Treatment preferences among people at risk of developing tuberculosis: A discrete choice experiment.

Diagnosing and treating people with bacteriologically-negative but radiologically-apparent tuberculosis (TB) may contribute to more effective TB care and reduce transmission. However, optimal treatment approaches for this group are unknown. It is important to understand peoples' preferences of treatment options for effective programmatic implementation of people-centred treatment approaches. We designed and implemented a discrete choice experiment (DCE) to solicit treatment preferences among adults (≥18 years) with TB symptoms attending a primary health clinic in Blantyre, Malawi. Treatment attributes included in the DCE were as follows: duration of treatment; number of tablets per dose; reduction in the risk of being unwell with TB disease; likelihood of infecting others; adverse effects from the treatment; frequency of follow up; and the annual travel cost to access care. Quantitative choice modelling with multinomial logit models estimated through frequentist and Bayesian approaches investigated preferences for the management of bacteriologically-negative, but radiographically-apparent TB. 128 participants were recruited (57% male, 43.8% HIV-positive, 8.6% previously treated for TB). Participants preferred to take any treatment compared to not taking treatment (odds ratio [OR] 5.78; 95% confidence interval [CI]: 2.40, 13.90). Treatments that reduced the relative risk of developing TB disease by 80% were preferred (OR: 2.97; 95% CI: 2.09, 4.21) compared to treatments that lead to a lower reduction in risk of 50%. However, there was no evidence for treatments that are 95% effective being preferred over those that are 80% effective. Participants strongly favoured the treatments that could completely stop transmission (OR: 7.87, 95% CI: 5.71, 10.84), and prioritised avoiding side effects (OR: 0.19, 95% CI: 0.12, 0.29). There was no evidence of an interaction between perceived TB disease risk and treatment preferences. In summary, participants were primarily concerned with the effectiveness of TB treatments and strongly preferred treatments that removed the risk of onward transmission. Person-centred approaches of preferences for treatment should be considered when designing new treatment strategies. Understanding treatment preferences will ensure that any recommended treatment for probable early TB disease is well accepted and utilized by the public.

Nanoassemblies of Chitosan-Based Polyelectrolyte Complexes as Nucleic Acid Delivery Systems.

Nucleic acid delivery requires vectorization for protection from nucleases, preventing clearance by the reticuloendothelial system, and targeting to allow cellular uptake. Nanovectors meeting the above specifications should be safe for the patient, simple to manufacture, and display long-term stability. Our nanovectors were obtained via the green process of polyelectrolyte complexation, carried out at 25 °C in water at a low shear rate using chitosan (a polycationic biocompatible polysaccharide of specific molar mass and acetylation degree) and dextran sulfate as a polyanionic biocompatible polysaccharide. These complexes formed nanoassemblies of primary nanoparticles (20-35 nm) and maintained their colloidal stability for over 1 year at 25 °C. They could be steam sterilized, and a model nucleic acid could be either encapsulated or surface adsorbed. A targeting agent was finally bound to their surface. This work serves as a proof of concept of the suitability of chitosan-based polyelectrolyte complexes as nanovectors by sequential multilayered adsorption of various biomacromolecules.

Saudi expert consensus on acquired hemophilia A diagnosis and management.

Objectives: Acquired hemophilia affects approximately one in 1 million people. Timely diagnosis is key to appropriate disease management and the prevention of life-threatening complications. Patients with this condition may initially be seen by inexperienced physicians and remain underdiagnosed for several years. This consensus statement is aimed at providing guidelines for all practitioners in the Kingdom of Saudi Arabia (KSA) to diagnose and manage acquired hemophilia A. Methods: This consensus statement reflects the opinions drafted by a group of hematology specialists, who used an explicit systematic process to identify areas of agreement and disagreement. Results: This consensus statement provides a guide for all practitioners in the KSA regarding the diagnosis of clinical presentation, relevance, characteristics of bleeding symptoms, and case management; it additionally provides guidance for non-specialists. All management aspects, including diagnosis and treatment modalities, are discussed. Conclusions: Patients with acquired hemophilia may initially be seen by physicians who lack appropriate expertise in diagnosing and managing this condition. This consensus statement from the premier experts on the disease in the KSA provides details for diagnosing and managing acquired hemophilia.

The Prevalence of Shoulder Pain and Awareness of Frozen Shoulder Among the General Population in Taif City, Saudi Arabia.

Background The global prevalence of shoulder pain varies widely across countries. Additionally, shoulder pain and frozen shoulder can significantly affect patients' quality of life due to high levels of pain and disability. Objective This study aimed to investigate the prevalence of shoulder pain and its risk factors. It also aims to assess the level of knowledge regarding frozen shoulders and its related factors in Taif City, Saudi Arabia. Methods A cross-sectional observational study was conducted in Taif City in December 2023 using a validated questionnaire comprised of socio-demographic characteristics, the prevalence of shoulder pain, and the awareness of frozen shoulders. Results A total of 378 participants enrolled in the study, with 54.8% being male and 62.7% being graduates and having jobs equally distributed among office (24.9%) and in the field (24.9%). Most participants were smokers (75.9%) and did not engage in body-building activities (79.6%). Around 26.5% of them had diabetes. The prevalence of shoulder pain was 32.8%. Aging from 35 to 44 years (p<0.001), having a higher salary from 6000 to 10000 SAR (p<0.001), retirement (p<0.001), engaging in body-building activities (p=0.035), having diabetes (p<0.001), and having other comorbidities (p<0.001) are significantly impacted having shoulder pain. Increased knowledge about the frozen shoulder is correlated with aging from 25-34 (p=0.026), smoking (p=0.002), engaging in bodybuilding (p<0.001), having diabetes (p=0.010), and having other medical conditions (p=0.010). Conclusion The study has shown that shoulder pain is prevalent among Taif City's population. Nevertheless, a low level of knowledge was observed. Therefore, enhancing the national educational programs is needed to increase public awareness of frozen shoulders.

Enhanced tuberculosis diagnosis with computer-aided chest X-ray and urine LAM in adults with HIV admitted to hospital (CASTLE study): A cluster randomised trial.

BACKGROUND: People with HIV (PHIV) admitted to hospital have high mortality, with tuberculosis (TB) being the major cause of death. Systematic use of new TB diagnostics could improve TB diagnosis and might improve outcomes. METHODS: We conducted a cluster randomised trial among adult PHIV admitted to Zomba Central Hospital, Malawi. Admission-days were randomly assigned to: enhanced TB diagnostics using urine lipoarabinomannan (LAM) antigen tests (SILVAMP-LAM, Fujifilm, Japan and Determine-LAM, Alere/Abbot, USA), digital chest X-ray with computer aided diagnosis (dCXR-CAD, CAD4TBv6, Delft, Netherlands), plus usual care ("enhanced TB diagnostics"); or usual care alone ("usual care"). The primary outcome was TB treatment initiation during admission. Secondary outcomes were 56-day mortality, TB diagnosis within 24-hours, and undiagnosed TB at discharge, ascertained by culture of one admission sputum sample. FINDINGS: Between 2 September 2020 and 15 February 2022, we recruited 419 people. Four people were excluded post-recruitment, leaving 415 adults recruited during 207 randomly assigned admission-days in modified intention-to-treat analysis. At admission, 90.8% (377/415) were taking antiretroviral therapy (ART) with median (IQR) CD4 cell count 240 cells/mm3. In the enhanced diagnostic arm, median CAD4TBv6 score was 60 (IQR: 51-71), 4.4% (9/207) had SILVAMP-LAM-positive and 14.4% (29/201) had Determine-LAM positive urine with three samples positive by both urine tests. TB treatment was initiated in 46/208 (22%) in enhanced TB diagnostics arm and 24/207 (12%) in usual care arm (risk ratio [RR] 1.92, 95% CI 1.20-3.08). There was no difference in mortality by 56 days (enhanced TB diagnosis: 54/208, 26%; usual care: 52/207, 25%; hazard ratio 1.05, 95% CI 0.72-1.53); TB treatment initiation within 24 hours (enhanced TB diagnosis: 8/207, 3.9%; usual care: 5/208, 2.4%; RR 1.61, 95% CI 0.53-4.71); or undiagnosed microbiological-confirmed TB at discharge (enhanced TB diagnosis, 0/207 (0.0%), usual care arm 2/208 (1.0%) (p = 0.50). INTERPRETATION: Urine SILVAMP-LAM/Determine-LAM plus dCXR-CAD diagnostics identified more hospitalised PHIV with TB than usual care. The increase in TB treatment appeared mainly due to greater use of Determine-LAM, rather than SILVAMP-LAM or dCXR-CAD. Poor concordance between Determine-LAM and SILVAMP-LAM urine tests requires further investigation. Inpatient mortality for adults with HIV remains unacceptability high.

Diversity and antimicrobial susceptibility patterns of clinical and environmental Salmonella enterica serovars in Western Saudi Arabia.

The diverse environmental distribution of Salmonella makes it a global source of human gastrointestinal infections. This study aimed to detect Salmonella spp. and explore their diversity and antimicrobial susceptibility patterns in clinical and environmental samples. Pre-enrichment, selective enrichment, and selective plating techniques were adopted for the Salmonella detection whereas the API 20E test and Vitek Compact 2 system were used to confirm the identity of isolates. Salmonella serovars were subjected to molecular confirmation by 16S rDNA gene sequencing. Disc diffusion method and Vitek 2 Compact system determined the antibiotic susceptibility of Salmonella serovars. Multiple antibiotic resistance index (MARI) was calculated to explore whether Salmonella serovars originate from areas with heavy antibiotic usage. Results depicted low Salmonella prevalence in clinical and environmental samples (3.5%). The main detected serovars included Salmonella Typhimurium, S. enteritidis, S. Infantis, S. Newlands, S. Heidelberg, S. Indian, S. Reading, and S. paratyphi C. All the detected Salmonella serovars (27) exhibited multidrug resistance to three or more antimicrobial classes. The study concludes that the overall Salmonella serovars prevalence was found to be low in environmental and clinical samples of Western Saudi Arabia (Makkah and Jeddah). However, antimicrobial susceptibility patterns of human and environmental Salmonella serovars revealed that all isolates exhibited multidrug-resistance (MDR) patterns to frequently used antibiotics, which might reflect antibiotic overuse in clinical and veterinary medicine. It would be suitable to apply and enforce rules and regulations from the One Health approach, which aim to prevent antibiotic resistance infections, enhance food safety, and improve human and animal health, given that all Salmonella spp. detected in this investigation were exhibiting MDR patterns.

The interplay of p38 MAPK signaling and mitochondrial metabolism, a dynamic target in cancer and pathological contexts.

Mitochondria play a crucial role in cellular metabolism and bioenergetics, orchestrating various cellular processes, including energy production, metabolism, adaptation to stress, and redox balance. Besides, mitochondria regulate cellular metabolic homeostasis through coordination with multiple signaling pathways. Importantly, the p38 mitogen-activated protein kinase (MAPK) signaling pathway is a key player in the intricate communication with mitochondria, influencing various functions. This review explores the multifaced interaction between the mitochondria and p38 MAPK signaling and the consequent impact on metabolic alterations. Overall, the p38 MAPK pathway governs the activities of key mitochondrial proteins, which are involved in mitochondrial biogenesis, oxidative phosphorylation, thermogenesis, and iron homeostasis. Additionally, p38 MAPK contributes to the regulation of mitochondrial responses to oxidative stress and apoptosis induced by cancer therapies or natural substances by coordinating with other pathways responsible for energy homeostasis. Therefore, dysregulation of these interconnected pathways can lead to various pathologies characterized by aberrant metabolism. Consequently, gaining a deeper understanding of the interaction between mitochondria and the p38 MAPK pathway and their implications presents exciting forecasts for novel therapeutic interventions in cancer and other disorders characterized by metabolic dysregulation.

Child acute illness presentation and referrals at primary health clinics in Malawi: a secondary analysis of ASPIRE.

OBJECTIVES: We aimed to assess the prevalence, presentation and referral patterns of children with acute illness attending primary health centres (PHCs) in a low-resource setting. DESIGN, SETTING AND PARTICIPANTS: We conducted a secondary analysis of ASPIRE. Children presenting at eight PHCs in urban Blantyre district in southern Malawi with both recorded clinician and mHealth (non-clinician) triage data were included, and patient records from different data collection points along the patient healthcare seeking pathway were consolidated and analysed. RESULTS: Between April 2017 and September 2018, a total of 204 924 children were triaged, of whom 155 931 had both recorded clinician and mHealth triage data. The most common presenting symptoms at PHCs were fever (0.3%), cough (0.2%) and difficulty breathing (0.2%). The most common signs associated with referral for under-5 children were trauma (26.7%) and temperature (7.4%). The proportion of emergency and priority clinician triage were highest among young infants <2 months (0.2% and 81.4%, respectively). Of the 3004 referrals (1.9%), 1644 successfully reached the referral facility (54.7%). Additionally, 372 children were sent home from PHC who subsequently self-referred to the referral facility (18.7%). CONCLUSIONS: Fever and respiratory symptoms were the most common presenting symptoms, and trauma was the most common reason for referral. Rates of referral were low, and of successful referral were moderate. Self-referrals constituted a substantial proportion of attendance at the referral facility. Reducing gaps in care and addressing dropouts as well as self-referrals along the referral pathway could improve child health outcomes.

THE EFFECT OF NUTRITIONAL GENOMICS ON CARDIOVASCULAR SYSTEM.

The idea that obesity and cardiovascular diseases together are considered for a sizable share of adult global morbidity and mortality is supported by epidemiological data. They have intricate systems in which environmental and genetic variables interact, including nutrition. As an environmental component, nutrition has a major and well-known role in managing health and preventing obesity and disorders connected to obesity, such as cardiovascular disease (CVD). Nonetheless, people with the same food pattern but obese exhibit a notable difference in CVD. This variance might be explained by the various genetic polymorphisms which gave rise to the field of nutrigenetics. The discipline known as nutritional genomics, or nutrigenetics, examines and describes gene variants linked to varying reactions to particular nutrients and links these variations to various disorders, including obesity-related cardiovascular disease (CVD). Therefore, tailored nutrition advice depending on a person's genetic background could enhance the results of a particular dietary intervention and offer a novel dietary technique to enhance health by lowering obesity and cardiovascular disease. With these suppositions, it seems reasonable to assume that understanding food and gene interactions will provide more targeted and efficacious dietary treatments in preventing obesity and CVD by nutrigenetics-based personalized nutrition. In addition to elucidating the connection between diet and gene expression and the major nutrition-related genes involved in obesity and CVD, this research seeks to provide a concise summary of the greater significant genes linked to obesity and CVD.

Airway Diseases Related to the Use of Cleaning Agents in Occupational Settings.

Exposure to disinfectants and cleaning products (DCPs) is now a well-established risk factor for work-related asthma (WRA). However, questions remain on the specific causal agents and pathophysiological mechanisms. Few studies have also reported an association between DCPs and rhinitis or chronic obstructive pulmonary disease. This review discusses the recent evidence pertaining to airway diseases attributable to occupational exposure to DCPs. In contrast to other agents, the incidence of WRA due to DCPs has increased over time. The use of DCPs in spray form has clearly been identified as an added risk factor. The mechanisms for WRA associated with DCPs remain poorly studied; however, both allergic and nonallergic responses have been described, with irritant mechanisms thought to play a major role. An early diagnostic workup based on clinical assessment accompanied by evaluation of lung function and immunological and airway inflammatory markers is important to guide optimal care and exposure avoidance to the implicated agent. Future research should focus on the effects of "green" products, pathophysiological mechanisms, and quantitative exposure assessment including the use of barcode-based methods to identify specific agents. There is an urgent need to strengthen preventive measures and interventions to reduce the burden of airway diseases associated with DCPs.

MicroRNA-targeting nanomedicines for the treatment of intervertebral disc degeneration.

Low back pain stands as a pervasive global health concern, afflicting almost 80% of adults at some point in their lives with nearly 40% attributable to intervertebral disc degeneration (IVDD). As only symptomatic relief can be offered to patients there is a dire need for innovative treatments.Given the accumulating evidence that multiple microRNAs (miRs) are dysregulated during IVDD, they could have a huge potential against this debilitating condition. The way miRs can profoundly modulate signaling pathways and influence several cellular processes at once is particularly exciting to tackle this multifaceted disorder. However, miR delivery encounters extracellular and intracellular biological barriers. A promising technology to address this challenge is the vectorization of miRs within nanoparticles, providing both protection and enhancing their uptake within the scarce target cells of the degenerated IVD. This comprehensive review presents the diverse spectrum of miRs' connection with IVDD and demonstrates their therapeutic potential when vectorized in nanomedicines.

Postoperative infectious complications worsen oncologic outcomes following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreaticoduodenectomy (PD) remains the only curative option for patients with pancreatic adenocarcinoma (PDAC). Infectious complications (IC) can negatively impact patient outcomes and delay adjuvant therapy in most patients. This study aims to determine IC effect on overall survival (OS) following PD for PDAC. STUDY DESIGN: Patients who underwent PD for PDAC between 2010 and 2020 were identified from a single institutional database. Patients were categorized into two groups based on whether they experienced IC or not. The relationship between postoperative IC and OS was investigated using Kaplan-Meier and Cox-regression multivariate analysis. RESULTS: Among 655 patients who underwent PD for PDAC, 197 (30%) experienced a postoperative IC. Superficial wound infection was the most common type of infectious complication (n = 125, 63.4%). Patients with IC had significantly more minor complications (Clavien-Dindo [CD] < 3; [59.4% vs. 40.2%, p < 0.001]), major complications (CD ≥ 3; [37.6% vs. 18.8%, p < 0.001]), prolonged LOS (47.2% vs 20.3%, p < 0.001), biochemical leak (6.1% vs. 2.8%, p = 0.046), postoperative bleeding (4.1% vs. 1.3%, p = 0.026) and reoperation (9.6% vs. 2.2%, p < 0.001). Time to adjuvant chemotherapy was delayed in patients with IC versus those without (10 vs. 8 weeks, p < 0.001). Median OS for patients who experienced no complication, noninfectious complication, and infectious complication was 33.3 months, 29.06 months, and 27.58 months respectively (p = 0.023). On multivariate analysis, postoperative IC were an independent predictor of worse OS (HR 1.32, p = 0.049). CONCLUSIONS: IC following PD for PDAC independently predict worse oncologic outcomes. Thus, efforts to prevent and manage IC should be a priority in the care of patients undergoing PD for PDAC.

Experimental and theoretical study of improved mesoporous titanium dioxide perovskite solar cell: The impact of modification with graphene oxide.

The present study serves experimental and theoretical analyses in developing a hybrid advanced structure as a photolysis, which is based on electrospun Graphene Oxide-titanium dioxide (GO-TiO2) nanofibers as an electron transfer material (ETMs) functionalized for perovskite solar cell (PVSCs) with GO. The prepared ETMs were utilized for the synthesis of mixed-cation (FAPbI3)0.8(MAPbBr3)0.2. The effect of GO on TiO2 and their chemical structure, electronic and morphological characteristic were investigated and discussed. The elaborated device, namely ITO/Bl-TiO2/3 wt% GO-TiO2/(FAPbI3)0.8(MAPbBr3)0.2/spiro-MeTAD/Pt, displayed 20.14% disposition and conversion solar energy with fill factor (FF) of 1.176%, short circuit current density (Jsc) of 20.56 mA/cm2 and open circuit voltage (VOC) 0.912 V. The obtained efficiency is higher than titanium oxide (18.42%) and other prepared GO-TiO2 composite nanofibers based ETMs. The developed materials and device would facilitate elaboration of advanced functional materials and devices for energy storage applications.

Poly (γ) glutamic acid: a unique microbial biopolymer with diverse commercial applicability.

Microbial biopolymers have emerged as promising solutions for environmental pollution-related human health issues. Poly-γ-glutamic acid (γ-PGA), a natural anionic polymeric compound, is composed of highly viscous homo-polyamide of D and L-glutamic acid units. The extracellular water solubility of PGA biopolymer facilitates its complete biodegradation and makes it safe for humans. The unique properties have enabled its applications in healthcare, pharmaceuticals, water treatment, foods, and other domains. It is applied as a thickener, taste-masking agent, stabilizer, texture modifier, moisturizer, bitterness-reducing agent, probiotics cryoprotectant, and protein crystallization agent in food industries. γ-PGA is employed as a biological adhesive, drug carrier, and non-viral vector for safe gene delivery in tissue engineering, pharmaceuticals, and medicine. It is also used as a moisturizer to improve the quality of hair care and skincare cosmetic products. In agriculture, it serves as an ideal stabilizer, environment-friendly fertilizer synergist, plant-growth promoter, metal biosorbent in soil washing, and animal feed additive to reduce body fat and enhance egg-shell strength.

The Antioxidant and anti-inflammatory Activity of Selenium and Lecithin Combination Against ethanol-induced Gastric Ulcer in mice via Modulating IGF-1/PTEN/Akt/FoxO3a Signaling.

Gastric ulcers are one of the most prevalent gastrointestinal disorders. The current study investigated the antioxidant and anti-inflammatory effects of selenium (Se) and lecithin (Lec) alone and in combination against ethanol-induced gastric ulcers in mice, and their ability to modulate insulin-like growth factor-1 (IGF-1)/ Phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/ Protein kinase B (Akt)/ Forkhead box O3a (FoxO3a) signaling. The mice were divided into normal, ethanol, Se + ethanol, Lec + ethanol, Se + Lec + ethanol, and omeprazole + ethanol groups. Treatment with the selected doses was continued for 14 days before a single dose of absolute ethanol (5 ml/kg body weight) was administered to induce gastric ulcers in mice. The results showed that pretreatment with Se and Lec combination effectively decreased both the macro- and microscopic gastric lesions and increased the protection index compared to the ethanol group. Remarkably, the Se and Lec combination decreased the levels of reactive oxygen species, malondialdehyde, and cytochrome c and increased glutathione, glutathione peroxidase, and thioredoxin reductase activities in gastric tissues. The Se and Lec combination increased prostaglandin E2 and interleukin-10 levels but decreased tumor necrosis factor-α, interleukin-6 and interleukin-1ß levels compared to either treatment alone. Interestingly, this combination decreased the expression of IGF-1, p-Akt, and FoxO3a proteins and increased PTEN expression in gastric tissues. The gastric tissues examination by hematoxylin and eosin staining confirmed these results. Therefore, the Se and Lec combination showed superior protective effects against ethanol-induced gastric ulcers in mice, compared to either treatment alone, through antioxidant, and anti-inflammatory activities, in addition to modulating IGF-1/PTEN/Akt/FoxO3a pathway signaling.

Efficiency of natural oils as alternative adjuvants to mineral oils in inactivated avian influenza vaccine formulation.

1. The effectiveness of inactivated vaccines depends on selecting the suitable adjuvant for vaccine formulation. The potency of vaccines with low antigen content can be improved with the appropriate adjuvant. This could allow production of more doses and lower the production cost.2. This study evaluated the efficiency of vaccines prepared using oil extracted from natural sources including argan oil, almond oil, sesame seed oil, pumpkin oil, cactus oil and black seed oil as alternative adjuvants for improving the protection capacity of inactivated influenza virus vaccine as compared to commonly used mineral oils.3. Each vaccine formulation was evaluated for stability, safety and immunogenicity in chickens, as well as for reducing the viral shedding after challenge infection.4. The cactus, sesame and pumpkin seed oil-based vaccines were found to be potent and successfully induced the production of humoral immunity in vaccinated chickens.

Deliveries in Lebanon, the Country with the Highest Refugee Density in the World: A Descriptive Review.

PURPOSE: The aim of this study is to analyze obstetrical and reproductive health parameters in Lebanon from 2015 until 2018 in the setting of the Syrian refugee influx in order to evaluate potential risks and provide a management plan to improve outcomes. DESCRIPTION: Data from the Lebanese Ministry of Public Health (LMPH) on all obstetrical deliveries that occurred in Lebanon between 2015 and 2018 was screened and analyzed. Number and mode of delivery as well as maternal and neonatal outcomes were included. Joinpoint regression analysis was used for trends of selected parameters. Independent two-sample t-tests were used for comparisons. ASSESSMENT: Women of non-Lebanese nationality residing in Lebanon had a significantly greater number of total deliveries (p-value < 0.001), vaginal deliveries (p-value = 0.002), cesarean sections (p-value = 0.02). When looking at delivery trends from 2015 to 2018, Lebanese women had a significant decrease in total number of deliveries (p-value < 0.001) and vaginal deliveries (p-value < 0.001). CONCLUSION: Total number of deliveries and cesarean sections is on the rise in Lebanon. Cesarean section practice should be audited by the LMPH and the Lebanese Order of Physicians (LOP). Local and international agencies should prioritize the implementation and management of family planning facilities in refugee hosting countries.

Impact of active case-finding for tuberculosis on case-notifications in Blantyre, Malawi: A community-based cluster-randomised trial (SCALE).

Active case-finding (ACF) for tuberculosis can help find the "missing millions" with undiagnosed tuberculosis. In a cluster-randomised trial, we investigated impact of ACF on case-notifications in Blantyre, Malawi, where ACF has been intensively implemented following 2014 estimates of ~1,000 per 100,000 adults with undiagnosed TB. Following a pre-intervention prevalence survey (May 2019 to March 2020), constrained randomisation allocated neighbourhoods to either door-to-door ACF (sputum microscopy for reported cough >2 weeks) or standard-of-care (SOC). Implementation was interrupted by COVID-19. Cluster-level bacteriologically-confirmed case-notification rate (CNR) ratio within 91 days of ACF was our redefined primary outcome; comparison between arms used Poisson regression with random effects. Secondary outcomes were 91-day CNR ratios comparing all tuberculosis registrations and all non-ACF registrations. Interrupted time series (ITS) analysis of CNRs in the SOC arm examined prevalence survey impact. (ISRCTN11400592). 72 clusters served by 10 study-supported tuberculosis registration centres were randomised to ACF (261,244 adults, 58,944 person-years follow-up) or SOC (256,713 adults, 52,805 person-years). Of 1,192 ACF participants, 13 (1.09%) were smear-positive. Within 91 days, 113 (42 bacteriologically-confirmed) and 108 (33 bacteriologically-confirmed) tuberculosis patients were identified as ACF or SOC cluster residents, respectively. There was no difference by arm, with adjusted 91-day CNR ratios 1.12 (95% CI: 0.61-2.07) for bacteriologically-confirmed tuberculosis; 0.93 (95% CI: 0.68-1.28) for all tuberculosis registrations; and 0.86 (95%CI: 0.63-1.16) for non-ACF (routinely) diagnosed. Of 7,905 ACF and 7,992 SOC pre-intervention survey participants, 12 (0.15%) and 17 (0.21%), respectively, had culture/Xpert-confirmed tuberculosis. ITS analysis showed no survey impact on SOC CNRs. Despite residual undiagnosed tuberculosis of 150 per 100,000 population, there was no increase in tuberculosis notifications from this previously successful approach targeting symptomatic disease, likely due to previous TB ACF and rapid declines in TB burden. In such settings, future ACF should focus on targeted outreach and demand creation, alongside optimised facility-based screening. Trial Registration: ISRCTN11400592.

Exploring marine-derived compounds for MET signalling pathway inhibition in cancer: integrating virtual screening, ADME profiling and molecular dynamics investigations.

The MET signalling pathway regulates fundamental cellular processes such as growth, division, and survival. While essential for normal cell function, dysregulation of this pathway can contribute to cancer by triggering uncontrolled proliferation and metastasis. Targeting MET activity holds promise as an effective strategy for cancer therapy. Among potential sources of anti-cancer agents, marine organisms have gained attention. In this study, we screened 47,450 natural compounds derived from marine sources within the CMNPD database against the Met crystal structure. By employing HTVS, SP, and XP docking modes, we identified three compounds (CMNPD17595, CMNPD14026, and CMNPD19696) that outperformed a reference molecule in binding affinity to the Met structure. These compounds demonstrated desirable ADME properties. Molecular Dynamics (MD) simulations for 200 ns confirmed the stability of their interactions with Met. Our findings highlight CMNPD17595, CMNPD14026, and CMNPD19696 as potential inhibitors against Met-dependent cancers. Additionally, these compounds offer new avenues for drug development, leveraging their inhibitory effects on Met to combat carcinogenesis.

Influences of high vs. low-intensity exercises on muscle strength, function, and quality of life in post-COVID-19 patients with sarcopenia: a randomized controlled trial.

OBJECTIVE: The aim of this study was to compare the effectiveness of high vs. low-intensity exercise training on muscle strength, physical function, and quality of life in post-COVID-19 patients with sarcopenia secondary to chronic kidney disease (CKD). PATIENTS AND METHODS: 82 subjects were randomized into 2 groups: high intensity (HIG, n=42), which received high-intensity resistance training, and low intensity (LIG, n=40), which conducted low-intensity aerobic activities. Exercises were performed for 30 min, 3 times per week for 6 weeks. A handheld dynamometer, pinch press, and 1 min sit-to-stand (STS) test were used to assess muscle strength. Modified physical performance test and sarcopenia Quality of Life questionnaire (SAR-QoL) were used to assess function and quality of life, respectively. Measures were collected before and at the end of the treatment program. RESULTS: Participants were similar at baseline. The within-group comparisons demonstrated statistically significant improvement in both HIG and LIG groups in all outcome measures (p<0.001). Between groups, comparisons revealed statistically significant better achievements with high effect size in Modified Physical Performance Test (MMPT) (p<0.001, d=1.28), handgrip (p<0.001, d=3.6), STS (p<0.001, d=2.38), and SAR-QoL (p<0.001, d=3.24) in favor of the HIG. On the other hand, pinch press strength was equally improved in both groups (p=0.09, d=0.36). CONCLUSIONS: High-intensity exercise is better than low-intensity exercises in post-COVID-19 patients with sarcopenia secondary to chronic kidney disease regarding muscle strength, physical function, and quality of life.