Seasonality of reproduction in an ever-wet lowland tropical forest in Amazonian Ecuador

We thank Pablo Alvia, Alvaro Pérez, Zornitza Aguilar, Paola Barriga, Matt Priest, Caroline Whitefoord, and Gorky Villa for assistance in collecting data or identifying species; Elina Gomez for entry of trap data; Hugo Navarrete, Katya Romoleroux and the QCA herbarium staff, and David Lasso and the ECY staff for help with logistics and needed permitting; Rick Condit, Elizabeth Losos, Robin Foster, and Henrik Balslev for initial encouragement to work within the Yasuní Forest Dynamics Plot; Hugo Romero for initially summarizing the YFDP and SSP weather data sets; Pablo Jarrin for setting up the TEAM weather station, and David Lasso and Carlos Padilla for maintaining that equipment and making the data available; and the Ecuadorian Ministerio del Ambiente for permission to work in Yasuní National Park [No 014-2019-IC-PNY-DPAO/AVS, No 012-2018-IC-PNY593-DPAO/AVS, No 008-2017-IC-PNY-DPAO/AVS, No 012-2016-IC-FAU-FLO-DPAO-PNY, No 594-014-2015-FLO-MAE-DPAO-PNY, and earlier permits]. The Forest Dynamics Plot of Yasuní National Park has been made possible through the generous support of the Pontifical Catholic University of Ecuador (PUCE) funds of donaciones del impuesto a la renta, the Government of Ecuador, the US National Science Foundation, the Andrew W. Mellon Foundation, the Smithsonian Tropical Research Institute, and the University of Aarhus of Denmark. The phenology project began while NCG was at the Natural History Museum, London, with funding (2000–2004) from the Department of Botany (NHM), the Andrew W. Mellon Foundation, British Airways, and the Natural Environment Research Council (GR9/04037). It continued with NCG at Southern Illinois University Carbondale (2005–2023). We thank the Center for Tropical Forest Science for transitional funding (2006–2008, 2017–2018) and the National Science Foundation LTREB program for long-term funding (2006–2020; DEB-0614525, DEB-1122634, DEB-1754632, DEB-1754668).Peer reviewedPublisher PD

Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG): a collaborative report from the International and European Society for Pediatric Oncology DIPG registries

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials

Real-world clinical experience with Idebenone in the treatment of Leber hereditary optic neuropathy

Background: Leber hereditary optic neuropathy (LHON) leads to bilateral central vision loss. In a clinical trial setting, idebenone has been shown to be safe and to provide a trend toward improved visual acuity, but long-term evidence of effectiveness in real-world clinical practice is sparse. Methods: Open-label, multicenter, retrospective, noncontrolled analysis of long-term visual acuity and safety in 111 LHON patients treated with idebenone (900 mg/day) in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrollment. Data on visual acuity and adverse events were collected as per normal clinical practice. Efficacy was assessed as the proportion of patients with either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS) of visual acuity. In the case of CRR, time to and magnitude of recovery over the course of time were also assessed. Results: At time of analysis, 87 patients had provided longitudinal efficacy data. Average treatment duration was 25.6 months. CRR was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. Average gain in best-corrected visual acuity for responders was 0.72 logarithm of the minimal angle of resolution (logMAR), equivalent to more than 7 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Furthermore, 50% of patients who had a visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. Idebenone was well tolerated, with most adverse events classified as minor. Conclusions: These data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy. Safety results were consistent with the known safety profile of idebenone

Long-term functional recovery and compensation after cerebral ischemia in rats

Cerebral ischemia is one of the most common causes of disabilities in adults and leads to long-term motor and cognitive impairments with limited therapeutic possibilities. Treatment options have proven efficient in preclinical models of cerebral ischemia but have failed in the clinical setting. This limited translation may be due to the suitability of models used and outcomes measured as most studies have focused on the early period after injury with gross motor scales, which have limited correlation to the clinical situation. The aim of this study was to determine long-term functional outcomes after cerebral ischemia in rats, focusing on fine motor function, social and depressive behavior as clinically relevant measures. A secondary objective was to evaluate the effects of an anti-inflammatory treatment (interleukin-1 receptor antagonist (IL-1Ra)) on functional recovery and compensation. Infarct volume was correlated with long-term (25 days) impairments in fine motor skills, but not with emotional components of behavior. Motor impairments could not be detected using conventional neurological tests and only detailed analysis allowed differentiation between recovery and compensation. Acute systemic administration of IL-1Ra (at reperfusion) led to a faster and more complete recovery, but delayed (24 h) IL-1Ra treatment had no effect. In summary functional assessment after brain injury requires detailed motor tests in order to address long-term impairments and compensation processes that are mediated by intact tissues. Functional deficits in skilled movement after brain injury represent ideal predictors of long-term outcomes and should become standard measures in the assessment of preclinical animal models

Predictors of chronic cerebrospinal venous insufficiency procedure use among older people with multiple sclerosis: a national case–control study

Background Following the initial reports of Chronic Cerebrospinal Venous Insufficiency (CCSVI) and the purported curative potential of venoplasty, (coined the ‘liberation’ procedure) Canadians living with multiple sclerosis (MS) began to travel abroad to receive the unregulated procedure, often placing them at odds with their health providers. The purpose of this study was to determine the factors influencing older MS patients’ decision to undergo the procedure in order to develop more specific and targeted health information. Methods We performed secondary analysis of data collected as part of the ‘Canadian Survey of Health Lifestyle and Aging with MS’ from people over the age of 55 years with MS symptoms for 20 or more years. The survey consisted of self-reported information on impairments, disability, participation, demographics, personal and environmental factors. In order to compare respondents who underwent the procedure to those who did not and to develop a predictive model, we created a comparison group using a case–control algorithm, controlling for age, gender and education, and matching procedure cases to controls 1:3. We used multivariate stepwise least likelihood regression of ‘a priori’ variables to determine predictive factors. Results The prevalence of the ‘liberation’ procedure in our sample was 12.8% (95/743), substantially lower than reported in previous studies of complementary/alternative treatments in MS. The predictive model contained five factors; living alone (Odds ratio 0.24, 95%CI 0.09-0.63), diagnosis of anxiety (Odds ratio 0.29, 95%CI 0.10 - 0.84), rating of neurologist’s helpfulness (Odds ratio 0.56, 95%CI 0.44 -0 .71), Body Mass Index (Odds ratio 0.93, 95%CI, 0.89 - 0.98) and perceived physical impact of MS (Odds ratio 1.02, 95%CI 1.01 - 1.04). Conclusions Predictive factors differed from previous studies of complementary/alternative treatment use likely due to both the invasiveness of the procedure and the advanced age of our study cohort. Our findings suggest that health professionals should target information on the risks and benefits of unregulated procedures to those patients who feel dissatisfied with their neurologist and they should include family members in discussions since they may be providing the logistical support to travel abroad and undergo the ‘liberation’ procedure. Our findings may be applicable to others with chronic disabling conditions who contemplate the user-pay unregulated invasive procedures available to them

Effects of maternal social isolation on adult rodent offspring cognition

Abstract Prenatal experiences can influence offspring physiology and behaviour through the lifespan. Various forms of prenatal stress impair adult learning and memory function and can lead to increased occurrence of anxiety and depression. Clinical work suggests that prenatal stress and maternal depression lead to similar outcomes in children and adolescents, however the long-term effects of maternal depression are less established, particularly in well controlled animal models. Social isolation is common in depressed individuals and during the recent COVID-19 pandemic. Accordingly, for this study we were interested in the effects of maternal stress induced via social isolation on adult offspring cognitive functions including spatial, stimulus–response, and emotional learning and memory that are mediated by different networks centered on the hippocampus, dorsal striatum, and amygdala, respectively. Tasks included a discriminative contextual fear conditioning task and cue-place water task. Pregnant dams in the social isolation group were single housed prior to and throughout gestation. Once offspring reached adulthood the male offspring were trained on a contextual fear conditioning task in which rats were trained to associate one of two contexts with an aversive stimulus and the opposing context remained neutral. Afterwards a cue-place water task was performed during which they were required to navigate to both a visible and invisible platform. Fear conditioning results revealed that the adult offspring of socially isolated mothers, but not controls, were impaired in associating a specific context with a fear-inducing stimulus as assessed by conditioned freezing and avoidance. Results from the water task indicate that adult offspring of mothers that were socially isolated showed place learning deficits but not stimulus-response habit learning on the same task. These cognitive impairments, in the offspring of socially isolated dams, occurred in the absence of maternal elevated stress hormone levels, anxiety, or altered mothering. Some evidence suggested that maternal blood-glucose levels were altered particularly during gestation. Our results provide further support for the idea that learning and memory networks, centered on the amygdala and hippocampus are particularly susceptible to the negative impacts of maternal social isolation and these effects can occur without elevated glucocorticoid levels associated with other forms of prenatal stress