The blue supergiant Sher 25 revisited in the Gaia era

Aims. The evolutionary status of the blue supergiant Sher 25 and its membership to the massive cluster NGC 3603 are investigated. Methods. A hybrid non-LTE (local thermodynamic equilibrium) spectrum synthesis approach is employed to analyse a high-resolution optical spectrum of Sher 25 and five similar early B-type comparison stars in order to derive atmospheric parameters and elemental abundances. Fundamental stellar parameters are determined by considering stellar evolution tracks, Gaia Data Release 3 (DR3) data and complementary distance information. Interstellar reddening and the reddening law along the sight line towards Sher 25 are constrained employing UV photometry for the first time in addition to optical and infrared data. The distance to NGC 3603 is reevaluated based on Gaia DR3 data of the innermost cluster O-stars. Results. The spectroscopic distance derived from the quantitative analysis implies that Sher 25 lies in the foreground of NGC 3603, which is found to have a distance of $d_\mathrm{NGC 3603}$ = 6250$\pm$150 pc. A cluster membership is also excluded as the hourglass nebula is unaffected by the vigorous stellar winds of the cluster stars and from the different excitation signatures of the hourglass nebula and the nebula around NGC 3603. Sher 25 turns out to have a luminosity of log L/L$_\odot$ = 5.48$\pm$0.14, equivalent to that of a $\sim$27 $M_\odot$ supergiant in a single-star scenario, which is about half of the mass assumed so far, bringing it much closer in its characteristics to Sk-69{\deg}202, the progenitor of SN 1987A. Sher 25 is significantly older than NGC 3603. Further arguments for a binary (merger) evolutionary scenario of Sher 25 are discussed.Comment: 27 pages, 22 figures, Accepted for publication in Astronomy & Astrophysics, Data: https://doi.org/10.5281/zenodo.823015

Long-term persistence with evolocumab treatment and sustained reductions in LDL-cholesterol levels over 30 months: final results from the European observational HEYMANS study

BACKGROUND AND AIMS: Variability in low-density lipoprotein-cholesterol (LDL-C) level control at a population level is associated with poor cardiovascular outcomes. Limited data exist on LDL-C level variability or long-term persistence with the monoclonal antibody evolocumab in routine clinical practice. Using data from the HEYMANS registry, this analysis aimed to assess evolocumab persistence and discontinuation over 30 months of evolocumab treatment and to evaluate at a population level the variability in LDL-C level reductions during the study period. METHODS: HEYMANS was a prospective registry of adults initiating evolocumab in routine clinical practice in 12 European countries. Data were collected for up to and including 6 months before evolocumab initiation and up to 30 months after. Evolocumab discontinuation was analysed for two time periods: 0-12 months and 12-30 months. RESULTS: In total, 1951 patients were included in the study. The median reduction in LDL-C levels was 58% within 3 months after evolocumab initiation; this reduction was maintained over 30 months. More than 90% of patients continued receiving evolocumab at 12 months and 30 months of follow-up. Of patients with an LDL-C level measurement during follow-up, approximately 85% achieved a ≥30% reduction from baseline at each follow-up visit and approximately 60% achieved a ≥50% reduction. CONCLUSIONS: Evolocumab therapy was associated with sustained LDL-C level reductions up to 30 months, and persistence with evolocumab remained high, both at 12 and 30 months. Expanding the use of monoclonal antibodies such as evolocumab could provide improvements in LDL-C level control at a population level in European clinical practice

Low-density lipoprotein cholesterol levels exceed the recommended European threshold for PCSK9i initiation: lessons from the HEYMANS study

Aims To describe the characteristics of patients receiving evolocumab in clinical practice across 12 European countries and simulate the association between low-density lipoprotein cholesterol (LDL-C) reduction and cardiovascular (CV) risk reduction. ......................................................................................................................................................................................... Methods and results The characteristics of hyperlipidaemic patients at initiation of evolocumab and treatment patterns study—HEYMANS (n = 1952) is a prospective registry of patients ≥18 years old who initiated evolocumab from 1 August 2015 onwards. Mean (standard deviation) age was 60 (10.8), 85% had a prior CV event, 45% were diagnosed with familial hypercholesterolaemia (FH), and 60% had statin intolerance. At evolocumab initiation, 43% were receiving any statin, 16% were receiving ezetimibe without statin, and 41% received no background lipid-lowering therapy (LLT), with LDL-C levels reflecting local proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) reimbursement criteria. Median LDL-C decreased from 3.98 to 1.63 mmol/L within 3 months of evolocumab initiation and was maintained over 24 months. Overall, 58% achieved risk-based 2019 European Society of Cardiology/European Atherosclerosis Society LDL-C goals but that proportion was higher (68%) in patients receiving background LLT compared with those not receiving background LLT (44%). In patients with atherosclerotic cardiovascular disease without FH, the simulated relative CV risk reduction associated with evolocumab treatment was 34% (25–44%). ......................................................................................................................................................................................... Conclusion Across Europe, LDL-C levels at evolocumab initiation were three times higher than recommended thresholds for PCSK9i initiation, reflecting disparities between implementation and guidelines. More patients attained risk-based LDLC goals when receiving evolocumab in combination with LLT vs. those not receiving combination therapy. Population health could be improved and LDL-C goals better attained if LDL-C thresholds for PCSK9i reimbursement were lowered, enabling more patients to receive combination therapy when neede

Homocysteine levels in preterm infants: is there an association with intraventricular hemorrhage? A prospective cohort study.

BACKGROUND: The purpose of this study was to characterize total homocysteine (tHcy) levels at birth in preterm and term infants and identify associations with intraventricular hemorrhage (IVH) and other neonatal outcomes such as mortality, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and thrombocytopenia. METHODS: 123 infants \u3c 32 weeks gestation admitted to our Level III nursery were enrolled. A group of 25 term infants were enrolled for comparison. Two blood spots collected on filter paper with admission blood drawing were analyzed by a high performance liquid chromatography (HPLC) method. Statistical analysis included ANOVA, Spearman\u27s Rank Order Correlation and Mann-Whitney U test. RESULTS: The median tHcy was 2.75 micromol/L with an interquartile range of 1.34 - 4.96 micromol/L. There was no difference between preterm and term tHcy (median 2.76, IQR 1.25 - 4.8 micromol/L vs median 2.54, IQR 1.55 - 7.85 micromol/L, p = 0.07). There was no statistically significant difference in tHcy in 31 preterm infants with IVH compared to infants without IVH (median 1.96, IQR 1.09 - 4.35 micromol/L vs median 2.96, IQR 1.51 - 4.84 micromol/L, p = 0.43). There was also no statistically significant difference in tHcy in 7 infants with periventricular leukomalacia (PVL) compared to infants without PVL (median 1.55, IQR 0.25 - 3.45 micromol/L vs median 2.85, IQR 1.34 - 4.82 micromol/L, p = 0.07). Male infants had lower tHcy compared to female; prenatal steroids were associated with a higher tHcy. CONCLUSION: In our population of preterm infants, there is no association between IVH and tHcy. Male gender, prenatal steroids and preeclampsia were associated with differences in tHcy levels

Effects of whole-body vibration on postural control in elderly: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>This systematic review was performed to summarize the current evidence for whole body vibration (WBV) interventions on postural control in elderly.</p> <p>Methods</p> <p>English and German language papers in Medline, PEDro, Cinahl and the Cochrane databases were searched. Two reviewers extracted data on patients' characteristics, type of WBV intervention and outcomes. Two independent reviewers rated the methodological quality of these studies. Data were pooled using random-effects meta-analysis.</p> <p>Results</p> <p>Fifteen papers reporting quantitative data were included. Results from 15 papers could be pooled for a meta-analysis. The studies involved 933 participants. In 7 studies the authors investigated the effects of vibration plates generating vertical sinusoidal vibrations (VS-WBV) and 7 papers described the use of side-alternating sinusoidal vibrations (SS-WBV). One study investigated both VS-WBV and SS-WBV.</p> <p>Weak to moderate evidence of an overall effect as a result of VS-WBV and SS-WBV was observed for (a) static balance for post-intervention values with a standardized mean difference (SMD) -0.06, 95% CI -0.31 to 0.18 and for change values SMD -0.26, 95% CI -1.09 to 0.57, and (b) dynamic balance for post-intervention-values SMD -0.34, 95% CI -0.60 to -0.08. For functional balance (c) an overall outcome for post-intervention values with SMD of 0.34, 95% CI -0.19 to 0.87 was found.</p> <p>Conclusions</p> <p>The 15 studies reviewed were of moderate methodological quality. In summary, SS-WBV seems to have a beneficial effect on dynamic balance in elderly individuals. However, the current results should be interpreted with caution because of the observed heterogeneity of training parameters and statistical methods. Future studies are warranted to evaluate the effects of WBV on postural control in an elderly population.</p

HIV gp41 Engages gC1qR on CD4+ T Cells to Induce the Expression of an NK Ligand through the PIP3/H2O2 Pathway

CD4+ T cell loss is central to HIV pathogenesis. In the initial weeks post-infection, the great majority of dying cells are uninfected CD4+ T cells. We previously showed that the 3S motif of HIV-1 gp41 induces surface expression of NKp44L, a cellular ligand for an activating NK receptor, on uninfected bystander CD4+ T cells, rendering them susceptible to autologous NK killing. However, the mechanism of the 3S mediated NKp44L surface expression on CD4+ T cells remains unknown. Here, using immunoprecipitation, ELISA and blocking antibodies, we demonstrate that the 3S motif of HIV-1 gp41 binds to gC1qR on CD4+ T cells. We also show that the 3S peptide and two endogenous gC1qR ligands, C1q and HK, each trigger the translocation of pre-existing NKp44L molecules through a signaling cascade that involves sequential activation of PI3K, NADPH oxidase and p190 RhoGAP, and TC10 inactivation. The involvement of PI3K and NADPH oxidase derives from 2D PAGE experiments and the use of PIP3 and H2O2 as well as small molecule inhibitors to respectively induce and inhibit NKp44L surface expression. Using plasmid encoding wild type or mutated form of p190 RhoGAP, we show that 3S mediated NKp44L surface expression on CD4+ T cells is dependent on p190 RhoGAP. Finally, the role of TC10 in NKp44L surface induction was demonstrated by measuring Rho protein activity following 3S stimulation and using RNA interference. Thus, our results identify gC1qR as a new receptor of HIV-gp41 and demonstrate the signaling cascade it triggers. These findings identify potential mechanisms that new therapeutic strategies could use to prevent the CD4+ T cell depletion during HIV infection and provide further evidence of a detrimental role played by NK cells in CD4+ T cell depletion during HIV-1 infection

Randomized clinical trial of surgery versus conservative therapy for carpal tunnel syndrome [ISRCTN84286481]

BACKGROUND: Conservative treatment remains the standard of care for treating mild to moderate carpal tunnel syndrome despite a small number of well-controlled studies and limited objective evidence to support current treatment options. There is an increasing interest in the usefulness of wrist magnetic resonance imaging could play in predicting who will benefit for various treatments. METHOD AND DESIGN: Two hundred patients with mild to moderate symptoms will be recruited over 3 1/2 years from neurological surgery, primary care, electrodiagnostic clinics. We will exclude patients with clinical or electrodiagnostic evidence of denervation or thenar muscle atrophy. We will randomly assign patients to either a well-defined conservative care protocol or surgery. The conservative care treatment will include visits with a hand therapist, exercises, a self-care booklet, work modification/ activity restriction, B6 therapy, ultrasound and possible steroid injections. The surgical care would be left up to the surgeon (endoscopic vs. open) with usual and customary follow-up. All patients will receive a wrist MRI at baseline. Patients will be contacted at 3, 6, 9 and 12 months after randomization to complete the Carpal Tunnel Syndrome Assessment Questionnaire (CTSAQ). In addition, we will compare disability (activity and work days lost) and general well being as measured by the SF-36 version II. We will control for demographics and use psychological measures (SCL-90 somatization and depression scales) as well as EDS and MRI predictors of outcomes. DISCUSSION: We have designed a randomized controlled trial which will assess the effectiveness of surgery for patients with mild to moderate carpal tunnel syndrome. An important secondary goal is to study the ability of MRI to predict patient outcomes

Vertical Heterophoria and Postural Control in Nonspecific Chronic Low Back Pain

The purpose of this study was to test postural control during quiet standing in nonspecific chronic low back pain (LBP) subjects with vertical heterophoria (VH) before and after cancellation of VH; also to compare with healthy subjects with, and without VH. Fourteen subjects with LBP took part in this study. The postural performance was measured through the center of pressure displacements with a force platform while the subjects fixated on a target placed at either 40 or 200 cm, before and after VH cancellation with an appropriate prism. Their postural performance was compared to that of 14 healthy subjects with VH and 12 without VH (i.e. vertical orthophoria) studied previously in similar conditions. For LBP subjects, cancellation of VH with a prism improved postural performance. With respect to control subjects (with or without VH), the variance of speed of the center of pressure was higher, suggesting more energy was needed to stabilize their posture in quiet upright stance. Similarly to controls, LBP subjects showed higher postural sway when they were looking at a target at a far distance than at a close distance. The most important finding is that LBP subjects with VH can improve their performance after prism-cancellation of their VH. We suggest that VH reflects mild conflict between sensory and motor inputs involved in postural control i.e. a non optimal integration of the various signals. This could affect the performance of postural control and perhaps lead to pain. Nonspecific chronic back pain may results from such prolonged conflict