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La Leucosis Enzoótica Bovina (LEB) es una enfermedad infecciosa que afecta principalmente a los rodeos lecheros. Su agente causal es el virus de la leucosis bovina (BLV), perteneciente a la familia Retroviridae. Aunque la mayoría de los animales infectados son asintomáticos, algunos desarrollan linfosarcoma. La transmisión de BLV ocurre principalmente por vía horizontal, a través de prácticas iatrogénicas como aplicaciones inyectables y palpaciones rectales. De manera vertical por vía transplacentaria, calostro y leche. Se ha sugerido la posibilidad de transmisión por insectos hematófagos. En Argentina, la enfermedad ha avanzado de manera exponencial desde la década de 1970 cuando se diagnosticó por primera vez. La prevalencia de LEB varía en diferentes regiones, y se observa una mayor tasa de infección en tambos en la región central del país. El presente estudio llevado a cabo en la provincia de Misiones durante el año 2019, tuvo como objetivo actualizar información sobre la situación de BLV en 135 tambos del sector de la agricultura Familiar en la provincia de Misiones, y su distribución espacial. Se encontró una tasa de infección del 13% en rodeos y se identificó un conglomerado espacial de alta tasa en la zona donde se concentran la mayor cantidad de tambos de la provincia. La infección fue más común en la categoría vacas y en aquellos tambos de mayor tamaño, aunque estas diferencias no fueron estadísticamente significativas. Estos resultados proporcionan información actualizada sobre la presencia de BLV en tambos de Agricultura Familiar en Misiones, sugiriendo una menor prevalencia en comparación con otras regiones lecheras de Argentina. Se destaca la importancia de abordar prácticas de manejo de riesgo para prevenir la transmisión de la enfermedad.

Abstract The aim of this study was to investigate the relationship between source-specific ambient particulate air pollution concentrations and the incidence of dementia. The study encompassed 70,057 participants from the Västerbotten intervention program cohort in Northern Sweden with a median age of 40 years at baseline. High-resolution dispersion models were employed to estimate source-specific particulate matter (PM) concentrations, such as PM10 and PM2.5 from traffic, exhaust, and biomass (mainly wood) burning, at the residential addresses of each participant. Cox regression models, adjusted for potential confounding factors, were used for the assessment. Over 884,847 person-years of follow-up, 409 incident dementia cases, identified through national registers, were observed. The study population’s average exposure to annual mean total PM10 and PM2.5 lag 1–5 years was 9.50 µg/m3 and 5.61 µg/m3, respectively. Increased risks were identified for PM10-Traffic (35% [95% CI 0–82%]) and PM2.5-Exhaust (33% [95% CI − 2 to 79%]) in the second exposure tertile for lag 1–5 years, although no such risks were observed in the third tertile. Interestingly, a negative association was observed between PM2.5-Wood burning and the risk of dementia. In summary, this register-based study did not conclusively establish a strong association between air pollution exposure and the incidence of dementia. While some evidence indicated elevated risks for PM10-Traffic and PM2.5-Exhaust, and conversely, a negative association for PM2.5-Wood burning, no clear exposure–response relationships were evident.

Abstract Mild mesial temporal lobe epilepsy (MTLE) patients may remain untreated for a considerable time after disease onset or achieve seizure control with a single anti‐seizures medication (ASM). Thus, they represent an optimal population to investigate whether ASMs might have influence on brain structure. We consecutively enrolled 56 mild MTLE patients (22/56 untreated, 34/56 on‐monotherapy) and 58 healthy controls, matched for age and gender. All subjects underwent 3T‐brain MRI, using FreeSurfer for automated morphometry. Differences in gray matter were assessed using one‐way Analysis of Covariance (ANCOVA), adjusting for age, disease duration and intracranial volume. No significant change was observed between treated and untreated patients. We observed a significant reduction in cortical thickness of left inferior parietal, inferior temporal, middle temporal gyri, and right inferior parietal gyrus, temporal pole in monotherapy patients compared to healthy controls, as well as an increase in left isthmus of cingulate gyrus in untreated MTLE subjects compared to controls. Surface and subcortical volumes analysis revealed no differences among groups. Our study demonstrated no substantial morphological abnormalities between untreated mild MTLE patients and those undergoing monotherapy. Although exploratory, these results may reassure about safety of commonly used drugs and their marginal role in influencing neuroimaging results. Plain Language Summary This study investigated the following question: can medications against epileptic seizures have an effect on brain structure in mild mesial temporal lobe? Preliminary results from our analyses suggest not, as we did not find any difference in brain gray matter between untreated patients and those treated with a single anti‐seizures medication. On the other hand, epilepsy patients presented cortical thinning compared to healthy controls in several regions of the temporal and parietal lobes, in line with previous studies investigating the disease.

Constituents of air pollution, the ultrafine particles (UFP) with a diameter of ≤0.1 μm, are considerably related to traffic emissions. Several studies link air pollution to Alzheimer's disease (AD), yet the exact relationship between the two remains poorly understood. Mitochondria are known targets of environmental toxicants, and their dysfunction is associated with neurodegenerative diseases. The olfactory mucosa (OM), located at the rooftop of the nasal cavity, is directly exposed to the environment and in contact with the brain. Mounting evidence suggests that the UFPs can impact the brain directly through the olfactory tract. By using primary human OM cultures established from nasal biopsies of cognitively healthy controls and individuals diagnosed with AD, we aimed to decipher the effects of traffic-related UFPs on mitochondria. The UFP samples were collected from the exhausts of a modern heavy-duty diesel engine (HDE) without aftertreatment systems, run with renewable diesel (A0) and petroleum diesel (A20), and from an engine of a 2019 model diesel passenger car (DI-E6d) equipped with state-of-the-art aftertreatment devices and run with renewable diesel (Euro6). OM cells were exposed to three different UFPs for 24-h and 72-h, after which cellular processes were assessed on the functional and transcriptomic levels. Our results show that UFPs impair mitochondrial functions in primary human OM cells by hampering oxidative phosphorylation (OXPHOS) and redox balance, and the responses of AD cells differ from cognitively healthy controls. RNA-Seq and IPA® revealed inhibition of OXPHOS and mitochondrial dysfunction in response to UFPs A0 and A20. Functional validation confirmed that A0 and A20 impair cellular respiration, decrease ATP levels, and disturb redox balance by altering NAD and glutathione metabolism, leading to increased ROS and oxidative stress. RNA-Seq and functional assessment revealed the presence of AD-related alterations in human OM cells and that different fuels and engine technologies elicit differential effects.

Abstract Mantle cell lymphoma (MCL) is an incurable B-cell malignancy characterized by a high clinical variability. Therefore, there is a critical need to define parameters that identify high-risk patients for aggressive disease and therapy resistance. B-cell receptor (BCR) signaling is crucial for MCL initiation and progression and is a target for therapeutic intervention. We interrogated BCR signaling proteins (SYK, LCK, BTK, PLCγ2, p38, AKT, NF-κB p65, and STAT5) in 30 primary MCL samples using phospho-specific flow cytometry. Anti-IgM modulation induced heterogeneous BCR signaling responses among samples allowing the identification of two clusters with differential responses. The cluster with higher response was associated with shorter progression free survival (PFS) and overall survival (OS). Moreover, higher constitutive AKT activity was predictive of inferior response to the Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib. Time-to-event analyses showed that MCL international prognostic index (MIPI) high-risk category and higher STAT5 response were predictors of shorter PFS and OS whilst MIPI high-risk category and high SYK response predicted shorter OS. In conclusion, we identified BCR signaling properties associated with poor clinical outcome and resistance to ibrutinib, thus highlighting the prognostic and predictive significance of BCR activity and advancing our understanding of signaling heterogeneity underlying clinical behavior of MCL.

Abstract Background Sarcopenia is an age-related clinical syndrome characterized by the progressive loss of muscle mass and muscle strength. It appears to be closely linked to dementia, particularly Alzheimer’s disease (AD); however, its prevalence among AD patients remains unclear. In this study, we assessed differences in sarcopenia prevalence between non-demented individuals and AD patients. Moreover, we assessed sex-specific differences in sarcopenia prevalence and explored the diagnostic value of the Muscle Quality Index (MQI) for diagnosing sarcopenia among AD patients. Method Cross-sectional study including 145 patients with probable AD and 51 older adults with normal cognition. Sarcopenia was diagnosed according to the criteria of the European Working Group on Sarcopenia in Older People (EWGSOP1 and EWGSOP2) and of the Foundation for the National Institutes of Health (FNIH). The MQI was computed as the ratio of handgrip strength to skeletal muscle mass. Results No significant difference in sarcopenia prevalence was observed between AD patients and controls. Prevalence ranged from 3.4 to 23.4% in AD patients and from 2 to 11.8% in controls, depending on diagnostic criteria. Prevalence was higher using EWGSOP1 and decreased using EWGSOP2 and FNIH. Prevalence was higher in males than in females with AD. The MQI was lower in AD patients than in controls (95%CI: − 0.23, − 0.05, p

Human mesenchymal stromal cells (hMSCs), whether used alone or together with three-dimensional scaffolds, are the best-studied postnatal stem cells in regenerative medicine. In this study, innovative composite scaffolds consisting of a core–shell architecture were seeded with bone-marrow-derived hMSCs (BM-hMSCs) and tested for their biocompatibility and remarkable capacity to promote and support bone regeneration and mineralization. The scaffolds were prepared by grafting three different amounts of gelatin–chitosan (CH) hydrogel into a 3D-printed polylactic acid (PLA) core (PLA-CH), and the mechanical and degradation properties were analyzed. The BM-hMSCs were cultured in the scaffolds with the presence of growth medium (GM) or osteogenic medium (OM) with differentiation stimuli in combination with fetal bovine serum (FBS) or human platelet lysate (hPL). The primary objective was to determine the viability, proliferation, morphology, and spreading capacity of BM-hMSCs within the scaffolds, thereby confirming their biocompatibility. Secondly, the BM-hMSCs were shown to differentiate into osteoblasts and to facilitate scaffold mineralization. This was evinced by a positive Von Kossa result, the modulation of differentiation markers (osteocalcin and osteopontin), an expression of a marker of extracellular matrix remodeling (bone morphogenetic protein-2), and collagen I. The results of the energy-dispersive X-ray analysis (EDS) clearly demonstrate the presence of calcium and phosphorus in the samples that were incubated in OM, in the presence of FBS and hPL, but not in GM. The chemical distribution maps of calcium and phosphorus indicate that these elements are co-localized in the same areas of the sections, demonstrating the formation of hydroxyapatite. In conclusion, our findings show that the combination of BM-hMSCs and PLA-CH, regardless of the amount of hydrogel content, in the presence of differentiation stimuli, can provide a construct with enhanced osteogenicity for clinically relevant bone regeneration.

Cancer cells require substantial amounts of energy and substrates for their metabolic hyperactivity, enabling the synthesis of new cells at the expense of healthy ones. Preliminary in vitro data suggest that a mix of free essential amino acids (EAA-mix) can promote cancer cell apoptosis by enhancing autophagy. This study aimed to confirm, both in vitro and in vivo, whether EAA intake could influence the development of colon cancer in mice. We investigated changes in cancer proliferation in CT26 cells treated with EAA-mix and in mice fed with EAA-rich modified diets (EAARD) as compared to those on a standard laboratory diet (StD). CT26 cells were injected subcutaneously (s.c.) or intraperitoneally (i.p.). After 21 days, tumors were removed and measured. In vitro data corroborated that EAA-mix impairs cancer growth by inducing apoptosis. In vivo data revealed that mice on StD developed significantly larger (s.c.) and more numerous (i.p.) cancers than those on EAARD. EAA administration appears to influence cancer cell survival with notable antiproliferative properties.

BackgroundSplit phenomena (SP) are characterized by patterns of differential muscle wasting and atrophy, which are highly prevalent in amyotrophic lateral sclerosis (ALS) patients. Several neurophysiological indicators, including the split-hand index (SHI), split-leg index (SLI), and split-elbow index (SEI), have been proposed to assess SP. Nevertheless, their cutoff values and the impact of age and sex on these measures remain unclear.MethodsWe prospectively collected neurophysiological data from 300 healthy adult subjects. The following indices were measured from compound muscle action potentials (CMAPs): SHI [abductor pollicis brevis (APBcmap) x first dorsal interosseous (FDI)cmap/adductor digiti minimi (ADMcmap)], SEI (BICEPScmap/TRICEPScmap), SLI (extensor digit brevis (EDB)cmap/abductor Hallucis (AH)cmap), and the neurophysiological ratios APBcmap /ADMcmap and FDIcmap/ADMcmap. Multiple linear regression analysis was used to investigate the association between age, sex, CMAPs, and neurophysiological indicators.ResultsThe median SHI was 10.4, with a median APBcmap/ADMcmap ratio of 0.9 and a median FDIcmap/ADMcmap ratio of 1.2. The median SEI was 1.6 (IQR:1.1–2.4) and the median SLI was 0.7 (IQR:0.5–1.0). Negative associations were observed between age, most of the CMAPs, and all the neurophysiological indices, except for SLI. The male subjects exhibited significantly higher CMAP values for the first dorsal interosseous (FDI), biceps, and SHI compared to the female participants.ConclusionOur findings highlight the importance of age- and sex-adjusted normative data for SP indices, which could enhance their diagnostic accuracy and clinical utility in patients with ALS. The SL index appears to be the most reliable indicator, as it showed no significant association with age or sex.

We describe a rare and extremely challenging case of transcatheter pulmonary valve implantation in repaired tetralogy of Fallot and anomalous origin of the left main coronary artery from the right coronary sinus. Procedural planning based on advanced multimodality imaging and 3-dimensional technology proved to be the key to procedural success.

Abstract Global neuropsychological impairments with intellectual disability (ID) seem to play a major role in the occurrence of psychogenic non‐epileptic seizures (PNES) in epilepsy. Conversely, the pathophysiology underlying PNES combined with epilepsy without ID remains elusive. We investigated the neuropsychiatric profile in 26 average intelligent subjects (15 women, mean age: 40.04 ± 13.53 years) with temporal lobe epilepsy (TLE) plus PNES (TLE + PNES), compared with 28 with TLE and 22 with PNES alone, matched for age and sex. All subjects underwent neuropsychiatric assessment, including Beck Depression Inventory‐2 (BDI‐2), State‐Trait Anxiety Inventory (STAI), Dissociative Experiences Scale (DES), Toronto Alexithymia Scale (TAS‐20), Traumatic Experience Checklist (TEC), and cognitive evaluation. TLE + PNES and PNES groups shared a similar psychiatric profile with higher levels of depression (BDI‐2, P

Background: Stent implantation has become the preferred method of treatment for treating vessel stenosis in congenital heart diseases. The availability of covered stents may decrease complications and have an important role in the management of patients with complex anatomy. Aim: This study aims to evaluate the feasibility and safety of the pre-mounted cobalt–chromium stent-graft-covered ePTFE Aortic BeGraft in a broad spectrum of vascular lesions. Methods: This is a multicenter retrospective results analysis of 107 implanted BeGraft stents between 2016 and 2022 in six different European centers. Results: One hundred and four patients with a mean age of thirteen years (range 1–70 years) and with the body weight of 56.5 kg (range 11–115 kg) underwent the BeGraft stent implantation. Stents were implanted in the following conditions: aortic coarctation (74 patients), RVOT dysfunction (12 patients), Fontan circulation (7 patients), and miscellaneous (11 subjects with complex CHD). All the stents were implanted successfully. The median stent diameter was 16 mm (range 7–24 mm), and the median length was 39 mm (range 19–49 mm). Major complications occurred in five subjects (4.7%). During a median follow-up of fourteen (1–70) months, stents’ re-dilatation was performed in five patients. Conclusions: The BeGraft stent can be used safely and effectively in a wide spectrum of congenital heart diseases. Whether these good results will be stable in the longer term still needs to be investigated in a follow-up given its recent introduction into clinical practice, in particular regarding stent fracture or neointimal proliferation.

Aim: Transcatheter Pulmonary Valve Implantation (TPVI), when feasible, is the first-line approach to pulmonary valve replacement. Our aim was to obtain a picture of current TPVI practice in Italy. Methods: After conducting a literature review on TPVI, online surveys were devised by an Advisory Board of 10 experts from the three Italian reference centers for congenital heart diseases and sent electronically to physicians working either in implanting center or in referral non-implanting cardiologic centers. Results: Approximately 450 physicians across Italy were invited to contribute. 82 (18%) physicians answered. EchoColorDoppler, electrocardiogram and cardiac magnetic resonance were considered the first line approach to monitor these patients, before and after TPVI.For non-implanting centers, reasons for non-referral of patients for PVR were: paucisymptomatic disease (67%) and patients’ poor adherence to disease management programs (41%), but also the lack of connections with specialized centers (33%). For implanters, the main reasons for refraining from TPVI were: high risk for coronary compression (67% first rank), the need for concomitant cardiac surgical procedures (39% first rank) and the unsuitable anatomy of the conduit (39% first rank). The availability of new larger valves of a self-expandable nature was indicated as a key technological development for expanding the cohort of patients currently eligible for TPVI. Conclusions: Despite a non-invasive imaging protocol for the follow up and selection of patients candidate to TPVI is well implemented in Italy, there is still a lack in connections between non-implanting and implanting centers.