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Introduction: This cross-sectional study investigates the prevalence of knowledge and awareness of Helicobacter pylori (H. pylori) infection among the urban population of the Kingdom of Saudi Arabia (KSA). The study is motivated by the need to understand the specific demographic segments within the urban setting and their awareness levels of this prevalent bacterial infection affecting the digestive system. Methodology: The cross-sectional study, employing a purposive sampling method and involving 840 participants from major cities in the KSA, utilized a structured survey questionnaire to gather data on demographic factors, awareness levels, attitudes, and experiences related to H. pylori infection, with subsequent statistical analysis and adherence to ethical guidelines for participant confidentiality and privacy protection. Result: The study involved 840 participants from major cities, revealing that 59.16 ​% were aware of H. pylori. Demographic variations included higher participation from Jeddah and Riyadh, with the majority being females aged 18–25, Saudi nationals, and individuals with undergraduate education. About 57.02 ​% reported experiencing suspected H. pylori symptoms, and 49.16 ​% had prior infections, with varying severity. Hesitancy toward screening (42.61 ​%), but 72.97 ​% believed in preventability. Limited awareness of treatments (15.35 ​%) and identification of factors like water and food were noted. Participants perceived the seriousness of H. pylori in the mid-range (5–7). Conclusion: The findings shed light on variations in awareness, knowledge gaps, and attitudes, emphasizing the need for targeted public health interventions, educational campaigns, and policy measures to address the challenges associated with H. pylori infections in urban areas.

Biological synthesis of silver nanoparticles (AgNPs) is an emerging method that avoids the need for costly equipment and hazardous chemicals. Therefore, in this study, Aloe vera (AV) extract and culture supernatant of Staphylococcus aureus (CS-S. aureus) were used to reduce and stabilise silver nanoparticles. The NPs were characterized using UV–vis spectrophotometry at 445 nm for AV-AgNP and 444.5 nm for CS-S.aureus AgNP, and the presence of silver was confirmed by energy dispersive X-ray (EDX). Furthermore, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that the AV-CS of S. aureus-AgNPs had irregular and spherical shapes, with average sizes of 18.5 nm for AvAgNPs and 7.03 nm for CS-S. aureus-AgNPs. Additionally, the minimum inhibitory concentration (MIC) of both AgNPs showed a similar reaction. K. pneumoniae, P. aeruginosa, and S. epidermidis were more sensitive to the AgNPs compared to methicillin-resistant Staphylococcus aureus (MRSA). In conclusion, our study used a green method to synthesise silver nanoparticles using AV extract and CS of S. aureus. The NPs showed a remarkable antibacterial effect, especially CS-S. aureus-AgNP, which could have application as a treatment against both Gram-positive and Gram-negative bacteria.

Mitochondrial metabolism and electron transport chain (ETC) function are essential for tumour proliferation and metastasis. However, the impact of ETC function on cancer immunogenicity is not well understood. In a recent study, Mangalhara et al. found that inhibition of complex II leads to enhanced tumour immunogenicity, T‐cell‐mediated cytotoxicity and inhibition of tumour growth. Surprisingly, this antitumour effect is mediated by succinate accumulation affecting histone methylation. Histone methylation promotes the transcriptional upregulation of major histocompatibility complex–antigen processing and presentation (MHC‐APP) genes in a manner independent of interferon signalling. Modulating mitochondrial electron flow to enhance tumour immunogenicity provides an exciting new therapeutic avenue and may be particularly attractive for tumours with reduced expression of MHC‐APP genes or dampened interferon signalling.

Abstract Introduction The prevalence of hyperthyroidism in Pakistan is 2.9%, which is two times higher than in the United States. Most high-quality hyperthyroidism clinical practice guidelines (CPGs) used internationally originate from high-income countries in the West. Local CPGs in Pakistan are not backed by transparent methodologies. We aimed to produce comprehensive, high-quality CPGs for the management of hyperthyroidism in Pakistan. Methods We employed the GRADE-ADOLOPMENT approach utilizing the 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis as the source CPG. Recommendations from the source guideline were either adopted as is, excluded, or adapted according to our local context. Results The source guideline included a total of 124 recommendations, out of which 71 were adopted and 49 were excluded. 4 recommendations were carried forward for adaptation via the ETD process, with modifications being made to 2 of these. The first addressed the need for liver function tests (LFTs) amongst patients experiencing symptoms of hepatotoxicity while being treated with anti-thyroid drugs (ATDs). The second pertained to thyroid status testing post-treatment by radioactive iodine (RAI) therapy for Graves’ Disease (GD). Both adaptations centered around the judicious use of laboratory investigations to reduce costs of hyperthyroidism management. Conclusion Our newly developed hyperthyroidism CPGs for Pakistan contain two context-specific modifications that prioritize patients’ finances during the course of hyperthyroidism management and to limit the overuse of laboratory testing in a resource-constrained setting. Future research must investigate the cost-effectiveness and risk-benefit ratio of these modified recommendations.

State-of-the-art technologies such as computer vision and machine learning, are revolutionizing the smart mushroom industry by addressing diverse challenges in yield prediction, growth analysis, mushroom classification, disease and deformation detection, and digital twinning. However, mushrooms have long presented a challenge to automated systems due to their varied sizes, shapes, and surface characteristics, limiting the effectiveness of technologies aimed at mushroom classification and growth analysis. Clean and well-labelled datasets are therefore a cornerstone for developing efficient machine-learning models. Bridging this gap in oyster mushroom cultivation, we present a novel dataset comprising 555 high-quality camera raw images, from which approximately 16.000 manually annotated images were extracted. These images capture mushrooms in various shapes, maturity stages, and conditions, photographed in a greenhouse using two cameras for comprehensive coverage. Alongside the images, we recorded key environmental parameters within the mushroom greenhouse, such as temperature, relative humidity, moisture, and air quality, for a holistic analysis. This dataset is unique in providing both visual and environmental time-point data, organized into four storage folders: “Raw Images”; “Mushroom Labelled Images and Annotation Files”; “Maturity Labelled Images and Annotation Files”; and “Sensor Data”, which includes time-stamped sensor readings in Excel files. This dataset can enable researchers to develop high-quality prediction and classification machine learning models for the intelligent cultivation of oyster mushrooms. Beyond mushroom cultivation, this dataset also has the potential to be utilized in the fields of computer vision, artificial intelligence, robotics, precision agriculture, and fungal studies in general.

The picture of bacterial biofilms as a colloidal gel composed of rigid bacterial cells protected by extracellular crosslinked polymer matrix has been pivotal in understanding their ability to adapt their microstructure and viscoelasticity to environmental assaults. This work explores if an analogous perspective exists in fungal biofilms with long filamentous cells. To this end, we consider biofilms of the fungus Neurospora discreta formed on the air-liquid interface, which has shown an ability to remove excess nitrogen and phosphorous from wastewater effectively. We investigated the changes to the viscoelasticity and the microstructure of these biofilms when the biofilms uptake varying concentrations of nitrogen and phosphorous, using large amplitude oscillatory shear flow rheology (LAOS) and field-emission scanning electron microscopy (FESEM), respectively. A distinctive peak in the loss modulus (G″) at 30–50 % shear strain is observed, indicating the transition from an elastic to plastic deformation state. Though a peak in G″ has been observed in several soft materials, including bacterial biofilms, it has eluded interpretation in terms of quantifiable microstructural features. The central finding of this work is that the intensity of the G″ peak, signifying resistance to large deformations, correlates directly with the protein and polysaccharide concentrations per unit biomass in the extracellular matrix and inversely with the shear-induced changes in filament orientation in the hyphal network. These correlations have implications for the rational design of fungal biofilms with tuneable mechanical properties.

Objective: To assess how well steroidal nasal sprays and oral steroids work for treating CRS. Methods: Two hundred patients with CRS were included in a randomized controlled experiment. The patients were split into two groups: Group B received steroidal nasal sprays (fluticasone propionate 110 mcg/day in each nostril for 12 weeks) and Group A received oral steroids (prednisolone 30 mg/day for 14 days, followed by tapering over 7 days). The “Sino-Nasal Outcome Test (SNOT-22)” was used to quantify improvement in symptoms, the “Rhinosinusitis Disability Index (RSDI)” was used to measure quality of life, and the recurrence rate was measured at the 6-month follow-up. Results: At 12 weeks, SNOT-22 and RSDI scores significantly improved with both oral steroids and steroidal nasal sprays (P < 0.05). At the 6-month follow-up, however, oral steroids had a greater recurrence rate (25% vs. 12%, P = 0.02) when compared to steroidal nasal sprays. The two groups’ adverse effects were similar and of low severity. Conclusion: In conclusion, nasal sprays containing steroids seem to be a safer and more successful option than oral steroids for treating CRS, making them worthy of being used as the first line of treatment.

Mushrooms are a nutritious food source, which can play a crucial role in providing affordable sources of proteins, vitamins and minerals for people worldwide, but their cultivation requires extensive training and considerable relevant expertise in order to fine-tune multiple environmental parameters.Internally displaced people in the Northern regions of Syria rely on very small-scale traditional oyster mushroom production, which cannot meet their local demand. Many international and local non-governmental organizations (NGOs) working for Syrian refugees, work on mushroom cultivation projects. They have reported significant difficulties and challenges in mushroom cultivation amongst the targeted beneficiaries. Therefore, the two main questions driving this research are: (1) How can organic mushroom cultivation be promoted using a robust and affordable intelligent mushroom farming system? (2) How can organic mushroom farming practices be simplified to support internally displaced and refugee Syrians?This research evaluates the process of automating mushroom cultivation by designing and implementing a smart oyster (Pleurotus ostreatus) mushroom farming system to remotely monitor and manage environmental parameters, such as temperature, humidity, air quality and illumination, inside the farm. Furthermore, ready and dedicated user-friendly web interfaces were also implemented to enable farmers to remotely monitor and manage their farms through the Internet. As a result, a dependable and cost-effective intelligent oyster mushroom cultivation system was designed and implemented in this work. The system includes remote monitoring and management via user-friendly interfaces. This simplifies mushroom cultivation for not only refugees and displaced communities, but also for mushroom farmers in low-income countries. This work can contribute to the eradication of poverty and hunger, in line with the United Nations Sustainable Development Goals one and two.

Abstract Bacillus Calmette-Guèrin - vaccination induces not only protection in infants and young children against severe forms of tuberculosis, but also against non-tuberculosis related all-cause mortality. To delineate different factors influencing mycobacterial growth control, here we first investigate the effects of BCG-vaccination in healthy Dutch adults. About a quarter of individuals already control BCG-growth prior to vaccination, whereas a quarter of the vaccinees acquires the capacity to control BCG upon vaccination. This leaves half of the population incapable to control BCG-growth. Single cell RNA sequencing identifies multiple processes associated with mycobacterial growth control. These data suggest (i) that already controllers employ different mechanisms to control BCG-growth than acquired controllers, and (ii) that half of the individuals fail to develop measurable growth control irrespective of BCG-vaccination. These results shed important new light on the variable immune responses to mycobacteria in humans and may impact on improved vaccination against tuberculosis and other diseases.

Summary: Background: There are limited global data on head-to-head comparisons of vaccine platforms assessing both humoral and cellular immune responses, stratified by pre-vaccination serostatus. The COVID-19 vaccination drive for the Indian population in the age group 18–45 years began in April 2021 when seropositivity rates in the general population were rising due to the delta wave of COVID-19 pandemic during April–May 2021. Methods: Between June 30, 2021, and Jan 28, 2022, we enrolled 691 participants in the age group 18–45 years across four clinical sites in India. In this non-randomised and laboratory blinded study, participants received either two doses of Covaxin® (4 weeks apart) or two doses of Covishield™ (12 weeks apart) as per the national vaccination policy. The primary outcome was the seroconversion rate and the geometric mean titre (GMT) of antibodies against the SARS-CoV-2 spike and nucleocapsid proteins post two doses. The secondary outcome was the frequency of cellular immune responses pre- and post-vaccination. Findings: When compared to pre-vaccination baseline, both vaccines elicited statistically significant seroconversion and binding antibody levels in both seronegative and seropositive individuals. In the per-protocol cohort, Covishield™ elicited higher antibody responses than Covaxin® as measured by seroconversion rate (98.3% vs 74.4%, p

The objective of the study is to clarify that the family participated in COVID-19 as a home-schooling family. The sample was selected according to the geographical distribution of schools in the eastern region of Khartoum. Data was collected through a questionnaire and interviews. The most important result is that there is an increasing interest from parents to support home-schooling despite the challenges of continuing learning, such as the widening digital divide in technology, previous experience, and poor network connectivity. This research paper focused on the point of view of parents in the city of Khartoum on supporting home-schooling according to social variables related to both mother and father, and the paper concluded that parents of students in private schools are more supportive of home education. Also, most of the parents of students who support home-schooling have reached their university level of education and post-university and belong to the youth age group. Although parents emphasize the importance of home-schooling during the COVID-19 infection, there are challenges associated with providing home-schooling for their children. Doi: 10.28991/ESJ-2023-07-05-021 Full Text: PDF

Abstract Detailed characterisation of immune responses induced by COVID-19 vaccines rolled out in India: COVISHIELDTM (CS) and COVAXIN® (CO) in a pre-exposed population is only recently being discovered. We addressed this issue in subjects who received their primary series of vaccination between November 2021 and January 2022. Both vaccines are capable of strongly boosting Wuhan Spike-specific neutralising antibody, polyfunctional Th1 cytokine producing CD4+ T-cells and single IFN-γ + CD8+ T-cells. Consistent with inherent differences in vaccine platform, the vector-based CS vaccine-induced immunity was of greater magnitude, breadth, targeting Delta and Omicron variants compared to the whole-virion inactivated vaccine CO, with CS vaccinees showing persistent CD8+ T-cells responses until 3 months post primary vaccination. This study provides detailed evidence on the magnitude and quality of CS and CO vaccine induced responses in subjects with pre-existing SARS-CoV-2 immunity in India, thereby mitigating vaccine hesitancy arguments in such a population, which remains a global health challenge.

Fractional order differential equations often possess inherent symmetries that play a crucial role in governing their dynamics in a variety of scientific fields. In this work, we consider numerical solutions for fractional-order linear delay differential equations. The numerical solution is obtained via the Laplace transform technique. The quadrature approximation of the Bromwich integral provides the foundation for several commonly employed strategies for inverting the Laplace transform. The key factor for quadrature approximation is the contour deformation, and numerous contours have been proposed. However, the highly convergent trapezoidal rule has always been the most common quadrature rule. In this work, the Gauss–Hermite quadrature rule is used as a substitute for the trapezoidal rule. Plotting figures of absolute error and comparing results to other methods from the literature illustrate how effectively the suggested approach works. Functional analysis was used to examine the existence of the solution and the Ulam–Hyers (UH) stability of the considered equation.

Introduction: Unexpected return to operation theater carries high rate of morbidity and mortality for patients, in addition to increased hospital stay. A close look at such cases would help in identifying high-risk patients thus improving outcome. The aim of the study was to evaluate the incidence of Obs/Gyn cases returning to OT due to postoperative complications in a tertiary care hospital. Methods: It was a retrospective observational study done at tertiary care hospital settings affiliated with academic center in the UAE. The records of patients were scrutinized, and all booked and non-booked pregnant patients of any age undergoing emergency or elective obstetrics or gynecological procedure from January 1, 2016 to December 31, 2020 were enrolled in the study. Relaparotomy was defined as cases opened within same admission and causally associated with previous primary obstetrics or gynecological operation. Result: A total of 21,276 operations were performed from 2016 to 2020. In these 4 years, 33 patients had unexpected return to operation theater making the incidence of re-exploration to 0.15% (33/21,276). There were 16 (48.48%) emergency operations and 17 (51.52%) elective operations previously done on these patients. The most common primary procedure for which re-exploration was done was lower segment caesarean section done in 11 (33.3%) of cases followed by laparoscopic adhesiolysis and myomectomy. Hematoma in the pelvic region and ooze from raw area were the most common per-operative finding in 48.48% of cases. There was no mortality in the abovementioned cases; however, 2 (6.06%) had early acute kidney injury and both recovered from it. Discussion: The incidence of relaparotomy in our hospital is comparable to international literature. Most patients returned to OT within 48 h. Bleeding was the most common indication for laparotomy, and lower segment cesarean section was most common primary operation. This study underscores the need for meticulous hemostasis before closing to avoid return to OT. Conclusion: Return to OT for the right indication saves life. Mortality in such cases may be reduced by earlier detection and treatment of postoperative problems, consideration of relaparotomy, active ICU monitoring, and postoperative care.

Control of tumour development and growth by the immune system critically defines patient fate and survival. What regulates the escape of colorectal tumours from destruction by the immune system remains currently unclear. Here, we investigated the role of intestinal synthesis of glucocorticoids in the tumour development during an inflammation‐induced mouse model of colorectal cancer. We demonstrate that the local synthesis of immunoregulatory glucocorticoids has dual roles in the regulation of intestinal inflammation and tumour development. In the inflammation phase, LRH‐1/Nr5A2‐regulated and Cyp11b1‐mediated intestinal glucocorticoid synthesis prevents tumour development and growth. In established tumours, however, tumour‐autonomous Cyp11b1‐mediated glucocorticoid synthesis suppresses anti‐tumour immune responses and promotes immune escape. Transplantation of glucocorticoid synthesis‐proficient colorectal tumour organoids into immunocompetent recipient mice resulted in rapid tumour growth, whereas transplantation of Cyp11b1‐deleted and glucocorticoid synthesis‐deficient tumour organoids was characterized by reduced tumour growth and increased immune cell infiltration. In human colorectal tumours, high expression of steroidogenic enzymes correlated with the expression of other immune checkpoints and suppressive cytokines, and negatively correlated with overall patients' survival. Thus, LRH‐1‐regulated tumour‐specific glucocorticoid synthesis contributes to tumour immune escape and represents a novel potential therapeutic target.

Abstract Diabetes Empowerment is important for diabetic control as it postpones the onset of complications. This study aimed to investigate the association of medication adherence, self-care behaviors, and diabetes knowledge with Diabetes Empowerment among patients with type II diabetes. A cross-sectional study was conducted on 451 type II diabetes patients attending Endocrinology clinics at OPD setting in Karachi. Data was collected electronically using a structured questionnaire comprising of tools to measure Diabetes Empowerment, medication adherence, self-care behaviors, diabetes knowledge, and socioeconomic scale. It also included health-related information from patients’ medical record. As outcome variable was continuous, so multiple linear regression analysis was used to assess the independent effect of Diabetes Empowerment on medication adherence, self-care behaviors and diabetes knowledge with other co-variates. The mean Diabetes Empowerment score was 3.62 (SD = 0.31). The mean age of the participants was 56.68 (SD = 11.76). 53.88% were females, 80.71% were married, 77.56% were obese, and 66.30% were upper-middle class with average diabetes duration of 11.7 years (SD = 7.89). HbA1c values were ≥ 7 in 63.41% of study participants. Diabetes Empowerment was significantly associated with medication adherence (P = 0.001), general diet (P

The formulation and sauce of Tamarindus indica (L.) and Prusnus dometica (L.) are very popular recipes across globe. But, not even a single study existed on free-radical scavenging activity (FRSA) of afore-mentioned recipes. So, the present study was designed to bridge this gap of information. The FRSA of individual samples were also determined and compared with that of combinations of both. The highest value for FRSA among all samples was that of T. indica (158.9732 ± 12.658 % at 100 μg ml-1 ). It was followed by that of individual extract of P. domestica fruit (96.647 ± 0.554 %). The percent FRSA of both combinations was less than that of individual sample extracts. The highest SA recorded was 93.886 ± 0.471 % and 77.64 ± 16.391 % respectively. The fruit length was 10.18 ± 0.34 cm and 4.7 ± 0.2 cm for T. indica and P. domestica respectively. The width of fruit was 1.6 ±0.3 cm and 4.55 ± 0.12 cm for T. indica and P. domestica respectively. The weight of fruit was 7.2 ± 0.6 g and 44.8 ± 0.37 g for T. indica and P. domestica respectively, Pulp weight was 48 ± 0.43 % and 94.58±0.352 % for T. indica and P. domestica respectively. The stone weight was 30 ± 0.421 % and 5.42±0.224 % for T. indica and P. domestica respectively. The values of squared R reflected that there was a strong correlation between the concentrations and percent SA for all the studied samples (p < 0.05) with values of R2 0.896 and 0.946 in case of T. indica and P. domestica extracts respectively and 0.980 and 0.875 for sauce and formulation respectively. It was concluded that the mixture of both ingredients has considerable potential for scavenging free radicals.

Summary: This study characterized mechanisms of Bacille Calmette-Guérin (BCG) revaccination-induced trained immunity (TI) in India. Adults, BCG vaccinated at birth, were sampled longitudinally before and after a second BCG dose. BCG revaccination significantly elevated tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 in HLA-DR+CD16−CD14hi monocytes, demonstrating induction of TI. Mycobacteria-specific CD4+ T cell interferon (IFN) γ, IL-2, and TNF-α were significantly higher in re-vaccinees and correlated positively with HLA-DR+CD16−CD14hi TI responses. This, however, did not translate into increased mycobacterial growth control, measured by mycobacterial growth inhibition assay (MGIA). Post revaccination, elevated secreted TNF-α, IL-1β, and IL-6 to “heterologous” fungal, bacterial, and enhanced CXCL-10 and IFNα to viral stimuli were also observed concomitant with increased anti-inflammatory cytokine, IL-1RA. RNA sequencing after revaccination highlighted a BCG and LPS induced signature which included upregulated IL17 and TNF pathway genes and downregulated key inflammatory genes: CXCL11, CCL24, HLADRA, CTSS, CTSC. Our data highlight a balanced immune response comprising pro- and anti-inflammatory mediators to be a feature of BCG revaccination-induced immunity.

Background: Covid-19 pandemic era introduce E-learning process in education system all over the world include medical science. Repeated researches should be conducted to explore the limitations and combat with the challenges of the E-learning process as well as find out the methods of suitable medical education system for future. Method: A cross-sectional study was performed among 334 MBBS (n = 114, 34.3%) and BDS (n = 218; 65.7%) students of four selected private Medical and Dental colleges in Bangladesh to reveal the perception of the students towards E-learning during the COVID-19 outbreak. Data was collected through an online platform using the snowball sampling technique in between October 2021 to March 2022. Result: Most of the participants use mobile phones (n = 308, 92.8%) and Wi-Fi connections (n = 153, 46.1%) for online classes. Majority of the participants had negative perception regarding E-learning. In addition, most of the participants responded that, E-learning is not better than traditional teaching (n = 292, 88%), the quality of E-learning is not satisfactory (n = 198, 59.6%), the usefulness of E-teaching regarding clinical and practical demonstrations is not satisfactory (n = 284, 85.5%), and the blend of E-learning will be beneficial in the future (n = 224, 67.5%), where female students (p = 0.049) and BDS students (p = 0.003) gave a more positive response in comparison to male students and MBBS students. BDS students gave more positive response about the satisfaction in quality of E-learning rather than MBBS students (p= 0.003). MBBS students significantly responded more negatively than did BDS students (p = 0.003) regarding student-teacher interactions during the e-learning process. Conclusion: Students adjusted themselves with the E-learning techniques but they believe that blending of E-learning, which combines both classroom and distance learning will be beneficial for them in future. The COVID-19 pandemic affects future approaches to teaching methodologies and changes to the medical education system. Update Dent. Coll. j: 2023; 13(1): 3-8

Diversity in research teams ties alternative perspectives into research projects, and this can fast‐forward scientific progress. Concerted efforts have been aimed at encouraging and supporting women to pursue a career in science, yet a gender disparity can still be observed at senior positions, with fewer women in leadership roles. To get insight into how the current landscape for women in science is perceived by different career stages, we interviewed female authors of Molecular Oncology from diverse career stages and disciplines about their inspiration, challenges they have faced as scientists as well as their thoughts on how gender diversity can be further enhanced.

Abstract Familial facial palsy is uncommon, accounting only for 4–14% of Bell's palsy cases. We report six families with single or recurrent episodes of familial facial palsy from Northern State, Sudan. The first family had two brothers with single episodes of Bell's palsy. The index case of the second family was a 19-year-old female who and nine other members of her family had a single or recurrent episodes of Bell's palsy. The third, fourth, fifth, and sixth families had eight, five, four, and five members, respectively, who developed either single or recurrent episodes of Bell's palsy. None of the index cases or other members of the six families who were examined showed evidence of facial swelling or fissured tongue suggestive of Melkersson-Rosenthal syndrome. Literature review revealed two studies on Bell's palsy from Sudan but no studies on familial facial palsy. The mode of inheritance was either autosomal dominant with variable penetrance or autosomal recessive. In the second family, there could be a possibility of autosomal recessive inheritance due to increased number of cases after consanguineous marriage. Steroids remain the mainstay of treatment together with protective eye regimens. The role of physiotherapy, although widely used, is controversial. Genetic analysis is recommended and family history should be considered in patients with Bell's palsy.

Introduction Most of the global non-communicable disease (NCD)-related death burden is borne by low and middle-income countries (LMICs). In LMICs like Pakistan, however, a major gap in responding to NCDs is a lack of high-quality research leading to policy development and implementation of NCDs. To assess institutional opportunities and constraints to NCD research and training we conducted a situational analysis for NCD research and training at Aga Khan University Pakistan.Methods We conducted a descriptive exploratory study using grounded theory as a qualitative approach: semistructured interviews of 16 NCD stakeholders (three excluded) and two focus group discussions with postgraduate and undergraduate trainees were conducted. A simple thematic analysis was done where themes were identified, and then recurring ideas were critically placed in their specific themes and refined based on the consensus of the investigators.Results The major themes derived were priority research areas in NCDs; methods to improve NCD research integration; barriers to NCD research in LMICs like Pakistan; design of NCD research programme and career paths; and NCD prevention at mass level, policy and link to the government. In general, participants opined that while there was an appetite for NCD research and training, but few high-quality research training programmes in NCDs existed, such programmes needed to be established. The ideal NCD research and training programmes would have in-built protected time, career guidance and dedicated mentorship. Most participants identified cardiovascular diseases as a priority thematic area and health information technology and data science as key methodological approaches to be introduced into research training.Conclusion We conclude from this qualitative study on NCD research and training that high-quality research training programmes for NCDs are rare. Such programmes need to be established with in-built protected time, career guidance and mentorship for the trainees to improve their research capacity in Pakistan.

A wide range of gastrointestinal (GI) illnesses is caused by foodborne bacteria that can arise from either a direct bacterial infection or bacterial toxin ingestion. The treatment of these infections has been hampered by the appearance of resistant strains. This current study aims to investigate the prevalence of Gastrointestinal tract (GIT) infections in Omani patients and their resistance pattern against commonly used antibiotics. Seven hundred and ninety fresh stool samples were obtained from Omani patients attending Sultan Qaboos University Hospital with GI manifestation from the 1st of June to the 30th of November 2019. Bacterial identification in stool samples was carried out by inoculation in culture media, microscopical examination and biochemical tests confirmed by MALDI. BD PhoenixTM. The antibiotics sensitivity testing was carried out by the Manual disk diffusion method and by MALDI. BD PhoenixTM. Out of 790 stool samples, 49 samples were positive for GIT bacterial infections. Salmonella spp. was the most prevalent isolate and more associated with children less than ten years old. Out of the 49 bacterial isolates, 3 (6.1%) were Clostridium difficili, 4 (8.2%) were Shigella flexneri, 5 (10.2%) were Campylobacter jejuni, and different Salmonella spp. serotypes were detected such as Salmonella Kentucky (8.2%), Salmonella enteritidis (6.1%), Salmonella infantis (4.1%), Salmonella welteverden (4.1%), Salmonella typhimurium (4.1%), Salmonella anatum (2.0%), Salmonella tesvia (2.0%), Salmonella Uganda (2.0%), Salmonella Arizona (2.0%) and (40.8%) of other Salmonella spp. serotypes. Eighty percent of isolated Campylobacter jejuni were resistant to Ciprofloxacin and Tetracycline. Salmonella spp. and Shigella flexneri were highly resistant to Amikacin, Gentamicin, and Cefuroxime. The low level of bacterial infection detected among screened patients in the present study indicates the excellent hand washing hygiene practice in reducing GIT infections among patients in Oman. This good hand washing hygiene practice is of great help in the efforts of controlling the spread of other severe diseases like COVID-19. However, detecting the emerging of antibiotic-resistant of GIT bacterial pathogens among patients in Oman, such as Salmonella and Shigella to a commonly used antibiotic such as Gentamicin, is alarming.

This proof-of-concept study tested if prior BCG revaccination can qualitatively and quantitively enhance antibody and T-cell responses induced by Oxford/AstraZeneca ChAdOx1nCoV-19 or COVISHIELD™, an efficacious and the most widely distributed vaccine in India. We compared COVISHIELD™ induced longitudinal immune responses in 21 BCG re-vaccinees (BCG-RV) and 13 BCG-non-revaccinees (BCG-NRV), all of whom were BCG vaccinated at birth; latent tuberculosis negative and SARS-CoV-2 seronegative prior to COVISHIELD™ vaccination. Compared to BCG-NRV, BCG-RV displayed significantly higher and persistent spike-specific neutralizing (n) Ab titers and polyfunctional CD4+ and CD8+ T-cells for eight months post COVISHIELD™ booster, including distinct CD4+IFN-γ+ and CD4+IFN-γ- effector memory (EM) subsets co-expressing IL-2, TNF-α and activation induced markers (AIM) CD154/CD137 as well as CD8+IFN-γ+ EM,TEMRA (T cell EM expressing RA) subset combinations co-expressing TNF-α and AIM CD137/CD69. Additionally, elevated nAb and T-cell responses to the Delta mutant in BCG-RV highlighted greater immune response breadth. Mechanistically, these BCG adjuvant effects were associated with elevated markers of trained immunity, including higher IL-1β and TNF-α expression in CD14+HLA-DR+monocytes and changes in chromatin accessibility highlighting BCG-induced epigenetic changes. This study provides first in-depth analysis of both antibody and memory T-cell responses induced by COVISHIELD™ in SARS-CoV-2 seronegative young adults in India with strong evidence of a BCG-induced booster effect and therefore a rational basis to validate BCG, a low-cost and globally available vaccine, as an adjuvant to enhance heterologous adaptive immune responses to current and emerging COVID-19 vaccines.

Objective Chronic liver disease continues to be a significant cause of morbidity and mortality yet remains challenging to prognosticate. This has been one of the barriers to implementing palliative care, particularly at an early stage. The Bristol Prognostic Score (BPS) was developed to identify patients with life expectancy less than 12 months and to act as a trigger for referral to palliative care services. This study retrospectively evaluated the BPS in a cohort of patients admitted to three Scottish hospitals.Method Routinely collated healthcare data were used to obtain demographics, BPS and analyse 1-year mortality for patients with decompensated liver disease admitted to three gastroenterology units over two 90-day periods. Statistical analysis was undertaken to assess performance of BPS in predicting mortality.Results 276 patients were included in the final analysis. Participants tended to be late middle-aged men, socioeconomically deprived and have alcohol-related liver disease. A similar proportion was BPS+ve (>3) in this study compared with the original Bristol cohort though had more hospital admissions, higher ongoing alcohol use and poorer performance status. BPS performed poorer in this non-Bristol group with sensitivity 54.9% (72.2% in original study), specificity 58% (83.8%) and positive predictive value (PPV) 43.4% (81.3%).Conclusion BPS was unable to accurately predict mortality in this Scottish cohort. This highlights the ongoing challenge of prognostication in patients with chronic liver disease, furthering the call for more work in this field.

Abstract Background Type 1 diabetes (T1D) has been increasing globally over the past three decades. Self-monitoring of blood glucose is a challenge in both developed as well as developing countries. Self-management guidelines include maintaining logbooks for blood glucose, physical activity, and dietary intake that affect glycated hemoglobin (HbA1c) and a multitude of life-threatening acute complications. Innovative, cost-effective interventions along with beneficial lifestyle modifications can improve home-based self-monitoring of blood glucose in T1D patients. The overall objective of this study is to evaluate the relationship between maintaining log books for blood glucose levels, reinforcement by e-messages, and/or daily step count and changes in HbA1c. Methods/design A randomized controlled trial will enroll participants aged 15 years and above in four groups. Each group of 30 participants will be working with a newly designed standard log book for documenting their blood glucose. The first group will be entirely on routine clinical care, the second group will be on routine care and will receive an additional e-device for recording step count (fit bit), the third group will receive routine care and daily motivational e-messages to maintain the log book, and the fourth group along with routine care will receive an e-device for measuring step count (fit bit) and e-messages about maintaining the log book. Patients will be enrolled from pediatric and endocrine clinics of a tertiary care hospital in Karachi. All groups will be followed up for a period of 6 months to evaluate outcomes. Log book data will be obtained every 3 months electronically or during a patient’s clinic visit. HbA1c as a main outcome will be measured at baseline and will be evaluated twice every 3 months. A baseline questionnaire will determine the socio-demographic, nutritional, and physical activity profile of patients. Clinical information for T1D and other co-morbidities for age of onset, duration, complications, hospitalizations, habits for managing T1D, and other lifestyle characteristics will be ascertained. Behavioral modifications for maintaining daily log books as a routine, following e-messages alone, fit bit alone, or e-messages plus using fit bit will be assessed for changes in HbA1c using a generalized estimated equation. Discussion The proposed interventions will help identify whether maintaining log books for blood glucose, motivational e-messages, and/or daily step count will reduce HbA1c levels. Trial registration ClinicalTrials.gov, NCT03864991 . March 6, 2019.

Two-dimensional (2D) materials such as semiconductors and ferroelectrics are promising for future energy-efficient logic devices because of their extraordinary electronic properties at atomic thickness. In this work, we investigated a van der Waals heterostructure composited of 2D semiconducting MoS _2 and 2D ferroelectric CuInP _2 S _6 (CIPS) and NiPS _3 . Instead of using 2D ferroelectrics as conventional gate dielectric layers, here we applied CIPS and NiPS _3 as a ferroelectric capping layer, and investigated a long-distance coupling effect with the gate upon the sandwiched 2D MoS _2 channels. Our experimental results showed an outstanding enhancement of the electrodynamic gating in 2D MoS _2 transistors, represented by a significant reduction of subthreshold swing at room temperature. This was due to the coupling-induced polarization of 2D ferroelectrics at 2D semiconductor surface which led to an effective and dynamic magnification of the gate capacitance. Meanwhile, the electrostatic gating was remained steady after adding the ferroelectric capping layer, providing ease and compatibility for further implementation with existing circuit and system design. Our work demonstrates the long-distance coupling effect of 2D ferroelectrics in a capping architecture, reveals its impacts from both electrodynamic and electrostatic perspectives, and expands the potential of 2D ferroelectrics to further improve the performance of energy-efficient nanoelectronics.

Abstract Background Maternal depression and anxiety have distinct constellations of symptom trajectories, which are associated with factors that may vary between different groups of women. The aim of this study was to identify subgroups of women who exhibit unique longitudinal trajectory patterns of depressive and anxiety symptoms from pregnancy to 5 years postpartum and the antenatal predictors associated with these maternal groups. Methods The study used a longitudinal data collected from 615 women in Saskatchewan from pregnancy to 5 years postpartum. Semiparametric group-based models were used to identify latent maternal depressive and anxiety trajectory groups. Multinomial logit models were then used to assess the association between maternal characteristics and the identified latent trajectory groups. Results We identified four trajectory groups of maternal depressive symptoms: low-stable (35%); moderate-stable (54%); moderate-increasing (5%); and high-decreasing (6%), and three trajectory groups of maternal anxiety symptoms: very low-stable (13%); low-stable (58%); and moderate-stable (29%). We also identified several risk factors, most notably history of depression and stress, that were significantly associated with these trajectories. Conclusion History of depression and increased stress are significant risk factors that can be identified during regular perinatal visits; therefore, clinicians should inquire about these risk factors to identify women at high risk of ongoing depression or anxiety.

Morchella conica (M. conica) Pers. is one of six wild edible mushrooms that are widely used by Asian and European countries for their nutritional value. The present study assessed the anti-diabetic potential of M. conica methanolic extract (100 mg/kg body weight) on streptozotocin (STZ)-induced diabetic mice. STZ was used in a single dose of 65 mg/kg to establish diabetic models. Body weights, water/food intake and fasting blood glucose levels were measured. Histopathological analysis of the pancreas and liver were performed to evaluate STZ-induced tissue injuries. In addition, in vitro assays such as α-amylase and protein tyrosine phosphatase 1B (PTP1B) inhibitory, antiglycation, antioxidant and cytotoxicity were performed. The in vitro study indicated potent PTP1B inhibitory potential of M. conica with an IC50 value of 26.5 μg/ml as compared to the positive control, oleanolic acid (IC50 36.2 μg/ml). In vivo investigation showed a gradual decrease in blood sugar level in M. conica-treated mice (132 mg/dl) at a concentration of 100 mg/kg as compared to diabetic mice (346 mg/dl). The extract positively improved liver and kidney damages as were shown by their serum glutamic pyruvic transaminase, serum glutamic oxaloacetate, alkaline phosphatase, serum creatinine and urea levels. Histopathological analysis revealed slight liver and pancreas improvement of mice treated with extract. Cytotoxicity assays displayed lower IC50 values. Based on the present results of the study, it may be inferred that M. conica are rich in bioactive compounds responsible for antidiabetic activity and this mushroom may be a potential source of antidiabetic drug. However, further studies are required in terms of isolation of bioactive compounds to validate the observed results.

La comunicación integrada de marketing (CIM) es un concepto que ha atraído gran interés y atención por parte de los académicos y de los profesionales del marketing. Sin embargo, la mayor parte de los estudios existentes se basa sobre la perspectiva organizativa, siendo la CIM percibida por el consumidor una de las lagunas de investigación más destacadas. Por tanto, este trabajo aborda la CIM desde la perspectiva del consumidor y se propone la consecución de un objetivo clave: determinar si la CIM contribuye a la obtención de una mayor satisfacción del cliente, que representa una variable crucial para el éxito de una empresa en el mercado actual. Para cumplir el objetivo propuesto, se llevó a cabo una encuesta online, de la que se obtuvo una muestra final de 252 clientes de la marca McDonald’s. El análisis de los resultados permitió demostrar una relación positiva y significativa entre la coherencia del mensaje y la interactividad, dos dimensiones clave de la CIM, y la satisfacción del cliente. Finalmente, el trabajo propone una serie de implicaciones y futuras líneas de investigación.

ABSTRACT: Objective: To shed light on a unique presentation of duplication of the pituitary gland (DPG)-plus syndrome. Methods: We present the case report gathered from the patient. Results: This patient uniquely had DPG-plus syndrome with a concurrent dermoid cyst. Conclusion: DPG is a very rare developmental anomaly and there are not many case reports published in the literature. The presence of DPG with dermoid cyst in our patient has not been reported previously. This case report discusses the various presentations of the syndrome and also provides an overview of investigations and management of these patients. Abbreviation: DPG duplication of the pituitary gland

The aim of this study is to design a new mathematical model biomass product with the help of the gasification reactor. This design will help in describing most of the internal parameters inside this process. This research also aims to study and analyze the kinetic reaction, mass and heat transfer for four zones of the gasification reactor. It has been found that the char concentration from zone one is almost 42% consumption and from zone three to four, the consumptions have found to be 72.06%. It means that the char conversion depends on oxygen consumptions in all zones to produce volatility gases, methane, and hydrogen. The mathematical model will help in optimizing best possible conditions so as to give a high quality product of methane and hydrogen to 2.2 kmol/m3 and 3 Kmol/m3 respectively. Thus, it appears to be important that important parameters of a chemical reaction are studied. Furthermore, all thermodynamic parameters of the reaction must be analyzed so as to optimize the best conditions through gasification reactor.

Abstract Background Refugee women are almost five times more likely to develop postpartum depression than Canadian-born women. This can be attributed to various difficulties they faced before coming to Canada as well as during resettlement. Moreover, refugee women usually face many obstacles when accessing health services, including language and cultural barriers, as well as unique help-seeking behaviors that are influenced by various cultural and practical factors. There has been a recent, rapid influx of Syrian refugees to Canada, and many of them are childbearing women. However, little is known about the experiences that these women have encountered pre- and post-resettlement, and their perceptions of mental health issues. Thus, there is an urgent need to understand refugee women’s experiences of having a baby in Canada from a mental health perspective. Methods A mixed methods research design included 12 Syrian refugee women who migrated to Saskatoon in 2015–16 and who were either pregnant or 1 year postpartum. The data were collected during a single focus group discussion and a structured questionnaire. Results Our results showed that more than half of participants have depressive symptoms, half of them have anxiety symptoms, and one sixth have PTSD symptoms. Three major themes emerged from the qualitative data: 1) Understanding of maternal depression; 2) Protective factors for mental health; and 3) Barriers to mental health services. Conclusions Maternal depression is an important feature in Syrian refugee women recently resettled in Canada. Reuniting these women with their families and engaging them in culturally appropriate support programs may improve their mental health outcomes.

Abstract Background Diabetes registry enables practitioners to measure the characteristics and patterns of diabetes across their patient population. They also provide insight into practice patterns which can be very effective in improving care and preventing complications. The aim of this study was to assess the patterns, control levels and complications at the baseline of the patients attending clinic at the large tertiary care hospital in Karachi, Pakistan with the help of the registry. This can be used as a reference to monitor the control and also for a comparison between peer groups. Methods This was a cross sectional study with the data obtained from diabetes registry collected with the help of pre-designed questionnaire. HbA1c was used as a central diabetes measure and other related factors and complications were assessed with it. Results Only 16.6% of the participants had optimal HbA1c ≤ 7.0%. 52.9% of the patients were classified as having poor control defined by HbA1c of >8%. Three fourth of the study population were obese according to Asian specific BMI cutoffs and majority had type 2 diabetes with duration of diabetes ranging from less than one to about 35 years, mean(SD) duration being 7.6 years (7.1). Overall only 4% of the patients were on combine target of HbA1c, LDL and BP. Results of multivariable logistic regression showed that the odds of having optimal glycemic control increased by 3% with every one year increase in age. In addition, having longer duration of diabetes was associated with 56% lower odds of having good glycemic control. Moreover, having higher triglyceride levels was associated with 1% lower odds of having good glycemic control. Conclusion This highlights the large burden of sub optimally controlled people with diabetes in Pakistani population, a low income country with huge diabetes prevalence and ineffective primary health care system creating enormous health and economic burden.

Abstract Background Atypical carcinoid arising from the mediastinal tissue is a rare neuroendocrine tumor and an association with parathyroid adenoma is very unusual. We report an unusual case of atypical carcinoid of mediastinum with metastasis in a patient presenting with parathyroid adenoma, which is the first case to be reported from Pakistan. Case presentation A 51-year-old Pakistani man was seen in postoperative intensive care after right parathyroidectomy and mediastinal mass resection for the management of postoperative hypocalcaemia. He had a background history of dyspnea. Examination was unremarkable. Preoperative laboratory evaluation revealed a calcium level of 12.7 mg/dl, phosphate of 1.9 mg/dl, serum albumin of 4.8 g/dl, alkaline phosphate of 94 U/L, and serum intact parathyroid hormone level 413.8 pg/ml. A technetium-99m sestamibi parathyroid scan showed right parathyroid increased tracer uptake. Further workup revealed a large mediastinal mass which was diagnosed as atypical carcinoid after Tru-Cut biopsy. He underwent right-sided parathyroidectomy and resection of the mediastinal mass. The histopathology confirmed it to be a parathyroid adenoma and atypical carcinoid tumor of his mediastinum with metastasis in his lymph node and parathyroid gland. Somatostatin receptor scintigraphy revealed a well-defined focus in his left hypochondriac region consistent with a somatostatin receptor scintigraphy-avid tumor. He was started on everolimus and planned for octreotide therapy. Conclusions We describe an incidental finding of atypical carcinoid of the mediastinum in a patient diagnosed as having parathyroid adenoma. Clinical manifestations of neuroendocrine syndromes are challenging. Some tumors cluster in a non-classic description with other common neoplasms. They rarely present in isolation, remain clinically silent, and need aggressive workup with the aid of imaging and histopathology.

Efficient diagnosis of tuberculosis (TB) is met with multiple challenges, calling for a shift of focus from pathogen-centric diagnostics towards identification of host-based multi-marker signatures. Transcriptomics offer a list of differentially expressed genes, but cannot by itself identify the most influential contributors to the disease phenotype. Here, we describe a computational pipeline that adopts an unbiased approach to identify a biomarker signature. Data from RNA sequencing from whole blood samples of TB patients were integrated with a curated genome-wide molecular interaction network, from which we obtain a comprehensive perspective of variations that occur in the host due to TB. We then implement a sensitive network mining method to shortlist gene candidates that are most central to the disease alterations. We then apply a series of filters that include applicability to multiple publicly available datasets as well as additional validation on independent patient samples, and identify a signature comprising 10 genes — FCGR1A, HK3, RAB13, RBBP8, IFI44L, TIMM10, BCL6, SMARCD3, CYP4F3 and SLPI, that can discriminate between TB and healthy controls as well as distinguish TB from latent tuberculosis and HIV in most cases. The signature has the potential to serve as a diagnostic marker of TB.

Disregarded the unsaturated soil behavior, like changes in volume and soil collapsing has caused a lot of damage to the foundations of the buildings and other structures. These behaviors relate to drying and wetting phenomena. An experimental study was carried out to investigate the variations of suction and stress - settlement relations under axial static loading on fine grain unsaturated soil (CL-ML) after 3 cycles wetting and drying. A prototype foundation model (100×100×35mm) was used in the testing program. Tests were carried out in a specially designed bearing capacity box (900×900×850) mm with soil suction measurements. Results showed an increase in the applied failure stress of about 19%after an application of three wetting-drying cycles. On the other hand, the sense record slight variation in amount of suction about 2 kPa (both recorded sensors S1,S2) during increasing axial load after wetting-drying cycles repetition. While the variation coincide with first applied load increment (before moisturizing drying case), and sense readings showed continue change (from 12 to 15 at S1,from 7 to 0 kPa at S2) with increasing load limit till failure happened. This could be attributed to the change in physical soil properties such as soil densification and hysteresis effects, consequently affected its ability on retention water in pore space.

Glucocorticoids (GCs) are steroid hormones predominantly produced in the adrenal glands in response to physiological cues and stress. Adrenal GCs mediate potent anti-inflammatory and immunosuppressive functions. Accumulating evidence in the past two decades has demonstrated other extra-adrenal organs and tissues capable of synthesizing GCs. This review discusses the role and regulation of GC synthesis in the intestinal epithelium in the regulation of normal immune homeostasis, inflammatory diseases of the intestinal mucosa, and the development of intestinal tumors.

There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR) rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

Chronic T cell activation is a hallmark of pulmonary tuberculosis (PTB). The mechanisms underpinning this important phenomenon are however, poorly elucidated, though known to rely on control of T effector cells (Teff) by regulatory T cells (Treg). Our studies show that circulating natural Treg cells in adults with PTB preserve their suppressive potential but Teff cells from such subjects are resistant to Treg-mediated suppression. We found this to be due to expansion of an activated Teff subset identified by Human Leukocyte Antigen (HLA)-DR expression. Sensitivity to suppression was restored to control levels by depletion of this subset. Comparative transcriptome analysis of Teff cells that contain HLA-DR+ cells versus the fraction depleted of this population identified putative resistance mechanisms linked to IFNG, IL17A, IL22, PD-L1 and β-chemokines CCL3L3, CCL4 expression. Antibody blocking experiments confirmed HLA-DR+ Teff cells, but not the fraction depleted of HLA-DR+ effectors, to be resistant to Treg suppression mediated via CCR5 and PD-L1 associated pathways. In the presence of HLA-DR+ Teff cells, activation of NFκB downstream of CCR5 and PD-L1 was perturbed. In addition, HLA-DR+ Teff cells expressed significantly higher levels of Th1/Th17 cytokines that may regulate Treg function through a reciprocal counter-balancing relationship. Taken together, our study provides novel insight on how activated HLA-DR+CD4+ T cells may contribute to disease associated inflammation by compromising Treg-mediated suppression in PTB.

Dental tooth restorative procedures may weaken the structural integrity of the tooth, with the possibility of leading to fracture. In this study we present findings of coronal dentin strength after different techniques of surface modification. The fracture strength of dentin beams after superficial material removal with a fine diamond bur high speed drill hand piece, Er:YAG (2.94 μm, 8 J/cm2), and Er,Cr:YSGG (2.78 μm, 7.8 J/cm2) laser irradiation slightly above the ablation threshold was measured by a four-point bending apparatus. Untreated dentin beams served as a control. A total of 58 dentin beams were manufactured from sterilized human extracted molars using the coronal part of the available dentin. Mean values of fracture strength were calculated as 82.0±27.3 MPa for the control group (n=10), 104.5±26.3 MPa for high speed drill treatment (n=10), 96.1±28.1 MPa for Er,Cr:YSGG laser irradiation (n=20), and 89.1±36.3 MPa for Er:YAG laser irradiation (n=18). Independent Student’s t-tests showed no significant difference between each two groups (p>0.05). Within the parameter settings and the limits of the experimental setup used in this study, both lasers systems as well as the high speed drill do not significantly weaken coronal dentin after surface treatment.

ESAT-6, an abundantly secreted protein of Mycobacterium tuberculosis (M. tuberculosis) is an important virulence factor, inactivation of which leads to reduced virulence of M. tuberculosis. ESAT-6 alone, or in complex with its chaperone CFP-10 (ESAT-6:CFP-10), is known to modulate host immune responses; however, the detailed mechanisms are not well understood. The structure of ESAT-6 or ESAT-6:CFP-10 complex does not suggest presence of enzymatic or DNA-binding activities. Therefore, we hypothesized that the crucial role played by ESAT-6 in the virulence of mycobacteria could be due to its interaction with some host cellular factors. Using a yeast two-hybrid screening, we identified that ESAT-6 interacts with the host protein beta-2-microglobulin (β2M), which was further confirmed by other assays, like GST pull down, co-immunoprecipitation and surface plasmon resonance. The C-terminal six amino acid residues (90-95) of ESAT-6 were found to be essential for this interaction. ESAT-6, in complex with CFP-10, also interacts with β2M. We found that ESAT-6/ESAT-6:CFP-10 can enter into the endoplasmic reticulum where it sequesters β2M to inhibit cell surface expression of MHC-I-β2M complexes, resulting in downregulation of class I-mediated antigen presentation. Interestingly, the ESAT-6:β2M complex could be detected in pleural biopsies of individuals suffering from pleural tuberculosis. Our data highlight a novel mechanism by which M. tuberculosis may undermine the host adaptive immune responses to establish a successful infection. Identification of such novel interactions may help us in designing small molecule inhibitors as well as effective vaccine design against tuberculosis.

BackgroundEver since its discovery the mycobacterial proline-proline-glutamic acid (PPE) family of proteins has generated a huge amount of interest. Understanding the role of these proteins in the pathogenesis of Mycobacterium tuberculosis (Mtb) is important. We have demonstrated earlier that the PPE18 protein of Mtb induces IL-10 production in macrophages with subsequent downregulation of pro-inflammatory cytokines like IL-12 and TNF-α and favors a T-helper (Th) 2-type of immune response.Methodology/principal findingsUsing a ppe18 genetic knock-out Mtb strain, we have now carried out infection studies in mice to understand the role of PPE18 in Mtb virulence. The studies reveal that lack of PPE18 leads to attenuation of Mtb in vivo. Mice infected with the ppe18 deleted strain have reduced infection burden in lung, liver and spleen and have better survival rates compared to mice infected with the wild-type Mtb strain.Conclusions/significanceTaken together our data suggest that PPE18 could be a crucial virulence factor for intracellular survival of Mtb.

Fixed drug eruptions (FDEs) are dermatological manifestations characterized by recurrent lesions at the same site upon re-exposure to the causative drug. We present a novel case of a 32-year-old female who developed bilateral symmetrical erythematous papules on her thighs following the use of chlorzoxazone for chronic back pain. This case is particularly significant as it underscores the potential for this specific drug, which is commonly prescribed, to induce FDE—a reaction previously unreported in the literature. The findings emphasize the necessity for clinicians to maintain a high index of suspicion for drug-induced skin reactions, even with medications considered safe and routinely used. This case serves as a critical reminder of the importance of thorough medication history assessments and the potential implications of drug interactions in dermatological care. [ABSTRACT FROM AUTHOR]