Junior doctors' experiences with interprofessional collaboration: Wandering the landscape.

CONTEXT: The transition from medical student to junior doctor is challenging. Junior doctors need to become part of the physician community of practice (CoP), while dealing with new responsibilities, tasks and expectations. At the same time, they need to learn how to navigate the frontiers and intersections with the other communities of practice that form the Landscape of Practice (LoP). This study aims to understand how junior doctors experience interprofessional collaboration (IPC) and what elements shape these experiences considering their transition to clinical practice. METHODS: In this multicentre qualitative study, 13 junior doctors individually drew two rich pictures of IPC experiences, one positive and one negative. A rich picture is a visual representation, a drawing of a particular situation intended to capture the complex and non-verbal elements of an experience. We used semi-structured interviews to deepen the understanding of junior doctors' depicted IPC experiences. We analysed both visual materials and interview transcripts iteratively, for which we adopted an inductive constructivist thematic analysis. RESULTS: While transitioning into a doctor, junior doctors become foremost members of the physician CoP and shape their professional identity based on perceived values in their physician community. Interprofessional learning occurs implicitly, without input from the interprofessional team. As a result, junior doctors struggle to bridge the gap between themselves and the interprofessional team, preventing IPC learning from developing into an integrative process. This professional isolation leaves junior doctors wandering the landscape of practice without understanding roles, attitudes and expectations of others. CONCLUSIONS: Learning IPC needs to become a collective endeavour and an explicit learning goal, based on multisource feedback to take advantage of the expertise already present in the LoP. Furthermore, junior doctors need a safe environment to embrace and reflect on the emotions aroused by interprofessional interactions, under the guidance of experienced facilitators.

All You Need Is Music: Supporting Medical Students' Emotional Development With a Music-Based Pedagogy.

PROBLEM: Although the practice of medicine is often emotionally challenging, medical curricula seldom systematically address the emotional development of medical students. To fill this gap, the authors developed and evaluated an innovative pedagogical activity based on music to nurture medical students' emotional development. The authors believe that the metaphoric nature of music offers an efficient venue for exploring emotion perception, expression, and regulation. APPROACH: The pedagogical activity Emotions in Medicine was carried out throughout 2020 and 2021 and consisted of 4 encounters to explore: (1) emotion perception, (2) emotion expression, (3) emotion regulation, and (4) the role of emotions in medical practice. During all encounters, the authors used music to evoke students' emotions and focused the discussions on the relevance of emotions for meaningful medical practice. Emotional intelligence before and after the workshop was tested using the Schutte Self-Report Emotional Intelligence Test (SSEIT), a validated psychometric scale. OUTCOMES: The workshop facilitated emotional connection among students and created a safe space to explore the role of emotions in medical practice. The mean total pretest SSEIT score was 110 (SD = 14.2); it increased to 116.8 (SD = 16.1) in the posttest ( P < .001). This increase was true across its 4 dimensions: (1) perception of emotions, (2) management of own emotions (3) management of others' emotions, and (4) use of emotions. NEXT STEPS: Music can be an active tool to explore the role of emotions in medical practice. It fosters students' capacity to identify and reflect on emotions while exploring their role in patient care. Further (qualitative) research is needed to explore the mechanisms by which music facilitates learning emotion perception, expression, and regulation.

A simplified ultrasound-based edema score to assess lung injury and clinical severity in septic patients.

BACKGROUND: Lung ultrasound (US) is an excellent tool to assess lung edema in a myriad of different clinical situations. We hypothesized that lung US might also be a good prognostic and management instrument in septic patients, regardless of disease severity. METHODS: This was a prospective observational cohort study at an urban academic emergency department (ED). Inclusion criteria were as follows: septic patients, at least 18 years old, admitted at the ED of a tertiary hospital. A simplified lung edema scoring system (SLESS) was developed, and 6 thoracic regions were evaluated. Four different lung US patterns were considered, from normal aeration to total consolidation. To evaluate disease severity, the SLESS was compared with the Mortality in Emergency Department Sepsis Score and the third version of the Simplified Acute Physiology Score scoring systems. Aiming to assess the effect of the lung edema in the gas exchange, the SLESS was compared with the Pao2/fraction of inspired oxygen ratio. RESULTS: Sixty-one patients were enrolled in a 3-month period. The SLESS had a good correlation with the Mortality in Emergency Department Sepsis Score and Simplified Acute Physiology Score (r = 0.53 and r = 0.55, respectively; P < .001 for both) and a negative correlation with the Pao2/fraction of inspired oxygen ratio (r = -0.62; P < .001). The SLESS also showed correlation with the respiratory rate (r = 0.45; P = .0003). The odds ratio for death related to the SLESS was 1.370 (95% confidence interval, 1.109-1.691; P = .0035). CONCLUSION: The SLESS is an easy and practical scoring system. It might be a useful tool to predict severity of disease in sepsis patients. The SLESS might also be able to be correlated with the oxygen exchange.

Anti-Black racism in clinical supervision: asynchronous simulated encounters facilitate reflective practice.

Background Racist interactions in clinical practice remain a pervasive reality for Black healthcare providers. We sought to develop a framework to inform supervisors' actions when confronting racism in clinical practice and protecting trainees under their oversight. Methods We conducted a qualitative study in which experienced supervisors responded to seven short, videotaped interactions between: 1) Black trainees and a simulated patient (SP) in a racist role; 2) the trainees and their respective supervisors; and 3) the trainees and their supervisors together with the SP. The clinical exchanges exemplified different types of racist (entrenching) or antiracist (uprooting) behaviors by the supervisors. After viewing each clip, participants wrote their reflections confidentially; they later joined a structured debriefing together. We used thematic analysis to identify supervisors' behavioral patterns when confronting racist interactions. Results Based on the input of 52 participants recruited into five two-hour-long sessions, we categorized the behaviors of supervisors facing anti-Black racial injuries involving learners under their oversight. We organized supervisor behaviors into five interlocking domains, each with a range of possible themes: 1) Joining: from conciliatory to confrontational in communicating with the aggressor; 2) Explicitness: from avoiding to naming racism; 3) Ownership: from individual to shared responsibility of the event and the response to it; 4) Involving: from excusing to including the aggrieved party when confronting the aggressor; and 5) Stance: from protective to paternalistic in supporting the learner's autonomy. Conclusions Our qualitative findings can provide a framework for facilitated discussion toward reflective practice among healthcare providers who may have experienced, witnessed, or intervened in anti-Black racist interactions. They can also help medical educators to inform faculty development to fight anti-Black racism in clinical practice. The video materials we developed are available for viewing and download and can be used or adapted as springboards for reflective discussion or faculty development activities.

The Effect of Information Presentation Order on Residents' Diagnostic Accuracy of Online Simulated Patients With Chest Pain.

Background: Physicians may receive diagnostic information in different orders, and there is a lack of empirical evidence that the order of presentation may influence clinical reasoning. Objective: We investigated whether diagnostic accuracy of chest pain cases is influenced by the order of presentation of the history and electrocardiogram (EKG) to cardiology residents. Methods: We conducted an experimental study during a resident training in 2019. Twelve clinical cases were presented in 2 diagnostic rounds. Residents were randomly allocated to seeing the EKG first (EKGF) or the history first (HF). The mean diagnostic accuracy scores (range 0-1) and confidence level (0-100) in each diagnostic round and time needed to make the diagnosis were evaluated. Results: The final diagnostic accuracy was higher than the initial in both groups. After the first round, diagnostic accuracy was higher in HF (n=24) than in EKGF (n=28). Time taken to judge the history was comparable in both groups. Time taken to judge the EKG was shorter in HF (40±11 vs 64±13 seconds; P<.01). Time invested in the second round was significantly correlated with changing the initial diagnosis. A significant difference was observed in confidence ratings after the initial diagnosis, with EKGF reporting less confidence relative to HF. Conclusions: The order in which history and EKG are presented influences the clinical reasoning process.

Making It Real: From Telling to Showing, Sharing, and Doing in Psychiatric Education.

OBJECTIVE: Innovations in contemporary medical education could inform remedies to address enduring challenges such as the marginalization and stigmatization of psychiatry, of mental illnesses, and of those affected by them. METHODS: In blending the works of Bleakley, Bligh, and Brown (2011) and of Kumagai and Naidu (2015), we developed an overarching heuristic with practical relevance and concrete applications to psychiatric education. RESULTS: We identify three areas to enhance psychiatric education embedded into this blended framework: 1) Showing, or the more accurate depiction or imaging of mental illnesses and of psychiatric practice, as exemplified by the incorporation into didactic content of asynchronous video-based clinical materials produced with specific educational objectives in mind; 2) Sharing, or addressing the image problem of mental illnesses, of those living with or affected by them, and of psychiatry as a profession, as exemplified by psychiatrists embracing their role as experts by professional and personal experience when sharing their own journeys with mental illness, treatment, and recovery; and 3) Doing, or reimagining reflective psychiatric practice, as exemplified by the novel methodology of co-constructive patient simulation (CCPS), through which learners can engage in reflective practice and supervision in a participatory and democratic setting that does not privilege participants' hierarchical standing. CONCLUSION: The blended model and the sample applications we describe offer a range of teaching, learning, and professional development opportunities, should psychiatric educators choose to pursue them and reap their promise.

Psychological distress among frontline workers during the COVID-19 pandemic: A mixed-methods study.

BACKGROUND: Novel virus outbreaks, such as the COVID-19 pandemic, may increase psychological distress among frontline workers. Psychological distress may lead to reduced performance, reduced employability or even burnout. In the present study, we assessed experienced psychological distress during the COVID-19 pandemic from a self-determination theory perspective. METHODS: This mixed-methods study, with repeated measures, used surveys (quantitative data) combined with audio diaries (qualitative data) to assess work-related COVID-19 experiences, psychological need satisfaction and frustration, and psychological distress over time. Forty-six participants (nurses, junior doctors, and consultants) completed 259 surveys and shared 60 audio diaries. Surveys and audio diaries were analysed separately. RESULTS: Quantitative results indicated that perceived psychological distress during COVID-19 was higher than pre-COVID-19 and fluctuated over time. Need frustration, specifically autonomy and competence, was positively associated with psychological distress, while need satisfaction, especially relatedness, was negatively associated with psychological distress. In the qualitative, thematic analysis, we observed that especially organisational logistics (rostering, work-life balance, and internal communication) frustrated autonomy, and unfamiliarity with COVID-19 frustrated competence. Despite many need frustrating experiences, a strong connection with colleagues and patients were important sources of relatedness support (i.e. need satisfaction) that seemed to mitigate psychological distress. CONCLUSION: The COVID-19 pandemic resulted in an increase of psychological distress among frontline workers. Both need frustration and need satisfaction explained unique variance of psychological distress, but seemed to originate from different sources. Challenging times require healthcare organisations to better support their professionals by tailored formal and informal support. We propose to address both indirect (e.g. organisation) and direct (e.g. colleagues) elements of the clinical and social environment in order to reduce need frustration and enhance need satisfaction.

Physico-chemical solid-state characterization of omeprazole sodium: thermal, spectroscopic and crystallinity studies.

The physical characterization of active pharmaceutical substances is crucial to the successful development of the final drug product. The different solid forms and variations in the degree of crystallinity can lead to significantly different physical and chemical properties, including color, morphology, stability, dissolution and bioavailability. In the case of omeprazole sodium (OMS), its chemical structures contain a specific number of water molecules (hydrate). The behavior of pharmaceutical hydrates has become the object of increasing attention over the past decade, primarily due to the potential impact of hydrates on the development process and dosage form performance. The present study was designed to characterize and evaluate the crystallinity of omeprazole sodium, dehydrated omeprazole sodium (DOMS) and omeprazole free base (OM) using a variety of techniques including thermal analysis (thermogravimetry/derivative thermogravimetry (TG/DTG) and differential scanning calorimetry (DSC)), diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, scanning electron microscopy (SEM) and X-ray powder diffraction (XRPD). Furthermore, an NMR spectroscopy study was also carried out to clarify the conformation and crystal structure.

Solid-State Characterization of Different Crystalline Forms of Sitagliptin.

Sitagliptin is an inhibitor of the enzyme dipeptidyl peptidase-4, used for the treatment of type 2 diabetes mellitus. The crystal structure of active pharmaceutical solids determines their physical and chemical properties. The polymorphism, solvates and hydrates can influence the free energy, thermodynamic parameters, solubility, solid-state stability, processability and dissolution rate, besides directly affecting the bioavailability. Thus, the physicochemical characterization of an active pharmaceutical ingredient is required to guarantee the rational development of new dosage forms. In this context, we describe herein the solid-state characterization of three crystalline forms of sitagliptin: sitagliptin phosphate monohydrate, sitagliptin phosphate anhydrous and sitagliptin base form. The investigation was carried out using differential scanning calorimetry (DSC), thermogravimetry (TG)/derivative thermogravimetry (DTG), spectroscopic techniques, X-ray powder diffraction (XRPD) and morphological analysis by scanning electron microscopy. The thermal analysis revealed that during the dehydration of sitagliptin phosphate monohydrate (Tpeak = 134.43 °C, ΔH = -1.15 J g-1) there is a characteristic crystalline transition event, which alters the physicochemical parameters of the drug, such as the melting point and solubility. The crystalline behavior of sitagliptin base form differs from that of sitagliptin phosphate monohydrate and sitagliptin phosphate anhydrous, mainly with regard to the lower temperature of the fusion event. The melting point (Tpeak) values obtained were 120.29 °C for sitagliptin base form, 206.37 °C for sitagliptin phosphate monohydrate and 214.92 °C for sitagliptin phosphate anhydrous. In relation to the thermal stability, sitagliptin phosphate monohydrate and sitagliptin phosphate anhydrous showed a slight difference; however, both are more thermostable than the base molecule. Therefore, through this study it was possible to establish the most suitable crystalline form of sitagliptin for the development of a safe, effective and appropriate pharmaceutical dosage form.

Inflammatory lung edema correlates with echocardiographic estimation of capillary wedge pressure in newly diagnosed septic patients.

PURPOSE: Lung ultrasound is an accurate and accessible tool to quantify lung edema. Furthermore, left ventricle filling pressures (LVFP) can be assessed with transthoracic echocardiography (TTE) by the E/e' ratio (E/e'). The present study aimed to assess the correlation between E/e' and lung edema quantified by a simplified lung ultrasound score (LUS) in newly admitted septic patients. MATERIALS AND METHODS: In this prospective observational cohort, septic adult patients admitted at the emergency department of a tertiary hospital were included. LUS consisted of four different patterns of lung edema (from normal aeration to parenchymal consolidation). To compare lung edema with LVFP, E/e' was calculated immediately before or within 5min of fluid therapy. RESULTS: Fifty patients were enrolled in 3months. The LUS correlated with E/e' (r=0.58, P<0.0001). The LUS also increased among E/e' quartiles (Q) (Q1: E/e'≤4.49; Q2: 4.497.11; P=0.0003 for Q1 and 4; 2 and 4); and LUS was significantly higher in abnormal (≥8) vs. normal (<8) values of E/e' (11.29 vs 8.49, P=0.007). CONCLUSION: In newly admitted septic patients, lung edema is positively correlated with LVFP prior to fluid therapy. This finding might help find future targets for fluid resuscitation in sepsis.

[Insulin and angiotensin II signaling pathways cross-talk: implications with the association between diabetes mellitus, arterial hypertension and cardiovascular disease]. / Cross-talk das vias de sinalização de insulina e angiotensina II: implicações com a associação entre diabetes mellitus e hipertensão arterial e doença cardiovascular.

Insulin (Ins) and angiotensin II (AII) play pivotal roles in the control of two vital and closely related systems: the metabolic and the circulatory, respectively. A failure in the proper action of each of these hormones results, to a variable degree, in the development of two highly prevalent and commonly overlapping diseases--diabetes mellitus (DM) and hypertension (AH). In recent years, a series of studies has revealed a tight connection between the signal transduction pathways that mediate Ins and AII actions in target tissues. This molecular cross-talk occurs at multiple levels and plays an important role in phenomena that range from the action of anti-hypertensive drugs to cardiac hypertrophy and energy acquisition by the heart. At the extracellular level, the angiotensin-converting enzyme controls AII synthesis but also interferes with Ins signaling through the proper regulation of AII and the accumulation of bradykinin. At an early intracellular level, AII, acting through JAK-2/IRS-1/PI3-kinase, JNK and ERK, may induce the serine phosphorylation and inhibition of key elements of the Ins-signaling pathway. Finally, by inducing the expression of the regulatory protein SOCS-3, AII may impose a late control on the Ins signal. This review will focus on the main advances obtained in this field and will discuss the implications of this molecular cross-talk in the common clinical association between DM and AH.

Suspected infection in afebrile patients: Are they septic?

We prospectively evaluated afebrile patients admitted to an emergency department (ED), with suspected infection and only tachycardia or tachypnea.The white blood cell count (WBC) was obtained, and patients were considered septic if leukocyte count was >12,000 µL-1 or <4000 µL-1 or with >10% of band forms. Clinical data were collected to examine whether sepsis could be predicted.Seventy patients were included and 37 (52.86%) met sepsis criteria. Self-measured fever showed an odds ratio (OR) of 5.936 (CI95% 1.450-24.295; P = 0.0133) and increased pulse pressure (PP) showed an OR of 1.405 (CI95% 1.004-1.964; P = 0.0471) on multivariate analysis. When vital signs were included in multivariate analysis, the heart rate showed an OR of 2.112 (CI95% 1.400-3.188; P = 0.0004). Self-measured fever and mean arterial pressure <70 mm Hg had high positive likelihood ratios (3.86 and 2.08, respectively). The nomogram for self-measured fever showed an increase of sepsis chance from 53% (pretest) to approximately 80% (post-test).The recognition of self-measured fever, increased PP, and the intensity of heart rate response may improve sepsis recognition in afebrile patients with tachycardia or tachypnea. These results are important for medical assessment of sepsis in remote areas, crowded and low-resourced EDs, and low-income countries, where WBC may not be readily available.

S-nitrosation of the insulin receptor, insulin receptor substrate 1, and protein kinase B/Akt: a novel mechanism of insulin resistance.

Evidence demonstrates that exogenous nitric oxide (NO) and the NO produced by inducible nitric oxide synthase (iNOS) can induce insulin resistance in muscle. Here, we investigated whether this insulin resistance could be mediated by S-nitrosation of proteins involved in early steps of the insulin signal transduction pathway. Exogenous NO donated by S-nitrosoglutathione (GSNO) induced in vitro and in vivo S-nitrosation of the insulin receptor beta subunit (IRbeta) and protein kinase B/Akt (Akt) and reduced their kinase activity in muscle. Insulin receptor substrate (IRS)-1 was also rapidly S-nitrosated, and its expression was reduced after chronic GSNO treatment. In two distinct models of insulin resistance associated with enhanced iNOS expression-diet-induced obesity and the ob/ob diabetic mice-we observed enhanced S-nitrosation of IRbeta/IRS-1 and Akt in muscle. Reversal of S-nitrosation of these proteins by reducing iNOS expression yielded an improvement in insulin action in both animal models. Thus, S-nitrosation of proteins involved in insulin signal transduction is a novel molecular mechanism of iNOS-induced insulin resistance.

Translational research into gut microbiota: new horizons on obesity treatment: updated 2014.

Obesity is currently a pandemic of worldwide proportions affecting millions of people. Recent studies have proposed the hypothesis that mechanisms not directly related to the human genome could be involved in the genesis of obesity, due to the fact that, when a population undergoes the same nutritional stress, not all individuals present weight gain related to the diet or become hyperglycemic. The human intestine is colonized by millions of bacteria which form the intestinal flora, known as gut flora. Studies show that lean and overweight human may present a difference in the composition of their intestinal flora; these studies suggest that the intestinal flora could be involved in the development of obesity. Several mechanisms explain the correlation between intestinal flora and obesity. The intestinal flora would increase the energetic extraction of non-digestible polysaccharides. In addition, the lipopolysaccharide from intestinal flora bacteria could trigger a chronic sub-clinical inflammatory process, leading to obesity and diabetes. Another mechanism through which the intestinal flora could lead to obesity would be through the regulation of genes of the host involved in energy storage and expenditure. In the past five years data coming from different sources established causal effects between intestinal microbiota and obesity/insulin resistance, and it is clear that this area will open new avenues of therapeutic to obesity, insulin resistance and DM2.

Debriefing as an opportunity to develop emotional competence in health profession students: faculty, be prepared! / Debriefing como uma oportunidade de desenvolver competência emocional em estudantes da área da saúde: docentes, preparem-se!

AIMS: In this article, we want to share our perspective on how simulation sessions could contribute to change reality, building a safe environment in which facilitators can role-modeling students to develop emotional competence. Noteworthy, acknowledging and legitimating emotions are also essential components of creating a safe environment for students. We also intend to stress how faculty development programs are essential to guarantee that facilitators will be prepared to accomplish this new learning goal, and how different cultural contexts can influence the process. METHODS: In this narrative review, we will focus on the importance of emotions. Emotions in the context of learning but also learners' emotions from the viewpoint of teachers, and teachers' emotions in the context of faculty development. RESULTS: Simulation in medical education is becoming increasingly important. Advances in technology give many opportunities to simulate almost anything you want, with high fidelity and enhanced reality. It creates the possibility of bringing the complexity of real clinical tasks to a controlled simulated environment. While performing these complex simulated tasks, students experience several and sometimes distinct emotions: the emotions of patients and their families, the emotions of the multi-professional team members, and their own emotions, as learners and as future health professionals. Unfortunately, the formal curricula of the majority of medical schools do not address the importance of emotional competence specifically, and students end with the general impression that emotions are mainly negative, and must be avoided and kept at a safe distance. However, there are plenty of data showing how emotions can influence learning and decision-making, and how important it is to create awareness of and modulate them to guarantee the safeguard of patients' interests. CONCLUSIONS: Emotions directly affect several dimensions of clinical work, such as communication, decision-making, teamwork, and leadership. We hope that including dealing with emotions as a natural goal of the learning activities in the health professions can catalyze the reconciliation between the technical and emotional aspects of clinical practice.

OBJETIVOS: Neste artigo, pretendemos compartilhar nossa perspectiva em relação a como a simulação pode ajudar a transformar a realidade, construindo um ambiente seguro em que os facilitadores das sessões de simulação sejam os modelos em que os estudantes podem se espelhar para desenvolver competência emocional. Vale ressaltar que reconhecer e dar legitimidade às emoções é passo essencial para a criação de um ambiente seguro para os estudantes. Também pretendemos reforçar como os programas de capacitação docente são fundamentais para garantir que os facilitadores estarão preparados para atingir esse novo objetivo de aprendizagem, e como contextos culturais diferentes podem influenciar esse processo. MÉTODOS: Nesta revisão narrativa, nos concentraremos na importância das emoções. Emoções no contexto da aprendizagem, mas também emoções dos aprendizes do ponto de vista dos professores, e emoções dos professores no contexto do desenvolvimento do corpo docente. RESULTADOS: A simulação está se tornando cada vez mais importante na educação médica. Os avanços tecnológicos permitem simular praticamente qualquer situação, com alta fidelidade e realidade. Isso cria a possibilidade de trazer a complexidade de situações clínicas reais para um ambiente simulado e controlado. Ao executar essas simulações de alta complexidade, os estudantes experimentam várias e diferentes emoções: as emoções dos pacientes e de suas famílias, as emoções dos membros da equipe, e as suas próprias emoções, como estudantes e como futuros profissionais da saúde. Infelizmente, a grade curricular formal da maioria das escolas médicas não aborda especificamente a importância de desenvolver competência emocional, e os estudantes acabam com a impressão geral de que as emoções são basicamente negativas, e que devem ser evitadas e mantidas a uma distância de segurança. No entanto, vários estudos mostram como as emoções influenciam o aprendizado e a tomada de decisões, e como é importante estar consciente delas e modulá-las de uma forma que garanta a salvaguarda dos interesses dos pacientes. CONCLUSÕES: As emoções afetam diretamente várias dimensões do trabalho clínico, como comunicação, tomada de decisão, trabalho em equipe e liderança. Esperamos que tratar das emoções como meta natural das atividades de aprendizagem nas profissões da saúde oportunize catalisar a reconciliação entre os aspectos técnicos e emocionais da prática clínica.

Modulation of double-stranded RNA-activated protein kinase in insulin sensitive tissues of obese humans.

OBJECTIVE: The double-stranded RNA-dependent protein kinase (PKR) was recently implicated in regulating molecular integration of nutrient- and pathogen-sensing pathways in obese mice. However, its modulation in human tissues in situations of insulin resistance has not been investigated. The present study was performed to first determine the tissue expression and phosphorylation levels of PKR in the liver, muscle, and adipose tissue in obese humans, and also the modulation of this protein in the adipose tissue of obese patients after bariatric surgery. DESIGN AND METHODS: Eleven obese subjects who were scheduled to undergo Roux-en-Y Gastric Bypass Procedure participated in this study. Nine apparently healthy lean subjects as a control group were also included. RESULTS: Our data show that PKR is activated in liver, muscle, and adipose tissue of obese humans and, after bariatric surgery, there is a clear reduction in PKR activation accompanied by a decrease in protein kinase-like endoplasmic reticulum kinase, c-Jun N-terminal kinase, inhibitor of kappa ß kinase, and insulin receptor substrate-1 serine 312 phosphorylation in subcutaneous adipose tissue from these patients. CONCLUSION: Thus, it is proposed that PKR is an important mediator of obesity-induced insulin resistance and a potential target for the therapy.

Targeted disruption of inducible nitric oxide synthase protects against aging, S-nitrosation, and insulin resistance in muscle of male mice.

Accumulating evidence has demonstrated that S-nitrosation of proteins plays a critical role in several human diseases. Here, we explored the role of inducible nitric oxide synthase (iNOS) in the S-nitrosation of proteins involved in the early steps of the insulin-signaling pathway and insulin resistance in the skeletal muscle of aged mice. Aging increased iNOS expression and S-nitrosation of major proteins involved in insulin signaling, thereby reducing insulin sensitivity in skeletal muscle. Conversely, aged iNOS-null mice were protected from S-nitrosation-induced insulin resistance. Moreover, pharmacological treatment with an iNOS inhibitor and acute exercise reduced iNOS-induced S-nitrosation and increased insulin sensitivity in the muscle of aged animals. These findings indicate that the insulin resistance observed in aged mice is mainly mediated through the S-nitrosation of the insulin-signaling pathway.

Translational research into gut microbiota: new horizons on obesity treatment: updated 2014

Obesity is currently a pandemic of worldwide proportions affecting millions of people. Recent studies have proposed the hypothesis that mechanisms not directly related to the human genome could be involved in the genesis of obesity, due to the fact that, when a population undergoes the same nutritional stress, not all individuals present weight gain related to the diet or become hyperglycemic. The human intestine is colonized by millions of bacteria which form the intestinal flora, known as gut flora. Studies show that lean and overweight human may present a difference in the composition of their intestinal flora; these studies suggest that the intestinal flora could be involved in the development of obesity. Several mechanisms explain the correlation between intestinal flora and obesity. The intestinal flora would increase the energetic extraction of non-digestible polysaccharides. In addition, the lipopolysaccharide from intestinal flora bacteria could trigger a chronic sub-clinical inflammatory process, leading to obesity and diabetes. Another mechanism through which the intestinal flora could lead to obesity would be through the regulation of genes of the host involved in energy storage and expenditure. In the past five years data coming from different sources established causal effects between intestinal microbiota and obesity/insulin resistance, and it is clear that this area will open new avenues of therapeutic to obesity, insulin resistance and DM2.