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.

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.

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.

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.

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.

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.

Improvement of child survival in Mexico: the diagonal approach.

Public health interventions aimed at children in Mexico have placed the country among the seven countries on track to achieve the goal of child mortality reduction by 2015. We analysed census data, mortality registries, the nominal registry of children, national nutrition surveys, and explored temporal association and biological plausibility to explain the reduction of child, infant, and neonatal mortality rates. During the past 25 years, child mortality rates declined from 64 to 23 per 1000 livebirths. A dramatic decline in diarrhoea mortality rates was recorded. Polio, diphtheria, and measles were eliminated. Nutritional status of children improved significantly for wasting, stunting, and underweight. A selection of highly cost-effective interventions bridging clinics and homes, what we called the diagonal approach, were central to this progress. Although a causal link to the reduction of child mortality was not possible to establish, we saw evidence of temporal association and biological plausibility to the high level of coverage of public health interventions, as well as significant association to the investments in women education, social protection, water, and sanitation. Leadership and continuity of public health policies, along with investments on institutions and human resources strengthening, were also among the reasons for these achievements.

Cholera in Mexico: the paradoxical benefits of the last pandemic.

OBJECTIVES: To describe the impact of preventive and control measures in Mexico prior to, and during, the cholera epidemic of 1991-2001. METHODS: When cholera appeared in Latin America in January 1991, the Mexican government considered that it represented a national security problem. Therefore, actions were implemented within the health sector (e.g. epidemiological surveillance, laboratory network and patient care) and other sectors (public education and basic sanitation). RESULTS: The first case occurred in Mexico in June 1991. The incidence rate remained below 17.9 per 100,000 inhabitants and affected mainly rural areas. The last cholera report occurred in 2001. The disease never became endemic. The population benefited not only from acquisition of knowledge about preventive measures, but also from modification of risky practices and from reinforcement of city and municipal drinking water supplies. CONCLUSION: Control strategies had an overall impact in decreasing diarrheal mortality among children under five years of age. Additionally the country did not suffer from a decrease in tourism or economic consequences. This experience can be considered as the operationalization of a new public health system spanning multisectorial activities, involving community participation, political will and with impact on public health and economic issues.

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.

Evidence-based health policy: three generations of reform in Mexico.

The Mexican health system has evolved through three generations of reform. The creation of the Ministry of Health and the main social security agency in 1943 marked the first generation of health reforms. In the late 1970s, a second generation of reforms was launched around the primary health-care model. Third-generation reforms favour systemic changes to reorganise the system through the horizontal integration of basic functions-stewardship, financing, and provision. The stability of leadership in the health sector is emphasised as a key element that allowed for reform during the past 60 years. Furthermore, there has been a transition in the second generation of reforms to a model that is increasingly based on evidence; this has been intensified and extended in the third generation of reforms. We also examine policy developments that will provide social protection in health for all. These developments could be of interest for countries seeking to provide their citizens with universal access to health care that incorporates equity, quality, and financial protection.