Dynamic knee valgus in competitive alpine skiers: Observation from youth to elite and influence of biological maturation

Numerous studies investigated the association between dynamic knee valgus and injury risk in post-pubertal and elite athletes; however, normative reference scores for competitive alpine skiers and observations on the development process throughout and beyond athletes' growth spurt are lacking. Thus, the aim of this study was to describe the dynamic knee valgus of competitive alpine skiers during drop jump landings (DJ) and single-leg squats (SLS) with respect to sex, sportive level, and biological maturation. Thirty-seven elite and 104 youth competitive alpine skiers around the growth spurt (U15) were examined for their maximal medial knee displacement (MKD) during DJ and SLS by a marker-based 3D motion analysis evaluating dynamic knee valgus. Additionally, skiers' age, anthropometry and biological maturation were assessed. MKD of youth and elite alpine skiers during DJ was comparable and did not improve with increasing training age. Female U15 skiers (on average further matured) had significantly larger MKD values during DJ than male U15 skiers (less matured) (P < .01). Moreover, MKD during DJ was directly associated with the athlete's individual biological maturation status. MKD values obtained from DJ significantly differed from those obtained during SLS (P < .01). The gender-specific difference in MKD values during DJ and their relationship with maturity offset highlight the fundamental changes to the neuromuscular control system during the growth spurt. Thus, biological maturation needs to be considered as a confounding factor for knee valgus screening. Caution is required when evaluating MKD by using high- and low-dynamic tasks, as corresponding information can differ.     

Stimulation of retrotrapezoid nucleus Phox2b‐expressing neurons rescues breathing dysfunction in an experimental Parkinson’s disease rat model

Emerging evidence from multiple studies indicates that Parkinson’s disease (PD) patients suffer from a spectrum of autonomic and respiratory motor deficiencies in addition to the classical motor symptoms attributed to substantia nigra degeneration of dopaminergic neurons. Animal models of PD show a decrease in the resting respiratory rate as well as a decrease in the number of Phox2b‐expressing retrotrapezoid nucleus (RTN) neurons. The aim of this study was to determine the extent to which substantia nigra pars compact (SNc) degeneration induced RTN biomolecular changes and to identify the extent to which RTN pharmacological or optogenetic stimulations rescue respiratory function following PD‐induction. SNc degeneration was achieved in adult male Wistar rats by bilateral striatal 6‐hydroxydopamine injection. For proteomic analysis, laser capture microdissection and pressure catapulting were used to isolate the RTN for subsequent comparative proteomic analysis and Ingenuity Pathway Analysis (IPA). The respiratory parameters were evaluated by whole‐body plethysmography and electromyographic analysis of respiratory muscles. The results confirmed reduction in the number of dopaminergic neurons of SNc and respiratory rate in the PD‐animals. Our proteomic data suggested extensive RTN remodeling, and that pharmacological or optogenetic stimulations of the diseased RTN neurons promoted rescued the respiratory deficiency. Our data indicate that despite neuroanatomical and biomolecular RTN pathologies, that RTN‐directed interventions can rescue respiratory control dysfunction.     

Effect of Dapagliflozin in DAPA-HF According to Background Glucose-Lowering Therapy

OBJECTIVETo determine whether the benefits of dapagliflozin in patients with heart failure and reduced ejection fraction (HFrEF) and type 2 diabetes in the Dapagliflozin And Prevention of Adverse-Outcomes in Heart Failure trial (DAPA-HF) varied by background glucose-lowering therapy (GLT).RESEARCH DESIGN AND METHODSWe examined the effect of study treatment by the use or not of GLT and by GLT classes and combinations. The primary outcome was a composite of worsening heart failure (hospitalization or urgent visit requiring intravenous therapy) or cardiovascular death.RESULTSIn the 2,139 type 2 diabetes patients, the effect of dapagliflozin on the primary outcome was consistent by GLT use or no use (hazard ratio 0.72 [95% CI 0.58–0.88] vs. 0.86 [0.60–1.23]; interaction P = 0.39) and across GLT classes.CONCLUSIONSIn DAPA-HF, dapagliflozin improved outcomes irrespective of use or no use of GLT or by GLT type used in patients with type 2 diabetes and HFrEF.     

Detection and evaluation of immunofunction of patients with severe fever with thrombocytopenia syndrome

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS virus (SFTSV) with a high fatality rate. But the immunofunction was still unclear. The objective of our study was to assess the immunofunction in SFTS patients. Immunofunction test with flow cytometry which contains CD3+, CD4+ and CD8+ T lymphocytes, B cells and NK cells would be used for detecting serum samples collected from 34 SFTS cases and 20 healthy donors. We found that CD3+ and CD4+ T lymphocytes were significantly diminished in SFTS compared to normal control. In contrast, the percentage of NK cells was elevated. Further analysis revealed that the number of CD3+ and CD4+ T lymphocytes showed that there was a more robust pattern of depression in acute phase and severe SFTS infection compared to the patients in recovery phase and mild SFTS infection. But NK cells were significantly increased in acute phase and severe SFTS. They reverted to the near normal levels in convalescent phase. Additionally, the levels of CD3+ and CD4+ T lymphocytes progressively decreased in death group when compared with the survival group, but the level of B cells was higher. The damages of immune system were obvious, and the immune dysfunction might be partly responsible for disease progression of patients with SFTSV infection.     

Tractostorm: The what,why, and how of tractography dissection reproducibility

Investigative studies of white matter (WM) brain structures using diffusion MRI (dMRI) tractography frequently require manual WM bundle segmentation, often called “virtual dissection.” Human errors and personal decisions make these manual segmentations hard to reproduce, which have not yet been quantified by the dMRI community. It is our opinion that if the field of dMRI tractography wants to be taken seriously as a widespread clinical tool, it is imperative to harmonize WM bundle segmentations and develop protocols aimed to be used in clinical settings. The EADC‐ADNI Harmonized Hippocampal Protocol achieved such standardization through a series of steps that must be reproduced for every WM bundle. This article is an observation of the problematic. A specific bundle segmentation protocol was used in order to provide a real‐life example, but the contribution of this article is to discuss the need for reproducibility and standardized protocol, as for any measurement tool. This study required the participation of 11 experts and 13 nonexperts in neuroanatomy and “virtual dissection” across various laboratories and hospitals. Intra‐rater agreement (Dice score) was approximately 0.77, while inter‐rater was approximately 0.65. The protocol provided to participants was not necessarily optimal, but its design mimics, in essence, what will be required in future protocols. Reporting tractometry results such as average fractional anisotropy, volume or streamline count of a particular bundle without a sufficient reproducibility score could make the analysis and interpretations more difficult. Coordinated efforts by the diffusion MRI tractography community are needed to quantify and account for reproducibility of WM bundle extraction protocols in this era of open and collaborative science.     

Angiogenesis as a novel component of inflammatory bowel disease pathogenesis

BACKGROUND & AIMS: Angiogenesis is a critical component of neoplastic and chronic inflammatory disorders, but whether angiogenesis also occurs in inflammatory bowel disease (IBD) has yet to be established. We assessed mucosal vascularization, expression of endothelial alphaVbeta3 integrin, angiogenic factors, and their bioactivity in Crohn's disease (CD) and ulcerative colitis (UC) mucosa. METHODS: Mucosal endothelium was immunostained for CD31 and factor VIII and quantified by digital morphometry. alphaVbeta3 expression was studied in vivo by confocal microscopy and in vitro by flow cytometric analysis of human intestinal microvascular endothelial cells (HIMECs). Vascular endothelial growth factor (VEGF), interleukin (IL)-8, and bFGF levels were measured in mucosal extracts and cells and angiogenic bioactivity shown by induction of HIMEC migration and the corneal and chorioallantoic membrane angiogenesis assays. RESULTS: Microvessel density was increased in IBD mucosa. Endothelial alphaVbeta3 was strongly expressed in IBD but only sporadically in normal mucosa and was up-regulated in HIMECs by VEGF, tumor necrosis factor alpha, and bFGF. IBD mucosal extracts induced a significantly higher degree of HIMEC migration than control mucosa, and this response was mostly dependent on IL-8 and less on basic fibroblast growth factor or vascular endothelial growth factor. Compared with normal mucosa, IBD mucosal extracts induced a potent angiogenic response in both the corneal and chorioallantoic membrane assays. CONCLUSIONS: These results provide morphological, phenotypic and functional evidence of potent angiogenic activity in both CD and UC mucosa, indicating that the local microvasculature undergoes an intense process of inflammation-dependent angiogenesis. Thus, angiogenesis appears to be an integral component of IBD pathogenesis, providing the practical and conceptual framework for anti-angiogenic therapies in IBD.     

Relationship between alcohol consumption and hypertension prevalence and control in a French population

Six thousand six hundred thirty two subjects, employed in 420 small and medium-sized companies in the Paris region were examined in a cross-sectional study. Their alcohol consumption, as obtained by interview was found to be higher among males than among females, among workers than among managers, executives, and clerks. Alcohol consumption was positively associated with age, body mass index, coffee and cigarette consumption, occupational exposure to noise and working nights or alternating shifts. A positive, continuous, relationship was observed, for men and women, between alcohol intake and both systolic and diastolic blood pressure. This association was highly significant in the multivariate analysis (multiple linear regression) where alcohol intake, following age and body mass index, was the third predictive factor of blood pressure level in the stepwise regression. The positive association between alcohol consumption and prevalence of arterial hypertension was aggravated by the poor control of hypertension which was found among drinkers. Awareness of hypertension, compliance with an antihypertensive treatment and its efficacy, were negatively associated with alcohol intake. The findings stress the importance of alcohol consumption which was found to be a major risk factor for arterial hypertension and noncompliance with antihypertensive treatment in this population.     

RAB-5 and RAB-10 cooperate to regulate neuropeptide release in Caenorhabditis elegans

Neurons secrete neuropeptides from dense core vesicles (DCVs) to modulate neuronal activity. Little is known about how neurons manage to differentially regulate the release of synaptic vesicles (SVs) and DCVs. To analyze this, we screened all Caenorhabditis elegans Rab GTPases and Tre2/Bub2/Cdc16 (TBC) domain containing GTPase-activating proteins (GAPs) for defects in DCV release from C. elegans motoneurons. rab-5 and rab-10 mutants show severe defects in DCV secretion, whereas SV exocytosis is unaffected. We identified TBC-2 and TBC-4 as putative GAPs for RAB-5 and RAB-10, respectively. Multiple Rabs and RabGAPs are typically organized in cascades that confer directionality to membrane-trafficking processes. We show here that the formation of release-competent DCVs requires a reciprocal exclusion cascade coupling RAB-5 and RAB-10, in which each of the two Rabs recruits the other’s GAP molecule. This contributes to a separation of RAB-5 and RAB-10 domains at the Golgi–endosomal interface, which is lost when either of the two GAPs is inactivated. Taken together, our data suggest that RAB-5 and RAB-10 cooperate to locally exclude each other at an essential stage during DCV sorting.