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The ruins of Persepolis, the ceremonial capital of the Achaemenid Empire (559–330 BCE), are celebrated as a cultural heritage site and national monument in Iran. In 1971, these ruins became the setting for the Celebration of the 2,500th Anniversary of the Founding of the Persian Empire, orchestrated by Mohammad Reza Pahlavi. The Pahlavi regime aimed to fabricate a monarchical lineage that positioned the Pahlavi dynasty as the pinnacle of an uninterrupted historical continuum beginning with the Achaemenids and Cyrus the Great. The ceremonies featured a grandiose military parade with soldiers in historical costumes symbolically reenacting theprocessions of foreign emissaries depicted on Persepolis' walls, emphasizing the glory and grandeur of Iran's imperial past and its uninterrupted history. Conversely, a decade earlier, Iranian filmmaker and poet Fereydoun Rahnema's short documentary captured Persepolis in a starkly different light, presenting it as enigmatic ruins devoid of grandeur, prompting reflections on their lost original meaning. Utilizing Walter Benjamin's concepts of natural history, melancholia, and allegory, this article explores the allegorical implications of Rahnema's film. It argues that the documentary signifies the disintegration of the sublime image of Iran’s imperial origin, marking a shift where the imperial past becomes too eclipsed a signifier to serve as a cornerstone of national identity.

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 items progression pace showed high heterogeneity across cohorts and SCAs. However, no combinations of items improved the responsiveness in all SCAs or populations taken separately.

BACKGROUND: Becker muscular dystrophy is an X-linked, genetic disorder causing progressive degeneration of skeletal and cardiac muscle, with a widely variable phenotype. OBJECTIVE: A 3-year, longitudinal, prospective dataset contributed by patients with confirmed Becker muscular dystrophy was analyzed to characterize the natural history of this disorder. A better understanding of the natural history is crucial to rigorous therapeutic trials. METHODS: A cohort of 83 patients with Becker muscular dystrophy (5-75 years at baseline) were followed for up to 3 years with annual assessments. Muscle and pulmonary function outcomes were analyzed herein. Age-stratified statistical analysis and modeling were conducted to analyze cross-sectional data, time-to-event data, and longitudinal data to characterize these clinical outcomes. RESULTS: Deletion mutations of dystrophin exons 45-47 or 45-48 were most common. Subgroup analysis showed greater pairwise association between motor outcomes at baseline than association between these outcomes and age. Stronger correlations between outcomes for adults than for those under 18 years were also observed. Using cross-sectional binning analysis, a ceiling effect was seen for North Star Ambulatory Assessment but not for other functional outcomes. Longitudinal analysis showed a decline in percentage predicted forced vital capacity over the life span. There was relative stability or improved median function for motor functional outcomes through childhood and adolescence and decreasing function with age thereafter. CONCLUSIONS: There is variable progression of outcomes resulting in significant heterogeneity of the clinical phenotype of Becker muscular dystrophy. Disease progression is largely manifest in adulthood. There are implications for clinical trial design revealed by this longitudinal analysis of a Becker natural history dataset.

Background: The GM1 and GM2 gangliosidoses and type 2 Gaucher disease (GD2) are inherited lysosomal storage disorders with most cases having symptom onset in infancy and reduced life expectancy. The conditions are rare, and there is therefore a need for accurate and up to date information concerning the disease course and survival to assist in the design of clinical trials. RETRIEVE is a natural history study aiming to: (1) collect data on the survival of patients with early-onset (onset of first neurological manifestation before 24 months of age) GM1, GM2, or GD2; (2) collect data that could constitute a historical control group for future clinical trials; and (3) evaluate whether the conditions can be assessed together in a single interventional clinical trial. Group A included patients who were deceased or with unknown survival status at enrollment and was thus limited to retrospective data. Group B included patients who were alive at enrollment, who were followed prospectively with additional retrospective data collection. Results: Group A included 185 patients (60 with GM1, 78 with GM2, and 47 with GD2), and Group B included 40 patients (18 with GM1, 16 with GM2, and 6 with GD2). Mean and median age at diagnosis and age at onset of first neurological manifestation were youngest in patients with GD2 and oldest in patients with GM2 in both groups. In Group A, median (95% CI) survival was 19.0 (18.0, 22.0), 44.0 (37.0, 51.9) and 14.0 (10.0, 16.0) months in patients with GM1, GM2 and GD2, respectively. In Group B, hypotonia was experienced by most patients with GM1 (17/18, 94.4%), and was less common in patients with GM2 (12/16, 75.0%) and GD2 (4/6, 66.7%). Strabismus and splenomegaly were reported in all six patients with GD2. Conclusions: RETRIEVE is one of the largest natural history studies of GM1, GM2, and GD2. Results were generally consistent with the published literature, with differences potentially due to variation in inclusion criteria. The difference in median survival between patients with early-onset GM1, GM2, and GD2 reported in this study suggests that the three diseases should not be pooled for study in clinical trials. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the natural history of elective autologous sperm cryostorage prior to gonadotoxic treatment? SUMMARY ANSWER We estimate large sample median times to transfer for use, to the man's death or to discard of sperm, and their determinants, as the key operational outcomes of sperm cryostorage. WHAT IS KNOWN ALREADY No large sample studies of the natural history of sperm cryostorage prior to gonadotoxic treatment are reported. STUDY DESIGN, SIZE, DURATION This observational single-centre study covered 45 years of outcomes with a survival analysis for sperm cryostorage prior to scheduled gonadotoxic treatment, and its determinants. PARTICIPANTS/MATERIALS, SETTING, METHODS This study included 3923 men (mean age 30 years) who sought sperm cryostorage for a wide range of cancers and other diseases requiring gonadotoxic treatments. MAIN RESULTS AND THE ROLE OF CHANCE The median time to transfer for use (n = 371 men 9%) was 2.4 years (quartiles 1.0, 6.0), the median time to death (n = 553 men, 14%) was 1.7 (0.9, 3.3) years, and the median time to discard (n = 1807 men, 46%) was 7.7 (1.7, 11.1) years. In multivariate Cox model regression, the underlying disease, number of storage visits and follow-up visits, and whether sperm were seen at follow-up visits were consistent predictors of times to outcomes. LIMITATIONS, REASONS FOR CAUTION This study did not investigate sperm cryostorage for reasons other than gonadotoxic treatment, nor the fertilization outcomes of the cryostored sperm. WIDER IMPLICATIONS OF THE FINDINGS These data provide estimates of the key operational factors for sperm cryostorage programs, prior to potentially sterilizing gonadotoxic treatments, and free from financial or insurance restrictions. STUDY FUNDING/COMPETING INTEREST(S) There was no specific funding for this study. D.J.H. has provided expert witness testimony to antidoping and professional standards tribunals and is supported by an NHMRC Investigator Grant. The other authors have no disclosures. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Les divers développements du programme de réintroduction du Gypaète dans les Alpes ont donné lieu à de nombreuses contributions dans les revues ornithologiques, y compris quant aux processus ayant mené à la disparition de cette espèce emblématique. Cependant, aucune mise au point historique intégrant l'ensemble des collections muséales de notre pays n'avait encore été entreprise. Cet article vise à combler cette lacune. [ABSTRACT FROM AUTHOR]

Widespread species often possess rapid population expansion capabilities, posing potential threats to global marine biodiversity. One key aspect is asexual reproduction involving anterior body regeneration. This process, while uncommon among Nemertea, has apparently evolved several times within the phylum. Evelineus mcintoshii (Langerhans, 1880), originally described from Madeira, has been reported from warm waters around the world under various names. This study reports the first observations of anterior regeneration in E. mcintoshii under captive conditions. Observations under a stereomicroscope revealed full wound recovery within one night, with complete anterior regeneration, including cephalic slits and orange bands, by 15 days postamputation. The rapid head regeneration in E. mcintoshii suggests potential for asexual reproduction, potentially resulting in its wide distribution. This regenerative ability may also indicate survival potential after fragmentation during transport, facilitating population expansion. [ABSTRACT FROM AUTHOR]

Objectives: This study describes aortic growth, survival and events in patients with aortic arch pathology. Methods: Patients with an index diameter ≥4.5 cm or other pathology of the native aortic arch, were followed with longitudinal computed tomography and clinical data collected retrospectively. Aortic growth was estimated using a linear mixed model. Survival and event rates were estimated using Kaplan-Meier methods. Cox analysis assessed clinical and radiological predictors with outcomes (death, local or remote aortic events (acute aortic syndromes or intervention)). Results. 186 patients underwent 683 CT scans during 638 of patient years. The estimated annual growth was 0.28 (mm/year). 47 (25%) patients had an event and a 66% five-year event-free survival. 29 patients died, of whom 11 suffered an aortic death. 19 events were local and 25 events were remote, mostly primary events were interventions. In Cox analysis, increasing descending aortic diameter was an independent predictor of all cause of death (hazard ratio [HR], 2.16), aortic death (HR 4.81), and local event (HR 1.71). Conclusions. In patients with aortic arch pathology, growth, and aortic events should be expected. Increasing descending aortic diameter could presage an added risk, but other variables appear needed to identify patients at risk, select them for intervention or surveillance. [ABSTRACT FROM AUTHOR]

Objectives. This study describes growth, local and remote aortic events, and survival in patients with proximal (root, ascending) aortic diameters just below threshold for operation. Methods. Patients with proximal aortic diameter of 4.5 to 5.4 cm at baseline, were followed with serial computed tomography studies and data collected retrospectively. Aortic growth rate was estimated using mixed effects modelling. Clinical and radiological features associated with outcomes (all-cause death, aortic death, local or remote aortic events (dissection, rupture, intramural hematoma, or intervention)) were assessed with Cox analysis. Survival and freedom from events were estimated using Kaplan-Meier methods. Results. 80 patients underwent 274 CT scans during 265 patient-years. Median proximal aortic growth was 0.2 cm in 3 years. 32 events occurred in 28 patients (35%). Eleven events were local, all elective proximal aortic surgery. Nine events were remote: 5 type B aortic dissections, 3 descending aneurysms undergoing elective repair, and one infrarenal aortic rupture. Twelve patients died, half of type B aortic dissection. Relative survival compared to a matched normal population was 82% (95% confidence limits 55–98%) at 10 years. In Cox analysis, increased descending aortic diameter was an independent predictor of all-cause death (hazard ratio [HR], 1.39) and aortic death (HR 1.96). Conclusions. Descending, but not proximal, aortic growth was predictive of lethal events. The decreased relative survival, the substantial number of remote aortic events and aortic deaths strongly suggest continuous serial CT surveillance of the entire aorta. Other indicators than proximal aortic diameter appear needed to improve management of this patient group. [ABSTRACT FROM AUTHOR]

The life cycles of bats are constrained by availability of resources such as food and shelter. Disruptions limiting otherwise naturally regulated access to these resources ultimately affect the fitness of bat populations and may eventually lead to local extinctions. We sampled bats before and after an Amazonian mega-dam water filling and retrieved data on their reproductive phenology, testing if and how sex ratio, seasonal abundance, and reproductive patterns respond to impacts of the newly operating hydroelectric dam. We analyzed data from 3,298 bat captures of 49 species. Females outnumbered males, previously and after the dam implementation, and we observed seasonal variations in the abundance of bats, which was lower after the implementation of the dam for most species. All species had at least 1 reproductive peak of pregnancy and/or lactation beginning at a variable time across seasons. Most species and functional ensembles were reproductively bimodal, with exceptions being the polymodal Artibeus obscurus and unimodal Phylostomus elongatus. Operations of the hydroelectric dam affected the abundance of both sexes equally, and effects were stronger in the rainy season, altering the timing of reproduction for females, delaying and shortening pregnancy and lactation. These changes expressed in female reproductive activity may be related to the shortfall of resources because of loss of irreplaceable vegetation caused by the dam filling. As we cannot predict the roles of variation of reproductive patterns observed after the filling in the long run we reinforce the importance of long-term, continuous monitoring and management to safeguard the reestablishment of reproductive patterns of females in order to repopulate and keep bat populations healthy in remaining areas along following dam construction. [ABSTRACT FROM AUTHOR]

During the mid-nineteenth century, the shifting boundaries of natural history and hunting practices were at the core of debates about general and practical knowledge, science and leisure, hunters and poachers. Focusing on the Swiss naturalist Johann Jakob von Tschudi and his travels to South America, this article reexamines the relationships of natural history and hunting skills in forging a kind of scientific "hegemonic" masculinity. For this purpose, it reconstructs Tschudi's social formation in bourgeois circles during the institutionalization of natural history in Switzerland. More than his natural history knowledge, Tschudi's hunting skills were crucial for the success of his Peruvian expedition (1838–1842), and thus his zoological treatise Fauna peruana could be considered a manual for hunting in the Amazonian rainforest and the Andes. Finally, this article analyzes the class and race intersections of Tschudi's scientific discourse about poachers in the German states and in the Brazilian empire. The study of Tschudi's biography, especially his roles as a global naturalist and a "true hunter," sheds light on natural history as a space for constructing class, gender, and race hierarchies during the mid-nineteenth century, in both South American and German-speaking contexts. [ABSTRACT FROM AUTHOR]

To assess the age and MECP2 variants of recently identified males and set the stage for further study of clinical features in males. Genetic information on the specific MECP2 variant was acquired from the coordinator (K.F.) of the Parent Group for Males. Data were collected indicating whether these variants were de novo or transmitted from the mother and whether males who appeared to meet the diagnostic criteria for Rett syndrome had mosaicism for the MECP2 variant. Fifty-nine males were identified through the parent group. Their ages ranged from 2 to 28 years, with the median age being 7.0 years and the mean age being 10.8 years. Of these variants, 46 (78.0%) were de novo , nine (15.3%) were maternally inherited, and for four (6.8%) inheritance was not known. Eleven (18.6%) were mosaic, 10 with somatic mosaicism and one with Klinefelter syndrome (47XXY). Together with males reported previously from the US Natural History Study, the total group represents 85 males, of whom 27 are deceased. These data on males with MECP2 variants are important to caregivers, physicians, and researchers to begin to characterize their historical and clinical features, improve diagnostic recognition and overall care, and accelerate access to therapeutic studies including gene replacement strategies. Equal access to such therapies for males is critical. [ABSTRACT FROM AUTHOR]

Developmental and epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS) is a rare neurodevelopmental spectrum of disorders marked by regression associated with spike-and-wave activation in sleep. As roughly 10% have a related genetic underpinning, we sought to describe narrative clinical histories of four patients at a single academic medical center with monogenic variants associated with DEE-SWAS. In sharing this case series, we aim to build on recent work investigating genetic DEE-SWAS. Findings from this case series not only aid in accurate diagnosis and prognosis for our patients but also may provide potential targets for future therapeutic interventions. This natural history case series also highlights the difficulty in differentiating genetic phenotype from the effects of DEE-SWAS. [ABSTRACT FROM AUTHOR]

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]

Background: Brain arteriovenous malformations (bAVMs) are vascular lesions that commonly present with intracranial haemorrhage. Pregnancy has been associated with an increased risk of bAVM rupture. However, their natural history in pregnant women is uncertain. Case description: A 27-year-old female at 28 weeks of gestation presented with a compromised neurological status secondary to a ruptured left frontal Spetzler-Martin scale (SM) III + bAVM. An emergent caesarean section was performed due to the high risk of foetal distress. Endovascular treatment successfully controlled the bleeding site, and stereotactic radiosurgery was offered as a subsequent treatment option. Conclusion: bAVMs should be considered in pregnant women with intracranial haemorrhage. The management of these lesions during pregnancy is controversial. Surgical risk and foetal development should be considered when selecting a management strategy. [ABSTRACT FROM AUTHOR]

Background: Cerebral arteriovenous malformations (AVMs) have historically been considered congenital lesions with treatment options including surgery, radiation therapy, and observation. Spontaneous resolution of cerebral AVMs remains an exceedingly rare event with poorly understood pathophysiology. Materials and methods: Herein we report a retrospective case review of a 28-year-old man with alcoholic cirrhosis who presented with a seizure 3 weeks after liver transplantation. Neuroimaging confirmed the presence of a Spetzler–Martin grade 2 AVM in the right frontal lobe. Due to the recent liver transplantation, treatment was deferred at the time of initial diagnosis and the patient was observed for a course of 1 year. Follow-up imaging 1 year later showed resolution of the AVM, confirmed by a catheter angiogram. Conclusion: Spontaneous resolution of cerebral AVMs is a rare event. Treatment of chronic liver disease resulted in the normalization of angiogenic factors that likely led to AVM resolution. This case provides valuable insight into the vital role of angiogenesis in the natural history of AVMs. [ABSTRACT FROM AUTHOR]

This essay discusses the use of description in early American natural history and in travel writing by Washington Irving and John Kirk Townsend. In Irving's A Tour on the Prairies (1835) and Townsend's Narrative of a Journey Across the Rocky Mountains, to the Columbia River (1839), both writers use description to stall narrative progress so as to avoid narrating the deaths of bison and other animals they hunt on journeys into the western United States. In so doing, they stave off the ethical and emotional consequences of killing nonhuman animals. Unlike the many scholarly accounts that emphasize description's diminishment or decentering of the human, here description amplifies human agency by masking actions about which these writers feel ambivalent. [ABSTRACT FROM AUTHOR]

Recent progress in therapeutics for amyotrophic lateral sclerosis (ALS) has spurred development and imbued the field of ALS with hope for more breakthroughs, yet substantial scientific gaps persist. This unmet need remains a stark reminder that innovative paradigms are needed to invigorate ALS research. To move toward more informative, targeted, and personalized drug development, the National Institutes of Health (NIH) established a national ALS clinical research consortium called Access for ALL in ALS (ALL ALS). This new consortium is a multi‐institutional effort that aims to organize the ALS clinical research landscape in the United States. ALL ALS is operating in partnership with several stakeholders to operationalize the recommendations of the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) Public Private Partnership. ALL ALS will provide a large‐scale, centralized, and readily accessible infrastructure for the collection and storage of a wide range of data from people living with ALS (symptomatic cohort) or who may be at risk of developing ALS (asymptomatic ALS gene carriers). Importantly, ALL ALS is designed to encourage community engagement, equity, and inclusion. The consortium is prioritizing the enrollment of geographically, ethnoculturally, and socioeconomically diverse participants. Collected data include longitudinal clinical data and biofluids, genomic, and digital biomarkers that will be harmonized and linked to the central Accelerating Medicines Partnership for ALS (AMP ALS) portal for sharing with the research community. The aim of ALL ALS is to deliver a comprehensive, inclusive, open‐science dataset to help researchers answer important scientific questions of clinical relevance in ALS. [ABSTRACT FROM AUTHOR]

The article discusses keratin-positive giant cell tumors of bone and soft tissue in children under 10 with HMGA2::NCOR2 fusion, focusing on three cases. The tumors are classified based on molecular alterations, with HMGA2::NCOR2 fusions distinguishing them from other giant cell-rich tumors. The youngest patient, a neonate with metastatic disease, showed a remarkable response to imatinib therapy. The study expands the understanding of these tumors and their response to targeted therapy, highlighting the importance of molecular characterization in diagnosis and treatment. [Extracted from the article]

Background and purpose: Spinal muscular atrophy (SMA) is a genetic disorder caused by SMN1 gene mutations. Although studies on available disease‐modifying treatments have reported their efficacy and safety, long‐term natural history data are lacking for comparison. The aim of this prospective study was to report 4‐year changes on the Hammersmith Functional Motor Scale Expanded (HFMSE) in type II and III SMA in relation to several variables such as age, functional status and SMN2 copy number. Methods: The study involves retrospective analysis of prospectively collected data from international datasets (Belgium, Italy, Spain, USA, UK). HFMSE longitudinal changes were analyzed using linear mixed effect models, examining annualized HFMSE change and its association with variables such as age at baseline, sex, motor function, SMN2 copy number. Results: In SMA type II (n = 226), the 4‐year mean change was −2.20 points. The largest mean changes were observed in sitters aged 5–14 years and the lowest in those who lost the ability to sit unsupported. In SMA type III (n = 162), the 4‐year mean change was −2.75 points. The largest mean changes were in those aged 7–15 years, whilst the lowest were in those below 7 and in the SMA type IIIa subgroup over 15. Age and score at baseline were predictive of 4‐year changes. Conclusions: Our findings provide natural history reference data for comparison with long‐term follow‐up of clinical trials or real‐world data, highlighting the need to define patterns of changes in smaller SMA subgroups instead of reporting mean changes across an entire SMA cohort. [ABSTRACT FROM AUTHOR]

The incidence of prosthetic joint infection (PJI) following elective primary total knee arthroplasty (TKA) is very low but serious risk remains. To identify unknown risk factors, we completed a natural history study of IgG specific for Staphylococcus aureus antigens previously phenotyped as protective (anti‐Atl) and pathogenic (anti‐Isd). Twenty‐five male and 25 female optimized patients 50–85 years of age and BMI 24–39 undergoing primary TKA were prospectively enrolled. Blood sampling was performed preoperatively, postoperative Day 1, and at 2, 6, and 12 weeks, to assess serum cytokine, anti‐staphylococcal IgG levels and anti‐tetanus toxoid IgG measured via custom Luminex assay. Clinical, demographic, and PROMIS‐10 data were collected with outcomes to 2 years postop. All participants completed the study and 2‐year follow‐up. No patients were readmitted or noted to develop a surgical site infection or serious adverse event, and patient‐reported outcomes were improved. Serology revealed a highly significant decrease in six out of eight antibody titers against specific S. aureus antigens on Day 1 (p < 0.0001), five of which normalized to preoperative levels within 2 weeks. These changes were commensurate with a decrease and recovery of anti‐tetanus toxoid titers, and a 20% drop in hemoglobin 13.8 ± 1.7 at preop to 11.1 ± 1.8 mg/dL on Day 1 (p < 0.0001). After TKA, a significant decrease in humoral immunity commensurate with blood loss and hemodilution was recorded. This decrease in circulating anti‐staphylococcal antibodies in the early postop period may represent a periprosthetic joint infection risk factor for patients. [ABSTRACT FROM AUTHOR]

Degenerative cerebellar ataxias comprise a heterogeneous group of rare and ultra‐rare genetic diseases. While disease‐modifying treatments are now on the horizon for many ataxias, robust trial designs and analysis methods are lacking. To better inform trial designs, we applied item response theory (IRT) modeling to evaluate the natural history progression of several ataxias, assessed with the widely used scale for assessment and rating of ataxia (SARA). A longitudinal IRT model was built utilizing real‐world data from the large autosomal recessive cerebellar ataxia (ARCA) registry. Disease progression was evaluated for the overall cohort as well as for the 10 most common ARCA genotypes. Sample sizes were calculated for simulated trials with autosomal recessive spastic ataxia Charlevoix–Saguenay (ARSACS) and polymerase gamma (POLG) ataxia, as showcased, across multiple design and analysis scenarios. Longitudinal IRT models were able to describe the changes in the latent variable underlying SARA as a function of time since ataxia onset for both the overall ARCA cohort and the common genotypes. The typical progression rates varied across genotypes between relatively high in POLG (~ 0.98 SARA points/year at SARA = 20) and very low in COQ8A ataxia (~ 0.003 SARA points/year at SARA = 20). Smaller trial sizes were required in case of faster progression, longer trials (~ 75–90% less with 5 years vs. 2 years), and larger drug effects (~ 70–80% less with 100% vs. 50% inhibition). Simulating under the developed IRT model, the longitudinal IRT model had the highest power, with a well‐controlled type I error, compared to total score models or end‐of‐treatment analyses. The established longitudinal IRT framework allows efficient utilization of natural history data and ultimately facilitates the design and analysis of treatment trials in rare and ultra‐rare genetic ataxias. [ABSTRACT FROM AUTHOR]

In the relentless pursuit of optimizing drug development, the intricate process of determining the ideal dosage unfolds. This involves "dose‐finding" studies, crucial for providing insights into subsequent registration trials. However, the challenges intensify when tackling rare diseases. The complexity arises from poorly understood pathophysiologies, scarcity of appropriate animal models, and limited natural history understanding. The inherent heterogeneity, coupled with challenges in defining clinical end points, poses substantial challenges, hindering the utility of available data. The small affected population, low disease awareness, and restricted healthcare access compound the difficulty in conducting dose‐finding studies. This white paper delves into critical dose selection aspects, focusing on key therapeutic areas, such as oncology, neurology, hepatology, metabolic rare diseases. It also explores dose selection challenges posed by pediatric rare diseases as well as novel modalities, including enzyme replacement therapies, cell and gene therapies, and oligonucleotides. Several examples emphasize the pivotal role of clinical pharmacology in navigating the complexities associated with these diseases and emerging treatment modalities. [ABSTRACT FROM AUTHOR]

The study explores the preservation policy and techniques employed in preserving library materials in three libraries in South Asia: Central University of Kashmir; Islamic University of Science and Technology; and University of Kashmir. The study aims to: investigate preservation policy/plan/division of selected libraries; investigate the current preservation technique used in the libraries; explore the category of staff responsible for preservation of library materials; and identify capacity building programs attended by staff at local, national/international level on preservation. Data collection was employed: results were tabulated, interpreted, and correlated with the published literature to ferret out meaningful findings and draw logical conclusions. The study reveals that: binding (sewing) and fumigation (solid fumigation) are widely employed techniques in preservation; manuscripts are mostly prioritized for preservation; and usually professionals are involved in dealing with preservation. However, none of the libraries possess preservation policies, which are crucial for the preservation of the library collection on a systematic and scientific basis. In order to cope with the changing environment of information preservation and management, libraries regularly organize seminars and conferences on preservation, and it is hoped that stakeholders continue to identify loopholes and to build capacity for preservation. [ABSTRACT FROM AUTHOR]

ABSTRACT Shprintzen‐Goldberg‐syndrome (SGS) is caused by pathogenic exon 1 variants of SKI. Symptoms include dysmorphic features, skeletal and cardiovascular comorbidities, and cognitive and developmental impairments. We delineated the neurodevelopmental and behavioral features of SGS, as they are not well‐documented. We collected physician‐reported data of people with molecularly confirmed SGS through an international collaboration. We identified and deep‐phenotyped the neurodevelopmental and behavioral features in four patients. Within our cohort, all exhibited developmental delays in motor skills and/or speech, with the average age of first words at 2 years and 6 months and independent walking at 3 years and 5 months. All four had learning disabilities and difficulties regulating emotions and behavior. Intellectual disability, ranging from borderline to moderate, was present in all four participants. Moreover, we reviewed the literature and identified 52 additional people with SGS, and summarized the features across both datasets. Mean age was 23 years (9–48 years). When combining our cohort and reported cases, we found that 80% (45/56) had developmental and/or cognitive impairment, with the remainder having normal intelligence. Our study elucidates the developmental, cognitive, and behavioral features in participants with SGS and contributes to a better understanding of this rare condition. [ABSTRACT FROM AUTHOR]

Taking the Flemish-born artist Roelant Savery’s Das Paradies (1626) as a starting point, this essay explores the role of European artistic cultures and collecting practices in inciting the ecocide of the post-1492 Anthropocene Extinction. In particular, I explore how Savery’s celebrated painting of Adam and Eve consuming the forbidden fruit amidst a verdant landscape inhabited by animals such as the now-extinct dodo, endemic to the Indian Ocean island of Mauritius, became the pivotal foundation for scientific and cultural perceptions of the extinction of nonhuman life in colonial worlds as the natural outcome of European modernity’s global flows. [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]

Aim Method Results Interpretation To identify, describe, and synthesize available evidence on the longitudinal relationship between hip displacement and hip function, using the International Classification of Functioning, Disability and Health (ICF) framework, in children and adolescents with cerebral palsy (CP) aged up to 18 years.Five databases were searched systematically from inception to May 2022. Study and sample characteristics, and hip displacement and hip function measures, mapped to the ICF domains, were extracted for narrative synthesis.Twenty‐nine studies were included: four longitudinal registry‐based studies; 12 prospective studies; 12 retrospective studies; and one randomized controlled trial. Sample size ranged from 11 to 267. Twenty‐seven (93%) studies entailed an intervention: surgery (n = 16); rehabilitation (n = 2); nerve block or botulinum neurotoxin A injection (n = 4); and combined surgery and injection (n = 2). Twenty‐six studies (90%) reported outcomes at the body structure and function and impairment domain of the ICF; 17 (59%) reported outcomes in the activity domain; and three (10%) included participation measures. The most common hip displacement measure was Reimers' migration percentage (79%).Because of the inclusion of interventions in most studies, and the preponderance of retrospective studies, the relationship between hip displacement and hip function in CP is unclear. More high‐quality prospective evidence on the natural history of hip displacement, and its effect on function, is needed to improve population‐wide screening of children with CP. [ABSTRACT FROM AUTHOR]

This article addresses the narrative desert that exists around the role of emeritus academics by considering how such colleagues fit within the narrative ecology of the university. By drawing on my personal experience of becoming emeritus, I illustrate how the dynamic tension of composing and de-composing processes of identity construction can be traced within an adaptive cycle of development. In this case, the anomic deconstruction of the academic is balanced by the salutogenic reconstruction of the post-academic professional identity. This offers a methodological exemplar that could be used to generate a patchwork of professional autoethnographies to inform the description of a neglected element of institutional natural history. The approach sees emeritus status as an active part of the process of professional identity development rather than as a passive endpoint and presents a departure from the perception of the frail elderly academic who lurks in the shadows of the zombie university. [ABSTRACT FROM AUTHOR]

The role of mesocarnivores in wildlife communities tends to be overlooked, which has led to a large gap in natural history knowledge. In northeastern Argentina, two mesocarnivore foxes, Cerdocyon thous and Lycalopex gymnocercus, live in sympatry in noncompetitive coexistence. Their feeding habits have been studied in many occasions; however, the studies related to trophic variability in a wider spatial scale remain scarce. In this study, we aimed to analyze how the diet of these foxes varies in three protected areas in Argentina: the Mburucuyá National Park (MNP), the “San Nicolás Portal” (SN), and the Natural Reserve Rincón de Santa María (RSM). We collected fecal samples in each area, identified them using thin layer chromatography at species level, and classified the found feeding items to obtained two parameters: occurrence and relative frequency. Furthermore, we compared the diet of the two species in each site and between sites using chi‐square and estimated trophic niche breadth and overlap between the species. We found that both species consumed different food categories, with variable frequencies across study sites. We observed that in each area, the foxes differed in diet composition. However, we found no differences between the diet compositions of C. thous and L. gymnocercus, showing high niche overlap in each site. Here, we show the plasticity of both fox species in changing their diets even with small geographical variation. Both species can coexist even with a high diet overlap, possibly explained by their noncompetitive coexistence which may occur due to the current changes in the ecosystem interactions, or partitioning may exist but on a smaller niche level. [ABSTRACT FROM AUTHOR]

The document "PM 3/98 (1) Inspection of growing media associated with consignments of plants for planting" details the standards and procedures for inspecting growing media, such as soil, to ensure it is free from pests when linked to plants for planting. It highlights the risks of soil and growing media in introducing quarantine pests and offers guidance on inspection methods, sampling, and laboratory testing. The document also identifies common types of growing media and their respective pest risks, stressing the importance of thorough inspections to prevent the introduction of regulated pests. Additionally, it provides comprehensive information on various insect pests related to soil, including their life stages, sampling, and identification methods, and underscores the significance of proper hygiene measures during inspection and sampling to prevent infestation spread. Specific instructions are included for sampling both visible pests and non-visible pests, like parasitic nematodes, in growing media, along with a brief procedure for inspectors outlining the steps to follow during inspection and sampling. [Extracted from the article]

Simple Summary: Captive breeding and headstarting programs are useful conservation tools to assist imperiled species in recovery. The eastern indigo snake (EIS) benefits from managed breeding colonies, but there are concerns regarding their reproductive fitness given the incidence of complications during egg-laying in first-time mothers. Potential causes include body overconditioning or nutrient imbalances, yet little information is available regarding snake nutrition, as domestic rodents are regarded as a nutritionally complete diet irrespective of the snake's natural history. In this study, we examined the health and nutritional status of adult EIS maintained on standard mixed-whole-prey diets or a "faux-snake" sausage diet aligned with the nutritional profile of the EIS's preferred prey. While domestic rodents are significantly higher in fat and lower in vitamin E compared to snakes predated by free-ranging EIS, our study demonstrated that current mixed-prey diets appear sufficient to meet the vitamin E and selenium needs of EIS, although further investigation into the vitamin D3 status of captive snakes is warranted. There were no ill effects associated with the consumption of an atypical diet in an atypical format, and longitudinal studies with juvenile snakes are suggested to examine the influence of nutrient composition on reproductive health in this species. The federally threatened eastern indigo snake (EIS; Drymarchon couperi) is an active ophiophagous snake once found throughout the southeastern US that is now restricted to southeastern Georgia and peninsular Florida. There are concerns regarding the potential impact of overconditioning or nutrient imbalances on the reproductive fitness of breeding programs due to the occurrence of dystocia in nulliparous dams and the differing nutritional profiles of domestic and free-range prey species. We examined the blood cell counts, plasma biochemistry, and circulating plasma levels of nutrients in snakes consuming standard or experimental diets over a one-year period. Treatments included mixed whole laboratory animal prey (rodents, birds), whole prey ground into sausage, or a sausage with similar nutrient profiles measured in prey found in free-ranging EIS stomach contents. Plasma concentrations of vitamin E (maximum = 0.80 mg/mL) and selenium (maximum = 371 ng/mL) were within range of and exceeded values reported in free-ranging EIS (0.0365 mg/mL and 107.45 ng/mL), while plasma vitamin D3 concentrations (maximum = 64.1 ng/mL) were typically below minimum values observed in free-ranging EIS (46 ng/mL). Additional dietary studies initiated on juvenile subjects throughout reproductive maturity would provide an ideal experimental design for studying the linkage between reproductive health and nutrition. [ABSTRACT FROM AUTHOR]

Simple Summary: Hymenoptera venom allergy (HVA) is a potentially life-threatening systemic hypersensitivity reaction. In this study, data from 178 dogs with insect sting allergic reactions were analyzed and several risk factors for severe systemic reactions to Hymenoptera stings were identified. Furthermore, a significant number of dogs suffered subsequent systemic reactions to Hymenoptera stings, indicating that venom immunotherapy may be a valuable intervention to prevent future reactions. This study should raise the awareness of dog owners that Hymenoptera stings are associated with HVA and its possible consequences. Hymenoptera, which includes honeybees, wasps, bumblebees, and hornets, is an order of the class Insecta, whose venom can induce anaphylactic reactions in dogs. While several studies have investigated the natural histories and risk factors of Hymenoptera venom allergy (HVA) in humans, only limited information is available on canine patients. Therefore, the aim of this study was to identify risk factors leading to severe systemic reactions (SSRs) and to explore the natural history of these patients. This was achieved with an inquiry into the case histories of 178 dogs that were stung by Hymenoptera and presented to the Vetsuisse Faculty Animal Hospital of the University of Zurich between 2018 and 2022. Dogs under two years old, dogs that weighed under 10 kg, purebred dogs, and dogs that were stung in the oral cavity were at a greater risk of developing SSRs. Almost two thirds of patients with SSRs experienced the same or worse symptoms after subsequent stings and >40% of patients with local reactions developed SSRs when stung again. Next to providing valuable clinical information about HVA in dogs, these findings strongly support the recommendation of venom immunotherapy (VIT) for patients with HVA. [ABSTRACT FROM AUTHOR]

Myeloproliferative neoplasms, polycythemia vera, essential thrombocytosis, and primary myelofibrosis are a unique group of clonal hematopoietic stem cell neoplasms that share somatic, gain-in-function driver mutations in JAK2, CALR, and MPL. As a consequence, these disorders exhibit similar phenotypic features, the most common of which are the ceaseless production of normal erythrocytes, myeloid cells, platelets alone or in combination, extramedullary hematopoiesis, myelofibrosis, and a potential for leukemic transformation. In the case of polycythemia vera and essential thrombocytosis, however, prolonged survival is possible. With an incidence value in the range of 0.5–2.0/100,000, myeloproliferative neoplasms are rare disorders, but they are not new disorders, and after a century of scrutiny, their clinical features and natural histories are well-defined, though their individual management continues to be controversial. With respect to polycythemia vera, there has been a long-standing dispute between those who believe that the suppression of red blood cell production by chemotherapy is superior to phlebotomy to prevent thrombosis, and those who do not. With respect to essential thrombocytosis, there is a similar dispute about the role of platelets in veinous thrombosis, and the role of chemotherapy in preventing thrombosis by suppressing platelet production. Linked to these disputes is another: whether therapy with hydroxyurea promotes acute leukemia in disorders with a substantial possibility of longevity. The 21st century revealed new insights into myeloproliferative neoplasms with the discovery of their three somatic, gain-of-function driver mutations. Almost immediately, this triggered changes in the diagnostic criteria for myeloproliferative neoplasms and their therapy. Most of these changes, however, conflicted with prior well-validated, phenotypically driven diagnostic criteria and the management of these disorders. The aim of this review is to examine these conflicts and demonstrate how genomic discoveries in myeloproliferative neoplasms can be used to effectively complement the known phenotypic features of these disorders for their diagnosis and management. [ABSTRACT FROM AUTHOR]

The article discusses Davian behavior and functional egg fertilization in the Italian Stream Frog Rana italica, focusing on a case of thanatophilia observed in Central Italy. The study highlights the reproductive ecology of the Italian Stream Frog, emphasizing the unique mating habitats and reproductive outcomes of the species. The observation of Davian behavior in R. italica sheds light on the rare occurrence of such behavior in anurans and calls for further research to understand the contextual factors influencing this behavior. [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]

In Lusaka, Zambia, we introduced liver fine-needle aspiration biopsy (FNAB) into a research cohort of adults with treatment-naive chronic hepatitis B virus (HBV) infection, with and without human immunodeficiency virus (HIV) coinfection, as well as with acute HBV infection. From 117 enrollment and 47 longitudinal FNABs (at 1-year follow-up), we established participant acceptability and safety. We also demonstrated the quality of the material through single-cell RNA sequencing of selected enrollment FNAs, which revealed a range of immune cells. This approach can drive new insights into HBV immunology, informing cure strategies, and can improve our understanding of HBV natural history in Africa. [ABSTRACT FROM AUTHOR]

Background: Giardia lamblia is an intestinal protozoan estimated to cause ~200 million symptomatic infections annually, mainly in children in low- and middle-income countries associated with intestinal damage, increased permeability, and malabsorption. Methods and results: We describe here the epidemiology, incidence, clinical characteristics, and risk factors of acute gastroenteritis episodes (AGE) with G. lamblia detection (GAGE) using a birth cohort of 443 Nicaraguan children followed weekly until 36 months of life. From June 2017 to July 2021, 1385 AGE samples were tested by qPCR. G. lamblia was detected in 104 (7.5%) of AGE episodes. In all, 69 (15.6%) children experienced at least one GAGE episode, and 25 of them (36.2%) experienced more than one episode. The incidence rate of the first episode of GAGE was 6.8/100 child-years (95% CI, 4.5–9.1). During GAGE, bloody stools, vomiting, and fever were uncommon, and children were less likely to be treated at a primary care clinic, suggesting that GAGE is typically mild and most cases did not receive medical attention, which could facilitate higher parasite loads with increased possibilities of establishing chronic carriage. GAGE was more common in children 12–24 months of age (13.9/100 child-years [95% CI, 10.7–17.1]) as compared to other age groups. In our birth-cohort, children living in a home with an indoor toilet (aHR, 0.52 [95%CI, 0.29–0.92]), and being breastfed in the first year of life (aHR: 0.10 [95%IC, 0.02, 0.57]) had a lower incidence of GAGE. In contrast, being breastfed for ≤ 6 months was associated with a higher incidence if the children were living in houses without indoor toilets and earthen floors (HR, 7.79 [95% CI, 2.07, 29.3]). Conclusion: Taken together, GAGE is more frequent under poor household conditions. However, breastfeeding significantly reduces the incidence of GAGE in those children. Author summary: G. lamblia is an intestinal protozoan having mixed associations with acute gastroenteritis, yet positive associations with impaired child growth. G. lamblia infects millions of people worldwide annually and is more prevalent in children residing in low- and middle-income countries, making it an important target for prevention and control efforts. Although G. lamblia carriage is widespread, its epidemiology, natural history, genetic diversity, host genetic susceptibility factors, and post-infectious sequelae in children are still under investigation. As no human vaccine is available, understanding its risk factors in an endemic country is the first step for reducing the burden and mitigating its sequelae. In a birth cohort in León, Nicaragua, we found that children living in households with poor sanitation conditions are at higher risk of AGE with G. lamblia detection (GAGE), but prolonged duration of breastfeeding despite these conditions may reduce the risk in these children. The study highlights the importance of breastfeeding and the need to better understand how G. lamblia contributes to the global burden of disease in children, and the mechanisms of host protection to guide future interventions. [ABSTRACT FROM AUTHOR]

The article traces and examines the history of some of the specimens used in teaching in Swedish secondary grammar schools from the mid-nineteenth century up until today. Previous research has focused on empirical analyses of teaching materials and school collections, while this paper adds new knowledge to the history of education using an object-biographic approach. Whilst focusing on the history of two distinct specimens, a bird and a small collection of butterflies, and how these were circulated and recontextualised, the paper raises wider questions about how different actors are involved as meanings and knowledge content change. Through the object-biographic approach, we show that the use of natural history objects was multifaceted and had several purposes at the same time, ranging from research to education to providing status or being a hobby. The use of natural history specimens changed with reforms of the Swedish educational system. New teaching materials and new educational ideals were developed, and from 1960 onwards the importance of these objects decreased. We show how the specimens have taken on new meanings today as selected and displayed museum objects. [ABSTRACT FROM AUTHOR]

The article discusses the discovery of an unidentified species of Hammerschmidtiella nematode isolated from the hindgut of Anthracophora rusticola beetles in Japan. Molecular profiling was conducted to determine its phylogenetic relationship, revealing its close relation to H. keeneyi found in the USA. The study suggests the existence of additional native Hammerschmidtiella species in Japan and explores the potential host switch or erratic parasitism of the nematode. Further research is recommended to deepen understanding of the nematode's host range and speciation. [Extracted from the article]

Background: The search for neuroprotective treatments for Parkinson's disease (PD) still relies largely on motor disability scales. A limitation of these tools is the strong influence of symptomatic dopaminergic treatment effects. Drawing on a wealth of published information, we conducted a systematic review and meta-analysis of motor progression in PD and its relationships with dopaminergic therapy. Methods: We searched Medline, Embase, and Central to identify 84 publications with adequate serial motor scores to calculate progression, expressed as an increase in the percentage of maximum disability. Results: A random-effects model showed motor progression at 2.0% p.a. (95% CI 1.7–2.4%). There were no significant differences by baseline age, sample size, or observation period. However, untreated patients, in 8 publications, progressed at 4.5% p.a. compared to 1.6% p.a. in 76 studies containing individuals on dopaminergic drugs (p = 0.0004, q = 0.003). This was supported by research on phenoconversion in prodromal PD, where motor progression exceeded 5% p.a. in the 2 years before diagnosis. Starting levodopa improved pre-treatment disability by 40.3 ± 15.2%. Practically defined off state measurements increase faster than on scores by a modest degree (p = 0.05). Conclusion: This survey suggests that accurate long-term measurements of motor progression to assess disease-modifying therapies can be conducted despite the sequential commencement of dopaminergic drugs and sample attrition over time. While study designs involving prodromal or untreated PD avoid confounding effects of symptomatic treatment, different assumptions about motor progression may be needed. A defined off state with the levodopa test dose method maximizes information about the medication cycle once dopaminergic therapy has begun. [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]

Acute intoxication with cholinesterase inhibiting organophosphates (OP) can produce life-threatening cholinergic crisis and status epilepticus (SE). Survivors often develop long-term neurological consequences, including spontaneous recurrent seizures (SRS) and impaired cognition. Numerous studies implicate OP-induced neuroinflammation as a pathogenic mechanism contributing to these chronic sequelae; however, little is known about the inflammatory phenotype of innate immune cells in the brain following acute OP intoxication. Thus, the aim of this study was to characterize the natural history of microglial and astrocytic inflammatory phenotypes following acute intoxication with the OP, diisopropylfluorophosphate (DFP). Adult male and female Sprague–Dawley rats were administered a single dose of DFP (4 mg/kg, sc) followed by standard medical countermeasures. Within minutes, animals developed benzodiazepine-resistant SE as determined by monitoring seizures using a modified Racine scale. At 1, 3, 7, 14, and 28 d post-exposure (DPE), neuroinflammation was assessed using translocator protein (TSPO) positron emission tomography (PET) and magnetic resonance imaging (MRI). In both sexes, we observed consistently elevated radiotracer uptake across all examined brain regions and time points. A separate group of animals was euthanized at these same time points to collect tissues for immunohistochemical analyses. Colocalization of IBA-1, a marker for microglia, with iNOS or Arg1 was used to identify pro- and anti-inflammatory microglia, respectively; colocalization of GFAP, a marker for astrocytes, with C3 or S100A10, pro- and anti-inflammatory astrocytes, respectively. We observed shifts in the inflammatory profiles of microglia and astrocyte populations during the first month post-intoxication, largely in hyperintense inflammatory lesions in the piriform cortex and amygdala regions. In these areas, iNOS+ proinflammatory microglial cell density peaked at 3 and 7 DPE, while anti-inflammatory Arg1+ microglia cell density peaked at 14 DPE. Pro- and anti-inflammatory astrocytes emerged within 7 DPE, and roughly equal ratios of C3+ pro-inflammatory and S100A10+ anti-inflammatory astrocytes persisted at 28 DPE. In summary, microglia and astrocytes adopted mixed inflammatory phenotypes post-OP intoxication, which evolved over one month post exposure. These activated cell populations were most prominent in the piriform and amygdala areas and were more abundant in males compared to females. The temporal relationship between microglial and astrocytic responses suggests that initial microglial activity may influence delayed, persistent astrocytic responses. Further, our findings identify putative windows for inhibition of OP-induced neuroinflammatory responses in both sexes to evaluate the therapeutic benefit of anti-inflammation in this context. [ABSTRACT FROM AUTHOR]