Search

Background: Currently no curative treatment exists for spinocerebellar ataxias (SCAs). Riluzole repurposing was proposed as a symptomatic treatment in different types of cerebellar ataxia. We report a long-term-follow up under riluzole treatment in SCA type 7. Methods: Six patients received Riluzole 50 mg twice daily on a compassionate use program for a mean of 4.8 years (range 3.5-9). We measured ataxia onset and progression through the Scale for the Assessment and Rating of Ataxia (SARA), and collected extensive ophthalmological data before and after Riluzole treatment. Electrocardiogram and laboratory profile for drug safety were performed every six months. Results: Riluzole treatment showed no effect on visual function in two patients with an advanced retinal damage. Improvements of visual function occurred in four patients followed by ophthalmologic stability up to 5 years after starting treatment. Two patients had a less steep deterioration of ataxia after treatment compared to pre-treatment, during the first 2,5 years of therapy. One showed soon after therapy an improvement of the SARA score, and then overall stability lasting 3,5 years, followed by ataxia worsening. One visually impaired patient without neurological impairment did not worse until the last visit after 3,5 years of follow-up. The remaining 2 patients showed an improvement of SARA scores soon after therapy, and an overall stability lasting respectively 5 and 3 years. No adverse event was registered during the observation period. Discussion: This study suggests a possible beneficial action of Riluzole in SCA7 and provides a detailed description of the ophthalmologic profile of these patients. [ABSTRACT FROM AUTHOR]

Purpose: To document the pre-operative rate of clinical deterioration in a cohort of patients with split cord malformation type 1 (SCM 1) and the early- and long-term surgical outcome in these patients. Methods: Data from 41 patients with SCM 1 operated upon by the same surgeon (VR) between January 2008 to June 2023 were retrospectively reviewed with respect to history of clinical deterioration prior to surgery and early and long-term surgical outcomes. Results: The mean age of the patients at presentation was 79.3 months and the male to female ratio was 1:1.93. Twelve (29%) patients had congenital deficits whereas 4 (10%) patients had no neurological deficits. Twenty-six (63%) patients had kyphoscoliosis and 25 (61%) patients had motor dysfunction. Thirty-three (81%) patients (8/12 (67%) with congenital deficits) had clinical deterioration prior to surgery. By the age of 2 years, 56% of patients had clinical deterioration. After surgery, 18 (55%) patients with progressive symptoms had improvement in one or more of their symptoms on long-term follow-up (mean, 63.4 months). There were no predictors of surgical outcome. Conclusions: Since over half of our patients with SCM 1 developed progression of congenital deficits or developed deficits by the age of 2 years, surgery should be performed as soon as possible in these children. On long-term follow-up after surgery, improvement can be expected in over half the patients. [ABSTRACT FROM AUTHOR]

Academic papers in the social sciences were once more essayistic in their form. The carefree launching of concepts and ideas of academic value were the order of the day, all without the security of the present standardized paper format inspired by the natural sciences. This text draws on the most cited paper by the acclaimed scholar Carol Weiss, as an outset to discussing academic writing; why we write as we do and what we may lose by doing so. This means exploring the history of academic writing as well as discussing the complex, yet exciting, relationship between writing, identity, language, and the very process of conducting research. [ABSTRACT FROM AUTHOR]

Ernst Hajek (1934-2024) was a pioneer of ecology in Chile, with a distinguished academic career that spanned several decades. He made significant contributions to ecological research, particularly in the areas of bioclimatology and ecosystem dynamics. Hajek's work extended beyond academia, as he also played a key role in promoting environmental awareness and establishing platforms for scientific dissemination in Chile. His legacy continues to influence ecological studies in the country, earning him recognition as a visionary in the field. [Extracted from the article]

Amblyomma maculatum sensu lato (s.l.) is an ixodid tick found in the semi-arid southwestern United States and northern Mexico where it is a parasite of medical and veterinary significance, including as a vector for Rickettsia parkeri, a cause of spotted fever rickettsiosis in the Americas. To describe the comprehensive natural history of this tick, monthly small mammal trapping and avian mist netting sessions were conducted at sites in Cochise County Arizona, within the Madrean Archipelago region where human cases of R. parkeri rickettsiosis and adult stages of A. maculatum s.l. were previously documented. A total of 1949 larvae and nymphs were removed from nine taxonomic groups of rodents and ten species of birds and were used in combination with records for adult stages collected both from vegetation and hunter-harvested animals to model seasonal activity patterns. A univoltine phenology was observed, initiated by the onset of the annual North American monsoon and ceasing during the hot, dry conditions preceding the following monsoon season. Cotton rats (Sigmodon spp.) were significantly more likely to be infested than other rodent taxa and carried the highest tick loads, reflecting a mutual affinity of host and ectoparasite for microhabitats dominated by grass. [ABSTRACT FROM AUTHOR]

We designed a prospective multicenter cohort study to clarify a long-term, > 10-year prevalence and aggravation of cervical spine instabilities in rheumatoid arthritis (RA). In 2001–2002, 634 outpatients were enrolled, and 233 (36.8%) were followed for > 10 years. Cervical spine instability was defined as atlantoaxial subluxation (AAS, > 3-mm atlantodental interval), vertical subluxation (VS, < 13-mm Ranawat value), and subaxial subluxation (SAS, ≥ 2-mm irreducible vertebral translation). The aggravation was determined as ≥ 2 mm decrease of the Ranawat value in VS, ≥ 2-mm increase of slippage in SAS, and these new developments. The prevalence of VS and SAS increased during both the initial and last > 5 years (all, p ≤ 0.049). While VS aggravation was associated with pre-existing AAS (p = 0.007) and VS (p = 0.002), SAS aggravation correlated with pre-existing VS (p = 0.002). Multivariable analysis found hand mutilating changes (odds ratio [OR] = 4.048, p = 0.008), RA duration ≥ 5 years (OR = 3.711, p = 0.013), C-reactive protein (CRP) level ≥ 3.8 mg/dL (OR = 2.187, p = 0.044), and previous joint surgery (OR = 2.147, p = 0.021) as predictors for VS aggravation. Pre-existing VS (OR = 2.252, p = 0.024) and CRP ≥ 1.0 mg/dL (OR = 2.139, p = 0.013) were disclosed as predictors for SAS aggravation. Low disease activity and clinical remission before the development of VS and advanced peripheral joint destruction are essential to prevent progressive cervical spine instability in RA. [ABSTRACT FROM AUTHOR]

Purpose: Alimentary tract duplications (ATDs) are rare congenital lesions often associated with anomalies such as spinal, urinary and GI tract malformations. The purpose of this study was to report the experience of a single center with ATDs in children, focusing on the natural history, associated malformations, and their impact on patient management. Methods: We performed a retrospective analysis over 14 years, collecting prenatal, clinical, surgical, and follow-up data. We focus on associated anomalies prenatal and postnatal management, and outcomes. Results: Sixty-three patients with ATD (thirty-six females, twenty-seven males, aged 1 day to 14 years) were enrolled in this study. Prenatal diagnosis was made in 22 patients (35%), of whom 8 showed compression signs. Elective surgery was performed at a mean age of 1.5 years in prenatally diagnosed cases. The others presented symptoms at a mean age of 5.2 years (55.5%) or were detected incidentally (9.5%) at a mean age of 10.7 years. In four patients (6.3%), we identified multiple duplications, and ten cases (15.8%) were found with associated anomalies. Conclusion: The wide spectrum of clinical appearance of ATDs and a comprehensive knowledge of human embryology might define surgical management, which should always be patient-tailored and respectful of the child's development. [ABSTRACT FROM AUTHOR]

Background: Ulcerative proctitis (UP) and ulcerative proctosigmoiditis (UPS) are special forms of ulcerative colitis. The disease burdens of UP and UPS are increasing. However, the natural history and prognosis of patients with mild-to-moderate UP or UPS have been poorly studied. Aims: The aim of this study is to evaluate the characteristics, short-term and long-term outcomes of patients with mild-to-moderate UP or UPS followed at a single center over a period of 3 years. Methods: A retrospective study of patients with UP and UPS followed at a single center from 2021 to 2023 was performed. After scanning for inclusion and exclusion criteria, patient demographics and clinical data were collected. Disease severity was accessed by Myao endoscopy scores and ulcerative colitis endoscopic index of severity. Endoscopic improvement was defined as decreased scores at the last follow-up. Disease extension was defined as endoscopic evidence of a greater extent of disease at the last follow-up. Results: A total of 414 patients were included for evaluation, of which 292 patients (70.53%) were at mild disease stage, and 122 patients (29.47%) had moderate diseases. At the last follow-up, 315 patients (76.09%) showed endoscopic improvement, and 247 patients (59.66%) showed endoscopic remission. An overall extension rate of 11.11% was observed at the last follow-up. Subgroup analysis revealed a better prognosis in younger patients. The disease extension rate was higher in moderate group and symptomatic patients. Conclusion: Promising outcomes were observed in patients with mild-to-moderate ulcerative proctitis or ulcerative proctosigmoiditis. Disease severity and symptoms are correlated with the risk of extension. [ABSTRACT FROM AUTHOR]

The functional Scale for the Assessment and Rating of Ataxia (f-SARA) assesses Gait, Stance, Sitting, and Speech. It was developed as a potentially clinically meaningful measure of spinocerebellar ataxia (SCA) progression for clinical trial use. Here, we evaluated content validity of the f-SARA. Qualitative interviews were conducted among individuals with SCA1 (n = 1) and SCA3 (n = 6) and healthcare professionals (HCPs) with SCA expertise (USA, n = 5; Europe, n = 3). Interviews evaluated symptoms and signs of SCA and relevance of f-SARA concepts for SCA. HCP cognitive debriefing was conducted. Interviews were recorded, transcribed, coded, and analyzed by ATLAS.TI software. Individuals with SCA1 and 3 reported 85 symptoms, signs, and impacts of SCA. All indicated difficulties with walking, stance, balance, speech, fatigue, emotions, and work. All individuals with SCA1 and 3 considered Gait, Stance, and Speech relevant f-SARA concepts; 3 considered Sitting relevant (42.9%). All HCPs considered Gait and Speech relevant; 5 (62.5%) indicated Stance was relevant. Sitting was considered a late-stage disease indicator. Most HCPs suggested inclusion of appendicular items would enhance clinical relevance. Cognitive debriefing supported clarity and comprehension of f-SARA. Maintaining current abilities on f-SARA items for 1 year was considered meaningful for most individuals with SCA1 and 3. All HCPs considered meaningful changes as stability in f-SARA score over 1–2 years, 1–2-point change in total f-SARA score, and deviation from natural history. These results support content validity of f-SARA for assessing SCA disease progression in clinical trials. [ABSTRACT FROM AUTHOR]

Museum specimens preserve genetic information that can help resolve phylogenetic relationships of now extinct species. The Caribbean monk seal, Neomonachus tropicalis, is the only marine mammal driven to extinction in tropical seas and one of the few marine mammals to go extinct in historical times. Prior to 1700 it was widely distributed throughout the coasts of North, Central and South America, and in the Bahamas, Greater and Lesser Antilles. The species was first taxonomically placed in the genus Monachus, along with the Hawaiian and Mediterranean monk seals and it was later moved together with the Hawaiian monk seal into the newly described genus Neomonachus. Here, we present the complete mitochondrial genome of the Caribbean monk seal and a phylogenetic reconstruction, confirming its sister taxa relationship with the Hawaiian monk seal, and thus the monophyly of the genus Neomonachus. Our estimates of divergence times are contemporaneous with or predate the emergence of the Isthmus of Panama. We also identify limited genetic variation among five specimens of Caribbean monk seal. [ABSTRACT FROM AUTHOR]

Purpose: Understanding idiopathic scoliosis (IS) natural history during growth is essential for shared decision-making between patients and physicians. We developed a retrospective model with the largest available sample in the literature and we aimed to investigate if using three peri-pubertal growth periods provides better prediction than a unique model. Methods: Secondary analysis of a previous study on IS natural history data from radiographs before and at the first consult. Three groups: BEFORE (age 6–10), AT (age 11-Risser 2) and AFTER (from Risser 3) the pubertal growth spurt. Available predictors: Cobb angle, curve type, sex, observation time, and Risser score. We used linear mixed-effects models to predict future Cobb angles in each group. We internally validated prediction accuracy with over 100 patients per group (3 to 5-fold cross-validation). Results: We included 1563 participants (275 BEFORE, 316 AFTER, 782 females and 190 males AT). Curves increased over time mostly in AT, importantly in BEFORE, but also in AFTER. All models performed better than the general one. In BEFORE, 74.2% of the predictions were within ± 5o, 71.8% in AFTER, 68.2% in AT females, and 60.4% in males. The predictors (baseline curve, observation time also squared and cubic, and Risser score) were similar in all the models, with sex influencing only AFTER. Conclusion: IS curve severities increase differently during growth with puberty stages. Model accuracy increases when tailored by growth spurt periods. Our models may help patients and clinicians share decisions, identify the risk of progression and inform treatment planning. [ABSTRACT FROM AUTHOR]

Abiogenesis is frequently envisioned as a linear, ladder-like progression of increasingly complex chemical systems, eventually leading to the ancestors of extant cellular life. This "pre-cladistics" view is in stark contrast to the well-accepted principles of organismal evolutionary biology, as informed by paleontology and phylogenetics. Applying this perspective to origins, I explore the paradigm of "Stem Life," which embeds abiogenesis within a broader continuity of diversification and extinction of both hereditary lineages and chemical systems. In this new paradigm, extant life's ancestral lineage emerged alongside and was dependent upon many other complex prebiotic chemical systems, as part of a diverse and fecund prebiosphere. Drawing from several natural history analogies, I show how this shift in perspective enriches our understanding of Origins and directly informs debates on defining Life, the emergence of the Last Universal Common Ancestor (LUCA), and the implications of prebiotic chemical experiments. [ABSTRACT FROM AUTHOR]

Purpose: This review focuses on extensive macular atrophy with pseudodrusen-like appearance (EMAP), a recently described maculopathy presenting with pseudodrusen-like lesions and chorioretinal atrophy more pronounced in the vertical axis. Methods: Narrative review of the literature published until May 2024. Results: The early onset age of EMAP (50–55 years) and its distinctive natural history, which includes night blindness followed by severe vision loss, differentiate it from atrophic age-related macular degeneration (AMD). A clear pathogenesis has not been determined, but risk factors include female gender and complement system abnormalities (altered levels of C3 and CH50). Moreover, lifelong exposure to pesticides has been suggested as risk factor for direct neuronal degeneration involving rods and cones. In the early phase of the disease, reticular pseudodrusen-like lesions appear in the superior perifovea and tend to coalescence horizontally into a flat, continuous, reflective material localized between the retinal pigmented epithelium and Bruch's membrane. Over time, EMAP causes profound RPE and outer retinal atrophy in the macular area, with a recent classification reporting a 3-stages evolution pattern. Blue autofluorescence showed rapidly evolving atrophy with either hyperautofluorescent or isoautofluorescent borders. Significant similarities between the diffuse-trickling phenotype of geographic atrophy and EMAP have been reported. Macular neovascularization is a possible complication. Conclusion: EMAP is specific form of early-onset atrophic macular degeneration with rapid evolution and no treatment. Further studies are needed to assess the best management. Key messages: What is known • Extensive Macular Atrophy with Pseudodrusen (EMAP) is a rapidly-progressive macular atrophy developing in the fifth-decade and leading to legal blindness. • Typical characteristics at multimodal imaging are reticular pseudodrusen-like lesions starting at the superior perifovea and vertically-oriented macular atrophy. What is new • Dysregulated complement cascade and pesticide-related toxicity have been proposed as possible etiologies. • In the late stages of the disease 50% of EMAP patients were legally blind by US standards and, after 7 years on average, atrophy reaches the mid-periphery. [ABSTRACT FROM AUTHOR]

Background and objectives: Non-polyglutamine CACNA1A variants underlie an extremely variable phenotypic spectrum encompassing developmental delay, hemiplegic migraine, epilepsy, psychiatric symptoms, episodic and chronic cerebellar signs. We provide our experience with the long-term follow-up of CACNA1A patients and their response to interval therapy. Methods: Patients with genetically confirmed non-polyglutamine CACNA1A disease were prospectively followed at the Center for Rare Movement Disorders of the Medical University of Innsbruck from 2004 to 2024. Results: We recruited 41 subjects with non-polyglutamine CACNA1A disease, of which 38 (93%) familial cases. The mean age at the first examination was 35 ± 22 years. Disease onset was in the childhood/adolescence in 31/41 patients (76%). Developmental delay and episodic symptoms were the first disease manifestation in 9/41 (22%) and 32/41 (78%) patients respectively. Chronic neurological signs encompassed a cerebellar syndrome in 35/41 (85%), which showed almost no progression during the observation period, as well as cognitive deficits in 9/20 (45%, MOCA test score < 26), psychiatric and behavioral symptoms in 11/41(27%). Seizures occurred in two patients concomitant to severe hemiplegic migraine. At the last visit, 27/41 patients (66%) required an interval prophylaxis (including acetazolamide, flunarizine, 4-aminopyridine, topiramate), which was efficacious in reducing the frequency and severity of episodic symptoms in all cases. In one patient in his 70ies with progressively therapy resistant hemiplegic migraine, treatment with the anti-CGRP antibody galcanezumab successfully reduced the frequency of migraine days from 4 to 1/month. Conclusions: Non-polyglutamine CACNA1A disease show an evolving age-dependent presentation. Interval prophylaxis is effective in reducing the burden of episodic symptoms. [ABSTRACT FROM AUTHOR]

Introduction/objectives: Among people with or without hand osteoarthritis, we aimed to identify characteristics of people (e.g., age and gender) with marginal erosions (MEs). We also examined changes in MEs during 48 months. We described radiographic severity and progression among joints with MEs, changes in MEs, or central erosions (CEs). Design: We studied participants from the Osteoarthritis Initiative with baseline and 48-month hand radiographs. A radiologist and rheumatologist evaluated the radiographs for disease severity (Kellgren-Lawrence grades) and erosions (central or marginal), respectively. We used descriptive statistics to characterize participants and calculated frequencies at the joint level. Results: Of the 3558 participants, 89 had a ME at baseline. People with MEs were more often male, older, and ever (former and current) smokers than those without a ME. There was no difference in inflammatory biomarkers or the presence of hand pain between individuals with and without a baseline ME. Almost all hands had only one ME (80%), whereas only 50% of individuals with CEs had only one CE at baseline. Compared to CEs, MEs appeared more frequently in joints without osteoarthritis (54% vs. < 1%). Approximately 18% of joints with an ME progressed in Kellgren-Lawrence grade versus 4% without ME. Among the joints with an ME at baseline, 10% resolved by 48 months. Less than 0.1% of joints developed a new ME. Conclusion: MEs appear to be distinct from CEs. MEs are predominantly present in males, isolated to one specific joint without osteoarthritis within a hand, and possibly predictive of radiographic progression. Key Points • Marginal erosions appear to be distinct from central erosions. • Most marginal erosions occur in joints without radiographic osteoarthritis. • Radiographic progression but not hand pain is more common in joints with a marginal erosion than without one. [ABSTRACT FROM AUTHOR]

Knowledge of behaviors surrounding reproduction in wild species is essential to the development of effective management and conservation strategies. Many carnivores use dens to increase the safety and survival of their neonatal young while females shift to central-place foraging to meet the energetic demands of raising young. Caracals (Caracal caracal), a medium-size wild cat, have a widespread geographic distribution but limited information from minimal observations exists on the behaviors associated with denning and caring for young. We report observations of dens used by four caracals in the surrounds of Cape Town, South Africa, including the duration of den use, maternal home ranges, and movements away from dens. Three of four females established denning in September and one in December, suggesting a birth pulse during the Southern Hemisphere spring and summer. Of seven den sites we documented, six were in dense shrubland fynbos vegetation and one among boulders; all of which had thick overhead cover. Females and neonatal young used 1–3 primary dens for approximately six weeks, followed by the use of short-term auxiliary dens. Female maternal home ranges were approximately 31% the size of their home ranges estimated using all their data. Trips away from the dens averaged 12 h while the average maximum distances across all trips away from dens for each female was 1135 m (range = 801–1327 m). Our observations inform our understanding of the timing and physical characteristics of caracal dens and help fill research gaps on the natural history of caracal denning behavior. [ABSTRACT FROM AUTHOR]

The blue-winged parrot Forpus xanthopterygius is widely distributed in South America, where it lives in groups in different types of environments and feeds on fruits, seeds, flowers and nectar. In 2023 we observed a group of these birds moving from a forested area to an area of aquatic vegetation on the bank of a water reservoir in Southeast Brazil. The birds landed among the leaves of a cluster of Polygonum ferrugineum, approximately 45 cm above the water surface, and consumed flower buds and flowers — a plant species not yet reported for their diet. This behavior occurred during the driest period of the year (April), and may represent an alternative diet due to the scarcity of the preferred resources of this bird species during this period. The species is known to use habitats associated with water and to feed at low heights or even on the ground. However, this behavior of searching for resources on aquatic vegetation at the water surface in the middle of an urban reservoir has not been described and shows the adaptability of these birds to human environments and their high capacity to find food in the most varied types of habitats. [ABSTRACT FROM AUTHOR]

The life shortening nature of Friedreich Ataxia (FRDA) demands the search for therapies that can delay, stop or reverse its relentless trajectory. This review provides a contemporary position of drug and gene therapies for FRDA currently in phase 1 clinical trials and beyond. Despite significant scientific advances in the specificity of both compounds and targets developed and investigated, challenges remain for the advancement of treatments in a limited recruitment population. Currently therapies focus on reducing oxidative stress and improving mitochondrial function, modulating frataxin controlled metabolic pathways and gene replacement and editing. Approval of omaveloxolone, the first treatment for individuals with FRDA aged 16 years and over, has created much excitement for both those living with FRDA and those that care for them. The process of approval of omaveloxolone by the US Food and Drug Administration highlighted the importance of sensitive outcome measures and the significant role of data from natural history studies. [ABSTRACT FROM AUTHOR]

The disposal of plastic materials in recent years has increased exponentially due to human activity. Thus, the accumulation of these residues represents a major concern due to the impact that has been observed, mainly in freshwater aquatic environments and their biota. This study aimed to analyze the presence of microplastics in the gills of fish from the Sorocaba River basin, relating the natural history of the species and the rivers where they were collected. 98 gill samples from eight species sampled at 9 different points of the 4 main Rivers of the basin were analyzed. A total of 385 particles were found, the majority being fibers (74%), predominantly black (63%) and sizes ranging from 2 to 5 mm. The presence of microplastics was verified in all individuals studied, as they are highly susceptible to exposure and retention of plastic microparticles. The highest occurrence of microparticles in fish occurred in the Tatuí River, being verified in the Principal Component Analysis (PCA), considered one of the most disturbed Rivers in the evaluated basin. The particles were identified as polyethylene, polyester, polymethyl methacrylate and polyethylene terephthalate. The present study showed that the gills constitute an important microplastic transfer route for freshwater fish species, and the ecological traits of the species may explain differences in contamination. Considering space–time sampling and different species that make up the fish community is vitally important to understand the scale of microplastic contamination and, subsequently, take effective mitigation measures. [ABSTRACT FROM AUTHOR]

Few studies have systematically analyzed how old aging is. Gaining a more accurate knowledge about the natural history of aging could however have several payoffs. This knowledge could unveil lineages with dated genetic hardware, possibly maladapted to current environmental challenges, and also uncover "phylogenetic modules of aging," i.e., naturally evolved pathways associated with aging or longevity from a single ancestry, with translational interest for anti-aging therapies. Here, we approximated the natural history of the genetic hardware of aging for five model fungal and animal species. We propose a lower-bound estimate of the phylogenetic age of origination for their protein-encoding gene families and protein–protein interactions. Most aging-associated gene families are hundreds of million years old, older than the other gene families from these genomes. Moreover, we observed a form of punctuated evolution of the aging hardware in all species, as aging-associated families born at specific phylogenetic times accumulate preferentially in genomes. Most protein–protein interactions between aging genes are also old, and old aging-associated proteins showed a reduced potential to contribute to novel interactions associated with aging, suggesting that aging networks are at risk of losing in evolvability over long evolutionary periods. Finally, due to reshuffling events, aging networks presented a very limited phylogenetic structure that challenges the detection of "maladaptive" or "adaptative" phylogenetic modules of aging in present-day genomes. [ABSTRACT FROM AUTHOR]

Background: Several studies have shown a higher risk of liver cancer from indeterminate liver nodules, but the exact occurrence and predictors of liver cancer in this group are still unclear. Our aim is to study the development of liver cancer in this population and identify any potential risk factors. Methods: This retrospective study evaluated cirrhotic patients with indeterminate liver nodules from 2013 to 2023.Data from electronic patient records was analyzed to assess the association between HCC and baseline factors. Subgroup exploratory analysis compared characteristics of patients with de novo HCC and those with nodule transformation HCC. Results: Out of 116 patients with liver nodules, 19 (16%) developed HCC in up to 7.5-year follow-up. Univariate Cox regression analysis showed a significant association between HCC incidence and smoking [hazard ratio (HR) 2.60, 95% Confidence Interval [CI] 1.01–6.74), nodule diameter exceeding 2 cm (HR 5.41, 95% CI 1.45–20.18), and baseline LI-RADS score 3 (HR 3.78, 95% CI 1.36–19.52). Multivariate Cox regression analysis revealed significant independent associations with nodule diameters 1 cm to < 2 cm (adjusted HR 3.35, 95% CI 1.06–10.60) and greater than 2 cm (adjusted HR 5.85, 95% CI 1.10–31.16), as well as with LI-RADS 3 lesions (adjusted HR 3.75, 95% CI 1.16–12.11) with adjusting other potential predictors and covariates. Conclusion: Our findings show a higher incidence of HCC in patients with indeterminate liver nodules, increasing over time and reaching 30% at seven years. Nodules larger than 1–2 cm or LI-RADS 3 lesions pose increased risk for HCC. Enhanced surveillance is necessary given the lack of clear management guidelines. [ABSTRACT FROM AUTHOR]

Meningiomas and their WHO histological diagnostic criteria is complex, especially for grade 2 tumors presenting a interobserver discordance as high as 12.2%. The 2016 edition of the WHO Classification of CNS tumors recommended brain invasion as a stand-alone grading criterion for diagnosing an atypical grade 2 meningioma (AM). To provide an overview of the classification of 2016 WHO impact on the natural history of atypical meningioma (AM) relative to previous classification. To achieve this goal, we selected articles from the period 2017–2024 in Medline search on atypical meningiomas and analyzed them after following the following criteria: 1) reports with confirmed histopathological diagnosis according to WHO 2016 and or 2021 criteria; 2) series and case reports; 3) detailed and individualized clinical outcomes for AM; and 4) papers written in English; after that a total of 3445 patients reported in 67 manuscripts from worldwide centers from 2017 to March 2024 were analyzed. The patient's age at the time of surgery ranged from 1 month to 97 years (mean 52.28 ± 18.7 years). The most common tumor site was the convexity, accounting for 67.8%, followed by the skull base in 30.6%, ventricle in 1%, and spine in 0.6%; Gross total resection (GTR) was performed in 71.25% and subtotal resection (STR) in 28.75%; 1021 patients (29.63%) underwent adjuvant radiotherapy, and 22 patients (0.6%) were treated with adjuvant chemotherapy; tumor recurrence was reported in 1221 patients (35.44%) and 859 deaths (24.93%). 1) AM prevalence in females; 2) AM age distribution similar to the distribution of meningiomas in general; 3) AM recurrence rate of 35.44%, despite the high rate of GTR, which was higher than previously reported; 4) deepening knowledge in molecular mechanism of tumor progression will provide alternative therapeutic approaches for AM. [ABSTRACT FROM AUTHOR]

A new computer application (app) that creates interactive checklists is described. NaturaList is a progressive web app that is simple to implement, requiring only minimal skills in information technology from the developer, while also providing the possibility of an abundance of filter/search tools and links to other resources. The data are supplied in a simple spreadsheet. Once the resulting checklist is established on a webserver, it can be easily modified and updated. After implementation by the developer, it is initially accessed by the user online (looking like a standard webpage), after which it can function offline as a mobile app on any device (laptop, tablet, smartphone, etc.). Two floristic examples (from Vanuatu and Niue) are used to illustrate some of the features of NaturaList, but the app could just as easily be applied to any group of organisms, or to folk taxonomies, and allows for multilingual content. [ABSTRACT FROM AUTHOR]

This study investigates nineteenth century natural history practices through the lens of the Actor-Network Theory, which posits that scientific practice is shaped by an intricate network of interactions between human and non-human actors. At the core of this research is the analysis of correspondence between Charles Darwin and his collaborators during the Cirripedia Project, which unveils a complex landscape of negotiations with illustrators, funders, specimen owners, and translators, among other stakeholders and interested parties. The study goes beyond the final outcomes of scientific research, delving into behind-the-scenes interactions, and hidden constructions, shedding light on the complex dynamics and actors that conventional scientific narratives often overlook. In general, this approach provides a detailed and insightful view of the underlying processes of nineteenth-century scientific practice, underscoring the importance of epistolary correspondence as a central element in producing scientific knowledge at the time, and in particular it reveals to us how much Darwin was himself involved in the production of his famous work on barnacles. By emphasizing the intricacies of research, this study enriches our understanding of Darwin's work as well as natural history practices in the 19th century, highlighting the complexity and diversity of actors and agents involved in shaping scientific knowledge. [ABSTRACT FROM AUTHOR]

Background: Hyposmia in Parkinson's disease (PD) had been studied before but had not been detailed by its temporal progression. This study observed how each olfactory subtype evolved in terms of motor symptoms, cardiac sympathetic innervation, and cognition. Methods: Two hundred and three early PD patients were classified as normosmia, hyposmia-converter (hypo-converter), and hyposmia. Their presynaptic monoamine availability at the time of diagnosis was assessed by positron emission tomography imaging using 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane and compared across the subtypes. Motor symptoms were evaluated in all patients, cardiac denervation was examined in 183 patients, and cognition in 195 patients were assessed using a neuropsychological battery. The domains were re-assessed 2–4 times, and the longitudinal data were analyzed to discern the natural course of each subtype. Results: Twenty-nine (14.3%) patients belonged to the normosmia group, 34 (16.7%) to the hypo-converter group, and the rest to the hyposmia (69.0%) group. 85.7% of the total population became hyposmic during an average 3 years of follow-up. The baseline motor symptoms, cardiac denervation, and cognition were comparable across the olfactory subtypes. Across the subtypes, a decline in the presynaptic monoamine densities of the caudate, especially the ventral-anterior subdivisions, correlated inversely with olfaction dysfunction. Over time, motor and cardiac denervation burdens worsened regardless of olfactory subtypes, but hypo-converters experienced faster cognitive deterioration than the other two groups. Conclusions: The results suggest that the olfactory subtypes have differential significance along the disease course, which might reflect the involvement of different neuro-biochemical circuitries. [ABSTRACT FROM AUTHOR]

As much as it is rooted in empirical facts, the concept of truth in natural sciences and technology has core dimensions marked by the sphere of the possible. As can be inferred from Cassirer's symbol theory, this is, in both cultural forms, a structuring mode of their symbolic constitution and differentiation. But when the coupling of the two increases (as currently happens with the new pictorial forms of scientific prediction), it is necessary to know the major repercussions imposed on the way of conceiving phenomena—among these, mainly those that concern the formation of our idea of nature. In addition to this theoretical imperative, it will be the purpose of this paper to show how Cassirer's thought helps us to recognize and reconstruct the relationships between experimental scientific knowledge and technological mediation. Keeping this in mind, a narrow articulation of truth's functional profile with the idea of the future that permeates both science (especially natural sciences) and technology will be conceived to see how the two symbolic forms reveal the prospective complexion of human thought and human action. [ABSTRACT FROM AUTHOR]

We argue that concepts from the social sciences can be as natural as those from physics and chemistry, thereby answering in the positive the question of whether social metaphysics is or can be substantive. The argument takes as a starting point Douven & Gärdenfors' (Mind & Language, 35, 313–334 2020) optimality account of natural concepts, according to which natural concepts are represented by the cells of an optimally partitioned similarity space. While the account applies straightforwardly to perceptual concepts, it does not apply as straightforwardly to more abstract concepts, such as many scientific concepts. We propose an extension of Douven and Gärdenfors' optimality account that pertains to scientific concepts as well. The proposal reuses ideas from Lewis' Best Systems Account of laws of nature, but rather than invoking natural concepts (as Lewis does) defines natural scientific concepts as those that figure in the or a best systematization of the totality of facts. On this proposal, there is nothing especially different between concepts from the natural sciences and those from the social sciences. [ABSTRACT FROM AUTHOR]

The concepts to be considered in this chapter are those that occur in everyday common human thought and language – the "natural history" of concepts in use. While many may appear to be constituted by similarity relations, which make them suitable for modelling in conceptual spaces for example, other concepts in everyday use may be differently constituted. These concepts include abstract concepts, essentialist kinds, natural kinds, and logical or mathematical concepts. I discuss the different sources, uses and epistemological bases of these different forms of concept, and propose a three-level hierarchy of concepts based on their sources of validation. [ABSTRACT FROM AUTHOR]

This article explores the molecular characteristics and growth patterns of meningiomas in patients with NF2-related schwannomatosis (NF2-SWN). The study involved 11 patients with NF2-SWN and a total of 23 resected meningiomas. The researchers used various techniques, including whole-exome sequencing, RNA sequencing, DNA methylation analysis, and immunohistochemistry, to assess the clinical and molecular characteristics of the tumors. The findings suggest that epigenetic mechanisms, particularly methylation clustering and immune activity, may play a role in the growth patterns of meningiomas in NF2-SWN patients. The study also highlights the presence of macrophage infiltration and immune response in these tumors. [Extracted from the article]

There is a significant focus on the role of the host microbiome in different outcomes of human parasitic diseases, including cystic echinococcosis (CE). This study was conducted to identify the intestinal microbiome of patients with CE at different stages of hydatid cyst compared to healthy individuals. Stool samples from CE patients as well as healthy individuals were collected. The samples were divided into three groups representing various stages of hepatic hydatid cyst: active (CE1 and CE2), transitional (CE3), and inactive (CE4 and CE5). One family member from each group was selected to serve as a control. The gut microbiome of patients with different stages of hydatid cysts was investigated using metagenomic next-generation amplicon sequencing of the V3–V4 region of the 16S rRNA gene. In this study, we identified 4862 Operational Taxonomic Units from three stages of hydatid cysts in CE patients and healthy individuals with a combined frequency of 2,955,291. The most abundant genera observed in all the subjects were Blautia, Agathobacter, Faecalibacterium, Bacteroides, Bifidobacterium, and Prevotella. The highest microbial frequency was related to inactive forms of CE, and the lowest frequency was observed in the group with active forms. However, the lowest OTU diversity was found in patients with inactive cysts compared with those with active and transitional cyst stages. The genus Agatobacter had the highest OTU frequency. Pseudomonas, Gemella, and Ligilactobacillus showed significant differences among the patients with different stages of hydatid cysts. Additionally, Anaerostipes and Candidatus showed significantly different reads in CE patients compared to healthy individuals. Our findings indicate that several bacterial genera can play a role in the fate of hydatid cysts in patients at different stages of the disease. [ABSTRACT FROM AUTHOR]

Eyelid dermatitis (ED) affects a cosmetically significant area and leads to patients' distress. Despite ongoing and recent research efforts, ED remains a multidisciplinary problem that needs further characterization. We aimed to evaluate the atopic eyelid dermatitis (AED) frequency in ED patients and to perform their clinical profiling. PubMed databases were searched from 01.01.1980 till 01.02.2024 to PRISMA guidelines using a search strategy: (eyelid OR periorbital OR periocular) AND (dermatitis or eczema). Studies with patch-tested ED patients were included. Proportional meta-analysis was performed using JBI SUMARI software. We included 65 studies across Europe, North America, Asia and Australia, with a total of 21,793 patch-tested ED patients. AED was reported in 27.5% (95% CI 0.177, 0.384) of patch-tested ED patients. Isolated ED was noted in 51.6% (95% CI 0.408, 0.623) of 8453 ED patients with reported lesion distribution, including 430 patients with isolated AED. Our meta-analysis demonstrated that the AED frequency in patch-tested ED patients exceeded the previous estimate of 10%. Isolated AED was noted in adult patients, attending contact allergy clinics. Future studies are needed to elucidate the global prevalence and natural history of isolated AED in adults. [ABSTRACT FROM AUTHOR]

Animal food is one of the most important ecological aspects of one species. Studying this factor is fundamental to understanding their life history, microhabitat use, and interactions with other species. Amphibians are an interesting group to understand the food chains because they interact with aquatic and terrestrial environments. Among them, Trachycephalus typhonius is a widespread treefrog in South America but there is still a lack of knowledge about its natural history. Therefore, we described the feeding habits of T. typhonius from a relictual humid forest mountain in Brazilian semiarid. The present study was conducted in the Maranguape mountain, Ceará state, Brazil during the rainy season from April to May 2019. We collected the individuals using visual and auditory searches. Overall, we found 24 specimens of T. typhonius, in which all of them had stomach contents. We identified 11 prey categories, in which coleopterans and orthopterans were the most important prey item for this species' diet. It is also important to point out that plant pieces were found in the stomach of eight individuals, which might suggest a purposeful consumption. Additionally, we found no significant differences regarding the abundance, richness, and composition of prey items consumed by males and females. In contrast, we observed individuals with largest mouth breadth tend to select prey items more volumetric. Overall, our study is the pioneer to investigate the feeding habits of T. typhonius from a montane ecosystem in Brazilian semiarid region and contributes to increasing the knowledge about its natural history. [ABSTRACT FROM AUTHOR]

The Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) manifests as impaired executive control, linguistic processing, visual spatial function, and affect regulation. The CCAS has been described in the spinocerebellar ataxias (SCAs), but its prevalence is unknown. We analyzed results of the CCAS/Schmahmann Scale (CCAS-S), developed to detect and quantify CCAS, in two natural history studies of 309 individuals Symptomatic for SCA1, SCA2, SCA3, SCA6, SCA7, or SCA8, 26 individuals Pre-symptomatic for SCA1 or SCA3, and 37 Controls. We compared total raw scores, domain scores, and total fail scores between Symptomatic, Pre-symptomatic, and Control cohorts, and between SCA types. We calculated scale sensitivity and selectivity based on CCAS category designation among Symptomatic individuals and Controls, and correlated CCAS-S performance against age and education, and in Symptomatic patients, against genetic repeat length, onset age, disease duration, motor ataxia, depression, and fatigue. Definite CCAS was identified in 46% of the Symptomatic group. False positive rate among Controls was 5.4%. Symptomatic individuals had poorer global CCAS-S performance than Controls, accounting for age and education. The domains of semantic fluency, phonemic fluency, and category switching that tap executive function and linguistic processing consistently separated Symptomatic individuals from Controls. CCAS-S scores correlated most closely with motor ataxia. Controls were similar to Pre-symptomatic individuals whose nearness to symptom onset was unknown. The use of the CCAS-S identifies a high CCAS prevalence in a large cohort of SCA patients, underscoring the utility of the scale and the notion that the CCAS is the third cornerstone of clinical ataxiology. [ABSTRACT FROM AUTHOR]

Background: Intracranial arachnoid cysts are benign collections of cerebrospinal fluid that are often asymptomatic and discovered incidentally. An interhemispheric location of these lesions is rare, with only a few such cases reported in the literature. Though spontaneous regression of arachnoid cysts has been described in other locations, to date this phenomenon has not been reported in interhemispheric fissure cysts. Observations: In this report, we describe a patient with a large, multiloculated interhemispheric arachnoid cyst diagnosed on prenatal ultrasound. She did not exhibit neurologic deficits or signs of increased intracranial pressure and was observed with serial imaging. After several years of observation, imaging revealed spontaneous and progressive decrease in the cyst size. Lessons: We illustrate a case of regression of an interhemispheric arachnoid cyst in a pediatric patient. To our knowledge, this is the first reported case of spontaneous shrinkage of an arachnoid cyst in this location. Although the current presentation is rare, this reporting adds to the current understanding of natural history of arachnoid cysts and provides an example of radiographical improvement without intervention of a cyst located within the interhemispheric fissure. [ABSTRACT FROM AUTHOR]

Background: Chronic respiratory insufficiency from progressive muscle weakness causes morbidity and mortality in late-onset Pompe disease (LOPD). Previous Pompe Registry (NCT00231400) analyses for ≤ 5 years' alglucosidase alfa treatment showed a single linear time trend of stable forced vital capacity (FVC) % predicted. Methods: To assess longer term Pompe Registry data, piecewise linear mixed model regression analyses estimated FVC% predicted trajectories in invasive-ventilator-free patients with LOPD aged ≥ 5 years. We estimated annual FVC change 0–6 months, > 6 months–5 years, and > 5–13 years from treatment initiation, adjusting for baseline age, sex, and non-invasive ventilation. Findings: Among 485 patients (4612 FVC measurements; 8.3 years median follow-up), median ages at symptom onset, diagnosis, and alglucosidase alfa initiation were 34.3, 41.1, and 44.9 years, respectively. FVC% increased during the first 6 months' treatment (slope 1.83%/year; 95% confidence interval: 0.66, 3.01; P = 0.0023), then modestly declined −0.54%/year (−0.79, −0.30; P < 0.0001) during > 6 months–5 years, and −1.00%/year (−1.36, −0.63; P < 0.0001) during > 5–13 years. The latter two periods' slopes were not significantly different from each other (Pdifference = 0.0654) and were less steep than published natural history slopes (−1% to −4.6%/year). Estimated individual slopes were ≥ 0%/year in 96.1%, 30.3%, and 13.2% of patients during the 0–6 month, > 6 month–5 year, and > 5–13 year periods, respectively. Conclusion: These real-world data indicate an alglucosidase alfa benefit on FVC trajectory that persists at least 13 years compared with published natural history data. Nevertheless, unmet need remains since most individuals demonstrate lung function decline 5 years after initiating treatment. Whether altered FVC trajectory impacts respiratory failure incidence remains undetermined. Trial registration: This study was registered (NCT00231400) on ClinicalTrials.gov on September 30, 2005, retrospectively registered. [ABSTRACT FROM AUTHOR]

The Atrial Flow Regulator (AFR) is a self-expandable double-disk device with a central fenestration, intended to maintain a calibrated communication across the interatrial septum. Only case reports and small case series have been published about its use in the pediatric and congenital heart disease (CHD) population. We described AFR implantation in three congenital patients with different anatomies and indications. In the first case, the AFR was deployed to create a stable fenestration in a Fontan conduit, while in the second, it was used to reduce a Fontan fenestration. In the third case, we implanted an AFR to decompress the left atrium of an adolescent with complex CHD in natural history, with complete mixing, ductal-dependent systemic circulation and combined pulmonary hypertension. This case series demonstrates the great potential of the AFR device in the CHD field, showing versatility, efficacy, and safety in establishing a calibrated and stable shunt, with promising hemodynamic and symptomatic benefits. [ABSTRACT FROM AUTHOR]

Objectives: To determine the natural history of hearing loss and tumor volume in patients with untreated neurofibromatosis type 2 (NF2)-related schwannomatosis. Moreover, we statistically examined the factors affecting hearing prognosis. Methods: This retrospective cohort study was conducted on 37 ears of 24 patients with NF2-related vestibular schwannomatosis followed up without treatment for more than 1 year. We obtained detailed chronological changes in the PTA and tumor volume in each case over time, and the rate of change per year was obtained. Multivariate analysis was also conducted to investigate factors associated with changes in hearing. Results: The average follow-up period was approximately 9 years, and hearing deteriorated at an average rate of approximately 4 dB/year. The rate of maintaining effective hearing decreased from 30 ears (81%) at the first visit to 19 ears (51%) at the final follow-up. The average rate of change in tumor growth for volume was approximately 686.0 mm3/year. This study revealed that most patients with NF2 experienced deterioration in hearing acuity and tumor growth during the natural course. A correlation was observed between an increase in tumor volume and hearing loss (r = 0.686; p < 0.001). Conclusions: Although the hearing preservation rate in NF2 cases is poor with the current treatment methods, many cases exist in which hearing acuity deteriorates, even during the natural course. Patients with an increased tumor volume during the follow-up period were more likely to experience hearing deterioration. Trial registration number 20140242 (date of registration: 27 October 2014). [ABSTRACT FROM AUTHOR]

This article discusses the use of on-animal cameras to study primate behavior, specifically focusing on chacma baboons in South Africa. The cameras were able to capture undocumented foraging behaviors, such as the baboons consuming the feces of other species, as well as interspecies interactions. The study highlights the potential benefits of using on-primate cameras for studying primate behavior, including the ability to capture rare and unanticipated behaviors, study predator-prey interactions, and accurately quantify activity budgets. The researchers hope that this work will encourage further use of on-animal cameras in primate research. [Extracted from the article]

Dysregulation of the immune system in individuals with Down syndrome is thought to play a major role in the pathophysiology of many clinical presentations. This natural history of disease study took a comprehensive evaluation of the prevalence of different immune related diagnoses in a cohort of 1299 patients with Down syndrome compared to a 2605 patient control cohort at the Mount Sinai Health System in New York, NY over the past 18 years. We conducted a stepwise analysis of the odds of receiving a diagnosis at the Chapter, Sub-chapter and Diagnosis level of the ICD-CM-10 code system. Individuals in our Down syndrome cohort had higher odds of a diagnosis with inflammatory and autoimmune presentations such as Alopecia areata (OR 6.06, p = 0.01), Other sepsis (OR 4.79, p < 0.001, Purpura and other hemorrhagic conditions (OR 2.31, p < 0.001), and Rosacea (OR 3.11, p < 0.001). They also presented with lower odds of a diagnosis of Herpesviral infection (OR 0.42, p = 0.01), and Viral warts (OR 0.51, p = 0.04). We posit that dysregulation of the immune system in individuals with Down syndrome has impact on infectious diseases, including lowering the incidence of viral disease and increasing its severity. Our data also suggests inflammation and autoimmune mediated diseases, in particular of the skin, are exacerbated in individuals with Down syndrome. Finally, there may be a need for greater clinical attention to non-emergent conditions within the Down syndrome patient population as those can also greatly affect quality of life. [ABSTRACT FROM AUTHOR]

REHem-AR was created in 2013. The progressive implementation of neonatal screening for haemoglobinopathies in Spanish autonomous communities where the registry had not been implemented, as well as the addition of new centres during this period, has considerably increased the sample of patients covered. In this study, we update our previous publication in this area, after a follow-up of more than 5 years. An observational, descriptive, multicentre and ambispective study of adult and paediatric patients with haemoglobinopathies and rare anaemias registered in REHem was performed. The data are from a cross-sectional analysis performed on 1 June, 2023. The study population comprised 1,756 patients, of whom 1,317 had SCD, 214 had thalassaemia and 224 were diagnosed with another condition. Slightly more than one third of SCD patients (37%) were diagnosed based on neonatal bloodspot screening, and the mean age at diagnosis was 2.5 years; 71% of thalassaemia patients were diagnosed based on the presence of anaemia. Vaso-occlusive crisis and acute chest syndrome continue to be the most frequent complications in SCD. HSCT was performed in 83 patients with SCD and in 50 patients with thalassaemia. Since the previous publication, REHem-AR has grown in size by more than 500 cases. SCD and TM are less frequent in Spain than in other European countries, although the data show that rare anaemias are frequent within rare diseases. REHem-AR constitutes an important structure for following the natural history of rare anaemias and enables us to calculate investment needs for current and future treatments. [ABSTRACT FROM AUTHOR]

Some parasitic fungi can increase fitness by modifying the behavior of their hosts. These behaviors are known as extended phenotypes because they favor parasitic gene propagation. Here, we studied three lineages of Ophiocordyceps, a fungus that infects ants, altering their conduct before death. According to fungal strategy, ants may die in leaf litter, with entwined legs in branches, under the moss mat, or biting plant tissue. It is critical for parasites that the corpses stay at these places because Ophiocordyceps exhibit iteroparity, possibly releasing spores in multiple life cycles. Thus, we assumed substrate cadaver permanence as a fungi reproductive proxy and corpse height as a proxy of cadaver removal. We hypothesize that biting vegetation and dying in higher places may increase the permanence of ant corpses while avoiding possible corpse predation on the forest floor. We monitored over a year more than 4000 zombie ants in approximately 15 km2 of undisturbed tropical forest in central Amazonia. Our results show a longer permanence of corpses with increasing ground height, suggesting that the parasites may have better chances of releasing spores and infecting new hosts at these places. We found that the zombie ants that last longer on the substrate die under the moss mat in tree trunks, not necessarily biting vegetation. The biting behavior appears to be the most derived and complex mechanism among Ophiocordyceps syndromes. Our results put these findings under a new perspective, proposing that seemingly less complex behavioral changes are ecologically equivalent and adaptative for other parasite lineages. [ABSTRACT FROM AUTHOR]

Background: With the advent of the first targeted therapy for Rett Syndrome (RTT), a comprehensive assessment of the journey of RTT is needed to elucidate on present unmet needs in this population. This study characterized females with RTT in the United States and their disease journey with respect to longitudinal treatment patterns, RTT-related outcomes, and changes in disease severity. Methods: This retrospective cohort study used registry data of females with RTT from the 5211 RTT Natural History Study (RNHS) (November 2015–July 2021). Pharmacological and supportive therapy use, RTT-related outcomes, and RTT severity, as measured by the Clinical Severity Scale and Motor Behavioral Assessment scale, were evaluated following the first RNHS visit. Analyses were conducted overall and in subgroups by RTT type (classic and atypical RTT) and age at first visit (pediatric and adult). Results: A total of 455 females with RTT were included in the study, of whom 90.5% had classic RTT and 79.8% were pediatric individuals. Over a median follow-up of 4 years, use of pharmacological therapies, including prokinetic agents (42.7% vs. 28.3%), and supportive therapies, including physical therapy (87.3% vs. 40.2%) and speech-language therapy (86.8% vs. 23.9%), were more common in pediatric than adult individuals (all p < 0.05). Nearly half (44.6%) of all individuals had a hospital or emergency room visit, with a higher proportion of visits in individuals with classic RTT than atypical RTT and pediatric than adult individuals (both p = 0.001). An increasing trend in clinical severity was observed in pediatric individuals (mean change per year: 0.24; 95% confidence interval [CI]: 0.03, 0.44), while an increasing trend in motor-behavioral dysfunction was observed in pediatric individuals (mean change per year: 1.12; 95% CI: 0.63, 1.60) and those with classic RTT (mean change per year: 0.97; 95% CI: 0.53, 1.41). Conclusions: Findings from this study highlight the considerable burden of RTT across disease subtype and age. Despite reliance on supportive therapies and healthcare encounters, individuals with RTT experience increasing disease severity and motor-behavioral dysfunction in childhood and adolescence, underscoring the unmet needs of this population and the value of early intervention to manage RTT in the long-term. [ABSTRACT FROM AUTHOR]

Background: The Scale for Assessment and Rating of Ataxia (SARA) is a widely used clinical scale to assess cerebellar ataxia but faces some criticisms about the relevancy of all its items. Objectives: To prepare for future clinical trials, we analyzed the progression of SARA and its items in several polyQ spinocerebellar ataxias (SCA) from various cohorts. Methods: We included data from patients with SCA1, SCA2, SCA3, and SCA6 from four cohorts (EUROSCA, RISCA, CRC-SCA, and SPATAX) for a total of 850 carriers and 3431 observations. Longitudinal progression of the SARA and its items was measured. Cohort, stage and genetic effects were tested. We looked at the respective contribution of each item to the total scale. Sensitivity to change of the scale and the impact of item removal was evaluated by calculating sample sizes needed in various scenarios. Results: Longitudinal progression was significantly different between cohorts in SCA1, SCA2 and SCA3, the EUROSCA cohort having the fastest progression. Advanced-stage patients were progressing slower in SCA2 and SCA6. Items were not contributing equally to the full scale through ataxia severity: gait, stance, hand movement, and heel-shin contributed the most in the early stage, and finger-chase, nose-finger, and sitting in later stages. Few items drove the sensitivity to the change of SARA, but changes in the scale structure could not improve its sensitivity in all populations. Conclusion: SARA and its item's progression pace showed high heterogeneity across cohorts and SCAs. However, no combinations of items improved the responsiveness in all SCAs or populations taken separately. [ABSTRACT FROM AUTHOR]

Objective: X-linked myopathy with excessive autophagy (XMEA) linked to the VMA21 gene leads to autophagy failure with progressive vacuolation and atrophy of skeletal muscles. Current knowledge of this rare disease is limited. Our objective was to define the clinical, radiological, and natural history of XMEA. Methods: We conducted a retrospective study collecting clinical, genetic, muscle imaging, and biopsy data of XMEA patients followed in France and reviewed the literature for additional cases. Results: Eighteen males had genetically confirmed XMEA in France, carrying four different VMA21 variants. Mean age at disease onset was 9.4 ± 9.9 (range 1–40) years. In 14/18 patients (77.8%), onset occurred during childhood (< 15 years); however in four patients, the disease started in adulthood. Patients had anterior and medial compartment thigh muscle weakness, distal contractures (56.3%), elevated CK levels (1287.9 ± 757.8 U/l) and autophagic vacuoles with sarcolemmal features on muscle histopathology. Muscle MRI (n = 10) showed a characteristic pattern of lower limb muscle involvement. In 11 patients, outcome measures were available for an average follow-up period of 10.6 ± 9.8 years and six of them show disease progression. Mean change of functional outcomes was 0.5 ± 1.2 points for Brooke and 2.2 ± 2.5 points for Vignos score, 7/16 patients (43.8%) needed a walking aid and 3/16 (18.8%) were wheelchair-bound (median age of 40 years old, range 39–48). The variant c.164-7 T > G was associated with a later onset of symptoms. Respiratory insufficiency was common (57.1%) but cardiac involvement rare (12.5%). Interpretation: XMEA has variable age of onset, but a characteristic clinical, histopathological, and muscle imaging presentation, guiding the diagnosis. Although slowly, motor disability progresses with time, and relevant genotype–phenotype correlations will help design future clinical trials. [ABSTRACT FROM AUTHOR]

Due to their natural history and ecological attributes, turtles are excellent organisms for studies of heavy metal contamination. Turtles have a large geographical distribution, occupy different aquatic habitats, and occupy various trophic levels. The present study investigated mercury bioaccumulation in the carnivorous chelonian Chelus fimbriata (Matamata turtle) and Hg biomagnification in relation to its aquatic food chain in the middle Rio Negro, AM-Brazil. Tissue samples of muscle, carapace and claws were collected from 26 C. fimbriata individuals, as well as collections of autotrophic energy sources found in the turtle's aquatic habitat area. The samples were collected in February-March/2014 and analyzed for THg concentrations and carbon (δ13C) and nitrogen (δ15N) stable isotopes. The highest THg levels were found in claws (3780 ng.g−1), carapace (3622 ng.g−1) and muscle (403 ng.g−1), which were found to be significantly different [F(2.73) = 49.02 p < 0.01]. However, THg concentrations in muscle tissue were below the consumption threshold indicated by the WHO and Brazilian Health Ministry. The average δ13C and δ15N values in Matamata samples were −31.7‰ and 11.9‰, respectively. The principal energy source sustaining the food chain of C. fimbriata was found to be terrestrial shrubs, with smaller contributions from emergent aquatic herbaceous plants and algae, while δ15N values showed its trophic position to be two levels above the autotrophic energy sources. There was a positive correlation between THg and turtle size, while a significant relationship was found between THg and δ15N, showing strong biomagnification in the food chain of C. fimbriata: y = 0.21x + 0.46; r2 = 0.45; p < 0.001, for which the slope presented a value of 0.21. [ABSTRACT FROM AUTHOR]

This article discusses a case of a 36-year-old male who presented with abdominal pain and diarrhea. After various tests and imaging, the patient was diagnosed with type 2 autoimmune pancreatitis (AIP) and ulcerative colitis (UC). The article explores the link between AIP and IBD, as well as the diagnostic criteria and treatment options for type 2 AIP. It also mentions that studies on the natural history of type 2 AIP in the setting of IBD are limited and mixed. The authors suggest considering the possibility of type 2 AIP in IBD patients with acute pancreatitis and using established criteria for determining IBD therapy. [Extracted from the article]

Phytophthora infestans (Peronosporaceae, Oomycota) is the causal agent of late blight of potato (Solanum tuberosum) and a native to Central America. When introduced to Europe, it rapidly spread in 1845, triggering the Irish Potato Famine, which claimed millions of lives and led to an exodus of Europeans to North America. The spread of the species was recently traced using historical specimens from various herbaria. However, there are critical spatial and temporal gaps in the documentation of the early spread of the species. Within the framework of a digitalization and restoration project of the mid-nineteenth century fungus collections of the herbarium of the State Museum of Natural History Karlsruhe, several specimens of Phytophthora infestans from North-East Germany collected in 1853, 1855 and 1856 were discovered. In addition, we revised already deposited material and identified a specimen of Ph. infestans that was collected no later than 1852. These specimens are among the oldest from Central Europe and are now available to the scientific public. Further, we searched for thus far overlooked specimens, using online catalogues. We found specimens from 23 European countries, with the oldest material from western Europe and almost no data from eastern Europe, south-eastern Europe and southern Europe. Our results emphasize the need for archiving and digitizing natural history collections in order to document the historical spread of agricultural and forest pathogens and to better understand current-day epidemic spreads. [ABSTRACT FROM AUTHOR]

The bark beetle Ips acuminatus is an important pest in pine-dominated forests of Eurasia. Recently, the frequency of I. acuminatus outbreaks and mortality of host trees have increased, most likely as a result of climate change-related alterations in environmental conditions. Therefore, detailed information on the species' natural history is essential to understand its potential to damage forests and to apply sustainable management measures. We provide a comprehensive overview on the life history of I. acuminatus, focusing on traits that might explain outbreaks and the ability to cause tree mortality. We review its importance for European forestry, outbreak behavior, host plant usage, reproductive biology, temperature-dependent development, diapause and overwintering behavior, and interactions with fungi, bacteria, nematodes and other arthropods. Interestingly, I. acuminatus has a strong nutritional dependency on the fungus Ophiostoma macrosporum, underlined by the presence of a prominent oral mycetangium, a spore-carrying organ, in females, which is not known for other Ips species. Moreover, I. acuminatus can reproduce sexually and asexually (pseudogamy). Additionally, information on the species' evolutionary past provides valuable insights into the origin of certain traits. We present a phylogeny of the genus Ips and examine selected life-history traits in an evolutionary context. Together with its sister species Ips chinensis, I. acuminatus forms a separate clade within Ips. The ancestor of Ips bark beetles originated about 20 million years ago and was a pine-colonizing species inhabiting the Holarctic. Finally, open fields of research are identified to guide future work on this ecologically and economically important pine bark beetle. [ABSTRACT FROM AUTHOR]

Background: A splenic artery pseudoaneurysm is a rare pathology that occurs mainly secondary to pancreatitis, abdominal trauma, peptic ulcers, pancreatic and gastric cancers, and infections. It is best diagnosed using computed tomography angiography and typically treated using endovascular embolization and, in some cases, open or laparoscopic surgery. In this report, we present a case of a ruptured mycotic splenic artery pseudoaneurysm containing Histoplasma capsulatum, which to our knowledge is the first case to report a mycotic splenic artery pseudoaneurysm of this nature. Case presentation: We report a case of a 42-year-old white male with past medical history of Hepatitis C and IV drug abuse who presented to the Emergency Department with a 24-h history of severe diffuse abdominal pain. He was tachycardic and peritonitic on exam. Work-up demonstrated leukocytosis and lactic acidosis. Computed tomography of the abdomen and pelvis with intravenous contrast showed hemoperitoneum and active extravasation of contrast from the splenic artery into the splenic hilum, associated with a surrounding hematoma measuring 5.3 × 5.0 cm, concerning for ruptured splenic artery pseudoaneurysm. The patient was taken emergently for exploratory laparotomy, where a large intraperitoneal hematoma was evacuated. A ruptured splenic artery pseudoaneurysm was identified, isolated, and controlled, followed by completion splenectomy. Final pathology demonstrated a 3.0 × 1.3 × 0.3 cm pseudoaneurysm wall and a 14 × 9.5 × 5.5 cm spleen containing multiple necrotizing granulomata positive for the presence of Histoplasmosis species. The patient recovered appropriately and was discharged on post-operative day five. Conclusions: This case demonstrates a successful approach to a ruptured mycotic splenic artery pseudoaneurysm resulting in a positive outcome. It is a unique case as it highlights, to our knowledge, the first report of splenic artery aneurysm secondary to Histoplasma capsulatum infection. This report helps further the understanding of the pathophysiology as well as the natural history of mycotic splenic pseudoaneurysms. [ABSTRACT FROM AUTHOR]

Developing students' scientific literacy is the most important educational goal and challenge of the 21st century. Many studies have confirmed that flipped learning has significantly impacted learning science. Researchers indicate that the lack of an appropriate learning guidance strategy in the pre-class stage for flipped learning will influence students' understanding of learning content and affect in-class learning activities. In order to tackle this problem, the present study proposed a flipped learning approach based on identification, summarization, self-reflective questioning, and application (ISSA), further exploring the influences on students' scientific literacy, communication tendency, problem-solving tendency, learning motivation, and cognitive load. In addition, the study used a true experimental design to assess the effectiveness of the proposed learning method, and 58 university students were recruited to participate in a natural science course. The experimental group (N = 29) adopted the proposed learning approach, while the control group adopted the conventional flipped learning approach. The results showed that the experimental group had higher scientific literacy, communication tendency, problem-solving tendency, and extrinsic motivation than the control group. The interviews showed that the ISSA flipped learning method could improve students' understanding of the learning content. In particular, the process of peer interaction promoted their self-reflection and scientific literacy skills. [ABSTRACT FROM AUTHOR]