The stepwise assembly of the neonatal virome is modulated by breastfeeding.

The gut of healthy human neonates is usually devoid of viruses at birth, but quickly becomes colonized, which-in some cases-leads to gastrointestinal disorders1-4. Here we show that the assembly of the viral community in neonates takes place in distinct steps. Fluorescent staining of virus-like particles purified from infant meconium or early stool samples shows few or no particles, but by one month of life particle numbers increase to 109 per gram, and these numbers seem to persist throughout life5-7. We investigated the origin of these viral populations using shotgun metagenomic sequencing of virus-enriched preparations and whole microbial communities, followed by targeted microbiological analyses. Results indicate that, early after birth, pioneer bacteria colonize the infant gut and by one month prophages induced from these bacteria provide the predominant population of virus-like particles. By four months of life, identifiable viruses that replicate in human cells become more prominent. Multiple human viruses were more abundant in stool samples from babies who were exclusively fed on formula milk compared with those fed partially or fully on breast milk, paralleling reports that breast milk can be protective against viral infections8-10. Bacteriophage populations also differed depending on whether or not the infant was breastfed. We show that the colonization of the infant gut is stepwise, first mainly by temperate bacteriophages induced from pioneer bacteria, and later by viruses that replicate in human cells; this second phase is modulated by breastfeeding.

Comprehensive Assessment of the Intrinsic Pancreatic Microbiome.

OBJECTIVE: We sought to comprehensively profile tissue and cyst fluid in patients with benign, precancerous, and cancerous conditions of the pancreas to characterize the intrinsic pancreatic microbiome. SUMMARY BACKGROUND DATA: Small studies in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) have suggested that intra-pancreatic microbial dysbiosis may drive malignant transformation. METHODS: Pancreatic samples were collected at the time of resection from 109 patients. Samples included tumor tissue (control, n=20; IPMN, n=20; PDAC, n=19) and pancreatic cyst fluid (IPMN, n=30; SCA, n=10; MCN, n=10). Assessment of bacterial DNA by quantitative PCR and 16S ribosomal RNA gene sequencing was performed. Downstream analyses determined the relative abundances of individual taxa between groups and compared intergroup diversity. Whole-genome sequencing data from 140 patients with PDAC in the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) were analyzed to validate findings. RESULTS: Sequencing of pancreatic tissue yielded few microbial reads regardless of diagnosis, and analysis of pancreatic tissue showed no difference in the abundance and composition of bacterial taxa between normal pancreas, IPMN, or PDAC groups. Low-grade dysplasia (LGD) and high-grade dysplasia (HGD) IPMN were characterized by low bacterial abundances with no difference in tissue composition and a slight increase in Pseudomonas and Sediminibacterium in HGD cyst fluid. Decontamination analysis using the CPTAC database confirmed a low-biomass, low-diversity intrinsic pancreatic microbiome that did not differ by pathology. CONCLUSIONS: Our analysis of the pancreatic microbiome demonstrated very low intrinsic biomass that is relatively conserved across diverse neoplastic conditions and thus unlikely to drive malignant transformation.

Deltex family E3 ligases specifically ubiquitinate the terminal ADP-ribose of poly(ADP-ribosyl)ation.

Poly(ADP-ribose) polymerases (PARPs) are critical to regulating cellular activities, such as the response to DNA damage and cell death. PARPs catalyze a reversible post-translational modification (PTM) in the form of mono- or poly(ADP-ribosyl)ation. This type of modification is known to form a ubiquitin-ADP-ribose (Ub-ADPR) conjugate that depends on the actions of Deltex family of E3 ubiquitin ligases (DTXs). In particular, DTXs add ubiquitin to the 3'-OH of adenosine ribose' in ADP-ribose, which effectively sequesters ubiquitin and impedes ubiquitin-dependent signaling. Previous work demonstrates DTX function for ubiquitination of protein-free ADPR, mono-ADP-ribosylated peptides, and ADP-ribosylated nucleic acids. However, the dynamics of DTX-mediated ubiquitination of poly(ADP-ribosyl)ation remains to be defined. Here we show that the ADPR ubiquitination function is not found in other PAR-binding E3 ligases and is conserved across DTX family members. Importantly, DTXs specifically target poly(ADP-ribose) chains for ubiquitination that can be cleaved by PARG, the primary eraser of poly(ADP-ribose), leaving the adenosine-terminal ADPR unit conjugated to ubiquitin. Our collective results demonstrate the DTXs' specific ubiquitination of the adenosine terminus of poly(ADP-ribosyl)ation and suggest the unique Ub-ADPR conjugation process as a basis for PARP-DTX control of cellular activities.

Psychometric Testing of the Thai Version of Self-Care of Chronic Illness Inventory Version 4c in Patients With Stroke.

BACKGROUND: Self-Care of Chronic Illness Inventory version 4c is a non-disease-specific self-care measure used in individuals with multiple chronic conditions. This instrument may be applied to patients with specific diseases such as stroke. OBJECTIVE: The aim of this study was to evaluate the psychometric properties of the Thai version of the Self-Care of Chronic Illness Inventory version 4c in patients with stroke. METHODS: This multicenter, cross-sectional study adhered to the COSMIN (Consensus-based Standards for the Selection of Health Measurement Instruments) guidelines and enrolled patients with stroke from 16 primary care centers in southern Thailand. Structural validity was assessed using confirmatory factor analysis, internal consistency reliability using Cronbach α coefficient and global reliability index, and test-retest reliability using intraclass correlation coefficients. RESULTS: The final analysis included a total of 350 participants. Confirmatory factor analysis supported the 2-factor Self-Care Maintenance scale structure, although the item allocation to the dimensions differed from that of the original model. The Self-Care Monitoring scale demonstrated a 1-factor structure with permitted residual covariance. The Self-Care Management scale maintained a 2-factor structure, similar to that of the original model. Simultaneous confirmatory factor analysis of the combined items supported the general model with the 3 scales. The Self-Care Maintenance scale exhibited marginally adequate α (0.68) and ω (0.66) coefficients, and an adequate composite reliability index (0.79). The other 2 scales demonstrated adequate α (range, 0.79-0.86), ω (range, 0.75-0.86), and composite reliability (range, 0.83-0.86) indices. Intraclass correlation coefficients showed adequate test-retest reliability for all scales (range, 0.76-0.90). CONCLUSIONS: The generic self-care measure, Self-Care of Chronic Illness Inventory version 4c, demonstrated strong psychometric properties in patients with stroke. This instrument may be a valuable tool for assessing stroke self-care in Thailand.

Can Dual Mobility Cups Reduce Revision and Dislocation Risks? An Analysis of 107,528 Primary Total Hip Arthroplasties in the United States.

BACKGROUND: Dual mobility acetabular cups (DMC) were designed to increase the effective femoral head size and improve stability with the goal of reducing revision risk at the potential cost of polyethylene thickness. We sought to evaluate revision risk following primary elective total hip arthroplasty with DMC compared to highly cross-linked polyethylene (XLPE). METHODS: A cohort study was conducted using data from a Kaiser Permanente's total joint arthroplasty registry. Patients ≥18 years who underwent primary elective total hip arthroplasty using DMC, unipolar Metal-on-XLPE (MoXLPE), or unipolar Ceramic-on-XLPE (CoXLPE) were identified (2010 to 2021). The final sample comprised 2,219 DMC, 48,251 MoXLPE, and 57,058 CoXLPE. Multiple Cox proportional hazard regressions were used to evaluate aseptic revision and any dislocation regardless of revision within 6 years follow-up. RESULTS: In adjusted analyses, no differences in aseptic revision risk were observed for MoXLPE (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 0.72 to 1.51) or CoXLPE (HR = 0.98, 95% CI = 0.69 to 1.40) compared to DMC. No differences in dislocation risk were observed for MoXLPE (HR = 1.42, 95% CI = 0.93 to 2.15) or CoXLPE (HR = 1.25, 95% CI = 0.84 to 1.87) compared to DMC. CONCLUSIONS: In a US-based cohort, 6-year aseptic revision risk of DMC was similar to metal or ceramic femoral head unipolar constructs. Furthermore, no difference in dislocation risk was observed. Continued longer-term follow-up may reveal if there is a reduced risk of dislocation that comes at the cost of increased late revision. LEVEL OF EVIDENCE: Level III.

Perspective: Connecting the dots between domestic livestock ownership and child linear growth in low- and middle-income countries.

Child stunting due to linear growth faltering remains a pervasive issue in low- and middle-income countries. Two schools of thought have existed pertaining to the role of domestic livestock ownership (DLO) in child linear growth. On one hand, it is argued that DLO leads to greater income and financial security, resulting in better child-raising conditions, including greater animal-source food (ASF) consumption, having protective effects towards child stunting. On the other hand, researchers argue that DLO contributes to faecal contamination and transmission of zoonotic enteric infections from animals to children, thus having destructive effects on child growth. Reviews of this association have revealed ambiguous findings. In this perspective, we argue that measuring the association between exposures to domesticated animals and child stunting is difficult and the ambiguous associations revealed are a result of confounding and differences in the management of DLO. We also argue that the increasingly prominent area of research of environmental enteric dysfunction, a sub-clinical condition of the small intestine thought to be due to frequent faecal pathogen exposure and associated with stunting, will be a useful tool to measure the potential destructive effects of DLO on child growth. We present our argument and identify challenges and considerations and directions for future research.

Twice-in-a-Lifetime Pandemics: An Exploratory Qualitative Life-History Analysis of the Longitudinal Experiences of Hospital Chaplains Who Served During Both the Early AIDS (1981-1995) and Early COVID-19 (2020-2021) Pandemics in the USA and United Kingdom.

The aim of this study was to document the longitudinal experiences of chaplains who served during both the early AIDS (1981-1995) and early COVID-19 (2020-2021) pandemics. A total of 11 hospital chaplains were interviewed across the USA and the United Kingdom. Interviews were analyzed using a Grounded theory approach. Chaplains reported multiple stressors during both pandemics, including barriers to integration into care teams, tensions with home religions institutions, burnout, and challenges arising from the politicization of disease. Despite these challenges, chaplains play a vital role during pandemics. Insights from their experiences can inform future strategies for compassionate crisis response.

Endothelial cell-specific roles for tetrahydrobiopterin in myocardial function, cardiac hypertrophy, and response to myocardial ischemia-reperfusion injury.

The cofactor tetrahydrobiopterin (BH4) is a critical regulator of nitric oxide synthase (NOS) function and redox signaling, with reduced BH4 implicated in multiple cardiovascular disease states. In the myocardium, augmentation of BH4 levels can impact on cardiomyocyte function, preventing hypertrophy and heart failure. However, the specific role of endothelial cell BH4 biosynthesis in the coronary circulation and its role in cardiac function and the response to ischemia has yet to be elucidated. Endothelial cell-specific Gch1 knockout mice were generated by crossing Gch1fl/fl with Tie2cre mice, generating Gch1fl/flTie2cre mice and littermate controls. GTP cyclohydrolase protein and BH4 levels were reduced in heart tissues from Gch1fl/flTie2cre mice, localized to endothelial cells, with normal cardiomyocyte BH4. Deficiency in coronary endothelial cell BH4 led to NOS uncoupling, decreased NO bioactivity, and increased superoxide and hydrogen peroxide productions in the hearts of Gch1fl/flTie2cre mice. Under physiological conditions, loss of endothelial cell-specific BH4 led to mild cardiac hypertrophy in Gch1fl/flTie2cre hearts. Endothelial cell BH4 loss was also associated with increased neuronal NOS protein, loss of endothelial NOS protein, and increased phospholamban phosphorylation at serine-17 in cardiomyocytes. Loss of cardiac endothelial cell BH4 led to coronary vascular dysfunction, reduced functional recovery, and increased myocardial infarct size following ischemia-reperfusion injury. Taken together, these studies reveal a specific role for endothelial cell Gch1/BH4 biosynthesis in cardiac function and the response to cardiac ischemia-reperfusion injury. Targeting endothelial cell Gch1 and BH4 biosynthesis may provide a novel therapeutic target for the prevention and treatment of cardiac dysfunction and ischemia-reperfusion injury.NEW & NOTEWORTHY We demonstrate a critical role for endothelial cell Gch1/BH4 biosynthesis in coronary vascular function and cardiac function. Loss of cardiac endothelial cell BH4 leads to coronary vascular dysfunction, reduced functional recovery, and increased myocardial infarct size following ischemia/reperfusion injury. Targeting endothelial cell Gch1 and BH4 biosynthesis may provide a novel therapeutic target for the prevention and treatment of cardiac dysfunction, ischemia injury, and heart failure.

Host microbiome-pathogen interactions in pediatric infections.

PURPOSE OF REVIEW: In this review, we discuss recent research that has furthered our understanding of microbiome development during childhood, the role of the microbiome in infections during this life stage, and emerging opportunities for microbiome-based therapies for infection prevention or treatment in children. RECENT FINDINGS: The microbiome is highly dynamic during childhood and shaped by a variety of host and environmental factors. In turn, the microbiome influences risk and severity of a broad range of infections during childhood, with recent studies highlighting potential roles in respiratory, gastrointestinal, and systemic infections. The microbiome exerts this influence through both direct interactions with potential pathogens and indirectly through modulation of host immune responses. The elucidation of some of these mechanisms by recent studies and the development of effective microbiome-based therapies for adults with recurrent Clostridioides difficile infection highlight the enormous promise that targeting the microbiome has for reducing the burden of infectious diseases during childhood. SUMMARY: The microbiome has emerged as a key modifier of infection susceptibility and severity among children. Further research is needed to define the roles of microbes other than bacteria and to elucidate the mechanisms underlying microbiome-host and microbiome-pathogen interactions of importance to infectious diseases in children.

Financial burden and recommended multilevel solutions among caregivers of pediatric hematopoietic stem cell transplant recipients.

BACKGROUND: The healthcare costs of patients who receive hematopoietic stem cell transplantation (HSCT) are substantial. At the same time, the increasing use of pediatric HSCT leaves more caregivers of pediatric HSCT recipients at risk for financial burden-an understudied area of research. METHODS: Financial burden experienced by caregivers of recipients who received autologous or allogeneic transplants was assessed using an explanatory mixed-methods design including a one-time survey and semi-structured interviews. Financial burden was assessed through an adapted COmprehensive Score for financial Toxicity (COST) as well as questions about the types of out-of-pocket costs and cost-coping behaviors. Chi-squared or Fisher's exact tests were used to assess differences in costs incurred and coping behaviors by financial toxicity and financial toxicity by demographic factors. Interviews were audio recorded, transcribed, and analyzed using directed content analysis. RESULTS: Of 99 survey participants, 64% experienced high financial toxicity (COST  ≤ $ \le \;$ 22). Caregivers with high financial toxicity were more likely to report costs related to transportation and diet. High financial toxicity was associated with nearly all cost-coping behaviors (e.g., borrowed money). High financial toxicity was also associated with increased use of hospital financial support and transportation assistance. Qualitative analysis resulted in four categories that were integrated with quantitative findings: (1) care-related out-of-pocket costs incurred, (2) cost-coping behaviors, (3) financial support resources used, and (4) multilevel recommendations for reducing financial burden. CONCLUSIONS: Considering the substantial, long-term financial burden among pediatric HSCT patients and their caregivers, this population would benefit from adapted and tailored financial burden interventions.

Association between greenness and cardiovascular risk factors: Results from a large cohort study in Thailand.

BACKGROUND: The risk of cardiovascular diseases may be reduced by residing in green environments. However, there are relatively few longitudinal cohort studies, especially in Southeast Asia, that focused on the health benefits of long-term greenness exposure in young adults. The present study examined the association between long-term exposure to residential greenness and self-reported morbidities in participants of the Thai Cohort Study (TCS) in Thailand from 2005 to 2013. METHODS: The self-reported outcomes, including high blood pressure, high blood cholesterol, and diabetes, were reported in 2005, 2009, and 2013, where the study participants provided the exact year of disease occurrence. Greenness was assessed by the satellite-based Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI), with a spatial resolution of 250 m. Long-term exposure to NDVI and EVI of each participant's sub-district was averaged over the period of person-time. We used Cox proportional hazards models to examine the association between greenness and health outcomes. Associations with self-reported morbidity were measured using hazard ratios (HRs) per interquartile range (IQR) increase in NDVI and EVI. RESULTS: After adjusting for potential confounders, we observed that an IQR increase in NDVI was associated with lower incidence of high blood pressure (HR = 0.92, 95% CI: 0.89, 0.97) and high blood cholesterol (HR = 0.89, 95%CI: 0.87, 0.92), but not significantly associated with diabetes (HR = 0.93, 95%CI: 0.85, 1.01). EVI was also inversely associated with self-reported high blood pressure (HR = 0.92, 95%CI: 0.88, 0.96), high blood cholesterol (HR = 0.89, 95%CI: 0.87, 0.91), and diabetes (HR = 0.92, 95%CI: 0.85, 0.99). CONCLUSIONS: Long-term exposure to residential greenness was inversely associated with self-reported high blood pressure, high blood cholesterol, and diabetes in participants of TCS. Our study provides evidence that greenness exposure may reduce cardiovascular disease risk factors in adult population.

Bridging Divides: art and religion in the early AIDS pandemic.

Throughout the 1980s and 1990s, visual artists created a canon of work examining the illness experience of people living with AIDS. Largely forgotten today is a subset of this canon that simultaneously engaged AIDS narratives and religion, thereby dialoguing across political, cultural, and ideological divides. The artists who crafted these works created spaces of sanctioned discourse, drawing together sexual and religious histories in a manner reminiscent of the confessional as analyzed in Michel Foucault's work. This article rediscovers an archive rich in interdisciplinary illness narratives, arguing that the unearthed art pieces articulate four themes that interrogate the relationship between people with AIDS and religious traditions. In addition to furthering our understanding of a forgotten expression of AIDS illness narratives, this analysis provides insight into art's capacity to dialogue between communities in the setting of internal divisions. These lessons may aid us as we endeavor to understand the diversity, function, and applications of illness narratives in the setting of the politicized diseases of the 21st century, including COVID-19.

The Singaporean foodscape - Convenience, choice, entertainment, and sociality for young workers.

Singapore is famous for its diverse, affordable, and exciting foodscape. This paper focuses on understanding the multifaceted role that the Singaporean food environment plays in working young adults' lives, and how young adults interact with this environment to make food choices. Using a focused ethnographic approach, including 33 semi-structured interviews and participant-observation, we explore the ways in which busy working young adults interact with the foodscape. The food environment provides young adults, who eat out frequently, with highly accessible food options that cater to their budgets and palates. They often dine at hawker centres and similar food establishments with colleagues, friends and family. These establishments offer accessible, affordable, and appealing food. Overall, the foodscape provides a source of popular entertainment through the exploration of diverse cuisines and novel shared social experiences. Young adults are heavy users of social media to maintain social networks and to explore the food environment. Capitalizing on this, food marketing on social media targets this group with the promotion of food-related experiences. While it may not always promote healthy eating, the Singaporean foodscape offers convenience, choice, entertainment, and sociality. In the process, it facilitates the formation of cultural and national identity and the protection of mental well-being through the maintenance and development of relationships, and a sense of belonging.

Influence of misconceptions and inappropriate eating behaviors on Opisthorchis viverrini infection among at-risk populations undergoing cholangiocarcinoma screening in Northeastern Thailand.

Raw or undercooked freshwater fish consumption contributes to persistent Opisthorchis viverrini infection in Northeast Thailand. This study aims to assess the relationship between misconceptions, unhealthy eating habits, and O. viverrini infection. Data were obtained from the Cholangiocarcinoma Screening and Care Program in Northeast Thailand from 2019 to 2021. Participants were screened for O. viverrini annually over the following 2 years using the Kato-Katz technique. Misconceptions and unhealthy eating habits were assessed through questionnaires. The relationship between these factors and O. viverrini infection was evaluated using adjusted risk ratios (ARRs) and 95% confidence intervals (CIs) from generalized estimating equations under binomial regression framework. Of 5375 participants screened for O. viverrini over 3 years, infection rates were 21.53%, 10.7%, and 4.6% each year, respectively. Out of those, 636 participants responded to questions regarding misconceptions. Results showed that participants who believed in the efficacy of putting lime or red ants in Koi pla (raw fish salad) or eating Koi pla with white whiskey to kill parasites, and early-stage cholangiocarcinoma can be cured, were 41% (ARR, 1.41; 95% CI, 1.03-1.94) and 57% (ARR, 1.57; 95% CI, 1.06-2.33), respectively, more likely to be infected with O. viverrini. Our study confirms that belief in using lime or red ants in Koi pla or eating Koi pla with white whiskey to make it cooked, or early-stage cholangiocarcinoma can be cured, increases O. viverrini infection risk in high-risk populations. Changing health beliefs and eating habits is necessary to reduce O. viverrini infection and its risk to cholangiocarcinoma.

Single Wedge Femoral Stem Designs are Associated With a Higher Risk for Revision After Cementless Primary Total Hip Arthroplasty.

BACKGROUND: Cementless total hip arthroplasty (THA) femoral stems are the most commonly selected prostheses in the United States. Optimal stem geometry remains controversial with excellent survivorship reported for many designs. We compared cause-specific stem revision of single-wedge versus double-wedge designs from a multicenter US cohort. METHODS: Data from an integrated healthcare network's total joint replacement registry were used to conduct a cohort study. Primary elective cementless THAs were identified (2001 to 2018). Implant exposure groups were classified by design geometry using the system proposed by Khanuja et al. Type 1 single-wedge (n = 11,082) and type 2 double-wedge (n = 32,380) designs were compared, and other design types were excluded; the final study cohort comprised 43,462 THAs. Cause-specific multivariable Cox regressions were used to evaluate risk for revision due to infection or aseptic reasons, including loosening, instability, periprosthetic fracture, or other reasons. RESULTS: After adjustment for covariates, a higher aseptic revision risk was observed for type 1 when compared to type 2 designs (hazard ratio = 1.91, 95% confidence interval = 1.33-2.75). When looking at specific revision reasons, revision for aseptic loosening (hazard ratio = 3.46, 95% confidence interval = 2.24-5.34) was higher for type 1 versus type 2 designs. No differences were found for septic revision, instability, periprosthetic fracture, or revisions for other reasons. CONCLUSIONS: Type 1 single-wedge designs were found to have a higher risk of revision due to aseptic loosening relative to type 2 double-wedge designs. Femoral stem geometry should be considered when selecting a cementless femoral implant. LEVEL OF EVIDENCE: Level III.

Regulating the marketing of foods for infants and young children: Lessons from assessment of gaps in monitoring and enforcement in Thailand.

Breast milk substitute (BMS) marketing harms breastfeeding and public health. To control BMS marketing, the Member States of the World Health Organization is called upon to adopt all provisions of the International Code of Marketing of Breastmilk Substitutes (the Code) into national law. In 2017, Thailand adopted many provisions of the Code through the Control of Marketing Promotion of Infant and Young Child Food Act B.E. 2560 (the Act), including the establishment of a compliance monitoring system and enforcement mechanisms. Nevertheless, recent research showed widespread violations. This study aims to assess gaps in the monitoring system and the Act's enforcement in its first three years of operation. This qualitative research study employed in-depth interviews between April and June 2020 with 34 key informants (KIs) from the Thai government, academia and civil society organisations. KIs identified gaps in six areas that could be mitigated to increase compliance with the Act. These gaps are unclear provisions on coverage of the Act; communications with retailers and the public; lack of strong direction and processes; inadequate budget allocations; skilled and confident human resources; and external factors which facilitate BMS marketing. Recommendations may be relevant for other countries and include revising and clarifying the Act, developing targeted communication strategies; providing clear monitoring direction including through setting key performance indicators related to the Act; and providing sufficient budget and training for authorised and support officers. Strengthening the health system and workplace support for breastfeeding and social marketing would also help address wider structural factors.

Evaluation of Recombinant Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccines RSV/ΔNS2/Δ1313/I1314L and RSV/276 in RSV-Seronegative Children.

BACKGROUND: This United States-based study compared 2 candidate vaccines: RSV/ΔNS2/Δ1313/I1314L, attenuated by NS2 gene-deletion and temperature-sensitivity mutation in the polymerase gene; and RSV/276, attenuated by M2-2 deletion. METHODS: RSV-seronegative children aged 6-24 months received RSV/ΔNS2/Δ1313/I1314L (106 plaque-forming units [PFU]), RSV/276 (105 PFU), or placebo intranasally. Participants were monitored for vaccine shedding, reactogenicity, and RSV serum antibodies, and followed over the subsequent RSV season. RESULTS: Enrollment occurred September 2017 to October 2019. During 28 days postinoculation, upper respiratory illness and/or fever occurred in 64% of RSV/ΔNS2/Δ1313/I1314L, 84% of RSV/276, and 58% of placebo recipients. Symptoms were generally mild. Cough was more common in RSV/276 recipients than RSV/ΔNS2/Δ1313/I1314L (48% vs 12%; P = .012) or placebo recipients (17%; P = .084). There were no lower respiratory illness or serious adverse events. Eighty-eight and 96% of RSV/ΔNS2/Δ1313/I1314L and RSV/276 recipients were infected with vaccine (shed vaccine and/or had ≥4-fold rises in RSV antibodies). Serum RSV-neutralizing titers and anti-RSV F IgG titers increased ≥4-fold in 60% and 92% of RSV/ΔNS2/Δ1313/I1314L and RSV/276 vaccinees, respectively. Exposure to community RSV during the subsequent winter was associated with strong anamnestic RSV-antibody responses. CONCLUSIONS: Both vaccines had excellent infectivity and were well tolerated. RSV/276 induced an excess of mild cough. Both vaccines were immunogenic and primed for strong anamnestic responses. CLINICAL TRIALS REGISTRATION: NCT03227029 and NCT03422237.

Age-Related Changes in the Nasopharyngeal Microbiome Are Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Symptoms Among Children, Adolescents, and Young Adults.

BACKGROUND: Children are less susceptible to SARS-CoV-2 infection and typically have milder illness courses than adults, but the factors underlying these age-associated differences are not well understood. The upper respiratory microbiome undergoes substantial shifts during childhood and is increasingly recognized to influence host defense against respiratory pathogens. Thus, we sought to identify upper respiratory microbiome features associated with SARS-CoV-2 infection susceptibility and illness severity. METHODS: We collected clinical data and nasopharyngeal swabs from 285 children, adolescents, and young adults (<21 years) with documented SARS-CoV-2 exposure. We used 16S ribosomal RNA gene sequencing to characterize the nasopharyngeal microbiome and evaluated for age-adjusted associations between microbiome characteristics and SARS-CoV-2 infection status and respiratory symptoms. RESULTS: Nasopharyngeal microbiome composition varied with age (PERMANOVA, P < .001; R2 = 0.06) and between SARS-CoV-2-infected individuals with and without respiratory symptoms (PERMANOVA, P  = .002; R2 = 0.009). SARS-CoV-2-infected participants with Corynebacterium/Dolosigranulum-dominant microbiome profiles were less likely to have respiratory symptoms than infected participants with other nasopharyngeal microbiome profiles (OR: .38; 95% CI: .18-.81). Using generalized joint attributed modeling, we identified 9 bacterial taxa associated with SARS-CoV-2 infection and 6 taxa differentially abundant among SARS-CoV-2-infected participants with respiratory symptoms; the magnitude of these associations was strongly influenced by age. CONCLUSIONS: We identified interactive relationships between age and specific nasopharyngeal microbiome features that are associated with SARS-CoV-2 infection susceptibility and symptoms in children, adolescents, and young adults. Our data suggest that the upper respiratory microbiome may be a mechanism by which age influences SARS-CoV-2 susceptibility and illness severity.

Neglected tropical diseases in Australia: a narrative review.

•Neglected tropical diseases (NTDs) represent a threat to the health, wellbeing and economic prosperity of billions of people worldwide, often causing serious disease or death. •Commonly considered diseases of low and middle-income nations, the presence of NTDs in high income countries such as Australia is often overlooked. •Seven of the 20 recognised NTDs are endemic in Australia: scabies, soil-transmitted helminths and strongyloidiasis, echinococcosis, Buruli ulcer, leprosy, trachoma, and snakebite envenoming. •Dengue, while not currently endemic, poses a risk of establishment in Australia. There are occasional outbreaks of dengue fever, with local transmission, due to introductions in travellers from endemic regions. •Similarly, the risk of introduction of other NTDs from neighbouring countries is a concern. Many NTDs are only seen in Australia in individuals travelling from endemic areas, but they need to be recognised in health settings as the potential consequences of infection can be severe. •In this review, we consider the status of NTDs in Australia, explore the risk of introducing and contracting these infections, and emphasise the negative impact they have on the health of Australians, especially Aboriginal and Torres Strait Islander peoples.