Reliability of infrared thermography in skin temperature evaluation of wheelchair users

To examine the reliability of infrared thermography (IRT) in wheelchair users (WCUs), as a noninvasive and risk-free technique to detect the natural thermal radiation emitted by human skin and to allow subsequent interpretations of temperature distributions

Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: results from long-term open-label study

OBJECTIVE: This study assessed the effect of 1-year administration of diazoxide choline extended-release tablet (DCCR) on hyperphagia and other complications of Prader-Willi syndrome (PWS). METHODS: The authors studied 125 participants with PWS, age ≥ 4 years, who were enrolled in the DESTINY PWS Phase 3 study and who received DCCR for up to 52 weeks in DESTINY PWS and/or its open-label extension. The primary efficacy endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score. Other endpoints included behavioral assessments, body composition, hormonal measures, and safety. RESULTS: DCCR administration resulted in significant improvements in HQ-CT (mean [SE] -9.9 [0.77], p  22). Improvements were seen in aggression, anxiety, and compulsivity (all p < 0.0001). There were reductions in leptin, insulin, and insulin resistance, as well as a significant increase in adiponectin (all p < 0.004). Lean body mass was increased (p < 0.0001). Disease severity was reduced as assessed by clinician and caregiver (both p < 0.0001). Common treatment-emergent adverse events included hypertrichosis, peripheral edema, and hyperglycemia. Adverse events infrequently resulted in discontinuation (7.2%). CONCLUSIONS: DCCR administration to people with PWS was well-tolerated and associated with broad-ranging improvements in the syndrome. Sustained administration of DCCR has the potential to reduce disease severity and the burden of care for families

Brain Abnormalities in Patients with Germline Variants in H3F3: Novel Imaging Findings and Neurologic Symptoms Beyond Somatic Variants and Brain Tumors

BACKGROUND AND PURPOSE: Pathogenic somatic variants affecting the genes Histone 3 Family 3A and 3B (H3F3) are extensively linked to the process of oncogenesis, in particular related to central nervous system tumors in children. Recently, H3F3 germline missense variants were described as the cause of a novel pediatric neurodevelopmental disorder. We aimed to investigate patterns of brain MR imaging of individuals carrying H3F3 germline variants. MATERIALS AND METHODS: In this retrospective study, we included individuals with proved H3F3 causative genetic variants and available brain MR imaging scans. Clinical and demographic data were retrieved from available medical records. Molecular genetic testing results were classified using the American College of Medical Genetics criteria for variant curation. Brain MR imaging abnormalities were analyzed according to their location, signal intensity, and associated clinical symptoms. Numeric variables were described according to their distribution, with median and interquartile range. RESULTS: Eighteen individuals (10 males, 56%) with H3F3 germline variants were included. Thirteen of 18 individuals (72%) presented with a small posterior fossa. Six individuals (33%) presented with reduced size and an internal rotational appearance of the heads of the caudate nuclei along with an enlarged and squared appearance of the frontal horns of the lateral ventricles. Five individuals (28%) presented with dysgenesis of the splenium of the corpus callosum. Cortical developmental abnormalities were noted in 8 individuals (44%), with dysgyria and hypoplastic temporal poles being the most frequent presentation. CONCLUSIONS: Imaging phenotypes in germline H3F3-affected individuals are related to brain features, including a small posterior fossa as well as dysgenesis of the corpus callosum, cortical developmental abnormalities, and deformity of lateral ventricles

Variability of Female Responses to Conspecific vs. Heterospecific Male Mating Calls in Polygynous Deer: An Open Door to Hybridization?

Males of all polygynous deer species (Cervinae) give conspicuous calls during the reproductive season. The extreme interspecific diversity that characterizes these vocalizations suggests that they play a strong role in species discrimination. However, interbreeding between several species of Cervinae indicates permeable interspecific reproductive barriers. This study examines the contribution of vocal behavior to female species discrimination and mating preferences in two closely related polygynous deer species known to hybridize in the wild after introductions. Specifically, we investigate the reaction of estrous female red deer (Cervus elaphus) to playbacks of red deer vs. sika deer (Cervus nippon) male mating calls, with the prediction that females will prefer conspecific calls. While on average female red deer preferred male red deer roars, two out of twenty females spent more time in close proximity to the speaker broadcasting male sika deer moans. We suggest that this absence of strict vocal preference for species-specific mating calls may contribute to the permeability of pre-zygotic reproductive barriers observed between these species. Our results also highlight the importance of examining inter-individual variation when studying the role of female preferences in species discrimination and intraspecific mate selection

Alterations in vasodilator-stimulated phosphoprotein (VASP) phosphorylation: associations with asthmatic phenotype, airway inflammation and β(2)-agonist use

BACKGROUND: Vasodilator-stimulated phosphoprotein (VASP) mediates focal adhesion, actin filament binding and polymerization in a variety of cells, thereby inhibiting cell movement. Phosphorylation of VASP via cAMP and cGMP dependent protein kinases releases this "brake" on cell motility. Thus, phosphorylation of VASP may be necessary for epithelial cell repair of damage from allergen-induced inflammation. Two hypotheses were examined: (1) injury from segmental allergen challenge increases VASP phosphorylation in airway epithelium in asthmatic but not nonasthmatic normal subjects, (2) regular in vivo β(2)-agonist use increases VASP phosphorylation in asthmatic epithelium, altering cell adhesion. METHODS: Bronchial epithelium was obtained from asthmatic and non-asthmatic normal subjects before and after segmental allergen challenge, and after regularly inhaled albuterol, in three separate protocols. VASP phosphorylation was examined in Western blots of epithelial samples. DNA was obtained for β(2)-adrenergic receptor haplotype determination. RESULTS: Although VASP phosphorylation increased, it was not significantly greater after allergen challenge in asthmatics or normals. However, VASP phosphorylation in epithelium of nonasthmatic normal subjects was double that observed in asthmatic subjects, both at baseline and after challenge. Regularly inhaled albuterol significantly increased VASP phosphorylation in asthmatic subjects in both unchallenged and antigen challenged lung segment epithelium. There was also a significant increase in epithelial cells in the bronchoalveolar lavage of the unchallenged lung segment after regular inhalation of albuterol but not of placebo. The haplotypes of the β(2)-adrenergic receptor did not appear to associate with increased or decreased phosphorylation of VASP. CONCLUSION: Decreased VASP phosphorylation was observed in epithelial cells of asthmatics compared to nonasthmatic normals, despite response to β-agonist. The decreased phosphorylation does not appear to be associated with a particular β(2)-adrenergic receptor haplotype. The observed decrease in VASP phosphorylation suggests greater inhibition of actin reorganization which is necessary for altering attachment and migration required during epithelial repair

Female sexual preferences toward conspecific and hybrid male mating calls in two species of polygynous deer, Cervus elaphus and C. nippon

The behavioral processes at the basis of hybridization and introgression are understudied in terrestrial mammals. We use a unique model to test the role of sexual signals as a reproductive barrier to introgression by investigating behavioral responses to male sexual calls in estrous females of two naturally allopatric but reproductively compatible deer species, red deer and sika deer. Previous studies demonstrated asymmetries in acoustic species discrimination between these species: most but not all female red deer prefer conspecific over sika deer male calls while female sika deer exhibit no preference differences. Here, we extend this examination of acoustic species discrimination to the role of male sexual calls in introgression between parent species and hybrids. Using two-speaker playback experiments, we compared the preference responses of estrous female red and sika deer to male sexual calls from conspecifics versus red × sika hybrids. These playbacks simulate early secondary contact between previously allopatric species after hybridization has occurred. Based on previous conspecific versus heterospecific playbacks, we predicted that most female red deer would prefer conspecific calls while female sika deer would show no difference in their preference behaviors toward conspecific and hybrid calls. However, results show that previous asymmetries did not persist as neither species exhibited more preferences for conspecific over hybrid calls. Thus, vocal behavior is not likely to deter introgression between these species during the early stages of sympatry. On a wider scale, weak discrimination against hybrid sexual signals could substantially contribute to this important evolutionary process in mammals and other taxa

The genome landscape of indigenous African cattle

Background: The history of African indigenous cattle and their adaptation to environmental and human selection pressure is at the root of their remarkable diversity. Characterization of this diversity is an essential step towards understanding the genomic basis of productivity and adaptation to survival under African farming systems. Results: We analyze patterns of African cattle genetic variation by sequencing 48 genomes from five indigenous populations and comparing them to the genomes of 53 commercial taurine breeds. We find the highest genetic diversity among African zebu and sanga cattle. Our search for genomic regions under selection reveals signatures of selection for environmental adaptive traits. In particular, we identify signatures of selection including genes and/ or pathways controlling anemia and feeding behavior in the trypanotolerant N’Dama, coat color and horn development in Ankole, and heat tolerance and tick resistance across African cattle especially in zebu breeds. Conclusions: Our findings unravel at the genome-wide level, the unique adaptive diversity of African cattle while emphasizing the opportunities for sustainable improvement of livestock productivity on the continent

Epistemic Consequentialism: Haters Gonna Hate

Epistemic consequentialism has been charged with ignoring the epistemic separateness of propositions and with (thereby) allowing trade-offs between propositions. Here, I do two things. First, I investigate the metaphor of the epistemic separateness of propositions. I argue that either (i) the metaphor is meaningfully unpacked in a way that is modeled on the moral separateness of persons, in which case it doesn’t support a ban on trade-offs or (ii) it isn’t meaningfully unpacked, in which case it really doesn’t support a ban on trade-offs. Second, I consider the strategy of arguing against the trade-off permitting conception of epistemic rationality that is central to epistemic consequentialism on the basis of our intuitive verdicts about the permissibility of trade-offs in cases. I argue the execution of this strategy suffers a methodological mistake that, once corrected, vitiates the probative value of those intuitive verdicts. Hence the conclusion: the separateness of propositions provides no support for a ban on trade-offs, and an influential independent argument for such a ban is flawed