Properties of Cosmic Deuterons Measured by the Alpha Magnetic Spectrometer.

Precision measurements by the Alpha Magnetic Spectrometer (AMS) on the International Space Station of the deuteron (D) flux are presented. The measurements are based on 21×10^{6} D nuclei in the rigidity range from 1.9 to 21 GV collected from May 2011 to April 2021. We observe that over the entire rigidity range the D flux exhibits nearly identical time variations with the p, ^{3}He, and ^{4}He fluxes. Above 4.5 GV, the D/^{4}He flux ratio is time independent and its rigidity dependence is well described by a single power law ∝R^{Δ} with Δ_{D/^{4}He}=-0.108±0.005. This is in contrast with the ^{3}He/^{4}He flux ratio for which we find Δ_{^{3}He/^{4}He}=-0.289±0.003. Above ∼13 GV we find a nearly identical rigidity dependence of the D and p fluxes with a D/p flux ratio of 0.027±0.001. These unexpected observations indicate that cosmic deuterons have a sizable primarylike component. With a method independent of cosmic ray propagation, we obtain the primary component of the D flux equal to 9.4±0.5% of the ^{4}He flux and the secondary component of the D flux equal to 58±5% of the ^{3}He flux.

BrainPepPass: A Framework Based on Supervised Dimensionality Reduction for Predicting Blood-Brain Barrier-Penetrating Peptides.

Peptides that pass through the blood-brain barrier (BBB) not only are implicated in brain-related pathologies but also are promising therapeutic tools for treating brain diseases, e.g., as shuttles carrying active medicines across the BBB. Computational prediction of BBB-penetrating peptides (B3PPs) has emerged as an interesting approach because of its ability to screen large peptide libraries in a cost-effective manner. In this study, we present BrainPepPass, a machine learning (ML) framework that utilizes supervised manifold dimensionality reduction and extreme gradient boosting (XGB) algorithms to predict natural and chemically modified B3PPs. The results indicate that the proposed tool outperforms other classifiers, with average accuracies exceeding 94% and 98% in 10-fold cross-validation and leave-one-out cross-validation (LOOCV), respectively. In addition, accuracy values ranging from 45% to 97.05% were achieved in the independent tests. The BrainPepPass tool is available in a public repository for academic use (https://github.com/ewerton-cristhian/BrainPepPass).

Auricular and laryngeal chondritis in nursery and finishing pigs.

This work aimed to characterize the clinic-pathological presentation of an outbreak of auricular and laryngeal chondritis in pigs. Visits were made to pig farms, where the clinical history was obtained, and clinical and postmortem examinations were performed. In those farms, 3% to 4% of pigs presented otohematomas, which started in the nursery and extended to the finishing phase. Moreover, some finishing pigs presented with respiratory distress, initially characterized as inspiratory dyspnea, associated by an uncommon respiratory stridor and culminating in death. Grossly, nursery piglets had enlarged ears, and on the cut surface, the cartilage was fragmented and associated with blood clots. In the finishing phase, in addition to auricular lesions, the epiglottis and arytenoid cartilages were thickened and distorted, which partially occluded the lumen. Microscopically, the laryngeal and auricular cartilages were fragmented, displayed a loss of matrix basophilia, and were surrounded by lymphohistiocytic inflammatory infiltrate, with occasional multinucleated giant cells and fibrosis. The lesions exclusively affected elastic cartilages. The disease in finishing pigs led to increased mortality and was a differential diagnosis to respiratory challenges. It was not possible to determine the factor that triggered this condition; however, a nutritional association is suspected. To the authors' knowledge, this is the first report of primary auricular and laryngeal chondritis in pigs.

Temporal Structures in Positron Spectra and Charge-Sign Effects in Galactic Cosmic Rays.

We present the precision measurements of 11 years of daily cosmic positron fluxes in the rigidity range from 1.00 to 41.9 GV based on 3.4×10^{6} positrons collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The positron fluxes show distinctly different time variations from the electron fluxes at short and long timescales. A hysteresis between the electron fluxes and the positron fluxes is observed with a significance greater than 5σ at rigidities below 8.5 GV. On the contrary, the positron fluxes and the proton fluxes show similar time variation. Remarkably, we found that positron fluxes are modulated more than proton fluxes with a significance greater than 5σ for rigidities below 7 GV. These continuous daily positron fluxes, together with AMS daily electron, proton, and helium fluxes over an 11-year solar cycle, provide unique input to the understanding of both the charge-sign and mass dependencies of cosmic rays in the heliosphere.

Cannabidiol Recovers Dopaminergic Neuronal Damage Induced by Reserpine or α-synuclein in Caenorhabditis elegans.

Progressive neurodegenerative disorders such as Parkinson Disease (PD) lack curative or long-term treatments. At the same time, the increase of the worldwide elderly population and, consequently, the extension in the prevalence of age-related diseases have promoted research interest in neurodegenerative disorders. Caenorhabditis elegans is a free-living nematode widely used as an animal model in studies of human diseases. Here we evaluated cannabidiol (CBD) as a possible neuroprotective compound in PD using the C. elegans models exposed to reserpine. Our results demonstrated that CBD reversed the reserpine-induced locomotor alterations and this response was independent of the NPR-19 receptors, an orthologous receptor for central cannabinoid receptor type 1. Morphological alterations of cephalic sensilla (CEP) dopaminergic neurons indicated that CBD also protects neurons from reserpine-induced degeneration. That is, CBD attenuates the reserpine-induced increase of worms with shrunken soma and dendrites loss, increasing the number of worms with intact CEP neurons. Finally, we found that CBD also reduced ROS formation and α-syn protein accumulation in mutant worms. Our findings collectively provide new evidence that CBD acts as neuroprotector in dopaminergic neurons, reducing neurotoxicity and α-syn accumulation highlighting its potential in the treatment of PD.

Fatal Simplexvirus humanalpha1 infection in howler-monkeys (Alouatta sp.) under human care: Clinical, molecular, and pathological findings.

BACKGROUND: Simplexvirus humanalpha1 (HuAHV-1) are common anthropozoonosis reported in marmosets but rare in howler monkeys (Alouatta sp.). METHODS: Necropsy of two brown-howler monkeys (A. caraya) and one red-howler monkey (A. guariba clamitans) from different zoo collections were performed. Fragments of all organs were examined through microscopy. Samples were submitted to IHC for Simplexvirus humanalpha 2 (HuAHV-2) [sin. Herpesvirus simplex type 2] and PCR. RESULTS: Grossly, only the A. guariba showed liver lesions characterized by multifocal, pinpoint white areas corresponding microscopically as random necrotizing herpetic hepatitis and ulcerative glossitis. Both A. caraya showed necrotizing meningoencephalitis with Cowdry A-type body inclusions within neurons and astrocytes. Immunolabeling for HuAHV-1/2 was observed in the tongue, liver, and brain. HuAHV-1 was confirmed in all samples by PCR, Sanger sequencing, and phylogenetic analyses. CONCLUSION: Necrotizing meningoencephalitis was appreciated in 2/3 of animals, and it is associated with neurologic signs. Along with ulcerative glossitis, a hallmark lesion in marmosets, it was present in one animal. Regarding herpetic hepatitis, it is not frequent in monkeys and occurs mainly in immunocompromised animals. HuAHV-1 infection was confirmed corroborating with a human source. This is the second report on captive black-howler monkeys and the first gross, histologic, immunohistochemical, and molecular description of herpetic hepatitis and ulcerative glossitis in red-howler monkeys (A. guariba).

Sex differences in the acute ethanol effects on object recognition memory: influence of estrous cycle.

Effects of acute ethanol (EtOH) on memory depend on several factors, including type of behavioral task. Sex differences in EtOH effects have been reported in humans and animals, and recognition memory can be influenced by circulating sex hormones. The aim of this study was to investigate the influence of sex and estrous cycle in the acute effects of EtOH on novel object recognition memory in rats. Male and female Wistar rats were part of one of the groups: control, 0.6-g/kg EtOH and 1.8-g/kg EtOH (administered intraperitoneally before the training session). The estrous cycle was evaluated by vaginal smear. The task was conducted in an open field arena. During training, animals were exposed to two identical objects, and test sessions were performed 1 h (short-term) and 24 h (long-term) later. One of the objects was changed in each test. Increased novel object exploration was shown by male and female controls in the short- and long-term tests, respectively. In the short-term test, females did not show preference for the novel object, and EtOH 1.8 g/kg impaired performance in males. In the long-term test, both sexes showed object discrimination, and 1.8-g/kg EtOH reduced preference for the new object in male rats. The phase of the cycle, the performance on proestrus was worse compared with other phases, and EtOH failed to impair performance mainly on estrous. In conclusion, while male rats displayed ethanol-induced recognition memory deficit, female rats were unaffected by EtOH impairing effects. In addition, the performance of female rats was influenced by the estrous cycle phases.

Correction: The molecular structure of the surface of water-ethanol mixtures.

Correction for 'The molecular structure of the surface of water-ethanol mixtures' by Johannes Kirschner et al., Phys. Chem. Chem. Phys., 2021, 23, 11568-11578, DOI: 10.1039/D0CP06387H.

The appropriate use criteria: Improvements for its integration into real world clinical practice.

The purpose of this position statement is to suggest ways in which future appropriate use criteria (AUC) for coronary revascularization might be restructured to: (1) incorporate improvement in quality of life and angina relief as primary goals of therapy, (2) integrate the findings of recent trials into quality appraisal, (3) employ the combined information of the coronary angiogram and invasive physiologic measurements together with the results of stress test imaging to assess risk, and (4) recognize the essential role that patient preference plays in making individualized therapeutic decisions. The AUC is a valuable tool within the quality assurance process; it is vital that interventionists ensure that percutaneous coronary intervention case selection is both evidence-based and patient oriented. Appropriate patient selection is an important quality indicator and adherence to evidence-based practice should be one metric in a portfolio of process and outcome indicators that measure quality.

Imaging Considerations in Spinal Cord Evaluation.

Multiple diverse pathologies result in the clinical presentation of myelopathy. The preferred way to image the spinal cord depends on clinical history, anatomic site of interest, and patient issues limiting certain imaging modalities. This radiology-focused article discusses pertinent physiological considerations, reviews basic and newer imaging techniques, and examines several distinct disease entities in order to highlight the key role of imaging in the work-up of myelopathy.

The molecular structure of the surface of water-ethanol mixtures.

Mixtures of water and alcohol exhibit an excess surface concentration of alcohol as a result of the amphiphilic nature of the alcohol molecule, which has important consequences for the physico-chemical properties of water-alcohol mixtures. Here we use a combination of intensity vibrational sum-frequency generation (VSFG) spectroscopy, heterodyne-detected VSFG (HD-VSFG), and core-level photoelectron spectroscopy (PES) to investigate the molecular properties of water-ethanol mixtures at the air-liquid interface. We find that increasing the ethanol concentration up to a molar fraction (MF) of 0.1 leads to a steep increase of the surface density of the ethanol molecules, and an increased ordering of the ethanol molecules at the surface. When the ethanol concentration is further increased, the surface density of ethanol remains more or less constant, while the orientation of the ethanol molecules becomes increasingly disordered. The used techniques of PES and VSFG provide complementary information on the density and orientation of ethanol molecules at the surface of water, thus providing new information on the molecular-scale properties of the surface of water-alcohol mixtures over a wide range of compositions. This information is invaluable in understanding the chemical and physical properties of water-alcohol mixtures.

Standardization of a SNP panel for parentage verification and identification in the domestic cat (Felis silvestris catus).

The domestic cat (Felis silvestris catus) is a valued companion animal throughout the world. Over 60 different cat breeds are accepted for competition by the cat fancy registries in different countries. Genetic markers, including short tandem repeats and SNPs, are available to evaluate and manage levels of inbreeding and genetic diversity, population and breed structure relationships, and individual identification for forensic and registration purposes. The International Society of Animal Genetics (ISAG) hosts the Applied Genetics in Companion Animals Workshop, which supports the standardization of genetic marker panels and genotyping for the identification of cats via comparison testing. SNP panels have been in development for many species, including the domestic cat. An ISAG approved core panel of SNPs for use in cat identification and parentage analyses is presented. SNPs (n = 121) were evaluated by different university-based and commercial laboratories using 20 DNA samples as part of the ISAG comparison testing procedures. Different SNP genotyping technologies were examined, including DNA arrays, genotyping-by-sequencing and mass spectroscopy, to select a robust and efficient panel of 101 SNPs as the ISAG core panel for cats. The SNPs are distributed across all chromosomes including two on the X chromosome and an XY pseudo-autosomal sexing marker (zinc-finger XY; ZFXY). A population study demonstrated that the markers have an average polymorphic information content of 0.354 and a power of exclusion greater than 0.9999. The SNP panel should keep testing affordable while also allowing for the development of additional panels to monitor health, phenotypic traits, hybrid cats and highly inbred cats.

Correlation between biochemical features and outcomes of preoperative imaging (SPECT-CT and Ultrasound) in primary hyperparathyroidism.

Background: Primary hyperparathyroidism is the third most common endocrine disorder, diagnosed by elevated parathyroid hormone (PTH) in hypercalcaemia. Several biochemical factors have been described to suggest severity of disease and may be correlated with preoperative imaging. Methods: This was a retrospective study of patients who underwent parathyroidectomy over a 3-year period. Preoperative calcium, PTH, vitamin D levels, ALP (alkaline phosphatase), vitamin D, serum phosphate and US and SPECT-CT positivity was noted. Results: 176 patients underwent parathyroidectomy and these were divided into 4 groups based on preoperative calcium. Overall, 61% of patients showed concordance between imaging and operative findings. Severe hypercalcaemia was associated with higher PTH levels, lower vitamin D levels, an increased rate of abnormal ALP levels, lower phosphate, male gender and highest rate of imaging concordance. Imaging positivity was associated with severe hypercalcaemia and elevated PTH levels. Level of PTH >125 pmol/L and hypercalcaemia >2.8 mmol/L are the most accurate cut-off levels for scan positivity. Conclusion: Biochemical factors associated with severity of the disease are directly correlated with positivity of preoperative imaging while ALP and vitamin D did not influence the preoperative imaging positivity but are associated with disease adversity. Serum phosphate level independently predicted results of parathyroid US.

Exploring Chloride Selectivity and Halogenase Regioselectivity of the SalL Enzyme through Quantum Mechanical/Molecular Mechanical Modeling.

The catalytic mechanism of SalL chlorinase has been investigated by combining quantum mechanical/molecular mechanical (QM/MM) techniques and umbrella sampling simulations to compute free energy profiles. Our results shed light on the interesting fact that the substitution of chloride with fluorine in SalL chlorinase leads to a loss of halogenase activity. The potential of mean force based on DFTB3/MM analysis shows that fluorination corresponds to a barrier 13.5 kcal·mol-1 higher than chlorination. Additionally, our results present a molecular description of SalL acting as a chlorinase instead of a methyl-halide transferase.

The Evolving Erythrocyte: Red Blood Cells as Modulators of Innate Immunity.

The field of red cell biology is undergoing a quiet revolution. Long assumed to be inert oxygen carriers, RBCs are emerging as important modulators of the innate immune response. Erythrocytes bind and scavenge chemokines, nucleic acids, and pathogens in circulation. Depending on the conditions of the microenvironment, erythrocytes may either promote immune activation or maintain immune quiescence. We examine erythrocyte immune function through a comparative and evolutionary lens, as this framework may offer perspective into newly recognized roles of human RBCs. Next, we review the known immune roles of human RBCs and discuss their activity in the context of sepsis where erythrocyte function may prove important to disease pathogenesis. Given the limited success of immunomodulatory therapies in treating inflammatory diseases, we propose that the immunologic function of RBCs provides an understudied and potentially rich area of research that may yield novel insights into mechanisms of immune regulation.

Validation of scoring system predicting permanent pacemaker implantation after transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is being increasingly performed in patients with severe aortic stenosis. Despite newer generation valves, atrioventricular (AV) conduction disturbance is a common complication, necessitating permanent pacemaker (PPM) implantation in about 10% of patients. Hence, it is imperative to improve periprocedural risk stratification to predict PPM implantation after TAVR. The objective of this study was to externally validate a novel risk-stratification model derived from the National Inpatient Sample (NIS) database that predicts risk of PPM from TAVR. METHODS: Components of the score included pre-TAVR left and right bundle branch block, sinus bradycardia, second-degree AV block, and transfemoral approach. The scoring system was applied to 917 patients undergoing TAVR at our institution from November 2011 to February 2017. We assessed its predictive accuracy by looking at two components: discrimination using the C-statistic and calibration using the Hosmer-Lemeshow goodness of fit test. RESULTS: Ninety patients (9.8%) required PPM. The scoring system showed good discrimination with C-statistic score of 0.6743 (95% CI: 0.618-0.729). Higher scores suggested increased PPM risk, that is, 7.3% with score ⩽3, 19.23% with score 4-6, and 37.50% with score ≥7. Patients requiring PPM were older (81.4 versus 78.7 years, P = .002). Length of stay and in-hospital mortality was significantly higher in PPM group. CONCLUSIONS: The NIS database derived PPM risk prediction model was successfully validated in our database with acceptable discriminative and gradation capacity. It is a simple but valuable tool for patient counseling pre-TAVR and in identifying high-risk patients.

Is motor competence associated with the risk of central obesity in preschoolers?

OBJECTIVES: To investigate the association between motor competence (MC) and central obesity in preschool children. METHODS: The sample comprised of 472 children aged 3 to 5 years (4.58 ± 0.70 years, 248 boys) from Recife, Brazil. MC was assessed using the Test of Gross Motor Development-2. Waist-to-height ratio (WHtR) was calculated and a cutoff of 0.5 was used to define central obesity. Logistic regression was used to examine the association between MC and WHtR ≥ 0.5. RESULTS: The prevalence of central obesity (WHtR) was 54.0% and 46.4% for boys and girls, respectively. Older children (OR = 0.61; CI = 0.44-0.84; P < .01) and those with higher MC in locomotor skills (OR = 0.96; CI = 0.93-0.99; P < .01) were less likely to present WHtR ≥ 0.5. Sex and object control skills were not associated with WHtR ≥ 0.5. CONCLUSIONS: To reduce the risks of central obesity in children, health practitioners should focus on increasing competence in locomotor skills since preschool years.

Systematic review of civilian intravascular ballistic embolism reports during the last 30 years.

BACKGROUND: Intravascular ballistic embolization is a rare complication of missile injury. Because of its rarity, much remains to be known about its presentation, pathophysiology, complications, and management. In this study, we analyze case reports of ballistic embolization in the last 30 years and available cases from our institution to determine the likely patient, the nature of the embolization, the possible complications, and a general management strategy. METHODS: A PubMed search was performed in search of missile embolization cases from 1988 to 2018 in the English language, including only cases of intravascular emboli. Cases resulting from combat and explosive devices were excluded. In addition, five cases from our institution were included in the analysis. RESULTS: A total of 261 cases were analyzed. The most common presentation was that of a young man (reflecting the demographics of those sustaining gunshot wound injuries) with injury to the anterior torso from a single gunshot wound. Venous entry was most common, most often through large-caliber vessels. There was roughly equal involvement of the right and left circulation. Left circulation emboli were frequently symptomatic, with ischemia being the most frequent sequela. In contrast, a right circulation embolus was rarely associated with significant complications. CONCLUSIONS: Despite its rarity, ballistic embolization should be considered in gunshot injury with known large-vessel injury when an exit wound is not identified. In particular, signs of ischemia distant from the injury site warrant timely investigation to maximize tissue salvageability. We present a management strategy model for consideration.

Training and accrediting international surgeons.

BACKGROUND: Formal international medical programmes (IMPs) represent an evolution away from traditional medical volunteerism, and are based on the foundation of bidirectional exchange of knowledge, experience and organizational expertise. The intent is to develop multidirectional collaborations and local capacity that is resilient in the face of limited resources. Training and accreditation of surgeons continues to be a challenge to IMPs, including the need for mutual recognition of competencies and professional certification. METHODS: MEDLINE, Embase and Google Scholar™ were searched using the following terms, alone and in combination: 'credentialing', 'education', 'global surgery', 'international medicine', 'international surgery' and 'training'. Secondary references cited by original sources were also included. The authors, all members of the American College of Academic International Medicine group, agreed advice on training and accreditation of international surgeons. RESULTS AND CONCLUSION: The following are key elements of training and accrediting international surgeons: basic framework built upon a bidirectional approach; consideration of both high-income and low- and middle-income country perspectives; sourcing funding from current sources based on existing IMPs and networks of IMPs; emphasis on predetermined cultural competencies and a common set of core surgical skills; a decentralized global system for verification and mutual recognition of medical training and certification. The global medical system of the future will require the assurance of high standards for surgical education, training and accreditation.

Views of Appropriate Use Criteria for catheterization and percutaneous coronary revascularization by practicing interventional cardiologists: Results of a survey of American College of Cardiology Interventional Section members.

OBJECTIVES: The American College of Cardiology (ACC) Interventional Section Council leadership sought to examine the views of interventional cardiologists regarding the practical implementation and the value of the Appropriate Use Criteria (AUC) in their clinical practice. BACKGROUND: The ACC AUC for revascularization were originally intended to assess trends in revascularization patterns by hospitals and physicians to ensure that both under- and over-utilization were minimized. As a quality assurance tool, the AUC were designed to allow physicians to obtain insight into their practice patterns and improve their practice. Recent trends toward tying payment to performance have raised concerns that these criteria will be incorrectly applied to individual patient reimbursement, which is not what they were designed to do. Consequently, the AUC have become controversial, not for their value in quality assessment, but for the manner in which agencies have used the AUC as a tool to potentially deny payment for certain patients. METHODS: Utilizing an online survey, members of the ACC Interventional Section were queried regarding the use of AUC, how they use them, and how they feel utilization impacts the care of patients. RESULTS: We found substantial variability in how the AUC were utilized and concern regarding the value of AUC. Among our findings was that respondents were split (51% vs 49%) regarding the value of AUC to patients and/or their laboratory. CONCLUSIONS: In this article, we discuss the implications of these findings and consider options on how AUC might be made a better-accepted and more impactful tool for clinicians and patients.