylprednisolone pulse therapy and dexamethasone. Patient with acute cerebellitis in addition required intravenous immunoglobulin infusion. All the patients responded to the treatment with complete neurological recovery.

The combination of Curcumin and Doxorubicin on targeting PI3K/AKT/mTOR signaling pathway: an in vitro and molecular docking study for inhibiting the survival of MDA-MB-231.

The process of tumorigenesis is highly associated with the disruption of cell-cycle regulators and derangement of various signaling pathways, which end up with the inhibition of apoptosis and hyper-activation of survival pathways. The PI3K medicated AKT/mTOR pathway is the widely explained mechanism for cancer cell survival which causes the overexpression of MDM2 and downregulates the p53-BAX mediated apoptotic pathway. Curcumin (CUR), the phyto-compound, derived from Curcuma longa is currently being focused on for its anticancer activities against breast cancer cells, MDA-MB-231, not only because of its minimal cytotoxicity against healthy cells (HEK293) but also because it synergistically sensitizes the activity of Doxorubicin (DOXO) in lower doses, which can be a promising source for complementary drug development. This study aims to investigate the combinatorial effect of CUR and DOXO on PI3K/AKT/mTOR pathway proteins by sequential molecular docking analysis and MD simulation studies. The lower binding affinity of the sequentially docked protein-ligand complex proves the increasing binding affinity of CUR and DOXO in the combinatorial dose. The mRNA expressions of different genes of this pathway are observed and quantified using rt-qPCR, where the decreasing fold change (2-∆∆Ct) indicates the suppression of the AKT/mTOR pathway after co-treatment of CUR and DOXO against MDA-MB-231 cells. These in silico and in vitro findings can be a new horizon for further in vitro and clinical trials of breast cancer treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00231-2.

Clinico-Hematological Profile and Management of Children With Non-Transfusion Dependent Thalassemia (NTDT) at a Pediatric Center in Northern India.

OBJECTIVE: To study the clinico-hematological profile, complications, and management of children with non-transfusion dependent thalassemia (NTDT) in northern India. METHOD: We retrieved and analyzed the data of 69 children with NTDT diagnosed between January, 2006 to December, 2018, aged under 18 years from our unit's records. RESULTS: The participants mean (SD) age was 4.4 (3.1) years, and they presented with anemia (29%), jaundice (13%), hemolytic facies (13%), splenomegaly (87%), thromboembolism (2.9%) and pathological short stature (28.5%). The most common cause of NTDT was b-thalassemia (45%), followed by either compound-heterozygous or homozygous for Eb-thalassemia mutation. The most frequent single genotype observed was compound heterozygous for IVS1-5 (G>C) and codon 26 (G>A). The mean (SD) follow-up duration was 3.5 (2.4) years. On follow-up, 27 children (%) remained transfusion free, and 30 (%) needed occasional transfusions. 63% of patients initially presenting with pathological short stature showed improvement in growth. Amongst children older than 10 years (n=20), subclinical hypothyroidism was detected in 6 children and impaired glucose tolerance test in 1 child. CONCLUSION: Eß-thalassemia was the commonest cause of NTDT in this population.

Nano-drug delivery system: a promising approach against breast cancer.

Breast cancer (BC) is among the most frequent malignancies women face around the globe. Nanotherapeutics are constantly evolving to overcome the limitations of conventional diagnostic and therapeutic approaches. Nanotechnology-based nanocarriers have a higher entrapment efficiency, low cytotoxicity, greater stability and improved half-life than conventional therapy. Nano-drug delivery systems have improved pharmacokinetics and pharmacodynamics parameters because of nanomeric size. Currently, various nano-formulations are in preclinical and clinical settings for breast cancer, like polymeric nanoparticles, micelles, nanobodies, magnetic nanoparticles, liposomes, niosomes, gold-nanoparticles, dendrimers and carbon-nanotubes. This review highlights the recent advancement in developing nano-drug delivery systems for BC treatment. This review will open the gateway to researchers to understand the current approaches to developing nano-formulation and improving problems associated with conventional therapy.

CRISPR/Cas9 encouraged CAR-T cell immunotherapy reporting efficient and safe clinical results towards cancer.

CRISPR is a customized genome-editing tool that snips DNA in a simpler, cheaper and more precise way than any other gene editing tool. In recent years CRISPR/Cas has completely transformed an existing discipline of genetic engineering. This 'review' focuses on the generations and modifications in CAR-T as an advanced cancer therapeutic tool and CAR-T-approved products. It also highlights three path-breaking successful autologous and allogenic ex vivo CAR-T clinical trials in treating cancer using CRISPR/Cas9 which reported successful results despite the controversies regarding the safety of this technique. Outcomes from the first successful clinical trial showed the beneficial long-term effect on genetically modified T-cells in targeting cancer cells which opens the door for CRISPR to be the most preferred technique to help treat cancer and other diseases in the future. We searched the MEDLINE, EMBASE and PUBMED databases for original studies and meta-analysis on the use of CRISPR/Cas9 to edit T-cells until 2021. We finally selected 15 pre-clinical and 26 clinical studies for the review.

Atypical presentation of acquired tracheo-oesophageal fistula in an adolescent girl with pulmonary tuberculosis.

We report a case of an adolescent girl presenting with acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. Initial presentation during the ongoing COVID-19 pandemic was compatible with multisystem inflammatory response in children associated with COVID-19 (MIS-C). Subsequently a diagnosis of tuberculosis was made. During ventilation, she developed significant abdominal distension which was not relieved with nasogastric decompression. There was a high index of suspicion of bronchoenteric fistula. Bronchoscopy with adjunct oesophagoscopy demonstrated tracheo-oesophageal fistula (TEF). The classical presentation of TEF has been masked by onset of ARDS. During the pandemic the diagnosis of tuberculosis in high-burden countries decreased for multiple reasons leading to development of complications which are often confused with MIS-C. While diagnosing MIS-C, maintaining a high level of suspicion for concomitant or alternative aetiologies is essential.

Fecal Iron Measurement in Studies of the Human Intestinal Microbiome.

Iron is an essential micronutrient for humans and their intestinal microbiota. Host intestinal cells and iron-dependent bacteria compete for intraluminal iron, so the composition and functions of the gut microbiota may influence iron availability. Studies of the effects of the microbiota or probiotic interventions on host iron absorption may be particularly relevant to settings with high burdens of iron deficiency and gastrointestinal infections, since inflammation reduces iron bioavailability and unabsorbed intraluminal iron may modify the composition of the microbiota. The quantification of stool iron content may serve as an indicator of the amount of intraluminal iron to which the intestinal microbiota is exposed, which is particularly relevant for studies of the effect of iron on the intestinal microbiome, where fecal samples collected for purposes of microbiome characterization can be leveraged for stool iron analysis. However, few studies are available to guide researchers in the selection and implementation of stool iron assays, particularly because cross-comparison of available methods is limited in literature. This review aims to describe the available stool iron quantification methods and highlight their potential application in studies of iron-microbiome relationships, with a focus on pediatric research. MS-based methods offer high sensitivity and precision, but the need for expensive equipment and the high per-sample and maintenance costs may limit their widespread use. Conversely, colorimetric assays offer lower cost, ease of use, and rapid turnaround times but have thus far been optimized primarily for blood-derived matrices rather than stool. Further research efforts are needed to validate and standardize methods for stool iron assessment and to determine if the incorporation of such analyses in human microbiome studies 1) yields insights into the interactions between intestinal microbiota and iron and 2) contributes to the development of interventions that mitigate iron deficiency and promote a healthy microbiome.

Prediction of QcrB Inhibition as a Measure of Antitubercular Activity with Machine Learning Protocols.

It has always been a challenge to develop interventional therapies for Mycobacterium tuberculosis. Over the years, several attempts at developing such therapies have hit a dead-end owing to rapid mutation rates of the tubercular bacilli and their ability to lay dormant for years. Recently, cytochrome bcc complex (QcrB) has shown some promise as a novel target against the tubercular bacilli, with Q203 being the first molecule acting on this target. In this paper, we report the deployment of several ML-based approaches to design molecules against QcrB. Machine learning (ML) models were developed based on a data set of 350 molecules using three different sets of molecular features, i.e., MACCS keys, ECFP6 fingerprints, and Mordred descriptors. Each feature set was trained on eight ML classifier algorithms and optimized to classify molecules accurately. The support vector machine-based classifier using the ECFP6 feature set was found to be the best classifier in this study. Further, screening of the known imidazopyridine amide inhibitors demonstrated that the model correctly classified the most potent molecules as actives, hence validating the model for future applications.

Measuring and predicting personal and household Black Carbon levels from 88 communities in eight countries.

Black Carbon (BC) is an important component of household air pollution (HAP) in low- and middle- income countries (LMICs), but levels and drivers of exposure are poorly understood. As part of the Prospective Urban and Rural Epidemiological (PURE) study, we analyzed 48-hour BC measurements for 1187 individual and 2242 household samples from 88 communities in 8 LMICs (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Light absorbance (10-5 m-1) of collected PM2.5 filters, a proxy for BC concentrations, was calculated via an image-based reflectance method. Surveys of household/personal characteristics and behaviors were collected after monitoring. The geometric mean (GM) of personal and household BC measures was 2.4 (3.3) and 3.5 (3.9)·10-5 m-1, respectively. The correlation between BC and PM2.5 was r = 0.76 for personal and r = 0.82 for household measures. A gradient of increasing BC concentrations was observed for cooking fuels: BC increased 53% (95%CI: 30, 79) for coal, 142% (95%CI: 117, 169) for wood, and 190% (95%CI: 149, 238) for other biomass, compared to gas. Each hour of cooking was associated with an increase in household (5%, 95%CI: 3, 7) and personal (5%, 95%CI: 2, 8) BC; having a window in the kitchen was associated with a decrease in household (-38%, 95%CI: -45, -30) and personal (-31%, 95%CI: -44, -15) BC; and cooking on a mud stove, compared to a clean stove, was associated with an increase in household (125%, 95%CI: 96, 160) and personal (117%, 95%CI: 71, 117) BC. Male participants only had slightly lower personal BC (-0.6%, 95%CI: -1, 0.0) compared to females. In multivariate models, we were able to explain 46-60% of household BC variation and 33-54% of personal BC variation. These data and models provide new information on exposure to BC in LMICs, which can be incorporated into future exposure assessments, health research, and policy surrounding HAP and BC.

Multinational prediction of household and personal exposure to fine particulate matter (PM2.5) in the PURE cohort study.

INTRODUCTION: Use of polluting cooking fuels generates household air pollution (HAP) containing health-damaging levels of fine particulate matter (PM2.5). Many global epidemiological studies rely on categorical HAP exposure indicators, which are poor surrogates of measured PM2.5 levels. To quantitatively characterize HAP levels on a large scale, a multinational measurement campaign was leveraged to develop household and personal PM2.5 exposure models. METHODS: The Prospective Urban and Rural Epidemiology (PURE)-AIR study included 48-hour monitoring of PM2.5 kitchen concentrations (n = 2,365) and male and/or female PM2.5 exposure monitoring (n = 910) in a subset of households in Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania and Zimbabwe. PURE-AIR measurements were combined with survey data on cooking environment characteristics in hierarchical Bayesian log-linear regression models. Model performance was evaluated using leave-one-out cross validation. Predictive models were applied to survey data from the larger PURE cohort (22,480 households; 33,554 individuals) to quantitatively estimate PM2.5 exposures. RESULTS: The final models explained half (R2 = 54%) of the variation in kitchen PM2.5 measurements (root mean square error (RMSE) (log scale):2.22) and personal measurements (R2 = 48%; RMSE (log scale):2.08). Primary cooking fuel type, heating fuel type, country and season were highly predictive of PM2.5 kitchen concentrations. Average national PM2.5 kitchen concentrations varied nearly 3-fold among households primarily cooking with gas (20 µg/m3 (Chile); 55 µg/m3 (China)) and 12-fold among households primarily cooking with wood (36 µg/m3 (Chile)); 427 µg/m3 (Pakistan)). Average PM2.5 kitchen concentration, heating fuel type, season and secondhand smoke exposure were significant predictors of personal exposures. Modeled average PM2.5 female exposures were lower than male exposures in upper-middle/high-income countries (India, China, Colombia, Chile). CONCLUSION: Using survey data to estimate PM2.5 exposures on a multinational scale can cost-effectively scale up quantitative HAP measurements for disease burden assessments. The modeled PM2.5 exposures can be used in future epidemiological studies and inform policies targeting HAP reduction.

Erratic journey of CRISPR/Cas9 in oncology from bench-work to successful-clinical therapy.

CRISPR is a customized molecular scissor, comprising genetic guide made of RNA and an enzyme, Cas9 which snips DNA in simpler, cheaper and more precise way than any other gene editing tools. In recent years CRISPR/Cas has taken the research world by storm being go-to genome editor for potential gene therapy to fix cancer as well as several hereditary disorders. This review explores the literature around the mechanism of Nobel winning CRISPR/Cas9 and its journey from its discovery to various pre-clinical and clinical trials in oncology, focusing mostly on PD-1 knockout CAR-T cell therapy. It also discusses the hurdles and ethical dispute associated with CRISPR, such as unintended on-target and off-target cuts, embryonic germ-line editing. Despite the controversies regarding the safety of this technique, many studies reported promising results on targeting cancer and other diseases using CRISPR/Cas9. Outcomes from the first successful clinical trial showed the beneficial long term effect on genetically modified T-cells in targeting cancer cells which opens the door for CRISPR to be the most preferred technique to help treating cancer and other diseases in future. As far as germ-line editing is concerned, further studies are needed to support the safety of this technique in humans fixing genetic disorders and mutations. Therefore till date only somatic cell editing is ethically approved.

Impact of COVID-19 Pandemic on Childhood Immunization in a Tertiary Health-Care Center.

BACKGROUND: After the emergence of COVID-19 pandemic, health facilities nationwide became the battleground for COVID-19. Many hospitals are designated as COVID-19 hospitals and various measures taken by the government to contain the spread of infection have disrupted the provision of routine health-care services including immunization. The aim of this study is to describe the impact of COVID-19 pandemic on immunization in a tertiary level health-care facility. MATERIALS AND METHODOLOGY: Data of children vaccinated as per the Universal immunization program (UIP) schedule were retrieved from immunizations records for a 7 month (January to July) period for the years 2019 and 2020. The trends of vaccination during COVID-19 pandemic are studied and are compared with the date matched data of the previous year. RESULTS: There was a significant drop in the vaccine counts after emergence of COVID-19 pandemic. Maximum drop (-87%) was seen during the month of April (76.52% ± 43.62% vs. 16.95% ± 42.55%; P < 0.001) followed by May and June when it was -67% and -33%, respectively. CONCLUSION: COVID-19 pandemic has created the gaps in immunization which requires immediate attention. Further failure in sustaining the vaccination services and weak catch-up plans can lead to the emergence of vaccine-preventable diseases which may result in increased childhood morbidity and mortality.

Newborn micronutrient status biomarkers in a cluster-randomized trial of antenatal multiple micronutrient compared with iron folic acid supplementation in rural Bangladesh.

BACKGROUND: Daily antenatal multiple micronutrient (MM) compared with iron folic acid (IFA) supplementation from early pregnancy improved birth outcomes and maternal micronutrient status in rural Bangladesh, but effects on newborn status are unknown. OBJECTIVE: We examined cord blood micronutrient biomarkers in relation to antenatal MM and IFA supplementation and maternal gestational micronutrient status in rural Bangladeshi newborns. DESIGN: In a double-blinded, cluster-randomized trial of antenatal IFA or MM (with the same IFA content), we analyzed cord blood plasma from 333 singleton births, and corresponding maternal plasma at 32.5 ± 2.6 wk of gestation, for ferritin (iron stores), folate, cobalamin (vitamin B-12), retinol (vitamin A), 25-hydroxyvitamin D [25(OH)D, vitamin D status], α-tocopherol (vitamin E), zinc, thyroglobulin, and free thyroxine (iodine status). Intervention effects and associations were determined using linear regression, exploring maternal status as a mediator of intervention effects on cord biomarkers. RESULTS: The MM intervention increased cord ferritin (mean: +12.4%; 95% CI: 1.3, 24.6%), 25(OH)D (mean: +14.7%; 95% CI: 4.8, 25.6%), and zinc (mean: +5.8%; 95% CI: 1.0, 10.8%). Cord folate (mean: +26.8%; 95% CI: 19.6, 34.5%), cobalamin (mean: +31.3%; 95% CI: 24.6, 38.3%), 25(OH)D (mean: +26.7%; 95% CI: 23.2, 30.3%), α-tocopherol (mean: +8.7%; 95% CI: 3.6, 13.7%), zinc (mean: +2.3%; 95% CI: 0.5, 4.2%), thyroglobulin (mean: +20.1%; 95% CI: 9.0, 32.2%) and thyroxine (mean: +1.5%; 95% CI: 0.0, 3.0%) increased per 1-SD increment in maternal status (all P < 0.05); ferritin and retinol changed by +2.0%; 95% CI: -8.9, 14.3%; P = 0.72; and +3.5%; 95% CI: -0.4, 7.3%; P = 0.07, respectively. Ferritin, folate, cobalamin, zinc, and thyroglobulin averaged 1.57-6.75 times higher and retinol, α-tocopherol, and 25(OH)D 0.30-0.84 times lower in cord than maternal plasma, suggesting preferential maternal-fetal transfer of iron, folate, cobalamin, and zinc; limited transfer of fat-soluble vitamins; and high fetal iodine demand. CONCLUSIONS: Antenatal MM supplementation increased newborn ferritin, 25(OH)D, and zinc, while maternal and newborn folate, vitamins B-12, D, and E, zinc, and iodine biomarkers were positively related. Despite limited effects of MM, better maternal micronutrient status was associated with improved micronutrient status of Bangladeshi newborns. This trial was registered at clinicaltrials.gov as NCT00860470.

Household and personal air pollution exposure measurements from 120 communities in eight countries: results from the PURE-AIR study.

BACKGROUND: Approximately 2·8 billion people are exposed to household air pollution from cooking with polluting fuels. Few monitoring studies have systematically measured health-damaging air pollutant (ie, fine particulate matter [PM2·5] and black carbon) concentrations from a wide range of cooking fuels across diverse populations. This multinational study aimed to assess the magnitude of kitchen concentrations and personal exposures to PM2·5 and black carbon in rural communities with a wide range of cooking environments. METHODS: As part of the Prospective Urban and Rural Epidemiological (PURE) cohort, the PURE-AIR study was done in 120 rural communities in eight countries (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Data were collected from 2541 households and from 998 individuals (442 men and 556 women). Gravimetric (or filter-based) 48 h kitchen and personal PM2·5 measurements were collected. Light absorbance (10-5m-1) of the PM2·5 filters, a proxy for black carbon concentrations, was calculated via an image-based reflectance method. Surveys of household characteristics and cooking patterns were collected before and after the 48 h monitoring period. FINDINGS: Monitoring of household air pollution for the PURE-AIR study was done from June, 2017, to September, 2019. A mean PM2·5 kitchen concentration gradient emerged across primary cooking fuels: gas (45 µg/m3 [95% CI 43-48]), electricity (53 µg/m3 [47-60]), coal (68 µg/m3 [61-77]), charcoal (92 µg/m3 [58-146]), agricultural or crop waste (106 µg/m3 [91-125]), wood (109 µg/m3 [102-118]), animal dung (224 µg/m3 [197-254]), and shrubs or grass (276 µg/m3 [223-342]). Among households cooking primarily with wood, average PM2·5 concentrations varied ten-fold (range: 40-380 µg/m3). Fuel stacking was prevalent (981 [39%] of 2541 households); using wood as a primary cooking fuel with clean secondary cooking fuels (eg, gas) was associated with 50% lower PM2·5 and black carbon concentrations than using only wood as a primary cooking fuel. Similar average PM2·5 personal exposures between women (67 µg/m3 [95% CI 62-72]) and men (62 [58-67]) were observed. Nearly equivalent average personal exposure to kitchen exposure ratios were observed for PM2·5 (0·79 [95% 0·71-0·88] for men and 0·82 [0·74-0·91] for women) and black carbon (0·64 [0·45-0·92] for men and 0·68 [0·46-1·02] for women). INTERPRETATION: Using clean primary fuels substantially lowers kitchen PM2·5 concentrations. Importantly, average kitchen and personal PM2·5 measurements for all primary fuel types exceeded WHO's Interim Target-1 (35 µg/m3 annual average), highlighting the need for comprehensive pollution mitigation strategies. FUNDING: Canadian Institutes for Health Research, National Institutes of Health.

A Comparative Study of Non-descent Vaginal Hysterectomy and Laparoscopic Hysterectomy.

OBJECTIVE: To compare intra- and post-op complications between non-descent vaginal hysterectomy and laparoscopic hysterectomy and establish the better method for hysterectomy in non-descent uterus. METHODS: A prospective comparative study of 80 hysterectomies was done over a period of January 2017-Dec 2017, with 40 cases each in one group of non-descent vaginal hysterectomy (NDVH) and other group of total laparoscopic hysterectomy (TLH). Demographic characteristics, co-morbid conditions, indications for surgery, operative time, intra-operative blood loss, post-operative analgesia requirements, post-operative hospital stay and post-operative complications were compared between both groups. RESULTS: The most common age in both groups was 41-50 years. Fibroid uterus was the most common indication for surgery in both groups. The mean operative time in NDVH group was 40 min while it was 120 min in TLH group, and the mean blood loss in NDVH group was 50 ml, while it was 120 ml in TLH group. P < 0.001 when intraoperative blood loss and operative time were compared between both groups. There were no conversions to laparotomy in NDVH group, while there were three conversions to laparotomy in TLH group. Both groups were similar in post-operative analgesia requirement and post-operative hospital stay. Post-operative complications were similar in both groups. CONCLUSIONS: Non-descent vaginal hysterectomy has advantage over laparoscopic hysterectomy as scarless surgery with fewer complications.

Ampicillin Silver Nanoformulations against Multidrug resistant bacteria.

The present study reported a single step synthesis of silver nanoparticles using ampicillin (Amp-AgNps), a second-generation ß lactam antibiotic to get nanoformulation having dual properties that of antibiotic and silver. The Amp-AgNps was characterized by UV-VIS spectroscopy, TEM, XRD, FTIR and TGA. FTIR and TGA results suggested that amine group of Ampicllin reduce the metalic silver into nano form. These results were further validated by computational molecular dynamics simulation. The antibacterial potential of Amp-AgNps was investigated against sensitive and drug resistant bacteria. MIC of Amp-AgNps against 6 different bacterial strains were in the range of 3-28 µg/ml which is much lower than the MIC of ampicillin (12-720 µg/ml) and chemically synthesized silver nanoparticles (280-640 µg/ml). The repeated exposure to drugs may lead to development of resistance mechanism in bacteria against that drug, so the efficacy of Amp-AgNps after repeated exposure to bacterial strains were also studied. The results indicate that bacterial strains do not show any resistance to these Amp-AgNps even after exposure up to 15 successive cycles. The biocompatibility of these Amp-AgNps was checked against cell lines by using Keratinocytes cell lines (HaCaT).