In vivo analysis of hip joint loading on Nordic walking novices

Objective: To evaluate the influence of Nordic walking (NW) on hip joint loads in order to determine whether it can be safely performed during postoperative physiotherapy in patients after orthopeadic surgery of the hip. Methods: Internal hip joint loads were directly measured in vivo in 6 patients using instrumented hip prostheses during NW and ordinary walking (OW). All patients received training in two different NW techniques (double-poling and the diagonal technique) by a certified NW instructor. Measurements were conducted on a treadmill at a speed of 4 km/h on level ground, at 10% inclination and at 10% slope as well as on a level lawn at a self chosen comfortable speed. Resultant contact force (F-res), bending moment (M-bend) and torsional torque (M-tors) were compared between NW and OW as well as between both NW techniques. Results: Joint loads showed a double peak pattern during all setups. Neither NW technique significantly influenced hip joint loads at the time of the first load peak during contralateral toe-off (CTO), which was also the absolute load peak, in comparison to OW. Compared to OW, double-poling significantly reduced F-res and M-bend at the time of the second load peak during the contralateral heel strike (CHS) on level ground both on the treadmill (- 6% and - 7%, respectively) and on the lawn (- 7% and - 9%). At 10% inclination, the diagonal technique increased F-res and M-bend at CHS (by + 6% and + 7%), but did not increase the absolute load peak at CTO. Conclusion: Joint loads during NW are comparable to those of OW. Therefore, NW can be considered a low-impact activity and seems to be safe for patients that are allowed full weight bearing, e.g. during postoperative rehabilitation after THA

In vivo loading on the hip joint in patients with total hip replacement performing gymnastics and aerobics exercises

A further increase in the number of total hip arthroplasty (THA) is predicted, in particular the number of young THA patients has raised and with it their demands. There is no standardized evidence-based rehabilitation program and no reliable guidelines for sports activities after THA. Stretching and strengthening gymnastics are routinely performed in rehabilitation and aerobics as a sport after THA. The aim of the investigation was to determine the in vivo force and moments acting on the hip prosthesis during gymnastics and aerobic exercises to provide a source for evidence-based recommendations. Hip joint loads were measured in six patients with instrumented hip implants. The resulting force F-Res, bending moment M-Bend at the neck and torsional moment M-Tors at the stem were examined during seven strengthening (with two different resistance bands) and four stretching gymnastic exercises and seven aerobic exercises with and without an aerobic step board compared to the loads during the reference activity walking. The stretching and strengthening gymnastics exercises and the aerobic exercises with and without a board demonstrated in their median peak force and moments mostly lower or similar values compared to walking. Significantly increased loads were recorded for the flexor stretching exercise in monopod stand (F-res and M-Bend), the strengthening abduction exercise on the chair (M-Tors) and the strengthening flexion exercise with the stronger resistance band (M-Tors). We also found a significant increase in median peak values in aerobic exercises with a board for the "Basic Step" (ipsilateral started F-res and M-Tors; contralateral started M-Tors), "Kickstep ipsilateral started" (F-res and M-Tors) and "Over the Top contralateral started" (F-res). The in vivo loads in THA patients during frequently performed stretching, strengthening and aerobic exercises were demonstrated for the first time. It was proved that stretching gymnastic exercises are safe in terms of resulting force, bending and torque moments for THA patients, although an external assistance for stabilization may be considered. Strengthening gymnastics exercises are reliable in terms of F-res, M-Bend and M-Tors, but, based on our data, we recommend to adhere to the communicated specific postoperative restrictions and select the resistance bands with lower tension. Aerobic exercises without an aerobic board can be considered as reliable activity in terms of force and moments for THA patients. Aerobic exercises with a board are not recommended for the early postoperative period and in our opinion need to be adapted to the individual muscular and coordinative resources

Urinary T Cells Identify Renal Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Predict Prognosis: A Proof of Concept Study

INTRODUCTION: Necrotizing crescentic glomerulonephritis is a major contributor to morbidity and mortality in Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). Because therapy relies on immunosuppressive agents with potentially severe adverse effects, a reliable noninvasive biomarker of disease activity is needed to guide treatment. METHODS: We used flow cytometry to quantify T cell subsets in blood and urine samples from 95 patients with AAV and 8 controls to evaluate their biomarker characteristics. These were compared to soluble markers, monocyte chemoattractant protein-1 (MCP-1), soluble CD163 (sCD163), soluble CD25 (sCD25), and complement C5a (C5a), measured using multiplex analysis. Available kidney biopsies (n = 21) were classified according to Berden. RESULTS: Patients with active renal AAV (rAAV) showed significantly higher urinary cell counts than those in remission, or those with extrarenal manifestation, or healthy controls. Urinary T cells showed robust discrimination of disease activity with superior performance compared to MCP-1 and sCD163. Patients whose kidney biopsies had been classified as “crescentic” according to Berden classification showed higher urinary T cell counts. Discordant regulatory T cells (Treg) proportions and CD4+/CD8+ ratio in blood and urine suggested that urinary cells reflect tissue migration rather than mere micro-bleeding. Furthermore, urinary Treg and T helper cells (TH17) patterns were associated with clinical response and risk of renal relapse. CONCLUSION: Urinary T cells reflect the renal inflammatory milieu in AAV and provide further insights into the pathogenesis of this chronic condition. Their promising potential as noninvasive diagnostic and prognostic biomarkers deserves further exploitation

Sharing Is Caring? International Society for Pharmacoepidemiology Review and Recommendations for Sharing Programming Code

Purpose: There is increasing recognition of the importance of transparency and reproducibility in scientific research. This study aimed to quantify the extent to which programming code is publicly shared in pharmacoepidemiology, and to develop a set of recommendations on this topic. Methods: We conducted a literature review identifying all studies published in Pharmacoepidemiology and Drug Safety (PDS) between 2017 and 2022. Data were extracted on the frequency and types of programming code shared, and other key open science practices (clinical codelist sharing, data sharing, study preregistration, and stated use of reporting guidelines and preprinting). We developed six recommendations for investigators who choose to share code and gathered feedback from members of the International Society for Pharmacoepidemiology (ISPE). Results: Programming code sharing by articles published in PDS ranged from 1.8% in 2017 to 9.5% in 2022. It was more prevalent among articles with a methodological focus, simulation studies, and papers which also shared record-level data. Conclusion: Programming code sharing is rare but increasing in pharmacoepidemiology studies published in PDS. We recommend improved reporting of whether code is shared and how available code can be accessed. When sharing programming code, we recommend the use of permanent digital identifiers, appropriate licenses, and, where possible, adherence to good software practices around the provision of metadata and documentation, computational reproducibility, and data privacy.</p

Expectations for time-delay measurements in active galactic nuclei with the Vera Rubin Observatory

The Vera Rubin Observatory will provide an unprecedented set of time-dependent observations of the sky. The planned Legacy Survey of Space and Time (LSST) operating for 10 years will provide dense lightcurves for thousands of active galactic nuclei (AGN) in Deep Drilling Fields (DDFs) and less dense lightcurves for millions of AGN. We model the prospects for measuring time delays for emission lines with respect to the continuum, using these data. We model the artificial lightcurves using Timmer-Koenig algorithm, we use the exemplary cadence to sample them, we supplement lightcurves with the expected contamination by the strong emission lines (Hbeta, Mg II and CIV as well as with Fe II pseudo-continuum and the starlight). We choose the suitable photometric bands appropriate for the redshift and compare the assumed line time delay with the recovered time delay for 100 statistical realizations of the light curves. We show that time delays for emission lines can be well measured from the Main Survey for the bright tail of the quasar distribution (about 15% of all sources) with the accuracy within 1 sigma error, for DDFs results for fainter quasars are also reliable when all 10 years of data are used. There are also some prospects to measure the time delays for the faintest quasars at the smallest redshifts from the first two years of data, and eventually even from the first season. The entire quasar population will allow obtaining results of apparently high accuracy but in our simulations, we see a systematic offset between the assumed and recovered time delay depending on the redshift and source luminosity which will not disappear even in the case of large statistics. Such a problem might affect the slope of the radius-luminosity relation and cosmological applications of quasars if simulations correcting for such effects are not performed.Comment: Submitted to Astronomy & Astrophysics, comments wellcom

Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate

During the late stages of the HIV-1 replication cycle, the viral polyprotein Pr55Gag is recruited to the plasma membrane (PM), where it binds phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and directs HIV-1 assembly. We show that Rab27a controls the trafficking of late endosomes carrying phosphatidylinositol 4-kinase type 2 α (PI4KIIα) toward the PM of CD4+ T cells. Hence, Rab27a promotes high levels of PM phosphatidylinositol 4-phosphate and the localized production of PI(4,5)P2, therefore controlling Pr55Gag membrane association. Rab27a also controls PI(4,5)P2 levels at the virus-containing compartments of macrophages. By screening Rab27a effectors, we identified that Slp2a, Slp3, and Slac2b are required for the association of Pr55Gag with the PM and that Slp2a cooperates with Rab27a in the recruitment of PI4KIIα to the PM. We conclude that by directing the trafficking of PI4KIIα-positive endosomes toward the PM, Rab27a controls PI(4,5)P2 production and, consequently, HIV-1 replication.Fil: Pereyra Gerber, Federico Pehuén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Cabrini, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Jancic, Carolina Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Paoletti, Luciana Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Banchio, Claudia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Von Bilderling, Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Sigaut, Lorena. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Microscopías Avanzadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pietrasanta, Lia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Microscopías Avanzadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Duette, Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Freed, Eric O.. National Cancer Institute at Frederick; Estados UnidosFil: Basile, Genevieve de Saint. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Moita, Catarina Ferreira. Instituto Gulbenkian de Ciencia; PortugalFil: Moita, Luis Ferreira. Instituto Gulbenkian de Ciencia; PortugalFil: Amigorena, Sebastian. Institute Curie; FranciaFil: Benaroch, Philippe. Institute Curie; FranciaFil: Geffner, Jorge Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Ostrowski, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

Headache onset after vaccination against SARS-CoV-2: A systematic literature review and meta-analysis

Background Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to reduce the risk of developing Coronavirus Disease 2019 (COVID-19). Despite the significant benefits in terms of reduced risk of hospitalization and death, different adverse events may present after vaccination: among them, headache is one of the most common, but nowadays there is no summary presentation of its incidence and no description of its main features. Methods We searched PubMed and EMBASE covering the period between January 1(st) 2020 and August 6(th), 2021, looking for record in English and with an abstract and using three main search terms (with specific variations): COVID-19/SARS-CoV-2; Vaccination; headache/adverse events. We selected manuscript including information on subjects developing headache after injection, and such information had to be derived from a structured form (i.e. no free reporting). Pooled estimates and 95% confidence intervals were calculated. Analyses were carried out by vaccine vs. placebo, by first vs. second dose, and by mRNA-based vs. "traditional" vaccines; finally, we addressed the impact of age and gender on post-vaccine headache onset. Results Out of 9338 records, 84 papers were included in the review, accounting for 1.57 million participants, 94% of whom received BNT162b2 or ChAdOx1. Headache was generally the third most common AE: it was detected in 22% (95% CI 18-27%) of subjects after the first dose of vaccine and in 29% (95% CI 23-35%) after the second, with an extreme heterogeneity. Those receiving placebo reported headache in 10-12% of cases. No differences were detected across different vaccines or by mRNA-based vs. "traditional" ones. None of the studies reported information on headache features. A lower prevalence of headache after the first injection of BNT162b2 among older participants was shown. Conclusions Our results show that vaccines are associated to a two-fold risk of developing headache within 7 days from injection, and the lack of difference between vaccine types enable to hypothesize that headache is secondary to systemic immunological reaction than to a vaccine-type specific reaction. Some descriptions report onset within the first 24 h and that in around one-third of the cases, headache has migraine-like features with pulsating quality, phono and photophobia; in 40-60% of the cases aggravation with activity is observed. The majority of patients used some medication to treat headache, the one perceived as the most effective being acetylsalicylic acid

Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients

Misguided Transcriptional Elongation Causes Mixed Lineage Leukemia

Investigation of the activity of a family of fusion proteins that cause aggressive leukemia suggests transcriptional elongation as a new mechanism for oncogenic transformation