Early Loss Research Articles

Good personality traits in bad times: Does conscientiousness mitigate the adverse effects of graduating in a recession?

This paper studies whether and how conscientiousness, a personality trait, helps individuals mitigate the adverse effects of graduating during a recession on early career outcomes. By analyzing college-educated individuals who graduated in the 1980s, we find that conscientiousness reduces the income losses of workers who graduated during a recession. This effect results mainly from workers’ adjustments in the labor supply. When graduating during a recession, college graduates high in conscientiousness are more likely to find full-time jobs and work more hours per week than their counterparts low in conscientiousness. Regarding the other four Big Five personality traits, while agreeableness has a modest effect on mitigating the effects of adverse labor market entry conditions on hourly wages, extraversion, openness to experience, and emotional stability do not appear to buffer against such early career losses. Additionally, cognitive ability does not offset the challenges posed by graduating during a recession.

Identification of apelin/APJ signaling dysregulation in a human iPSC-derived granulosa cell model of Turner syndrome.

The interaction between germ cells and somatic cells in the ovaries plays a crucial role in establishing the follicle reserve in mammals. Turner syndrome (TS) predominantly affects females who have a partial or complete loss of one X chromosome. Our understanding of the role that granulosa cells (GCs) play in TS disease progression and pathogenesis remains limited. In this study, we achieved GC differentiation efficiency of up to 80% from iPSCs. When attempting to replicate the differentiation process of embryonic granulosa cells, we observed the downregulation of specific genes-GATA4, FOXL2, AMHR2, CYP19A1, and FSH-in Turner syndrome-derived granulosa cells (TS-GCs). Additionally, we identified dysregulation of the cell cycle in TS-GCs. To uncover the endogenous defects in TS-GCs, we compared global transcriptome patterns between iPSC-derived granulosa cells from healthy individuals and those with Turner syndrome. The apelin/APJ pathway exhibited differential signaling between the healthy and TS groups. Supplementation with apelin ligands and activation of apelin/APJ downstream signaling via Akt/PKB restored cell cycle progression and marker gene expression. We hypothesize that during early embryonic development, failures in apelin/APJ signaling in GCs of Turner syndrome patients lead to abnormalities in ovarian development, ultimately resulting in early oocyte loss and infertility.

Clinical and radiographic assessment of the association between orthodontic mini-screws and periodontal health.

Proper anchorage control is crucial for predictable tooth movement and preventing inadequate torque during orthodontic treatment. Through clinical and radiographic parameters; this study assesses the association between mini-screws and periodontal health. A prospective observational study included 16 systemically healthy non-smoking individuals requiring mini-screws. Mini-screws with a rough, titanium oxide-coated surface were placed. Periodontal assessments (Plaque index, gingival index, probing pocket depth, gingival recession, bleeding on probing, mucosal discomfort, mucosal redness, keratinized tissue width, supracrestal tissue height, and transmucosal soft tissue thickness) were performed at 2nd week and 3 months post-placement. Radiographic evaluations measured distances between mini-screws and adjacent teeth using Image J software. The study included 13 females and 3 males (mean age 21.9 ± 1.8 years) with 24 mini-screws. Early mini-screw loss was not observed. Significant reductions in site-level Gingival Index and bleeding on probing (p < 0.05) and full-mouth bleeding on probing (p < 0.05) were noted over time. Absence of significant differences was found in mucosal discomfort and redness, keratinized tissue width, or transmucosal soft tissue thickness, but supracrestal tissue height decreased significantly (p < 0.05). Radiographically, significant bone reduction around mini-screws was observed at 3 months, with torque gauge values significantly decreased as well (p < 0.05). Orthodontic mini-screws can be effectively utilized in orthodontic treatment with proper planning and monitoring. While improvements in gingival health were observed with targeted oral care, the study underscores the need for careful consideration of potential risks to periodontal tissues, such as reductions in supracrestal tissue height and bone levels. A balanced approach that integrates preventive strategies with precise screw placement is essential to maximize the benefits of mini-screws while minimizing potential periodontal complications. While proper oral hygiene can help control inflammation around mini-screw sites, clinicians must also be mindful of potential risks, such as reductions in bone levels and tissue height. Careful patient selection, precise placement, and regular follow-up are crucial to ensure the stability of mini-screws' stability and to prevent complications, ultimately contributing to better treatment outcomes in orthodontic care. This study was registered on ClinicalTrials.gov with the registration number NCT06491849 on June 28, 2024.

Effects of elevated intraocular pressure on alpha ganglion cells in experimental glaucoma mice

Glaucoma is a leading cause of blindness worldwide and glaucoma patients exhibit an early diffuse loss of retinal sensitivity followed by focal loss of RGCs. Combining some previous published results and some new data, this paper provides our current view on how high IOP (H-IOP) affects the light response sensitivity of a subset of RGCs, the alpha-ganglion cells (αGCs), as well as their presynaptic bipolar cells (DBCs and HBCs) and A2 amacrine cells (AIIACs) in dark-adapted mouse retinas. Our data demonstrate that H-IOP in experimental glaucoma mice significantly decreases light-evoked spike response sensitivity of sONαGCs and sOFFαGCs (i.e., raises thresholds by 1.5–2.5 log units), but not that of the tONαGCs and tOFFαGCs. The sensitivity loss in sONαGCs and sOFFαGCs is mediated by a H-IOP induced suppression of AIIAC response which is caused by a decrease of transmission efficacy of the DBCR→AIIAC synapse. We also provide evidence supporting the hypothesis that BK channels in the A17AC→DBCR feedback synapse are the H-IOP sensor that regulates the DBCR→AIIAC synaptic efficacy, as BK channel blocker IBTX mimics the action of H-IOP. Our results provide useful information for designing strategies for early detection and possible treatments of glaucoma as physiological changes occur before irreversible structural damage.

Similar disease progression in nonsense Duchenne Muscular Dystrophy boys as general natural history: single Brazilian center 15 years registry view.

Duchenne muscular dystrophy is a progressive and fatal X-linked neuromuscular disease. Emergent disease-modifying therapy (DMT) in nonsense Duchenne muscular dystrophy (nmDMD) has brought new perspectives to slow down functional decline in this fatal disease. To investigate if there are differences in natural history between nmDMD and other genotypes, we described a retrospective cohort analysis of 25 nonsense mutation DMD (nmDMD) boys without disease-modifying therapy, aged between 1 and 22 years, over the last 15 years (2007-2022) in a single neuromuscular center in Rio de Janeiro and use published data on DMD natural history for comparison. Regarding prognostic factors, there were remarkable and statistically significant early loss of ambulation (at 9.1y ±2.1) and shortening of life expectancy (17.6y ±2.1) in our nmDMD group. Late acquisition of neurodevelopmental milestones and annual rates of decline in respiratory, cardiac, and timed motor function tests are the same between nmDMD patients with standard care and other DMD genotypes as described in the literature. Our data indicates the similarity of natural history and disease progression among DMD boys with nmDMD mutations compared to different mutations.

Mechanical and suture-holding properties of a UV-cured atelocollagen membrane with varied crosslinked architecture

The mechanical competence and suturing ability of collagen-based membranes are paramount in guided bone regeneration (GBR) therapy, to ensure damage-free implantation, fixation and space maintenancein vivo. However, contact with the biological medium can induce swelling of collagen molecules, yielding risks of membrane sinking into the bone defect, early loss of barrier function, and irreversibly compromised clinical outcomes. To address these challenges, this study investigates the effect of the crosslinked network architecture on both mechanical and suture-holding properties of a new atelocollagen (AC) membrane. UV-cured networks were obtained via either single functionalisation of AC with 4-vinylbenzyl chloride (4VBC) or sequential functionalisation of AC with both 4VBC and methacrylic anhydride. The wet-state compression modulus (Ec) and swelling ratio (SR) were significantly affected by the UV-cured network architecture, leading up to a three-fold reduction in SR and about two-fold increase inEcin the sequentially functionalised, compared to the single-functionalised, samples. Electron microscopy, dimensional analysis and compression testing revealed the direct impact of the ethanol series dehydration process on membrane microstructure, yielding densification of the freshly synthesised porous samples and a pore-free microstructure with increasedEc. Nanoindentation tests via spherical bead-probe atomic force microscopy (AFM) confirmed an approximately two-fold increase in median (interquartile range (IQR)) elastic modulus in the sequentially functionalised (EAFM= 40 (13) kPa), with respect to single-functionalised (EAFM= 15 (9) kPa), variants. Noteworthy, the single-functionalised, but not the sequentially functionalised, samples displayed higher suture retention strength (SRS = 28 ± 2-35 ± 10 N∙mm-1) in both the dry state and following 1 h in phosphate buffered saline (PBS), compared to Bio-Gide® (SRS: 6 ± 1-14 ± 2 N∙mm-1), while a significant decrease was measured after 24 h in PBS (SRS= 1 ± 1 N∙mm-1). These structure-property relationships confirm the key role played by the molecular architecture of covalently crosslinked collagen, aimed towards long-lasting resorbable membranes for predictable GBR therapy.

Melanoma arising from pre-existing naevus in carriers of a germline CDKN2A pathogenic variant.

In this study we used total body photography (TBP) to determine whether melanoma emerges from a preexisting naevi or normal-appearing skin in individuals with pathogenic CDKN2a variant. In total, 60 melanoma cases occurred in 44 CDKN2a germline carriers. In addition, we observed that 78% of the 60 included melanoma cases developed from preexisting naevi, significantly higher than the 30% reported for sporadic melanoma. This high incidence may be due to the numerous atypical naevi and early bi-allelic loss of CDKN2A. Our findings underscore the importance of routine TBP in these patients for early detection of melanoma. More than previously appreciated, the surgical removal of melanocytic naevi in these high-risk patients may prevent melanoma development.

The association between low serum vitamin D level &amp; periodontal diseases in Bangladeshi population- An observational study

Aims: Bangladeshi population (20-45 age) presents early loss of tooth without any history of systemic disease. Low serum vitamin D level is one of the factors of early tooth loss. The aim of the study is to assess the significance of low or insufficient serum vitamin D level as a factor of early tooth loss in Bangladesh perspective. Materials and Methods: An observational study was performed in dental unit of TMSS Medical College from January 2021 to December 2022 after ethical clearance of IRB of this institute. Total number of patients was 70 selected by non-random sampling (judgment sampling) who fulfilled the inclusion and exclusion criteria. We assessed the variable like gingivitis, periodontal pocket &amp; tooth mobility clinically. The depth of the periodontal pocket &amp; gingivitis was assessed by the periodontal probe &amp; the mobility by using a blunt instrument &amp; feel with the fingers before &amp; after Vit D supplementation. Data were processed and analyzed using computer software SPSS version 26.0. Results: Deficiency of low serum vit D level has significant effect on periodontal bone resorption and after correction of serum vit D level resulted clinical improvement on periodontal health. Conclusion: Vitamin D deficiency may place subject at risk of developing chronic periodontitis. J Bangladesh Coll Phys Surg 2024; 42: 363-367

ADGRU: Adaptive DenseNet with gated recurrent unit for automatic diagnosis of periodontal bone loss and stage periodontitis with tooth segmentation mechanism.

Periodontics and gingivitis are two of the most widely prevalent illnesses that affect people nowadays. The sixth most common disease in the world is periodontitis, and detecting periodontal bone loss is essential in the earlier condition and is crucial for the development of the proper diagnosis. Early bone loss detection can be assisted by using computer-assisted radiography examination. Understanding disease progression helps to select the most effective treatment action. An effective deep model is suggested to detect periodontal bone loss at an earlier stage for preventing the progression of Periodontics bone loss. This work is intimated by collecting images from online resources. Further, the images gathered from the dataset are preceded by the tooth segmentation which is done using DenseUNet + + . Further, the segmented images are given to the Adaptive DenseNet with Gated Recurrent Unit (AD-GRU) for detecting periodontal bone loss and this diagnosis is used for the periodontitis stage, where the ADGRU performance is augmented by optimizing the attributes using the Refined Red Kite Optimization Algorithm (RRKOA). The offered approach attained an accuracy of 94.45% which is higher than the88.63%, 90.58%, 89.54%, and 92.96% attained by the LSTM, DenseNet, GRU, DenseNet-GRU. The findings of the simulation proved the designed framework outperformed the traditional model with high accuracy. The developed effectual deep model-based periodontal bone loss and stage periodontitis diagnosis structure is used in healthcare applications.

Loss of a Parent in Disney and Pixar Films: What We Can Learn?

Early parental loss is a tragic experience for children causing complex reactions to the loss. Providing a supportive environment where they can express their feelings is crucial to help them cope with this challenging experience. This study analyses the depiction of parental death in animated films by Disney and Pixar using a multimethod design and including the QUAGOL approach. We identified 13 films showing the death of one or both parents. The qualitative analysis of the films, published from 1937 until 2022, revealed seven concepts that potentially affect the way children see their grieving process reflected in the films: The representational techniques, finding protection and relationships, searching for identity, being different and having alternative skills, talking about death, dealing with emotions and coping with the loss. The identified films can be used to open a conversation with children who have lost one or both parents to discuss their situation.

Intraoperative Complications as Predictors of Flap Failure in Autologous Breast Reconstruction.

Intraoperative microvascular complications in autologous breast reconstruction significantly increase the risk of postoperative complications. No study has identified which specific intraoperative complications contribute to partial or total flap loss. A retrospective chart review of microsurgical breast reconstructions by five surgeons between 2009 and 2020 analyzed operative variables and patient outcomes, with complications determined from the operative report. Flap loss rates were compared between cases with and without intraoperative complications. Statistical analysis was performed using Fisher's exact and t-tests for discrete and continuous variables, respectively. Intraoperative complications were analyzed for 1,465 autologous breast flaps performed in 916 patients. Early partial flap loss was predicted by arterial anastomosis revision (2.90 vs. 0.44%, p = 0.03) and alternate venous outflow (14.29 vs. 0.41%, p = 0.002), with no association with intraoperative thrombosis, venous revision, or difficult recipient or flap dissection. In comparison, early total flap loss was predicted by intraoperative arterial revision (5.80 vs. 0.51%, p = 0.001), venous revision (5.45 vs. 0.57%, p = 0.007), intraoperative thrombosis (12.12 vs. 0.49%, p < 0.001), and difficult flap dissection (2.91 vs. 0.59%, p = 0.04). Difficult flap dissection was the only intraoperative variable associated with late partial flap loss (6.80 vs. 1.69%, p = 0.004). Late total flap loss only occurred in 6/1,465 flaps, the sole association being difficult recipient vessel dissection (2.78 vs. 0.29%, p = 0.03). Postoperative arterial and venous compromise occurred in 1.10% (13/1,187) and 2.53% (30/1,187) of cases with no intraoperative complications, respectively, compared with 3.2% (9/278, p = 0.02) and 6.12% (17/278, p = 0.002) in cases with an intraoperative complication. Alternate venous outflow predicts early partial flap loss, while intraoperative thrombosis and arterial and venous revision predict early total loss. Difficult flap dissection was associated with early total and late partial flap loss, while difficult recipient vessel dissection was associated with late total flap loss.

Delineating three distinct spatiotemporal patterns of brain atrophy in Parkinson's disease.

The clinical manifestation of Parkinson's disease exhibits significant heterogeneity in the prevalence of non-motor symptoms and the rate of progression of motor symptoms, suggesting that Parkinson's disease can be classified into distinct subtypes. In this study, we aimed to explore this heterogeneity by identifying a set of subtypes with distinct patterns of spatiotemporal trajectories of neurodegeneration. We applied Subtype and Stage Inference (SuStaIn), an unsupervised machine learning algorithm that combined disease progression modelling with clustering methods, to cortical and subcortical neurodegeneration visible on 3 T structural MRI of a large cross-sectional sample of 504 patients and 279 healthy controls. Serial longitudinal data were available for a subset of 178 patients at the 2-year follow-up and for 140 patients at the 4-year follow-up. In a subset of 210 patients, concomitant Alzheimer's disease pathology was assessed by evaluating amyloid-β concentrations in the CSF or via the amyloid-specific radiotracer 18F-flutemetamol with PET. The SuStaIn analysis revealed three distinct subtypes, each characterized by unique patterns of spatiotemporal evolution of brain atrophy: neocortical, limbic and brainstem. In the neocortical subtype, a reduction in brain volume occurred in the frontal and parietal cortices in the earliest disease stage and progressed across the entire neocortex during the early stage, although with relative sparing of the striatum, pallidum, accumbens area and brainstem. The limbic subtype represented comparative regional vulnerability, which was characterized by early volume loss in the amygdala, accumbens area, striatum and temporal cortex, subsequently spreading to the parietal and frontal cortices across disease stage. The brainstem subtype showed gradual rostral progression from the brainstem extending to the amygdala and hippocampus, followed by the temporal and other cortices. Longitudinal MRI data confirmed that 77.8% of participants at the 2-year follow-up and 84.0% at the 4-year follow-up were assigned to subtypes consistent with estimates from the cross-sectional data. This three-subtype model aligned with empirically proposed subtypes based on age at onset, because the neocortical subtype demonstrated characteristics similar to those found in the old-onset phenotype, including older onset and cognitive decline symptoms (P < 0.05). Moreover, the subtypes correspond to the three categories of the neuropathological consensus criteria for symptomatic patients with Lewy pathology, proposing neocortex-, limbic- and brainstem-predominant patterns as different subgroups of α-synuclein distributions. Among the subtypes, the prevalence of biomarker evidence of amyloid-β pathology was comparable. Upon validation, the subtype model might be applied to individual cases, potentially serving as a biomarker to track disease progression and predict temporal evolution.

A 10-year Retrospective Clinical Study to Identify Risk Indicators for Peri-Implant Bone Loss and Implant Failure.

To evaluate long-term survival and success of dental implants and evaluate indicators affecting the long-term outcome. Implant survival, success and crestal bone loss (BL) over time were evaluated. For covariates at patient level, Kaplan-Meier estimates of implant survival were compared between groups with the log-rank test. Observed mean bone loss (MBL) was plotted as a function of time. Cumulative frequencies of BL were plotted for different post-op times. Uni- and multivariate analysis was performed. Simple linear mixed and multiple linear mixed models for BL at 1, 5 and 10 years were fitted. 407 patients (221 women, 186 men; mean age 64.86 years (range 28-92, SD 10.11)), with 1482 implants, responded. Absolute implant survival was 94.74%; MBL was 0.81 mm (SD 1.58, range 0.00-17.00) after an average follow-up of 10.66 years (range 10-14, SD 0.87). Implant survival was influenced on implant level by smoking, implant width and early bone loss (EBL) > 0.5 mm; on patient level by a history of periodontitis. Indicators influencing MBL after the 1st year were abutment height, type of surgery and implant width, while after 5 and 10 years of function were abutment height, EBL > 0.5 mm and smoking. Implant survival was significantly affected by a history of periodontitis on patient level and by smoking, implant width and EBL > 0.5 mm on implant level. Late bone loss was significantly affected by abutment height, EBL > 0.5 mm and smoking. B670201524796.

Seasonal changes in the viability and abundance of bacterial cells in the snowpack ecosystem of a High Arctic ice cap

ABSTRACT Microbes play an essential role in nutrient turnover within Arctic environments, and their contribution to biogeochemical cycles can depend on several factors, including but not limited to cell viability. In this study, we employed the SYBR-PI dual cell stain to epifluorescence microscopy to enumerate proportions of potentially viable and non-viable bacterial cell populations within a melting snowpack on an ice cap, Foxfonna in Svalbard. Non-viable cells dominated on Foxfonna (2.5 ± 0.36 × 107 cells m−2) during the June to early July period, when biological production was usually at its peak. Furthermore, non-viable cells also dominated the total cell abundance within superimposed ice (223 ± 242 cells mL−1) and glacial ice (695 ± 717 cells mL−1) beneath the snow. We propose that the rapid, early loss of cell viability was caused by a number of abiotic and biotic factors. Hence, necromass (dead cell residue) contributed to the export of organic matter to downstream ecosystems.

Accelerated Frostbite-Induced Acroosteolysis in Pediatric Insensate Hand: A Case Report and Literature Review.

In pediatric patients, frostbite is a well-documented cause of epiphyseal cartilage destruction and subsequent growth deformity of the affected phalanges. Cases of full acroosteolysis, also referred to as phalangeal osteolysis, of distal phalanges as soon as three months after cold exposure have yet to be reported. We describe a complicated case of frostbite-associated phalangeal osteolysis in the dominant hand of a nine-year-old patient, in the context of post-traumatic insensate hand after sustaining prior electrical burn injuries. This case demonstrates the unique sequela of pediatric frostbite injury involving early loss of the distal phalanx through resorption of the bone and parallel soft tissue retraction, rendering early plastic surgery reconstruction impractical. Reconstructive strategies for frostbite injury in pediatric patients will need to account for the individualized dynamic tissue changes that develop in the months after cold exposure.

Albuminuria and Rapid Kidney Function Decline as Selection Criteria for Kidney Clinical Trials in Type 1 Diabetes Mellitus.

The optimal criteria to select individuals with type 1 diabetes mellitus (T1D) and albuminuric or normoalbuminuric diabetic kidney disease (DKD), who are at risk of rapid kidney function decline, for clinical trials are unclear. This study analyzed data from the Preventing Early Renal Loss in Diabetes (PERL) clinical trial, which investigated whether allopurinol slowed kidney function decline in persons with T1D and early-to-moderate DKD. Rates of iohexol GFR (iGFR) and estimated GFR (eGFR) decline during the three-year study were compared by linear mixed effect regression between participants enrolled based on a history of moderately or severely increased albuminuria (N=394) and those enrolled based on a recent history of rapid kidney function decline (≥3 ml/min/1.73 m2/year) in the absence of a history of albuminuria (N=124). The association between baseline albuminuria and iGFR/eGFR decline during the trial was also evaluated. Rates of eGFR decline during the trial were higher in participants with a history of albuminuria than in those with a history of rapid kidney function decline (-3.56 [95% confidence intervals {CI} -3.17, -3.95] versus -2.35 [95% CI: -1.86, -2.84] ml/min/1.73 m2/year, p=0.001). Results were similar for iGFR decline, although the difference was not significant (p=0.07). Within the history of albuminuria group, the rate of eGFR decline was -5.30 (95% CI -4.52, -6.08) ml/min/1.73m2/year in participants with severely increased albuminuria as compared to -2.97 (95% CI 2.44, -3.50) and -2.32 (95% CI -1.61, -3.03) ml/min/1.73m2/year in those with moderately increased or normal/mildly increased albuminuria at baseline (p<0.001). Severely increased albuminuria at screening is a powerful criterion for selecting persons with T1D at high risk of kidney function decline. A history of rapid eGFR decline without a history of albuminuria is less effective for this purpose but it can still identify individuals with T1D who will lose kidney function more rapidly than expected from physiological aging. ClinicalTrials.gov, NCT02017171.

The Added Value of Controlling Nutritional Status (Conut) Score for Preoperative Counselling on Significant Early Loss of Renal Function After Radical Nephrectomy for Renal Cell Carcinoma

Background and Objectives: We aimed at evaluating the impact of Controlling Nutritional Status (CONUT) score on clinically significant decline in estimated glomerular filtration rate (eGFR) in patients with non-metastatic Clear Cell Renal Cell Carcinoma (ccRCC) undergoing radical nephrectomy (RN). Materials and methods: We retrospectively analyzed a multi-institutional cohort of 140 patients with ccRCC who underwent RN between 2016 and 2018 at three Urological Centers. The CONUT score was calculated with an algorithm including serum albumin, total lymphocyte count, and cholesterol. Clinical and pathologic features were analyzed using Fisher’s exact test for categorical variables and a Mann–Whitney U test for continuous variables. To define the independent predictors of clinically significant eGFR decline, univariable (UVA) and multivariable (MVA) binomial logistic regression analyses were performed in order to assess the Odds Ratio (OR) with 95% Confidence Intervals (CIs). Results: The optimal cut-off value to discriminate between a low and high CONUT score was assessed by calculating the ROC curve. The area under the curve (AUC) was 0.67 (95%CI 0.59–0.78) with the most appropriate cut-off value at 2 points. Overall, 46 patients (32.9%) had a high CONUT score (&gt;2). Statistically significant variables associated with eGFR decline at 24 months were age ≥ 70 (OR 2.01; 95%CI 1.17–3.09; p 0.05), stage II–III chronic kidney disease (CKD) (OR 6.05; 95%CI 1.79–28.3; p 0.001), and a high CONUT score (OR 3.98; 95%CI 1.58–10.4; p 0.004). Conclusions: The CONUT score is a low-time-consuming, cost-effective, and promising tool able to preoperatively screen patients at risk of developing CKD after a RN.

Multiple System Atrophy: Pathology, Pathogenesis, and Path Forward.

Multiple system atrophy (MSA) is a fatal neurodegenerative disease characterized by autonomic failure and motor impairment. The hallmark pathologic finding in MSA is widespread oligodendroglial cytoplasmic inclusions rich in aggregated α-synuclein (αSyn). MSA is widely held to be an oligodendroglial synucleinopathy, and we outline lines of evidence to support this assertion, including the presence of early myelin loss. We consider emerging data that support the possibility of neuronal or immune dysfunction as primary drivers of MSA. These hypotheses are placed in the context of a major recent discovery that αSyn is conformationally distinct in MSA versus other synucleinopathies such as Parkinson's disease. We outline emerging techniques in epidemiology, genetics, and molecular pathology that will shed more light on this mysterious disease. We anticipate a future in which cutting-edge developments in personalized disease modeling, including with pluripotent stem cells, bridge mechanistic developments at the bench and real benefits at the bedside.

Early regional cerebral grey matter damage predicts long-term cognitive impairment phenotypes in multiple sclerosis: a 20-year study.

Despite grey matter atrophy in cortical and subcortical regions has been related to cognitive impairment in multiple sclerosis, only a few studies evaluated its predictive value for alterations in the long-term. We aimed to determine early predictors of cognitive status after 20 years of multiple sclerosis. In this longitudinal retrospective study, participants underwent a 1.5 T MRI scanning at diagnosis (T0) and after two years (T2), which included the evaluation of regional grey matter volume loss patterns. All individuals with multiple sclerosis underwent a comprehensive neuropsychological assessment at the end of the study and were classified considering their global and specific cognitive domains status (memory, attention/information processing speed, executive functioning). Clinical and MRI characteristics were assessed as predictors of long-term cognitive impairment. Analysis of covariance, t-test, unadjusted and adjusted (for age, sex, disease duration, volume of white matter lesions, volume of cortical lesions) logistic regression were conducted. One hundred seventy-five people with multiple sclerosis (118 females; mean ± SD age at the end of study = 47.7 ± 9.4 years) clinically followed for 20 years from onset (mean ± SD = 19.9 ± 5.1) were evaluated. At the end of the study, 81 (47%) were classified as cognitively impaired: 38 as mildly impaired (22%), and 43 as severely impaired (25%). In particular, 46 were impaired in memory (27%), 66 were impaired in attention/information processing speed (38%), and 71 were impaired in executive functioning (41%). Regression models identified precuneus (adjusted odds ratio = 3.37; P < 0.001), insula (adjusted odds ratio = 2.33; P = 0.036), parahippocampal gyrus (adjusted odds ratio = 2.07; P < 0.001) and cingulate (adjusted odds ratio = 1.81; P = 0.009) as the most associated regions with global cognitive impairment and domains-specific cognitive alterations after a mean of 20 years of multiple sclerosis, after adjusting for demographic and clinical variables as well as for focal white matter and grey matter damage. Early grey matter volume loss of specific cortical and deep grey matter regions predicts global and domain cognitive alterations after 20 years from multiple sclerosis diagnosis.

Oro-Dental Characteristics in Patients With Adult-Onset Hypophosphatasia Compared to a Healthy Control Group-A Case-Control Study.

Hypophosphatasia (HPP) is a rare inherited disease that affects multiple organ systems including bone and teeth. Limited knowledge exists on dental and oral health in patients with adult-onset HPP (aHPP). The aim of this study was to investigate oro-dental characteristics in patients with aHPP compared to healthy controls. This case-control study included 20 patients with aHPP compared to 31 healthy controls. Oro-dental manifestations were examined by standardised interviews, clinical examinations as well as radiological registrations on panoramic radiograph (OP) and cone-beam computed tomography (CBCT) scans. The subjective experience of tooth fractures (p = 0.010), caries in permanent teeth (p = 0.032) and early loss of permanent teeth (p = 0.002) was significantly higher in patients with aHPP compared to the controls. In the aHPP group, the presence of specific teeth (p ≤ 0.045) and attrition of 11 were significantly lower (p = 0.012) compared to the controls. Opacity of a few teeth (p ≤ 0.049), presence of denticles (p = 0.024), the distance between the enamel-cement junction (CEJ) and the marginal bone level at specific sites (p ≤ 0.021) and crown height of 11 (p = 0.017) were significantly higher in patients with aHPP than in healthy controls. The results indicate that patients with aHPP have a subjective experience of having poorer dental health. Loss of permanent teeth, less attrition, tooth opacities, denticles and larger distance between CEJ and marginal bone level are possible oro-dental findings in patients with aHPP.