Living in mangroves: a syntrophic scenario unveiling a resourceful microbiome.

BACKGROUND: Mangroves are complex and dynamic coastal ecosystems under frequent fluctuations in physicochemical conditions related to the tidal regime. The frequent variation in organic matter concentration, nutrients, and oxygen availability, among other factors, drives the microbial community composition, favoring syntrophic populations harboring a rich and diverse, stress-driven metabolism. Mangroves are known for their carbon sequestration capability, and their complex and integrated metabolic activity is essential to global biogeochemical cycling. Here, we present a metabolic reconstruction based on the genomic functional capability and flux profile between sympatric MAGs co-assembled from a tropical restored mangrove. RESULTS: Eleven MAGs were assigned to six Bacteria phyla, all distantly related to the available reference genomes. The metabolic reconstruction showed several potential coupling points and shortcuts between complementary routes and predicted syntrophic interactions. Two metabolic scenarios were drawn: a heterotrophic scenario with plenty of carbon sources and an autotrophic scenario with limited carbon sources or under inhibitory conditions. The sulfur cycle was dominant over methane and the major pathways identified were acetate oxidation coupled to sulfate reduction, heterotrophic acetogenesis coupled to carbohydrate catabolism, ethanol production and carbon fixation. Interestingly, several gene sets and metabolic routes similar to those described for wastewater and organic effluent treatment processes were identified. CONCLUSION: The mangrove microbial community metabolic reconstruction reflected the flexibility required to survive in fluctuating environments as the microhabitats created by the tidal regime in mangrove sediments. The metabolic components related to wastewater and organic effluent treatment processes identified strongly suggest that mangrove microbial communities could represent a resourceful microbial model for biotechnological applications that occur naturally in the environment.

Novel Leptin-Cardiac TRH pathway responsible for the cardiac alterations in the Hyperleptinemic obesity.

The association between hypertension and obesity-induced cardiac damage is usually accepted. However, no studies have been focused on cardiac alterations in obesity, independently of blood pressure increase. It is well known that Cardiac TRH induces Left Ventricular Hypertrophy (LVH) and fibrosis, and its inhibition prevents the development of hypertrophy. Also, it has been described that the adiponectin leptin induces TRH expression. Thus, we hypothesized that in obesity, the increase in TRH induced by hyperleptinemia is responsible for LVH, until now mostly attributed to pressure load. We studied obese Agouti mice suffering from hypertension with hyperleptinemia and found a significant LVH development with increased TRH gene expression. Consequently, we found higher fibrotic (collagens and TGF-ß) and hypertrophic markers (BNP and ß-MHC) expression vs lean black controls. As pressure could explain these results, we treated obese mice with diuretic (hydrochlorothiazide 20 mg/kg/day) since weaning. Diuretic treatment was successful as the diuretic group was normotensive in contrast to control obese mice. Nevertheless, both groups showed LVH development, higher cardiac precursor TRH gene and peptide expressions and elevated fibrotic and hypertrophic markers expression, pointing out that obesity-induced LVH is not due to hypertension. In addition, we performed Cardiac TRH inhibition by specific siRNA injection compared to control siRNA treatment and evaluated cardiac damage. As expected, expressions and protein increase in hypertrophic and fibrotic markers observed in the AG mouse with the native cTRH system were not seen in the AG mouse with the cTRH silencing. Indeed, the AG + TRH-siRNA group showed hypertrophic markers expression and fibrosis measurements similar to the lean BL mice. On the whole, these results point out that the novel Leptin-Cardiac TRH pathway is responsible for the cardiac alterations present in hyperleptinemic obesity, independent of blood pressure, and cTRH long-term silencing since early stages totally prevent LVH development and cardiac fibrosis.

Finding microbial composition and biological processes as predictive signature to access the ongoing status of mangrove preservation.

Mangroves are complex land-sea transition ecosystems whose microbiota are essential for their nutrient recycling and conservation. Brazil is the third-largest estuarine area in the world and "Baía de Todos os Santos" (BTS) is one of the largest bays of the country, with wide anthropogenic exploration. Using a metagenomic approach, we investigated composition and functional adaptability as signatures of the microbiome of pristine and anthropized areas of BTS, including those under petroleum refinery influence. The taxonomic analysis showed dominance of sulfate-reducing Desulfobacteraceae, Rhodobacteraceae, and Flavobacteriaceae. Taxa were significantly diverse between pristine and disturbed areas. Disturbed mangroves showed a notary increase in abundance of halophilic, sulfur-related, and hydrocarbon-degrading genera and a decrease in diatoms compared to pristine area. The metabolic profile of BTS mangroves was correlated with the differentially abundant microbiota. Two ecological scenarios were observed: one marked by functions of central metabolism associated with biomass degradation and another by mechanisms of microbial adaptability to pollution conditions and environmental degradation. Part of the microbiome was distinct and not abundant in Brazilian estuarine soils. The microbiome signature observed in each BTS mangrove reflects how human actions impact the diversity of these ecosystems and also emphasize their role in attempting to restore disturbed mangroves. The microbiome may act as a potential biological indicator of the preservation status of these soils, despite the limitation of soil property conditions. Additionally, our data pointed to metagenomics as an additional tool for environmental assessment and reinforced the need for protective measures for the mangroves under study.

Impact of anti-coagulant choice on blood elongational behavior.

Blood is a highly complex fluid with rheological properties that have a significant impact on various flow phenomena. In particular, it exhibits a non-Newtonian elongational viscosity that is comparable to polymer solutions. In this study, we investigate the effect of three different anticoagulants, namely EDTA (ethylene diamine tetraacetic acid), heparin, and citrate, on the elongational properties of both human and swine blood. We observe a unique two stage thinning process and a strong dependency of the characteristic relaxation time on the chosen anticoagulant, with the longest relaxation time and thus the highest elongational viscosity being found for the case of citrate. Our findings for the latter are consistent with the physiological values obtained from a dripping droplet of human blood without any anticoagulant. Furthermore, our study resolves the discrepancy found in the literature regarding the reported range of characteristic relaxation times, confirming that the elongational viscosity must be taken into account for a full rheological characterization of blood. These results have important implications for understanding blood flow in various physiological, pathological and technological conditions.

A Feasible Estimation of a "Corrected" EQ-5D Social Tariff.

OBJECTIVES: To demonstrate the feasibility of estimating a social tariff free of utility curvature and probability weighting biases and to test transferability between riskless and risky contexts. METHODS: Valuations for a selection of EQ-5D-3L health states were collected from a large and representative sample (N = 1676) of the Spanish general population through computer-assisted personal interviewing. Two elicitation methods were used: the traditional time trade-off (TTO) and a novel risky-TTO procedure. Both methods are equivalent for better than death states, which allowed us to test transferability of utilities across riskless and risky contexts. Corrective procedures applied are based on rank-dependent utility theory, identifying parameter estimates at the individual level. All corrections are health-state specific, which is a unique feature of our corrective approach. RESULTS: Two corrected value sets for the EQ-5D-3L system are estimated, highlighting the feasibility of developing national tariffs under nonexpected utility theories, such as rank-dependent utility. Furthermore, transferability was not supported for at least half of the health states valued by our sample. CONCLUSIONS: It is feasible to estimate a social tariff by using interviewing techniques, sample sizes, and sample representativeness equivalent to prior studies designed to generate national value sets for the EQ-5D. Utilities obtained in distinct contexts may not be interchangeable. Our findings caution against routinely taking transferability of utility for granted.

Inhibition of protein tyrosine phosphatase 1B by serratane triterpenes from Huperzia serrata and their molecular docking study.

During the search for protein tyrosine phosphatase 1B (PTP1B) inhibitory compounds from the natural resources, two new serratane triterpenes, 3-O-dihydro-p-coumaroyltohogenol (1) and 21-O-acetyltohogenol (2), along with four known serratane triterpenes (3-6), were isolated from the whole plant of Huperzia serrata. The chemical structures of compounds 1 and 2 were determined by NMR study, HRMS analysis, and chemical modification. All isolates were evaluated for their PTP1B inhibitory activities. Among the isolates, compounds 1, 3, 5 and 6 exhibit moderate inhibitory activities against PTP1B. Kinetic studies demonstrated that they are competitive inhibitors. Molecular docking studies support these experimental results by showing that compounds 1, 3, 5 and 6 interact with the active site of PTP1B, clarifying the structure-activity relationship. This study suggests that serratane triterpenes from H. serrata have potential as starting skeletons for anti-diabetes or anti-obesity agents.

Chalcone-Monoterpene Derivatives from the Buds of Cleistocalyx operculatus and Their Potential as Protein Tyrosine Phosphatase 1B Inhibitors.

Four new compounds, racemic chalcone-monoterpene hybrids (1-3) and a chalcone (9), along with nine known compounds (4-8, 10-13), have been isolated from the buds of Cleistocalyx operculatus. The chemical structures of the isolated compounds were identified through NMR data analysis and confirmed by computational methods, including electronic circular dichroism (ECD) calculations, and further synthetic approaches. Compounds 1-5 were synthesized via a Diels-Alder reaction, a process informed by biomimetic condensation studies that combined chalcones and monoterpenes. These synthetic approaches also yielded various unnatural chalcone-monoterpene derivatives (14-23). The inhibitory effects on protein tyrosine phosphatase 1B (PTP1B) of both naturally isolated and synthetically obtained compounds were evaluated. Compounds 4, 9, 13, and 16b exhibited potent PTP1B inhibitory activity, with IC50 values ranging from 0.9 ± 0.2 to 3.9 ± 0.7 µM. The enantiomers (+)-4 and (-)-16b showed enhanced activity compared to their respective enantiomers. Kinetic studies indicate that all active compounds inhibit PTP1B through mixed mechanisms, and molecular docking simulations agree with the experimental assays on PTP1B. Our results suggest that chalcone-meroterpene adducts from the buds of C. operculatus exhibit potential as antidiabetic agents, partly due to their PTP1B enzyme inhibition.

Loss of Cognitive Function in Mexican children due to lead exposure and the associated economic costs.

BACKGROUND: Lead exposure reduces the cognitive development and future economic prospects of children. While previous studies in high-income settings have explored productivity losses associated with lead exposure, limited research has focused on low and middle-income countries like Mexico. OBJECTIVES: This study aims to provide a comprehensive assessment of the economic implications of lead exposure on Mexican children using, for the first time, nationally representative Blood lead levels (BLLs) measurements in children aged 1-4, specifically focusing on the costs of forgone lifetime income due to cognitive losses. METHODS: BLLs of children aged 1-4 were extracted from the 2018-2019 National Health and Nutrition Survey (ENSANUT). Estimations of cognitive losses were derived from a log-linear relationship between BLLs and IQ loss. Lost lifetime economic productivity per child was calculated, assuming a 2% reduction in lifetime potential productivity for each IQ point lost due to lead exposure, based on previous literature (Attina and Trasande, 2013; Larsen and Sanchez-Triana, 2023). Productivity data were obtained from representative sources for Mexico. RESULTS: The estimated economic loss amounted to US $33.02 billion, equivalent to 2.76% of Mexico's Gross Domestic Product (GDP) in 2019 (calculated for a 1-year cohort). On a national scale, the long-term loss of cognition for children 1-4 years old is 4.14 IQ points per child due to lead exposure, with significant variability across States (range: 3.26 to 5.26). Lead-poisoned children (≥5 µg/dL) suffered an average loss of 6.42 IQ points (range: 0 to 6.97). In terms of economic impact, some States like Chiapas experienced losses of 7.08% of its GDP, while others had losses as low as 0.67%. Intriguingly, states with lower Human Development Indexes (HDIs) exhibited relatively higher economic losses despite lower average blood lead levels. DISCUSSION: The heterogeneous impact of lead exposure across Mexican states underscores the necessity for tailored regional policies. These findings emphasize the urgency for targeted interventions and informed policy measures to mitigate the socioeconomic consequences of lead exposure on Mexican children.

Dual Antiplatelet Therapy vs Alteplase in Adult Patients with Acute Minor Ischemic Stroke: A Systematic Review and Meta-Analysis.

The efficacy and safety of dual antiplatelet therapy (DAPT) relative to intravenous (IV) alteplase in patients with acute minor ischemic stroke are insufficiently established. Therefore, we aimed to perform a meta-analysis to compare DAPT with IV alteplase in patients with acute minor stroke. MEDLINE, Embase, and Cochrane were searched for studies comparing DAPT with IV alteplase in patients with minor stroke. Functional and safety outcomes in 90 days were analyzed. Statistical analysis was performed using Rstudio 4.3.1. Subanalyses were performed restricted to non-disabling minor strokes and NIHSS score ≤ 3. PROSPERO (CRD42023440986). We included five studies with a total of 6,340 patients, of whom 4,050 (63.9%) received DAPT. The follow-up period for all included studies was 90 days. There was no significant difference for individual outcomes of mRS 0-1 (OR 1.26; 95% CI 0.85-1.89; p = 0.25), mRS 0-2 (OR 0.99; 95% CI 0.69-1.43; p = 0.97), or all-cause mortality (OR 0.80; 95% CI 0.20-3.13; p = 0.75) between groups. Symptomatic intracranial hemorrhage (sICH) was significantly lower (OR 0.11; 95% CI 0.003-0.36; p < 0.001) in patients treated with DAPT compared with IV alteplase. In terms of mRS 0-1 and mRS 0-2, we found no significant difference in both subgroup analyses. We found no statistically significant difference between DAPT and IV alteplase regarding functional outcome (mRS scores of 0-1 and 0-2) or all-cause mortality at 90 days in patients with minor ischemic stroke. Additionally, DAPT was associated with a significantly lower rate of sICH.

Design of a multiple criteria decision analysis framework for prioritizing high-impact health technologies in a regional health service.

OBJECTIVES: This study aims to develop a framework for establishing priorities in the regional health service of Murcia, Spain, to facilitate the creation of a comprehensive multiple criteria decision analysis (MCDA) framework. This framework will aid in decision-making processes related to the assessment, reimbursement, and utilization of high-impact health technologies. METHOD: Based on the results of a review of existing frameworks for MCDA of health technologies, a set of criteria was proposed to be used in the context of evaluating high-impact health technologies. Key stakeholders within regional healthcare services, including clinical leaders and management personnel, participated in a focus group (n = 11) to discuss the proposed criteria and select the final fifteen. To elicit the weights of the criteria, two surveys were administered, one to a small sample of healthcare professionals (n = 35) and another to a larger representative sample of the general population (n = 494). RESULTS: The responses obtained from health professionals in the weighting procedure exhibited greater consistency compared to those provided by the general public. The criteria more highly weighted were "Need for intervention" and "Intervention outcomes." The weights finally assigned to each item in the multicriteria framework were derived as the equal-weighted sum of the mean weights from the two samples. CONCLUSIONS: A multi-attribute function capable of generating a composite measure (multicriteria) to assess the value of high-impact health interventions has been developed. Furthermore, it is recommended to pilot this procedure in a specific decision context to evaluate the efficacy, feasibility, usefulness, and reliability of the proposed tool.

Early metabolic and transcriptomic regulation in rainbow trout (Oncorhynchus mykiss) liver by 11-deoxycorticosterone through two corticosteroid receptors pathways.

Cortisol hormone is considered the main corticosteroid in fish stress, acting through glucocorticoid (GR) or mineralocorticoid (MR) receptor. The 11-deoxycorticosterone (DOC) corticosteroid is also secreted during stress and could complement the cortisol effects, but this still not fully understood. Hence, we evaluated the early transcriptomic response of rainbow trout (Oncorhynchus mykiss) liver by DOC through GR or MR. Thirty juvenile trout were pretreated with an inhibitor of endogenous cortisol synthesis (metyrapone) by intraperitoneal injection in presence or absence of GR (mifepristone) and MR (eplerenone) pharmacological antagonists for one hour. Then, fish were treated with a physiological DOC dose or vehicle (DMSO-PBS1X as control) for three hours (n = 5 per group). We measured several metabolic parameters in plasma, together with the liver glycogen content. Additionally, we constructed cDNA libraries from liver of each group, sequenced by HiseqX Illumina technology and then analyzed by RNA-seq. Plasma pyruvate and cholesterol levels decreased in DOC-administered fish and only reversed by eplerenone. Meanwhile, DOC increased liver glycogen contents depending on both corticosteroid receptor pathways. RNA-seq analysis revealed differential expressed transcripts induced by DOC through GR (448) and MR (1901). The enriched biological processes to both were mainly related to stress response, protein metabolism, innate immune response and carbohydrates metabolism. Finally, we selected sixteen genes from enriched biological process for qPCR validation, presenting a high Pearson correlation (0.8734 average). These results describe novel physiological effects of DOC related to early metabolic and transcriptomic responses in fish liver and differentially modulated by MR and GR.

Effects of the pyriproxyfen and fenthion on the gonadal morphology of Nile tilapia (Oreochromis niloticus: Perciformes, Cichlidae).

Commercially available insecticides present acute toxicity to the health of fish and other aquatic organisms, which may impair the local aquaculture. This study evaluated the gonadal morphology of freshwater fish exposed to pyriproxyfen and fenthion. Forty-five juvenile male Nile tilapias (Oreochromis niloticus) were divided into control, pyriproxyfen-exposed (0.01 g/L), and fenthion-exposed (0.001 g/L) groups. They were evaluated in three moments (30, 60, and 90 days). The variables analyzed were the gonadosomatic index (GSI), weight to length ratio, seminiferous tubules morphometry (diameter and height), tissue damage, and immunohistochemical analysis for caspase-3, tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF). Pyriproxyfen and fenthion injured the seminiferous tubule tissue, and the damage progressed according to the exposure time. In addition, the GSI gradually reduced over time in all groups compared with the first moment (30 days), while caspase-3, TNF-α, and VEGF values increased only in the fenthion-exposed group. Therefore, pyriproxyfen and fenthion changed the gonadal morphology of male Oreochromis niloticus, which may affect their reproduction in the wild or captivity.

A longitudinal study of free leptin index in pre-eclamptic pregnancies.

The ratio between circulating levels of leptin and soluble leptin receptor (sOB-R), the free leptin index (FLI), is used as a marker of leptin resistance. Therefore, the aim of our study was to investigate the FLI in mild pre-eclamptic pregnancies in a nested case-control study within a prospective observational study. Circulating levels of leptin and sOB-R levels rise significantly during pregnancy in healthy (p < 0.05) (n = 46) and pre-eclamptic pregnancies (p < 0.05) (n = 20). Serum levels of leptin were significantly higher in pre-eclamptic compared to healthy pregnancies at second and third trimesters of pregnancy (p < 0.05). Additionally, serum levels of sOB-R were significantly lower in pre-eclamptic pregnancies during the second and third trimesters of pregnancy compared to healthy pregnancies (p < 0.05). Moreover, we found that FLI did not vary significantly during pregnancy in healthy women (p > 0.05), while it increases in pre-eclamptic pregnancies (p < 0.05). Indeed, FLI was significantly higher at second and third trimesters of pregnancy in pre-eclamptic compared to healthy pregnancies (p < 0.05). In addition, FLI was significantly higher in the luteal phase compared with the follicular phase of the menstrual cycle in eumenorrheic women (p < 0.05). Receiver operating characteristic (ROC) curve analysis revealed the ability of leptin (AUC = 0.72) and FLI (AUC = 0.67) as a reliable predictor for mild pre-eclampsia during the second trimester of pregnancy. In conclusion, our findings show that FLI were significantly increased in mild pre-eclamptic pregnancies and allowed us to hypothesize that this rise might alter leptin bioavailability and bioactivity which might lead to the sympathetic hyperactivity and the hypertensive disorders during pregnancy.

Gßγ mediates activation of Rho guanine nucleotide exchange factor ARHGEF17 that promotes metastatic lung cancer progression.

Metastatic lung cancer is a major cause of death worldwide. Dissemination of cancer cells can be facilitated by various agonists within the tumor microenvironment, including by lysophosphatidic acid (LPA). We postulate that Rho guanine nucleotide exchange factors (RhoGEFs), which integrate signaling cues driving cell migration, are critical effectors in metastatic cancer. Specifically, we addressed the hypothetical role of ARHGEF17, a RhoGEF, as a potential effector of Gßγ in metastatic lung cancer cells responding to LPA. Here, we show that ARHGEF17, originally identified as a tumor endothelial marker, is involved in tumor growth and metastatic dissemination of lung cancer cells in an immunocompetent murine model. Gene expression-based analysis of lung cancer datasets showed that increased levels of ARHGEF17 correlated with reduced survival of patients with advanced-stage tumors. Cellular assays also revealed that this RhoGEF participates in the invasive and migratory responses elicited by Gi protein-coupled LPA receptors via the Gßγ subunit complex. We demonstrate that this signaling heterodimer promoted ARHGEF17 recruitment to the cell periphery and actin fibers. Moreover, Gßγ allosterically activates ARHGEF17 by the removal of inhibitory intramolecular restrictions. Taken together, our results indicate that ARHGEF17 may be a valid potential target in the treatment of metastatic lung cancer.

Viscoelastic response of confined powder under large strain oscillations, characterized by its noise temperature.

We report a study on granular matter with and without small additions of silicon oil, under low-frequency and large amplitude oscillatory shear strain under constant normal pressure, by running experiments with a rotational rheometer with a cup-and-plate geometry. We analysed the expansion with the Chebyshev polynomials of the orthogonal decomposition of stress-strain Lissajous-Bowditch loops. We found the onset of the strain amplitude for the yielding regime indicated a regime change from filament-like structures of grains to grain rearrangements for the dry granulate and from oscillations to the breaking and regeneration of liquid bridges for wet granulates. We have shown that this viscoelastic dynamics can be characterized by a noise temperature following Sollich et al. (Phys Rev Lett https://doi.org/10.1103/PhysRevLett.78.2020 , 1997). The analysis of the first harmonics of the Chebyshev expansion showed that the state of disorder of dry and wet granular matter in pre-yielding and yielding regimes involved ensembles of different inherent states; thus, each of them was governed by a different noise temperature. The higher-order harmonics of the Chebyshev expansion revealed a proportionality between the viscous nonlinearity and the variation in the elastic nonlinearity induced by the deformation, which shows the coupling between the elastic deformation and the viscous flow of mesoscopic-scale structures.

Oxindole and Benzoxazinone Alkaloids from the Seeds of Persea americana (Avocado) and Their SIRT1 Stimulatory Activity.

Persea americana Mill. (Lauraceae), commonly known as avocado, is a well-known food because of its nutrition and health benefits. The seeds of avocado are major byproducts, and thus their phytochemicals and bioactivities have been of interest for study. The chemical components of avocado seeds were investigated by using UPLC-qTOF-MS/MS-based molecular networking, resulting in the isolation of seven new oxindole alkaloids (1-7) and two new benzoxazinone alkaloids (8 and 9). The chemical structures of the isolated compounds were identified by the analysis of NMR data in combination with computational approaches, including NMR and ECD calculations. Bioactivities of the isolated compounds toward silent information regulation 2 homologue-1 (SIRT1) in HEK293 cells were assessed. The results showed that compound 1 had the most potent effect on SIRT1 activation with an elevated NAD+/NADH ratio with potential for further investigation as an anti-aging agent.

Advanced echocardiography techniques (AETs) to assess left atrial structure and function in individuals with resistant hypertension.

AIMS: Resistant hypertension (RH) is a challenging phenotype within the hypertension (HTN) spectrum, requiring careful assessment and follow-up. Evaluation of left atrial function may be clinically informative, but is usually neglected. Advanced Echocardiography Techniques (AETs), such as Strain Analysis and three-dimensional echocardiography (3D ECHO) may be useful complementary tools to assess atrial function in patients with RH. METHODS AND RESULTS: Ninety-six eligible adult patients were categorized into three groups: resistant hypertensive (RH), controlled hypertensive (CH), and normotensive (N), and underwent AETs to identify morphofunctional changes in the left atrium (LA) across different HTN phenotypes. The LA reservoir strain was significantly lower among RH than in N and CH patients (p < .001). Accordingly, LA conduit strain showed a gradient through the groups: higher among N, followed by CH and RH patients (p = .015). LA contraction strain was higher among CH than in N and RH patients (p = .02). Maximum indexed, pre-A, and minimum atrial volumes obtained by 3D ECHO showed differences between N and the others (p < .001), but not between CH and RH. N patients showed a higher fraction of passive emptying of the LA than the others (p = .02), with no difference between CH and RH. Total emptying of the LA only differed between N and RH patients, while active emptying of the LA showed no difference between the groups (p = .82). CONCLUSION: The left atrium may present early functional changes in response to HTN, which are detectable by AETs. AETs, especially S-LA, allowed to identify markers of atrial myocardial damage in both RH and CH patients.

Estimating the cost of HIV services for key populations provided by the LINKAGES program in Kenya and Malawi.

BACKGROUND: Data remain scarce on the costs of HIV services for key populations (KPs). The objective of this study was to bridge this gap in the literature by estimating the unit costs of HIV services delivered to KPs in the LINKAGES program in Kenya and Malawi. We estimated the mean total unit costs of seven clinical services: post-exposure prophylaxis (PEP), pre-exposure prophylaxis (PrEP), HIV testing services (HTS), antiretroviral therapy (ART), sexually transmitted infection (STI) services, sexual and reproductive health (SRH) services, and management of sexual violence (MSV). These costs take into account the costs of non-clinical services delivered alongside clinical services and the pre-service and above-service program management integral to the LINKAGES program. METHODS: Data were collected at all implementation levels of the LINKAGES program including 30 drop-in-centers (DICs) in Kenya and 15 in Malawi. This study was conducted from the provider's perspective. We estimated economic costs for FY 2019 and cost estimates include start-up costs. Start-up and capital costs were annualized using a discount rate of 3%. We used a combination of top-down and bottom-up costing approaches. Top-down methods were used to estimate the costs of headquarters, country offices, and implementing partners. Bottom-up micro-costing methods were used to measure the quantities and prices of inputs used to produce services in DICs. Volume-weighted mean unit costs were calculated for each clinical service. Costs are presented in 2019 United States dollars (US$). RESULTS: The mean total unit costs per service ranged from US$18 (95% CI: 16, 21) for STI services to US$635 (95% CI: 484, 785) for PrEP in Kenya and from US$41 (95% CI: 37, 44) for STI services to US$1,240 (95% CI 1156, 1324) for MSV in Malawi. Clinical costs accounted for between 21 and 59% of total mean unit costs in Kenya, and between 25 and 38% in Malawi. Indirect costs-including start-up activities, the costs of KP interventions implemented alongside clinical services, and program management and data monitoring-made up the remaining costs incurred. CONCLUSIONS: A better understanding of the cost of HIV services is highly relevant for budgeting and planning purposes and for optimizing HIV services. When considering all service delivery costs of a comprehensive HIV service package for KPs, costs of services can be significantly higher than when considering direct clinical service costs alone. These estimates can inform investment cases, strategic plans and other budgeting exercises.

Population size regulation is density-dependent in Rhodnius prolixus (Hemiptera: Reduviidae) through an irritability mechanism.

BACKGROUND: Physical factors can determine the level of triatomine abundance, but do not regulate their population densities, and neither do natural enemies. OBJECTIVES: To identify the processes associated with density-dependent triatomine population regulation. METHODS: We set-up a laboratory experiment with four interconnected boxes; the central box harbored Rhodnius prolixus bugs and one hamster. Stage 5 and adult densities of 10, 20, 30, 40, and 60 bugs per hamster, were replicated four times (except the density of 60 bugs). Hamster's irritability and several triatomine responses were measured: feeding, development time and longevity, mortality, fecundity, dispersal, and the net reproductive value (R o ). FINDINGS: Density had a statistically significant effect on irritability, but not on the percent of bugs feeding. Density was significant on blood meal size ingested in bugs that did not move between boxes, but not significant when the bugs moved. Density and irritability affected the proportion of stage 5 nymphs molting, and the proportion of adult bugs dying per day and over a three-week period. There was a highly significant effect of density and irritability on R o . MAIN CONCLUSIONS: We showed that a density-dependent mechanism, acting through the irritability of the host, seems the most plausible process regulating populations in triatomines.

Espacios cardioprotegidos en México: acciones para prevenir la muerte súbita cardiaca. Una postura de profesionales de la salud.

La muerte súbita cardiaca es un problema de salud pública a nivel mundial. Aunque su incidencia no es conocida, se estima que causa hasta 50% de la mortalidad de origen cardíaco y hasta 20% de la mortalidad total en los adultos. En México, estimaciones previas sugieren que causa en promedio 33 000 muertes al año; sin embargo, los datos no son precisos. La  mitad de los eventos por muerte súbita cardiaca se deben a un paro cardiaco súbito extrahospitalario que, de no ser atendido oportunamente, deriva en una muerte súbita cardiaca. Por tanto, la capacidad de responder pronta y adecuadamente a estos eventos con las maniobras y equipos necesarios mejora la sobrevida de las víctimas. Para atender este problema, en algunos estados del país se han creado espacios cardioprotegidos que permiten realizar maniobras de reanimación cardiopulmonar y desfibrilación cardiaca de acceso público oportunamente. Como objetivo, los profesionales de la salud establecen la importancia de implementar espacios cardioprotegidos y crear políticas públicas al respecto en todo el país.