A naturally occurring 22-amino acid fragment of human hemoglobin A inhibits autophagy and HIV-1.

Autophagy is an evolutionarily ancient catabolic pathway and has recently emerged as an integral part of the innate immune system. While the core machinery of autophagy is well defined, the physiological regulation of autophagy is less understood. Here, we identify a C-terminal fragment of human hemoglobin A (HBA1, amino acids 111-132) in human bone marrow as a fast-acting non-inflammatory inhibitor of autophagy initiation. It is proteolytically released from full-length HBA1 by cathepsin E, trypsin or pepsin. Biochemical characterization revealed that HBA1(111-132) has an in vitro stability of 52 min in human plasma and adopts a flexible monomeric conformation in solution. Structure-activity relationship studies revealed that the C-terminal 13 amino acids of HBA1(120-132) are sufficient to inhibit autophagy, two charged amino acids (D127, K128) mediate solubility, and two serines (S125, S132) are required for function. Successful viruses like human immunodeficiency virus 1 (HIV-1) evolved strategies to subvert autophagy for virion production. Our results show that HBA1(120-132) reduced virus yields of lab-adapted and primary HIV-1. Summarizing, our data identifies naturally occurring HBA1(111-132) as a physiological, non-inflammatory antagonist of autophagy. Optimized derivatives of HBA1(111-132) may offer perspectives to restrict autophagy-dependent viruses.

The C-terminal 32-mer fragment of hemoglobin alpha is an amyloidogenic peptide with antimicrobial properties.

Antimicrobial peptides (AMPs) are major components of the innate immune defense. Accumulating evidence suggests that the antibacterial activity of many AMPs is dependent on the formation of amyloid-like fibrils. To identify novel fibril forming AMPs, we generated a spleen-derived peptide library and screened it for the presence of amyloidogenic peptides. This approach led to the identification of a C-terminal 32-mer fragment of alpha-hemoglobin, termed HBA(111-142). The non-fibrillar peptide has membranolytic activity against various bacterial species, while the HBA(111-142) fibrils aggregated bacteria to promote their phagocytotic clearance. Further, HBA(111-142) fibrils selectively inhibited measles and herpes viruses (HSV-1, HSV-2, HCMV), but not SARS-CoV-2, ZIKV and IAV. HBA(111-142) is released from its precursor by ubiquitous aspartic proteases under acidic conditions characteristic at sites of infection and inflammation. Thus, HBA(111-142) is an amyloidogenic AMP that may specifically be generated from a highly abundant precursor during bacterial or viral infection and may play an important role in innate antimicrobial immune responses.

First-attempt awake tracheal intubation success rate using a hyperangulated unchannelled videolaryngoscope vs. a channelled videolaryngoscope in patients with anticipated difficult airway: a randomised controlled trial.

INTRODUCTION: There is uncertainty about the optimal videolaryngoscope for awake tracheal intubation in patients with anticipated difficult airway. The use of channelled and unchannelled videolaryngoscopy has been reported, but there is a lack of evidence on which is the best option. METHODS: We conducted a randomised clinical trial to compare the efficacy of the C-MAC D-Blade® vs. Airtraq® in adult patients (aged ≥ 18 y) scheduled for elective or emergency surgery under general anaesthesia with anticipated difficult airway who required awake tracheal intubation under local anaesthesia and conscious sedation. The primary endpoint was the first-attempt tracheal intubation success rate. Secondary outcomes included the overall success rate; number of tracheal intubation attempts; Cormack and Lehane glottic view; level of difficulty (visual analogue score); patient discomfort (visual analogue score); and incidence of complications. RESULTS: Ninety patients (70/90 male (78%); mean (SD) age 65 (12) y) with anticipated difficult airways were randomly allocated to C-MAC D-Blade or Airtraq videolaryngoscopy. First-attempt successful tracheal intubation rate was higher in patients allocated to the C-MAC D-Blade group compared with those allocated to the Airtraq group (38/45 (84%) vs. 28/45 (62%), respectively; p = 0.006). The proportion of patients' tracheas that were intubated at the second and third attempt was 4/45 (9%) and 3/45 (7%) in those allocated to the C-MAC D-Blade group compared with 14/45 (31%) and 1/45 (2%) in those allocated to the Airtraq group (p = 0.006). There was no significant difference in overall tracheal intubation success rate (C-MAC D-Blade group 45/45 (100%) vs. Airtraq group 43/45 (96%), p = 0.494). DISCUSSION: In patients with anticipated difficult airway, first-attempt awake tracheal intubation success rate was higher with the C-MAC D-Blade compared with Airtraq laryngoscopy. No difference was found between the two videolaryngoscopes in overall tracheal intubation success rate.

Fourier uniqueness in even dimensions.

In recent work, methods from the theory of modular forms were used to obtain Fourier uniqueness results in several key dimensions ([Formula: see text]), in which a function could be uniquely reconstructed from the values of it and its Fourier transform on a discrete set, with the striking application of resolving the sphere packing problem in dimensions [Formula: see text] and [Formula: see text] In this short note, we present an alternative approach to such results, viable in even dimensions, based instead on the uniqueness theory for the Klein-Gordon equation. Since the existing method for the Klein-Gordon uniqueness theory is based on the study of iterations of Gauss-type maps, this suggests a connection between the latter and methods involving modular forms. The derivation of Fourier uniqueness from the Klein-Gordon theory supplies conditions on the given test function for Fourier interpolation, which are hoped to be optimal or close to optimal.

What do we know About the Usefulness of 18F-FDG PET-CT for the Management of Invasive Fungal Infection? An International Survey.

BACKGROUND: Recent data support 18F-FDG PET-CT for the management of infections in immunocompromised patients, including invasive fungal infection (IFI). However, its role is not well established in clinical practice. We performed an international survey to evaluate the knowledge of physicians about the usefulness of 18F-FDG PET-CT in IFI, in order to define areas of uncertainty. METHODS: An online survey was distributed to infectious diseases working groups in December 2023-January 2024. It included questions regarding access to 18F-FDG PET-CT, knowledge on its usefulness for IFI and experience of the respondents. A descriptive analysis was performed. RESULTS: 180 respondents answered; 60.5% were Infectious Diseases specialists mainly from Spain (52.8%) and Italy (23.3%). 84.4% had access to 18F-FDG PET-CT at their own center. 85.6% considered that 18F-FDG PET-CT could be better than conventional tests for IFI. In the context of IFI risk, 81.1% would consider performing 18F-FDG PET-CT to study fever without a source and around 50% to evaluate silent lesions and 50% to assess response, including distinguishing residual from active lesions. Based on the results of the follow-up 18F-FDG PET-CT, 56.7% would adjust antifungal therapy duration. 60% would consider a change in the diagnostic or therapeutic strategy in case of increased uptake or new lesions. Uncovering occult lesions (52%) and diagnosing/excluding endocarditis (52.7%) were the situations in which 18F-FDG PET-CT was considered to have the most added value. There was a great variability in responses about timing, duration of uptake, the threshold for discontinuing treatment or the influence of immune status. CONCLUSION: Although the majority considered that 18F-FDG PET-CT may be useful for IFI, many areas of uncertainty remain. There is a need for protocolized research to improve IFI management.

An Optimized Peptide Antagonist of CXCR4 Limits Survival of BCR-ABL1-Transformed Cells in Philadelphia-Chromosome-Positive B-Cell Acute Lymphoblastic Leukemia.

Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is characterized by reciprocal chromosomal translocation between chromosome 9 and 22, leading to the expression of constitutively active oncogenic BCR-ABL1 fusion protein. CXC chemokine receptor 4 (CXCR4) is essential for the survival of BCR-ABL1-transformed mouse pre-B cells, as the deletion of CXCR4 induces death in these cells. To investigate whether CXCR4 inhibition also effectively blocks BCR-ABL1-transformed cell growth in vitro, in this study, we explored an array of peptide-based inhibitors of CXCR4. The inhibitors were optimized derivatives of EPI-X4, an endogenous peptide antagonist of CXCR4. We observed that among all the candidates, EPI-X4 JM#170 (referred to as JM#170) effectively induced cell death in BCR-ABL1-transformed mouse B cells but had little effect on untransformed wild-type B cells. Importantly, AMD3100, a small molecule inhibitor of CXCR4, did not show this effect. Treatment with JM#170 induced transient JNK phosphorylation in BCR-ABL1-transformed cells, which in turn activated the intrinsic apoptotic pathway by inducing cJun, Bim, and Bax gene expressions. Combinatorial treatment of JM#170 with ABL1 kinase inhibitor Imatinib exerted a stronger killing effect on BCR-ABL1-transformed cells even at a lower dose of Imatinib. Surprisingly, JM#170 actively killed Sup-B15 cells, a BCR-ABL1+ human ALL cell line, but had no effect on the BCR-ABL1- 697 cell line. This suggests that the inhibitory effect of JM#170 is specific for BCR-ABL1+ ALL. Taken together, JM#170 emerges as a potent novel drug against Ph+ ALL.

Effects of a water-soluble formulation of tylvalosin on disease caused by porcine reproductive and respiratory syndrome virus alone in sows or in combination with Mycoplasma hyopneumoniae in piglets.

BACKGROUND: The effect of a water-soluble formulation of tylvalosin (Aivlosin® 625 mg/g granules) on disease caused by porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae (Mhyop) was investigated in two animal studies. In a PRRSV challenge model in pregnant sows (n = 18), six sows received water medicated at target dose of 5 mg tylvalosin/kg body weight/day from 3 days prior to challenge until the end of gestation. Six sows were left untreated, with a third group remaining untreated and unchallenged. Sows were challenged with PRRSV-2 at approximately 85 days of gestation. Cytokines, viremia, viral shedding, sow reproductive parameters and piglet performance to weaning were evaluated. In a dual infection study (n = 16), piglets were challenged with Mhyop on days 0, 1 and 2, and with PRRSV-1 on day 14 and euthanized on day 24. From day 10 to 20, eight piglets received water medicated at target dose of 20 mg tylvalosin/kg body weight/day and eight piglets were left untreated. Cytokines, viremia, bacteriology and lung lesions were evaluated. RESULTS: In the PRRSV challenge study in pregnant sows, tylvalosin significantly reduced the levels of serum IL-8 (P < 0.001), IL-12 (P = 0.032), TNFα (P < 0.001) and GM-CSF (P = 0.001). IL-8 (P = 0.100) tended to be lower in uterus of tylvalosin sows. All piglets from tylvalosin sows surviving to weaning were PRRSV negative in faecal swabs at weaning compared to 33.3% PRRSV positive piglets from untreated sows (P = 0.08). In the dual challenge study in piglet, tylvalosin reduced serum IL1ß, IL-4, IL-6, IL-8, IL-10, IL-12, IL-1α, IL-13, IL-17A, IL-18, GM-CSF, TGFß1, TNFα, CCL3L1, MIG, PEPCAM-1 (P < 0.001) and increased serum IFNα, IL-1ra and MIP-1b (P < 0.001). In the lungs, tylvalosin reduced IL-8, IL-10 and IL-12 compared to untreated pigs (P < 0.001) and tended to reduce TNFα (P = 0.082). Lung lavage samples from all tylvalosin treated piglets were negative for Mhyop (0 cfu/mL) compared to the untreated piglets which had mean Mhyop counts of 2.68 × 104 cfu/mL (P = 0.023). CONCLUSION: Overall, tylvalosin reduced both local and systemic proinflammatory cytokines after challenge with respiratory pathogens in sows and in piglets. Tylvalosin was effective in reducing Mhyop recovery from the lungs and may reduce virus shedding in piglets following transplacental PRRSV infection in sows.

The Influence of Pitch Dimensions during Small-Sided Games to Reach Match Physical and Physiological Demands on the Youth Soccer Players.

The aims of this study were to (i) analyze the physical and physiological responses of four matches competition and (ii) to investigate the relationships among three different pitch dimensions of small-sided game (SSG) on the youth soccer players. Fifteen male U19 soccer players (age 17.3 ± 0.5 years, height 175.7 ± 5.6 cm, weight 68.5 ± 8.6 kg, playing experience 7.8 ± 1.4 years) were randomly assigned to three play areas: small (50 m2), medium (SSG-m, 150 m2) and large (SSG-l, 250 m2) area per player including goalkeeper. During the 4-week intervention, both groups performed three sets of 8 min with a passive rest period of 5 min between games. Differences in time-motion characteristics of players were measured with the Global Positioning System and assessed using a repeated measures ANOVA to compare the three game conditions and the magnitude-based inference to evaluate the pairwise comparison effects. The results showed that only the variables distance covered between 7.0-12.9 km·h-1 was not statistically significantly different among game conditions (p < 0.05; η = 0.21; small) and physiological response (i.e., hear rate of playing time spent 85-89% HRmax) also showed differences (p < 0.05; η = 0.25; small). The responses in SSG-m and SSG-l established them ass the format sizes ideal for replicating the physical responses during match competition. These findings could provide relevant information for coaches for use adequate pitch size (areas of 150 m2 and 250 m2) to reach the match-play scenarios found in match competition.

Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review.

The ongoing pandemic of COVID-19 has caused more than 6.7 million tragic deaths, plus, a large percentage of people who survived it present a myriad of chronic symptoms that last for at least 6 months; this has been named as long COVID. Some of the most prevalent are painful symptoms like headache, joint pain, migraine, neuropathic-like pain, fatigue and myalgia. MicroRNAs are small non-coding RNAs that regulate genes, and their involvement in several pathologies has been extensively shown. A deregulation of miRNAs has been observed in patients with COVID-19. The objective of the present systematic review was to show the prevalence of chronic pain-like symptoms of patients with long COVID and based on the expression of miRNAs in patients with COVID-19, and to present a proposal on how they may be involved in the pathogenic mechanisms of chronic pain-like symptoms. A systematic review was carried out in online databases for original articles published between March 2020 to April 2022; the systematic review followed the PRISMA guidelines, and it was registered in PROSPERO with registration number CRD42022318992. A total of 22 articles were included for the evaluation of miRNAs and 20 regarding long COVID; the overall prevalence of pain-like symptoms was around 10 to 87%, plus, the miRNAs that were commonly up and downregulated were miR-21-5p, miR-29a,b,c-3p miR-92a,b-3p, miR-92b-5p, miR-126-3p, miR-150-5p, miR-155-5p, miR-200a, c-3p, miR-320a,b,c,d,e-3p, and miR-451a. The molecular pathways that we hypothesized to be modulated by these miRNAs are the IL-6/STAT3 proinflammatory axis and the compromise of the blood-nerve barrier; these two mechanisms could be associated with the prevalence of fatigue and chronic pain in the long COVID population, plus they could be novel pharmacological targets in order to reduce and prevent these symptoms.

Antiangiogenic Effect of Dopamine and Dopaminergic Agonists as an Adjuvant Therapeutic Option in the Treatment of Cancer, Endometriosis, and Osteoarthritis.

Dopamine (DA) and dopamine agonists (DA-Ag) have shown antiangiogenic potential through the vascular endothelial growth factor (VEGF) pathway. They inhibit VEGF and VEGF receptor 2 (VEGFR 2) functions through the dopamine receptor D2 (D2R), preventing important angiogenesis-related processes such as proliferation, migration, and vascular permeability. However, few studies have demonstrated the antiangiogenic mechanism and efficacy of DA and DA-Ag in diseases such as cancer, endometriosis, and osteoarthritis (OA). Therefore, the objective of this review was to describe the mechanisms of the antiangiogenic action of the DA-D2R/VEGF-VEGFR 2 system and to compile related findings from experimental studies and clinical trials on cancer, endometriosis, and OA. Advanced searches were performed in PubMed, Web of Science, SciFinder, ProQuest, EBSCO, Scopus, Science Direct, Google Scholar, PubChem, NCBI Bookshelf, DrugBank, livertox, and Clinical Trials. Articles explaining the antiangiogenic effect of DA and DA-Ag in research articles, meta-analyses, books, reviews, databases, and clinical trials were considered. DA and DA-Ag have an antiangiogenic effect that could reinforce the treatment of diseases that do not yet have a fully curative treatment, such as cancer, endometriosis, and OA. In addition, DA and DA-Ag could present advantages over other angiogenic inhibitors, such as monoclonal antibodies.

Towards an approach of disability along a continuum from robustness, pre-frailty, frailty to disability.

BACKGROUND: frailty and disability are very prevalent in older age and although both are distinct clinical entities, they are commonly used indistinctly in order to identify vulnerable older adults. OBJECTIVE: to propose a hierarchical indicator between frailty and disability among older adults along a single continuum. DESIGN: population-based cohort study. SETTING: the Bordeaux Three-City Study and the Aging Multidisciplinary Investigation (AMI) cohort. SUBJECTS: the sample included 1800 participants aged 65 and older. METHODS: an additive hierarchical indicator was proposed by combining the phenotype of frailty (robustness, pre-frailty and frailty), instrumental activities of daily living (IADL) and basic activities of daily living (ADL). To test the relevance of this indicator, we estimated the 4-year mortality risk associated with each stage of the indicator. RESULTS: in total, 34.0% were Robust (n = 612), 29.9% were Pre-frail (n = 538), 3.2% were Robust with IADL-disability (n = 58), 4.6% had pure Frailty (no disability) (n = 82), 11.9% were Pre-frail + IADL (n = 215), 8.6% were Frail + IADL (n = 154) and 7.8% Frail + IADL + ADL (n = 141). After grouping grades with similar mortality risks, we obtained a five-grade hierarchical indicator ranging from robustness to severe stage of the continuum. Each state presented a gradually increasing risk of dying compared to the robust group (from Hazard Ratio (HR) = 2.20 [1.49-3.25] to 15.10 [9.99-22.82]). CONCLUSIONS: We confirmed that combining pre-frailty, frailty, IADL- and ADL-disability into a single indicator may improve our understanding of the aging process. Pre-frailty identified as the 'entry door' into the process may represent a key stage that could offer new opportunities for early, targeted, individualized and tailored interventions and care in clinical geriatrics.

Advanced EPI-X4 Derivatives Covalently Bind Human Serum Albumin Resulting in Prolonged Plasma Stability.

Advanced derivatives of the Endogenous Peptide Inhibitor of CXCR4 (EPI-X4) have shown therapeutic efficacy upon topical administration in animal models of asthma and dermatitis. Here, we studied the plasma stability of the EPI-X4 lead compounds WSC02 and JM#21, using mass spectrometry to monitor the chemical integrity of the peptides and a functional fluorescence-based assay to determine peptide function in a CXCR4-antibody competition assay. Although mass spectrometry revealed very rapid disappearance of both peptides in human plasma within seconds, the functional assay revealed a significantly higher half-life of 9 min for EPI-X4 WSC02 and 6 min for EPI-X4 JM#21. Further analyses demonstrated that EPI-X4 WSC02 and EPI-X4 JM#21 interact with low molecular weight plasma components and serum albumin. Albumin binding is mediated by the formation of a disulfide bridge between Cys10 in the EPI-X4 peptides and Cys34 in albumin. These covalently linked albumin-peptide complexes have a higher stability in plasma as compared with the non-bound peptides and retain the ability to bind and antagonize CXCR4. Remarkably, chemically synthesized albumin-EPI-X4 conjugates coupled by non-breakable bonds have a drastically increased plasma stability of over 2 h. Thus, covalent coupling of EPI-X4 to albumin in vitro before administration or in vivo post administration may significantly increase the pharmacokinetic properties of this new class of CXCR4 antagonists.

Comparison of training and match load between metabolic and running speed metrics of professional Spanish soccer players by playing position.

The aims of this study were to compare the training and match load of professional soccer players according to the playing position, and analyse the relationship between the metabolic and running speed metrics. Thirty professional male soccer players belonging to a Spanish First Division team were analysed using global positioning system devices (GPEXE Pro 18.18 Hz) during training and competition (n = 36 training weeks and n = 41 matches). The results showed significant differences between positions on match day; central midfielders covered higher total distance and low- and medium-speed running distance (moderate to large effect size) than central defenders, external defenders and forwards; forwards performed more metabolic power events than central defenders, central midfielders and wide midfielders; and central defenders showed the lowest very-high-speed running. Different patterns were observed in training. Furthermore, the equivalent-distance index showed a strong correlation with accelerations and decelerations events. The main findings were that the physical responses found in training did not correspond with match demands by position; both metabolic and traditional approaches should be used together for load monitoring in professional soccer players; and finally, metabolic power events and the equivalent-distance index seem to be variables that help to differentiate more clearly the characteristics of the player, taking into account their playing position.

A New Approach for Training-load Quantification in Elite-level Soccer: Contextual Factors.

The aims of this study were to analyse the physical responses of professional soccer players during training considering the contextual factors of match location, season period, and quality of the opposition; and to establish prediction models of physical responses during training sessions. Training data was obtained from 30 professional soccer players from Spanish La Liga using global positioning technology (N=1365 performances). A decreased workload was showed during training weeks prior to home matches, showing large effects in power events, equivalent distance, total distance, walk distance and low-speed running distance. Also, the quality of the opposition also affected the training workload (p<0.05). All regression-models showed moderate effects, with an adjusted R2 of 0.37 for metabolic-work, 0.34 for total distance covered, 0.25 for high-speed running distance (18-21 km·h-1), 0.29 for very high-speed running distance (21-24 km·h-1), 0.22 for sprint running distance (>24 km·h-1) and 0.34 for equivalent distance. The main finding of this study was the great association of match location, season period and quality of opposition on the workload performed by players in the training week before the match; and the development of workload prediction-models considering these contextual factors, thus proposing a new and innovative approach to quantify the workload in soccer.

Internal and External Loads in Training Week Before the Competition in U19 High-Level Soccer Players.

ABSTRACT: Martín-López, Á, Mendes, RS, and Castillo-Rodríguez, A. Internal and external loads in training week before the competition in U19 high-level soccer players. J Strength Cond Res 35(6): 1766-1772, 2021-Nowadays, the information about the load in training sessions (TRs) and the relationship of these TRs with official competition are necessary to gain the sport success in soccer. The aim of this study was to quantify the different loads in TRs according to days before the competition (P-4, P-2, and P-1) on soccer players U19 based on their playing position and their sport success. Twenty-four male Spanish high-level players (age: 16.5 ± 0.5 years; height: 1.69 ± 0.04 m; and body mass: 63.0 ± 6.3 kg) participated in the study. They were grouped according to their playing position: external defenders, internal defenders (ID), external midfielders, internal midfielders (IM), and forwards (FO). To conduct the study, global positioning system technology was used, and a 1-way analysis of variance and Pearson correlation were performed. The main results revealed that the highest physical and physiological responses in the TRs were shown by ID, IM, and players without sport success (p < 0.05), and during P-2. In addition, sport success is predicted by the mean heart rate (R2 = 0.33; p < 0.001). As conclusion, players covering central positions in the playing field performed higher physical and physiological demands than players covering exterior or forward positions. Furthermore, physical and physiological responses during the TRs P-2 may be similar to the responses produced in competition match and are notably different depending on the sport success of the soccer player.

Acute administration of levetiracetam in tonic pain model modulates gene expression of 5HT1A and 5HT7 receptors in the thalamus of rats (Rattus norvergicus).

The nociceptive effect of Levetiracetam (LEV) on the expression of 5-HT1A and 5-HT7 receptors found in the thalamus was evaluated. Thirty-six male rats (Wistar) were randomized into six groups: in the Control group without treatment; LEV50 group LEV was administered in a single dose of 50 mg/kg i.g.; in the LEV300 group LEV dose of 300 mg/kg i.g.; in the FORMALIN group the formalin test was performed; in the LEV50/FORMALIN group LEV dose of 50 mg/kg i.g and the formalin test was performed; in the LEV300/FORMALIN group LEV dose of 300 mg/kg i.g and the formalin test was performed, subsequently the thalamus was dissected in all groups. In the formalin tests LEV exhibited an antinociceptive effect in the LEV300/FORMALIN group (p < 0.05) and a pronociceptive effect in the LEV50/FORMALIN group (p < 0.001). The results obtained by Real-time PCR confirmed the expression of the 5-HT1A and 5-HT7 receptors in the thalamus, 5-HT1A receptors increased significantly in the FORMALIN group and the LEV300/FORMALIN group (p < 0.05). 5-HT7 receptors are only over expressed at a dose of 300 mg/Kg of LEV with formalin (p < 0.05). This suggests that LEV modulates the sensation of pain by controlling the expression of 5-HT1A and 5-HT7 in a tonic pain model, and that changes in the expression of 5-HT1A and 5-HT7 receptors are associated with the sensation of pain, furthermore its possibility to be used in clinical treatments for pain.

The disability process: is there a place for frailty?

BACKGROUND: frailty and disability are very common in older adults; they share some risk factors and pathophysiological mechanisms. Yet, they are different clinical entities. OBJECTIVES: this study aimed to explore a potential hierarchical relationship between frailty and disability along the continuum of the disablement process. DESIGN: prospective cohort study. SETTING: the French Three-City (3C) study. SUBJECTS: the sample included 943 participants aged 75 and older. METHODS: the Fried frailty phenotype, Instrumental Activities of Daily Living (IADL) and basic Activities of Daily Living (ADL) were used. We distinguished between four mutually excluding groups: (i) robust (no frailty and no disability); (ii) pure frailty (no disability); (iii) frailty with IADL disability (no ADL disability) and (iv) frailty with IADL and ADL disabilities. We used Cox's regression models to study the 4-year mortality risk associated with each status. RESULTS: Eight-two per cent of participants were classified according to the assumed hierarchy: 61.3% was robust, 5.4% frail, 10.5% frail and IADL-disabled and 4.8% frail, IADL and ADL-disabled. An extra group of 17% was identified with IADL-disabled individuals without frailty. This extra group was similar to pure frailty in terms of characteristics and risk of death, placing them along the continuum at an intermediate stage between robustness and the two most disabled sub-groups. CONCLUSIONS: our findings suggest that including frailty along the continuum could be relevant to describe the whole disablement process. Frailty would occur upstream of the process and might be relevant to identify an opportune time window, where specific monitoring and clinical interventions could be implemented in order to interrupt the process at a potentially more reversible stage.

A dysfunctional family environment and a high body fat percentage negatively affect telomere length in Mexican boys aged 8-10 years.

AIM: The aim of this study was to determine whether a direct relationship existed between absolute telomere length (aTL), obesity and familial functionality in a group of Mexican children. METHODS: We recruited 134 children (52% boys) aged 8-10 years during regular primary care check-ups in 2016 and evaluated physical activity (PA), feeding practices, anthropometrics, body fat percentage (BF%) and family dysfunction. Optimised quantitative PCR determined aTL from genomic deoxyribonucleic acid isolated from saliva samples. RESULTS: Boys with a healthy BF% showed a higher aTL than their high BF% counterparts (P < .01). aTL was higher in children who performed PA than their sedentary counterparts (P < .05). Alarmingly, 90% of the children belonged to dysfunctional families and a dysfunctional family was correlated with a higher BF% (r = -.57). Negative correlations between the BF% and aTL (r = -.1765) and the BF% and time dedicated to PA (r = -.031) were observed in boys. On the contrary, we found a positive correlation between the aTL and weekly PA (r = .1938). These correlations were not observed in girls. CONCLUSION: Telomere shortening was associated with a high BF% in boys, but not girls. Dysfunctional families were also a key factor. School PA programmes should be mandatory.

Lumen area change (Delta Lumen) between inspiratory and expiratory multidetector computed tomography as a measure of severe outcomes in asthmatic patients.

BACKGROUND: Quantitative computed tomographic (QCT) biomarkers of airway morphology hold potential for understanding and monitoring regional airway remodeling in asthmatic patients. OBJECTIVE: We sought to determine whether the change in airway lumen area between total lung capacity (TLC) and functional residual capacity (FRC) lung volumes measured from CT imaging data was correlated with severe outcomes in asthmatic patients. METHODS: We studied 152 asthmatic patients (90 female and 62 male patients) and 33 healthy subjects (12 female and 21 male subjects) using QCT. Postprocessing of airways at generations 1 to 5 (1 = trachea) was performed for wall area percentage, wall thickness percentage (WT%), lumen area at baseline total lung capacity (LATLC), lumen area at baseline functional residual capacity (LAFRC), and low attenuation area at FRC. A new metric (reflecting remodeling, distal air trapping, or both), Delta Lumen, was determined as follows: Percentage difference in lumen area (LATLC - LAFRC)/LATLC × 100. RESULTS: Postprocessing of 4501 airway segments was performed (3681 segments in the 152 patients with asthma and 820 segments in the 33 healthy subjects; range, 17-28 segments per subject). Delta Lumen values were negatively correlated with WT% and low attenuation area (P < .01) in asthmatic patients. Delta Lumen values were significantly lower for airway generations 3 to 5 (segmental airways) in subjects undergoing hospitalization because of exacerbation and in patients with refractory asthma requiring treatment with systemic corticosteroids. WT% and low attenuation area were positively and Delta Lumen values were negatively associated with systemic corticosteroid treatment (P < .05), suggesting that a reduced Delta Lumen value is a potential outcome biomarker in patients with severe asthma. CONCLUSION: Reduced Delta Lumen value in the central airways measured by using QCT is a promising exploratory biomarker of unstable refractory asthma that warrants further study.

Somatotype and Body Composition in Young Soccer Players According to the Playing Position and Sport Success.

Cárdenas-Fernández, V, Chinchilla-Minguet, JL, and Castillo-Rodríguez, A. Somatotype and body composition in young soccer players according to the playing position and sport success. J Strength Cond Res 33(7): 1904-1911, 2019-Soccer players undergo an evolution in their body composition throughout the growth and passage through the different base stages, that is, childhood, puberty, and adolescence. The aim of this study was to analyze the morphology and body composition of U14, U16, and U19 soccer players, taking into account in addition, their sport success endorsed through the regularity participation and their relation with the different playing positions occupied during competition (goalkeeper, external defender, central defender, midfielder, and forward/extreme). For that, a total of 174 male young soccer players were evaluated anthropometrically. Dominant somatotype of the players was, according to their playing position, meso-endomorphic in goalkeepers, central for external defenders, balanced ectomorph in central defenders, balanced mesomorph in the case of midfielders, and meso-ectomorph in forwards/extremes. Taking into account that sport performance is directly mediated by the body composition of athletes, the differences found suggest a marked specialization between the goalkeepers and forwards, establishing significant differences between them. Further studies would be needed to evaluate the influence of individual maturation development vs. sports training on the conformation of a certain anthropometric profile of a soccer player and its relation with the different playing positions occupied on the pitch during the game.