A comparison of fixation disparity in real and simulated environment

A comparison of fixation disparity in real and simulated environmen

Early postoperative pain as a risk factor of shoulder stiffness after arthroscopic rotator cuff repair

Background: The role of postoperative pain in incidence of shoulder stiffness (SS) after shoulder arthroscopy has not been thoroughly investigated. The present study was conducted to assess the effects of early postoperative pain (EPOP) on onset of SS after arthroscopic rotator cuff (RC) repair. Materials and methods: In a retrospective analysis of a prospectively collected database, 335 patients who underwent arthroscopic RC repair were evaluated. RC tendons were sutured to the bone using the double-row technique. EPOP was evaluated 1 week after surgery using the visual analog scale (VAS). SS was assessed 3 months after surgery and was categorized into moderate or severe based on shoulder range of motion (ROM). Each type of complication including SS was identified and recorded. Results: Postoperative shoulder stiffness (POSS) was identified in 121 patients (36.2) that was moderate in 86 patients (70.1) and severe in 35 patients (28.9). After 1 week, VAS pain score was equal to 7.7 ± 3.1 and 4.5 ± 2.1 in the patients with and without stiffness, respectively (p < 0.001). Diabetes and traumatic tear were found to be associated with postoperative stiffness (p = 0.046 and p < 0.001, respectively). Similar associations were found on multivariate analysis of data. VAS pain score was higher in the patients with severe stiffness compared with those with moderate stiffness (p < 0.001). Conclusions: Our findings revealed that EPOP is associated with shoulder stiffness after arthroscopic RC repair. Therefore, strategies to ameliorate EPOP could be opted to decrease rate of POSS. Level of evidence: Level IV © 2021, The Author(s)

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Decreased radioassay values for folate after serum extraction when pteroylglutamic acid standards are used.

Abstract Radoiassay values for folate in protein-denautured (extracted) sera are compared with values obtained by individual serum blank correction. Lower folate values are reported for sera extracted at pH 1.3, 7.6, 10.5, and 12.4 when pterolyglutamic acid (PGA) calibration standards are used. The results are unchanged when ascorbate added to the sera is increased from 1 to 20 g/liter and when [3H]PGA is substituted for 125I-labeled PGA. However, a higher mean value for extracted serum is reported when N-5-methyltetrahydrofolic acid calibration standards are substituted for PGA. Because both patients' samples and assay calibrators were subjected to the same extraction methods, our results suggest that serum folate behaves differently from PGA during the extractions.</jats:p

Gestational diabetes mellitus in mothers and long term cardiovascular disease in both parents: Results of over a decade follow-up of the Iranian population

Background and aims: We aimed at evaluating whether the presence of gestational diabetes mellitus (GDM) in mothers is associated with increased risk of incident cardiovascular disease (CVD) in both mothers and fathers. Methods: In this population-based study, 4308 Iranian women, aged 18�64 years, with at least 1 live-birth delivery, and free of CVD at baseline, were followed. Corresponding spouses were identified in 2547 cases. The association between history of GDM and incident CVD was assessed using multivariate Cox's proportional hazard in 3 models: model 1, unadjusted; model 2, adjusted for age, body mass index, smoking (for men), maternal parity, miscarriage, physical activity, hypertension and hypercholesterolemia, and model 3, further adjusted for diabetes mellitus. Results: After a median follow-up of 14.1 years, 314 mothers and 424 fathers experienced CVD. Women with history of GDM had an adjusted hazard ratio (HR), 95 CI of 1.85 (1.38�2.48) and 1.29 (0.96�1.75) for CVD in models 1 and 2, respectively. Furthermore, an independent association with CVD was observed in fathers with an adjusted HR of 1.35 (1.02�1.79) in the confounder adjusted model and even after further controlling for diabetes 1.36 (1.03�1.80). Moreover, all traditional risk factors, excluding BMI, showed an independent risk for CVD in both genders. Conclusions: Women with prior GDM showed an increased risk of CVD that was not independent of important CVD risk factors. However, among men, spousal history of GDM was an independent risk factor for incident CVD, even after considering important traditional risk factors, including diabetes. © 2019 Elsevier B.V

Abstract 5058: Expansion and validation of the prostate-specific antigen substrate degradome.

Abstract Kallikrein-related peptidase 3 (KLK3), better known as prostate-specific antigen (PSA), remains the most important serum biomarker in all of cancer. Its continued expression by tumors throughout the progression of prostate cancer in most patients has led to some speculation as to the possibility of PSA playing an active role in the disease. Although the use of PSA as a biomarker continues to be the subject of great discussion, our understanding of its functions in physiological and pathophysiological contexts is in its infancy. PSA is a secreted serine protease with substrate cleavage preferences similar to chymotrypsin. The principal physiological substrates of PSA in reproduction are semenogelins I and II. Currently, the number of PSA substrates, the so-called substrate degradome, has been identified by a candidate gene approach, and is limited to less than 20 gene products. Our working hypothesis is that the PSA substrate degradome is greatly understated, and that candidate identification by a bioinformatics approach, followed by biochemical validation would serve to dramatically expand the known substrates and help further our understanding of the roles played by this protease in reproduction and prostate cancer biology. Using the Merops database, a series of 32 unique consensus PSA substrate recognition sites was generated, based on reported P4-P1 residues on the N-terminal of known substrate cleavage sites. These peptide sequences were each used to search the PIR (Protein information resource) and IPA (Ingenuity Pathway Analysis) databases for the corresponding genes containing matching sequences. The resulting gene list was consolidated and filtered based on cellular localization. Cell-surface and extracellular gene products were retained for further analysis. Novel, highly active recombinant PSA was expressed, isolated, and used to biochemically validate a subset of the candidate substrates identified in silico. Finally, immunoblotting was used to determine PSA-induced cleavage of candidate substrates. The series of 32 consensus PSA substrate recognition sequences matched almost 10,000 gene products. Of these, approximately 90% were proteins not secreted or found on cell surfaces, and therefore not considered accessible to PSA. The remaining 900 gene products included cytokines, cell surface receptors, proteases, extracellular matrix proteins and immume modulators, many with reported roles in prostate cancer. They were organized by function prior to being subjected to cell-free biochemical validation for time-dependant cleavage. This study has used a combination of bioinformatics-based strategies and biochemistry to dramatically increase the list of potential PSA substrates. The information will be of great use in increasing our understanding of PSA and its functions in reproduction and cancer biology. Citation Format: Sangmi Nam, Niquiche Sangster-Guity, Theodore E. Ewachiw, Samuel R. Denmeade, Simon A. Williams. Expansion and validation of the prostate-specific antigen substrate degradome. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5058. doi:10.1158/1538-7445.AM2013-5058</jats:p