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Abstract Background Nonspecific neck pain (NSNP) is a well-established global burden affecting. It is also a common problem in Pakistan. The burden of neck pain is also increasing day by day due to poor work ergonomics, and increased use of computers and mobiles after the pandemic. An individual’s poor posture is often associated with forward head posture (FHP). Limited evidence is available about the effects of neck stabilization (NSE) and dynamic exercises (NDE) for nonspecific neck pain particularly in patients with FHP. This aimed to compare the effects of NSE versus NDE among patients having NSNP with FHP in reducing pain, disability, forward head posture and improving neck range of motion. Methods It is a single-blinded randomized clinical trial with 60 patients aged 18–40 years, with moderate intensity NSNP for > 3 weeks and 0.05) for post-treatment mean VAS, neck ROM, NDI and plumb line measurement. Conclusion Between NSE and NDE, no one is more beneficial than another. Both are equally effective in alleviating pain, increasing ROM, decreasing functional disability, and improving forward head posture in patients with NSNP. Trial Registration Registered trial at ClinicalTrials.gov Identifier: NCT05298631, 28/03/2022, prospectively registered.

Background: Pain in the sacroiliac joint is the most prevalent and often overlooked. The sacroiliac joints are thought to be sources of pain in roughly 10% to 25% of patients with chronic lower back pain. Due to the biomechanical nature of the joint, muscle imbalance is the most important cause of sacroiliac joint dysfunction. The hamstring and gluteus medius are the primary muscles involved in postural dysfunction-related muscle imbalance; however, the quadratus lumborum’s role in the compensatory mechanism is becoming more apparent, and its potential for treatment in conjunction with gluteus medius strengthening has not yet been investigated. Gluteus medius exercises, along with conventional treatment, are routinely given to patients with sacroiliac joint dysfunction; however, the aim of this study is to explore the additional effects of the muscle energy technique (MET) on the quadratus lumborum along with strengthening of the gluteus medius on pain, disability and quality of life of patients with sacroiliac joint dysfunction. Methods: Using a computer-generated random number table, seventy patients with unilateral sacroiliac joint pain were divided equally and randomly into two groups. Prior to initiating treatment, baseline measurements were taken using a hand-held dynamometer, visual analog scale (VAS), Oswestry Disability Index (ODI-U) and short form 36-item survey (SF-36v2) to assess strength, pain, functional disability and quality of life, respectively. Over the course of four weeks, all patients received twelve sessions, and both the pre- and post-intervention outcome measures were documented. Results: After 4 weeks of treatment, both groups showed statistically significant (p < 0.005) mean improvements in muscle strength, pain, disability and quality of life before and after intervention. However, the mean improvements in post-intervention on a dynamometer, VAS, ODI and SF-36 were better in the MET with exercise group (METGME) as compared to the conventional group with exercise (CTGME), with a larger effect size. Conclusions: The muscle energy technique, applied to the quadratus lumborum in combination with gluteus medius strengthening, is more effective clinically and significantly in improving pain, disability and quality of life in comparison to conventional treatment of sacroiliac joints with gluteus medius exercises.

BackgroundDiabetes and cancer are the leading causes of mortality all over the world. Infectious diseases are more common and/or life-threatening in patients with diabetes. Cancer patients with diabetes are individuals that are more susceptible to the current COVID-19 pandemic. We investigated the clinical features of survivor and non-survivor COVID-19-infected cancer patients with diabetes.Patients and MethodsWe did a retrospective study of 43 diabetic cancer patients with PCR-confirmed COVID-19 infection from Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan between March 03, 2020, and May 18, 2021. These patients either were discharged from the hospital or had died by Jun 16, 2021. Clinicopathological and radiological features were compared between survivors and non-survivors by fisher’s exact test and chi-square test.ResultsForty-three diabetic cancer patients with SARS-CoV-2 infection were enrolled and the majority were males 26 (60.5%). The overall mean age was 61.67 ± 11.80. 39 (90.7%) had solid tumors and 3 (7.0%) had hematological malignancies. Fever (74.4%) and dyspnea (58.1%) were the most common symptoms. Complications were reported in 36 (83.7%) patients; during the course of the disease. Additionally, all the deceased patients (n=15) had acquired the complications. 11 (25.6%) patients were admitted to an intensive care unit (ICU). Furthermore, 29 (67.4%) out of 43 patients showed abnormal features in the radiological findings. We found significantly elevated levels of C-reactive protein (P=0.005), serum lactate (P=0.01), albumin (P=0.02), alkaline phosphate (P=0.03), and neutrophil count (P=0.04) in the non-survivors as compared to the survivors.ConclusionCancer patients with diabetes are a vulnerable population in the current pandemic. Identifying how diabetes in cancer patients affects the severity of SARS-CoV-2 infection is crucial for the clinical management of these patients. Rigorous scrutiny of clinicopathological features of COVID-19 infected cancer patients with diabetes especially values of C-reactive protein, lactate, albumin, alkaline phosphate, neutrophils, and regular monitoring of blood glucose levels may play a critical role in the outcome of the disease.

Introduction: Erythrocytes have flexible, non-nucleated bi-concave shape with lipid bilayer cytoskeleton. Any alterations of erythrocyte shape make it susceptible to hemolysis. Blood for transfusion purpose is routinely stored in Citrate Phosphate Dextrose Adenine (CPDA-1) containing blood bags. During storage, blood undergoes an array of different morphological changes termed as “storage lesions” which makes it more fragile. This study was aimed to determine the structural and functional modifications in erythrocytes in CPDA-1 blood stored in local blood bank of KPK. Material & Methods: Blood from twenty healthy volunteer donors was taken and kept in CPDA-1 containing blood bags at Institute of Basic Medical Sciences (IBMS), Khyber Medical University (KMU). Hb-levels and Erythrocyte, Reticulocyte counts, Mechanical Fragility Index (MFI) and immunofluorescence staining for ankiyrin1 protein were performed on fresh blood samples. Samples for reticulocyte count was taken for 5 consecutive days while for the remaining parameters, blood was taken at 5 days interval till day 20th. The light and fluorescence micrographs were obtained accordingly and osmotic fragility tests were performed. Results: A significant mean reduction in erythrocyte counts and Hb-level was observed from day 0 to 20 (p=0.001), while MFI increased from day 0 to day 20 (12.88%±7.58 p=0.001). Reticulocyte count also decreased from day 0 up to day 5 (p=0.001). A weak association was observed between changes in MFI and erythrocyte morphology from day 0 to 20 (r=0.349), while the intensity and pattern of ankyrin1 protein expression appeared to change from day 10. Conclusion: Blood stored for a week has same properties as fresh blood, however, important structural alterations start to appear after the first week of storage and worsen with time. Therefore, to gain better transfusion results, blood stored for up to one week can safely be transfused.

There is recently an increasing reports of reduction in sperm counts along with other reproductive disorders that is ascribe to the use of drugs and environmental chemicals. In this regard conducting toxicological studies on male reproductive is of paramount importance. This study evaluates salicylidene salicylhydrazide (SCS) for any possible toxicological effects on male reproductive system. Male BALB/c mice were daily administered withSCSat 5, 25, and 50 mg/kg for 7 and 14 days. The body and testes weights were measuredand the testes were subjected to histological tissue processing techniques. The extent of testicular toxicity was evaluated by using modified Johnsen scoring system for assessing the level of spermatogenesis, and morphometric analysis by measuring the diameter of the seminiferous tubules, thickness of germinal epithelium, and area of interstitial cells of Leydig. The body and testes weights showed that the various doses of SCS have no substantial effects after 7 and 14 days. The tested doses of SCS did not produce any distinguishable change in the normal histological features of seminiferous tubules and interstitium after 7 days. However, after 14 days, the 50 mg/kg dose of SCS was associated with vacuolization and loosening of germinal epithelium. These mild-to-moderate histopathological aberrations was confirmed from morphometric analysis in this dose group in which a decrease in the seminiferous tubules diameter and reduction in the thickness of germinal epithelium along with an increase in the interstitial area were observed. These findings concluded that SCS is considered to be relatively safe.

Objective: To assess the knowledge, attitude and practices ofbreast self examination (BSE) in women attendinggynecological units of major public sector hospitals ofKarachi. Study Design: Cross sectional survey. Patients and Methods: All women of age between 20-50 years of either marital status attending Gynae OPDof Civil Hospital and Jinnah Postgraduate Medical Center, Karachi from May 2010 to December 2010 wereincluded in the study. A verbal consent of each participant was obtained before collecting the data. The datawas collected through a structured questionnaire have information on socio economic data, knowledge aboutBreast SelfExamination, symptoms, risk factors and preventive methods regarding breast cancer, attitude ofthe respondent and practices regarding Breast Self Examination. Results: Out of 412 respondents, majority belongs to 30-39 years age group (43.7%). Knowledge about breastself examination was found in only 22.8% respondents. Knowledge about symptoms, risk factors and preventivemeasures regarding Breast cancer were 25.3%, 28.7% and 26.0% respectively. However majority of the women98.9% who have the knowledge were practice the Breast SelfExamination monthly or fortnightly. The attituderegarding Breast Self Examination was very encouraging as 97.3% of the respondents promised not only toadopt it in future but also recommend it to their relatives and other friends. Conclusion: The knowledge about Breast SelfExamination was very low in the respondent which is the easierway of early detection of different breast diseases specially, breast cancer. However those who know it aredoing it well. The attitude of the respondents was very encouraging. Awareness programme should be developedto promote it for early detection of Breast cancer.

Introduction: Malnutrition contributes to approximately 45% of deaths among under 5 years children in low and middle-income countries. Poor maternal knowledge and failure to comply with recommended Infant and Young Child Feeding (IYCF) practices are known risk factors for malnutrition but there are inconsistencies in the literature. Therefore, this cross-sectional study of 100 mother-child pairs in district Gujranwala aimed to assess maternal nutritional literacy (MNL) and maternal feeding practices (MFP) and their ultimate impacts on child growth., Methods: A researcher administered questionnaire that was the combination of WHO model questionnaires and FAO Nutrition-related KAP model questionnaires was used to collect the data from mothers while and anthropometric measurements of children were taken by following the standard methods., Results: Results showed that 57% of mothers had average nutritional knowledge and feeding practices were not satisfactory. Only 12% of mothers-initiated breastfeeding within the first hour of birth, 7% of infants were exclusively breastfed, while 27.27% continued to be breastfed beyond 1 year. Complementary foods were timely introduced to 53% of infants, 47% received minimum meal frequency and 34% met the minimum dietary diversity criteria. Additionally, the consumption of unhealthy foods, sugar-sweetened beverages, and zero consumption of fruits and vegetables was practiced by 71, 23, and 27% of infants and young children, respectively. Prevalence of stunting, wasting, underweight and overweight was 19, 9, 12, and 12%, respectively. A non-significant association was observed between MNL and MFP with growth outcomes with a few exceptions. The odds of being wasted ( β = 1.903, OR = 6.706, p < 0.05) and underweight ( β = 1.732, OR = 5.654, p < 0.05) are higher among children who had vaginal birth. Higher odds of being stunted ( β = 2.173, OR = 8.788, p < 0.05) were observed among those whose mothers had middle school education compared to those having higher education., Conclusion: Overall results indicated a dire need not only to create nutritional awareness among mothers in Gujranwala but also to provide a support system for mothers to help them implement standard feeding practices., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Tahreem, Rakha, Anwar, Rabail, Maerescu, Socol, Criste, Abdi and Aadil.)

Background and Objectives: Analgesia trials often demands multiple comparisons to assess various treatment arms, outcomes, or repeated assessments. These multiple comparisons risk inflating the false positive rate. Multiplicity correction in recent analgesic randomized controlled trials (RCTs) remains unclear despite statistical method advancements and regulatory guidelines. Our study aimed to identify reporting inadequacies in multiple analysis adjustments and explanations to understand these deficiencies., Databases and Data Treatment: This review analysed RCTs from the European Journal of Pain, the Journal of Pain, and PAIN, published between January 2018 and December 2022. We included randomized, double-blind trials focusing on pain outcomes. Data extraction, managed by three researchers using predefined criteria, included trial characteristics, multiplicity presence, and correction methods. Descriptive statistical analyses included Fisher's exact, and Holm method for multiple comparisons., Results: Out of 112 articles, 48 pre-specified a primary analysis plan. Multiple analyses were observed in 65 articles, with 60% adjusting for all comparisons, primarily using the Bonferroni method. Compared with previous studies, no significant changes in multiplicity correction practices were noted when stratified by trial type, size, and sponsor., Conclusions: The study reveals a persistent reliance on multiple comparisons in analgesic clinical trials without a corresponding increase in multiplicity corrections emphasizing a need for enhanced reporting and implementation of statistical adjustments. We acknowledge limitations in categorizing studies, the use of a surrogate for the trial stage, and sourcing data from journal webpages rather than a database., Significance Statement: This study flags inadequate reporting on multiplicity correction in analgesic trials, stressing the risk of false positives and the urgent need for enhanced reporting to boost reproducibility., (© 2024 European Pain Federation ‐ EFIC ®.)

The purpose of the current study was to analyze and validate the existing gap in knowledge, by conducting a differential expression analysis and validation of NEK6, NEK7, and NEK9 in breast, cervical, and glioblastoma cancer and targeting these proteins through development of novel site specific inhibitor with favorable pharmacokinetic and safety profile, using open-source databases. The analysis revealed that the targeted kinases were overexpressed in all three types of cancer. Their expression was significantly linked to overall survival rates, which suggests that they play a major role in the development and progression of these cancers. After, having the prognostic importance of These findings provided a rationale for synthesizing novel compound i.e., dimethyl 2,2'-((methylenebis(2-(2H-benzo[d][1,2,3]triazol-2-yl)-4-(2,4,4-trimethylpentan-2-yl)-6,1phenylene))bis(oxy))diacetate (TAJ4)), capable of effectively targeting these proteins using in-vitro cytotoxicity assays and comprehensive computational approaches. Then the inhibitory potential of TAJ4 was evaluated against cell lines of the respective cancers (HeLa cells, MCF-7 cells, and Vero cells). The growth inhibitory values (GI 50 ) suggested that TAJ4 exhibited strong inhibitory potential towards MCF-7 cells (GI 50  = 3.18 ± 0.11 µM) in comparison to the HeLa cell line (GI 50  = 8.12 ± 0.43 µM), surpassing that of standard drugs. Furthermore, in-silico investigations, including density functional theory (DFT) calculations and molecular docking studies, revealed a substantial reactivity profile of TAJ4, with promising molecular interactions against NEK7, NEK9, TP53, NF-KAPPA-B, and caspase-3 proteins. Further investigation using in-vitro and in-vivo approaches is recommended to fully establish the therapeutic efficacy and safety profile of TAJ4., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Context: A significant class of solid-state materials, Ruddlesden-Popper (RP) perovskites are well-known for their rich chemical compositions that make them excellent electrocatalysts. Therefore, in this work, we conduct thorough analysis of RP perovskites, specifically Ca 2 XO 4 (X = Zr, Hf). We delve into the structural, electronic, optical, and mechanical properties presenting their insights for the first time. Our investigations reveal that Ca 2 XO 4 (X = Zr, Hf) exhibits stable tetragonal phase structures, with energies (E 0 ) of - 10,522.93 eV and - 33,520.14 eV, respectively. The calculated E cohsive / atom in terms of the ground state determines to possess distinct values such as - 4.79 eV/atom for LiScTe 2 and - 3.95 eV/atom for Ca 2 ZrO 4 and Ca 2 HfO 4 . Notably, the semiconductor characteristics of Ca 2 ZrO 4 and Ca 2 HfO 4 are underscored by their respective wide direct band gap of 5.02 eV and 5.30 eV. Then, we discuss the optical parameters encompassing the dielectric function, absorption coefficient, optical conductivity, refractive index, and energy loss function. Ca 2 ZrO 4 is described as ductile, whereas Ca 2 HfO 4 is defined as brittle. Our outcomes underscore remarkable ability of these materials to absorb ultraviolet radiation from the electromagnetic spectrum, positioning them as promising candidates for optoelectronic applications., Methods: We made these calculations by employing first-principles approach rooted in density functional theory (DFT) and utilizing the Perdew-Burke-Ernzerhof-Generalized Gradient Approximation (PBE-GGA) and Tran and Blaha-modified Becke-Johnson (TB-mBJ) functional within the WEIN2K framework. In this framework, Kramers-Kronig relations are used to obtain crucial optical parameters. Mechanical behavior is assessed by employing Voigt-Reuss-Hill approximation (VRH) fulfilling the Born's criteria which emphasizes that these materials are equally appropriate for a broad range of mechanical applications., Competing Interests: Declarations. Ethical approval: Not applicable. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: We aimed to investigate the factors impacting stone clearance following retrograde intrarenal surgery (RIRS) for lower pole kidney stones and to determine whether there is a significant relationship between the infundibular pelvic angle (IPA) of the kidney's lower pole and stone fragment clearance., Methods: We retrospectively reviewed patients who underwent flexible ureteroscopy (f-URS) for lower pole renal calculi between December 2020 and July 2023 at our institution. Patient demographics and stone parameters were recorded, including stone size, number, volume, density, and IPA. Intraoperative data, including total operative time, lasing time, type of laser used, and stone composition, were collected and analyzed. All patients underwent a computed tomography (CT) scan at three months followup. We recorded the presence of residual stones and the percentage of stone volume reduction. Patients with a stone size ≤3 mm were deemed stone-free. All patients were discharged home on the same operative day., Results: A total of 123 patients were included in the study: 71 in the stone-free group (group 1) and 52 in the residual stones group (group 2). On univariate analysis, there were significant differences between the two groups in terms of stone size, IPA, and the type of ureteroscopy used. At three-month followup, 96% (24/25) of patients with an IPA <30° had residual stones compared to 28.6% (28/98) of patients with an IPA >30° (p<0.001). There was no significant difference in the intraoperative or postoperative complications between the two groups. On multivariate analysis, IPA and stone size were the only predictive factors for the presence of residual stones. Twelve patients (23.1%) from group 2 required retreatment., Conclusions: RIRS is an effective treatment option for the management of lower pole kidney stones. IPA, in conjunction with stone size, appears to dictate the stone clearance rates of RIRS for lower pole stones.

Dual carbon metabolisms and the synergism contribute to improving nutrient recovery under mixotrophy. However, how synergism influences nutrient recovery has yet to be understood, which is revealed in the current study. Due to dual carbon metabolisms and synergism,the PO 4 - -P recovery rate under mixotrophy reached 0.34 mg L -1  h -1 . Due to the internal cycling of respiratory CO 2 , the mutualistic index (MI) in terms of synergism helped Scenedesmus accumulate 27.49 % more biomass under mixotrophy than sum of the two controls. In contrast, MI contributed 0.26 g L -1  d -1 to the total modeled mixotrophic productivity of 1.15 g L -1  d -1 . To total modeled PO 4 - -P recovery, mixotrophic-auto, and mixotrophic-hetero shares were 42 % and 58 %. The synergism under mixotrophy contributed 20 % in total PO 4 - -P recovery. The PO 4 - -P recovery rate under mixotrophywas comparable to other biological P removal methods. These findings emphasize the potential of synergism in improving productivityand promoting resource recovery for sustainable wastewater treatment., 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.)

Background: Classically, there are two techniques for establishing pneumoperitoneum in laparoscopic and robotic surgeries: the closed Veress needle technique and Hasson's technique for open placement of laparoscopic ports. Most surgeons prefer the open Hasson technique, even though it is not the gold standard. Some surgeons still favour the Veress needle technique despite literature linking it to visceral and vascular damage., Aims: This study aimed at determining the safety index of the two techniques of establishing pneumoperitoneum in laparoscopic and robotic surgeries by evaluating the risk of injuries associated with Veress and Hasson's techniques., Materials and Methods: This is a retrospective cohort study evaluating the incidence of primary port placement injuries (PPPI) using Hasson's open trocar technique and Veress needle technique in 200 laparoscopic and robotic cases (emergency vs. elective) over a three-month period (January to March 2024) at Newcross Hospital. The exclusion criteria were secondary port injuries. IBM SPSS Statistics for Windows, Version 24 (Released 2016; IBM Corp., Armonk, New York) and Microsoft Excel (Microsoft Corporation, Redmond, Washington) were used for data analysis., Results: Hasson's open technique of primary port placement was used in 74% of emergency cases, while the Veress needle technique was used in 26% of emergency surgeries. Similarly, the most common technique for establishing pneumoperitoneum employed in elective surgical procedures was Hasson's open technique (77%). When comparing the safety index of the two techniques for establishing pneumoperitoneum, we found that there were no major PPPI associated with either technique, with minimal incidence of minor PPPI associated with both techniques. While some cases did involve injuries from secondary port insertions (bowel and vascular injuries), these were excluded according to our exclusion criteria. Additionally, no perioperative mortality associated with primary trocar placement was observed., Conclusion: Although the literature describes the association of the Veress technique with visceral and vascular injuries, our study found it to be as safe as Hasson's open port placement technique. Therefore, either technique can be employed for the safe establishment of pneumoperitoneum in laparoscopic and robotic surgeries., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. The Royal Wolverhampton NHS Trust issued approval N/A. All patient identifiable data were omitted from the publication. 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, Syed et al.)

Background: Population-based studies of ideal cardiovascular health (CVH) and gestational diabetes mellitus (GDM) are scarce., Methods: We conducted a cross-sectional analysis of 2007-2018 National Health Examination and Nutrition Survey women aged ≥ 20 years, who had data on Life's Simple 7 (LS7) metrics and self-reported GDM history. Each LS7 metric was assigned a score of 0 (non-ideal) and 1(ideal) and summed to obtain total ideal CVH scores (0-7). We used logistic regression models to assess associations between LS7 ideal CVH scores (0-7) and GDM history, accounting for socio-demographic factors., Results: Among 9199 women (mean age: 46 years, 8 % with a GDM history), there was a progressive decrease in the odds of past GDM history across increasing ideal CVH scores. Compared to females with 0-1 ideal CVH scores, females with ideal CVH scores of 3, 4 and 5-7 had an associated 39 % lower [odds ratio: 0.61 (95 % CI: 0.41-0.90)], 50 % lower [0.50 (0.33-0.76)] and 66 % lower [0.34 (0.20-0.56)] odds of past GDM history, respectively. There were notable racial/ethnic and citizenship/nativity differences in these associations., Conclusions: Women with higher ideal CVH scores had lower odds of GDM history. Our findings underscore the importance of optimizing cardiometabolic health among women with GDM history., 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 B.V. 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.)

Persistent, severe pain negatively impacts health and wellbeing, but half of patients do not receive adequate relief from current treatments. Understanding signals that modulate central pain processing could point to new strategies to manage severe pain. Administering Neurotensin (Nts) or Nts receptor (NtsR) agonists into the brain provides analgesia comparable to pharmacologic opioids. However, the endogenous sources of Nts that modify pain processing and might be leveraged for pain relief remained unknown. We previously characterized a large population of Nts-expressing neurons in the lateral hypothalamic area (LHA Nts neurons) that project to brain regions that participate in descending control of pain processing. We hypothesized that LHA Nts neurons are an endogenous source of Nts and activating them would alleviate pain dependent on Nts signaling via NtsRs. To test this, we injected Nts Cre mice in the LHA with AAVs to cre-dependently express either mCherry (Control) or the excitatory hM3Dq in LHA Nts neurons, permitting their stimulation after treatment with the hM3Dq ligand clozapine N-oxide (CNO). Activating LHA Nts neurons had no effect on thermal pain and mechanical responses in naïve mice. By contrast, both spared nerve injury- (SNI) and complete Freund's adjuvant (CFA)-induced mechanical hypersensitivity was completely reversed by CNO-stimulation of LHA Nts neurons. Pretreatment with the Nts receptor antagonist SR142948 reduced CNO-mediated analgesia, indicating that LHA Nts neurons alleviate chronic pain in an Nts receptor-dependent manner. Taken together these data identify LHA Nts neurons as an endogenous source of Nts that modulates central pain processing and may inform future development of Nts-based targets to treat severe pain., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Restless leg syndrome (RLS) is a neurological disorder characterized by an irresistible urge to move the legs, particularly during rest. It significantly affects the quality of life of hemodialysis patients with high prevalence in this population. While pharmacological treatments, especially dopamine agonists (DAs), are commonly used, they often come with side effects and augmentation phenomena. This systematic review examines the effectiveness of exercise interventions in managing RLS among hemodialysis patients. Eight studies, including randomized controlled trials and quasi-experimental studies, were analyzed. The interventions primarily consisted of aerobic exercises (cycling) and stretching exercises, with durations ranging from eight weeks to six months. The primary outcome measure was RLS severity, assessed using validated scales such as the International Restless Legs Syndrome Study Group (IRLSSG) scale or the Restless Legs Syndrome Questionnaire (RLSQ). Secondary outcomes included sleep quality, depression, and physical performance. The results consistently demonstrated that both aerobic and stretching exercises significantly reduced RLS severity and improved related outcomes. The intradialytic nature of some interventions offered a practical approach to incorporating exercise into patient routines. While exercise showed comparable efficacy to DAs in reducing RLS symptoms and improving depression scores, only DAs significantly enhanced sleep quality in one comparative study. These findings suggest that exercise interventions may be a viable non-pharmacological approach to managing RLS in hemodialysis patients, potentially complementing or reducing reliance on pharmacological treatments., Competing Interests: 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, Altayb Ismail et al.)

This case report describes a 32-year-old male with a familial history of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), presenting with right-sided weakness and visual disturbances. The symptoms, consistent with a transient ischemic attack (TIA), resolved spontaneously. Subsequent evaluation, including MRI brain imaging, revealed a high T2 signal in subcortical white matter in the frontal and parietal lobes, consistent with CADASIL. Positive NOTCH3 testing confirmed the diagnosis, leading to the initiation of antiplatelet and statin therapy under the care of both stroke and neurology teams., 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, Karim et al.)

Background: Increasing cardiac, hepatic, and metabolic diseases have raised the need to modify our contemporary lifestyles toward balancing and diversifying the nutrients in our daily diet. Objective: Dietary fats should be modified to healthier versions by blending different vegetable oils. Therefore, in this study, an oil blend with health-protective and promoting fatty acid combinations was investigated to bring down the progression of cardiac and other metabolic diseases., Methodology: A bio-efficacy trial was performed to investigate the therapeutic potential of an oil blend in 30 hyperlipidemic rats. Five rats were allocated to each group (coconut, flaxseed, olive, sunflower, and blended oil) for 42 days and were compared with the initial values of hyperlipidemic rats. Methodological investigations were performed for the body weight, naso-anal length, various obesity indices, visceral fat accumulation, blood and serum, cardiovascular risk indices, and echocardiograph., Results: Blended oil consumption indicated significant reductions of 53.12% in body fat content (3.98 ± 0.96), 6.82% in Lee index (289.60 ± 8.27), 16.84% in BMI (0.15 ± 0.003), 57.37% in total cholesterol (52.00 ± 9.03), 68.57% in triacylglycerides (99.00 ± 9.19), 61.16% in atherogenic index (0.88 ± 0.12), and 58.72% in coronary risk index (2.88 ± 0.12), when compared with the initial values., Conclusion: Blended oil consumption has significantly reduced various obesity indices, improved lipid profile, and provided significant protection against cardiovascular risk indices. Moreover, the results of blended oil indicated significant health protective ameliorations in electrocardiographs. Its regular consumption could help to reduce the onset of obesity and metabolic diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer TP declared a past co-authorship with the author RA to the handling editor., (Copyright © 2024 Rabail, Altemimi, Maerescu, Socol, Criste, Khalid, Mahwish, Hussain, Liu and Aadil.)

Chronic pain and obesity frequently occur together. An ideal therapy would alleviate pain without weight gain, and most optimally, could promote weight loss. The neuropeptide neurotensin (Nts) has been separately implicated in reducing weight and pain but could it be a common actionable target for both pain and obesity? Here we review the current knowledge of Nts signaling via its receptors in modulating body weight and pain processing. Evaluating the mechanism by which Nts impacts ingestive behavior, body weight, and analgesia has potential to identify common physiologic mechanisms underlying weight and pain comorbidities, and whether Nts may be common actionable targets for both., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest related to this work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To present a case of acute B-cell lymphoblastic leukemia (B-ALL) ocular relapse treated with chimeric antigen receptor T-cell (CAR T) therapy. Methods: A retrospective case review was evaluated. Results: A 69-year-old woman with a history of B - ALL presented with bilateral hypopyons and 3+ anterior chamber cells that responded to topical prednisolone. Six months later, she developed recurrent hypopyons, iris neovascularization, and iris nodularity in both eyes. A fine-needle aspiration biopsy confirmed ocular infiltration of B-ALL. A single infusion of CAR T therapy resulted in remission of the systemic and ocular findings. The clinical course was complicated by cytokine release syndrome and neurotoxicity, which improved with medical management. The patient remained in remission for 7 months after a single CAR T infusion. Conclusions: CAR T therapy may be effective in treating systemic leukemia and uveal infiltration, with an ocular side-effect profile and visual outcomes. The systemic side effects of CAR T therapy may be managed medically., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of the article., (© The Author(s) 2024.)

We present the case of a 59-year-old immunocompetent female with a mild cough, fever, and rash. She was diagnosed with mild pneumonitis caused by Capnocytophaga canimorsus , with no history of dog bites. An indolent clinical course with transmission via canine face licking in immunocompetent individuals is a rare occurrence according to the literature. The diagnosis was made on positive blood cultures and polymerase chain reaction, following which the patient was treated with beta-lactam antibiotics. C. canimorsus is a gram-negative bacterium found in the saliva of dogs and cats. The incidence of human infections is rare, particularly affecting immunocompromised patients exposed to the saliva of these animals. Typical manifestations include severe sepsis, with a high case fatality., 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, Naseem et al.)

Background: A coordinated care system helps provide timely access to treatment for suspected acute stroke. In Northwestern Ontario (NWO), Canada, communities are widespread with several hospitals offering various diagnostic equipment and services. Thus, resources are limited, and health care providers must often transfer patients with stroke to different hospital locations to ensure the most appropriate care access within recommended time frames. However, health care providers frequently situated temporarily (locum) in NWO or providing care remotely from other areas of Ontario may lack sufficient information and experience in the region to access care for a patient with a time-sensitive condition. Suboptimal decision-making may lead to multiple transfers before definitive stroke care is obtained, resulting in poor outcomes and additional health care system costs., Objective: We aimed to develop a tool to inform and assist NWO health care providers in determining the best transfer options for patients with stroke to provide the most efficient care access. We aimed to develop an app using a comprehensive geomapping navigation and estimation system based on machine learning algorithms. This app uses key stroke-related timelines including the last time the patient was known to be well, patient location, treatment options, and imaging availability at different health care facilities., Methods: Using historical data (2008-2020), an accurate prediction model using machine learning methods was developed and incorporated into a mobile app. These data contained parameters regarding air (Ornge) and land medical transport (3 services), which were preprocessed and cleaned. For cases in which Ornge air services and land ambulance medical transport were both involved in a patient transport process, data were merged and time intervals of the transport journey were determined. The data were distributed for training (35%), testing (35%), and validation (30%) of the prediction model., Results: In total, 70,623 records were collected in the data set from Ornge and land medical transport services to develop a prediction model. Various learning models were analyzed; all learning models perform better than the simple average of all points in predicting output variables. The decision tree model provided more accurate results than the other models. The decision tree model performed remarkably well, with the values from testing, validation, and the model within a close range. This model was used to develop the "NWO Navigate Stroke" system. The system provides accurate results and demonstrates that a mobile app can be a significant tool for health care providers navigating stroke care in NWO, potentially impacting patient care and outcomes., Conclusions: The NWO Navigate Stroke system uses a data-driven, reliable, accurate prediction model while considering all variations and is simultaneously linked to all required acute stroke management pathways and tools. It was tested using historical data, and the next step will to involve usability testing with end users., (©Ayman Hassan, Rachid Benlamri, Trina Diner, Keli Cristofaro, Lucas Dillistone, Hajar Khallouki, Mahvareh Ahghari, Shalyn Littlefield, Rabail Siddiqui, Russell MacDonald, David W Savage. Originally published in JMIR Formative Research (https://formative.jmir.org), 01.08.2024.)

Delayed conceiving is a failure of a female to attain clinical pregnancy within a year without the use of contraception or any precautionary measure. The females of reproductive age (20-49 years) are the sufferers, that is, about 1.5 million or 10% of couples globally are facing this issue. Delayed conception can be caused by several reasons including diet, lifestyle, and genetic and clinical problems. Deficiencies or overconsumption of any nutrient may also cause delayed conception in females. Dietary deficits such as iron, iodine, zinc, folate, and vitamin D reduce the ovarian reserve. Heavy metals such as copper, manganese, lead, and cadmium also have an impact on fertility. Overconsumption of fast foods and nonhome-made foods increases the likelihood of infertility by 2-3. Smoking, physical activity, age, polycystic ovary syndrome (PCOS), obesity, and depression have all been considered lifestyle and clinical factors. If women have a sedentary lifestyle, too much exercise or obesity both contribute to infertility. In clinical factors, type 1 diabetes, insulin resistance, and hypertension mainly cause infertility. Our focus in this review is on the studies probe that how these variables contributed to delayed conception and how it can be controlled to help combat infertility. Prevention from delayed conception involves consuming a healthy and balanced diet that contains essential nutrients engaging in physical activity and abstaining from smoking, PCOS, and medical issues., Competing Interests: None., (© 2024 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC.)

Background: The optimal management of breech presentation remains a debate among obstetricians worldwide. The Term Breech Trial (2000) highlighted elective caesarean section as a preferable method over vaginal delivery for breech presentations. This study investigates delivery modes in women who had an elective caesarean section for breech presentation in their first pregnancy. Objective was to evaluate delivery outcomes in the second pregnancy of women who had an elective caesarean section for breech presentation in their first pregnancy., Methods: A cross-sectional study was conducted at Jinnah International Hospital Abbottabad from October 10, 2018, to April 10, 2019. Data was collected from 321 women who had an elective caesarean section for breech presentation during their first pregnancy. The study used per-abdominal examination and obstetrical ultrasound to assess foetal presentation and recorded the mode of delivery in the second pregnancy., Results: Participants' ages ranged from 18 to 49 years, with a mean age of 28.87±4.07 years. The average interval between deliveries was 1.92±0.92 years, labour duration averaged 5.56±2.41 hours, and foetal head engagement averaged 2.92±1.35. Of the participants, 18.7% achieved a vaginal delivery, while 81.3% had a repeat caesarean section. Reasons for repeat caesarean included recurrent breech presentation in 44.9% and foetal distress in 32.4%., Conclusions: Approximately 18.7% of women who had an elective caesarean section for breech presentation in their first pregnancy achieved vaginal delivery in their second pregnancy, whereas the majority underwent another elective caesarean section.

AT-rich interaction domain protein 1A (ARID1A), a SWI/SNF chromatin remodeling complex subunit, is frequently mutated across various cancer entities. Loss of ARID1A leads to DNA repair defects. Here, we show that ARID1A plays epigenetic roles to promote both DNA double-strand breaks (DSBs) repair pathways, non-homologous end-joining (NHEJ) and homologous recombination (HR). ARID1A is accumulated at DSBs after DNA damage and regulates chromatin loops formation by recruiting RAD21 and CTCF to DSBs. Simultaneously, ARID1A facilitates transcription silencing at DSBs in transcriptionally active chromatin by recruiting HDAC1 and RSF1 to control the distribution of activating histone marks, chromatin accessibility, and eviction of RNAPII. ARID1A depletion resulted in enhanced accumulation of micronuclei, activation of cGAS-STING pathway, and an increased expression of immunomodulatory cytokines upon ionizing radiation. Furthermore, low ARID1A expression in cancer patients receiving radiotherapy was associated with higher infiltration of several immune cells. The high mutation rate of ARID1A in various cancer types highlights its clinical relevance as a promising biomarker that correlates with the level of immune regulatory cytokines and estimates the levels of tumor-infiltrating immune cells, which can predict the response to the combination of radio- and immunotherapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: This study determined the impact of pre-operative abdominal MRI on all-cause mortality for patients with resected PDAC., Methods: All adult (≥18 years) PDAC patients who underwent pancreatectomy between January 2011 and December 2022 in Ontario, Canada, were identified for this population-based cohort study (ICD-O-3 codes: C250, C251, C252, C253, C257, C258). Patient demographics, comorbidities, PDAC stage, medical and surgical management, and survival data were sourced from multiple linked provincial administrative databases at ICES. All-cause mortality was compared between patients with and without a pre-operative abdominal MRI after controlling for multiple covariates., Findings: A cohort of 4579 patients consisted of 2432 men (53.1%) and 2147 women (46.9%) with a mean age of 65.2 years (standard deviation: 11.2 years); 2998 (65.5%) died while 1581 (34.5%) survived. Median follow-up duration post-resection was 22.4 months (interquartile range: 10.8-48.8 months), and median survival post-pancreatectomy was 25.9 months (95% confidence interval [95% CI]: 24.8, 27.5). Patients who underwent a pre-operative abdominal MRI had a median survival of 33.1 months (95% CI: 30.7, 37.2) compared to 21.1 months (95% CI: 19.8, 22.6) for all others. A total of 2354/4579 (51.4%) patients underwent a pre-operative abdominal MRI, which was associated with a 17.2% (95% CI: 11.0, 23.1) decrease in the rate of all-cause mortality, with an adjusted hazard ratio (aHR) of 0.828 (95% CI: 0.769, 0.890)., Interpretation: Pre-operative abdominal MRI was associated with improved overall survival for PDAC patients who underwent pancreatectomy, possibly due to better detection of liver metastases than CT., Funding: Northern Ontario Academic Medicine Association (NOAMA) Clinical Innovation Fund., Competing Interests: Dr. Brandon Meyers has received research support from Abbvie, ALX, Astra-Zeneca, GSK, Eisai, Roche, advises Amgen, Astra-Zeneca, Bayer, BMS, Eisai, EMD Serono, Incyte, Ipsen, Merck, Roche, Sanofi Genzyme, Servier, is an expert consultant for Roche, CADTH, Cancer Care Ontario (CCO), Health Canada, and has received travel stipends from Eisai and Ipsen; Dr. David W. Savage is a co-investigator and a Principal Investigator on a Northern Ontario Academic Medicine Association (NOAMA) grant, a co-investigator on a Canadian Institutes of Health Research (CIHR) grant and is the Interim Site Director of ICES North; Dr. Pablo E. Serrano has provided consulting services for Incyte Biosciences Canada and received an honorarium from Hoffman La Roche; and Dr. Michael Patlas receives royalties from Elsevier. None of the other authors have conflicts of interest to disclose. This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care (MLTC). This document used data adapted from the Statistics Canada Postal CodeOM Conversion File, which is based on data licensed from Canada Post Corporation, and/or data adapted from the Ontario Ministry of Health Postal Code Conversion File, which contains data copied under license from ©Canada Post Corporation and Statistics Canada. Parts of this material are based on data and/or information compiled and provided by Ontario Health (OH), Canadian Institute for Health Information (CIHI), and the Ontario MOH. The analyses, conclusions, opinions, and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement is intended or should be inferred., (© 2024 The Author(s).)

Background: The coronavirus pandemic highlighted the need for remote patient monitoring to deliver and provide access to patient care and education. A mobile-based app providing interactive tools for patient education and monitoring was piloted at Thunder Bay Regional Health Sciences Centre (TBRHSC) in November 2020. We aimed to examine the platform's impact on postoperative length of stay, hospital readmissions, and emergency department (ED) visits 60 days postsurgery in total hip and knee arthroplasty patients in Northwestern Ontario., Methods: Data were assessed from patients undergoing primary total hip or knee arthroplasties at TBRHSC from March 1, 2020, to February 28, 2022. Patients were divided into 2 cohorts based on enrollment with the mobile-based app (SeamlessMD). Statistical differences in outcomes were determined using Mann-Whitney or χ 2 tests. An odds ratio was calculated for ED visits., Results: Patients enrolled in the mobile-based app had statistically lower length of stay ( U  = 7779.0, P < .001) and fewer ED visits (χ 2 (1,212)  = 5.570, P  = .018) than patients not enrolled in the program. Patients not enrolled had 2.31 times greater odds of visiting the ED postsurgery (odds ratio = 0.432, 95% confidence interval = 0.213-0.877, P  = .022). There were no statistical differences found in readmission rates., Conclusions: The implementation of the mobile-based app at TBRHSC showed its potential value as a tool to reduce costs in the healthcare system and improve patient outcomes. Consequentially, more formal studies are required to elucidate the magnitude of this effect., (© 2024 The Authors.)

Praecitrullus fistulosus, commonly known as round gourd or tinda, is a remarkable source of bioactive substances like polyphenols, antioxidants, carotene, magnesium, and vitamin C. It is considered one of the Cucurbitaceae family due to its medicinal features. Plant lectins are carbohydrate-binding proteins that can bind and identify the carbohydrate moieties upon cancerous cells demonstrated some anticancer potentials. Several plant lectins are helpful as cancer biomarkers because they can find cancer cells and contribute to cell death initiation via apoptosis and autophagy, suggesting the possible role of cancer-inhibiting pathways. Therefore, round gourd and lectins might be useful in the controlling of cancer. This study compiled the most recent scientific literature regarding the round gourd and numerous plant lectins, and the clinical trials of lectins exploring their effects on cancer were examined. Research according to the literature, round gourd, and lectins demonstrated pharmacological alterations not only in cancer but in many other disorders as well. Thus, clinical investigations proved the beneficial impacts of round gourd and lectins on cancer due to their antioxidants, anti-inflammatory, and anticarcinogenic properties. Further studies are required to fully comprehend the potential applications of these plant-derived compounds against cancer, as well as to identify the round gourd components and clarify their mode of action., Competing Interests: Declaration of competing interest The authors declare no conflicts of interst., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: History taking and clinical reasoning are important skills that require knowledge, cognition and meta-cognition. It is important that a trainee must experience multiple encounters with different patients to practice these skills. However, patient safety is also important, and trainees are not allowed to handle critically ill patients. To address this issue, a randomized controlled trial was conducted to determine the effectiveness of using Virtual Patients (VP) versus Standardized Patients (SP) in acquiring clinical reasoning skills in ophthalmology postgraduate residents., Methods: Postgraduate residents from two hospitals in Lahore, Pakistan, were randomized to either the VP group or the SP group and were exposed to clinical reasoning exercise via the VP or SP for 30 min after the pretest. This was followed by a posttest. One month after this activity, a follow-up posttest was conducted. The data were collected and analysed using IBM-SPSS version 25. Repeated measures ANOVA was used to track the effect of learning skills over time., Results: The mean age of the residents was 28.5 ± 3 years. The male to female ratio was 1:1.1. For the SP group, the mean scores were 12.6 ± 3.08, 16.39 ± 3.01 and 15.39 ± 2.95, and for the VP group, the mean scores were 12.7 ± 3.84, 16.30 ± 3.19 and 15.65 ± 3.18 for the pretest, posttest and follow-up posttest, respectively (p value < 0.00). However, the difference between the VP and SP groups was not statistically significant (p = 0.896). Moreover, there was no statistically significant difference between the VP and SP groups regarding the retention of clinical reasoning ability. In terms of learning gain, compared with the VP group, the SP group had a score of 51.46% immediately after clinical reasoning exercise as compared to VP group, in which it was 49.1%. After one month, it was 38.01 in SP and 40.12% in VP group., Conclusion: VPs can be used for learning clinical reasoning skills in postgraduate ophthalmology residents in a safe environment. These devices can be used repeatedly without any risk to the real patient. Although similarly useful, SP is limited by its nonavailability for repeated exercises., (© 2024. The Author(s).)

It is increasingly evident that the association of glycans with the prion protein (PrP), a major post-translational modification, significantly impacts the pathogenesis of prion diseases. A recent bioassay study has provided evidence that the presence of PrP glycans decreases spongiform degeneration and disease-related PrP (PrPD) deposition in a murine model. We challenged (PRNPN181Q/197Q) transgenic (Tg) mice expressing glycan-free human PrP (TgGlyc-), with isolates from sporadic Creutzfeldt-Jakob disease subtype MM2 (sCJDMM2), sporadic fatal insomnia and familial fatal insomnia, three human prion diseases that are distinct but share histotypic and PrPD features. TgGlyc- mice accurately replicated the basic histotypic features associated with the three diseases but the transmission was characterized by high attack rates, shortened incubation periods and a greatly increased severity of the histopathology, including the presence of up to 40 times higher quantities of PrPD that formed prominent deposits. Although the engineered protease-resistant PrPD shared at least some features of the secondary structure and the presence of the anchorless PrPD variant with the wild-type PrPD, it exhibited different density gradient profiles of the PrPD aggregates and a higher stability index. The severity of the histopathological features including PrP deposition appeared to be related to the incubation period duration. These findings are clearly consistent with the protective role of the PrP glycans but also emphasize the complexity of the conformational changes that impact PrPD following glycan knockout. Future studies will determine whether these features apply broadly to other human prion diseases or are PrPD-type dependent., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

In the current study, Azo-Thiohydantoins derivatives were synthesized and characterized by using various spectroscopic techniques including FTIR, 1 H-NMR, 13 C-NMR, elemental and HRMS analysis. The compounds were evaluated for alkaline phosphatase activity and it was observed that among all the synthesized compounds, derivative 7e exhibited substantial inhibitory activity (IC 50  = 0.308 ± 0.065 µM), surpassing the standard inhibitor (L-Phenyl alanine, IC 50  = 80.2 ± 1.1 µM). Along with this, these derivatives were comprehensively examined regarding the electronic properties and reactivity of the synthesized compounds using Density Functional Theory (DFT) calculations, where the results were found very promising and the synthesized compound were found stable. After that, SwissADME evaluations highlighted compounds for their favorable physicochemical properties, including solubility and drug-likeness. Molecular docking exhibited the strong binding affinities of 7f and 7e derivatives with intestinal alkaline phosphatase (IAP), further supported by Molecular Dynamics (MD) simulations. This comprehensive integration of experimental and computational approaches sheds the light on the potential therapeutic applications of the synthesized compounds. By providing a detailed investigation of these aspects, this research opens the avenues for the development of novel pharmacologically active compounds with diverse applications., (© 2024. The Author(s).)

The efficiency of mixotrophic microalgae in enhancing the recovery of waste nutrients has been well established; however, the recovery rate is crucial in meeting the needs of field applications. This study evaluated the impact of media characteristics on nutrient recovery under mixotrophic conditions. The mixotrophic N recovery rate with S. acuminatus in modified BG-11 reached 2.59 mg L -1 h -1 . A mixotrophic growth optimization strategy was applied to achieve a high-rate nutrient recovery from municipal wastewater treatment plant effluents. The contribution of waste chemical oxygen demand (COD) to nutrient recovery was assessed using secondary effluent (SE) under heterotrophy. The results highlighted a significant increase in total nitrogen (TN) and total phosphorus (TP) recovery rates when glucose was supplied, indicating the additional carbon requirements for efficient nutrient recovery. The TN and TP recovery rates under mixotrophic conditions with the addition of trace metals and high cell density were enhanced by 91.94% and 92.53%, respectively, resulting in recovery rates of 3.43 mg L -1 h -1 and 0.30 mg L -1 h -1 . The same conditions were used for nutrient recovery from primary effluent (PE), and the results were more satisfactory as the TN and TP recovery rates reached 4.79 and 0.55 mg L -1 h -1 , respectively. Additionally, the study estimated the carbon footprints (C-footprints) and areal footprints of mixotrophy-based nitrogen recovery. The findings revealed carbon footprints and areal footprints of -15.93 ± 4.57 tCO 2 e t -1 N recovery and 0.53 ± 0.19 m 3  m -2 d -1 wastewater, respectively. This high-rate nutrient recovery, achieved under a carbon-negative (C-negative) budget through mixotrophy, presents a novel strategy for efficiently recovering resources from municipal wastewater, thus facilitating resource recycling and ensuring environmental sustainability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing interests that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Patients with kidney failure experience symptoms that are often under-recognised and undermanaged. These symptoms negatively impact health-related quality of life and are associated with adverse clinical outcomes. Regular symptom assessment, using electronic patient reported outcomes measure (ePROMs) linked to systematic symptom management, could improve such outcomes. Clinical implementation of ePROMs have been successful in routine oncology care, but not used for patients on dialysis. In this study, we describe a pilot study of ePROM-based systematic symptom monitoring and management intervention in patients treated with in-centre haemodialysis., Methods and Analysis: This is a parallel-arm, controlled pilot of adult patients receiving in-centre maintenance haemodialysis. Participants in the intervention arm will complete ePROMs once a month for 6 months. ePROMs will be scored real time and the results will be shared with participants and with the clinical team. Moderate-severe symptoms will be flagged using established cut-off scores. Referral options for those symptoms will be shared with the clinical team, and additional symptom management resources will also be provided for both participants and clinicians. Participants in the control arm will be recruited at a different dialysis unit, to prevent contamination. They will receive usual care, except that they will complete ePROMs without the presentation of results to participants of the clinical team. The primary objectives of the pilot are to assess (1) the feasibility of a larger, randomised clinical effectiveness trial and (2) the acceptability of the intervention. Interviews conducted with participants and staff will be assessed using a content analysis approach., Ethics and Dissemination: Ethical approval for this study was obtained from the University Health Network (REB#21-5199) and the William Osler Health System (#23-0005). All study procedures will be conducted in accordance with the standards of University Health Network research ethics board and with the 1964 Helsinki declaration and its later amendments. Results of this study will be shared with participants, patients on dialysis and other stakeholders using lay language summaries, oral presentations to patients and nephrology professionals. We will also be publishing the results in a peer-reviewed journal and at scientific meetings., Protocol Version: 4 (16 November 2022)., Trial Registration Number: NCT05515991., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Mangiferin (MGF) is a phenolic compound, which is a major source of MGF is the mango tree. MGF possesses some antioxidant, anti-inflammatory, and cytoprotective properties, enabling it to play its role against various diseases such as diabetes, obesity, lung injuries, and cancer. The word "Cancer" depicts an uncontrolled and abnormal growth of cells. This review paper reveals MGF's therapeutic, curative and protective potential impact against lung, liver, ovarian, prostate, breast, stomach, and oral cancers. MGF is used in various types of research in the form of powder, liquid extract, intramuscular, intravenous, nanoparticles coated with gold, in the form of a solution, or in combination with other drugs to evaluate synergistic effects. Many studies showed that MGF is safe to use but has less bioavailability in the body and 0.111 mg/mL solubility in water. However, certain studies indicated that its bioavailability and retention time increased when taken in the form of nanoparticles and in combination with other drugs. MGF also increases the sensitivity of other drugs (i.e., cisplatin) resistant to tumors. MGF has different mechanisms of action for different cancers. It mainly targets enzymes, interleukins, tumor growth factors, signaling pathways, apoptotic proteins, and genes to inhibit the growth of tumors, volume, angiogenesis, cellular functionality, further progression, and movement to other areas of the body. Moreover, MGF increases apoptosis and body weight with no or fewer side effects on normal cells. MGF unveiled a novel gate toward the treatment of cancer. Further research and human trials are needed in this regard., Competing Interests: None., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

In the current study, a novel compound, bis(3-(2 H -benzo[ d ][1,2,3]triazol-2-yl)-2-(prop-2-yn-1-yloxy)-5-(2,4,4-trimethylpentan-2-yl)phenyl)methane (TAJ1), has been synthesized by the reaction of 6,6'-methylenebis(2-(2 H -benzo[ d ][1,2,3]triazol-2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol) (1), propargyl bromide (2) and potassium carbonate. Spectroscopic (FTIR, 1 H-NMR, 13 C-NMR) and single-crystal assays proved the structure of the synthesized sample. XRD analysis confirmed the structure of the synthesized compound, showing that it possesses two aromatic parts linked via a -CH 2 carbon with a bond angle of 108.40°. The cell line activity reported a percent growth reduction for different cell types (HeLa cells, MCF-7 cells, and Vero cells) under various treatment conditions (TAJ1, cisplatin, and doxorubicin) after 24 hours and 48 hours. The percent growth reduction represents a decrease in cell growth compared to a control condition. Furthermore, density functional theory (DFT) calculations were utilized to examine the frontier molecular orbitals (FMOs) and overall chemical reactivity descriptors of TAJ1. The molecule's chemical reactivity and stability were assessed by determining the HOMO-LUMO energy gap. TAJ1 displayed a HOMO energy level of -0.224 eV, a LUMO energy level of -0.065 eV, and a HOMO-LUMO gap of 0.159 eV. Additionally, molecular docking analysis was performed to assess the binding affinities of TAJ1 with various proteins. The compound TAJ1 showed potent interactions with NEK2, exhibiting -10.5 kcal mol -1 binding energy. Although TAJ1 has demonstrated interactions with NEK7, NEK9, TP53, NF-KAPPA-B, and caspase-3 proteins, suggesting its potential as a therapeutic agent, it is important to evaluate the conformational stability of the protein-ligand complex. Hence, molecular dynamics simulations were conducted to assess this stability. To analyze the complex, root mean square deviation (RMSD) and root mean square fluctuation analyses were performed. The results of these analyses indicate that the top hits obtained from the virtual screening possess the ability to act as effective NEK2 inhibitors. Therefore, further investigation of the inhibitory potential of these identified compounds using in vitro and in vivo approaches is recommended., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Regardless of etiology, hepatocarcinogenesis is frequently preceded by a distinctive sequence of chronic necroinflammation, compensatory hepatic regeneration, development of hepatic fibrosis, and ultimately cirrhosis. The liver being central immunomodulators, closely maintains immunotolerance. Any dysregulation in this management of immunotolerance is a hallmark of chronic hepatic disease and hepatocellular carcinoma (HCC). Apart from other malignancies, hepatocellular carcinoma accounts for 90% of liver cancers. Several emerging evidences have recognized diet as lifestyle associated risk factor in HCC development. However, natural compounds have the potential to fight hepatoma aggressiveness via inhibition of cellular proliferation and modulation of oncogenic pathways. This review aimed to identify the several plant-based foods for their protective role in HCC prevention by understating the molecular mechanisms involved in inhibition of progression and proliferation of cancer. Information from relevant publications in which several plant-based foods demonstrated protective potential against HCC has been integrated as well as evaluated. For data integration, Science direct, Google scholar, and Scopus websites were used. Nutrition-based approaches in the deterrence of several cancers offer a substantial benefit to currently used medical therapies and should be implemented more often as an adjunct to first-line medical therapy. Furthermore, the inclusion of these plant-based foods (vegetables, fruits, herbs, and spices) may improve general health and decline cancer incidence.

T-wave inversions on electrocardiograms (ECGs) can present a diagnostic challenge due to their association with various underlying causes. One less-explored cause is memory T-waves, a phenomenon characterized by T-wave inversions, often seen in chest and inferior leads, following a period of abnormal ventricular conduction. In this case report, we discuss the intriguing case of an 80-year-old woman who recently underwent percutaneous coronary intervention (PCI) for a myocardial infarction and subsequently developed memory T-waves. We are also discussing how important it can be to understand and recognize memory T-waves, as it will avoid further unnecessary tests and longer hospital stays., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Malik et al.)

Background: Peripheral arterial disease (PAD) affects a substantial proportion of the global population, particularly older individuals, affecting around 200 million people worldwide highlighting its significant impact on human health. Critical limb ischemia (CLI) is the most severe clinical presentation of PAD characterized by ischemic rest pain tissue ulceration or gangrene. The objective of the study is to assess the efficacy of infra popliteal angioplasty (in terms of wound healing and limb salvage) in patients with below-the-knee total chronic occlusion (TCO)., Methods: In this cross-sectional study, all consecutive patients in one year with TCO and fulfilling the inclusion criteria were included., Results: A total of 64 limbs underwent angioplasty. The mean age was 55.38 ± 13.12 (Range 22-88) years and there were 73% (n=47) males. Diabetes mellitus was the most prevalent risk factor in 59.4% (n=38) of patients. 48.4 % (n=31) of patients had below-knee TCO in all three arteries. Technical Success was achieved in 95.3% (n=61/64). All 3 patients who had technical failure ended up with below-the-knee amputation. Furthermore, 2 more patients who had technical success also ended up with below-the-knee amputation. The difference between these two rates was significant (100% vs 3.3%; p-value =0.004). In terms of wound healing, statistically significant improvement was noted within the first 6 months (p-value = 0.05). The limb salvage rate was 90.6% (n=59/64). The primary patency rate was 81.3% (n=52) and 76.6% (n=49) at 6 and 12 months respectively., Conclusions: Angioplasty results in statistically significant wound healing leading to a higher limb salvage rate, in patients with TCO of infrapopliteal arteries.

Objectives: In this study, we aim to assess the efficacy of revision using distal inflow (RUDI) in patients with symptomatic dialysis access-associated steal syndrome (DASS). Materials and Methods: All consecutive patients who were diagnosed with grade 3 or 4 DASS and have undergone RUDI in 4 years were included in this study. Results: In total, 35 patients were included in this study; participants had a mean age of 47.5±7.52 years and 54% (n=19) were males. As per our findings, significant improvement was noted in terms of paresthesia (81.2%, p-value: 0.012), coolness (79.4%, p-value: 0.006), pain (78.1%, p-value: 0.006), discoloration (76.4%, p-value: 0.044), paresis (71.4%, p-value: 0.016), and ulcer healing (50%, p-value: 0.044). Gangrene did not further progress in all patients (n=35). Reduction in fistula flow rate after RUDI was 57.5% (682±121 ml/min, p-value: 0.001). Digital systolic pressure was noted to improve by 71.4% (60±9.2 mmHg, p-value: 0.002) after RUDI. Peak systolic velocity increased in both ulnar (66.1±8.2 cm/s, p-value: 0.04) and radial (64.2±7.6 cm/s, p-value: 0.024) arteries of the wrist. Cumulative patency of RUDI graft was 100%, 91.4%, and 85.7% at 3, 6, and 12 months, respectively. Conclusion: RUDI has resulted in significant improvements in terms of DASS symptoms. Using a native vein as conduit, RUDI should be considered a procedure of choice for patients with high-flow DASS., Competing Interests: Disclosure StatementAll authors have no conflict of interest., (© 2023 The Editorial Committee of Annals of Vascular Diseases.)

Aims: Little is known regarding the association of multiple social risk factors and gestational diabetes mellitus (GDM)., Methods: We analyzed the 2007-2018 National Health and Nutrition Examination Surveys including 10,439 women aged ≥20 years (8 % with history of GDM). We created a cumulative social risk score (CSR) by adding scores assigned to each of the following: race/ethnicity, citizenship status and country of birth, education, and family income (score of 0 used as reference group). Using logistic regression, we assessed the associations of individual social risk factors (education, income, race/ethnicity and citizenship status) and CSR score with GDM, adjusting for age, parity, insurance status, care access, smoking, diet, physical activity, and body mass index., Results: Among individual social risk factors, being a non-U.S. citizen (OR:1.51, 95% CI: 1.06-2.15) or belonging to a minority racial/ethnic group (OR:1.30, 95% CI: 1.04-1.59) was significantly associated with a greater odds of GDM. When examining the combined effects of social risk factors, a CSR score ≥3 was associated with an increased odds of GDM (OR:1.64, 95% CI: 1.22-2.1)., Conclusions: Women with a greater burden of social risk factors are more likely to have GDM, thus should be the focus of interventions to prevent and treat GDM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Energetic heterocycles, including pyridines, triazoles, and tetrazoles, exhibit greater density, heats of formation, and oxygen balance compared to their carbocyclic counterparts, making them a promising approach for synthesizing novel bis-tetrazole acetamides. Synthesized compounds A-F, some of which feature a chlorine atom attached to the phenyl ring, serve as valuable synthons for aryl coupling reactions. Analysis via 1 H-NMR and 13 C-NMR spectroscopy, as well as density functional considerations through B3LYP functional correlation with 6-311 +  + G(d) and 6-31G(d) basis set, revealed the observed LUMO/HOMO energies and charge transfer within the molecule. Additionally, the dipole moment, chemical hardness, softness, ionization potential, local reactivity potential via Fukui indices and thermodynamic properties (entropy, enthalpy, and Gibbs free energy) of the molecule were calculated through density functional theory studies. In addition, Molecular Docking studies were conducted to investigate the anti-cancer potential of synthesized heterocyclic compounds against caspase 3, NF-KAPPA-B and P53 protein. Molecular docking analysis demonstrated a potent interaction between 2,2'-(5,5'-(1,4-phenylene)bis(1H-tetrazole-5,1-diyl))bis-N-(2,4-dinitrophenyl) acetamides (6d) and TP53 and NF-KAPPA-B with binding energies of - 11.8 kJ/mol and - 10.9 kJ/mol for TP53 and NF-KAPPA-B, respectively. Similarly, 2,2'-(5,5'-(1,4-phenylene)bis(1H-tetrazole-5,1-diyl))bis-N-(2-chlorophenyl) acetamides (6f) exhibited a strong interaction with caspase-3 with binding energy of -10.0 kJ/mol, indicating their potential as therapeutic agents against these proteins. Furthermore, the findings of current study was further strengthen by 100 ns molecular dynamics (MD) simulations. Finally, theoretical studies of oxygen balance and nitrogen percentage suggest that these molecules can be utilized as energetic materials., (© 2023. Springer Nature Switzerland AG.)

A new compound, C 23 H 20 BrN 3 OS, containing a quinoline-based iminothiazoline with a thiazoline ring, was synthesized and its crystal and molecular structures were analyzed through single crystal X-ray analysis. The compound belongs to the triclinic system P - 1 space group, with dimensions of a = 9.2304 (6) Å, b = 11.1780 (8) Å, c = 11.3006 (6) Å, α = 107.146 (5)°, β = 93.701 (5)°, γ = 110.435 (6)°, Z = 2 and V = 1025.61 (12) Å 3 . The crystal structure showed that C-H···N and C-H···O hydrogen bond linkages, forming infinite double chains along the b-axis direction, and enclosing R 2 (14) and R 2 (14) and R 2 2 (16) ring motifs. The Hirshfeld surface analysis revealed that H…H (44.1%) and H…C/C…H (15.3%) interactions made the most significant contribution. The newly synthesized (Z)-4-bromo-N-(4-butyl-3 (quinolin-3-yl)thiazol-2(3H)-ylidene)benzamide, in comparison to oleanolic acid, exhibited more strong potential against elastase with an inhibition value of 1.21 µM. Additionally, the derivative was evaluated using molecular docking and molecular dynamics simulation studies, which showed that the quinoline based iminothiazoline derivative has the potential to be a novel inhibitor of elastase enzyme. Both theoretical and experimental findings suggested that this compound could have a number of biological activities., (© 2023. Springer Nature Switzerland AG.)

The presence of amyloid kuru plaques is a pathological hallmark of sporadic Creutzfeldt-Jakob disease (sCJD) of the MV2K subtype. Recently, PrP plaques (p) have been described in the white matter of a small group of CJD (p-CJD) cases with the 129MM genotype and carrying resPrP D type 1 (T1). Despite the different histopathological phenotype, the gel mobility and molecular features of p-CJD resPrP D T1 mimic those of sCJDMM1, the most common human prion disease. Here, we describe the clinical features, histopathology, and molecular properties of two distinct PrP plaque phenotypes affecting the gray matter (p GM ) or the white matter (p WM ) of sCJD cases with the PrP 129MM genotype (sCJDMM). Prevalence of p GM - and p WM -CJD proved comparable and was estimated to be ~ 0.6% among sporadic prion diseases and ~ 1.1% among the sCJDMM group. Mean age at onset (61 and 68 years) and disease duration (~ 7 months) of p WM - and p GM -CJD did not differ significantly. PrP plaques were mostly confined to the cerebellar cortex in p GM -CJD, but were ubiquitous in p WM -CJD. Typing of resPrP D T1 showed an unglycosylated fragment of ~ 20 kDa (T1 20 ) in p GM -CJD and sCJDMM1 patients, while a doublet of ~ 21-20 kDa (T1 21-20 ) was a molecular signature of p WM -CJD in subcortical regions. In addition, conformational characteristics of p WM -CJD resPrP D T1 differed from those of p GM -CJD and sCJDMM1. Inoculation of p WM -CJD and sCJDMM1 brain extracts to transgenic mice expressing human PrP reproduced the histotype with PrP plaques only in mice challenged with p WM -CJD. Furthermore, T1 20 of p WM -CJD, but not T1 21 , was propagated in mice. These data suggest that T1 21 and T1 20 of p WM -CJD, and T1 20 of sCJDMM1 are distinct prion strains. Further studies are required to shed light on the etiology of p-CJD cases, particularly those of T1 20 of the novel p GM -CJD subtype., (© 2023. The Author(s).)

Sesame seeds perform many therapeutic functions against several health issues especially those related to bones because they possess a rich content of calcium, vitamins, proteins, oil, and carbohydrates. Using the PubMed, ScienceDirect, and Google Scholar databases, we performed a comprehensive search of the literature from 2013 to date on reports related to sesame seeds and their bioactive ingredients. Sesamin, sesamol, sesamolin, and sesamol are the major bioactive lignans found in sesame seeds. Our comprehensive review of the literature revealed the protective role of sesame seeds towards bone health in postmenopausal osteoporosis. It was observed that sesame seeds have a positive impact on postmenopausal women experiencing bone-related problems, i.e. osteoporosis and arthritis. Therefore, this review is focused on exploring the effect of sesame seeds on bone mineralization in women experiencing menopause. Furthermore, to aid balancing the hormones in women after their disturbance by the postmenopausal phase, we highlight the effect of the daily intake of sesame seeds in women. Finally, we conclude that the supplementation of sesame seeds in a regular diet shows a positive impact on the bone health of post-menopausal osteoporosis.

Background: Patients with knee osteoarthritis (OA) in northwestern Ontario are referred by their primary care provider (PCP) to a centralized assessment clinic for evaluation by an advanced practice physiotherapist (APP) to determine if they will require surgical management. However, many patients are found to not require surgical management, resulting in delays for patients who do. A decision-support tool was developed to address this issue and to guide treatment options by determining the need for surgical or nonsurgical approaches., Methods: We used a proof-of-concept method to assess the use of the decision-support tool in northwestern Ontario. Data from 100 consecutive patients assessed for knee OA management were collected from the Thunder Bay centralized assessment clinic. Two levels of agreement analyses (calculated using Cohen κ statistic) were performed, between the APP assessment decision (surgical or non-surgical) and the decision-support tool recommendation, and between the surgeon's decision (surgical or non-surgical) and the decision-support tool recommendation., Results: We found a near-perfect agreement (κ = 0.870, n = 65) between the APP decision and the decision-support tool recommendation, when controlled for patient preference. There was a substantial level of agreement (κ = 0.618, n = 72) between the decision-support tool recommendation and the surgeon's decision., Conclusion: The decision-support tool recommendation showed considerable agreement with the decisions of the APP and surgeon indicating that it could be a valuable tool to guide PCPs caring for patients with knee OA. The applicability of a decision-support tool in northwestern Ontario displayed promising results, but further research is needed to examine the feasibility in a primary care setting., Competing Interests: Competing interests: None declared., (© 2023 CMA Impact Inc. or its licensors.)