Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications.

Based on recent results, the determination of the easily accessible red blood cell (RBC) membrane proteins may provide new diagnostic possibilities for assessing mutations, polymorphisms or regulatory alterations in diseases. However, the analysis of the current mass spectrometry-based proteomics datasets and other major databases indicates inconsistencies-the results show large scattering and only a limited overlap for the identified RBC membrane proteins. Here, we applied membrane-specific proteomics studies in human RBC, compared these results with the data in the literature, and generated a comprehensive and expandable database using all available data sources. The integrated web database now refers to proteomic, genetic and medical databases as well, and contains an unexpected large number of validated membrane proteins previously thought to be specific for other tissues and/or related to major human diseases. Since the determination of protein expression in RBC provides a method to indicate pathological alterations, our database should facilitate the development of RBC membrane biomarker platforms and provide a unique resource to aid related further research and diagnostics

Signaling via PI3K/FOXO1A pathway modulates formation and survival of human embryonic stem cell-derived endothelial cells

Vascular derivatives of human embryonic stem cells (hESC) are being developed as sources of tissue-specific cells for organ regeneration. However, identity of developmental pathways that modulate the specification of endothelial cells is not known yet. We studied phosphatidylinositol 3-kinase (PI3K)-Forkhead box O transcription factor 1A (FOXO1A) pathways during differentiation of hESC toward endothelial lineage and on proliferation, maturation, and cell death of hESC-derived endothelial cells (hESC-EC). During differentiation of hESC, expression of FOXO1A transcription factor was linked to the expression of a cluster of angiogenesis- and vascular remodeling-related genes. PI3K inhibitor LY294002 activated FOXO1A and induced formation of CD31(+) hESC-EC. In contrast, differentiating hESC with silenced FOXO1A by small interfering RNA (siRNA) showed lower mRNA levels of CD31 and angiopoietin2. LY294002 decreased proliferative activity of purified hESC-EC, while FOXO1A siRNA increased their proliferation. LY294002 inhibits migration and tube formation of hESC-EC; in contrast, FOXO1A siRNA increased in vitro tube formation activity of hESC-EC. After in vivo conditioning of cells in athymic nude rats, cells retain their low FOXO1A expression levels. PI3K/FOXO1A pathway is important for function and survival of hESC-EC and in the regulation of endothelial cell fate. Understanding these properties of hESC-EC may help in future applications for treatment of injured organs

Treatment of Full-Thickness Acetabular Chondral Flaps during Hip Arthroscopy: Bone Marrow Aspirate Concentrate versus Microfracture

Background: The optimal treatment strategy for patients with full-thickness chondral flaps undergoing hip arthroscopy is controversial. Purpose: To compare functional outcomes of patients who underwent bone marrow aspirate concentrate (BMAC) application with those of patients who underwent microfracture. Study Design: Cohort study; Level of evidence, 3. Methods: This was a retrospective case series of prospectively collected data on patients who underwent arthroscopic acetabular labral repair by 1 surgeon between June 2014 and April 2020. The inclusion criteria for this study were age ≥18 years, preoperative radiographs of the pelvis, arthroscopic acetabular labral repair, exposed subchondral bone with overlying chondral flap seen at the time of hip arthroscopy, microfracture or BMAC to address this lesion, and completed patient-reported outcome measures (PROMs) (International Hip Outcome Tool-33 [iHOT-33], Hip Outcome Score-Activities of Daily Living [HOS-ADL], Hip Outcome Score-Sports Subscale [HOS-Sport], modified Harris Hip Score [mHHS], and visual analog scale [VAS] for pain) at enrollment and 12-month follow-up. Clinical outcomes were assessed using PROM scores. Results: A total of 81 hips with full-thickness chondral flaps were included in this study: 50 treated with BMAC and 31 treated with microfracture. There were no significant differences between groups in age, sex, body mass index, tear size, radiographic osteoarthritis, or radiographic femoroacetabular impingement. In the BMAC cohort, all PROM scores improved significantly from preoperatively to follow-up: 41.7 to 75.6 for iHOT-33, 67.6 to 91.0 for HOS-ADL, 41.5 to 72.3 for HOS-Sport, 59.4 to 87.2 for mHHS, and 6.2 to 2.2 for VAS pain (P \u3c .001 for all). In the microfracture cohort, the score improvements were 48.0 to 65.1 for iHOT-33 (P = .001), 80.5 to 83.3 for HOS-ADL (P = .275), 59.2 to 62.4 for HOS-Sport (P = .568), 70.4 to 78.3 for mHHS (P = .028), and 4.9 to 3.6 for VAS pain (P = .036). Regarding clinically meaningful outcomes, 77.6% of the BMAC group and 50.0% of the microfracture group met the minimal clinically important difference for iHOT-33 at the 12-month follow-up (P = .013). Conclusion: Patients with full-thickness chondral flaps at the time of hip arthroscopy experienced greater improvements in functional outcome scores at the 12-month follow-up when treated with BMAC as opposed to microfracture

Effects of weight loss via high fat vs. low fat alternate day fasting diets on free fatty acid profiles

Cardiovascular disease risk is associated with excess body weight and elevated plasma free fatty acid (FFA) concentrations. This study examines how an alternate-day fasting (ADF) diet high (HF) or low (LF) in fat affects plasma FFA profiles in the context of weight loss, and changes in body composition and lipid profiles. After a 2-week weight maintenance period, 29 women (BMI 30–39.9 kg/m2) 25–65 years old were randomized to an 8-week ADF-HF (45% fat) diet or an ADF-LF (25% fat) diet with 25% energy intake on fast days and ad libitum intake on feed days. Body weight, BMI and waist circumference were assessed weekly and body composition was measured using dual x-ray absorptiometry (DXA). Total and individual FFA and plasma lipid concentrations were measured before and after weight loss. Body weight, BMI, fat mass, total cholesterol, LDL-C and triglyceride concentrations decreased (P < 0.05) in both groups. Total FFA concentrations also decreased (P < 0.001). In the ADF-LF group, decreases were found in several more FFAs than in the ADF-HF group. In the ADF-HF group, FFA concentrations were positively correlated with waist circumference. Depending on the macronutrient composition of a diet, weight loss with an ADF diet decreases FFA concentrations through potentially different mechanisms

Puncture Capsulotomy Technique for Hip Arthroscopy: Midterm Functional Outcomes

Background: The most common surgical approaches in hip arthroscopy are interportal and T-capsulotomy. However, these methods may introduce capsular instability. Puncture capsulotomy preserves capsuloligamentous integrity by avoiding iatrogenic transection of the iliofemoral capsular ligament. Purpose: To present minimum 2-year functional outcomes for patients who underwent arthroscopic treatment for acetabular labral tears and concomitant femoroacetabular impingement using the puncture capsulotomy technique. Study design: Case series; Level of evidence, 4. Methods: The authors conducted a retrospective review of prospectively collected data on patients who underwent arthroscopic acetabular labral tear treatment between December 2013 and May 2019. Included were patients aged ≥18 years who underwent hip arthroscopy by a single surgeon and completed a minimum of 2 years of patient-reported outcome measure (PROM) surveys. Intraoperatively, patients underwent hip arthroscopy via puncture capsulotomy to treat labral tears and any concomitant femoroacetabular impingement. Clinical outcome data consisted of PROMs. Results: A total of 163 hips were included; the mean patient follow-up was 30.4 months (range, 24-60 months; 95% CI, 28.5-32.3 months). Patients had a mean age of 37.9 years (range, 36.1-39.6 years), with a mean body mass index of 25.9 (range, 25.2-26.5). There were significant improvements in mean [95% CI] baseline to final follow-up scores for the 33-Item International Hip Outcome Tool (iHOT-33) (39.6 [36.8-42.4] vs 76.1 [72.7-79.6]), Hip Outcome Score-Activities of Daily Living (70.0 [67.0-73.0] vs 89.3 [87.3-91.3]), modified Harris Hip Score (60.1 [57.9-62.4] vs 84.9 [82.5-87.2]), and Hip Outcome Score-Sports Specific Subscale (41.8 [37.9-45.6] vs 75.7 [71.7-79.7]) (P \u3c .001 for all). Additionally, the mean [95% CI] visual analog scale pain scores were noted to significantly improve throughout the duration of the postoperative period (from 6.3 [5.9-6.7] to 2.2 [1.8-2.6]; P \u3c .001). There were no incidences of infection, avascular necrosis of the femoral head, dislocation/instability, or femoral neck fracture. At the 2-year follow-up, 81.0%, 62.0%, and 58.9% of hips achieved previously published clinically meaningful iHOT-33 thresholds for minimally clinically important difference, Patient Acceptable Symptom Score, and substantial clinical benefit, respectively. Conclusion: Puncture capsulotomy demonstrated significantly improved functional and clinically meaningful outcomes at a minimum 2-year follow-up, along with a minimal complication rate

The decline and rise of neighbourhoods: the importance of neighbourhood governance

There is a substantial literature on the explanation of neighbourhood change. Most of this literature concentrates on identifying factors and developments behind processes of decline. This paper reviews the literature, focusing on the identification of patterns of neighbourhood change, and argues that the concept of neighbourhood governance is a missing link in attempts to explain these patterns. Including neighbourhood governance in the explanations of neighbourhood change and decline will produce better explanatory models and, finally, a better view about what is actually steering neighbourhood change