Inhibitory to non-inhibitory evolution of the ζ subunit of the F1FO-ATPase of Paracoccus denitrificans and α-proteobacteria as related to mitochondrial endosymbiosis.

Introduction: The ζ subunit is a potent inhibitor of the F1FO-ATPase of Paracoccus denitrificans (PdF1FO-ATPase) and related α-proteobacteria different from the other two canonical inhibitors of bacterial (ε) and mitochondrial (IF1) F1FO-ATPases. ζ mimics mitochondrial IF1 in its inhibitory N-terminus, blocking the PdF1FO-ATPase activity as a unidirectional pawl-ratchet and allowing the PdF1FO-ATP synthase turnover. ζ is essential for the respiratory growth of P. denitrificans, as we showed by a Δζ knockout. Given the vital role of ζ in the physiology of P. denitrificans, here, we assessed the evolution of ζ across the α-proteobacteria class. Methods: Through bioinformatic, biochemical, molecular biology, functional, and structural analyses of several ζ subunits, we confirmed the conservation of the inhibitory N-terminus of ζ and its divergence toward its C-terminus. We reconstituted homologously or heterologously the recombinant ζ subunits from several α-proteobacteria into the respective F-ATPases, including free-living photosynthetic, facultative symbiont, and intracellular facultative or obligate parasitic α-proteobacteria. Results and discussion: The results show that ζ evolved, preserving its inhibitory function in free-living α-proteobacteria exposed to broad environmental changes that could compromise the cellular ATP pools. However, the ζ inhibitory function was diminished or lost in some symbiotic α-proteobacteria where ζ is non-essential given the possible exchange of nutrients and ATP from hosts. Accordingly, the ζ gene is absent in some strictly parasitic pathogenic Rickettsiales, which may obtain ATP from the parasitized hosts. We also resolved the NMR structure of the ζ subunit of Sinorhizobium meliloti (Sm-ζ) and compared it with its structure modeled in AlphaFold. We found a transition from a compact ordered non-inhibitory conformation into an extended α-helical inhibitory N-terminus conformation, thus explaining why the Sm-ζ cannot exert homologous inhibition. However, it is still able to inhibit the PdF1FO-ATPase heterologously. Together with the loss of the inhibitory function of α-proteobacterial ε, the data confirm that the primary inhibitory function of the α-proteobacterial F1FO-ATPase was transferred from ε to ζ and that ζ, ε, and IF1 evolved by convergent evolution. Some key evolutionary implications on the endosymbiotic origin of mitochondria, as most likely derived from α-proteobacteria, are also discussed.

Telehealth Actions to Address COVID-19 in Latin American Countries.

Introduction: This study set out to examine the use of telehealth resources to tackle the coronavirus disease 2019 (COVID-19) pandemic in Latin America within the scope of national telehealth projects (NTPs). Methods: A qualitative study developed using ethnomethodology for appropriate understanding of how telehealth actions were carried out in practice during the COVID-19 pandemic within the scope of NTPs, in the following countries: Argentina, Colombia, Costa Rica, Ecuador, El Salvador, Guatemala, Honduras, Mexico, Peru, and Uruguay. The study was carried out from October to 2020 to March 2021. The number of participations in the discussion groups, formed by coordinating teams of NTPs, totaled 90. Results were described in the worksheet completed according to the script. Each country reviewed its respective data, three times on average, in an effort to clarify actions developed. Results: Three groups of countries were identified: (1) Countries with a telehealth background that used these resources to tackle COVID-19 and thereby refined telehealth activities. Countries with greater experience in NTP design, such as Mexico, Colombia, Peru, and Argentina, were able to use a wide range of telehealth activities to tackle the pandemic, with offers of teleconsultation, teleguidance, telemonitoring to patients, and training of health professionals; (2) Countries with some telehealth activities to address COVID-19. Uruguay, Ecuador, El Salvador, and Costa Rica; and (3) Countries with no evidence of telehealth resource use during the pandemic. Honduras and Guatemala. Discussion: Most NTPs in Latin America have improved their telehealth activities, contributing to address the COVID-19 pandemic in Latin America.

A Low-Power IoT Device for Measuring Water Table Levels and Soil Moisture to Ease Increased Crop Yields.

The simultaneous measurement of soil water content and water table levels is of great agronomic and hydrological interest. Not only does soil moisture represent the water available for plant growth but also water table levels can affect crop productivity. Furthermore, monitoring soil saturation and water table levels is essential for an early warning of extreme rainfall situations. However, the measurement of these parameters employing commercial instruments has certain disadvantages, with a high cost of purchase and maintenance. In addition, the handling of commercial devices makes it difficult to adapt them to the specific requirements of farmers or decision-makers. Open-source IoT hardware platforms are emerging as an attractive alternative to developing flexible and low-cost devices. This paper describes the design of a datalogger device based on open-source hardware platforms to register water table levels and soil moisture data for agronomic applications. The paper begins by describing energy-saving and wireless transmission techniques. Then, it summarizes the linear calibration of the phreatimeter sensor obtained with laboratory and field data. Finally, it shows how non-linear machine-learning techniques improve predictions over classical tools for the moisture sensor (SKU: SEN0193).

Tele-revistas en unidades de terapia intensiva: Coordinación asistencial y aprendizaje en el marco de la pandemia / Tele-Rounding in intensive care units: healthcare coordination and learning within the context of the pandemic

INTRODUCCIÓN: En el marco de la pandemia por COVID-19 y frente a la necesidad de capacitar a los equipos de salud para minimizar el impacto sanitario, el Ministerio de Salud de la Nación implementó un proyecto basado en la utilización de tecnologías de la información y comunicación, que reunió en un entorno de coordinación asistencial a equipos de establecimientos de todo el país y de la Sociedad Argentina de Terapia Intensiva. El objetivo del estudio fue describir el proceso y los resultados de la implementación de las Tele-Revistas realizadas entre el 2 de abril y el 21 de mayo de 2020. MÉTODOS: Se realizaron encuentros virtuales en tiempo real bajo el formato de Tele-Revistas en unidades de terapia intensiva, en los cuales se presentaron casos de COVID-19 mediante asistencia de expertos. La participación se ponderó a través de dos registros y la valoración de los participantes, mediante encuestas. Los temas recurrentes se compilaron a partir de informes semanales. RESULTADOS: Se realizaron 81 Tele-Revistas con 897 participantes, y se presentaron y discutieron 67 casos de COVID-19. Se generaron espacios de formación y aprendizaje colaborativo, que facilitaron el acceso a asesoramiento experto e integraron a los profesionales. Los actores involucrados evaluaron el proceso positivamente. DISCUSIÓN: Este enfoque, basado en la actualización continua de especialistas, contribuye a una atención integral que mejora el abordaje de pacientes críticos, brinda apoyo y fomenta el desarrollo de los talentos humanos en salud.

Políticas de planificación y gestión de talento humano del Ministerio de Salud de Argentina durante la pandemia de COVID-19 / Human talent planning and management policies of the Ministry of Health of Argentina during the COVID-19 pandemic

INTRODUCCIÓN: La Dirección Nacional de Talento Humano y Conocimiento (DNTHyC) del Ministerio de Salud de la Nación se abocó a la planificación y gestión de la fuerza de trabajo en salud en Argentina durante la pandemia de la enfermedad por el nuevo coronavirus (COVID-19). Se detectaron cuatro problemas: escasez de profesionales en áreas críticas, vulnerabilidad del personal de salud, distribución desigual del conocimiento y falta de evidencia científica sobre el virus. El objetivo del artículo es describir el abordaje de la política de talento humano en la emergencia. MÉTODOS: Las políticas para dar respuesta fueron el incremento de la fuerza de trabajo disponible para la atención, la elaboración de un plan de cuidado de los trabajadores de la salud, la capacitación de los profesionales a cargo del manejo de la pandemia y la difusión y democratización del conocimiento. RESULTADOS: La fuerza de trabajo se incrementó en 15 200 profesionales. Se elaboraron programas con más de veinte universidades nacionales y más de 5000 estudiantes, y se creó el Plan Nacional de Cuidado de Trabajadores y Trabajadoras de la Salud, que llegó a más de 70 hospitales y más de 15 000 trabajadores. Se realizaron capacitaciones en línea y supervisión de servicios de terapias intensivas de todo el país mediante Tele-Revista, que alcanzó a 1200 profesionales. DISCUSIÓN: El aislamiento social, preventivo y obligatorio permitió encarar el trabajo necesario para alcanzar una dotación de personas, desarrollos tecnológicos y programas específicos que configuran una situación gobernable de la emergencia. No obstante, el nuevo virus y la crisis sanitaria derivada obligaron a repensar las condiciones de la formación de profesionales en Argentina

Argentinian Digital Health Strategy.

Digital Health is one of the three pillars for the effective implementation of Universal Health Coverage in Argentina. The Ministry of Health published the National Digital Health Strategy 2018-2024 in order to establish the conceptual guidelines for the design and development of interoperable health information systems as a state policy. The World Health Organization "National eHealth Strategy Toolkit", "Global Strategy on Digital Health" and other international and local evidence and expert recommendations were taken into account. The path to better healthcare involves adopting systems at the point of care, allowing for the primary recording of information and enabling information exchange through real interoperability. In that way, people, technology and processes will synergize to enhance integrated health service networks. In this paper, we describe the plan and the first two years of implementation of the strategy.

Mi Argentina/Mi Salud: The Argentinian Citizen Digital Health Portal.

The Ministry of Health (MoH) stated the National Digital Health Strategy 2018-2024 in order to establish the conceptual guidelines for the design and development of interoperable health information systems. It included the creation of a National Digital Health Network, and a Citizen Health Portal to inform and empower patients about their rights. For instance, the Digital Vaccination Card is already available and has equal legal validity as its paper version. The platform also works as a personal privacy manager, to configure the consent for Health Information Exchange through the network, or to check the access logs. This paper outlines the implementation experience of this powerful tool at a national level.

Results of the Use of the Teleconsultation Platform After 2 Months of Implementation.

The Ministry of Health (MoH) set the National Digital Health Strategy 2018-2024 as a state policy. It included a National TeleHealth Plan to enhance access and quality of healthcare in a wide territory like Argentina, leveraging more than 20 years of national telemedicine experiences and coordinating it with the territorial integrated health service networks proposed by the Universal Health Coverage strategy. In collaboration with the Ministry of Modernisation, the MoH developed and implemented a new TeleHealth Web Platform to perform eReferrals and eConsultations nationwide. This poster describes the first 2 months of usage.

Elucidating the mechanism of action of alpha-1-antitrypsin using retinal pigment epithelium cells exposed to high glucose. Potential use in diabetic retinopathy.

BACKGROUND: Alpha-1-antitrypsin is a protein involved in avoidance of different processes that are seen in diabetic retinopathy pathogenesis. These processes include apoptosis, extracellular matrix remodeling and damage of vessel walls and capillaries. Furthermore, because of its anti-inflammatory effects, alpha-1-antitrypsin has been proposed as a possible therapeutic approach for diabetic retinopathy. Our group tested alpha-1-antitrypsin in a type 1 diabetes mouse model and observed a reduction of inflammation and retinal neurodegeneration. Thus, shedding light on the mechanism of action of alpha-1-antitrypsin at molecular level may explain how it works in the diabetic retinopathy context and show its potential for use in other retinal diseases. METHODS: In this work, we evaluated alpha-1-antitrypsin in an ARPE-19 human cell line exposed to high glucose. We explored the expression of different mediators on signaling pathways related to pro-inflammatory cytokines production, glucose metabolism, epithelial-mesenchymal transition and other proteins involved in the normal function of retinal pigment epithelium by RT-qPCR and Western Blot. RESULTS: We obtained different expression patterns for evaluated mediators altered with high glucose exposure and corrected with the use of alpha-1-antitrypsin. CONCLUSIONS: The expression profile obtained in vitro for the evaluated proteins and mRNA allowed us to explain our previous results obtained on mouse models and to hypothesize how alpha-1-antitrypsin hinder diabetic retinopathy progression on a complex network between different signaling pathways. GENERAL SIGNIFICANCE: This network helps to understand the way alpha-1-antitrypsin works in diabetic retinopathy and its scope of action.

Alpha-1-antitrypsin ameliorates inflammation and neurodegeneration in the diabetic mouse retina.

Diabetic retinopathy (DR) is the most common cause of blindness in the working age population. Early events of DR are accompanied by neurodegeneration of the inner retina resulting in ganglion cell loss. These findings together with reduced retinal thickness are observed within the first weeks of experimental DR. Besides, an inflammatory process is triggered in DR in which the innate immune response plays a relevant role. Alpha 1 antitrypsin (AAT), an inhibitor of serine proteases, has shown anti-inflammatory properties in several diseases. We aimed at evaluating the use of AAT to prevent the early changes induced by DR. Diabetic AAT-treated mice showed a delay on ganglion cell loss and retinal thinning. These animals showed a markedly reduced inflammatory status. AAT was able to preserve systemic and retinal TNF-α level similar to that of control mice. Furthermore, retinal macrophages found in the AAT-treated diabetic mouse exhibited M2 profile (F4/80+CD206+) together with an anti-inflammatory microenvironment. We thus demonstrated that AAT-treated mice show less retinal neurodegenerative changes and have reduced levels of systemic and retinal TNF-α. Our results contribute to shed light on the use of AAT as a possible therapeutic option in DR.

Possible neuroprotective role of P2X2 in the retina of diabetic rats.

BACKGROUND: Purinergic receptors are expressed in different tissues including the retina. These receptors are involved in processes like cell growth, proliferation, activation and survival. ATP is the major activator of P2 receptors. In diabetes, there is a constant ATP production and this rise of ATP leads to a persistent activation of purinergic receptors. Antagonists of these receptors are used to evaluate their inhibition effects. Recently, the P2X2 has been reported to have a neuroprotective role. METHODS: We carried out a study in groups of diabetic and non-diabetic rats (N = 5) treated with intraperitoneal injections of PPADS, at 9 and 24 weeks of diabetes. Control group received only the buffer. Animals were euthanized at 34 weeks of diabetes or at a matching age. Rat retinas were analyzed with immunohistochemistry and western blot using antibodies against GFAP, P2X2, P2Y2 and VEGF-A. RESULTS: Diabetic animals treated with PPADS disclosed a much more extended staining of VEGF-A than diabetics without treatment. A lower protein expression of VEGF-A was found at the retina of diabetic animals without treatment of purinergic antagonists compared to diabetics with the antagonist treatment. Inhibition of P2X2 receptor by PPADS decreases cell death in the diabetic rat retina. CONCLUSION: Results might be useful for better understanding the pathophysiology of diabetic retinopathy.

Corneal Neovascularization: A Combined Approach of Bevacizumab and Suramin Showed Increased Antiangiogenic Effect Through Downregulation of BFGF and P2X2.

PURPOSE: The objective is to analyze the antiangiogenic mechanism of suramab, a pharmaceutical compound of bevacizumab and suramin, in a rabbit model of corneal angiogenesis. MATERIAL AND METHODS: Corneal neovascularization was induced in four groups of six New Zealand White rabbits by applying a filter paper disk soaked in 1 M Na (OH) on the central cornea. Group one was treated after injury with intravenous suramab at a dose equivalent to 3 mg/kg of bevacizumab and 10 mg/kg of suramin. Group two was treated with intravenous bevacizumab (5 mg/kg). Group three was treated with 10 mg/kg of suramin while the control group received no treatment. Digital photographs were taken at days 9, 15, 21, and 35. Neovessel formation was quantified giving a 0-4 score to each quadrant according to the centripetal growth of the longest vessel (neovessel index, NVI). Animals were sacrificed at day 35. Corneas were processed for histology, immunohistochemistry, and Western-blot using primary antibodies against P2X2, basic fibroblast growth factor (bFGF), LYVE-1, PECAM-1, and vascular endothelial growth factor-A (VEGF-A). RESULTS: Suramab significantly reduced neovessel growth (mean NVI: 4.2) compared to bevacizumab (8.4), suramin (7.22), and control animals (12.2) at 35 days post-injury (p < 0.01). A lower protein expression of P2X2, bFGF, LYVE-1, PECAM-1, and VEGF-A was found in the cornea of suramab animals than in the other groups of animals. CONCLUSIONS: Joint downregulation of bFGF, P2X2, bFGF, and LYVE-1 constitutes a mechanism that induces greater and longer inhibition of corneal angiogenesis. Results might be relevant to ophthalmic care. Ocular administration of suramab is currently being investigated.

Telemedicine Enables Broader Access to Movement Disorders Curricula for Medical Students.

Background: The impact of tele-education for movement disorders on medical students is unknown. The present study had three objectives. First, to create a tele-education program for medical students in regions with limited access to movement disorders curricula. Second, to analyze the feasibility, satisfaction, and improvement of medical knowledge. Third, to assess the main reasons of medical students for attending this course. Methods: In 2016, a program was piloted in a low-middle income (Cameroon) and a middle-high income (Argentina) country. Medical students were offered a free movement disorder tele-education program (four medical schools in Argentina, and 1 medical school in Cameroon). Six real-time videoconferences covering hyperkinetic and hypokinetic movement disorders were included. Evaluations included attendance, pre- and post-medical knowledge, and satisfaction questionnaires. Results: The study included 151 undergraduate medical students (79.4% from Argentina, 20.6% from Cameroon). Feasibility was acceptable with 100% and 85.7% of the videoconferences completed in Argentina and Cameroon, respectively. Attendance was higher in Argentina compared to Cameroon (75% vs. 33.1%). According to student reports, the topics and innovative educational environment were the main reasons for attendance. Both groups ranked satisfaction as moderate to high, and medical knowledge improved similarly in both countries. Discussion: Tele-education can improve movement disorders knowledge in medical schools in high-middle and low-middle income countries lacking access to other educational opportunities.

Evaluation of the Performance of an Ophthalmic Thermosensitive Hydrogel Containing Combination of Suramin and Bevacizumab.

Suramab (SUM) is a new pharmaceutical combination made up of suramine (SUR) and bevacizumab (BVM), which showed a high synergistic effect when administered jointly. As the pharmaceutical vehicle, poloxamer aqueous dispersions were used since this system is able to maintain their fluidity at low temperatures (<15ºC) but which become gel in the corporal environment (>35ºC). In the present study we aimed at evaluating the effect of Poloxamer to prolong the effect of SUM. These formulations were characterized using rheological, biopharmaceutical (drug release) and morphological (SEM) technique. Corneal NV was induced in Sprague Dawley rats Corneal. At 15 days of follow up animals were sacrificed and perfused with black drawing ink. Digital photographs were taken and the area of neovascularisation (ANV) was calculated using the image programmed. The rheological behavior was influenced by the addition of drugs, resulting in a decrease in the gelation temperature (Tsol/gel). Both drugs were released from poloxamer gels by means of an anomalous mechanism. However, BVM was released faster than SUR, with their combination (SUM) to appearing to reduce delivery, probably due to interactions between the drugs or with the polymeric matrix. The in vivo studies showed that SUM-poloxamer gel was able to increase the corneal antiangiogenic effect compared to the SUM solution and BVM alone at 15 days of follow-up. Furthermore no injurious effects were observed in the histological tissue examination after drug administration. The presence of Poloxamer, known to modulate control release of biological agents, seems to have a favorable effect on SUM subconjunctival administered.

[Splenic infarction. Ergotism induced by ritonavir?]. / Infarto esplénico. ¿Ergotismo inducido por ritonavir?

Ergotism is a clinical condition known since old times and whose main characteristics are ischemia and even limb gangrene. Some drugs have the capacity of interacting with small amounts of ergotamine or its derivatives producing ergotism as a side effect. This is the case of ritonavir, a widely used anti-HIV drug. Here we present a case of ergotism that developed in an HIV positive 39 year old male under treatment with ritonavir, after taking 1 mg of ergotamine tartrate. His clinical picture, apart from showing the basic manifestations of the disease, was associated with splenic infarction. For this reason, we consider important to advise patients about the potential pharmacological interaction between ergotamines and others common drugs and, in particular, ritonavir in HIV positive patients.

Infarto esplénico ¿Ergotismo inducido por ritonavir? / Splenic infarction: Ergotism induced by ritonavir?

El ergotismo es una enfermedad conocida desde la antig³edad, que se caracteriza por isquemia y, en algunos casos, gangrena de las extremidades. Muchas drogas de uso corriente tienen la capacidad de interactuar con los ergotamínicos desarrollando ergotismo como efecto adverso. Un ejemplo de ello es el ritonavir, un inhibidor de la proteasa utilizado en pacientes con el virus de la inmunodeficiencia humana (HIV). Presentamos un caso de ergotismo en un varón de 39 años con infección por HIV en tratamiento con ritonavir que, después de ingerir 1 mg de tartrato de ergotamina, además de presentar manifestaciones clásicas de la enfermedad, desarrolló un infarto esplénico. Por lo tanto, consideramos importante advertir a los pacientes sobre la posible interacción farmacológica entre los ergotamínicos y otras drogas de uso frecuente y, en particular, el ritonavir en pacientes portadores de HIV.(AU)

Ergotism is a clinical condition known since old times and whose main characteristics are ischemia and even limb gangrene. Some drugs have the capacity of interacting with small amounts of ergotamine or its derivatives producing ergotism as a side effect. This is the case of ritonavir, a widely used anti-HIV drug. Here we present a case of ergotism that developed in an HIV positive 39 year old male under treatment with ritonavir, after taking 1 mg of ergotamine tartrate. His clinical picture, apart from showing the basic manifestations of the disease, was associated with splenic infarction. For this reason, we consider important to advise patients about the potential pharmacological interaction between ergotamines and others common drugs and, in particular, ritonavir in HIV positive patients.(AU)