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Assessing the Impact of Heyndrickxia coagulans Administered Through Sugar-Free Chewing Gum on Dental Biofilm: A Double-Blind Randomized Controlled Trial
No full textBackground: Heyndrickxia coagulans has emerged as a candidate for oral health applications, and chewing gum offers a promising delivery method. This study evaluates whether H. coagulans delivered via sugar-free chewing gum can induce detectable changes in plaque microbial ecology. Methods: A randomized, double-blind, placebo-controlled clinical trial was conducted on 52 healthy adults. Participants consumed probiotic or control gum for 4 weeks. Dental plaque was collected at baseline (T0), mid-intervention (T1), end of intervention (T2), and one week post-intervention (T3). qPCR quantified H. coagulans, while 16S rRNA gene profiling assessed microbial diversity and taxonomic composition. Statistical analyses included rank-based difference-in-differences models, Wilcoxon and Mann–Whitney tests, and differential abundance inference based on negative binomial modeling. Results: Forty-four subjects completed the study. In the Intervention group, the strain was detected in 71.4% of participants at T1 and 61.9% at T2, and it persisted in 9.5% at T3. Differential abundance analysis revealed a broad depletion of taxa linked to oral dysbiosis at T2 with partial persistence at T3, along with selective enrichment of beneficial strains. Conclusions: H. coagulans delivered via chewing gum can reach the dental biofilm and induce modest, transient shifts in microbial composition. However, these biofilm ecology findings should be interpreted in the context of clinical outcomes
Beta cell function and insulin sensitivity during elexacaftor/tezacaftor/ivacaftor therapy in people with cystic fibrosis
No full textBackground: Cystic fibrosis-related diabetes (CFRD) is the most common extra-pulmonary complication in adults with cystic fibrosis (CF) and is primarily driven by progressive beta-cell dysfunction. The impact of CFTR modulators, particularly elexacaftor/tezacaftor/ivacaftor (ETI), on glucose metabolism remains unclear. This study aimed to assess the effect of ETI on beta-cell function and insulin sensitivity in people with CF (pwCF) without a history of CFRD. Methods: We conducted a prospective study involving pwCF who underwent oral glucose tolerance tests (OGTT) at baseline (prior to ETI initiation) and at 6 and 18 months after starting ETI therapy. Mathematical modelling of OGTT data was used to assess beta-cell function through two physiologically distinct components of insulin secretion: derivative control (DC), reflecting the early insulin secretory response to changes in plasma glucose, and proportional control (PC), representing the insulin secretory response to prevailing glucose concentrations. PC was expressed as the stimulus–response relationship between plasma glucose and insulin secretion rate (ISR) at predefined glucose levels (4.0, 5.5, 8.0, and 11.0 mmol/L). Insulin sensitivity was estimated using the oral glucose insulin sensitivity (OGIS) index. Results: Sixty-eight pwCF (median age 20 years) were included. At baseline, 8 (11.8%) had impaired fasting glucose and 15 (22.1%) had impaired glucose tolerance. These proportions did not significantly change over time, with no new cases of diabetes. Plasma glucose at 120 minutes post-OGTT and ISR at 5.5 mmol/L glucose decreased significantly at both 6 and 18 months. ISR at 5.5 mmol/L glucose also decreased at 18 months, whereas DC, ISR at higher glucose levels, and OGIS values did not significantly change over time. Conclusion: ETI therapy was not associated with reversal of existing glucose tolerance abnormalities but may contribute to preservation of beta-cell function and insulin sensitivity. This is supported by stable DC values over time, in contrast to the progressive decline typically observed in CF populations
RAG1/2 expression in IGH-switched follicular lymphoma associated with transformation to high-grade B-cell lymphoma
No full textJNK3 quanti cation in plasma: a novel biomarker for neuronal damage in Parkinson’s disease
No full textDiagnosis of Parkinson's disease (PD) remains challenging due to the lack of reliable biomarkers. To address this need, we quantified plasma levels of brain-specific c-Jun N-terminal kinase 3 (JNK3), a protein involved in neurodegeneration. A total of 108 participants were enrolled, including 25 individuals with isolated REM sleep behavior disorder (iRBD), 26 patients with De Novo PD, 29 with Late PD, and 28 age-matched healthy controls (HC). All subjects underwent clinical assessment, blood sampling, and skin biopsy. Plasma JNK3 levels were significantly elevated in PD and iRBD compared to HC, a finding that remained robust after adjustment for age and sex in multivariate logistic regression. ROC analysis demonstrated that JNK3 levels distinguished PD from HC with 100% specificity and 65% sensitivity in Late PD. In contrast, Neurofilament Light Chain showed non-significant group differences and weak discriminative performance. Notably, while JNK3 declined with age in HC, it increased with age in Late PD (P = 0.048, B = 0.105) and negatively correlated with motor impairment. Elevated JNK3 was also associated with pathological α-Synuclein in skin biopsy. These findings highlight JNK3 as a promising blood biomarker for PD, with meaningful diagnostic and prognostic value, suggesting that its implementation could refine patient stratification and improve clinical trial efficiency
Storia del teatro : Scena e spettacolo in Occidente
No full textIl testo offre una ricostruzione dei fenomeni emergenti dell'arte teatrale nelle diverse nazioni europee attraverso i secoli. Partendo dalla puntuale e diffusa trattazione dell'antichità e del periodo moderno, si spinge fino al secondo Novecento, analizzando le dinamiche di un periodo di profondi rivolgimenti e grandi protagonisti. Questa nuova edizione presenta aggiornamenti nel capitolo dedicato al teatro contemporaneo e vede l'aggiunta, in ogni capitolo, dalla rubrica 'Teatro sulla scena dell'oggi', che analizza un'opera teatrale del periodo preso in esame attraverso le riletture sceniche contemporanee (arricchita da QR con video delle rappresentazioni analizzate)
Optimizing diagnostic thresholds of total vitamin B12 (B12) for identifying cobalamin deficiency in adults with macrocytic anemia
No full textObjectives: Identifying individuals with vitamin B12 (B12)
deficiency is challenging due to poor harmonization across
total B12 assays. To establish clinically meaningful thresh
olds for the Roche assay, we characterized B12 concentra
tions associated with deficiency by comparing individuals
with macrocytic anemia and other anemia subtypes or no
anemia.
Methods: We retrospectively analysed 10 years of labora
tory data from adults tested for total B12 and folate (Roche
Cobas), homocysteine (Abbott Architect), and haemato
logical parameters (Sysmex XE/XN). Individuals receiving
vitamin supplementation or with isolated folate deficiency were excluded. Anemia subtypes (normocytic, microcytic,
macrocytic) were classified using red blood cell count,
hemoglobin concentration, and mean corpuscular volume
relative to reference intervals.
Results: Among 5,147 subjects (median age 65 years;
25th–75th percentile: 49–77), 36.8 % had anemia. Total B12
concentrations decreased by 2.3 ng/L for each 1μmol/L in
crease in homocysteine and by 6.8ng/L per decade of age
increase (p<0.0001). Macrocytic anemia (9.4 % of subjects),
was associated with a mean reduction of 18.6ng/L in B12
levels compared with no anemia and microcytic anemia.
Meanhomocysteineconcentrationsroseprogressively,from
15.9 to 21.5 μmol/L and then to 34.9μmol/L, as total B12 con
centrations fell in the intervals: 342–447 ng/L, 341–258 ng/L,
and 257– <50ng/L, respectively.
Conclusions: Among individuals investigated for anemia,
macrocytosis,ahallmarkofB12depletion,supportsthattotal
B12 concentrations ≤257ng/L measured using the Roche
assaylikelyreflectseveredeficiency.Levelsbetween258and
341 ng/L may indicate early depletion and warrant confir
mation through elevated homocysteine concentrations
Il sistema di gestione del rischio nei sistemi di IA ad alto rischio. Commento all’art. 9
No full textUpdate on US-guided Interventional Procedures for Tendinopathies
No full textTendinopathies are a leading cause of chronic musculoskeletal pain and functional limitation. When conservative measures fail, ultrasound-guided interventions are safe, minimally invasive alternatives to surgery. These procedures include injections of corticosteroids or platelet-rich plasma, percutaneous needle tenotomy, percutaneous irrigation of calcific deposits, and mechanical release techniques. Although some interventions are well established in clinical practice, others are only supported by limited or emerging evidence. Ultrasound plays a central role by enabling precise targeting of pathologic tissues and adjacent structures. This review provides an updated overview of current ultrasound-guided interventional procedures for tendinopathies, focusing on their mechanisms, clinical indications, and evidence base
Healing dynamics and surgery in breast cancer: rethinking a timeless challenge in light of advancing therapies and technologies
No full textBackground: During the last century, surgery became the primary approach for treating breast cancer. However, the introduction of new surgical techniques, increasingly less invasive and more conservative, did not always provide consistent benefits in inhibiting tumor progression. Main body: Inflammatory mechanisms involved in wound repair of surgical damage play a significant role in the progression of cancer. In this review we focused on the healing-induced inflammation processes that can favor residual tumor cells and on the latest current methods, which improve the rate of total tumor excision during the first operation or contribute to diminish host systemic inflammation boosting immune system activation in breast cancer patients. Conclusions: Surgery is still a crucial area of breast cancer research that attempts to understand how it might affect breast cancer progression and, ultimately, survival outcomes
ON-FARM APPLICATION OF PLF TECHNOLOGIES TO DETECT EARLY BEHAVIOURAL AND PHYSIOLOGICAL INDICATORS OF DISEASE AND WELFARE IN PAIR - HOUSED DAIRY CALVES BEFORE WEANING.
No full textThis thesis investigates the welfare implications of pair housing for pre-weaned dairy calves, evaluated through the lens of Precision Livestock Farming (PLF) technologies. The aim was to assess whether behavioural and physiological indicators collected by non-invasive sensors could provide insights into welfare status and disease risk, with a particular focus on accelerometer-based monitoring and infrared thermography.
Study 1 applied triaxial accelerometers to monitor lying behaviour and synchronisation in calves reared individually or in pairs during the pre-weaning phase, under commercial conditions. Results demonstrated that pair housing improved growth without compromising health and promoted behavioural synchronisation, supporting its value as a positive welfare indicator. While the first study relied on continuous data provided by accelerometers, Study 2 explored the use of infrared thermography to measure ocular temperature and asymmetry at selected timepoints in pre-weaned dairy calves housed individually or in pairs. The aim was to investigate ocular asymmetry as potential measure of positive emotional states linked to social housing. While no evidence of lateralisation emerged, pair-housed calves exhibited higher absolute eye temperatures, suggesting subtle physiological differences associated with higher arousal states. Whereas lying synchronisation appeared more promising for the assessment of positive welfare in pair-housed calves, Study 3 further investigated rest and sleep quality, reported as positive welfare indicators, and to sensor-based approaches for their assessment. A systematic review was conducted on the application of PLF technologies to monitor lying, rest, and sleep in calves. The review highlighted the widespread use of accelerometers for lying behaviour, while identifying critical gaps in assessing rest and sleep, behaviours essential for development and welfare. Since previous studies found significant changes in cattle heart rate variability with sleep stages, Study 4 validated a wearable smart-textile sensor for measuring heart rate variability (HRV) against a standard ECG in calves. The device showed strong agreement across key HRV parameters, supporting its potential as a low-stress tool for assessing calf welfare and, prospectively, sleep quality.
Together, these studies demonstrate that pair housing supports calf growth and social cohesion, while PLF technologies provide novel opportunities for continuous, non-invasive welfare assessment. By integrating behavioural, physiological, and sensor-based perspectives, this thesis contributes to advancing management practices that align animal welfare with the goals of sustainable and cage-free dairy production