Correction: Crespo et al. Protective Effect of Protocatechuic Acid on TNBS-Induced Colitis in Mice Is Associated with Modulation of the SphK/S1P Signaling Pathway. Nutrients 2017, 9, 288.

In the original publication [...].

Injury characteristics of young elite inline speed skaters: A one season retrospective study.

OBJECTIVES: Determining the rate of injuries related to a certain sport is accepted as the primary step toward designing, implementing and evaluating injury prevention programs. This observational and retrospective study was to examine the injuries sustained by elite young Spanish inline speed skaters during a season. METHODS: Athletes participating in the national championship (n = 80) were surveyed via an anonymous online questionnaire to screen for injury characteristics: incidence, location, and tissue affected; plus training information and demographics. RESULTS: A total of 52 injuries were recorded across 33,351 hours of exposure, which gives a rate of 1.65/1,000 h. The lower body comprised 79% of the total amount of injuries (1.3/1000 h), and the main areas affected were the thigh and foot, accounting for 25% and 19.2% of the recorded injuries, respectively. Musculotendinous injuries were the most frequent, with an incidence of 0.92/1000 h. No significant gender differences were observed for any of the variables studied. CONCLUSION: Speed skating can be considered a low injury rate sport based on our findings. The risk of sustaining an injury was independent of gender, age, and BMI.

Epidemiology of Rink Hockey-Related Injuries.

CONTEXT: Determining the rate of injuries related to a certain sport is accepted as the primary step toward designing, implementing, and evaluating injury prevention programs. The aim of this study was to examine the injuries sustained by semiprofessional Spanish rink hockey players and to compare data per playing position. DESIGN: Observational and retrospective. METHODS: Athletes from 21 teams were surveyed via a self-reported questionnaire to screen for incidence, injury burden, location, tissue, and onset of injuries. RESULTS: Overall, 101 time loss injuries were reported across 22,241 hours of exposure, giving rise to an incidence rate of 4.5/1000 hours. The main body regions injured were the hip/groin, shoulder, thigh, and head, accounting altogether for 47.5% of all injuries. Musculotendinous injuries were the most frequent, comprising 27.7% of all injuries. Incidence accounted for 3.1/1000 hours during training and 23/1000 hours during games (P < .001). A high number of injuries were caused by contact (46.5%). No differences were found for any of the variables analyzed between outfield players and goalkeepers. CONCLUSION: The injury incidence in rink hockey is moderate, occurring mainly due to a contact mechanism. Preventative measurements should be implemented in rink hockey with a special concern for injuries affecting the hip/groin and head.

Transcriptomic clustering of critically ill COVID-19 patients.

BACKGROUND: Infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause a severe disease, termed coronavirus disease 2019 (COVID-19), with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms and their modulation has shown a mortality benefit. METHODS: In a cohort of 56 critically ill COVID-19 patients, peripheral blood transcriptomes were obtained at admission to an intensive care unit (ICU) and clustered using an unsupervised algorithm. Differences in gene expression, circulating microRNAs (c-miRNAs) and clinical data between clusters were assessed, and circulating cell populations estimated from sequencing data. A transcriptomic signature was defined and applied to an external cohort to validate the findings. RESULTS: We identified two transcriptomic clusters characterised by expression of either interferon-related or immune checkpoint genes, respectively. Steroids have cluster-specific effects, decreasing lymphocyte activation in the former but promoting B-cell activation in the latter. These profiles have different ICU outcomes, despite no major clinical differences at ICU admission. A transcriptomic signature was used to identify these clusters in two external validation cohorts (with 50 and 60 patients), yielding similar results. CONCLUSIONS: These results reveal different underlying pathogenetic mechanisms and illustrate the potential of transcriptomics to identify patient endotypes in severe COVID-19 with the aim to ultimately personalise their therapies.

Characterising groin pain in rink hockey: Function and five-second squeeze in Spanish players.

OBJECTIVES: To assess the relationship between history of past season groin pain and current pain during the five-second squeeze test (5SST) with groin function and adductor strength in rink hockey players. DESIGN: Cross-sectional. SETTING: First (Ok Liga), Second (Plata) and third division (Bronce) clubs. PARTICIPANTS: Sixty-eight female and 183 male hockey players. MAIN OUTCOME MEASURES: Seasonal prevalence of groin pain (time/non-time-loss). Adductor strength and pain during the 5SST. Function was evaluated with the Hip and Groin Outcome Score (HAGOS). RESULTS: Seasonal time-loss groin pain prevalence was 21%. Male players had 3.5 higher odds of having had an episode of time-loss groin pain during the previous season compared to female players. The adductor relative strength was no different between players with and without previous season groin injury (p = 0.53-0.55), while the HAGOS results differed between groups, with past season groin injury players obtaining lower values in all subscales. HAGOS scores differed between the 5SST pain intensity groups (p < 0.01). CONCLUSIONS: Male players had higher odds of having had a groin injury in the previous season compared to female players. Players with pain during 5SST and previous season groin injury reported functional deficits, while strength remains identical to their healthy counterparts.

Injury Characteristics among Young Adults during and Immediately after the COVID-19 Lockdown.

The lockdown due to the COVID-19 pandemic inherently changed people's lifestyles. Forty-eight days of isolation led to worsening physical fitness in addition to the development of other unhealthy habits. The aim of this study was to describe sport-related injuries in the active general population. Physical therapy centres and sports medicine clinics were contacted via e-mail, seeking patients who had sustained an injury during or immediately (up to two weeks) after the lockdown. Patients who agreed to participate completed an online survey that followed the International Olympic Committee Statement. The questionnaire focused on physical exercise habits, type of injury, location and tissue affected. A total of 51 females and 67 males (30.5, SD = 8.8 years) participated in the study. Eighty percent of the participants performed aerobic training sessions, while the rest dedicated their workouts to strength training. Two in every three injuries were located in the lower limbs, and 80% affected the musculoskeletal tissue. Of all the injuries recorded, 67% occurred during the first week after lockdown. The number of aerobic exercise sessions was positively correlated with lower limb injuries (χ2 = 17.12, p < 0.05). Exercise habits should be considered when planning to return to a sport after a period of confinement to avoid injury.

Effects of IFIH1 rs1990760 variants on systemic inflammation and outcome in critically ill COVID-19 patients in an observational translational study.

Background: Variants in IFIH1, a gene coding the cytoplasmatic RNA sensor MDA5, regulate the response to viral infections. We hypothesized that IFIH1 rs199076 variants would modulate host response and outcome after severe COVID-19. Methods: Patients admitted to an intensive care unit (ICU) with confirmed COVID-19 were prospectively studied and rs1990760 variants determined. Peripheral blood gene expression, cell populations, and immune mediators were measured. Peripheral blood mononuclear cells from healthy volunteers were exposed to an MDA5 agonist and dexamethasone ex-vivo, and changes in gene expression assessed. ICU discharge and hospital death were modeled using rs1990760 variants and dexamethasone as factors in this cohort and in-silico clinical trials. Results: About 227 patients were studied. Patients with the IFIH1 rs1990760 TT variant showed a lower expression of inflammation-related pathways, an anti-inflammatory cell profile, and lower concentrations of pro-inflammatory mediators. Cells with TT variant exposed to an MDA5 agonist showed an increase in IL6 expression after dexamethasone treatment. All patients with the TT variant not treated with steroids survived their ICU stay (hazard ratio [HR]: 2.49, 95% confidence interval [CI]: 1.29-4.79). Patients with a TT variant treated with dexamethasone showed an increased hospital mortality (HR: 2.19, 95% CI: 1.01-4.87) and serum IL-6. In-silico clinical trials supported these findings. Conclusions: COVID-19 patients with the IFIH1 rs1990760 TT variant show an attenuated inflammatory response and better outcomes. Dexamethasone may reverse this anti-inflammatory phenotype. Funding: Centro de Investigación Biomédica en Red (CB17/06/00021), Instituto de Salud Carlos III (PI19/00184 and PI20/01360), and Fundació La Marató de TV3 (413/C/2021).

Patients with severe COVID-19 often need mechanical ventilation to help them breathe and other types of intensive care. The outcome for many of these patients depends on how their immune system reacts to the infection. If the inflammatory response triggered by the immune system is too strong, this can cause further harm to the patient. One gene that plays an important role in inflammation is IFIH1 which encodes a protein that helps the body to recognize viruses. There are multiple versions of this gene which each produce a slightly different protein. It is possible that this variation impacts how the immune system responds to the virus that causes COVID-19. To investigate, Amado-Rodríguez, Salgado del Riego et al. analyzed the IFIH1 gene in 227 patients admitted to an intensive care unit in Spain for severe COVID-19 between March and December 2020. They found that patients with a specific version of the gene called TT experienced less inflammation and were more likely to survive the infection. Physicians typically treat patients with moderate to severe COVID-19 with corticosteroid drugs that reduce the inflammatory response. However, Amado-Rodríguez, Salgado del Riego et al. found that patients with the TT version of the IFIH1 gene were at greater risk of dying if they received corticosteroids. The team then applied the distribution of IFIH1 variants among different ethnic ancestries to data from a previous clinical trial, and simulated the effects of corticosteroid treatment. This 'mock' clinical trial supported their findings from the patient-derived data, which were also validated by laboratory experiments on immune cells from individuals with the TT gene. The work by Amado-Rodríguez, Salgado del Riego et al. suggests that while corticosteroids benefit some patients, they may cause harm to others. However, a real-world clinical trial is needed to determine whether patients with the TT version of the IFIH1 gene would do better without steroids.

Injury in CrossFit®: A Systematic Review of Epidemiology and Risk Factors.

OBJECTIVE: To review the characteristics of the injuries among CrossFit® practitioners, including prevalence and incidence, nature, location, and risk factors. METHODS: PubMed/MEDLINE, EMBASE, Web of Science, Scopus, and SPORTDiscus databases were searched from inception through August 2020, and English-language articles reporting on CrossFit®-related injuries were included. Data including sample (sex, age, and demographics) and injuries' characteristics (prevalence, incidence rate, nature, location, percentage of injuries requiring surgery and risk factors) were extracted. RESULTS: Overall, twenty-five studies involving a total of 12,079 CrossFit® practitioners met the inclusion criteria. The mean prevalence of injuries among the included studies was 35.3%, with an incidence rate varying between 0.2 and 18.9 per 1000 hours of training. The most injured areas were shoulder (26%), spine (24%), and knee (18%). Among the studies that reported the injuries requiring surgery, the mean percentage was 8.7%. Regarding the risk factors associated with injuries, older age, male sex, a greater body mass index, the existence of previous injuries, the lack of coach supervision, the experience on CrossFit® and the participation in competitions were reported by the studies. CONCLUSIONS: CrossFit® training has an injury incidence rate similar to weightlifting and powerlifting. Findings from the studies suggest that the most affected areas are shoulder, spine, and knee. The limited quality of the studies prevents us from drawing solid conclusions about injury risk factors.

Mechanical ventilation promotes lung tumour spread by modulation of cholesterol cell content.

BACKGROUND: Mechanical stretch of cancer cells can alter their invasiveness. During mechanical ventilation, lungs may be exposed to an increased amount of stretch, but the consequences on lung tumours have not been explored. METHODS: To characterise the influence of mechanical ventilation on the behaviour of lung tumours, invasiveness assays and transcriptomic analyses were performed in cancer cell lines cultured in static conditions or under cyclic stretch. Mice harbouring lung melanoma implants were submitted to mechanical ventilation and metastatic spread was assessed. Additional in vivo experiments were performed to determine the mechanodependent specificity of the response. Incidence of metastases was studied in a cohort of lung cancer patients that received mechanical ventilation compared with a matched group of nonventilated patients. RESULTS: Stretch increases invasiveness in melanoma B16F10luc2 and lung adenocarcinoma A549 cells. We identified a mechanosensitive upregulation of pathways involved in cholesterol processing in vitro, leading to an increase in pro-protein convertase subtilisin/kexin type 9 (PCSK9) and LDLR expression, a decrease in intracellular cholesterol and preservation of cell stiffness. A course of mechanical ventilation in mice harbouring melanoma implants increased brain and kidney metastases 2 weeks later. Blockade of PCSK9 using a monoclonal antibody increased cell cholesterol and stiffness and decreased cell invasiveness in vitro and metastasis in vivo. In patients, mechanical ventilation increased PCSK9 abundance in lung tumours and the incidence of metastasis, thus decreasing survival. CONCLUSIONS: Our results suggest that mechanical stretch promote invasiveness of cancer cells, which may have clinically relevant consequences. Pharmacological manipulation of cholesterol endocytosis could be a novel therapeutic target in this setting.

Activation of p21 limits acute lung injury and induces early senescence after acid aspiration and mechanical ventilation.

The p53/p21 pathway is activated in response to cell stress. However, its role in acute lung injury has not been elucidated. Acute lung injury is associated with disruption of the alveolo-capillary barrier leading to acute respiratory distress syndrome (ARDS). Mechanical ventilation may be necessary to support gas exchange in patients with ARDS, however, high positive airway pressures can cause regional overdistension of alveolar units and aggravate lung injury. Here, we report that acute lung injury and alveolar overstretching activate the p53/p21 pathway to maintain homeostasis and avoid massive cell apoptosis. A systematic pooling of transcriptomic data from animal models of lung injury demonstrates the enrichment of specific p53- and p21-dependent gene signatures and a validated senescence profile. In a clinically relevant, murine model of acid aspiration and mechanical ventilation, we observed changes in the nuclear envelope and the underlying chromatin, DNA damage and activation of the Tp53/p21 pathway. Absence of Cdkn1a decreased the senescent response, but worsened lung injury due to increased cell apoptosis. Conversely, treatment with lopinavir and/or ritonavir led to Cdkn1a overexpression and ameliorated cell apoptosis and lung injury. The activation of these mechanisms was associated with early markers of senescence, including expression of senescence-related genes and increases in senescence-associated heterochromatin foci in alveolar cells. Autopsy samples from lungs of patients with ARDS revealed increased senescence-associated heterochromatin foci. Collectively, these results suggest that acute lung injury activates p53/p21 as an antiapoptotic mechanism to ameliorate damage, but with the side effect of induction of senescence.

Vigorous Aerobic Exercise in the Management of Parkinson Disease: A Systematic Review.

OBJECTIVE: To summarize the findings from studies examining the effects of vigorous-intensity aerobic exercise in the management of Parkinson disease. TYPE: Systematic review. LITERATURE SURVEY: PubMed/MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Library, SPORTDiscus, and ScienceDirect databases were searched up to May 2020. Reference lists of the included articles were also searched for additional studies. Searches were restricted to English language. METHODOLOGY: Seven papers, including six studies, five randomized controlled trials and one controlled trial, were identified. The studies examined the effects of vigorous-intensity aerobic exercise in participants with Parkinson disease. Studies in which the minimal intensity required was ≥77% of maximum heart rate, 60% of heart rate reserve or 64% of maximal oxygen uptake met the inclusion criteria. Method appraisal showed a mean score of 5.3 in the Physiotherapy Evidence Database (PEDro) scale. SYNTHESIS: No statistically significant differences were found between vigorous-intensity aerobic exercise and moderate/low-intensity aerobic exercise for the main outcomes (disease severity and motor function). Only one study concluded a significant higher aerobic fitness in favor of the group that exercised at vigorous intensity compared to the moderate intensity group. CONCLUSIONS: Vigorous-intensity aerobic exercise has not shown statistically significant improvements in motor and nonmotor impairments in individuals with Parkinson disease as compared to moderate/low-intensity aerobic exercise. Hence, the current evidence is too limited to allow recommendations for clinical practice.

Role of nutrition in the development and prevention of age-related hearing loss: A scoping review.

Age-related hearing loss (ARHL) is a major and increasingly prevalent health problem worldwide, causing disability and social isolation in the people who present it. This impairment is caused by genetic and environmental factors. Nutritional status has been identified as a related risk associated with hearing loss (HL). This scoping review aimed to characterize the links between HL and nutritional status. PubMed, Embase, Cochrane and Scopus databases were searched up to December 2019. Studies examining the relation between nutrition and dietary habits and HL were included. After screening 3510 citations, 22 publications were selected for inclusion in the current review, all of which were published between 2010 and 2019. Diets rich in saturated fats and cholesterol have deleterious effects on hearing that could be prevented by lower consumption. Conversely, greater consumption of fruit and vegetables, and of polyunsaturated fatty acids (omega-3) and anti-oxidants in the form of vitamins A, C, and E, prevent the development of ARHL. The current literature suggests a possible association between nutritional status and hearing loss. More studies are needed to better characterize the clinical consequences of this association.

Cellular and molecular features of senescence in acute lung injury.

A wide range of insults can trigger acute injury in the lungs, which eventually may lead to respiratory failure and death of patients. Current treatment relies mainly on supportive measures and mechanical ventilation. Even so, survivors frequently develop important sequels that compromise quality of life. In the search for new approaches to prevent and treat acute lung injury, many investigations have focused on molecular and cellular pathways which could exert a pathogenic role in this disease. Herein, we review recent findings in the literature suggesting that cellular senescence could be involved in lung injury and discuss the potential use of senotherapies to prevent disease progression.

Kinematic Gait Analysis After Primary Total Hip Replacement: A Systematic Review: Gait After Total Hip Replacement: A Systematic Review.

Total hip replacement (THR) is a surgical procedure indicated for patients affected by severe hip osteoarthritis. Although this technique has proved to be effective in relieving pain and restoring function, gait limitations may persist following this procedure. The objective of this systematic review was to evaluate gait kinematics after THR and compare the results with those of the pre-operative state and with healthy control individuals. PubMed/MEDLINE, Embase, Web of Science, CENTRAL and Scopus databases were searched until December 2019. Methodological quality and internal validity score of each study were assessed using the PEDro and the Newcastle-Ottawa scales. In all, ten studies met our inclusion criteria. Following THR, statistically significant improvements were seen in dynamic hip and knee range of motion of both the affected and the contralateral limb, single-limb support time symmetry, step length, stride length, walking speed and gait pattern. However, deficits were observed in all the previous parameters, as well as in hip adduction angle in comparison with healthy subjects. In conclusion, gait patterns improve after THR in comparison with the pre-operative state, although there are deficits relative to healthy individuals.

Medial Tibial Stress Syndrome in Novice and Recreational Runners: A Systematic Review.

This systematic review evaluates the existing literature about medial tibial stress syndrome (MTSS) in novice and recreational runners. PubMed/MEDLINE, EMBASE, Web of Science, Scopus, SPORTDiscus and CINAHL databases were searched until July 2020. Studies covering risk factors, diagnostic procedures, treatment methods and time to recovery of MTSS in novice and recreational runners were selected. Eleven studies met the inclusion criteria and were included. The risk factors of MTSS are mainly intrinsic and include higher pelvic tilt in the frontal plane, peak internal rotation of the hip, navicular drop and foot pronation, among others. Computed tomography (CT) and pressure algometry may be valid instruments to corroborate the presence of this injury and confirm the diagnosis. Regarding treatment procedures, arch-support foot orthoses are able to increase contact time, normalize foot pressure distribution and similarly to shockwave therapy, reduce pain. However, it is important to take into account the biases and poor methodological quality of the included studies, more research is needed to confirm these results.