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Background:. Congenital vertical talus (CVT) and congenital oblique talus (COT) are rocker-bottom foot deformities that have similar names and no objective definitions. This has led to confusion for practitioners, as well as scientific challenges for researchers. Our goal was to provide objective radiographic criteria to define and differentiate CVT and COT. Methods:. We evaluated 62 pairs of maximum dorsiflexion and plantar flexion lateral radiographs of infant feet that had been clinically diagnosed with CVT. The dorsiflexion tibiotalar angle, the plantar flexion talus-first metatarsal angle, and the plantar flexion foot center of rotation of angulation (foot-CORA) were measured using transparent overlay tools. Freehand measurements were made on a subset of 10 pairs of radiographs to confirm clinical applicability. Nine contralateral pairs of radiographs of normal feet were measured for comparison. Results:. Specific values for the radiographic measurements were identified that, together, reliably differentiated the shapes of rocker-bottom feet with CVT, COT, and flexible flatfoot with a short tendo-Achilles (FFF-STA), as well as the shape of the normal foot. More severe and rigid rocker-bottom foot deformities were diagnosed with CVT. Less severe and more flexible deformities were diagnosed with COT. Conclusions:. CVT, COT, FFF-STA, and normal feet can be reliably differentiated using 2 angular measurements and 1 bone position measurement on dorsiflexion and plantar flexion lateral radiographs. Our data indicated that the differentiation of CVT and COT is based primarily on the rigidity of the navicular dislocation rather than the verticality of the talus. The data further supported the proposition that COT is a foot deformity along a spectrum of valgus/eversion deformities of the hindfoot that requires early treatment. Application of these diagnostic criteria should lead to clinical studies that identify a specific treatment, treatment outcome, and prognosis for each deformity. Level of Evidence:. Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

MYC is a transcription factor crucial for maintaining cellular homeostasis, and its dysregulation is associated with highly aggressive cancers. Despite being considered “undruggable” due to its unstable protein structure, MYC gains stability through its interaction with its partner protein, MAX. The MYC-MAX heterodimer orchestrates the expression of numerous genes that contribute to an oncogenic phenotype. Previous efforts to develop small molecules, disrupting the MYC-MAX interaction, have shown promise in vitro but none have gained clinical approval. Our current computer-aided study utilizes an approach to explore drug repurposing as a strategy for inhibiting the c-MYC-MAX interaction. We have focused on compounds from DrugBank library, including Food and Drug Administration-approved drugs or those under investigation for other medical conditions. First, we identified a potential druggable site on flat interface of the c-MYC protein, which served as the target for virtual screening. Using both activity-based and structure-based screening, we comprehensively assessed the entire DrugBank library. Structure-based virtual screening was performed on AutoDock Vina and Glide docking tools, while activity-based screening was performed on two independent quantitative structure-activity relationship models. We focused on the top 2% of hit molecules from all screening methods. Ultimately, we selected consensus molecules from these screenings—those that exhibited both a stable interaction with c-MYC and superior inhibitory activity against c-MYC-MAX interaction. Among the evaluated molecules, we identified a protein kinase inhibitor (tyrosine kinase inhibitor [TKI]) known as nilotinib as a promising candidate targeting c-MYC-MAX dimer. Molecular dynamic simulations demonstrated a stable interaction between MYC and nilotinib. The interaction with nilotinib led to the stabilization of a region of the MYC protein that is distorted in apo-MYC and is important for MAX binding. Further analysis of differentially expressed gene revealed that nilotinib, uniquely among the tested TKIs, induced a gene expression program in which half of the genes were known to be responsive to c-MYC. Our findings provide the foundation for subsequent in vitro and in vivo investigations aimed at evaluating the efficacy of nilotinib in managing MYC oncogenic activity.

Background IDH1 mutations are common in many cancers, however, their role in promoting the Warburg effect remains elusive. This study elucidates the putative involvement of mutant-IDH1 in regulating hypoxia-inducible factor (HIF1-α) and Sine-Oculis Homeobox-1 (SIX-1) expression. Methodology Genetic screening was performed using the ARMS-PCR in acute myeloid leukemia (AML), brain, and breast cancer (BC) cohorts, while transcript expression was determined using qPCR. Further, a meta-analysis of risk factors associated with the R132 mutation was performed. Results Approximately 32% of AML and ∼60% of glioma cases were mutants, while no mutation was found in the BC cohort. ‘AA’ and TT’ were associated with higher disease risk (OR = 12.18 & 4.68) in AML and had significantly upregulated IDH1 expression. Moreover, downregulated HIF1-α and upregulated SIX-1 expression was also observed in these patients, suggesting that mutant-IDH1 may alter glucose metabolism. Perturbed IDH1 and HIF-α levels exhibited poor prognosis in univariate and multivariate analysis, while age and gender were found to be contributory factors as well. Based on the ROC model, these had a good potential to be used as prognostic markers. A significant variation in frequencies of R132 mutations in AML among different populations was observed. Cytogenesis ( R 2 = 12.2%), NMP1 mutation status ( R 2 = 18.5%), and ethnic contributions ( R 2 = 73.21%) were critical moderators underlying these mutations. Women had a higher risk of R132 mutation (HR = 1.3, P < 0.04). The pooled prevalence was calculated to be 0.29 (95% CI 0.26-0.33, P < 0.01), indicating that IDH1 mutations are a significant prognostic factor in AML. Conclusion IDH1 and HIF1-α profiles are linked to poor survival and prognosis, while high SIX-1 expression in IDH1 mutants suggests a role in leukemic transformation and therapy response in AML.

ABSTRACT: Hip Arthroscopy in the pediatric and adolescent hip has evolved from its role as a diagnostic tool to a primary modality of management of variety of hip pathologies in children and adolescents. This article reviews current concepts and advances in hip arthroscopy in this population. We discuss the indications, techniques, outcomes, and complications of hip arthroscopy in children and adolescents. We explore the newer indications of hip arthroscopy in the treatment of SCFE (Slipped Capital Femoral Epiphysis) deformity correction, borderline hip dysplasia, septic arthritis, infantile developmental dysplasia, Perthes disease, and the existing and developing evidence. Finally, we address the challenges and future directions in research, education, and training, unique to the pediatric and adolescent population. Key Concepts: (1) Hip arthroscopy has significant surgical applications in the pediatric and adolescent population, and can be used to help address several intra-articular as well as extra-articular pathologies. (2) The indications and potential for arthroscopic interventions and associated arthroscopic techniques is growing and developing rapidly, along with improving technology, techniques, and training. (3) FAI (Femoro Acetabular Impingement) and labral pathology are the most common indications for surgery in the adolescent, and clinical outcome studies show excellent results. However, nonoperative optimization should be strongly emphasized before surgical consideration. (4) Hip arthroscopy is minimally invasive and relatively low risk, though main risks and complications to be aware of is the potential need for revision or further surgery, transient neuropraxia of the pudendal nerve, surgical site infection, implant/tool-related breakage or failure, failed surgery, and venous thromboembolism. (5) Continued research and innovation in the field of pediatric hip arthroscopy are essential for further improving outcomes and expanding treatment options for young patients with hip disorders, and more pediatric-specific clinical research is needed.

Objective: To characterize the development and performance of a cataract surgery episode-based cost measure for the Medicare Quality Payment Program. Design: Claims-based analysis. Participants: Medicare clinicians with cataract surgery claims between June 1, 2016, and May 31, 2017. Methods: We limited the analysis to claims with procedure code 66984 (routine cataract surgery), excluding cases with relevant ocular comorbidities. We divided episodes into subgroups by surgery location (Ambulatory Surgery Center [ASC] or Hospital Outpatient Department [HOPD]) and laterality (bilateral when surgeries were within 30 days apart). For the episode-based cost measure, we calculated costs occurring between 60 days before surgery and 90 days after surgery, limited to services identified by an expert committee as related to cataract surgery and under the influence of the cataract surgeon. We attributed costs to the clinician submitting the cataract surgery claim, categorized costs into clinical themes, and calculated episode cost distribution, reliability in detecting clinician-dependent cost variation, and costs with versus without complications. We compared episode-based cost scores with hypothetical “nonselective” cost scores (total Medicare beneficiary costs between 60 days before surgery and 90 days after surgery). Main Outcome Measures: Episode costs with and without complications, clinician-dependent variation (proportion of total cost variance), and proportion of costs from cataract surgery-related clinical themes. Results: We identified 583 356 cataract surgery episodes attributed to 10 790 clinicians and 8189 with ≥ 10 episodes during the measurement period. Most surgeries were performed in an ASC (71%) and unilateral (66%). The mean episode cost was $2876. The HOPD surgeries had higher costs; geography and episodes per clinician did not substantially affect costs. The proportion of cost variation from clinician-dependent factors was higher in episode-based compared with nonselective cost measures (94% vs. 39%), and cataract surgery-related clinical themes represented a higher proportion of total costs for episode-based measures. Episodes with complications had higher costs than episodes without complications ($3738 vs. $2276). Conclusions: The cataract surgery episode-based cost measure performs better than a comparable nonselective measure based on cost distribution, clinician-dependent variance, association with cataract surgery-related clinical themes, and quality alignment (higher costs in episodes with complications). Cost measure maintenance and refinement will be important to maintain clinical validity and reliability. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Background: Although the classic open Latarjet has a low recurrence rate in unstable shoulders, this advantage may be offset by the higher number of complications. We aimed to report the safety-driven nuanced steps and the resulting short-term complications of the Latarjet-Walch technique. Methods: Between 2016 and 2022, 150 patients who underwent the Latarjet procedure following the key safety-driven technical steps were retrospectively evaluated for intraoperative and short-term (3 months) complications. The complications were divided into 3 types: Any adverse event that did not need a change in the treatment protocol was a type 1 complication. An event that resulted in a prolongation of rehabilitation protocol or an additional medical line of treatment was classified as type 2, and an event that resulted in readmission, a resurgery, or one that affected the outcome was classified as a type 3 complication. Results: There were 12 (8%) short-term complications in 9 patients. Neurological complications were noted in 3 (2%) patients (1 axillary nerve injury, 1 suprascapular nerve injury, and 1 musculocutaneous nerve injury). Type 1 complications were noted in 2 patients: 2 patients had hematoma that was detected as superficial swelling, but no surgical drainage was needed, and both resolved at their 1-month follow-up. Type 2 complications were noted in 4 patients. One patient had surgical site infection and a second patient had superficial wound dehiscence in the lower part of the wound. The third patient had suprascapular nerve paresis and the fourth had musculocutaneous nerve paresis and shoulder stiffness. Both nerve injuries recovered completely after 6 months of rehabilitation. Type 3 complications were noted in 3 patients. One patient had axillary nerve paresis and shoulder stiffness. The axillary nerve palsy had recovered partially by 8 months. One patient had an intraoperative graft fracture and postoperative shoulder stiffness, and the third patient had shoulder stiffness. Conclusion: Following the safety-driven nuanced steps in the Latarjet-Walch procedure, the short-term complication rate was 8%, and the neurological complication was 2% (n = 3). The musculocutaneous and suprascapular nerves completely recovered, and the axillary nerve had partially recovered.

Background. Kidneys from potential deceased donors with brain cancer are often foregone due to concerns of cancer transmission risk to recipients. There may be uncertainty around donors’ medical history and their absolute transmission risk or risk-averse decision-making among clinicians. However, brain cancer transmissions are rare, and prolonging waiting time for recipients is harmful. Methods. We assessed the cost-effectiveness of increasing utilization of potential deceased donors with brain cancer using a Markov model simulation of 1500 patients waitlisted for a kidney transplant, based on linked transplant registry data and with a payer perspective (Australian government). We estimated costs and quality-adjusted life-years (QALYs) for three interventions: decision support for clinicians in assessing donor risk, improved cancer classification accuracy with real-time data-linkage to hospital records and cancer registries, and increased risk tolerance to allow intermediate-risk donors (up to 6.4% potential transmission risk). Results. Compared with current practice, decision support provided 0.3% more donors with an average transmission risk of 2%. Real-time data-linkage provided 0.6% more donors (1.1% average transmission risk) and increasing risk tolerance (accepting intermediate-risk 6.4%) provided 2.1% more donors (4.9% average transmission risk). Interventions were dominant (improved QALYs and saved costs) in 78%, 80%, and 87% of simulations, respectively. The largest benefit was from increasing risk tolerance (mean +18.6 QALYs and AU$2.2 million [US$1.6 million] cost-savings). Conclusions. Despite the additional risk of cancer transmission, accepting intermediate-risk donors with brain cancer is likely to increase the number of donor kidneys available for transplant, improve patient outcomes, and reduce overall healthcare expenditure.

Spontaneous spinal epidural hematoma is a rare predominantly idiopathic entity which can prompt acute neurologic symptoms and if not managed in time can lead to devastating outcomes. High index of suspicion is required for early diagnosis on MRI for a prompt management of patients showing sudden neurologic deficits. Our patient was 42-year-old female who presented with sudden onset of numbness followed by weakness in both lower limbs and urinary retention without any comorbidity or any medication. MRI whole spine done within 14 hours of symptom onset showed ventral epidural hematoma without any vascular malformation. Immediate decompressive laminectomy with evacuation of hematoma improved power in both lower limbs with regaining bowel and bladder function. The key here is timely surgical decompression of the hematoma for a favorable neurosurgical outcome. Although there is a recent development towards non–surgical treatment, it needs to be well established yet and require such approach on case-to-case basis.

Background:. Collagen nerve wraps (CNWs) theoretically allow for improved nerve gliding and decreased perineural scarring, and create a secluded environment to allow for nerve myelination and axonal healing. The goal of this study was to investigate the effect of CNWs on nerve gliding as assessed by pull-out strength and nerve changes in a rabbit model of peripheral neuropathy. Methods:. Ten New Zealand rabbits were included. Sham surgery (control) was performed on left hindlimbs. To simulate compressive neuropathy, right sciatic nerves were freed of the mesoneurium, and the epineurium was sutured to the wound bed. Five rabbits were euthanized at 6 weeks [scarred nerve (SN); n = 5]. Neurolysis with CNW was performed in the remaining rabbits at 6 weeks (CNW; n = 5), which were euthanized at 22 weeks. Outcomes included peak pull-out force and histopathological markers of nerve recovery (axonal and Schwann cell counts). Results:. The CNW group demonstrated significantly higher pull-out forces compared with the CNW sham control group (median: 4.40N versus 0.37N, P = 0.043) and a trend toward greater peak pull-out forces compared with the SN group (median: 4.40N versus 2.01N, P = 0.076). The CNW group had a significantly higher median Schwann cell density compared with the CNW control group (CNW: 1.30 × 10−3 cells/μm2 versus CNW control: 7.781 × 10−4 cells/μm2, P = 0.0431) and SN group (CNW: 1.30 × 10−3 cells/μm2 versus SN: 7.31 × 10−4 cells/μm2, P = 0.009). No significant difference in axonal density was observed between groups. Conclusion:. Our findings suggest using a CNW does not improve nerve gliding, but may instead play a role in recruiting and/or supporting Schwann cells and their proliferation.

Background: There remains a paucity of data regarding long-term patient-reported outcomes following Lisfranc injuries. We sought to collect long-term clinical outcome data following Lisfranc injuries using PROMIS Physical Function (PROMIS-PF) and visual analog scale–foot and ankle (VAS-FA). Methods: A chart review was performed to identify all patients who had surgical treatment of an acute Lisfranc injury at our institution from 2005 to 2014. Of the 45 patients identified, we were able to recruit 19 for a follow-up clinic visit consisting of physical examination, administration of questionnaires addressing pain and medication usage, radiographs, and completion of outcome surveys including PROMIS-Physical Function and visual analog scale–foot and ankle. Results: There were 14 female and 5 male patients enrolled in the study with a mean time of 6.25 years from the time of injury. Within this cohort, the mean PROMIS-PF score was 52.4±8.2 and the mean VAS–foot and ankle score was 76.6±22.3. Conclusion: We report satisfactory long-term patient-reported outcomes using PROMIS-PF and VAS-FA. Level of Evidence: Level III, retrospective cohort study.

Purpose: Postoperative radiation therapy (RT) is commonly used for World Health Organization grade II-III intracranial ependymoma. Clinicians generally aim to begin RT ≤5 weeks after surgery, but postoperative recovery and need for second look surgery can delay the initiation of adjuvant therapy. On ACNS 0831, patients were required to enroll ≤8 weeks after initial surgery and begin adjuvant therapy within 3 weeks after enrollment. The purpose of this study was to determine the optimal timing of RT after surgery. Methods and Materials: The National Cancer Database was queried for patients (aged 1-39 years) with localized World Health Organization grade II-III intracranial ependymoma treated with surgery and postoperative RT. Overall survival (OS) curves were plotted based on RT timing (≤5 weeks, 5-8 weeks, and >8 weeks after surgery) and were compared by log-rank test. Factors associated with OS were identified by multivariate analysis. After 2009, complete data were available on whether patients underwent gross total resection or subtotal resection. Planned subset analysis was performed to examine the effect of RT timing on OS in patients with known extent of resection. Results: In the final analytical data set of 1043 patients, no difference in 3-year OS was observed in patients who initiated RT ≤5 weeks, 5 to 8 weeks, and >8 weeks after surgery (89.8% vs 89.1% vs 88.4%; P = .796). On multivariate analysis, grade III tumors (hazard ratio, 2.752; 95% confidence interval, 1.969-3.846, P < .001) and subtotal resection (hazard ratio, 2.253; 95% confidence interval, 1.405-3.611, P < .001) were significantly associated with reduced OS. Timing of RT, total RT dose, age, and other factors were not significant. These findings were affirmed in the subset of patients treated between 2010 and 2016, when extent of resection was routinely recorded. Conclusions: Delayed postoperative RT was not associated with inferior survival in patients with intracranial ependymoma. Delayed RT initiation may be acceptable in patients who require longer postoperative recovery or referral to an appropriate RT center, but should be minimized whenever practical.

Category: Hindfoot Introduction/Purpose: Tibiotalocalcaneal (TTC) fusion is a salvage procedure for post-traumatic as well as neuropathic cases. Many of these cases are characterised by some or other form of loss of talus resulting in a defect. At TTC fusion, prevention of shortening following such a defect is a challenge. Though allografts have helped solve this issue, they may not be easily available in developing countries. A retrospective analysis of prospectively collected data of 14 cases of TTC fusion with loss of talus is presented here. Cases were managed with innovative defect bridging ‘Bamboo Hut’ technique. Methods: Cases with either preoperative or perioperative loss of talus who required bridging of defect were included in the present study. Resultant defect following excision of the talus was bridged with two or three vertically placed fibular strut grafts. Grafts were snugly tied with each other with sutures to prepare a construct like a hut supported with wooden steaks (Bamboo). Fixation was carried out with indigenous TTC nail with a built-in compression device to generate compression of grafts between tibia and calcaneus. Results: Present series comprised of 6 post-traumatic cases, 7 cases of diabetic Charcot neuroarthropathy and 1 case of neuroarthropathy following operated meningomyelocele. Cases were followed up for an average period of 36 months with the average time to union being six months. All posttraumatic cases went on to the bony union but two out of eight neuropathy cases ended up in fibrous union with collapse & loss of fixation. Wound healing issues were noticed in two cases. None of the cases required amputation. Conclusion: With non-availability of allografts, prevention of shortening at TTC fusion is a challenge. This issue can be successfully managed with innovative ‘Bamboo Hut’ grafting technique, supported with in-built compression of the fusion site with the use of an indigenous nail.

Category: Trauma Introduction/Purpose: Primary subtalar fusion for Sander IV calcaneus fractures was considered to be the standard of care till recent past. Presently debate is on whether to manage Sander IV calcaneus fracture cases with primary subtalar fusion or with open reduction and internal fixation. Bilateral Sander IV calcaneus fractures are seen in cases with fall from height. No study has ever been conducted till date to compare the results of primary fusion of a Sander IV calcaneus fracture on one side and open reduction and internal fixation on another side in cases with bilateral Sander IV calcaneus fractures. We present a study comparing the results of primary fusion versus open reduction and internal fixation for bilateral sander IV calcaneus fracture cases. Methods: Twelve cases with bilateral closed Sander IV calcaneus fractures where included in the present study. Cases were operated between four to six weeks by a single surgeon after the appearance of wrinkles. All right sided fractures underwent open reduction and internal fixation with proximal tibia grafting. While all left-sided fractures underwent subtalar fusion with the use of ipsilateral anterior iliac crest grafts. Cases were followed up for 24 months. Results: Though operative time was more in the fusion group wound problems were equal in both the groups. Four months of average time to union was the same in both the groups and so was time to return to work. At two years, the AOFAS score was slightly better in the fusion group but it was not statistically significant. Conclusion: Primary subtalar fusion is with almost similar results as those with open reduction and internal fixation in bilateral Sander IV at 24 months. Long term follow up with more number of cases is required to prove the benefit of one over other.

This research investigates the strategies for the Sustainable Rural Development in Pakistan. The current scenario is quiet dismal warrants the urgent need on the part of the governments of the world, organization, and all other stake-holders to come together to take stock of the grim situation and act collectively to protect environment in the interest of present of future generations. If we don't act swiftly at this critical and juncture the future cost of inaction would be very high perhaps beyond the means of developing countries. Data were collected from 30 organizations by using simple random technique and data were analyzed by using SPSS software. It was revealed that sustainable development of the rural sector in Pakistan produces evidences of the degradation of the rural resources such as land, water, air, forest, biodiversity, ecology, and also erosion of social values. [ABSTRACT FROM AUTHOR]

The aim of this paper is to investigate the Globalization and recent trends in Strategic management and corporate Governance in Pakistan. The data were collected from various secondary sources. It was revealed that As Global corporations are confronted with the challenges of balancing control and collaboration, many have turned to interorganization relationship, to compete in the global market place. The engagement in interorganization relationships results in the emergence of new organizational forms such as strategic alliances, joint ventures, and cooperative net work. For many reasons the efforts to drive down costs, to speed up innovation and time to markets and to tap into a firm-specific repertoire of knowledge and technology-TNCs often prefer to cooperate in order to compete. [ABSTRACT FROM AUTHOR]

Asian Americans (AA) are thought to have the lowest rates of substance use. This study examined substance use prevalence among 494 urban-dwelling Southeast Asians using snowball techniques. Prevalence estimates were age-adjusted proportionate to the U.S. Asian population. Findings show beer and alcohol consumption approximated the national percentage among 25-44 year olds. U.S.-born were about three times likelier to have past month substance use. Foreign-born Vietnamese were likelier than U.S.-born to use all substances except for beer. U.S.- and foreign-born beer consumption rates were similar. Future research is needed to delineate substance use determinants and patterns in foreign and U.S.-born AA sub-groups. [ABSTRACT FROM AUTHOR]

Background: In Malaysia, the recent COVID-19 pandemic had increased the workload of all health professionals, especially primary care doctors (PCDs). Hence, this study aimed to determine the level of work-related stress and factors associated with higher levels of work-related stress among PCDs in Malaysia during this pandemic., Methods: A cross-sectional study was conducted online using Google Forms™. Sociodemographic as well as work and workplace data were collected. The Job Demand Inventory, Physicians' Lack of Professional Autonomy, and Health Professions Stress Inventory questionnaires were used to assess the job demand score, job autonomy score, and the level of work-related stress, respectively. Multiple linear regression was performed to determine the significant factors associated with higher work-related stress., Results: A total of 301 PCDs participated in this study with the majority being female (76.1%), Malay (67.8%), married (73.1%), medical officers (68.8%), and worked in urban (70.4%) and public primary care clinics (83%). The mean (SD) score for work-related stress was 62.8 (18.4), (score range 0-120). PCDs who had any degree of worry about being alienated by friends and relatives because of close contact with COVID-19 patients had higher work-related stress levels compared to PCDs who did not have any worry [rarely (b = 10.23, 95% CI:5.57, 14.89), sometimes (b = 10.41, 95% CI:5.68, 15.13), often (b = 10.12, 95% CI:4.16, 16.08), and always (b = 14.65, 95% CI:7.43, 21.89)]. The other significant factor was higher job demand scores (b = 1.13, 95% CI:0.91, 1.35). In contrast, PCDs who always received support from supervisors at their workplace were found to have lower work-related stress levels compared to those who did not receive any support (b=-5.65, 95% CI:-10.38, -0.93)., Conclusions: The level of work-related stress among Malaysian PCDs during the COVID-19 pandemic was higher compared to American PCDs and Malaysian physicians before the pandemic but lower compared to Australian emergency physicians during the pandemic. Urgent measures to address the above-mentioned associated factors should be implemented as another pandemic may be just around the corner., Competing Interests: Declarations. Ethical approval: The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of Universiti Teknologi MARA (UiTM) Selangor, Malaysia and the Malaysia Research Ethics Committee (MREC) from the National Medical Research Register (NMRR). The approval reference number from UiTM Research Ethics Committee is [REC/12/2021 (MR/927)] and NMRR Project ID: NMRR ID-21-02232-U2A (IIR). Consent to participate: Informed consent was obtained from all subjects involved in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Bowel regimens (BR) before radical cystectomy (RC) are currently not recommended by Enhanced Recovery After Surgery (ERAS) protocols, as prior studies have shown BRs lead to worsened outcomes. However, many of those studies have used historic literature before recent surgical advancements such as minimally invasive RC and have not investigated the impact BRs have by type of urinary diversion. Our goal is to determine the outcomes of preoperative BR in patients undergoing RC based on diversion type using a modern patient cohort., Methods: RCs performed between 2019 and 2020 with BR information available were identified in the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP). Patients were grouped by type of BR received: no BR, both mechanical bowel preparation (MBP) and preoperative oral antibiotic BR (OABR), MBP only, and OABR only. We conducted propensity score matching based on factors influencing the operative approach. Baseline demographics and 30-day complication rates were compared between matched groups. We analyzed hospital length of stay (LOS) via multivariate regression with a Poisson distribution., Results: In total, 2054 RCs were identified with 2.4% receiving OABR, 21.3% receiving MBP, 5.3% receiving both, and 71.0% receiving no BR. For patients with ileal conduit diversions, outcomes with BRs appeared mixed, as OABR leads to increased LOS. For patients with neobladder diversions, BRs were not associated with any worsened outcomes and were associated with reduced length of stay., Conclusions: BRs such as OABR may associated with improved outcomes in patients receiving RC with neobladder diversion, a finding that warrants further investigation., (© 2025 The Japanese Urological Association.)

Introduction: Placing ureteral stents at the ureteroileal anastomosis for radical cystectomy with ileal conduit (RCIC) has long been common practice. Recently, some providers have begun omitting stents. We sought to investigate differences in perioperative and 30-day outcomes between patients who underwent RCIC with and without stents placed at the ureteroileal anastomosis., Methods: We identified RCICs performed between 2019 and 2021 in the National Surgical Quality Improvement Program database and corresponding Cystectomy-Targeted Participant Use File. Baseline demographics, comorbidities, and operative parameters were compared via Pearson's χ 2 and t tests between stented and stentless RCICs. Outcomes of interest, including rates of UTIs, acute kidney injury, renal failure requiring dialysis, ileoileal anastomotic leaks, ureteral obstruction, urinary leak or fistula formation, reoperations, and 30-day hospital readmissions, were compared using Pearson's χ 2 . All statistical tests were 2-tailed with P < .05 considered significant., Results: A total of 5418 RCICs were identified. Four hundred ninety-eight (9.2%) were stentless. There were no differences in baseline demographics or comorbidities. Significantly fewer stented patients had robotic-assisted operations (23% vs 29%, P < .01). Stented patients had lower rates of urinary leak or fistula formation (3.1% vs 4.8%, P = .04). There was no significant difference in 30-day rates of UTIs, acute kidney injuries, renal failure, ileoileal anastomotic leaks, ureteral obstruction, reoperations, and readmissions. Limitations include retrospective design and lack of longitudinal tracking past 30 days., Conclusions: Stentless patients had noninferior outcomes compared to stented patients in most important 30-day outcomes. Our analysis suggests that stents may not be necessary in ileal conduit urinary diversion procedures.

Transfusion dependent thalassemia (TDT) patients require a regular blood transfusion to survive. Without adequate transfusion support, they suffer many complications, and have a short life span. Near about 200 milligrams of iron remains within a single Red cell concentrate (RCC) unit. So, blood transfusion acts as a double-edged sword, prolonging life while eventually leading to iron overload. For patients who are receiving transfusions for several years, iron accumulation causes different types of morbidity including thyroid failure. Though serum ferritin is a simple tool for measuring the iron load of the body, it is often misleading. Because, in first 100 unit of blood transfusion serum ferritin levels increase steadily. After that, this relation is not simple. Serum ferritin may increase in chronic inflammation or decrease in vitamin C deficiency, which may be misleading. The study aimed to identify a simple predictor of hypothyroidism in TDT patients. This cross-sectional study conducted from April 2018 to September 2019 includes 64 TDT patients according to selection criteria. Among them 43 were male and 21 were female TDT patients, with a mean age of 25.5 years. Body iron load was estimated by serum ferritin level. Pearson correlation test was done to measure the correlation of serum TSH level with serum ferritin, unit of blood transfused so far and duration of receiving transfusion therapy. All of these three variables had positive correlation with serum TSH level (r value 0.241, 0.319 and 0.332 respectively). Level of correlation of serum TSH was statistically significant with unit of blood transfused (p=0.010) and with duration of transfusion therapy taken (p=0.007) but not with serum ferritin level (p=0.055). Meticulous transfusion history taking is more important than investigation reports like serum ferritin level to predict hypothyroidism in TDT patients.

Von Hippel-Lindau (vHL) is a hereditary disease characterized by the development of benign and malignant tumors across multiple organ systems. It is seen in approximately 1 in 36,000 live births. Given that vHL is a rare disease, studies that seek to characterize vHL are often hampered by small sample sizes. The TriNetX database, which contains data from over 100 million patients, may offer the ability to define and describe a large number of vHL patients. The primary objectives of this study were to describe the prevalence of vHL-associated conditions and investigate clinical outcomes using TriNetX. The secondary objective was to compare the results of this analysis to what has been reported in the published vHL literature. TriNetX was queried to establish a cohort of patients with a diagnosis of vHL. This cohort was then used to define the prevalence of the following conditions: reproductive organ (epididymal and broad ligament) cystadenomas, renal cell carcinoma (RCC), pheochromocytomas, endolymphatic sac tumors (ESLTs), central nervous system (CNS) and retinal hemangioblastomas, and pancreatic neuroendocrine tumor (pNETs). A total of 1232 patients in TriNetX had a recorded diagnosis of vHL. Of this, 34 (6.0% of males) patients had epididymal cystadenoma, 21 (3.4% of females) had broad ligament cystadenoma, 352 (28.6%) had RCC, 251 (20.4%) had pheochromocytoma, <10 had ELST, 171 (13.9%) had CNS hemangioblastoma, 34 (2.8%) had pNETs, and 66 (5.4%) had retinal hemangioma. Compared to the existing literature, vHL and associated conditions are underdiagnosed in TriNetX, suggesting its limited use in studying this disease., Competing Interests: The authors declare no potential conflicts of interest with respect to research, authorship, and/or publication of this article., (Copyright: Metwalli AR., et al.)

The function of spargel/dPGC-1 in Drosophila oogenesis has been unequivocally established. Here, we sought to assess whether Spargel protein or RNA is essential for developmentally competent eggs. The trans-heterozygotic combination of two spargel mutant alleles allowed us to decrease Spargel expression to very low levels. Using this model, we now demonstrated the requirement for Spargel in eggshell patterning and embryonic development, which led us to establish that spargel is a maternal effect gene. Further examination of Spargel's potential mechanism of action in eggshell biogenesis revealed that low levels of Spargel in the adult ovary cause diminished Cyclin E activity, resulting in reduced chorion gene amplification levels, leading to eggshell biogenesis defects. Thus, another novel role for spargel/dPGC-1 is exposed whereby, through Cyclin E activity, this conserved transcriptional coactivator regulates the chorion gene amplification process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze antibiotic prescribing trends, particularly the decline in fluoroquinolone use for various genitourinary infection (GUI) and procedures and the growing preference for alternative treatments., Methods: The TriNetX database was queried for antibiotic utilization rates from 2016 to 2022. We analyzed cases of cystitis, pyelonephritis, prostatitis, and other GUIs, as well as periprocedure utilization for benign prostatic hyperplasia, urethral stricture disease, pelvic organ prolapse/stress urinary incontinence, and overactive bladder/interstitial cystitis (OAB/IC). We determined the top four to six antibiotics prescribed within 5 days of diagnosis or procedure. Statistical analysis included linear regression modeling., Results: From 2016 to 2022, fluoroquinolone use decreased in cystitis (P <.001), pyelonephritis (P <.001), and prostatitis (P <.01). These infections were increasingly treated with beta-lactams (P <.0001, P <.01, P <.01, respectively). Additionally, we found a decrease in fluoroquinolone utilization in procedures for benign prostatic hyperplasia (P <.001), urethral stricture (P <.01), pelvic organ prolapse/stress urinary incontinence (P <.001), and OAB/IC (P <.001). All cohorts except for OAB/IC showed a significant increase in beta-lactam use (P <.001, P <.01, P <.01, respectively)., Conclusion: We noted a significant decline in fluoroquinolone use for GUI and procedures, accompanied by increased beta-lactam use, reflecting changes in prescribing practices. Judicious use is essential to promote antimicrobial stewardship and mitigate severe adverse effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Periprosthetic joint infections (PJIs) present a growing challenging complication in joint surgeries, with increasing incidence and significant clinical implications. The complexity of PJIs lies in its interaction between microbes and the host immune response. While Enterobacter infections are rare in PJIs, they pose severe risks due to their resistance and virulence. PJIs burden healthcare systems and profoundly impact patients, especially those unable to access necessary treatments due to socioeconomic limitations, like our patient who had suffered from excruciating pain and immobility for 6 years. To the best of our knowledge, this is the first case report of its kind., Case Report: A 55-year-old woman presented to us with severe right hip pain for 10 years and recurrent swelling over the incisional site with discharging sinus and intermittent fever for 6 years. She underwent through a unipolar hemiarthroplasty due to right-sided femoral neck fracture 10 years back. Severe pain and recurrent infections led to functional limitations and deteriorating quality of life. History, clinical examination, serological, and radiological investigations confirmed the diagnosis. Two-stage revision total hip arthroplasty was performed. Regular follow-ups were done after the surgical procedure. After revision, she experienced no pain or recurrence of infection. Her Harris Hip Scores were 9 and 80 before and after two-stage revision surgery, indicating a favorable outcome., Conclusion: This case highlights the challenges of PJI management, especially in patients from poor socioeconomic condition. Despite obstacles, intervention with two-stage revision arthroplasty resulted in significant clinical and psychological improvement. Enhanced healthcare accessibility and tailored interventions are crucial for optimizing PJI outcomes., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

This study focuses on the distribution of some selected organochlorine pesticides and emerging contaminants within the surface sediments of an Arctic fjord, Kongsfjorden and nearby lakes. Organochlorine pesticides (OCPs) such as dicloran, p,p'-DDT, p,p'-DDE, p,p'-DDD were studied along with five emerging contaminants namely diuron, chlorpyrifos, dicofol, pendimethalin and bifenthrin. The highest values of OCPs recorded among the fjord and lake environments during the time of study was 0.3355 ng/g (dicloran), 0.0152 ng/g (p,p'-DDT), 0.0117 ng/g (p,p'-DDE), and 0.0137 ng/g (p,p'-DDD). Except dicofol, all other pesticides were found in both the years (2018 & 2019) with an elevated concentration during 2019. The presence of fresh as well as past input of contaminants was obtained from the values of DDTs ratio. The sediment quality guidelines of DDTs confirm that the fjord and lakes are clean to marginally polluted in which the adverse effects can rarely occur at this present juncture., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anu Gopinath reports travel was provided by National Centre for Polar and Ocean Research., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Atrial fibrillation, the most prevalent cardiac arrhythmia, has witnessed significant advancements in treatment modalities, transitioning from invasive procedures like the maze procedure to minimally invasive catheter ablation techniques. This review focuses on recent improvements in anesthetic approaches that enhance outcomes in catheter atrial fibrillation ablation. We highlight the efficacy of contact force sensing catheters with steerable introducer sheaths, which outperform traditional catheters by ensuring more effective contact time and lesion formation. Comparing general anesthesia with conscious sedation, we find that general anesthesia provides superior catheter stability due to reduced respiratory variability, resulting in more effective lesion formation, and reduced pulmonary vein reconnection. The use of high-frequency jet ventilation under general anesthesia, delivering low tidal volumes, effectively minimizes left atrial movement, decreasing catheter displacement and procedure time, and reducing recurrence in paroxysmal atrial fibrillation. An alternative, high-frequency low tidal volume ventilation using conventional ventilators, also shows improved catheter stability and lesion durability compared to traditional ventilation methods. However, a detailed comparative study of high-frequency jet ventilation, high-frequency low tidal volume ventilation, and conventional mechanical ventilation in catheter ablation for atrial fibrillation is lacking. This review emphasizes the need for such studies to identify optimal anesthetic techniques, potentially enhancing patient outcomes in atrial fibrillation treatment. Our findings suggest that careful selection of anesthetic methods, including ventilation strategies, plays a crucial role in the success of catheter ablation for atrial fibrillation, warranting further research for evidence-based practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mn-doped NiO nanoparticles (NPs), denoted as Ni 1- x Mn x O with x values of 0.00, 0.02, 0.04, 0.06, and 0.08, were synthesized using a chemical precipitation process. These NPs were comprehensively analyzed for their structural, optical, and electrical properties, along with their surface morphology and elemental composition. X-ray Diffraction (XRD) confirmed the single-phase cubic crystal structure and revealed a reduction in crystallite size from 15.26 nm to 10.38 nm as Mn doping increased. Field Emission Scanning Electron microscopy (FE-SEM) determined the average particle sizes ranging from 26.03 nm to 23.30 nm. The optical properties, assessed by UV-visible spectroscopy (UV-vis), revealed a widening of the bandgap from 3.49 eV to 4.10 eV with increasing Mn doping, suggesting tunable optical characteristics. X-ray Photoelectron Spectroscopy (XPS) confirmed the presence of nickel (Ni), oxygen (O), and manganese (Mn) within the NPs. The highest mobility, 1.31 ± 0.03 × 10 3 cm 2 V -1 s -1 , was observed in the 6 wt% Mn-doped NiO NPs thin film, as determined by Hall measurements. To assess their practical utility, SCAPS-1D simulation was employed, demonstrating the potential of Mn-doped NiO NPs as a hole transport layer (HTL) in perovskite solar cells (PSCs). The enhanced electrical and optical properties, combined with structural tunability, highlight Mn-doped NiO as a promising material for advanced optoelectronic applications. This study provides valuable insights into the development of efficient and stable solar cells, offering a pathway to optimize material design for improved performance in photovoltaic applications., Competing Interests: The authors declare that they have no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Background: Antibiotic-associated diarrhea (AAD) is a prevalent complication of antibiotic therapy, attributed to disruptions in gut microbiota. Probiotics are increasingly studied for their potential in preventing AAD by restoring microbial balance., Objective: The aim of this investigation was to assess the efficacy of probiotics in reducing AAD in adult patients when compared to a placebo., Methodology: This research was conducted from March 2023 to March 2024 using a randomized, placebo-controlled design at multiple institutions: Khyber Teaching Hospital, Peshawar; Prime Teaching Hospital, Peshawar; Mufti Mahmood Memorial Teaching Hospital, Dera Ismail Khan; Shalamar Hospital, Lahore; University Hospitals of Leicester; and DHQ Teaching Hospital Kohat, enrolling 340 adult patients prescribed systemic antibiotics. Eligible participants were aged 18 years and older, while those with chronic diarrhea, inflammatory bowel disease, immunodeficiency, recent probiotic or antibiotic use, or inability to provide informed consent were excluded. The sample size was calculated using WHO guidelines, resulting in a target of 340 to ensure adequate power. Participants were randomized to receive either probiotics (Lactobacillus rhamnosus GG and Bifidobacterium longum BB536) or placebo, administered within 24 hours of starting antibiotics. Daily monitoring of bowel habits and symptoms was performed using standardized diaries, and adherence was evaluated through pill counts. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 27 (Released 2020; IBM Corp., Armonk, New York, United States), comparing the incidence, severity, and duration of AAD between groups, with a significance threshold of p < 0.05., Results: In the probiotic group, 31 patients (18.23%) developed AAD compared to 53 patients (31.17%) in the placebo group (p=0.01). Among those with AAD, the probiotic group experienced a shorter duration (mean 3.5 ± 1.2 days) compared to placebo (mean 5.1 ± 1.8 days, p=0.002). Adherence rates were high in both groups (probiotic: 96.4%, placebo: 95.9%). Significant improvements in bowel habits were reported more frequently in the probiotic group (77.06%) than placebo (50.59%, p=0.02). The hospital stay duration was similar between groups (probiotic: mean 7.8 ± 2.1 days, placebo: mean 8.3 ± 2.4 days, p=0.15)., Conclusion: Probiotics significantly reduced the incidence and duration of AAD compared to placebo, with high adherence and favorable patient-reported outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board (IRB) of Khyber Teaching Hospital and Khyber Medical College Peshawar Institutional Research and Ethical Review Board (IREB) issued approval 624/DME/KMC. This study received ethical approval in December 2022. Permission for data collection was obtained from the Head of Department of all the involved institutes. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shah et al.)

The increasing clinical significance of Mycobacterium abscessus is owed to its innate high-level, broad-spectrum resistance to antibiotics and therefore rapidly evolves as an important human pathogen. This warrants the identification of novel targets for aiding the discovery of new drugs or drug combinations to treat M. abscessus infections. This study is inspired by the drug-hypersensitive profile of a mutant M. abscessus (U14) with transposon insertion in MAB&#95;1915 . We validated the role of MAB&#95;1915 in intrinsic drug resistance in M. abscessus by constructing a selectable marker-free in-frame deletion in MAB&#95;1915 and complementing the mutant with the same or extended version of the gene and then followed by drug susceptibility testing. Judging by the putative function of MAB&#95;1915, cell envelope permeability was studied by ethidium bromide accumulation assay and susceptibility testing against dyes and detergents. In this study, we established genetic evidence of the role of MAB&#95;1915 in intrinsic resistance to rifampicin, rifabutin, linezolid, clarithromycin, vancomycin, and bedaquiline. Disruption of MAB&#95;1915 has also been observed to cause a significant increase in cell envelope permeability in M. abscessus . Restoration of resistance is observed to depend on at least 27 base pairs upstream of the coding DNA sequence of MAB&#95;1915 . MAB&#95;1915 could therefore be associated with cell envelope permeability, and hence its role in intrinsic resistance to multiple drugs in M. abscessus , which presents it as a novel target for future development of effective antimicrobials to overcome intrinsic drug resistance in M. abscessus ., Importance: This study reports the role of a putative fadD (MAB&#95;1915) in innate resistance to multiple drugs by M. abscessus , hence identifying MAB&#95;1915 as a valuable target and providing a baseline for further mechanistic studies and development of effective antimicrobials to check the high level of intrinsic resistance in this pathogen., Competing Interests: The authors declare no conflict of interest.

Introduction: Patients seek support from online resources when facing a troubling urologic cancer diagnosis. Physician-written resources exceed the recommended 6-8th grade reading level, creating confusion and driving patients towards unregulated online materials like AI chatbots. We aim to compare the readability and quality of patient education on ChatGPT against Epic and Urology Care Foundation (UCF)., Materials and Methods: We analyzed prostate, bladder, and kidney cancer content from ChatGPT, Epic, and UCF. We further studied readability-adjusted responses using specific AI prompting (ChatGPT-a) and Epic material designated as Easy to Read. Blinded reviewers completed descriptive textual analysis, readability analysis via six validated formulas, and quality analysis via DISCERN, PEMAT, and Likert tools., Results: Epic met the recommended grade level, while UCF and ChatGPT exceeded it (5.81 vs. 8.44 vs. 12.16, p < 0.001). ChatGPT text was longer with more complex wording (p < 0.001). Quality was fair for Epic, good for UCF, and excellent for ChatGPT (49.5 vs. 61.67 vs. 64.33). Actionability was overall poor but particularly lowest (37%) for Epic. On qualitative analysis, Epic lagged on all quality measures. When adjusted for user education level (ChatGPT-a and Epic Easy to Read), readability improved (7.50 and 3.53), but only ChatGPT-a retained high quality., Conclusions: Online urologic oncology patient materials largely exceed the average American's literacy level and often lack real-world utility for patients. Our ChatGPT-a model indicates that AI technology can improve accessibility and usefulness. With development, a healthcare-specific AI program may help providers create content that is accessible and personalized to improve shared decision-making for urology patients.

Purpose: The genetic underpinning of neurodevelopmental disorders (NDDs) in diverse ethnic populations, especially those with high rates of consanguinity, remains largely unexplored. Here, we aim to elucidate genomic insight from 576 well-phenotyped and highly consanguineous (16%) NDD cohort., Methods: We used chromosomal microarray (CMA; N:247), exome sequencing (ES; N:127), combined CMA and ES (N:202), and long-read genome sequencing to identify genetic etiology. Deep clinical multivariate data were coupled with genomic variants for stratification analysis., Results: Genetic diagnosis rates were 17% with CMA, 29.92% with ES, and 37.13% with combined CMA and ES. Notably, children of consanguineous parents showed a significantly higher diagnostic yield (P < .01) compared to those from nonconsanguineous parents. Among the ES-identified pathogenic variants, 36.19% (38/105) were novel, implicating 35 unique genes. Long-read sequencing of seizure participants unresolved by combined test identified expanded FMR1 trinucleotide repeats. Additionally, we identified 2 recurrent X-linked variants in the G6PD in 3.65% (12/329) of NDD participants. These variants were absent in large-population control cohorts and cohort comprising neurodevelopmental and neuropsychiatric populations of European descendants, indicating a possible associated risk factor potentially resulting from ancient genetic drift., Conclusion: This study unveils unique clinical and genomic insights from a consanguinity rich Bangladeshi NDD cohort, highlighting a strong association of G6PD with NDD in this population., Competing Interests: Conflict of Interest Corresponding author, Mohammed Uddin owns share of GenomeArc. All other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: No comprehensive meta-analysis has evaluated the efficacy and safety of ertugliflozin compared to a placebo in patients with Type 2 diabetes (T2D) until now. This meta-analysis fills this gap in knowledge. Methods: A systematic search was carried out in electronic databases to identify randomized controlled trials (RCTs) that included patients with T2D receiving ertugliflozin in the treatment group and placebo in the control group. The change in HbA1c from the baseline values was the primary outcome, whereas changes in plasma glucose and other metabolic parameters and adverse events (AEs), including hypoglycemia, were the secondary outcomes. Results: Seven RCTs involving 7283 subjects met the inclusion criteria. Ertugliflozin outperformed placebo in reducing HbA1c in both 5 mg (MD -0.62%, 95% CI [-0.80, -0.44], p < 0.00001, I 2 = 91%) and 15 mg (MD -0.69%, 95% CI [-0.91, -0.47], p < 0.00001, I 2 = 93%) doses. A higher proportion of patients achieved HbA1c < 7.0% with ertugliflozin than with placebo. Ertugliflozin was also superior to placebo in lowering fasting plasma glucose (FPG), body weight, and systolic and diastolic blood pressure (BP). Ertugliflozin and placebo had comparable AE profiles, including urinary tract infection (UTI) and hypoglycemia, except for the greater risk of genital mycotic infections (GMIs) with ertugliflozin. Ertugliflozin 5 and 15 mg have equivalent efficacy and safety profiles except for greater weight reduction with ertugliflozin 15 mg. Conclusion: Ertugliflozin has a good glycemic efficacy and a reassuring safety profile in managing T2D. Trial Registration: Registration number: CRD42023456450., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 A. B. M. Kamrul-Hasan et al.)

In this study, we investigated the interaction between arsenate (As V ) and phosphate (PO 4 ) in freshwater phytoplankton using single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS). This study aimed to elucidate the influence of varying PO 3- ) in freshwater phytoplankton using single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS). This study aimed to elucidate the influence of varying PO 4 3- in a controlled laboratory environment. Scenedesmus acutus, a species with strong salt tolerance, and Pediastrum duplex, known for its weak salt tolerance, were selected based on their contrasting behaviors in previous studies. SC-ICP-MS revealed non-uniform uptake of As by individual phytoplankton cells, with distinct variations in response to PO 4 3- and As V in a controlled laboratory environment. Scenedesmus acutus, a species with strong salt tolerance, and Pediastrum duplex, known for its weak salt tolerance, were selected based on their contrasting behaviors in previous studies. SC-ICP-MS revealed non-uniform uptake of As by individual phytoplankton cells, with distinct variations in response to PO 4 3- availability. Arsenic uptake by both species declined with a high PO 4 3- level after 7 days of exposure. However, after 14 days, As uptake increased in S. acutus with higher PO 4 3- levels and underscores the advantages of SC-ICP-MS over conventional ICP-MS in providing detailed, cellular level insights. These findings are crucial for understanding and managing As pollution in aquatic ecosystems.V and various PO 4 3- concentrations. S. acutus maintained cell integrity under all experimental culture conditions, whereas P. duplex experienced cell lysis at elevated As V and PO 4 3- concentrations. This study highlights the varying responses of freshwater phytoplankton to changes in As V and PO 4 3- levels and underscores the advantages of SC-ICP-MS over conventional ICP-MS in providing detailed, cellular level insights. These findings are crucial for understanding and managing As pollution in aquatic ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To compare the peri-operative outcomes of radical prostatectomy (RP) for locally advanced, node-positive, and metastatic prostate cancer (PCa), as determined through pathological staging, using the American College of Surgeons National Surgical Quality Improvement Project., Methods: We identified RP procedures performed between 2019 and 2021. Patients were stratified by pathological staging to compare the effect of locally advanced disease (T3-4), node positivity (N+) and metastasis (M+) vs localised PCa (T1-2 N0 M0). Baseline demographics and 30-day outcomes, including operating time, length of hospital stay (LOS), 30-day mortality, readmissions, reoperations, major complications, minor complications and surgery-specific complications, were compared between groups., Results: Pathological staging data were available for 9276 RPs. Baseline demographics were comparable. There was a slightly higher rate of minor complications in the locally advanced cohort, but no significant difference in major complications, 30-day mortality, readmissions, or rectal injuries. Node positivity was associated with longer operating time, LOS, and some slightly increased rates of 30-day complications. RP in patients with metastatic disease appeared to be similarly safe to RP in patients with M0 disease, although it was associated with a longer LOS and slightly increased rates of certain complications., Conclusions: For patients with pathologically determined locally advanced, node-positive, and metastatic PCa, RP appears to be safe, and is not associated with significantly higher rates of 30-day mortality or major complications compared to RP for localised PCa. This study adds to the growing body of literature investigating the role of RP for advanced PCa; further studies are needed to better characterise the risks and benefits of surgery in such patients., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background and objective Iron deficiency and iron deficiency anemia are related but distinct conditions. Iron deficiency refers to a state where the body has insufficient iron stores, which can lead to anemia if not addressed. Iron deficiency anemia, on the other hand, is a more severe condition where the lack of iron has resulted in decreased hemoglobin levels, impacting oxygen transport in the blood. Helicobacter pylori ( H. pylori ) infection can contribute to iron deficiency through mechanisms such as chronic gastrointestinal bleeding and impaired iron absorption, potentially progressing to iron deficiency anemia. The objective of this study was to determine the prevalence of iron deficiency, including its potential progression to iron deficiency anemia, among patients diagnosed with H. pylori infection. Methodology This cross-sectional study was conducted at Bolan Medical Complex Hospital, Quetta, and included 200 patients diagnosed with H. pylori infection via endoscopic biopsy or urea breath test, from January to June 2023. Participants were aged 18 years and older, excluding those with chronic diseases affecting iron metabolism, current iron supplement users, and pregnant women. Data were collected through questionnaires and medical records, and blood samples were analyzed for serum ferritin and hemoglobin levels. Statistical analysis included chi-square tests and logistic regression was performed in SPSS (version 27; IBM Corp, Armonk, NY); p-value <0.05 was significant. Results Out of 200 patients, 80 (40%) were iron deficient. The prevalence was highest among those over 60 years (n = 15, 75%) compared to the 18-30 age group (n = 10, 20%). Males had a slightly higher prevalence of iron deficiency (n = 50, 45.5%) compared to females (n = 30, 33.3%). Patients with H. pylori infection for more than three years exhibited a higher prevalence of iron deficiency (n = 30, 50%) compared to those with less than one year of infection (10/60, 16.7%). Dietary habits also played a role, with vegetarians showing a higher prevalence (n = 20, 50%) compared to non-vegetarians (n = 60, 37.5%). Hemoglobin levels were significantly lower in iron-deficient participants, averaging 10.8 ± 0.9 g/dL, and logistic regression indicated significant associations between iron deficiency and both age (OR = 1.05, p = 0.001) and infection duration (OR = 1.10, p < 0.001). Conclusions The study revealed a significant prevalence of iron deficiency among H. pylori -infected patients, particularly in older adults, males, those with longer infection duration, and vegetarians. The findings underscore the need for routine monitoring and targeted treatment of iron deficiency in this population., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Bolan Medical Complex Hospital Institutional Review Board issued approval BMCH/IRB/2022/Car-08/10. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Khan et al.)

Lead-containing halide perovskites show promise for solar energy but pose ecological and health risks. To address these, researchers are exploring inorganic binary metal perovskites. This study proposes an eco-friendly, durable hole transport layer (HTL)-free design of CsSn 0.5 Ge 0.5 I 3 with high power conversion efficiency (PCE). Using the SCAPS-1D simulator, we assessed the efficiency of an HTL-free planar heterojunction, while the Density Functional Theory (DFT)-based CASTEP simulator evaluated the optical properties of CsSn 0.5 Ge 0.5 I 3 in an orthorhombic structure. Key findings highlight enhanced performance under 100 Wm -2 AM 1.5G illumination by optimizing absorber layer thickness to 800 nm and reducing defect densities in both the perovskite absorber layer and interfaces to 1 × 10 14 cm -3 .Additonally, the effects of different electron transport materials (ETMs), optimization of electron transport layer (ETL) thickness (30-50 nm), and back contact design improvements were examined. The simulation's results included an increase over the highest values reported in the literature: an open circuit voltage (Voc) of 1.06 V, a short circuit current density (Jsc) of 28.52 mA/cm 2 , a fill factor (FF) of 86.57%, and a PCE of 26.18% for the FTO/Zn 0.875 Mg 0.125 O/CsSn 0.5 Ge 0.5 I 3 /Se perovskite solar cell (PSC). This research provides theoretical insights for developing high-efficiency power modules without HTLs with significant industrial and research potential., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Global Challenges published by Wiley‐VCH GmbH.)

Imaging for prostate cancer defines the extent of disease. Guidelines recommend against imaging low-risk prostate cancer patients with a computed tomography (CT) scan or bone scan due to the low probability of metastasis. We reviewed imaging performed for men diagnosed with low-risk prostate cancer across the Pennsylvania Urologic Regional Collaborative (PURC), a physician-led data sharing and quality improvement collaborative. The data of 10 practices were queried regarding the imaging performed in men diagnosed with prostate cancer from 2015 to 2022. The cohort included 13,122 patients with 3502 (27%) low-risk, 2364 (18%) favorable intermediate-risk, 3585 (27%) unfavorable intermediate-risk, and 3671 (28%) high-risk prostate cancer, based on the AUA guidelines. Amongst the low-risk patients, imaging utilization included pelvic MRI (59.7%), bone scan (17.8%), CT (16.0%), and PET-based imaging (0.5%). Redundant imaging occurred in 1022 patients (29.2%). There was variability among the PURC sites for imaging used in the low-risk patients, and iterative education reduced the need for CT and bone scans. Approximately 15% of low-risk patients had staging imaging performed using either a CT or bone scan, and redundant imaging occurred in almost one-third of men. Such data underscore the need for continued guideline-based education to optimize the stewardship of resources and reduce unnecessary costs to the healthcare system.

A girl who was born at 40 weeks of gestation weighing 3800 g presented with bilious vomiting and abdominal distension shortly after birth. A lower gastrointestinal contrast study showed a microcolon with small bowel atresia. Subsequently, laparotomy, small bowel resection and anastomosis were done. Intra-operative findings noted jejunal atresia type 3a. Post-operatively, the patient developed persistent conjugated hyperbilirubinaemia and hence, magnetic resonance cholangiopancreatography (MRCP) was performed. MRCP revealed possible biliary atresia (BA) of which the patient underwent Kasai hepato-porto-enterostomy. We reported a rare case of double pathology involving jejunal atresia and BA, describing its aetiology, characteristics and treatment availability based on literature., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Choong Yew Hoe et al.)

The reniform nematode ( Rotylenchulus reniformis Linford and Oliveira) adversely impacts the quality and quantity of sweetpotato storage roots. Management of R. reniformis in sweetpotato remains a challenge because host plant resistance is not available, fumigants are detrimental to the environment and health, and crop rotation is not effective. We screened a core set of 24 sweetpotato plant introductions (PIs) against R. reniformis . Four PIs were resistant, and 10 were moderately resistant to R. reniformis , suggesting these PIs can serve as sources of resistance for sweetpotato resistance breeding programs. PI 595869, PI 153907, and PI 599386 suppressed 83 to 89% egg production relative to the susceptible control 'Beauregard', and these PIs were employed in subsequent experiments to determine if their efficacy against R. reniformis can be further increased by applying nonfumigant nematicides oxamyl, fluopyram, and fluensulfone. A 34 to 93% suppression of nematode reproduction was achieved by the application of nonfumigant nematicides, with oxamyl providing the best suppression followed by fluopyram and fluensulfone. Although sweetpotato cultivars resistant to R. reniformis are currently not available and there is a need for the development of safer yet highly effective nonfumigant nematicides, results from the current study suggest that complementing host plant resistance with nonfumigant nematicides can serve as an important tool for effective and sustainable nematode management., Competing Interests: The author(s) declare no conflict of interest.

Limited objective data exist on the comparison of post-endoscopic retrograde cholangiopancreatography (ERCP) complications in patients with cirrhosis based on the severity of the disease. We evaluated the effectiveness of the Child-Turcotte-Pugh (CTP) score system in anticipating the risk of post-ERCP complications in patients with cirrhosis. The PubMed, Scopus, Embase, and Cochrane databases were searched from inception through September 2022 to identify studies comparing post-ERCP complications in patients with cirrhosis based on CTP score. Odds ratios (ORs) and their associated 95% CIs were pooled using a random-effect model to calculate effect size. The reference group for analysis was the CTP class C patient group. Seven studies comprising 821 patients who underwent 1068 ERCP procedures were included. The CTP class C patient population exhibited a higher risk of overall post-ERCP adverse events compared with those with class A or B (OR: 2.87, 95% CI: 1.77-4.65, P = 0.00 and OR: 2.02, 95% CI: 1.17-3.51, P = 0.01, respectively). Moreover, CTP class B patients had a significantly higher complication rate than CTP class A patients (OR: 1.62, 95% CI: 1.04-2.53, P = 0.03). However, no statistically significant differences were found in the occurrence of specific types of complications, including bleeding, pancreatitis, cholangitis, perforation, or mortality across the three CTP groups. We demonstrated that the CTP classification system is a reliable predictor of ERCP complications in patients with cirrhosis. Consequently, caution should be exercised when performing ERCP in patients classified as CTP class C., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The increasing prevalence of drought events poses a major challenge for upcoming crop production. Melatonin is a tiny indolic tonic substance with fascinating regulatory functions in plants. While plants can respond in several ways to alleviate drought stress, the processes underpinning stress sensing and signaling are poorly understood. Hereafter, the objectives of this investigation were to explore the putative functions of melatonin in the regulation of sugar metabolism and abscisic acid biosynthesis in drought-stressed tomato seedlings. Melatonin (100 μM) and/or water were foliar sprayed, followed by the plants being imposed to drought stress for 14 days. Drought stress significantly decreased biomass accumulation, inhibited photosynthetic activity, and stimulated senescence-associated gene 12 (SAG12) expression. Melatonin treatment effectively reversed drought-induced growth retardation as evidenced by increased leaf pigment and water balance and restricted abscisic acid (ABA) accumulation. Sugar accumulation, particularly sucrose content, was higher in drought-imposed seedlings, possibly owing to higher transcription levels of sucrose non-fermenting 1-related protein kinase 2 (SnKR2.2) and ABA-responsive element binding factors 2 (AREB2). Melatonin addition further uplifted the sucrose content, which coincided with increased activity of sucrose synthase (SS, 130%), sucrose phosphate synthase (SPS, 137%), starch degradation encoding enzyme β-amylase (BAM, 40%) and α-amylase (AMY, 59%) activity and upregulated their encoding BAM1(10.3 folds) and AMY3 (8.1 folds) genes expression at day 14 relative to the control. Under water deficit conditions, melatonin supplementation decreased the ABA content (24%) and its biosynthesis gene expressions. Additionally, sugar transporter subfamily genes SUT1 and SUT4 expression were upregulated by the addition of melatonin. Collectively, our findings illustrate that melatonin enhances drought tolerance in tomato seedlings by stimulating sugar metabolism and negatively regulating ABA synthesis., (© 2024 Scandinavian Plant Physiology Society.)

Background: Flibanserin, approved for the treatment of hypoactive sexual desire disorder (HSDD) in females, has demonstrated diverse therapeutic and adverse effect (AE) prospects in the extant randomized controlled trials (RCTs). This meta-analysis aimed to characterize the outcomes of flibanserin use in these patients comprehensively., Methods: RCTs involving women with HSDD receiving flibanserin in the intervention arm and placebo in the control arm were sought after throughout the electronic databases. The primary outcomes were the changes from baseline in satisfying sexual events (SSE) per month and sexual desire score per month measured using an electronic diary (eDiary)., Results: From 478 initially screened articles, data from 8 RCTs involving 7906 women with HSDD were analyzed. In premenopausal women, flibanserin 100 mg was superior to placebo in improving the number of SSE per month (mean difference, MD 0.69, 95% CI [0.39, 0.99]), eDiary sexual desire score (MD 1.71, 95% CI [0.43, 2.98]), Female Sexual Function Index (FSFI) desire domain (FSFI-d) score (MD 0.30, 95% CI [0.29, 0.31]), FSFI total score (MD 2.51, 95% CI [1.47, 3.55]), Female Sexual Distress Scale-Revised (FSDS-R) Item 13 score (MD -0.30, 95% CI [-0.31, -0.29]), and FSDS-R total score (MD -3.30, 95% CI [-3.37, -3.23]). Compared to placebo, a higher number of premenopausal women using flibanserin 100 mg achieved improvements in the Patient's Global Impression of Improvement score (OR 1.93, 95% CI [1.58, 2.36], P < .00001) and responded positively at Patient Benefit Evaluation (PBE) (odds ratio, OR 1.76, 95% CI [1.34, 2.31], P < .0001). Postmenopausal women receiving flibanserin 100 mg also benefited in terms of the number of SSE per month, FSFI-d and total scores, FSDS-R Item 13 and total scores, and PBE response. Although flibanserin use was associated with higher risks of dizziness, fatigue, nausea, somnolence, and insomnia, these adverse events were mild in nature; the serious AEs and severe AEs were comparable between the flibanserin and placebo groups., Conclusion: While flibanserin has demonstrated efficacy in the treatment of HSDD in both pre- and postmenopausal women, its therapeutic advantages may be overshadowed by the higher likelihood of AEs., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Stereoscopic cameras, such as those in mobile phones and various recent intelligent systems, are becoming increasingly common. Multiple variables can impact the stereo video quality, e.g., blur distortion due to camera/object movement. Monocular image/video deblurring is a mature research field, while there is limited research on stereoscopic content deblurring. This paper introduces a new Transformer-based stereo video deblurring framework with two crucial new parts: a self-attention layer and a feed-forward layer that realizes and aligns the correlation among various video frames. The traditional fully connected (FC) self-attention layer fails to utilize data locality effectively, as it depends on linear layers for calculating attention maps The Vision Transformer, on the other hand, also has this limitation, as it takes image patches as inputs to model global spatial information. 3D convolutional neural networks (3D CNNs) process successive frames to correct motion blur in the stereo video. Besides, our method uses other stereo-viewpoint information to assist deblurring. The parallax attention module (PAM) is significantly improved to combine the stereo and cross-view information for more deblurring. An extensive ablation study validates that our method efficiently deblurs the stereo videos based on the experiments on two publicly available stereo video datasets. Experimental results of our approach demonstrate state-of-the-art performance compared to the image and video deblurring techniques by a large margin., (© 2024. The Author(s).)