The Pesticide Chlordecone Promotes Parkinsonism-like Neurodegeneration with Tau Lesions in Midbrain Cultures and C. elegans Worms.

Chlordecone (CLD) is an organochlorine pesticide (OCP) that is currently banned but still contaminates ecosystems in the French Caribbean. Because OCPs are known to increase the risk of Parkinson's disease (PD), we tested whether chronic low-level intoxication with CLD could reproduce certain key characteristics of Parkinsonism-like neurodegeneration. For that, we used culture systems of mouse midbrain dopamine (DA) neurons and glial cells, together with the nematode C. elegans as an in vivo model organism. We established that CLD kills cultured DA neurons in a concentration- and time-dependent manner while exerting no direct proinflammatory effects on glial cells. DA cell loss was not impacted by the degree of maturation of the culture. The use of fluorogenic probes revealed that CLD neurotoxicity was the consequence of oxidative stress-mediated insults and mitochondrial disturbances. In C. elegans worms, CLD exposure caused a progressive loss of DA neurons associated with locomotor deficits secondary to alterations in food perception. L-DOPA, a molecule used for PD treatment, corrected these deficits. Cholinergic and serotoninergic neuronal cells were also affected by CLD in C. elegans, although to a lesser extent than DA neurons. Noticeably, CLD also promoted the phosphorylation of the aggregation-prone protein tau (but not of α-synuclein) both in midbrain cell cultures and in a transgenic C. elegans strain expressing a human form of tau in neurons. In summary, our data suggest that CLD is more likely to promote atypical forms of Parkinsonism characterized by tau pathology than classical synucleinopathy-associated PD.

Trends in facility-based childbirth and barriers to care at a birth center and community hospital in rural Chiapas, Mexico: A mixed-methods study.

OBJECTIVE: To assess trends in childbirth at a hospital-birth center among women living in Compañeros En Salud (CES)-affiliated communities in Chiapas, Mexico and explore barriers to childbirth care. Our hypothesis was that despite interventions to support and incentivize childbirth at the hospital-birth center, the proportion of births at the hospital-birth center among women from Compañeros En Salud-affiliated communities has not significantly changed after two years. We suspected that this may be due to structural factors impacting access to care and/or perceptions of care impacting desire to deliver at the birth center. DESIGN: This explanatory mixed-methods study included a retrospective Compañeros En Salud maternal health census review followed by quantitative surveys and semi-structured qualitative interviews. PARTICIPANTS AND SETTING: Participants were women living in municipalities in the mountainous Sierra Madre region of Chiapas, Mexico who received prenatal care in one of 10 community clinics served by Compañeros En Salud. Participants were recruited if they gave birth anywhere other than the primary-level rural hospital and adjacent birth center supported by Compañeros En Salud, either at home or at other facilities. MEASUREMENTS: We compared rates of birth at the hospital-birth center, other health facilities, and at home from 2017-2018. We conducted surveys and interviews with women who gave birth between January 2017-July 2018 at home or at facilities other than the hospital-birth center to understand perceptions of care and decision-making surrounding childbirth location. FINDINGS: We found no significant difference in rates of overall number of women birthing at the hospital-birth center from Compañeros En Salud-affiliated communities between 2017 and 2018 (p=0.36). Analysis of 158 surveys revealed distance (30.4%), time (27.8%), and costs (25.9%) as reasons for not birthing at the hospital-birth center. From 27 interviews, negative perceptions and experiences of the hospital included low-quality and disrespectful care, low threshold for medical interventions, and harm and suffering. Partners or family members influenced most decisions about childbirth location. KEY CONCLUSIONS: Interventions to minimize logistical barriers may not be sufficient to overcome distance and perceptions of low-quality, disrespectful care. IMPLICATIONS FOR PRACTICE: Better understanding of complex decision-making around childbirth will guide Compañeros En Salud in developing interventions to further meet the needs and preferences of birthing women in rural Chiapas.

Rethinking referral systems in rural chiapas: A mixed methods study.

Background: Despite the assurance of universal health coverage, large disparities exist in access to surgery in the state of Chiapas. The purpose of this study was to determine the effectiveness of the surgical referral system at hospitals operated by the Ministry of Health in Chiapas. Methods: 13 variables were extracted from surgical referrals data from three public hospitals in Chiapas over a three-year period. Interviews were performed of health care workers involved in the referral system and surgical patients. The quantitative and qualitative data was analyzed convergently and reported using a narrative approach. Findings: In total, only 47.4% of referred patients requiring surgery received an operation. Requiring an elective, gynecological, or orthopedic surgery and each additional surgery cancellation were significantly associated with lower rates of receiving surgery. The impact of gender and surgical specialty, economic fragility of farmers, dependence upon economic resources to access care, pain leading people to seek care, and futility leading patients to abandon the public system were identified as main themes from the mixed methods analysis. Interpretation: Surgical referral patients in Chiapas struggle to navigate an inefficient and expensive system, leading to delayed care and forcing many patients to turn to the private health system. These mixed methods findings provide a detailed view of often overlooked limitations to universal health coverage in Chiapas. Moving forward, this knowledge must be applied to improve referral system coordination and provide hospitals with the necessary workforce, equipment, and protocols to ensure access to guaranteed care. Funding: Harvard University and the Abundance Fund provided funding for this project. Funding sources had no role in the writing of the manuscript or decision to submit it for publication.

Integrating multi-national teams: over a decade of lessons learned in Chiapas with Partners in Health-Mexico.

In a globalized world where pathology and risk can flow freely across borders, the discipline of global health equity has proposed to meet this challenge with an equal exchange of solutions, and people working toward those solutions. Considering the history of colonialism, ongoing economic exploitation, and gaping inequities across and within countries, these efforts must be taken with care. The Partners In Health program in Chiapas, Mexico was founded in 2011 by a team of leaders from both the United States and Mexico to strengthen the public health and care delivery systems serving impoverished rural populations. Key to the strategy has been to marshal funding, knowledge, and expertise from elite institutions in both the United States and Mexico for the benefit of an area that previously had rarely seen such inputs, but always in close partnership with local leaders and community processes. With now over a decade of experience, several key lessons have emerged in both what was done well and what continues to present ongoing challenges. Top successes include: effective recruitment and retention strategies for attracting talented Mexican clinicians to perform their social service year in previously unappealing rural placements; using effective fund-raising strategies from multinational sources to ensure the health care delivered can be exemplary; and effectively integrating volunteer clinicians from high-income contexts in a way that benefits the local staff, the foreign visitors, and their home institutions. A few chief ongoing challenges remain: how to work with local communities to receive foreign visitors; how to hire, develop, and appropriately pay a diverse workforce that comes with differing expectations for their professional development; and how to embed research in non-extractive ways. Our community case study suggests that multinational global health teams can be successful if they share the goal of achieving mutual benefit through an equity lens, and are able to apply creativity and humility to form deep partnerships.

Effects of a New Natural Catechol-O-methyl Transferase Inhibitor on Two In Vivo Models of Parkinson's Disease.

A tetrahydroisoquinoline identified in Mucuna pruriens ((1R,3S)-6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline-1,3-dicarboxylic acid, compound 4) was synthesized and assessed for its in vitro pharmacological profile and in vivo effects in two animal models of Parkinson's disease. Compound 4 inhibits catechol-O-methyltransferase (COMT) with no affinity for the dopaminergic receptors or the dopamine transporter. It restores dopamine-mediated motor behavior when it is co-administered with L-DOPA to C. elegans worms with 1-methyl-4-phenylpyridinium-damaged dopaminergic neurons. In a 6-hydroxydopamine rat model of Parkinson's disease, its co-administration at 30 mg/kg with L-DOPA enhances the effect of L-DOPA with an intensity similar to that of tolcapone 1 at 30 mg/kg but for a shorter duration. The effect is not dose-dependent. Compound 4 seems not to cross the blood-brain barrier and thus acts as a peripheral COMT inhibitor. COMT inhibition by compound 4 further validates the traditional use of M. pruriens for the treatment of Parkinson's disease, and compound 4 can thus be considered as a promising drug candidate for the development of safe, peripheral COMT inhibitors.

Interpersonal challenges in surgical care provision in rural Mexico: A qualitative study.

Background: Chiapas is among the states with the lowest access to health care in Mexico. A better understanding of the role of interpersonal relationships in referral systems could improve access to care in the region. The purpose of this study was to analyze the underlying barriers and facilitators to accessing surgical care at public hospitals run by the Ministry of Health in Chiapas. Methods: In this qualitative interview study, we performed semi-structured interviews with 19 surgical patients and 18 healthcare workers at three public hospitals in the Fraylesca Region of Chiapas to explore barriers and facilitators to successfully accessing surgical treatment. Transcripts were coded and analyzed using an inductive, thematic approach to data analysis. Findings: The five major themes identified as barriers to surgical care were dehumanization of patients, the toll of rehumanizing patients, animosity in the system, the refraction of violence onto patients, and poor resource coordination. Three themes identified as facilitators to receiving care were teamwork, social capital, and accompaniment. Interpretation: Health care workers described a culture of demoralization and mistrust within the health system worsened by a scarcity of resources. As a result, patient care is hampered by conflict, miscommunication, and feelings of dehumanization. Efforts to improve access to surgical care in the region should consider strategies to improve teamwork and expand patient accompaniment. Funding: Harvard University and the Abundance Fund provided funding for this project. Funding sources had no role in the writing of the manuscript or decision to submit it for publication.Resumen. Antecedentes: Chiapas es uno de los estados en Mexico con el menor acceso a la atención médica, y a los servicios quirúrgicos. Una mejor comprensión del papel de las relaciones interpersonales en los sistemas de referencias podría mejorar el acceso a la atención medica en la región. El objetivo del estudio es analizar las barreras y facilitadores para acceder a la atención quirúrgica en los hospitales públicos pertenecientes a la Secretaria de Salud del estado de Chiapas. Método: En este estudio cualitativo, realizamos entrevistas semiestructuradas con 19 pacientes quirúrgicos y 18 trabajadores de la salud en tres hospitales públicos en la región de la Frailesca de Chiapas para explorar barreras y facilitadores para acceder al tratamiento quirúrgico. Las transcripciones se codificaron y analizaron utilizando un enfoque temático. Resultados: Las cinco barreras principales identificadas fueron la deshumanización de los pacientes, el costo a re humanizar pacientes, la animosidad en el sistema, la refracción de la violencia sobre los pacientes y la mala coordinación de recursos. Tres facilitadores para recibir cirugía fueron el trabajo en equipo, el capital social, y el acompañamiento. Interpretaciones: Los trabajadores de la salud describieron una cultura de desmoralización y desconfianza en el sistema de salud que se agrava con la escasez de recursos. Como resultado se obtiene, conflicto, falta de comunicación, y sentimientos de deshumanización que empeoran la atención al paciente. Recomendaciones para mejorar el acceso a los servicios quirúrgicos en la región incluyen estrategias para mejorar el trabajo en equipo y ampliar el acompañamiento de los pacientes. Financiamiento: La Universidad de Harvard y the Abundance Fund proporcionaron fondos para este proyecto. Las fuentes de financiamiento no influyen en la redacción ni en la publicación del manuscrito.

Assessment of surgical capacity in Chiapas, Mexico: a cross-sectional study of the public and private sector.

INTRODUCTION: Surgical, anaesthesia and obstetric (SAO) care are essential, life-saving components of universal healthcare. In Chiapas, Mexico's southernmost state, the capacity of SAO care is unknown. This study aims to assess the surgical capacity in Chiapas, Mexico, as it relates to access, infrastructure, service delivery, surgical volume, quality, workforce and financial risk protection. METHODS: A cross-sectional study of Ministry of Health public hospitals and private hospitals in Chiapas was performed. The translated Surgical Assessment Tool (SAT) was implemented in sampled hospitals. Surgical volume was collected retrospectively from hospital logbooks. Fisher's exact test and Mann-Whitney U test were used to compare public and private hospitals. Catastrophic expenditure from surgical care was calculated. RESULTS: Data were collected from 17 public hospitals and 20 private hospitals in Chiapas. Private hospitals were smaller than public hospitals and public hospitals performed more surgeries per operating room. Not all hospitals reported consistent electricity, running water or oxygen, but private hospitals were more likely to have these basic infrastructure components compared with public hospitals (84% vs 95%; 60% vs 100%; 94.1% vs 100%, respectively). Bellwether surgical procedures performed in private hospitals cost significantly more, and posed a higher risk of catastrophic expenditure, than those performed in public hospitals. CONCLUSION: Capacity limitations are greater in public hospitals compared with private hospitals. However, the cost of care in the private sector is significantly higher than the public sector and may result in catastrophic expenditures. Targeted interventions to improve the infrastructure, workforce availability and data collection are needed.

Access to Essential Surgical Care in Chiapas, Mexico: A System-Wide Geospatial Analysis.

BACKGROUND: Long travel times to reach essential surgical care in Chiapas, Mexico's poorest state, can delay lifesaving procedures and contribute to adverse outcomes. Geographical access to surgical facilities is 1 of the 6 indicators of the Lancet Commission on Global Surgery and has been measured extensively worldwide. Our objective is to determine the population with 2-h geographical access to facilities capable of performing the Bellwether procedures (laparotomy, cesarean delivery, and open fracture repair). This is the first study in Mexico to assess access to surgical facilities, including both the fragmented public sector and the private sector. METHODS: In this cross-sectional study, conducted from June 2019 to January 2020, Bellwether capable surgical facilities from all health systems in Chiapas were geocoded and assessed through on-site data collection, Ministry of Health databases, and verified via telephone. Geospatial analyses were performed on Redivis. RESULTS: We identified 59 Bellwether capable hospitals, with 17.5% (n = 954,460) of the state residing more than 2 h from surgical care in public and private health systems. Of those, 22 facilities had confirmed 24/7 Bellwether capability, and 23% (n = 1,178,383) of the affiliated population resided more than 2 h from these hospitals. CONCLUSIONS: Our study shows that the Ministry of Health and employment-based health coverage could provide timely access to essential surgical care for the majority of the population. However, the fragmentation of the healthcare system leaves a gap that contributes to delays in care and unmet emergency surgical needs.

Bridging the gap: an economic case study of the impact and cost effectiveness of comprehensive healthcare intermediaries in rural Mexico.

BACKGROUND: In rural settings where patients face significant structural barriers to accessing healthcare services, the formal existence of government-provided health coverage does not necessarily translate to meaningful care delivery. This paper analyses the effectiveness of an innovative approach to overcome these barriers, the Right to Health Care programme offered by Compañeros en Salud in Chiapas, Mexico. This programme provides comprehensive free coverage of all additional direct and indirect medical costs as well as accompaniment through the medical system. Over 550 patients had participated from 2013 until November 2018. METHODS: Focusing on ten of the most frequently treated conditions, including hernias, cataracts and congenital heart defects, we performed a retrospective case study analysis of the quality-adjusted life years (QALYs) gained from treatment and the cost per QALY for 69 patients. This analysis used disability weights and uncertainty intervals from the Global Burden of Disease study and organisational micro-costing data for each patient. Each patient was compared to their own hypothetical counterfactual health outcome had they not received the secondary and tertiary care required for the specific condition. A mixed methods approach is used to establish this counterfactual baseline, drawing on pre-intervention observations, qualitative interviews and established literature precedent. RESULTS: The programme was found to deliver an average of 14.4 additional QALYs (95% uncertainty interval 12.4-15.8) without time discounting. The mean cost per QALY over these conditions was $388 USD (95% UI $262-588) at purchasing power parity. CONCLUSIONS: These numbers compare favourably with studies of other health services and international cost per QALY guidelines. They reflect the on-treatment effect for the ten conditions analysed and are presented as a case study indicative of the promise of healthcare intermediaries rather than a definitive assessment of cost-effectiveness. Nonetheless, these results show the potential feasibility and cost effectiveness of a more comprehensive approach to healthcare provision in a resource-limited rural setting. TRIAL REGISTRATION: This study involves economic analysis of a programme facilitating access to public healthcare services. Thus, there was no associated clinical trial to be registered.

Assessment of diagnostics capacity in hospitals providing surgical care in two Latin American states.

BACKGROUND: Diagnostic services are an essential component of high-quality surgical, anesthesia and obstetric (SAO) care. Efforts to scale up SAO care in Latin America have often overlooked diagnostics capacity. This study aims to analyze the capacity of diagnostic services, including radiology, pathology, and laboratory medicine, in hospitals providing SAO care in the states of Chiapas, Mexico and Amazonas, Brazil. METHODS: A stratified cross-sectional evaluation of diagnostic capacity in hospitals performing surgery in Chiapas and Amazonas was performed using the Surgical Assessment Tool (SAT). National data sources were queried for indicators of diagnostics capacity in terms of workforce, infrastructure and diagnosis utilization. Fisher's exact tests and chi-square tests were used to compare categorical variables between the private and public sector in Chiapas while descriptive statistics are used to compare Amazonas and Chiapas. FINDINGS: In Chiapas, 53% (n = 17) of public and 34% (n = 20) of private hospitals providing SAO care were assessed. More private hospitals than public hospitals could always provide x-rays (35% vs 23.5%) and ultrasound (85% vs 47.1%). However neither sector could consistently perform basic laboratory testing such as complete blood counts (70.6% public, 65% private). In Amazonas, 30% (n = 18) of rural hospitals were surveyed. Most had functioning x-ray machine (77.8%) and ultrasound (55.6%). The majority of hospitals could provide complete blood count (66.7%) but only one hospital (5.6%) could always perform an infectious panel. Both Chiapas and Amazonas had dramatically fewer diagnostic practitioners per capita in each state compared to the national average capacity. INTERPRETATION: Facilities providing SAO care in low-resource states in Mexico and Brazil often lack functioning diagnostics services and workforce. Scale-up of diagnostic services is essential to improve SAO care and should occur with emphasis on equitable and adequate resource allocation.