Cardiovascular and cerebrovascular effects of caffeine maintenance in preterm infants during the transitional period.

BACKGROUND AND AIM: Caffeine is routinely used for the prophylaxis of prematurity-related apnoeas. We aimed to evaluate the effect of caffeine maintenance on cardiovascular and cerebrovascular haemodynamics using a non-invasive multimodal monitoring in preterm infants during the transitional period. METHODS: Infants <32 weeks' gestational age (GA) were enrolled in this observational prospective study. The following parameters were recorded before and after the administration of caffeine citrate 5 mg/kg using near-infrared spectroscopy, pulse oximetry and electrical velocimetry: heart rate, cardiac output, stroke volume, cardiac contractility, systemic vascular resistance (SVR), perfusion index, peripheral and cerebral oxygenation, cerebral fractional oxygen extraction, correlation index between cerebral oxygenation and heart rate (TOHRx, marker of cerebrovascular reactivity). Multilevel mixed-effects linear models were used to assess the impact of caffeine and of relevant clinical covariates on each parameter. RESULTS: Seventy-seven infants (mean GA 29.3 ± 2.5 weeks, mean birthweight 1148 ± 353 g) were included. Caffeine administration was associated with increased SVR (B = 0.623, p = 0.004) and more negative TOHRx values (B = -0.036, p = 0.022), which suggest improved cerebrovascular reactivity. CONCLUSIONS: Caffeine administration at maintenance dosage during postnatal transition is associated with increased systemic vascular tone and improved cerebrovascular reactivity. A possible role for caffeine-mediated inhibition of adenosine receptors may be hypothesized. IMPACT: This study provides a thorough and comprehensive overview of multiple cerebrovascular and cardiovascular parameters, monitored non-invasively by combining near-infrared spectroscopy, electrical velocimetry and pulse oximetry, before and after the administration of caffeine at maintenance dosage in preterm infants during postnatal transition. Caffeine was associated with an improvement in cerebrovascular reactivity and with a slight but significant increase in systemic vascular resistance, with no additional effects on other cardiovascular and cerebrovascular parameters. Our results support the safety of caffeine treatment even during a phase at risk for haemodynamic instability such as postnatal transition and suggest potential beneficial effects on cerebral haemodynamics.

The power of coaches' emotions: A case study on how coaches' facial expressions impact performance of young female synchronized ice-skaters.

OBJECTIVES: The present study aimed to investigate the impact of coaches' pleasant and unpleasant facial expressions on affects and team performance of young elite female synchronized ice-skaters. METHODS: Initially, the coach provided a neutral explanation of the exercise, which was followed by the athletes' execution. The ice-skaters then received either pleasant or unpleasant feedback from the coach, completed two questionnaires, and performed the exercise again. The study involved two familiar and two unfamiliar coaches. RESULTS: Coaches' pleasant expressions increased athletes' arousal/hedonic tone and positive affect, while coaches' unpleasant expressions heightened athletes' negative affect. Moreover, participants significantly performed better after receiving an unpleasant facial expression by the coach. Receiving pleasant/unpleasant feedback from a familiar or unfamiliar coach did not have a significant impact on team pre- and post-feedback performance. CONCLUSIONS: The findings suggest that coaches' facial expressions impacted athletes' positive/negative affect, and that, under specific circumstances, receiving unpleasant feedback from the coach can improve team performance.

Serum Neurofilament and Free Light Chain Levels in Patients Undergoing Treatment for Chronic Inflammatory Demyelinating Polyneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disorder affecting the peripheral nervous system. Despite the established diagnostic criteria, monitoring disease activity and treatment remains challenging. To address this limitation, we investigated serum neurofilament light chain (sNfL) and serum free light chains (sFLCs) as potential biomarkers. A total of 32 CIDP patients undergoing immunoglobulin therapy and 32 healthy controls enrolled in the present study, and agreed to have their blood plasma sNfL and sFLCs analyzed, while CIDP severity was assessed through the modified Rankin Scale (mRS) and the Overall Neuropathy Limitations Scale (ONLS). In line with the immunoglobulin treatment aimed at limiting neuronal damage administered to the majority of patients, sNfL levels did not exhibit significant differences between the two groups. However, CIDP patients showed significantly elevated sFLC and sFLC ratios, while the marker levels did not correlate with the clinical scores. The study confirms the potential of sFLCs as a sensitive biomarker of inflammatory processes in CIDP. Additionally, the present study results regarding neurofilaments strengthen the role of sNfL in monitoring CIDP treatments, confirming the effectiveness of immunoglobulin therapy. Overall, our results demonstrate how combining these markers can lead to better patient characterization for improved treatment.

Umbrella Systematic Review and Meta-Analysis: Physical Activity as an Effective Therapeutic Strategy for Improving Psychosocial Outcomes in Children and Adolescents.

OBJECTIVE: Physical activity (PA) interventions are part of many interdisciplinary programs for the management of children and adolescents with or without physical or psychological conditions or disabilities. Aiming to summarize the available evidence, we conducted an umbrella review of meta-analyses of PA interventions that included psychosocial outcomes in populations of children and adolescents. METHOD: Literature searches were conducted in PubMed, Cochrane Central, Web of Science, Medline, SPORTDiscus, and PsychInfo from January 1, 2010, to May 6, 2022. Meta-analyses of randomized and quasi-randomized studies investigating the efficacy of PA interventions for psychosocial outcomes in children and adolescents were included. Summary effects were recalculated using common metric and random-effects models. We assessed between-study heterogeneity, predictive intervals, publication bias, small study effects, and whether the results of the observed positive studies were greater than expected due to chance. On the basis of these calculations, strength of associations was assessed using quantitative umbrella review criteria, and credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Quality was assessed using the AMSTAR 2 tool. This study is registered with the Open Science Framework, https://osf.io/ap8qu. RESULTS: A total of 112 studies from 18 meta-analyses generating 12 new meta-analyses comprising 21,232 children and adolescents in population groups including attention-deficit/hyperactivity disorder, cancer, cerebral palsy, chronic respiratory diseases, depression, neuromotor impairment, and obesity and in general populations were included. PA interventions were efficacious in reducing psychological symptoms in all meta-analyses across the different population groups using random-effects models. However, umbrella review criteria suggested a weak strength of association for this outcome, and GRADE credibility of evidence ranged from moderate to very low. For psychological well-being, 3 out of 5 meta-analyses identified significant effects, but the strength of these associations was weak, and GRADE credibility of evidence ranged from moderate to very low. Similarly, for social outcomes, meta-analyses reported a significant summary effect, but the strength of association was weak, and GRADE credibility of evidence ranged from moderate to very low. For self-esteem, one meta-analysis in children with obesity failed to show any effect. CONCLUSION: Even though existing meta-analyses suggested a beneficial effect of PA interventions on psychosocial outcomes across different population groups, the strength of associations was weak, and the credibility of evidence was variable depending on the target population, outcome, and condition or disability. Randomized studies of PA interventions in children and adolescents with and without different physical and psychological conditions or disabilities should always include psychosocial outcomes as an important dimension of social and mental health. STUDY PREREGISTRATION INFORMATION: Prenatal Maternal Infection and Adverse Neurodevelopment: A Structural Equation Modelling Approach to Downstream Environmental Hits; https://osf.io/; ap8qu.

FEPSAC Position Statement: Athletes' dual careers in the European context.

The aim of this FEPSAC Position Statement is to summarize current knowledge about athletes' dual careers (DCs) in the European context and propose recommendations for future DC research, practice, and policy. Inspired by the European Union's Guidelines on Dual Careers of Athletes (European Commission, 2012), researchers, practitioners, and policy makers collaborated over the last decade to create the European DC discourse as a context-informed and negotiated body of DC knowledge. In this paper, we proceed from analyzing this body of knowledge using recent review papers and European DC psychological research projects to formulating seven postulates summarizing DC research findings on factors influencing athletes in their striving for DC excellence. These factors include (1) context, (2) pathways and transitions, (3) challenges, (4) resources and coping, (5) support and empowerment, (6) student-athletes' mental health, and (7) DC development environments. In the final section, we acknowledge the contributions of European DC discourse in serving athletes in their pursuit of DC excellence and European DC culture. We also provide a critical discussion on DC knowledge gaps and, on behalf of FEPSAC, offer recommendations for DC research, practice, and policy in Europe.

Early detection of nerve involvement in presymptomatic TTR mutation carriers: exploring potential markers of disease onset.

BACKGROUND: Hereditary transthyretin (ATTRv) amyloidosis is a heterogeneous, progressive, multisystemic disease with a life-threatening course if left untreated. Given the current availability of effective therapies, close follow-up of presymptomatic TTR mutation carriers is essential to recognize disease onset at the earliest sign. In addition to routine techniques, in recent years several novel tools have been proposed, although a consensus on their use has not been reached yet. In this paper, we aimed to evaluate possible markers of neuropathic disease onset intended to discriminate clinically asymptomatic carriers from early symptomatic patients, thus allowing timely treatment initiation. METHODS: Thirty-eight presymptomatic carriers were enrolled. Clinical and electrophysiological findings at first evaluation and follow-up were collected. All carriers underwent an extensive clinical and instrumental evaluation according to the standard clinical practice. One or more non-routine investigations, whose use in this field is not yet validated (henceforth "unconventional"), were additionally assessed in a subgroup of individuals. RESULTS: Based on the exclusive use of routine investigations, it was possible to define disease onset in 4/38 carriers during the follow-up. Employing additionally one or more "unconventional" tests, abnormal findings, indicative of a possible "conversion" to symptomatic disease, were detected in further 12 cases. More than half of our study cohort showed findings suggestive of small nerve fiber (SF) involvement at either invasive or non-invasive tests. CONCLUSIONS: A close, multidisciplinary monitoring of presymptomatic TTR mutation carriers is fundamental, and diagnostic workup should include both routine and "unconventional" tests. Assessment of SF involvement is important also in non-endemic countries.

Serum neurofilament light chain: a promising early diagnostic biomarker for hereditary transthyretin amyloidosis?

BACKGROUND AND PURPOSE: Hereditary transthyretin amyloidosis (ATTRv) is a life-threatening disease caused by mutations in the gene encoding transthyretin (TTR). The recent therapeutic advances have underlined the importance of easily accessible, objective biomarkers of both disease onset and progression. Preliminary evidence suggests a potential role in this respect for neurofilament light chain (NfL). In this study, the aim was to determine serum NfL (sNfL) levels in a late-onset ATTRv population and evaluate whether it might represent a reliable biomarker of disease onset (i.e., 'conversion' from the asymptomatic status to symptomatic disease in TTR mutation carriers). METHODS: In all, 111 individuals harbouring a pathogenic TTR variant (61 symptomatic ATTRv patients and 50 presymptomatic carriers) were consecutively enrolled. Fifty healthy volunteers were included as the control group. Ella™ apparatus was used to assess sNfL levels. RESULTS: Serum NfL levels were increased in ATTRv patients compared to both presymptomatic carriers and healthy controls, whilst not differing between carriers and healthy controls. An sNfL cut-off of 37.10 pg/mL could discriminate between asymptomatic and symptomatic individuals with high diagnostic accuracy (area under the curve 0.958; p < 0.001), sensitivity (81.4%) and specificity (100%). CONCLUSIONS: Serum NfL seems to be a promising biomarker of peripheral nerve involvement in ATTRv amyloidosis and might become a reliable, objective measure to detect the transition from the presymptomatic stage to the onset of symptomatic disease. Further longitudinal studies are needed to confirm such a role and determine whether it could equally represent a biomarker of disease progression and response to therapy.

Talent identification and development in an English Premiership rugby union club: the perspectives of players and coaches.

The pathway towards senior professional status in sport is affected by a multitude of factors. An abductive examination of the talent identification and development processes at an English Premiership rugby union (RU) club was undertaken for the present study. Part one examined the perspectives on the selection and development processes of senior academy male players (n = 8), whereas part two explored the perceptions of male coaches (n = 7). A total of three focus groups were used. Three main themes were confirmed by players and coaches: (a) task constraints, (b) performer constraints, and (c) environmental constraints. Specifically, although athletes and coaches believed that performer constraints were highly impactful on players' career in RU, there were inconsistencies surrounding the task and environmental constraints. Despite an indication that three common themes impacted an players path, this preliminary study shows an imbalance in the understanding of some of the key factors perceived to be important for talent progression in the present rugby academy. More research using similar qualitative methods is recommended to better understand the differences in opinions between players and coaches. Meanwhile, practitioners should consider implementing objective and holistic strategies to improve the talent pathway in English RU academies.

Breast cancer therapies reduce risk of Alzheimer's disease and promote estrogenic pathways and action in brain.

Worldwide, an ever-increasing number of women are prescribed estrogen-modulating therapies (EMTs) for the treatment of breast cancer. In parallel, aging of the global population of women will contribute to risk of both breast cancer and Alzheimer's disease. To address the impact of anti-estrogen therapies on risk of Alzheimer's and neural function, we conducted medical informatic and molecular pharmacology analyses to determine the impact of EMTs on risk of Alzheimer's followed by determination of EMT estrogenic mechanisms of action in neurons. Collectively, these data provide both clinical and mechanistic data indicating that select EMTs exert estrogenic agonist action in neural tissue that are associated with reduced risk of Alzheimer's disease while simultaneously acting as effective estrogen receptor antagonists in breast.

Nerve MR in the Differential Diagnosis of Neuropathies: A Case Series from a Single Center.

In the present study, through a case series, we highlighted the role of magnetic resonance (MR) in the identification and diagnosis of peripheral neuropathies. MR neurography allows the evaluation of the course of nerves through 2D and 3D STIR sequences with an isotropic voxel, whereas the relationship between nerves, vessels, osteo-ligamentous and muscular structures can be appraised with T1 sequences. Currently, DTI and tractography are mainly used for experimental purposes. MR neurography can be useful in detecting subtle nerve alterations, even before the onset of symptoms. However, despite being sensitive, MR neurography is not specific in detecting nerve injury and requires careful interpretation. For this reason, MR information should always be supported by instrumental clinical tests.

Impact of patent ductus arteriosus on non-invasive assessments of lung fluids in very preterm infants during the transitional period.

This prospective observational study aimed to evaluate whether lung fluids, assessed by lung ultrasonography and transthoracic electrical bioimpedance (TEB), may be influenced by the presence of a haemodynamically significant patent ductus arteriosus (hsPDA) in very preterm infants during the transitional period. Infants < 32 weeks of gestational age (GA) admitted to the neonatal intensive care units of IRCCS AOU Bologna and Niguarda Metropolitan Hospital of Milan (Italy) underwent a daily assessment of a lung ultrasound score (LUS) and of a TEB-derived index of thoracic fluid contents (TFC) during the first 72 h after birth. Echocardiographic scans were simultaneously performed to evaluate the concomitant ductal status (hsPDA vs. restrictive or closed duct). The correlation between LUS, TFC, and the ductal status was tested using generalized estimating equations. Forty-six infants (median GA: 29 [interquartile range, IQR: 27-31] weeks; median birth weight: 1099 [IQR: 880-1406] g) were included. At each daily evaluation, the presence of a hsPDA was associated with significantly higher LUS and TFC compared with a restrictive or closed ductus (p < 0.01 for all comparisons). These results were confirmed significant even after adjustment for GA and for the ongoing modality of respiratory support. Conclusion: Even during the first 72 h of life, the presence of a hsPDA determines a significant increase in pulmonary fluids which can be non-invasively detected and monitored over time using lung ultrasonography and TEB. What is Known: • Lung ultrasonography provides a non-invasive assessment of lung fluids and is widely used in neonatal settings. • In preterm infants, the persistence of a haemodynamically significant patent ductus arteriosus (hsPDA) over the first weeks can negatively affect pulmonary outcomes. What is New: • The presence of aan hsPDA is associated with increased lung fluids since early postnatal phases. • Lung ultrasonography and transthoracic electrical bioimpedance can effectively monitor lung fluid clearance in preterm infants with a hsPDA during the transitional period, with potential clinical implications.

Machine Learning for Early Diagnosis of ATTRv Amyloidosis in Non-Endemic Areas: A Multicenter Study from Italy.

BACKGROUND: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv) is an adult-onset multisystemic disease, affecting the peripheral nerves, heart, gastrointestinal tract, eyes, and kidneys. Nowadays, several treatment options are available; thus, avoiding misdiagnosis is crucial to starting therapy in early disease stages. However, clinical diagnosis may be difficult, as the disease may present with unspecific symptoms and signs. We hypothesize that the diagnostic process may benefit from the use of machine learning (ML). METHODS: 397 patients referring to neuromuscular clinics in 4 centers from the south of Italy with neuropathy and at least 1 more red flag, as well as undergoing genetic testing for ATTRv, were considered. Then, only probands were considered for analysis. Hence, a cohort of 184 patients, 93 with positive and 91 (age- and sex-matched) with negative genetics, was considered for the classification task. The XGBoost (XGB) algorithm was trained to classify positive and negative TTR mutation patients. The SHAP method was used as an explainable artificial intelligence algorithm to interpret the model findings. RESULTS: diabetes, gender, unexplained weight loss, cardiomyopathy, bilateral carpal tunnel syndrome (CTS), ocular symptoms, autonomic symptoms, ataxia, renal dysfunction, lumbar canal stenosis, and history of autoimmunity were used for the model training. The XGB model showed an accuracy of 0.707 ± 0.101, a sensitivity of 0.712 ± 0.147, a specificity of 0.704 ± 0.150, and an AUC-ROC of 0.752 ± 0.107. Using the SHAP explanation, it was confirmed that unexplained weight loss, gastrointestinal symptoms, and cardiomyopathy showed a significant association with the genetic diagnosis of ATTRv, while bilateral CTS, diabetes, autoimmunity, and ocular and renal involvement were associated with a negative genetic test. CONCLUSIONS: Our data show that ML might potentially be a useful instrument to identify patients with neuropathy that should undergo genetic testing for ATTRv. Unexplained weight loss and cardiomyopathy are relevant red flags in ATTRv in the south of Italy. Further studies are needed to confirm these findings.

Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration.

Astrocytes provide key neuronal support, and their phenotypic transformation is implicated in neurodegenerative diseases. Metabolically, astrocytes possess low mitochondrial oxidative phosphorylation (OxPhos) activity, but its pathophysiological role in neurodegeneration remains unclear. Here, we show that the brain critically depends on astrocytic OxPhos to degrade fatty acids (FAs) and maintain lipid homeostasis. Aberrant astrocytic OxPhos induces lipid droplet (LD) accumulation followed by neurodegeneration that recapitulates key features of Alzheimer's disease (AD), including synaptic loss, neuroinflammation, demyelination and cognitive impairment. Mechanistically, when FA load overwhelms astrocytic OxPhos capacity, elevated acetyl-CoA levels induce astrocyte reactivity by enhancing STAT3 acetylation and activation. Intercellularly, lipid-laden reactive astrocytes stimulate neuronal FA oxidation and oxidative stress, activate microglia through IL-3 signalling, and inhibit the biosynthesis of FAs and phospholipids required for myelin replenishment. Along with LD accumulation and impaired FA degradation manifested in an AD mouse model, we reveal a lipid-centric, AD-resembling mechanism by which astrocytic mitochondrial dysfunction progressively induces neuroinflammation and neurodegeneration.

ANCA-negative microscopic polyangiitis with neuromuscular involvement: When pathology could make the difference.

Microscopic polyangiitis (MPA) is a necrotizing small vessel vasculitis with little or absent immune deposits (pauci-immune vasculitis), usually associated with the presence of antineutrophil cytoplasmic autoantibodies (ANCA) and a wide spectrum of organ manifestations. In our report we describe the case of a 74-year-old Asian man, who rapidly developed lower limb weakness and impaired renal and pulmonary functions. ANCA detection remained borderline throughout the disease course. Electrophysiological and instrumental studies revealed a picture of neuromuscular involvement; renal and muscle biopsies disclosed a small vessel vasculitis. He was started on a targeted immunosuppressive combination therapy and his clinical status progressively improved. In the framework of a multi-organ disease, microscopic polyangiitis should be considered as a differential diagnosis in case of acute/subacute onset of muscle weakness, even in the absence of ANCA detection.

Serum Inflammatory Profile in Hereditary Transthyretin Amyloidosis: Mechanisms and Possible Therapeutic Implications.

Hereditary transthyretin (ATTRv) amyloidosis is a severe, progressive, and heterogeneous multisystemic condition due to mutations in the TTR gene. Although multiple aspects of its molecular pathophysiological mechanisms have been elucidated over the years, it is possible to hypothesize different pathogenetic pathways. Indeed, we extensively investigated the serum levels of several molecules involved in the immune response, in a cohort of ATTRv patients and healthy controls (HCs). Sixteen ATTRv patients and twenty-five HCs were included in the study. IFN-alpha levels were higher in ATTRv patients than in HCs, as well as IFN-gamma levels. By contrast, IL-7 levels were lower in ATTRv patients than in HCs. No significant difference between groups was found regarding IL-1Ra, IL-6, IL-2, IL-4, and IL-33 levels. Correlation analysis did not reveal any significant correlation between IFN-α, IFN-γ, IL-7, and demographic and clinical data. Larger and longitudinal studies using ultrasensitive methods to perform a full cytokine profiling are needed to better elucidate the role of inflammation in ATTRv pathogenesis and to test the reliability of these molecules as possible biomarkers in monitoring patients' progression.