Development of novel Streptococcus equi vaccines with an assessment of their immunizing potentials and protective efficacies.

Strangles is a highly contagious disease of the equine upper respiratory tract caused by Streptococcus equi subspecies. Streptococcus equi subsp. equi (S. equi) and Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) was isolated, as local, hot, and field strains, from horses clinically suffering from respiratory distress. The isolated Streptococci were identified using bacteriological and molecular techniques. Four formulations of inactivated S. equi vaccines were developed and evaluated. The first formulation was prepared using the S. equi isolates, adjuvanted with MONTANIDE GEL adjuvant, while the second formulation was adjuvanted with MONTANIDE ISA-70 adjuvant. The other 2 formulations were inactivated combined vaccines prepared from both S. equi and S. zooepidemicus isolates. The 3rd formulation was the combined isolates adjuvanted with MONTANIDE GEL while the 4th formulation was the combined isolates adjuvanted with MONTANIDE ISA-70. The developed vaccines' physical properties, purity, sterility, safety, and potency were ensured. The immunizing efficacy was determined in isogenic BALB/c mice and white New Zealand rabbits using the passive hemagglutination test. Also, the antibodies' titer of the combined S. equi and S. zooepidemicus vaccine adjuvanted with MONTANIDE ISA-70 in foals was tracked using an indirect enzyme-linked immunosorbent assay. The protective efficacy of the developed vaccines was determined using a challenge test in both laboratory and field animal models, where a 75% protection rate was achieved. The combined vaccine proved to be more efficacious than the monovalent vaccine. Also, the MONTANIDE ISA-70 adjuvant provided significant protective efficacy than the MONTANIDE GEL. The current work is introducing a very promising mitigative and strategic controlling solution for strangles.

The Effect of Virtual Reality Application on Pain and Anxiety During Episiotomy Repair: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION AND HYPOTHESIS: There is a rising trend among women towards nonpharmacological approaches owing to their minimally invasive nature and limited adverse effects. Virtual reality (VR) has recently gained popularity as a new technology for reducing pain and anxiety in medical settings. Our research sought to investigate the impact of VR on pain and anxiety levels while undergoing episiotomy repair. METHODS: A comprehensive search was carried out across PubMed, Scopus, Cochrane Library, and ISI Web of Science to find relevant randomized clinical trials (RCTs) up to January 2024. These trials investigated the use of VR as a treatment during episiotomy repair compared with a control group that did not receive VR intervention. Meta-analysis was performed using Review Manager software to analyze the data collected. Our primary outcomes were pain scores reported during and after episiotomy repair measured by a visual analog scale. Secondary outcomes analyzed included anxiety scores during and after the procedure, as well as the duration of episiotomy repair. RESULTS: Seven RCTs, involving 578 patients, met the inclusion criteria. VR resulted in a significant reduction in pain scores both during and after episiotomy repair (p < 0.001). Additionally, anxiety levels during and after the procedure were significantly reduced in the VR group compared with the control group. Moreover, the duration of episiotomy repair was significantly shorter in the VR group. CONCLUSION: Using VR has proven to be an effective technique in reducing pain and anxiety during and after episiotomy repair, as well as potentially speeding up the procedure.

Gender Differences in Pain, Function, and Quality of Life Five Years Following Primary Total Knee Arthroplasty.

BACKGROUND: Multiple authors have sought to determine what patient characteristics influence outcomes after total knee arthroplasty (TKA). The impact of gender on outcomes after TKA remains controversial. Previous studies had less than 5 years of follow-up after TKA. The aim of this evaluation was to determine what differences in pain, function, and quality of life (QoL) exist between female and male patients 5 years after primary TKA. METHODS: A prospective, multicenter cohort of 11,602 unilateral primary TKA patients (7,284 females and 4,318 males) was prospectively evaluated. All patients were enrolled in the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement. Demographic data, musculoskeletal and medical comorbid conditions, and patient-reported outcome measures, including the Knee Injury and Osteoarthritis Outcome (KOOS) and Short-Form (36-item) Health Survey mental component score (MCS) and physical component score (PCS) were collected preoperatively and at 5 years after TKA. Descriptive statistics were generated, and stratified by gender, and differences in pain, function, and QoL between female and male patients were evaluated. Multivariate regression models with a 95% confidence interval (CI) were used to assess the role of patient gender as a predictive factor for KOOS pain and function in daily living (ADL) scores reported 5 years after primary TKA, while adjusting for other variables. RESULTS: Prior to surgery, female patients reported worse pain (KOOS pain 46 versus 52), function (KOOS ADL 53 versus 59), and QoL (KOOS QoL 26 versus 29) than male patients. The differences in preoperative scores ranged from 2.70 (KOOS QoL) to 6.12 (KOOS ADL). At 5 years after TKA, female patients reported slightly worse pain (87 versus 89), function (85 versus 87), and QoL (74 versus 75) when compared to male patients. The differences in the mean 5-year postoperative KOOS scores (range, 0.99 to 2.73), although statistically significant (P < .001), were clinically negligible. Female patients achieved greater improvement in pain (41 versus 37), function (32 versus 29), and QoL (48 versus 46) scores in comparison to male patients. Female patients also reported lower preoperative PCS global function (33 versus 35) scores, 5-year postoperative PCS scores (45 versus 46), and MCS global mental function scores (52 versus 54). Similarly, the differences in the 5-year postoperative Short-Form (36-item) Health Survey MCS and PCS scores were clinically negligible. Multivariate regression analysis showed that female gender was not independently predictive for either pain (ß = -1.08; 95% CI [-1.25 to 1.03] [P = .85]) or function (ß = 0.64; 95% CI [-0.51 to 1.79] [P = .28]) 5 years after surgery. CONCLUSIONS: There are no clinically significant gender differences in pain, function, or QoL 5 years after TKA. Female patients typically have worse symptoms prior to surgery, improve more than male patients, and end up with pain, function, and QoL scores clinically equal to male patients. These data can enhance the shared decision-making process between female patients and surgeons and assist in setting appropriate patient expectations prior to TKA.

Predictive Factors of Pain and Functional Outcome 5 Years Following Total Hip Arthroplasty: A Prospective Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement Cohort Study.

BACKGROUND: Previous reports have identified a number of potential predictors of pain and function after total hip arthroplasty (THA). However, the results of these studies were conflicting, and most had a short follow-up after THA. The purpose of this study was to identify factors predictive of pain and function 5 years after THA. METHODS: A multicenter cohort of 7,934 primary unilateral THA patients was prospectively enrolled in the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement consortium. Demographic data, comorbidities, and patient-reported outcome measures were collected preoperatively and postoperatively at 5 years, including the Hip Disability and OSteoarthritis Outcome Score (HOOS) pain and activities of daily living (ADL) scores. Multivariate logistic regression models with 95% confidence interval were used to identify independent predictors of pain and function at 5 years. RESULTS: The patient dissatisfaction percentage was 8.2% at 5 years after THA. The multivariate regression identified the following predictive factors for the HOOS pain score at 5 years: age, educational level, insurance, smoking, race, Charlson Comorbidity Index, back pain severity, number of other lower extremity painful joints, the Knee Injury and Osteoarthritis Outcome Score pain severity of the ipsilateral knee, preoperative Short-Form Health Survey 36-item (SF-36) mental component summary score, and HOOS pain scores. The multivariate regression identified the following predictor factors for HOOS ADL score at 5 years: body mass index, insurance, smoking, race, back pain severity, number of other lower extremity painful joints, Knee Injury and Osteoarthritis Outcome Score pain severity of ipsilateral knee, preop HOOS ADL, and preoperative SF-36 mental component summary score and SF-36 physical component summary score. CONCLUSIONS: Overall, 8.2% of patients were dissatisfied 5 years after primary THA. We have identified a number of factors that predict less improvement in pain and function 5 years after THA. These potentially modifiable factors can be targeted with preoperative patient optimization programs to improve patient outcomes and satisfaction after primary THA. Knowledge of these factors that predict less improvement in pain and function can assist the surgeon and patient during shared decision-making, and in setting appropriate patient expectations preoperatively.

Homology Modeling, Molecular Dynamics Simulation, and Prediction of Bovine TLR2 Heterodimerization.

Toll-like receptor 2 (TLR2) is a major membrane-bound receptor with ligand and species specificity that activates the host immune response. Heterodimerization of TLR2 with TLR1 (TLR2/1) or TLR6 (TLR2/6), triggered by ligand binding, is essential to initiating the signaling pathway. Bovine TLR2 (bTLR2) heterodimerization has not been defined yet compared with human and mouse TLR2s (hTLR2 and mTLR2). The aim of the present study was to model bovine TLRs (TLRs 1, 2 and 6) and create the heterodimeric forms of the bovine TLR2 using molecular dynamics (MD) simulations. We compared the intermolecular interactions in bTLR2/1-PAM3 and bTLR2/6-PAM2 with the hTLR2 and mTLR2 complexes through docking simulations and subsequent MD analyses. The present computational findings showed that bTLR2 dimerization could have a biological function and activate the immune response, similar to hTLR2 and mTLR2. Agonists and antagonists that are designed for hTLR2 and mTLR2 can target bTLR2. However, the experimental approaches to comparing the functional immune response of TLR2 across species were missing in the present study. This computational study provides a structural analysis of the bTLR2 interaction with bTLR1 and bTLR6 in the presence of an agonist/antagonist and reveals the three-dimensional structure of bTLR2 dimerization. The present findings could guide future experimental studies targeting bTLR2 with different ligands and lipopeptides.

How Back Pain Affects Patient Satisfaction After Primary Total Knee Arthroplasty.

BACKGROUND: Although back pain (BP) has been shown to be a predictor of dissatisfaction after total knee arthroplasty (TKA) in some reports, these studies did not use a scale to quantify the degree of pain. The purpose of this study was to quantify the effect of BP intensity on patient satisfaction reported at 1 year after TKA. METHODS: A multicenter prospective cohort was taken in which 9,057 patients undergoing primary unilateral TKA were enrolled in FORCE-TJR and demographic and clinical data were collected. Back pain (BP) intensity was assessed using the Oswestry back disability index (ODI) pain intensity questionnaire. Patients were classified into 4 categories based on the severity of BP. Patient-reported outcomes (PROs) were collected preoperatively and postoperatively after 1 year including the Knee injury and Osteoarthritis Outcome Score (KOOS) (total score, pain, Activities of Daily Living (ADL), and Quality of Life (QOL), Short-Form health survey 36-item (SF-36) Physical Component Score (PCS), and Mental Component Score (MCS)). We used a validated 5-point Likert satisfaction scale. Univariate analyses of the difference between the satisfied and dissatisfied patients' groups was performed. Multivariate logistic regression models with 95% confidence interval (CI) were used to quantify the effect of BP intensity on patient dissatisfaction at 1 year. Receiver operating characteristic (ROC) analyses were performed with measurement of area under curve (AUC). RESULTS: At 1 year, a total of 1,657 TKA patients (18.3%) were dissatisfied. A total of 4,765 patients (52.6%) reported back pain at the time of surgery, including mild BP in 2,264 patients (24.9%), moderate BP in 1,844 patients (20.3%), and severe BP in 657 patients (7.2%). Severe back pain was significantly associated with patient dissatisfaction at 1 year after TKA (P = .0006). The multivariate regressions showed that patients who had severe BP were 1.6 times more likely to be dissatisfied when compared to patients who had no BP [odds ratio (OR) 1.63; 95% confidence interval (CI) (1.23-2.16), P = .0006]. While patients who had mild BP [OR 0.98; 95% CI (0.82-1.17), P = .87] or moderate BP [OR 0.97; 95% CI (0.80-1.18), P = .78] were not associated with an increased likelihood of dissatisfaction. Other predictive variables for dissatisfaction, include age [OR for younger patients <65 years versus older patients ≥65 years, 0.74; 95% CI (0.59-0.92)], educational level [OR for post high school versus less, 0.83; 95% CI (0.71, 0.97)], smoking [OR for nonsmoker versus current smoker, 0.63; 95% CI (0.45, 0.87)], and Charlson comorbidity index [OR for CCI ≥2 versus 0, 1.25; 95% CI (1.05, 1.49)]. CONCLUSION: Increased BP intensity was associated with increased risk of dissatisfaction 1 year after TKA. Only patients who had severe BP were 1.6 times more likely to be dissatisfied. The data presented here can help to improve shared decision-making and patient counseling before surgery. Surgeons should consider a spine evaluation in patients who have severe BP prior to TKA.

Age-Related Differences in Pain, Function, and Quality of Life Following Primary Total Knee Arthroplasty: Results From a FORCE-TJR (Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement) Cohort.

BACKGROUND: The impact of age on patient outcomes after total knee arthroplasty (TKA) remains controversial. Age has shown no effect on outcome in some studies, while others have reported better or worse outcome in younger patients. The aims of this study were to determine the differences in pain, function, and quality of life (QoL) reported 1 year after TKA across different age groups. METHODS: A prospective, multicenter cohort of 11,602 unilateral primary TKA patients was evaluated. Demographic data, comorbid conditions, and patient-reported outcome measures including the knee injury and osteoarthritis outcome score (KOOS), KOOS-12, KOOS Joint Replacement, and Short-Form health survey (12-item) were collected preoperatively and at 1-year postoperatively. Descriptive statistics were generated, stratified by age [<55 years (younger adult), 55 to 64 years (older adult), 65 to 74 years (early elder), and ≥ 75 years (late elder)], and differences in pain, function, and QoL among the 4 age groups were evaluated using Chi-square and Kruskal-Wallis tests. Multivariate regression models with 95% confidence interval were performed to determine if age was predictive for KOOS pain and function scores. RESULTS: Prior to surgery, younger patients (<55 years) reported worse KOOS pain (39), function (50), and QoL (18) scores with poor mental health score (47) than other older patient groups. The mean preoperative score differences across the age groups in the KOOS total score (9.37), KOOS pain (11.61), KOOS-12 pain (10.14), and KOOS/KOOS-12 QoL (12.60) reached the calculated minimal clinically important difference. At 1 year after TKA, younger patients (<55 years) reported lower KOOS pain, function, and QoL scores when compared to older patients (≥ 75 years). The differences in 1-year postop scores among the 4 age groups (ranging from 4.0 to 12.2) reached the minimal clinically important difference for pain (10.4) and QoL (12.2). Younger patients (<55 years) achieved higher baseline to 1-year pain (36.8 points), function (30.3 points), and QoL (40.7 points) score changes when compared to older patients aged ≥ 75 years. Although statistically significant, the differences in score changes among the age groups were clinically irrelevant. The multivariate regression analyses showed that age was a significant predictor for pain, but not for function at 1 year where KOOS pain score was predicted to be higher (less pain) (ß = 6.17; 95% confidence interval 4.12- 8.22) (P < .001) in older patients (≥ 75 years) when compared to younger patients (<55 years). CONCLUSION: A TKA provides a dramatic improvement in pain, function, and QoL in all age groups. However, there are age-related clinically significant differences in preoperative pain, QoL, and mental health and in final postoperative pain and QoL scores with younger patients (<55 years) reporting more pain, less QoL, and worse preoperative mental health. The patient-reported outcome measure data presented here can be used clinically to improve shared decision-making and patient expectations prior to TKA.

Investigation of the Radiographer's adherence and compliance with radiation protection and infection control practices during COVID-19 mobile radiography.

Radiological staff, especially radiographers, work as front liners against the COVID-19 outbreak. This study aims to assess compliance with radiation protection and infection control practices during COVID-19 mobile radiography procedures. This cross-sectional study included 234 radiographers (females, 56%, n = 131; males, 44%, n = 103) who were asked to complete an online questionnaire consisting of demographic data, radiation protection and infection control practices during COVID-19 portable cases, and knowledge and awareness. After informed consent was completed, SPSS statistical software was used for the data analysis. The most common age group of participants ranged from 18 to 25 years old (30.3%, n = 71). Bachelor's degree holders were 74.4% (n = 174). Most radiographers (39.7%, n = 93) had a working experience of 1-5 years, followed by 27.8% (n = 65) with more than 16 years of experience. Most respondents (62.4%, n = 146) handled approximately 1-5 cases daily, the majority of them (56%, n = 131) stated affirmatively they had obtained special training to handle COVID-19, and when inquired if they had received any special allowances for handling COVID-19 suspected/confirmed cases most of them stated negative (73.9%, n = 173). Most participants stated that they always wear a TLD during portable cases (67.1%, n = 157) and a lead apron (51.7%, n = 121). Around 73% (n = 171) knew the latest information on COVID-19 and attended the COVID-19 awareness course. A significant association was found between the work experience of the radiographers and their responses to following the best practices (p = 0.018, α = 0.05). Radiographers who had COVID-19 training (µ = 48.78) tend to adhere more to best practices than those who have not (p = 0.04, α = 0.05). Further, respondents who handled more than 16/more COVID-19 suspected/confirmed cases followed the best practices more (µ = 50.38) than those who handled less (p = 0.04, α = 0.05). This study revealed detailed information on radiation protection and infection control practices during COVID-19 mobile radiography. It has been observed that the participants/radiographers have good knowledge and awareness of radiation protection and infection-control practices. The present results may be used to plan future requirements regarding resources and training to ensure patient safety.

The Prevalence and Predictors of Patient Dissatisfaction 5-years Following Primary Total Knee Arthroplasty.

BACKGROUND: Previous studies have evaluated patient dissatisfaction after total knee arthroplasty (TKA) at 1 year, but there is no data about the prevalence of dissatisfaction among TKA patients after prolonged follow-up. The purpose of this study is to determine patient dissatisfaction 5-years after TKA and to identify patient factors predictive of dissatisfaction. METHODS: Demographic and clinical data on 4402 patients undergoing primary unilateral TKA between 2012 and 2015 were collected prospectively through the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR) comparative effectiveness consortium including diverse community and academic practices distributed across 23 states in the United States. Data collected at 1 year preoperatively and 5 years postoperatively included patient satisfaction (using a 5-point Likert satisfaction scale) and patient-reported outcome measures (PROMs) including the Knee injury and Osteoarthritis Outcome Score (KOOS) and Short-Form health survey (36-item). A univariate analysis of the difference between the satisfied and dissatisfied patients' groups was performed. A multivariate logistic regression model with 95% confidence interval (CI) was used to identify independent predictors of dissatisfaction at 5 years. The regression model was performed after adjusting the following variables: age, gender, body mass index (BMI), Charlson Comorbidity Index (CCI), marital status, smoking, education, and insurance type. The Receiver Operating Characteristic (ROC) analysis was performed with the measurement of area under curve (AUC). Hosmer-Lemeshow goodness of fit test was performed to evaluate the validity of the model. RESULTS: A total of 12.7% patients (559/4402) reported dissatisfaction 5-years after TKA. Increased BMI, higher CCI, higher Oswestry disability index, and increased number of other painful lower extremities (LE) joints were significantly associated with dissatisfaction. Higher rates of dissatisfaction were present in young patients, patients with less education, and non-White patients. Patient dissatisfaction was significantly associated with poor preoperative and 5-year postoperative PROMs scores and less score improvement from baseline to 5 years (P < .001). The multivariate regression analysis showed that an increased number of other painful LE joints (OR = 1.81; 95% CI (1.14-2.88) (P = .01), increased Oswestry back disability index (OR = 1.40; 95% CI (1.07-1.82) (P = .01), non-White patients (OR = 1.74; 95% CI (1.26-2.40) (P = .001), and minimal preoperative functional disability with KOOS function in daily living (ADL) score ≥70 (OR = 0.64; 95% CI (0.43-0.95) (P = .02) were independent predictive factors for dissatisfaction at 5 years. CONCLUSION: A total of 12.7% patients reported dissatisfaction 5-years after TKA. Clinical profiles of the satisfied and dissatisfied patients were captured 5-years after TKA with differences in the preoperative demographic and clinical characteristic variables identified. Risk factors for long-term patient dissatisfaction after TKA have been identified and should be considered during shared decision making while planning for TKA. Surgeons should use these identified risk factors to set realistic expectations for patients at an increased risk for dissatisfaction aiming to optimize their outcomes and increase their long-term satisfaction after TKA.

Do Patient Outcomes Vary by Patient Age Following Primary Total Hip Arthroplasty?

BACKGROUND: Multiple authors have sought to determine what patient characteristics influence outcome after total hip arthroplasty (THA). Age has shown no effect on outcome in some evaluations, while others have reported higher functional improvement in younger patients. The aim of this study was to determine if outcome after THA varies based on patient age. METHODS: A prospective, multicenter cohort of 7,934 unilateral primary THA patients from the FORCE-TJR comparative effectiveness consortium was evaluated. Demographic data, comorbid conditions, and Patient-Reported Outcome Measures, including (HOOS), HOOS-12, HOOS JR, and SF-36 (PCS) and (MCS), were collected preop and at 1-year postop. Descriptive statistics were generated, stratified by age (<55 years [younger adult], 55-64 years [older adult], 65-74 years [early elder], and ≥75 years [late elder]), and differences in pain, function, and quality of life among the 4 age groups were evaluated. A multivariate regression model with 95% confidence interval (CI) was used to assess the role of patient age as a predictive factor for HOOS pain and function scores reported 1 year after primary THA. RESULTS: Prior to surgery, younger patients (<55 years) reported worse pain, function, and quality of life than the other 3 patient groups. At 1 year after THA, younger patients (<55 years) reported slightly worse pain and quality of life but better function scores than the 3 older patients' groups. Younger patients (<55 years) achieved higher baseline to 1-year pain, and function score changes when compared to the older patients' groups. The quality of life score changes was not different among the 4 age groups. The differences in 1-year postop scores (ranging from 2.74 to 8.46) and the magnitude of score changes from baseline to 1 year (ranging from 1.9 to 5.85), although statistically significant (P < .001), did not reach the minimal clinically important difference (MCID). The multivariate regression analysis shows that age is a significant predictor for pain at 1 year but not for function. Although HOOS pain score is predicted to be higher by 4.38 points (less pain) 1 year after THA in older patients (≥75), when compared to younger patients (<55 years), again the difference is well below the MCID and is clinically insignificant. CONCLUSION: Although there are statistically significant differences in pain relief, functional improvement, and quality of life between younger and older patients among different patients' age groups, there is no clinically significant difference. THA provides an improvement in quality of life by decreasing pain and increasing function in all 4 age groups, with large improvements in Patient-Reported Outcome Measures scores (>2 standard deviations) without clinically significant age-related differences in THA outcome at 1 year.

Impact of the COVID-19 pandemic on endoscopic retrograde cholangiopancreatography: a single center experience.

BACKGROUND: the COVID-19 pandemic has impacted on several aspects of health care services worldwide. The aim of the study was to determine its influence on the case volume, success rate and complication rate of endoscopic retrograde cholangiopancreatography (ERCP). METHOD: all patients who underwent ERCP one-year before and after applying COVID-19 safety measures at the Qena University Hospital were included. Data were collected from the patients' records, analyzed and compared. RESULTS: a total of 250 patients underwent ERCP between April 1st, 2019 and March 31st, 2021, and the mean age of participants was 52 ± 18 years. There was a 5 % increase in case volume after applying COVID-19 safety measures (128 vs 122) and the total procedure time was significantly shorter (42 vs 46 minutes, p = 0.04). There was no significant difference in the overall success rate and complication rate. Procedure success significantly correlated with cannulation attempts and total procedure time in both groups, and serum bilirubin and cannulation time in the pre-COVID-19 patients and alkaline phosphatase (ALP) in post-COVID patients. ERCP-related complications significantly correlated with cannulation attempts in both groups, and ALP, international normalized ratio (INR), cannulation time and total procedure time in pre-COVID-19 patients, and platelet count and amylase in post-COVID patients. Two patients were confirmed COVID-19 cases at the time of ERCP; therapeutic targets were achieved in both with a smooth post-ERCP recovery. Three out of nine ERCP team members caught a mild to moderate COVID-19 infection and recovered after receiving proper management. CONCLUSION: our result show that there was no negative impact of using COVID-19 safety measures and precautions on the case-volume, indications, overall outcome or complication rate of ERCP.

Long-term effects of one-anastomosis gastric bypass on liver histopathology in NAFLD cases: a prospective study.

PURPOSE: Weight reduction can effectively improve nonalcoholic fatty liver disease (NAFLD), which is a constant companion of severe obesity. This study aimed to determine the effect of one-anastomosis gastric bypass (OAGB) on pathological liver changes in severely obese cases with NAFLD. METHODS: The present prospective research comprised 67 subjects with morbid obesity scheduled for OAGB during the period from February 2015 to August 2018. Clinical, biological, and histologic data were evaluated pre and 15 months postoperatively. RESULTS: Fifteen months after surgery, a considerable reduction was noted in the grades of fat deposition, liver cell ballooning, and lobular inflammatory changes, in addition to the total NAS score. Fifteen months after surgery, nonalcoholic steatohepatitis (NASH) disappeared in 42% of the patients. A significant regression of fibrosis stage occurred after surgery in 79.1% of patients (p < 0.001). After surgery, patients had substantial reductions in aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, HbA1c, total cholesterol, and Low-density lipoprotein (p < 0.001, for all comparisons). Diabetes mellitus, hypertension, and dyslipidemia resolved in 54%, 59%, and 69% of the patients, respectively. CONCLUSION: OAGB resolved NASH from nearly 42% of patients and reduced the histological features of NAFLD 15 months after surgery. Bariatric procedures might be adopted as a therapeutic modality in severely obese cases with NAFLD after the failure of lifestyle modifications.

Impact of laparoscopic sleeve gastrectomy on fibrosis stage in patients with child-A NASH-related cirrhosis.

PURPOSE: Bariatric surgery can improve non-alcoholic fatty liver disease (NAFLD). Yet data on the effect on fibrosis are insufficient and controversial. This work endeavored to evaluate the safety of laparoscopic sleeve gastrectomy (LSG) in cases that have compensated non-alcoholic steatohepatitis (NASH)-related cirrhosis and its impact on fibrosis stage. METHODS: The current prospective work involved 132 cases with Child-A NASH-related cirrhosis suffering from morbid obesity scheduled for LSG. They were subjected to preoperative assessment, wedge biopsy, and ultrasound-guided true-cut liver biopsy after 30 months. Patients were included if proved to have F4 fibrosis initially. The liver condition was assessed based on the NALFD Activity Score (NAS). The primary outcome measure was the impact of LSG on fibrosis stage and its relation to weight loss. RESULTS: The analysis included only 71 patients who completed the 30-month follow-up period. By the end of the follow-up interval, there was a substantial weight loss with a reasonable resolution of comorbidities. The median NAS decreased significantly from 6 (1-8) to 3 (0-6) after surgery. Fibrosis score regressed to F2 in 19 patients (26.8%) and F3 in 29 (40.8%). Patients with improved scores had a significantly higher amount of weight loss (p < 0.001). Improvement was more frequent in males (p = 0.007). By 30 months after treatment, 53.8% of cases with borderline NASH and 36.8% of those with probable NASH showed complete resolution, and 44.7% of patients with NASH showed improvement. Steatosis improved in 74.6% of patients (p < 0.001). CONCLUSION: In patients with NASH-related liver cirrhosis of Child class A, LSG may be a secure approach for the management of morbid obesity. It has a long-term benefit for both obesity and liver condition with significant improvement of steatosis, steatohepatitis, and fibrosis.

Mercury and Alzheimer's disease: a look at the links and evidence.

This review paper investigates a specific environmental-disease interaction between mercury exposure and Alzheimer's disease hallmarks. Alzheimer's disease is a neurodegenerative disorder affecting predominantly the memory of the affected individual. It prevails mostly in the elderly, rendering many factors as possible causative agents, which potentially contribute to the disease pathogenicity cumulatively. Alzheimer's disease affects nearly 50 million people worldwide and is considered one the most devastating diseases not only for the patient, but also for their families and caregivers. Mercury is a common environmental toxin, found in the atmosphere mostly due to human activity, such as coal burning for heating and cooking. Natural release of mercury into the atmosphere occurs by volcanic eruptions, in the form of vapor, or weathering rocks. The most toxic form of mercury to humans is methylmercury, to which humans are exposed to by ingestion of fish. Methylmercury was found to exert its toxic effects on different parts of the human body, with predominance on the brain. There is no safe concentration for mercury in the atmosphere, even trace amounts can elicit harm to humans in the long term. Mercury's effect on Alzheimer's disease hallmarks formation, extracellular senile plaques and intracellular neurofibrillary tangles, has been widely studied. This review demonstrates the involvement of mercury, in its different forms, in the pathway of amyloid beta deposition and tau tangles formation. It aims to understand the link between mercury exposure and Alzheimer's disease so that, in the future, prevention strategies can be applied to halt the progression of this disease.

Design and synthesis of novel isatin-based derivatives targeting cell cycle checkpoint pathways as potential anticancer agents.

In recent years, cell cycle and checkpoint pathways regulation are offering new therapeutic approaches against cancer. Isatin, is a well exploited scaffold in the anticancer domain. Accordingly, the current work describes the design and synthesis of two series of (Z)-3-substituted-2-(((E/Z)-5-substituted-2-oxo-1-substituted-indolin-3-ylidene)hydrazinylidene)-thiazolidin-4-ones, 4(a-s) and (E/Z)-1-substituted-3-(((Z)-3-substituted-4-methylthiazol-2(3H)-ylidene)hydrazineylidene)-5-substituted-indolin-2-ones, 5(a-s). The structures of the synthesized molecules were confirmed by spectral and elemental methods of analyses. Pure diastereomers were further identified with 1H-1H-NOESY and confirmed with X-ray crystallography. The target compounds were tested in vitro for their cytotoxicity against three human epithelial cell lines, liver (HepG2), breast (MCF-7), and colon (HT-29) in addition to the diploid human normal cells (WI-38) compared to doxorubicin as a reference drug. Variable cytotoxic effects (IC50 3.29-100 µmol) were reported on the three cancer cell lines with pronounced selectivity compared to the normal one WI-38. The potency of the most active compounds, 4o, 4s, 5e, 5f, 5l, 5m and 5o (IC50 3.29-9.92 µmol), in both series associated with the (Z) configurations of N = thiazolidin/ene or one, however, the configuration of the N = isatin moiety seemed to be of no importance to the activity. The tested compounds were grouped for their possible mechanism of action into 4 categories. Compound 4o with no apparent effect on all genes examined. Compounds 4s and 5o affected all genes investigated and seem to have multiple cellular targets; induced the expression of p53 and caspases, and downregulated that of CDK1. Compounds 5l and 5m directly elevated the expression of initiator and effector caspases without going through p53 pathway. Finally, compounds 5e and 5f elevated the expression of p53 and inhibited CDK1. Compounds 4s, 5e, 5f, 5l, 5m, and 5o caused a significant elevation in the activity of cleaved caspase 3 as well. Docking studies on CDK1 revealed that the active molecules bind to the tested enzyme by the same manner of the co-crystallized ligands and the isatin-thiazoldinone/ene scaffold is essential for binding of these molecules.

Reconstruction of complex hand defects using trapezoidal osteocutaneous free fibular flap.

BACKGROUND: Traumatic defects of multiple metacarpal bones can be addressed using conventional or vascularized bone grafts. When associated with extensive skin and tendon loss, the treatment becomes more challenging. The aim of the study was to describe the results of using free osteocutaneous fibular flap placed in a new fashion for the reconstruction of complex hand defects. PATIENTS AND METHODS: Six patients with complex hand defects underwent reconstruction using free osteocutaneous fibular flap placed in trapezoidal fashion with two-stage tendon reconstruction using fascia lata graft. The mean age at the time of injury was 34.7 years (range: 14-54 years). The injury was caused by motor vehicle accident in four patients, machine injury in one patient, and falling from height in one patient. All patients had extensive three or four metacarpal bones defects, segmental loss of tendons, and large skin defect ranging from 6 × 10 cm to 10 × 15 cm. The fibular graft was divided into three segments and positioned in a trapezoidal fashion with the middle bone segment placed transversely to support the bases of the proximal phalanges while the first and third bone segments were placed obliquely along the metacarpal axis converging toward the remaining metacarpal bases and/or carpal bones. At final follow-up visit, the finger range of motion was assessed using the total active motion (TAM) scoring system. Functional outcome was evaluated by the disabilities of the arm, shoulder and hand (DASH) score. Active range of motion (AROM) of the pseudo-metacarpophalangeal (MP) joint was measured. The handgrip strength was measured using Jamar hydraulic dynamometer. RESULTS: The mean length of the harvested fibular graft was 18 cm (range: 17-19). The mean size of the skin paddle was 7.5 × 13.1 cm (range: 6 × 10 cm to 10 × 15 cm). Fibular flaps survived in all patients. The mean follow-up period was 30.8 months (range: 24-40 months). The mean time to achieve bone healing was 3.8 months (range: 3-5 months). The mean TAM was 185° (range: 165-204°) and TAM percentage was described as excellent in two patients and good in four patients. The mean AROM at the pseudo-MP joint was 53.8° (range: 42-70°). The mean injured handgrip strength was 27.3 kg (range: 23-31 kg) and the mean grip strength ratio was 74.8% (range: 69-80%). The mean DASH score was 19.6 (range: 11.67-26.67). Pin tract infection, partial skin paddle necrosis, and wound infection were reported. CONCLUSION: The fibular osteocutaneous flap arranged in trapezoidal fashion is a viable choice for the reconstruction of complex hand defects, particularly when the metacarpophalangeal joints are not preserved.

Ovulatory follicular fluid induces sperm phagocytosis by neutrophils, but oviductal fluid around oestrus suppresses its inflammatory effect in the buffalo oviduct in vitro.

We have recently shown that the conditioned media from bovine oviductal epithelial cell culture suppress sperm phagocytosis by neutrophils, suggesting that the oviduct around oestrus supplies the anti-inflammatory microenvironment. To investigate the immune response of neutrophils toward the sperm at ovulation in the buffalo oviduct, we examined (a) a detailed distribution of neutrophils in the oviduct in buffaloes, (b) the effect of ovulatory follicular fluid (FF) and oviductal fluid (OF) on sperm phagocytosis by neutrophils, and (c) the interaction of the ovulatory FF with OF on sperm phagocytosis by neutrophils in vitro. Buffalo oviducts were collected from healthy reproductive tracts at a local slaughterhouse. A detailed observation by histological examination and transmission electron microscopy revealed that neutrophils exist in the oviduct epithelium and lumen throughout the oestrous cycle in buffaloes. The number of neutrophils at the oestrus stage was higher in ampulla compared with those in isthmus, whereas they remained relatively constant at the dioestrus stage. Two hours of preincubation of neutrophils with FF enhanced sperm phagocytosis through the formation of neutrophil extracellular traps (NETs) together with H2 O2 production, whereas OF around oestrus (eOF) suppressed sperm phagocytosis, NETs formation, and H2 O2 production and relieved the above FF-induced inflammatory response. Our findings show that neutrophils exist in the healthy cyclic oviduct across bovine species, and the OF supplies a strong anti-inflammatory environment that could minimize the inflammatory effect of the FF that flows into the oviduct lumen after ovulation and supports the occurrence of fertilization.

High numbers of myeloid derived suppressor cells in peripheral blood and ascitic fluid of cirrhotic and HCC patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is the 3rd most common cause of cancer-related death worldwide. It has evolved different immune escape mechanisms, which might include emergence of lymphoid and myeloid regulatory cells. Aim of this work: To determine the numbers of Myeloid-derived suppressor cells (MDSCs) in peripheral blood and ascitic fluid in cirrhosis and HCC and their relation to IFN-γ and α-fetoprotein (α-FP). PATIENTS AND METHODS: Sixty individuals were enrolled in this study; forty cirrhotic patients with ascites; twenty without HCC (Group I), and twenty with HCC (group II) as well as twenty healthy individuals as a control group (group III). The phenotype and numbers of MDSCs were analyzed in peripheral blood of all the individuals and ascitic fluid of the patients using flow cytometry. Intracellular IFN-γ and serum alfa-fetoprotein were measured. RESULTS: Significant increases in the relative and the mean number of peripheral blood MDSCs were found in the cirrhosis and HCC groups than in the control group, with the HCC group showing the highest number. MDSC count was negatively correlated with IFN-γ levels, while α-FP was positively correlated with MDSC% in the HCC group. MDSC count was low in ascitic fluid of both HCC and cirrhosis groups with no significant difference between the 2 groups. CONCLUSION: A high frequency of MDSCs was detected in the peripheral blood of cirrhotic and HCC patients, indicating presence of immunosuppressive arms. These cells could be targeted to develop a new effective immunotherapy or an adjuvant to current therapies.

Pulmonary Function Tests Abnormalities in Children With Inflammatory Bowel Disease: Is It Common?

OBJECTIVE: The aim of the study was to evaluate the frequency and type of pulmonary dysfunction in newly diagnosed children with inflammatory bowel disease (IBD) and the correlation between pulmonary function tests (PFTs) and IBD activity. METHODS: It is an observational case-control study. One hundred newly diagnosed children with IBD were enrolled as the patient group, which was further subdivided into 52 with Crohn disease (CD) and 48 with ulcerative colitis (UC). Fifty healthy children matched for age, sex, height, and body mass index (BMI) served as the control group. PFTs in the form of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, residual volume (RV), total lung capacity (TLC), mid-forced expiratory flow of 25% to 75% (FEF 25%-75%) and diffusing capacity of the lung for carbon monoxide (DLCO) were evaluated in all studied children. PFTs were measured at diagnosis, every 6 months for a period of 3 years, during remission and at least once during activity in patient group. RESULTS: There was significant progressive deterioration in all PFTs in IBD patients compared with their PFTs at the start of the study (P < 0.05) except for FEV1/FVC, RV, and TLC (P > 0.05). There was significant deterioration during disease activity compared with remission state as regards FEV1, FVC, FEF 25% to 75%, and DLCO (P < 0.05). Significant negative correlation was found between disease activity in both UC and CD groups and FEV1, FVC, FEF 25% to 75%, and DLCO. CONCLUSIONS: Subclinical PFTs abnormalities are common in pediatric IBD even during remission period. So, periodic PFTs evaluation should be considered in the routine follow-up of IBD children.

Evaluation of postoperative fever after surgical correction of neuromuscular scoliosis: implication on management.

BACKGROUND: Scoliosis is a common deformity in patients with neuromuscular disorders which usually necessitates surgical correction. Patients with neuromuscular scoliosis are characterized by increased incidence of associated medical co-morbidities and higher postoperative complication rate; therefore, these patients are often managed with a wide multidisciplinary care team. Postoperative fever is a frequent complication after surgery which is often routinely investigated using different workup tests to rule out infection. These tests lack clear evidence on how they impact the patient care and are associated with increased cost and burden on the health system. OBJECTIVE: The objective of our study was to evaluate the incidence of postoperative fever after surgical correction of neuromuscular scoliosis and evaluate the clinical usefulness of fever diagnostic workup. METHODS: Demographic and clinical data on patients who underwent neuromuscular scoliosis corrective surgery between March 1, 2014 and February 28, 2017 were reviewed at a single institution. The occurrence of postoperative fever (defined by body temperature ≥ 38 °C during the 1st week after surgery) was characterized by maximum temperature (T max), postoperative day of occurrence (POD), and frequency as described by either single or multiple temperature spikes. The diagnostic tests performed for the assessment of postoperative fever were reviewed. The cost per health effect was calculated by dividing the total costs of performed fever workup tests by the number of tests that resulted in change of the patient care. RESULTS: Seventy-six patients (47 females and 29 males) were identified. Cerebral palsy was the most common aetiology in 40 patients (52.6%). The mean age at surgery was 13.5 years (range 3-18 years). The operative time was 490.34 ± 127.21 min. The intraoperative blood loss was 912.3 ± 627.8 cc. The hospital stay was 9.79 ± 5.3 days and the intensive care unit (ICU) stay was 3.26 ± 3.7 days. Wound drains were used in 71 patients for a period of 3.6 ± 2.3 days. Urinary catheters were used for a period of 3.6 ± 1.8 days. Forty-nine patients (64.5%) developed postoperative fever with a temperature of 38.7° ± 0.45° (range 38.10°-39.9°). The most frequent POD for occurrence of fever was the 2nd day in 22 patients (44.9%) The frequency of fever was in the form of multiple temperature spikes in 32 patients (65.3%) or in the form of a single spike in 17 patients (34.7%). There were a total of 20 positive tests out of 132 performed fever workup tests (15.2%). These included nine positive urine analysis (n = 32), five positive urine cultures (n = 28), one positive blood culture (n = 23), and two positive chest X-ray (n = 24). The occurrence of postoperative fever was statistically correlated with the operative time and increased hospital stay and ICU days. The most common identified cause of infection was urinary tract infection in 11 patients followed by respiratory tract infection in four patients and wound infection in one patient. The calculated cost per health effect was $3763. CONCLUSION: Sixty-four percent of patients who underwent surgical correction of neuromuscular scoliosis developed postoperative fever. Postoperative fever was sign of infection in 32.7% of patients and urinary tract infection was the most frequent finding. Only 15.2% of fever diagnostic workup tests were positive. Diagnostic urine tests account for 70% of the positive diagnostic workup. The routine use of blood cultures for the assessment of postoperative fever in such population should be avoided due to the low rate of positive tests and the associated high cost.