Protein Science Meets Artificial Intelligence: A Systematic Review and a Biochemical Meta-Analysis of an Inter-Field.

Proteins are some of the most fascinating and challenging molecules in the universe, and they pose a big challenge for artificial intelligence. The implementation of machine learning/AI in protein science gives rise to a world of knowledge adventures in the workhorse of the cell and proteome homeostasis, which are essential for making life possible. This opens up epistemic horizons thanks to a coupling of human tacit-explicit knowledge with machine learning power, the benefits of which are already tangible, such as important advances in protein structure prediction. Moreover, the driving force behind the protein processes of self-organization, adjustment, and fitness requires a space corresponding to gigabytes of life data in its order of magnitude. There are many tasks such as novel protein design, protein folding pathways, and synthetic metabolic routes, as well as protein-aggregation mechanisms, pathogenesis of protein misfolding and disease, and proteostasis networks that are currently unexplored or unrevealed. In this systematic review and biochemical meta-analysis, we aim to contribute to bridging the gap between what we call binomial artificial intelligence (AI) and protein science (PS), a growing research enterprise with exciting and promising biotechnological and biomedical applications. We undertake our task by exploring "the state of the art" in AI and machine learning (ML) applications to protein science in the scientific literature to address some critical research questions in this domain, including What kind of tasks are already explored by ML approaches to protein sciences? What are the most common ML algorithms and databases used? What is the situational diagnostic of the AI-PS inter-field? What do ML processing steps have in common? We also formulate novel questions such as Is it possible to discover what the rules of protein evolution are with the binomial AI-PS? How do protein folding pathways evolve? What are the rules that dictate the folds? What are the minimal nuclear protein structures? How do protein aggregates form and why do they exhibit different toxicities? What are the structural properties of amyloid proteins? How can we design an effective proteostasis network to deal with misfolded proteins? We are a cross-functional group of scientists from several academic disciplines, and we have conducted the systematic review using a variant of the PICO and PRISMA approaches. The search was carried out in four databases (PubMed, Bireme, OVID, and EBSCO Web of Science), resulting in 144 research articles. After three rounds of quality screening, 93 articles were finally selected for further analysis. A summary of our findings is as follows: regarding AI applications, there are mainly four types: 1) genomics, 2) protein structure and function, 3) protein design and evolution, and 4) drug design. In terms of the ML algorithms and databases used, supervised learning was the most common approach (85%). As for the databases used for the ML models, PDB and UniprotKB/Swissprot were the most common ones (21 and 8%, respectively). Moreover, we identified that approximately 63% of the articles organized their results into three steps, which we labeled pre-process, process, and post-process. A few studies combined data from several databases or created their own databases after the pre-process. Our main finding is that, as of today, there are no research road maps serving as guides to address gaps in our knowledge of the AI-PS binomial. All research efforts to collect, integrate multidimensional data features, and then analyze and validate them are, so far, uncoordinated and scattered throughout the scientific literature without a clear epistemic goal or connection between the studies. Therefore, our main contribution to the scientific literature is to offer a road map to help solve problems in drug design, protein structures, design, and function prediction while also presenting the "state of the art" on research in the AI-PS binomial until February 2021. Thus, we pave the way toward future advances in the synthetic redesign of novel proteins and protein networks and artificial metabolic pathways, learning lessons from nature for the welfare of humankind. Many of the novel proteins and metabolic pathways are currently non-existent in nature, nor are they used in the chemical industry or biomedical field.

Appealing to Tacit Knowledge and Axiology to Enhance Medical Practice in the COVID-19 Pandemic: A Systematic Review and Hermeneutic Bioethical Analysis.

Background: The pressure of coronavirus disease 2019 (COVID-19) pandemic, epidemiological and demographic changes, personnel-patient relationship in healthcare, and the development of biotechnologies do not go unnoticed by the healthcare professional. Changes are so wide and at a high rate that guidelines and mere scientific knowledge, which are represented by evidence-based medicine, are not sufficient to lead actions, thus the experiential aspects in the configuration of an ethos present as a fundamental part of the resources to deal with critical scenarios, such as a pandemic. In this regard, the recognition of tacit knowledge as a way of teaching and learning skills related to ethical aspects such as principles, virtues, and values, revealed as a fundamental part of the clinical field. The challenge is to strengthen binomial evidence-based medicine and values-based in order to achieve excellence in the health care of the patients and the well-being of the clinical personnel. Method: A 2-fold analysis was conducted taking pediatric endocrinology as an example. First, a systematic review was carried out in electronic databases BIREME, PubMed, and PhilPapers following PEO and PRISMA approaches. A total of 132 articles were garnered. After reading their title and abstract, 30 articles were obtained. Quantitative information was arranged in an Excel database according to three themes: ethics, axiology, and tacit knowledge. A quality criterion that meets our research question was assigned to each article and those which had a quality criterion of 3 (9) were taken to carry out the hermeneutic bioethical analysis, which consisted of three stages, namely naïve reading, codification, and interpretation. The results were analyzed in Atlas.ti. to elucidate the relations between the three main themes in accordance with the objective. Results: Although there was no difference in the frequency of tacit knowledge skills, including cognitive, social, and technical, for medical practice, there is an intrinsic relationship between epistemic and ethical values with cognitive skills, this means that professionals who practice honesty, authenticity and self-control are capable of seeing patients as persons and thus respect their dignity. This suggested that there is a strong partnership between evidence-based medicine and value-based medicine, which reinforced this binomial as the two feet on which medical practice decisions rested. With regard to tacit knowledge in terms of the context of the COVID-19 pandemic, the challenges refer to (1) adapting and learning a new way of establishing trust with the patient and (2) how to capitalize on the new knowledge that new experiences have posed. Discussion: The analysis of ethical-tacit knowledge in medicine is a recent phenomenon and is in full development. Although no references were found that dealt with any of the main topics in pediatric endocrinology, there is an interest in pediatrics to explore and discuss educational strategies in ethics related to its tacit dimension as a vector of enhancement in the clinical practice. Educational strategies ought to take into consideration the development of skills that promote reflection and discussion of experiences, even more vigorously in the context of the COVID-19 pandemic.

Decision-Making at End-of-Life for Children With Cancer: A Systematic Review and Meta-Bioethical Analysis.

BACKGROUND: Evidence shows that medical education includes a variety of basic and clinical skills. Ethical and human values are not typically considered in medical school curricula, and this is evident in medical practice in certain scenarios such as decision-making at pediatric cancer patients' end of life. METHODS: This study explores a bioethical approach to address complex decision-making at the end of life in children and adolescents with cancer. We are a cross-functional group of scientists from several academic disciplines who conducted a systematic review of the literature using our newly developed meta-bioethical analysis and synthesis of findings. The search was carried out in five databases, resulting in 10 research papers. Following quality screening, seven articles were ultimately selected for further analysis. RESULTS: Our focus is on the state of the art to better understand the bioethical deliberation at the end of life in pediatric oncology. Here, we report a systematic review that includes (i) classification of the screened articles by the type of decision-making they use, ii) the system values that are at the core of the decision-making at the end of life, and iii) bioethical and ethical discernment queries. We conclude with a discussion regarding the best practices of ethical discernment and decision-making at the end of life.This study highlights the need to develop more research to better understand the influence and origin of these multidimensional factors determining critical decisions that define the quality of life of patients in a highly sensitive moment. CONCLUSION: We conclude that personal aspects of the physician define their actions more than knowledge or organized structure. It is thus necessary that pediatric oncologists receive ethics and humanistic education.

What can we learn from ß-cell failure biomarker application in diabetes in childhood? A systematic review.

BACKGROUND: The prevalence of diabetes as a catastrophic disease in childhood is growing in the world. The search for novel biomarkers of ß-cell failure has been an elusive task because it requires several clinical and biochemical measurements in order to integrate the risk of metabolic syndrome. AIM: To determine which biomarkers are currently used to identify ß-cell failure among children and adolescents with high risk factors for diabetes mellitus. METHODS: This systematic review was carried out using a modified version of the PICO protocol (Participants/Intervention/Comparison/Outcome). Once our research question was established, terms were individually researched on three different databases (PubMed, BIREME and Web of Science). The total articles obtained underwent a selection process from which the 78 most relevant articles were retrieved to undergo further analysis. They were assessed individually according to quality criteria. RESULTS: First, we made the classification of the ß-cell-failure biomarkers by the target tissue and the evolution of the disease, separating the biomarkers in relation to the types of diabetes. Second, we demonstrated that most biomarkers currently used as early signs of ß-cell failure are those that concern local or systemic inflammation processes and oxidative stress as well as those related to endothelial dysfunction processes. Third, we explored the novelties of diabetes as a protein conformational disease and the novel biomarker called real human islet amyloid polypeptide amyloid oligomers. Finally, we ended with a discussion about the best practice of validation and individual control of using different types of biomarkers in type 1 and type 2 diabetes in order to assess the role they play in the progress of diabetes in childhood. CONCLUSION: This review makes widely evident that most biomarkers currently used as early signs of ß-cell failure are those that concern local or systemic inflammation processes and oxidative stress as well as those related to endothelial dysfunction processes. Landing in the clinical practice we propose that real human islet amyloid polypeptide amyloid oligomers is good for identifying patients with ß-cell damage and potentially could substitute many biomarkers.

Bibliotherapy as a Non-pharmaceutical Intervention to Enhance Mental Health in Response to the COVID-19 Pandemic: A Mixed-Methods Systematic Review and Bioethical Meta-Analysis.

Background: A non-pharmaceutical treatment offered as psychological support is bibliotherapy, which can be described as the process of reading, reflecting, and discussing literature to further a cognitive shift. The coronavirus disease 2019 (COVID-19) pandemic demands a response to prevent a peak in the prevalence of mental health problems and to avoid the collapse of mental health services, which are scarce and inaccessible due to the pandemic. Thus, this study aimed to review articles on the effectiveness of bibliotherapy on different mental health problems. Methods: A systematic review was conducted to examine relevant studies that assess the effectiveness of bibliotherapy in different clinical settings as a treatment capable of enhancing a sense of purpose and its surrounding values. To achieve this, a systematic review, including a bioethical meta-analysis, was performed. A variant of the PICO (Participants, Intervention, Comparison, and Outcome) model was used for the search strategy, and the systematic review was conducted in three databases: PubMed, Bireme, and OVID. Inclusion criteria were relevant studies that included the keywords, excluding documents with irrelevant topics, studies on subjects 15 years or younger, and in languages besides Spanish or English. Starting with 707 studies, after three rounds of different quality criteria, 13 articles were selected for analysis, including a hermeneutic analysis, which was followed by a fourth and final recovery round assessing bibliotherapy articles concerning healthcare workers. Results: Our findings showed that through bibliotherapy, patients developed several capacities, including the re-signification of their own activities through a new outlook of their moral horizon. There are no research road maps serving as guides to conduct research on the use of bibliotherapy to enhance mental health. Additionally, values such as autonomy and justice were closely linked with positive results in bibliotherapy. This implies that bibliotherapy has the potential to have a positive impact in different settings. Conclusions: Our contribution is to offer a road map that presents state-of-the-art bibliotherapy research, which will assist institutions and healthcare professionals to plan clinical and specific interventions with positive outcomes.

Towards medicine of excellence in Mexico: the "Código Infarto" protocol, a view from the perspective of translational bioethics.

INTRODUCTION: Mexico is the country with the highest mortality due to ST-elevation acute myocardial infarction (STEMI), and the IMSS has therefore developed the protocol of care for emergency departments called Código Infarto (Infarction Code). In this article, aspects of translational medicine are discussed with a bioethical and comprehensive perspective. OBJECTIVE: To analyze the Código Infarto protocol from the perspective of translational bioethics. METHOD: A problem-centered approach was carried out through reflective equilibrium (or Rawls' method), as well as by applying the integral method for ethical discernment. RESULTS: The protocol of care for emergency services Código Infarto is governed by evidence-based medicine and value-based medicine; it is guided by a principle of integrity that considers six dimensions of quality for the care of patients with STEMI. CONCLUSION: The protocol overcomes some adverse social determinants that affect STEMI medical care, reduces mortality and global economic disease burden, and develops medicine of excellence with high social reach.

INTRODUCCIÓN: México es el país con mayor mortalidad por infarto agudo de miocardio con elevación del segmento ST (IAM CEST), por lo que el Instituto Mexicano del Seguro Social desarrolló el protocolo de atención para los servicios de urgencias denominado Código Infarto. En este artículo se discuten aspectos de la medicina traslacional con una perspectiva bioética e integral. OBJETIVO: Analizar el protocolo Código Infarto desde la perspectiva de la bioética traslacional. MÉTODO: Se realizó una aproximación centrada en el problema a través del equilibrio reflexivo, así como la aplicación del método integral para el discernimiento ético. RESULTADOS: El protocolo de atención para los servicios de urgencias Código Infarto se rige por la medicina basada en la evidencia y la medicina basada en valores; se orienta por el principio de integridad que considera las seis dimensiones de la calidad para la atención de pacientes con IAM CEST. CONCLUSIÓN: El protocolo supera algunos determinantes sociales adversos que afectan la atención médica del IAM CEST, disminuye la mortalidad, la carga económica global de la enfermedad y desarrolla una medicina de excelencia de alto alcance social.

Hacia una medicina de excelencia en México: el protocolo Código Infarto, una visión desde la bioética traslacional / Towards medicine of excellence in Mexico: the "Código Infarto" protocol, a view from the perspective of translational bioethics

Resumen Introducción: México es el país con mayor mortalidad por infarto agudo de miocardio con elevación del segmento ST (IAM CEST), por lo que el Instituto Mexicano del Seguro Social desarrolló el protocolo de atención para los servicios de urgencias denominado Código Infarto. En este artículo se discuten aspectos de la medicina traslacional con una perspectiva bioética e integral. Objetivo: Analizar el protocolo Código Infarto desde la perspectiva de la bioética traslacional. Método: Se realizó una aproximación centrada en el problema a través del equilibrio reflexivo, así como la aplicación del método integral para el discernimiento ético. Resultados: El protocolo de atención para los servicios de urgencias Código Infarto se rige por la medicina basada en la evidencia y la medicina basada en valores; se orienta por el principio de integridad que considera las seis dimensiones de la calidad para la atención de pacientes con IAM CEST. Conclusión: El protocolo supera algunos determinantes sociales adversos que afectan la atención médica del IAM CEST, disminuye la mortalidad, la carga económica global de la enfermedad y desarrolla una medicina de excelencia de alto alcance social.

Abstract Introduction: Mexico is the country with the highest mortality due to ST-elevation acute myocardial infarction (STEMI), and the IMSS has therefore developed the protocol of care for emergency departments called Código Infarto (Infarction Code). In this article, aspects of translational medicine are discussed with a bioethical and comprehensive perspective. Objective: To analyze the Código Infarto protocol from the perspective of translational bioethics. Method: A problem-centered approach was carried out through reflective equilibrium (or Rawls' method), as well as by applying the integral method for ethical discernment. Results: The protocol of care for emergency services Código Infarto is governed by evidence-based medicine and value-based medicine; it is guided by a principle of integrity that considers six dimensions of quality for the care of patients with STEMI. Conclusion: The protocol overcomes some adverse social determinants that affect STEMI medical care, reduces mortality and global economic disease burden, and develops medicine of excellence with high social reach.

Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early ß-cell damage in obesity and diabetes.

BACKGROUND AND AIMS: This is the first time that obesity and diabetes mellitus (DM) as protein conformational diseases (PCD) are reported in children and they are typically diagnosed too late, when ß-cell damage is evident. Here we wanted to investigate the level of naturally-ocurring or real (not synthetic) oligomeric aggregates of the human islet amyloid polypeptide (hIAPP) that we called RIAO in sera of pediatric patients with obesity and diabetes. We aimed to reduce the gap between basic biomedical research, clinical practice-health decision making and to explore whether RIAO work as a potential biomarker of early ß-cell damage. MATERIALS AND METHODS: We performed a multicentric collaborative, cross-sectional, analytical, ambispective and blinded study; the RIAO from pretreated samples (PTS) of sera of 146 pediatric patients with obesity or DM and 16 healthy children, were isolated, measured by sound indirect ELISA with novel anti-hIAPP cytotoxic oligomers polyclonal antibody (MEX1). We carried out morphological and functional studied and cluster-clinical data driven analysis. RESULTS: We demonstrated by western blot, Transmission Electron Microscopy and cell viability experiments that RIAO circulate in the blood and can be measured by ELISA; are elevated in serum of childhood obesity and diabetes; are neurotoxics and works as biomarkers of early ß-cell failure. We explored the range of evidence-based medicine clusters that included the RIAO level, which allowed us to classify and stratify the obesity patients with high cardiometabolic risk. CONCLUSIONS: RIAO level increases as the number of complications rises; RIAOs > 3.35 µg/ml is a predictor of changes in the current indicators of ß-cell damage. We proposed a novel physio-pathological pathway and shows that PCD affect not only elderly patients but also children. Here we reduced the gap between basic biomedical research, clinical practice and health decision making.

Unpacking the aggregation-oligomerization-fibrillization process of naturally-occurring hIAPP amyloid oligomers isolated directly from sera of children with obesity or diabetes mellitus.

The formation of amyloid oligomers and fibrils of the human islet amyloid polypeptide (hIAPP) has been linked with ß- cell failure and death which causes the onset, progression, and comorbidities of diabetes. We begin to unpack the aggregation-oligomerization-fibrillization process of these oligomers taken from sera of pediatric patients. The naturally occurring or real hIAPP (not synthetic) amyloid oligomers (RIAO) were successfully isolated, we demonstrated the presence of homo (dodecamers, hexamers, and trimers) and hetero-RIAO, as well as several biophysical characterizations which allow us to learn from the real phenomenon taking place. We found that the aggregation/oligomerization process is active in the sera and showed that it happens very fast. The RIAO can form fibers and react with anti-hIAPP and anti-amyloid oligomers antibodies. Our results opens the epistemic horizon and reveal real differences between the four groups (Controls vs obesity, T1DM or T2DM) accelerating the process of understanding and discovering novel and more efficient prevention, diagnostic, transmission and therapeutic pathways.

El horizonte de la atención médica en pediatría: ¿qué hacer en el caso de niños que se encuentran en situación de abandono, conflicto, daño o peligro, aunado a una enfermedad grave? / The horizon of medical attention in pediatrics: what to do in the case of children who are in abandonment, conflict, harm or danger situations in combination with a severe disease?

Resumen: Introducción: Las leyes refieren que los menores no tienen la capacidad para dar su consentimiento informado para su propia atención médica; sin embargo, hay condiciones especiales en las que se les permite determinar lo referente a su salud. Cuanto mayores sean las limitaciones de juicio y experiencia en los menores, menos peso se otorga a los valores y objetivos que expresan; cuanto más adversas sean las consecuencias, se deberá exigir un nivel más alto de autoridad para decidir en nombre del menor, dejando al Estado la capacidad de garantizar el bienestar del menor. Caso clínico: Niña de 12 años con diagnóstico de leucemia linfoblástica aguda LI, con antecedentes familiares y sociales precarios; evolución entorpecida por el desapego al tratamiento y sus condiciones insalubres y pobreza extrema. Ambos padres fallecieron al poco tiempo de iniciar su tratamiento, quedando ella al cuidado de su medio hermana mayor de edad. Se exponen la labor y el dilema ético del oncólogo tratante y del personal del Hospital Infantil de México Federico Gómez en la creación de redes de apoyo con el objetivo de priorizar el bienestar de la menor, sin dar lugar al quebrantamiento y la desintegración familiar, consiguiendo exitosamente su recuperación. Conclusiones: El caso fue sometido al Comité de Bioética Hospitalaria. Se formaron redes de apoyo interinstitucionales para intervenir en la dinámica familiar, resolviendo los requerimientos de la menor, y se consiguió con éxito superar la enfermedad.

Abstract: Background: Laws refer that minors do not have the capability to give informed consent for their own medical attention. However, there are special conditions in which they are allowed to decide about their health. The greater the judgement and experience limitations in minors, the less weight is given to the values and objectives they express. Also, the more adverse consequences might be, the higher the level of authority that is demanded to decide on behalf of the minor, thus granting the State the capability to guarantee the well-being of the minor. Case report: 12-year-old female patient with a diagnosis of acute lymphoblastic leukemia, with precarious social and family background; evolution of the disease obstructed by the disregard of the treatment due to her unsanitary and extreme poverty conditions. Both of her parents died soon after the start of the treatment and she was kept under the care of her half-sister of legal age. The work and the ethical dilemma of the pediatrician and the staff of Hospital Infantil de México Federico Gómez are exposed within the building of support networks with the objective of prioritizing the minor's well-being, without allowing family break-up or disintegration, thus succeeding in her recovery. Conclusions: The case was submitted to the Hospital Bioethics Committee. Inter-institutional support networks were built in order to improve dynamics of the family, thus solving the needs of the minor. Despite the misfortune of the situation, the disease was successfully overcome.

[The horizon of medical attention in pediatrics: what to do in the case of children who are in abandonment, conflict, harm or danger situations in combination with a severe disease?] / El horizonte de la atención médica en pediatría: ¿qué hacer en el caso de niños que se encuentran en situación de abandono, conflicto, daño o peligro, aunado a una enfermedad grave?

Background: Laws refer that minors do not have the capability to give informed consent for their own medical attention. However, there are special conditions in which they are allowed to decide about their health. The greater the judgement and experience limitations in minors, the less weight is given to the values and objectives they express. Also, the more adverse consequences might be, the higher the level of authority that is demanded to decide on behalf of the minor, thus granting the State the capability to guarantee the well-being of the minor. Case report: 12-year-old female patient with a diagnosis of acute lymphoblastic leukemia, with precarious social and family background; evolution of the disease obstructed by the disregard of the treatment due to her unsanitary and extreme poverty conditions. Both of her parents died soon after the start of the treatment and she was kept under the care of her half-sister of legal age. The work and the ethical dilemma of the pediatrician and the staff of Hospital Infantil de México Federico Gómez are exposed within the building of support -networks with the objective of prioritizing the minor's well-being, without allowing family break-up or disintegration, thus succeeding in her recovery. Conclusions: The case was submitted to the Hospital Bioethics Committee. Inter-institutional support networks were built in order to improve dynamics of the family, thus solving the needs of the minor. Despite the misfortune of the situation, the disease was successfully overcome.

Introducción: Las leyes refieren que los menores no tienen la capacidad para dar su consentimiento informado para su propia atención médica; sin embargo, hay condiciones especiales en las que se les permite determinar lo referente a su salud. Cuanto mayores sean las limitaciones de juicio y experiencia en los menores, menos peso se otorga a los valores y objetivos que expresan; cuanto más adversas sean las consecuencias, se deberá exigir un nivel más alto de autoridad para decidir en nombre del menor, dejando al Estado la capacidad de garantizar el bienestar del menor. Caso clínico: Niña de 12 años con diagnóstico de leucemia linfoblástica aguda LI, con antecedentes familiares y sociales precarios; evolución entorpecida por el desapego al tratamiento y sus condiciones insalubres y pobreza extrema. Ambos padres fallecieron al poco tiempo de iniciar su tratamiento, quedando ella al cuidado de su medio hermana mayor de edad. Se exponen la labor y el dilema ético del oncólogo tratante y del personal del Hospital Infantil de México Federico Gómez en la creación de redes de apoyo con el objetivo de priorizar el bienestar de la menor, sin dar lugar al quebrantamiento y la desintegración familiar, consiguiendo exitosamente su recuperación. Conclusiones: El caso fue sometido al Comité de Bioética Hospitalaria. Se formaron redes de apoyo interinstitucionales para intervenir en la dinámica familiar, resolviendo los requerimientos de la menor, y se consiguió con éxito superar la enfermedad.

Diabetes Drug Discovery: hIAPP1-37 Polymorphic Amyloid Structures as Novel Therapeutic Targets.

Human islet amyloid peptide (hIAPP1-37) aggregation is an early step in Diabetes Mellitus. We aimed to evaluate a family of pharmaco-chaperones to act as modulators that provide dynamic interventions and the multi-target capacity (native state, cytotoxic oligomers, protofilaments and fibrils of hIAPP1-37) required to meet the treatment challenges of diabetes. We used a cross-functional approach that combines in silico and in vitro biochemical and biophysical methods to study the hIAPP1-37 aggregation-oligomerization process as to reveal novel potential anti-diabetic drugs. The family of pharmaco-chaperones are modulators of the oligomerization and fibre formation of hIAPP1-37. When they interact with the amino acid in the amyloid-like steric zipper zone, they inhibit and/or delay the aggregation-oligomerization pathway by binding and stabilizing several amyloid structures of hIAPP1-37. Moreover, they can protect cerebellar granule cells (CGC) from the cytotoxicity produced by the hIAPP1-37 oligomers. The modulation of proteostasis by the family of pharmaco-chaperones A-F is a promising potential approach to limit the onset and progression of diabetes and its comorbidities.

Amyloid Biomarkers in Conformational Diseases at Face Value: A Systematic Review.

Conformational diseases represent a new aspect of proteomic medicine where diagnostic and therapeutic paradigms are evolving. In this context, the early biomarkers for target cell failure (neurons, ß-cells, etc.) represent a challenge to translational medicine and play a multidimensional role as biomarkers and potential therapeutic targets. This systematic review, which follows the PICO and Prisma methods, analyses this new-fangled multidimensionality, its strengths and limitations, and presents the future possibilities it opens up. The nuclear diagnosis methods are immunoassays: ELISA, immunodot, western blot, etc., while the therapeutic approach is focused on pharmaco- and molecular chaperones.

Novel insight into streptozotocin-induced diabetic rats from the protein misfolding perspective.

Protein folding is a process of self-assembly defined by the sequence of the amino acids of the protein involved. Additionally, proteins tend to unfold, misfold and aggregate due to both intrinsic and extrinsic causes. Human islet amyloid polypeptide (hIAPP) aggregation is an early step in diabetes mellitus. However, the aggregation of rat IAPP (rIAPP) remains an open question. Adult female Sprague-Dawley rats weighing 150-250 g were divided into two groups. The experimental group (streptozotocin [STZ]) (n = 21) received an intraperitoneal injection of a single dose of 40 mg/kg STZ. We used the mouse anti-IAPP antibody and the anti-amyloid oligomer antibody to study the temporal course of rIAPP oligomerization during STZ-induced diabetes using a wide array of methods, strategies and ideas derived from biochemistry, cell biology, and proteomic medicine. Here, we demonstrated the tendency of rIAPP to aggregate and trigger cooperative processes of self-association or hetero-assembly that lead to the formation of amyloid oligomers (trimers and hexamers). Our results are the first to demonstrate the role of rIAPP amyloid oligomers in the development of STZ-induced diabetes in rats. The IAPP amyloid oligomers are biomarkers of the onset and progression of diabetes and could play a role as therapeutic targets.

Today´s medical self and the other: Challenges and evolving solutions for enhanced humanization and quality of care.

BACKGROUND: Recent scientific developments, along with growing awareness of cultural and social diversity, have led to a continuously growing range of available treatment options; however, such developments occasionally lead to an undesirable imbalance between science, technology and humanism in clinical practice. This study explores the understanding and practice of values and value clusters in real-life clinical settings, as well as their role in the humanization of medicine and its institutions. The research focuses on the values of clinical practice as a means of finding ways to enhance the pairing of Evidence-Based Medicine (EBM) with Values-based Medicine (VBM) in daily practice. METHODS AND FINDINGS: The views and representations of clinical practice in 15 pre-CME and 15 post-CME interviews were obtained from a random sampling of active healthcare professionals. These views were then identified and qualitatively analyzed using a three-step hermeneutical approach. A clinical values space was identified in which ethical and epistemic values emerge, grow and develop within the biomedical, ethical, and socio-economic dimensions of everyday health care. Three main values-as well as the dynamic clusters and networks that they tend to form-were recognized: healthcare personnel-patient relationships, empathy, and respect. An examination of the interviews suggested that an adequate conceptualization of values leads to the formation of a wider axiological system. The role of clinician-as-consociate emerged as an ideal for achieving medical excellence. CONCLUSIONS: By showing the intricate clusters and networks into which values are interwoven, our analysis suggests methods for fine-tuning educational interventions so they can lead to demonstrable changes in attitudes and practices.

[Teenager]. / Adolescente.

The bone mass peak is the maximum bone quantity to be achieved through bone modeling. About 40% of the total bone mass is achieved at puberty; therefore, adolescence is critical on the skeletal development. This paper is about the transfunctional analysis of nutrition, mineral metabolism, endocrinology and life style in adolescence. Core factors to achieve the maximum potential of bone modeling through puberty and prevent osteoporosis from a pediatric stage are addressed.

Reexamining Healthcare Justice in the Light of Empirical Data.

This article discusses the notion of justice from a capabilities approach. We undertake an empirical analysis of the concepts of justice held by healthcare personnel, gleaned from a qualitative analysis of interviews on the subject of ethical dilemmas in everyday practice. The article states that Justice undoubtedly presents a work in progress, which implicates the link between justice as capability and human dignity. We empirically found a contrast between the views of justice based on the patient's own perceptions and those based on the perceptions of healthcare personnel. We establish the kind of actions, communication skills and justice required to build a stronger relationship between patients and healthcare professionals, which would improve prognosis, treatment efficiency and therapeutic adhesion.

Drug Development in Conformational Diseases: A Novel Family of Chemical Chaperones that Bind and Stabilise Several Polymorphic Amyloid Structures.

The increasing prevalence of conformational diseases, including Alzheimer's disease, type 2 Diabetes Mellitus and Cancer, poses a global challenge at many different levels. It has devastating effects on the sufferers as well as a tremendous economic impact on families and the health system. In this work, we apply a cross-functional approach that combines ideas, concepts and technologies from several disciplines in order to study, in silico and in vitro, the role of a novel chemical chaperones family (NCHCHF) in processes of protein aggregation in conformational diseases. Given that Serum Albumin (SA) is the most abundant protein in the blood of mammals, and Bovine Serum Albumin (BSA) is an off-the-shelf protein available in most labs around the world, we compared the ligandability of BSA:NCHCHF with the interaction sites in the Human Islet Amyloid Polypeptide (hIAPP):NCHCHF, and in the amyloid pharmacophore fragments (Aß17-42 and Aß16-21):NCHCHF. We posit that the merging of this interaction sites is a meta-structure of pharmacophore which allows the development of chaperones that can prevent protein aggregation at various states from: stabilizing the native state to destabilizing oligomeric state and protofilament. Furthermore to stabilize fibrillar structures, thus decreasing the amount of toxic oligomers in solution, as is the case with the NCHCHF. The paper demonstrates how a set of NCHCHF can be used for studying and potentially treating the various physiopathological stages of a conformational disease. For instance, when dealing with an acute phase of cytotoxicity, what is needed is the recruitment of cytotoxic oligomers, thus chaperone F, which accelerates fiber formation, would be very useful; whereas in a chronic stage it is better to have chaperones A, B, C, and D, which stabilize the native and fibril structures halting self-catalysis and the creation of cytotoxic oligomers as a consequence of fiber formation. Furthermore, all the chaperones are able to protect and recondition the cerebellar granule cells (CGC) from the cytotoxicity produced by the hIAPP20-29 fragment or by a low potassium medium, regardless of their capacity for accelerating or inhibiting in vitro formation of fibers. In vivo animal experiments are required to study the impact of chemical chaperones in cognitive and metabolic syndromes.

New frontiers in the future of palliative care: real-world bioethical dilemmas and axiology of clinical practice.

BACKGROUND: In our time there is growing interest in developing a systematic approach to oncologic patients and end-of-life care. An important goal within this domain is to identify the values and ethical norms that guide physicians' decisions and their recourse to technological aids to preserve life. Though crucial, this objective is not easy to achieve. The purpose of this study is to evaluate empirically the real-life bioethical dilemmas with which palliative physicians are confronted when treating terminal cancer patients. METHODS: A quasi-experimental, observational, comparative, prospective and mixed (qualitative and quantitative) study was conducted in order to analyse the correlation between the palliative doctor-patient relationship and ethical judgments regarding everyday bioethical dilemmas that arise in palliative clinical practice. The values at stake in decision-making on a daily basis were also explored. From February 2012 to march 2014, palliative healthcare personnel were invited to participate in a research project on axiology of clinical practice in palliative medicine. Each participant answered to a set of survey instruments focusing on ethical dilemmas, views, and representations of clinical practice. For this analysis we selected a convenience sample of 30 physicians specialized in pain medicine and palliative care (algologists and palliativists), with two or more years of experience with oncologic patients and end-of-life care. RESULTS: 113 dilemmas were obtained, the most frequent of which were those regarding sedation, home administration of opioids, and institutional regulations. We observed that the ethical nucleus of palliative medicine is truth-telling, implying bidirectional trust between patients and healthcare providers. The two most prominent virtues among the participants in our study were justice and professional humility. The outstanding roles of the physician in palliative medicine are as educator and as adviser, followed by that of provider of medical assistance. CONCLUSIONS: This investigation opens up new horizons in a career path where professional wearing is rampant. The rediscovery of values and virtues in palliative clinical practice will renew and replenish the motivation of healthcare providers who carry out these duties, giving them a new professional and personal perspective of growth.

Revisión de modelos para el análisis de dilemas éticos / Review of models for the analysis of ethical dilemmas

Resumen:En la práctica médica pediátrica es frecuente encontrar a pacientes en circunstancias que representan un dilema ético para los profesionales de la salud. Un dilema corresponde a una situación en la que los preceptos morales o las obligaciones de similar obligatoriedad ética se encuentran en conflicto, de forma que cualquier solución posible al dilema es moralmente intolerable.Una revisión de la literatura permitió identificar diferentes modelos que abordan esta clase de dilemas. Se localizaron artículos utilizando las bases de datos Ebsco Host, ProQuest, Ovid e InMex, así como metabuscadores como metacrawler. Algunos de los modelos analizados fueron los siguientes: el Modelo de Anne Davis, el Método de Nijmegen, el Método de Diego Gracia, el Método Integral, el Modelo del Centro de Ética Médica de Bochum, el Modelo de Brody y Payton, el Modelo de Curtin y Flaherty, el Modelo de Thompson y Thompson, la Fórmula SAD, el Modelo de Javier Morata, el Modelo de Elaine Congress, el Modelo IFSW, el Modelo de Loewenberg y Dolgoff, el Modelo de la Ley Social, el Método DOER, el Modelo de Brommer, el Modelo de Corey y Callanan, el Modelo de Pope y Vasquez, el Modelo de Bush, Connell y Denney, el Modelo de Ferrell, Gresham y Fraedrich y el Modelo de Hunt y Vitell.Los criterios compartidos entre los diferentes modelos fueron los siguientes: a) la especificación del dilema ético; b) la descripción de los hechos a considerar; c) la definición de valores, principios y la postura ética que será tomada en consideración; y d) la toma de decisiones con la identificación de alternativas de solución. De acuerdo con la literatura revisada, se explican algunos modelos con el fin de identificar y ejemplificar elementos críticos que pudieran ser utilizados de manera práctica por los Comités de Ética Clínica u Hospitalaria en las instituciones de salud pediátrica en México.

Abstract:In pediatric medical practice it is common to encounter situations that represent a dilemma for health professionals. A dilemma occurs when ethical problems found in professional practice cause serious internal conflicts because they imply actions that contradict their colleagues, employees, or their own personal values and are classified as personal value conflicts, conflicts with other professionals, conflicts with clients and with organizations.A literature review allowed identifying different models to debate these types of dilemmas. The present work is a review of the search of scientific articles using databases such as Ebsco Host, ProQuest, Ovid, and InMex as well as metasearch tools such as metacrawler. The models found are as follows: Model of Anne Davis, Nijmegen method, Method of Diego Gracia, Integral method, Bochum Center Ethics model, Model of Brody and Payton, Model of Curtin and Flaherty, Model of Thompson and Thompson, SAD method, Model of Javier Morata, Model of Elaine Congress, IFSW model, Model of Loewenberg and Dolgoff, Ley Social Model, DOER method, Model of Brommer, Model of Corey and Callanan, Model of Pope and Vasquez, Model of Bush, Connell and Denney, Model of Ferrell, Gresham and Fraedrich, and Model of Hunt and Vitell.The key criteria shared in the different models are a) specifying the ethical dilemma, b) description of the facts, c) value definition, moral code and facts, decision making and d) identifying alternative solutions. In order to review the literature, some models are explained with the purpose of identifying and representing critical elements that clinical ethics committees could use in a practical manner in pediatric health institutions in Mexico.