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ObjectivesTo characterize ablaCMYvariant associated with ceftazidime-avibactam (CZA) resistance from a serially collectedEscherichia coliisolate.MethodsA patient with an intra-abdominal infection due to recurrentE. coliwas treated with CZA. On day 48 of CZA therapy,E. coliwith a CZA MIC of >256 mg/L was identified from abdominal drainage. Illumina WGS was performed on all isolates to identify potential resistance mechanisms. Site-directed mutants of CMY β-lactamase were constructed to identify amino acid residues responsible for CZA resistance.ResultsWGS revealed that all three isolates wereE. coliST410. The CZA-resistant strain uniquely acquired a novel CMY β-lactamase gene, herein calledblaCMY-185, harbored on an IncIγ-type conjugative plasmid. The CMY-185 enzyme possessed four amino acid substitutions relative to CMY-2 including A114E, Q120K, V211S, and N346Y and conferred high-level CZA resistance with an MIC of 32 mg/L. Single CMY-2 mutants did not confer reduced CZA susceptibility. However, double and triple mutants containing N346Y previously associated with CZA resistance in other AmpC enzymes, conferred CZA MICs ranging between 4 and 32 mg/L as well as reduced susceptibility to the newly developed cephalosporin, cefiderocol. Molecular modelling suggested that the N346Y substitution confers the reduction of avibactam inhibition due to the steric hindrance between the side chain of Y346 and the sulfate group of avibactam.ConclusionWe identified CZA resistance inE. coliassociated with a novel CMY variant. Unlike other AmpC enzymes, CMY-185 appears to require an additional substitution on top of N346Y to confer CZA resistance.

The health system of Pakistan has multiple threats like political instability, recession, disparitiesin access to health services, infrastructure, development challenges, emergence of COVID-19pandemic. Beginning of 2022 was marked with unusual surge in cholera cases. According toNational Institute of Health (NIH), Islamabad, varied number of suspected cholera cases werereported across four provinces. Floods hit the country in mid-July which further aggravated thesituation of healthcare services. Ministry of Health along with World Health Organization(WHO) need to implement preventive and supporting actions to control cholera and otherwaterborne diseases.

Nearly three decades ago the UN World Conference on Women at Beijing appeared to be uniting the international community around the most progressive platform for women’s rights in history. Instead of steady advancement, we have seen uneven progress, backsliding, co-option, and a recent rising tide of patriarchal backlash. The global phenomenon of ‘backlash’ is characterised by resurgent misogyny, homo/transphobia, and attacks on sexual and reproductive rights. It is articulated through new forms of patriarchal politics associated with racialised hyper-nationalist agendas, traditionalism, authoritarianism, and alterations to civic space that have become all too familiar both in the global North and South. A wide range of actors and articulations are involved and influenced by underlying drivers and dynamics. A clearer view of the patriarchal nature of current backlash is a prerequisite for building a cohesive movement to counter it, strategically engaging researchers, activists, policymakers and donors in development.

Background. Pakistan’s contraceptive prevalence rate (CPR) has remained static (less than 1% annual increase since 2006) due to several demand and supply issues. The Akhter Hameed Khan Foundation implemented a community-driven, demand-generation intervention with complementary supply side family planning (FP) services in a large urban informal settlement in Rawalpindi, Pakistan. Methods. The intervention recruited local women as outreach workers called Aapis (sisters), who conducted household outreach and provided counseling, contraceptives, and referrals. Program data were used to guide in-program corrections, identify the most willing to use married women of reproductive age (MWRA), and target specific geographic locations. The evaluation compared results from two surveys. The baseline survey included 1485 MWRA while the endline included 1560 MWRA that were sampled using the same methodology. A logit model was used with survey weights and clustered standard errors, to estimate the odds of using a contraceptive method. Results. CPR in Dhok Hassu increased from 33% at the baseline to 44% at endline. Long-acting reversible contraceptives (LARCs) usage increased from 1% at baseline to 4% at endline. Increase in CPR is correlated with increasing number of children and education of MWRA and is the highest between the ages of 25 and 39 and for working women. Qualitative evaluation of the intervention provided lessons about in-program corrections using data and empowerment of the female outreach workers and MWRA. Conclusion. The Aapis Initiative is a unique community-based demand-supply side intervention that successfully increased modern contraceptive prevalence rate (mCPR) by economically engaging the women from within the community as outreach workers and enabling healthcare providers to establish a sustainable ecosystem for increasing knowledge and access to family planning services.

Background Daptomycin (DAP) is an important antibiotic for enterococci. Our previous studies identified LiaX as a surface-exposed protein that is a mediator of cell envelope homeostasis in Enterococcus faecalis (Efs) upon exposure to DAP via activation of the LiaFSR system. LiaX encodes for a soluble protein with an N-terminal of α-helices, and a C-terminus which is β-pleated sheets. Its role in E. faecium, a species of clinical relevance, remains unknown. In this work, we aim to elucidate the function of LiaX of E. faecium (Efm). Methods We used the commensal strain of Efm TX1330RF (DAP minimum inhibitory concentration [MIC] 3 μg/ml), its ΔliaR derivative (TX1330RFΔliaR [DAP MIC 0.125 μg/ml]) and targeted the liaX gene for mutagenesis. Using the PheS* counterselection system, we aimed to create a truncation or in-frame deletion of liaX. Mutants were characterized by determination of DAP MIC and visualization of anionic phospholipid domains by 10-N-nonyl-acridine orange (NAO). The nisin-controlled expression vector, pMSP3535, was used to express LiaX from Efm (LiaXTX1330RF) in Efs host OG1RFΔliaX, which lacks liaX. Expression of LiaX of Efs (LiaXOG1RF) was used as a control. Results In the presence of liaR, we were unable to create truncation or in-frame deletion of liaX after many attempts. In Efm TX1330RFΔliaR, we successfully created an in-frame deletion of liaX, TX1330RFΔliaRliaX (DAP MIC 0.125 μg/ml). NAO staining of all strains of TX1330RF, TX1330RFΔliaR and its ΔliaX mutant showed localization of anionic phospholipid domains at septa of the cells. Interestingly, multiple attempts to complement liaR in TX1330RFΔliaRliaX were also futile. NAO staining of Efs OG1RFΔliaX demonstrated that anionic phospholipid microdomains redistributed away from septa. Expression of LiaXOG1RF in Efs OG1RFΔliaX successfully restored microdomains to septal and polar regions of Efs while expression of LiaXTX1330RF did not show any significant difference in the fluorescence staining compared to its parental host (Efs OG1RFΔliaX). Conclusion Our findings suggest that LiaX has divergent functions as a mediator of cell envelope homeostasis in enterococci and may be essential in the Efm redponse to DAP. Efforts to elucidate its role in DAP resistance in Efm are ongoing. Disclosures Cesar A. Arias, MD, PhD, Entasis Phramceuticals: Grant/Research Support|MeMed Diagnostics: Grant/Research Support|Merck: Grant/Research Support.

Background Daptomycin (DAP) is a lipopeptide antibiotic targeting membrane anionic phospholipids (APLs) at the division septum. DAP resistance (DAP-R) has been associated with activation of the LiaFSR system resulting in redistribution of APL microdomains (likely containing cardiolipin, CL) away from the septum. E. faecalis (Efs) possess two CL synthase genes, (cls1 and cls2) and changes in Cls1 are associated with DAP-R. However, the roles of each enzyme are unknown. Here, we characterize the roles of cls genes in DAP-R in the context of LiaFSR activation. Methods cls1 and/or cls2 were deleted from Efs OG117 and OG117ΔliaX (DAP-R strain with an activated LiaFSR response). qRT-PCR was used to study gene expression of cls1 and cls2 in the cls mutants. Membrane lipid content was analyzed using hydrophilic interaction chromatography-mass spectrometry. Mutants were characterized by DAP minimum inhibitory concentration (MIC) using E-test and localization of APL microdomains with 10-N-nonyl-acridine orange. Results cls1 and cls2 are upregulated in exponential phase of DAP-R Efs OG117ΔliaX relative to DAP-S Efs OG117, with only cls1 upregulated in stationary phase. Deletion of cls1 or cls2 resulted in upregulation of the other cls gene, independent of activation of LiaFSR. Lipidomics analysis confirmed that deletion of both cls resulted in complete absence of cell membrane CL content. When comparing CL profiles of Δcls1 relative to Δcls2 in both DAP-S and DAP-R, both strains produced similar levels and species of CL. However, development of DAP-R caused a change in membrane lipid content, namely, an increase in CL with no significant difference in phosphatidylglycerol compared to DAP-S strain. Evaluation of CL species in DAP-R shows a shift towards species containing longer fatty acid chains and higher saturation. Independent deletions of cls1 or cls2 did not revert the DAP phenotype. In contrast, deletion of both cls genes decreased the DAP MIC (2-3 fold) relative to the parent strain and restored septal localization of APL microdomains. DAP MIC was restored upon trans complementation of either cls1 or cls2 into the double deletion mutant. Conclusion Our results support a major role of Cls in changes in cell membrane architecture and DAP-R in enterococci, with overlapping roles for Cls1 and Cls2. Disclosures Cesar A. Arias, MD, PhD, Entasis Phramceuticals: Grant/Research Support|MeMed Diagnostics: Grant/Research Support|Merck: Grant/Research Support.

Background Limited literature on the impact of COVID-19 infection in persons living with HIV infection (PLWHIV) has shown conflicting results, especially on the degree of disease severity and morbidity/mortality risk impact. The advent of vaccinations against COVID-19 infection helped combat this horrific pandemic. However, their efficacy in immunocompromised hosts is understudied. The measurement of anti-spike antibody levels makes them an ideal surrogate to study the efficacy of the immune response conferred after vaccination. Methods A quality improvement project was conducted between 03/2020 and 03/2022 at Positive Health Clinic (PHC), a Pittsburgh urban Ryan White-funded HIV clinic, where approximately 930 PLWHIV receive care. PHC patients who tested positive for COVID-19 were followed up for their clinical presentations and outcomes. Goals were to observe longitudinal clinical impact with or without vaccinations; the COVID-19 vaccination acceptance and its serum anti-spike antibody response (AS-Ab); and COVID-19 variants impact on protection by vaccination. Results By 02/21, a 70% vaccination rate was achieved for PHC PLWHIV. 136 serum AS-Ab tests were collected at least 28 days after completing the primary vaccination series. Five non-responders were noted (2 renal transplant recipients, 2 with advanced AIDS with uncontrolled HIV, and 1 with liver cirrhosis). Low AS-Ab titers were observed in patients with CD4 < 200 or HIV VL > 200. A total of 109 COVID-19 infections in 105 patients were seen. From 03/20 – 11/21, there were 53 infections noted (45 unvaccinated: 5 with severe disease; 8 vaccinated: 0 severe disease). 58 infections (8 unvaccinated, 2 severe, 50 vaccinated (including four 2nd infections: 0 severe) were observed during 11/221 – 03/22. No mortality was noted. Figure 1.Figure 2.Figure 3Demographics of PHC Conclusion This report did not show mortality directly associated with COVID-19 infection in PLWHIV. Moreover, COVID-19 vaccination is known to reduce the risk and severity of COVID-19 infection in the general population, which was consistent across our study. Interestingly, there were very few COVID-19 infections diagnosed in PLWHIV who had low CD4 count and uncontrolled HIV (CD4 < 200 & HIV VL > 500 copies) even after the surge of the Omicron variant. Disclosures All Authors: No reported disclosures.

Background Daptomycin (DAP) resistance in enterococci is regulated by the LiaFSR three-component regulatory system. Mutations in liaF have been linked to activation of this system, with increased expression of the protein LiaX, and resistance to DAP in clinical isolates. LiaX functions by recognizing DAP in the extracellular medium, and serves as a signal transduction molecule. However, the role of LiaF in signaling and its relationship with LiaX are unknown. Methods We generated a liaF null mutant in E. faecalis OG117 by adding four stop codons at amino acid positions 11–14 (OG117liaF*11-14) using a CRISPR-Cas9 system. The mutant was complemented by restoring wild-type liaF in its chromosomal location (OG117liaF*11-14::liaF). Mutants were confirmed with whole genome sequencing (WGS). Anionic phospholipid (AP) microdomain distribution was assessed on microscopy using 10-N-nonyl-acridine-orange (NAO). LiaFSR activation was assessed by surface expression of LiaX via ELISA. DAP MICs were performed by broth microdilution in the presence/absence of exogenous LiaX (eLiaX). LL37 (50µg/ml) and DAP (1.5µg/ml) killing assays with eLiaX were also performed in triplicate. Results Truncation of liaF did not have any effect on DAP MICs, AP microdomain distribution or LiaX surface expression compared to OG117. No additional mutations were observed by WGS in the mutants. In the presence eLiaX, DAP MIC increased 8-fold in wild-type OG117 but remained the same (1 µg/mL) in OG117liaF*11-14. Complementation of liaF restored the increase in DAP MIC in the presence of eLiaX. In the LL37 killing assay, survival of OG117 was significantly increased on the addition of eLiaX (2.9% vs 11.8%, respectively, P < .002). Addition of eLiaX was unable to rescue OG117liaF*11-14 in the presence of LL-37 (2.4% vs 2.5% respectively, P=0.51), but was able to increase survival in the complemented strain (2.8% vs 7.6%, respectively, P < .002). A similar trend was seen in the DAP killing assay, with increased survival for OG117 (8.7% vs 20%) and OG117liaF*11-14::liaF (11.6% vs 17%), but not OG117liaF*11-14 (0.38% vs 1%). Conclusion LiaF is required for full tolerance to the cathelicidin LL37 and DAP in E. faecalis OG1RF. These results suggest that LiaF may interact with LiaX as a part of the LiaFSR stress response. Disclosures William R. Miller, MD, Entasis: Grant/Research Support|UpToDate: Honoraria Cesar A. Arias, MD, PhD, Entasis: Grant/Research Support|MeMed Diagnostics Ltd: Grant/Research Support|Merck: Grant/Research Support.

Aim: To find out the prevalence of psoriasis vulgaris and its associated risk factors. Study Design: Descriptive cross-sectional. Place and Duration of Study: Study was conducted at Rawalpindi Leprosy Hospital during January 2019 to December 2019. Methodology: The diagnosed cases of Psoriasis Vulgaris (PsV) were included in the study. All the patients were investigated on the basis of an in depth Performa. The Performa include all the relevant clinical and family history of the patient along with the personal details. Data was analyzed by using Statistical Package for the Social Sciences (SPSS) version 20. All the numerical variables were presented as mean with standard deviation while categorical data as frequency and percentages. The association of risk factors with the Psoriasis was calculated by using the Chi-square test. p-value less than 0.05 was considered as significant. Results: Mean age with standard deviation of patients was 34.7±14. Most of the diagnosed patients were male and below 40 years of age, only 4.2% cases were having positive family history of Psoriasis and found significant correlation. The frequency of onset of symptoms in adolescent was more as compared to childhood i.e. 95.3% and 4.7% respectively. Majority of psoriasis cases (65.3%) were from non-smoker group and having strong association with smoking. The frequency of arthritis among psoriasis patients was 23.7% and majority of the patients, who developed arthritis were those having age

Colorectal cancer (CRC) is the second most frequent cause of cancer-related mortality among all types of malignancies. Sedentary lifestyles, obesity, smoking, red and processed meat, low-fiber diets, inflammatory bowel disease, and gut dysbiosis are the most important risk factors associated with CRC pathogenesis. Alterations in gut microbiota are positively correlated with colorectal carcinogenesis, as these can dysregulate the immune response, alter the gut’s metabolic profile, modify the molecular processes in colonocytes, and initiate mutagenesis. Changes in the daily diet, and the addition of plant-based nutraceuticals, have the ability to modulate the composition and functionality of the gut microbiota, maintaining gut homeostasis and regulating host immune and inflammatory responses. Spices are one of the fundamental components of the human diet that are used for their bioactive properties (i.e., antimicrobial, antioxidant, and anti-inflammatory effects) and these exert beneficial effects on health, improving digestion and showing anti-inflammatory, immunomodulatory, and glucose- and cholesterol-lowering activities, as well as possessing properties that affect cognition and mood. The anti-inflammatory and immunomodulatory properties of spices could be useful in the prevention of various types of cancers that affect the digestive system. This review is designed to summarize the reciprocal interactions between dietary spices and the gut microbiota, and highlight the impact of dietary spices and their bioactive compounds on colorectal carcinogenesis by targeting the gut microbiota.

Background and objective Preeclampsia is a hypertensive disorder that usually arises after 20 weeks of pregnancy. It is considered a major cause of maternal and fetal mortality worldwide. High blood pressure and high proteinuria are the two main characteristics of preeclamptic patients. Preeclampsia leads to either severe or mild conditions, but in both cases, it affects the organs of the mother and fetus. This study was conducted to determine the prevalence of preeclampsia and associated risk factors (family history, age, hypertension, and diabetes) and to investigate its fetal and maternal outcomes. Methodology This prospective study was conducted at three healthcare units in the Multan district and involved patients with gestational hypertension. Patients were diagnosed on the basis of blood pressure values, urine tests, and through Doppler ultrasound. Further investigations were conducted, including a complete hemogram and a 24-hour test for proteinuria. Results for preeclampsia-related maternal and perinatal outcomes were documented and statistical analysis was performed to analyze the data. Results A total of 142 patients were diagnosed with gestational hypertension and preeclampsia during the two-year study period. Our findings showed 8.67% cases of gestational hypertension and 3% of preeclampsia. The majority of the preeclamptic patients were less than 24 years of age (33.3%), belonged to lower socioeconomic classes (44.4%), and had low educational levels (81.1%). A close association of family history (36.67%) with diabetes (15.5%) and chronic hypertension (5.55%) was observed in these patients. Maternal and fetal outcomes were related to maternal blood pressure. A significant incidence of premature births (45.6%) and a majority of cesarean cases (63.4%) with severe complications were observed. Data from preeclamptic patients showed high albuminuria levels (42.2%) with problems like renal infection, pulmonary edema, and severe anemia. During the study period, a neonatal death rate of 11.1% was observed as well as issues like respiratory tract syndrome, asphyxia, and growth retardation. Conclusion This study showed that poor economic and educational levels are significantly associated with this disease. A high rate of maternal and neonatal morbidity with neonatal mortality was investigated. Mild to severe outcomes were observed in the form of cesarean deliveries and preterm births. Serious complications lead to ICU admissions causing a serious burden on healthcare units. Paying more attention to the healthcare needs of pregnant women helps to identify preeclampsia earlier and also minimizes the complications associated with it.

Graphene and its derivatives (graphene oxide (GO), reduced GO (rGO), doped graphene, and functionalized graphene (F-graphene) nanomaterials (NMs)) possess unique chemical and physical features, and thus huge efforts have been devoted to their study, achieving substantial advances in fuel cell (FC) applications. Herein, we provide a summary of the latest performance and progress in the synthesis, properties, and application of graphene-based NMs in membranes, bipolar plates (BPPs), and as electrocatalysts in various types of FC technological applications. Specifically, in this review, we explain in detail the effect of introducing an increased electrochemically active specific surface area (SSA) to achieve better electro-catalytic activity toward fuel oxidation and oxidant reduction processes using graphene-based NM dispersions on electrodes. Using materials based on graphene, the problem of the device stack durability and performance degradation brought by the corrosion of the BPPs is highlighted. Graphene-based NMs have demonstrated outstanding performances in different membrane devices with respect to high ionic conductivity and power density. The use of graphene in FC technology has demonstrated admirable performances, and thus has a promising future for industrial applications.

The aim of this systematic review is to summarize and conclude findings to reveal the stress ranges developed by various post materials by finite element analysis. This, in turn, aids in the selection of better post material clinically. The electronic databases PubMed and Google Scholar were searched in this review by using specific inclusion and exclusion criteria. Among 14586 articles, 22 articles were included in this systematic review, as they satisfied the eligibility criteria. The search covered all articles published from 1997 to December 2021. All records identified were retrieved and imported into the Rayyan bibliographic software, which is a systematic review screening software. Later, data extraction and analysis of 22 articles were done. Twenty-two articles, which were all finite element analysis studies, were included. Among these, 18 studies used maxillary central incisor scanned models, two studies used a maxillary canine model, and the remaining two used the mandibular premolar model for finite element analysis. All these tooth models are restored with post models made of different materials. This systematic review revealed a difference in stress distribution in endodontically treated teeth when using different post materials. Among 22 studies, 15 studies evaluated glass fiber posts and the results showed that they induce less stress on restored endodontically treated teeth when compared to other posts, with maximum stress concentration at the cervical third of the root. Prefabricated posts like stainless steel and Titanium showed more stress on the restored tooth structure with stress concentration at the cervical and apical third of the root. Prefabricated zirconia also showed more stress on the restored tooth with maximum stress concentration at the middle third of the root.

Chronic fatigue syndrome (CFS) is a pathological state of extreme tiredness that lasts more than six months and may possess an impact on the social, emotional, or occupational functioning of an individual. CFS is characterized by profound disabling fatigue associated with infectious, rheumatological, and neurological symptoms. The current pharmacological treatment for CFS does not offer a complete cure for the disease, and none of the available treatments show promising results. The exact mechanism of the pathogenesis of the disease is still unknown, with current suggestions indicating the overlapping roles of the immune system, central nervous system, and neuroendocrine system. However, the pathological mechanism revolves around inflammatory and oxidative stress markers. Polyphenols are the most abundant secondary metabolites of plant origin, with potent antioxidant and anti-inflammatory effects, and can exert protective activity against a whole range of disorders. The current review is aimed at highlighting the emerging role of polyphenols in CFS from both preclinical and clinical studies. Numerous agents of this class have shown promising results in different in vitro and in vivo models of chronic fatigue/CFS, predominantly by counteracting oxidative stress and the inflammatory cascade. The clinical data in this regard is still very limited and needs expanding through randomized, placebo-controlled studies to draw final conclusions on whether polyphenols may be a class of clinically effective nutraceuticals in patients with CFS. Graphical abstract

BACKGROUND: Medical image processing has gained much attention in developing computer-aided diagnosis (CAD) of diseases. CAD systems require deep understanding of X-rays, MRIs, CT scans and other medical images. The segmentation of the region of interest (ROI) from those images is one of the most crucial tasks. OBJECTIVE: Although active contour model (ACM) is a popular method to segment ROIs in medical images, the final segmentation results highly depend on the initial placement of the contour. In order to overcome this challenge, the objective of this study is to investigate feasibility of developing a fully automated initialization process that can be optimally used in ACM to more effectively segment ROIs. METHODS: In this study, a fully automated initialization algorithm namely, an adaptive Otsu-based initialization (AOI) method is proposed. Using this proposed method, an initial contour is produced and further refined by the ACM to produce accurate segmentation. For evaluation of the proposed algorithm, the ISIC-2017 Skin Lesion dataset is used due to its challenging complexities. RESULTS: Four different supervised performance evaluation metrics are employed to measure the accuracy and robustness of the proposed algorithm. Using this AOI algorithm, the ACM significantly (p≤0.05) outperforms Otsu thresholding method with 0.88 Dice Score Coefficients (DSC) and 0.79 Jaccard Index (JI) and computational complexity of 0(mn). CONCLUSIONS: After comparing proposed method with other state-of-the-art methods, our study demonstrates that the proposed methods is superior to other skin lesion segmentation methods, and it requires no training time, which also makes the new method more efficient than other deep learning and machine learning methods.

Silk, seen as a material, is a fiber made from silkworm cocoons and spiders. They have standard structural components and hierarchical structures. Different manufacturing techniques allow obtaining silk in films, fibers, hydrogels, microspheres, and sponges. We can tune the properties through the structure of secondary proteins. The paper explores the application in biomedical, optics, and electronic fields by analyzing the technological trend.

Hysterosalpingography is a commonly used imaging modality to assess the pathology of uterine cavity and fallopian tubes of patient with infertility. Hysterosalpingography has an established role in the assessment of tubal factor in patients with subfertility. Objective: To compare hysterosalpingographic findings in patients of primary and secondary subfertility. Materials and methods: A prospective study spanning six months duration was carried out in radiology department of private clinic in Multan. A total of 602 patient both primary and secondary subfertility were included in the study. Clinical notes and x-ray findings were analyzed for demographic data such as age and duration of subfertility and tubal and uterine abnormalities. Results: Out of 602 patient 66.8% had primary subfertility and 33.2% were in the secondary subfertility group. Tubal blockage was most common abnormalities in both groups i.e. 21.1% of patients with primary subfertility and 27.5% with secondary subfertility had tubal blockage. Key words: Subfertlity, hysterosalpingography, tubal blockage

Objective: To determine patient preferences in the surgical options of early breast cancers and surgeon’s role in the decisionmaking. Study Design: cross-sectional study. Place and Duration of Study: Breast Surgery Department, Combined Military Hospital Rawalpindi Pakistan, from Nov 2020 to May 2021. Methodology: Patients having early carcinoma breast were studied, i.e., clinical stage 1 or 2, and their surgical preference was recorded. The cases were discussed in multidisciplinary meetings, and a discussion session with patient conducted and then final decision taken from the patient was recorded again, and the results compared. Results: A total of 28 patients were included in this study and their surgical preferences recorded. Of these patients 22 (78.5%) agreed to breast conservation initially, whereas one of the patients wanted mastectomy. Five (17.8%) patients were undecided between the two. After multidisciplinary team recommendation and discussion with surgeon, only one patient opted for mastectomy (3.6%). Conclusion: Patients with early breast cancer when offered a surgical decision between breast conservation and mastectomy mostly opt for breast conservation; those who select mastectomy do so because of the fear of recurrence.

Considerable variation in clozapine utilization exists across the United States, and little is known about the perspective of psychiatrists in states with low clozapine use. To better understand clozapine practices, attitudes, and barriers, a survey was administered to a group of southeastern state conference attendees (SSCA; N = 86). The same survey was administered to psychiatrists belonging to a national community psychiatry organization (AACP; N = 57), and differences were analyzed across the two samples. In comparison to the AACP, the SSCA group felt less comfortable, perceived clozapine as less safe and effective, had fewer patients on clozapine, and were more likely to prefer antipsychotic polypharmacy to clozapine use. Across the sample, use of a myocarditis screening protocol was rare (N = 14/76; 18%) and less than half used plasma antipsychotic levels to guide dosage (N = 60/129; 47%). Continuing professional education on clozapine are needed for psychiatrists who see individuals with psychotic disorders.

The forkhead transcription factor FOXE3 is critical for vertebrate eye development. Recessive and dominant variants cause human ocular disease but the full range of phenotypes and mechanisms of action for the two classes of variants are unknown. We identified FOXE3 variants in individuals with congenital eye malformations and carried out in vitro functional analysis on selected alleles. Sixteen new recessive and dominant families, including six novel variants, were identified. Analysis of new and previously reported genetic and clinical data demonstrated a broad phenotypic range with an overlap between recessive and dominant disease. Most families with recessive alleles, composed of truncating and forkhead-domain missense variants, had severe corneal opacity (90%; sclerocornea in 47%), aphakia (83%) and microphthalmia (80%), but some had milder features including isolated cataract. The phenotype was most variable for recessive missense variants, suggesting that the functional consequences may be highly dependent on the type of amino acid substitution and its position. When assessed, aniridia or iris hypoplasia were noted in 89% and optic nerve anomalies in 60% of recessive cases, indicating that these defects are also common and may be underrecognized. In dominant pedigrees, caused by extension variants, normal eye size (96%), cataracts (99%) and variable anterior segment anomalies were seen in most, but some individuals had microphthalmia, aphakia or sclerocornea, more typical of recessive disease. Functional studies identified variable effects on the protein stability, DNA binding, nuclear localization and transcriptional activity for recessive FOXE3 variants, whereas dominant alleles showed severe impairment in all areas and dominant-negative characteristics.

Summary Background COBRA-BPS (Control of Blood Pressure and Risk Attenuation-Bangladesh, Pakistan, Sri Lanka), a multi-component hypertension management programme that is led by community health workers, has been shown to be efficacious at reducing systolic blood pressure in rural communities in Bangladesh, Pakistan, and Sri Lanka. In this study, we aimed to assess the budget required to scale up the programme and the incremental cost-effectiveness ratios. Methods In a cluster-randomised trial of COBRA-BPS, individuals aged 40 years or older with hypertension who lived in 30 rural communities in Bangladesh, Pakistan, and Sri Lanka were deemed eligible for inclusion. Costs were quantified prospectively at baseline and during 2 years of the trial. All costs, including labour, rental, materials and supplies, and contracted services were recorded, stratified by programme activity. Incremental costs of scaling up COBRA-BPS to all eligible adults in areas covered by community health workers were estimated from the health ministry (public payer) perspective. Findings Between April 1, 2016, and Feb 28, 2017, 11 510 individuals were screened and 2645 were enrolled and included in the study. Participants were examined between May 8, 2016, and March 31, 2019. The first-year per-participant costs for COBRA-BPS were US$10·65 for Bangladesh, $10·25 for Pakistan, and $6·42 for Sri Lanka. Per-capita costs were $0·63 for Bangladesh, $0·29 for Pakistan, and $1·03 for Sri Lanka. Incremental cost-effectiveness ratios were $3430 for Bangladesh, $2270 for Pakistan, and $4080 for Sri Lanka, per cardiovascular disability-adjusted life year averted, which showed COBRA-BPS to be cost-effective in all three countries relative to the WHO-CHOICE threshold of three times gross domestic product per capita in each country. Using this threshold, the cost-effectiveness acceptability curves predicted that the probability of COBRA-BPS being cost-effective is 79·3% in Bangladesh, 85·2% in Pakistan, and 99·8% in Sri Lanka. Interpretation The low cost of scale-up and the cost-effectiveness of COBRA-BPS suggest that this programme is a viable strategy for responding to the growing cardiovascular disease epidemic in rural communities in low-income and middle-income countries where community health workers are present, and that it should qualify as a priority intervention across rural settings in south Asia and in other countries with similar demographics and health systems to those examined in this study. Funding The UK Department of Health and Social Care, the UK Department for International Development, the Global Challenges Research Fund, the UK Medical Research Council, Wellcome Trust.

Objectives: To identify patient characteristics and treatment factors of patients presenting to the emergency department (ED) with cancer-related pain that may affect patient outcomes. Methods: We conducted a retrospective cohort study to evaluate adult patients with active cancer, who presented to the ED with a chief complaint of pain between June first, 2012 and January first, 2016. We utilized multivariable logistic regression to evaluate the association of several exposure variables, including disease and demographic characteristics, primary pain site, and treatment methods, on ED disposition and revisit rate. Results: We included 483 patients with active cancer with a chief complaint of pain. Patients with severe pain on arrival tended to be younger than those who did not present with severe pain (median: 58 vs 62 respectively, OR 8.0 p

Dietary fiber exerts beneficial effects on human health reducing the risk factors of metabolic related diseases such as hyperglycemia, insulin resistance, and hypercholesterolemia. The aim of this study is to demonstrate the efficacy of a food supplement based on brewer’s spent grain (BSG) extract in the reduction of postprandial glycemia and insulinemia in normoglycemic subjects. BSG was chemically characterized, revealing the presence of resistant starch (14.64 g/100 g), arabinoxylans (7.50 g/100 g), β-glucans (1.92 g/100 g) and other soluble fibers (6.43 g/100 g), and bioaccessible ferulic acid (91.3 mg/100 g). For the clinical study, 40 normoglycemic subjects were randomized into two groups, 1 and 2 (n = 20), for a cross-over clinical design and received either BSG extract-based food supplement or placebo. Postprandial blood glucose values were significantly lower than corresponding values in the placebo group after 90 and 120 min, while at the baseline and in the first 60 min, the two glycemic curves overlapped substantially. This improved clinical outcome was corroborated by significant reductions in postprandial insulinemia. None of the subjects reported adverse effects. This study showed that the tested BSG extract-based food supplement improves glucose metabolism and insulinemic response in normoglycemic subjects with at most a mild insulin resistance.

With the rising need for energy resources, considerable work has done for building novel energy storage technologies. Supercapacitors (SCs) and batteries are a highly competitive choice for electrochemical energy storage devices (EESDs) due to their ultrahigh power density, improved rate capability, long-term cyclability, and remarkable safety. Because of their novel properties such as high mechanical flexibility, large specific surface area (SSA), chemical stability, and superior electric and thermal conductivities, graphene-based nanomaterials (NMs) have attracted considerable attention as alternative electrode materials for EESDs. Graphene is gaining a lot of interest since it has amazing qualities including 230 000 cm2 V-1 s-1 charge mobility, 3000 W m-1 K-1 thermal conductivity, 2.3% visible light absorption, 130 GPa mechanical strength, and 2600 m2 g-1 specific surface area (SSA). Mechanical exfoliation, reduction of graphene-oxide, chemical vapor deposition (CVD), and epitaxial growth of graphene-NMs are some of the synthetic procedures that can change these characteristics. Despite much effort, the detailed screening of high-performance electrode materials, such as graphene-based NMs, is still necessary. We covered the recent advancements in graphene-based NM research and development for high-performance batteries and SCs for specific applications in the next generation and smart electronics in this study. First, we discuss rechargeable batteries, a new-concept based on graphene with high energy density, longer life, improved safety, and shape-diversity capabilities in order to meet the needs of future electronics. Second, we discuss SCs for the present advanced nanotechnologies that outperform batteries with respect to power density, cyclability, quick charging/discharging rates capability, straightforward principles, high activity of the charge circulation, and low maintenance expenditure, including electrical double layer capacitors (EDLCs) and pseudocapacitors (PCs). Finally, graphene-based electrodes used in ESDs with their prospects and problems are briefly reviewed.