Balneotherapy and cortisol levels: an updated systematic review and meta-analysis.

The main objective of this review is to examine the impact of balneotherapy on serum and salivary cortisol concentrations. A systematic search was conducted in PubMed, Scopus, Web of Science, PEDro, and Google Scholar. The databases were screened from inception up until April 2024. After screening the scientific literature, 845 articles were retrieved and 17 studies, involving a total of 765 participants, were eventually included in the review. Among them, four were randomized controlled trials, five were non-randomized studies, and eight were pre-post studies with no control group. The evidence gathered in this review indicates a significant short-term reduction in cortisol levels in healthy individuals undergoing balneotherapy, particularly those experiencing high levels of stress. Conversely, in patients with rheumatic conditions (especially if elderly), increases in cortisol levels induced by balneotherapy can act as beneficial hormetic stress, reducing inflammatory mediators and improving pain and functional quality of life. The meta-analysis shows an overall trend of reduction in stress hormone levels, more pronounced in the intervention group undergoing mud-balneotherapy compared to the control group, a finding that, however, does not reach statistical significance (g=-0.11 [95% CI: -0.30; 0.08]; p > 0.05). Current scientific evidence demonstrates that balneotherapy has a positive impact on the regulation of cortisol levels. The regulation of the hypothalamic-pituitary-adrenal axis and the beneficial effects observed on health parameters and quality of life allow mud-balneotherapy to be classified as eustressful stimuli useful in preventing stress-related pathologies in healthy individuals and in alleviating symptoms in patients with chronic conditions. Future research on the topic is advised.

A Higher Kick Frequency Swimming Training Program Optimizes Swim-to-Cycle Transition in Triathlon.

ABSTRACT: Ambrosini, L, Presta, V, Vitale, M, Menegatti, E, Guarnieri, A, Bianchi, V, De Munari, I, Condello, G, and Gobbi, G. A higher kick frequency swimming training program optimizes swim-to-cycle transition in triathlon. J Strength Cond Res 38(5): 976-984, 2024-The purpose of this study was to evaluate the effect of an 8-week swimming training program on biomechanical and physiological responses during a swim-to-cycle simulation. Fifteen triathletes were randomly allocated to 3 groups: a 6-beat-kick group (K6), a 4-beat-kick group (K4), and a control group (CG). Biomechanical and physiological parameters were evaluated during a 400-m swim and a 10-minute cycle segment before (Pretraining) and after (Posttraining) the program. A lower stroke frequency ( p = 0.004) and a higher stroke length ( p = 0.002) was found in K6 compared with CG at Posttraining. A reduction in the K6 emerged between Pretraining and Posttraining during cycling for heart rate ( p = 0.005), V̇O 2 ( p = 0.014), and energy expenditure ( p = 0.008). A positive association emerged between swim kick index and cycling cadence in the K6 group. The improvement in stroke frequency and length observed in the K6 group could be explained as an improvement in swimming technique. Similarly, the reduction in energy expenditure during cycling at Posttraining for the K6 group suggests an improvement in the working economy. Triathlon coaches and athletes should consider the inclusion of high swim kick into their training programs to enhance swim and cycling performance, which can ultimately lead to an improvement in the swim-to-cycle transition and the overall triathlon performance.

Clinical efficacy of medical hydrology: an umbrella review.

The aim of this research was to summarize available scientific evidence on the efficacy of medical hydrology for the management of any health condition. The search was conducted on 26th March 2021, in the following databases: Medline (via PubMed), EMBASE, Web of Science, Cochrane Library, and Google Scholar. All relevant literature reviews investigating the clinical efficacy of interventions characterized by the use of natural mineral waters and muds were included. The quality of studies was assessed with the "AMSTAR 2" tool. After article screening, 49 reviews were included in this work. Overall, retrieved scientific evidence suggests that spa therapy is beneficial for patients affected by some specific musculoskeletal conditions, with improvements potentially lasting up to 9 months. Moreover, balneotherapy can be an integrative support for the management of chronic venous insufficiency and some inflammatory skin diseases like psoriasis. The role of spa therapy in rehabilitation appears relevant as well. More limited, although interesting evidence exists for inhalation and hydropinic therapies. Globally, retrieved evidence suggests that, besides individual wellbeing, medical hydrology can be useful for public health. In particular, higher-quality studies seem to support the integrative use of spa-related interventions for conditions like osteoarthritis, fibromyalgia, low back pain of rheumatic origin, and chronic venous insufficiency. However, the body of evidence has some limitations and further clinical trials should be designed for each relevant application to consolidate and expand acquired knowledge.

Guide Cells Support Muscle Regeneration and Affect Neuro-Muscular Junction Organization.

Muscular regeneration is a complex biological process that occurs during acute injury and chronic degeneration, implicating several cell types. One of the earliest events of muscle regeneration is the inflammatory response, followed by the activation and differentiation of muscle progenitor cells. However, the process of novel neuromuscular junction formation during muscle regeneration is still largely unexplored. Here, we identify by single-cell RNA sequencing and isolate a subset of vessel-associated cells able to improve myogenic differentiation. We termed them 'guide' cells because of their remarkable ability to improve myogenesis without fusing with the newly formed fibers. In vitro, these cells showed a marked mobility and ability to contact the forming myotubes. We found that these cells are characterized by CD44 and CD34 surface markers and the expression of Ng2 and Ncam2. In addition, in a murine model of acute muscle injury and regeneration, injection of guide cells correlated with increased numbers of newly formed neuromuscular junctions. Thus, we propose that guide cells modulate de novo generation of neuromuscular junctions in regenerating myofibers. Further studies are necessary to investigate the origin of those cells and the extent to which they are required for terminal specification of regenerating myofibers.

Spa therapy and rehabilitation of musculoskeletal pathologies: a proposal for best practice in Italy.

Spa therapy is a heterogeneous collection of treatments and methods based on natural resources. It is often considered as an option in the common therapeutic approach to many musculoskeletal disorders, as well as respiratory, vascular, and dermatological disorders. The objective of this paper is to highlight possible interactions between rehabilitation and spa medicine in the field of musculoskeletal disorders, through an analysis of the scientific literature, in order to give the practitioner the ability to integrate good clinical practice in the field of rehabilitation through practical application involving spa therapies. The literature search was conducted using Medline, PEDro, Cochrane Database, and Google Scholar. Only studies published in English and works concerning the implementation of spa thermal treatment in neuro-musculoskeletal diseases were included. Specifically, the publications analyzed dealt with the treatment of diseases such as arthritis, rheumatic arthritis, ankylosing spondylitis, and low back pain through the use of thermal spa therapies. In conjunction with its widespread use in clinical practice, many studies in the literature suggest the effectiveness of crenobalneotherapy for a number of musculoskeletal disorders, generally those which are chronic and debilitating, finding significant clinical improvement both in terms of pain and functional limitations. Some of the guidelines formulated by national and international bodies on the treatment of specific diseases, such as the Italian Rheumatology Society (SIR) and the Osteoarthritis Research Society International (OARSI) guidelines, recognize the value of thermal medicine as a complement, but not a replacement, for conventional therapy (pharmacological or not).

ROS in Platelet Biology: Functional Aspects and Methodological Insights.

Reactive oxygen species (ROS) and mitochondria play a pivotal role in regulating platelet functions. Platelet activation determines a drastic change in redox balance and in platelet metabolism. Indeed, several signaling pathways have been demonstrated to induce ROS production by NAPDH oxidase (NOX) and mitochondria, upon platelet activation. Platelet-derived ROS, in turn, boost further ROS production and consequent platelet activation, adhesion and recruitment in an auto-amplifying loop. This vicious circle results in a platelet procoagulant phenotype and apoptosis, both accounting for the high thrombotic risk in oxidative stress-related diseases. This review sought to elucidate molecular mechanisms underlying ROS production upon platelet activation and the effects of an altered redox balance on platelet function, focusing on the main advances that have been made in platelet redox biology. Furthermore, given the increasing interest in this field, we also describe the up-to-date methods for detecting platelets, ROS and the platelet bioenergetic profile, which have been proposed as potential disease biomarkers.

PKCε promotes human Th17 differentiation: Implications in the pathophysiology of psoriasis.

PKCε is implicated in T cell activation and proliferation and is overexpressed in CD4+ -T cells from patients with autoimmune Hashimoto's thyroiditis. Although this might induce the suspicion that PKCε takes part in autoimmunity, its role in the molecular pathophysiology of immune-mediated disorders is still largely unknown. We studied PKCε expression in circulating CD4+ -T cells from patients with psoriasis, a skin disorder characterized by an increased amount of Th17 cells, a CD4+ subset that is critical in the development of autoimmunity. Although the mechanisms that underlie Th17 differentiation in humans are still unclear, we here show that: (i) PKCε is overexpressed in CD4+ -T cells from psoriatic patients, and its expression positively correlates with the severity of the disease, being reduced by effective phototherapy; (ii) PKCε interacts with Stat3 during Th17 differentiation and its overexpression results in an enhanced expression of Stat3 and pStat3(Ser727); iii) conversely, when PKCε is forcibly downregulated, CD4+ -T cells show lower levels of pStat3(Ser727) expression and defective in vitro expansion into the Th17-lineage. These data provide a novel insight into the molecular mechanisms of Th17 cell polarization that is known to play a crucial role in autoimmunity, pinpointing PKCε as a potential target in Th17-mediated diseases.

Sulphurous thermal water inhalation impacts respiratory metabolic parameters in heavy smokers.

Sulphurous thermal water inhalations have been traditionally used in the treatment of airway diseases. In vivo and in vitro studies reported that they ameliorate mucus rheology, mucociliary clearance and reduce inflammation. Cigarette smoking induces an inflammatory damage, with consequent remodeling of respiratory airways, which in turn affect pulmonary functions. Despite the anti-inflammatory effects of H2S are clinically documented in several airway inflammatory diseases, data on the effects of sulphurous thermal water treatment on pulmonary function and biomarkers of airways inflammation in smokers are still scant. Therefore, we investigated whether a conventional cycle of sulphurous thermal water inhalation produced changes in markers of respiratory inflammation and function. A cohort of 504 heavy current and former smokers underwent 10-day cycles of sulphurous thermal water inhalation. Pulmonary function and metabolic analyses on exhaled breath condensate were then performed at day 0 and after the 10-day treatment. Spirometric data did not change after spa therapy, while exhaled breath condensate analysis revealed that a single 10-day cycle of sulphurous water inhalation was sufficient to induce a statistically significant increase of citrulline levels along with a decrease in ornithine levels, thus shifting arginine metabolism towards a reduced nitric oxide production, i.e. an anti-inflammatory profile. Overall, sulphurous thermal water inhalation impacts on arginine catatabolic intermediates of airways cells, shifting their metabolic balance towards a reduction of the inflammatory activity, with potential benefits for smokers.

Roles and clinical implications of microRNAs in acute lymphoblastic leukemia.

MicroRNAs (miRNAs) are a class of small noncoding RNAs which regulate the expression of target genes by binding to messenger RNAs. miRNAs play a role in various biological processes, including proliferation, apoptosis, and tumorigenesis. Dysregulation of miRNAs is implicated in invasion and metastasis in several human cancer types, and leukemia is not an exception. Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by the proliferation of early lymphoid precursors that replace normal hematopoietic cells of the bone marrow. The expression profiling of miRNAs in ALL could be used for the classification of the disease establishing specific diagnoses and offering prognostic values in the near future. The correlation of miRNAs dysregulation and biology of ALL demonstrates that specific miRNA may be a potential therapeutic target. In this review we have focused our attention on the correlations between ALL and miRNAs, their link with signaling pathways and transcription factors in the disease and miRNA targeting therapeutic strategies with their advantages and potential use in clinical applications.

Targeting the phosphatidylinositol 3-kinase/Akt/mechanistic target of rapamycin signaling pathway in B-lineage acute lymphoblastic leukemia: An update.

Despite considerable progress in treatment protocols, B-lineage acute lymphoblastic leukemia (B-ALL) displays a poor prognosis in about 15-20% of pediatric cases and about 60% of adult patients. In addition, life-long irreversible late effects from chemo- and radiation therapy, including secondary malignancies, are a growing problem for leukemia survivors. Targeted therapy holds promising perspectives for cancer treatment as it may be more effective and have fewer side effects than conventional therapies. The phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway is a key regulatory cascade which controls proliferation, survival and drug-resistance of cancer cells, and it is frequently upregulated in the different subtypes of B-ALL, where it plays important roles in the pathophysiology, maintenance and progression of the disease. Moreover, activation of this signaling cascade portends a poorer prognosis in both pediatric and adult B-ALL patients. Promising preclinical data on PI3K/Akt/mTOR inhibitors have documented their anticancer activity in B-ALL and some of these novel drugs have entered clinical trials as they could lead to a longer event-free survival and reduce therapy-associated toxicity for patients with B-ALL. This review highlights the current status of PI3K/Akt/mTOR inhibitors in B-ALL, with an emphasis on emerging evidence of the superior efficacy of synergistic combinations involving the use of traditional chemotherapeutics or other novel, targeted agents.

Small bowel lymphoma presenting as inguinal hernia: case report and literature review.

BACKGROUND: Inguinal hernia is one of the most common benign pathologies that primarily affects men. Primary gastrointestinal non-Hodgkin's lymphoma (PGI NHL) is the most common type of extranodal lymphoma. This study reports a rare case in which these two conditions co-exist. CASE PRESENTATION: An 85-year-old male complained of bowel movement pattern change, abdominal distension and loss of weight, without vomiting but with nausea. A computed tomographic scan of the abdomen showed a small bowel obstruction caused by a migration of a small bowel loop in the right inguinal canal, with a clinically non-reducible inguinal hernia. The patient underwent surgery. The histopathological report showed small bowel large B cell non-Hodgkin's lymphoma. CONCLUSION: When the diagnosis of the contents of an inguinal hernia is not well-established, surgery should be performed as soon as possible to ensure the cure of the disease and the correct diagnosis of the contents.

Claimed effects, outcome variables and methods of measurement for health claims on foods proposed under European Community Regulation 1924/2006 in the area of appetite ratings and weight management.

All the requests for authorisation to bear health claims under Articles 13(5) and 14 in the context of appetite ratings and weight management have received a negative opinion by the European Food Safety Authority (EFSA), mainly because of the insufficient substantiation of the claimed effects (CEs). This manuscript results from an investigation aimed to collect, collate and critically analyse the information related to outcome variables (OVs) and methods of measurement (MMs) in the context of appetite ratings and weight management compliant with Regulation 1924/2006. Based on the literature review, the appropriateness of OVs and MMs was evaluated for specific CEs. This work might help EFSA in the development of updated guidance addressed to stakeholders interested in bearing health claims in the area of weight management. Moreover, it could drive the applicants during the design of randomised controlled trials aimed to substantiate such claims.

Claimed effects, outcome variables and methods of measurement for health claims on foods related to the gastrointestinal tract proposed under regulation (EC) 1924/2006.

Most of the requests of authorisation to the use of health claims pursuant to Regulation EC 1924/2006 related to the gastrointestinal (GI) tract have received a negative opinion by the European Food Safety Authority (EFSA), mainly because of an insufficient substantiation of the claimed effect (CE). The present manuscript refers to the collection, collation and critical analysis of outcome variables (OVs) and methods of measurement (MMs) related to the GI tract compliant with Regulation 1924/2006. The critical evaluation of OVs and MMs was based on the literature review, with the final aim of defining their appropriateness in the context of a specific CE. The results obtained are relevant for the choice of the best OVs and MMs to be used in randomised controlled trials aimed to substantiate the claims on the GI tract. Moreover, the results can be used by EFSA for updating the guidance for the scientific requirements of such health claims.

Human thrombopoiesis depends on Protein kinase Cδ/protein kinase Cε functional couple.

A deeper understanding of the molecular events driving megakaryocytopoiesis and thrombopoiesis is essential to regulate in vitro and in vivo platelet production for clinical applications. We previously documented the crucial role of PKCε in the regulation of human and mouse megakaryocyte maturation and platelet release. However, since several data show that different PKC isoforms fulfill complementary functions, we targeted PKCε and PKCδ, which show functional and phenotypical reciprocity, at the same time as boosting platelet production in vitro. Results show that PKCδ, contrary to PKCε, is persistently expressed during megakaryocytic differentiation, and a forced PKCδ down-modulation impairs megakaryocyte maturation and platelet production. PKCδ and PKCε work as a functional couple with opposite roles on thrombopoiesis, and the modulation of their balance strongly impacts platelet production. Indeed, we show an imbalance of PKCδ/PKCε ratio both in primary myelofibrosis and essential thrombocythemia, featured by impaired megakaryocyte differentiation and increased platelet production, respectively. Finally, we demonstrate that concurrent molecular targeting of both PKCδ and PKCε represents a strategy for in vitro platelet factories.

Giocampus school: a "learning through playing" approach to deliver nutritional education to children.

To improve nutritional knowledge of children, single-group educational interventions with pre/post knowledge assessment were performed in primary schools in Parma, Italy, participating to the Giocampus Program. A total of 8165 children (8-11 years old) of 3rd, 4th and 5th grades of primary school were involved in 3 hours per class nutritional lessons, with specifically designed games and activities for each school grade. To evaluate children learning, a questionnaire was administered before and after three months of educational intervention. A total of 16330 questionnaires were analysed. Children nutritional knowledge significantly increased (p< 0.001) in all school grades. The integrated "learning through playing" approach, including the educational figures, tools and games, was successful in improving children's nutritional knowledge. A stable integration of this method in primary school settings could prepare a new generation of citizens, better educated on health-promotion lifestyles.

Monitoring inflammation and airway remodeling by fluorescence molecular tomography in a chronic asthma model.

BACKGROUND: Asthma is a multifactorial disease for which a variety of mouse models have been developed. A major drawback of these models is represented by the transient nature of the airway pathology peaking 24-72 h after challenge and resolving in 1-2 weeks. We characterized the temporal evolution of pulmonary inflammation and tissue remodeling in a recently described mouse model of chronic asthma (8 week treatment with 3 allergens: Dust mite, Ragweed, and Aspergillus; DRA). METHODS: We studied the DRA model taking advantage of fluorescence molecular tomography (FMT) imaging using near-infrared probes to non-invasively evaluate lung inflammation and airway remodeling. At 4, 6, 8 or 11 weeks, cathepsin- and metalloproteinase-dependent fluorescence was evaluated in vivo. A subgroup of animals, after 4 weeks of DRA, was treated with Budesonide (100 µg/kg intranasally) daily for 4 weeks. RESULTS: Cathepsin-dependent fluorescence in DRA-sensitized mice resulted significantly increased at 6 and 8 weeks, and was markedly inhibited by budesonide. This fluorescent signal well correlated with ex vivo analysis such as bronchoalveolar lavage eosinophils and pulmonary inflammatory cell infiltration. Metalloproteinase-dependent fluorescence was significantly increased at 8 and 11 weeks, nicely correlated with collagen deposition, as evaluated histologically by Masson's Trichrome staining, and airway epithelium hypertrophy, and was only partly inhibited by budesonide. CONCLUSIONS: FMT proved suitable for longitudinal studies to evaluate asthma progression, showing that cathepsin activity could be used to monitor inflammatory cell infiltration while metalloproteinase activity parallels airway remodeling, allowing the determination of steroid treatment efficacy in a chronic asthma model in mice.

Proplatelet generation in the mouse requires PKCε-dependent RhoA inhibition.

During thrombopoiesis, megakaroycytes undergo extensive cytoskeletal remodeling to form proplatelet extensions that eventually produce mature platelets. Proplatelet formation is a tightly orchestrated process that depends on dynamic regulation of both tubulin reorganization and Rho-associated, coiled-coil containing protein kinase/RhoA activity. A disruption in tubulin dynamics or RhoA activity impairs proplatelet formation and alters platelet morphology. We previously observed that protein kinase Cepsilon (PKCε), a member of the protein kinase C family of serine/threonine-kinases, expression varies during human megakaryocyte differentiation and modulates megakaryocyte maturation and platelet release. Here we used an in vitro model of murine platelet production to investigate a potential role for PKCε in proplatelet formation. By immunofluorescence we observed that PKCε colocalizes with α/ß-tubulin in specific areas of the marginal tubular-coil in proplatelets. Moreover, we found that PKCε expression escalates during megakarocyte differentiation and remains elevated in proplatelets, whereas the active form of RhoA is substantially downregulated in proplatelets. PKCε inhibition resulted in lower proplatelet numbers and larger diameter platelets in culture as well as persistent RhoA activation. Finally, we demonstrate that pharmacological inhibition of RhoA is capable of reversing the proplatelet defects mediated by PKCε inhibition. Collectively, these data indicate that by regulating RhoA activity, PKCε is a critical mediator of mouse proplatelet formation in vitro.

Cytofluorimetric platelet analysis.

Blood platelets are highly specialized cells that drive hemostatic events and tissue repair mechanisms at the site of vascular injury. Their peculiar morphology and certain functional characteristics can be analyzed by flow cytometry (FCM). Specifically, platelet activation, a hallmark of prothrombotic states and inflammatory conditions, is associated with changes in expression of both surface and intracellular antigens that are recognized by specific monoclonal antibodies. Assessment of platelet activation status as ex vivo or in vitro reactivity to specific agonists has become relevant in particular conditions (namely, cardiovascular diseases, hematological malignancies, monitoring of pharmacological antiaggregation). In addition, aberrant surface marker expression that characterizes inherited and acquired platelet function disorders is also detected by FCM. This review discusses the main applications of FCM in platelet analyses, which are relevant for both research and clinical settings.

Laboratory diagnostics of inherited platelet disorders.

Abstract Inherited platelet disorders (IPDs) are the general and common denomination of a broad number of different rare and congenital pathologies affecting platelets. Even if these disorders are characterized by widely heterogeneous clinical presentations, all of them are commonly present as defects in hemostasis. Platelet number and/or function are affected by a wide spectrum of severity. IPDs might be associated with defects in bone marrow megakaryocytopoiesis and, rarely, with somatic defects. Although in the last few years new insights in the genetic bases and pathophysiology of IPDs have greatly improved our knowledge of these disorders, much effort still needs to be made in the field of laboratory diagnosis. This review discusses the laboratory approach for the differential diagnosis of the most common IPDs, suggesting a common multistep flowchart model which starts from the simpler test (platelet count) ending with the more selective and sophisticated analyses.