Neural correlates of metacognition: Disentangling the brain circuits underlying prospective and retrospective second-order judgments through noninvasive brain stimulation.

Metacognition encompasses the capability to monitor and control one's cognitive processes, with metamemory and metadecision configuring among the most studied higher order functions. Although imaging experiments evaluated the role of disparate brain regions, neural substrates of metacognitive judgments remain undetermined. The aim of this systematic review is to summarize and discuss the available evidence concerning the neural bases of metacognition which has been collected by assessing the effects of noninvasive brain stimulation (NIBS) on human subjects' metacognitive capacities. Based on such literature analysis, our goal is, at first, to verify whether prospective and retrospective second-order judgments are localized within separate brain circuits and, subsequently, to provide compelling clues useful for identifying new targets for future NIBS studies. The search was conducted following the preferred reporting items for systematic reviews and meta-analyses guidelines among PubMed, PsycINFO, PsycARTICLES, PSYNDEX, MEDLINE, and ERIC databases. Overall, 25 studies met the eligibility criteria, yielding a total of 36 experiments employing transcranial magnetic stimulation and 16 ones making use of transcranial electrical stimulation techniques, including transcranial direct current stimulation and transcranial alternating current stimulation. Importantly, we found that both perspective and retrospective judgments about both memory and perceptual decision-making performances depend on the activation of the anterior and lateral portions of the prefrontal cortex, as well as on the activity of more caudal regions such as the premotor cortex and the precuneus. Combining this evidence with results from previous imaging and lesion studies, we advance ventromedial prefrontal cortex as a promising target for future NIBS studies.

Loosening research ethical standards in Brazil? An analysis of bill 6007/2023 / Flexibilizando padrões éticos em pesquisa no Brasil? Uma análise do PL 6007/2023

Bill 6007/2023 proposes significant changes to the National System of Ethics in Clinical Research with Human Beings. The justification is that the debureaucratization of the system would contribute to scientific progress. The article analyzes the main points of the bill, to verify the adequacy between what is proposed and the expected outcomes: normative level; time of analysis; role of the central organ; consent; post-study treatment; placebo; monitoring; and measures resulting from non-compliance. Although the normative level and the proscription of placebo, except when there is no proven effective intervention, offer a protective effect. The other changes either do not contribute to increasing the protection of the participants or effectively loosen moral obligations towards them. The lack of protections and guarantees does not speed up research, as is often argued, but, on the contrary, can cause more risk to participants and lead to discredit and distrust of science.

O Projeto de Lei (PL) 6007/2023 propõe reformulações significativas do Sistema Nacional de Ética em Pesquisa Clínica com Seres Humanos. A justificativa apresentada é que a desburocratização do Sistema contribuiria para o avanço científico. O artigo analisa os aspectos mais significativos do PL, a fim de verificar a adequação entre a proposta e os efeitos esperados: nível normativo; tempo da análise; papel do órgão central; consentimento; tratamento pós-estudo; placebo; monitoramento; e, medidas resultantes de descumprimento. Embora o nível normativo e a vedação do uso de placebo quando da existência de tratamento comprovadamente eficaz ofereçam efeito protetivo, as demais alterações ou não contribuem para aumentar a proteção do participante ou efetivamente flexibilizam obrigações éticas presentes na atual regulamentação. A desproteção dos participantes não acelera pesquisas, como se costuma argumentar, podendo, ao contrário, além de causar mais risco, levar ao descrédito e desconfiança em relação à ciência.

Taking biological rhythms into account: From study design to results reporting.

Numerous physiological and behavioral processes in living organisms exhibit strong rhythmicity and are regulated within a 24-hour cycle. These include locomotor activity and sleep patterns, feeding-fasting cycles, hormone synthesis, body temperature, and even mood and cognitive abilities, all of which are segregated into different phases throughout the day. These processes are governed by the internal timing system, a hierarchical multi-oscillator structure conserved across all organisms, from bacteria to humans. Circadian rhythms have been seen across multiple taxonomic kingdoms. In mammals, a hierarchical internal timing system is comprised of so-called central and periphereal clocks. Although these rhythms are intrinsic, they are under environmental influences, such as seasonal temperature changes, photoperiod variations, and day-night cycles. Recognizing the existence of biological rhythms and their primary external influences is crucial when designing and reporting experiments. Neglecting these physiological variations may result in inconsistent findings and misinterpretations. Thus, here we propose to incorporate biological rhythms into all stages of human and animal research, including experiment design, analysis, and reporting of findings. We also provide a flowchart to support decision-making during the design process, considering biological rhythmicity, along with a checklist outlining key factors that should be considered and documented throughout the study. This comprehensive approach not only benefits the field of chronobiology but also holds value for various other research disciplines. The insights gained from this study have the potential to enhance the validity, reproducibility, and overall quality of scientific investigations, providing valuable guidance for planning, developing, and communicating scientific studies.

[The genesis of informed consent in the context of medical research ethics 1900-1931]. / Die Genese des Informed Consent im Kontext der medizinischen Forschungsethik 1900­1931.

At the turn of the 20th century, the problem of human experimentation and the need to obtain consent became more important among medical practitioners and the general public. The case of the venereologist Albert Neisser, among others, is used to trace the development of research ethics standards in Germany between the end of the 19th century and 1931. The concept of informed consent, which originated in research ethics, is also of central importance in clinical ethics today.

Social control, transparency, accountability, and scientific integrity in medical research / Control social, transparencia, responsabilidad y integridad de la investigación médica / CONTROLE SOCIAL, TRANSPARÊNCIA, INTEIREZA CIENTÍFICA E RESPONSABILIDADE EM PESQUISAS MÉDICAS

The CEP/CONEP System, submitted to social control, is responsible for the ethical approval of research in Brazil to protect research participants. The Informed Consent Form (ICF) is the public document that implements the protection of participants. The paper presents two cases of medical research in the Amazon region on malaria and the use of chloroquine for treating COVID-19. The participants were uninformed in the ICF on relevant aspects of the two studies, with serious health risks. For the sake of increasing transparency and social control, it is proposed the mandatory publication of the ICF in studies supported by public funds, presentation of an objective summary of the study at the beginning of the ICF, publication of central elements of the protocol of clinical trials in open access Brazilian virtual platforms, and promulgation of a dedicated law to improve scientific and ethical integrity in Brazilian medical research.

El Sistema CEP/CONEP es responsable del análisis ético de la investigación en Brasil, sometida al control social, con la misión de proteger a los participantes en la investigación.  El Formulario de Consentimiento Libre e Informado es el documento público que implementa la protección de los participantes. El artículo presenta dos casos de investigación médica en la región amazónica sobre malaria y tratamiento con cloroquina para COVID-19, en que los participantes no fueron informados, en el documento de consentimiento informado, aprobado por el sistema CEP/CONEP, sobre aspectos relevantes de los estudios, con graves riesgos para la salud.  Para aumentar la transparencia y el control social, el artículo propone la divulgación obligatoria del modelo de consentimiento informado en estudios financiados con recursos públicos, la presentación de un resumen objetivo del estudio al inicio del documento de consentimiento, la publicación de elementos centrales del protocolo de ensayos clínicos en plataformas virtuales brasileñas de acceso abierto, y la promulgación de una ley para perfeccionar la integridad científica y ética en la investigación médica brasileña.

O Sistema CEP/CONEP é responsável pela regulação ética de pesquisas no Brasil, comprometido com o controle social, para proteger os direitos dos participantes em pesquisas. O Termo de Consentimento Livre e Esclarecido (TCLE) é o documento público que concretiza a proteção dos participantes. O artigo aborda dois casos de pesquisas médicas na região amazônica, sobre malária e tratamento com cloroquina para COVID-19, em que os participantes foram desinformados no TCLE, aprovado pelo sistema CEP/CONEP, sobre aspectos relevantes dos estudos, com sérios riscos à saúde.  Para ampliar a transparência e  controle social, propõe-se a divulgação obrigatória do modelo de TCLE em pesquisas que usem recursos públicos, apresentação de resumo itemizado no início do TCLE, publicação de elementos centrais do protocolo de ensaios clínicos em plataformas virtuais brasileiras de acesso aberto e promulgação de lei para aprimorar a inteireza científica e ética nas pesquisas médicas brasileiras.

Ethical considerations and clinical trials during a pandemic: A blessing with a burden.

Any healthcare systems during a pandemic undergo tremendous pressure in pursuit of effective treatment to treat and limit the spread of the disease and its implications. Conducting clinical trials to find the potential therapy is the only way to battle the current coronavirus disease-2019 pandemic. The majority of the countries have joined the cause and are carrying out clinical studies in various capacities. As a result, the ethical committees have encountered a sudden inflow of a large number of trial proposals that have placed them under pressure. Although ethical committees play a vital role in protecting patient safety and preserving research integrity, they need to make sure the efficiency and integrity of review are preserved and the standards of review are not relaxed. Thus, the participants' dignity is well guarded while keeping a close check on their safety.

Does the light at the end of the tunnel shine for everyone? The need for early paediatric participation in vaccine trials during infectious pandemics.

While most of the mortality associated with severe acute respiratory syndrome coronavirus 2 has been in elderly populations and adults with significant medical comorbidities, there has been death and morbidity in paediatric populations. As vaccine trial data is released to the public, many people look to the future with hope ; with good vaccine uptake there is the opportunity to reduce the spread of infectious pandemics. Initial vaccine trials were completed with adults and were expanded to include paediatric populations delaying paediatric COVID-19 vaccine initiatives. The exclusion of children from initial vaccine trials during a pandemic is not morally justifiable and fosters distrust with the pharmaceutical and medical industries and inevitably postpones vaccinating children when there is a surplus of available vaccines. The delayed vaccination of children under twelve may have significant public health and economic consequences as there may be ongoing viral transmission in the context of reopening strategies. The safety and efficacy of these candidate vaccines in children should be assessed expeditiously so that distribution to vulnerable paediatric populations is not impacted. Vaccine uptake compliance in the general population is important in establishing herd immunity and ensuring that there is thorough scientific evidence to support vaccination for children is important in establishing community trust.

Living bioethics, clinical ethics committees and children's consent to heart surgery.

This discussion paper considers how seldom recognised theories influence clinical ethics committees. A companion paper examined four major theories in social science: positivism, interpretivism, critical theory and functionalism, which can encourage legalistic ethics theories or practical living bioethics, which aims for theory-practice congruence. This paper develops the legalistic or living bioethics themes by relating the four theories to clinical ethics committee members' reported aims and practices and approaches towards efficiency, power, intimidation, justice, equality and children's interests and rights. Different approaches to framing ethical questions are also considered. Being aware of the four theories' influence can help when seeking to understand and possibly change clinical ethics committee routines. The paper is not a research report but is informed by a recent study in two London paediatric cardiac units. Forty-five practitioners and related experts were interviewed, including eight members of ethics committees, about the work of informing, preparing and supporting families during the extended process of consent to children's elective heart surgery. The mosaic of multidisciplinary teamwork is reported in a series of papers about each profession, including this one on bioethics and law and clinical ethics committees' influence on clinical practice. The qualitative social research was funded by the British Heart Foundation, in order that more may be known about the perioperative views and needs of all concerned. Questions included how disputes can be avoided, how high ethical standards and respectful cooperation between staff and families can be encouraged, and how minors' consent or refusal may be respected, with the support of clinical ethics committees.

Potential of Whole-Body Vibration in Parkinson's Disease: A Systematic Review and Meta-Analysis of Human and Animal Studies.

(1) Background: When the severity of Parkinson's Disease (PD) increases, patients often have difficulties in performing exercises. Whole-Body Vibration (WBV) may be a suitable alternative. This systematic review aims to clarify if WBV shows potential as rehabilitative therapy for PD patients. (2) Methods: We searched several databases for controlled trials investigating the effects of WBV (1) on PD populations and (2) PD neuropathological mechanisms. We included both human and animal studies and performed meta-analyses. (3) Results: The studies on PD populations (14 studies) show an overall significant, but small, effect in favor of WBV (Hedges' g = 0.28), for which the effects on stability (Hedges' g = 0.39) and balance (Hedges' g = 0.30) are the most prominent. The studies on the neuropathological mechanisms (18 studies) show WBV effects on neuroinflammation (Hedges' g = -1.12) and several specific WBV effects on neurotransmitter systems, growth factors, neurogenesis, synaptic plasticity and oxidative stress. (4) Conclusions: The effects of WBV on human PD patients remains inconclusive. Nevertheless, WBV protocols with sufficient duration (≥3 weeks), session frequency (≥3 sessions/week) and vibration frequency (≥20 Hz) show potential as a treatment method, especially for motor function. The potential of WBV for PD patients is confirmed by the effects on the neuropathological mechanisms in mostly non-PD populations. We recommend high-quality future studies on both PD patients and PD mouse models to optimize WBV protocols and to examine the neuropathological mechanisms in PD populations.

The philosopher as partner: an introduction to the scholarship of Robert M. Veatch.

A diverse group of scholars reflect on the scholarship of Robert M. Veatch, the breadth of which is unmatched in modern day bioethics. Essays were written by both philosophers and clinician-philosophers, by contemporaries and mentees. They span the breadth of Bob's work and include analyses of his ideas about death, dying and organ transplantation, human experimentation and research ethics, disability, equality and justice, the doctor-patient relationship, the history of bioethics, as well as his pedagogical approach to teaching bioethics to clinicians across the health care spectrum. Recognition of Bob's influence in the modern field of bioethics and the challenges that persist are clearly identified.

Effects of different forms of practicing a sport on athletes' nerve function / Efeitos de diferentes modos de prática de um esporte no desempenho neural de atletas / Efectos de diferentes modos de práctica de un deporte en el desempeño neural de atletas

ABSTRACT Introduction: Poor reaction time can cause irritability, easier distractions, and interfere with normal activities that require concentration. Objective: To study the impact of simulated hypoxic training on the immune system of female middle- and long-distance runners. Methods: Observation of 50 female middle- and long-distance runners living high and training low (HiHiLo) in regard to changes in CD3+, CD4+, CD8+, NK cells and NKT cells during the process of living low and training high (LoHi). Research indicates: HiHiLo training does have a significant effect on these indicators to enhance the antioxidant capacity of the brain and nervous system. Results: Living high and training low (HiHiLo) can improve the excitability of the nervous system of long-distance endurance athletes and has a very significant impact on the stability of the nervous system. This improves cardiopulmonary function under hypoxic conditions and has a role in promoting the ability to mobilize the skeletal muscles. Conclusions: It has been proved that different forms of exercise can effectively improve the athlete's nervous response. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: Um tempo de reação precário pode levar a irritabilidade, falta de concentração, e interferir em atividades diárias que exigem raciocínio. Objetivo: Estudar o impacto de treinamento hipóxico simulado no sistema imune de corredoras de média e longa distância. Métodos: Observação de 50 corredoras de média e longa distância que vivem em elevadas altitudes e treinam em baixas altitudes (HiHiLo) quanto a mudanças em CD3+, CD4+, CD8+, células NK e NKT, durante o processo de viver em regiões de baixa altitude e treinar em regiões de alta atitude (LoHi). A pesquisa indica que o treino HiHiLo tem um efeito significativo nesses indicadores no que diz respeito ao aumento da capacidade antioxidante do cérebro e do sistema nervoso. Resultados: O treino HiHiLo pode aumentar a excitação do sistema nervoso de atletas de resistência e longa distância, e tem um impacto muito significativo na estabilidade do sistema nervoso. Isso traz melhorias à função cardiopulmonar em condições de hipóxia e age de modo a promover a habilidade de movimentar os músculos esqueléticos. Conclusões: Foi provado que diferentes tipos de exercício podem efetivamente aprimorar a resposta nervosa de atletas. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.

RESUMEN Introducción: Un tiempo de reacción precario puede causar irritabilidad, falta de concentración e interferir en actividades diarias que exigen raciocinio. Objetivo: Estudiar el impacto de entrenamiento hipóxico simulado en el sistema inmune de corredores de media y larga distancia. Métodos: Observación de 50 corredores de media y larga distancia que viven en altitudes elevadas y entrenan en altitudes bajas (HiHiLo) en relación con los cambios en las células CD3+, CD4+, CD8+, NK y NKT durante el proceso de vivir en regiones de baja altitud y entrenar en regiones de alta actitud (LoHi). La investigación indica que el entrenamiento HiHiLo tiene un efecto significativo sobre estos indicadores en lo que respecta al aumento de la capacidad antioxidante del cerebro y del sistema nervioso. Resultados: El entrenamiento HiHiLo puede aumentar la excitación del sistema nervioso de atletas de resistencia y larga distancia y tiene un impacto significativo en la estabilidad del sistema nervioso. Esto aporta mejorías en la función cardiopulmonar en condiciones de hipoxia y actúa favoreciendo en la capacidad de movimiento de los músculos esqueléticos. Conclusiones: Fue probado que diferentes tipos de ejercicio pueden efectivamente mejorar la respuesta nerviosa de atletas. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.

Solidarity and the ethics of exposing others to risk in medical research.

The ethical justifiability of the invitation of others to participate in research and their deliberate exposure to risks of harm is not a common topic in bioethics. If, however, some offers ought not to be made and the corresponding actions ought not to be facilitated, invitations to, and the conduct of, a medical study involving humans needs justification. This paper addresses this issue by linking the search for medical knowledge with solidarity. The argument begins with the observation that scientific research is aimed at general knowledge, which is a necessary condition of the social value of research. The applicability of this knowledge to many makes it potentially a public good; that is, a good that is available freely to all. For knowledge to be a public good, a social decision to make it freely available to all needs to be made. It is proposed that this decision be grounded in society's, and so in both researchers' and potential research participants', commitment to solidarity and its obligations of provision, sharing, support, and loyalty. These obligations imply, among other things, an imperfect obligation to participate in research and the corresponding entitlement of the investigators to invite others to participate in research, and so to expose them to its risks during implementation. This entitlement is exercised in an environment shaped by the standards and protections of research ethics and the relevant institutional arrangements.

A Scientific Method to the Madness of Unit 731's Human Experimentation and Biological Warfare Program.

The Japanese Imperial Army Unit 731's Biological Warfare (BW) research program committed atrocious crimes against humanity in their pursuit of biological weapons development during the Second World War. Due to an American cover-up, the details behind Unit 731's human experimentation were slow to be revealed. The recent literature discloses the gruesome details of the experiments but characterizes the human trials as crude in nature. Further, there is a lack of clarity as to how human trial results were extrapolated for use in real world missions. Through an examination of testimony from the Soviet Union's Khabarovsk War Crime Trials, this paper argues that Unit 731's inoculation and airborne warfare experiments on prisoners of war were scientifically rigorous. The scientific method is used as the basis against which the scientific rigor of the experiments is tested. The paper reveals that the successes and failures of the human trials were extrapolated to BW missions during the Sino-Japanese war. American researchers' expectations of BW data were fulfilled, thus paving the way for an immunity deal. Ethical standards in medicine before WWII were not well established, but wartime medical practices and experimentation reveal the context in which the pursuit of scientific knowledge has no boundaries.

La experimentación humana con plutonio en España / Human experimentation with plutonium in Spain

En 1966 cayeron sobre los cielos de Palomares (Almería) cuatro bombas de hidrógeno; cada una sesenta y ocho veces más potentes que la de Hiroshima. Un bombardero estratégico B-52 colisionó con su avión nodriza. Tres cayeron en tierra y una en el mar. Dos de las que impactaron en tierra diseminaron su carga de plutonio (Pu239) por varios cientos d hectáreas. En el núcleo urbano y alrededores de Palomares fue abandonada la mayor parte del combustible nuclear. Al mismo tiempo, aprovecharon para dejar un laboratorio donde estudiar, a instancia de los Estados Unidos, la interacción del plutonio con las personas y el medioambiente a través del acuerdo secreto, denominado en clave “Proyecto Indalo”. El plutonio llevaba 26 años descubierto y se ignoraban sus consecuencias a largo plazo en el hombre. El objetivo del presente trabajo es el de dar a conocer cuáles fueron las condiciones, motivaciones, objetivos, génesis y desarrollo del Proyecto Indalo, independientemente de sus resultados. Se trata del proyecto de experimentación con humanos más dilatado y desconocido de la ciencia española, también uno de los más singulares, por el secreto que lo ha envuelto, debido a la ausencia de cualquier garantía bioética. Un proyecto creado a partir de una historia oficial ficticia, sustentada en una supuesta descontaminación completa, forjada en dictadura, pero mantenida durante 37 años en democracia. Para ello, contamos con la exposición y análisis de la reciente historiografía aparecida en español, la evidencia contenida en la documentación inédita del Departamento de Energía (DoE) de los EE.UU. y fuentes orales de los afectados (AU)

Festina lente.

The provisions adopted in Italy for clinical trials on medicinal products and medical devices for the epidemiological emergency caused by COVID-19 had an impact also on the functioning of Ethics Committees (ECs). All COVID-19 clinical trials are evaluated preliminarily by the Technical Scientific Committee of the Italian Medicines Agency (AIFA). They are then evaluated by the Clinical Trial Office of the Competent Authority (AIFA) and by the EC of the Lazzaro Spallanzani National Institute for Infectious Diseases. On the basis of this experience, several parties have recommended the adoption of a new structure that envisages the involvement of a single EC for the activation of new studies, similar to the system put in place for studies on COVID-19. Rather than a single EC with jurisdiction over the entire country, we could envisage the accreditation of a certain number of ECs, possibly subdivided by therapeutic fields, with the trials to be evaluated distributed among them, so that each is authorised to issue an opinion that is valid nationally.

The investigation of the influence of thermal plume and breathing on sleeping microenvironment.

Most of humans' lifetime was spent indoor, especially in bedroom. Thus, understanding the characteristics of the sleep microenvironment is a prerequisite for better control and improvement of our sleeping environment. This study investigated the temperature and velocity field above the heads of sleeping people with supine postures, and explored the interactions between the thermal plume and the breathing airflow, where both the thermal manikins and real human subjects were used in our experiment settings. Three different breathing modes were considered in this study, where the non-breathing mode was used to investigate the characteristics of the thermal plume, and the synergy of the mouth and nose breathing mode on the thermal plume was also investigated. The results showed that the thermal plume of a supine posture person was not strong compared to that of a standing or sitting person, and the breathing airflow could influence the development of the thermal plume. Over the head of a sleeping person, the velocity of the thermal plume could be increased by both of the breathing modes, but no significant difference in the velocity and temperature field was found for the two breathing modes. It was also found that pollutants near the bed surface could be brought to the breathing zone with low velocity airflow, but could be blocked by the nasal exhalation jet. The findings in this study could provide theoretical support and guidance to improve the air quality in the breathing zone.

Panorama de pesquisas com seres humanos sobre covid-19 no Brasil / Covid-19 research with humans in Brazil / Panorama de investigaciones con seres humanos sobre covid-19 en Brasil

Resumo A pandemia de covid-19 desafia instituições de pesquisa pela urgência de responder à morbimortalidade provocada pelo vírus. O objetivo deste estudo foi traçar panorama das pesquisas com humanos sobre essa doença no primeiro trimestre de 2020 no Brasil. Dados oficiais de saúde da população e de protocolos de pesquisa sobre a covid-19, distribuídos por estados brasileiros, subsidiaram a análise temporal. Houve crescimento exponencial da incidência do vírus, principalmente nas regiões Norte e Nordeste, apesar da difusão discreta, lenta e assimétrica das pesquisas, concentradas no Sudeste. Os poucos ensaios clínicos entraram na Fase II. A distribuição geográfica de comitês de ética em pesquisa, instituições de ensino superior, investimentos em ciência e tecnologia e unidades assistenciais básicas e hospitalares gera vulnerabilidades estaduais para enfrentar a doença. Acompanhamento longitudinal atento deve ser realizado diante das iniquidades regionais, em defesa dos preceitos bioéticos e da vida humana.

Abstract The Covid-19 pandemic challenges research institutions with the urgent need of responding to the morbidity and mortality caused by the virus. This study aimed to overview studies with humans on this disease in the first three months of 2020, in Brazil. Official data of the population and research protocols on Covid-19, distributed by Brazilian states, supported this temporal analysis. The incidence of the virus has grown exponentially, especially in the North and Northeast regions. Despite the discrete, slow, and asymmetric diffusion of studies, they are concentrated in the Southeast, and few clinical trials have entered Phase II. The geographical distribution of research ethics committees, higher education institutions, investments in science and technology, health centers and hospitals generate state vulnerabilities when addressing the disease. Close longitudinal follow-up should be carried out in the face of regional inequities, to defend bioethical principles and human life.

Resumen La pandemia de covid-19 desafía a las instituciones de investigación en la urgencia de responder a la morbilidad y mortalidad causadas por el virus. El objetivo de este estudio fue esbozar una visión general de la investigación con humanos sobre esta enfermedad en el primer trimestre de 2020 en Brasil. Los datos oficiales sobre salud, población y protocolos de investigación sobre covid-19 distribuidos por la unidad federativa brasileña respaldaron un análisis temporal. Hubo un crecimiento exponencial en la incidencia de covid-19, especialmente en las regiones del Norte y Nordeste, a pesar de la diseminación discreta, lenta y asimétrica de la investigación, concentrada en el Sudeste. Los pocos ensayos clínicos estaban en Fase II. La distribución geográfica de los comités de ética de la investigación, las instituciones de educación superior, las inversiones en ciencia y tecnología y las unidades de atención desde la red básica hasta el hospital identificaron los potenciales y vulnerabilidades estatales para hacer frente a la enfermedad. Se debe llevar a cabo un monitoreo longitudinal atento ante las desigualdades regionales, en defensa de los preceptos bioéticos y de la vida humana.

[Georg Schaltenbrand (1897-1979) and his research without moral boundaries on multiple sclerosis]. / Georg Schaltenbrand (1897­1979) und seine "entgrenzte Forschung" zur Multiplen Sklerose.

In 1953 the prominent German neurologist Georg(es) Schaltenbrand became president of the German Neurological Society (DGN) and in 1967 honorary president. Less well known is the fact that from 1933 to 1936 he was member of the "Stahlhelm" and the Storm Troopers (SA). In 1937 he joined the National Socialist German Workers' Party (NSDAP) and other Nazi organizations. For the last three decades Schaltenbrand's name has primarily been associated with human experiments performed in 1940. His objective was to prove the viral etiology of multiple sclerosis (MS). To that end he injected cerebrospinal fluid (CSF) drawn from allegedly infected monkeys and MS patients into severely handicapped patients from the psychiatric asylum Werneck near Schweinfurt as well as into severely ill patients from the University Hospital of Würzburg without their consent. Weeks later he withdrew CSF samples from the recipients, sometimes repeatedly to control parameters of inflammation. Although not all details of his test series can be clarified, there is no doubt that he violated prevailing laws and ethical standards. According to the present state of knowledge, he was the only German professor of neurology during the Nazi era who performed such experiments on humans in terms of "research without moral boundaries". He later justified his actions by arguing that he had intended to exert a positive effect on the mentally ill. Judicial investigations ended in 1948 without an indictment. Long after his death, in 1994 the "Schaltenbrand experiments" became known to a wider public and three years later the Medical Faculty of Würzburg condemned the unethical research and distanced itself from its former member. Today, Schaltenbrand's study is assessed as an unacceptable form of research on particularly vulnerable patients for the benefit of third parties. As a result, ethical norms formulated in the 1930s were reinforced by international guidelines, e.g. the Declaration of Helsinki drafted by the World Medical Association.

Combinations of Epidemiological and Experimental Studies in Air Pollution Research: A Narrative Review.

Scientific literature is evolving to include more systematic reviews that encompass epidemiological and experimental papers so that the whole picture can be examined. The aim of this narrative review is to bridge that gap by combining epidemiological and experimental studies based on the same setting: Examples of Bitterfeld, Utah Valley, Beijing Olympic Games, and Viadana. This review looks at four examples that incorporate multiple epidemiological and experimental papers about air pollution exposure and health effects. The Bitterfeld (spatial) and Utah Valley (temporal) examples showed that particle composition causes the biggest difference in lung injury. In Beijing, a temporal difference of before/after and during the Olympics showed that traffic and industry air pollution-related health effects like lung cancer and cardiovascular disease could be reduced by improvement of air quality. The Viadana example showed a spatial difference in respiratory injury caused by particle composition and interactions with genotoxicity. Combining experimental and epidemiological methods gives a more in-depth look into the whole picture of exposure and health effects. Our review exemplifies the strength of this strategy and encourages further use of it.