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Introduction Many patients experience unrelieved neuropathic cancer-related pain. Most current analgesic therapies have psychoactive side effects, lack efficacy data for this indication and have potential medication-related harms. The local anaesthetic lidocaine (lignocaine) has the potential to help manage neuropathic cancer-related pain when administered as an extended, continuous subcutaneous infusion. Data support lidocaine as a promising, safe agent in this setting, warranting further evaluation in robust, randomised controlled trials. This protocol describes the design of a pilot study to evaluate this intervention and explains the pharmacokinetic, efficacy and adverse effects evidence informing the design.Methods and analysis A mixed-methods pilot study will determine the feasibility of an international first, definitive phase III trial to evaluate the efficacy and safety of an extended continuous subcutaneous infusion of lidocaine for neuropathic cancer-related pain. This study will comprise: a phase II double-blind randomised controlled parallel-group pilot of subcutaneous infusion of lidocaine hydrochloride 10% w/v (3000 mg/30 mL) or placebo (sodium chloride 0.9%) over 72 hours for neuropathic cancer-related pain, a pharmacokinetic substudy and a qualitative substudy of patients’ and carers’ experiences. The pilot study will provide important safety data and help inform the methodology of a definitive trial, including testing proposed recruitment strategy, randomisation, outcome measures and patients’ acceptability of the methodology, as well as providing a signal of whether this area should be further investigated.Ethics and dissemination Participant safety is paramount and standardised assessments for adverse effects are built into the trial protocol. Findings will be published in a peer-reviewed journal and presented at conferences. This study will be considered suitable to progress to a phase III study if there is a completion rate where the CI includes 80% and excludes 60%. The protocol and Patient Information and Consent Form have been approved by Sydney Local Health District (Concord) Human Research Ethics Committee 2019/ETH07984 and University of Technology Sydney ETH17-1820.Trial registration number ANZCTR ACTRN12617000747325.

Abstract Arthropod vectors play a crucial role in the transmission of hemotropic mycoplasmas, small bacteria that infect red blood cells in a wide range of animals and humans globally, leading to intravascular infections. Traditional Giemsa-stained thin blood smears, used for diagnosing hemotropic mycoplasmas through microscopic examination, have low sensitivity and are effective only when bacteremia levels are high. This study aimed to employ molecular methods to detect and genetically characterize hemotropic mycoplasmas in goats as well as investigate the potential role of fleas as vectors. Blood and flea samples were collected concurrently from goats on 16 farms across seven provinces in Thailand from January 2017 to October 2023. The 16 S rRNA, 23 S rRNA, and rnpB genes of hemoplasmas were amplified and sequenced. All fleas were identified morphologically and molecularly through DNA barcoding of the cytochrome oxidase I gene. A total of 78 out of 500 goats (15.6%), three pooled flea samples (3/6, 50%), and one individual flea (1/49, 2.04%) tested positive for hemoplasmas and all fleas were identified as Ctenocephalides orientis. BLASTN searches utilizing the three genetic markers revealed that the hemoplasmas detected in this study showed 97.81–100% similarity to Mycoplasma ovis and Candidatus Mycoplasma haemovis, which have been previously reported in sheep, goats, and humans, suggesting their zoonotic potential. The sequences were grouped into 28 unique nucleotide sequence types (ntSTs) based on minor variations in the 16 S rRNA gene. Hemotropic mycoplasma infection was significantly associated with farm locations and seasonality of sample collection (p

The major challenge in large-scale industrial use of lipopeptide surfactin is the low yield by indigenous bacterial strains and the higher cost of its production that have been proved as a limiting factor in commercial applications. Therefore, there is an urgent demand for high-yielding strains that can be achieved through strain improvement. A first report on the use of a combination of UV and gamma-irradiation mutagenesis for the development of surfactin hyperproducing mutants of Bacillus spp. proved to be significant and resulted in a twofold enhancement in surfactin yield. The mutant was able to grow and produce surfactin on all the tested carbon and nitrogen sources, while 2% glycerol favored maximum surfactin yield (1.62 g/L) as compared to the wild-type strain that showed a maximum 0.85 g/L surfactin yield at 3% sucrose. Additionally, the mutant exhibited a good yield of pure surfactin, that is, 1.55 g/L as compared to the wild strain (0.411 g/L) by using corn steep liquor as the main component of the fermentation medium. The study concluded overall a threefold enhancement in the relative abundance of purified surfactin and its isoforms detected by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis in mutant strain AF-UVγ2500.

Introduction The global prevalence of people living with overweight has tripled since 1975 and more than 40% of Danish women enter pregnancy being overweight. With the increasing rates of obesity observed in children, adolescents and adults, there is an urgent need for preventive measures. Risk factors for childhood obesity include maternal overweight or obesity before conception and excessive weight gain during pregnancy. Interventions aimed at modifying maternal lifestyle during pregnancy have demonstrated minimal positive or no impact on the health of the children. The ‘healthy lifestyle before and during pregnancy to prevent childhood obesity — the PRE-STORK trial’ aims to provide insights into the effect of a lifestyle intervention initiated before conception and continued during pregnancy in women with overweight or obesity, on neonatal adiposity in their children.Methods and analysis In this randomised, two-arm, parallel-group, controlled trial, we will include 360 women with overweight or obesity (aged 18–40; body mass index 25–44 kg/m2) and their partners. The women will be randomised to receive either standard of care or a lifestyle intervention focused on preconception body weight reduction, regular physical exercise, healthy diet and support from a mentor before and during pregnancy. The primary outcome is the difference in neonatal adiposity measured in their children at birth. Children conceived during the trial will constitute a birth cohort, monitoring the effects on their health until the age of 18 years.Ethics and dissemination The trial has been approved by the Regional Committee on Health Research Ethics in the Capital Region of Denmark (identification number H-22011403) and will be conducted in agreement with the Declaration of Helsinki. All results, whether positive, negative and inconclusive, will be disseminated at national or international scientific meetings and in peer-reviewed scientific journals.Trial registration number ClinicalTrials.gov: NCT05578690 (October 2022).

Objective: To perform a systematic literature review analyzing visual outcomes of immediate, early, and delayed vitrectomy in the treatment of acute endophthalmitis after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. Methods: We conducted a literature search using the Ovid Medline, Embase.com, and Web of Science databases, and relevant articles were selected from original English papers published from 2005 to 2021. Inclusion criteria were studies reporting cases of acute post-anti-VEGF endophthalmitis, defined as occurring within 6 weeks of injection treatment. Exclusion criteria were pediatric cases and cases explicitly reported to be caused by injections of contaminated drugs. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal tool for case reports and case series. The study dataset for descriptive and statistical analysis comprised patient-level data extracted from included studies. The timing of vitrectomy compared were defined as (1) immediate vitrectomy as occurring within 24 h of endophthalmitis diagnosis; (2) early vitrectomy as occurring between 24 and 48 h of endophthalmitis diagnosis; (3) late vitrectomy as occurring after 48 h of endophthalmitis diagnosis. Primary outcome was final visual acuity following treatment with vitrectomy. Results: Twenty-five articles were published that met our inclusion and exclusion criteria for a total of 86 cases. Thirty-seven were immediate vitrectomy, 25 were early, and 24 were late vitrectomy treatment groups, respectively. We observed differences in final visual outcomes and in improvement from diagnosis to final visual acuity, with patients receiving immediate and late vitrectomy to have better final visual outcomes than those patients receiving early vitrectomy ( p

Background: Mechanical low back pain is the pain in the lumbar area caused by aberrant stresses on the spine's vertebrae, ligaments, soft tissues, intervertebral discs, muscles and other soft tissues Objective: To determine the association between non-specific mechanical low back pain and limited ankle dorsiflexion among female students. Methodology: This cross-sectional study was conducted at Agile Institute of Rehabilitation Sciences from November 2021-March 2022. A total of 133 female students of age 18-30 years were included in this study. Students wearing high heels were excluded. The data was collected using Numeric Pain Rating Scale questionnaire for low back pain and goniometry for measuring ankle dorsiflexion. Data was analyzed using Statistical Package for Social Sciences version 22.0 to create graphs and tables. Chi square test was used for statistical analysis to find the association between low back pain and limited ankle dorsiflexion. Results: A total of 133 participants were screened for low back pain. Out of total, 61 (45.86%) participants with mechanical low back pain had limited ankle dorsiflexion range of motion (≤10 degree) on left side while 64 (48.12%) participants with mechanical low back pain had limited ankle dorsiflexion range of motion (≤10 degree) on right side ankle. P value of chi square association of low back pain and ankle dorsiflexion was 0.078 for right ankle and 0.114 for left ankle. Conclusions: This study concluded that there was no association found between non-specific mechanical low back pain and limited ankle dorsiflexion range of motion. Keywords: Ankle joint, Dorsiflexion, Mechanical Low Back Pain

Brain tumors necessitate swift detection and classification for optimal patient outcomes. Deep learning has been extensively utilized to recognize complex tumor patterns in magnetic resonance imaging (MRI) images, aiding in tumor diagnosis, treatment, and prognostication. However, model complexity and limited generalizability with unfamiliar data hinder appropriate clinical integration. The objective of this study is to develop a clean-energy cloud-based deep learning platform to classify brain tumors. Three datasets of a total of 2611 axial MRI images were used to train our multi-layer convolutional neural network (CNN). Our platform automatically optimized every transfer learning and data augmentation feature combination to provide the highest predictive accuracy for our classification task. Our proposed system identified and classified brain tumors successfully and efficiently with an overall precision value of 96.8% [95% CI; 93.8–97.6]. Using clean energy supercomputing resources and cloud platforms cut our workflow to 103 min, $0 in total cost, and a negligible carbon footprint (0.0014 kg eq CO2). By leveraging automated optimized learning, we developed a cost-effective deep learning (DL) platform that accurately classified brain tumors from axial MRI images of different levels. Although studies have identified machine learning tools to overcome these obstacles, only some are cost-effective, generalizable, and usable regardless of experience.

Generative-AI (GAI) models like ChatGPT are becoming widely discussed and utilized tools in medical education. For example, it can be used to assist with studying for exams, shown capable of passing the USMLE board exams. However, there have been concerns expressed regarding its fair and ethical use. We designed an electronic survey for students across North American medical colleges to gauge their views on and current use of ChatGPT and similar technologies in May, 2023. Overall, 415 students from at least 28 medical schools completed the questionnaire and 96% of respondents had heard of ChatGPT and 52% had used it for medical school coursework. The most common use in pre-clerkship and clerkship phase was asking for explanations of medical concepts and assisting with diagnosis/treatment plans, respectively. The most common use in academic research was for proof reading and grammar edits. Respondents recognized the potential limitations of ChatGPT, including inaccurate responses, patient privacy, and plagiarism. Students recognized the importance of regulations to ensure proper use of this novel technology. Understanding the views of students is essential to crafting workable instructional courses, guidelines, and regulations that ensure the safe, productive use of generative-AI in medical school.

Background: Wastewater is a major source of Antibiotic-Resistant Bacteria (ARB) and a hotspot for the exchange of Antibiotic-Resistant Genes (ARGs). The occurrence of Carbapenem-Resistant Bacteria (CRB) in wastewater samples is a major public health concern. Objectives: This study aimed to analyze Antibiotic resistance in bacteria from wastewater sources in Pakistan. Methods: We analyzed 32 bacterial isolates, including 18 Escherichia coli, 4 Klebsiella pneumoniae, and 10 other bacterial isolates using phenotypic antibiotic susceptibility assay and whole-genome sequencing. This study identified the ARGs, plasmid replicons, and integron genes cassettes in the sequenced isolates. One representative isolate was further sequenced using Illumina and Oxford nanopore sequencing technologies. Results: Our findings revealed high resistance to clinically important antibiotics: 91% of isolates were resistant to cefotaxime, 75% to ciprofloxacin, and 62.5% to imipenem, while 31% showed non-susceptibility to gentamicin. All E. coli isolates were resistant to cephalosporins, with 72% also resistant to carbapenems. Sequence analysis showed a diverse resistome, including carbapenamases (blaNDM-5, blaOXA-181), ESBLs (blaCTX-M-15, blaTEM), and AmpC-type β-lactamases (blaCMY). Key point mutations noticed in the isolates were pmrB_Y358N (colistin) and ftsI_N337NYRIN, ftsI_I336IKYRI (carbapenem). The E. coli isolates had 11 different STs, with ST410 predominating (28%). Notably, the E. coli phylogroup A isolate 45EC1, (ST10886) is reported for the first time from wastewater, carrying blaNDM-5, blaCMY-16, and pmrB_Y358N with class 1 integron gene cassette of dfrA12-aadA2-qacEΔ1 on a plasmid-borne contig. Other carbapenamase, blaNDM-1 and blaOXA-72, were detected in K. pneumoniae 22EB1 and Acinetobacter baumannii 51AC1, respectively. The integrons with the gene cassettes encoding antibiotic resistance, and the transport and bacterial mobilization protein, were identified in the sequenced isolates. Ten plasmid replicons were identified, with IncFIB prevalent in 53% of isolates. Combined Illumina and Oxford nanopore sequencing revealed blaNDM-5 on an IncFIA/IncFIC plasmid and is identical to those reported in the USA, Myanmar, and Tanzania. Conclusions: These findings highlight the environmental prevalence of high-risk and WHO-priority pathogens with clinically important ARGs, underscoring the need for a One Health approach to mitigate ARB isolates.

Abstract Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.

Objective: To assess the effectiveness of functional endoscopies sinus surgery in improving olfaction in patients diagnosed with chronic rhinosinusitis with nasal polyps, as measured by changes in Sniffin’s Stick scores and olfaction scores pre and post operatively. Methodology: The clinical observational study was conducted at the ENT department, Services Hospital, Lahore for 6 months from 01-03-2022 to 31-08- 2022. Sixty-six patients (66) diagnosed with chronic rhinosinusitis with nasal polyps were enrolled, and evaluated by using Sniffin’s Stick score and olfaction baseline score. The inclusion criteria were patients aged 10-60 years of age diagnosed with this condition and willing to undergo surgery. Operative time was noted. After surgery, patients were discharged and were followed-up in OPD for 3 months. After 3 months, patients were re-evaluated for Sniffin’s Stick score and olfaction score. Results: The mean age of the patients was 36.18±13.87 years, 49(74.24%) patients were male. On pre-op evaluation the mean Sniffin’s Stick score of the patients was 6.14±0.41 which improved to 7.34±0.41 on postop evaluation. Similarly on pre-op evaluation the mean olfaction score of the patients was 8.30±5.84 which improved to 21.12±5.95 on post-op evaluation. Conclusion: There is significant improved outcome observed in terms snuffiness and olfaction score for functional endoscopic sinus surgery in patents of chronic rhino-sinusitis with nasal polyps

Abstract Background Current standard therapy for seizure prophylaxis in Neuro-surgical patients involves the use of Phenytoin (PHY). However, a new drug Levetiracetam (LEV) is emerging as an alternate treatment choice. We aimed to conduct a meta-analysis to compare these two drugs in patients with brain injury. Methods An electronic search was performed in using Pubmed, Embase, and CENTRAL. We included studies that compared the use of LEV vs. PHY for seizure prophylaxis for brain injured patients (Traumatic brain injury, intracranial hemorrhage, intracranial neoplasms, and craniotomy). Data of all eligible studies was extracted on to a standardized abstraction sheet. Data about baseline population characteristics, type of intervention, study design and outcome was extracted. Our primary outcome was seizures. Results The literature search identified 2489 unduplicated papers. Of these 2456 papers were excluded by reading the abstracts and titles. Another 25 papers were excluded after reading their complete text. We selected 8 papers which comprised of 2 RCTs and 6 observational studies. The pooled estimate’s Odds Ratio 1.12 (95% CI = 0.34, 3.64) demonstrated no superiority of either drug at preventing the occurrence of early seizures. In a subset analysis of studies in which follow up for seizures lasted either 3 or 7 days, the effect estimate remained insignificant with an odds ratio of 0.96 (95% CI = 0.34, 2.76). Similarly, 2 trials reporting seizure incidence at 6 months also had insignificant pooled results while comparing drug efficacy. The pooled odds ratio was 0.96 (95% CI = 0.24, 3.79). Conclusions Levetiracetam and Phenytoin demonstrate equal efficacy in seizure prevention after brain injury. However, very few randomized controlled trials (RCTs) on the subject were found. Further evidence through a high quality RCT is highly recommended.

Unmanned aerial vehicles (UAVs) play a crucial role in enhancing search and rescue (SAR) operations by accessing inaccessible areas, accomplishing challenging tasks, and providing real-time monitoring and modeling in situations where human presence is unsafe. Multi-UAVs can collaborate more efficiently and cost-effectively than a single large UAV for performing SAR operations. In multi-UAV systems, task allocation (TA) is a critical and complex process involving cooperative decision making and control to minimize the time and energy consumption of UAVs for task completion. This paper offers an exhaustive review of both static and dynamic TA algorithms, confidently assessing their strengths, weaknesses, and limitations. It provides valuable insights into addressing research questions related to specific UAV operations in SAR. The paper rigorously discusses outstanding issues and challenges and confidently presents potential directions for the future development of task assignment algorithms. Finally, it confidently highlights the challenges of multi-UAV dynamic TA methods for SAR. This work is crucial for gaining a comprehensive understanding of multi-UAV dynamic TA algorithms and confidently emphasizes critical open issues and research gaps for future SAR research and development, ensuring that readers feel informed and knowledgeable.

Objective To assess the impact of HRQoL in patients hospitalised with COVID-19-related SARI at 1 year post discharge, focusing on the potential impact of age, frailty, and disease severity.Method Routinely collected outcome data on 1207 patients admitted with confirmed COVID-19 related SARI across all three secondary care sites in our NHS trust over 3 months were assessed in this retrospective cohort study. Of those surviving 1 year, we prospectively collected 36-item short form (SF-36) HRQoL questionnaires, comparing three age groups (

Background. The relationship of the root of the maxillary third molars and the maxillary sinus (MS) is an important predictor of the anticipated difficulty in extraction. The aim of this study was to assess the location of maxillary third molars to the inferior wall of the MS in a sample of Pakistani population evaluated using cone-beam computed tomography (CBCT) imaging and to assess if age or gender has any influence on third molar to MS distance. Methods. The CBCT scans of adult patients, carried out keeping image volume at 8 cm×8 cm, and the voxel size 0.2 and 0.1 mm. Images retrieved from the hospital database were included in the study. The relationship of root apices of maxillary third molar with the MS was assessed according to the vertical, horizontal and Winter’s classification. Descriptive statistics, t test and chi-square test of association were applied. Results. CBCT scans of 93 patients, 56 males and 37 females were evaluated. The mean age was 41.12±17.13 years. The mean distance of third molar roots to the MS wall was 2.38±1.54 mm for males and 1.86±1.04 mm for females, on the left and 2.67±1.81 mm for males and 2.58±1.54 mm in females, on the right side. Independent sample t test showed that there was no significant difference for third molar to sinus wall distance in the two genders. No significant difference was found between the two sides. Conclusion. In a sub-population of Pakistani adults, the mean distance between the roots of the upper third molar and MS wall is around 2 mm. Only 5% males and 8% females had their upper third molars roots protruding into the MS.

Confronted with the rapid technological changes and increased global competition, training of employees now focused on self-directed development (SDD). Despite the recognition of self-directed development, only few empirical studies have investigated the combined relationship of both predictors and outcomes simultaneously. This research attempted to develop and test a conceptual model of SDD, which includes both individual and contextual factors as predictors and outcomes, following an input--process--output perspective. The model was validated through SEM analysis from a sample of 383 working business students. In general, results indicate that SDD is a mix of both individual and contextual factors that lead to positive outcomes. The findings offer new insights into the way organizations can improve employee development through SDD. However, unexpected findings were also noted. Job autonomy has an insignificant relationship, whereas empowerment and proactive personality were weakly associated with SDD.