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Bluetongue virus (BTV) is the etiologic agent of bluetongue (BT), a viral WOAH-listed disease affecting wild and domestic ruminants, primarily sheep. The outermost capsid protein VP2, encoded by S2, is the virion’s most variable protein, and the ability of reference sera to neutralize an isolate has so far dictated the differentiation of 24 classical BTV serotypes. Since 2008, additional novel BTV serotypes, often referred to as “atypical” BTVs, have been documented and, currently, the full list includes 36 putative serotypes. In March 2015, a novel atypical BTV strain was detected in the blood of asymptomatic goats in Sardinia (Italy) and named BTV-X ITL2015. The strain re-emerged in the same region in 2021 (BTV-X ITL2021). In this study, we investigated the pathogenicity and kinetics of infection of BTV-X ITL2021 following subcutaneous and intravenous infection of small ruminants. We demonstrated that, in our experimental settings, BTV-X ITL2021 induced a long-lasting viraemia only when administered by the intravenous route in goats, though the animals remained healthy and, apparently, did not develop a neutralizing immune response. Sheep were shown to be refractory to the infection by either route. Our findings suggest a restricted host tropism of BTV-X and point out goats as reservoirs for this virus in the field.

Adropin is a highly-conserved peptide that has been shown to preserve endothelial barrier function. Blood-brain barrier (BBB) disruption is a key pathological event in cerebral ischemia. However, the effects of adropin on ischemic stroke outcomes remain unexplored. Hypothesizing that adropin exerts neuroprotective effects by maintaining BBB integrity, we investigated the role of adropin in stroke pathology utilizing loss- and gain-of-function genetic approaches combined with pharmacological treatment with synthetic adropin peptide. Long-term anatomical and functional outcomes were evaluated using histology, MRI, and a battery of sensorimotor and cognitive tests in mice subjected to ischemic stroke. Brain ischemia decreased endogenous adropin levels in the brain and plasma. Adropin treatment or transgenic adropin overexpression robustly reduced brain injury and improved long-term sensorimotor and cognitive function in young and aged mice subjected to ischemic stroke. In contrast, genetic deletion of adropin exacerbated ischemic brain injury, irrespective of sex. Mechanistically, adropin treatment reduced BBB damage, degradation of tight junction proteins, matrix metalloproteinase-9 activity, oxidative stress, and infiltration of neutrophils into the ischemic brain. Adropin significantly increased phosphorylation of endothelial nitric oxide synthase (eNOS), Akt, and ERK1/2. While adropin therapy was remarkably protective in wild-type mice, it failed to reduce brain injury in eNOS-deficient animals, suggesting that eNOS is required for the protective effects of adropin in stroke. These data provide the first causal evidence that adropin exerts neurovascular protection in stroke through an eNOS-dependent mechanism. We identify adropin as a novel neuroprotective peptide with the potential to improve stroke outcomes.

A multi-technique approach combining petrographic, cathodoluminescence, and stable isotope analyses is commonly used in provenance studies of archaeological marbles. In the present paper, this characterization approach transcends provenance, and it is applied to the reconstruction of fragmented sculptures. The potential of this novel application of archaeometric measurements is illustrated with a case study consisting in 16 scattered marble fragments retrieved from a Roman villa (Els Munts) near Tarraco (presently Northeastern Spain). The samples were grouped taking into account their similarity in quantified parameters such as the cathodoluminescence color clusters and the stable carbon and oxygen isotopic ratios. The results permitted classification of the fragments into three groups corresponding to three different statues depicting Antinous (7 fragments), Minerva goddess (4 fragments), and an undetermined character (3 fragments). Two other fragments could not be ascribed to any particular statue. The archaeometric grouping provides arguments that can be used to confirm or refute archaeological hypotheses of statue reconstructions.

Tenofovir disoproxil fumarate (TDF) is increasingly used in the highly active antiretroviral therapy (HAART) regimens of pregnant women, but limited data exist on the pregnancy pharmacokinetics of chronically dosed TDF. This study described tenofovir pharmacokinetics during pregnancy and postpartum. Methods: International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s is a prospective, nonblinded pharmacokinetic study of HIV-infected pregnant women that included a cohort receiving 300mg TDF once daily. Steady-state 24-hour pharmacokinetic profiles were measured at the second and third trimesters, postpartum, and in maternal and umbilical cord samples collected at delivery. Tenofovir was measured by liquid chromatography-mass spectrometry (LC-MS). The target area under the concentration versus time curve from time 0 to 24h post dose (AUC) was ≥1.99μg h/mL (nonpregnant historical control 10th percentile). Results: The median tenofovir AUC was decreased during the second (1.9μg h/mL) and third (2.4μg h/mL; P=0.005) trimesters versus postpartum (3.0μg h/mL). Tenofovir AUC exceeded the target for two of four women (50%) in the second trimester, 27 of 37 women [73%; 95% confidence interval (CI) 56%, 86%] in the third trimester, and 27 of 32 women (84%; 95% CI 67%, 95%) postpartum (P>0.05). Median second/third-trimester troughs were lower (39/54ng/mL) than postpartum (61ng/mL). Median third-trimester weight was greater for subjects below the target AUC versus those above the target (97.9 versus 74.2kg, respectively; P=0.006). The median ratio of cord blood to maternal concentrations was 0.88. No infants were HIV infected. Conclusions: This study found lower tenofovir AUC and troughs during pregnancy. Transplacental passage with chronic TDF use during pregnancy was high. Standard TDF doses appear to be appropriate for most HIV-infected pregnant women but therapeutic drug monitoring with dose adjustment should be considered in pregnant women with high weight (>90kg) or inadequate HIV RNA response.

PurposeHispanic/Latino adolescents and young adults are disproportionately impacted by the HIV/AIDS epidemic; yet little is known about the best strategies to increase HIV testing in this group. Network-based approaches are feasible and acceptable means for screening at-risk adults for HIV infection, but it is unknown whether these approaches are appropriate for at-risk young Hispanics/Latinos. Thus, we compared an alternative venue-based testing (AVT) strategy with a social and sexual network-based interviewing and HIV testing (SSNIT) strategy.MethodsAll participants were Hispanics/Latinos aged 13-24 years with self-reported HIV risk; they were recruited from 11 cities in the United States and Puerto Rico and completed an audio computer-assisted self-interview and underwent HIV screening.ResultsA total of 1,596 participants (94.5% of those approached) were enrolled: 784 (49.1%) through AVT and 812 (50.9%) through SSNIT. HIV infection was identified in three SSNIT (.37%) and four AVT (.51%) participants (p = .7213).ConclusionsDespite high levels of HIV risk, a low prevalence of HIV infection was identified with no differences by recruitment strategy. We found overwhelming support for the acceptability and feasibility of AVT and SSNIT for engaging and screening at-risk young Hispanics/Latinos. Further research is needed to better understand how to strategically implement such strategies to improve identification of undiagnosed HIV infection.

Functional dyspepsia (FD) is a common but heterogeneous upper gastrointestinal disorder that causes recurrent and/or chronic epigastric symptoms, with an estimated prevalence in children between 3% and 27%. Etiologies include genetic predisposition and events that cause disruption of the brain-gut-microbiota axis, such as environmental and psychosocial stressors, disturbance of the gut microbiota, and early life events that lead to hyperalgesia such as cow’s milk protein. FD results in impaired quality of life and increased health care costs, with an estimated $5 billion in annual costs. Unfortunately, treatment options are limited given the complexity of its pathophysiology and the fact that most therapies are studied in adults and not children, thus making FD difficult to manage in pediatrics.

Inflammatory bowel disease (IBD) comprises ulcerative colitis (UC) and Crohn’s disease (CD). IBD etiopathology is multifactorial and involves alteration of immune cells and chronic activation of the inflammatory cascade against yet unknown environmental factors that trigger the disease. IBD therapy aims at improving the quality of life and reducing the risk of disease-related complications to avoid the need for surgery. There is no specific cure for IBDs, and the focus of therapy is supportive measures and use of anti-inflammatory and immunosuppressive drugs. Glucocorticoids (GCs) are powerful anti-inflammatory and immunomodulatory agents used to treat many acute and chronic inflammatory diseases. GCs remain basic treatment for moderate-to-severe IBD, but their use is limited by several important adverse drug effects. Topical administration of a second-generation of GCs, such as budesonide and beclomethasone dipropionate (BDP), represents a valid alternative to use of older, systemic GCs. Administration of second-generation GCs shows promisingly high topical activity and less systemic toxicity, but maintenance therapy with these new GCs in IBD patients is associated with multiple adverse effects. In this review, we make a comparative analysis of the efficacy of first-generation and second-generation GCs in IBD treatment. Unraveling GC biology at the molecular level to uncouple their clinical benefits from detrimental effects is important. One approach is to consider new GC mediators, such as glucocorticoid-induced leucine zipper, which may have similar anti-inflammatory properties, but avoids the side effects of GCs. This in-depth analysis can help to improve the development and the clinical outcomes of GC therapies in IBD.