Impact of Apolipoprotein E ε4 in Alzheimer's Disease: A Meta-Analysis of Voxel-Based Morphometry Studies.

BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is the most-prevalent form of dementia and imposes substantial burdens at the personal and societal levels. The apolipoprotein E (APOE) ε4 allele is a genetic factor known to increase AD risk and exacerbate brain atrophy and its symptoms. We aimed to provide a comprehensive review of the impacts of APOE ε4 on brain atrophy in AD as well as in mild cognitive impairment (MCI) as a transitional stage of AD. METHODS: We performed a coordinate-based meta-analysis of voxel-based morphometry studies to compare gray-matter atrophy patterns between carriers and noncarriers of APOE ε4. We obtained coordinate-based structural magnetic resonance imaging data from 1,135 individuals who met our inclusion criteria among 12 studies reported in PubMed and Google Scholar. RESULTS: We found that atrophy of the hippocampus and parahippocampus was significantly greater in APOE ε4 carriers than in noncarriers, especially among those with AD and MCI, while there was no significant atrophy in these regions in healthy controls who were also carriers. CONCLUSIONS: The present meta-analysis has highlighted the significant link between the APOE ε4 allele and hippocampal atrophy in both AD and MCI, which emphasizes the critical influence of the allele on neurodegeneration, especially in the hippocampus. These findings improve the understanding of AD pathology, potentially facilitating progress in early detection, targeted interventions, and personalized care strategies for individuals at risk of AD who carry the APOE ε4 allele.

Clinical outcomes of total joint arthroplasty in patients with bowel ostomies.

INTRODUCTION: The influence of prior colostomy or ileostomy on patients undergoing joint arthroplasty remains poorly understood. Our study aimed to assess whether patients with an ostomy undergoing hip and knee arthroplasties have worse postoperative outcomes and increased rates of revisions. METHOD: A single-center, retrospective review of patients with a history of bowel ostomy who underwent a primary total hip arthroplasty (THA), hemiarthroplasty (HA), and total knee arthroplasty (TKA) from 2012 to 2021. A total of 24 THAs, 11 HAs, and 25 TKAs in patients with open small or large bowel stoma were identified. A ten-to-one propensity score match was utilized to establish cohorts with comparable demographics but no prior ostomy procedure. RESULTS: Patients with stomas undergoing elective THA showed greater 90-day ED visits (20.0 vs. 5.0%, P = 0.009), 90-day all-cause readmissions (20.0 vs. 5.0%, P = 0.009), 90-day non-orthopedic readmissions (10.0 vs. 0.5%, P < 0.001), 90-day readmissions for infection (5.0 vs. 0.5%, P = 0.043), all-cause revisions (15.0 vs. 0.5%, P < 0.001), revisions for PJI (5.0 vs. 0%, P = 0.043), and revisions for peri-prosthetic fracture (10.0 vs. 0%, P < 0.001). Patients with stomas undergoing non-elective hip arthroplasties exhibited a longer mean LOS (12.1 vs. 7.0 days, P < 0.001) and increased 90-day all-cause readmissions (40.0 vs. 17.3%, P = 0.034), 90-day orthopedic readmissions (26.7 vs. 6.0%, P = 0.005), all-cause revisions (13.3 vs. 2.0%, P = 0.015), revisions for peri-prosthetic fracture (6.7 vs. 0%, P = 0.002), and revisions for aseptic loosening (6.7 vs. 0%, P = 0.002). There were no significant differences in readmission or revision rates between ostomy patients undergoing TKA and a matched control group. CONCLUSION: Patients undergoing hip arthroplasties with an open stoma are at an increased risk of hospital encounters and revisions, whereas TKA patients with stomas are not at increased risk of complications. These findings emphasize the importance of recognizing and addressing the unique challenges associated with this patient population.

Equivalent Survivorship of Total Hip Arthroplasty in Patients Who Have Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) can have orthopaedic manifestations related to decreased bone mineral density and increased fracture risk. The impact of IBD-spectrum diseases, including Crohn's disease (CD) and ulcerative colitis (UC), on the overall performance of total hip arthroplasty (THA), is not well understood. The present study sought to evaluate whether patients who have IBD were at increased risk of THA failure compared to those who did not have IBD. METHODS: The Statewide Planning and Research Cooperative System (SPARCS) was used to compare postoperative outcomes between patients who have IBD (CD and UC) and patients who do not have IBD from 2010 to 2020. A total of 119,094 patients were included in the study, of whom 1,165 had a diagnosis of IBD. Overall, 501 of those had CD, while 664 had UC. RESULTS: When controlling for comorbidities, patients who had CD had longer hospital length of stay (CD: 3.6 +/- 2.5 versus UC: 3.4 +/- 2.1 versus control: 3.2 +/- 2.3 days, P < 0.001), higher rates of 90-day readmission (CD: 13.6 versus UC: 8.3 versus control: 7.7%, P < 0.001) and 1-year readmission (CD: 20.4 versus UC: 15.1 versus control: 12.8%, P < 0.001), and higher rates of 90-day emergency room visits (CD: 15.4 versus UC: 12 versus control: 11.1%, P = 0.007). There were no differences in all-cause revision or revision for periprosthetic joint infection (PJI) between CD and UC compared with control patients. CONCLUSIONS: Patients who have UC had more emergency room visits and hospital readmissions following THA, however, survival analysis demonstrated that IBD patients are not at increased risk of revision or PJI after THA.

Individualized MRI-based stroke PRediction scOre using plaque Vulnerability for symptomatic carotid artEry disease patients (IMPROVE).

Objective: In TIA and stroke patients with carotid stenosis, estimations of future ipsilateral ischemic stroke risk and treatment decisions are currently primarily based on the degree of stenosis. Intraplaque hemorrhage (IPH), which can be readily visualized on carotid MRI, is increasingly established as an easy to assess and a very strong and independent predictor for ipsilateral stroke risk, stronger than any clinical risk factor. We developed a clinical prediction model (IMPROVE) incorporating IPH, degree of stenosis, and clinical risk factors to select patients with symptomatic carotid stenosis at high risk for stroke. Methods: IMPROVE was developed on pooled clinical and MRI data from five cohort studies of 760 recent TIA or minor stroke patients with carotid plaque who received optimal medical treatment. We used Cox proportional hazards models to determine the coefficients of IMPROVE. IMPROVE was internally validated using bootstrapping and converted to one- and three-year ipsilateral ischemic stroke risk. Results: The development dataset contained 65 ipsilateral incident ischemic strokes that occurred during a median follow-up of 1.2 years (IQR: 0.5-4.1). The IMPROVE model includes five predictors, which are in order of importance: degree of stenosis, presence of IPH on MRI, classification of last event (cerebral vs ocular), sex, and age. Internal validation revealed a good accuracy (C-statistic: 0.82; 95% CI: 0.77-0.87) and no evidence for miscalibration (calibration slope: 0.93). Interpretation: Using presence of IPH on MRI and only four conventional parameters, the IMPROVE model provides accurate individual stroke risk estimates, which may facilitate stratification for revascularization.

Total Hip Arthroplasty Patients Who Have Ostomies Have an Increased Risk of Revisions for Periprosthetic Joint Infection, But Total Knee Arthroplasty Patients Do Not.

INTRODUCTION: Patient comorbidities can lead to worse outcomes and increase the risk of revisions after total hip (THA) and total knee arthroplasty (TKA). Sparse research is available on the effects of ostomies on postoperative outcomes. Our study aimed to assess whether patients who have ostomies who underwent TKA or THA have worse outcomes and increased rates of all-cause and periprosthetic joint infection (PJI) -related revisions. METHODS: We performed a retrospective cohort study comparing the outcomes of THA and TKA patients who have and do not have a history of ostomy using the Statewide Planning and Research Cooperative System. Patient demographics, ostomy diagnosis, 3-month emergency department visits and readmissions, and revisions were collected. A total of 126,414 THA and 216,037 TKA cases were included. Log-rank testing and a Cox proportional hazards model were used to account for covariates. RESULTS: In total, 463 THA patients (0.4%) had ostomies. They had a longer length of stay (LOS) (4.0 versus 3.1 days, P < 0.001) and were less likely to be discharged home (55.3 versus 62.2%). They had higher rates of PJI-related revisions (1.9 versus 0.9%, P = 0.02) and had increased odds of PJI-related revision (OR [odds ratio] = 2.2, P = 0.02). Of TKA patients, 619 patients (0.3%) had an ostomy. They had a longer LOS (3.6 versus 3.3 days, P = 0.02) and was less likely to be discharged home (49.4 versus 52.4%, P = 0.16). However, there was no difference in the rate (1.8 versus 1.4%, P = 0.49) or odds (OR = 1.2, P = 0.53) of PJI-related revision. CONCLUSION: Total hip arthroplasty, but not TKA, patients who have ostomies have an increased risk of PJI-related revisions. The proximity of the surgical incision to the ostomy site may play a role in the risk of PJI in THA patients.

Treating Osteoarthritis in Jehovah's Witness Patients.

This article addresses the challenges surrounding hip and knee osteoarthritis (OA) treatment in Jehovah's Witnesses (JWs), focusing on the complexities arising from their refusal of blood products and transfusions. Acknowledging the heightened risk of blood loss anemia during joint replacement surgery, this review explores documented strategies that enable safe elective joint arthroplasty in JW patients, emphasizing comparable initial diagnostic methods and non-operative treatments up until the pre-operative stage. Special considerations should be taken in the perioperative and intraoperative stage. Despite these challenges, safe arthroplasty is feasible with satisfactory outcomes through a combination of careful preoperative optimization, blood saving protocols, and cultural sensitivity.

Challenges and aspirations of neurosurgery residents in Germany: Insights from a questionnaire-based survey.

OBJECTIVE: Neurosurgery residents in Germany face numerous challenges including receiving comprehensive surgical training with adequate learning opportunities, achieving balanced work life equilibrium, maintaining a positive work environment and navigating career prospects. The objectives of this study are to assess overall satisfaction with the training program, identify factors contributing to dissatisfaction, explore various dimensions of the training program, evaluate the psychological well-being of residents, and ascertain their preferences for future subspecialties. METHODS: A questionnaire-based survey was conducted anonymously among neurosurgery residents from various training hospitals, nationwide. The survey utilized a quantitative questionnaire as data collection tool. The data collection took place from June 2021 to January 2023. RESULTS: The survey encompassed 120 neurosurgery residents, with a gender distribution of 55 % male and 45 % female. The respondents were primarily from university hospitals (53 %), followed by community hospitals (38 %) and private hospitals (9 %). In terms of training program satisfaction, 37 % reported moderate satisfaction, 39 % indicated below-moderate satisfaction, and 28 % experienced above-moderate satisfaction. The predominant causes of dissatisfaction identified were insufficient surgical exposure (reported by 39 % of respondents), suboptimal educational content (38 %), and inadequate research opportunities (32 %). Additionally, 24 % of respondents highlighted psychological stress, and 36 % reported frequent experiences of burnout. A majority (63 %) indicated a workload of 60-80 h weekly. About half of the residents indicated a future specialization interest in neurosurgical oncology. CONCLUSION: The results of the survey findings provide valuable insights into the challenges and aspirations of neurosurgery trainees in Germany. These results serve as a basis for improving the training system, enhancing the working environment, and guiding future planning in this field. To optimize the training of residents, it is important to address issues such as limited surgical and research opportunities and psychological well-being. The expressed interest in subspecializing offers guidance for shaping the training program's future direction.

In vitro and in silico evaluation of bioactivities and chemical composition of the aerial parts of Anchusa officinalis L. methanol extract.

The main objective of the study is to evaluate the antioxidant, anticancer, and antimicrobial activities of Anchusa officinalis L. in vitro and in silico. The dried aerial parts of A. officinalis L. were extracted with methanol. Total phenolic and flavonoid content was analyzed. Antioxidant and antimicrobial effects were tested against both gram-positive and gram-negative bacteria. Gas chromatography-mass spectrometry analysis revealed the presence of 10 phytochemical compounds, and cyclobutane (26.07%) was identified as the major photochemical compound. The methanol extract exhibited the maximum amount of total phenolic content (118.24 ± 4.42 mg QE/g dry weight of the dry extract) (R2 = 0.994) and the total flavonoid content was 94 ± 2.34 mg QE/g dry weight of the dry extract (R2 = 0.999). The IC50 value for 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid was 107.12 ± 3.42 µg/mL, and it was high for 1,1-diphenyl-2-picryl hydrazyl (123.94 ± 2.31 µg/mL). The IC50 value was 72.49 ± 3.14 against HepG2 cell lines, and a decreased value was obtained (102.54 ± 4.17 g/mL) against MCF-7 cell lines. The methanol extract increased the expression of caspase mRNA and Bax mRNA levels when compared to the control experiment (p < .05). The conclusions, A. officinalis L. aerial parts extract exhibited antibacterial, antifungal, and antioxidant activities.

Metabolism of FAD, FMN and riboflavin (vitamin B2) in the human parasitic blood fluke Schistosoma mansoni.

BACKGROUND: Schistosomiasis is a parasitic disease caused by trematodes of the genus Schistosoma. The intravascular worms acquire the nutrients necessary for their survival from host blood. Since all animals are auxotrophic for riboflavin (vitamin B2), schistosomes too must import it to survive. Riboflavin is an essential component of the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD); these support key functions of dozens of flavoenzymes. METHODS: Here, using a combination of metabolomics, enzyme kinetics and in silico molecular analysis, we focus on the biochemistry of riboflavin and its metabolites in Schistosoma mansoni (Sm). RESULTS: We show that when schistosomes are incubated in murine plasma, levels of FAD decrease over time while levels of FMN increase. We show that live schistosomes cleave exogenous FAD to generate FMN and this ability is significantly blocked when expression of the surface nucleotide pyrophosphatase/phosphodiesterase ectoenzyme SmNPP5 is suppressed using RNAi. Recombinant SmNPP5 cleaves FAD with a Km of 178 ± 5.9 µM and Kcat/Km of 324,734 ± 36,347 M- 1.S- 1. The FAD-dependent enzyme IL-4I1 drives the oxidative deamination of phenylalanine to produce phenylpyruvate and H2O2. Since schistosomes are damaged by H2O2, we determined if SmNPP5 could impede H2O2 production by blocking IL-4I1 action in vitro. We found that this was not the case; covalently bound FAD on IL-4I1 appears inaccessible to SmNPP5. We also report that live schistosomes can cleave exogenous FMN to generate riboflavin and this ability is significantly impeded when expression of a second surface ectoenzyme (alkaline phosphatase, SmAP) is suppressed. Recombinant SmAP cleaves FMN with a Km of 3.82 ± 0.58 mM and Kcat/Km of 1393 ± 347 M- 1.S- 1. CONCLUSIONS: The sequential hydrolysis of FAD by tegumental ecto-enzymes SmNPP5 and SmAP can generate free vitamin B2 around the worms from where it can be conveniently imported by the recently described schistosome riboflavin transporter SmaRT. Finally, we identified in silico schistosome homologs of enzymes that are involved in intracellular vitamin B2 metabolism. These are riboflavin kinase (SmRFK) as well as FAD synthase (SmFADS); cDNAs encoding these two enzymes were cloned and sequenced. SmRFK is predicted to convert riboflavin to FMN while SmFADS could further act on FMN to regenerate FAD in order to facilitate robust vitamin B2-dependent metabolism in schistosomes.

Effect of Shearing and Annealing on the Pasting Properties of Different Starches.

The functional characteristics of starch can be altered by shear force, which makes the impact on its microstructure of great importance to the food industry. This study investigated the effects of freeze-drying on the gel texture, pasting capabilities, and swelling power of starches made from sweet potatoes (SP), chickpeas (CP), and wheat (WS) combined with Cordia (CG) and Ziziphus gum (ZG). The samples were annealed in water without shearing and in a rapid visco-analyzer (RVA) for 30 min at 60 °C while being spun at 690 rpm. Both native and freeze-dried samples were mixed with 1% or 3% ZG and CG. After annealing, the starches were examined using a texture analyzer and RVA. The results showed that freeze-drying had a substantial (p > 0.05) impact on the starch granule, in addition to the effect of annealing. The peak viscosity of freeze-dried native CP and SP starches increased, but the peak viscosity of freeze-dried wheat starch decreased. The setbacks for CP and WS increased, whereas the setbacks for SP varied slightly. Furthermore, it was demonstrated that annealing in an RVA exhibited a substantially lower peak viscosity than annealing in a water bath; the RVA's shearing effect may have been the cause of this difference. Cordia gum fared better than ZG in terms of peak viscosity, although ZG significantly reduced setback in comparison to CG. Among the various blends, the native WB sample had the lowest hardness (100 ± 4.9 g), while the freeze-dried WB SP sample had the greatest (175.5 ± 4.8 g). Shearing of starches broke up the granules into smaller pieces, which made them gel at lower temperatures. This could be a good thing when they are needed for food uses that require little cooking.

The impact of APOE ε4 in Alzheimer's disease: a meta-analysis of voxel-based morphometry studies.

Background: Alzheimer's disease (AD) is the most prevalent form of dementia, exerting substantial personal and societal impacts. The apolipoprotein E (APOE) ε4 allele is a known genetic factor that increases the risk of AD, contributing to more severe brain atrophy and exacerbated symptoms. Purpose: We aim to provide a comprehensive review of the impacts of the APOE ε4 allele on brain atrophy in AD and mild cognitive impairment (MCI) as a transitional stage of AD. Methods: We performed a coordinate-based meta-analysis of voxel-based morphometry (VBM) studies to identify the patterns of grey matter atrophy in APOE ε4 carriers vs. non-carriers. We obtained coordinate-based structural magnetic resonance imaging (MRI) data for 1135 individuals from 12 studies on PubMed and Google Scholar that met our inclusion criteria. Results: We found significant atrophy in the hippocampus and parahippocampus of APOE ε4 carriers compared to non-carriers, especially within the AD and MCI groups, while healthy controls showed no significant atrophy in these regions. Conclusion: Our meta-analysis sheds light on the significant link between the APOE ε4 allele and hippocampal atrophy in both AD and MCI, emphasizing the allele's critical influence on neurodegeneration, especially in the hippocampus. Our findings contribute to the understanding of the disease's pathology, potentially facilitating progress in early detection, targeted interventions, and personalized care strategies for individuals with the APOE ε4 allele who are at risk for Alzheimer's Disease.

Metabolism of FAD, FMN and riboflavin (vitamin B2) in the human parasitic blood fluke Schistosoma mansoni.

Schistosomiasis is a parasitic disease caused by trematode worms of the genus Schistosoma. The intravascular worms acquire the nutrients necessary for their survival from host blood. Since all animals are auxotrophic for riboflavin (vitamin B2), schistosomes too must import it to survive. Riboflavin is an essential component of the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD); these support key functions of dozens of flavoenzymes. In this work we focus on the biochemistry of riboflavin and its metabolites in Schistosoma mansoni. We show that when schistosomes are incubated in murine plasma, levels of FAD decrease over time while the levels of FMN increase. We show that live schistosomes can cleave exogenous FAD to generate FMN and this ability is significantly blocked when expression of the surface ectoenzyme SmNPP5 is suppressed using RNAi. Recombinant SmNPP5 cleaves FAD with a Km of 178 ± 5.9 µM. The FAD-dependent enzyme IL-4I1 drives the oxidative deamination of phenylalanine to produce phenylpyruvate and H2O2 in the extracellular environment. Since schistosomes can be damaged by H2O2, we determined if SmNPP5 could impede H2O2 production by blocking IL-4I1 action in vitro. We found that this was not the case, suggesting that covalently bound FAD on IL-4I1 is inaccessible to SmNPP5. We also report here that live schistosomes can cleave exogenous FMN to generate riboflavin and this ability is significantly impeded when expression of a second surface ectoenzyme (alkaline phosphatase, SmAP) is suppressed. Recombinant SmAP cleaves FMN with a Km of 3.82 ± 0.58 mM. Thus, the sequential hydrolysis of FAD by tegumental ecto-enzymes SmNPP5 and SmAP can generate free vitamin B2 around the worms from where it can be conveniently imported by, we hypothesize, the recently described schistosome riboflavin transporter SmaRT. In this work we also identified in silico schistosome homologs of enzymes that are involved in intracellular vitamin B2 metabolism. These are riboflavin kinase (SmRFK) as well as FAD synthase (SmFADS); cDNAs encoding these two enzymes were cloned and sequenced. SmRFK is predicted to convert riboflavin to FMN while SmFADS could further act on FMN to regenerate FAD in order to facilitate robust vitamin B2-dependent metabolism in schistosomes.

Socioeconomic Disparities in Online Patient Portal Utilization Among Total Knee Arthroplasty Recipients.

BACKGROUND: Since 2021, the Centers for Medicare and Medicaid Services have mandated that patients have open access to their medical records. Many institutions use online portals, which allow patients to access their health information and communicate with care teams. Our research aimed to evaluate demographic patterns for online patient portal utilization in patients undergoing total knee arthroplasty (TKA). Further, we assessed if and how portal engagement contributes to perioperative outcomes. METHODS: This study retrospectively reviewed primary and elective TKA from 2017 to 2022 at a single academic institution. Patients were stratified into 2 groups based on their online portal status: activated (A) or not-activated (NA). Baseline characteristics and postoperative outcomes were collected from the electronic medical record and compared. RESULTS: In total, 10,995 patients were included: 8,330 (75.8%) were A and 2,625 (24.2%) were NA. The NA group was significantly older (P < .001); more likely to be Black (P < .001), women (P < .001), single/divorced/widowed (P < .001), non-English speaking (P < .001), and Medicare or Medicaid insured (P < .001); from zip codes with median incomes below $50,000 (P < .001), and more likely to be American Society of Anesthesiologists class III or IV (P < .001). Patient-reported outcome measure completion rates were significantly lower in the NA group (15.3 versus 47.7%, P < .001). Lengths of stay (LOS) were significantly higher in the NA group (2.7 versus 2.1 days, P < .001). The NA group was significantly more likely to be discharged to skilled nursing facilities (P < .001). Comparable rates of 90-day emergency department visits, readmissions, as well as 90-day and 2-year revisions, were observed across groups. CONCLUSIONS: There are significant disparities in online portal activation status based on patient demographics. Patients who have A portals had significantly higher Patient-reported outcome measure completion rates, shorter LOS, and higher rates of home discharge. Further research should determine which other factors may affect patient portal utilization and inform interventions to improve portal utilization among minority populations.

The riboflavin (vitamin B2) transporter protein (SmaRT) of the human intravascular parasitic trematode Schistosoma mansoni.

Schistosomes are intravascular parasitic worms infecting >200 million people globally. Here we examine how the worms acquire an essential nutrient - vitamin B2 (riboflavin). We demonstrate that all intravascular life stages (schistosomula, adult males and females) take up radiolabeled riboflavin. This process is impeded in the presence of excess unlabeled riboflavin and at 4 °C. We have identified a transporter homolog in worms designated SmaRT (Schistosoma mansoni riboflavin transporter) that localizes to the tegument and internal tissues of adults. CHO-S cells transfected with plasmid encoding SmaRT import significantly more radiolabeled riboflavin compared to controls. Uptake of radiolabel is impeded when SmaRT-expressing cells are incubated in an excess of unlabeled riboflavin but not by an excess of an irrelevant metabolite. Uptake is mediated in a sodium-independent manner and over a wide range of pH values (pH 5.5-9). This is the first identification of a bone fide riboflavin transporter in any platyhelminth.

Memory impairment in Amyloidß-status Alzheimer's disease is associated with a reduction in CA1 and dentate gyrus volume: In vivo MRI at 7T.

INTRODUCTION: In Alzheimer's disease (AD), early diagnosis facilitates treatment options and leads to beneficial outcomes for patients, their carers and the healthcare system. The neuropsychological battery of the Uniform Data Set (UDSNB3.0) assesses cognition in ageing and dementia, by measuring scores across different cognitive domains such as attention, memory, processing speed, executive function and language. However, its neuroanatomical correlates have not been investigated using 7 Tesla MRI (7T MRI). METHODS: We used 7T MRI to investigate the correlations between hippocampal subfield volumes and the UDSNB3.0 in 24 individuals with Amyloidß-status AD and 18 age-matched controls, with respective age ranges of 60 (42-76) and 62 (52-79) years. AD participants with a Medial Temporal Atrophy scale of higher than 2 on 3T MRI were excluded from the study. RESULTS: A significant difference in the entire hippocampal volume was observed in the AD group compared to healthy controls (HC), primarily influenced by CA1, the largest hippocampal subfield. Notably, no significant difference in whole brain volume between the groups implied that hippocampal volume loss was not merely reflective of overall brain atrophy. UDSNB3.0 cognitive scores showed significant differences between AD and HC, particularly in Memory, Language, and Visuospatial domains. The volume of the Dentate Gyrus (DG) showed a significant association with the Memory and Executive domain scores in AD patients as assessed by the UDSNB3.0.. The data also suggested a non-significant trend for CA1 volume associated with UDSNB3.0 Memory, Executive, and Language domain scores in AD. In a reassessment focusing on hippocampal subfields and MoCA memory subdomains in AD, associations were observed between the DG and Cued, Uncued, and Recognition Memory subscores, whereas CA1 and Tail showed associations only with Cued memory. DISCUSSION: This study reveals differences in the hippocampal volumes measured using 7T MRI, between individuals with early symptomatic AD compared with healthy controls. This highlights the potential of 7T MRI as a valuable tool for early AD diagnosis and the real-time monitoring of AD progression and treatment efficacy. CLINICALTRIALS: GOV: ID NCT04992975 (Clinicaltrial.gov 2023).

Mid-term outcomes of a kinematically designed cruciate retaining total knee arthroplasty.

BACKGROUND: Advances in implant material and design have allowed for improvements in total knee arthroplasty (TKA) outcomes. A cruciate retaining (CR) TKA provides the least constraint of TKA designs by preserving the native posterior cruciate ligament. Limited research exists that has examined clinical outcomes or patient reported outcome measures (PROMs) of a large cohort of patients undergoing a CR TKA utilizing a kinematically designed implant. It was hypothesized that the studied CR Knee System would demonstrate favorable outcomes and a clinically significant improvement in pain and functional scores. AIM: To assess both short-term and mid-term clinical outcomes and PROMs of a novel CR TKA design. METHODS: A retrospective, multi-surgeon study identified 255 knees undergoing a TKA utilizing a kinematically designed CR Knee System (JOURNEY™ II CR; Smith and Nephew, Inc., Memphis, TN) at an urban, academic medical institution between March 2015 and July 2021 with a minimum of two-years of clinical follow-up with an orthopedic surgeon. Patient demographics, surgical information, clinical outcomes, and PROMs data were collected via query of electronic medical records. The PROMs collected in the present study included the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR) and Patient-Reported Outcomes Measurement Information System (PROMIS®) scores. The significance of improvements in mean PROM scores from preoperative scores to scores collected at six months and two-years postoperatively was analyzed using Independent Samples t-tests. RESULTS: Of the 255 patients, 65.5% were female, 43.8% were White, and patients had an average age of 60.6 years. Primary osteoarthritis (96.9%) was the most common primary diagnosis. The mean surgical time was 105.3 minutes and mean length of stay was 2.1 d with most patients discharged home (92.5%). There were 18 emergency department (ED) visits within 90 d of surgery resulting in a 90 d ED visit rate of 7.1%, including a 2.4% orthopedic-related ED visit rate and a 4.7% non-orthopedic-related ED visit rate. There were three (1.2%) hospital readmissions within 90 d postoperatively. With a mean time to latest follow-up of 3.3 years, four patients (1.6%) required revision, two for arthrofibrosis, one for aseptic femoral loosening, and one for peri-prosthetic joint infection. There were significant improvements in KOOS JR, PROMIS Pain Intensity, PROMIS Pain Interference, PROMIS Mobility, and PROMIS Physical Health from preoperative scores to six month and two-year postoperative scores. CONCLUSION: The evaluated implant is an effective, novel design offering excellent outcomes and low complication rates. At a mean follow up of 3.3 years, four patients required revisions, three aseptic and one septic, resulting in an overall implant survival rate of 98.4% and an aseptic survival rate of 98.8%. The results of our study demonstrate the utility of this kinematically designed implant in the setting of primary TKA.

Endophytic Aspergillus hiratsukae mediated biosynthesis of silver nanoparticles and their antimicrobial and photocatalytic activities.

In the current study, endophytic Aspergillus hiratsukae was used for the biosynthesis of silver nanoparticles (Ag-NPs) for the first time. The characterizations were performed using X ray diffraction (XRD), Transmission electron microscopy (TEM), Scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX), Dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), and UV-Vis spectroscopy. The obtained results demonstrated the successful formation of crystalline, spherical Ag-NPs with particle diameters ranging from 16 to 31 nm. The FT-IR studied and displayed the various functional groups involved, which played a role in capping and reducing agents for Ag-NPs production. The SEM-EDX revealed that the main constituent of the AS-formed sample was primarily Ag, with a weight percentage of 64.2%. The mycosynthesized Ag-NPs were assessed for antimicrobial as well as photocatalytic activities. The antimicrobial results indicated that the synthesized Ag-NPs possess notable antibacterial efficacy against Staphylococcus aureus, Bacillus subtilis, and Escherichia coli, with minimum inhibitory concentrations (MICs) of Ag-NPs ranging from 62.5 to 250 µg/mL. Moreover, the biosynthesized Ag-NPs demonstrated weak antifungal activity against Aspergillus brasiliensis and Candida albicans, with MICs of 500 and 1,000 µg/mL, respectively. In addition, the mycosynthesized Ag-NPs exhibited photocatalytic activity toward acid black 2 (nigrosine) dye under both light and dark stimulation. Notably, After 300 min exposure to light, the nigrosine dye was degraded by 93%. In contrast, 51% degradation was observed after 300 min in darkness. In conclusion, Ag-NPs were successfully biosynthesized using endophytic A. hiratsukae and also exhibited antimicrobial and photocatalytic activities that can be used in environmental applications.

GLYCOLYTIC ENZYMES AS VACCINES AGAINST SCHISTOSOMIASIS: TESTING SCHISTOSOMA MANSONI PHOSPHOGLYCERATE MUTASE IN MICE.

Schistosomiasis is a globally burdensome parasitic disease caused by flatworms (blood flukes) in the genus Schistosoma. The current standard treatment for schistosomiasis is the drug praziquantel, but there is an urgent need to advance novel interventions such as vaccines. Several glycolytic enzymes have been evaluated as vaccine targets for schistosomiasis, and data from these studies are reviewed here. Although these parasites are canonically considered to be intracellular, proteomic analysis has revealed that many schistosome glycolytic enzymes are additionally found at the host-interactive surface. We have recently found that the intravascular stage of Schistosoma mansoni (Sm) expresses the glycolytic enzyme phosphoglycerate mutase (PGM) on the tegumental surface. Live parasites display PGM activity, and suppression of PGM gene expression by RNA interference diminishes surface enzyme activity. Recombinant SmPGM (rSmPGM) can cleave its glycolytic substrate, 3-phosphoglycerate and can both bind to plasminogen and promote its conversion to an active form (plasmin) in vitro, suggesting a moonlighting role for this enzyme in regulating thrombosis in vivo. We found that antibodies in sera from chronically infected mice recognize rSmPGM. We also tested the protective efficacy of rSmPGM as a vaccine in the murine model. Although immunization generates high titers of anti-SmPGM antibodies (against both recombinant and native SmPGM), no significant differences in worm numbers were found between vaccinated and control animals.

Shock wave lithotripsy in the era of COVID-19.

Objective: The objective of the study y was to evaluate factors which can improve shock wave lithotripsy (SWL) results to keep up with COVID-19 pandemic. Methods: Between June 2020 and June 2021, patients with radio-opaque or faint radio-opaque upper urinary tract stones, stone attenuation value ≤1200 HU, and stones size <2.5 cm were treated by electrohydraulic SWL. Patients with respiratory tract symptoms elevated temperature, contact with COVID-19 patients, or positive COVID-19 swab 2 weeks preoperatively, skin-to-stone distance >11 cm, and body mass index >30 kg/m2 were excluded from the study. Patients were prospectively enrolled in SWL done at a rate of 40-50 SWs/min under combined ultrasound and fluoroscopy-guided, ramped into high power in the 1st 300 shocks. Success rate and complications were recorded. Results: Five hundred and ninety patients completed the study. The success rate after 1st session was 408/590 patients (69.15%) which was augmented by 2nd session to reach 527/590 patients 89.3%. The success rate was 96.2% at 3 months postoperatively. Most complications were mild (Grade 1 or 2). Conclusions: SWL results improved using slow rate high power from the start of the session under combined fluoroscopy and ultrasound guidance. SWL may be a preferred option during a pandemic.

Innovations in the Isolation and Treatment of Biofilms in Periprosthetic Joint Infection: A Comprehensive Review of Current and Emerging Therapies in Bone and Joint Infection Management.

Periprosthetic joint infections (PJIs) are a devastating complication of joint arthroplasty surgeries that are often complicated by biofilm formation. The development of biofilms makes PJI treatment challenging as they create a barrier against antibiotics and host immune responses. This review article provides an overview of the current understanding of biofilm formation, factors that contribute to their production, and the most common organisms involved in this process. This article focuses on the identification of biofilms, as well as current methodologies and emerging therapies in the management of biofilms in PJI.