Whale Baleen To Monitor Per- and Polyfluoroalkyl Substances (PFAS) in Marine Environments

Per- and polyfluoroalkyl substances (PFAS) comprise \u3e10 000 synthetic compounds that are globally distributed and highly persistent but remain challenging to monitor. Here we assess the utility of baleen─an accreting, keratinaceous tissue that baleen whales use for filter-feeding─to track PFAS dynamics in marine food webs. In six species investigated, PFAS were detected in all baleen tested (n = 18 plates, 220 samples, ∑10PFAS range of 0.02–60.5 ng/g of dry weight), at levels higher than those of other tissue types besides liver. Three of the species in our data set had not been tested for PFAS contamination previously, and two of those species (blue whale and North Atlantic right whale) are internationally endangered species. Apparent links were observed between PFAS and life-history events by testing successive subsamples along the growth axis of the baleen plates. These results establish baleen as a viable sample matrix for assessing PFAS contamination in marine ecosystems by enabling multiyear time-series analyses through single-tissue sampling with seasonal resolution

Placebo‐controlled crossover assessment of mecasermin for the treatment of Rett syndrome

Abstract Objective: To measure the efficacy of mecasermin (recombinant human insulin‐like growth factor 1, rhIGF‐1), for treating symptoms of Rett syndrome (RTT) in a pediatric population using a double‐blind crossover study design. Methods: Thirty girls with classic RTT in postregression stage were randomly assigned to placebo or rhIGF‐1 in treatment period 1 and crossed over to the opposite assignment for period 2 (both 20 weeks), separated by a 28‐week washout period. The primary endpoints were as follows: Anxiety Depression and Mood Scale (ADAMS) Social Avoidance subscale, Rett Syndrome Behaviour Questionnaire (RSBQ) Fear/Anxiety subscale, Parent Target Symptom Visual Analog Scale (PTSVAS) top three concerns, Clinical Global Impression (CGI), Parent Global Impression (PGI), and the Kerr severity scale. Cardiorespiratory‐ and electroencephalography (EEG)‐based biomarkers were also analyzed. Results: There were no significant differences between randomization groups. The majority of AEs were mild to moderate, although 12 episodes of serious AEs occurred. The Kerr severity scale, ADAMS Depressed Mood subscale, Visual Analog Scale Hyperventilation, and delta average power change scores significantly increased, implying worsening of symptoms. Electroencephalography (EEG) parameters also deteriorated. A secondary analysis of subjects who were not involved in a placebo recall confirmed most of these findings. However, it also revealed improvements on a measure of stereotypic behavior and another of social communication. Interpretation As in the phase 1 trial, rhIGF‐1 was safe; however, the drug did not reveal significant improvement, and some parameters worsened

Medical student education program in Alzheimer’s disease: <it>The PAIRS Program</it>

<p>Abstract</p> <p>Background</p> <p>As life expectancy increases, dementia incidence will also increase, creating a greater need for physicians well-trained to provide integrated geriatric care. However, research suggests medical students have limited knowledge or interest in pursuing geriatric or dementia care. The purpose of this study is to evaluate the <it>PAIRS Program</it> and its effectiveness in enhancing medical education as a service-learning activity and replication model for the Buddy Program^TM.</p> <p>Methods</p> <p>Between 2007 and 2011, four consecutive classes of first year Boston University School of Medicine students (n = 45; 24 ± 3 years, 58% female, 53% White) participated in a year-long program in which they were paired with a patient with early-stage Alzheimer’s disease (AD). Assessments included pre- and post-program dementia knowledge tests and a post-program reflective essay.</p> <p>Results</p> <p>Program completion was 100% (n = 45). A paired-sample <it>t</it>-test revealed a modest improvement in dementia knowledge post-program (p < 0.001). Using qualitative coding methods, 12 overarching themes emerged from the students’ reflective essays, such as observing care partner burden, reporting a human side to AD, reporting experiences from the program that will impact future clinical practice, and obtaining a greater understanding of AD.</p> <p>Conclusions</p> <p>Quantitative and qualitative findings suggest that the <it>PAIRS Program</it> can enhance the acquisition of knowledge, skills, and positive attitudes regarding geriatric healthcare in future generations of physicians, a skill set that is becoming increasingly relevant in light of the rapidly aging population. Furthermore, results suggest that The Buddy Program^TM model can be successfully replicated.</p

Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder mainly affecting females and is associated with mutations in MECP2, the gene encoding methyl CpG-binding protein 2. Mouse models suggest that recombinant human insulin-like growth factor 1 (IGF-1) (rhIGF1) (mecasermin) may improve many clinical features. We evaluated the safety, tolerability, and pharmacokinetic profiles of IGF-1 in 12 girls with MECP2 mutations (9 with RTT). In addition, we performed a preliminary assessment of efficacy using automated cardiorespiratory measures, EEG, a set of RTT-oriented clinical assessments, and two standardized behavioral questionnaires. This phase 1 trial included a 4-wk multiple ascending dose (MAD) (40–120 μg/kg twice daily) period and a 20-wk open-label extension (OLE) at the maximum dose. Twelve subjects completed the MAD and 10 the entire study, without evidence of hypoglycemia or serious adverse events. Mecasermin reached the CNS compartment as evidenced by the increase in cerebrospinal fluid IGF-1 levels at the end of the MAD. The drug followed nonlinear kinetics, with greater distribution in the peripheral compartment. Cardiorespiratory measures showed that apnea improved during the OLE. Some neurobehavioral parameters, specifically measures of anxiety and mood also improved during the OLE. These improvements in mood and anxiety scores were supported by reversal of right frontal alpha band asymmetry on EEG, an index of anxiety and depression. Our data indicate that IGF-1 is safe and well tolerated in girls with RTT and, as demonstrated in preclinical studies, ameliorates certain breathing and behavioral abnormalities.Rett Syndrome Foundation (Grant 2534)Autism Speaks (Organization) (Grant 5795)National Institutes of Health (U.S.) (Harvard Clinical and Translational Science Center, Grant 1 UL1 RR 025758-01)Boston Children’s Hospital (Translational Research Program)Boston Children’s Hospital (Intellectual and Developmental Disabilities Research Center P30 HD18655