Effects of a similar amount of regular non-structured or competitive physical activity across late adulthood: a cross-sectional study.

Introduction: Master athletes are examples of successful aging. It is not clear whether it is the competitive-oriented training or just the amount of total regular exercise that reduces the age-related decline in physiological functions. We aimed to compare health-related parameters in competitive (C) and physically active older adults (A) that performed the same weekly physical activity (PA) amount. Methods: Seventeen C and 17 A were matched for age (8 and 9 male participants under and over 70 years old respectively, for both groups) and weekly PA amount (GPAQ). Body composition, leg and arm maximal strength, balance and reaction time were measured; moreover, leg and arm exercise efficiency, estimated VO2max, and VO2/HR relationships were evaluated. Perception of life and sleep quality was also assessed through specific questionnaires (SF-36 and PSQI). The effect of group (C vs. A), age (U70 vs. O70) and their interaction was examined through a Two-Way ANOVA test. Results: C dedicated more time to vigorous PA compared to A (p = 0.03), while less to moderate daily work (p < 0.01) and active commuting (p = 0.06). C exhibited better body composition (all p < 0.05), higher leg maximal strength (p < 0.05) and a trend for elevated arm strength (p = 0.06). Reaction time, leg and arm cycling efficiency were similar in the two groups (all p > 0.05), while balance reduced in A O70. Estimated VO2max was higher for C in leg cycling (p = 0.05) and remained constant across ages (all p > 0.05). VO2/HR relationship, life and sleep quality did not differ for groups and ages. Conclusions: Regular physical exercise of about 6,000 METs/week seems to have a beneficial effect on health-related parameters, both in non-structured and competitive PA, when compared to sedentary behaviour. However, the older adults engaged in competitive training exhibit further advantages: better body composition, higher arm and leg muscle strength, and higher leg VO2max. This study highlights the importance of encouraging active lifestyles for maintaining long-term health, high levels of life quality perception and reducing age-related decline. However, vigorous training suitability needs to be verified by a team of PA specialists.

A cross-sectional study evaluating the exercise discussion with oncologist during cancer consultation: the CONNECT study.

BACKGROUND: Evidence demonstrates that physical exercise confers several psycho-physical benefits on patients with cancer. This study aims to investigate the role of oncologists in exercise promotion. PATIENTS AND METHODS: A multicenter, cross-sectional study was conducted by distributing an anonymous, self-administered questionnaire to patients with cancer. The questionnaire enclosed demographic, health, and exercise variables. The exercise-related questions included in the study used the Godin-Shephard Leisure-Time Physical Activity Questionnaire to measure the amount of physical exercise. In addition, the survey gathered information on whether exercise was discussed with patients, and whether oncologists followed the assess, advise, reinforce, and refer (AARR) process regarding exercise. The survey also asked if patients preferred that exercise be discussed during their consultations. Descriptive statistics and logistic regression were applied. RESULTS: With a response rate of 75%, a total of 549 patients completed the survey. Regarding the exercise discussion, 38% of patients stated that their oncologist initiated an exercise discussion, 14% started the discussion themselves, and 48% said that the issue was not considered. Overall, 35% of patients reported that the oncologist assessed their exercise level, 22% and 42% received advice or reinforcement to increase their exercise, respectively, and 10% were referred to a dedicated service. Regarding preferences, 72% of patients thought that the oncologists should initiate an exercise discussion, 2% that only patients should start the discussion, and 26% thought that the issue should not be discussed. Similarly, 74% of patients are willing to receive the exercise assessment, 59% and 75% the advice and reinforcement to increase their exercise, and 46% to be referred to an exercise service. CONCLUSIONS: Although exercise promotion rates are low, patients are willing to receive exercise information. Dedicated strategies should be developed to support oncologists in promoting exercise to their patients.

Independent, additive and interactive effects of acute normobaric hypoxia and cold on submaximal and maximal endurance exercise.

PURPOSE: To evaluate the independent and combined effects of hypoxia (FiO2 = 13.5%) and cold (- 20 °C) on physiological and perceptual responses to endurance exercise. METHODS: 14 trained male subjects ( V . O2max: 64 ± 5 mL/kg/min) randomly performed a discontinuous maximal incremental test to exhaustion on a motorized treadmill under four environmental conditions: Normothermic-Normoxia (N), Normothermic-Hypoxia (H), Cold-Normoxia (C) and Cold-Hypoxia (CH). Performance and physiological and perceptual responses throughout exercise were evaluated. RESULTS: Maximal WorkLoad (WL) and WL at lactate threshold (LT) were reduced in C (- 2.3% and - 3.5%) and H (- 18.0% and - 21.7%) compared to N, with no interactive (p = 0.25 and 0.81) but additive effect in CH (- 21.5% and - 24.6%). Similarly, HRmax and Vemax were reduced in C (- 3.2% and - 14.6%) and H (- 5.0% and - 7%), showing additive effects in CH (- 7.7% and - 16.6%). At LT, additive effect of C (- 2.8%) and H (- 3.8%) on HR reduction in CH (- 5.7%) was maintained, whereas an interactive effect (p = 0.007) of the two stressors combined was noted on Ve (C: - 3.1%, H: + 5.5%, CH: - 10.9%). [La] curve shifted on the left in CH, displaying an interaction effect between the 2 stressors on this parameter. Finally, RPE at LT was exclusively reduced by hypoxia (p < 0.001), whereas TSmax is synergistically reduced by cold and hypoxia (interaction p = 0.047). CONCLUSION: If compared to single stress exposure, exercise performance and physiological and perceptual variables undergo additive or synergistic effects when cold and hypoxia are combined. These results provide new insight into human physiological responses to extreme environments.

Comparison between conventional and neuronavigated strategies to assess corticospinal responsiveness in unfatigued and fatigued knee-extensor muscles.

In studying neuromuscular fatigability, researchers commonly use functional criteria to position and hold the transcranial magnetic stimulation (TMS) coil during testing sessions. This could influence the magnitude of corticospinal excitability and inhibition responses due to imprecise and unsteady positions of the coil. To reduce coil position and orientation variability, neuronavigated TMS (nTMS) could be used. We evaluated the accuracy of nTMS and a standardized function-guided procedure for maintaining TMS coil position both in unfatigued and fatigued knee extensors. Eighteen participants (10F/8M) volunteered in two identical and randomized sessions. Maximal and submaximal neuromuscular evaluations were performed with TMS three times before (PRE_1) and three times after (PRE_2) a 2 min resting session and one time immediately after (POST) a 2-min sustained maximal voluntary isometric contraction (MVIC). The located "hotspot" [the location that evoked the largest motor-evoked potential (MEP) responses in the rectus femoris] was maintained either with or without nTMS. MEP, silent period (SP) and the distance between the "hotspot" and the actual coil position were recorded. A time × contraction intensity × testing session × muscle interaction was not observed for MEP, SP, and distance. Bland-Altman plots presented adequate agreements for MEP and SP. Spatial accuracy of TMS coil position over the motor cortex did not influence corticospinal excitability and inhibition in unfatigued and fatigued knee extensors. The variability in MEP and SP responses may be due to spontaneous fluctuations in corticospinal excitability and inhibition, and it is not altered by the spatial stability of the stimulation point.

Uphill versus downhill high-intensity training effectiveness in preserving vascular function and exercise performance in runners who reduce their regular endurance training.

Purpose: The COVID-19 restrictions have limited outdoor physical activities. High-intensity training (HIT) may be a valid indoor alternative. We tested whether an indoor HIT is effective in maintaining vascular function and exercise performance in runners who reduce their usual endurance training, and whether a downhill HIT is as effective as an uphill one for such purposes. Methods: Sixteen runners performed the same 6-week HIT either uphill (UP, eight runners) or downhill (DOWN, eight runners). Eight runners continuing their usual endurance training acted as a control group (CON). The following data were collected before vs after our HIT: vascular conductance during rapid leg vasodilation to assess vasodilation capacity; V̇O2max through running incremental test to exhaustion; 2000 m running time; neuromuscular indexes related to lower-limb muscle strength. Results: Both uphill and downhill HIT failed in maintaining the pre-HIT leg vasodilation capacity compared to CON, which was, however, blunted more after uphill than downhill HIT. V̇O2max and 2000 m time were similar after downhill HIT compared to CON, and augmented after uphill HIT compared to CON and DOWN. Indexes of lower-limb muscle strength were similar before vs after HIT and among groups. Conclusion: Our HIT was ineffective in maintaining the pre-HIT leg vasodilation capacity compared to runners continuing their usual low-intensity endurance training, but did not lead to reductions in V̇O2max, 2000 m time performance, and indexes related to lower-limb muscle strength. Our data show an appealing potential for preserving exercise performance with low cardiorespiratory effort via downhill running.

NMR-based metabolomic study of Apulian Coratina extra virgin olive oil extracted with a combined ultrasound and thermal conditioning process in an industrial setting.

The innovative combination of ultrasound (Us) with a thermal exchanger to produce high quality extra virgin olive oil (EVOO) was studied using Nuclear Magnetic Resonance (NMR) spectroscopy and multivariate analysis (MVA). Major and minor metabolomic components of Apulian Coratina EVOO obtained using the two methods were compared. Early and late olive ripening stages were also considered. An increased amount of polyphenols was found for EVOOs obtained using the Us with respect to the conventional method for both early and late ripening stages (900.8 ± 10.3 and 571.9 ± 9.9 mg/kg versus 645.1 ± 9.3 and 440.8 ± 10.4 mg/kg). NMR spectroscopy showed a significant increase (P < 0.05) in polyunsaturated fatty acids (PUFA) as well as in the tyrosol and hydroxytyrosol derivatives, such as oleocanthal, oleacein, and elenolic acid, for both ripening stages. In conclusion, NMR spectroscopy provides information about the metabolomic components of EVOOs to producers, while the Us process increases the levels of healthy bioactive components.

Walking for subjects with type 2 diabetes: A systematic review and joint AMD/SID/SISMES evidence-based practical guideline.

AIMS: Regular exercise is considered a cornerstone in the management of type 2 diabetes mellitus (T2DM). It improves glucose control and cardiovascular risk factors, contributes to weight loss, and also improves general well-being, likely playing a role in the prevention of chronic complications of diabetes. However, compliance to exercise recommendations is generally inadequate in subjects with T2DM. Walking is the most ancestral form of physical activity in humans, easily applicable in daily life. It may represent, in many patients, a first simple step towards lifestyle changes. Nevertheless, while most diabetic patients do not engage in any weekly walking, exercise guidelines do not generally detail how to improve its use. The aims of this document are to conduct a systematic review of available literature on walking as a therapeutic tool for people with T2DM, and to provide practical, evidence-based clinical recommendations regarding its utilization in these subjects. DATA SYNTHESIS: Analysis of available RCTs proved that regular walking training, especially when supervised, improves glucose control in subjects with T2DM, with favorable effects also on cardiorespiratory fitness, body weight and blood pressure. Moreover, some recent studies have shown that even short bouts of walking, used for breaking prolonged sitting, can ameliorate glucose profiles in diabetic patients with sedentary behavior. CONCLUSIONS: There is sufficient evidence to recognize that walking is a useful therapeutic tool for people with T2DM. This document discusses theoretical and practical issues for improving its use. This article is co-published in the journals Sport Sciences for Health and Nutrition, Metabolism and Cardiovascular Diseases.

Management of the mother-infant dyad with suspected or confirmed SARS-CoV-2 infection in a highly epidemic context.

In the context of SARS-CoV-2 pandemic, the hospital management of mother-infant pairs poses to obstetricians and neonatologists previously unmet challenges. In Lombardy, Northern Italy, 59 maternity wards networked to organise the medical assistance of mothers and neonates with suspected or confirmed SARS-CoV-2 infection. Six "COVID-19 maternity centres" were identified, the architecture and activity of obstetric and neonatal wards of each centre was reorganised, and common assistance protocols for the management of suspected and proven cases were formulated. Here, we present the key features of this reorganization effort, and our current management of the mother-infant dyad before and after birth, including our approach to rooming-in practice, breastfeeding and neonatal follow-up, based on the currently available scientific evidence. Considered the rapid diffusion of COVID-19 all over the world, we believe that preparedness is fundamental to assist mother-infant dyads, minimising the risk of propagation of the infection through maternity and neonatal wards.

From the bench to practice - Field integration of community-based services for older citizens with different levels of functional limitation across European Regions.

The meeting of the European Innovation Partnership on Active and Healthy Ageing (EIPonAHA) action group A3 together with members of the Reference site collaborative network (RSCN) in December 2019 in Rome focused on integration of evidence-based approaches on health and care delivery for older citizens at different levels of needs with expertise coming from stakeholder across Europe. It was the final aim of the group to co-create culturally sensitive pathways and facilitate co-ownership for further implementation of the pathways in different care systems across Europe. The study design is a mixed method approach. Based on data analysis from a cohort of community-dwelling over-65 citizens in the framework of a longitudinal observational study in Rome, which included health, social and functional capacity data, three personas profiles were developed: the pre-frail, the frail and the very frail personas. Based on these data, experts were asked to co-create care pathways due to evidence and eminence during a workshop and included into a final report. All working groups agreed on a common understanding that integration of care means person-centered integration of health and social care, longitudinally provided across primary and secondary health care including citizens' individual social, economic and human resources. Elements for consideration during care for pre-frail people are loneliness and social isolation, which, lead to limitation of physical autonomy in the light of reduced access to social support. Frail people need adaption of environmental structures and, again, social resource allocation to maintain at home. Very frail are generally vulnerable patients with complex needs. Most of them remain at home because of a strong individual social support and integrated health care delivery. The approach described in this publication may represent a first approach to scaling-up care delivery in a person-centered approach.

Increased Gene Expression of RUNX2 and SOX9 in Mesenchymal Circulating Progenitors Is Associated with Autophagy during Physical Activity.

Lack of physical exercise is considered an important risk factor for chronic diseases. On the contrary, physical exercise reduces the morbidity rates of obesity, diabetes, bone disease, and hypertension. In order to gain novel molecular and cellular clues, we analyzed the effects of physical exercise on differentiation of mesenchymal circulating progenitor cells (M-CPCs) obtained from runners. We also investigated autophagy and telomerase-related gene expression to evaluate the involvement of specific cellular functions in the differentiation process. We performed cellular and molecular analyses in M-CPCs, obtained by a depletion method, of 22 subjects before (PRE RUN) and after (POST RUN) a half marathon performance. In order to prove our findings, we performed also in vitro analyses by testing the effects of runners' sera on a human bone marrow-derived mesenchymal stem (hBM-MSC) cell line. PCR array analyses of PRE RUN versus POST RUN M-CPC total RNAs put in evidence several genes which appeared to be modulated by physical activity. Our results showed that physical exercise promotes differentiation. Osteogenesis-related genes as RUNX2, MSX1, and SPP1 appeared to be upregulated after the run; data showed also increased levels of BMP2 and BMP6 expressions. SOX9, COL2A1, and COMP gene enhanced expression suggested the induction of chondrocytic differentiation as well. The expression of telomerase-associated genes and of two autophagy-related genes, ATG3 and ULK1, was also affected and correlated positively with MSC differentiation. These data highlight an attractive cellular scenario, outlining the role of autophagic response to physical exercise and suggesting new insights into the benefits of physical exercise in counteracting chronic degenerative conditions.

Metabolic stress-dependent regulation of the mitochondrial biogenic molecular response to high-intensity exercise in human skeletal muscle.

KEY POINTS: Low-volume high-intensity exercise training promotes muscle mitochondrial adaptations that resemble those associated with high-volume moderate-intensity exercise training. These training-induced mitochondrial adaptations stem from the cumulative effects of transient transcriptional responses to each acute exercise bout. However, whether metabolic stress is a key mediator of the acute molecular responses to high-intensity exercise is still incompletely understood. Here we show that, by comparing different work-matched low-volume high-intensity exercise protocols, more marked metabolic perturbations were associated with enhanced mitochondrial biogenesis-related muscle mRNA responses. Furthermore, when compared with high-volume moderate-intensity exercise, only the low-volume high-intensity exercise eliciting severe metabolic stress compensated for reduced exercise volume in the induction of mitochondrial biogenic mRNA responses. The present results, besides improving our understanding of the mechanisms mediating exercise-induced mitochondrial biogenesis, may have implications for applied and clinical research that adopts exercise as a means to increase muscle mitochondrial content and function in healthy or diseased individuals. ABSTRACT: The aim of the present study was to examine the impact of exercise-induced metabolic stress on regulation of the molecular responses promoting skeletal muscle mitochondrial biogenesis. Twelve endurance-trained men performed three cycling exercise protocols characterized by different metabolic profiles in a randomized, counter-balanced order. Specifically, two work-matched low-volume supramaximal-intensity intermittent regimes, consisting of repeated-sprint (RS) and speed endurance (SE) exercise, were employed and compared with a high-volume continuous moderate-intensity exercise (CM) protocol. Vastus lateralis muscle samples were obtained before, immediately after, and 3 h after exercise. SE produced the most marked metabolic perturbations as evidenced by the greatest changes in muscle lactate and pH, concomitantly with higher post-exercise plasma adrenaline levels in comparison with RS and CM. Exercise-induced phosphorylation of CaMKII and p38 MAPK was greater in SE than in RS and CM. The exercise-induced PGC-1α mRNA response was higher in SE and CM than in RS, with no difference between SE and CM. Muscle NRF-2, TFAM, MFN2, DRP1 and SOD2 mRNA content was elevated to the same extent by SE and CM, while RS had no effect on these mRNAs. The exercise-induced HSP72 mRNA response was larger in SE than in RS and CM. Thus, the present results suggest that, for a given exercise volume, the initial events associated with mitochondrial biogenesis are modulated by metabolic stress. In addition, high-intensity exercise seems to compensate for reduced exercise volume in the induction of mitochondrial biogenic molecular responses only when the intense exercise elicits marked metabolic perturbations.

Shared and task-specific muscle synergies of Nordic walking and conventional walking.

Nordic walking is a form of walking that includes a poling action, and therefore an additional subtask, with respect to conventional walking. The aim of this study was to assess whether Nordic walking required a task-specific muscle coordination with respect to conventional walking. We compared the electromyographic (EMG) activity of 15 upper- and lower-limb muscles of 9 Nordic walking instructors, while executing Nordic walking and conventional walking at 1.3 ms-1 on a treadmill. Non-negative matrix factorization method was applied to identify muscle synergies, representing the spatial and temporal organization of muscle coordination. The number of muscle synergies was not different between Nordic walking (5.2 ± 0.4) and conventional walking (5.0 ± 0.7, P = .423). Five muscle synergies accounted for 91.2 ± 1.1% and 92.9 ± 1.2% of total EMG variance in Nordic walking and conventional walking, respectively. Similarity and cross-reconstruction analyses showed that 4 muscle synergies, mainly involving lower-limb and trunk muscles, are shared between Nordic walking and conventional walking. One synergy acting during upper limb propulsion is specific to Nordic walking, modifying the spatial organization and the magnitude of activation of upper limb muscles compared to conventional walking. The inclusion of the poling action in Nordic walking does not increase the complexity of movement control and does not change the coordination of lower limb muscles. This makes Nordic walking a physical activity suitable also for people with low motor skill.

Cross-country skiing movement factorization to explore relationships between skiing economy and athletes' skills.

We investigated the relationships between the biomechanics of the double poling (DP) technique in cross-country skiing, its economy, and athletes' skill. To this aim, skiers' motion has been factorized into components through principal component analysis (PCA). Eight high-level (HL) and eight regional level (RL) male cross-country skiers performed a 5-minute submaximal DP trial while roller skiing on a treadmill at 14 km h-1 and 2° incline. Whole-body kinematics was recorded with a motion capture system. PCA was applied to markers coordinates to extract principal movements (PMk ), which were ranked by their variance. Energy cost (EC) of locomotion was calculated from ergospirometric measurements. Results showed that 96.7%±0.6% of total skiing pattern variance can be described with the first three PMk. (Shoulder and trunk flexion-extension are described PM1 and PM2 and elbow flexion-extension are mainly represented in PM2 and PM3. The variance of further components, consisting of residual movements (eg, slow postural changes or high-frequency vibrations), was greater for the RL than the HL skiers (4.0%±0.5% vs 2.6%±0.3%; P<.001) and was positively correlated with EC (R2 =.646; P<.001). PCA permitted to describe the biomechanics of the DP technique through a limited set of principal movements. Skiing skills and economy appeared to be related to a skier's ability to simplify movement complexity, suggesting that an efficient skier is better able to reduce superfluous movement components during DP.

Metabolic and kinematic parameters during walking with poles in Parkinson's disease.

In healthy people, energy expenditure is generally higher during walking with poles (WP) than during conventional walking (W). In persons with Parkinson's disease (PD), walking is slower and may be associated with greater energy consumption, stride-to-stride variability, and difficulty in regulating stride length. The aim of this study was to determine whether treadmill WP at three different speeds could induce changes in gait kinematics and oxygen consumption in PD patients. The study sample was 20 patients with mild-to-moderate PD and 20 age-matched healthy controls. Subjects underwent 5-min W and WP treadmill tests at three different speeds (2.5, 3.5, and 4.5 km/h). Metabolic and gait parameters (ventilation, gas exchange, stride count and length) were recorded. As compared with the healthy controls, higher energy consumption (P < 0.05) (and other metabolic parameters), shorter stride, and reduced cadence (P < 0.05) were observed for the PD patients, independent of the walking technique. All subjects were noted to take longer strides during WP (P < 0.001), especially at the lowest treadmill speed. However, significantly higher energy consumption was observed only for the healthy controls (P < 0.05). No changes in metabolic parameters during WP were recorded; however, a substantial improvement in gait cycle length was noted for the PD patients.

Central and peripheral fatigue in knee and elbow extensor muscles after a long-distance cross-country ski race.

Although elbow extensors (EE) have a great role in cross-country skiing (XC) propulsion, previous studies on neuromuscular fatigue in long-distance XC have investigated only knee extensor (KE) muscles. In order to investigate the origin and effects of fatigue induced by long-distance XC race, 16 well-trained XC skiers were tested before and after a 56-km classical technique race. Maximal voluntary isometric contraction (MVC) and rate of force development (RFD) were measured for both KE and EE. Furthermore, electrically evoked double twitch during MVC and at rest were measured. MVC decreased more in KE (-13%) than in EE (-6%, P = 0.016), whereas the peak RFD decreased only in EE (-26%, P = 0.02) but not in KE. The two muscles showed similar decrease in voluntary activation (KE -5.0%, EE -4.8%, P = 0.61) and of double twitch amplitude (KE -5%, EE -6%, P = 0.44). A long-distance XC race differently affected the neuromuscular function of lower and upper limbs muscles. Specifically, although the strength loss was greater for lower limbs, the capacity to produce force in short time was more affected in the upper limbs. Nevertheless, both KE and EE showed central and peripheral fatigue, suggesting that the origins of the strength impairments were multifactorial for the two muscles.

Changes in upper and lower body muscle involvement at increasing double poling velocities: an ecological study.

This study evaluated muscle activity changes in different body compartments during on-snow double poling at increasing velocities. 21 well-trained, male cross-country skiers performed five 3-min double poling trials on a snowy track at 15, 16.5, 18, 19.5, and 21 km/h (set by an audio-pace system). A sixth trial was performed by maintaining a constant maximal speed. Actual skiing velocities were verified using a photocell system. Only 11 subjects met the pre-defined inclusion criteria during the trials and were included in the data analysis. Electromyographical signals from seven muscles, wrist acceleration and heart rate during the last minute of each trial were recorded. Cycle and poling times were measured from acceleration signals; mean muscular activation over a cycle was calculated for each muscle. With increasing double poling velocities from aerobic to maximal intensity (from 65% to 100% of maximal heart rate), upper limb muscles activation was maintained constant (P > 0.05), while trunk and lower limb involvement increased significantly (P < 0.01) with a linear trend. Rectus abdominis and rectus femoris muscles showed the higher rate of change. Trunk and lower limbs provide a progressively greater contribution to the propulsion when increasing double poling velocities are performed, to support the limited capacity of exercise response of upper body muscles. The remarkable rate of involvement of the muscles near the core region of the body becomes strategic to cope with the increased demands of propulsive power.

Multiple rare genetic variants co-segregating with familial IgA nephropathy all act within a single immune-related network.

BACKGROUND: IgA nephropathy (IgAN) is a common complex disease with a strong genetic involvement. We aimed to identify novel, rare, highly penetrant risk variants combining family-based linkage analysis with whole-exome sequencing (WES). METHODS: Linkage analysis of 16 kindreds of South Italian ancestry was performed using an 'affected-only' strategy. Eight most informative trios composed of two familial cases and an intrafamilial control were selected for WES. High-priority variants in linked regions were identified and validated using Sanger sequencing. Custom TaqMan assays were designed and carried out in the 16 kindreds and an independent cohort of 240 IgAN patients and 113 control subjects. RESULTS: We found suggestive linkage signals in 12 loci. After sequential filtering and validation of WES data, we identified 24 private or extremely rare (MAF <0.0003) linked variants segregating with IgAN status. These were present within coding or regulatory regions of 23 genes that merged into a common functional network. The genes were interconnected by AKT, CTNNB1, NFKB, MYC and UBC, key modulators of WNT/ß-catenin and PI3K/Akt pathways, which are implicated in IgAN pathogenesis. Overlaying publicly available expression data, genes/proteins with expression notably altered in IgAN were included in this immune-related network. In particular, the network included the glucocorticoid receptor gene, NR3C1, which is the target of corticosteroid therapy routinely used in the treatment of IgAN. CONCLUSION: Our findings suggest that disease susceptibility could be influenced by multiple rare variants acting in a common network that could provide the starting point for the identification of potential drug targets for personalized therapy.

Injury and Illness Rates During Ultratrail Running.

This study aimed to describe injury/illness rates in ultratrail runners competing in a 65-km race to build a foundation for injury prevention and help race organizers to plan medical provision for these events. Prospectively transcribed medical records were analysed for 77 athletes at the end of the race. Number of injuries/illnesses per 1 000 runners and per 1 000-h run, overall injury/illness rate and 90% confidence intervals and rates for major and minor illnesses, musculoskeletal injuries, and skin disorders were analysed. A total of 132 injuries/illnesses were encountered during the race. The overall injuries/illnesses were 1.9 per runner and 13.1 per 1 000-h run. Medical illnesses were the most prominent medical diagnoses encountered (50.3%), followed by musculoskeletal injuries (32.8%), and skin-related disorders (16.9%). Despite the ultra-long nature of the race, the majority of injuries/illnesses were minor in nature. Medical staff and runners should prepare to treat all types of injuries and illnesses, especially the fatigue arising throughout the course of an ultratrail run and injuries to the lower limbs. Future studies should attempt to systematically identify injury locations and mechanisms in order to better direct injury prevention strategies and plan more accurate medical care.

Gokyo Khumbu/Ama Dablam Trek 2012: effects of physical training and high-altitude exposure on oxidative metabolism, muscle composition, and metabolic cost of walking in women.

PURPOSE: We investigated the effects of moderate-intensity training at low and high altitude on VO2 and QaO2 kinetics and on myosin heavy-chain expression (MyHC) in seven women (36.3 yy ± 7.1; 65.8 kg ± 11.7; 165 cm ± 8) who participated in two 12- to 14-day trekking expeditions at low (598 m) and high altitude (4132 m) separated by 4 months of recovery. METHODS: Breath-by-breath VO2 and beat-by-beat QaO2 at the onset of moderate-intensity cycling exercise and energy cost of walking (Cw) were assessed before and after trekking. MyHC expression of vastus lateralis was evaluated before and after low-altitude and after high-altitude trekking; muscle fiber high-resolution respirography was performed at the beginning of the study and after high-altitude trekking. RESULTS: Mean response time of VO2 kinetics was faster (P = 0.002 and P = 0.001) and oxygen deficit was smaller (P = 0.001 and P = 0.0004) after low- and high-altitude trekking, whereas ˙ QaO2 kinetics and Cw did not change. Percentages of slow and fast isoforms of MyHC and mitochondrial mass were not affected by low- and high-altitude training. After training altitude, muscle fiber ADP-stimulated mitochondrial respiration was decreased as compared with the control condition (P = 0.016), whereas leak respiration was increased (P = 0.031), leading to a significant increase in the respiratory control ratio (P = 0.016). CONCLUSIONS: Although training did not significantly modify muscle phenotype, it induced beneficial adaptations of the oxygen transport-utilization systems witnessed by faster VO2 kinetics at exercise onset.