The Impact of Social Determinants of Health on Transition from Pediatric to Adult Cardiology Care.

Social determinants of health (SDoH) are the economic, social, environmental, and psychosocial factors that influence health. Adolescents and young adults with congenital heart disease (CHD) require lifelong cardiology follow-up and therefore coordinated transition from pediatric to adult healthcare systems. However, gaps in care are common during transition, and driven in part by pervasive disparities in SDoH including race, ethnicity, socioeconomic status, access to insurance, and remote location of residence. These disparities often co-exist, and compound challenges faced by patients and families. For example, Black and Indigenous individuals are more likely to be subject to systemic racism and implicit bias within healthcare and other settings, be unemployed and poor, have limited access to insurance, and have a lower likelihood of transfer of care to adult CHD specialists. SDoH are also associated with acquired cardiovascular disease, a co-morbidity that adults with CHD face. This review summarizes existing evidence regarding the impact of SDoH on transition to adult care and proposes strategies at the individual, institutional, and population/system levels to reduce inequities faced by transition-age youth. These include routinely screening for SDoH in clinical settings with referral to appropriate services for those who screen positive, providing formal transition education for all transition-age youth including training on navigating complex medical systems, creating satellite cardiology clinics to facilitate access to care for those who live remote from tertiary centers, advocating for lifelong insurance coverage where applicable, mandating cultural sensitivity training for providers, and increasing the diversity of healthcare providers in pediatric and adult CHD care.

Clinical and economic burden of systemic lupus erythematosus in Colombia.

AIMS: Our cost-of-illness (COI) model adopted payer and societal perspectives over five years to measure the economic burden of Systemic Lupus Erythematosus (SLE) in Colombia. MATERIALS AND METHODS: A prevalence-based model was constructed to estimate costs and economic consequences for SLE patients in Colombia. The model included four health states: three phenotypes of SLE representing mild, moderate, and severe states and death. The clinical inputs were captured from the published literature and validated by the Delphi panel. Our model measured direct medical and indirect costs, including disease management, transient events, and indirect costs. One-way sensitivity analysis was also performed. RESULTS: The number of Colombian SLE patients was 37,498. The number of SLE patients with mild, moderate, and severe phenotypes was 5343, 28757 and 3,397, respectively. SLE-patients with moderate (Colombian pesos; COP 146 billion) and severe phenotypes (COP276 billion) incurred higher costs than those with mild phenotypes (COP2 billion), over 5 years. The total SLE cost in Colombia over five years from the payer and societal perspectives was estimated to be COP 915 billion and 8 trillion, respectively. The costs per patient per year from the payer and societal perspectives were COP 4,881,902 ($3,510) and COP 46,637,054 ($33,528), respectively. CONCLUSION: The burden of SLE in Colombia over five years is substantially high, mainly due to the consequences of economic loss because it affects women and men of working age, in addition to the costs of SLE management and its consequences, such as flares, infection, and organ damage. Our COI indicated that disease management costs among patients with moderate and severe SLE were substantially higher than those among patients with a mild phenotype. Therefore, more attention should be paid to limiting the progression of SLE and the occurrence of flares, with the need for further economic evaluation of novel treatment strategies that help in disease control.

National, regional, and global estimates of low birthweight in 2020, with trends from 2000: a systematic analysis.

BACKGROUND: Low birthweight (LBW; <2500 g) is an important predictor of health outcomes throughout the life course. We aimed to update country, regional, and global estimates of LBW prevalence for 2020, with trends from 2000, to assess progress towards global targets to reduce LBW by 30% by 2030. METHODS: For this systematic analysis, we searched population-based, nationally representative data on LBW from Jan 1, 2000, to Dec 31, 2020. Using 2042 administrative and survey datapoints from 158 countries and areas, we developed a Bayesian hierarchical regression model incorporating country-specific intercepts, time-varying covariates, non-linear time trends, and bias adjustments based on data quality. We also provided novel estimates by birthweight subgroups. FINDINGS: An estimated 19·8 million (95% credible interval 18·4-21·7 million) or 14·7% (13·7-16·1) of liveborn newborns were LBW worldwide in 2020, compared with 22·1 million (20·7-23·9 million) and 16·6% (15·5-17·9) in 2000-an absolute reduction of 1·9 percentage points between 2000 and 2020. Using 2012 as the baseline, as this is when the Global Nutrition Target began, the estimated average annual rate of reduction from 2012 to 2020 was 0·3% worldwide, 0·85% in southern Asia, and 0·59% in sub-Saharan Africa. Nearly three-quarters of LBW births in 2020 occurred in these two regions: of 19 833 900 estimated LBW births worldwide, 8 817 000 (44·5%) were in southern Asia and 5 381 300 (27·1%) were in sub-Saharan Africa. Of 945 300 estimated LBW births in northern America, Australia and New Zealand, central Asia, and Europe, approximately 35·0% (323 700) weighed less than 2000 g: 5·8% (95% CI 5·2-6·4; 54 800 [95% CI 49 400-60 800]) weighed less than 1000 g, 9·0% (8·7-9·4; 85 400 [82 000-88 900]) weighed between 1000 g and 1499 g, and 19·4% (19·0-19·8; 183 500 [180 000-187 000]) weighed between 1500 g and 1999 g. INTERPRETATION: Insufficient progress has occurred over the past two decades to meet the Global Nutrition Target of a 30% reduction in LBW between 2012 and 2030. Accelerating progress requires investments throughout the lifecycle focused on primary prevention, especially for adolescent girls and women living in the most affected countries. With increasing numbers of births in facilities and advancing electronic information systems, improvements in the quality and availability of administrative LBW data are also achievable. FUNDING: The Children's Investment Fund Foundation; the UNDP-UNFPA-UNICEF-WHO World Bank Special Programme of Research, Development and Research Training in Human Reproduction; and the Bill & Melinda Gates Foundation.

PTCH1 gene variants rs357564, rs2236405, rs2297086 and rs41313327, mRNA and tissue expression in basal cell carcinoma patients from Western Mexico.

BACKGROUND: Basal cell carcinoma (BCC) represents about 80% of all cases of skin cancer. The PTCH1 is a transmembrane protein of the Sonic Hedgehog signaling pathway that regulates cell proliferation. Genetic variants in PTCH1 gene have been previously described in association with BCC development. In addition, PTCH1 mRNA and protein expression analysis are also significant to understand its role in skin cancer physiopathology. METHODS: An analytical cross-sectional study was performed, and a total of 250 BCC patients and 290 subjects from the control group (CG) were included, all born in western Mexico. The genotypes and relative expression of the mRNA were determined by TaqMan® assay. The protein expression was investigated in 70 BCC paraffin-embedded samples with PTCH1 antibodies. Semi-quantitative analysis was performed to determine the expression level in the immunostained cells. RESULTS: We did not find evidence of an association between PTCH1 rs357564, rs2297086, rs2236405, and rs41313327 genetic variants and susceptibility to BCC. Likewise, no statistically significant differences were found in the comparison of the mRNA level expression between BCC and CG (p > 0.05). The PTCH1 protein showed a low expression in 6 of the analyzed samples and moderate expression in 1 sample. No association was found between genetic variants, protein expression, and demographic-clinical characteristics (p > 0.05). CONCLUSION: The studied PTCH1 variants may not be associated with BCC development in the Western Mexico population. The PTCH1 mRNA levels were lower in patients with BCC compared to the control group, but its protein was underexpressed in the tissue samples.

Incidence of Respiratory Syncytial Virus-Associated Lower Respiratory Tract Illness in Infants in Low- and Middle-Income Regions During the Coronavirus Disease 2019 Pandemic.

Background: Incidence data of respiratory syncytial virus-associated lower respiratory tract illness (RSV-LRTI) are sparse in low- and middle-income countries (LMICs). We estimated RSV-LRTI incidence rates (IRs) in infants in LMICs using World Health Organization case definitions. Methods: This prospective cohort study, conducted in 10 LMICs from May 2019 to October 2021 (largely overlapping with the coronavirus disease 2019 [COVID-19] pandemic), followed infants born to women with low-risk pregnancies for 1 year from birth using active and passive surveillance to detect potential LRTIs, and quantitative reverse-transcription polymerase chain reaction on nasal swabs to detect RSV. Results: Among 2094 infants, 32 (1.5%) experienced an RSV-LRTI (8 during their first 6 months of life, 24 thereafter). Seventeen (0.8%) infants had severe RSV-LRTI and 168 (8.0%) had all-cause LRTI. IRs (95% confidence intervals [CIs]) of first RSV-LRTI episode were 1.0 (.3-2.3), 0.8 (.3-1.5), and 1.6 (1.1-2.2) per 100 person-years for infants aged 0-2, 0-5, and 0-11 months, respectively. IRs (95% CIs) of the first all-cause LRTI episode were 10.7 (8.1-14.0), 11.7 (9.6-14.0), and 8.7 (7.5-10.2) per 100 person-years, respectively. IRs varied by country (RSV-LRTI: 0.0-8.3, all-cause LRTI: 0.0-49.6 per 100 person-years for 0- to 11-month-olds). Conclusions: RSV-LRTI IRs in infants in this study were relatively low, likely due to reduced viral circulation caused by COVID-19-related nonpharmaceutical interventions. Clinical Trials Registration: NCT03614676.

Caracterización de los resultados de biopsia por trucut en pacientes con BI-RADS 4 y 5 sin criterio quirúrgico

Introducción: La biopsia percutánea se ha convertido, en nuestros días, en el método diagnóstico más utilizado para la evaluación de las lesiones de mama sospechosas de malignidad. Objetivo: Caracterizar los resultados de biopsia por trucut en pacientes con categorías BI-RADS 4 y 5 sin criterio quirúrgico. Materiales y métodos: Se realizó un estudio observacional, descriptivo y transversal de 70 pacientes que presentaron lesión sospechosa de malignidad por ultrasonografía y que requirieron la realización de biopsia por aguja gruesa de la imagen reportada, entre enero de 2019 y diciembre de 2020. Se realizaron en la Consulta de Intervencionismo Mamario del Departamento de Imagenología del Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, de Matanzas. Se analizaron las variables edad, categoría BI-RADS, resultado histopatológico, tamaño tumoral y complicaciones. Resultados: El grupo etario predominante fue el de 70-79 años (27,1). Se clasificaron 48 pacientes con categoría BI-RADS 5, para un 68,6 %. El carcinoma ductal infiltrante resulto ser el tipo histológico predominante, con 40 pacientes, representando el 57,1 % del total. Se obtuvo una media de 28,91 mm de diámetro de las lesiones biopsiadas. Todas las muestras resultaron útiles, aun en diámetros transversales inferiores a 2 cm. En la serie, las complicaciones reportadas fueron escasas. Conclusiones: La biopsia realizada con aguja gruesa bajo guía ecográfica con técnica de manos libres, es un método confiable para el diagnóstico de cáncer de mama, seguro y sin complicaciones graves. Se confirma que la categoría BI-RADS 5 coincide con diagnóstico histopatológico de cáncer mamario.

Introduction: Percutaneous biopsy has become, nowadays, the most used diagnostic method to evaluate breast lesions suspected of malignancy. Objective: To characterize the Tru-cut biopsy results in patients with BI-RADS 4 and 5 categories without surgical criteria. Materials and methods: An observational, descriptive and cross-sectional study was carried out between January 2019 and December 2020 on 70 patients who presented who presented a lesion suspicious of malignancy by ultrasonography and required a thick-needle biopsy of the reported image. They were performed at the Breast Intervention Clinic of the Imaging Department of the Clinical Surgical University Hospital Comandante Faustino Pérez Hernández, from Matanzas. The variables age, BI-RADS category, histopathological result, tumor size and complications were analyzed. Results: The predominant age group was the 70-79 years-old one (27.1). 48 patients were classified with BI-RADS 5 category, for 68.6%. Infiltrating ductal carcinoma resulted the predominant histological type, with 40 patients representing 57.1% of the total. An average diameter of 28.91 mm was obtained from the biopsied lesions. All samples were useful, even in transverse diameters less than 2cm. In the series, few complications were reported. Conclusion: Biopsy performed with thick needle under ultrasound guidance with free-hands technique, is a reliable method for breast cancer diagnosis, safe and without serious complications. It is confirmed that BI-RADS 5 category coincides with breast cancer pathological diagnosis.

Estudio multicéntrico sobre multimorbilidad en internados en áreas clínicas / Multicenter Study on Multimorbidity in Patients in Clinical Areas

Introducción: El estudio de la comorbilidad requiere de un enfoque multilateral con vistas a mejorar la calidad de la atención de los enfermos por el sistema de atención. Objetivos: Explorar la magnitud de la comorbilidad de enfermedades crónicas en adultos internados en los hospitales. Métodos: Se realizó un estudio prospectivo-observacional-longitudinal-analítico. Se incluyeron pacientes internados en las Salas de Clínica Médica o pacientes clínicos en Salas de Internación Indiscriminada. Se realizó un estudio multicéntrico en 42 centros en un período de 2 años, con un muestreo consecutivo. Para el estudio se tuvo en cuenta la estadística descriptiva, inferencial y de regresión. Resultados: El total de pacientes en el estudio fue de 5925, masculinos con el 50,3 por ciento de edad 60,66 ± 0,25 años. Principal procedencia desde la guardia el 73 por ciento. La estadía hospitalaria de 12,61 ± 0,24 días, mayormente en pacientes quirúrgicos (15,45 ± 0,67 vs 11,76 ± 0,23; p < 0,00001). El 23 por ciento recibió tratamiento quirúrgico. El principal nivel educativo: secundario completo 21,6 por ciento. Dificultades económicas: 20 por ciento, mortalidad 9,26 por ciento; prevalencia de dislipemia, diabetes e hipertensión: 22,53 por ciento; 28,82 por ciento y 51,86 por ciento con 473 nuevos diagnósticos, IMC: 27,88 ± 0,65, Charlson global 2,09 ± 0,02 y en óbitos 3,84 ± 0,11. La media de patologías por paciente fue de 2,14 ± 0,01 y aumentó con la edad (p valor regresión lineal < 0,00001). Conclusiones: La hipertensión, la diabetes y la dislipemia representaron las entidades más prevalentes en Salas de Internación Clínica, Las enfermedades cardiovasculares, respiratorias, infectológicas, oncológicas, neurológicas, metabólicas y nefrológicas fueron predictores independientes de mortalidad(AU)

Introduction: The study of comorbidity requires a multilateral approach with a view to improving the quality of care for these patients by the care system. Objectives: To explore the magnitude of the comorbidity of chronic diseases in adults admitted to hospitals. Methods: Prospective-observational-longitudinal-analytical study. Patients hospitalized in a medical clinic room or clinical patients in indiscriminate hospitalization rooms are included, Multicenter study in 42 centers, with 2 years of recruitment. Consecutive sampling. Descriptive, inferential and regression statistics. Results: 5925 recruited, male gender 50,3percent, age 60,66 ± 0,25 years, main origin from the guard 73percent, stay 12,61 ± 0,24 days, longer in surgical (15,45 ± 0,67 vs 11,76 ± 0,23, p < 0,00001), 23percent received surgical treatment. Main educational level: complete secondary school 21,6%. Economic difficulties: 20percent, mortality 9,26percent, prevalence of dyslipidemia, diabetes and hypertension: 22,53percent, 28,82percent and 51,86percent with 473 new diagnoses in said pathologies, BMI: 27,88 ± 0,65, Global Charlson 2,09 ± 0,02 and in deaths 3,84 ± 0,11. The average number of pathologies per patient was 2,14 ± 0,01 and increased with age (p value for linear regression < 0,00001). Conclusions: Hypertension, diabetes and dyslipidemia represented the most prevalent entities in the clinical hospitalization room, cardiovascular, respiratory, infectious, oncological, neurological, metabolic and nephrological diseases were independent predictors of mortality(AU)

National, regional, and global estimates of preterm birth in 2020, with trends from 2010: a systematic analysis.

BACKGROUND: Preterm birth is the leading cause of neonatal mortality and is associated with long-term physical, neurodevelopmental, and socioeconomic effects. This study updated national preterm birth rates and trends, plus novel estimates by gestational age subgroups, to inform progress towards global health goals and targets, and aimed to update country, regional, and global estimates of preterm birth for 2020 in addition to trends between 2010 and 2020. METHODS: We systematically searched population-based, nationally representative data on preterm birth from Jan 1, 2010, to Dec 31, 2020 and study data (26 March-14 April, 2021) for countries and areas with no national-level data. The analysis included 679 data points (86% nationally representative administrative data [582 of 679 data points]) from 103 countries and areas (62% of countries and areas having nationally representative administrative data [64 of 103 data points]). A Bayesian hierarchical regression was used for estimating country-level preterm rates, which incoporated country-specific intercepts, low birthweight as a covariate, non-linear time trends, and bias adjustments based on a data quality categorisation, and other indicators such as method of gestational age estimation. FINDINGS: An estimated 13·4 million (95% credible interval [CrI] 12·3-15·2 million) newborn babies were born preterm (<37 weeks) in 2020 (9·9% of all births [95% CrI 9·1-11·2]) compared with 13·8 million (12·7-15·5 million) in 2010 (9·8% of all births [9·0-11·0]) worldwide. The global annual rate of reduction was estimated at -0·14% from 2010 to 2020. In total, 55·6% of total livebirths are in southern Asia (26·8% [36 099 000 of 134 767 000]) and sub-Saharan Africa (28·7% [38 819 300 of 134 767 000]), yet these two regions accounted for approximately 65% (8 692 000 of 13 376 200) of all preterm births globally in 2020. Of the 33 countries and areas in the highest data quality category, none were in southern Asia or sub-Saharan Africa compared with 94% (30 of 32 countries) in high-income countries and areas. Worldwide from 2010 to 2020, approximately 15% of all preterm births occurred at less than 32 weeks of gestation, requiring more neonatal care (<28 weeks: 4·2%, 95% CI 3·1-5·0, 567 800 [410 200-663 200 newborn babies]); 28-32 weeks: 10·4% [9·5-10·6], 1 392 500 [1 274 800-1 422 600 newborn babies]). INTERPRETATION: There has been no measurable change in preterm birth rates over the last decade at global level. Despite increasing facility birth rates and substantial focus on routine health data systems, there remain many missed opportunities to improve preterm birth data. Gaps in national routine data for preterm birth are most marked in regions of southern Asia and sub-Saharan Africa, which also have the highest estimated burden of preterm births. Countries need to prioritise programmatic investments to prevent preterm birth and to ensure evidence-based quality care when preterm birth occurs. Investments in improving data quality are crucial so that preterm birth data can be improved and used for action and accountability processes. FUNDING: The Children's Investment Fund Foundation and the UNDP, United Nations Population Fund-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction.

First isolation of Rickettsia amblyommatis from Amblyomma mixtum in Colombia.

BACKGROUND: Rickettsiae are obligate intracellular Gram-negative bacteria that are the causative agent of rickettsioses and are spread to vertebrate hosts by arthropods. There are no previous reports of isolation of Rickettsia amblyommatis for Colombia. METHODS: A convenience sampling was executed in three departments in Colombia for direct collection of adult ticks on domestic animals or over vegetation. Ticks were screened for the presence of Rickettsia spp. by real-time polymerase chain reaction (qPCR) amplifying the citrate synthase gene (gltA), and the positive sample was processed for isolation and further molecular characterization by conventional PCR. The absolute and relative frequencies were calculated for several tick species variables. All products from conventional PCR were further purified and sequenced by the Sanger technique. Representative sequences of 18 Rickettsia species were downloaded from GenBank. Consensus phylogenetic trees were constructed for the gltA, ompB, ompA, and htrA genes with 1000 replicates, calculating bootstrap values through the maximum likelihood method and the generalized time reversible substitution model in the MEGA 7.0 software program. RESULTS: One female Amblyomma mixtum collected on vegetation was amplified by qPCR (gltA), indicating a frequency of 1.6% (1/61) for Rickettsia spp. INFECTION: Sequence analysis of a rickettsial isolate from this tick in BLASTn showed 100% identity with gltA (340 base pairs [bp]), 99.87% for ompB (782 bp), 98.99% for htrA (497 bp), and 100% for ompA (488 bp) to R. amblyommatis. Concatenated phylogenetic analysis confirmed these findings indicating that the isolate is grouped with other sequences of Amblyomma cajennense complex from Panama and Brazil within the R. amblyommatis clade. CONCLUSIONS: This paper describes the isolation and early molecular identification of a R. amblyommatis strain from A. mixtum in Colombia.

Human Monkeypox: A Comprehensive Overview of Epidemiology, Pathogenesis, Diagnosis, Treatment, and Prevention Strategies.

Monkeypox virus (MPXV) is an emerging zoonotic virus that belongs to the Orthopoxvirus genus and presents clinical symptoms similar to those of smallpox, such as fever and vesicular-pustular skin lesions. However, the differential diagnosis between smallpox and monkeypox is that smallpox does not cause lymphadenopathy but monkeypox generates swelling in the lymph nodes. Since the eradication of smallpox, MPXV has been identified as the most common Orthopoxvirus to cause human disease. Despite MPXV being endemic to certain regions of Africa, the current MPXV outbreak, which began in early 2022, has spread to numerous countries worldwide, raising global concern. As of the end of May 2023, over 87,545 cases and 141 deaths have been reported, with most cases identified in non-endemic countries, primarily due to human-to-human transmission. To better understand this emerging threat, this review presents an overview of key aspects of MPXV infection, including its animal reservoirs, modes of transmission, animal models, epidemiology, clinical and immunological features, diagnosis, treatments, vaccines, and prevention strategies. The material presented here provides a comprehensive understanding of MPXV as a disease, while emphasizing the significance and unique characteristics of the 2022 outbreak. This offers valuable information that can inform future research and aid in the development of effective interventions.

Using geometric morphometrics to determine the "fittest" floral shape: A case study in large-flowered, buzz-pollinated Meriania hernandoi.

PREMISE: Floral shape (relative arrangement and position of floral organs) is critical in mediating fit with pollinators and maximizing conspecific pollen transfer particularly in functionally specialized systems. To date, however, few studies have attempted to quantify flowers as the inherently three-dimensional (3D) structures they are and determine the effect of intraspecific shape variation on pollen transfer. We here addressed this research gap using a functionally specialized system, buzz pollination, in which bees extract pollen through vibrations, as a model. Our study species, Meriania hernandoi (Melastomataceae), undergoes a floral shape change from pseudocampanulate corollas with more actinomorphically arranged stamens (first day) to open corollas with a more zygomorphic androecium (second day) over anthesis, providing a natural experiment to test how variation in floral shape affects pollination performance. METHODS: In one population of M. hernandoi, we bagged 51 pre-anthetic flowers and exposed half of them to bee pollinators when they were in either stage of their shape transition. We then collected flowers, obtained 3D flower models through x-ray computed tomography for 3D geometric morphometric analyses, and counted the pollen grains remaining per stamen (male pollination performance) and stigmatic pollen loads (female pollination performance). RESULTS: Male pollination performance was significantly higher in open flowers with zygomorphic androecia than in pseudo-campanulate flowers. Female pollination performance did not differ among floral shapes. CONCLUSIONS: These results suggest that there is an "optimal" shape for male pollination performance, while the movement of bees around the flower when buzzing the spread-out stamens results in sufficient pollen deposition regardless of floral shape.

Atypical Systemic Neonatal Herpes Diagnosed Incidentally in Twin Infants.

Neonatal herpes simplex virus (HSV) infections are serious infections that usually occur in the first few weeks of life. Infants generally present with mucocutaneous lesions, central nervous system infection, and/or systemic disease. In this case report, we describe a set of twins that had unexpected presentations of neonatal HSV. Twin A was diagnosed incidentally on routine eye exam, and Twin B was diagnosed only because his twin was found to be infected; both infants were still hospitalized and were beyond 1 month of age. These twins exhibited atypical manifestations that diverge from the 3 main categories of neonatal HSV and expand our understanding of the spectrum of disease.

Differential Susceptibility of Aedes aegypti and Aedes albopictus Mosquitoes to Infection by Mayaro Virus Strains.

Mayaro virus (MAYV) is an arthropod-borne virus (arbovirus) belonging to the family Togaviridae, genus Alphavirus. In recent years, the geographic distribution of MAYV may have expanded north from South and Central America into the Caribbean Islands. Although Haemagogus janthinomys is considered the main vector for MAYV, the virus has also been isolated from other mosquitoes, including Aedes aegypti, a widespread species that serves as the main vector for highly epidemic viruses. Given the possible expansion and outbreaks of MAYV in Latin America, it is possible that MAYV might be adapting to be efficiently transmitted by urban vectors. Therefore, to investigate this possibility, we evaluated the vector competence of Ae. aegypti and Ae. albopictus mosquitoes to transmit MAYV isolated during a year of low or high MAYV transmission. Adult Ae. aegypti and Ae. albopictus were orally infected with the MAYV strains, and the infection, dissemination, and transmission rates were calculated to evaluate their vector competence. Overall, we found higher infection, dissemination, and transmission rates in both Ae. aegypti and Ae. albopictus mosquitoes infected with the strain isolated during a MAYV outbreak, whereas low/no transmission was detected with the strain isolated during a year of low MAYV activity. Our results confirmed that both Ae. aegypti and Ae. albopictus are competent vectors for the emergent MAYV. Our data suggest that strains isolated during MAYV outbreaks might be better fit to infect and be transmitted by urban vectors, raising serious concern about the epidemic potential of MAYV.

West Nile Virus and Epizootic Hemorrhagic Disease Virus Co-Infection in a Novel Host at the Nashville Zoo.

On August 30, 2017, one of five bontebok in a mixed-species exhibit at the Nashville Zoo at Grassmere exhibited acute hind-limb ataxia and altered demeanor. Pathological examination demonstrated meningoencephalitis and spinal myelitis. Coinfection of West Nile virus (WNV) and epizootic hemorrhagic disease virus (EHDV) was revealed by quantitative real-time and traditional reverse transcription-polymerase chain reaction assays and virus isolation/whole genome sequencing from brain tissue, respectively. Whole genome sequencing was conducted for EHDV. Mosquito testing from September 19 to October 13, 2017, demonstrated a higher WNV infection rate in mosquitoes at the zoo compared with the rest of Nashville-Davidson County. EHDV is endemic in wild white-tailed deer (family Cervidae) in Tennessee, and the prevalence in wildlife depends on environmental influences. This case illustrates the potential susceptibility of exotic zoo animals to endemic domestic arthropod-borne viruses (arboviruses) and reinforces the importance of cooperative antemortem and postmortem surveillance strategies among human, wildlife, and domestic animal health agencies.

Population-based genomic study of Plasmodium vivax malaria in seven Brazilian states and across South America.

Background: Brazil is a unique and understudied setting for malaria, with complex foci of transmission associated with human and environmental conditions. An understanding of the population genomic diversity of P. vivax parasites across Brazil can support malaria control strategies. Methods: Through whole genome sequencing of P. vivax isolates across 7 Brazilian states, we use population genomic approaches to compare genetic diversity within country (n = 123), continent (6 countries, n = 315) and globally (26 countries, n = 885). Findings: We confirm that South American isolates are distinct, have more ancestral populations than the other global regions, with differentiating mutations in genes under selective pressure linked to antimalarial drugs (pvmdr1, pvdhfr-ts) and mosquito vectors (pvcrmp3, pvP45/48, pvP47). We demonstrate Brazil as a distinct parasite population, with signals of selection including ABC transporter (PvABCI3) and PHIST exported proteins. Interpretation: Brazil has a complex population structure, with evidence of P. simium infections and Amazonian parasites separating into multiple clusters. Overall, our work provides the first Brazil-wide analysis of P. vivax population structure and identifies important mutations, which can inform future research and control measures. Funding: AI is funded by an MRC LiD PhD studentship. TGC is funded by the Medical Research Council (Grant no. MR/M01360X/1, MR/N010469/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1). SC is funded by Medical Research Council UK grants (MR/M01360X/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1) and Bloomsbury SET (ref. CCF17-7779). FN is funded by The Shloklo Malaria Research Unit - part of the Mahidol Oxford Research Unit, supported by the Wellcome Trust (Grant no. 220211). ARSB is funded by São Paulo Research Foundation - FAPESP (Grant no. 2002/09546-1). RLDM is funded by Brazilian National Council for Scientific and Technological Development - CNPq (Grant no. 302353/2003-8 and 471605/2011-5); CRFM is funded by FAPESP (Grant no. 2020/06747-4) and CNPq (Grant no. 302917/2019-5 and 408636/2018-1); JGD is funded by FAPESP fellowships (2016/13465-0 and 2019/12068-5) and CNPq (Grant no. 409216/2018-6).

Targeting inflammasome-dependent mechanisms as an emerging pharmacological approach for osteoarthritis therapy.

Arthritic diseases have attracted enormous scientific interest because of increased worldwide prevalence and represent a significant socioeconomic burden. Osteoarthritis (OA) is the most prevalent form of arthritis. It is a disorder of the diarthrodial joints, characterized by degeneration and loss of articular cartilage associated with adjacent subchondral bone changes. Chronic and unresolving inflammation has been identified as a critical factor driving joint degeneration and pain in OA. Despite numerous attempts at therapeutic intervention, no effective disease-modifying agents targeting OA inflammation are available to the patients. Inflammasomes are protein complexes known to play a critical role in the inflammatory pathology of several diseases, and their roles in OA pathogenesis have become evident over the last decade. In this sense, it is relevant to evaluate the vital role of inflammasomes as potential modulators of pathogenic features in OA. This review will provide an overview and perspectives on why understanding inflammasome activation is critical for identifying effective OA therapies. We elaborate on the contribution of extracellular mediators from the circulatory system and synovial fluid as well as intracellular activators within the synovial fibroblasts and articular chondrocytes toward invoking the inflammasome in OA. We further discuss the merits of emerging inflammasome targeting therapies and speculate on the potential strategies for inflammasome blockade for OA therapy.

APOA1 (-75 G>A and 83 C>T) and APOB (2488 C>T) polymorphisms and their association with myocardial infarction, lipids and apolipoproteins in patients with type 2 diabetes mellitus.

Introduction: The increased risk of myocardial infarction (MI) in type 2 diabetes mellitus (T2DM) is well documented. Polymorphisms in APOA1 and APOB genes allow us to identify new genetic markers in the Mexican population with T2DM and MI. Material and methods: We studied 135 patients with DMT2 and MI (DI); another 85 non-infarcted diabetic individuals with DMT2 but without previous ischemic events (NID) and 242 healthy subjects (HS). All three groups were selected with the aim to investigate the association between the polymorphisms and infarction when T2DM is present or absent. Results: -75 G>A polymorphism: Differences were found in genotype distribution between DI and NID individuals (OR = 2.01, 95% CI: 1.117-3.623, p = 0.019) with an increased risk for A in the dominant model (OR = 1.77, 95% CI: 1.020-3.084, p = 0.042); also concentrations of ApoA-I for A/A were lower in comparison with G/A (p = 0.038) and LDL-C and HDL-C levels were lower in G/A compared to G/G carriers. 83 C>T polymorphism of APOA1: For DI individuals, HDL-C was lower in T/T compared to C/C and triglyceride levels were lower in C/T compared to C/C carriers. Conclusions: The -75 G>A APOA1 polymorphism could be considered as a susceptibility factor for myocardial infarction in individuals with T2DM and 2488 C>T APOB polymorphism is associated with changes in HDL-C and LDL-C and triglycerides in the same group.

Arbovirus Antibody Seroprevalence in the Human Population from Cauca, Colombia.

Several arboviruses have emerged or reemerged into the New World during the past several decades, causing outbreaks of significant proportion. In particular, the outbreaks of Dengue virus (DENV), Zika virus, and Chikungunya virus (CHIKV) have been explosive and unpredictable, and have led to significant adverse health effects. These viruses are considered the leading cause of acute undifferentiated febrile illnesses in Colombia. However, Venezuelan equine encephalitis virus (VEEV) is endemic in Colombia, and arboviruses such as the Mayaro virus (MAYV) and the Oropouche virus (OROV) cause febrile illnesses in neighboring countries. Yet, evidence of human exposure to MAYV and OROV in Colombia is scarce. In this study, we conducted a serosurvey study in healthy individuals from the Cauca Department in Colombia. We assessed the seroprevalence of antibodies against multiple arboviruses, including DENV serotype 2, CHIKV, VEEV, MAYV, and OROV. Based on serological analyses, we found that the overall seroprevalence for DENV serotype 2 was 30%, 1% for MAYV, 2.6% for CHIKV, 4.4% for VEEV, and 2% for OROV. This study provides evidence about the circulation of MAYV and OROV in Colombia, and suggests that they-along with VEEV and CHIKV-might be responsible for cases of acute undifferentiated febrile illnesses that remain undiagnosed in the region. The study results also highlight the need to strengthen surveillance programs to identify outbreaks caused by these and other vector-borne pathogens.