Petrologic features of mesoproterozoic lamprophyric dykes from Montevideo (Piedra Alta terrane, South Uruguay)

Mafic dykes of lamprophyric affinity cropping out along the coastal area of Montevideo city are described. These dykes trend N75º-85º and crosscut 2.1 Ga Paleoproterozoic metamorphic units of the Rio de la Plata craton. They show mainly porphyritic textures with phlogopite and clinopyroxene macrocrysts in a groundmass composed of carbonates, phlogopite, augite, and feldspathoids. Ocellar structures filled with leucite, carbonates, and fibrous alkaline amphibole are present. The mineralogical assembly allows their classification as lamprophyres (minettes), but according to their chemical nature, they can be classified as alkaline lamprophyres. A crystallization age of 1.42 Ga by Ar-Ar method (on biotite/phlogopite) was obtained

Clinical expression of facioscapulohumeral muscular dystrophy in carriers of 1-3 D4Z4 reduced alleles: Experience of the FSHD Italian National Registry

OBJECTIVES: Facioscapulohumeral muscular dystrophy type 1 (FSHD1) has been genetically linked to reduced numbers ( 64 8) of D4Z4 repeats at 4q35. Particularly severe FSHD cases, characterised by an infantile onset and presence of additional extra-muscular features, have been associated with the shortest D4Z4 reduced alleles with 1-3 repeats (1-3 DRA). We searched for signs of perinatal onset and evaluated disease outcome through the systematic collection of clinical and anamnestic records of de novo and familial index cases and their relatives, carrying 1-3 DRA. SETTING: Italy. PARTICIPANTS: 66 index cases and 33 relatives carrying 1-3 DRA. OUTCOMES: The clinical examination was performed using the standardised FSHD evaluation form with validated inter-rater reliability. To investigate the earliest signs of disease, we designed the Infantile Anamnestic Questionnaire (IAQ). Comparison of age at onset was performed using the non-parametric Wilcoxon rank-sum or Kruskal-Wallis test. Comparison of the FSHD score was performed using a general linear model and Wald test. Kaplan-Meier survival analysis was used to estimate the age-specific cumulative motor impairment risk. RESULTS: No patients had perinatal onset. Among index cases, 36 (54.5%) showed the first signs by 10 years of age. The large majority of patients with early disease onset (26 out of 36, 72.2%) were de novo; whereas the majority of patients with disease onset after 10 years of age were familial (16, 53.3%). Comparison of the disease severity outcome between index cases with age at onset before and over 10 years of age, failed to detect statistical significance (Wald test p value=0.064). Of 61 index cases, only 17 (27.9%) presented extra-muscular conditions. Relatives carrying 1-3 DRA showed a large clinical variability ranging from healthy subjects, to patients with severe motor impairment. CONCLUSIONS: The size of the D4Z4 allele is not always predictive of severe clinical outcome. The high degree of clinical variability suggests that additional factors contribute to the phenotype complexity

Persistent Inflammation Alters the Function of the Endogenous Brain Stem Cell Compartment

Endogenous neural stem/precursor cells (NPCs) are considered a functional reservoir for promoting tissue homeostasis and repair after injury, therefore regenerative strategies that mobilize these cells have recently been proposed. Despite evidence of increased neurogenesis upon acute inflammatory insults (e.g. ischaemic stroke), the plasticity of the endogenous brain stem cell compartment in chronic CNS inflammatory disorders remains poorly characterized. Here we show that persistent brain inflammation, induced by immune cells targeting myelin, extensively alters the proliferative and migratory properties of subventricular zone (SVZ)-resident NPCs in vivo leading to significant accumulation of non-migratory neuroblasts within the SVZ germinal niche. In parallel, we demonstrate a quantitative reduction of the putative brain stem cells proliferation in the SVZ during persistent brain inflammation, which is completely reversed after in vitro culture of the isolated NPCs. Together, these data indicate that the inflamed brain microenvironment sustains a non cell-autonomous dysfunction of the endogenous CNS stem cell compartment and challenge the potential efficacy of proposed therapies aimed at mobilizing endogenous precursors in chronic inflammatory brain disorders

Electrical structure of the lithosphere from Rio de la Plata craton to Paraná basin: amalgamation of cratonic and refertilized lithospheres in SW Gondwanaland

We conducted a magnetotelluric (MT) study from Paleoproterozoic Rio de la Plata Craton, in Uruguay, toward Paleozoic-Mesozoic Paraná Basin, in Brazil. The 850-km-long MT transect comprises 35 evenly spaced broadband electromagnetic soundings sites. In the Paraná Basin, 11 additional long-period measurements were acquired to extend the maximum depth of investigation. All data were inverted using two- and three-dimensional approaches obtaining the electrical resistivity structure from the surface down to 200 km. The Rio de la Plata Craton is>200-km thick and resistive (~2,000Ωm). Its northern limit is electrically defined by a lithosphere scale lateral transition and lower crust conductive anomalies (1–10Ωm) interpreted as a Paleoproterozoic suture at the southern edge of Rivera-Taquarembó Block. The latter is characterized by an approximately 100-km thick and moderate resistive (>500Ωm) upper mantle. The Ibaré shear zone is another suture where an ocean-ocean subduction generated the 120-km thick and resistive (>1,000Ωm) São Gabriel juvenile arc. Proceeding northward, a 70- to 80-km thick, 150-km wide, and inclined resistive zone is imaged. This zone could be remnant of an oceanic lithosphere or island arcs accreted at the southern border of Paraná Basin. The MT transect terminates within the southern Paraná Basin where a 150- to 200-km-thick less resistive lithosphere (<1,000Ωm) may indicate refertilization processes during plate subduction and ocean closure in Neoproterozoic-Cambrian time. Our MT data support a tectonic model of NNE– SSW convergence for this segment of SW Gondwanaland

Mesozoic magmatism in east uruguay: petrological constraints related to the sierra san miguel region

This work presents new results of a detailed geological and structural investigation focusing the easternmost Uruguayan Mesozoic magmatic occurrences related to the south Atlantic opening. Lithological descriptions, their stratigraphic relationships and complimentary lithochemical characterizations carried out in the San Miguel region (East Uruguay) are presented. Three volcanic/sub-volcanic units have been recognized. The felsic volcanic association is composed by rhyolitic - dacitic flows, mainly with porphyritic textures and sub-alkalinenature and related pyroclastic rocks. The felsic sub-volcanic association is characterized by granophyres of about 25 km2 of exposed area, cross- cut by mafic and felsic dykes. Finally, a mafic association has been identified characterized by dykes and a small intrusion of gabbroic composition.All these units are Mesozoic in age (130 - 127 Ma) and according to their chemical nature they correspond tosub-alkaline to weak peralkaline magmas

State of art of micronuclei assay in exfoliative cytology as a clinical biomarker of genetic damage in oral carcinogenesis: A systematic review and meta-analysis

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy, often preceded by oral potentially malignant disorders (OPMDs). Currently, no clinical biomarker exists to predict malignancy, necessitating OPMD follow-up. Habits and environmental factors, such as smoking, and alcohol consumption, influence OSCC onset. Increased micronuclei (MNs) formation has been observed in the development of OSCC. Non-invasive diagnostic tests like exfoliative cytology offer painless and regular monitoring options. This study evaluates the impact of tobacco, alcohol, and pesticide exposure on MNs occurrence in exfoliative cytology-collected oral mucosal cells, assessing their potential as non-invasive biomarker for OSCC development prediction and monitoring in high-risk patients. Despite results from this meta-analysis supporting the existence of a stepwise increase from controls to patients with OPMD to OSCC, the translation of these findings into clinical practice is limited due to intra- and inter-individual heterogeneity, as well as methodological variability in MNs quantification. Various factors contribute to this heterogeneity, including demographic variables, methodological variability of different laboratories, staining techniques, sample collection location, and patient characteristics. All these points were discussed to provide further insights and improve standardization for future studies

MYELOID MICROVESICLES ARE A MARKER AND THERAPEUTIC TARGET FOR NEUROINFLAMMATION

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Physical activity practiced at a young age is associated with a less severe subsequent clinical presentation in facioscapulohumeral muscular dystrophy

Background: In facioscapulohumeral muscular dystrophy (FSHD), it is not known whether physical activity (PA) practiced at young age is associated with the clinical presentation of disease. To assess this issue, we performed a retrospective cohort study concerning the previous practice of sports and, among them, those with medium-high cardiovascular commitment in clinically categorized carriers of a D4Z4 reduced allele (DRA). Methods: People aged between 18 and 60 were recruited as being DRA carriers. Subcategory (classical phenotype, A; incomplete phenotype, B; asymptomatic carriers, C; complex phenotype, D) and FSHD score, which measures muscle functional impairment, were assessed for all participants. Information on PAs was retrieved by using an online survey dealing with the practice of sports at a young age. Results: 368 participants were included in the study, average age 36.6 years (SD = 9.4), 47.6% male. The FSHD subcategory A was observed in 157 (42.7%) participants with average (± SD) FSHD score of 5.8 ± 3.0; the incomplete phenotype (category B) in 46 (12.5%) participants (average score 2.2 ± 1.7) and the D phenotype in 61 (16.6%, average score 6.5 ± 3.8). Asymptomatic carriers were 104 (subcategory C, 28.3%, score 0.0 ± 0.2). Time from symptoms onset was higher for patients with A (15.8 ± 11.1 years) and D phenotype (13.3 ± 11.9) than for patients with B phenotype (7.3 ± 9.0). The practice of sports was associated with lower FSHD score (-17%) in participants with A phenotype (MR = 0.83, 95% CI = 0.73-0.95, p = 0.007) and by 33% in participants with D phenotype (MR = 0.67, 95% CI = 0.51-0.89, p = 0.006). Conversely, no improvement was observed in participants with incomplete phenotype with mild severity (B). Conclusions: PAs at a young age are associated with a lower clinical score in the adult A and D FSHD subcategories. These results corroborate the need to consider PAs at the young age as a fundamental indicator for the correct clinical stratification of the disease and its possible evolution

Refining patient selection for next-generation immunotherapeutic early-phase clinical trials with a novel and externally validated prognostic nomogram

IntroductionIdentifying which patient may benefit from immunotherapeutic early-phase clinical trials is an unmet need in drug development. Among several proposed prognostic scores, none has been validated in patients receiving immunomodulating agents (IMAs)-based combinations.Patients and methodsWe retrospectively collected data of 208 patients enrolled in early-phase clinical trials investigating IMAs at our Institution, correlating clinical and blood-based variables with overall survival (OS). A retrospective cohort of 50 patients treated with IMAs at Imperial College (Hammersmith Hospital, London, UK) was used for validation.ResultsA total of 173 subjects were selected for analyses. Most frequent cancers included non-small cell lung cancer (26%), hepatocellular carcinoma (21.5%) and glioblastoma (13%). Multivariate analysis (MVA) revealed 3 factors to be independently associated with OS: line of treatment (second and third vs subsequent, HR 0.61, 95% CI 0.40-0.93, p 0.02), serum albumin as continuous variable (HR 0.57, 95% CI 0.36–0.91, p 0.02) and number of metastatic sites (&lt;3 vs ≥3, HR 0.68, 95% CI 0.48-0.98, p 0.04). After splitting albumin value at the median (3.84 g/dL), a score system was capable of stratifying patients in 3 groups with significantly different OS (p&lt;0.0001). Relationship with OS reproduced in the external cohort (p=0.008). Then, from these factors we built a nomogram.ConclusionsPrior treatment, serum albumin and number of metastatic sites are readily available prognostic traits in patients with advanced malignancies participating into immunotherapy early-phase trials. Combination of these factors can optimize patient selection at study enrollment, maximizing therapeutic intent