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Symbol of retrograde tau spreading alongside Braak levels as well as functional connectivity pathways.
Results In anesthetized rats, single intracorneal injection resulted, after 30 min, in respectively >300 ng/mg and >260 ng/mg cornea concentrations, dropping to low levels within hours, while staying low in plasma. The effect of hourly posaconazole eye drops resulted in >10 ng/mg cornea concentration, which was maintained with instillations every 2 and then every 4 hours.Conclusion Our results show that there is little interest of intrastromal triazole administration due to the short duration of high cornea concentrations obtained after intracorneal injection. Posaconazole eye drops maintain therapeutic cornea concentrations in rats and could be used to treat severe infectious keratitis.Aim Describe rates of prespecified adverse events in patients who switched from olaparib capsules to tablets. Patients & methods Retrospective, observational cohort analysis using self-controlled, pre-post design. Data on patients with ovarian cancer who switched from olaparib capsules to tablets between January 2015 and February 2019 were obtained from a US claims database. Results Among all patients (n = 48), proportion with any prespecified adverse event was 45.8% (95% confidence interval 31.4-60.8) during initial 90 days' capsule use and 35.4% (22.2-50.5) during initial 90 days' tablets use; difference -10.4% (-28.8-9.0). Conclusion Switching from olaparib capsules to tablets was manageable with no evidence of increased toxicity. This real-world study supports the manageable tolerability of olaparib in women with ovarian cancer.Objective To assess the levels of pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (fb-hCG) in cases of diabetic pregnancy, to determine whether these biomarkers can be considered significant predictors for macrosomia, preeclampsia (PE), intrauterine growth restriction (IUGR), and preterm birth in mothers with different types of pregestational diabetes mellitus (DM).Methods It was a retrospective cohort study. Study groups were presented type 1 DM (n = 100), type 2 DM (n = 50), and controls (n = 25). At 11 + 0 to 13 + 6 week's gestation, we recorded maternal characteristics and medical history, and performed a combined test for the detection of risk of chromosomal abnormalities. To assess the performance of the markers in the prediction of the main obstetrical complications (PE, IUGR, preterm birth, and macrosomia), receiver-operating characteristic (ROC) curves were produced and area under the curves was calculated.Results The study has shown that DM is associated with a high rate of perinatal complications PE, IUGR, macrosomia, and preterm birth. The median level of PAPP-A was significantly lower in case of type 1 DM- 0.89 (inter quartile range (IQR), 0.51-1.1), and type 2 DM-0.88 (IQR, 0.42-1.15) compared to the unaffected group 1.03 (IQR, 0.96-1.12; p = .025). There were no significant differences in the fb-hCG multiples of the normal median (MoM; p = .14) between the diabetic and unaffected groups. More significant results were obtained when calculated by percentile in diabetic pregnancies, PAPP-A and fb-hCG MoMs values were lower in the 5-10% ranges and higher in the 95% range, compared to the control group. ROC-analysis did not show any significant data that first-trimester PAPP-A and fb-hCG serum levels are predictors for PE, IUGR, macrosomia, and preterm birth.Conclusion The routine first-trimester serum screening of fetal Down syndrome cannot be used as a tool of risk identification for PE, IUGR, macrosomia, and preterm birth in case of diabetic pregnancy.Xylan is the second most abundant polysaccharide group in plants and has a wide variety of food and pharmaceutical applications. However, little information on the safety assessment of extracted xylan as dietary supplement is available. As part of a comprehensive toxicological assessment, this study examined the potential toxicity of xylan extracted from sugarcane bagasse by three genotoxicity studies (Ames test, in vivo mice bone marrow micronucleus test, and mice sperm abnormality test) and a teratogenicity study in rats. In the Ames test, xylan showed no mutagenic activity on histidine dependent strains of Salmonella typhimurium at concentrations up to 5000 μg/plate; results of the in vivo mice bone marrow micronucleus test and mice sperm abnormality test indicated no significant effect on sperm morphology and micronucleus rate of polychromatic erythrocytes in mice at doses up to 5 g/kg body weight. In the teratogenicity study, a total of 60 pregnant rats were exposed to 10, 5, and 2.5% xylan in diet, from gestation days 7 to 16, and the no-observed-adverse-effect levels (NOAEL) of xylan was determined to be 9.8 g/kg body weight. The safe dose of xylan for human was estimated to be 98 mg/kg/day (i.e., 6.86 g/day for a 70-kg person), using a 100-fold safety factor. Taken together, results of this study indicated that xylan is practically nontoxic in terms of potential dietary consumption by humans in food or as a dietary supplement.This paper is a critical evaluation of the effect of mixing on biogas production rates in an anaerobic digester. Mixing plays a prominent role in determining the efficiency of the anaerobic digestion process. This review analyzes the miscellaneous effects of mixing (on the microbial community, methane content and volatile fatty acids) at various mixing intensities and during different stages of the digestion process. Intermittent mixing (mixing at intervals) seems preferable in terms of the quality and quantity of biogas produced, and results in lower power consumption and maintenance costs associated with large-scale biogas production. Preferable mixing time (the length at intervals) and the intensity depends on the geometry of the digester and impeller.The conclusion is drawn that the study of the slurry rheology is very crucial in the designing of the mixing equipment, the shape and size of the digester, and the pipe transport system which can assist in minimizing the initial investment and operational cos favorable when compared to continuous mixing.The geometry of the digester and mixer is essential to evaluate digester mixing.Objective Assess regional differences in categorization of preterm delivery outcomes and impact on variation in reported infant mortality rates.Study design A 27-item questionnaire was distributed to 1072 practitioners associated with U.S. birth hospitals. Five clinical scenarios were created to identify how participants classify delivery outcomes. Statistical analysis included Chi-square analysis and multinomial logistic regression.Results 234 questionnaires were completed (response rate 22%). While >90% respondents classified a 14-week pregnancy loss with no sign of life as a miscarriage, only 22% would provide a fetal death certificate. Likewise, 37% would provide a certificate of live birth for a loss at 16 weeks with signs of life. There was notable regional variation in classifying these as live births (Northeast 41%, Midwest 44%, South 13%, and West 18%, p = .003).Conclusion Regional practice variation in recording both live births and stillbirths was noted. Greater standardization in reporting practices may be warranted to improve the accuracy of reported birth outcomes in the U.S.AIMS To compare patients undergoing total knee arthroplasty (TKA) with ≤ 80° range of movement (ROM) operated with a 2 mm increase in the flexion gap with matched non-stiff patients with at least 100° of preoperative ROM and balanced flexion and extension gaps. METHODS In a retrospective cohort study, 98 TKAs (91 patients) with a preoperative ROM of ≤ 80° were examined. Mean follow-up time was 53 months (24 to 112). All TKAs in stiff knees were performed with a 2 mm increased flexion gap. Data were compared to a matched control group of 98 TKAs (86 patients) with a mean follow-up of 43 months (24 to 89). Knees in the control group had a preoperative ROM of at least 100° and balanced flexion and extension gaps. In all stiff and non-stiff knees posterior stabilized (PS) TKAs with patellar resurfacing in combination with adequate soft tissue balancing were used. RESULTS Overall mean ROM in stiff knees increased preoperatively from 67° (0° to 80°) to 114° postoperatively (65° to 135°) (p less then 0.001). Mean an improvement in ROM (p less then 0.001) and KSS Knee Score (p = 0.017) were greater in knees with preoperative stiffness compared with the control group, but the KSS Functional Score improvement was comparable (p = 0.885). CONCLUSION TKA with a 2 mm increased flexion gap provided a significant improvement of ROM in knees with preoperative stiffness. While the improvement in ROM was greater, the absolute postoperative ROM was less than in matched non-stiff knees. PS TKA with patellar resurfacing and a 2 mm increased flexion gap, in combination with adequate soft tissue balancing, provides excellent ROM and knee function when stiffness of the knee had been present preoperatively. Cite this article Bone Joint J 2020;102-B(4)426-433.AIMS Early cases of cauda equina syndrome (CES) often present with nonspecific symptoms and signs, and it is recommended that patients undergo emergency MRI regardless of the time since presentation. This creates substantial pressure on resources, with many scans performed to rule out cauda equina rather than confirm it. We propose that compression of the cauda equina should be apparent with a limited sequence (LS) scan that takes significantly less time to perform. METHODS In all, 188 patients with suspected CES underwent a LS lumbosacral MRI between the beginning of September 2017 and the end of July 2018. These images were read by a consultant musculoskeletal radiologist. All images took place on a 3T or 1.5T MRI scanner at Stoke Mandeville Hospital, Aylesbury, UK, and Royal Berkshire Hospital, Reading, UK. RESULTS The 188 patients, all under the age of 55 years, underwent 196 LS lumbosacral MRI scans for suspected CES. Of these patients, 14 had cauda equina compression and underwent emergency decompression. No cases of CES were missed. Patients spent a mean 9.9 minutes (8 to 10) in the MRI scanner. CONCLUSION Our results suggest that a LS lumbosacral MRI could be used to diagnose CES safely in patients under the age of 55 years, but that further research is needed to assess safety and efficacy of this technique before changes to existing protocols can be recommended. In addition, work is needed to assess if LS MRIs can be used throughout the spine and if alternative pathology is being considered. Cite this article Bone Joint J 2020;102-B(4)501-505.AIMS The aim of this study was to determine the impact of the severity of anaemia on postoperative complications following total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS A retrospective cohort study was conducted using the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) database. All patients who underwent primary TKA or THA between January 2012 and December 2017 were identified and stratified based upon hematocrit level. In this analysis, we defined anaemia as packed cell volume (Hct) less then 36% for women and less then 39% for men, and further stratified anaemia as mild anaemia (Hct 33% to 36% for women, Hct 33% to 39% for men), and moderate to severe (Hct less then 33% for both men and women). Univariate and multivariate analyses were used to evaluate the incidence of multiple adverse events within 30 days of arthroplasty. RESULTS Following adjustment, patients in the THA cohort with moderate to severe anaemia had an increased odds of 6.194 (95% confidence interval (CI) 5.
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