AKT and EZH2 inhibitors kill TNBCs by hijacking mechanisms of involution.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and has the highest rate of recurrence1. The predominant standard of care for advanced TNBC is systemic chemotherapy with or without immunotherapy; however, responses are typically short lived1,2. Thus, there is an urgent need to develop more effective treatments. Components of the PI3K pathway represent plausible therapeutic targets; more than 70% of TNBCs have alterations in PIK3CA, AKT1 or PTEN3-6. However, in contrast to hormone-receptor-positive tumours, it is still unclear whether or how triple-negative disease will respond to PI3K pathway inhibitors7. Here we describe a promising AKT-inhibitor-based therapeutic combination for TNBC. Specifically, we show that AKT inhibitors synergize with agents that suppress the histone methyltransferase EZH2 and promote robust tumour regression in multiple TNBC models in vivo. AKT and EZH2 inhibitors exert these effects by first cooperatively driving basal-like TNBC cells into a more differentiated, luminal-like state, which cannot be effectively induced by either agent alone. Once TNBCs are differentiated, these agents kill them by hijacking signals that normally drive mammary gland involution. Using a machine learning approach, we developed a classifier that can be used to predict sensitivity. Together, these findings identify a promising therapeutic strategy for this highly aggressive tumour type and illustrate how deregulated epigenetic enzymes can insulate tumours from oncogenic vulnerabilities. These studies also reveal how developmental tissue-specific cell death pathways may be co-opted for therapeutic benefit.

Annual hepatitis C testing and positive tests among gay and bisexual men in Australia from 2016 to 2022: a serial cross-sectional analysis of sentinel surveillance data.

OBJECTIVE: Guidelines recommend annual hepatitis C virus (HCV) testing for gay and bisexual men (GBM) with HIV and GBM prescribed HIV pre-exposure prophylaxis (PrEP). However, there is a limited understanding of HCV testing among GBM. We aimed to examine trends in HCV testing and positivity from 2016 to 2022. METHODS: Using sentinel surveillance data, we examined the proportion of GBM with at least one test and the proportion with a positive test in each year for HCV antibody testing among GBM with no previous HCV positive test, HCV RNA testing among GBM with a positive antibody test but no previous positive RNA test (naïve RNA testing), and HCV RNA testing among people who had a previous RNA positive test and a subsequent negative test (RNA follow-up testing). Trends were examined using logistic regression from 2016 to 2019 and 2020 to 2022. RESULTS: Among GBM with HIV, from 2016 to 2019 antibody testing was stable averaging 55% tested annually. Declines were observed for both naïve HCV RNA testing (75.4%-41.4%: p<0.001) and follow-up HCV RNA testing (70.1%-44.5%: p<0.001). Test positivity declined for HCV antibody tests (2.0%-1.3%: p=0.001), HCV RNA naïve tests (75.4%-41.4%: p<0.001) and HCV RNA follow-up tests (11.3%-3.3%: p=0.001). There were minimal or no significant trends from 2020 to 2022.Among GBM prescribed PrEP, antibody testing declined from 2016 to 2019 (79.4%-69.4%: p<0.001) and was stable from 2020 to 2022. Naïve and follow-up HCV RNA testing was stable with an average of 55% and 60% tested each year, respectively. From 2016-2019, the proportion positive from HCV RNA naïve tests declined (44.1%-27.5%: p<0.046) with no significant change thereafter. Positive follow-up HCV RNA tests fluctuated with no or one new positive test among this group in most years. CONCLUSION: The proportion of GBM with positive HCV tests has declined, however a substantial proportion are not tested annually. A renewed focus on HCV testing, and treatment where required, is warranted to achieve HCV elimination among GBM in Australia.

Examining the Role of Aguas Frescas in Assessment of Sugary-Drink Intake among Mexican and Mexican American Adults.

BACKGROUND: Aguas frescas are Mexican drinks that are typically made with water, sugar, and fruit. Aguas frescas may be a significant component of sugary-drink intake among Mexican and Mexican-American (MA) adults. However, it is unclear whether survey respondents report aguas frescas consumption when it is not specifically queried in standardized beverage frequency instruments. OBJECTIVES: This study examined the prevalence of aguas frescas consumption, the sociodemographic correlates of aguas frescas intake, and how specifically querying aguas frescas intake affects sugary-drink estimates among Mexican and MA adults. METHODS: Cross-sectional, online surveys were conducted in 2021 with 5377 Mexican and 3073 MA adults as part of the International Food Policy Study. Past 7-d consumption of sugar-sweetened beverages (SSBs), sugary drinks, and aguas frescas were assessed along with relevant covariates. Weighted analyses included logistic and linear regression, including models with correlation structure. RESULTS: An estimated 61.7% of Mexican and 28.7% of MA adults consumed aguas frescas. In Mexico, consumption was associated with females, low education, perceiving oneself as having about the right weight, being good to excellent health, and consuming an unhealthy amount of sugary drinks. For MAs, intake was associated with being younger, speaking Spanish, and perceiving oneself as being underweight or about the right weight. Among Mexican adults who consumed aguas frescas but did not report them unless specifically queried, the volume of SSB intake was 67.9% higher for females and 64.3% higher for males when aguas frescas were included. Among MAs, SSB intake was 56.9% higher for females and 44.1% higher for males. Most participants (79.9%-85.2%) remained in the same sugary-drink tertiles when including compared with excluding aguas frescas. CONCLUSIONS: Aguas frescas should be queried during beverage intake assessments, as they contribute a nontrivial amount of added sugars to the diets of many Mexican and MA adults.

Hepatitis C virus reinfection incidence among gay and bisexual men with HIV in Australia from 2016 to 2020.

BACKGROUND: There is some concern that hepatitis C virus (HCV) reinfection might impact HCV micro-elimination efforts among gay and bisexual men (GBM) with HIV. However, there is a limited understanding of reinfection incidence in the context of unrestricted government-funded HCV treatment. We aimed to estimate HCV reinfection incidence among GBM with HIV in Australia from 2016 to 2020. METHODS: Data were from 39 clinics participating in ACCESS, a sentinel surveillance network for blood borne viruses and sexually transmissible infections across Australia. GBM with HIV who had evidence of treatment or spontaneous clearance with at least one positive HCV RNA test, a subsequent negative HCV RNA test, and at least one additional HCV RNA test between 1st January 2016 and 31st December 2020 were eligible for inclusion. A new HCV RNA positive test and/or detectable viral load was defined as a reinfection. Generalised linear modelling was used to examine trends in reinfection. RESULTS: Among 12 213 GBM with HIV who had at least one HCV test, 540 were included in the reinfection incidence analysis, of whom 38 (7%) had evidence of reinfection during the observation period. Over 1124 person-years of follow-up, the overall rate of reinfection was 3.4/100PY (95% CI 2.5-4.6). HCV reinfection incidence declined on average 30% per calendar year (Incidence Rate Ratio 0.70, 95% CI 0.54-0.91). CONCLUSION: HCV reinfection incidence has declined among GBM with HIV in Australia since government-funded unrestricted DAAs were made available. Ongoing HCV RNA testing following cure and prompt treatment for anyone newly diagnosed is warranted to sustain this.

Late lesion growth following endovascular therapy: is 24 hours too early to assess acute infarct size including the effects of secondary injury?

Introduction Stroke lesion volume on MRI or CT provides objective evidence of tissue injury as a consequence of ischemic stroke. Measurement of "final" lesion volume at 24hr following endovascular therapy (post-EVT) has been used in multiple studies as a surrogate for clinical outcome. However, despite successful recanalization, a significant proportion of patients do not experience favorable clinical outcome. The goals of this study were to quantify lesion growth during the first week after treatment, identify early predictors, and explore the association with clinical outcome. Methods This is a prospective study of stroke patients at two centers who met the following criteria: i) anterior large vessel occlusion (LVO) acute ischemic stroke, ii) attempted EVT, and iii) had 3T MRI post-EVT at 24hr and 5-day. We defined "Early" and "Late" lesion growth as ≥10mL lesion growth between baseline and 24hr DWI, and between 24hr DWI and 5-day FLAIR, respectively. Complete reperfusion was defined as >90% reduction of the volume of tissue with perfusion delay (Tmax>6sec) between pre-EVT and 24hr post-EVT. Favorable clinical outcome was defined as modified Rankin scale (mRS) of 0-2 at 30 or 90 days. Results One hundred twelve patients met study criteria with median age 67 years, 56% female, median admit NIHSS 19, 54% received IV or IA thrombolysis, 66% with M1 occlusion, and median baseline DWI volume 21.2mL. Successful recanalization was achieved in 87% and 68% had complete reperfusion, with an overall favorable clinical outcome rate of 53%. Nearly two thirds (65%) of the patients did not have Late lesion growth with a median volume change of -0.3mL between 24hr and 5-days and an associated high rate of favorable clinical outcome (64%). However, ~1/3 of patients (35%) did have significant Late lesion growth despite successful recanalization (87%: 46% mTICI 2b/ 41% mTICI 3). Late lesion growth patients had a 27.4mL change in Late lesion volume and 30.1mL change in Early lesion volume. These patients had an increased hemorrhagic transformation rate of 68% with only 1 in 3 patients having favorable clinical outcome. Late lesion growth was independently associated with incomplete reperfusion, hemorrhagic transformation, and unfavorable outcome. Conclusion Approximately 1 out of 3 patients had Late lesion growth following EVT, with a favorable clinical outcome occurring in only 1 out of 3 of these patients. Most patients with no Early lesion growth had no Late lesion growth. Identification of patients with Late lesion growth could be critical to guide clinical management and inform prognosis post-EVT. Additionally, it can serve as an imaging biomarker for the development of adjunctive therapies to mitigate reperfusion injury.

Assessing transnational spillover effects of Mexico's front-of-package nutritional labeling system among Mexican Americans in the US.

OBJECTIVE: In 2020, Mexico implemented innovative front-of-package nutrition warning labels (FoPWLs) for packaged foods to increase the salience and understanding of nutrition information. This study evaluated Mexican Americans' self-reported exposure to Mexican FoPWLs and self-reported effects of FoPWLs on purchasing behavior. METHODS: The 2021 International Food Policy Study surveyed online panels of adult Mexican Americans in the US (n = 3361) to self-report on buying food at Mexican-oriented stores, noticing Mexican FoPWLs, and being influenced by FoPWLs to purchase less of eight different unhealthy foods (each assessed separately). After recoding the frequency of buying foods in Mexican stores and noticing FoPWLs (i.e., "often" or "very often" vs. less often), logistic models regressed these outcomes on sociodemographics, adjusting for post-stratification weights. RESULTS: Most participants (88.0%) purchased foods in Mexican stores. Of these, 64.1% reported noticing FoPWLs, among whom many reported that FoPWLs influenced them to buy fewer unhealthy foods (range = 32% [snacks like chips] - 44% [colas]). Participants were more likely to buy foods in Mexican stores and notice FoPWLs if they were younger, had ≥two children at home vs no children (AOR = 1.40, 95%CI = 1.15-1.71; AOR = 1.37, 95%CI = 1.03-1.80, respectively), and more frequently used Spanish (AOR = 1.91, 95%CI = 1.77-2.07; AOR = 1.87, 95%CI = 1.69-2.07). Also, high vs. low education (AOR = 1.51, 95%CI = 1.17-1.94) and higher income adequacy (AOR = 1.37, 95%CI = 1.25-1.51) were positively associated with noticing FoPWLs. Being female and more frequent Spanish use were consistently associated with reporting purchase of fewer unhealthy foods because of FoPWLs. CONCLUSIONS: Many Mexican Americans report both exposure to Mexican FOPWLs and reducing purchases of unhealthy foods because of them.

Characteristics of attrition within the SuperMIX cohort of people who inject drugs: a multiple event discrete-time survival analysis.

BACKGROUND: Compared to the general population, people who inject drugs have poor health and wellbeing. Longitudinal studies can provide insight into factors driving these worse health outcomes but are subject to methodological challenges, such as cohort attrition. The aim of this study was to assess and characterise attrition in a prospective cohort of people who inject drugs in Victoria, Australia. METHODS: Using annually collected self-reported data from The Melbourne Injecting Drug User Cohort Study (SuperMIX) from September 2008 to January 2021, we estimated the incidence of participants being lost-to-follow-up (LTFU), with an episode of being LTFU defined as participants not undertaking a follow-up interview within two years of their last interview. We utilised a multiple event discrete-time survival analysis on participant period-observation data to estimate the associations between key factors and LTFU. Key areas of exposure measurement in analyses were sociodemographic, drug use and mental health. RESULTS: A total of n = 1328 SuperMIX participants completed a baseline interview, with n = 489 (36.8%) LTFU, i.e. not completing a follow-up interview in the following two years. Increased attrition was observed among SuperMIX participants who were: born outside Australia, younger than 30 years, reporting having completed fewer years of education, not residing in stable accommodation, not in stable employment and not on opioid agonist therapy (OAT). CONCLUSIONS: The attrition rate of the SuperMIX cohort has largely been stable throughout the duration of the study. Higher attrition rates among individuals at greater sociodemographic disadvantage and not on OAT suggest that additional efforts are required to retain these participants. Findings also suggest that SuperMIX might not be capturing data on adverse health and wellbeing outcomes among subpopulations at high risk of harm.

Smelly shark, smelly ray: what is infecting you?

AIMS: Although elasmobranchs are consumed worldwide, bacteriological assessments for this group are still sorely lacking. In this context, this study assessed bacteria of sharks and rays from one of the most important landing ports along the Rio de Janeiro coast. METHODS AND RESULTS: Bacteria were isolated from the cloacal swabs of the sampled elasmobranchs. They were cultured, and Vibrio, Aeromonas, and Enterobacterales were isolated and identified. The isolated bacteria were then biochemically identified and antimicrobial susceptibility assays were performed. Antigenic characterizations were performed for Salmonella spp. and Polymerase Chain Reaction (PCR) assays were performed to identify Escherichia coli pathotypes. Several bacteria of interest in the One Health context were detected. The most prevalent Enterobacterales were Morganella morganii and Citrobacter freundii, while Vibrio harveyi and Vibrio fluvialis were the most prevalent among Vibrio spp. and Aeromonas allosacharophila and Aeromonas veronii bv. veronii were the most frequent among Aeromonas spp. Several bacteria also displayed antimicrobial resistance, indicative of Public Health concerns. A total of 10% of Vibrio strains were resistant to trimethoprim-sulfamethoxazole and 40% displayed intermediate resistance to cefoxitin. Salmonella enterica strains displayed intermediate resistance to ciprofloxacin, nalidixic acid and streptomycin. All V. cholerae strains were identified as non-O1/non-O139. The detected E. coli strains did not exhibit pathogenicity genes. This is the first study to perform serology assessments for S. enterica subsp. enterica isolated from elasmobranchs, identifying the zoonotic Typhimurium serovar. Salmonella serology evaluations are, therefore, paramount to identify the importance of elasmobranchs in the epidemiological salmonellosis chain. CONCLUSIONS: The detection of several pathogenic and antibiotic-resistant bacteria may pose significant Public Health risks in Brazil, due to high elasmobranch consumption rates, indicating the urgent need for further bacteriological assessments in this group.

Ecotoxicological assessments of atmospheric biomonitors exposed to urban pollution in a Brazilian metropolis.

Subcellular metal distribution assessments are the most adequate biomonitoring approach to evaluate metal toxicity, instead of total metal assessments This study aimed to assess subcellular metal distributions and associations to the main metal exposure biomarker, metallothionein (MT), in two bromeliad species (Tillandsia usneoides and Tillandsia stricta) exposed established in industrial, urban, and port areas in the metropolitan region of Rio de Janeiro, southeastern Brazil, through an active biomonitoring approach conducted one year. Metals and metalloids in three subcellular fractions (insoluble, thermolabile and thermostable) obtained from the MT purification process were determined by inductively coupled plasma mass spectrometry (ICP-MS). Lower MT concentrations were observed both during the dry sampling periods, associated to the crassulacean acid metabolism (CAM) and during the COVID-19 pandemic, due to reduced urban mobility, decreasing pollutant emissions. The percentage of non-bioavailable metals detected in the insoluble fraction increased throughout the sampling period for both species. Several metals (Cr, Co, Cu, Cd, Mn, Ni, Se, and Zn), most associated with vehicle emissions, the main pollutant source in urban centers, were detected in the thermostable fraction and are, thus, associated with MT through the MT-metal detoxification route. Insoluble metal concentrations were higher in T. stricta, indicating that this species seems less susceptible to cellular metal exposure damage. A potential protective effect of Se and Fe was detected against Pb, suggested by a strong negative correlation, which may be attributed to antioxidant roles and similar uptake routes, respectively.

Lithium and the living kidney donor: Science or stigma?

Nearly 10 000 people are removed from the kidney transplant waiting list each year either due to becoming too ill for transplant or due to death. Live donor kidney transplant (LDKT) provides superior outcomes and survival benefit relative to deceased donor transplant, but the number of LDKT has decreased over the past few years. Therefore, it is of paramount importance that transplant centers employ evaluation processes that safely maximize LDKT. Decisions about donor candidacy should be based on the best available data, rather than on processes prone to bias. Here, we examine the common practice of declining potential donors based solely on treatment with lithium. We conclude that the risk of end-stage renal disease related to lithium treatment is comparable to other generally accepted risks in LDKT. We present this viewpoint to specifically challenge the carte blanche exclusion of individuals taking lithium and highlight the importance of using the best available data relevant to any risk factor, rather than relying on biases, when evaluating potential living kidney donors.

Cultural Sensitivity and Cultural Tailoring: Lessons Learned and Refinements After Two Decades of Incorporating Culture in Health Communication Research.

In this article, we examine progress and challenges in designing, implementing, and evaluating culturally sensitive behavioral interventions by tailoring health communication to groups or individuals. After defining common tailoring constructs (i.e., culture, race, and ethnicity), cultural sensitivity, and cultural tailoring, we examine when it is useful to culturally tailor and address cultural sensitivity in health communication by group tailoring or individual tailoring and when tailoring health communication may not be necessary or appropriate for achieving behavior change. After reviewing selected approaches to cultural tailoring, we critique the quality of research in this domain with a focus on the internal validity of empirical findings. Then we explore the ways in which cultural sensitivity, group targeting, and individual tailoring have incorporated culture in health promotion and health communication. We conclude by articulating yet unanswered questions and suggesting future directions to move the field forward. Expected final online publication date for the Annual Review of Public Health, Volume 45 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

A novel report on the emerging and zoonotic neurotropic fungus Trichosporon japonicum in the brain tissue of the endangered Brazilian guitarfish (Pseudobatos horkelii) off the southeastern coast of Brazil.

Yeast infections have gained significant attention in the field of marine biology in recent years. Among the broad diversity of marine organisms affected by these infections, elasmobranchs (sharks and rays) have emerged as highly susceptible, due to climate change effects, such as increasing water temperatures and pollution, which can alter the composition and abundance of fungal communities. Additionally, injuries, or compromised immune systems resulting from pollution or disease may increase the likelihood of fungal infections in elasmobranchs. Studies are, however, still lacking for this taxonomic group. In this context, this study aimed to screen yeast species in cell cultures obtained from the brain of artisanally captured Pseudobatos horkelii, a cartilaginous fish that, although endangered, is highly captured and consumed worldwide. Fungi were isolated during an attempt to establish primary cultures of elasmobranch neural cells. Culture flasks were swabbed and investigated using morphological, phenotypic, and molecular techniques. Two isolates of the emerging opportunistic pathogen Trichosporon japonicum were identified, with high scores (1.80 and 1.85, respectively) by the MALDI-ToF technique. This is the first report of the basidiomycetous yeast T. japonicum in Pseudobatos horkelii in Brazil. This finding highlights the need for further research to determine the potential impact on elasmobranch health, ecology, as well as on commercial fisheries.

Sustained Inflammation of Breast Tumors after Needle Biopsy.

INTRODUCTION: Needle biopsy is essential for definitive diagnosis of breast malignancy. Significant histologic changes due to tissue damage have been reported in solid tumors. This study investigated the association between time from needle biopsy and inflammation in breast tumors. METHODS: A total of 73 stage I-II invasive breast cancer cases diagnosed by image-guided needle biopsy who had surgery as their first definitive treatment were retrospectively analyzed. Time from biopsy to surgical excision ranged from 8 to 252 days. Histological sections of surgically resected tumors with a visible needle tract were reviewed by histologic evaluation. Data were analyzed by McNemar's test for proportional differences, and the Benjamini-Hochberg procedure was used to assess the association between immune cell prevalence and clinical variables. RESULTS: Characteristic histology changes, including foreign body giant-cell reaction, synovial-cell metaplasia, desmoplastic repair changes, granulation tissue, fat necrosis, and inflammation, were frequently detected adjacent to the needle tract. Spatial comparison indicated that a higher proportion of cases had neutrophils, eosinophils, and macrophages adjacent to the needle tract than tumors distant from it. The presence of inflammatory cells adjacent to the needle tract was not associated with time from biopsy or subtype. Still, plasma cells were associated with residual carrier material from biopsy markers. CONCLUSION: Macrophages and eosinophils are highly abundant and retained adjacent to the needle tract regardless of time from the biopsy.

Effects of front-of-package caffeine and sweetener disclaimers in Mexico: cross-sectional results from the 2020 International Food Policy Study.

OBJECTIVE: Front-of-package warning labels introduced in Mexico in 2020 included disclaimers that caution against allowing children to consume products with non-sugary sweeteners and caffeine. We examined the awareness and use of the disclaimers among Mexican adults and youth 1 month after the regulation was implemented. We also investigated their impact on the perceived healthfulness of industrialised beverages designed for children. DESIGN: Data on the awareness and use of the disclaimers were analysed. Two between-subjects experiments examined the effect of a sweetener disclaimer (Experiment 1, youth and adults) or a caffeine disclaimer (Experiment 2, only adults) on the perceived healthfulness of industrialised beverages. Interactions between experimental conditions and demographic characteristics were tested. SETTING: Online survey in 2020. PARTICIPANTS: Mexican adults (≥18 years, n 2108) and youth (10-17 years, n 1790). RESULTS: Most participants (>80 %) had seen the disclaimers at least rarely, and over 60 % used them sometimes or frequently. The sweetener disclaimer led to a lower perceived healthfulness of a fruit drink (adults: 2·74 ± 1·44; youth: 2·04 ± 0·96) compared with the no-disclaimer condition (adults: 3·17 ± 1·54; youth: 2·32 ± 0·96) (t's: >4·0, P values: <0·001). This effect was larger among older adults and male youth. The caffeine disclaimer did not affect adult's perceived healthfulness of a caffeinated drink (t = 0·861, P value = 0·3894). CONCLUSIONS: There were high awareness and use of the sweeteners and caffeine disclaimers shortly after the warning labels were implemented. The sweetener disclaimer appears to be helping consumers modify their perceptions regarding industrialised beverages for children. Findings may help decision-makers improve the regulation and better target communication strategies.

COVID-19 epidemic modelling for policy decision support in Victoria, Australia 2020-2021.

BACKGROUND: Policy responses to COVID-19 in Victoria, Australia over 2020-2021 have been supported by evidence generated through mathematical modelling. This study describes the design, key findings, and process for policy translation of a series of modelling studies conducted for the Victorian Department of Health COVID-19 response team during this period. METHODS: An agent-based model, Covasim, was used to simulate the impact of policy interventions on COVID-19 outbreaks and epidemic waves. The model was continually adapted to enable scenario analysis of settings or policies being considered at the time (e.g. elimination of community transmission versus disease control). Model scenarios were co-designed with government, to fill evidence gaps prior to key decisions. RESULTS: Understanding outbreak risk following incursions was critical to eliminating community COVID-19 transmission. Analyses showed risk depended on whether the first detected case was the index case, a primary contact of the index case, or a 'mystery case'. There were benefits of early lockdown on first case detection and gradual easing of restrictions to minimise resurgence risk from undetected cases. As vaccination coverage increased and the focus shifted to controlling rather than eliminating community transmission, understanding health system demand was critical. Analyses showed that vaccines alone could not protect health systems and need to be complemented with other public health measures. CONCLUSIONS: Model evidence offered the greatest value when decisions needed to be made pre-emptively, or for questions that could not be answered with empiric data and data analysis alone. Co-designing scenarios with policy-makers ensured relevance and increased policy translation.

Awareness, use and understanding of nutrition labels among adults from five countries: Findings from the 2018-2020 International Food Policy Study.

Few studies have compared the effects of different front-of-package label (FOPL) systems in the 'real world'. This study assessed adults' awareness, use and understanding of nutrition facts labels (NFLs) and nationally implemented FOPLs such as Health Star Ratings (HSR), Traffic lights, and Guideline Daily Amounts (GDAs) in five countries, including before and after implementation of Mexico's warning FOPLs in 2020. Data were from the International Food Policy Study, an annual repeat cross-sectional study conducted in 2018-2020 among adults (N=64,032) in Australia, Canada, Mexico, the UK and the US. Self-reported awareness, use, and understanding of NFLs (in all five countries) and FOPLs (in Australia, Mexico, and UK) were assessed over time, between countries, and between NFLs and FOPLs. Most respondents in all countries reported seeing their country's NFLs (awareness) 'often' or 'all the time' across all three years, with one third to half of respondents using NFLs 'often' or 'all the time' (Australia: 43-45%; Canada: 47-50%; Mexico: 36-39%; UK: 32-34%; US: 47-49%), and approximately one half to two thirds finding NFLs 'easy' or 'very easy to understand' (56-57%; 67-69%; 51-54%; 48-51%; 70-71%). In 2020, awareness, use and self-reported understanding of the Warning FOPLs in Mexico were highest among all countries with a FOPL (p<0.001), whereas awareness and use were lowest for Australia's HSR (p<0.001). In countries with FOPLs, self-reported understanding was higher for FOPLs than NFLs, except for the GDA FOPL in Mexico. Only modest changes were observed over time. Warning FOPLs were associated with greater levels of self-reported awareness, use and understanding among adults compared to NFLs and GDA-based FOPLs. FOPLs implemented on a voluntary basis, such as Australia's HSR, may be less likely to be seen and used.

Social networks, perceived social support, and HbA1c in individuals with type 2 diabetes mellitus in urban Ghana.

OBJECTIVES: Although links between social relationships and health are well established, few studies have concurrently examined the effects of compositional, structural, and functional dimensions of social networks on glycemic (HbA1c) control in low- and middle-income countries such as Ghana. In these settings where informal social relationships are critical for access to resources, evaluating the links between social network characteristics, social support, and glycemic control may provide clarity about important relationships that facilitate the well-being of individuals with type 2 diabetes mellitus (T2DM). DESIGN: In 2018, we conducted a hospital-based, cross-sectional survey of noninstitutionalized adults with T2DM in Ghana. Using data from 247 study participants, multivariable linear regression models were used to estimate associations between: 1) HbA1c and three social network characteristics (kin composition, household composition, and network density); 2) social support and the three social network characteristics; and 3) HbA1c and social support. We also examined gender differences in these associations and applied mediation techniques to determine if network characteristics operated through social support to affect HbA1c. RESULTS: Findings indicated that higher kin composition and higher household composition were each significantly associated with increased social support. Neither social support nor social network characteristics were significantly related to HbA1c, and there were no gender differences in any of these associations. CONCLUSION: Although family and household members were identified as important sources of social support for diabetes management, the ways in which they influence HbA1c control among Ghanaians require further investigation. Future studies can examine whether changes in social support over time, social support satisfaction, or other dimensions of social relationships improve T2DM outcomes in countries like Ghana.

Carbonic anhydrase in elasmobranchs and current climate change scenario implications.

The enzyme carbonic anhydrase (CA) has well-known functions in acid-base balance, respiratory gas exchange, and osmoregulation in teleost fishes. However, studies concerning the role of CA in elasmobranchs are still scarce. Therefore, the aim of this study is to present the current status of CA studies in sharks and rays, as well as to identify gaps and emerging needs, in order to guide future studies. This review is organized according to the main roles of CA, with further considerations on climate change and CA effects indicated as paramount, as strategies in the face of climate change can be crucial for species response. The literature review revealed a reduction in publications on CA over the years. In addition, a historical research differentiation is noted, where the first assessments on the subject addressed investigations on basic CA functions, while the most recent studies present a comparative approach among species as well as interdisciplinary discussions, such as ecology and phylogeny. Considering that several elasmobranchs are threatened, future studies should prioritize non-lethal methodologies, in addition to expanding studies to climate change effects on CA.

A pilot study of multi-modal pain management for same-day discharge after minimally invasive repair of pectus excavatum (Nuss procedure) in children.

BACKGROUND: Despite advancements in minimally invasive repair of pectus excavatum (MIRPE), Nuss procedure, postoperative pain control remains challenging. This report covers a multimodal regimen using bilateral single-shot paravertebral block (PVB) and bilateral thoracoscopic intercostal nerve (T3-T7) cryoablation, leading to significant reduction in length of stay (LOS) and high rate of same-day discharge. METHODS: This is a comparative study of pain management protocols for patients undergoing the Nuss procedure at a single center from 2016 through 2020. All patients underwent the the same surgical technique for the treatment of pectus excavatum at a single center. Patients received bilateral PVB with continuous infusion (Group 1, n = 12), bilateral PVB with infusion and right-side cryoablation (Group 2, n = 9), or bilateral single-shot PVB and bilateral cryoablation (Group 3, n = 17). The primary outcome was LOS with focus on same-day discharge, and the secondary outcome was decreased opioid usage. RESULTS: Eleven of 17 patients in Group 3 (65%) (bilateral single-shot PVB and bilateral cryoablation) were discharged the same day as surgery. The remaining Group 3 patients were discharged the following day with no complications or interventions. Compared to Group 1 (no cryoablation), Group 3 had shorter LOS (median 4.4 days vs. 0.7 days, respectively, p < 0.001) and significantly decreased median opioid use on the day of surgery (0.92 mg/kg vs. 0.47 mg/kg, p = 0.006). CONCLUSION: Findings demonstrate the feasibility of multimodal pain management for same-day discharge after the Nuss procedure. Future multisite studies are needed to investigate the superiority of this approach to established methods. LEVEL OF EVIDENCE: III.

The Incidence of Hepatitis C Among Gay, Bisexual, and Other Men Who Have Sex With Men in Australia, 2009-2019.

BACKGROUND: Hepatitis C virus (HCV) infection has been reported among gay, bisexual, and other men who have sex with men (GBM) globally including GBM with human immunodeficiency virus (HIV) and HIV-negative GBM, particularly those using HIV preexposure prophylaxis (PrEP). In Australia, HCV direct-acting antiviral treatment (DAA) was government-funded from 2016. Large implementation studies of PrEP also began in 2016. We examined HCV incidence among GBM to assess whether HCV incidence has changed since 2015. METHODS: Data were drawn from the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance. We included GBM who tested HCV antibody negative at their first test and had ≥1 subsequent test. Generalized linear modeling (Poisson distribution) was used to examine HCV incidence from 2009 to 2019 stratified by HIV status, and among HIV-negative GBM prescribed PrEP from 2016 to 2019. RESULTS: Among 6744 GBM with HIV, HCV incidence was 1.03 per 100 person-years (PY). Incidence declined by 78% in 2019 compared to 2015 (incidence rate ratio [IRR], 0.22 [95% confidence interval {CI}: .09-.55]). Among 20 590 HIV-negative GBM, HCV incidence was 0.20/100 PY, with no significant change over time. Among 11 661 HIV-negative GBM prescribed PrEP, HCV incidence was 0.29/100 PY. Compared to 2016, incidence among GBM prescribed PrEP declined by 80% in 2019 (IRR, 0.20 [95% CI: .06-.64]). CONCLUSIONS: HCV incidence among GBM living with HIV declined following DAA availability. There was no observed change in HCV incidence among HIV-negative GBM overall. Among GBM prescribed PrEP, incidence declined since the early years of PrEP implementation in Australia. Australia is on track to eliminate HCV among GBM before global 2030 targets.