Search

Ahmed A Almazroa,1– 3 Maria A Woodward,1,4 Paula Anne Newman-Casey,1,4 Manjool M Shah,1 Angela R Elam,1 Shivani S Kamat,1 Carrie A Karvonen-Gutierrez,5 Sarah D Wood,1 Navasuja Kumar,1 Sayoko E Moroi1,4 1Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, MI, USA; 2Medical Imaging, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 3Medical Imaging, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 4Institute for Healthcare Policy & Innovation, University of Michigan, Ann Arbor, MI, USA; 5Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USACorrespondence: Ahmed A AlmazroaKing Abdullah International Medical Research Center, P.O. Box 3660, Riyadh 11481, Saudi ArabiaTel +966 (11)4294324Email almazroaah@ngha.med.saPurpose: The purpose of this study was to evaluate the ability to screen for glaucoma using a Food Drug Administration (FDA) Class II diagnostic digital fundus photography system used for diabetic retinopathy screening (DRS).Methods: All research participants underwent a comprehensive eye examination as well as non-mydriatic 45°single photograph retinal imaging centered on the macula. Optic nerve images within the 45° non-mydriatic and non-stereo DRS image were evaluated by two methods: 1) grading by three glaucoma specialists, and 2) a computer-aided automated segmentation system to determine the vertical cup-to-disc ratio (VCDR). Using VCDR from clinical assessment as gold standard, VCDR results from two methods were compared to that from clinical assessment. Inter-grader agreement was assessed by computing intraclass correlation coefficient (ICC). In addition, sensitivity and specificity were calculated.Results: Among 245 fundus photos, 166 images met quality specifications for analysis. Fifty images were not processed by the automated system due to the poor quality of the optic disc, and 29 images did not include the optic nerve head due to the patient movement during the photo acquisition. The ICC value for the VCDR between the gold standard clinical exam and the automated system was 0.41, indicating fair agreement. The ICC value between the three ophthalmologists and the gold standard was 0.51, 0.56, and 0.69, respectively, indicating fair to moderate agreement.Discussion: Assessing the VCDR on non-mydriatic and non-stereo DRS fundus photographs by either the computer-aided automated segmentation system or by glaucoma specialists showed similar fair to moderate agreement. In summary, optic nerve assessment for glaucoma from these 45° non-mydriatic and non-stereo DRS images is not yet suitable for tele-glaucoma screening.Keywords: telemedicine, tele-glaucoma, automated screening system, diabetic retinopathy screening, glaucoma screening

A total of 37 original cDNA libraries and 9 derivative libraries enriched for rare sequences were produced from Chinese Spring wheat (Triticum aestivum L.), five other hexaploid wheat genotypes (Cheyenne, Brevor, TAM W101, BH1146, Butte 86), tetraploid durum wheat (T. turgidum L.), diploid wheat (T. monococcum L.), and two other diploid members of the grass tribe Triticeae (Aegilops speltoides Tausch and Secale cereale L.). The emphasis in the choice of plant materials for library construction was reproductive development subjected to environmental factors that ultimately affect grain quality and yield, but roots and other tissues were also included. Partial cDNA expressed sequence tags (ESTs) were examined by various measures to assess the quality of these libraries. All ESTs were processed to remove cloning system sequences and contaminants and then assembled using CAP3. Following these processing steps, this assembly yielded 101,107 sequences derived from 89,043 clones, which defined 16,740 contigs and 33,213 singletons, a total of 49,953 "unigenes." Analysis of the distribution of these unigenes among the libraries led to the conclusion that the enrichment methods were effective in reducing the most abundant unigenes and to the observation that the most diverse libraries were from tissues exposed to environmental stresses including heat, drought, salinity, or low temperature.

Background and objective Beta-blockers are a cornerstone in the management of acute coronary syndrome (ACS), effectively reducing myocardial oxygen demand, preventing recurrent ischemia, and lowering the risk of arrhythmias and reinfarction. Despite several established guidelines, such as those by the American College of Cardiology/American Heart Association (ACC/AHA), advocating their use within 24 hours for eligible patients, beta-blockers remain underutilized in clinical practice. This study aimed to analyze beta-blocker utilization patterns in ACS management and evaluate the impact of targeted improvement initiatives on their appropriate use in eligible ACS patients. Methods A two-phase study was conducted at Tata Main Hospital, Jamshedpur, India. Phase I (October 2019 to May 2021) retrospectively analyzed the records of 1100 ACS patients. Phase II (July 2021 to October 2023) evaluated post-implementation outcomes of improvement measures, including physician education and a standardized prescription checklist. Patients were categorized based on adherence to beta-blocker guidelines and analyzed for utilization gaps. Statistical analysis was conducted using SPSS Statistics version 21 (IBM Corp., Armonk, NY), with significance set at a p-value <0.05. Results Post-intervention, beta-blocker adherence significantly improved from 74.5% to 92.7% (p<0.001). Late initiation without valid reasons (Group B) decreased from 15.5 to 3.6%, and non-initiation despite eligibility (Group C) decreased from 10 to 3.6%. These changes were statistically significant, highlighting the effectiveness of the improvement initiatives. Barriers to beta-blocker use included physician hesitancy when treating patients with relative contraindications. Targeted interventions, such as education and protocol standardization, helped to bridge this gap, aligning practices with global guideline recommendations. Conclusions Early and appropriate beta-blocker use in ACS management is crucial for improving patient outcomes. This study demonstrates that targeted interventions can significantly enhance guideline adherence, optimizing ACS care in resource-limited settings., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Institutional Ethic Committee, Tata Main Hospital issued approval TMH/IEC/APR/004/2022. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Prakash et al.)

Objective: Anemia is a condition characterized by a shortage of red blood cells (RBCs) and hemoglobin (Hb). A peripheral blood smear (PBS) test involves examining a blood sample to identify important abnormalities in the red blood cells, white blood cells (WBC), and platelets. The aim of this study was to correlate the red cell distribution width (RDW) with peripheral blood smear findings in anemic patients presenting to a tertiary care hospital in Peshawar., Methodology: This cross-sectional study was conducted at Hayatabad Medical Complex, Peshawar, from January 15, 2023, to July 14, 2023. A total of 450 patients aged 18 years and above with confirmed or suspected anemia (Hb of <13 g/dL in men and <12 g/dL in women), hemolytic disorders, or conditions affecting RBC morphology were included. Peripheral blood smear analysis was performed by two independent hematologists to minimize observer bias. Spearman's rank correlation coefficient was applied to determine the correlation between red cell distribution width and the morphological findings on the peripheral blood smear., Results: Among 450 anemic patients, 232 (51.6%) were women, and 218 (48.4%) were men. The mean age was 25.72 ± 23.23 years. RBC indices showed microcytic RBCs in 270 (60.0%) patients, normocytic RBCs in 157 (34.9%), and macrocytic RBCs in 23 (5.1%). Hypochromic RBCs were found in 301 (66.9%) cases and normochromic in 109 (24.2%). Peripheral blood smear analysis revealed polychromasia in 37 (8.2%) patients and hypochromia in 247 (54.9%). Statistically significant correlations were observed between red cell distribution width and most PBS findings., Conclusion: Microcytic hypochromic anemia was the most prevalent type on the peripheral blood smear, showing a significant correlation with red cell distribution width. The strong correlation between RDW and anisocytosis suggests the potential utility of RDW as a screening tool in clinical practice., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. The Medical Teaching Institute (MTI)-Hayatabad Medical Complex Hospital Research and Ethical Committee (IREB) issued approval HMC/ERC/2023/2286 on 11/02/2023. The MTI-Hayatabad Medical Complex Hospital Research and Ethical Committee (IREB) has reviewed the synopsis/article (title: Correlation of red cell distribution width with peripheral blood smear: a study from a tertiary care hospital in Peshawar) in accordance with the Declaration of Helsinki (2013) and found it to meet the requirements and approved it. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Abbas et al.)

Background Beta-thalassemia major is a genetic blood disease complicated by splenomegaly, and splenectomy is a standard therapy for this medical condition. Although splenectomy results not only in the improvement of the hematological status, the long-term consequences to the cardiovascular system are still questionable. Objective The aim of the study was to assess and compare the cardiovascular impact of splenomegaly and splenectomy in patients with beta-thalassemia major. Methodology This is a cross-sectional survey conducted at Hayatabad Medical Complex, Peshawar, from January 2024 to June 2024. A total of 88 beta-thalassemia major patients were divided into two groups: 44 patients with splenomegaly were recruited and compared with 44 post-splenectomy patients. Outcomes that were assessed in this study from the medical records were cardiac function test, ejection fraction, left ventricular hypertrophy, thromboembolic incidences, pulmonary embolism, deep vein thrombosis, blood pressure level, and the biochemical markers, B-type natriuretic peptide (BNP) and troponin. The data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 26 (IBM Corp., Armonk, USA). Results Patients with splenectomy exhibited slightly lower hemoglobin levels and higher transfusion requirements but had better ejection fractions compared to those with splenomegaly. In contrast, the splenomegaly group demonstrated worse cardiovascular outcomes, including higher rates of left ventricular hypertrophy, pulmonary hypertension, arrhythmias, thromboembolic events, and elevated BNP levels, indicating increased cardiovascular morbidity and hemodynamic strain. Logistic regression analysis further suggested that splenectomy reduces the risk of cardiomyopathy, particularly in younger patients, while the splenomegaly group experiences a greater burden of acute cardiovascular complications. Conclusion Splenectomy in beta-thalassemia major patients offers improved cardiac function and hemoglobin levels while reducing transfusion needs, but it does not eliminate the risks of long-term cardiovascular and thromboembolic complications, such as deep vein thrombosis and pulmonary embolism. On the other hand, patients with splenomegaly face more severe and immediate cardiovascular risks, including hypertension, arrhythmias, and thromboembolic events. These findings underscore the importance of tailored management strategies to optimize outcomes for both groups., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Institutional Research and Ethical Board of Hayatabad Medical Complex (HMC) issued approval Ethical Approval No: 2289, Doc. No: HMC-QAD-F, Approval Date: 16.10.2023. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Abbas et al.)

Background Salmonella Typhi ( S. Typhi) is increasingly resistant to multiple antibiotics, posing a challenge in treatment, particularly in multidrug-resistant (MDR) cases. Carbapenems, including doripenem, ertapenem, and meropenem, have been considered last-resort options. This study evaluates the effectiveness of these carbapenems against S. Typhi isolates in a clinical setting in Peshawar, Pakistan. Objective To assess the effectiveness of the carbapenem antibiotics, doripenem, ertapenem, and meropenem, against S. Typhi. Methods This study collected data from blood cultures of patients diagnosed with S. Typhi infections at the Hayatabad Medical Complex in Peshawar, Pakistan for two years: from January 1, 2022, to December 31, 2023. Sensitivity testing was performed using the disk diffusion method in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines. The analysis examined the sensitivity rates of the three antibiotics and compared their effectiveness. Results A total of 626 S. Typhi isolates were tested. Only 11.98% of the isolates were sensitive to doripenem, while 88.02% were resistant to it. In contrast, 35.5% of the isolates responded to ertapenem, with 64.5% being resistant. Meropenem showed the highest efficacy, with 42.7% of the isolates demonstrating sensitivity. These findings highlight the growing challenge of managing multidrug-resistant (MDR) S. Typhi infections, especially in regions where resistance to carbapenems is becoming prevalent. Conclusion Meropenem proved to be more effective against S. Typhi compared to doripenem and ertapenem. The study emphasizes the need for ongoing monitoring of resistance patterns and the exploration of alternative or combination treatment options. These findings have immediate clinical implications for empiric therapy choices and highlight the urgent need for antibiotic stewardship programs in endemic regions., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Medical Teaching Institution (MTI), Hayatabad Medical Complex, Peshawar, Pakistan issued approval 2222, dated December 8, 2021. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shah et al.)

Myasthenia gravis (MG) is an antibody-mediated disorder that disrupts postsynaptic acetylcholine receptors with consequent fatigable weakness, bulbar symptoms, and respiratory fragility. MG patients can be challenging to manage during open abdominal surgery given the unpredictable efficacy of neuromuscular and reversal agents and the risk of precipitating an MG crisis. Regional neuraxial anesthesia eliminates the need for these agents and endotracheal intubation. Here, we report the case of a 66-year-old male with a history of advanced MG, vasovagal episodes with bradycardia and asystolic arrest, and complicated diverticulitis who underwent an uncomplicated open sigmoid colectomy achieved with epidural anesthesia-analgesia. Neuraxial anesthesia can be considered and further investigated as an effective approach in optimizing high-risk patients undergoing open laparotomy for colorectal surgical care., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shah et al.)

Background: Pulmonary embolism (PE) is a quite common condition and is a potentially lethal form of venous thromboembolic phenomenon associated with multiple inherited and acquired risk factors. Despite improvements in diagnostic techniques, delays in recognition and treatment are still common, contributing to increased morbidity and mortality. This study aimed to assess the time from the onset of symptoms to hospital arrival and to analyze delays in diagnosing and initiating treatment for patients with high and intermediate-to-high risk PE., Materials and Methods: A retrospective analysis was performed on 23 patients with high and intermediate-to-high risk PE admitted to a tertiary hospital from January 2021 to December 2023. Patients with pre-existing heart or lung conditions, low-risk PE, or those without follow-up were excluded. Routine blood tests, D-dimer measurement, 2D echocardiography, and CT pulmonary angiography (CTPA) were used to diagnose PE. Thrombolysis with streptokinase was administered in confirmed cases, and patient outcomes were monitored post-hospitalization., Results: The study included 23 patients, with a mean age of 47.1 years, 65% of whom were male. The most frequent symptom was shortness of breath (78%), followed by chest pain (13%) and syncope (9%). Elevated D-dimer levels were found in 96% of patients, and right ventricular overload was seen in all cases through echocardiography. CTPA confirmed PE in 91% of patients. Significant delays were observed in both hospital arrival and in-hospital diagnosis, with an average delay of more than seven hours before treatment began. Early diagnosis followed by thrombolysis led to favorable outcomes, while delayed diagnosis resulted in poorer outcomes, including residual symptoms and right ventricular dysfunction., Conclusion: Early diagnosis and treatment of PE greatly enhance patient outcomes, especially with timely thrombolysis. Echocardiography should be utilized promptly in emergency settings to facilitate early treatment. Quick recognition of PE, particularly in patients with risk factors, is essential to reduce mortality and long-term complications., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kumar et al.)

Introduction Parasitic infection is an overlooked cause of diarrhea in adults. It can cause persistent or chronic diarrhea that contributes to a significant burden on the overall morbidity of the population. Stool sampling would aid in the diagnosis of parasitic infection in adults presenting with diarrhea. Methods A cross-sectional study was conducted from January to June 2024 at Medical Teaching Institution (MTI)-Hayatabad Medical Complex, Peshawar, Pakistan. A total of 500 stool samples were collected using non-probability consecutive sampling. All the patients presenting with complaints of persistent or chronic diarrhea to the medical outpatient department or admitted to the medical units were included in the study. Patients with bloody diarrhea and those less than 13 years of age were excluded from the study. Verbal and written informed consent was obtained from all the patients included in the study. The stool samples of all the patients were collected, reported, and verified by the microbiology department. Results Out of 500 stool samples of the patients with persistent or chronic diarrhea, 174 (34.8%) were found to be infected with cysts or trophozoites of parasites. Gender distribution of parasitic infections showed that 89 out of 245 females (36.3%) and 85 out of 255 males (33.3%) were affected. The comparison between genders yielded a p-value of 0.482. All the patients showed mono parasitism. The most common isolate was Giardia lamblia in 90 (51.72%) cases, followed by H-Nana in 49 (28.17%) isolates, Entamoeba histolytica in 16 (9.20%), Ascaris lumbricoides in 14 (8.04%), Trichuris trichura in two (1.15%), Taenia saginata in two (1.15%), and Cryptosporidium in one (0.6%) infected patient.  Conclusion Parasitic intestinal infections, particularly Giardia and H-Nana, are prevalent yet overlooked causes of persistent and chronic diarrhea in adults. These findings underscore the importance of routine stool examination as a cost-effective diagnostic tool, potentially improving patient outcomes and reducing unnecessary medical interventions.​​​​​​​​​., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Institutional Research and Ethical Board of Hayatabad Medical Complex issued approval 2019 (dated 13-12-2023). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Iftikhar et al.)

Introduction Obesity is measured scientifically by calculating body mass index (BMI). Body mass index in men is linked to various hormonal imbalances. This study aims to observe the relationships between BMI, vitamin D, and testosterone levels in patients attending the outpatient clinic at Hayatabad Medical Complex, Peshawar, Pakistan. Methods This observational cross-sectional study involved 272 patients, presenting to the medical outpatient department from January 1 st , 2023, to December 31 st , 2023. Body mass index, serum vitamin D, and testosterone levels were measured for each participant. Body mass index was categorized into normal, overweight, and obese. Statistical analysis was calculated, including descriptive statistics, logistic regression, and correlation analysis to evaluate associations between these variables. Results The mean BMI of the participants was 25.82 ± 7.88 kg/m². A significant inverse correlation was observed between BMI and vitamin D levels (r = -0.79, p < 0.001) and between BMI and testosterone levels (r = -0.87, p < 0.001). A positive correlation was found between vitamin D and testosterone levels (r = 0.87, p < 0.001). Logistic regression analysis revealed that higher BMI in the range of overweight or above was associated with a 2.5-fold increase in the likelihood of vitamin D deficiency (odds ratio (OR) = 2.50, 95% CI = 1.8-3.5, p < 0.001) and a 3.1-fold increase in the likelihood of low testosterone levels (OR = 3.10, 95% CI = 2.2-4.3, p < 0.001). Conclusion In this study, higher BMI is significantly associated with lower vitamin D and testosterone levels. These findings suggest that addressing obesity could help mitigate hormonal imbalances, such as vitamin D deficiency and low testosterone, which are linked to metabolic health risks. It can also be hypothesized that obesity can be a risk factor for vitamin D and testosterone deficiency., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Ethical Board (IREB) committee of Medical Teaching Institute (MTI)-Hayatabad Medical Complex Peshawar issued approval (Doc No. HMC-QAD-F-00; Approval no. 2211). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Iftikhar et al.)

Adults aged ≥65 years experience the highest risk for COVID-19-related hospitalization and death, with risk increasing with increasing age; outpatient antiviral treatment reduces the risk for these severe outcomes. Despite the proven benefit of COVID-19 antiviral treatment, information on differences in use among older adults with COVID-19 by age group is limited. Nonhospitalized patients aged ≥65 years with COVID-19 during April 2022-September 2023 were identified from the National Patient-Centered Clinical Research Network. Differences in use of antiviral treatment among patients aged 65-74, 75-89, and ≥90 years were assessed. Multivariable logistic regression was used to estimate the association between age and nonreceipt of antiviral treatment. Among 393,390 persons aged ≥65 years, 45.9% received outpatient COVID-19 antivirals, including 48.4%, 43.5%, and 35.2% among those aged 65-75, 76-89, and ≥90 years, respectively. Patients aged 75-89 and ≥90 years had 1.17 (95% CI = 1.15-1.19) and 1.54 (95% CI = 1.49-1.61) times the adjusted odds of being untreated, respectively, compared with those aged 65-74 years. Among 12,543 patients with severe outcomes, 2,648 (21.1%) had received an outpatient COVID-19 antiviral medication, compared with 177,874 (46.7%) of 380,847 patients without severe outcomes. Antiviral use is underutilized among adults ≥65 years; the oldest adults are least likely to receive treatment. To prevent COVID-19-associated morbidity and mortality, increased use of COVID-19 antiviral medications among older adults is needed., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Faraz S. Ahmad reports receipt of consulting fees and editorial support from Pfizer. Thomas W. Carton reports receipt of grant support from the Task Force for Global Health. No other potential conflicts of interest were disclosed.

The present study evaluates the amelioration of fat clay by blending it with cohesive non-swelling soil (CNS) and cohesionless silty sandy soil (Kassu). The fat clay sample with a liquid limit (LL) of 50 and a plasticity index (PI) of 26 was collected from Narowal, while CNS and Kassu samples were procured from Lahore's outskirts. Geotechnical tests on the virgin soil indicated its unsuitability for construction. Laboratory tests, including modified Proctor compaction, unconfined compression, California bearing ratio (CBR), and one-dimensional consolidation, were performed on samples blended with 0-35% CNS or Kassu in 5% intervals. The LL and PI of fat clay decreased significantly with the addition of 35% CNS (LL: 50-32%, PI: 24 to 13) and Kassu (LL: 50-29%, PI: 24-12). The CBR value increased from 4 to 7%, making the blended soil suitable for subgrade use. Unconfined compression tests showed a strength increase from 102 to 185 kPa with 35% CNS and up to 140 kPa with 25% Kassu. Compaction tests revealed improved maximum dry unit weight and reduced optimum moisture content. Swell potential decreased from 4 to 1.2 and 0.26% with CNS and Kassu additions. Regression models predict swell pressure and ultimate swell potential. The study concludes that blending fat clay with CNS and Kassu significantly improves its geotechnical properties, with CNS being more effective in controlling swell characteristics., (© 2024. The Author(s).)

Competing Interests: There are no conflicts of interest.

Importance: Long-term symptoms, lasting more than 4 consecutive weeks after acute COVID-19 disease, are an important consequence of SARS-CoV-2 infection. Many prior studies have lacked a non-SARS-CoV-2-infected control population to distinguish background prevalence of symptoms from the direct impact of COVID-19 disease., Objective: To examine the prevalence of long-term physical and mental health symptoms associated with SARS-CoV-2 infection in a large population of blood donors based on self-report and serologic test results., Design, Setting, and Participants: This cross-sectional study included American Red Cross blood donors (aged ≥18 years) who were surveyed between February 22 and April 21, 2022, about new long-term symptoms arising after March 2020 and their SARS-CoV-2 infection status. All participants underwent at least 1 serologic test for antinucleocapsid antibodies between June 15, 2020, and December 31, 2021., Exposures: SARS-CoV-2 infection as defined by a self-reported, confirmed acute infection or antinucleocapsid antibody positivity., Main Outcomes and Measures: New long-term symptoms since March 2020, including 5 symptom categories (neurologic, gastrointestinal, respiratory and cardiac, mental health, and other)., Results: Among 818 361 individuals who received the survey, 272 965 (33.4%) responded, with 238 828 meeting the inclusion criteria (138 576 [58.0%] female; median [IQR] age, 59.0 [47.0-67.0] years). Of the 83 015 individuals with a history of SARS-CoV-2 infection, 43.3% reported new long-term symptoms compared with 22.1% of those without a history of SARS-CoV-2 infection. After controlling for age, sex, race and ethnicity, and number of underlying conditions, those with a history of SARS-CoV-2 infection had an increased odds of new long-term symptoms compared with those without (adjusted odds ratio [AOR], 2.55; 95% CI, 2.51-2.61). Female sex and a history of chronic conditions were associated with new long-term symptoms. Long-term symptoms in the other category (AOR, 4.14; 95% CI, 4.03-4.25), which included changes in taste or smell, and the respiratory and cardiac symptom categories (AOR, 3.21; 95% CI, 3.12-3.31) were most associated with prior SARS-CoV-2 infection. Mental health long-term symptoms were also associated with prior SARS-CoV-2 infection (AOR, 1.05; 95%, CI, 1.02-1.08)., Conclusions and Relevance: This study's findings suggest that long-term symptoms lasting more than 4 weeks are common in the adult population, but there is a significantly higher prevalence among those with SARS-CoV-2 infection. Continued efforts to define and track long-term sequelae of SARS-CoV-2 using a control group without infection and serologic information to include those who had asymptomatic or unidentified infections are needed.

The incidence and prevalence of brain tumours have steadily increased within low- and middle-income countries, similar to patterns seen in high-income countries. In addition to the epidemiological landscape of brain tumours in Pakistan, it is important to consider the economics of brain tumour diagnosis and management to inform policy on neuro-oncological healthcare service delivery. The challenges associated with conducting economic evaluations in LMICs include the ability to receive funding for country-specific estimates, dearth of existing data and methodological development, and the need for investment in economic evaluations of health. Economic evaluations are most useful when funding support is given to country-specific initiatives to allocate resources. Cost and cost components must also be meticulously collected to enable accurate calculations of economic evidence for the decision-making process. To put neuro-oncological care at the forefront of the national health agenda, it is crucial for vigorous epidemiological and economic evidence to be available for policymakers.

Guidelines for low- and middle-income countries (LMICs) are needed in complex, multidisciplinary areas such as oncology, requiring mobilising considerable resources and specialists for coordinated care. Neuro-oncology guidelines have been primarily established in countries where technological advancements and robust care pathways facilitate broad resource utilisation. In contrast, LMICs require complex and region-specific interventions to provide equitable care. The present opinion paper is a culmination of our own centre's experience collaborating and developing loco-regional guidelines for brain tumour care, keeping in mind LMIC experiences and expertise available. We intend for the process and methodology to apply to a broader audience of other LMIC authors and clinicians collaborating with LMIC institutions to develop guidelines and clinical recommendations.

Over the past few decades, the global healthcare community has achieved remarkable success in controlling many communicable diseases across various regions. However, non-communicable diseases now constitute a significant portion of disease morbidity and mortality, particularly in low- and middle-income countries (LMICs). Among these, cancer, in particular, is witnessing a notable increase in incidence in many LMICs. Among cancers, neurological tumours bear significant impact in terms of long-term disability, escalating costs of comprehensive multidisciplinary care, and often encounter resource-related and systemic delays in care leading to worse outcomes. This opinion paper discusses key concepts in developing global neuro-oncology care, with specific case examples from Pakistan to illustrate methods for improving care in these underserved regions. Additionally, it outlines strategic approaches and potential solutions to address these challenges, aiming to provide a roadmap for enhancing neuro-oncology care in LMICs.

Background: Oculocutaneous albinism (OCA) is a group of skin depigmentation disorders. Clinical presentation of OCA includes defects in melanocyte differentiation, melanin biosynthesis, and melanosome maturation and transport., Objectives: A molecular diagnostics study of families presenting oculocutaneous albinism., Methods: In this study, 17 consanguineous OCA families consisting of 93 patients were investigated. Whole Exome Sequencing (WES) of the index patient in each family were performed. Short listed variants of WES were Sanger validated for Mendelian segregation in obligate carriers and other available family members. Variant prioritization and pathogenicity were classified as per the criteria of American College Medical Genetics and Genomics (ACMG). Comparative computational modelling was performed to predict the potential damaging effect of the altered proteins., Results: 15 pathogenic variations: c.132 T > A, c.346C > T, c.488C > G, c.1037G > A in TYR, c.1211C > T, c.1441G > A, c.1706&#95;1707insT, c.2020C > G, c.2402G > C, c.2430del, in OCA2, c.1067G > A in TYRP1 and c.451C > T, c.515G > T, c.766C > T, c.917G > A in MC1R genes were identified. Three variants in OCA2 gene were characterized: c.1706&#95;1707insT, c.2430del, and c.2402G > C, all of which were not reported before in OCA families., Conclusion: A few studies focusing on mutation screening of OCA patients have been reported before; however, this study has uniquely presents the Pakhtun ethnic population residing on the North-Western boarder. It explains that TYR, OCA2, TYRP1, and MC1R variations lead to non-syndromic OCA phenotype The overlapping phenotypes of OCA can precisely be diagnosed for its molecular pathogenicity using WES. This study recommends WES as a first-line molecular diagnostic tool, and provides a basis for developing customized genetic tests i.e. pre-marital screening to reduce the disease burden in the future generations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Importance: The association of adjuvant chemotherapy (AC) with survival in the general population of patients with resected biliary tract cancer (BTC) remains controversial. As such, the role of this treatment in the treatment of older adult patients (aged ≥70 years) needs to be evaluated., Objective: To describe the patterns of use of AC and compare survival outcomes of AC and observation in older adult patients following resection of BTC., Design, Setting, and Participants: This retrospective cohort study included 8091 older adult patients with resected BTC with data available in the National Cancer Database from January 1, 2004, to December 31, 2019. Patients were divided into 2 cohorts: AC and observation. The AC cohort was subdivided into single-agent and multiagent AC treatment., Exposures: Adjuvant chemotherapy vs observation following BTC resection., Main Outcomes and Measures: The primary outcome was overall survival (OS) of patients who received AC compared with observation following resection of BTC as evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Inverse probability of treatment weighting and propensity score matching were performed to address indication bias., Results: Between 2004 and 2019, of 8091 older adult patients with resected BTC identified (median [range] age, 77 [70-90] years; 5136 women [63.5%]; 2955 men [36.5%]), only one-third (2632 [32.5%]) received AC. There was an increase in the use of AC across the study period from 20.7% (n = 495) in 2004 to 2009 to 41.2% (n = 856) in 2016 to 2019. Age 80 years or older (odds ratio, 0.29; 95% CI, 0.25-0.33; P < .001) and gallbladder primary site (odds ratio, 0.71; 95% CI, 0.61-0.83; P < .001) were associated with a lower odds of AC. Following inverse probability of treatment weighting, as a composite, AC was not associated with improved survival (median OS, 20.5 months; 95% CI, 19.2-21.7 months) compared with observation (median OS, 19.0 months; 95% CI, 18.1-20.3 months). A longer median OS was associated with single-agent AC (21.5 months; 95% CI, 19.9-24.0 months) but not multiagent AC (19.1 months; 95% CI, 17.5-21.1 months) compared with observation (median OS, 17.3 months; 95% CI, 16.1-18.4 months). This improvement in OS with single-agent AC was not apparent on multivariable analysis (hazard ratio [HR], 0.97; 95% CI, 0.89-1.05; P = .44). However, age at diagnosis of 80 years or older (HR, 1.35; 95% CI, 1.28-1.42; P < .001) and treatment at nonacademic centers (HR, 1.14; 95% CI, 1.07-1.20, P < .001) were associated with worse OS., Conclusions and Relevance: In this cohort study of older adult patients, AC was not associated with an improvement in survival compared with observation following BTC resection. These findings suggest the need for further study of AC for older adult patients who may benefit after curative intent surgery for BTC.

Background: The Federal Ministry of National Health Services, Regulations and Coordination (MNHSR&C) in Pakistan has committed to progress towards universal health coverage (UHC) by 2030 by providing an Essential Package of Health Services (EPHS). Starting in 2019, the Disease Control Priorities 3rd edition (DCP3) evidence framework was used to guide the development of Pakistan's EPHS. In this paper, we describe the methods and results of a rapid costing approach used to inform the EPHS design process., Methods: A total of 167 unit costs were calculated through a context-specific, normative, ingredients-based, and bottom-up economic costing approach. Costs were constructed by determining resource use from descriptions provided by MNHSR&C and validated by technical experts. Price data from publicly available sources were used. Deterministic univariate sensitivity analyses were carried out., Results: Unit costs ranged from 2019 US$ 0.27 to 2019 US$ 1478. Interventions in the cancer package of services had the highest average cost (2019 US$ 837) while interventions in the environmental package of services had the lowest (2019 US$ 0.68). Cost drivers varied by platform; the two largest drivers were drug regimens and surgery-related costs. Sensitivity analyses suggest our results are not sensitive to changes in staff salary but are sensitive to changes in medicine pricing., Conclusion: We estimated a large number of context-specific unit costs, over a six-month period, demonstrating a rapid costing method suitable for EPHS design., (© 2024 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

As benign as its nature is, a febrile seizure (FS) can be one of the most frightening experiences for parents to witness. It is a seizure that occurs in infants and children aged six months to five years, accompanied by a fever (with a temperature of at least 100.4°F or 38.0°C by any method), without any infection in the central nervous system. FS is typically benign and tends to resolve on its own. Overall, the risk of recurrence after an FS is high, so there is still a sizable knowledge discrepancy that needs to be addressed for better understanding and management of the disease. Thus, the objective of this review is to evaluate current therapeutic modalities available for FS and summarize recent recommendations on the management of this condition. On June 25, 2023, a review was undertaken using the Medical Subject Headings Tool (MeSH), and the following keywords yielded 867 results: seizures, febrile/drug therapy [Mesh] and seizures, and febrile/therapy [Mesh]. A total of 21 relevant articles were chosen for the research. Seizures were classified as simple and complex FS (CFS) based on clinical features. CFS usually results in recurrence. Certain investigations like computed tomography (CT) scans, magnetic resonance imaging (MRIs), and electroencephalography (EEG) are helpful, along with laboratory investigations, to rule out other causes of FS. After reviewing the current literature, we have tried to conclude whether the current pharmacotherapy is effective in treating FS., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Patel et al.)

Background: Cellulase is an important bioprocessing enzyme used in various industries. This study was conducted with the aim of improving the biodegradation activity of cellulase obtained from the Bacillus subtilis AG-PQ strain. For this purpose, AgO and FeO NPs were fabricated using AgNO 3 and FeSO 4 ·7H 2 O salt respectively through a hydro-thermal method based on five major steps; selection of research-grade materials, optimization of temperature, pH, centrifuge, sample washed with distilled water, dry completely in the oven at the optimized temperature and finally ground for characterization. The synthesized NPs were characterized by scanning electron microscope (SEM), energy dispersive X-ray (EDX), and X-ray diffraction (XRD) to confirm the morphology, elemental composition, and structure of the sample respectively. The diameter of the NPs was recorded through SEM which lay in the range of 70-95 nm., Results: Cultural parameters were optimized to achieve better cellulase production, where incubation time of 56 h, inoculum size of 5%, 1% coconut cake, 0.43% ammonium nitrate, pH 8, and 37 °C temperature were found optimal. The enhancing effect of AgO NPs was observed on cellulase activity (57.804 U/ml/min) at 50 ppm concentration while FeO NPs exhibited an inhibitory effect on cellulase activity at all concentrations. Molecular docking analysis was also performed to understand the underlying mechanism of improved enzymatic activity by nanocatalysts., Conclusion: This study authenticates AgO NPs as better nanocatalysts for improved thermostable cellulase biodegradation activity with the extraordinary capability to be potentially utilized in bioethanol production., (© 2023. The Author(s).)

Glioblastoma (GBM) is the most common lethal primary brain cancer in adults. Despite treatment regimens including surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy, growth of residual tumor leads to therapy resistance and death. At recurrence, a quarter to a third of all gliomas have hypermutated genomes, with mutational burdens orders of magnitude greater than in normal tissue. Here, we quantified the mutational landscape progression in a patient's primary and recurrent GBM, and we uncovered Cas9-targetable repeat elements. We show that CRISPR-mediated targeting of highly repetitive loci enables rapid elimination of GBM cells, an approach we term "genome shredding." Importantly, in the patient's recurrent GBM, we identified unique repeat sequences with TMZ mutational signature and demonstrated that their CRISPR targeting enables cancer-specific cell ablation. "Cancer shredding" leverages the non-coding genome and therapy-induced mutational signatures for targeted GBM cell depletion and provides an innovative paradigm to develop treatments for hypermutated glioma., Competing Interests: Declaration of interests The Regents of the University of California and the J. David Gladstone Institutes have filed a patent related to this work, on which C.F. is listed as inventor. Silico Therapeutics has filed a patent related to this work, on which A.R.P. and X.S. are listed as inventors. J.A.D. is a co-founder of Caribou Biosciences, Editas Medicine, Intellia Therapeutics, Scribe Therapeutics, and Mammoth Biosciences. J.A.D. is a scientific advisory board member of Caribous Biosciences, Intellia Therapeutics, eFFECTOR Therapeutics, Scribe Therapeutics, Synthego, Metagenomi, Mammoth Biosciences, and Inari. J.A.D. is a member of the board of directors at Driver and Johnson & Johnson. C.F. is a co-founder of Mirimus, Inc., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

COVID-19 vaccines protect against severe COVID-19-associated outcomes, including hospitalization and death. As SARS-CoV-2 has evolved, and waning vaccine effectiveness has been noted, vaccine formulations and policies have been updated to provide continued protection against severe illness and death from COVID-19. Since September 2022, bivalent mRNA COVID-19 vaccines have been recommended in the United States, but the variants these vaccines protect against are no longer circulating widely. On September 11, 2023, the Food and Drug Administration (FDA) approved the updated (2023-2024 Formula) COVID-19 mRNA vaccines by Moderna and Pfizer-BioNTech for persons aged ≥12 years and authorized these vaccines for persons aged 6 months-11 years under Emergency Use Authorization (EUA). On October 3, 2023, FDA authorized the updated COVID-19 vaccine by Novavax for use in persons aged ≥12 years under EUA. The updated COVID-19 vaccines include a monovalent XBB.1.5 component, which is meant to broaden vaccine-induced immunity and provide protection against currently circulating SARS-CoV-2 XBB-sublineage variants including against severe COVID-19-associated illness and death. On September 12, 2023, the Advisory Committee on Immunization Practices recommended vaccination with updated COVID-19 vaccines for all persons aged ≥6 months. These recommendations will be reviewed as new evidence becomes available or new vaccines are approved and might be updated., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

The whiteflies of Bemisia tabaci complex, composed of >44 cryptic species, are economically important pests of tomatoes for their direct feeding and virus transmission. The present study aimed to evaluate the impact of leaf trichomes on the host selection and development of whitefly; comparative invasiveness between B. tabaci Q and A cryptic species; and the ability of weeds as hosts of the population of insect whitefly. We carried out our investigation through adult host selection and oviposition in multi-choice conditions, immature development and survival, and adult survival and oviposition in no-choice conditions. We investigated leaf trichomes type and densities on the leaves of four tomato varieties and two weed species. Results showed that the leaf trichomes of tomatoes and weeds impact the host selection and immature development differently on the cryptic species B. tabaci Q and A. In the multi-choice case, B. tabaci Q adults preferred tomato varieties Ao-Ni-Er and He-Fen for both settling and oviposition whereas B. tabaci A preferred Ao-Ni-Er, He-Fen, and Billy-Goat-Weed for settling but oviposited more eggs on both weed species Billy-Goat-Weed and False-Mallow. Both B. tabaci Q and A adults refused Ye-Sheng either settling or oviposition. In the case of immature development, B. tabaci Q developed faster than B. tabaci A. Concerning plant, B. tabaci Q developed faster on Ao-Ni-Er, He-Fen and Billy-Goat-Weed but B. tabaci A on Billy-Goat-Weed, False-Mallow and Ao-Ni-Er. The immature survival of Q was higher than that of A. Immature of B. tabaci Q survived well (68.6-86.8%) on all plants except Ye-Sheng (49.3%) but B. tabaci A survived very less (0-17.6%) on any tomatoes where 70.4% on Billy-Goat-Weed and 60.5% on False-Mallow. After seven days of adult infestation, both B. tabaci Q and A died on Ye-Sheng where 52.5-78.1% survivorships were observed on other plants. In seven days, B. tabaci Q laid more eggs compared to B. tabaci A. Considering the plants, both species laid more eggs on Ao-Ni-Er, He-Fen and False-Mallow, whereas the lowest number was laid on Ye-Sheng. The highest number of glandular trichome Type IV was observed on Ye-Sheng which showed resistance against both B. tabaci Q and A cryptic species. The cryptic species B. tabaci Q showed a wider range adaptation ability on plants than that of A. Weeds can play a significant role as an infestation source of whiteflies to tomatoes and other crops. These findings suggest that glandular trichomes may be used in plant breeding programmes for the development of whitefly-resistant crop cultivars., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction An intertrochanteric (IT) femur fracture is an extra-capsular fracture between greater and lesser trochanters. Unstable IT fractures are those where there is poor contact between fracture fragments (especially medial and posterior cortices), comminution, and fracture pattern, such that the weight-bearing forces tend to displace the fracture further or a reverse oblique type. Proximal femoral nailing (PFN) is one of the modalities for proximal femoral fractures. A newer modality for proximal femoral fracture is PFNA2, i.e., PFN anti-rotation, which makes use of a helical blade for a better compaction of bone. Both nail designs (PFN and PFNA2) are available in short and long sizes (so a total of four variants). Only a few studies have compared the treatment of IT femur fracture concerning fracture geometry, design, and length using either of the two nail types. In our study, we assessed the surgical and functional outcomes of PFN and PFNA2. Materials and methods This prospective observational study was carried out on 30 patients who had sustained IT fractures of the femur. All cases of IT femur fractures more than 18 years of age, closed injuries, and the patients who consented to participate in this program were included in the study. All open injuries, the patients who refused to participate in this program, patients who have associated injuries, patients with a subtrochanteric femur fracture, and patients with less than six months of follow-up were excluded. The patients were randomized into two types of implant groups. All patients were operated with a standard protocol. The study was conducted for 18 months from February 2021 to August 2022. The results were analyzed (of all four variants) by comparing patient demographics, implant size, implant type, locking methods, union time, and other parameters. Results Most of the patients were operated on with a 10 mm nail diameter (17/30 patients), 380 mm length (long-nail group) (five/11 patients), and 250 mm length (short-nail group). With the use of PFNA2, the overall duration of hospital stay was less. The overall operative time (incision to wound closure) with the use of the short PFNA2 was lesser than that with the use of other designs due to the use of the zig for distal screws. The use of a distal dynamic locking screw in a majority of the patients can get better compression at the fracture site once the patient starts weight bearing and decrease the chances of the Z-effect, reverse Z-effect, screw back-out, and screw cut-out. The union time was nearly the same in the majority of the patients, with an early union seen with the use of PFNA2 nails. The overall modified Harris hip score (HHS) at the final follow-up was nearly the same with slightly better results with the use of PFNA2. Conclusions PFNA2 is the implant of choice in elderly patients with osteoporotic bone. It has less operative time, which is required in such patients with medical comorbidities; hence, it has marginal superiority over PFN. Short-nail design results in less operative time and less blood loss., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Shah et al.)

Dorsal and ventral medial entorhinal cortex (mEC) regions have distinct neural network firing patterns to differentially support functions such as spatial memory. Accordingly, mEC layer II dorsal stellate neurons are less excitable than ventral neurons. This is partly because the densities of inhibitory conductances are higher in dorsal than ventral neurons. Here, we report that T-type Ca 2+ currents increase 3-fold along the dorsal-ventral axis in mEC layer II stellate neurons, with twice as much Ca V 3.2 mRNA in ventral mEC compared with dorsal mEC. Long depolarizing stimuli trigger T-type Ca 2+ currents, which interact with persistent Na + currents to elevate the membrane voltage and spike firing in ventral, not dorsal, neurons. T-type Ca 2+ currents themselves prolong excitatory postsynaptic potentials (EPSPs) to enhance their summation and spike coupling in ventral neurons only. These findings indicate that T-type Ca 2+ currents critically influence the dorsal-ventral mEC stellate neuron excitability gradient and, thereby, mEC dorsal-ventral circuit activity., Competing Interests: Declaration of interests The authors declare no completing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Streptococcus pneumoniae is the major bacterial pathogen causing high pneumonia morbidity and mortality in children <5 years of age. This study aimed to determine the molecular epidemiology of S. pneumoniae detected among hospitalized pediatric ARI cases at Khanh Hoa General Hospital, Nha Trang, Vietnam, from October 2015 to September 2016 (pre-PCV). We performed semi-quantitative culture to isolate S. pneumoniae . Serotyping, antimicrobial susceptibility testing, resistance gene detection and multi-locus sequence typing were also performed. During the study period, 1300 cases were enrolled and 413 (31.8%) S. pneumoniae were isolated. School attendance, age <3 years old and prior antibiotic use before admission were positively associated with S. pneumoniae isolation. Major serotypes were 6A/B (35.9%), 19F (23.7%) and 23F (12.7%), which accounted for 80.3% of vaccine-type pneumococci. High resistance to Clarithromycin, Erythromycin and Clindamycin (86.7%, 85%, 78.2%) and the mutant drug-resistant genes pbp1A (98.1%), pbp2b (98.8%), pbp2x (99.6%) ermB (96.6%) and mefA (30.3%) were detected. MLST data showed high genetic diversity among the isolates with dominant ST 320 (21.2%) and ST 13223 (19.3%), which were mainly found in Vietnam. Non-typeables accounted for most of the new STs found in the study. Vaccine-type pneumococcus and macrolide resistance were commonly detected among hospitalized pediatric ARI cases.

Oncological outcomes are improving in gastrointestinal cancer with advancements in systemic therapies, and there is notable potential in combining immunotherapy and radiation therapy (RT) to allow for further improvements. Various preclinical and early phase II studies have shown promising synergy with immunotherapy and RT in gastrointestinal cancer. A few recent phase III studies have shown improved survival with the addition of immunotherapy to standard treatment for gastrointestinal cancer. The timing, duration, sequencing, and integration with other anti-cancer treatments are still areas of ongoing research. We have reviewed the published and ongoing studies of the combinations of immunotherapy and RT in gastrointestinal cancers.

Multidrug-resistant Vibrio cholerae O1 strains have long been observed in Africa, and strains exhibiting new resistance phenotypes have emerged during recent epidemics in Kenya. This study aimed to determine the epidemiological aspects, drug resistance patterns, and genetic elements of V. cholerae O1 strains isolated from two cholera epidemics in Kenya between 2007 and 2010 and between 2015 and 2016. A total of 228 V. cholerae O1 strains, including 226 clinical strains isolated from 13 counties in Kenya during the 2007-2010 and 2015-2016 cholera epidemics and two environmental isolates (from shallow well water and spring water isolates) isolated from Pokot and Kwale Counties, respectively, in 2010 were subjected to biotyping, serotyping, and antimicrobial susceptibility testing, including the detection of antibiotic resistance genes and mobile genetic elements. All V. cholerae isolates were identified as El Tor biotypes and susceptible to ceftriaxone, gentamicin, and ciprofloxacin. The majority of isolates were resistant to trimethoprim-sulfamethoxazole (94.6%), streptomycin (92.8%), and nalidixic acid (64.5%), while lower resistance was observed against ampicillin (3.6%), amoxicillin (4.2%), chloramphenicol (3.0%), and doxycycline (1.8%). Concurrently, the integrating conjugative (SXT) element was found in 95.5% of the V. cholerae isolates; conversely, class 1, 2, and 3 integrons were absent. Additionally, 64.5% of the isolates exhibited multidrug resistance patterns. Antibiotic-resistant gene clusters suggest that environmental bacteria may act as cassette reservoirs that favor resistant pathogens. On the other hand, the 2015-2016 epidemic strains were found susceptible to most antibiotics except nalidixic acid. This revealed the replacement of multidrug-resistant strains exhibiting new resistance phenotypes that emerged after Kenya's 2007-2010 epidemic. IMPORTANCE Kenya is a country where cholera is endemic; it has experienced three substantial epidemics over the past few decades, but there are limited data on the drug resistance patterns of V. cholerae at the national level. To the best of our knowledge, this is the first study to investigate the antimicrobial susceptibility profiles of V. cholerae O1 strains isolated from two consecutive epidemics and to examine their associated antimicrobial genetic determinants. Our study results revealed two distinct antibiotic resistance trends in two separate epidemics, particularly trends for multidrug-associated mobile genetic elements and chromosomal mutation-oriented resistant strains from the 2007-2010 epidemic. In contrast, only nalidixic acid-associated chromosomal mutated strains were isolated from the 2015-2016 epidemic. This study also found similar patterns of antibiotic resistance in environmental and clinical strains. Continuous monitoring is needed to control emerging multidrug-resistant isolates in the future., Competing Interests: The authors declare no conflict of interest.

T cells are a critical component of the response to SARS-CoV-2, but their kinetics after infection and vaccination are insufficiently understood. Using "spheromer" peptide-MHC multimer reagents, we analyzed healthy subjects receiving two doses of the Pfizer/BioNTech BNT162b2 vaccine. Vaccination resulted in robust spike-specific T cell responses for the dominant CD4 + (HLA-DRB1 ∗ 15:01/S191) and CD8 + (HLA-A ∗ 02/S691) T cell epitopes. Antigen-specific CD4 + and CD8 + T cell responses were asynchronous, with the peak CD4 + T cell responses occurring 1 week post the second vaccination (boost), whereas CD8 + T cells peaked 2 weeks later. These peripheral T cell responses were elevated compared with COVID-19 patients. We also found that previous SARS-CoV-2 infection resulted in decreased CD8 + T cell activation and expansion, suggesting that previous infection can influence the T cell response to vaccination., Competing Interests: Declaration of interests V.M. and M.M.D. are inventors on a patent application (PCT/US2021/064378) on the spheromer technology described in this work., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Global climate change and extreme weather events are associated with epigenetic modifications in immune cells, leading to the possible increased risk and prevalence of allergies and autoimmune diseases., (© 2023 The Authors.)

Background: Esophagectomy is an important, but potentially morbid, operation used to treat benign and malignant conditions that may significantly impact patient quality of life (QOL). Patient-reported outcomes (PROs) are measures of QOL that come directly from patient self-report. This study characterizes patterns of change and recovery in PROs in the first year after esophagectomy., Methods: Longitudinal QOL scores measuring physical function, pain, and dyspnea were obtained from esophagectomy patients during all clinic visits. PRO scores were obtained using the National Institutes of Health-sponsored Patient-Reported Outcomes Measurement Information System from April 2018 to February 2021. Mean PRO scores over 100 days after surgery were compared with baseline PRO scores using mixed-effects modeling with compound symmetry correlational structure., Results: One hundred three patients with PRO results were identified. Reasons for esophagectomy were malignancy (87.4%), achalasia (5.8%), stricture (5.8%), and dysplasia (1.0%). When comparing mean PRO scores at visits ≤ 50 days after surgery with preoperative PRO scores, physical function scores declined by 27.3% (P < .001), whereas dyspnea severity and pain interference scores had increased by 24.5% (P < .001) and 17.1% (P < .001), respectively. Although recovery occurred over the course of the 100 days after surgery, mean physical function scores and dyspnea scores were still 12.7% (P = .02) and 26.4% (P = .001) worse, respectively, than mean preoperative levels., Conclusions: Despite declines in QOL scores immediately after esophagectomy, recovery back toward baseline was observed during the first 100 days. These findings are of considerable importance when counseling patients regarding esophagectomy, tracking recovery, and implementing quality improvement initiatives. Further long-term follow-up is needed to determine recovery beyond 100 days., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Endocrine-disrupting chemicals (EDCs) are a class of man-made substances with potential to disrupt the standard function of the endocrine system. These EDCs include phthalates, perchlorates, phenols, some heavy metals, furans, dimethoate, aromatic hydrocarbons, some pesticides, and per- and polyfluoroalkyl substances (PFAS). EDCs are widespread in the environment given their frequent use in daily life. Their production, usage, and consumption have increased many-fold in recent years. Their ability to interact and mimic normal endocrine functions makes them a potential threat to human health, aquatics, and wild life. Detection of these toxins has predominantly been done by mass spectroscopy and/or chromatography-based methods and to a lesser extent by advanced sensing approaches such as electrochemical and/or colorimetric methods. Instrument-based analytical techniques are often not amenable for onsite detection due to the lab-based nature of these detecting systems. Alternatively, analytical approaches based on sensor/biosensor techniques are more attractive because they are rapid, portable, equally sensitive, and eco-friendly. Advanced sensing systems have been adopted to detect a range of EDCs in the environment and food production systems. This review will focus on advances and developments in portable sensing techniques for EDCs, encompassing electrochemical, colorimetric, optical, aptamer-based, and microbial sensing approaches. We have also delineated the advantages and limitations of some of these sensing techniques and discussed future developments in sensor technology for the environmental sensing of EDCs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shah, Ahmad, Boota, Jensen, La Frano and Irudayaraj.)

Background: Bacterial and viral infections can occur with SARS-CoV-2 infection, but prevalence, risk factors, and associated clinical outcomes are not fully understood., Methods: We used the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system, to investigate the occurrence of bacterial and viral infections among hospitalized adults with laboratory-confirmed SARS-CoV-2 infection between March 2020 and April 2022. Clinician-driven testing for bacterial pathogens from sputum, deep respiratory, and sterile sites were included. The demographic and clinical features of those with and without bacterial infections were compared. We also describe the prevalence of viral pathogens including respiratory syncytial virus, rhinovirus/enterovirus, influenza, adenovirus, human metapneumovirus, parainfluenza viruses, and non-SARS-CoV-2 endemic coronaviruses., Results: Among 36 490 hospitalized adults with COVID-19, 53.3% had bacterial cultures taken within 7 days of admission and 6.0% of these had a clinically relevant bacterial pathogen. After adjustment for demographic factors and co-morbidities, bacterial infections in patients with COVID-19 within 7 days of admission were associated with an adjusted relative risk of death 2.3 times that of patients with negative bacterial testing. Staphylococcus aureus and Gram-negative rods were the most frequently isolated bacterial pathogens. Among hospitalized adults with COVID-19, 2766 (7.6%) were tested for seven virus groups. A non-SARS-CoV-2 virus was identified in 0.9% of tested patients., Conclusions: Among patients with clinician-driven testing, 6.0% of adults hospitalized with COVID-19 were identified to have bacterial coinfections and 0.9% were identified to have viral coinfections; identification of a bacterial coinfection within 7 days of admission was associated with increased mortality., Competing Interests: Ms. Leegwater and Ms. Reeg report grants from Michigan Department of Health and Human Services during the conduct of the study. Dr. Anderson reports grants from Pfizer, Merck, PaxVax, Micron, Sanofi‐Pasteur, Janssen, MedImmune, and GSK. Dr. Anderson reports personal fees from Sanofi‐Pasteur, Pfizer, Medscape, Kentucky Bioprocessing, Inc, Sanofi‐Pasteur, Janssen, GSK, WCG and ACI Clinical, and Moderna outside the submitted work. His institution has also received funding from NIH to conduct clinical trials of Moderna and Janssen COVID‐19 vaccines. Mr. Weigel reports grants from CDC/CSTE Cooperative Agreement, during the conduct of the study and grants from CDC/CSTE outside the submitted work. Mr. Teno reports grants from CDC/CSTE Cooperative Agreement during the conduct of the study and grants from CDC/CSTE outside the submitted work. Mrs. Billing reports grants from Council of State and Territorial Epidemiologists (CSTE) during the conduct of the study and grants from Centers for Disease Control and Prevention (CDC) outside the submitted work. Mr. Meek reports grants from CDC during the conduct of the study. Dr. Schaffner reports grants from CDC during the conduct of the study. Dr. Sutton reports grants from CDC Emerging Infections Program during the conduct of the study. Dr. Talbot reports grants from Centers for Disease Control and Prevention, during the conduct of the study. Ms. Yousey‐Hindes reports grants from CDC during the conduct of the study., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Betanin, a natural food color and the only betalain, is approved for use in pharmaceutical and food industries as natural antioxidative and preservative agent, respectively. However, the antioxidant power and health-promoting properties of betanin have been disregarded due to its low stability in physiological conditions. Therefore, this study is designed to synthesize and evaluate in vitro pharmacological characteristics of betanin-encapsulated chitosan nanoparticles (ChBetNPs). ChBetNPs were synthesized by ionic gelation method and characterized by DLS, UV, FTIR, SEM and zeta potential analysis. The encapsulation efficiency (EE) and in vitro release kinetics were analyzed using spectrophotometric technique for quantifying the encapsulated amount of betanin in ChBetNPs as a function of time. The antioxidant activity of ChBetNPs was analyzed by DPPH and H 2 O 2 radical scavenging assays, anti-inflammatory activity by protein denaturation and human RBCs stabilization assays, and anti-acetylcholinesterase activity using standard protocol with minor modifications. Unloaded chitosan nanoparticles (CSNPs) were found to be sized at 161.4 ± 5.75 nm while an increase in the size to 270.3 ± 8.50 nm was noticed upon encapsulating betanin. EE of ChBetNPs was measured to be ∼87.5%. The IC 50 of ChBetNPs depicted significant free radical scavenging activities as compared to CSNPs. Similarly, a strong anti-inflammatory activity of ChBetNPs was noted. Significant decrease in acetylcholinesterase activity by ChBetNPs was measured (IC 50 0.5255 μg/mL vs. control 26.09 μg/mL). The vegetables coated with 3% ChBetNPs showed decreased weight loss as compared to uncoated control. ChBetNPs was shown to exhibit strong antioxidant, anti-inflammatory and anti-acetylcholinesterase activities thus making it a significant therapeutic agent for the management of Alzheimer's disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)