An Exploration of the Goodness of Fit of Web-Based Tools for Maori: Qualitative Study Using Interviews and Focus Groups.

BACKGROUND: Indigenous communities often have poorer health outcomes and services under traditional models of care. In New Zealand, this holds true for Maori people who are tangata whenua (the indigenous people). Several barriers exist that decrease the likelihood of indigenous communities often have poorer health outcomes and poor service fit under traditional models of care, including access issues, systemic and provider racism, and a lack of culturally safe and responsive services. Web-based interventions (WBIs) have been shown to be effective in supporting mental health and well-being and can overcome some of these barriers. Despite the large number of WBIs developed, more investigation is needed to know how well WBIs fit with an indigenous worldview and how they meet the needs of indigenous communities so that a digitally based future does not drive social and health inequities. OBJECTIVE: This study aims to explore the goodness-of-fit of WBIs of Maori individuals, the indigenous people of Aotearoa/New Zealand. METHODS: We used interviews (n=3) and focus groups (n=5) with 30 Maori participants to explore their views about WBIs. Interviews were analyzed using reflexive thematic analysis by members of the research team. RESULTS: Overall, there was a perception that the design of WBIs did not align with the Maori worldview, which centers around people, relationships, spirituality, and holistic views of well-being. A total of 4 key themes and several subthemes emerged, indicating that WBIs were generally considered a poor fit for Maori. Specifically, the themes were as follows: (1) WBIs are disconnected from the core values of te ao Maori (the Maori worldview), (2) WBIs could be helpful in the right context, (3) there are significant barriers that may make it harder for Maori to use WBIs than other groups, and (4) ways to improve WBIs to help engagement with Maori. CONCLUSIONS: While WBIs are often considered a way to reduce barriers to care, they may not meet the needs of Maori when used as a stand-alone intervention. If WBIs are continued to be offered, developers and researchers need to consider how to develop WBIs that are responsive and engaging to the needs of indigenous communities rather than driving inequities. Ideally, WBIs should be developed by the people they are intended for to fit with those populations' world views.

Investigating Machine Learning Techniques for Predicting Risk of Asthma Exacerbations: A Systematic Review.

Asthma, a common chronic respiratory disease among children and adults, affects more than 200 million people worldwide and causes about 450,000 deaths each year. Machine learning is increasingly applied in healthcare to assist health practitioners in decision-making. In asthma management, machine learning excels in performing well-defined tasks, such as diagnosis, prediction, medication, and management. However, there remain uncertainties about how machine learning can be applied to predict asthma exacerbation. This study aimed to systematically review recent applications of machine learning techniques in predicting the risk of asthma attacks to assist asthma control and management. A total of 860 studies were initially identified from five databases. After the screening and full-text review, 20 studies were selected for inclusion in this review. The review considered recent studies published from January 2010 to February 2023. The 20 studies used machine learning techniques to support future asthma risk prediction by using various data sources such as clinical, medical, biological, and socio-demographic data sources, as well as environmental and meteorological data. While some studies considered prediction as a category, other studies predicted the probability of exacerbation. Only a group of studies applied prediction windows. The paper proposes a conceptual model to summarise how machine learning and available data sources can be leveraged to produce effective models for the early detection of asthma attacks. The review also generated a list of data sources that other researchers may use in similar work. Furthermore, we present opportunities for further research and the limitations of the preceding studies.

Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother-child pairs.

Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother-child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.6 million mother-child pairs between 2001 and 2014 with follow-up until 2020. Children who were born to mothers with any type of diabetes during pregnancy had a higher risk of ADHD than unexposed children (pooled hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 1.08-1.24). Higher risks of ADHD were also observed for both GDM (pooled HR = 1.10, 95% CI = 1.04-1.17) and PGDM (pooled HR = 1.39, 95% CI = 1.25-1.55). However, siblings with discordant exposure to GDM in pregnancy had similar risks of ADHD (pooled HR = 1.05, 95% CI = 0.94-1.17), suggesting potential confounding by unmeasured, shared familial factors. Our findings indicate that there is a small-to-moderate association between MDM and ADHD, whereas the association between GDM and ADHD is unlikely to be causal. This finding contrast with previous studies, which reported substantially higher risk estimates, and underscores the need to reevaluate the precise roles of hyperglycemia and genetic factors in the relationship between MDM and ADHD.

Comparison of the function of two novel human dopamine D2 receptor variants identifies a likely mechanism for their pathogenicity.

Two recently discovered DRD2 mutations, c.634A > T, p.Ile212Phe and c.1121T > G, p.Met374Arg, cause hyperkinetic movement disorders that have overlapping features but apparently differ in severity. The two known carriers of the Met374Arg variant had early childhood disease onset and more severe motor, cognitive, and neuropsychiatric deficits than any known carriers of the Ile212Phe variant, whose symptoms were first apparent in adolescence. Here, we evaluated if differences in the function of the two variants in cultured cells could explain differing pathogenicity. Both variants were expressed less abundantly than the wild type receptor and exhibited loss of agonist-induced arrestin binding, but differences in expression and arrestin binding between the variants were minor. Basal and agonist-induced activation of heterotrimeric Gi/o/z proteins, however, showed clear differences; agonists were generally more potent at Met374Arg than at the Ile212Phe or wild type variants. Furthermore, all Gα subtypes tested were constitutively activated more by Met374Arg than by Ile212Phe. Met374Arg produced greater constitutive inhibition of cyclic AMP accumulation than Ile212Phe or the wild type D2 receptor. Met374Arg and Ile212Phe were more sensitive to thermal inactivation than the wild type D2 receptor, as reported for other constitutively active receptors, but Ile212Phe was affected more than Met374Arg. Additional pharmacological characterization suggested that the mutations differentially affect the shape of the agonist binding pocket and the potency of dopamine, norepinephrine, and tyramine. Molecular dynamics simulations provided a structural rationale for enhanced constitutive activation and agonist potency. Enhanced constitutive and agonist-induced G protein-mediated signaling likely contributes to the pathogenicity of these novel variants.

Using interRAI Assessment for Research: Developing a National Research Agenda in Aotearoa New Zealand.

interRAI provides a suite of standardized, validated instruments used to assess health and psychosocial well-being, and to inform person-centered care planning. Data obtained from these standardized tools can also be used at a population level for research and to inform policy, and interRAI is currently used in more than 40 countries globally. We present a brief overview of the use of interRAI internationally within research and policy settings, and then introduce how interRAI is used within the universal public health system in Aotearoa New Zealand (NZ), including considerations relating to Maori, the Indigenous people of NZ. In NZ, improvement in interRAI data utilization for research purposes was called for from aged care, health providers, and researchers, to better use these data for quality improvement and health advancement for New Zealanders. A national research network has been established, providing a medium for researchers to form relationships and collaborate on interRAI research with a goal of translating routinely collected interRAI data to improve clinical care, patient experience, service development, and quality improvement. In 2023, the network members met (hybrid: in-person and online) and identified research priorities. These were collated and developed into a national interRAI research agenda by the NZ interRAI Research Network Working Group. Research priorities included reviewing the interRAI assessment processes, improving methods for data linkage to national data sets, exploring how Indigenous Data Sovereignty can be upheld, as well as a variety of clinically focused research topics. Implications for Practice, Policy, and Research: This appears to be the first time national interRAI research priorities have been formally identified. Priorities identified have the potential to inform quality and clinical improvement activities and are likely of international relevance. The methodology described to cocreate the research priorities will also be of wider significance for those looking to do so in other countries.

Engaging Alkenes in Metallaphotoredox: A Triple Catalytic, Radical Sorting Approach to Olefin-Alcohol Cross-Coupling.

Metallaphotoredox cross-coupling is a well-established strategy for generating clinically privileged aliphatic scaffolds via single-electron reactivity. Correspondingly, expanding metallaphotoredox to encompass new C(sp3)-coupling partners could provide entry to a novel, medicinally relevant chemical space. In particular, alkenes are abundant, bench-stable, and capable of versatile C(sp3)-radical reactivity via metal-hydride hydrogen atom transfer (MHAT), although metallaphotoredox methodologies invoking this strategy remain underdeveloped. Importantly, merging MHAT activation with metallaphotoredox could enable the cross-coupling of olefins with feedstock partners such as alcohols, which undergo facile open-shell activation via photocatalysis. Herein, we report the first C(sp3)-C(sp3) coupling of MHAT-activated alkenes with alcohols by performing deoxygenative hydroalkylation via triple cocatalysis. Through synergistic Ir photoredox, Mn MHAT, and Ni radical sorting pathways, this branch-selective protocol pairs diverse olefins and methanol or primary alcohols with remarkable functional group tolerance to enable the rapid construction of complex aliphatic frameworks.

The prokaryotic and eukaryotic microbiome of Pacific oyster spat is shaped by ocean warming but not acidification.

Pacific oysters (Magallana gigas, a.k.a. Crassostrea gigas), the most widely farmed oysters, are under threat from climate change and emerging pathogens. In part, their resilience may be affected by their microbiome, which, in turn, may be influenced by ocean warming and acidification. To understand these impacts, we exposed early-development Pacific oyster spat to different temperatures (18°C and 24°C) and pCO2 levels (800, 1,600, and 2,800 µatm) in a fully crossed design for 3 weeks. Under all conditions, the microbiome changed over time, with a large decrease in the relative abundance of potentially pathogenic ciliates (Uronema marinum) in all treatments with time. The microbiome composition differed significantly with temperature, but not acidification, indicating that Pacific oyster spat microbiomes can be altered by ocean warming but is resilient to ocean acidification in our experiments. Microbial taxa differed in relative abundance with temperature, implying different adaptive strategies and ecological specializations among microorganisms. Additionally, a small proportion (~0.2% of the total taxa) of the relatively abundant microbial taxa were core constituents (>50% occurrence among samples) across different temperatures, pCO2 levels, or time. Some taxa, including A4b bacteria and members of the family Saprospiraceae in the phyla Chloroflexi (syn. Chloroflexota) and Bacteroidetes (syn. Bacteroidota), respectively, as well as protists in the genera Labyrinthula and Aplanochytrium in the class Labyrinthulomycetes, and Pseudoperkinsus tapetis in the class Ichthyosporea were core constituents across temperatures, pCO2 levels, and time, suggesting that they play an important, albeit unknown, role in maintaining the structural and functional stability of the Pacific oyster spat microbiome in response to ocean warming and acidification. These findings highlight the flexibility of the spat microbiome to environmental changes.IMPORTANCEPacific oysters are the most economically important and widely farmed species of oyster, and their production depends on healthy oyster spat. In turn, spat health and productivity are affected by the associated microbiota; yet, studies have not scrutinized the effects of temperature and pCO2 on the prokaryotic and eukaryotic microbiomes of spat. Here, we show that both the prokaryotic and, for the first time, eukaryotic microbiome of Pacific oyster spat are surprisingly resilient to changes in acidification, but sensitive to ocean warming. The findings have potential implications for oyster survival amid climate change and underscore the need to understand temperature and pCO2 effects on the microbiome and the cascading effects on oyster health and productivity.

Health and illness beliefs in adults with tuberculosis infection during the COVID-19 pandemic in the UK.

Background: COVID-19 disrupted the TB prevention programme in the UK, especially for TB infection (TBI) care. We explore whether experience of the COVID-19 pandemic impacted on patients' perceptions of TBI and its treatment. Methods: Semi-structured interviews were conducted as part of the Research to Improve Detection and Treatment of TBI (RID-TB) programme, exploring perceptual and practical barriers to TBI treatment. Nineteen people diagnosed with TBI were interviewed between August 2020 and April 2021. Recordings were transcribed and analysed using a constant comparative approach, allowing for a dynamic and iterative exploration of themes. Themes are organised using the Perceptions and Practicalities Approach. Findings: Some participants perceived TBI as a risk factor for increased susceptibility to COVID-19, while some thought that treatment for TBI might protect against COVID-19 or mitigate its effects. Adaptations to TB services (e.g., remote follow-up) and integrated practices during the COVID-19 restrictions (e.g., medication being posted) addressed some practical barriers to TBI treatment. However, we identified beliefs about TBI and COVID-19 that are likely to act as barriers to engagement with TBI treatment, including: interpreting service delays as an indication of TBI not being serious enough for treatment and concerns about contracting COVID-19 in TB clinics. Interpretation: COVID-19 and TBI service delays influence people's perceptions and practical barriers to TBI treatment adherence. Failure to address these beliefs may lead to people's concerns about their treatment not being fully addressed. Utilised service adaptations like remote consultations to address practical barriers may be relevant beyond COVID-19. Funding: NIHR RID-TB Program (RP-PG-0217-20009).

Persistent Opioid Use After Hospital Admission From Surgery in New Zealand: A Population-Based Study.

BACKGROUND: Persistent opioid use (POU) is common after surgery and is associated with an increased risk of mortality and morbidity. There have been no population-based studies exploring POU in opioid-naïve surgical patients in New Zealand (NZ). This study aimed to determine the incidence and risk factors for POU in opioid-naïve patients undergoing surgery in all NZ hospitals. METHOD: We included all opioid-naïve patients who underwent surgery without a concomitant trauma diagnosis and received opioids after discharge from any NZ hospital between January 2007 and December 2019. Patients were considered opioid naïve if no opioids had been dispensed to them or if they did not have a prior diagnosis of an opioid-use disorder up to 365 days preceding the index date. The primary outcome was the incidence of POU, defined a priori as opioid use after discharge between 91 and 365 days. We used a multivariable logistic regression to identify risk factors for POU. RESULTS: We identified 1789,407 patients undergoing surgery with no concomitant diagnosis of trauma; 377,144 (21.1%) were dispensed opioids and 260,726 patients were eligible and included in the analysis. Of those included in the final sample, 23,656 (9.1%; 95% confidence interval [CI], 9.0%-9.2%) developed POU. Risk factors related to how opioids were prescribed included: changing to different opioid(s) after discharge (adjusted odds ratio [aOR], 3.21; 95% CI, 3.04-3.38), receiving multiple opioids on discharge (aOR, 1.37; 95% CI, 1.29-1.45), and higher total oral morphine equivalents (>400 mg) (aOR, 1.23; 95% CI, 1.23-1.45). Conversely, patients who were coprescribed nonopioid analgesics on discharge had lower odds of POU (aOR, 0.91; 95% CI, 0.87-0.95). Only small differences were observed between different ethnicities. Other risk factors associated with increased risk of POU included undergoing neurosurgery (aOR, 2.02; 95% CI, 1.83-2.24), higher comorbidity burden (aOR, 1.90; 95% CI, 1.75-2.07), preoperative nonopioid analgesic use (aOR, 1.65; 95% CI, 1.60-1.71), smoking (aOR, 1.44; 95% CI, 1.35-1.54), and preoperative hypnotics use (aOR, 1.35; 95% CI, 1.28-1.42). CONCLUSIONS: Approximately 1 in 11 opioid-naïve patients who were dispensed opioids on surgical discharge, developed POU. Potentially modifiable risk factors for POU, related to how opioids were prescribed included changing opioids after discharge, receiving multiple opioids, and higher total dose of opioids given on discharge. Clinicians should discuss the possibility of developing POU with patients before and after surgery and consider potentially modifiable risk factors for POU when prescribing analgesia on discharge after surgery.

Vaccine decision making in New Zealand: a discrete choice experiment.

BACKGROUND: Vaccine hesitancy is a significant threat to global health. A key part of addressing hesitancy is to ensure that public health messaging prioritises information that is considered important to the public. This study aimed to examine how different vaccine characteristics affect public preferences for vaccines in New Zealand, what trade-offs they are willing to make between different vaccine characteristics, and how their preferences are affected by their vaccine-related conspiracy beliefs and COVID-19 vaccination status. METHODS: An online discrete choice experiment (DCE) was designed to elicit individual preferences about vaccines using the 1000minds platform. Members of the general population of New Zealand aged ≥ 18 years were invited to complete the DCE. Participants were asked to indicate their preference between two options showing different combinations of vaccine characteristics. Data on sociodemographic characteristics were collected. Beliefs were measured using the vaccine conspiracy beliefs scale (VCBS) with scores ≥ 19 indicating strong vaccine-related conspiracy beliefs. The DCE was analysed using the PAPRIKA method (Potentially All Pairwise RanKings of all possible Alternatives) and preferences compared between respondents with high versus low VCBS scores and vaccinated versus unvaccinated respondents for COVID-19. RESULTS: A total of 611 respondents from 15 regions completed the DCE. Mean (SD) age was 45.9 (14.7) years with most having had 2 or more doses of the coronavirus vaccine (86%). Mean (SD) VCBS score was 18.5 (12.4) indicating moderate vaccine-related conspiracy beliefs. Risk of severe adverse effects was the most highly valued vaccine characteristic, followed by vaccine effectiveness and duration of protection. Vaccine origin and route of administration were ranked least important. Respondents scoring high on the VCBS placed less value on the effectiveness of vaccines but greater value on development time and total number of doses (p < 0.001). COVID-19 unvaccinated respondents ranked development time and total number of doses more highly than those vaccinated respondents (p < 0.001). CONCLUSIONS: Risk of severe adverse effects, vaccine effectiveness and duration of protection were rated by the New Zealand public as the top three most important vaccine characteristics. This information is important for informing public health messaging to promote vaccine uptake and inform vaccine decision-making.

Evaluating the Feasibility of a Community Pharmacy-Delivered Behaviour Change Intervention to Reduce Reliever Reliance in Asthma.

Purpose: The aim of this study was to evaluate the feasibility of a community pharmacy-delivered intervention to shift patients' beliefs about short-acting beta2 agonists (SABA) in asthma management. The study targeted individual beliefs about SABA and assessed actual SABA use, focusing on reducing SABA use as well as adherence to inhaled corticosteroids (ICS) as a preventive measure. Patients and Methods: This non-randomized, before-and-after feasibility study enrolled participants with asthma from four community pharmacies in Auckland, New Zealand. Eligible participants were aged 18 years and above and were prescribed a SABA for their asthma. The intervention included the SABA reliance questionnaire to determine the degree of SABA reliance, verbal discussions with pharmacists personalised according to the degree of SABA reliance identified, and referral to general practitioners as appropriate. Results: Of the 44 patients who consented into the study, 19 were in the control group and 16 in the intervention group. Recruitment and retention were modest, with 10 control and five intervention participants completing the 90-day follow-up. Although not statistically significant, preliminary results indicated reduced SABA reliance and increased ICS adherence in the intervention group, and reduced SABA refill. Feedback showed that 78% of intervention participants found the information easy to understand, and 56% expressed intent to consult their general practitioners. Pharmacy staff found the intervention feasible but noted time constraints as a barrier to intervention delivery. Conclusion: The study demonstrates that a community pharmacy-delivered intervention is feasible and acceptable to both patients and pharmacists. While preliminary results show a positive effect on reducing SABA reliance and improvement of ICS adherence, the results were not statistically significant due to the small numbers recruited. This suggests a larger randomised trial is indicated. This intervention holds promise for addressing the over-reliance on SABA in asthma management and improving adherence to preventive therapies.

Carcinoma In Situ (CIS): Is There a Difference in Efficacy between Various BCG Strains? A Comprehensive Review of the Literature.

Introduction: Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy is the standard of care for high-risk and intermediate-risk non-muscle-invasive bladder cancer (NMIBC) as well as for Carcinoma in situ (CIS). Evidence supports that the different BCG strains, despite genetic variability, are equally effective clinically for preventing the recurrence and progression of papillary NMIBC. The available evidence regarding possible differences in clinical efficacy between various BCG strains in CIS is lacking. Methods: We reviewed the literature on the efficacy of different BCG strains in patients with CIS (whether primary, secondary, concomitant, or unifocal/multifocal), including randomized clinical trials (RCTs), phase II/prospective trials, and retrospective studies with complete response rates (CRR), recurrence-free survival (RFS), or progression-free survival (PFS) as endpoints. Results: In most studies, being RCTs, phase II prospective trials, or retrospective studies, genetic differences between BCG strains did not translate into meaningful differences in clinical efficacy against CIS, regardless of the CIS subset (primary, secondary, or concurrent) or CIS focality (unifocal or multifocal). CRR, RFS, and PFS were not statistically different between various BCG strains. None of these trials were designed as head-to-head comparisons between BCG strains focusing specifically on CIS. Limitations include the small sample size of many studies and most comparisons between strains being indirect rather than head-to-head. Conclusions: This review suggests that the clinical efficacy of the various BCG strains appears similar, irrespective of CIS characteristics. However, based on the weak level of evidence available and underpowered studies, randomized studies in this space should be encouraged as no definitive conclusion can be drawn at this stage.

Patterns of opioid use in New Zealand older adults, 2007-2018.

OBJECTIVES: Opioid use has increased globally, dramatically increasing opioid overdose, dependence, abuse and mortality. Limited research is available on opioid use patterns in older adults in New Zealand and internationally. This study aims to address this gap by determining the incidence and prevalence of opioid use among older adults (age ≥65 years) in New Zealand from 2007 to 2018. METHODS: This was a population-based retrospective cohort study conducted using New Zealand national administrative healthcare databases. The annual opioid use incidence (2008-2018) and prevalence (2007-2018) in older adults were determined and stratified by sex, age, and opioid type and strength. We used descriptive statistics to summarise the patterns of opioid dispensing. Data analysis was conducted using MS Excel, and data linking was performed using SQL software. RESULTS: A total of 820,349 older adults were initiated on opioids during the study period. The overall incidence of opioid use in older adults showed a steady increase from 2008 to 2015; similarly, the prevalence steadily increased from 2007 to 2015, and thereafter, both rates fluctuated. A slight decrease in both prevalence and incidence rates was observed in 2018. Codeine and tramadol were the most commonly dispensed opioids during the study period. Females had a higher incidence and prevalence of all opioids than males. CONCLUSIONS: The incidence and prevalence of opioid dispensing increased in New Zealand older adults over time. Monitoring the trends of opioid use in older adults is critical to enable clinicians and policymakers to deliver early interventions to prevent future opioid-related adverse events.

Changes in the Incidence and Human Papillomavirus-Positive Portion of Oropharyngeal Squamous Cell Carcinoma in Hong Kong.

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is rising in the West, but little is known in Asia. This study elucidated changes in the incidence and HPV-positive portion of OPSCC in Hong Kong. Data from population-based cancer registry were used to analyze the incidence of OPSCC in association with other head and neck cancers. Archived tumor tissues were tested for HPV. From 1986 to 2020, there was a marked decrease in the incidence of nasopharyngeal and laryngeal cancers, but a persistent increase in OPSCC from 36 cases in 1986 to 116 cases in 2020. The average positive rate for high-risk HPV was 36.1% (112/310) among OPSCC diagnosed in 2010-2020. The HPV-positive rate in recent years was significantly higher than earlier cases (tonsil SCC: 64.7% (55/85) in 2016-2020 vs. 40.4% (19/47) in 2010-2015, p = 0.007). Patients with HPV-positive tonsil cancers were significantly younger than those negative (mean [SD]: 58.9 [9.9] vs. 64.3 [13.3] years, p = 0.006), but no significant difference was observed between genders. A persistent increase in the incidence of oropharyngeal cancer over the last few decades was observed in Hong Kong, which can be explained by the remarkable increase in HPV-positive tonsil cancers.

Prevalence and interpretation of AFF immunostain of DEK::AFF2 fusion-associated papillary squamous cell carcinoma in a retrospective cohort of recurrent sinonasal papillomas.

DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a novel entity characterized by its unique translocation and malignant clinical course. In this study, AFF immunohistochemistry (IHC) was performed in recurrent sinonasal papillomas for reviewing the prevalence of undiagnosed DEK::AFF2 carcinomas and to investigate the performance of AFF IHC in diagnosis of DEK::AFF2 carcinomas. Recurrent sinonasal papillomas after surgical excision in a two-decade period were retrieved. Histologic slides were reviewed for features of DEK::AFF2 carcinoma. AFF IHC was performed, and cases with any (> 1%) nuclear positivity were validated by DEK break apart fluorescence in situ hybridization. Totally 43 cases were included, comprising 28 inverted, 6 exophytic, one oncocytic, and 8 non-specified sinonasal papillomas. Five (11.6%) cases exhibited positivity to AFF IHC. Three cases exhibited patchy weak to moderate staining intensity predominantly in a granular cytoplasmic pattern. Two cases exhibited strong and diffuse (> 90%) nuclear staining. Cases showing weak staining were negative for DEK rearrangement, while those with strong staining were positive. Both cases of DEK::AFF2 carcinoma showed aggressive behavior with extensive local invasion and nodal metastasis. Background stromal plasma cells, when present, consistently showed strong and diffuse staining. AFF IHC was further performed in plasmacytoma samples as control and showed strong and diffuse immunoreactivity. A significant minority of recurrent sinonasal papillomas represent DEK::AFF2 carcinomas. Granular, cytoplasmic, or incomplete AFF staining should be considered as negative. In view of the rarity of DEK::AFF2 carcinomas, plasma cells and plasma cell neoplasms are potential for internal and surrogate external controls.

Beliefs about antibiotics, perceptions of antimicrobial resistance, and antibiotic use: initial findings from a multi-country survey.

OBJECTIVES: To examine public beliefs about antibiotics, AMR, and knowledge of antibiotic use, and how these relate to self-reported antibiotic use. METHODS: Two hundred and fifty participants from 23 countries completed a cross-sectional, online survey assessing beliefs about antibiotics and AMR, knowledge of antibiotics, and antibiotic use. Descriptive statistics, Mann-Whitney U tests and Spearman's ρ correlations were used to understand relationships between outcomes. KEY FINDINGS: Respondents generally viewed antibiotics positively, with particularly strong beliefs regarding their benefit (M = 16.48 out of 20, SD = 2.62) and few concerns regarding their harm (M = 3.98 out of 10, SD = 1.82). Greater benefit beliefs about antibiotics were associated with fewer concerns about their overuse (P < .0001) and harm (P < .0001). Stronger perceived importance of AMR was associated with greater beliefs about the benefits of antibiotics (P = .006), greater concerns about their overuse (P = .009), and increased knowledge of appropriate use (P = .006). Those who reported inappropriately using their last antibiotics had greater concerns about overuse (P = .12) and less knowledge regarding appropriate use (P = .015), compared to those who did not. CONCLUSIONS: Generally, the public tends to view antibiotics as having strong benefits and have few concerns about their harm, which may have implications for inappropriate use. These initial findings highlight beliefs that could be targeted in messages to reduce inappropriate demand for antibiotics.

Poor sleep quality and its associated neurocognitive function in children with obesity with or without obstructive sleep apnea.

OBJECTIVE: To evaluate the associations of OSA severity, snoring symptoms, subjective sleep quality, and daytime sleepiness with executive functioning and behaviors in children with obesity. METHODS: This was a cross-sectional study of children aged 8-18 years with obesity and symptoms suggestive of OSA. All participants underwent an overnight polysomnography and completed a set of questionnaires to assess their sleep-related breathing disordered (SRBD) symptoms [Pediatric Sleep Questionnaire (SRBD-PSQ)], sleep quality [Pittsburgh Sleep Quality Index (PSQI)], executive function [Behavior Rating Inventory of Executive Function (BRIEF)], and inattention and hyperactivity symptoms (Conners-3 Parent Short Form). RESULTS: A total of 85 children (62% male, mean age: 13.9 ± 3.0 years) were included in this analysis, of whom 36, 16, and 33 were categorized into the non-OSA (obstructive apnea hypopnea index, OAHI < 1.5/h), mild OSA (OAHI 1.5-5/h), and moderate-severe OSA (OAHI ≥ 5/h) groups, respectively. Of 85 participants, 27 (32%) were classified with poor sleep quality (PSQI composite score ≥ 8). From multiple linear regression analyses, poor sleep quality and sleepiness were both independently associated with higher BRIEF behavioral regulation T-score, metacognition T-score, and global executive composite T-score in the fully adjusted model. In addition, poor sleep quality was also independently associated with higher Conners-3 inattention and executive functioning T-scores, while greater sleepiness was also associated with a higher learning problem T-score. The presence of OSA and snoring were not associated with any cognitive outcomes. CONCLUSIONS: Subjective sleep quality and daytime sleepiness, but not OSA severity and snoring symptoms, were independently associated with executive functioning and behavioral problems in children with obesity.

Uncovering the magnitude of African pangolin poaching with extensive nanopore DNA genotyping of seized scales.

Trade in pangolins is illegal, and yet tons of their scales and products are seized at various ports. These large seizures are challenging to process and comprehensively genotype for upstream provenance tracing and species identification for prosecution. We implemented a scalable DNA barcoding pipeline in which rapid DNA extraction and MinION sequencing were used to genotype a substantial proportion of pangolin scales subsampled from 2 record shipments seized in Singapore in 2019 (37.5 t). We used reference sequences to match the scales to phylogeographical regions of origin. In total, we identified 2346 cytochrome b (cytb) barcodes of white-bellied (Phataginus tricuspis) (from 1091 scales), black-bellied (Phataginus tetradactyla) (227 scales), and giant (Smutsia gigantea) (1028 scales) pangolins. Haplotype diversity was higher for P. tricuspis scales (121 haplotypes, 66 novel) than that for P. tetradactyla (22 haplotypes, 15 novel) and S. gigantea (25 haplotypes, 21 novel) scales. Of the novel haplotypes, 74.2% were likely from western and west-central Africa, suggesting potential resurgence of poaching and newly exploited populations in these regions. Our results illustrate the utility of extensively subsampling large seizures and outline an efficient molecular approach for rapid genetic screening that should be accessible to most forensic laboratories and enforcement agencies.

Revelación de la magnitud de la caza furtiva del pangolín africano mediante el genotipo extenso de nanoporos de ADN de escamas incautadas Resumen Aunque el mercado de pangolines es ilegal, se incautan toneladas de sus escamas y productos derivados en varios puertos comerciales. Es un reto procesar estas magnas incautaciones y obtener el genotipo completo para usarlo en la trazabilidad logística ascendente e identificación de la especie y así imponer sanciones. Implementamos una canalización escalable del código de barras de ADN en el cual usamos la extracción rápida de ADN y la secuenciación MinION para obtener el genotipo de una proporción sustancial de las escamas de pangolín submuestreadas en dos cargamentos incautados en 2019 en Singapur (37.5 t). Usamos secuencias referenciales para emparejar las escamas con las regiones filogeográficas de origen. Identificamos en total 2,346 códigos de citocromo b (cytb) del pangolín de vientre blanco (Phataginus tricuspis) (de 1,091 escamas), de vientre negro (P. tetradactyla) (227 escamas) y del pangolín gigante (Smutsia gigantea) (1,028 escamas). La diversidad de haplotipos fue mayor en las escamas de P. tricuspis (121 haplotipos, 66 nuevos) que en las de P. tetradactyla (22 haplotipos, 15 nuevos) y S. gigantea (25 haplotipos, 21 nuevos). De los haplotipos nuevos, el 74.2% probablemente provenía del occidente y centro­occidente de África, lo que sugiere un resurgimiento potencial de la caza furtiva y poblaciones recién explotadas en estas regiones. Nuestros resultados demuestran la utilidad de submuestrear extensivamente las grandes incautaciones y esboza una estrategia molecular eficiente para un análisis genético rápido que debería ser accesible para la mayoría de los laboratorios forenses y las autoridades de aplicación.

Asthma control and associated risk factors among adults with current asthma: Findings from 2019 behavioral risk factor surveillance system asthma call-back survey.

BACKGROUND: Despite the availability of effective treatments, many adults with asthma have uncontrolled asthma. Uncontrolled asthma can lead to severe exacerbations. This study aimed to determine the prevalence and predictors of uncontrolled asthma among adults (≥18 years) with current asthma in the United States. METHODS: We analyzed the 2019 Behavior Risk Factor Surveillance System Asthma Call-Back Survey data from 27 states. Asthma control status was classified as "well-controlled" or "uncontrolled" according to the National Asthma Education and Prevention guidelines. The study population consisted of 7937 adults (weighted n = 13,793,220) with current asthma. We used multivariable logistic regression models to identify predictors of uncontrolled asthma. RESULTS: Overall, 62 % of adults with asthma reported having uncontrolled asthma, and 26 % had emergency or urgent care visits or hospitalizations in the past year. Potentially modifiable risk factors associated with uncontrolled asthma included cost barriers to asthma-related healthcare (OR = 2.94; 95%CI 1.96-4.40), complementary and alternative medicine use (OR = 1.84; 95%CI 1.45-2.32), current smoking (OR = 2.25; 95%CI 1.48-3.44), obesity (OR = 1.39; 95%CI 1.02-1.89), COPD (OR = 1.98; 95%CI 1.43-2.74), depression (OR = 1.47; 95%CI 1.16-1.88), fair/poor general health (OR = 1.54; 95%CI 1.14-2.07), household income <$15,000 (OR = 2.59; 95%CI 1.42-4.71), and less than high school education (OR = 2.59; 95%CI 1.42-4.71). Non-modifiable risk factor was Hispanic ethnicity (OR = 1.73; 95%CI 1.09-2.73). CONCLUSION: Our findings suggest that uncontrolled asthma is common among adults and can be impacted by several factors. Effective asthma control programs are needed to improve asthma management and reduce unnecessary healthcare utilization.

Visualisation and detection of latent DNA deposited by pangolin scales onto plastic packaging materials.

We report on the detection and visualisation of latent DNA from pangolin scales deposited onto a plastic packaging material through the use of a nucleic acid staining dye. This latent DNA deposited by pangolin scales was subsequently isolated and analysed using DNA barcoding method. Pangolins are the most illegally traded mammalian species due to the demand for their scales and meat. The demand for their scales were mostly fuelled by its use in traditional medicines. The scales are usually packed into bags and transported globally via sea routes. This is the first report detailing the detection of trace latent DNA from processed wildlife products, on surfaces of bags that they were packaged in. Prior to this report, it was not known if the dried pangolin scales contained transferable quantities of biological material for DNA analyses. To address this, scales were removed from a roadkill Sunda pangolin (Manis javanica), processed by drying and packaged into one of five plastic bags. The presence of pangolin latent DNA was detected on the surface of the plastic bags and visualised using Diamond™ nucleic acid dye. Swabs were then used to recover the stained biological material from various locations in the five bags. The DNA was isolated and quantified using a newly designed quantitative PCR (qPCR) specific to M. javanica to amplify a fragment of the mitochondrial DNA cytochrome b gene. There was a positive correlation between the number of stained particles and DNA quantity, and a greater number of stained particles were found at the bottom of the bag than were found at the top. Conventional PCR targeting part of the cyt b gene amplified a product from all 30 samples taken from the bags and in all cases, sequence data generated matched that of the Sunda pangolin, as expected. All negative controls yielded no results. The method described here is the very first use of a nucleic acid staining dye to detect latent DNA from a mammalian species, other than humans, and highlights the opportunity for further use of Diamond™ nucleic acid dye in wildlife forensic science. It is anticipated that this method will be invaluable in retrieving latent DNA deposited by wildlife products from the environment in which they were contained, to determine the presence of these illegal wildlife products even when previously hidden, inaccessible, or no longer present physically. Further research is required to understand if the use on non-human mammalian wildlife species is feasible.