Revolutionising infection control: building the next generation of phage banks.

The escalating global burden of antimicrobial resistance (AMR) represents a critical public health challenge. This rise in antibiotic resistance is concomitant with heightened antibiotic consumption, with an estimated annual usage of 100,000 to 200,000 tons. A recent systematic review, which analysed data from 204 countries, reported that AMR was responsible for 4.95 million deaths in 2019 (Murray et al., 2022). The growing threat of AMR is imposing a significant financial burden on the global economy, with the CDC reporting an additional annual cost of $20 billion in the U.S. and €9 billion in Europe. The emerging field of bacteriophage therapy offers promising potential as a game-changer in the era of AMR. However, existing literature reveals numerous research gaps and technological challenges, including insufficient information on phage pharmacology, genomics, and a lack of preclinical and clinical data. In addition to conducting further research to address existing knowledge gaps, establishing phage banks in clinical facilities could be a transformative advancement in the fight against AMR.

Unveiling Endogenous Serum Peptides as Potential Biomarkers for Hepatocellular Carcinoma in Patients with Liver Cirrhosis.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, mainly associated with liver cirrhosis. Current diagnostic methods for HCC have limited sensitivity and specificity, highlighting the need for improved early detection and intervention. In this study, we used a comprehensive approach involving endogenous peptidome along with bioinformatics analysis to identify and evaluate potential biomarkers for HCC. Serum samples from 40 subjects, comprising 20 HCC cases and 20 patients with liver cirrhosis (CIRR), were analyzed. Among 2568 endogenous peptides, 67 showed significant differential expression between the HCC vs CIRR. Further analysis revealed three endogenous peptides (VMHEALHNHYTQKSLSLSPG, NRFTQKSLSLSPG, and SARQSTLDKEL) that showed far better performance compared to AFP in terms of area under the receiver operating characteristic curve (AUC), showcasing their potential as biomarkers for HCC. Additionally, endogenous peptide IAVEWESNGQPENNYKT that belongs to the precursor protein Immunoglobulin heavy constant gamma 4 was detected in 100% of the HCC group and completely absent in the CIRR group, suggesting a promising diagnostic biomarker. Gene ontology and pathway analysis revealed the potential involvement of these dysregulated peptides in HCC. These findings provide valuable insights into the molecular basis of HCC and may contribute to the development of improved diagnostic methods and therapeutic targets for HCC.

Synthesis of Pyrazolo[3,4-b]pyridine Derivatives and Their In-Vitro and In-Silico Antidiabetic Activities.

In the current study, new pyrazolo[3,4-b]pyridine esters, hydrazides, and Schiff bases have been synthesized starting from 3-methyl-1-phenyl-1H-pyrazol-5-amine. The first step involved solvent-free synthesis of pyrazolo[3,4-b]pyridine-6-carboxylate derivatives (2a-d) with 55%-70% yield in the minimum time frame compared with the conventional refluxing method, which was followed by the synthesis of corresponding hydrazides (3a-d) and hydrazones (4a-e). The structures of the synthesized derivatives were confirmed using element analysis, FT-IR, 1H NMR, 13C NMR, and LC-MS techniques. Synthesized hydrazides (3a-d) and hydrazones (4a-e) were also tested for their in-vitro antidiabetic activity and found that all the compounds exhibited significant antidiabetic activity, while 3c (IC50 = 9.6 ± 0.5 µM) among the hydrazides and 4c (IC50 = 13.9 ± 0.7 µM) among the hydrazones were found to be more active in comparison to other synthesized derivatives. These in-vitro results were further validated via docking studies against the α-amylase enzyme using the reference drug acarbose (200.1 ± 10.0 µM). The results were greatly in agreement with their in-vitro studies and these derivatives can be encouraging candidates for further in-vivo studies in mice models.

Improved pediatric ICU mortality prediction for respiratory diseases: machine learning and data subdivision insights.

The growing concern of pediatric mortality demands heightened preparedness in clinical settings, especially within intensive care units (ICUs). As respiratory-related admissions account for a substantial portion of pediatric illnesses, there is a pressing need to predict ICU mortality in these cases. This study based on data from 1188 patients, addresses this imperative using machine learning techniques and investigating different class balancing methods for pediatric ICU mortality prediction. This study employs the publicly accessible "Paediatric Intensive Care database" to train, validate, and test a machine learning model for predicting pediatric patient mortality. Features were ranked using three machine learning feature selection techniques, namely Random Forest, Extra Trees, and XGBoost, resulting in the selection of 16 critical features from a total of 105 features. Ten machine learning models and ensemble techniques are used to make accurate mortality predictions. To tackle the inherent class imbalance in the dataset, we applied a unique data partitioning technique to enhance the model's alignment with the data distribution. The CatBoost machine learning model achieved an area under the curve (AUC) of 72.22%, while the stacking ensemble model yielded an AUC of 60.59% for mortality prediction. The proposed subdivision technique, on the other hand, provides a significant improvement in performance metrics, with an AUC of 85.2% and an accuracy of 89.32%. These findings emphasize the potential of machine learning in enhancing pediatric mortality prediction and inform strategies for improved ICU readiness.

Systemic lupus erythematosus is associated with increased risk of mortality and acute kidney injury in patients with COVID-19 hospitalization: Insights from a National Inpatient Sample analysis.

INTRODUCTION: The COVID-19 pandemic has significantly impacted global health, especially for patients with chronic diseases that may compromise the immune system. This study investigates the association between systemic lupus erythematosus (SLE) and COVID-19 outcomes. METHODS: Data from the National Inpatient Sample (NIS) were analyzed to create a retrospective cohort of COVID-19 hospitalizations, comparing patients with and without SLE. Propensity-score matched analysis was conducted to assess the association between SLE and clinical outcomes in COVID-19 hospitalizations. RESULTS: The study included over a million COVID-19 hospitalizations, with approximately 0.5% having a secondary diagnosis of SLE. The SLE-COVID hospitalizations were predominantly female and younger, with a median age of 57.2, while the non-SLE-COVID group had a median age of 64.8 years. Comorbidities such as chronic obstructive pulmonary disease, renal failure, liver disease, and others were more prevalent in the SLE-COVID group. Patients with SLE and COVID-19 had a significantly higher incidence of acute kidney injury requiring dialysis than those without SLE. In-hospital mortality was higher in the SLE group, particularly in the 18-44 year age group (6.15% vs 2.47%, p = .022). CONCLUSION: COVID-19 patients with SLE are at an increased mortality risk, especially in the younger age group, and a higher incidence of acute kidney injury requiring dialysis. The elevated risk of adverse outcomes underscores the vulnerability of SLE patients to COVID-19. These findings emphasize the importance of special precautions and patient education for individuals with SLE to mitigate the risks associated with COVID-19.

Effects of exercise on sex steroid hormones (estrogen, progesterone, testosterone) in eumenorrheic females: A systematic to review and meta-analysis.

BACKGROUND: The sex steroid hormones fluctuate during the menstrual cycle, which affects the strength and postural stability of females and leads to injuries and risk of falls. These hormones may be modulated by exercise to impact the overall health of females. OBJECTIVE: To determine the effects of exercise on sex steroid hormones in eumenorrheic females. METHODS: This review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) guidelines in Lahore, Pakistan. The full-length articles were searched using these databases/search engines (PubMed, Web of Science and Google Scholar, Sci-Hub). Randomized controlled trials along with single group experimental studies were also included. All types of exercises were compared with no exercise in the control group. The Cochrane Risk of Bias assessment tool assessed and screened the articles. The data were then analyzed. The primary outcomes were the levels of estrogen, progesterone and testosterone. RESULTS: Eleven studies were included (5 randomized controlled trials and 6 quasi-experimental studies). The effects of exercise on free estradiol concentration and serum progesterone level were not significant [p = 0.37 (SMD = 0.33, 95% CI = 0.14 to 0.74, I2 = 0%) and p = 0.84 (S.D= -0.65, C.I= -6.92 to 5.62, I2 = 94%)] respectively, whereas, the effects on testosterone levels were significant [p value < 0.00001 (M.D = 0.89, 95% C.I= -2.16 to 3.95, I2 = 94%)]. CONCLUSION: A blinded randomized controlled trial should be conducted in which a structured approach should be followed by women along with warm-ups, cool down and rest intervals. TRIAL REGISTRATION NUMBER: The systematic review was registered prospectively on PROSPERO with registration number CRD42023473767.

Comparison of physical activity levels and dietary habits between women with polycystic ovarian syndrome and healthy controls of reproductive age: a case-control study.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a reproductive hormonal anomaly prevalent among women of reproductive age, with an alarmingly high prevalence of 52% among Pakistani women. This study aims to compare the daily physical activity and dietary habits of women with PCOS with age-matched healthy controls living in Lahore, Pakistan. METHODS: A case-control study design was used to collect data from a private hospital situated in Lahore, Pakistan. Data was collected from 115 participants of reproductive age (18-45 years) using a researcher-administered questionnaire. Demographic variables, reproductive characteristics, anthropometric measurements, and seven days of physical activity levels using the international physical activity questionnaire (IPAQ-Short version) and seven days of dietary intake using the food frequency questionnaire (7 days-FFQ) were used to measure the dietary habits of the participants. Mosby's Nutritac v4.0 software was used to estimate the macronutrients, vitamins, and minerals present in dietary intake. The glycaemic index and glycaemic load were calculated to compare the quality and quantity of carbohydrate consumption between the two groups. RESULTS: The 49 PCOS cases, newly identified using the Rotterdam criteria, mean age 24.63 years (SD ± 4.76), and 66 healthy controls, mean age 23.24 years (SD ± 5.45), were compared. A significant difference (p ≤ 0.05) was found for reproductive characteristics, daily physical activity, and polyunsaturated fat and vitamin intake between the two groups. A binary logistic regression analysis showed that food with a low glycaemic index (GI ≤ 40) reduced the odds of PCOS occurrence by OR = 1.94. Similarly, food nutrients with a low glycaemic load (GL ≤ 10) can reduce PCOS occurrence by OR = 1.60. CONCLUSION: The daily physical activity levels and dietary habits of women of reproductive age can influence their reproductive characteristics and polycystic ovarian morphology. A diet with a low glycaemic load and index can produce beneficial reproductive health effects among women of reproductive age.

Application of the Boruta algorithm to assess the multidimensional determinants of malnutrition among children under five years living in southern Punjab, Pakistan.

BACKGROUND: Malnutrition causes nutrient deficiencies that have both physical and clinical consequences in severe acute malnutrition children. Globally, there were 47 million wasted children under the age of five in 2019. One in four were located in sub-Saharan Africa, with half being in South Asia. This study aims to apply the Boruta algorithm to identify the determinants of undernutrition among children under five living in Dera Ghazi Khan, one of the marginalized districts of densely populated Punjab Province in Pakistan. METHODS: A multicenter cross-sectional study design was used to collect data from 185 children with severe acute malnutrition aged under five years visiting the OTPs centers located in Dera Ghazi Khan, Punjab, Pakistan. A purposive sampling technique was used to collect data using a pretested structured questionnaire from parents/caregivers regarding family sociodemographic characteristics, child nutrition, and biological and healthcare characteristics. Anthropometric measurements, including height, weight, and mid-upper arm circumference, were collected. The Boruta models were used to incorporate the children's anthropometric, nutritional, and household factors to determine the important predictive variables for undernutrition using the Boruta package in R studio. RESULTS: This study included 185 children, with a mean age of 15.36 ± 10.23 months and an MUAC of 10.19 ± 0.96 cm. The Boruta analysis identifies age, mid-upper arm circumference, weaning practices, and immunization status as important predictors of undernutrition. Income per month, exclusive breastfeeding, and immunization status were found to be key factors of undernutrition in children under the age of five. CONCLUSION: This study highlights age, mid-upper arm circumference, weaning practices, and immunization status as key determinants of weight-for-height and weight-for-age in children under five years. It also suggests that economic context may influence undernutrition. The findings can guide targeted strategies for combating undernutrition.

Effects of sustained natural apophyseal glides versus rocabado 6 × 6 program in subjects with cervicogenic headache.

BACKGROUND: Cervicogenic headache is designated as the most common type of secondary headache that results from conditions affecting the neck's bony components, muscles, and intervertebral discs rather than the head itself. OBJECTIVE: The purpose was to determine the effects of Sustained Natural Apophyseal Glides (SNAGs) versus the Rocabado 6 × 6 program in subjects with cervicogenic headaches. METHODS: This study was a randomized clinical trial. The sample size was 38, and participants aged 20-60 years (mean age 40.22 ± 9.66) suffering from cervicogenic headaches were randomly allocated using the lottery method into two groups with 19 participants in each group. Assessment of subjects was done before starting treatment and by the end of the 8th week for all the variables. Outcome measures were the Neck Disability Index (NDI), 6-item Headache Impact Test (HIT-6), Flexion-Rotation test (FRT) to assess the rotation range of motion at the level of C1-C2 (goniometer) and the Numeric Pain Rating Scale (NPRS) for the intensity of pain. Data analysis was done by SPSS (IBM) 25. To check the normality of the data the Shapiro-Wilk test was used. RESULTS: In the Shapiro-Wilk test p-value of all the testing variables i.e. NDI, HIT-6 score, FRT and NPRS was > 0.05, data was normally distributed and parametric tests were used. Group A showed a considerable improvement (p < 0.05) in all variables compared to Group B, while within-group analysis of both groups shows that all outcome measures show significant results (p < 0.05). CONCLUSION: It was concluded that both SNAGs and Rocabado's 6 × 6 exercises were effective for the treatment of cervicogenic headache but the effects of headache SNAG were superior and produced more improvement in intensity of headache, disability, frequency of headache, duration of headache as compared to Rocabado 6 × 6 exercises. TRIAL REGISTRATION NUMBER: This study was registered at ClinicalTrials.gov ID: NCT05865808 on date 19/05/2023.

Mucosal organs exhibit distinct response signatures to hydrogen sulphide in Atlantic salmon (Salmo salar).

Hydrogen sulphide (H2S) is considered an immunotoxicant, and its presence in the water can influence the mucosal barrier functions of fish. However, there is a significant knowledge gap on how fish mucosa responds to low environmental H2S levels. The present study investigated the consequences of prolonged exposure to sub-lethal levels of H2S on the mucosal defences of Atlantic salmon (Salmo salar). Fish were continuously exposed to two levels of H2S (low: 0.05 µM; and high: 0.12 µM) for 12 days. Unexposed fish served as control. Molecular and histological profiling focused on the changes in the skin, gills and olfactory rosette. In addition, metabolomics and proteomics were performed on the skin and gill mucus. The gene expression profile indicated that the gills and olfactory rosette were more sensitive to H2S than the skin. The olfactory rosette showed a dose-dependent response, but not the gills. Genes related to stress responses were triggered at mucosal sites by H2S. Moreover, H2S elicited strong inflammatory responses, particularly in the gills. All mucosal organs demonstrated the key molecular repertoire for sulphide detoxification, but their temporal and spatial expression was not substantially affected by sub-lethal H2S levels. Mucosal barrier integrity was not considerably affected by H2S. Mucus metabolomes of the skin and gills were unaffected, but a matrix-dependent response was identified. Comparing the high-concentration group's skin and gills mucus metabolomes identified altered amino acid biosynthesis and metabolism pathways. The skin and gill mucus exhibited distinct proteomic profiles. Enrichment analysis revealed that proteins related to immunity and metabolism were affected in both mucus matrices. The present study expands our knowledge of the defence mechanisms against H2S at mucosal sites in Atlantic salmon. The findings offer insights into the health and welfare consequences of sub-lethal H2S, which can be incorporated into the risk assessment protocols in salmon land-based farms.

Magnetic nanocomposite of maize offal biomass for effective sequestration of Congo red and methyl orange dyes from contaminated water: modeling, kinetics and reusability.

The current study aims to use a facile and novel method to remove Congo red (CR) and Methyl Orange (MO) dyes from contaminated water with Maize offal biomass (MOB) and its nanocomposite with magnetic nanoparticles (MOB/MNPs). The MOB and MOB/MNPs were characterized with Fourier-transform infrared (FTIR), scanning electron microscopy (SEM), BET, XRD and point of zero charge (pHPZC). The influence of initial CR and MO levels (20-320 mg/L), adsorbent dosage (1-3 g/L), pH (3-9), co-exiting ions, temperature (25-45 °C) and time (15-180 min) was estimated. The findings demonstrated that MOB/MNPs exhibited excellent adsorption of 114.75 and 29.0 mg/g for CR and MO dyes, respectively while MOB exhibited 81.35 and 23.02 mg/g adsorption for CR and MO dyes, respectively at optimum pH-5, and dose 2 g/L. Initially, there was rapid dye removal which slowed down until equilibrium was reached. The interfering/competing ions in contaminated water and elevated temperature favored the dyes sequestration. The MOB/MNPs exhibited tremendous reusability and stability. The dyes adsorption was spontaneous, and exothermic with enhanced randomness. The adsorption effects were well explained with Freundlich model, pseudo second order and Elovich models. It is concluded that MOB/MNPs showed excellent, eco-friendly, and cost-effective potential to decontaminate the water.

Nanocomposite of Maize offal biomass demonstrated higher dyes removal.FTIR, SEM, BET, XRD and pH_PZC provided vital evidence for dyes adsorption.MOB/MNPs displayed excellent stability and reusability for dyes adsorption.Groundwater samples exposed a higher dyes removal.Results were validated with equilibrium and kinetic adsorption models.

Balancing growth and sustainability: COP 28 policy implications of green energy, industrialization, foreign direct investment, and globalization in South Asia.

This research investigates the intricate relationships between economic variables and how they affect South Asian nation's ability to develop sustainably. Given the growing concerns about climate change and global warming brought on by emissions of greenhouse gases, this study looks into the connection between emissions of CO2, green energy, industrialization, foreign direct investment, economic globalization, and financial development from 1995 to 2022. Second-generation panel techniques were employed in this study to look at the relationship between variables because of the potential of residual cross-sectional dependency and heterogeneity. The empirical outcomes display that green energy, economic globalization, and financial development reduce CO2 emissions by 1.839%, 1.223%, and 3.902% respectively. Industrialization and foreign direct investment degrade the environment by 4.302% and 1.893% respectively. A bidirectional causality link between green energy, industrialization, economic globalization, and CO2 emissions was found by Dumitrescu and Hurlin (D-H). Based on our findings, we recommend legislative support for renewable energy, cleaner technologies, and strict environmental regulations, aligning with the Sustainable Development Goals (SDGs). Encouraging FDI, sustainable practices, and financial development can drive economic growth while preserving the environment. As we approach COP28, this holistic approach to sustainable development becomes increasingly vital for South Asian countries to achieve their SDG targets and combat climate change.

Can urea-coated fertilizers be an effective means of reducing greenhouse gas emissions and improving crop productivity?

Given the significance of nitrogen (N) as the most constraining nutrient in agro-ecosystems, it is crucial to develop an updated model for N fertilizers management to achieve higher crop yields while minimizing the negative impacts on the environment. Coated urea is touted as one of the most important controlled-release N fertilizers used in agriculture to reduce cropland emissions and improve nitrogen use efficiency (NUE) for optimal crop yields. The sustainability of coated urea depends on the trade-offs between crop productivity, NUE and greenhouse gas emissions (CO2, CH4 and N2O); however, role of various agro-edaphic factors in influencing these trade-offs remains unclear. To determine the effects of soil properties, climatic conditions, experimental conditions, and type of coated urea on greenhouse gas emissions, NH3 losses, crop productivity, and NUE, we conducted a meta-analysis using data from 76 peer-reviewed studies. Our results showed that the application of coated urea under field conditions contributed to a greater reduction in N2O emissions (-48.67%) and higher NUE (58.72%), but crop yields were not significant. Across different climate regions, subtropical monsoon climate showed a perceptible mitigation for CO2, CH4 and NH3 (-78.38%; -83.33%; -27.46%), while temperate climate reduced N2O emissions by -70.36%. For different crops, only rice demonstrated reduction in CO2, CH4, N2O and NH3 losses. On the other hand, our findings revealed a mitigating trade-off between CO2 and CH4 emissions on medium-textured soils and N2O emissions on fine-textured soils. A significant reduction in N2O and NH3 losses was evident when coated urea was applied to soils with a pH > 5.5. Interestingly, application of coated urea to soils with higher C/N ratios increased NH3 losses but showed a noticeable N2O reduction. We found that polymer-coated urea reduced CH4 and N2O emissions and NH3 losses at the expense of higher CO2 emissions. Moreover, application of a lower dose of coated urea (0-100 kg N ha-1) enhanced CO2 and CH4 mitigation, while N2O mitigation increased linearly with increasing dose of coated urea. Most importantly, our results showed that the application of coated urea leads to a large mismatch between NUE, crop yields and greenhouse gas mitigation. By and large, the application of coated urea did not correspond with higher crop yields despite significant reduction in the emissions and improved NUE. Overall, these results suggest that site-specific agro-edaphic conditions should be considered when applying coated urea to reduce these emissions and N volatilization losses for increasing NUE and crop yields.

Comparative effects of post isometric relaxation technique and Bowen's therapy on pain, range of motion and function in patients with temporomandibular joint disorder.

BACKGROUND: The most common cause of mouth and facial pain is a temporomandibular joint disorder, which affects the patient's quality of life and interferes with their ability to perform daily tasks. OBJECTIVE: The purpose was to compare the effects of the Post-Isometric Relaxation Technique and Bowen's Therapy on pain, range of motion and functional activity in patients with temporomandibular joint disorders. METHODS: This study was a randomized clinical trial. A total of 24 participants were randomly allocated into two groups using the lottery method. Baseline treatment was the same (ultrasound and tapping) in both groups. Group 1 (12 participants) was treated with a post-isometric relaxation technique, and Group 2 (12 participants) with Bowen's therapy for two sessions per week (total duration of 4 weeks). Outcome measures were the Numeric Pain Rating Scale, Maximal mouth opening inter-incisal rural and jaw functional limitation scale-20. SPSS version 25 was used for statistical analysis. RESULTS: A significant improvement in pain, range of motions and functional activities in the post-isometric group showed significant results (p < 0.05) as compared to Bowen's group (independent t-test). However, within-group comparison (paired t-test), both groups showed significant results (p < 0.05). CONCLUSION: This study concluded that post-isometric relaxation was more effective in terms of pain, range of motions for mouth opening, lateral deviations and functional activity of temporomandibular joint disorder patients. However, both groups showed clinical results according to minimal clinical difference values. TRIAL REGISTRY NUMBER: The trial is registered under ClinicalTrials.govt with reference no. ID: NCT05392049 registered on 26/05/2022.

Characteristics of Immune Checkpoint Inhibitor-Associated Gastritis: Report from a Major Tertiary Care Center.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have increased our ability to treat an ever-expanding number of cancers. We describe a case series of 25 patients who were diagnosed with gastritis following ICI therapy. MATERIALS AND METHODS: This was a retrospective study involving 1712 patients treated for malignancy with immunotherapy at Cleveland Clinic from January 2011 to June 2019 (IRB 18-1225). We searched electronic medical records using ICD-10 codes for gastritis diagnosis confirmed on endoscopy and histology within 3 months of ICI therapy. Patients with upper gastrointestinal tract malignancy or documented Helicobacter pylori-associated gastritis were excluded. RESULTS: Twenty-five patients were found to meet the criteria for diagnosis of gastritis. Of these 25 patients, most common malignancies were non-small cell lung cancer (52%) and melanoma (24%). Median number of infusions preceding symptoms was 4 (1-30) and time to symptom onset 2 (0.5-12) weeks after last infusion. Symptoms experienced were nausea (80%), vomiting (52%), abdominal pain (72%), and melena (44%). Common endoscopic findings were erythema (88%), edema (52%), and friability (48%). The most common diagnosis of pathology was chronic active gastritis in 24% of patients. Ninety-six percent received acid suppression treatment and 36% of patients also received steroids with an initial median dose of prednisone 75 (20-80) mg. Within 2 months, 64% had documented complete resolution of symptoms and 52% were able to resume immunotherapy. CONCLUSION: Patients presenting with nausea, vomiting, abdominal pain, or melena following immunotherapy should be assessed for gastritis and if other causes are excluded, may require treatment as consideration for complication of immunotherapy.

Volatile Organic Compounds from Pythium oligandrum Play a Role in Its Parasitism on Plant-Pathogenic Pythium myriotylum.

The oomycete Pythium oligandrum is a soil-inhabiting parasite and predator of both fungi and oomycetes, and uses hydrolytic enzymes extensively to penetrate and hydrolyze its host or prey. Other mechanisms have been studied less, and we investigated the contribution of P. oligandrum-produced volatile organic compounds (VOCs) to parasitism. The growth-inhibiting activity of P. oligandrum VOCs was tested on Pythium myriotylum-a host or prey of P. oligandrum-coupled with electron microscopy, and biochemical and transcriptomic analyses. The P. oligandrum-produced VOCs reduced P. myriotylum growth by 80% and zoospore levels by 60%. Gas chromatography-mass spectrometry (GC-MS) identified 23 VOCs, and methyl heptenone, d-limonene, 2-undecanone, and 1-octanal were potent inhibitors of P. myriotylum growth and led to increased production of reactive oxygen species at a concentration that did not inhibit P. oligandrum growth. Exposure to the P. oligandrum VOCs led to shrinkage of P. myriotylum hyphae and lysis of the cellular membranes and organelles. Transcriptomics of P. myriotylum exposed to the P. oligandrum VOCs at increasing levels of growth inhibition initially showed a strong upregulation of putative detoxification-related genes that was not maintained later. The inhibition of P. myriotylum growth continued immediately after the exposure to the VOCs was discontinued and led to the reduced infection of its plant hosts. The VOCs produced by P. oligandrum could be another factor alongside hydrolytic enzymes contributing to its ecological role as a microbial parasite in particular ecological niches such as in soil, and may also contribute to the biocontrol of diseases using P. oligandrum commercial preparations. IMPORTANCE Microbe-microbe interactions in nature are multifaceted, with multiple mechanisms of action, and are crucial to how plants interact with microbes. Volatile organic compounds (VOCs) have diverse functions, including contributing to parasitism in ecological interactions and potential applications in biocontrol. The microbial parasite P. oligandrum is well known for using hydrolytic enzymes as part of its parasitism. We found that P. oligandrum VOCs reduced the growth of, and caused major damage to, the hyphae of P. myriotylum (a host or prey of P. oligandrum). Transcriptomic analyses of P. myriotylum exposed to the VOCs revealed the upregulation of genes potentially involved in an attempt to detoxify the VOCs. The inhibitory effects of the VOCs had a knock-on effect by reducing the virulence of P. myriotylum toward its plant hosts. The P. oligandrum VOCs could contribute to its ecological role as a microbial parasite. The VOCs analyzed here may also contribute to the biocontrol of diseases using P. oligandrum commercial preparations.

Lung Cancer Treatment Advances in 2022.

The therapeutic landscape of lung cancer treatment is changing rapidly, and new data was presented at the recently concluded American Society of Clinical Oncology 2022 (ASCO22) meeting. We highlight studies of clinical relevance that represent significant updates in the current management of non-small cell lung cancer (SCLC) and small cell lung cancer (NSCLC). We summarize the updates in early-stage NSCLC, mutated and non-mutated advanced NSCLC as well as small cell lung cancer (SCLC), and discuss these advances in the context of the current clinical standard of care.

Urdu translation and validation of the international consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS).

INTRODUCTION AND HYPOTHESIS: The International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) is a tool for the evaluation of lower urinary tract symptoms and their impact on the quality of life. The purpose of this research was the translation of ICIQ-FLUTS into the Urdu language and to determine its validity and reliability. METHODS: Two bilingual translators translated the ICIQ-FLUTS Questionnaire into the Urdu language. Three experts compared the Urdu ICIQ-FLUTS with the original version of ICIQ-FLUTS. Urdu version was translated back into English by two translators. The pre-final version was drafted after tracking the forward and backward translation differences. The final Urdu version was drafted after application to ten patients (pilot study). Final Urdu ICIQ-FLUTS was applied to 120 participants for validity and reliability. RESULTS: Urdu version was drafted after the consensus of the experts. The content validity index ranged between 0.81-0.93. The mean age of the participants was 45.2 ± 7.79 years. The test-retest reliability was analyzed through intraclass correlation coefficient (ICC) 0.972 and internal consistency by Cronbach's alpha 0.986. The concurrent validity was determined by correlating the ICIQ-FLUTS with ICIQ-UI SF (0.82) and UDI-6 (0.72). CONCLUSION: It was concluded that the Urdu version of ICIQ-FLUTS is an assessment questionnaire for the signs and symptoms of urinary incontinence. It has good content validity, concurrent validity, and test-retest reliability.

Translation and validation of Incontinence Impact Questionnaire Short Form in the Urdu language.

INTRODUCTION AND HYPOTHESIS: The Incontinence Impact Questionnaire Short Form (IIQ-7 SF) is a self-administered questionnaire that is used to assess the impact of urinary incontinence on the quality of life in women. It is translated into different languages; however, there is currently no official Urdu version of this tool. The main purpose of this study was to translate the IIQ-7 SF into the Urdu language and to find out its validity and reliability in women with urinary incontinence. METHODS: The IIQ-7 was translated into the Urdu language by following the standardized steps. The original version was translated into Urdu by two translators and the back translation into English was done by an independent translator. A panel of experts reviewed the translations and a final version was drafted. Fifteen women with urinary incontinence were involved in the pilot study. The validity and reliability were then assessed on 70 women with urinary incontinence. RESULTS: The content validity index (CVI) of each question ranged from 0.91 to 0.94. The convergent validity with UDI-6 was determined by using Spearman's correlation coefficient (r=0.90). Cronbach's α showed the internal consistency, which is 0.87. The test-retest reliability was calculated by the intra-class correlation coefficient, ICC=0.95. The scree plot showed the two components have eigen values greater than 1. CONCLUSIONS: The Urdu version of the IIQ-7 has shown good validity and reliability in incontinence patients, according to the findings.

Translation and validation of the Pelvic Girdle Questionnaire in the Urdu language.

INTRODUCTION AND HYPOTHESIS: The Pelvic Girdle Questionnaire (PGQ) is designed to determine pain and limited activities in pregnant and postpartum women with pelvic girdle pain (PGP). The purpose of this study was to translate the PGQ into the Urdu language and find out the cross-cultural validity and reliability of the Urdu PGQ among pregnant and postpartum women. METHODS: A translation and cultural adaptation study was performed following international guidelines. The PGQ (the Urdu version) was drafted and a pilot study was conducted on 16 pregnant and postpartum women. A total of 125 pregnant and postpartum females participated in this study for validity and test-retest reliability. SPSS 25 was used for data analysis. RESULTS: Content validity was analyzed by the content validity index ranging from (0.92 to 1). Convergent validity was determined by correlating the Urdu version of the PGQ with the Oswestry Disability Index (ODI). Pearson rank correlation coefficient between the PGQ and the ODI (p=0.84) showed convergent validity. Internal consistency and test-retest reliability of the Urdu version of the PGQ were calculated by Cronbach's alpha (α=0.98), and intra-class correlation coefficient (ICC=0.98) respectively. CONCLUSION: The Urdu version of the PGQ showed good content and convergent validity as well as high internal consistency and test-retest reliability.