Using co-design to develop the Adolescent Health Literacy Questionnaire for adolescents in Ireland.

Health literacy measurement studies are important for the success of health promotion efforts targeting adolescents. However, the majority of health literacy measurement tools were originally developed for adult populations and may not be reflective of health literacy in the context of adolescence. The present study sought to co-design a health literacy questionnaire and vignettes for adolescents in Ireland aged 12-18 years. This article describes the qualitative phase of the study. In 2019-2021, eight adolescents from the Irish Heart Foundation's Youth Advisory Panel participated in two concept mapping workshops during which they defined healthy living. Results of the thematic analysis indicated that adolescents defined 'healthy living' as a life that was balanced, prioritizing mental health and sleep. According to their definition, healthy living was comprised of six main constructs, namely, knowledge; sources of quality health information; facilitators and barriers; influence of others; self-efficacy, self-management and resilience; and citizenship and communication. These constructs were used to develop vignettes and items for the Adolescent Health Literacy Questionnaire (AHLQ). These were tested on a sample of 80 adolescents to check whether the respondents understood the items and vignettes as intended. Results of the nine cognitive interviews indicated that the adolescents understood the content of the 10 vignettes and 41 items. While the vignettes and AHLQ were developed with Irish adolescents, the approaches taken can be generalized to adolescents living in other countries. This will allow for the development of tailored and relevant solutions for health literacy development and health promotion for this sub-population.

Predicting the Safety and Effectiveness of Inferior Vena Cava Filters (PRESERVE): Outcomes at 12 months.

OBJECTIVE: To determine the safety and effectiveness of vena cava filters (VCFs). METHODS: A total of 1429 participants (62.7 ± 14.7 years old; 762 [53.3% male]) consented to enroll in this prospective, nonrandomized study at 54 sites in the United States between October 10, 2015, and March 31, 2019. They were evaluated at baseline and at 3, 6, 12, 18, and 24 months following VCF implantation. Participants whose VCFs were removed were followed for 1 month after retrieval. Follow-up was performed at 3, 12, and 24 months. Predetermined composite primary safety (freedom from perioperative serious adverse events [AEs] and from clinically significant perforation, VCF embolization, caval thrombotic occlusion, and/or new deep vein thrombosis [DVT] within 12-months) and effectiveness (composite comprising procedural and technical success and freedom from new symptomatic pulmonary embolism [PE] confirmed by imaging at 12-months in situ or 1 month postretrieval) end points were assessed. RESULTS: VCFs were implanted in 1421 patients. Of these, 1019 (71.7%) had current DVT and/or PE. Anticoagulation therapy was contraindicated or had failed in 1159 (81.6%). One hundred twenty-six (8.9%) VCFs were prophylactic. Mean and median follow-up for the entire population and for those whose VCFs were not removed was 243.5 ± 243.3 days and 138 days and 332.6 ± 290 days and 235 days, respectively. VCFs were removed from 632 (44.5%) patients at a mean of 101.5 ± 72.2 days and median 86.3 days following implantation. The primary safety end point and primary effectiveness end point were both achieved. Procedural AEs were uncommon and usually minor, but one patient died during attempted VCF removal. Excluding strut perforation greater than 5 mm, which was demonstrated on 31 of 201 (15.4%) patients' computed tomography scans available to the core laboratory, and of which only 3 (0.2%) were deemed clinically significant by the site investigators, VCF-related AEs were rare (7 of 1421, 0.5%). Postfilter, venous thromboembolic events (none fatal) occurred in 93 patients (6.5%), including DVT (80 events in 74 patients [5.2%]), PE (23 events in 23 patients [1.6%]), and/or caval thrombotic occlusions (15 events in 15 patients [1.1%]). No PE occurred in patients following prophylactic placement. CONCLUSIONS: Implantation of VCFs in patients with venous thromboembolism was associated with few AEs and with a low incidence of clinically significant PEs.

Predicting the Safety and Effectiveness of Inferior Vena Cava Filters (PRESERVE): Outcomes at 12 months.

OBJECTIVE: To determine the safety and effectiveness of vena cava filters (VCFs). METHODS: A total of 1429 participants (62.7 ± 14.7 years old; 762 [53.3% male]) consented to enroll in this prospective, nonrandomized study at 54 sites in the United States between October 10, 2015, and March 31, 2019. They were evaluated at baseline and at 3, 6, 12, 18, and 24 months following VCF implantation. Participants whose VCFs were removed were followed for 1 month after retrieval. Follow-up was performed at 3, 12, and 24 months. Predetermined composite primary safety (freedom from perioperative serious adverse events [AEs] and from clinically significant perforation, VCF embolization, caval thrombotic occlusion, and/or new deep vein thrombosis [DVT] within 12-months) and effectiveness (composite comprising procedural and technical success and freedom from new symptomatic pulmonary embolism [PE] confirmed by imaging at 12-months in situ or 1 month postretrieval) end points were assessed. RESULTS: VCFs were implanted in 1421 patients. Of these, 1019 (71.7%) had current DVT and/or PE. Anticoagulation therapy was contraindicated or had failed in 1159 (81.6%). One hundred twenty-six (8.9%) VCFs were prophylactic. Mean and median follow-up for the entire population and for those whose VCFs were not removed was 243.5 ± 243.3 days and 138 days and 332.6 ± 290 days and 235 days, respectively. VCFs were removed from 632 (44.5%) patients at a mean of 101.5 ± 72.2 days and median 86.3 days following implantation. The primary safety end point and primary effectiveness end point were both achieved. Procedural AEs were uncommon and usually minor, but one patient died during attempted VCF removal. Excluding strut perforation greater than 5 mm, which was demonstrated on 31 of 201 (15.4%) patients' computed tomography scans available to the core laboratory, and of which only 3 (0.2%) were deemed clinically significant by the site investigators, VCF-related AEs were rare (7 of 1421, 0.5%). Postfilter, venous thromboembolic events (none fatal) occurred in 93 patients (6.5%), including DVT (80 events in 74 patients [5.2%]), PE (23 events in 23 patients [1.6%]), and/or caval thrombotic occlusions (15 events in 15 patients [1.1%]). No PE occurred in patients following prophylactic placement. CONCLUSIONS: Implantation of VCFs in patients with venous thromboembolism was associated with few AEs and with a low incidence of clinically significant PEs.

Viral dynamics and immune responses to foot-and-mouth disease virus in African buffalo (Syncerus caffer).

Foot-and-mouth disease (FMD) is one of the most important livestock diseases restricting international trade. While African buffalo (Syncerus caffer) act as the main wildlife reservoir, viral and immune response dynamics during FMD virus acute infection have not been described before in this species. We used experimental needle inoculation and contact infections with three Southern African Territories serotypes to assess clinical, virological and immunological dynamics for thirty days post infection. Clinical FMD in the needle inoculated buffalo was mild and characterised by pyrexia. Despite the absence of generalised vesicles, all contact animals were readily infected with their respective serotypes within the first two to nine days after being mixed with needle challenged buffalo. Irrespective of the route of infection or serotype, there were positive associations between the viral loads in blood and the induction of host innate pro-inflammatory cytokines and acute phase proteins. Viral loads in blood and tonsil swabs were tightly correlated during the acute phase of the infection, however, viraemia significantly declined after a peak at four days post-infection (dpi), which correlated with the presence of detectable neutralising antibodies. In contrast, infectious virus was isolated in the tonsil swabs until the last sampling point (30 dpi) in most animals. The pattern of virus detection in serum and tonsil swabs was similar for all three serotypes in the direct challenged and contact challenged animals. We have demonstrated for the first time that African buffalo are indeed systemically affected by FMD virus and clinical FMD in buffalo is characterized by a transient pyrexia. Despite the lack of FMD lesions, infection of African buffalo was characterised by high viral loads in blood and oropharynx, rapid and strong host innate and adaptive immune responses and high transmissibility.

A decade of proboscis monkey (Nasalis larvatus) population monitoring in Balikpapan Bay: Confronting predictions with empirical data.

Systematic and well-structured monitoring is essential for taxa with high extinction risk such as primates. Endangered proboscis monkeys Nasalis larvatus are endemic to Borneo, where they are found scattered across lowland habitats of the island, which are under strong anthropogenic pressure. A large population of proboscis monkeys in Balikpapan Bay, Indonesian Borneo, was predicted to decline due to the ongoing habitat loss and degradation, notably because of forest fires. We examined changes in the number and composition of groups of a part of this population from 2007 to 2017, which included a period of forest fires linked to the El Niño-Southern Oscillation events. We conducted a census from a boat; attempting to locate all proboscis monkey groups within the Balikpapan City administrative area in 2007, 2012, and 2017. During the most recent census, we observed a total number of 60 proboscis monkey groups in two subpopulations. The population density was 1.14 group per km2 of suitable habitat. Contrary to previously published predictions, we did not find evidence of a population decline. Contrary to predictions, the 2015 El Niño induced fires impacted mainly forests on ridges and slopes, thus affecting only a small part of the proboscis monkey habitat located close to rivers and mangrove swamps. However, the increasing population density of monkeys, coupled with ongoing habitat degradation and habitat loss in one of the subpopulations, suggests that proboscis monkey population in Balikpapan Bay may be approaching a limit of resilience to habitat changes. In case it proves infeasible to census all individuals in the whole population, we recommend using a group-level census, connected with systematic group counts to obtain a reasonably precise proboscis monkey population size estimate.

Efficacy of SAT2 Foot-and-Mouth Disease Vaccines Formulated with Montanide ISA 206B and Quil-A Saponin Adjuvants.

The effective control of foot-and-mouth disease (FMD) relies strongly on the separation of susceptible and infected livestock or susceptible livestock and persistently infected wildlife, vaccination, and veterinary sanitary measures. Vaccines affording protection against multiple serotypes for longer than six months and that are less reliant on the cold chain during handling are urgently needed for the effective control of FMD in endemic regions. Although much effort has been devoted to improving the immune responses elicited through the use of modern adjuvants, their efficacy is dependent on the formulation recipe, target species and administration route. Here we compared and evaluated the efficacy of two adjuvant formulations in combination with a structurally stabilized SAT2 vaccine antigen, designed to have improved thermostability, antigen shelf-life and longevity of antibody response. Protection mediated by the Montanide ISA 206B-adjuvanted or Quil-A Saponin-adjuvanted SAT2 vaccines were comparable. The Montanide ISA 206B-adjuvanted vaccine elicited a higher SAT2 neutralizing antibody response and three times higher levels of systemic IFN-γ responses at 14- and 28-days post-vaccination (dpv) were observed compared to the Quil-A Saponin-adjuvanted vaccine group. Interestingly, serum antibodies from the immunized animals reacted similarly to the parental vaccine virus and viruses containing mutations in the VP2 protein that simulate antigenic drift in nature.

Endemic persistence of a highly contagious pathogen: Foot-and-mouth disease in its wildlife host.

Extremely contagious pathogens are a global biosecurity threat because of their high burden of morbidity and mortality, as well as their capacity for fast-moving epidemics that are difficult to quell. Understanding the mechanisms enabling persistence of highly transmissible pathogens in host populations is thus a central problem in disease ecology. Through a combination of experimental and theoretical approaches, we investigated how highly contagious foot-and-mouth disease viruses persist in the African buffalo, which serves as their wildlife reservoir. We found that viral persistence through transmission among acutely infected hosts alone is unlikely. However, the inclusion of occasional transmission from persistently infected carriers reliably rescues the most infectious viral strain from fade-out. Additional mechanisms such as antigenic shift, loss of immunity, or spillover among host populations may be required for persistence of less transmissible strains.

Day-to-day opioid withdrawal symptoms, psychological distress, and opioid craving in patients with chronic pain prescribed opioid therapy.

BACKGROUND: Research has shown that opioid craving is one of the strongest determinants of opioid misuse in patients with chronic pain. To date, however, little is known on the factors that contribute to opioid craving in these patients. It is possible that patients' physical dependence to opioids, manifested by opioid withdrawal symptoms in between daily opioid doses, contribute to opioid craving. Physical dependence symptoms might also lead to psychological distress, which in turn might contribute to opioid craving. The first objective of this study was to examine the day-to-day association between opioid withdrawal symptoms and opioid craving among patients with chronic pain. We also examined whether negative affect and catastrophic thinking mediated this association. METHODS: In this longitudinal study, chronic pain patients (n = 79) prescribed short-acting opioids completed daily diaries for 14 consecutive days. Diaries assessed a host of pain, psychological, and opioid-related variables. RESULTS: Day-to-day elevations in opioid withdrawal symptoms were associated with heightened opioid craving (p < .001). Results of a multilevel mediation analysis revealed that this association was mediated by patients' daily levels of negative affect and catastrophizing (p < .001). CONCLUSIONS: Our study provides valuable new insights into our understanding of factors that may contribute to prescription opioid craving among patients with chronic pain.

Mucocutaneous nasal histoplasmosis in an immunocompetent dog.

BACKGROUND: Histoplasma (H.) capsulatum is a dimorphic fungus, and infection is typically via inhalation of microconidia. After conversion to the yeast phase within the lung, the organism is subsequently disseminated to other tissues by macrophages. Nasal histoplasmosis appears to be a rare condition in dogs. CASE PRESENTATION: We report the clinical case of a 4.5-year-old male neutered Cocker spaniel/Poodle mix, 7.7 kg, body condition score 6/9, that presented with a 3-month history of sneezing and left-sided mucoid nasal discharge. The history also included a mild swelling (transient) of the right carpus with a lameness (grade II-III/IV), coinciding with the onset of sneezing and nasal discharge. The dog lived primarily indoors in the Texas Gulf Coast area. On physical examination, the dog was febrile, and the left nostril was swollen, ulcerative, deformed, and hypopigmented. Mandibular lymph nodes were firm and mildly enlarged bilaterally. Mild lymphopenia, thrombocytopenia, and hyperglobulinemia were noted. Thoracic radiographs were unremarkable. Computed tomography and rhinoscopy revealed swelling of the rostral portion of the left and right nasal passages. Cytology and histology of biopsies of the affected nasal tissue showed pyogranulomatous inflammation and yeast organisms consistent with H. capsulatum. Weak antigenuria was detected on the MVista H. capsulatum antigen test. Treatment with oral itraconazole led to a resolution of the nasal signs and normalization of the appearance of the nostril over 13 weeks, and neither antigenuria nor antigenemia was detected on several recheck examinations. The dog remained in good general and physical condition and showed no signs of disease recurrence more than 6 years after the last examination. CONCLUSION: We report a rare case of nasal mucocutaneous histoplasmosis in an immunocompetent dog, with an excellent clinical response to oral itraconazole. This case documents that histoplasmosis in dogs can affect primarily the nasal cavity, which responds rapidly to triazole antifungal therapy and has a good prognosis. A similar case has only been reported in human medicine in a young adult.

Evaluation of genome-wide DNA methylation profile of human embryos with different developmental competences.

STUDY QUESTION: Do embryos with different developmental competence exhibit different DNA methylation profiles at the blastocyst stage? SUMMARY ANSWER: We established genome-wide DNA methylome analysis for embryo trophectoderm (TE) biopsy samples and our findings demonstrated correlation of methylation profile of trophectoderm with euploidy status and with maternal age, indicating that genome-wide methylation level might be negatively correlated with embryo quality. WHAT IS KNOWN ALREADY: DNA methylation is a fundamental epigenetic regulatory mechanism that affects differentiation of cells into their future lineages during pre-implantation embryo development. Currently there is no established approach available to assess the epigenetic status of the human preimplantation embryo during routine IVF treatment. STUDY DESIGN, SIZE, DURATION: In total, we collected trophectoderm biopsy samples from 30 randomly selected human blastocysts and conducted whole-genome bisulfite sequencing (WGBS) to evaluate their DNA methylation profile. Nested linear models were used to assess association between DNA methylation level and ploidy status (aneuploidy [n = 20] vs. euploidy [n = 10]), maternal age (29.4-42.5 years old), and time of blastulation (day 5 [n = 16] vs. day 6 [n = 14]), using embryo identity as a covariate. PARTICIPANTS/MATERIALS, SETTING, METHODS: TE biopsy samples were obtained and submitted to bisulfite conversion. For WGBS, whole-genome sequencing libraries were then generated from the converted genome. An average of 75 million reads were obtained for each sample, and about 63% of the reads aligned to human reference. An average of 40 million reads used for the final analysis after the unconverted reads were filtered out. MAIN RESULTS AND THE ROLE OF CHANCE: We revealed an increase of genome-wide DNA methylation level in aneuploid embryo TE biopsies compared to euploid embryos (25.4% ± 3.2% vs. 24.7% ± 3.2%, P < 0.005). We also found genome-wide DNA methylation level to be increased with the maternal age (P < 0.005). On a chromosomal scale, we found monosomic embryos have lower methylation levels on the involved chromosome while no drastic change was observed for the involved chromosome in trisomies. Additionally, we revealed that WGBS data precisely revealed the chromosome copy number variance. LIMITATIONS, REASONS FOR CAUTION: Though our results demonstrated a negative correlation of genome-wide methylation level and embryo quality, further WGBS analysis on a greater number of embryos and specific investigation of its correlation with implantation and live birth are needed before any practical use of this approach for evaluation of embryo competence. WIDER IMPLICATIONS OF THE FINDINGS: This study revealed a change in genome-wide DNA methylation profile among embryos with different developmental potentials, reinforcing the critical role of DNA methylation in early development. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received for this study. Intramural funding was provided by the Foundation for Embryonic Competence (FEC). E.S. is a consultant for and receives research funding from the Foundation for Embryonic Competence; he is also co-founder and a shareholder of ACIS LLC and coholds patent US2019/055906 issued for utilizing electrical resistance measurement for assessing cell viability and cell membrane piercing. TRIAL REGISTRATION NUMBER: N/A.

Day-to-day hedonic and calming effects of opioids, opioid craving, and opioid misuse among patients with chronic pain prescribed long-term opioid therapy.

ABSTRACT: Concerns have been raised regarding the misuse of opioids among patients with chronic pain. Although a number of factors may contribute to opioid misuse, research has yet to examine if the hedonic and calming effects that can potentially accompany the use of opioids contribute to opioid misuse. The first objective of this study was to examine the degree to which the hedonic and calming effects of opioids contribute to opioid misuse in patients with chronic pain. We also examined whether the hedonic and calming effects of opioids contribute to patients' daily levels of opioid craving, and whether these associations were moderated by patients' daily levels of pain intensity, catastrophizing, negative affect, or positive affect. In this longitudinal diary study, patients (n = 103) prescribed opioid therapy completed daily diaries for 14 consecutive days. Diaries assessed a host of pain, psychological, and opioid-related variables. The hedonic and calming effects of opioids were not significantly associated with any type of opioid misuse behavior. However, greater hedonic and calming effects were associated with heightened reports of opioid craving (both P's < 0.005). Analyses revealed that these associations were moderated by patients' daily levels of pain intensity, catastrophizing, and negative affect (all P's < 0.001). Results from this study provide valuable new insights into our understanding of factors that may contribute to opioid craving among patients with chronic pain who are prescribed long-term opioid therapy. The implications of our findings for the management of patients with chronic pain are discussed.

Oral Lesions in Captive Nondomestic Felids With a Focus on Odontogenic Lesions.

Odontogenic lesions are well described in domestic cats, but published literature describing these lesions in nondomestic felids is limited. This study reports oral lesions in 109 captive, non-domestic felids. Ten cases of odontogenic lesions were diagnosed, including 9 with fibromatous epulis of periodontal ligament origin (FEPLO) and one odontogenic cyst in a cougar. FEPLO was common in lions. FEPLO did not recur after surgical removal in any of the 3 cases for which follow-up information was available. Increased occurrences of oral papillomas in snow leopards and eosinophilic granulomas in tigers were identified, which is consistent with the reported literature. With the exception of oral papillomas in snow leopards and FEPLO in lions, the spectrum of oral lesions in nondomestic felids was similar to what is reported in domestic cats, with squamous cell carcinoma being the most common oral malignancy, and stomatitis/gingivitis/glossitis accounting for approximately one third of all cases. Rare diagnoses with one case each included hemangioma, fibrosarcoma, melanoma, cleft palate, and glossal amyloidosis.

Pathogenesis, biophysical stability and phenotypic variance of SAT2 foot-and-mouth disease virus.

Foot-and-mouth disease (FMD) is a highly contagious vesicular disease of cloven-hoofed animals, which severely decreases livestock productivity. FMD virus (FMDV), the causative agent, initiates infection by interaction with integrin cellular receptors on pharyngeal epithelium cells, causing clinical signs one to four days after transmission to a susceptible host. However, some Southern African Territories (SAT) viruses have been reported to cause mild or subclinical infections that may go undiagnosed in field conditions and are likely to be more common than previously expected. The studies presented here demonstrate that not all SAT2 viruses are equally virulent in cattle. The two SAT2 viruses, ZIM/5/83 and ZIM/7/83, were both highly attenuated in cattle, as evidenced by the mild clinical signs observed after needle challenge, while two incongruent SAT2 viruses showed significantly different clinical signs in challenged cattle. We then explored the ability of the SAT2 viruses to infect different cell types with defined receptors that are utilised by FMDV and found differences in their ability to lyse cells in culture and to compete in a controlled cell culture environment. The population sequence variation between ZIM/5/83 and ZIM/7/83 revealed multiple sites of single nucleotide variants of low frequency between the predominant virus populations, as could be expected from the genome of an RNA virus. An assessment of the biophysical stability of SAT2 virions during acidification indicated that the SAT2 virus EGY/09/12 was more resilient to acidification than the ZIM/5/83 and ZIM/7/83 viruses; however, whether this difference relates to differences in virulence in vivo is unclear. This study is a consolidated view of the key findings of SAT2 viruses studied over a 14-year period involving many different experiments.

Negative Cooperativity in NAD(P)H Quinone Oxidoreductase 1 (NQO1).

NAD(P)H quinone oxidoreductase-1 (NQO1) is a homodimeric protein that acts as a detoxifying enzyme or as a chaperone protein. Dicourmarol interacts with NQO1 at the NAD(P)H binding site and can both inhibit enzyme activity and modulate the interaction of NQO1 with other proteins. We show that the binding of dicoumarol and related compounds to NQO1 generates negative cooperativity between the monomers. This does not occur in the presence of the reducing cofactor, NAD(P)H, alone. Alteration of Gly150 (but not Gly149 or Gly174) abolished the dicoumarol-induced negative cooperativity. Analysis of the dynamics of NQO1 with the Gaussian network model indicates a high degree of collective motion by monomers and domains within NQO1. Ligand binding is predicted to alter NQO1 dynamics both proximal to the ligand binding site and remotely, close to the second binding site. Thus, drug-induced modulation of protein motion might contribute to the biological effects of putative inhibitors of NQO1.

Persistent Infection of African Buffalo (Syncerus caffer) with Foot-and-Mouth Disease Virus: Limited Viral Evolution and No Evidence of Antibody Neutralization Escape.

African buffaloes (Syncerus caffer) are the principal "carrier" hosts of foot-and-mouth disease virus (FMDV). Currently, the epithelia and lymphoid germinal centers of the oropharynx have been identified as sites for FMDV persistence. We carried out studies in FMDV SAT1 persistently infected buffaloes to characterize the diversity of viruses in oropharyngeal epithelia, germinal centers, probang samples (oropharyngeal scrapings), and tonsil swabs to determine if sufficient virus variation is generated during persistence for immune escape. Most sequencing reads of the VP1 coding region of the SAT1 virus inoculum clustered around 2 subpopulations differing by 22 single-nucleotide variants of intermediate frequency. Similarly, most sequences from oropharynx tissue clustered into two subpopulations, albeit with different proportions, depending on the day postinfection (dpi). There was a significant difference between the populations of viruses in the inoculum and in lymphoid tissue taken at 35 dpi. Thereafter, until 400 dpi, no significant variation was detected in the viral populations in samples from individual animals, germinal centers, and epithelial tissues. Deep sequencing of virus from probang or tonsil swab samples harvested prior to postmortem showed less within-sample variability of VP1 than that of tissue sample sequences analyzed at the same time. Importantly, there was no significant difference in the ability of sera collected between 14 and 400 dpi to neutralize the inoculum or viruses isolated at later time points in the study from the same animal. Therefore, based on this study, there is no evidence of escape from antibody neutralization contributing to FMDV persistent infection in African buffalo.IMPORTANCE Foot-and-mouth disease virus (FMDV) is a highly contagious virus of cloven-hoofed animals and is recognized as the most important constraint to international trade in animals and animal products. African buffaloes (Syncerus caffer) are efficient carriers of FMDV, and it has been proposed that new virus variants are produced in buffalo during the prolonged carriage after acute infection, which may spread to cause disease in livestock populations. Here, we show that despite an accumulation of low-frequency sequence variants over time, there is no evidence of significant antigenic variation leading to immune escape. Therefore, carrier buffalo are unlikely to be a major source of new virus variants.

Possible Male Infanticide in Wild Orangutans and a Re-evaluation of Infanticide Risk.

Infanticide as a male reproductive tactic is widespread across mammals, and is particularly prevalent in catarrhine primates. While it has never been observed in wild orangutans, infanticide by non-sire males has been predicted to occur due to their extremely long inter-birth intervals, semi-solitary social structure, and the presence of female counter-tactics to infanticide. Here, we report on the disappearance of a healthy four-month-old infant, along with a serious foot injury suffered by the primiparous mother. No other cases of infant mortality have been observed at this site in 30 years of study. Using photographic measurements of the injury, and information on the behavior and bite size of potential predators, we evaluate the possible causes of this injury. The context, including the behavior of the female and the presence of a new male at the time of the injury, lead us to conclude that the most likely cause of the infant loss and maternal injury was male infanticide. We suggest that in orangutans, and other species where nulliparous females are not preferred mates, these females may be less successful at using paternity confusion as an infanticide avoidance tactic, thus increasing the likelihood of infanticide of their first-born infants.

Inherent biophysical stability of foot-and-mouth disease SAT1, SAT2 and SAT3 viruses.

Foot-and-mouth disease (FMD) virus (FMDV) isolates show variation in their ability to withstand an increase in temperature. The FMDV is surprisingly thermolabile, even though this virus is probably subjected to a strong extracellular selective pressure by heat in hot climate regions where FMD is prevalent. The three SAT serotypes, with their particularly low biophysical stability also only yield vaccines of low protective capacity, even with multiple booster vaccinations. The aim of the study was to determine the inherent biophysical stability of field SAT isolates. To characterise the biophysical stability of 20 SAT viruses from Southern Africa, the thermofluor assay was used to monitor capsid dissociation by the release of the RNA genome under a range of temperature, pH and ionic conditions. The SAT2 and SAT3 viruses had a similar range of thermostability of 48-54 °C. However, the SAT1 viruses had a wider range of thermostability with an 8 °C difference but with many viruses being unstable at 43-46 °C. The thermostable A-serotype A24 control virus had the highest thermostability of 55 °C with some SAT2 and SAT3 viruses of similar thermostability. There was a 10 °C difference between the most unstable SAT virus (SAT1/TAN/2/99) and the highly stable A24 control virus. SAT1 viruses were generally more stable compared to SAT2 and SAT3 viruses at the pH range of 6.7-9.1. The effect of ionic buffers on capsid stability showed that SAT1 and SAT2 viruses had an increased stability of 2-9 °C and 2-6 °C, respectively, with the addition of 1 M NaCl. This is in contrast to the SAT3 viruses, which did not show improved stabilisation after addition of 1 M or 0.5 M NaCl buffers. Some buffers showed differing results dependent on the virus tested, highlighting the need to test SAT viruses with different solutions to establish the most stabilising option for storage of each virus. This study confirms for the first time that more stable SAT field viruses are present in the southern Africa region. This could facilitate the selection of the most stable circulating field strains, for adaptation to cultured BHK-21 cells or manipulation by reverse genetics and targeted mutation to produce improved vaccine master seed viruses.

Chimeric O1K foot-and-mouth disease virus with SAT2 outer capsid as an FMD vaccine candidate.

Foot-and-mouth disease virus (FMDV) is highly contagious and infects cloven-hoofed domestic livestock leading to foot-and-mouth disease (FMD). FMD outbreaks have severe economic impact due to production losses and associated control measures. FMDV is found as seven distinct serotypes, but there are numerous subtypes within each serotype, and effective vaccines must match the subtypes circulating in the field. In addition, the O and Southern African Territories (SAT) serotypes, are relatively more thermolabile and their viral capsids readily dissociate into non-immunogenic pentameric subunits, which can compromise the effectiveness of FMD vaccines. Here we report the construction of a chimeric clone between the SAT2 and O serotypes, designed to have SAT2 antigenicity. Characterisation of the chimeric virus showed growth kinetics equal to that of the wild type SAT2 virus with better thermostability, attributable to changes in the VP4 structural protein. Sequence and structural analyses confirmed that no changes from SAT2 were present elsewhere in the capsid as a consequence of the VP4 changes. Following exposure to an elevated temperature the thermostable SAT2-O1K chimera induced higher neutralizing-antibody titres in comparison to wild type SAT2 virus.

Celiac disease is not more prevalent in patients undergoing in vitro fertilization and does not affect reproductive outcomes with or without treatment: a large prospective cohort study.

OBJECTIVE: To study the prevalence of celiac disease in the infertile population undergoing in vitro fertilization (IVF) and assess outcomes. DESIGN: Prospective cohort study. SETTING: A single infertility center from January 2016 to March 2017. PATIENT(S): Women 18-45 years of age participating in IVF. INTERVENTION(S): Patients had serum tissue transglutaminase (tTG) and endomysial (EMA) IgA testing to screen for celiac disease and completed a 10-question "yes or no" survey to assess their medical history, previous testing, dietary habits, and pertinent symptoms. MAIN OUTCOME MEASURE(S): IVF cycle outcomes were compared between seronegative and seropositive patients. RESULT(S): Of 1,000 patients enrolled, 995 completed serologic screening and 968 underwent oocyte retrieval. Eighteen patients screened positive for both tTG and EMA (1.8%) and 10 additional patients (1.0%) screened positive for one of the two antibodies. The number of mature oocytes retrieved, fertilization rates, and blastulation rates were equivalent between seronegative and seropositive patients. There were 987 patients who completed the questionnaire (98.7%), and 84 reported being gluten free (8.5%). Those who reported being gluten free were no more likely to be antibody positive than the general population. Furthermore, a low-gluten diet was not associated with markers of ovarian reserve, oocytes retrieved, fertilization, blastulation, sustained implantation and pregnancy loss rates. CONCLUSION(S): The prevalence of seropositive celiac disease was consistent with that of the general population (2.8%). Patients who were seropositive for celiac disease-related antibodies had outcomes equivalent to seronegative patients, and patients with a gluten-free diet did not have improved outcomes.