SARS-CoV-2-related bat viruses evade human intrinsic immunity but lack efficient transmission capacity.

Circulating bat coronaviruses represent a pandemic threat. However, our understanding of bat coronavirus pathogenesis and transmission potential is limited by the lack of phenotypically characterized strains. We created molecular clones for the two closest known relatives of SARS-CoV-2, BANAL-52 and BANAL-236. We demonstrated that BANAL-CoVs and SARS-CoV-2 have similar replication kinetics in human bronchial epithelial cells. However, BANAL-CoVs have impaired replication in human nasal epithelial cells and in the upper airway of mice. We also observed reduced pathogenesis in mice and diminished transmission in hamsters. Further, we observed that diverse bat coronaviruses evade interferon and downregulate major histocompatibility complex class I. Collectively, our study demonstrates that despite high genetic similarity across bat coronaviruses, prediction of pandemic potential of a virus necessitates functional characterization. Finally, the restriction of bat coronavirus replication in the upper airway highlights that transmission potential and innate immune restriction can be uncoupled in this high-risk family of emerging viruses.

A New Quantitative Tool for the Ultrasonographic Assessment of Tendons: A Reliability and Validity Study on the Patellar Tendon.

Ultrasound is widely used for tendon assessment due to its safety, affordability, and portability, but its subjective nature poses challenges. This study aimed to develop a new quantitative analysis tool based on artificial intelligence to identify statistical patterns of healthy and pathological tendons. Furthermore, we aimed to validate this new tool by comparing it to experts' subjective assessments. A pilot database including healthy controls and patients with patellar tendinopathy was constructed, involving 14 participants with asymptomatic (n = 7) and symptomatic (n = 7) patellar tendons. Ultrasonographic images were assessed twice, utilizing both the new quantitative tool and the subjective scoring method applied by an expert across five regions of interest. The database contained 61 variables per image. The robustness of the clinical and quantitative assessments was tested via reliability analyses. Lastly, the prediction accuracy of the quantitative features was tested via cross-validated generalized linear mixed-effects logistic regressions. These analyses showed high reliability for quantitative variables related to "Bone" and "Quality", with ICCs above 0.75. The ICCs for "Edges" and "Thickness" varied but mostly exceeded 0.75. The results of this study show that certain quantitative variables are capable of predicting an expert's subjective assessment with generally high cross-validated AUC scores. A new quantitative tool for the ultrasonographic assessment of the tendon was designed. This system is shown to be a reliable and valid method for evaluating the patellar tendon structure.

Revisiting Hypertension Treatment in Patients With Chronic Kidney Disease.

Despite being the world's top risk factor for death and disability, hypertension awareness and control within the chronic kidney disease (CKD) population have decreased. This is particularly important considering the heightened severity and management challenges of hypertension in CKD patients, whose outcomes are often worse compared with persons with normal kidney function. Therefore, finding novel therapeutics to improve blood pressure control within this vulnerable group is paramount. Although medications that target the renin-angiotensin-aldosterone system remain a mainstay for blood pressure control in most stages of CKD, we discuss novel approaches that may expand their use in advanced CKD. We also review newer tools for blood pressure management that have emerged in recent years, including aldosterone synthase inhibitors, endothelin receptor antagonists, and renal denervation. Overall, the future of hypertension management in CKD appears brighter, with a growing arsenal of tools and a deeper understanding of this complex disease.

Central inhibition of HDAC6 re-sensitizes leptin signaling during obesity to induce profound weight loss.

Leptin resistance during excess weight gain significantly contributes to the recidivism of obesity to leptin-based pharmacological therapies. The mechanisms underlying the inhibition of leptin receptor (LepR) signaling during obesity are still elusive. Here, we report that histone deacetylase 6 (HDAC6) interacts with LepR, reducing the latter's activity, and that pharmacological inhibition of HDAC6 activity disrupts this interaction and augments leptin signaling. Treatment of diet-induced obese mice with blood-brain barrier (BBB)-permeable HDAC6 inhibitors profoundly reduces food intake and leads to potent weight loss without affecting the muscle mass. Genetic depletion of Hdac6 in Agouti-related protein (AgRP)-expressing neurons or administration with BBB-impermeable HDAC6 inhibitors results in a lack of such anti-obesity effect. Together, these findings represent the first report describing a mechanistically validated and pharmaceutically tractable therapeutic approach to directly increase LepR activity as well as identifying centrally but not peripherally acting HDAC6 inhibitors as potent leptin sensitizers and anti-obesity agents.

Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract.

Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are accessible and effective are urgently needed, especially in countries that are disproportionately affected. Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon-stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota. Prophylactic or therapeutic administration of neomycin provided significant protection against upper respiratory infection and lethal disease in a mouse model of COVID-19. Furthermore, neomycin treatment protected Mx1 congenic mice from upper and lower respiratory infections with a highly virulent strain of influenza A virus. In Syrian hamsters, neomycin treatment potently mitigated contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In healthy humans, intranasal application of neomycin-containing Neosporin ointment was well tolerated and effective at inducing ISG expression in the nose in a subset of participants. These findings suggest that neomycin has the potential to be harnessed as a host-directed antiviral strategy for the prevention and treatment of respiratory viral infections.

Observer-based differential evolution constrained control for safe reference tracking in robots.

Big torque inputs in controls could increase energy consumption, and big estimated perturbations in observers could produce device damages. Therefore, it would be interesting to propose a constrained control for safe reference tracking and a constrained observer for safe perturbation estimation in robots. Furthermore, the best gains in controls produce a balance between safe reference tracking and save energy consumption. Therefore, it would be interesting to propose a method to find the best gains. In this paper, an observer-based differential evolution constrained control is proposed for safe reference tracking in robots. The contributions are described as follows: (1) a constrained observer is proposed for safe perturbation estimation in robots, (2) a constrained control is proposed for safe reference tracking in robots, (3) a differential evolution optimizer is used to find the best gains in an observer-based constrained control, (4) the robust stability in an observer-based constrained control is assured, (5) the pseudo-code of an observer-based differential evolution constrained control is detailed. The proposed observer-based differential evolution constrained control is applied for safe reference tracking in two robots.

Comparative single-cell transcriptomic profile of hybrid immunity induced by adenovirus vector-based COVID-19 vaccines.

In this study, antibody response and a single-cell RNA-seq analysis were conducted on peripheral blood mononuclear cells from five different groups: naïve subjects vaccinated with AZD1222 (AZ) or Ad5-nCoV (Cso), individuals previously infected and later vaccinated (hybrid) with AZD1222 (AZ-hb) or Ad5-nCoV (Cso-hb), and those who were infected and had recovered from COVID-19 (Inf). The results showed that AZ induced more robust neutralizing antibody responses than Cso. The single-cell RNA data revealed a high frequency of memory B cells in the Cso and Cso-hb. In contrast, AZ and AZ-hb groups exhibited the highest proportion of activated naïve B cells expressing CXCR4. Transcriptomic analysis of CD4+ and CD8+ T cells demonstrated a heterogeneous response following vaccination, hybrid immunity, or natural infection. However, a single dose of Ad5-nCoV was sufficient to strongly activate CD4+ T cells (naïve and memory) expressing ANX1 and FOS, similar to the hybrid response observed with AZ. An interesting finding was the robust activation of a subset of CD8+ T cells expressing GZMB, GZMH, and IFNG genes in the Cso-hb group. Our findings suggest that both vaccines effectively stimulated the cellular immune response; however, the Ad5-nCoV induced a more robust CD8+ T-cell response in previously infected individuals.

Sex differences in symptomatology and immune profiles of Long COVID.

Strong sex differences in the frequencies and manifestations of Long COVID (LC) have been reported with females significantly more likely than males to present with LC after acute SARS-CoV-2 infection 1-7 . However, whether immunological traits underlying LC differ between sexes, and whether such differences explain the differential manifestations of LC symptomology is currently unknown. Here, we performed sex-based multi-dimensional immune-endocrine profiling of 165 individuals 8 with and without LC in an exploratory, cross-sectional study to identify key immunological traits underlying biological sex differences in LC. We found that female and male participants with LC experienced different sets of symptoms, and distinct patterns of organ system involvement, with female participants suffering from a higher symptom burden. Machine learning approaches identified differential sets of immune features that characterized LC in females and males. Males with LC had decreased frequencies of monocyte and DC populations, elevated NK cells, and plasma cytokines including IL-8 and TGF-ß-family members. Females with LC had increased frequencies of exhausted T cells, cytokine-secreting T cells, higher antibody reactivity to latent herpes viruses including EBV, HSV-2, and CMV, and lower testosterone levels than their control female counterparts. Testosterone levels were significantly associated with lower symptom burden in LC participants over sex designation. These findings suggest distinct immunological processes of LC in females and males and illuminate the crucial role of immune-endocrine dysregulation in sex-specific pathology.

Design and Implementation of an Electronic Health Record-Integrated Hypertension Management Application.

BACKGROUND: High blood pressure affects approximately 116 million adults in the United States. It is the leading risk factor for death and disability across the world. Unfortunately, over the past decade, hypertension control rates have decreased across the United States. Prediction models and clinical studies have shown that reducing clinician inertia alone is sufficient to reach the target of ≥80% blood pressure control. Digital health tools containing evidence-based algorithms that are able to reduce clinician inertia are a good fit for turning the tide in blood pressure control, but careful consideration should be taken in the design process to integrate digital health interventions into the clinical workflow. METHODS: We describe the development of a provider-facing hypertension management platform. We enumerate key steps of the development process, including needs finding, clinical workflow analysis, treatment algorithm creation, platform design and electronic health record integration. We interviewed and surveyed 5 Stanford clinicians from primary care, cardiology, and their clinical care team members (including nurses, advanced practice providers, medical assistants) to identify needs and break down the steps of clinician workflow analysis. The application design and development stage were aided by a team of approximately 15 specialists in the fields of primary care, hypertension, bioinformatics, and software development. CONCLUSIONS: Digital monitoring holds immense potential for revolutionizing chronic disease management. Our team developed a hypertension management platform at an academic medical center to address some of the top barriers to adoption and achieving clinical outcomes. The frameworks and processes described in this article may be used for the development of a diverse range of digital health tools in the cardiovascular space.

Digital Health Interventions for Heart Failure Management in Underserved Rural Areas of the United States: A Systematic Review of Randomized Trials.

BACKGROUND: Heart failure disproportionately affects individuals residing in rural areas, leading to worse health outcomes. Digital health interventions have been proposed as a promising approach for improving heart failure management. This systematic review aims to identify randomized trials of digital health interventions for individuals living in underserved rural areas with heart failure. METHODS AND RESULTS: We conducted a systematic review by searching 6 databases (CINAHL, EMBASE, MEDLINE, Web of Science, Scopus, and PubMed; 2000-2023). A total of 30 426 articles were identified and screened. Inclusion criteria consisted of digital health randomized trials that were conducted in underserved rural areas of the United States based on the US Census Bureau's classification. Two independent reviewers screened the studies using the National Heart, Lung, and Blood Institute tool to evaluate the risk of bias. The review included 5 trials from 6 US states, involving 870 participants (42.9% female). Each of the 5 studies employed telemedicine, 2 studies used remote monitoring, and 1 study used mobile health technology. The studies reported improvement in self-care behaviors in 4 trials, increased knowledge in 2, and decreased cardiovascular mortality in 1 study. However, 3 trials revealed no change or an increase in health care resource use, 2 showed no change in cardiac biomarkers, and 2 demonstrated an increase in anxiety. CONCLUSIONS: The results suggest that digital health interventions have the potential to enhance self-care and knowledge of patients with heart failure living in underserved rural areas. However, further research is necessary to evaluate their impact on clinical outcomes, biomarkers, and health care resource use. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022366923.

Resident training in interventional pathology: Ultrasound-guided fine-needle aspiration and rapid on site evaluation-5 years of teaching experience in a single university hospital.

INTRODUCTION: Despite the established role of the interventional pathologist, their diagnostic performance is difficult to establish. At least in Spain training of pathology residents in ultrasound-guided interventional procedures for specimen collection is limited or absent in most institutions. We present our teaching experience in the instruction of ultrasound-guided fine-needle aspiration (FNA) to pathology residents in a tertiary-level hospital. MATERIALS AND METHODS: The training of pathology residents who rotated through the interventional unit of the pathology department and the application of ultrasound-guided FNA and rapid on-site evaluation (U-ROSE) was documented over 5 years. The training period was broken down into learning phases and included the number of ultrasound-guided FNA performed, anatomical location, and their diagnostic performance, among other aspects. RESULTS: Nineteen (19) pathology residents were trained in U-ROSE, and performed a total of 4003 procedures, with a mean of 211 per resident. In 53% of cases only one pass was required for an adequated sample. The specimen was diagnostic in more than 97% of cases. The most frequently sampled anatomical sites were the thyroid gland (n = 2347), followed by lymph node (n = 667), soft tissues (n = 663) and salivary glands (n = 322). CONCLUSION: The results support the training programme followed by pathology residents in learning U-ROSE, which is essential to lay the foundations for the future interventional pathologist.

Evidence of the acupuncture points stimulation for the treatment of hypogalactia: A systematic review and meta-analysis.

OBJECTIVE: To perform a literature review aimed to analyze if acupoint stimulation increases lactation quantity. METHOD: Studies were collected from five electronic databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews. Eligibility criteria were full-text articles in English or Spanish with clinical trial design and observational studies, with no restriction on time of publication, in which the effect of acupoint stimulation on improving the quantity of lactation by conventional acupuncture, electroacupuncture, laser, fire needling, manual stimulation, tuina or catgut had been evaluated. Two authors independently extracted data for the characteristics and main outcomes of the studies selected for inclusion. The risk of bias (RoB 2 and Robins-I) and the quality assessments (GRADE) were performed. For the quantitative synthesis, the standardized mean difference was calculated for each individual study selected and then the data were combined using a random-effects meta-analysis. RESULTS: A total of 14 studies were included in the present review. Most of the included studies exhibited some concerns in the risk of bias assessment. The quality of the studies was moderate. The meta-analysis showed that manual acupoint stimulation improves the lactation quantity (SMD 95% CI = 1.63 [1.13-2.13]; p < 0.0001). CONCLUSION: The literature suggests that manual stimulation of acupuncture points improves the amount of milk produced during lactation.

Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID.

Background: Long COVID contributes to the global burden of disease. Proposed root cause hypotheses include the persistence of SARS-CoV-2 viral reservoir, autoimmunity, and reactivation of latent herpesviruses. Patients have reported various changes in Long COVID symptoms after COVID-19 vaccinations, leaving uncertainty about whether vaccine-induced immune responses may alleviate or worsen disease pathology. Methods: In this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naïve individuals with Long COVID. Surveys were administered before vaccination and then at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were quantified before vaccination and at 6 and 12 weeks after vaccination. Results: Self-report at 12 weeks post-vaccination indicated 10 out of 16 participants had improved health, 3 had no change, 1 had worse health, and 2 reported marginal changes. Significant elevation in SARS-CoV-2-specific TCRs and Spike protein-specific IgG were observed 6 and 12 weeks after vaccination. No changes in reactivities were observed against herpes viruses and self-antigens. Within this dataset, higher baseline sIL-6R was associated with symptom improvement, and the two top features associated with non-improvement were high IFN-ß and CNTF, among soluble analytes. Conclusions: Our study showed that in this small sample, vaccination improved the health or resulted in no change to the health of most participants, though few experienced worsening. Vaccination was associated with increased SARS-CoV-2 Spike protein-specific IgG and T cell expansion in most individuals with Long COVID. Symptom improvement was observed in those with baseline elevated sIL-6R, while elevated interferon and neuropeptide levels were associated with a lack of improvement.

Acute pesticide poisoning: Comparison of epidemiological characteristics between the rural and urban population

Objective: To analyze the behavior of pesticide poisoning associated with lethality in rural and urban populations in Colombia from 2007 to 2017. Methodology: Retrospective observational study that included a descriptive cross-sectional study and an ecological design that analyzed aggregate measures of morbidity, mortality, and risk attributable to the population in rural and urban areas. In the cross-sectional study, the relative risk was estimated to measure the factors associated with lethality among intoxications using Poisson regression with logarithmic function. For the time series, the trends were established with simple linear regression, and the seasonal decomposition was performed using the multiplicative model. Autocorrelations were tested using the Box-Ljung statistic. Results: Between 2007-2017; 89 490 cases were reported. The Morbidity due to poisoning showed a higher proportion in the rural population 36.03 cases per 100 000; this indicator was three times higher than in urban areas (12.33 cases per 100 000). The mortality rates in rural and urban areas were 1.00 and 0.13 cases per 100 000, respectively. The relative risk of fatality in case of intoxication was associated with the intention of suicide in the rural population Relative Risk (RR): 5.9 (95% CI: 5.0-6.9). Conclusion: A higher proportion of lethality associated with these events occurred in populations living in rural areas and reporting cases of suicidal intent. In addition, morbidity and mortality due to pesticide poisoning had the highest proportion in rural areas and a growing trend over time.

Objetivo: Analizar el comportamiento de las intoxicaciones por plaguicidas en poblaciones rurales y urbanas asociadas a la letalidad en Colombia durante 2007-2017. Metodología: Estudio observacional retrospectivo que incluyó: un estudio descriptivo transversal y un diseño ecológico que analizó medidas agregadas de morbilidad, mortalidad y riesgo atribuibles a la población en áreas rurales y urbanas. En el estudio transversal se estimó el riesgo relativo para medir los factores asociados a la letalidad entre las intoxicaciones mediante regresión de Poisson con función logarítmica. Para la serie de tiempo, las tendencias se establecieron con regresión lineal simple y la descomposición estacional se realizó mediante el modelo multiplicativo. Las autocorrelaciones se probaron mediante el estadístico Box-Ljung. Resultados: Entre 2007-2017; Se notificaron 89 490 casos. La Morbilidad por intoxicación presentó mayor proporción en la población rural 36,03 casos por 100 000; este indicador fue tres veces mayor que en las áreas urbanas (12,33 casos por 100 000). Las tasas de mortalidad en el área rural y urbana fueron de 1,00 y 0,13 casos por 100 000, respectivamente. El riesgo relativo de fatalidad en caso de intoxicación se asoció con la intención de suicidio en la población rural RR: 5,9 (IC 95%: 5,0-6,9). Conclusión: Una mayor proporción de letalidad asociada a estos eventos ocurrió en poblaciones que viven en áreas rurales y reportan casos de intención suicida. Además, la morbilidad y mortalidad por intoxicación por plaguicidas tuvo la mayor proporción en las zonas rurales y una tendencia creciente en el tiempo.

Objetivo: Analisar o comportamento das intoxicações por agrotóxicos em populações rurais e urbanas associadas à letalidade na Colômbia durante 2007-2017. Metodologia: Estudo observacional retrospectivo que incluiu: estudo transversal descritivo e delineamento ecológico que analisou medidas agregadas de morbidade, mortalidade e risco atribuíveis à população em áreas rurais e urbanas. No estudo transversal, o risco relativo foi estimado para medir os fatores associados à letalidade entre as intoxicações por meio da regressão de Poisson com função logarítmica. Para as séries temporais, as tendências foram estabelecidas com regressão linear simples e a decomposição sazonal foi realizada usando o modelo multiplicativo. As autocorrelações foram testadas usando a estatística Box-Ljung. Resultados: Entre 2007-2017; 89.490 casos foram notificados. A Morbidade por intoxicação apresentou maior proporção na população rural 36,03 casos por 100.000; este indicador foi três vezes superior ao das zonas urbanas (12,33 casos por 100 000). As taxas de mortalidade nas áreas rural e urbana foram de 1,00 e 0,13 casos por 100.000 habitantes, respectivamente. O risco relativo de fatalidade em caso de intoxicação associou-se à intenção de suicídio na população rural RR: 5,9 (IC 95%: 5,0-6,9). Conclusão: Maior proporção de letalidade associada a esses eventos ocorreu em populações residentes em áreas rurais e com relato de casos de intenção suicida. Além disso, a morbimortalidade por intoxicação por agrotóxicos teve maior proporção na zona rural e tendência crescente ao longo do tempo.

Evidencia de la efectividad del uso de aparatología ortopédica prequirúrgica en pacientes con labio y paladar hendido: revisión sistemática / Evidence of the effectiveness of the use of presurgical orthopedic appliances in patients with cleft lip and palate: a systematic review

Resumen El objetivo de este artículo fue evaluar la evidencia sobre el uso de una aparatología ortopédica prequirúrgica (AOP) en pacientes con labio y paladar hendido. Se realizó una búsqueda en las siguientes bases de datos: Medline/PubMed, Google Scholar, Clinical Trails.gov, ProQuest y Web of Science. En la búsqueda, se encontraron 7.926 registros, de los cuales se analizaron 105 artículos de texto completo; de éstos se incluyeron 23 estudios en pacientes con uso de AOP, asi como su grupo control sin el uso del AOP, previo al mismo tipo de cirugía. Los aparatos más utilizados para la AOP en el manejo de LPH fueron: el paladar pasivo (Paladar de Hotz), el modelador nasolaveolar (NAM), aparato McNeil y por último el T-traction; los principales desenlaces evaluados fueron: la estética facial y apariencia nasal; la evaluación de medidas cefalométricas, de vías aéreas superiores, nasales, del ancho de la fisura y así como puntos de referencia anatómicos como la distancia inter-canina e inter-tuberosidad. Además, se encontraron estudios que evaluaron oclusión y la fonación. La evidencia de esta literatura sugiere que el uso de aparatos activos tiene un mejor efecto que la placa pasiva, en términos de estética facial y aproximación de los segmentos maxilares para el cierre de la fisura. Sin embargo, la heterogeneidad, el riesgo de sesgo y la baja calidad de los estudios no permite tener conclusiones sólidas.

Abstract This review article aimed to evaluate the evidence on the use of a presurgical orthopedic appliance (POP) in patients with cleft lip and palate. The search was conducted using Medline/PubMed, Scholar Google, Clinical Trails, ProQuest, Scopus, and Web of Science databases. During the search, 7,926 records were found, of which 105 full-text articles were analyzed, and 23 studies included analysis in patients with the use of POP, and their control groups without the use of POP prior to the same type of surgery. The devices most used for POP in the management of LPH were: the passive palate (Hotz palate), the nasolaveolar moulding (NAM), the McNeil device, and finally, the T-traction. The primary outcomes evaluated were: facial aesthetics and nasal appearance; the evaluation of cephalometric measurements, upper airways, nasal fissure width, as well as anatomical references such as inter-canine and intertuberosity distances. In addition, studies that evaluated occlusion and phonation were found. The evidence from this literature suggests that the use of active appliances had a better effect than passive appliances in terms of facial aesthetics and approximation of the maxillary segments for the closure of the fissure. However, the heterogeneity, the risk of bias, and the low quality of the studies do not allow to state firm conclusions.

The Role of Neuroglobin in the Sleep-Wake Cycle.

Neuroglobin (Ngb) is a protein expressed in the central and peripherical nervous systems of the vertebrate. The Ngb has different functions in neurons, including regulating O 2 homeostasis, oxidative stress, and as a neuroprotector after ischemia/hypoxia events. The Ngb is a hemoprotein of the globin family, structurally like myoglobin and hemoglobin. Ngb has higher expression in the cortex, hypothalamus, thalamus, brainstem, and cerebellum in mammals. Interestingly, Ngb immunoreactivity oscillates according to the sleep-wake cycle and decreases after 24 hours of sleep deprivation, suggesting that sleep homeostasis regulates Ngb expression. In addition, Ngb expresses in brain areas related to REM sleep regulation. Therefore, in the present review, we discuss the potential role of the Ngb in the sleep-wake regulation of mammals.

Sistemas universales de protecciones sociales como alternativa a la Cobertura Universal en Salud (CUS) / Universal social protection systems as an alternative to Universal Health Coverage (UHC)

RESUMEN Los organismos financieros internacionales y de Naciones Unidas han promovido la estrategia de la Cobertura Universal en Salud (CUS) como la mejor forma de garantizar el acceso a los servicios de salud. Este artículo debate esta propuesta desde el punto de vista de su eficacia para la garantía del derecho a la salud, además de su funcionalidad para la acumulación de capital en el llamado 'complejo médico industrial y financiero' de la salud, en el marco de la financiarización y el capitalismo cognitivo. El caso colombiano, ejemplo de la aplicación de la CUS en más de veinte años, pone en evidencia los límites de la propuesta. Como alternativa se presenta la opción de los sistemas universales de protección social, apoyado en un debate público abierto y de movilización social local y global por la defensa de la vida, no solo humana, y no reducida al acceso a servicios de salud.

ABSTRACT The international financial organizations and United Nations have promoted the strategy of Universal Health Coverage (UHC) as the best way to guarantee access to health care services. This article discusses this proposal from the point of view of its effectiveness for the guarantee of the right to health as well as its functionality for the accumulation of capital in the so-called 'financial and industrial medical complex' of health, within the framework of financialization and cognitive capitalism. The Colombian case, an example of the application of the CUS in more than twenty years, highlights the limits of the proposal. As an alternative, the option of universal social protection systems is presented, supported by an open public debate and local and global social mobilization for the defense of life, not only human, and not reduced to access to health care services.

Endothelial lesion and complement activation in patients with Scleroderma Renal Crisis / Lesão endotelial e ativação do complemento em pacientes com crise renal esclerodérmica

Abstract In kidney biopsies reviews, scleroderma renal crisis (SRC) is characterized by vascular endothelial injuries, C4d deposits on peritubular vessels, and acute and chronic injuries coexisting on the same biopsy. The clinical signs of thrombotic microangiopathy (TMA) are described in systemic sclerosis (SSc), nevertheless, it has not been related to acute injuries described on kidney biopsies. We report a case of SRC in a patient with scleroderma-dermatomyositis overlap syndrome, which also showed clinical and histopathological data of TMA. On fundus examination, a severe acute hypertensive retinopathy was found. The kidney biopsy showed severe endothelial damage with widening of mucoid cells at the level of the intima, focal concentric proliferation on most small arterioles, and C3, C4d, and IgM deposits along the capillary walls. The genetic study of complement only showed the presence of membrane cofactor protein (MCP) risk haplotypes, without other genetic complement disorders. We understand that in a patient with TMA and SSc, the kidney damage would be fundamentally endothelial and of an acute type; moreover, we would observe clear evidence of complement activation. Once further studies correlate clinical-analytical data with anatomopathological studies, it is likely that we will be forced to redefine the SRC concept, focusing on the relationship between acute endothelial damage and complement activation.

Resumo Nas revisões de biópsias renais, a crise renal esclerodérmica (CRE) é caracterizada por lesões endoteliais vasculares, depósitos de C4d em vasos peritubulares e lesões agudas e crônicas que coexistem na mesma biópsia. Os sinais clínicos de microangiopatia trombótica (MAT) são descritos na esclerose sistêmica (ES); no entanto, não foram relacionados às lesões agudas descritas nas biópsias renais. Relatamos um caso de CRE em um paciente com síndrome de superposição de esclerodermia-dermatomiosite, que também apresentou dados clínicos e histopatológicos de MAT. No exame de fundo do olho, foi encontrada uma retinopatia hipertensiva aguda grave. A biópsia renal mostrou lesão endotelial grave com alargamento das células mucoides ao nível da íntima, proliferação concêntrica focal na maioria das pequenas arteríolas e depósitos de C3, C4d e IgM ao longo das paredes dos capilares. O estudo genético do complemento mostrou apenas a presença de haplótipos de risco da proteína cofator de membrana (PCM), sem outros distúrbios genéticos do complemento. Entendemos que em um paciente com MAT e ES, o dano renal seria fundamentalmente endotelial e do tipo agudo; além disso, observaríamos evidências claras de ativação do complemento. Uma vez que novos estudos correlacionam dados clínico-analíticos com estudos anatomopatológicos, é provável que sejamos forçados a redefinir o conceito de CRE, enfocando a relação entre dano endotelial agudo e ativação do complemento.