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The pig is an important translational model for studying intestinal physiology and disorders for its many homologies with humans, including the organization of the enteric nervous system (ENS), the major regulator of gastrointestinal functions. This study focused on the quantification and neurochemical characterization of substance P (SP) neurons in the pig ascending (AC) and descending colon (DC) in wholemount preparations of the inner submucosal plexus (ISP), outer submucosal plexus (OSP), and myenteric plexus (MP). We used antibodies for the pan-neuronal marker HuCD, and choline acetyltransferase (ChAT) and neuronal nitric oxide synthase (nNOS), markers for excitatory and inhibitory transmitters, for multiple labeling immunofluorescence and high-resolution confocal microscopy. The highest density of SP immunoreactive (IR) neurons was in the ISP (222/mm2 in the AC, 166/mm2 in the DC), where they make up about a third of HuCD-IR neurons, compared to the OSP and MP (19-22% and 13-17%, respectively, P

Abstract Background Cardiopulmonary resuscitation-associated lung edema (CRALE) is a phenomenon that has been recently reported in both experimental and out-of-hospital cardiac arrest patients. We aimed to explore the respiratory and cardiovascular pathophysiology of CRALE in an experimental model of cardiac arrest undergoing prolonged manual and mechanical chest compression (CC). Oxygen delivery achieved during mechanical or manual CC were also investigated as a secondary aim, to describe CRALE evolution under different hemodynamic supports generated during CPR. Methods Ventricular fibrillation (VF) was induced and left untreated for 5 min prior to begin cardiopulmonary resuscitation (CPR), including CC, ventilation with oxygen, epinephrine administration and defibrillation. Continuous mechanical and manual CC was performed alternating one of the two strategies every 5 min for a total of 25 min. Unsynchronized mechanical ventilation was resumed simultaneously to CC. A lung computed tomography (CT) was performed at baseline and 1 h after return of spontaneous circulation (ROSC) in surviving animals. Partitioned respiratory mechanics, gas exchange, hemodynamics, and oxygen delivery were evaluated during the experimental study at different timepoints. Lung histopathology was performed. Results After 25 min of CPR, a marked decrease of the respiratory system compliance with reduced oxygenation and CO2 elimination were observed in all animals. The worsening of the respiratory system compliance was driven by a significant decrease in lung compliance. The presence of CRALE was confirmed by an increased lung weight and a reduced lung aeration at the lung CT, together with a high lung wet-to-dry ratio and reduced airspace at histology. The average change in esophageal pressure during the 25-min CPR highly correlated with the severity of CRALE, i.e., lung weight increase. Conclusions In this porcine model of cardiac arrest followed by a 25-min interval of CPR with mechanical and manual CC, CRALE was consistently present and was characterized by lung inhomogeneity with alveolar tissue and hemorrhage replacing alveolar airspace. Despite mechanical CPR is associated with a more severe CRALE, the higher cardiac output generated by the mechanical compression ultimately accounted for a greater oxygen delivery. Whether specific ventilation strategies might prevent CRALE while preserving hemodynamics remains to be proved.

BackgroundThe study investigates the impact of tele-exercise on physical fitness and psychological well-being in healthy individuals. Tele-exercise, facilitated by technology, offers a flexible and accessible alternative to traditional exercise, particularly beneficial during restricted in-person interactions.MethodsIn this study, 52 participants were divided into three groups: athletes, women, and young adults. They took part in an eight-week tele-exercise program, either synchronously or asynchronously. Physical fitness was evaluated using tests such as the 2-Minute Step and Curl Up Test, while psychological well-being was assessed using the Psychological General Well-Being Index (PGWBI) and Perceived Stress Scale (PSS-10).ResultsSignificant improvements in physical fitness and psychological well-being were observed in post-intervention across all groups, regardless of training mode. In the fitness tests, a significant improvement was obtained in the 2-Minute-Step (p = 0.004), in the curls up (p = 0.017), and in squats test (p = 0.004). In the forward bending test, the increment was very close to the significance (p = 0.051). In the psychological well-being tests, both PGWBI and WHO-5 scores increased after the training (p = 0.024 and p = 0.001 respectively) with no significant change in the PSS-10 score. The study found that tele-exercise can effectively introduce physical activity to previously inactive individuals and motivate them to adopt healthier lifestyle behaviors.ConclusionsThe TELEexe4ALL project demonstrates the potential of tele-exercise to improve physical fitness and psychological well-being. The study suggests that tele-exercise is a feasible and well-accepted approach for enhancing overall wellness in healthy populations.

Introduction: Peyronie’s disease (PD) is characterized by fibrosis of the penile tunica albuginea. Conservative treatment options may involve oral and/or injectable medications. Materials and methods: This case series includes four patients with PD in the first phase. The diagnosis of PD included a medical history; penile palpation; a physical examination of the penis, documenting penile deformity (Kelâmi method); penile dynamic Doppler ultrasound (PDDU) + elastography, measuring the plaque and calculating its volume (cm3), and the deformation index (strain ratio); and the completion of the following questionnaires: IIEF to assess erectile function, VAS to assess pain, and Peyronie's Disease Questionnaire (PDQ) symptom bother to evaluate the psychosexual impact of the disease. Diagnostic follow-up evaluations were conducted before and every 6-12 months throughout the conservative treatment. The four patients were treated at our andrology clinic between January 2019 and November 2023. Our treatment included the following: bilberry, propolis, ginkgo biloba, silymarin, L-carnitine, coenzime Q-10, Boswellia, superoxide dismutase, vitamin E, vitamin C, topical diclofenac gel, propolis cream, and perilesional penile injections with pentoxifylline for cases involving penile plaques with volumes of > 0.100 cm3. Results: Complete resorption of the PD plaque after treatment occurred in all cases. The disappearance of Peyronie's plaque occurred over a period ranging from 18 to 36 months, in relation to the volume of the plaque. Conclusions: Despite the limited sample size in our study, these patients verifiably achieved the complete resorption of the affected disease area. Our results will provide useful insights for uroandrological clinical practice. Nevertheless, randomized controlled trials with a larger number of PD patients are needed to demonstrate the effectiveness of multimodal antioxidant treatment.

Background: B-mode ultrasound (US) medical imaging is very effective in localizing and describing Peyronie's disease (PD). Moreover, elastography is a new technique used to evaluate tissue elasticity to detect penile Peyronie's plaques that are not visible using standard B-mode US. Objective: The main objective of this study was to evaluate the diagnostic efficacy of real-time elastography (RTE) in PD patients and to determine whether its combined use with standard US improved diagnostic accuracy. RTE is also known as strain elastography (SE). Additionally, this study aimed to assess whether RTE was useful for monitoring PD patients undergoing conservative treatment. Methods: A group of 37 PD patients in the active phase was selected based on US examination showing isoechoic or hypo-isoechoic plaques, with or without associated hyperechoic or calcified plaque areas. All patients underwent traditional US combined with RTE before starting conservative treatment with antioxidants, during treatment and after treatment. After each examination with RTE, a specific “Strain Ratio”(SR) was used to identify the specific elasticity of the tissue. Results: Using B-mode US with RTE, we detected all 13 non-palpable penile plaques present in the 37 PD patients (100% of cases). Using only B-mode US, we detected only 8 of the 13 non-palpable plaques (61.5% of cases). The DI of the plaque decreased during and after treatment in all cases, indicating that RTE is effective for monitoring conservative PD treatment. A statistically significant correlation was found between the DI and plaque volume in all patients (p=0.002). Conclusion: Our study has shown that the combination of US and RTE methods allowed for a more accurate diagnosis in PD patients.

Abstract Systemic inflammation and neuroinflammation affect the natural course of the sporadic form of Alzheimer’s disease (AD), as supported by epidemiological and preclinical data, and several epidemiological studies indicate a higher prevalence of AD in patients with inflammatory bowel disease. In this study, we explored whether colitis induced by dextran sulfate sodium (DSS) in young, presymptomatic/preplaque mice worsens and/or anticipates age-dependent cognitive impairment in Tg2576, a widely used mouse model of AD. We demonstrated that DSS colitis induced in young Tg2576 mice anticipates the onset age of learning and memory deficit in the Morris water maze test. To explore potential mechanisms behind the acceleration of cognitive decline in Tg2576 mice by DSS colitis, we focused on gut microbiota, systemic inflammation and neuroinflammation markers. We observed a Firmicutes/Bacteroidetes ratio change in Tg2576 DSS animals comparable to that of elderly Tg2576 mice, suggesting accelerated microbiota aging in Tg2576 DSS mice, a change not observed in C57BL6 DSS mice. We also observed substantial differences between Tg2576 and WT mice in several inflammation and neuroinflammation-related parameters as early as 3 months of age, well before plaque deposition, a picture which evolved rapidly (between 3 and 5.5 months of age) in contrast to Tg2576 and WT littermates not treated with DSS. In detail, following induction of DSS colitis, WT and Tg2576 mice exhibited contrasting features in the expression level of inflammation-evoked astrocyte-associated genes in the hippocampus. No changes in microglial features occurred in the hippocampus between the experimental groups, whereas a reduced glial fibrillary acidic protein immunoreactivity was observed in Tg2576 vs. WT mice. This finding may reflect an atrophic, “loss-of-function” profile, further exacerbated by DSS where a decreased of GFAP mRNA expression level was detected. In conclusion, we suggest that as-yet unidentified peripheral mediators evoked by DSS colitis and involving the gut-brain axis emphasize an astrocyte “loss-of-function” profile present in young Tg2576 mice, leading to impaired synaptic morphological and functional integrity as a very early sign of AD.

Background and Purpose: Aiming to achieve light sedation via intranasal administration, this study showed that propofol (PPF) did not permeate across the rabbit nasal mucosa ex vivo from its marketed emulsion for injection. Experimental approach: Dilution of the emulsion with methyl-b-cyclodextrin in saline solution increased propofol solubility in water and diffusion across the nasal epithelium. Key results and conclusion: Despite these positive effects of the cyclodextrin, the amount of PPF permeated was minimal in 3 h, exceeding the formulation residence time in the nose. These results highlight the key role of formulation and the need for innovation in solubility and transmucosal transport enhancement techniques to optimize drug delivery and therapeutic efficacy.

Takotsubo syndrome (TS) is a transient cardiac condition characterized by regional systolic dysfunction, often precipitated by emotional or physical stressors. The pathophysiology of TS is not fully understood, but evidence suggests that it may be influenced by multiple factors. We present a case of TS following a traumatic left humerus fracture in an 82-year-old male patient with hypertension. Diagnosis was confirmed through comprehensive clinical evaluation, identification of ECG abnormalities, echocardiographic findings, and exclusion of other diseases. The patient’s management consisted of β-blockers, aspirin, and supportive care. Despite initial concerns, the patient's clinical course was uneventful, illustrating the various presentations of TS. This case emphasizes that TS can occur as a result of a traumatic event, particularly among older individuals with comorbidities. Early recognition and appropriate management are essential for optimizing outcomes.

Chronic kidney disease (CKD) globally represents a significant health challenge, particularly among patients undergoing chronic hemodialysis. A careful nutritional and pharmacological prescription plays a key role in the effective management of these patients to optimize serum electrolytes, such as potassium, phosphorus, and protein intake. Furthermore, these patients can suffer psychological distress due to dietary restrictions and tight medication schedules. The present study explores the effectiveness of the person-centered IARA model in improving physiological markers and quality of life in CKD patients undergoing hemodialysis treatment. To demonstrate the effectiveness of the IARA model, 60 patients (M = 40; F = 20; 60.5 ± 9.9 years) undergoing thrice-weekly hemodialysis sessions were enrolled and randomly and blindly assigned to the Control or IARA group. The reduction in abnormal blood potassium, phosphorus, and total protein levels was investigated, alongside the psychological state through the SF-12 questionnaire. Preliminary findings showed a discernible reduction in the frequency of abnormal blood K (> 5.0 mmol/L) and P (> 4.5 mmol/L) levels in the IARA group compared to the Control group. In particular, such reductions were approximately 40% for K (OR = 0.57; 95% CL = 0.23/1.46) and about 15% for P (OR = 0.86; 95% CL = 0.27/2.74). A similar tendency was also observed for patient fluid intake during each hemodialysis session, with the frequency of higher-risk patients in the IARA group being 50% lower (OR = 0.50; 95% CL = 0.07/3.79) than that of the Control group. Although preliminary findings from this study suggest that the IARA model may have a positive effect on CKD patients’ subjective wellbeing and quality of life (QoL), further research is needed to understand the long-term impact of the IARA intervention.

Literature highlights how education in the twenty-first century begins to advocate multiple new concepts, such as new technology, new pedagogies, interdisciplinary curricula, open learning, etc. Among these concepts, the recognition and awareness about one's character strengths are demonstrated to improve emotional management and individual/group's quality of life. We studied three fifth-grade Italian classes using an emerging educational model called IARA to verify if it can truly improve emotional literacy, characters strengths awareness, and cohesion in ten-years children. To demonstrate its efficacy, we used Bloom's Taxonomy and Sociogrammatic study. We proved that the IARA could be an efficient model to improve one's character strengths and class milieu awareness.

Abstract Mitochondria are cytoplasmic organelles having a fundamental role in the regulation of neural stem cell (NSC) fate during neural development and maintenance. During embryonic and adult neurogenesis, NSCs undergo a metabolic switch from glycolytic to oxidative phosphorylation with a rise in mitochondrial DNA (mtDNA) content, changes in mitochondria shape and size, and a physiological augmentation of mitochondrial reactive oxygen species which together drive NSCs to proliferate and differentiate. Genetic and epigenetic modifications of proteins involved in cellular differentiation (Mechanistic Target of Rapamycin), proliferation (Wingless-type), and hypoxia (Mitogen-activated protein kinase)–and all connected by the common key regulatory factor Hypoxia Inducible Factor-1A–are deemed to be responsible for the metabolic shift and, consequently, NSC fate in physiological and pathological conditions. Both primary mitochondrial dysfunction due to mutations in nuclear DNA or mtDNA or secondary mitochondrial dysfunction in oxidative phosphorylation (OXPHOS) metabolism, mitochondrial dynamics, and organelle interplay pathways can contribute to the development of neurodevelopmental or progressive neurodegenerative disorders. This review analyses the physiology and pathology of neural development starting from the available in vitro and in vivo models and highlights the current knowledge concerning key mitochondrial pathways involved in this process.

Abstract Background Pediatric chronic intestinal pseudo-obstruction (PIPO) is a rare disease characterized by symptoms and radiological signs suggestive of intestinal obstruction, in the absence of lumen-occluding lesions. It results from an extremely severe impairment of propulsive motility. The intestinal endocrine system (IES) jointly with the enteric nervous system (ENS) regulates secreto-motor functions via different hormones and bioactive messengers/neurotransmitters. The neurotransmitter 5-hydroxytryptamine (5-HT) (or serotonin) is linked to intestinal peristalsis and secretory reflexes. Gut microbiota and its interplay with ENS affect 5-HT synthesis, release, and the subsequent serotonin receptor activation. To date, the interplay between 5-HT and gut microbiota in PIPO remains largely unclear. This study aimed to assess correlations between mucosa associated microbiota (MAM), intestinal serotonin-related genes expression in PIPO. To this purpose, biopsies of the colon, ileum and duodenum have been collected from 7 PIPO patients, and 7 age-/sex-matched healthy controls. After DNA extraction, the MAM was assessed by next generation sequencing (NGS) of the V3-V4 region of the bacterial RNA 16 S, on an Illumina Miseq platform. The expression of genes implicated in serotoninergic pathway (TPH1, SLC6A4, 5-HTR3 and 5-HTR4) was established by qPCR, and correlations with MAM and clinical parameters of PIPO have been evaluated. Results Our results revealed that PIPO patients exhibit a MAM with a different composition and with dysbiosis, i.e. with a lower biodiversity and fewer less connected species with a greater number of non-synergistic relationships, compared to controls. qPCR results revealed modifications in the expression of serotonin-related intestinal genes in PIPO patients, when compared to controls. Correlation analysis do not reveal any kind of connection. Conclusions For the first time, we report in PIPO patients a specific MAM associated to underlying pathology and an altered intestinal serotonin pathway. A possible dysfunction of the serotonin pathway, possibly related to or triggered by an altered microbiota, may contribute to dysmotility in PIPO patients. The results of our pilot study provide the basis for new biomarkers and innovative therapies targeting the microbiota or serotonin pathways in PIPO patients.

Background & Aims: Although chronic diarrhea and constipation are common, the treatment is symptomatic because their pathophysiology is poorly understood. Accumulating evidence suggests that the microbiota modulates gut function, but the underlying mechanisms are unknown. We therefore investigated the pathways by which microbiota modulates gastrointestinal motility in different sections of the alimentary tract. Methods: Gastric emptying, intestinal transit, muscle contractility, acetylcholine release, gene expression, and vasoactive intestinal polypeptide (VIP) immunoreactivity were assessed in wild-type and Myd88-/-Trif-/- mice in germ-free, gnotobiotic, and specific pathogen-free conditions. Effects of transient colonization and antimicrobials as well as immune cell blockade were investigated. VIP levels were assessed in human full-thickness biopsies by Western blot. Results: Germ-free mice had similar gastric emptying but slower intestinal transit compared with specific pathogen-free mice or mice monocolonized with Lactobacillus rhamnosus or Escherichia coli, the latter having stronger effects. Although muscle contractility was unaffected, its neural control was modulated by microbiota by up-regulating jejunal VIP, which co-localized with and controlled cholinergic nerve function. This process was responsive to changes in the microbial composition and load and mediated through toll-like receptor signaling, with enteric glia cells playing a key role. Jejunal VIP was lower in patients with chronic intestinal pseudo-obstruction compared with control subjects. Conclusions: Microbial control of gastrointestinal motility is both region- and bacteria-specific; it reacts to environmental changes and is mediated by innate immunity-neural system interactions. By regulating cholinergic nerves, small intestinal VIP plays a key role in this process, thus providing a new therapeutic target for patients with motility disorders.

Previous research has demonstrated that stretching can enhance athletic performance and induce cardiovascular adaptations. This study aims to assess whether a 4-week preventative stretching routine can enhance heart rate variability and heart rate recovery, faster blood lactate clearance, and improve performance following submaximal strength exercises. Twenty-four healthy adults were recruited and randomly allocated to either the experimental group or the control group. Both groups engaged in submaximal strength exercises (5 sets to voluntary failure at 60% of 1RM) comprising bench press and back squat exercises under baseline conditions and after stretching protocol. The experimental group followed the Stretching Protocol, while the control group adhered to their regular training routine. ANOVA analysis revealed a significant pre-post interaction effect between groups in the variable of squat repetitions, although no notable pre- or post-differences were observed in heart rate variability, heart rate recovery, blood lactate concentration, or bench repetitions in either group. A 4-week preventative stretching program does not appear adequate to enhance lactate clearance and cardiovascular adaptation after submaximal strength exercises in resistance-trained individuals compared to the control group. However, it is plausible that such a stretching routine may mitigate muscle fatigue, though further investigation is warranted to substantiate this hypothesis.

IntroductionThe accurate distinction between periprosthetic joint infections (PJI) and aseptic failures (AF) is of paramount importance due to differences in treatment. However, this could be challenging by using the current criteria. Various synovial fluid biomarkers are being assessed to improve the diagnostic accuracy. Myeloperoxidase (MPO), an enzyme contained in the granules of neutrophils, may be a promising biomarker for PJI.MethodsSynovial fluids of 99 patients (n = 65 PJI according to EBJIS criteria; n = 34 AF) were collected in two specialized orthopedic centers. PJI were divided into acute (n = 33) and low-grade (n = 32) according to previously published classification. An activity assay specific for active MPO was performed in each sample. Ability of MPO to correctly discriminate patients with PJI from AF was determined by ROC analysis. The best discriminating cut-off value was determined by calculating the J Youden index. For all analyses, a P value < 0.05 was considered statistically significant.ResultsActive MPO was higher in PJI than AF (P < 0.0001). The ROC analysis revealed a significant area under the curve (AUC: 0.86; 95% CI: 0.78–0.93, P < 0.0001). A cut-off value of 561.9 U/mL, with good sensitivity (0.69) and specificity (0.88), discriminated between AF and PJI (accuracy 75.76%, 95% CI: 66.11–83.81%, positive likelihood ratio 5.88, 95% CI: 2.31–14.98 and negative likelihood ratio 0.35, 95%CI: 0.24–0.51). No difference in MPO levels was found between acute and chronic low-grade PJI.ConclusionThe proposed assay appears to be a reliable and affordable tool for detecting the active MPO in synovial fluid, with promising characteristics of sensitivity and specificity in discriminating both acute and low-grade PJI from AF. Further studies are needed to confirm MPO diagnostic cut-off values and validate their use in the routine clinical practice.

The beginnings of the dialogue as genre in the 4th a. C., understood as an autonomous literary work rather than a single dialogical sequence, bear the mark of a very particular teacher, Socrates, and the wide diffusion of the logoi sokratikoi. Together with this this revered yet subversive teaching figure, other experiments in the relationship between teacher and pupil are developed, such as the conversation between a father and his son, or the lesson of a sophist, all of which share a style of writing defined as a teaching practice, an exchange of questions and answers. In Greece as in Rome, the practice of dialogue makes it possible to question the teaching situation, addressing both the content and the method of acquiring knowledge. The articles in this dossier shed light on the ancient practices of dialogue and teaching, the articulation of a form marked by orality and its written transcriptions, the strength of a model of pedagogical writing in works as diverse as the speeches of Isocrates, Latin comedy, Horatian epistles, Greek epigrams, textbooks and grammars, Ciceronian dialogues and Varron’s technical treatises, which found a modern application in Fontenelle’s practice of scientific dialogue.

Summary: Background: Argon (Ar) has been proposed as a potential therapeutic agent in multiple clinical conditions, specifically in organ protection. However, conflicting data on pre-clinical models, together with a great variability in Ar administration protocols and outcome assessments, have been reported. The aim of this study was to review evidence on treatment with Ar, with an extensive investigation on its neuroprotective effect, and to summarise all tested administration protocols. Methods: Using the PubMed database, all existing pre-clinical and clinical studies on the treatment with Ar were systematically reviewed (registration: https://doi.org/10.17605/OSF.IO/7983D). Study titles and abstracts were screened, extracting data from relevant studies post full-text review. Exclusion criteria included absence of full text and non-English language. Furthermore, meta-analysis was also performed to assess Ar potential as neuroprotectant agent in different clinical conditions: cardiac arrest, traumatic brain injury, ischemic stroke, perinatal hypoxic-ischemic encephalopathy, subarachnoid haemorrhage. Standardised mean differences for neurological, cognitive and locomotor, histological, and physiological measures were evaluated, through appropriate tests, clinical, and laboratory variables. In vivo studies were evaluated for risk of bias using the Systematic Review Center for Laboratory Animal Experimentation tool, while in vitro studies underwent assessment with a tool developed by the Office of Health Assessment and Translation. Findings: The systematic review detected 60 experimental studies (16 in vitro, 7 ex vivo, 31 in vivo, 6 with both in vitro and in vivo) investigating the role of Ar. Only one clinical study was found. Data from six in vitro and nineteen in vivo studies were included in the meta-analyses. In pre-clinical models, Ar administration resulted in improved neurological, cognitive and locomotor, and histological outcomes without any change in physiological parameters (i.e., absence of adverse events). Interpretation: This systematic review and meta-analysis based on experimental studies supports the neuroprotective effect of Ar, thus providing a rationale for potential translation of Ar treatment in humans. Despite adherence to established guidelines and methodologies, limitations in data availability prevented further analyses to investigate potential sources of heterogeneity due to study design. Funding: This study was funded in part by Italian Ministry of Health-Current research IRCCS and by Ministero della Salute Italiano, Ricerca Finalizzata, project no. RF 2019-12371416.

Abstract Amyotrophic lateral sclerosis (ALS) is a poorly treated multifactorial neurodegenerative disease associated with multiple cell types and subcellular organelles. As with other multifactorial diseases, it is likely that drugs will need to target multiple disease processes and cell types to be effective. We review here the role of Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) signalling in ALS, confirm the association of this signalling with fundamental ALS disease processes using the BenevolentAI Knowledge Graph, and demonstrate that inhibitors of this pathway could reduce the ALS pathophysiology in neurons, glia, muscle fibres, and blood cells. Specifically, we suggest that inhibition of the JAK enzymes by approved inhibitors known as Jakinibs could reduce STAT3 activation and modify the progress of this disease. Analysis of the Jakinibs highlights baricitinib as a suitable candidate due to its ability to penetrate the central nervous system and exert beneficial effects on the immune system. Therefore, we recommend that this drug be tested in appropriately designed clinical trials for ALS.

Sports foods and supplements can play a significant role in the sports nutrition plans of high-level athletes. It has been found that taking specific dietary supplements can have ergogenic and performance-enhancing effects. Over the past two decades, there have been no major changes in the recommendations for caffeine supplementation. However, scientific knowledge has been significant in recent times, such that the state of the art needs to be updated. This study aims to confirm that caffeine (1,3,7-trimethylxanthine), a substance found in beverages such as coffee, tea and energy drinks, can be both an ergogenic support for individuals engaged in physical activity and an effective cognitive support. In this context, this review outlines the current framework of knowledge. The relationship between the uses and effects of caffeine in power and endurance sports has been demonstrated. In order to achieve and maintain the high levels of performance required in sporting events, planning proper sports diet supplementation can only strengthen and revitalize athletes after strenuous training. Furthermore, the effects of caffeine intake on the state of alertness have been evaluated in the military as well. Significant physical performance, such as marching over rough terrain, sometimes with very heavy loads, may be required during military training and tactical operations. In addition, operational situations with reduced or sleep deprivation may occur.Thus, several studies argue that genetic background, diet, gender identity and hormonal status have a bearing on the absorption, metabolism and physiological and functional effects of caffeine. Regarding the key points - individualized dosages and timing of caffeine intake - it would be desirable to go further with the studies to optimize the effects of caffeine.

Abstract Background Pulmonary embolism (PE) is one of the most common causes of death from cardiovascular disease. Although deep vein thrombosis (DVT) is the leading cause of PE, its prognostic role is unclear. This study investigated the incidence and prognostic value of DVT in predicting in‐hospital mortality (IHM) in patients admitted from the emergency department (ED) for PE. Methods This retrospective cohort study was conducted in the ED of a third‐level university hospital. Patients over 18 years admitted for PE between 1 January 2018 and 31 December 2022 were included. Results Five hundred and thirty patients (mean age 73.13 years, 6% IHM) were included. 69.1% of cases had DVT (36.4% unilateral femoral vein, 3.6% bilateral, 39.1% unilateral popliteal vein, 2.8% bilateral, 45.7% distal vein thrombosis and 7.4% iliocaval involvement). Patients who died in hospital had a higher Pulmonary Embolism Severity Index (PESI) (138.6 vs. 99.65, p II, right ventricular dysfunction, increased blood markers of myocardial damage and involvement of the iliocaval venous axis were independent predictors of IHM on multivariate analysis. Conclusions Although further studies are needed to confirm the prognostic role of DVT at PE, involvement of the iliocaval venous axis should considered to be a sign of a higher risk of IHM and may be a key factor in prognostic stratification.

Stuttering is a speech disorder characterized by frequent and significant problems with normal fluency and flow of speech. People who stutter perceive themselves as poor communicators and develop negative speech attitudes. This development of a negative communicative attitude could be related to the expectations and high demands made by their parents about fluency. When these expectations exceed the stuttering individual’s abilities to produce fluent verbal communication, a stuttering episode occurs. This is perceived by the individual as a communicative performance not adequately meeting the requests. Consequently, these individuals often resort to various avoidance and escape behaviors and generally avoid discussing their experiences and feelings related to stuttering. Therefore, stimulating communication is essential during speech therapy sessions to expose experiences otherwise kept hidden both from children/adolescents and their parents. However, encouraging communication is far from simple. In an attempt to facilitate communication and foster a more effective relationship between persons who stutter and their parents, we implemented the so-called awareness drawing according to the IARA model at the opening of the stuttering assessment session. Fourteen children (M=10; F=4; mean age=10.42; SD=1.65) and eight adolescents (M=6; F=2; mean age = 15.25; SD=1.03) diagnosed with stuttering were involved in this study, along with their relatives (28 parents; M=10; F=18; mean age=31.14; SD=4.66 years). The results of the study revealed that the drawings and comments of children and adolescents with stuttering, along with their parents, can offer valuable insights into their experiences and perceptions of stuttering. Children and adolescents expressed a desire for acceptance and a wish to be recognized beyond their stuttering. They depicted solutions that encompass the involvement of both parents and speech therapists. The utilization of awareness drawing can have a substantial impact on speech therapists. During the stuttering assessment session, it can provide valuable insights into the emotions, thoughts of person who stutter, as well as the experiences of their parents. This, in turn, can enhance the design of therapeutic intervention.

Abstract Background Exposure to alcohol in utero is a known cause of mental retardation. Although a certain degree of motor impairment is always associated with fetal alcohol spectrum disorder, little is known about the neurobiological basis of the defective motor control. We have studied the striatal interneurons containing parvalbumin in a rat model of fetal alcohol spectrum disorder. Methods Newborn rats received ethanol by inhalation from postnatal day two through six and parvalbumin striatal neurons were labeled by immunohistochemistry on postnatal day 60. The spatial distribution of parvalbumin interneurons was studied using Voronoi spatial tessellation and their dendritic trees were completely reconstructed. Results Parvalbumin interneurons of ethanol-treated animals showed a clustered spatial distribution similar to that observed in control animals. The dendritic tree of parvalbumin interneurons was significantly reduced in ethanol-treated animals, as compared with controls. Conclusions Striatal parvalbumin interneurons are crucial components of the brain network serving motor control. Therefore, the shrinkage of their dendrites could contribute to the motor and cognitive symptoms observed in fetal alcohol spectrum disorder.