Mulheres com síndrome do ovário policísticos que desenvolveram diabetes melitus 2 antes dos 35 anos: ansiedade, má qualidade do sono e não controle glicêmico / Women with polycystic ovarian syndrome who developed diabetes mellitus 2 before the age of 35: anxiety, poor sleep quality and lack of glycemic control / Mujeres con síndrome de ovario poliquístico que desarrollaron diabetes melitus 2 antes de los 35 años: ansiedad, mala calidad del sueño y sin control glucémico

Introdução: A síndrome dos ovários policísticos (SOP) consiste em uma desordem de origem endocrinológica de grande prevalência nas mulheres em idade fértil, sendo acometidas por ela aproximadamente de 6 a 16% da população feminina - em consonância com diversos critérios diagnósticos 1-4. Essa síndrome é associada ao hiperandrogenismo e à resistência insulínica (RI), com manifestações clínicas relacionadas a alterações reprodutivas 4, desenvolvimento de diabetes mellitus (DM2) e obesidade. Esta pesquisa objetiva compreender o perfil das mulheres com DM 2 antes dos 35 anos e os fatores que podem levar a esta condição. Metodologia: Este estudo se deu por meio de inquérito on-line feito a mulheres diagnosticadas com SOP, e com menos de 35 anos de idade. Foi desenvolvido de maneira virtualizada via plataforma GoogleForms® em função da pandemia do COVID-19. Tratou-se de um levantamento sobre presença de fatores de risco para DM 2, como sobrepeso e alimentação, sedentarismo e qualidade do sono; em grupos de mulheres com SOP diabéticas e não diabéticas, para efeito de comparação. Resultados e discussão: Um total de 198 mulheres responderam ao questionário, sendo divididas em Diabéticas (DM) e não diabéticas (NDM). O grupo DM foi o que mais apresentou IMC elevado (acima de 30), e o que mais se declarou seguir orientações nutricionais. Atividade física não diferenciou entre os grupos. O grupo DM foi o que declarou dormir mais tarde (pós 23:00) quando comparado com o grupo NDM. O sobrepeso indica ser um fator importante para o advento da DM 2 neste grupo, sendo as orientações nutricionais não tão efetivas, devido muito a dificuldade de aderir às orientações. O hábito de dormir tarde implica em alterações que levam a aumento da RI via estresse oxidativo, contribuindo para obesidade e DM 2. Conclusões: A obesidade é um fator decisivo para a precocidade da DM 2 em mulheres com SOP, e sua condição é multifatorial, associada a seguimento de orientações nutricionais, atividade física e qualidade do sono. O evitar da precocidade da DM 2 neste grupo passa por esta compreensão.

Introduction: Polycystic ovary syndrome (PCOS) is an endocrinological disorder with high prevalence in women of childbearing age, affected by approximately 6 to 16% of the female population - in line with several diagnostic criteria 1-4. This syndrome is associated with hyperandrogenism and insulin resistance (IR), with clinical manifestations related to reproductive changes 4, development of diabetes mellitus (DM2) and obesity. This research aims to understand the profile of women with DM 2 before the age of 35 and the factors that can lead to this condition. Methodology: This study was carried out through an online survey made to women diagnosed with PCOS, and under 35 years of age. It was developed in a virtualized way via the GoogleForms® platform due to the COVID-19 pandemic. This was a survey on the presence of risk factors for DM 2, such as overweight and diet, sedentary lifestyle and sleep quality; in groups of women with diabetic and non-diabetic PCOS for comparison purposes. Results and discussion: A total of 198 women answered the questionnaire, divided into Diabetic (DM) and non-diabetic (NDM). The DM group was the one with the highest BMI (above 30), and the one that most declared to follow nutritional guidelines. Physical activity did not differ between groups. The DM group was the one who reported sleeping later (after 11 pm) when compared to the NDM group. Overweight is an important factor for the advent of DM 2 in this group, and nutritional guidelines are not so effective, due to the difficulty in adhering to the guidelines. The habit of sleeping late implies changes that lead to increased IR via oxidative stress, contributing to obesity and DM 2. Conclusions: Obesity is a decisive factor for the precocity of DM 2 in women with PCOS, and its condition is multifactorial, associated with following nutritional guidelines, physical activity and sleep quality. Avoiding the precocity of DM 2 in this group involves this understanding.

Introducción: El síndrome de ovario poliquístico (SOP) es un trastorno de origen endocrinológico de alta prevalencia en mujeres en edad fértil, afectando aproximadamente entre el 6 y el 16% de la población femenina, de acuerdo con diversos criterios diagnósticos 1- 4 . Este síndrome se asocia con hiperandrogenismo y resistencia a la insulina (RI), con manifestaciones clínicas relacionadas con cambios reproductivos 4, desarrollo de diabetes mellitus (DM2) y obesidad. Esta investigación tiene como objetivo conocer el perfil de las mujeres con DM 2 antes de los 35 años y los factores que pueden conducir a esta condición. Metodología: Este estudio se realizó a través de una encuesta online realizada entre mujeres diagnosticadas con SOP y menores de 35 años. Fue desarrollado de manera virtualizada a través de la plataforma GoogleForms® debido a la pandemia de COVID-19. Se realizó una encuesta sobre la presencia de factores de riesgo para DM 2, como sobrepeso y alimentación, sedentarismo y calidad del sueño; en grupos de mujeres diabéticas y no diabéticas con síndrome de ovario poliquístico, con fines de comparación. Resultados y discusión: Respondieron al cuestionario un total de 198 mujeres, divididas en diabéticas (DM) y no diabéticas (NDM). El grupo DM fue el que presentó un IMC más elevado (superior a 30), y el que más declaró seguir las pautas nutricionales. La actividad física no difirió entre los grupos. El grupo DM fue el que reportó dormir más tarde (después de las 11:00 pm) en comparación con el grupo NDM. El sobrepeso indica que es un factor importante en la aparición de DM 2 en este grupo, siendo las pautas nutricionales no tan efectivas, en gran parte por la dificultad para cumplirlas. El hábito de dormir tarde implica cambios que conducen a un aumento de la RI vía estrés oxidativo, contribuyendo a la obesidad y la DM 2. Conclusiones: La obesidad es un factor decisivo en la aparición temprana de la DM 2 en mujeres con SOP, y su condición es multifactorial, asociado con el seguimiento de pautas nutricionales, actividad física y calidad del sueño. Evitar la precocidad de la DM 2 en este grupo requiere esta comprensión.

Antimicrobial peptides: A plausible approach for COVID-19 treatment.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), which emerged as a major public health threat, has affected >400 million people globally leading to >5 million mortalities to date. Treatments of COVID-19 are still to be developed as the available therapeutic approaches are not able to combat the virus causing the disease (severe acute respiratory syndrome coronavirus-2; SARS-CoV-2) satisfactorily. However, antiviral peptides (AVPs) have demonstrated prophylactic and therapeutic effects against many coronaviruses (CoVs). AREAS COVERED: This review critically discusses various types of AVPs evaluated for the treatment of COVID-19 along with their mechanisms of action. Furthermore, the peptides inhibiting the entry of the virus by targeting its binding to angiotensin-converting enzyme 2 (ACE2) or integrins, fusion mechanism as well as activation of proteolytic enzymes (cathepsin L, transmembrane serine protease 2 (TMPRSS2), or furin) are also discussed. EXPERT OPINION: Although extensively investigated, successful treatment of COVID-19 is still a challenge due to emergence of virus mutants. Antiviral peptides are anticipated to be blockbuster drugs for the management of this serious infection because of their formulation and therapeutic advantages. Although they may act on different pathways, AVPs having a multi-targeted approach are considered to have the upper hand in the management of this infection.

Orchestration of Obesolytic Activity of Microbiome: Metabiotics at Centre Stage.

Metabiotics have emerged as the safer alternatives to probiotics in last decade. Unlike probiotics that are live microbes, metabiotics are the low molecular weight bioactive metabolites produced by the gut microbiota. While offering a similar profile of health benefits as that of probiotics, metabiotics are free from the risks and uncertain responses associated with administration of live bacteria into the body. Metabiotics have demonstrated substantial effectiveness across the ethnicities, age, gender and nutritional habits in a number of metabolic disorders, including obesity. Obesity is attributed to the offsetting of the energy homeostasis of the body due to a number of genetic, endocrinological, and environmental factors leading to obesity. The obesogenic mechanisms are quite complicated as they result from a complex interplay among a number of factors. Owing to a variety of constituents exerting their action through different pathways, metabiotics offer a pragmatic option for treatment as well as prevention of obesity by addressing heterogeneous aspects of its aetiology. In this review, we categorize various components of metabiotics and discuss their cross-talk with host cells at the molecular level. We also discuss the challenges in understanding these interactions and their potential effects on obesity treatment and prevention strategies. Considering the alarming rise in obesity all over the world, metabiotics offer an attractive non-pharmacological approach to spearhead the strategies being designed to combat the challenges posed by the obesity epidemic.

Discovery and Development of Antibacterial Agents: Fortuitous and Designed.

Today, antibacterial drug resistance has turned into a significant public health issue. Repeated intake, suboptimal and/or unnecessary use of antibiotics, and, additionally, the transfer of resistance genes are the critical elements that make microorganisms resistant to conventional antibiotics. A substantial number of antibacterials that were successfully utilized earlier for prophylaxis and therapeutic purposes have been rendered inadequate due to this phenomenon. Therefore, the exploration of new molecules has become a continuous endeavour. Many such molecules are at various stages of the investigation. A surprisingly high number of new molecules are currently in the stage of phase 3 clinical trials. A few new agents have been commercialized in the last decade. These include solithromycin, plazomicin, lefamulin, omadacycline, eravacycline, delafloxacin, zabofloxacin, finafloxacin, nemonoxacin, gepotidacin, zoliflodacin, cefiderocol, BAL30072, avycaz, zerbaxa, vabomere, relebactam, tedizolid, cadazolid, sutezolid, triclosan, and afabiacin. This article aims to review the investigational and recently approved antibacterials with a focus on their structure, mechanisms of action/resistance, and spectrum of activity. Delving deep, their success or otherwise in various phases of clinical trials is also discussed while attributing the same to various causal factors.

Characterisation of insulin analogues therapeutically available to patients.

The structure and function of clinical dosage insulin and its analogues were assessed. This included 'native insulins' (human recombinant, bovine, porcine), 'fast-acting analogues' (aspart, glulisine, lispro) and 'slow-acting analogues' (glargine, detemir, degludec). Analytical ultracentrifugation, both sedimentation velocity and equilibrium experiments, were employed to yield distributions of both molar mass and sedimentation coefficient of all nine insulins. Size exclusion chromatography, coupled to multi-angle light scattering, was also used to explore the function of these analogues. On ultracentrifugation analysis, the insulins under investigation were found to be in numerous conformational states, however the majority of insulins were present in a primarily hexameric conformation. This was true for all native insulins and two fast-acting analogues. However, glargine was present as a dimer, detemir was a multi-hexameric system, degludec was a dodecamer (di-hexamer) and glulisine was present as a dimer-hexamer-dihexamer system. However, size-exclusion chromatography showed that the two hexameric fast-acting analogues (aspart and lispro) dissociated into monomers and dimers due to the lack of zinc in the mobile phase. This comprehensive study is the first time all nine insulins have been characterised in this way, the first time that insulin detemir have been studied using analytical ultracentrifugation and the first time that insulins aspart and glulisine have been studied using sedimentation equilibrium. The structure and function of these clinically administered insulins is of critical importance and this research adds novel data to an otherwise complex functional physiological protein.

Glargine and degludec: Solution behaviour of higher dose synthetic insulins.

Single, double and triple doses of the synthetic insulins glargine and degludec currently used in patient therapy are characterised using macromolecular hydrodynamic techniques (dynamic light scattering and analytical ultracentrifugation) in an attempt to provide the basis for improved personalised insulin profiling in patients with diabetes. Using dynamic light scattering and sedimentation velocity in the analytical ultracentrifuge glargine was shown to be primarily dimeric under solvent conditions used in current formulations whereas degludec behaved as a dihexamer with evidence of further association of the hexamers ("multi-hexamerisation"). Further analysis by sedimentation equilibrium showed that degludec exhibited reversible interaction between mono- and-di-hexamer forms. Unlike glargine, degludec showed strong thermodynamic non-ideality, but this was suppressed by the addition of salt. With such large injectable doses of synthetic insulins remaining in the physiological system for extended periods of time, in some case 24-40 hours, double and triple dose insulins may impact adversely on personalised insulin profiling in patients with diabetes.

The Effectiveness of Lifestyle Adaptation for the Prevention of Prediabetes in Adults: A Systematic Review.

Diabetes prevalence is increasing exceptionally worldwide and with this come associated healthcare costs. The primary outcome of this systematic review was to assess glycaemic control and incidence of Type 2 diabetes mellitus (T2DM) diagnosis after exercise and dietary intervention (measured with any validated scale). The secondary outcome assessed body mass index change, weight change, and physical exercise capacity after diet and exercise intervention (measured with any validated scale). 1,780 studies were identified from searching electronic databases. Relevant studies went through a selection process. The inclusion criteria for all studies were people with prediabetes diagnosed by either impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). Lifestyle adaptation reduced the incidence of diabetes development more than standard treatment. Furthermore, better glycaemic control, improved physical exercise capacity, and increased weight reduction were observed with lifestyle intervention over standard treatment. Finally, improvements over the long term deteriorated, highlighting problems with long-term adherence to lifestyle changes. Overall, cumulative incidence of diabetes is drastically reduced in the intervention groups compared to control groups (standard care). Furthermore, glycaemic control was improved in the short term, with many participants reverting to normoglycaemia.

A novel analytical ultracentrifugation based approach to the low resolution structure of gum arabic.

Under investigation are the structural properties of gum arabic, an industrially important biopolymer for use as a stabilizer or in drug delivery, using Analytical Ultracentrifugation-a well-established, matrix-free probe for macromolecular size and shape. These results are combined with chromatographically-coupled methods (multi-angle light scattering, differential press imbalance viscometry) to provide a global analysis of its structure in varying ionic strength conditions. This analysis indicates that gum Arabic may have a compact, elliptical structure in solution, the significance of which for biotechnological use is indicated. This modelling method can be applied to other biopolymers and synthetic polymers. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 618-625, 2016.

Ultracentrifuge Methods for the Analysis of Polysaccharides, Glycoconjugates, and Lignins.

Although like proteins, polysaccharides are synthesized by enzymes, unlike proteins there is no template. This means that they are polydisperse, do not generally have compact folded structures, and are often very large with greater nonideality behavior in solution. This chapter considers the relevant analytical ultracentrifuge methodology available for characterizing these and related carbohydrate-based systems and information this methodology supplies, in terms of sizes, shapes, and interactions using a comprehensive range of examples, including glycoconjugates and lignins. The relevance and potential of recent software developments such as SEDFIT-MSTAR, the Extended Fujita algorithm, and HYDFIT are considered.