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Brain dissection is typically an important part of teaching neuroscience in health professional programs. This results in the need to effectively remove brains, which is often performed in a gross anatomy laboratory in the same curriculum. The aim of this study was to determine the most effective method of brain removal based on the time required for removal, difficulty of removal, and preservation of key brain structures for educational purposes. Six different dissectors performed each of the three calvaria removal approaches and three different spinal cord transection methods rating them for difficulty and tracking the time required. The combination of calvaria and brainstem approaches and the order of completion was randomized to control for fatigue and previous individual experience. After all brains were removed, each was evaluated by neuroscience faculty for utility in education contexts. The study found little difference between the individual approaches for both calvaria removal and spinal cord transection in regards to quality of outcome. The use of a circumferential cut only proved to be the most time-effective method for calvaria removal while a posterior cut between C1 and C2 was the most time-effective and least difficult method for brainstem release. There was no one technique that proved to be most beneficial across all three measures. However, different approaches resulted in a different combination of benefits across the time, difficulty, and outcome ratings that should be considered in light of the individual needs of any program or researcher.

Abstract Introduction Similar Patient-Reported Outcomes (PROs) at diagnosis for localized prostate cancer among countries may indicate that different treatments are recommended to the same profile of patients, regardless the context characteristics (health systems, medical schools, culture, preferences…). The aim of this study was to assess such comparison. Methods We analyzed the EPIC-26 results before the primary treatment of men diagnosed of localized prostate cancer from January 2017 onwards (revised data available up to September 2019), from a multicenter prospective international cohort including seven regions: Australia/New Zealand, Canada, Central Europe (Austria / Czech Republic / Germany), United Kingdom, Italy, Spain, and the United States. The EPIC-26 domain scores and pattern of three selected items were compared across regions (with Central Europe as reference). All comparisons were made stratifying by treatment: radical prostatectomy, external radiotherapy, brachytherapy, and active surveillance. Results The sample included a total of 13,483 men with clinically localized or locally advanced prostate cancer. PROs showed different domain patterns before treatment across countries. The sexual domain was the most impaired, and the one with the highest dispersion within countries and with the greatest medians’ differences across countries. The urinary incontinence domain, together with the bowel and hormonal domains, presented the highest scores (better outcomes) for all treatment groups, and homogeneity across regions. Conclusions Patients with localized or locally advanced prostate cancer undergoing radical prostatectomy, EBRT, brachytherapy, or active surveillance presented mainly negligible or small differences in the EPIC-26 domains before treatment across countries. The results on urinary incontinence or bowel domains, in which almost all patients presented the best possible score, may downplay the baseline data role for evaluating treatments’ effects. However, the heterogeneity within countries and the magnitude of the differences found across countries in other domains, especially sexual, support the need of implementing the PRO measurement from diagnosis.

This visualization provides a snapshot of social isolation in America over a 20-year period. The author leverages data from the American Time Use Survey to estimate the percentage of Americans who report a complete lack of social contact during a single day. Contrary to prior claims, there was no clear evidence of increasing isolation during the 2000s and 2010s. There was, however, a marked increase in the percentage of Americans who were socially isolated during the coronavirus pandemic. Adopting a micro view of social isolation contributes to contemporary debates by highlighting social interactions rather than broad assessments of social integration such as social relationships or group participation. Although these latter concepts are important in their own ways, focusing on social interactions speaks to issues that are often considered synonymous with social integration such as the exchange of support, resources, and feelings of belongingness.

At the cellular level, membrane damage is a fundamental cause of yield loss at high temperatures (HT). We report our investigations on a subset of a peanut (Arachis hypogaea) recombinant inbred line population, demonstrating that the membrane lipid remodeling occurring at HT is consistent with homeoviscous adaptation to maintain membrane fluidity. A major alteration in the leaf lipidome at HT was the reduction in the unsaturation levels, primarily through reductions of 18:3 fatty acid chains, of the plastidic and extra-plastidic diacyl membrane lipids. In contrast, levels of 18:3-containing triacylglycerols (TGs) increased at HT, consistent with a role for TGs in sequestering fatty acids when membrane lipids undergo remodeling during plant stress. Polyunsaturated acyl chains from membrane diacyl lipids were also sequestered as sterol esters (SEs). The removal of 18:3 chains from the membrane lipids decreased the availability of susceptible molecules for oxidation, thereby minimizing oxidative damage in membranes. Our results suggest that transferring 18:3 chains from membrane diacyl lipids to TGs and SEs is a key feature of lipid remodeling for HT adaptation in peanut. Finally, QTL-seq allowed the identification of a genomic region associated with heat-adaptive lipid remodeling, which would be useful for identifying molecular markers for heat tolerance.

Huntington’s disease (HD) is a neurodegenerative disease characterized by movement and cognitive dysfunction. HD is caused by a CAG expansion in exon 1 of the HTT gene that leads to a polyglutamine (PQ) repeat in the huntingtin protein, which aggregates in the brain and periphery. Previously, we used Drosophila models to determine that Htt-PQ aggregation in the heart causes shortened lifespan and cardiac dysfunction that is ameliorated by promoting chaperonin function or reducing oxidative stress. Here, we further study the role of neuronal mutant huntingtin and how it affects peripheral function. We overexpressed normal (Htt-PQ25) or expanded mutant (Htt-PQ72) exon 1 of huntingtin in Drosophila neurons and found that mutant huntingtin caused age-dependent Htt-PQ aggregation in the brain and could cause a loss of synapsin. To determine if this neuronal dysfunction led to peripheral dysfunction, we performed a negative geotaxis assay to measure locomotor performance and found that neuronal mutant huntingtin caused an age-dependent decrease in locomotor performance. Next, we found that rapamycin reduced Htt-PQ aggregation in the brain. These results demonstrate the role of neuronal Htt-PQ in dysfunction in models of HD, suggest that brain-periphery crosstalk could be important to the pathogenesis of HD, and show that rapamycin reduces mutant huntingtin aggregation in the brain.

Darier, Hailey-Hailey, and Grover diseases are rare acantholytic skin diseases. While these diseases have different underlying causes, they share defects in cell-cell adhesion in the epidermis and desmosome organization. To better understand the underlying mechanisms leading to disease in these conditions, we performed RNA-seq on lesional skin samples from patients. The transcriptomic profiles of Darier, Hailey-Hailey, and Grover diseases were found to share a remarkable overlap, which did not extend to other common inflammatory skin diseases. Analysis of enriched pathways showed a shared increase in keratinocyte differentiation, and a decrease in cell adhesion and actin organization pathways in Darier, Hailey-Hailey, and Grover diseases. Direct comparison to atopic dermatitis and psoriasis showed that the downregulation in actin organization pathways was a unique feature in the acantholytic skin diseases. Furthermore, upstream regulator analysis suggested that a decrease in SRF/MRTF activity was responsible for the downregulation of actin organization pathways. Staining for MRTFA in lesional skin samples showed a decrease in nuclear MRTFA in patient skin compared with normal skin. These findings highlight the significant level of similarity in the transcriptome of Darier, Hailey-Hailey, and Grover diseases, and identify decreases in actin organization pathways as a unique signature present in these conditions.

Abstract Objective Charcot–Marie–Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsy (HNPP) are caused by mutations to the peripheral myelin protein 22 (PMP22) gene. A need exists for sensitive and reliable biomarkers of progression and treatment response. Magnetic resonance imaging (MRI) metrics of nerve pathology and morphology were investigated for this purpose. Methods MRI was performed at 3.0 T in the thigh of CMT1A (N = 11) and HNPP patients (N = 12) and controls (N = 23). Three potential imaging biomarkers of the sciatic nerve were investigated: 1) magnetization transfer ratio (MTR), which assays myelin content, and 2) cross‐sectional area (CSA) and 3) circularity, which assay morphological changes. Potential imaging biomarkers were compared across cohorts and assessed for relationships with disability in the legs (CMTESL), compound motor action potentials (CMAP), and motor conduction velocities (MCV). Inter‐rater reliability and test–retest repeatability were established for each imaging metric. Results Significant differences in MTR, CSA, and circularity were observed in CMT1A relative to controls (p = 0.02, p 0.999, CV = 0.30%) and repeatable (ICC = 0.84, CV = 3.16%). Interpretation MTR, CSA, and circularity showed promise as reliable and sensitive biomarkers of CMT1A, but not HNPP. These warrant longitudinal investigation as response biomarkers in upcoming clinical trials of CMT1A, while other methods should be considered for HNPP.