Geographic variation in sodium-glucose cotransporter 2 inhibitor and glucagon-like peptide-1 receptor agonist use in people with type 2 diabetes in New South Wales, Australia.

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycaemic control and cardio-renal outcomes for people with type 2 diabetes (T2D). However, geographic and socio-economic variation in use is not well understood. METHODS: We identified 367 829 New South Wales residents aged ≥40 years who dispensed metformin in 2020 as a proxy for T2D. We estimated the prevalence of use of other glucose-lowering medicines among people with T2D and the prevalence of SGLT2i and GLP-1RA use among people using concomitant T2D therapy (i.e. metformin + another glucose-lowering medicine). We measured the prevalence by small-level geography, stratified by age group, and characterized by remoteness and socio-economic status. RESULTS: The prevalence of SGLT2i (29.7%) and GLP-1RA (8.3%) use in people with T2D aged 40-64 increased with geographic remoteness and in areas of greater socio-economic disadvantage, similar to other glucose-lowering medicines. The prevalence of SGLT2i (55.4%) and GLP-1RA (15.4%) among people using concomitant T2D therapy varied across geographic areas, with lower SGLT2i use in more disadvantaged areas and localized areas of high GLP-1RA use (2.5 times the median). Compared with people aged 40-64 years, the prevalence of SGLT2i and GLP-1RA use was lower in older age groups, but with similar patterns of variation across geographic areas. CONCLUSIONS: The prevalence of SGLT2i and GLP-1RA use varied by geography, probably reflecting a combination of system- and prescriber-level factors. Socio-economic variation in GLP-1RA use was overshadowed by localized patterns of prescribing. Continued monitoring of variation can help shape interventions to optimize use among people who would benefit the most.

Use of, time to, and type of first add-on anti-hyperglycaemic therapy to metformin in Australia, 2018-2022.

AIMS: The aim of this study was to examine contemporary trends in the use of, time to, and type of first add-on anti-hyperglycaemic therapy to metformin in Australia. METHODS: We used the dispensing records of a 10% random sample of Pharmaceutical Benefits Scheme (PBS) eligible people. We included people aged 40 years and older initiating metformin from 1 January 2018 to 31 December 2020. Our primary outcome was first add-on anti-hyperglycaemic medicine within 2 years of metformin initiation. We analysed time to dispensing of first add-on therapy. All analyses were stratified by metformin initiation year. RESULTS: Overall, 38 747 people aged 40 years and older initiated metformin between 2018 and 2020. Approximately one-third (n = 12 946) of people received add-on therapy with the proportion increasing slightly by year of metformin initiation (32.3% in 2018 to 34.8% in 2020). Amongst people with add-on therapy following metformin initiation, sodium-glucose cotransporter 2 inhibitor (SGLT2i) use increased from 28.8% (2018) to 35.0% (2020), and glucagon-like peptide-1 receptor agonists (GLP-1 RA) increased from 3.0% to 9.6%, respectively. Dipeptidyl peptidase-4 inhibitors and sulfonylureas as first add-on therapy decreased and insulin remained stable. One-third of people with add-on therapy initiated the therapy on the same day metformin was initiated, i.e. initial combination therapy. CONCLUSIONS: Amongst people initiating metformin from 2018 to 2020, there was an increasing proportion of SGLT2i and GLP-1 RA being used as first add-on therapy. However, the overall prevalence of add-on therapy was low. Advocacy to promote add-on therapy with cardiorenal beneficial medicines is critical to reduce type 2 diabetes morbidity and mortality.

Anti-Inflammatory Activity and Acute Toxicity Of Pereskia aculeata, In Zophobas morio Larvae.

Pereskia aculeata has been widely investigated due to its anti-inflammatory potential. Among the metabolites found in this species are the phytosterols beta-sitosterol (ß-SIT) and stigmasterol (STIG). The objective of the study was to evaluate the anti-inflammatory and toxicity activities of the hexane partition of P. aculeata (PHEX), as well as ß-SIT and STIG. PHEX was prepared and the phytosterols were quantified. In terms of toxicity against L929 fibroblast cells, PHEX showed toxicity up to 200 µg/mL; STIG and ß-SIT showed toxicity up to 25 µg/mL. PHEX inhibited 66 % of nitric oxide radicals, while STIG and ß-SIT inhibited 33.73 % and 34.94 %, respectively. In an anti-inflammatory test against Zophobas morio larvae, all samples significantly reduced hemocyte levels. Additionally, the LD50 values were calculated: 229.6 mg/kg for PHEX, 101.5 mg/kg for STIG, and 103.8 mg/kg for ß-SIT. In conclusion, the study indicates that the phytosterols present in PHEX may contribute to its anti-inflammatory activity.

Chronic Cadmium Exposure can Alter Energy Allocation to Physiological Functions in the Shrimp Penaeus vannamei.

Environmental stressors in aquatic organisms can be assessed using a bioenergetic approach based on the evaluation of changes in their physiological parameters. We evaluated the chronic effects of cadmium (Cd2+) on the energy balance as well as the survival, growth, metabolism, nitrogen excretion, hepatosomatic index, oxidized energy substrate, and osmoregulation of the shrimp Penaeus vannamei with the hypothesis that the high energy demand related to the homeostatic regulation of Cd2+could disrupt the energy balance and as a consequence, their physiological functions. The shrimp exposed to Cd2+ had higher mortality (30%), directed more energy into growth (33% of energy intake), ingested 10% more energy, and defecated less than control animals. Cd2+ exposure caused a tendency to decrease metabolism and ammonia excretion but did not alter the hepatosomatic index, type of energy substrate oxidized, and the hyperosmorregulatory pattern of the species. The Cd+2 exposure may have induced a trade-off response because there was a growth rate increase accompanied by increased mortality.

Effect of paediatric early warning systems (PEWS) implementation on clinical deterioration event mortality among children with cancer in resource-limited hospitals in Latin America: a prospective, multicentre cohort study.

BACKGROUND: Paediatric early warning systems (PEWS) aid in the early identification of clinical deterioration events in children admitted to hospital. We aimed to investigate the effect of PEWS implementation on mortality due to clinical deterioration in children with cancer in 32 resource-limited hospitals across Latin America. METHODS: Proyecto Escala de Valoración de Alerta Temprana (Proyecto EVAT) is a quality improvement collaborative to implement PEWS in hospitals providing childhood cancer care. In this prospective, multicentre cohort study, centres joining Proyecto EVAT and completing PEWS implementation between April 1, 2017, and May 31, 2021, prospectively tracked clinical deterioration events and monthly inpatient-days in children admitted to hospital with cancer. De-identified registry data reported between April 17, 2017, and Nov 30, 2021, from all hospitals were included in analyses; children with limitations on escalation of care were excluded. The primary outcome was clinical deterioration event mortality. Incidence rate ratios (IRRs) were used to compare clinical deterioration event mortality before and after PEWS implementation; multivariable analyses assessed the correlation between clinical deterioration event mortality and centre characteristics. FINDINGS: Between April 1, 2017, and May 31, 2021, 32 paediatric oncology centres from 11 countries in Latin America successfully implemented PEWS through Proyecto EVAT; these centres documented 2020 clinical deterioration events in 1651 patients over 556 400 inpatient-days. Overall clinical deterioration event mortality was 32·9% (664 of 2020 events). The median age of patients with clinical deterioration events was 8·5 years (IQR 3·9-13·2), and 1095 (54·2%) of 2020 clinical deterioration events were reported in male patients; data on race or ethnicity were not collected. Data were reported per centre for a median of 12 months (IQR 10-13) before PEWS implementation and 18 months (16-18) after PEWS implementation. The mortality rate due to a clinical deterioration event was 1·33 events per 1000 patient-days before PEWS implementation and 1·09 events per 1000 patient-days after PEWS implementation (IRR 0·82 [95% CI 0·69-0·97]; p=0·021). In the multivariable analysis of centre characteristics, higher clinical deterioration event mortality rates before PEWS implementation (IRR 1·32 [95% CI 1·22-1·43]; p<0·0001), being a teaching hospital (1·18 [1·09-1·27]; p<0·0001), not having a separate paediatric haematology-oncology unit (1·38 [1·21-1·57]; p<0·0001), and having fewer PEWS omissions (0·95 [0·92-0·99]; p=0·0091) were associated with a greater reduction in clinical deterioration event mortality after PEWS implementation; no association was found with country income level (IRR 0·86 [95% CI 0·68-1·09]; p=0·22) or clinical deterioration event rates before PEWS implementation (1·04 [0·97-1·12]; p=0·29). INTERPRETATION: PEWS implementation was associated with reduced clinical deterioration event mortality in paediatric patients with cancer across 32 resource-limited hospitals in Latin America. These data support the use of PEWS as an effective evidence-based intervention to reduce disparities in global survival for children with cancer. FUNDING: American Lebanese Syrian Associated Charities, US National Institutes of Health, and Conquer Cancer Foundation. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Potential drug-drug interactions due to concomitant medicine use among people living with HIV on antiretroviral therapy in Australia.

AIMS: We quantified concomitant medicine use and occurrence of potential drug-drug interactions in people living with HIV in Australia who are treated with antiretroviral therapy (ART). METHODS: In this cohort study using dispensing claims of a 10% random sample of Australians, we identified 2230 people dispensed ART between January 2018 and December 2019 (mean age 49.0 years, standard deviation 12.0 years, 88% male). We examined concomitant medicine use by identifying nontopical medicines dispensed within 90-days of any antiretroviral medicine dispensing during a 12-month follow-up period. For every antiretroviral and nonantiretroviral pair, we identified and classified possible drug-drug interactions using the University of Liverpool HIV drug interactions database. RESULTS: A total of 1728 (78%) people were dispensed at least 1 and 633 (28%) 5 or more unique medicines in addition to ART in a 12-month period; systemic anti-infectives and medicines acting on the nervous system were the most common (68% and 56%, respectively). Among comedicated people, 1637 (95%) had at least 1 medicine combination classified as weak interactions, 558 (32%) interactions requiring close monitoring/dose adjustment and 94 (5%) that should not be coadministered. Contraindication or interactions requiring close monitoring/dose adjustment were more common among people receiving protease inhibitors (50-73% across different antiretrovirals), non-nucleoside reverse transcriptase inhibitors (35-64%), people using single-tablet combinations containing elvitegravir (30-46%) and those using tenofovir disoproxil (26-30%). CONCLUSION: Concomitant medicine use is widespread among people living with HIV in Australia. Despite a relatively low prevalence of contraindicated medicines, almost a third received medicines that require close monitoring or dose adjustment.

Bacterial Communities Along Environmental Gradients in Tropical Soda Lakes.

Soda lake environments are known to be variable and can have distinct differences according to geographical location. In this study, we investigated the effects of different environmental conditions of six adjacent soda lakes in the Pantanal biome (Mato Grosso do Sul state, Brazil) on bacterial communities and their functioning using a metagenomic approach combined with flow cytometry and chemical analyses. Ordination analysis using flow cytometry and water chemistry data from two sampling periods (wet and dry) clustered soda lakes into three different profiles: eutrophic turbid (ET), oligotrophic turbid (OT), and clear vegetated oligotrophic (CVO). Analysis of bacterial community composition and functioning corroborated this ordination; the exception was one ET lake, which was similar to one OT lake during the wet season, indicating drastic shifts between seasons. Microbial abundance and diversity increased during the dry period, along with a considerable number of limnological variables, all indicative of a strong effect of the precipitation-evaporation balance in these systems. Cyanobacteria were associated with high electric conductivity, pH, and nutrient availability, whereas Actinobacteria, Alphaproteobacteria, and Betaproteobacteria were correlated with landscape morphology variability (surface water, surface perimeter, and lake volume) and with lower salinity and pH levels. Stress response metabolism was enhanced in OT and ET lakes and underrepresented in CVO lakes. The microbiome dataset of this study can serve as a baseline for restoring impacted soda lakes. Altogether, the results of this study demonstrate the sensitivity of tropical soda lakes to climate change, as slight changes in hydrological regimes might produce drastic shifts in community diversity.

Assessing the impact of implementing multiple adherence measures to antiretroviral therapy from dispensing data: a short report.

Pharmacy dispensing data are useful for estimating adherence to therapy. Here, we implement multiple adherence measures to antiretroviral therapy (ART) and provide an online tool for visualising results. We conducted a cohort study for 2,042 people dispensed ART in Australia. We assessed adherence using the Proportion of Days Covered (PDC) within 360 days of follow-up as a continuous measure and dichotomised (PDC ≥80%). We defined a covered day as the 1) exposure to ≥3 antiretrovirals at the same time 2) exposure to any antiretroviral 3) lowest number of days covered per antiretroviral 4) average of days covered over all antiretrovirals 5) highest number of days covered per antiretroviral. For each method, we conducted sensitivity analyses. The median PDC ranged between 93.3%-98.3%. Between 67.0%-87.7% of individuals were classified as adherent, with higher values for measure 2 (85.5%-89.7%) and lower values for measure 3 (67.0%-70.9%). Censoring loss to follow-up had a higher impact on adherence estimates than considering a grace period. The variation in adherence estimates can be substantial, especially when dichotomising adherence. Researchers should consider operationalising multiple measures to estimate adherence bounds and identify a range of people at risk of non-adherence for targeted interventions.

Levels of adherence to contemporary antiretroviral regimens and the likelihood of viral suppression: a cohort study in a Brazilian metropolis.

Levels of adherence to antiretroviral therapy (ART) can affect the likelihood of viral suppression differentially among ART regimens. In this prospective cohort conducted in Belo Horizonte, Brazil, we included 354 individuals who initiated ART containing tenofovir disoproxil fumarate/lamivudine/efavirenz in fixed-dose combination (TDF/3TC/EFV) or tenofovir disoproxil fumarate/lamivudine associated with dolutegravir (TDF/3TC + DTG). Viral suppression (viral load <50 copies/mL) was evaluated within six months of follow-up at different adherence levels and by therapeutic regimen. Adherence was measured by the Proportion of Days Covered (PDC) and classified into low (≤84%), intermediate (85-89%) or high (≥90%). The association between viral suppression, adherence levels, and other explanatory variables was analyzed using chi-square and multivariable logistic regression. Viral suppression was achieved by 76.0% of individuals and was more frequent among those who achieved higher levels of adherence (high adherence: 79.3%, intermediate: 71.4% and low: 45.2%), those on TDF/3TC + DTG, and those who had viral load ≤100,000 copies/mL at the onset of treatment (p < 0.05). Moreover, individuals on TDF/3TC + DTG had an approximately 90% probability of achieving viral suppression at intermediate adherence levels. These results add new insights on the possibility of lower adherence levels for contemporary antiretroviral regimens currently used as first-line therapy worldwide.

In-hospital outcomes by insurance type among patients undergoing percutaneous coronary interventions for acute myocardial infarction in New South Wales public hospitals.

BACKGROUND: International evidence suggests patients receiving cardiac interventions experience differential outcomes by their insurance status. We investigated outcomes of in-hospital care according to insurance status among patients admitted in public hospitals with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). METHODS: We conducted a cohort study within the Australian universal health care system with supplemental private insurance. Using linked hospital and mortality data, we included patients aged 18 + years admitted to New South Wales public hospitals with AMI and undergoing their first PCI from 2017-2020. We measured hospital-acquired complications (HACs), length of stay (LOS) and in-hospital mortality among propensity score-matched private and publicly funded patients. Matching was based on socio-demographic, clinical, admission and hospital-related factors. RESULTS: Of 18,237 inpatients, 30.0% were privately funded. In the propensity-matched cohort (n = 10,630), private patients had lower rates of in-hospital mortality than public patients (odds ratio: 0.59, 95% CI: 0.45-0.77; approximately 11 deaths avoided per 1,000 people undergoing PCI procedures). Mortality differences were mostly driven by STEMI patients and those from major cities. There were no significant differences in rates of HACs or average LOS in private, compared to public, patients. CONCLUSION: Our findings suggest patients undergoing PCI in Australian public hospitals with private health insurance experience lower in-hospital mortality compared with their publicly insured counterparts, but in-hospital complications are not related to patient health insurance status. Our findings are likely due to unmeasured confounding of broader patient selection, socioeconomic differences and pathways of care (e.g. access to emergency and ambulatory care; delays in treatment) that should be investigated to improve equity in health outcomes.

Machine learning toward high-performance electrochemical sensors.

The so-coined fourth paradigm in science has reached the sensing area, with the use of machine learning (ML) toward data-driven improvements in sensitivity, reproducibility, and accuracy, along with the determination of multiple targets from a single measurement using multi-output regression models. Particularly, the use of supervised ML models trained on large data sets produced by electrical and electrochemical bio/sensors has emerged as an impacting trend in the literature by allowing accurate analyses even in the presence of usual issues such as electrode fouling, poor signal-to-noise ratio, chemical interferences, and matrix effects. In this trend article, apart from an outlook for the coming years, we present examples from the literature that demonstrate how helpful ML algorithms can be for dispensing the adoption of experimental methods to address the aforesaid interfering issues, ultimately contributing to translate testing technologies into on-site, practical, and daily applications.

Trends in use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) in Australia in the era of increased evidence of their cardiovascular benefits (2014-2022).

PURPOSE: To investigate trends in SGLT2i and GLP-1RA use in Australia in the era of increased evidence of their cardiovascular benefits. METHODS: We used national dispensing claims for a 10% random sample of Australians to estimate the number of prevalent and new users (no dispensing in the prior year) of SGLT2i or GLP-1RA per month from January 2014 to July 2022. We assessed prescriber specialty and prior use of other antidiabetic and cardiovascular medicines as a proxy for evidence of type 2 diabetes (T2D) and cardiovascular conditions, respectively. RESULTS: We found a large increase in the number of prevalent users (216-fold for SGLT2i; 11-fold for GLP-1RA); in July 2022 approximately 250,000 Australians were dispensed SGLT2i and 120,000 GLP-1RA. Most new users of SGLT2i or GLP-1RA had evidence of both T2D and cardiovascular conditions, although from 2022 onwards, approximately one in five new users of SGLT2i did not have T2D. The proportion of new users initiating SGLT2i by cardiologists increased after 2021, reaching 10.0% of initiations in July 2022. Among new users with evidence of cardiovascular conditions, empagliflozin was the most commonly prescribed SGLT2i, while dulaglutide or semaglutide was the most common GLP-1RA. CONCLUSION: SGLT2i and GLP-1RA use is increasing in Australia, particularly in populations with higher cardiovascular risk. The increased use of SGLT2i among people without evidence of T2D suggests that best-evidence medicines are adopted in Australia across specialties, aligning with new evidence and expanding indications.

Changes in antidepressant use in Australia: A nationwide analysis (2015-2021).

BACKGROUND: Depression and anxiety affect 4-14% of Australians every year; symptoms may have been exacerbated during the COVID-19 pandemic. We examined recent patterns of antidepressant use in Australia in the period 2015-2021, which includes the first year of the pandemic. METHODS: We used national dispensing claims for people aged ⩾10 years to investigate annual trends in prevalent and new antidepressant use (no antidepressants dispensed in the year prior). We conducted stratified analyses by sex, age group and antidepressant class. We report outcomes from 2015 to 2019 and used time series analysis to quantify changes during the first year of the COVID-19 pandemic (March 2020-February 2021). RESULTS: In 2019, the annual prevalence of antidepressant use was 170.4 per 1000 women and 101.8 per 1000 men, an increase of 7.0% and 9.2% from 2015, respectively. New antidepressant use also increased for both sexes (3.0% for women and 4.9% for men) and across most age groups, particularly among adolescents (aged 10-17 years; 46-57%). During the first year of the COVID-19 pandemic, we observed higher than expected prevalent use (+2.2%, 95% CI = [0.3%, 4.2%]) among females, corresponding to a predicted excess of 45,217 (95% CI = [5,819, 84,614]) females dispensed antidepressants. The largest increases during the first year of the pandemic occurred among female adolescents for both prevalent (+11.7%, 95% CI = [4.1%, 20.5%]) and new antidepressant use (+15.6%, 95% CI = [8.5%, 23.7%]). CONCLUSION: Antidepressant use continues to increase in Australia overall and especially among young people. We found a differential impact of the COVID-19 pandemic in treated depression and anxiety, greater among females than males, and greater among young females than other age groups, suggesting an increased mental health burden in populations already on a trajectory of increased use of antidepressants prior to the pandemic. Reasons for these differences require further investigation.

Recent patent applications for coffee and coffee by-products as active ingredients in cosmetics.

OBJECTIVE: Coffee is one of the most consumed beverages worldwide, and its production and consumption generate large amounts of by-products annually. Coffee by-products and coffee beans are rich in bioactive compounds of great commercial value, including potential applications as active ingredients in skin care products and cosmetic formulations. In addition, there has been growing interest in the use of natural ingredients for cosmetic purposes. Considering the importance of coffee in the world economy, its chemical constituents with potential for cosmetic and dermatological application, and the importance of patents for innovation and technological development, the present study aimed to review recent patents involving coffee and coffee by-product use in cosmetics. METHODS: This review was carried out using Espacenet. The following inclusion criteria were established: patents that included the terms "coffee" and "skin" in the title, abstract and claims and belonged to the classification A61Q, which is related to the "specific use of cosmetics or similar toilet preparations" considering the International Patent Classification (IPC) or Cooperative Patent Classification (CPC). RESULTS: Considering the 52 patents analysed, the bean was the main way to obtain extracts (39), followed by green beans (7), silverskin (3), peel and pulp (1), pulp (1) and beans and leaves (1). The formulations are mainly intended for use in nonspecific areas of skin (29), eye areas (12), scalp hair (9) and lip skin (2) with claims of anti-ageing, moisturizers, sun protection, hair growth, anti-dandruff, etc. CONCLUSION: Coffee and its residues have high amounts of phenolic compounds, caffeine, fatty acids and other substances known to have important biological properties for the skin. Coffee and its by-products are promising ingredients to be incorporated into topical formulations, ensuring skin health benefits and reducing the environmental impact.

OBJECTIF: Le café est l'une des boissons les plus consommées dans le monde, et sa production et sa consommation génèrent chaque année de grandes quantités de sous-produits. Les sous-produits du café et les grains de café sont riches en composés bioactifs d'une grande valeur commerciale, y compris des applications potentielles en tant qu'ingrédients actifs dans les produits de soins de la peau et les formulations cosmétiques. De plus, il y a eu un intérêt croissant pour l'utilisation d'ingrédients naturels à des fins cosmétiques. Compte tenu de l'importance du café dans l'économie mondiale, de ses constituants chimiques ayant un potentiel d'application cosmétique et dermatologique, et de l'importance des brevets pour l'innovation et le développement technologique, la présente étude visait à examiner les brevets récents concernant l'utilisation du café et des sous-produits du café dans les cosmétiques. MÉTHODES: Cette revue a été réalisée à l'aide d'Espacenet. Les critères d'inclusion suivants ont été établis: les brevets qui incluaient les termes "café" et "peau" dans le titre, l'abrégé et les revendications et appartenaient à la classification A61Q, qui est liée à "l'utilisation spécifique de cosmétiques ou de préparations de toilette similaires" compte tenu de la Classification internationale des brevets ou Classification coopérative des brevets. RÉSULTATS: Considérant les 52 brevets analysés, le grain était le principal moyen d'obtenir des extraits (39), suivi du grain vert (7), du silverskin (3), de la peau et de la pulpe (1), de la pulpe (1) et des grains et des feuilles (1). Les formulations sont principalement destinées à être utilisées dans des zones non spécifiques de la peau (29), des yeux (12), des cheveux du cuir chevelu (9) et de la peau des lèvres (2) avec des revendications anti-âge, hydratantes, protection solaire, croissance des cheveux, antipelliculaire, etc. CONCLUSION: Le café et ses résidus contiennent de grandes quantités de composés phénoliques, de caféine, d'acides gras et d'autres substances connues pour avoir des propriétés biologiques importantes pour la peau. Le café et ses sous-produits sont des ingrédients prometteurs à incorporer dans des formulations topiques, garantissant des bienfaits pour la santé de la peau et réduisant l'impact environnemental.

MicroRNA roles in regeneration: Multiple lessons from zebrafish.

MicroRNAs (miRNAs) are small noncoding RNAs with pivotal roles in the control of gene expression. By comparing the miRNA profiles of uninjured vs. regenerating tissues and structures, several studies have found that miRNAs are potentially involved in the regenerative process. By inducing miRNA overexpression or inhibition, elegant experiments have directed regenerative responses validating relevant miRNA-to-target interactions. The zebrafish (Danio rerio) has been the epicenter of regenerative research because of its exceptional capability to self-repair damaged tissues and body structures. In this review, we discuss recent discoveries that have improved our understanding of the impact of gene regulation mediated by miRNAs in the context of the regeneration of fins, heart, retina, and nervous tissue in zebrafish. We compiled what is known about the miRNA control of regeneration in these tissues and investigated the links among up-regulated and down-regulated miRNAs, their putative or validated targets, and the regenerative process. Finally, we briefly discuss the forthcoming prospects, highlighting directions and the potential for further development of this field.

Model for regional collaboration: Successful strategy to implement a pediatric early warning system in 36 pediatric oncology centers in Latin America.

BACKGROUND: Pediatric early warning systems (PEWS) aid in the early identification of deterioration in hospitalized children with cancer; however, they are under-used in resource-limited settings. The authors use the knowledge-to-action framework to describe the implementation strategy for Proyecto Escala de Valoracion de Alerta Temprana (EVAT), a multicenter quality-improvement collaborative, to scale-up PEWS in pediatric oncology centers in Latin America. METHODS: Proyecto EVAT mentored participating centers through an adaptable implementation strategy to: (1) monitor clinical deterioration in children with cancer, (2) contextually adapt PEWS, (3) assess barriers to using PEWS, (4) pilot and implement PEWS, (5) monitor the use of PEWS, (6) evaluate outcomes, and (7) sustain PEWS. The implementation outcomes assessed included the quality of PEWS use, the time required for implementation, and global program impact. RESULTS: From April 2017 to October 2021, 36 diverse Proyecto EVAT hospitals from 13 countries in Latin America collectively managing more than 4100 annual new pediatric cancer diagnoses successfully implemented PEWS. The time to complete all program phases varied among centers, averaging 7 months (range, 3-13 months) from PEWS pilot to implementation completion. All centers ultimately implemented PEWS and maintained high-quality PEWS use for up to 18 months after implementation. Across the 36 centers, more than 11,100 clinicians were trained in PEWS, and more than 41,000 pediatric hospital admissions had PEWS used in their care. CONCLUSIONS: Evidence-based interventions like PEWS can be successfully scaled-up regionally basis using a systematic approach that includes a collaborative network, an adaptable implementation strategy, and regional mentorship. Lessons learned can guide future programs to promote the widespread adoption of effective interventions and reduce global disparities in childhood cancer outcomes. LAY SUMMARY: Pediatric early warning systems (PEWS) are clinical tools used to identify deterioration in hospitalized children with cancer; however, implementation challenges limit their use in resource-limited settings. Proyecto EVAT is a multicenter quality-improvement collaborative to implement PEWS in 36 pediatric oncology centers in Latin America. This is the first multicenter, multinational study reporting a successful implementation strategy (Proyecto EVAT) to regionally scale-up PEWS. The lessons learned from Proyecto EVAT can inform future programs to promote the adoption of clinical interventions to globally improve childhood cancer outcomes.

Infection by Moniliophthora perniciosa reprograms tomato Micro-Tom physiology, establishes a sink, and increases secondary cell wall synthesis.

Witches' broom disease of cacao is caused by the pathogenic fungus Moniliophthora perniciosa. By using tomato (Solanum lycopersicum) cultivar Micro-Tom (MT) as a model system, we investigated the physiological and metabolic consequences of M. perniciosa infection to determine whether symptoms result from sink establishment during infection. Infection of MT by M. perniciosa caused reductions in root biomass and fruit yield, a decrease in leaf gas exchange, and down-regulation of photosynthesis-related genes. The total leaf area and water potential decreased, while ABA levels, water conductance/conductivity, and ABA-related gene expression increased. Genes related to sugar metabolism and those involved in secondary cell wall deposition were up-regulated upon infection, and the concentrations of sugars, fumarate, and amino acids increased. 14C-glucose was mobilized towards infected MT stems, but not in inoculated stems of the MT line overexpressing CYTOKININ OXIDASE-2 (35S::AtCKX2), suggesting a role for cytokinin in establishing a sugar sink. The up-regulation of genes involved in cell wall deposition and phenylpropanoid metabolism in infected MT, but not in 35S::AtCKX2 plants, suggests establishment of a cytokinin-mediated sink that promotes tissue overgrowth with an increase in lignin. Possibly, M. perniciosa could benefit from the accumulation of secondary cell walls during its saprotrophic phase of infection.

Trends in HIV post-exposure prophylaxis following sexual exposure in Brazil (2011-2019).

We examined trends in the prevalence of post-exposure prophylaxis following sexual exposure (PEPSE) per million population (2011-2019) and the proportion of repeated PEPSE within 365 days of the first PEPSE dispensing (2011-2018) in Brazil. We also compared the prevalence of repeated PEPSE according to patient and health services characteristics in 2018. The prevalence of PEPSE increased 55.5% from 2011 to 2019. Repeated PEPSE increased 11.8%, reaching 8.4% among people with their first dispensing in 2018. The prevalence of repeated PEPSE was higher in cis men or trans women (versus cisgender women); homosexuals (versus heterosexuals); and people aged 25-29 years (versus other age groups). We also observed greater prevalence of repeated PEPSE in HIV services in populous cities or services with elevated caseloads. Our findings highlight the need for strategies to reduce repeated PEPSE and promote other HIV-prevention technologies, particularly among young adults, cisgender men, transgender women, and homosexuals.

RESUMEN: Examinamos las tendencias de la prevalencia de uso de la profilaxis posterior a la exposición sexual (PEPSE) por millón de población (2011­2019) y la proporción de PEPSE repetida dentro de los 365 días de la primera dispensación de PEPSE (2011­2018) en Brasil. También comparamos la prevalencia de PEPSE repetida según las características del paciente y de los servicios de salud en 2018. La prevalencia de PEPSE aumentó un 55,5% de 2011 a 2019. La PEPSE repetida aumentó un 11,8%, alcanzando el 8,4% entre las personas con su primera dispensación en 2018. La prevalencia de PEPSE repetida fue mayor en hombres cis o mujeres trans (versus mujeres cisgénero); homosexuales (versus heterosexuales); y personas de 25 a 29 años (versus otros grupos de edad). También observamos una mayor prevalencia de repetición en los servicios de VIH de las ciudades más pobladas o con un elevado número de clientes. Nuestros hallazgos ponen de manifiesto la necesidad de estrategias para reducir la repetición de la PEPSE y promover otras tecnologías de prevención del VIH entre los adultos jóvenes, especialmente los hombres, las trans y los homosexuales.

Chemical characterisation by UPLC-Q-ToF-MS/MS and antibacterial potential of Coffea arabica L. leaves: A coffee by-product.

INTRODUCTION: Coffea arabica L. leaves are considered a by-product of the coffee industry however they are sources of several bioactive compounds. OBJECTIVES: This study aimed to evaluate the chemical composition and the in vitro antibacterial activity of the lyophilised ethanol extract of arabica coffee leaves (EE-CaL). MATERIAL AND METHODS: The chemical characterisation of EE-CaL was performed using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-ToF-MS/MS). The in vitro antibacterial effect of EE-CaL was evaluated using the broth microdilution method and the adapted drop plate agar method to determine the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC), respectively. RESULTS: The chemical analysis of EE-CaL revealed the presence of compounds from the alkaloid class, such as trigonelline and caffeine, in addition to the phenolic compounds such as quinic acid, 5-caffeoylquinic acid, caffeic acid-O-hexoside, mangiferin, (epi)catechin, (epi)catechin monoglucoside and procyanidin trimer. Regarding the antibacterial potential, EE-CaL was active against Gram-positive and Gram-negative bacteria, being more effective against Escherichia coli (ATCC 25922) (MIC = 2500 µg/mL and bactericidal effect). CONCLUSION: The results of this research suggest that coffee leaves, a by-product, possess compounds with antibacterial properties. Thus, further studies with coffee leaf extracts must be carried out to relate the compounds present in the extract with the antibacterial activity and find the mechanisms of action of this extract against bacteria.

M1 Polarized Macrophages Persist in Skin of Post-Bariatric Patients after 2 Years.

BACKGROUND: Obesity is considered a condition of systemic chronic inflammation. Under this condition, adipose tissue macrophages switch from an M2 (anti-inflammatory) activation pattern to an M1 (proinflammatory) activation pattern. OBJECTIVE: The study aimed to verify the profile of skin macrophage activation after bariatric surgery as well as the role of MMP-1 in extracellular tissue remodeling. METHODS: This is a prospective, controlled and comparative study with 20 individuals split into two groups according to their skin condition: post-bariatric and eutrophic patients. Histological and morphometric analyses based on hematoxylin-eosin, picrosirius red (collagen), orcein (elastic fiber systems), and alcian blue (mast cells)-stained sections and immunohistochemical analysis (CD68, iNOS, and mannose receptor) for macrophages and metalloproteinase-1 were performed. RESULTS: Post-bariatric skin showed an increase in inflammation, angiogenesis, CD68, M1 macrophages (P< 0.001), and mast cells (P< 0.01); a decrease in M2 macrophages (P< 0.01); and a significant decrease in the collagen fiber network (P< 0.001). MMP-1 was increased in the papillary dermis of post-bariatric skin and decreased in the epidermis compared to eutrophic skin (P< 0.05). CONCLUSION: This study shows that post-bariatric skin maintains inflammatory characteristics for two years. Mast cells and M1 macrophages maintain and enhance the remodeling of the dermal extracellular matrix initiated during obesity in part due to the presence of MMP-1 in the papillary dermis. EBM LEVEL IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .