COVID-19 vaccine uptake and barriers among Indigenous language speakers in Mexico: Results from a nationally representative survey.

Mexico faced a significant burden from the COVID-19 pandemic. Since the pandemic's onset in 2020, numerous studies have underscored the substantial risk of COVID-19 death among Indigenous individuals. This study aims to assess COVID-19 vaccine uptake among Indigenous language speakers in Mexico, focusing on understanding the barriers they face in obtaining access to vaccines. We used Encuesta Nacional de Salud y Nutrición Continua (ENSANUT) 2022, a nationally representative health survey in Mexico to analyze data on self-reported COVID-19 vaccine status, reasons for not getting vaccinated, and other relevant covariates. We employed logistic regression to estimate odds ratios (ORs) for vaccine uptake and uptake barriers, all models were adjusted for potential confounders. Among 34,051 participants, 1793 individuals (5.23%) reported speaking an Indigenous language. Indigenous language speakers were found to have a lower vaccination rate (63%) compared to non-Indigenous language speakers (81%) (p <0.005). They were also 59% less likely to be vaccinated against COVID-19 (OR 0.41, 95% CI 0.27-0.62), even when adjusted for confounders. Among unvaccinated individuals, Indigenous language speakers were more likely to cite negative beliefs about the vaccine or fear as reasons for not being vaccinated (OR 1.82, 95% CI 1.11-3.00) while being less likely to report access barriers (OR 0.62, CI 95% 0.42-0.91). This study highlights disparities in COVID-19 vaccine uptake among Indigenous language speakers in Mexico. The findings underscore the urgent need for targeted, culturally appropriate public health interventions and the consideration of social and ethnic vulnerability in prioritizing vaccinations.

Cocirculation and replacement of SARS-CoV-2 variants in crowded settings and marginalized populations along the US-Mexico border.

OBJECTIVE: To interrogate the circulating SARS-CoV-2 lin-eages and recombinant variants in persons living in migrant shelters and persons who inject drugs (PWID). MATERIALS AND METHODS: We combined data from two studies with marginalized populations (migrants in shelters and persons who inject drugs) in Tijuana, Mexico. SARS-CoV-2 variants were identified on nasal swabs specimens and compared to publicly available genomes sampled in Mexico and California. RESULTS: All but 2 of the 10 lineages identified were predomi-nantly detected in North and Central America. Discrepan-cies between migrants and PWID can be explained by the temporal emergence and short time span of most of these lineages in the region. CONCLUSION: The results illustrate the temporo-spatial structure for SARS-CoV-2 lineage dispersal and the potential co-circulation of multiple lineages in high-risk populations with close social contacts. These conditions create the potential for recombination to take place in the California-Baja California border.

Interrupted transit and common mental disorders among migrants in Tijuana, Mexico.

BACKGROUND: Policies of migration contention can interrupt the transit of people on the move, forcing them to remain in wait in non-destination countries. This liminal condition might impact negatively on migrants' mental health. AIMS: To assess the relationship between interrupted transit and common mental disorders (CMD; symptoms of depression or anxiety), among migrants in shelters in Tijuana, Mexico. METHODS: Cross-sectional survey conducted in November to December 2020 and February to April 2021. We assessed depressive symptoms with the Centers for Epidemiological Studies Depression scale (CES-D-7), and symptoms of anxiety with the Generalized Anxiety Disorder scale (GAD-2). We evaluated the association of being in interrupted transit (sent back from the United States to Mexico), as compared to having not crossed to the United States yet or planning to stay in Mexico, with having a CMD (either depressive or anxiety symptoms), as well as the association of other migration-related variables with CMD. RESULTS: Being in interrupted transit (OR = 1.74, 95% CI [1.12, 2.71]), and having experienced violence during transit (OR = 2.50, 95% CI [1.63, 3.82]) were associated with CMD. CONCLUSIONS: Interrupted transit is a potential risk factor for mental health problems among migrants. Migration and public health policies should consider the mental health consequences of interrupted transit, and promote initiatives to address the mental health needs of migrants on the move.

The impact of the COVID-19 pandemic among migrants in shelters in Tijuana, Baja California, Mexico.

INTRODUCTION: Migrants, especially those in temporary accommodations like camps and shelters, might be a vulnerable population during the COVID-19 pandemic, but little is known about the impact of the pandemic in these settings in low-income and middle-income countries. We assessed SARS-CoV-2 seropositivity and RNA prevalence, the correlates of seropositivity (emphasising socially determined conditions), and the socioeconomic impacts of the pandemic among migrants living in shelters in Tijuana, a city on the Mexico-US border. METHODS: We conducted a cross-sectional, non-probability survey of migrants living in shelters in Tijuana in November-December 2020 and February-April 2021. Participants completed a questionnaire and provided anterior nasal swab and blood samples for detection of SARS-CoV-2 RNA and antibodies (IgG and IgM), respectively. We explored whether SARS-CoV-2 infection was associated with sociodemographic and migration-related variables, access to sanitation, protective behaviours and health-related factors. RESULTS: Overall, 481 participants were enrolled, 67.7% from Northern Central America, 55.3% women, mean age 33.2 years. Seven (1.5%) participants had nasal swabs positive for SARS-CoV-2 RNA and 53.0% were SARS-CoV-2 seropositive. Avoiding public transportation (OR 0.59, 95% CI 0.39 to 0.90) and months living in Tijuana (OR 1.06, 95% CI 1.02 to 1.10) were associated with seropositivity. Sleeping on the streets or other risky places and having diabetes were marginally associated with seropositivity. Most participants (90.2%) had experienced some socioeconomic impact of the pandemic (eg, diminished income, job loss). CONCLUSION: Compared with results from other studies conducted in the general population in Mexico at a similar time, migrants living in shelters were at increased risk of acquiring SARS-CoV-2, and they suffered considerable adverse socioeconomic impacts as a consequence of the pandemic. Expanded public health and other social support systems are needed to protect migrants from COVID-19 and reduce health inequities.

Divergent acyl carrier protein decouples mitochondrial Fe-S cluster biogenesis from fatty acid synthesis in malaria parasites.

Most eukaryotic cells retain a mitochondrial fatty acid synthesis (FASII) pathway whose acyl carrier protein (mACP) and 4-phosphopantetheine (Ppant) prosthetic group provide a soluble scaffold for acyl chain synthesis and biochemically couple FASII activity to mitochondrial electron transport chain (ETC) assembly and Fe-S cluster biogenesis. In contrast, the mitochondrion of Plasmodium falciparum malaria parasites lacks FASII enzymes yet curiously retains a divergent mACP lacking a Ppant group. We report that ligand-dependent knockdown of mACP is lethal to parasites, indicating an essential FASII-independent function. Decyl-ubiquinone rescues parasites temporarily from death, suggesting a dominant dysfunction of the mitochondrial ETC. Biochemical studies reveal that Plasmodium mACP binds and stabilizes the Isd11-Nfs1 complex required for Fe-S cluster biosynthesis, despite lacking the Ppant group required for this association in other eukaryotes, and knockdown of parasite mACP causes loss of Nfs1 and the Rieske Fe-S protein in ETC complex III. This work reveals that Plasmodium parasites have evolved to decouple mitochondrial Fe-S cluster biogenesis from FASII activity, and this adaptation is a shared metabolic feature of other apicomplexan pathogens, including Toxoplasma and Babesia. This discovery unveils an evolutionary driving force to retain interaction of mitochondrial Fe-S cluster biogenesis with ACP independent of its eponymous function in FASII.

Daily muscle stretching enhances blood flow, endothelial function, capillarity, vascular volume and connectivity in aged skeletal muscle.

KEY POINTS: In aged rats, daily muscle stretching increases blood flow to skeletal muscle during exercise. Daily muscle stretching enhanced endothelium-dependent vasodilatation of skeletal muscle resistance arterioles of aged rats. Angiogenic markers and capillarity increased in response to daily stretching in muscles of aged rats. Muscle stretching performed with a splint could provide a feasible means of improving muscle blood flow and function in elderly patients who cannot perform regular aerobic exercise. ABSTRACT: Mechanical stretch stimuli alter the morphology and function of cultured endothelial cells; however, little is known about the effects of daily muscle stretching on adaptations of endothelial function and muscle blood flow. The present study aimed to determine the effects of daily muscle stretching on endothelium-dependent vasodilatation and muscle blood flow in aged rats. The lower hindlimb muscles of aged Fischer rats were passively stretched by placing an ankle dorsiflexion splint for 30 min day-1 , 5 days week-1 , for 4 weeks. Blood flow to the stretched limb and the non-stretched contralateral limb was determined at rest and during treadmill exercise. Endothelium-dependent/independent vasodilatation was evaluated in soleus muscle arterioles. Levels of hypoxia-induced factor-1α, vascular endothelial growth factor A and neuronal nitric oxide synthase were determined in soleus muscle fibres. Levels of endothelial nitric oxide synthase and superoxide dismutase were determined in soleus muscle arterioles, and microvascular volume and capillarity were evaluated by microcomputed tomography and lectin staining, respectively. During exercise, blood flow to plantar flexor muscles was significantly higher in the stretched limb. Endothelium-dependent vasodilatation was enhanced in arterioles from the soleus muscle from the stretched limb. Microvascular volume, number of capillaries per muscle fibre, and levels of hypoxia-induced factor-1α, vascular endothelial growth factor and endothelial nitric oxide synthase were significantly higher in the stretched limb. These results indicate that daily passive stretching of muscle enhances endothelium-dependent vasodilatation and induces angiogenesis. These microvascular adaptations may contribute to increased muscle blood flow during exercise in muscles that have undergone daily passive stretch.

Exercise training reverses age-induced diastolic dysfunction and restores coronary microvascular function.

KEY POINTS: In a rat model of ageing that is free of atherosclerosis or hypertension, E/A, a diagnostic measure of diastolic filling, decreases, and isovolumic relaxation time increases, indicating that both active and passive ventricular relaxation are impaired with advancing age. Resting coronary blood flow and coronary functional hyperaemia are reduced with age, and endothelium-dependent vasodilatation declines with age in coronary resistance arterioles. Exercise training reverses age-induced declines in diastolic and coronary microvascular function. Thus, microvascular dysfunction and inadequate coronary perfusion are likely mechanisms of diastolic dysfunction in aged rats. Exercise training, initiated at an advanced age, reverses age-related diastolic and microvascular dysfunction; these data suggest that late-life exercise training can be implemented to improve coronary perfusion and diastolic function in the elderly. ABSTRACT: The risk for diastolic dysfunction increases with advancing age. Regular exercise training ameliorates age-related diastolic dysfunction; however, the underlying mechanisms have not been identified. We investigated whether (1) microvascular dysfunction contributes to the development of age-related diastolic dysfunction, and (2) initiation of late-life exercise training reverses age-related diastolic and microvascular dysfunction. Young and old rats underwent 10 weeks of exercise training or remained as sedentary, cage-controls. Isovolumic relaxation time (IVRT), early diastolic filling (E/A), myocardial performance index (MPI) and aortic stiffness (pulse wave velocity; PWV) were evaluated before and after exercise training or cage confinement. Coronary blood flow and vasodilatory responses of coronary arterioles were evaluated in all groups at the end of training. In aged sedentary rats, compared to young sedentary rats, a 42% increase in IVRT, a 64% decrease in E/A, and increased aortic stiffness (PWV: 6.36 ± 0.47 vs.4.89 ± 0.41, OSED vs. YSED, P < 0.05) was accompanied by impaired coronary blood flow at rest and during exercise. Endothelium-dependent vasodilatation was impaired in coronary arterioles from aged rats (maximal relaxation to bradykinin: 56.4 ± 5.1% vs. 75.3 ± 5.2%, OSED vs. YSED, P < 0.05). After exercise training, IVRT, a measure of active ventricular relaxation, did not differ between old and young rats. In old rats, exercise training reversed the reduction in E/A, reduced aortic stiffness, and eliminated impairment of coronary blood flow responses and endothelium-dependent vasodilatation. Thus, age-related diastolic and microvascular dysfunction are reversed by late-life exercise training. The restorative effect of exercise training on coronary microvascular function may result from improved endothelial function.

Mexico's path towards the Sustainable Development Goal for health: an assessment of the feasibility of reducing premature mortality by 40% by 2030.

BACKGROUND: The United Nations Sustainable Development Goal for health (SDG3) poses complex challenges for signatory countries that will require clear roadmaps to set priorities over the next 15 years. Building upon the work of the Commission on Investing in Health and published estimates of feasible global mortality SDG3 targets, we analysed Mexico's mortality to assess the feasibility of reducing premature (0-69 years) mortality and propose a path to meet SDG3. METHODS: We developed a baseline scenario applying 2010 age-specific and cause-specific mortality rates from the Mexican National Institute of Statistics and Geography (INEGI) to the 2030 UN Population Division (UNPD) population projections. In a second scenario, INEGI age-specific and cause-specific trends in death rates from 2000 to 2014 were projected to 2030 and adjusted to match the UNPD 2030 mortality projections. A third scenario assumed a 40% reduction in premature deaths across all ages and causes. By comparing these scenarios we quantified shortfalls in mortality reductions by age group and cause, and forecasted life expectancy pathways for Mexico to converge to better performing countries. FINDINGS: UNPD-projected death rates yield a 25·9% reduction of premature mortality for Mexico. Accelerated reductions in adult mortality are necessary to reach a 40% reduction by 2030. Mortality declines aggregated across all age groups mask uneven gains across health disorders. Injuries, particularly road traffic accidents and homicides, are the main health challenge for young adults (aged 20-49 years) whereas unabated diabetes mortality is the single most important health concern for older adults (aged 50-69 years). INTERPRETATION: Urgent action is now required to control non-communicable diseases and reduce fatal injuries in Mexico, making a 40% reduction in premature mortality by 2030 feasible and putting Mexico back on a track of substantial life expectancy convergence with better performing countries. Our study provides a roadmap for setting national health priorities. Further analysis of the equity implications of following the suggested pathway remains a subject of future research. FUNDING: Mexico's Ministry of Health, University of California, San Francisco, and Bill & Melinda Gates Foundation.

Profesionales de la salud para el nuevo siglo: transformando la educación para fortalecer los sistemas de salud en un mundo interdependiente / Health professionals for a new century: transforming education to strengthen health systems in an interdependent world

Hace 100 años, diversos estudios sobre la educación de los profesionales de la salud dieron lugar a reformas innovadoras. Los nuevos retos del siglo xxiobligan a rediseñar nuevamente la educación profesional en salud. La Comisión sobre la Educación de los Profesionales de la Salud para el Siglo XXI se reunió para desarrollar una visión compartida y una estrategia común para la educación en medicina, enfermería y salud pública. Esta comisión ofrece una visión que llama a una nueva era de la educación profesional que promueva un aprendizaje transformativo y domine el poder que genera la interdependencia en la educación. Así como las reformas de principios del Siglo XX se apoyaron en la teoría microbiana de la enfermedad y las ciencias médicas modernas, esta comisión cree que el futuro será moldeado por la adaptación de competencias a contextos específicos basándose en el poder de los flujos globales de información y conocimiento. Materializar esta visión requerirá de reformas en la instrucción y el desarrollo institucional, guiadas por los dos resultados que se persiguen: el aprendizaje transformativo y la interdependencia en la educación. Sobre la base de estas nociones esenciales, la comisión ofrece diez recomendaciones específicas. La puesta en práctica de estas reformas requerirá de acciones que faciliten su implantación, entre las que destacan la movilización del liderazgo, la expansión de la inversión en educación profesional en salud, el alineamiento de los procesos de acreditación y el fortalecimiento del aprendizaje global. La implantación de estas recomendaciones deberá contar asimismo con el impulso de un movimiento global que involucre a todos los actores como parte de un esfuerzo concertado para fortalecer los sistemas de salud

100 years ago, a series of studies about the education of health professionals sparked groundbreaking reforms. The challenges of the 21st century demand a new redesign of professional health education. The Commission on Education of Health Professionals for the 21st Century came together to develop a shared vision and a common strategy for postsecondary education in medicine, nursing, and public health. The Commission provides a vision that calls for a new era of professional education that advances transformative learning and harnesses the power of interdependence in education. Just as reforms in the early 20th century were advanced by the germ theory and the establishment of the modern medical sciences, so too the Commission believes that the future will be shaped by adaptation of competencies to specific contexts drawing on the power of global flows of information and knowledge. Undertaking of this vision requires a series of instructional and institutional reforms, which are guided by the two expected outcomes, transformative learning and interdependence in education. On the basis of these core notions, the Commission offers 10 specific recommendations. The implementation of these recommendations require a series of enabling actions, including the mobilization of leadership, the enhancement of investments in health education, the alignment of the accreditation processes, and the strengthening of global learning. These recommendations also demand the support of a global movement engaging all stakeholders as part of a concerted effort to strengthen health systems

Avoiding 40% of the premature deaths in each country, 2010-30: review of national mortality trends to help quantify the UN sustainable development goal for health.

BACKGROUND: The UN will formulate ambitious Sustainable Development Goals for 2030, including one for health. Feasible goals with some quantifiable, measurable targets can influence governments. We propose, as a quatitative health target, "Avoid in each country 40% of premature deaths (under-70 deaths that would be seen in the 2030 population at 2010 death rates), and improve health care at all ages". Targeting overall mortality and improved health care ignores no modifiable cause of death, nor any cause of disability that is treatable (or also causes many deaths). 40% fewer premature deaths would be important in all countries, but implies very different priorities in different populations. Reinforcing this target for overall mortality in each country are four global subtargets for 2030: avoid two-thirds of child and maternal deaths; two-thirds of tuberculosis, HIV, and malaria deaths; a third of premature deaths from non-communicable diseases (NCDs); and a third of those from other causes (other communicable diseases, undernutrition, and injuries). These challenging subtargets would halve under-50 deaths, avoid a third of the (mainly NCD) deaths at ages 50-69 years, and so avoid 40% of under-70 deaths. To help assess feasibility, we review mortality rates and trends in the 25 most populous countries, in four country income groupings, and worldwide. METHODS: UN sources yielded overall 1970-2010 mortality trends. WHO sources yielded cause-specific 2000-10 trends, standardised to country-specific 2030 populations; decreases per decade of 42% or 18% would yield 20-year reductions of two-thirds or a third. RESULTS: Throughout the world, except in countries where the effects of HIV or political disturbances predominated, mortality decreased substantially from 1970-2010, particularly in childhood. From 2000-10, under-70 age-standardised mortality rates decreased 19% (with the low-income and lower-middle-income countries having the greatest absolute gains). The proportional decreases per decade (2000-10) were: 34% at ages 0-4 years; 17% at ages 5-49 years; 15% at ages 50-69 years; 30% for communicable, perinatal, maternal, or nutritional causes; 14% for NCDs; and 13% for injuries (accident, suicide, or homicide). INTERPRETATION: Moderate acceleration of the 2000-10 proportional decreases in mortality could be feasible, achieving the targeted 2030 disease-specific reductions of two-thirds or a third. If achieved, these reductions avoid about 10 million of the 20 million deaths at ages 0-49 years that would be seen in 2030 at 2010 death rates, and about 17 million of the 41 million such deaths at ages 0-69 years. Such changes could be achievable by 2030, or soon afterwards, at least in areas free of war, other major effects of political disruption, or a major new epidemic. FUNDING: UK Medical Research Council, Norwegian Agency for Development Cooperation, Centre for Global Health Research, and Bill & Melinda Gates Foundation.

The state of global health in 2014.

The global health landscape looks more promising than ever, although progress has been uneven. Here, we describe the current global burden of disease throughout the life cycle, highlighting regional differences in the unfinished agenda of communicable diseases and reproductive, maternal, and child health and the additive burden of emerging noncommunicable diseases and injuries. Understanding this changing landscape is an essential starting point for effective allocation of both domestic and international resources for health.

Duplicación del tubo digestivo manifestada como quiste lingual: Caso clínico y revisión de la literatura / Enteric duplication presented as lingual cyst: Case report and literature review

Introducción: Los quistes de duplicación intestinal son anormalidades poco frecuentes que se presentan principalmente en el período perinatal, y pueden causar problemas respiratorios y para la alimentación. Los quistes sublinguales de duplicación intestinal pueden presentar solo epitelio del aparato digestivo, del respiratorio o de ambos. En los dos últimos casos se denominan coristomas. Caso clínico: Se describe un caso de un paciente de 10 meses de edad que presentó una masa quística sublingual desde el nacimiento. Se realizó la resección total con abordaje transoral y la reconstrucción de la lengua en planos. La pieza quirúrgica resultó una estructura quística de contenido mucoide, de 23 × 17 × 11 mm y color marrón. El revestimiento del quiste estaba formado por mucosa gástrica, con epitelio foveolar y glándulas formadas por células parietales y principales. Conclusiones: El quiste de duplicación intestinal es una entidad extremadamente rara. El abordaje quirúrgico es eficaz y curativo con mínima morbilidad y mortalidad, sin recurrencia en su seguimiento.

Background: Intestinal duplication cysts are rare abnormalities that occur primarily during the perinatal period and may cause problems for feeding and/or breathing. Sublingual intestinal duplication cysts can present either gastrointestinal epithelium or respiratory or both; the latter two cases are called choristomas. Case report: We describe a 10-month-old infant who presented a sublingual cystic mass at birth. Total successful transoral resection and reconstruction of the tongue was performed in planes. The surgical specimen was a brown cystic structure of mucoid content with dimensions of 23 × 17 × 11 mm. The cyst lining consists of gastric mucosa with foveolar epithelium and glands composed of parietal and chief cells. Conclusions: The intestinal duplication cyst is an extremely rare entity. The surgical approach is effective and curative with minimal morbidity and mortality and without recurrence in follow-up.

Hacia la cobertura universal en salud: protección social para todos en México

México alcanzará la cobertura universal en salud en 2012. El seguro nacional de salud denominado Seguro Popular, introducido en 2003, garantiza el acceso a un paquete de servicios de salud integrales con protección financiera a más de 50 millones de mexicanos previamente excluidos de la seguridad social. La cobertura universal en México es sinónimo de protección social en salud. Este informe analiza el camino hacia la cobertura universal en sus tres dimensiones de protección: a) contra riesgos para la salud, b) de los pacientes a través de la garantía de calidad de la atención a la salud y c) contra las consecuencias financieras de la enfermedad y las lesiones. Se presenta una discusión conceptual sobre la transición de una seguridad social basada en la condición laboral a la protección social en salud, que implica el acceso a una atención integral de la salud como derecho universal basado en la ciudadanía, plataforma ética de la reforma mexicana. Se describen asimismo las condiciones que llevaron a la reforma, así como su diseño y puesta en marcha, y se discute el proceso de implantación a nueve años de iniciado y las evidencias que dieron origen a actualizaciones y mejoras del programa original. El núcleo del informe se centra en los efectos e impactos de la reforma que se desprenden de la literatura sobre el tema, que incluye artículos científicos y otras publicaciones disponibles. La evidencia indica que el Seguro Popular está mejorando el acceso a los servicios de salud y reduciendo la prevalencia de los gastos en salud catastróficos y empobrecedores, especialmente entre los pobres. Estudios recientes muestran asimismo una mejora en la cobertura efectiva. También se discuten los desafíos prevalentes, incluyendo la necesidad de traducir los recursos financieros en servicios de salud más efectivos, equitativos y sensibles a las expectativas de los usuarios. Se requiere una nueva generación de reformas que incluya medidas sistémicas para consolidar la reorganización del sistema de salud por funciones. El artículo concluye con una discusión sobre las implicaciones de la búsqueda de la cobertura universal de salud en México y su importancia para otros países de ingresos bajos y medios.

The quest for universal health coverage: achieving social protection for all in Mexico.

Mexico is reaching universal health coverage in 2012. A national health insurance programme called Seguro Popular, introduced in 2003, is providing access to a package of comprehensive health services with financial protection for more than 50 million Mexicans previously excluded from insurance. Universal coverage in Mexico is synonymous with social protection of health. This report analyses the road to universal coverage along three dimensions of protection: against health risks, for patients through quality assurance of health care, and against the financial consequences of disease and injury. We present a conceptual discussion of the transition from labour-based social security to social protection of health, which implies access to effective health care as a universal right based on citizenship, the ethical basis of the Mexican reform. We discuss the conditions that prompted the reform, as well as its design and inception, and we describe the 9-year, evidence-driven implementation process, including updates and improvements to the original programme. The core of the report concentrates on the effects and impacts of the reform, based on analysis of all published and publically available scientific literature and new data. Evidence indicates that Seguro Popular is improving access to health services and reducing the prevalence of catastrophic and impoverishing health expenditures, especially for the poor. Recent studies also show improvement in effective coverage. This research then addresses persistent challenges, including the need to translate financial resources into more effective, equitable and responsive health services. A next generation of reforms will be required and these include systemic measures to complete the reorganisation of the health system by functions. The paper concludes with a discussion of the implications of the Mexican quest to achieve universal health coverage and its relevance for other low-income and middle-income countries.