Two Decades of Huntington Disease Testing: Patient’s Demographics and Reproductive Choices

Predictive testing for Huntington disease (HD) has been available in the United States (US) since 1987, and the Indiana University Predictive Testing Program has been providing this testing since 1990. To date there has been no published description of those who present for such testing in the US. Here we describe demographics of 141 individuals and reproductive decision making of a subset of 16 of those individuals who underwent predictive HD testing between 1990 and 2010 at one site in the US. This study is a retrospective chart review of the “Personal History Questionnaire” participants completed prior to testing. As seen in other studies, most participants were female (64.5 %), in their mid-30s (mean = 34), and had at least one child prior to testing (54 %). Multiple demographic datum points are described, and the reproductive decision making of these at-risk individuals was analyzed using Fisher’s Exact Tests. Of those women who had children before learning of their risk to inherit HD, those who attended church more frequently, had three or more children total, or whose mother was affected with HD were more likely to be comfortable with their choice to have children. We conclude that these demographic factors influence the reproductive decision-making of individuals at risk for HD. Psychologists, clinical geneticists, and genetic counselors may be able to use this information to help counsel at-risk patients regarding current or past reproductive decision making

GeorgeOral Immunization of Rhesus Macaques with Adenoviral HIV Vaccines Using Enteric-coated Capsules

Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag and a string of six highly-conserved HIV-1 envelope peptides representing broadly cross-reactive CD4+ and CD8+ T cell epitopes. Oral immunization of rhesus macaques with these capsules primed antigen-specific mucosal and systemic immune responses and subsequent intranasal delivery of the envelope peptide cocktail using a mutant cholera toxin adjuvant boosted cellular immune responses including, antigen-specific intracellular IFN-γ-producing CD4+ and CD8+ effector memory T cells in the intestine. These results suggest that the combination of oral adenoviral vector priming followed by intranasal protein/peptide boosting may be an effective mucosal HIV vaccination strategy for targeting viral antigens to the GI tract and priming systemic and mucosal immunity

Characteristics associated with requests by pathologists for second opinions on breast biopsies.

AIMS: Second opinions in pathology improve patient safety by reducing diagnostic errors, leading to more appropriate clinical treatment decisions. Little objective data are available regarding the factors triggering a request for second opinion despite second opinion consultations being part of the diagnostic system of pathology. Therefore we sought to assess breast biopsy cases and interpreting pathologists characteristics associated with second opinion requests. METHODS: Collected pathologist surveys and their interpretations of 60 test set cases were used to explore the relationships between case characteristics, pathologist characteristics and case perceptions, and requests for second opinions. Data were evaluated by logistic regression and generalised estimating equations. RESULTS: 115 pathologists provided 6900 assessments; pathologists requested second opinions on 70% (4827/6900) of their assessments 36% (1731/4827) of these would not have been required by policy. All associations between case characteristics and requesting second opinions were statistically significant, including diagnostic category, breast density, biopsy type, and number of diagnoses noted per case. Exclusive of institutional policies, pathologists wanted second opinions most frequently for atypia (66%) and least frequently for invasive cancer (20%). Second opinion rates were higher when the pathologist had lower assessment confidence, in cases with higher perceived difficulty, and cases with borderline diagnoses. CONCLUSIONS: Pathologists request second opinions for challenging cases, particularly those with atypia, high breast density, core needle biopsies, or many co-existing diagnoses. Further studies should evaluate whether the case characteristics identified in this study could be used as clinical criteria to prompt system-level strategies for mandating second opinions

Trajectories of Depressive Symptoms Among a Population of HIV-Infected Men and Women in Routine HIV Care in the United States

Depressive symptoms vary in severity and chronicity. We used group-based trajectory models to describe trajectories of depressive symptoms (measured using the Patient Health Questionnaire-9) and predictors of trajectory group membership among 1493 HIV-infected men (84%) and 292 HIV-infected women (16%). At baseline, 29% of women and 26% of men had depressive symptoms. Over a median of 30 months of follow-up, we identified four depressive symptom trajectories for women (labeled “low” [experienced by 56% of women], “mild/moderate” [24%], “improving” [14%], and “severe” [6%]) and five for men (“low” [61%], “mild/moderate” [14%], “rebounding” [5%], “improving” [13%], and “severe” [7%]). Baseline antidepressant prescription, panic symptoms, and prior mental health diagnoses were associated with more severe or dynamic depressive symptom trajectories. Nearly a quarter of participants experienced some depressive symptoms, highlighting the need for improved depression management. Addressing more severe or dynamic depressive symptom trajectories may require interventions that additionally address mental health comorbidities

Humoral Immune Response to Messenger RNA COVID-19 Vaccines Among Patients With Inflammatory Bowel Disease

Early indicators suggest that highly effective messenger RNA (mRNA) vaccinations (BNT 162b2 [Pfizer-BioNTech] and mRNA-1273 [NIH-Moderna]) are beginning to curb the coronavirus disease 2019 (COVID-19) pandemic that has already taken the lives of 3 million individuals worldwide. However, questions about vaccine effectiveness remain for individuals with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, who are frequently treated with immune suppression. An early study among transplant recipients indicated low humoral immune response after an initial vaccination, in contrast to the robust response observed in healthy individuals in phase III clinical trials. Similarly, a recent study in IBD patients suggested that treatment with infliximab is associated with an attenuated level of anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike after a single dose of mRNA vaccine

A Randomized Study Comparing Digital Imaging to Traditional Glass Slide Microscopy for Breast Biopsy and Cancer Diagnosis.

BACKGROUND: Digital whole slide imaging may be useful for obtaining second opinions and is used in many countries. However, the U.S. Food and Drug Administration requires verification studies. METHODS: Pathologists were randomized to interpret one of four sets of breast biopsy cases during two phases, separated by ≥9 months, using glass slides or digital format (sixty cases per set, one slide per case, RESULTS: Sixty-five percent of responding pathologists were eligible, and 252 consented to randomization; 208 completed Phase I (115 glass, 93 digital); and 172 completed Phase II (86 glass, 86 digital). Accuracy was slightly higher using glass compared to digital format and varied by category: invasive carcinoma, 96% versus 93% ( CONCLUSIONS: In this large randomized study, digital format interpretations were similar to glass slide interpretations of benign and invasive cancer cases. However, cases in the middle of the spectrum, where more inherent variability exists, may be more problematic in digital format. Future studies evaluating the effect these findings exert on clinical practice and patient outcomes are required

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Washboard Terrain on Pluto

Washboard texture or patterning consists of fields of parallel to sub-parallel ridges typically spaced ~1-2 km crest to crest and a few 100 m in amplitude (Fig. 4a in Moore et al., 2016, Science, 351, 1284-1293). For the most part, underlying topography can be easily discerned. We will refer to discrete, well-bounded patches of these landforms as Washboard Terrain (WT). WT is observed to occur along the rim, and just beyond the rim, of Sputnik basin from the West to NNW. Where it is seen in high-resolution data, it has clearly defined limits, beyond which it would be able to be seen if it were there. WT doesn't occur at very low latitudes or very high latitudes (ranging from 22degN to 62degN). WT seems to occur most conspicuously on relatively level, gently sloping terrain. It is restricted to elevations between approximately 2 km to less than +1.5 km (i.e. not at high elevations). The most noticeable regional aspect of the area in which WT occurs is the sinuous valley network, which is suspected to have been formed, or at least substantially modified, by glaciation. WT also appears to occur mainly on an intermediate-albedo reddish material, where seen in enhanced color data. Where it occurs in level terrain, WT tends to trend ENE - there doesn't seem to be a strong local control of its orientation in response to valley drainage directions. WT can display a greater range of orientations where it occurs in higher-relief (not higher elevation) settings such as spurs. WT appears superposed on very ancient landscapes, but is itself cratered locally by clusters of small (approximately 1-3 km) craters, which may be secondaries. This implies that WT may be intermediate in age. Of several working hypotheses, we currently provisionally favor that WT may be akin to terrestrial recessional moraines (or de Geer moraines) associated with the retreat of a higher stand of N2 glaciation that once overfilled Sputnik basin. These putative moraine features may owe their spacing to superseasonal retreat on Milankovitch timescales of approximately 1 Ma. If this hypothesis has validity, then perhaps the intermediate-albedo reddish material may be akin to ground moraine deposits