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IntroductionSARS-CoV-2 mRNA vaccinations elicit both virus-specific humoral and T-cell responses, but a complex interplay of different influencing factors, such as natural immunity, gender, and age, guarantees host protection. The present study aims to assess the immune dynamics of humoral, T-cell response, and influencing factors to stratify individual immunization status up to 10 months after Comirnaty-vaccine administration.MethodsTo this aim, we longitudinally evaluated the magnitude and kinetics of both humoral and T-cell responses by serological tests and enzyme-linked immunospot assay at 5 time points. Furthermore, we compared the course over time of the two branches of adaptive immunity to establish an eventual correlation between adaptive responses. Lastly, we evaluated putative influencing factors collected by an anonymized survey administered to all participants through multiparametric analysis. Among 984 healthcare workers evaluated for humoral immunity, 107 individuals were further analyzed to describe SARS-CoV-2-specific T-cell responses. Participants were divided into 4 age groups: ResultsThe disaggregated evaluation of humoral responses highlighted antibody levels decreased in older subjects. The humoral responses were higher in females than in males (p=0.002) and previously virus-exposed subjects compared to naïve subjects (pDiscussionThese findings suggest prospects for rescheduling vaccination strategies by considering individual immunization status, personal characteristics, and the appropriate laboratory tests to portray immunity against SARS-CoV-2 accurately. Deepening our knowledge about T and B cell dynamics might optimize the decision-making process in vaccination campaigns, tailoring it to each specific immune response.

Hemoglobin and its associated blood values are important laboratory biomarkers that mirror the strength of constitution of patients undergoing spine surgery. Along with the clinical determinants available during the preadmission visit, it is important to explore their potential for predicting clinical success from the patient's perspective in order to make the pre-admission visit more patient-centered. We analyzed data from 1,392 patients with spine deformity, disc disease, or spondylolisthesis enrolled between 2016 and 2019 in our institutional Spine Registry. Patient-reported outcome measure at 17 months after surgery was referred to the Oswestry disability index. High preoperative hemoglobin was found to be the strongest biochemical determinant of clinical success along with high red blood cells count, while low baseline disability, prolonged hospitalization, and long surgical times were associated with poor recovery. The neural network model of these predictors showed a fair diagnostic performance, having an area under the curve of 0.726 and a sensitivity of 86.79%. However, the specificity of the model was 15.15%, thus providing to be unreliable in forecasting poor patient-reported outcomes. In conclusion, preoperative hemoglobin may be one of the key biomarkers on which to build appropriate predictive models of long-term recovery after spine surgery, but it is necessary to include multidimensional variables in the models to increase the reliability at the patient's level.

Background. Modification of gene expression profile, a first step in adaptation to exercise, leads to changes in the level of those molecules associated with skeletal muscle activity and energy metabolism, e.g., myokines, as well as those involved in their transcriptional regulation, e.g., microRNA. This study was aimed to investigate the influence of strenuous exercise on circulating microRNAs and their possible association with myokines response. Methods. Pre-competition and post-competition plasma samples were collected from 14 male athletes participating in a vertical run (+1000 m gain, 3600 m length). Circulating total (t-miRNA) and extracellular vesicles-associated (EV-miRNA) miRNAs were extracted from pooled plasma. Nanoparticle tracking analysis was performed to investigate pre- and post-competition EV concentration and size distribution. A panel of 179 miRNAs was assayed by qPCR and analyzed by Exiqon GenEx v6. Relative expression was calculated by the 2-ΔΔCT method. t-miRNA and EV-miRNAs whose level was ≥5-fold up- or down-regulated were validated in each single subject. Target prediction on MirWalk 3.0, Gene-Ontology and pathway enrichment analysis on Panther were performed to define the potential biological role of the identified miRNAs. A panel of 14 myokines was assayed in each sample by a multiplex immunoassay. Results. In whole plasma, 5 miRNAs were upregulated and 2 miRNAs were downregulated; in the EV fraction, 5 miRNAs were upregulated and 3 miRNAs were downregulated. Nanoparticle tracking analysis revealed a similar EV size distribution in pre- and post-competition samples and a decreased concentration in post-competition samples related to pre-competition samples. Gene-Ontology and pathway enrichment analysis revealed that the identified t-miRNAs and EV-miRNAs were potentially involved in metabolism regulation in response to exercise. Correlation between fold-change of post-competition relative to pre-competition plasma level of both t-miRNAs and EV-miRNAs and myokines further confirm these results. Conclusion. This study provides an example of the systemic response to acute endurance exercise, in wich circulating miRNAs play a pivotal role. Trial registration: ClinicalTrials.gov, (SportMarker NCT03386981), retrospectively registered on 4th January 2018.

The aim of this study was to examine the impact of two different post-match training interventions on the subsequent recovery of perceptual and biochemical parameters after the game. In a crossover design, eight sub-elite players underwent a soccer-specific training (SST) and an active recovery (AR) regimen on the second day after a match (+48 h). Muscle soreness as well as muscle damage (creatine kinase, CK), inflammatory (C-reactive protein and interleukin 6), immunological (e.g., lymphocytes, neutrophils, and monocytes), and endocrine (cortisol) markers were obtained at baseline (−72 h), immediately after (0 h), and 72 h post-match (+72 h). AR promoted a higher restoration of muscle soreness values (P = 0.004, η2p = 0.49) together with a better restoration of CK within 72 h post-match compared with SST (P = 0.04, η2p = 0.36). Conversely, no significant (P > 0.05, η2p < 0.91) differences were observed in the recovery timeframe of inflammatory, immunological, and endocrine responses between SST and AR. Overall, AR elicited a quicker muscle soreness and CK restoration compared to SST intervention at 72 h post-match. Such information provides novel evidence-based findings on the appropriateness of different recovery strategies and may aid to improve the practitioners’ decision-making process when two consecutive games are played within 3 days.

Italy was one of the worst affected European countries during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. More than 50% of Italian cases occurred in the northern region of Lombardy, where the saturation of health services between March and April 2020 forced hospitals to allocate patients according to available resources. Eighteen severe coronavirus disease 2019 (COVID-19) patients were admitted to our hospital needing intensive support. Given the disease fatality, we investigated the patients' characteristics to identify mortality predictors. We counted seven deaths from multiple organ failure, two from septic shock, and two from collapsed lungs. The maximum case fatality was observed in patients who contracted SARS-CoV-2 in hospitals. The fatal outcome was associated with the following baseline characteristics: polymorbidity (OR 2.519, p = 0.048), low body mass index (OR 2.288, p = 0.031), low hemoglobin (OR 3.012, p = 0.046), and antithrombin III (OR 1.172, p = 0.048), along with a worsening of PaO2/FiO2 ratio in the first 72 h after admission (OR 1.067, p = 0.031). The occurrence of co-infections during hospitalization was associated with a longer need for intensive care (B = 4.511, p = 0.001). More information is needed to inform intensive care for patients with severe COVID-19, but our findings would certainly contribute to shed some light on this unpredictable and multifaceted disease.

Background: Muscular dystrophy causes weakness and muscle loss. The effect of muscular exercise in these patients remains controversial. Objective: To assess the effects of muscular exercise vs. no exercise in patients with muscular dystrophy. Methods: We performed a comprehensive systematic literature search in the Medline, Embase, Web of Science, Scopus, and Pedro electronic databases, as well as in the reference literature. We included randomized clinical trials (RCTs) that reported the effect of muscular exercise on muscle strength, endurance during walking, motor abilities, and fatigue. Data were extracted independently by two reviewers. Mean difference (MD) and 95% confidence intervals (CI) were used to quantify the effect associated with each outcome. We performed pairwise meta-analyses and trial sequential analyses (TSA) and used GRADE to rate the overall certainty of evidence. Results: We identified 13 RCTs involving 617 patients. The median duration of exercise interventions was 16 weeks [interquartile range [IQR] 12–24]. In the patients with facio-scapulo-humeral dystrophy and myotonic dystrophy, no significant difference in extensor muscle strength was noted between the exercise and the control groups [four studies, 115 patients, MD 4.34, 95% CI −4.20 to 12.88, I2 = 69%; p = 0.32; minimal important difference [MID] 5.39 m]. Exercise was associated with improved endurance during walking [five studies, 380 patients, MD 17.36 m, 95% CI 10.91–23.81, I2 = 0; p < 0.00001; MID 34 m]. TSA excluded random error as a cause of the findings for endurance during walking. Differences in fatigue and motor abilities were small. Not enough information was found for other types of dystrophy. Conclusions: Muscular exercise did not improve muscle strength and was associated with modest improvements in endurance during walking in patients with facio-scapulo-humeral and myotonic dystrophy. Future trials should explore which type of muscle exercise could lead to better improvements in muscle strength. PROSPERO: CRD42019127456.

The effect of sleep–wake rhythm disruption on neuromuscular control and muscle fatigue has received little attention. Because nurse shift work is so varied, including overnight duty, rotating shift schedules, early awakening, and interrupted nocturnal sleep, it offers an interesting model to study this paradigm. It has been investigated so far using only subjective markers. A combined approach based on the simultaneous analysis of surface electromyographic (sEMG) and force signals can objectively detect possible deficits in neuromuscular control and muscle fatigue. With this study we investigated neuromuscular activation and muscle contraction capacity at submaximum and maximum level in nurses working two night-shift schedules and compared them to levels in nurses working entirely in day shifts. Sleep quality and activity levels were also assessed. The study sample was 71 nurses grouped by their shift work schedule: night shift for 5 days (NS5, n = 46), night shift for 10 days (NS10, n = 9), and only day/swing shift (DS, n = 16). Before and after the shift-work cycle, maximum voluntary contraction (MVC) force and muscle activation, neuromuscular control, and muscle fatigability were measured in the finger flexor muscles. Activity level and sleep quality during the shift-work cycle were recorded with a wrist actigraph. After the shift-work cycles, MVC force and muscle activation were decreased (−11 ± 3% and −33 ± 3%, p < 0.001) as was neuromuscular control (−36 ± 8%, p = 0.007), whereas muscle fatigability was increased (+ 19 ± 9%, p = 0.006) in the NS5 and the NS10 group. Sleep quality was lower in the NS5 and the NS10 group (−8 ± 1.8% and −15%3, respectively, p < 0.001), while the activity level for the three groups was similar. There was a clear reduction in neuromuscular control and an increase in muscle fatigue in the nurses working the night shift. These findings may inform of work schedule planning or recommendations for devising new recovery strategies to counteract neuromuscular alterations in night shift nurses.

Aging is associated with an increased incidence of age-related bone diseases. Current diagnostics (e.g., conventional radiology, biochemical markers), because limited in specificity and sensitivity, can distinguish between healthy or osteoporotic subjects but they are unable to discriminate among different underlying causes that lead to the same bone pathological condition (e.g., bone fracture risk). Among recent, more sensitive biomarkers, miRNAs — the non-coding RNAs involved in the epigenetic regulation of gene expression, have emerged as fundamental post-transcriptional modulators of bone development and homeostasis. Each identified miRNA carries out a specific role in osteoblast and osteoclast differentiation and functional pathways (osteomiRs). miRNAs bound to proteins or encapsulated in exosomes and/or microvesicles are released into the bloodstream and biological fluids where they can be detected and measured by highly sensitive and specific methods (e.g., quantitative PCR, next-generation sequencing). As such, miRNAs provide a prompt and easily accessible tool to determine the subject-specific epigenetic environment of a specific condition. Their use as biomarkers opens new frontiers in personalized medicine. While miRNAs circulating levels are lower than those found in the tissue/cell source, their quantification in biological fluids may be strategic in the diagnosis of diseases that affect tissues, such as bone, in which biopsy may be especially challenging. For a biomarker to be valuable in clinical practice and support medical decisions, it must be (easily) measurable, validated by independent studies, and strongly and significantly associated with a disease outcome. Currently, miRNAs analysis does not completely satisfy these criteria, however. Starting from in vitro and in vivo observations describing their biological role in bone cell development and metabolism, this review describes the potential use of bone-associated circulating miRNAs as biomarkers for determining predisposition, onset, and development of osteoporosis and bone fracture risk. Moreover, the review focuses on their clinical relevance and discusses the pre-analytical, analytical, and post-analytical issues in their measurement, which still limits their routine application. Taken together, research and clinical findings may be helpful for creating miRNA-based diagnostic tools in the diagnosis and treatment of bone diseases.

Bone tissue can be seen as a physiological hub of several stimuli of different origin (e.g., dietary, endocrine, nervous, immune, skeletal muscle traction, biomechanical load). Their integration, at the bone level, results in: (i) changes in mineral and protein composition and microarchitecture and, consequently, in shape and strength; (ii) modulation of calcium and phosphorous release into the bloodstream, (iii) expression and release of hormones and mediators able to communicate the current bone status to the rest of the body. Different stimuli are able to act on either one or, as usual, more levels. Physical activity is the key stimulus for bone metabolism acting in two ways: through the biomechanical load which resolves into a direct stimulation of the segment(s) involved and through an indirect load mediated by muscle traction onto the bone, which is the main physiological stimulus for bone formation, and the endocrine stimulation which causes homeostatic adaptation. The third way, in which physical activity is able to modify bone functions, passes through the immune system. It is known that immune function is modulated by physical activity; however, two recent insights have shed new light on this modulation. The first relies on the discovery of inflammasomes, receptors/sensors of the innate immunity that regulate caspase-1 activation and are, hence, the tissue triggers of inflammation in response to infections and/or stressors. The second relies on the ability of certain tissues, and particularly skeletal muscle and adipose tissue, to synthesize and secrete mediators (namely, myokines and adipokines) able to affect, profoundly, the immune function. Physical activity is known to act on both these mechanisms and, hence, its effects on bone are also mediated by the immune system activation. Indeed, that immune system and bone are tightly connected and inflammation is pivotal in determining the bone metabolic status is well-known. The aim of this narrative review is to give a complete view of the exercise-dependent immune system-mediated effects on bone metabolism and function.

In this paper we present the findings of a systematic literature review covering the articles published in the last two decades in which the authors described the application of a machine learning technique and method to an orthopedic problem or purpose. By searching both in the Scopus and Medline databases, we retrieved, screened and analyzed the content of 70 journal articles, and coded these resources following an iterative method within a Grounded Theory approach. We report the survey findings by outlining the articles' content in terms of the main machine learning techniques mentioned therein, the orthopedic application domains, the source data and the quality of their predictive performance.