Composition and Conformation of Hetero- versus Homo-Fluorinated Triazolamers Influence their Activity on Islet Amyloid Polypeptide Aggregation.

Novel fluorinated foldamers based on aminomethyl-1,4-triazolyl-difluoroacetic acid (1,4-Tz-CF2) units were synthesized and their conformational behaviour was studied by NMR and molecular dynamics. Their activity on the aggregation of the human islet amyloid polypeptide (hIAPP) amyloid protein was evaluated by fluorescence spectroscopy and mass spectrometry. The fluorine labelling of these foldamers allowed the analysis of their interaction with the target protein. We demonstrated that the preferred extended conformation of homotriazolamers of 1,4-Tz-CF2 unit increases the aggregation of hIAPP, while the hairpin-like conformation of more flexible heterotriazolamers containing two 1,4-Tz-CF2 units mixed with natural amino acids from the hIAPP sequence reduces it, and more efficiently than the parent natural peptide. The longer heterotriazolamers having three 1,4-Tz-CF2 units adopting more folded hairpin-like and ladder-like structures similar to short multi-stranded ß-sheets have no effect. This work demonstrates that a good balance between the structuring and flexibility of these foldamers is necessary to allow efficient interaction with the target protein.

Occupational Balance and Emotional Regulation in People With and Without Serious Mental Illness.

Background. Serious mental illness affects daily functioning, including occupational balance. Purpose. This study aims to compare occupational balance and emotional regulation between people with serious mental illness and the healthy population and to examine the relationship between occupational balance and emotional regulation. Method. A cross-sectional study was performed. Occupational balance and emotional regulation were measured using the Occupational Balance Questionnaire and the Emotional Regulation Questionnaire, respectively. A multivariate analysis (analysis of covariance) was conducted. Findings. The sample consisted of 112 individuals, divided into two groups: the serious mental illness group (n = 55); and the healthy group (n = 57). People with serious mental illness reported lower occupational balance and lower cognitive reappraisal than the healthy population. Furthermore, the higher cognitive reappraisal, the higher the occupational balance, and the higher the expressive suppression, the lower the occupational balance. Conclusion. The results provide preliminary evidence of the relationship between occupational balance and emotional regulation.

[Milestones on the road to health equity at the Pan American Health OrganizationMomentos-chave no caminho rumo à equidade em saúde na Organização Pan-Americana da Saúde]. / Momentos clave en el camino hacia la equidad en salud en la Organización Panamericana de la Salud.

Equity has become a key objective for the Pan American Health Organization (PAHO). This is the result of multidimensional movements with a history that can only be understood in the light of social relations that structure the processes we refer to as "health". From an initial concern for maritime trade to a current interest in the social determinants of health, PAHO has strengthened its efforts to make the concept of health equity the ultimate goal of its actions. The idea of health focused on the individual has given way to the idea of health for all people, which considers the differences between being and doing in the world. These changes have produced policies, analyses, and studies in which gender and cultural diversity are cross-cutting themes that must be considered in all planning and implementation of health policies in the Region of the Americas. This article discusses milestones on the road to health equity in the Region from a historical perspective.

Hoje, a equidade é um objetivo central para a Organização Pan-Americana da Saúde (OPAS). Esse objetivo é fruto de movimentos multidimensionais que têm uma história e que só podem ser compreendidos à luz das relações sociais que estruturam os processos que chamamos de "saúde". Da preocupação com o comércio marítimo ao interesse pelos determinantes sociais da saúde, a OPAS tem intensificado seus esforços para colocar no cerne de suas ações a ideia da equidade em saúde como objetivo final. Passou de uma ideia de saúde centrada no indivíduo a uma ideia de saúde para todas as pessoas, que contempla as diferenças entre o ser e o fazer no mundo. Essas mudanças produziram políticas, análises e estudos onde o gênero e a diversidade cultural são eixos transversais que devem ser considerados em todo planejamento e execução de políticas de saúde na Região das Américas. Este artigo analisa momentos-chave no caminho rumo à equidade em saúde na região, a partir de uma perspectiva histórica.

Momentos clave en el camino hacia la equidad en salud en la Organización Panamericana de la Salud / Milestones on the road to health equity at the Pan American Health Organization / Momentos-chave no caminho rumo à equidade em saúde na Organização Pan-Americana da Saúde

RESUMEN Hoy en día la equidad es un objetivo central para la Organización Panamericana de la Salud (OPS). Este objetivo es el resultado de movimientos multidimensionales que tienen una historia y que sólo pueden comprenderse a la luz de las relaciones sociales que estructuran los procesos que llamamos de "salud". De una preocupación por el comercio marítimo a un interés por los determinantes sociales de la salud, la OPS ha fortalecido sus esfuerzos por poner en el centro de sus acciones la idea de la equidad en salud como fin último. Se ha pasado de una idea de salud enfocada en el individuo, a una idea de salud para todas las personas, que contemple las diferencias de ser y hacer en el mundo. Estos cambios han producido políticas, análisis y estudios donde el género y la diversidad cultural son ejes transversales que deben ser contemplados en toda planificación y ejecución de políticas de salud en la Región de las Américas. En este artículo se analizan momentos clave en el camino hacia la equidad en salud en la Región desde una perspectiva histórica.

ABSTRACT Equity has become a key objective for the Pan American Health Organization (PAHO). This is the result of multidimensional movements with a history that can only be understood in the light of social relations that structure the processes we refer to as "health". From an initial concern for maritime trade to a current interest in the social determinants of health, PAHO has strengthened its efforts to make the concept of health equity the ultimate goal of its actions. The idea of health focused on the individual has given way to the idea of health for all people, which considers the differences between being and doing in the world. These changes have produced policies, analyses, and studies in which gender and cultural diversity are cross-cutting themes that must be considered in all planning and implementation of health policies in the Region of the Americas. This article discusses milestones on the road to health equity in the Region from a historical perspective.

RESUMO Hoje, a equidade é um objetivo central para a Organização Pan-Americana da Saúde (OPAS). Esse objetivo é fruto de movimentos multidimensionais que têm uma história e que só podem ser compreendidos à luz das relações sociais que estruturam os processos que chamamos de "saúde". Da preocupação com o comércio marítimo ao interesse pelos determinantes sociais da saúde, a OPAS tem intensificado seus esforços para colocar no cerne de suas ações a ideia da equidade em saúde como objetivo final. Passou de uma ideia de saúde centrada no indivíduo a uma ideia de saúde para todas as pessoas, que contempla as diferenças entre o ser e o fazer no mundo. Essas mudanças produziram políticas, análises e estudos onde o gênero e a diversidade cultural são eixos transversais que devem ser considerados em todo planejamento e execução de políticas de saúde na Região das Américas. Este artigo analisa momentos-chave no caminho rumo à equidade em saúde na região, a partir de uma perspectiva histórica.

5-Fluoro-1,2,3-triazole motif in peptides and its electronic properties.

The 5-fluoro triazole amino acid scaffold prepared by halogen exchange has been incorporated into peptides. From the X-ray diffraction of the 5-fluoro triazole motif, the main observation was an important localization on one side of the negative potential surface. The fluorine atom reveals a cylindrical shape in its deformation electron density.

Feasibility of an Activity Control System in Patients with Diabetes: A Study Protocol of a Randomised Controlled Trial.

Purpose: Patients with diabetes mellitus have an increased risk of developing various serious health problems that could be life-threatening. These problems are associated with the difficulty of these patients in managing their lifestyle, which may even lead to the abandonment of treatment. The present study was designed to evaluate the feasibility of a multipurpose activity control solution for home activity (home activity control system), which will provide information on the activities of daily living carried out outside in real time, to improve adherence to each of the therapeutic objectives agreed on with the diabetic patient. Patients and Methods: A pilot randomised controlled feasibility study will be carried out to evaluate a home activity control system (Beprevent) in managing patients with type 2 diabetes mellitus. Twenty patients with type 2 diabetes mellitus will be included (10 in the intervention group and 10 in the control group). Data on satisfaction with the tool will be collected from professionals and patients, as well as other clinical/epidemiological data from their digital health records and several questionnaires, at baseline and six months. In addition, data will also be recorded regarding the degree of adherence to the behaviors agreed on with the patients before starting the study to assess changes throughout the study and their relationship with clinical results (glycosylated haemoglobin (HbA1c), cholesterol, etc), and to compare these outcomes between two study groups. Discussion: This project involves the incorporation of telemedicine in the management of patients with diabetes. Thus, according to the currently published bibliography, the use of smart devices in this population could help improve the quality of life of these people, reduce medical visits and improve adherence to home care patterns for diabetes mellitus. There are currently no published clinical trials or protocols that monitor activities of daily living in patients with diabetes individually using artificial intelligence (AI) devices.

The stigma of mental health professionals towards users with a mental disorder.

Individuals with mental disorders are labeled in such a way that it leads to stigmatization. This generates a disadvantage as regards to the rest of the members of the society, limiting their participation as active members within it and at the same time being deleterious to their way of life. Mental health professionals are not safe from internalizing these stereotypes and prejudices assumed from their environment, thereby showing stigmatizing attitudes and behaviors towards the users in the different mental health resources.

Occupational Therapy in Severe Mental Disorder-A Self-Controlled Quasi-Experimental Study.

Severe mental disorder (SMD) produces a significant functional limitation that affects the performance of daily activities. The occupational therapist intervenes on this limitation by seeking greater autonomy of these patients through specific activities. This study aims to identify the main limitations of people with SMD and to examine whether an occupational intervention has any effect in helping to overcome or ameliorate these limitations. A quasi-experimental study including 103 participants was carried out. An evaluation using the World Health Organization Disability Assessment Schedule (WHODAS 2.0) questionnaire was performed before and after the intervention. Within the activity program, those with a higher attendance rating during cognitive stimulation, cooking workshop, therapeutic walks, relaxation, and creative activities were mainly men. Both patients and professionals indicated that Understanding and Communicating, Participation in Society, and Activities of Daily Living were the main perceived limitations. Upon discharge, patients and professionals reported positive outcomes. The intervention programs carried out by occupational therapy, along with the other aspects of the treatment that SMD patients received, played an important part in improving the performance and occupational interests of these patients.

Compression Behavior of Hybrid Tubes for Lightweight Steel Structures.

This research shows the results of an experimental investigation carried out on the compression behavior of hybrid steel tubes formed by two concentric steel tubes and four different fillers of non-metallic material interposed between both tubes: polyurethane foam, polyurethane, epoxy and a cement-based mortar. The tests show that the incorporation of a resistant filler in the double tube allows it to improve its mechanical behavior by allowing a second load cycle. Furthermore, the strain energy absorbed during the two cycles led to the conclusion that the epoxy-filled tube absorbed more energy per unit of weight than the other resistant fillers.

Antitumor Activity against Human Colorectal Adenocarcinoma of Silver Nanoparticles: Influence of [Ag]/[PVP] Ratio.

Silver nanoparticles (AgNPs) not only have shown remarkable results as antimicrobial and antiviral agents but also as antitumor agents. This work reports the complete characterization of five polyvinylpyrrolidone-coated AgNP (PVP-AgNP) formulations, their cytotoxic activity against human colon tumor cells (HCT-15), their cytotoxic effect on primary mouse cultures, and their lethal dose on BALB/c mice. The evaluated AgNP formulations have a composition within the ranges Ag: 1.14-1.32% w/w, PVP: 19.6-24.5% and H2O: 74.2-79.2% with predominant spherical shape within an average size range of 16-30 nm according to transmission electron microscopy (TEM). All formulations assessed increase mitochondrial ROS concentration and induce apoptosis as the leading death pathway on HCT-15 cells. Except for AgNP1, the growth inhibition potency of AgNP formulations of human colon tumor cancer cells (HCT-15) is 34.5 times higher than carboplatin, one of the first-line chemotherapy agents. Nevertheless, 5-10% of necrotic events, even at the lower concentration evaluated, were observed. The cytotoxic selectivity was confirmed by evaluating the cytotoxic effect on aorta, spleen, heart, liver, and kidney primary cultures from BALB/c mice. Despite the cytotoxic effects observed in vitro, the lethal dose and histopathological analysis showed the low toxicity of these formulations (all of them on Category 4 of the Globally Harmonized System of Classification and Labelling of Chemicals) and minor damage observed on analyzed organs. The results provide an additional example of the rational design of safety nanomaterials with antitumor potency and urge further experiments to complete the preclinical studies for these AgNP formulations.

Wegener's granulomatosis and differential diagnosis of mucosal leishmaniasis.

Granulomatosis with polyangiitis with nasal septal perforation can be confused with infectious diseases such as mucosal leishmaniasis, so these cases warrant an in-depth study in order to provide the correct treatment. Among the main characteristics to consider to define a Wegener's granulomatosis as opposed to an infectious disease are vasculitis, lymphadenopathy, and sinusopathy.

Fluorinated Triazole Foldamers: Folded or Extended Conformational Preferences.

The Ministère de l'Enseignement Supérieur et de la Recherche (MESR) is thanked for financial support for José Laxio Arenas. The China Scholarship Council is thanked for financial support for Yaochun Xu. The authors thank Pr. Vadim Soloshonok and TOSOH F-TECH, Inc. for the kind gift of N-terbutyl-sulfinylimine.

Nutritional Status Measurement Instruments for Diabetes: A Systematic Psychometric Review.

BACKGROUND: Diabetes is a serious chronic disease associated with a large number of complications and an increased risk of premature death. A dietary evaluation is of utmost importance for health promotion, disease prevention and individual treatment plans in patients with diabetes. METHODS: An exhaustive search was carried out in various databases-Medline, Web of Science, Open Gray Cochrane Library and Consensus-based Standards for the selection of health status Measurement Instruments (COSMIN)-for systematic review of the measurement properties of instruments that evaluate the dietary intake of people with diabetes mellitus type 1 and/or 2 according to COSMIN standards. RESULTS: Seven instruments were identified. There was no instrument measuring nutritional status for which all the psychometric properties were evaluated. The methodological quality for each of the psychometric properties evaluated was 'inadequate' or 'doubtful' for all instruments. The Food Frequency Questionnaire (FFQ) evaluated the most psychometric characteristics and with a better score in terms of quality of the evidence. CONCLUSIONS: Several instruments have been developed for the evaluation of dietary intake in people with diabetes. Evaluation of this construct is very useful, both in clinical practice and in research, requiring new knowledge in this area. The FFQ is the best instrument available to assess dietary intake in people with diabetes.

Mucinous cystic neoplasms of the pancreas associated with pregnancy: Two case reports.

RATIONALE: Although rare, pancreatic neoplasms can occur during pregnancy, both in benign and malignant forms. Mucinous cystic neoplasms (MCNs) of the pancreas, a type of these neoplasms, are precursor lesions to invasive pancreatic cancer. The presence of the ovarian-type stroma is a defining feature. PATIENT CONCERNS: The first case was a 38-year-old woman in her 18th week of pregnancy with abdominal pain that worsens a few weeks later. The second case was a 30-year-old woman in her 17th week of pregnancy with abdominal pain in the left hypochondrium. DIAGNOSIS: The patients were under clinical examination and laboratory test including carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA). Both patients had magnetic resonance imaging (MRI). The diagnosis of a MCNs of the pancreas was done preoperatively in the 2 cases. INTERVENTIONS: Both patients underwent distal pancreatectomy during pregnancy. One of them was an emergency laparotomy because of a ruptured MCN. OUTCOMES: Both patients were completely recovered from distal pancreatectomy and continued to full term, delivering a healthy baby by Caesarean section. After 6 years of follow-up, the first patient underwent a total gastrectomy, because of a gastric cancer with carcinomatosis. Currently the 2 patients are still alive after 8 years and 5 years of follow-up, respectively. LESSONS: Surgical resection of MCNs during pregnancy should be considered during the second trimester given common distal pancreas location, rapid growth, risk of spontaneous rupture, and malignant potential.

Gene flow between subpopulations of gray snapper (Lutjanus griseus) from the Caribbean and Gulf of Mexico.

BACKGROUND: The gray snapper (Lutjanus griseus) has a tropical and subtropical distribution. In much of its range this species represents one of the most important fishery resources because of its high quality meat and market value. Due to this, this species is vulnerable to overfishing, and population declines have been observed in parts of its range. In recent decades, it has been established that knowing the level of genetic connectivity is useful for establishing appropriate management and conservation strategies given that genetic isolation can drive towards genetic loss. Presently the level of genetic connectivity between subpopulations of L. griseus of the southern region of the Gulf of Mexico and the Caribbean Sea remains unknown. METHODS: In the present study we analyze genetic structure and diversity for seven subpopulations in the southern Gulf of Mexico and the Mexican Caribbean Sea. Eight microsatellite primers of phylogenetically closely related species to L. griseus were selected. RESULTS: Total heterozygosity was 0.628 and 0.647 in the southern Gulf of Mexico and the Mexican Caribbean Sea, however, results obtained from AMOVA and R ST indicated a lack of genetic difference between the major basins. We also found no association between genetic difference and geographic distance, and moderately high migration rates (N m = > 4.1) suggesting ongoing gene flow among the subpopulations. Gene flow within the southern Gulf of Mexico appears to be stronger going from east-to-west. CONCLUSIONS: Migration rates tended to be higher between subpopulations within the same basin compared to those across basins indicating some regionalization. High levels of genetic diversity and genetic flow suggest that the population is quite large; apparently, the fishing pressure has not caused a bottleneck effect.

Peptides and peptidomimetics as inhibitors of protein-protein interactions involving ß-sheet secondary structures.

Protein-protein interactions involving ß-sheet secondary structures have been questioned in many fatal human diseases such as cancer, autoimmune and neurodegenerative diseases. Small selective peptide derivatives and analogues are promising drug candidates for inhibiting this poorly known class of PPIs. In this review, we will highlight the main strategies developed for designing linear and cyclic peptide and peptidomimetic inhibitors of PPIs involving ß-sheet structures. These compounds either do not adopt preferred conformations or can mimic protein secondary structures such as ß-strands, ß-hairpins or α-helices.

[Esophageal actinomycosis in patients with HIV infection]. / Actinomicosis esofágica en pacientes con infección por VIH.

Esophageal pathology is common in patients with HIV, frequently due to Candida, cytomegalovirus or herpes virus. However, esophageal actinomycosis is a rare infection, even in patients with HIV. We report the case of a 33-year-old male patient, with a recent diagnosis of HIV who was admitted for fever, odynophagia, dysphagia and retrosternal pain. Upper gastrointestinal endoscopy evidenced multiple esophageal ulcers and the histopathological report of the esophageal biopsy described a chronic esophagitis with colonies of PAS positive bacilli, compatible with Actinomyces, initiating favorable antimicrobial therapy. Although it is an uncommon disease, about one-third of cases of esophageal actinomycosis occur in patients with HIV infection, and endoscopic biopsies are required to define diagnosis and appropriate treatment.

Actinomicosis esofágica en pacientes con infección por VIH / Esophageal actinomycosis in patients with HIV infection

La patología esofágica es común en pacientes con VIH, frecuentemente debido a Candida, citomegalovirus o virus herpes simple. Sin embargo, la actinomicosis esofágica es una infección rara, incluso en pacientes con infección VIH. Reportamos el caso en un paciente varón de 33 años, con diagnóstico reciente de VIH que acudió a consulta por fiebre, odinofagia, disfagia y dolor retroesternal. La endoscopia digestiva alta evidenció múltiples úlceras esofágicas y el informe histopatológico de la biopsia esofágica describió una esofagitis crónica con presencia de colonias de bacilos PAS positivos, compatibles con Actinomyces, iniciando tratamiento antimicrobiano con evolución favorable. Aunque es una enfermedad no común, cerca de un tercio de los casos de actinomicosis esofágica se presentan en pacientes con infección VIH, y es preciso el estudio endoscópico con toma de biopsia para definir el diagnóstico y manejo apropiado.

Esophageal pathology is common in patients with HIV, frequently due to Candida, cytomegalovirus or herpes virus. However, esophageal actinomycosis is a rare infection, even in patients with HIV. We report the case of a 33-year-old male patient, with a recent diagnosis of HIV who was admitted for fever, odynophagia, dysphagia and retrosternal pain. Upper gastrointestinal endoscopy evidenced multiple esophageal ulcers and the histopathological report of the esophageal biopsy described a chronic esophagitis with colonies of PAS positive bacilli, compatible with Actinomyces, initiating favorable antimicrobial therapy. Although it is an uncommon disease, about one-third of cases of esophageal actinomycosis occur in patients with HIV infection, and endoscopic biopsies are required to define diagnosis and appropriate treatment.

Incorporating a Monofluoroalkene into the Backbones of Short Peptides: Evaluating the Impact on Local Hydrophobicity.

The local hydrophobicity of an amino acid residue in a peptide sequence can be determined by measuring the hydrophobicity index (φ0 ) by reversed-phase (RP) HPLC. Herein, the impact on the local hydrophobicity of the replacement of an amide by a monofluoroalkene unit in short peptides is discussed. Monofluoroalkene-containing dipeptides and tripeptides were synthesized, as well as their natural parent compounds, and the hydrophobicity indexes of these short peptides and peptidomimetics were determined. Comparison between the natural parent peptides and their alkene-containing analogues was made, and the dependence of the peptidomimetic analogues' behaviour on the pH and the solvent was studied. It was found that the presence of a monofluoroalkene unit enhanced a peptide's hydrophobicity.

Baseline Characteristics of Patients With Heart Failure and Preserved Ejection Fraction in the PARAGON-HF Trial.

BACKGROUND: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. METHODS AND RESULTS: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), ß-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464-1610), and structural heart disease. CONCLUSIONS: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711.