Effects of Mindful Eating in Patients with Obesity and Binge Eating Disorder.

INTRODUCTION: Binge eating disorder (BED) is a psychiatric illness related to a high frequency of episodes of binge eating, loss of control, body image dissatisfaction, and suffering caused by overeating. It is estimated that 30% of patients with BED are affected by obesity. "Mindful eating" (ME) is a promising new eating technique that can improve self-control and good food choices, helping to increase awareness about the triggers of binge eating episodes and intuitive eating training. OBJECTIVES: To analyze the impact of ME on episodes of binge eating, body image dissatisfaction, quality of life, eating habits, and anthropometric data [weight, Body Mass Index (BMI), and waist circumference] in patients with obesity and BED. METHOD: This quantitative, prospective, longitudinal, and experimental study recruited 82 patients diagnosed with obesity and BED. The intervention was divided into eight individual weekly meetings, guided by ME sessions, nutritional educational dynamics, cooking workshops, food sensory analyses, and applications of questionnaires [Body Shape Questionnaire (BSQ); Binge Eating Scale (BES); Quality of Life Scale (WHOQOL-BREF)]. There was no dietary prescription for calories, carbohydrates, proteins, fats, and fiber. Patients were only encouraged to consume fewer ultra-processed foods and more natural and minimally processed foods. The meetings occurred from October to November 2023. STATISTICAL ANALYSIS: To carry out inferential statistics, the Shapiro-Wilk test was used to verify the normality of variable distribution. All variables were identified as non-normal distribution and were compared between the first and the eighth week using a two-tailed Wilcoxon test. Non-Gaussian data were represented by median ± interquartile range (IQR). Additionally, α < 0.05 and p < 0.05 were adopted. RESULTS: Significant reductions were found from the first to the eighth week for weight, BMI, waist circumference, episodes of binge eating, BSQ scale score, BES score, and total energy value (all p < 0.0001). In contrast, there was a significant increase in the WHOQOL-BREF score and daily water intake (p < 0.0001). CONCLUSIONS: ME improved anthropometric data, episodes of binge eating, body image dissatisfaction, eating habits, and quality of life in participants with obesity and BED in the short-term. However, an extension of the project will be necessary to analyze the impact of the intervention in the long-term.

Nutritional Strategies for the Management of Type 2 Diabetes Mellitus: A Narrative Review.

BACKGROUND: Thinking about greater adherence to dietary planning, it is extremely important to be aware of all nutritional strategies and dietary prescriptions available in the literature, and of which of them is the most efficient for the management of T2DM. METHODS: A search was carried out in 2023 for randomized clinical trials, systematic reviews, meta-analyses, and guidelines in the following databases: Pubmed, Scielo, Web of Science, CrossRef and Google Scholar. In total, 202 articles were collected and analyzed. The period of publications was 1983-2023. RESULTS: There is still no consensus on what the best nutritional strategy or ideal dietary prescription is, and individuality is necessary. In any case, these references suggest that Mediterranean Diet may of greater interest for the management of T2DM, with the following recommended dietary prescription: 40-50% carbohydrates; 15-25% proteins; 25-35% fats (<7% saturated, 10% polyunsaturated, and 10% monounsaturated); at least 14 g of fiber for every 1000 kcal consumed; and <2300 mg sodium. CONCLUSIONS: Individuality is the gold standard for dietary prescriptions, however, the Mediterranean diet with low levels of carbohydrates and fats seems to be the most promising strategy for the management of T2DM.

Pathophysiological effects of SARS-CoV-2 infection on the cardiovascular system and its clinical manifestations-a mini review.

Coronavirus disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 may have a mild presentation, with few symptoms, or progress to a severe condition, characterized by generalized inflammation, systemic microvascular involvement, coagulopathy, and pulmonary and cardiovascular complications. Men present with more severe symptoms than women, especially men who are older and who present with comorbidities such as hypertension, diabetes mellitus, and a history of atherosclerotic diseases. Owing to its association with endothelial dysfunction, inflammation, thrombosis, and microvascular obstruction, SARS-CoV-2 infection can cause lesions in several organs, including the myocardium and the coronary arterial bed, which can result in clinical manifestations involving the cardiovascular system. In this mini review, we summarize the effects of SARS-CoV-2 infection on the cardiovascular system in both children and adults and characterize the various clinical manifestations associated with this disease.

The Role of Heart Rate Variability (HRV) in Different Hypertensive Syndromes.

Cardiac innervation by the parasympathetic nervous system (PNS) and the sympathetic nervous system (SNS) modulates the heart rate (HR) (chronotropic activity) and the contraction of the cardiac muscle (inotropic activity). The peripheral vasculature is controlled only by the SNS, which is responsible for peripheral vascular resistance. This also mediates the baroreceptor reflex (BR), which in turn mediates blood pressure (BP). Hypertension (HTN) and the autonomic nervous system (ANS) are closely related, such that derangements can lead to vasomotor impairments and several comorbidities, including obesity, hypertension, resistant hypertension, and chronic kidney disease. Autonomic dysfunction is also associated with functional and structural changes in target organs (heart, brain, kidneys, and blood vessels), increasing cardiovascular risk. Heart rate variability (HRV) is a method of assessing cardiac autonomic modulation. This tool has been used for clinical evaluation and to address the effect of therapeutic interventions. The present review aims (a) to approach the heart rate (HR) as a CV risk factor in hypertensive patients; (b) to analyze the heart rate variability (HRV) as a "tool" to estimate the individual risk stratum for Pre-HTN (P-HTN), Controlled-HTN (C-HTN), Resistant and Refractory HTN (R-HTN and Rf-HTN, respectively), and hypertensive patients with chronic renal disease (HTN+CKD).

Cardiovascular Autonomic Responses to Aerobic, Resistance and Combined Exercises in Resistance Hypertensive Patients.

Here, we report the acute effects of aerobic (AER), resistance (RES), and combined (COM) exercises on blood pressure, central blood pressure and augmentation index, hemodynamic parameters, and autonomic modulation of resistant (RH) and nonresistant hypertensive (NON-RH) subjects. Twenty participants (10 RH and 10 NON-RH) performed three exercise sessions (i.e., AER, RES, and COM) and a control session. Hemodynamic (Finometer®, Beatscope), office blood pressure (BP), and autonomic variables (accessed through spectral analysis of the pulse-to-pulse BP signal, in the time and frequency domain-Fast Fourrier Transform) were assessed before (T0), one-hour (T1), and twenty-four (T2) hours after each experimental session. There were no changes in office BP, pulse wave behavior, and hemodynamic parameters after (T0 and T1) exercise sessions. However, AER and COM exercises significantly reduced sympathetic modulation in RH patients. It is worth mentioning that more significant changes in sympathetic modulation were observed after AER as compared to COM exercise. These findings suggest that office blood pressure, arterial stiffness, and hemodynamic parameters returned to baseline levels in the first hour and remained stable in the 24 hours after the all-exercise sessions. Notably, our findings bring new light to the effects of exercise on RH, indicating that RH patients show different autonomic responses to exercise compared to NON-RH patients. This trial is registered with trial registration number NCT02987452.

Pseudo and resistant hypertension: A chaotic perspective.

Systemic blood pressure (BP) may oscillate for homeostatic needs (equilibrium by constancy) or just as shifts in other intrinsic and extrinsic variables known as allostatic changes. This transitory pressure often rises alerts physicians to out-of-control hypertension or even hypertensive crisis. There is a very complex theory underlying these stochastic phenomena, which physicists and mathematicians translate into a single word: chaos. These changes happen according to a stochastic probabilistic pattern that presumes chaotic but somewhat predictable and nonlinear modeling of BP-related dynamics as a mathematical approach. Based on the chaos theory, small changes at the initial BP (baseline overtime) values could disturb the homeostasis leading to extreme BP chaotic shifts. These almost insignificant oscillations may also affect other variables and systems, leading to the misdiagnosis of hypertension, "out-of-control" BP levels, and resistant hypertension (RHT). Thus, these unpredictable and transient increases in BP values may be improperly diagnosed as the white coat and masked or resistant hypertension. Indeed, the interference of the chaos in any phenotype of (true or false) hard to control BP is not considered in clinical settings. This review provides some basic concepts on chaos theory and BP regulation. Besides pseudoresistant hypertension (lack of adherence, circadian variations, and others (white-coat, masked, early morning effects or hypertension), chaotic changes can be responsible for out-of-control hypertension.

Hypertension telemonitoring and home-based physical training programs.

PURPOSE: Hypertensive patients with access to telemedicine can receive telemonitoring of blood pressure and cardiovascular risk factors such as sedentary lifestyle, diet, and remote supervision of treatment compliance. Faced with this challenge, electronic devices for telemonitoring of BP have gained space. They have shown to be effective in the follow-up of hypertensive patients and assist in the adherence and control of associated risk factors such as physical inactivity and obesity. MATERIALS AND METHODS: Narrative Review. RESULTS: The use of advanced smartwatches, smartphone apps, and online software for monitoring physical activity is increasingly common. Electronic equipment is briefly presented here as a support for better addressing some cardiovascular variables. Using various automated feedback services with a follow-up multidisciplinary clinical team is the ideal strategy. CONCLUSION: Mobile health can improve risk factors and health status, particularly for hypertensive patients, improving access to cardiac rehabilitation and reducing the cost.

Effects of Anti-TNF alpha Therapy on Blood Pressure in Resistant Hypertensive Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Study. / Efeitos da Terapia com Anti-TNF alfa na Pressão Arterial em Pacientes com Hipertensão Resistente: Um Estudo Piloto Randomizado, Duplo-Cego e Controlado por Placebo.

BACKGROUND: The cytokine tumor necrosis factor-alpha (TNF-α) is elevated in resistant hypertension (RH), but the effects of a TNF-α inhibitor in this population is unknown. OBJECTIVE: The aim of this trial was to evaluate whether a single dose of infliximab controlled by placebo acutely reduces blood pressure (BP) in RH subjects. METHODS: A double-blind, placebo-controlled, crossover trial was conducted, and randomized RH subjects received either infliximab or placebo. The primary endpoint was the change in mean BP levels relative to the baseline immediately after the infusion obtained by continuously beat-to-beat non-invasive hemodynamic assessment. Secondary endpoints included changes in office, ambulatory and central BP measurements; endothelial function; and inflammatory biomarkers after 7 days. The level of significance accepted was alpha=0.05. RESULTS: Ten RH subjects were enrolled. The primary endpoint analysis showed an acute decrease in mean BP values (mean of differences ± standard deviation = -6.3 ± 7.2 mmHg, p=0.02) from baseline, after the application of infliximab compared with placebo. Diastolic BP levels (-4.9 ± 5.5 mmHg, p=0.02), but not systolic BP levels (-9.4 ± 19.7 mmHg, p=0.16), lowered after infliximab infusion. No further significant differences were identified in either the other hemodynamic parameters or in secondary endpoints, except for TNF-α levels, which increased continuously after infliximab infusion. No adverse events were reported during the protocol. CONCLUSIONS: A single-dose of infliximab decreased the mean and diastolic BP levels immediately after its infusion, when compared to the placebo in RH. The anti-TNF-α therapy was found to be safe and well-tolerated. The results of this proof-of-concept are hypothesis-generating and need to be further investigated. (Arq Bras Cardiol. 2021; 116(3):443-451).

FUNDAMENTO: A citocina fator de necrose tumoral alfa (TNF-α) é elevada na hipertensão resistente (HAR), mas os efeitos dos inibidores de TNF-α nessa população ainda são desconhecidos. OBJETIVOS: O objetivo deste estudo foi avaliar se uma única dose de infliximabe controlada por placebo reduz a pressão arterial (PA) de forma aguda em pacientes com HAR. MÉTODOS: Realizamos um estudo cruzado, randomizado, duplo-cego e controlado por placebo em que pacientes com HAR receberam infliximabe ou placebo. O desfecho primário foi a alteração dos níveis de PA média em relação ao basal imediatamente após a infusão, obtida por avaliação hemodinâmica não invasiva contínua, batimento a batimento. Os desfechos secundários incluíram alterações em medidas de PA central, ambulatorial e em consultório, na função endotelial, e nos biomarcadores inflamatórios após 7 dias. O nível de significância aceito foi alfa=0,05. RESULTADOS: Foram incluídos dez portadores de HAR. O resultado do desfecho primário demonstrou uma redução aguda dos níveis de PA média (média das diferenças ± desvio padrão = -6,3 ± 7,2 mmHg, p=0,02) em relação ao basal, após o uso de infliximabe, em comparação com o placebo. Os níveis de PA diastólica (-4,9 ± 5,5 mmHg, p=0,02), mas não os níveis de PA sistólica (-9,4 ± 19,7 mmHg, p=0,16), reduziram após a infusão de infliximabe. Não foram identificadas diferenças significativas nos demais parâmetros hemodinâmicos, nem nos resultados dos desfechos secundários, com exceção dos níveis de TNF-α, que aumentaram continuamente após o uso de infliximabe. Não foram relatados eventos adversos durante o protocolo. CONCLUSÕES: Uma dose única de infliximabe reduziu os níveis de PA média e diastólica imediatamente após sua infusão, em comparação com placebo em HAR. A terapia com anti-TNF-α foi considerada segura e bem tolerada. Os resultados desse estudo prova de conceito são geradores de hipótese e precisam ser investigados em maior detalhe. (Arq Bras Cardiol. 2021; 116(3):443-451).

Efeitos da Terapia com Anti-TNF alfa na Pressão Arterial em Pacientes com Hipertensão Resistente: Um Estudo Piloto Randomizado, Duplo-Cego e Controlado por Placebo / Effects of Anti-TNF alpha Therapy on Blood Pressure in Resistant Hypertensive Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

Resumo Fundamento: A citocina fator de necrose tumoral alfa (TNF-α) é elevada na hipertensão resistente (HAR), mas os efeitos dos inibidores de TNF-α nessa população ainda são desconhecidos. Objetivos: O objetivo deste estudo foi avaliar se uma única dose de infliximabe controlada por placebo reduz a pressão arterial (PA) de forma aguda em pacientes com HAR. Métodos: Realizamos um estudo cruzado, randomizado, duplo-cego e controlado por placebo em que pacientes com HAR receberam infliximabe ou placebo. O desfecho primário foi a alteração dos níveis de PA média em relação ao basal imediatamente após a infusão, obtida por avaliação hemodinâmica não invasiva contínua, batimento a batimento. Os desfechos secundários incluíram alterações em medidas de PA central, ambulatorial e em consultório, na função endotelial, e nos biomarcadores inflamatórios após 7 dias. O nível de significância aceito foi alfa=0,05. Resultados: Foram incluídos dez portadores de HAR. O resultado do desfecho primário demonstrou uma redução aguda dos níveis de PA média (média das diferenças ± desvio padrão = -6,3 ± 7,2 mmHg, p=0,02) em relação ao basal, após o uso de infliximabe, em comparação com o placebo. Os níveis de PA diastólica (-4,9 ± 5,5 mmHg, p=0,02), mas não os níveis de PA sistólica (-9,4 ± 19,7 mmHg, p=0,16), reduziram após a infusão de infliximabe. Não foram identificadas diferenças significativas nos demais parâmetros hemodinâmicos, nem nos resultados dos desfechos secundários, com exceção dos níveis de TNF-α, que aumentaram continuamente após o uso de infliximabe. Não foram relatados eventos adversos durante o protocolo. Conclusões: Uma dose única de infliximabe reduziu os níveis de PA média e diastólica imediatamente após sua infusão, em comparação com placebo em HAR. A terapia com anti-TNF-α foi considerada segura e bem tolerada. Os resultados desse estudo prova de conceito são geradores de hipótese e precisam ser investigados em maior detalhe. (Arq Bras Cardiol. 2021; 116(3):443-451)

Abstract Background: The cytokine tumor necrosis factor-alpha (TNF-α) is elevated in resistant hypertension (RH), but the effects of a TNF-α inhibitor in this population is unknown. Objective: The aim of this trial was to evaluate whether a single dose of infliximab controlled by placebo acutely reduces blood pressure (BP) in RH subjects. Methods: A double-blind, placebo-controlled, crossover trial was conducted, and randomized RH subjects received either infliximab or placebo. The primary endpoint was the change in mean BP levels relative to the baseline immediately after the infusion obtained by continuously beat-to-beat non-invasive hemodynamic assessment. Secondary endpoints included changes in office, ambulatory and central BP measurements; endothelial function; and inflammatory biomarkers after 7 days. The level of significance accepted was alpha=0.05. Results: Ten RH subjects were enrolled. The primary endpoint analysis showed an acute decrease in mean BP values (mean of differences ± standard deviation = -6.3 ± 7.2 mmHg, p=0.02) from baseline, after the application of infliximab compared with placebo. Diastolic BP levels (-4.9 ± 5.5 mmHg, p=0.02), but not systolic BP levels (-9.4 ± 19.7 mmHg, p=0.16), lowered after infliximab infusion. No further significant differences were identified in either the other hemodynamic parameters or in secondary endpoints, except for TNF-α levels, which increased continuously after infliximab infusion. No adverse events were reported during the protocol. Conclusions: A single-dose of infliximab decreased the mean and diastolic BP levels immediately after its infusion, when compared to the placebo in RH. The anti-TNF-α therapy was found to be safe and well-tolerated. The results of this proof-of-concept are hypothesis-generating and need to be further investigated. (Arq Bras Cardiol. 2021; 116(3):443-451)

Transcranial direct current stimulation modulates autonomic nervous system and reduces ambulatory blood pressure in hypertensives.

Purpose: Transcranial direct current stimulation (tDCS) seems to positively modulate the autonomic nervous system in different clinical conditions and healthy subjects; however, its effects on hypertensive (HTN) patients are not completely known. This study aimed to evaluate the effects of a tDCS or SHAM session (20 min) on blood pressure (BP) and autonomic variables of HTN patients.Materials and Methods: Subjects (n = 13) were randomly submitted to SHAM and tDCS sessions (1 week of washout). Hemodynamic and autonomic variables were measured at baseline, during, and immediately after tDCS or SHAM stimulation (Finometer®, Beatscope). Ambulatory BP measurement (ABPM) was evaluated after the experimental period.Results: Hemodynamic variables were not changed by tDCS, except for the fall in peripheral vascular resistance (Δ = -1696.51 ± 204.65 dyn.s/cm5). After the tDCS, sympathetic modulation was decreased (-61.47%), and vagal modulation was increased (+38.09%). Such acute autonomic changes may have evoked positive results observed in 24 hs-systolic blood pressure (Δ = -8.4 ± 6.2; P = .0022) and 24hs-diastolic blood pressure (Δ = -5.4 ± 4.2; P = .0010) in tDCS subjects compared with that in SHAM.Conclusion: These findings suggest that the tDCS could promote positive acute adjustments on cardiac autonomic control and reduced values on 24-hs BP of HTN patients. More than a proof-of-concept, these results may point out to the future, where brain stimulation (tDCS) can be used to HTN syndromes, such as refractory HTN.

Obstructive sleep apnea and ambulatory blood pressure monitoring: current evidence and research gaps.

Obstructive Sleep Apnea (OSA) is a common condition characterized by intermittent collapse of the upper airway during sleep, resulting in partial (hypopnoeas) and total obstructions (apneas). These respiratory events observed in OSA may trigger multiple pathways involved in the blood pressure (BP) instability during the night and potentially influencing daytime BP as well (carry-over effects). This review provides an update about the impact of OSA and its treatments on 24-h BP control. Overall, there is growing evidence suggest that OSA is associated with higher frequency of nondipping BP pattern and nocturnal hypertension in a dose-dependent manner. The presence of nondiping BP (especially the reverse pattern) is independently associated with OSA regardless of sleep-related symptoms suggesting a potential tool for screening OSA in patients with clinical indication for performing ABPM. Beyond dipping BP, preliminary evidence associated OSA with white-coat effect and higher frequency of masked hypertension and BP variability than the control group (no OSA). Unfortunately, most of the evidence on the evidence addressing the impact of OSA treatment on BP was limited to office measurements. In the last years, data from observational and randomized studies pointed that CPAP is able to promote 24-h BP decrease especially in patients with resistant and refractory hypertension. A randomized trial suggests that CPAP is able to decrease the rate of masked hypertension as compared to no treatment in patients with severe OSA. Interestingly, nondipping BP is a good predictor of BP response to CPAP making ABPM an interesting tool for better OSA management.

Sodium activates human monocytes via the NADPH oxidase and isolevuglandin formation.

AIMS: Prior studies have focused on the role of the kidney and vasculature in salt-induced modulation of blood pressure; however, recent data indicate that sodium accumulates in tissues and can activate immune cells. We sought to examine mechanisms by which salt causes activation of human monocytes both in vivo and in vitro. METHODS AND RESULTS: To study the effect of salt in human monocytes, monocytes were isolated from volunteers to perform several in vitro experiments. Exposure of human monocytes to elevated Na+ex vivo caused a co-ordinated response involving isolevuglandin (IsoLG)-adduct formation, acquisition of a dendritic cell (DC)-like morphology, expression of activation markers CD83 and CD16, and increased production of pro-inflammatory cytokines tumour necrosis factor-α, interleukin (IL)-6, and IL-1ß. High salt also caused a marked change in monocyte gene expression as detected by RNA sequencing and enhanced monocyte migration to the chemokine CC motif chemokine ligand 5. NADPH-oxidase inhibition attenuated monocyte activation and IsoLG-adduct formation. The increase in IsoLG-adducts correlated with risk factors including body mass index, pulse pressure. Monocytes exposed to high salt stimulated IL-17A production from autologous CD4+ and CD8+ T cells. In addition, to evaluate the effect of salt in vivo, monocytes and T cells isolated from humans were adoptively transferred to immunodeficient NSG mice. Salt feeding of humanized mice caused monocyte-dependent activation of human T cells reflected by proliferation and accumulation of T cells in the bone marrow. Moreover, we performed a cross-sectional study in 70 prehypertensive subjects. Blood was collected for flow cytometric analysis and 23Na magnetic resonance imaging was performed for tissue sodium measurements. Monocytes from humans with high skin Na+ exhibited increased IsoLG-adduct accumulation and CD83 expression. CONCLUSION: Human monocytes exhibit co-ordinated increases in parameters of activation, conversion to a DC-like phenotype and ability to activate T cells upon both in vitro and in vivo sodium exposure. The ability of monocytes to be activated by sodium is related to in vivo cardiovascular disease risk factors. We therefore propose that in addition to the kidney and vasculature, immune cells like monocytes convey salt-induced cardiovascular risk in humans.

A Novel Analysis via Micro-CT Imaging Indicates That Chemically Modified Tetracycline-3 (CMT-3) Inhibits Tooth Relapse after Orthodontic Movement: A Pilot Experimental Study.

OBJECTIVE: To evaluate the effect of chemically modified tetracycline-3 (CMT-3) and simvastatin on tooth relapse after orthodontic movement in rats using a novel analysis method employing high-resolution micro-CT (Micro-CT) images. In addition, the correlation between bone density and orthodontic relapse was also evaluated for each experimental group. METHODS: Forty adult male Wistar rats had stainless steel springs installed on their left upper first molars in order to generate tooth movement for 18 days. After this initial period, the animals were divided into three groups: (1) 30 mg/kg of CMT-3; (2) 5 mg/kg of simvastatin; and (3) 0.5% carboxymethylcellulose, and each group was treated for 20 days. Micro-CT images were analyzed (conventional method and 3D reconstruction) on the 7th and 18th days following spring fixation and finally, 20 days after treatment either with CMT-3 or simvastatin (38th day). Bone mineral density (BMD) of the mesial and distal roots of the upper first molar was also analyzed. RESULTS: The difference was statistically significant between the groups as to recurrence (p=0.048), and the post hoc test identified the value of p=0.007 between the control group and the CMT-3 group. Simvastatin was not able to inhibit tooth relapse. The bone mineral densities of both the mesial and distal roots were different between the three groups, after the 20th day of drug use (p=0001 and p < 0001). CONCLUSION: Our findings support the initial evidence that CMT-3 is able to prevent relapse after tooth movement. Future trials in humans should evaluate such treatment as a promising approach to preventing this common phenomenon. CLINICAL RELEVANCE: Considering the results obtained, CMT-3 can be used to avoid relapse after tooth movement.

Glycated hemoglobin correlates with arterial stiffness and endothelial dysfunction in patients with resistant hypertension and uncontrolled diabetes mellitus.

This study aimed to evaluate the effects of glycated hemoglobin (HbA1c ) on flow-mediated dilation, intima-media thickness, pulse wave velocity, and left ventricular mass index in patients with resistant hypertension (RHTN) comparing RHTN-controlled diabetes mellitus and RHTN-uncontrolled type 2 diabetes mellitus. Two groups were formed: HbA1c <7.0% (RHTN-controlled diabetes mellitus: n = 98) and HbA1c ≥7.0% (RHTN-uncontrolled diabetes mellitus: n = 122). Intima-media thickness and flow-mediated dilation were measured by high-resolution ultrasound, left ventricular mass index by echocardiography, and arterial stiffness by carotid-femoral pulse wave velocity. No differences in blood pressure levels were found between the groups but body mass index was higher in patients with RHTN-uncontrolled diabetes mellitus. Endothelial dysfunction and arterial stiffness were worse in patients with RHTN-uncontrolled diabetes mellitus. Intima-media thickness and left ventricular mass index measurements were similar between the groups. After adjustments, multiple linear regression analyses showed that HbA1c was an independent predictor of flow-mediated dilation and pulse wave velocity in all patients with RHTN. In conclusion, HbA1c may predict the grade of arterial stiffness and endothelial dysfunction in patients with RHTN, and superimposed uncontrolled diabetes mellitus implicates further impairment of vascular function.

Oral lichen planus and malignant transformation: The role of p16, Ki-67, Bub-3 and SOX4 in assessing precancerous potential.

The association of oral lichen planus (OLP) lesions with malignant transformation risk has remained a controversial topic and is of clinical importance. Therefore, the present study evaluated the expression levels of p16, Ki-67, budding uninhibited by benzimidazoles 3 (Bub-3) and sex-determining region Y-related high mobility group box 4 (SOX4), and their roles as precancerous biomarkers in OLP. A retrospective study was performed, in which tissue blocks of OLP, oral dysplasia (OD), cutaneous lichen planus (CLP) and oral fibrous hyperplasia (OFH) were used (n=120). A positivity index (PI) for p16, BUB3, Ki-67 and SOX4 expression was calculated in each group. The PI for p16 was 20.65% for OLP, 7.85% for OD, 86.59% for CLP and 11.8% for OFH, and the difference between these groups was statistically significant (P<0.001). PIs of Ki-67 were indicated as 11.6% for OLP, 14.4% for OD, 8.24% for CLP and 5.5% for OFH, and a statistically significant difference was observed between the groups (P<0.001). Notably, the expression levels of BUB3 were not statistically different among groups. The highest expression levels of SOX4 were identified in CLP (P<0.001 vs. OLP/CLP; P=0,001 vs. CLP/OD). The determined expression levels of p16 and Ki-67 suggest that specific OLP lesions may have an intermediate malignant potential and should be carefully followed up. The intense SOX4 staining in CLP indicated a different proliferation pattern of epithelium compared with oral mucosa cells. These findings suggest that SOX4 expression may also be associated with the different clinical courses of OLP and CLP.

Resistant Hypertension On Treatment (ResHypOT): sequential nephron blockade compared to dual blockade of the renin-angiotensin-aldosterone system plus bisoprolol in the treatment of resistant arterial hypertension - study protocol for a randomized controlled trial.

BACKGROUND: Resistant hypertension is characterized when the blood pressure (BP) remains above the recommended goal after taking three antihypertensive drugs with synergistic actions at their maximum recommended tolerated doses, preferably including a diuretic. Identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether acting on the control of intravascular volume or sodium balance, or acting on the effects of the renin-angiotensin-aldosterone system (RAAS) on the kidney. METHODS/DESIGN: This is a randomized, open-label, clinical trial is designed to compare sequential nephron blockade and its contribution to the intravascular volume component with dual blockade of the RAAS plus bisoprolol and the importance of serum renin in maintaining BP levels. The trial has two arms: sequential nephron blockade versus dual blockade of the RAAS (with an angiotensin converting enzyme (ACE) inhibitor plus a beta-blocker) both added-on to a thiazide diuretic, a calcium-channel blocker and an angiotensin receptor-1 blocker (ARB). Sequential nephron blockade consists in a progressive increase in sodium depletion using a thiazide diuretic, an aldosterone-receptor blocker, furosemide and, finally, amiloride. On the other hand, the dual blockade of the RAAS consists of the progressive addition of an ACE inhibitor until the maximum dose and then the administration of a beta-blocker until the maximum dose. The primary outcomes will be reductions in the systolic BP, diastolic BP, mean BP and pulse pressure (PP) after 20 weeks of treatment. The secondary outcomes will evaluate treatment safety and tolerability, biochemical changes, evaluation of renal function and recognition of hypotension (ambulatory BP monitoring (ABPM)). The sample size was calculated assuming an alpha error of 5% to reject the null hypothesis with a statistical power of 80% giving a total of 40 individuals per group. DISCUSSION: In recent years, the cost of resistant hypertension (RH) treatment has increased. Thus, identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether by acting on the control of intravascular volume or sodium balance, or by acting on the effects of the RAAS on the kidney. TRIAL REGISTRATION: Sequential Nephron Blockade vs. Dual Blockade Renin-angiotensin System + Bisoprolol in Resistant Arterial Hypertension (ResHypOT). ClinicalTrials.gov, ID: NCT02832973 . Registered on 14 July 2016. First received: 12 June 2016. Last updated: 18 July 2016.

The rs243866/243865 polymorphisms in MMP-2 gene and the relationship with BP control in obese resistant hypertensive subjects.

We sought to investigate whether the polymorphisms rs243865 (-1306C>T); rs243866 (-1575G>A) and rs2285053 (-735C>T) in metalloproteinases 2 - MMP-2 gene and rs17576 (Q279R), rs17577 (Q668R) and rs3918242 (-1562C>T) in MMP-9 gene are associated with clinical outcomes in obese resistant hypertensive (RH) subjects. One hundred and twenty RH were enrolled in this cross-sectional study and divided into obese (n=63) and non-obese (n=57) according to body mass index. Genotypes were determined by real-time PCR using TaqMan probes. We determined pulse wave velocity (PWV), microalbuminuria and left ventricular mass index (LVMI) to assess TODs. Obese and non-obese RH had similar allele, genotype and haplotype distributions for all polymorphisms assessed but obese RH subjects carrying the low frequency allele for SNPs in MMP-2 gene had higher ambulatory diastolic blood pressure. Also, PWV and LVMI were higher in subjects carrying the low frequency allele for SNPs in MMP-2 gene. Regarding MMP-9 gene, office diastolic BP levels were higher in the AA genotype individuals compared to the G allele group for rs17576 polymorphism, while the opposite was found regarding the microalbuminuria level. Independent multiple linear regression analyses revealed that both A allele for rs243865 and T allele for rs243866 in MMP-2 gene were associated with ambulatory diastolic levels in obese RH subjects, apart from potential confounders. Our study suggests that rs243866/rs243865 in the MMP-2 gene are related to BP levels in obese RH subjects, although TODs present in this population seem to be dependent of a combination of other factors besides the genetic polymorphisms.