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    Influence of occlusal thickness on the fracture resistance of chairside milled lithium disilicate posterior full-coverage single-unit prostheses containing virgilite: A comparative in vitro study.

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    PURPOSE To evaluate the fracture resistance of chairside computer-aided design and computer-aided manufacturing (CAD-CAM) lithium disilicate mandibular posterior crowns with virgilite of different occlusal thicknesses and compare them to traditional lithium disilicate crowns. MATERIALS AND METHODS Seventy-five chairside CAD-CAM crowns were fabricated for mandibular right first molars, 60 from novel lithium disilicate with virgilite (CEREC Tessera, Dentsply Sirona), and 15 from traditional lithium disilicate (e.max CAD, Ivoclar Vivadent). These crowns were distributed across five groups based on occlusal thickness and material: Group 1 featured CEREC Tessera crowns with 0.8 mm thickness, Group 2 had 1.0 mm thickness, Group 3 had 1.2 mm thickness, Group 4 with 1.5 mm thickness, and Group 5 included e.max CAD crowns with 1.0 mm thickness. These crowns were luted onto 3D-printed resin dies using Multilink Automix resin cement (Ivoclar Vivadent). Subsequently, they underwent cyclic loading (2,000,000 cycles at 1 Hz with a 275 N force) and loading until fracture. Scanning electron microscopy (SEM) assessed the fractured specimens. Statistical analysis involved one-way ANOVA and the Kruskal-Wallis Test (α = 0.05). RESULTS Fracture resistance varied significantly (<0.001) across mandibular molar crowns fabricated from chairside CAD-CAM lithium disilicate containing virgilite, particularly between crowns with 0.8 mm and those with 1.2 and 1.5 mm occlusal thickness. However, no significant differences were found when comparing crowns with 1, 1.2, and 1.5 mm thicknesses. CEREC Tessera crowns with 1.5 mm thickness exhibited the highest resistance (2119 N/mm2), followed by those with 1.2 mm (1982 N/mm2), 1.0 mm (1763 N/mm2), and 0.8 mm (1144 N/mm2) thickness, whereas e.max CAD crowns with 1.0 mm occlusal thickness displayed the lowest resistance (814 N/mm2). CONCLUSIONS The relationship between thickness and fracture resistance in the virgilite lithium disilicate full-coverage crowns was directly proportional, indicating that increased thickness corresponded to higher fracture resistance. No significant differences were noted among crowns with thicknesses ranging from 1 to 1.5 mm. This novel ceramic exhibited superior fracture resistance compared to traditional lithium disilicate

    Cardiorespiratory fitness, perceived fitness and autonomic function in in-patients with different depression severity compared with healthy controls.

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    Over 300 million individuals worldwide suffer from major depressive disorder (MDD). Individuals with MDD are less physically active than healthy people which results in lower cardiorespiratory fitness (CRF) and less favorable perceived fitness compared with healthy controls. Additionally, individuals with MDD may show autonomic system dysfunction. The purpose of the present study was to evaluate the CRF, perceived fitness and autonomic function in in-patients with MDD of different severity compared with healthy controls. We used data from 212 in-patients (age: 40.7 ± 12.6 y, 53% female) with MDD and from 141 healthy controls (age: 36.7 ± 12.7 y, 58% female). We assessed CRF with the Åstrand-Rhyming test, self-reported perceived fitness and autonomic function by heart rate variability (HRV). In specific, we used resting heart rate, time- and frequency-based parameters for HRV. In-patients completed the Beck Depression Inventory-II (BDI-II) to self-assess the subjectively rated severity of depression. Based on these scores, participants were grouped into mild, moderate and severe MDD. The main finding was an inverse association between depression severity and CRF as well as perceived fitness compared with healthy controls. Resting heart rate was elevated with increasing depression severity. The time-based but not the frequency-based autonomic function parameters showed an inverse association with depression severity. The pattern of results suggests that among in-patients with major depressive disorder, those with particularly high self-assessed severity scores show a lower CRF, less favorable perceived fitness and partial autonomic dysfunction compared to healthy controls. To counteract these conditions, physical activity interventions may be effective

    Atypical connectome topography and signal flow in temporal lobe epilepsy.

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    Temporal lobe epilepsy (TLE) is the most common pharmaco-resistant epilepsy in adults. While primarily associated with mesiotemporal pathology, recent evidence suggests that brain alterations in TLE extend beyond the paralimbic epicenter and impact macroscale function and cognitive functions, particularly memory. Using connectome-wide manifold learning and generative models of effective connectivity, we examined functional topography and directional signal flow patterns between large-scale neural circuits in TLE at rest. Studying a multisite cohort of 95 patients with TLE and 95 healthy controls, we observed atypical functional topographies in the former group, characterized by reduced differentiation between sensory and transmodal association cortices, with most marked effects in bilateral temporo-limbic and ventromedial prefrontal cortices. These findings were consistent across all study sites, present in left and right lateralized patients, and validated in a subgroup of patients with histopathological validation of mesiotemporal sclerosis and post-surgical seizure freedom. Moreover, they were replicated in an independent cohort of 30 TLE patients and 40 healthy controls. Further analyses demonstrated that reduced differentiation related to decreased functional signal flow into and out of temporolimbic cortical systems and other brain networks. Parallel analyses of structural and diffusion-weighted MRI data revealed that topographic alterations were independent of TLE-related cortical thinning but partially mediated by white matter microstructural changes that radiated away from paralimbic circuits. Finally, we found a strong association between the degree of functional alterations and behavioral markers of memory dysfunction. Our work illustrates the complex landscape of macroscale functional imbalances in TLE, which can serve as intermediate markers bridging microstructural changes and cognitive impairment

    Documenting Media Histories of documenta 6

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    Effect of patient-specific scapular morphology on the glenohumeral joint force and shoulder muscle force equilibrium: a study of rotator cuff tear and osteoarthritis patients.

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    Introduction: Osteoarthritis (OA) and rotator cuff tear (RCT) pathologies have distinct scapular morphologies that impact disease progression. Previous studies examined the correlation between scapular morphology and glenohumeral joint biomechanics through critical shoulder angle (CSA) variations. In abduction, higher CSAs, common in RCT patients, increase vertical shear force and rotator cuff activation, while lower CSAs, common in OA patients, are associated with higher compressive force. However, the impact of the complete patient-specific scapular morphology remains unexplored due to challenges in establishing personalized models. Methods: CT data of 48 OA patients and 55 RCT patients were collected. An automated pipeline customized the AnyBody™ model with patient-specific scapular morphology and glenohumeral joint geometry. Biomechanical simulations calculated glenohumeral joint forces and instability ratios (shear-to-compressive forces). Moment arms and torques of rotator cuff and deltoid muscles were analyzed for each patient-specific geometry. Results and discussion: This study confirms the increased instability ratio on the glenohumeral joint in RCT patients during abduction (mean maximum is 32.80% higher than that in OA), while OA patients exhibit a higher vertical instability ratio in flexion (mean maximum is 24.53% higher than that in RCT) due to the increased inferior vertical shear force. This study further shows lower total joint force in OA patients than that in RCT patients (mean maximum total force for the RCT group is 11.86% greater than that for the OA group), attributed to mechanically advantageous muscle moment arms. The findings highlight the significant impact of the glenohumeral joint center positioning on muscle moment arms and the total force generated. We propose that the RCT pathomechanism is related to force magnitude, while the OA pathomechanism is associated with the shear-to-compressive loading ratio. Overall, this research contributes to the understanding of the impact of the complete 3D scapular morphology of the individual on shoulder biomechanics

    The effect of care interruptions on mortality in adults resuming antiretroviral therapy.

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    OBJECTIVE To estimate the relative rate of all-cause mortality amongst those on antiretroviral treatment (ART) with a history of interruptions compared with those with no previous interruptions in care. DESIGN Retrospective cohort study. METHODS We used data from four South African cohorts participating in the International epidemiology Databases to Evaluate AIDS Southern Africa collaboration. We included adults who started ART between 2004 and 2019. We defined a care interruption as a gap in contact longer than 180 days. Observation time prior to interruption was allocated to a 'no interruption' group. Observation time after interruption was allocated to one of two groups based on whether the first interruption started before 6 months of ART ('early interruption') or later ('late interruption'). We used Cox regression to estimate hazard ratios. RESULTS Sixty-three thousand six hundred and ninety-two participants contributed 162 916 person-years of observation. There were 3469 deaths. Most participants were female individuals (67.4%) and the median age at ART initiation was 33.3 years (interquartile range: 27.5-40.7). Seventeen thousand and eleven (26.7%) participants experienced care interruptions. Those resuming ART experienced increased mortality compared with those with no interruptions: early interrupters had a hazard ratio of 4.37 (95% confidence interval (CI) 3.87-4.95) and late interrupters had a hazard ratio of 2.74 (95% CI 2.39-3.15). In sensitivity analyses, effect sizes were found to be proportional to the length of time used to define interruptions. CONCLUSION Our findings highlight the need to improve retention in care, regardless of treatment duration. Programmes to encourage return to care also need to be strengthened

    MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature.

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    Epigenetic dysregulation has emerged as an important etiological mechanism of neurodevelopmental disorders (NDDs). Pathogenic variation in epigenetic regulators can impair deposition of histone post-translational modifications leading to aberrant spatiotemporal gene expression during neurodevelopment. The male-specific lethal (MSL) complex is a prominent multi-subunit epigenetic regulator of gene expression and is responsible for histone 4 lysine 16 acetylation (H4K16ac). Using exome sequencing, here we identify a cohort of 25 individuals with heterozygous de novo variants in MSL complex member MSL2. MSL2 variants were associated with NDD phenotypes including global developmental delay, intellectual disability, hypotonia, and motor issues such as coordination problems, feeding difficulties, and gait disturbance. Dysmorphisms and behavioral and/or psychiatric conditions, including autism spectrum disorder, and to a lesser extent, seizures, connective tissue disease signs, sleep disturbance, vision problems, and other organ anomalies, were observed in affected individuals. As a molecular biomarker, a sensitive and specific DNA methylation episignature has been established. Induced pluripotent stem cells (iPSCs) derived from three members of our cohort exhibited reduced MSL2 levels. Remarkably, while NDD-associated variants in two other members of the MSL complex (MOF and MSL3) result in reduced H4K16ac, global H4K16ac levels are unchanged in iPSCs with MSL2 variants. Regardless, MSL2 variants altered the expression of MSL2 targets in iPSCs and upon their differentiation to early germ layers. Our study defines an MSL2-related disorder as an NDD with distinguishable clinical features, a specific blood DNA episignature, and a distinct, MSL2-specific molecular etiology compared to other MSL complex-related disorders

    Klauengesundheit (6/6): Das Grippeli, besonders auf Rinderalpen ein Problem. Sumpfstellen sind ein Risiko

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    Das Grippeli ist bei Alprindern ein Problem, das den Tieren Schmerzen und den Hirten Mehraufwand für Behandlungen bereitet. Befestigte Tränkestellen und die Trennung trächtiger und nicht trächtiger Rinder helfen

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