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Sodium-glucose cotransporter 2 inhibitors (SGLT2is), initially developed for type 2 diabetes (T2D) treatment, have demonstrated significant cardiovascular and renal benefits in heart failure (HF) and chronic kidney disease (CKD), irrespective of T2D. This review provides an analysis of the multifaceted mechanisms underlying the cardiorenal benefits of SGLT2i in HF and CKD outside of the T2D context. Eight major aspects of the protective effects of SGLT2i beyond glycemic control are explored: 1) the impact on renal hemodynamics and tubuloglomerular feedback; 2) the natriuretic effects via proximal tubule Na+/H+ exchanger NHE3 inhibition; 3) the modulation of neurohumoral pathways with evidence of attenuated sympathetic activity; 4) the impact on erythropoiesis, not only in the context of local hypoxia but also systemic inflammation and iron regulation; 5) the uricosuria and mitigation of the hyperuricemic environment in cardiorenal syndromes; 6) the multiorgan metabolic reprogramming including the potential induction of a fasting-like state, improvement in glucose and insulin tolerance, and stimulation of lipolysis and ketogenesis; 7) the vascular endothelial growth factor A (VEGF-A) upregulation and angiogenesis, and 8) the direct cardiac effects. The intricate interplay between renal, neurohumoral, metabolic, and cardiac effects underscores the complexity of SGLT2i actions and provides valuable insights into their therapeutic implications for HF and CKD. Furthermore, this review sets the stage for future research to evaluate the individual contributions of these mechanisms in diverse clinical settings. [ABSTRACT FROM AUTHOR]

Schizophrenia is a mental illness that affects an estimated 21 million people worldwide. The literature establishes that electroencephalography (EEG) is a well-implemented means of studying and diagnosing mental disorders. However, it is known that speech and language provide unique and essential information about human thought. Semantic and emotional content, semantic coherence, syntactic structure, and complexity can thus be combined in a machine learning process to detect schizophrenia. Several studies show that early identification is crucial to prevent the onset of illness or mitigate possible complications. Therefore, it is necessary to identify disease-specific biomarkers for an early diagnosis support system. This work contributes to improving our knowledge about schizophrenia and the features that can identify this mental illness via speech and EEG. The emotional state is a specific characteristic of schizophrenia that can be identified with speech emotion analysis. The most used features of speech found in the literature review are fundamental frequency (F0), intensity/loudness (I), frequency formants (F1, F2, and F3), Mel-frequency cepstral coefficients (MFCC’s), the duration of pauses and sentences (SD), and the duration of silence between words. Combining at least two feature categories achieved high accuracy in the schizophrenia classification. Prosodic and spectral or temporal features achieved the highest accuracy. The work with higher accuracy used the prosodic and spectral features QEVA, SDVV, and SSDL, which were derived from the F0 and spectrogram. The emotional state can be identified with most of the features previously mentioned (F0, I, F1, F2, F3, MFCCs, and SD), linear prediction cepstral coefficients (LPCC), linear spectral features (LSF), and the pause rate. Using the event-related potentials (ERP), the most promissory features found in the literature are mismatch negativity (MMN), P2, P3, P50, N1, and N2. The EEG features with higher accuracy in schizophrenia classification subjects are the nonlinear features, such as Cx, HFD, and Lya.

Few studies demonstrated a percentage decrease in the estimated glomerular filtration rate (eGFR) at a single time and the rate of hypoaldosteronism after adrenalectomy for primary aldosteronism (PA). Our aim was to investigate the evolution of renal function and the hypoaldosteronism risk after adrenalectomy for PA. Aldosterone, renin, eGFR, and electrolyte levels were determined before and at 1 week, 1, 3 and 6 months after unilateral adrenalectomy in 94 PA patients (40 men and 54 women). The main outcome was the postoperative eGFR decline using analysis of covariance with the preoperative eGFR as a covariate. eGFR decreased during first postoperative week compared to 3 months before surgery. During the first 6 months, eGFR remained stable at similar levels to the first week after surgery. Age (p=0.001), aldosterone levels (p=0.021) and eGFR 3 months before surgery (p+<+0.0001) had a significant correlation with eGFR during first postoperative week. High aldosterone levels at diagnosis were correlated with decline in renal function in the univariate model (p=0.033). In the multivariate analysis, aldosterone levels at diagnosis had a tendency to be an independent predictor of renal function after surgery (p=0.059). Postoperative biochemical hypoaldosteronism was diagnosed in 48% of the cases after adrenalectomy, but prolonged hyperkalemia occurred in only 4 cases (4.5%). Our findings showed a decrease of eGFR after unilateral adrenalectomy for PA. Additionally, aldosterone levels at diagnosis correlated with postoperative renal function. Postoperative biochemical hypoaldosteronism occurred in almost half of the patients, but prolonged hyperkalemia with fludrocortisone replacement was less frequent. [ABSTRACT FROM AUTHOR]

Background Post-exercise hypotension (PEH) is greater after evening than morning exercise, but antihypertensive drugs may affect the evening potentiation of PEH. Objective: To compare morning and evening PEH in hypertensives receiving angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB). Methods Hypertensive men receiving ACEi (n = 14) or ARB (n = 15) underwent, in a random order, two maximal exercise tests (cycle ergometer, 15 watts/min until exhaustion) with one conducted in the morning (7 and 9 a.m.) and the other in the evening (8 and 10 p.m.). Auscultatory blood pressure (BP) was assessed in triplicate before and 30 min after the exercises. Changes in BP (post-exercise – pre-exercise) were compared between the groups and the sessions using a two-way mixed ANOVA and considering P

Pruritus is a key symptom in allergology and dermatology, contributing to the global and huge impact on quality of life related to skin disorders, both those which are not related to a primary dermatosis (illness) and those which are linked with primary skin lesions (disease). This is particularly evident within psychophysiological dermatoses, a group of psychodermatological diseases where there is a primary dermatosis, where psychological stress plays a role, and where pruritus may represent a major and shared symptom. The etiopathogenesis of pruritus in those disorders sheds light on the link among psychopathological features, psychological stress and the subtle interface between allergic and autoimmune mechanisms, where mast cells play a pivotal role. Allergy has long been recognised as an altered reactivity to exogenous antigens (allergens), defined as an immediate hypersensitivity mediated by immunoglobulin E (IgE). In turn, the immunological understanding of atopy is related to an immediate hypersensitivity reaction to environmental antigens involving T-helper 2 (Th2) responses and the IgE production. Mast cells are major cells in the early phase of allergy, releasing the mediators involved in the symptoms associated with the allergic disease, including pruritus, when the allergen cross-links with IgE, whose mechanisms can be observed in acute urticaria and atopy. Some allergic reactions may persist and allergy may eventually lead to autoimmunity, with the development of a T-helper 1 (Th1) and then IgE-independent inflammation. For instance, in chronic spontaneous urticaria, the mast cell activation may include autoimmune mechanisms, where autoantibodies against the extracellular α subunit of the high-affinity IgE receptor (FcεRIα) and to IgE are observed, with the involvement of Th1 lymphocytes and the production of interferon-γ (INF-γ). The role of autoimmunity is also suggested in the etiopathogenesis of other psychophysiological dermatoses, namely psoriasis, atopic dermatitis and alopecia areata. In the latter, for example, mast cells were reported to be linked with the loss of immune privilege and they are the key cells involved in the experience of pruritus, whose intensity was reported to precede and be correlated with the onset of the hair loss. Furthermore, considering that the role of hair and skin is wide, from psychosocial aspects (communication and social interaction) to vital functions (such as, temperature control), it is straightforward that they are central in our interactions and synchronization with others and the world; thereby, we may admit that the psychophysiological dermatoses could represent a loss of such synchronization. Furthermore, they are often linked with psychopathology which strongly connects with the concept of desynchronization, namely, sleep disorders and depressive symptoms, the clinical expression of a dysfunction in the interplay among mast cells, pineal gland and melatonin, thus the circadian rhythm, as well as their connection with the hypothalamic corticotrophin-releasing hormone (CRH), well-known for its key role in stress response. Moreover, increasing evidence has supported the existence of cutaneous equivalents for these mechanisms, connecting with those central pathways. Thereby, taking all these concepts into consideration, this review intends to look into the updated evidence on the shared biological mechanisms between allergy and autoimmunity, underlining pruritus as a core element, then revisiting the key role of mast cells and discussing the connection with melatonin and immune-inflammatory pathways in the physiopathology of psychophysiological dermatoses, thus paving the way for the understanding of their psychosomatic correlates and a comprehensive psychodermatological approach.

OBJECTIVES: To describe the MORPHEOS (Morbidity in patients with uncontrolled HTN and OSA) trial, and describe the challenges imposed by the COVID-19 pandemic. METHODS: MORPHEOS is a multicenter (n=6) randomized controlled trial designed to evaluate the blood pressure (BP) lowering effects of treatment with continuous positive airway pressure (CPAP) or placebo (nasal strips) for 6 months in adult patients with uncontrolled hypertension (HTN) and moderate-to-severe obstructive sleep apnea (OSA). Patients using at least one antihypertensive medication were included. Uncontrolled HTN was confirmed by at least one abnormal parameter in the 24-hour ABPM and ≥80% medication adherence evaluated by pill counting after the run-in period. OSA was defined by an apnea-hypopnea index ≥15 events/hours. The co-primary endpoints are brachial BP (office and ambulatory BP monitoring, ABPM) and central BP. Secondary outcomes include hypertension-mediated organ damage (HMOD) to heart, aorta, eye, and kidney. We pre-specified several sub-studies from this investigation. Visits occur once a week in the first month and once a month thereafter. The programmed sample size was 176 patients but the pandemic prevented this final target. A post-hoc power analysis will be calculated from the final sample. ClinicalTrials.gov: NCT02270658. RESULTS: The first 100 patients are predominantly males (n=69), age: 52±10 years, body mass index: 32.7±3.9 kg/m2 with frequent co-morbidities. CONCLUSIONS: The MORPHEOS trial has a unique study design including a run-in period; pill counting, and detailed analysis of hypertension-mediated organ damage in patients with uncontrolled HTN that will allow clarification of the impact of OSA treatment with CPAP.

Context Confirmatory tests represent a fundamental step in primary aldosteronism (PA) diagnosis, but they are laborious and often require a hospital environment due to the risks involved. Objective To evaluate the efficacy of oral furosemide as a new confirmatory test for PA diagnosis. Methods We prospectively evaluated the diagnostic performance of 80 mg of oral furosemide in 64 patients with PA and 22 with primary hypertension (controls). Direct renin concentration (DRC) was measured before, and 2 hours and 3 hours after the oral furosemide. In addition, the oral furosemide test was compared with 2 other confirmatory tests: the furosemide upright test (FUT) and saline infusion test (SIT) or captopril challenge test (CCT) in all patients with PA. Results The cut-off of 7.6 µU/mL for DRC at 2 hours after oral furosemide had a sensitivity of 92%, specificity of 82%, and accuracy of 90% for PA diagnosis. In 5 out of 6 controls with low-renin hypertension, which might represent a PA spectrum, renin remained suppressed. Excluding these 6 controls with low-renin hypertension, the DRC cut-off of 10 µU/mL at 2 hours after oral furosemide had a sensitivity of 95.3%, specificity of 93.7% and accuracy of 95% for PA diagnosis. DRC after 3 hours of oral furosemide did not improve diagnostic performance. Using the cut-off of 10 µU/mL, the oral furosemide test and the FUT were concordant in 62 out of 64 (97%) patients with PA. Only 4 out of 64 cases with PA (6.4%) ended the oral furosemide test with potassium <3.5 mEq/L. Hypotension was not evidenced in any patient with PA during the test. Conclusion The oral furosemide test was safe, well-tolerated and represents an effective strategy for PA investigation. [ABSTRACT FROM AUTHOR]

Background. Salt sensitivity is associated with an increased cardiovascular risk, but the gold standard method (diet cycles) requires 24-h urine samples and has poor patient compliance. Objectives. Test the hypothesis that oral fludrocortisone (0.4 mg per day for 7 days) is a good alternative in identifying salt-sensitive patients. Methodology. We conducted a randomized crossover study with 30 hypertensive individuals comprising the following steps: (1) washout; (2) phase A (low- and high-sodium diet cycles); (3) washout 2; (4) phase B (fludrocortisone test). Phase A and B steps were performed in a random way. Consistent with the literature, we found that 53.3% were salt-sensitive according to the reference test. Using the ROC curve, the fludrocortisone test defined salt sensitivity by a median blood pressure increase of ≥3 mmHg. A good accuracy of fludrocortisone in detecting salt sensitivity was observed (AUC: 0.732±0.065; p

Context: Primary aldosteronism (PA) screening relies on an elevated aldosterone to renin ratio with a minimum aldosterone level, which varies from 10 to 15 ng/dL (277-415.5 pmol/L) using immunoassay. Objective: To evaluate intra-individual coefficient of variation (CV) of aldosterone and aldosterone to direct renin concentration ratio (A/DRC) and its impact on PA screening. Methods: A total of 671 aldosterone and DRC measurements were performed by the same chemiluminescence assays in a large cohort of 216 patients with confirmed PA and at least 2 screenings. Results: The median intra-individual CV of aldosterone and A/DRC was 26.8% and 26.7%. Almost 40% of the patients had at least one aldosterone level <15 ng/dL, 19.9% had at least 2 aldosterone levels <15 ng/dL, and 16.2% had mean aldosterone levels <15 ng/dL. A lower cutoff of 10 ng/dL was associated with false negative rates for PA screening of 14.3% for a single aldosterone measurement, 4.6% for 2 aldosterone measurements, and only 2.3% for mean aldosterone levels. Considering the minimum aldosterone, true positive rate of aldosterone thresholds was 85.7% for 10 ng/dL and 61.6% for 15 ng/dL. An A/DRC >2 ng/dL/µIU/mL had a true positive rate for PA diagnosis of 94.4% and 98.4% when based on 1 or 2 assessments, respectively. CV of aldosterone and A/DRC were not affected by sex, use of interfering antihypertensive medications, PA lateralization, hypokalemia, age, and number of hormone measurements. Conclusion: Aldosterone concentrations had a high CV in PA patients, which results in an elevated rate of false negatives in a single screening for PA. Therefore, PA screening should be based on at least 2 screenings with concomitant aldosterone and renin measurements. [ABSTRACT FROM AUTHOR]

Objective: To compile data on Tourette's syndrome (TS), tics and associated disorders.Methods: A systematic review of the literature was conducted using the 5S levels of organization of healthcare research evidence (systems, summaries, synopses, syntheses, studies), based on the model described by Haynes. The search keywords were Tourette, tics and comorbidity, which were cross-referenced. Studies provided by publishers and articles being processed on July 31, 2013, were also included.Results: Of all studies retrieved during the search, 64 were selected because they analyzed the epidemiology, clinical features and etiopathogenesis of TS and its comorbidities. TS is classified as a hyperkinetic movement disorder, and at least 90% of the patients have neuropsychiatric comorbidities, of which attention deficit hyperactivity and obsessive-compulsive disorders are the most common. The syndrome is clinically heterogeneous and has been associated with a dysfunction of cortico-striatal-thalamic-cortical circuits involving various neurotransmitters. Although its genetic etiology has been widely studied, other factors may be important to understand this syndrome and its associated disorders.Conclusions: TS is a neurodevelopmental disorder that results from the impact of stress factors on a vulnerable biological substrate during the critical periods of neurodevelopment. The study of TS and its comorbidities may contribute, at different levels, to the understanding of several neuropsychiatric disorders of clinical and therapeutic relevance.

A psicose puerperal (PP) é um quadro clínico exuberante, com uma frequência estimada de 1 caso por cada 1.000 puerpérios, e que tem sido associado com maior consistência ao espectro bipolar. A evidência científica disponível é escassa, nomeadamente no respeitante à orientação terapêutica. Os autores apresentam o caso clínico de uma mulher primípara de 28 anos, sem antecedentes psiquiátricos, que iniciou nas primeiras semanas de puerpério um quadro psicótico florido, composto por agitação psicomotora, confusão, desorganização do pensamento e comportamento, sintomatologia psicótica e insônia grave. Por ausência de resposta ao tratamento farmacológico, houve recurso à eletroconvulsoterapia (ECT), com melhoria clínica rápida e evidente. Nesse contexto, os autores realizaram uma apreciação da literatura e evidência referentes ao uso de ECT na psicose puerperal.