The unfolded protein response transcription factor XBP1s ameliorates Alzheimer's disease by improving synaptic function and proteostasis.

Alteration in the buffering capacity of the proteostasis network is an emerging feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) is the main adaptive pathway to cope with protein folding stress at the ER. Inositol-requiring enzyme-1 (IRE1) operates as a central ER stress sensor, enabling the establishment of adaptive and repair programs through the control of the expression of the transcription factor X-box binding protein 1 (XBP1). To artificially enforce the adaptive capacity of the UPR in the AD brain, we developed strategies to express the active form of XBP1 in the brain. Overexpression of XBP1 in the nervous system using transgenic mice reduced the load of amyloid deposits and preserved synaptic and cognitive function. Moreover, local delivery of XBP1 into the hippocampus of an 5xFAD mice using adeno-associated vectors improved different AD features. XBP1 expression corrected a large proportion of the proteomic alterations observed in the AD model, restoring the levels of several synaptic proteins and factors involved in actin cytoskeleton regulation and axonal growth. Our results illustrate the therapeutic potential of targeting UPR-dependent gene expression programs as a strategy to ameliorate AD features and sustain synaptic function.

Intravenous Vitamin C as an Add-on Therapy for the Treatment of Sepsis in an Intensive Care Unit: A Prospective Cohort Study.

Background and Objectives: According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection". The increased presence of free radicals causes an increase in oxidative stress. Vitamin C is an essential water-soluble vitamin with antioxidant activity and immunoregulatory effects that plays a potential role in the treatment of bacterial infections. Our aim was to evaluate the effectiveness of adding vitamin C to the conventional treatment of sepsis to decrease its mortality rate. Materials and Methods: In a prospective cohort study, we included patients with a diagnosis of sepsis and a SOFA score ≥ 9 who were evaluated in an Intensive Care Unit at a secondary-care hospital. According to the intensive care specialist, they were treated using two different strategies: Group 1-patients with sepsis treated with conventional treatment without vitamin C; Group 2-patients with sepsis with the addition of vitamin C to conventional treatment. Results: We included 34 patients with sepsis. The incidence of mortality was 38%, and 47% of patients used vitamin C as an adjuvant to the basic treatment of sepsis. In the basal analyses, patients treated with use of vitamin C compared to patients treated without vitamin C required less use of glucocorticoids (75% vs. 100%, p = 0.039). At follow-up, patients treated without vitamin C had higher mortality than patients treated with vitamin C as an adjuvant for the treatment of sepsis (55.6% vs. 18.8%, p = 0.03). We observed that the use of vitamin C was a protective factor for mortality in patients with sepsis (RR: 0.54, 95% CI: 0.31-0.96, p = 0.03). Conclusions: The use of vitamin C as an adjuvant to treatment decreases the risk of mortality by 46% in patients with sepsis and SOFA ≥ 9 compared to patients treated without vitamin C as an adjuvant to sepsis.

Blood pressure telemonitoring and telemedicine, a Latin America perspective.

PURPOSE: To share a Latin-American perspective of the use of telemedicine, together with blood pressure measurements outside the medical office, as a potential contribution to improving access to the health system, diagnosis, adherence, and persistence in hypertension treatment. MATERIAL AND METHODS: A document settled by a Writing Group of Mexico Hypertension Experts Group, Interamerican Society of Hypertension, Epidemiology and Cardiovascular Prevention Council of the Interamerican Society of Cardiology, and National Cardiologist Association of Mexico. RESULTS: In almost all Latin American countries, the health sector faces two fundamental challenges: (1) ensure equitable access to quality care services in a growing population that faces an increase in the prevalence of chronic diseases, and (2) optimise the growing costs of health services, maintaining equity, accessibility, universality, and quality. Telehealth proposes an innovative approach to patient management, especially for chronic conditions, intending to provide remote consultation, education, and follow-up to achieve measurements and goals. It is a tool that promises to improve access, empower the patient, and somehow influence their behaviour about lifestyle changes, improving prevention and reducing complications of hypertension. The clinical practitioner has seen increased evidence that the use of out-of-office blood pressure (BP) measurement and telemedicine are helpful tools to keep patients and physicians in contact and promote better pharmacological adherence and BP control. A survey carried out by medical and scientific institutions showed that practitioners are up-to-date with telemedicine, had internet access, and had hardware availability. CONCLUSIONS: A transcendent issue is the need to make the population aware of the benefits of taking blood pressure to avoid complications of hypertension, and in this scenario, promote the creation of teleconsultation mechanisms for the follow-up of patients diagnosed with hypertension.

What is the context?In almost all Latin American countries, the health sector faces two fundamental challenges: (1) ensure equitable access to quality care services in a growing population that faces an increase in the prevalence of chronic diseases, and (2) optimise the growing costs of health services, maintaining equity, accessibility, universality, and quality.What is new?Telehealth proposes an innovative approach to patient management, especially for chronic conditions, intending to provide remote consultation, education, and follow-up to achieve measurements and goals. It is a tool that promises to improve access, empower the patient, and somehow influence their behaviour about lifestyle changes, improving prevention and reducing complications of hypertension.What is the impact?Needs are always infinite, and resources are finite, so according to the World Health Organisation (WHO), advances in electronic, information, and communication technology point to more significant equity in the provision of services, considering the effectiveness, possibility of refining the rationalisation of health spending, and improving health care for remote populations.A transcendent issue is the need to make the population aware of the benefits of taking blood pressure to avoid complications of hypertension, and in this scenario, promote the creation of teleconsultation mechanisms for the follow-up of patients diagnosed with hypertension.

Guselkumab for the treatment of patients with moderate-to-severe hidradenitis suppurativa: A phase 2 randomized study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that causes substantial physical, emotional and psychological burdens. Guselkumab, a monoclonal antibody that binds to the p19 subunit of interleukin-23, has demonstrated high levels of efficacy in the treatment of inflammatory diseases, including psoriasis and psoriatic arthritis. OBJECTIVE: To evaluate the effect of guselkumab on the treatment of HS, a phase 2, multicentre, randomized, placebo-controlled, double-blind, proof-of-concept study was conducted. METHODS: Patients ≥18 years of age with moderate-to-severe HS for ≥1 year were randomized to (1) guselkumab 200 mg by subcutaneous (SC) injection every 4 weeks (q4w) through Week 36 (guselkumab SC); (2) guselkumab 1200 mg intravenously (IV) q4w for 12 weeks, then switched to guselkumab 200 mg SC q4w from Weeks 12 through 36 (guselkumab IV); or (3) placebo for 12 weeks, with re-randomization to guselkumab 200 mg SC q4w at Weeks 16 through 36 (placebo → guselkumab 200 mg) or guselkumab 100 mg SC at Weeks 16, 20, 28 and 36 and placebo at Weeks 24 and 32 (placebo → guselkumab 100 mg). End points included HS clinical response (HiSCR) and patient-reported outcomes. RESULTS: Although guselkumab SC or guselkumab IV resulted in numerically higher HiSCR versus placebo at Week 16 (50.8%, 45.0%, 38.7%, respectively), statistical significance was not achieved. Numerically greater improvements in patient-reported outcomes were also observed for guselkumab SC and guselkumab IV versus placebo at Week 16. Through Week 40, no clear differences to suggest a dose response were observed for HiSCR and patient-reported outcomes. CONCLUSIONS: Despite modest improvements, the primary end point was not met and the overall findings do not support the efficacy of guselkumab in the treatment of HS. CLINICALTRIALS: gov: NCT03628924.

Percentage of change and increment of the glucose level after a normal oral tolerance curve between 24 and 28 weeks of pregnancy.

AIM: To determine the percentage of change and increment in glucose levels after a normal oral glucose tolerance test between 24 and 28 weeks of pregnancy. METHODS: We studied 3510 pregnant women who attended their obstetric delivery at a tertiary care hospital in Guadalajara, Mexico in 2018, according to characteristics and risk 1647 (47%) patients were screened for diabetes diagnosis using the oral glucose tolerance test, 501 patients reported normal values between their 24th and 28th week of pregnancy, only 400 patients had their fasting glucose level measured on the same day of their obstetric delivery, to be compared. RESULTS: Average age was 30 years, with an average of 25.3 weeks of pregnancy. The fasting serum glucose levels taken after 28 weeks of pregnancy and before the obstetrical delivery showed an increase of 1.1 mmol/L in women who develop gestational diabetes mellitus, in contrast to women who did not develop gestational diabetes mellitus after 28 weeks their blood glucose only increased on average 0.4 mmol/L. The incidence of gestational diabetes mellitus in the study population during 2018 was 32.7%. Patients who developed gestational diabetes mellitus after a normal oral glucose tolerance test had greater body mass index before the pregnancy and newborns had a higher weight than babies born to mothers without gestational diabetes mellitus. CONCLUSION: Changes in glucose levels after the oral tolerance test of normal glucose require strict monitoring, in that it was demonstrated that 3% of patients developed gestational diabetes mellitus after week 28 of gestation.

The Role of the Oxidative State and Innate Immunity Mediated by TLR7 and TLR9 in Lupus Nephritis.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) and is considered one of the leading causes of mortality. Multiple immunological pathways are involved in the pathogenesis of SLE, which makes it imperative to deepen our knowledge about this disease's immune-pathological complexity and explore new therapeutic targets. Since an altered redox state contributes to immune system dysregulation, this document briefly addresses the roles of oxidative stress (OS), oxidative DNA damage, antioxidant enzymes, mitochondrial function, and mitophagy in SLE and LN. Although adaptive immunity's participation in the development of autoimmunity is undeniable, increasing data emphasize the importance of innate immunity elements, particularly the Toll-like receptors (TLRs) that recognize nucleic acid ligands, in inflammatory and autoimmune diseases. Here, we discuss the intriguing roles of TLR7 and TLR9 in developing SLE and LN. Also included are the essential characteristics of conventional treatments and some other novel and little-explored alternatives that offer options to improve renal function in LN.

Machine Learning Techniques Based on Primary User Emulation Detection in Mobile Cognitive Radio Networks.

Mobile cognitive radio networks (MCRNs) have arisen as an alternative mobile communication because of the spectrum scarcity in actual mobile technologies such as 4G and 5G networks. MCRN uses the spectral holes of a primary user (PU) to transmit its signals. It is essential to detect the use of a radio spectrum frequency, which is where the spectrum sensing is used to detect the PU presence and avoid interferences. In this part of cognitive radio, a third user can affect the network by making an attack called primary user emulation (PUE), which can mimic the PU signal and obtain access to the frequency. In this paper, we applied machine learning techniques to the classification process. A support vector machine (SVM), random forest, and K-nearest neighbors (KNN) were used to detect the PUE in simulation and emulation experiments implemented on a software-defined radio (SDR) testbed, showing that the SVM technique detected the PUE and increased the probability of detection by 8% above the energy detector in low values of signal-to-noise ratio (SNR), being 5% above the KNN and random forest techniques in the experiments.

Single-cell RNA sequencing of psoriatic skin identifies pathogenic Tc17 cell subsets and reveals distinctions between CD8+ T cells in autoimmunity and cancer.

BACKGROUND: Psoriasis is an inflammatory, IL-17-driven skin disease in which autoantigen-induced CD8+ T cells have been identified as pathogenic drivers. OBJECTIVE: Our study focused on comprehensively characterizing the phenotypic variation of CD8+ T cells in psoriatic lesions. METHODS: We used single-cell RNA sequencing to compare CD8+ T-cell transcriptomic heterogeneity between psoriatic and healthy skin. RESULTS: We identified 11 transcriptionally diverse CD8+ T-cell subsets in psoriatic and healthy skin. Among several inflammatory subsets enriched in psoriatic skin, we observed 2 Tc17 cell subsets that were metabolically divergent, were developmentally related, and expressed CXCL13, which we found to be a biomarker of psoriasis severity and which achieved comparable or greater accuracy than IL17A in a support vector machine classifier of psoriasis and healthy transcriptomes. Despite high coinhibitory receptor expression in the Tc17 cell clusters, a comparison of these cells with melanoma-infiltrating CD8+ T cells revealed upregulated cytokine, cytolytic, and metabolic transcriptional activity in the psoriatic cells that differed from an exhaustion program. CONCLUSION: Using high-resolution single-cell profiling in tissue, we have uncovered the diverse landscape of CD8+ T cells in psoriatic and healthy skin, including 2 nonexhausted Tc17 cell subsets associated with disease severity.

Antiphospholipid Antibodies and Lipids in Hematological Malignancies.

One of the main groups of lipids is phospholipids, which are mainly involved in forming cell membranes. Neoplastic processes such as cell replication have increased lipid synthesis, making tumor cells dependent on this synthesis to maintain their requirements. Antiphospholipid antibodies attack phospholipids in the cell membranes. Three main types of antiphospholipid antibodies are recognized: anti-ß2 glycoprotein I (anti-ß2GP-I), anticardiolipin (aCL), and lupus anticoagulant (LA). These types of antibodies have been proven to be present in hematological neoplasms, particularly in LH and NHL. This review on antiphospholipid antibodies in hematological neoplasms describes their clinical relationship as future implications at the prognostic level for survival and even treatment.

The Influence of the Severity of Early Chronic Kidney Disease on Oxidative Stress in Patients with and without Type 2 Diabetes Mellitus.

Early Chronic Kidney Disease (CKD) is a condition that tends to progress to End-Stage Kidney Disease (ESKD). Early diagnosis of kidney disease in the early stages can reduce complications. Alterations in renal function represent a complication of diabetes mellitus (DM). The mechanisms underlying the progression of CKD in diabetes could be associated with oxidative and inflammatory processes. This study aimed to evaluate the state of inflammation and oxidative stress (OS) on the progression of CKD in the early stages in patients with and without type 2 diabetes mellitus (T2DM). An analytical cross-sectional study was carried out in patients with CKD in early stages (1, 2, 3) with and without T2DM. The ELISA method determined the expression of pro-inflammatory cytokines IL-6 and TNF-α as well as lipoperoxides (LPO), nitric oxide (NO), and superoxide dismutase activity (SOD). Colorimetric methods determined glutathione peroxidase (GPx) and total antioxidant capacity (TAC). Patients with CKD and T2DM had significantly decreased antioxidant defenses for SOD (p < 0.01), GPx (p < 0.01), and TAC (p < 0.01) compared to patients without T2DM. Consequently, patients with T2DM had higher concentrations of oxidant markers, NO (p < 0.01), inflammation markers, IL-6 (p < 0.01), and TNF-α than patients without T2DM. CKD stages were not related to oxidative, antioxidant, and inflammatory marker outcomes in T2DM patients. Patients without T2DM presented an increase in SOD (p = 0.04) and a decrease in NO (p < 0.01) when the stage of CKD increased. In conclusion, patients with T2DM present higher levels of oxidative and inflammatory markers accompanied by a decrease in antioxidant defense. However, these oxidative status markers were associated with CKD stage progression in patients without T2DM. Thus, NO and SOD markers could help detect the early stages of CKD in patients who have not yet developed metabolic comorbidities such as T2DM.

Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.

BACKGROUND: Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A1c (HbA1c) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control. METHODS: This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952. FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66·2 years [SD 6·5], median HbA1c 7·2% [IQR 6·6-8·1], 4589 [46·3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5·4 years (IQR 5·1-5·9), the primary composite outcome occurred in 594 (12·0%) participants at an incidence rate of 2·4 per 100 person-years in the dulaglutide group and in 663 (13·4%) participants at an incidence rate of 2·7 per 100 person-years in the placebo group (hazard ratio [HR] 0·88, 95% CI 0·79-0·99; p=0·026). All-cause mortality did not differ between groups (536 [10·8%] in the dulaglutide group vs 592 [12·0%] in the placebo group; HR 0·90, 95% CI 0·80-1·01; p=0·067). 2347 (47·4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34·1%) participants assigned to placebo (p<0·0001). INTERPRETATION: Dulaglutide could be considered for the management of glycaemic control in middle-aged and older people with type 2 diabetes with either previous cardiovascular disease or cardiovascular risk factors. FUNDING: Eli Lilly and Company.

Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial.

BACKGROUND: Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease. METHODS: REWIND was a multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes), secondary outcomes (including a composite microvascular outcome), and safety outcomes of this trial have been reported elsewhere. In this exploratory analysis, we investigate the renal component of the composite microvascular outcome, defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01394952. FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). At baseline, 791 (7·9%) had macroalbuminuria and mean eGFR was 76·9 mL/min per 1·73 m2 (SD 22·7). During a median follow-up of 5·4 years (IQR 5·1-5·9) comprising 51 820 person-years, the renal outcome developed in 848 (17·1%) participants at an incidence rate of 3·5 per 100 person-years in the dulaglutide group and in 970 (19·6%) participants at an incidence rate of 4·1 per 100 person-years in the placebo group (hazard ratio [HR] 0·85, 95% CI 0·77-0·93; p=0·0004). The clearest effect was for new macroalbuminuria (HR 0·77, 95% CI 0·68-0·87; p<0·0001), with HRs of 0·89 (0·78-1·01; p=0·066) for sustained decline in eGFR of 30% or more and 0·75 (0·39-1·44; p=0·39) for chronic renal replacement therapy. INTERPRETATION: Long-term use of dulaglutide was associated with reduced composite renal outcomes in people with type 2 diabetes. FUNDING: Eli Lilly and Company.

Total cardiovascular or fatal events in people with type 2 diabetes and cardiovascular risk factors treated with dulaglutide in the REWIND trail: a post hoc analysis.

BACKGROUND: The Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) double blind randomized trial demonstrated that weekly subcutaneous dulaglutide 1.5 mg, a glucagon like peptide-1 receptor agonist, versus matched placebo reduced the first outcome of major adverse cardiovascular event (MACE), cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (594 versus 663 events) in 9901 persons with type 2 diabetes and either chronic cardiovascular disease or risk factors, and followed during 5.4 years. These findings were based on a time-to-first-event analysis and preclude relevant information on the burden of total major events occurring during the trial. This analysis reports on the total cardiovascular or fatal events in the REWIND participants METHODS: We compared the total incidence of MACE or non-cardiovascular deaths, and the total incidence of expanded MACE (MACE, unstable angina, heart failure or revascularization) or non-cardiovascular deaths between participants randomized to dulaglutide and those randomized to placebo. Incidences were expressed as number per 1000 person-years. Hazard ratios (HR) were calculated using the conditional time gap and proportional means models. RESULTS: Participants had a mean age of 66.2 years, 46.3% were women and 31% had previous cardiovascular disease. During the trial there were 1972 MACE or non-cardiovascular deaths and 3673 expanded MACE or non-cardiovascular deaths. The incidence of total MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 35.8 and 40.3 per 1000 person-years, respectively [absolute reduction = 4.5 per 1000 person-years; conditional time gap HR 0.90 (95% CI, 0.82-0.98) p = 0.020, and proportional means HR 0.89 (95% CI, 0.80-0.98) p = 0.022]. The incidence of total expanded MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 67.1 and 74.7 per 1000 person-years, respectively [absolute reduction = 7.6 per 1000 person-years; conditional time gap HR 0.93 (95% CI, 0.87-0.99) p = 0.023, and proportional means HR 0.90 (95% CI, 0.82-0.99) p = 0.028]. CONCLUSIONS: These findings suggest that weekly subcutaneous dulaglutide reduced total cardiovascular or fatal event burden in people with type 2 diabetes at moderate cardiovascular risk. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gouv . Unique Identifier NCT01394952).

Aortic stiffness and central hemodynamics in treatment-naïve HIV infection: a cross-sectional study.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with a greater risk of cardiovascular disease (CVD). HIV infection causes a chronic inflammatory state and increases oxidative stress which can cause endothelial dysfunction and arterial stiffness. Aortic stiffness measured by carotid femoral-pulse wave velocity (cfPWV) and central hemodynamics are independent cardiovascular risk factors and have the prognostic ability for CVD. We assessed cfPWV and central hemodynamics in young individuals with recent HIV infection diagnosis and without antiretroviral therapy. We hypothesized that individuals living with HIV would present greater cfPWV and central hemodynamics (central systolic blood pressure and pulse pressure) compared to uninfected controls. METHODS: We recruited 51 treatment-naïve individuals living with HIV (HIV(+)) without previous CVD and 51 age- and sex-matched controls (HIV negative (-)). We evaluated traditional CVD risk factors including metabolic profile, blood pressure (BP), smoking, HIV viral load, and CD4+ T-cells count. Arterial stiffness and central hemodynamics were evaluated by cfPWV, central systolic BP, and central pulse pressure (cPP) via applanation tonometry. RESULTS: HIV(+) individuals presented a greater prevalence of smoking, reduced high-density lipoprotein cholesterol, and body mass index. 65.9% of HIV(+) individuals exhibited lymphocyte CD4+ T-cells count < 500 cells/µL. There was no difference in brachial or central BP between groups; however, HIV(+) individuals showed significantly lower cPP. We observed a greater cfPWV (mean difference = 0.5 m/s; p < 0.01) in HIV(+) compared to controls, even after adjusting for heart rate, mean arterial pressure and smoking. CONCLUSION: In the early stages of infection, non-treated HIV individuals present a greater prevalence of traditional CVD risk factors, arterial stiffness, and normal or in some cases central hemodynamics.

Rényi Entropy-Based Spectrum Sensing in Mobile Cognitive Radio Networks Using Software Defined Radio.

A very important task in Mobile Cognitive Radio Networks (MCRN) is to ensure that the system releases a given frequency when a Primary User (PU) is present, by maintaining the principle to not interfere with its activity within a cognitive radio system. Afterwards, a cognitive protocol must be set in order to change to another frequency channel that is available or shut down the service if there are no free channels to be found. The system must sense the frequency spectrum constantly through the energy detection method which is the most commonly used. However, this analysis takes place in the time domain and signals cannot be easily identified due to changes in modulation, power and distance from mobile users. The proposed system works with Gaussian Minimum Shift Keying (GMSK) and Orthogonal Frequency Division Multiplexing (OFDM) for systems from Global System for Mobile Communication (GSM) to 5G systems, the signals are analyzed in the frequency domain and the Rényi-Entropy method is used as a tool to distinguish the noise and the PU signal without prior knowledge of its features. The main contribution of this research is that uses a Software Defined Radio (SDR) system to implement a MCRN in order to measure the behavior of Primary and Secondary signals in both time and frequency using GNURadio and OpenBTS as software tools to allow a phone call service between two Secondary Users (SU). This allows to extract experimental results that are compared with simulations and theory using Rényi-entropy to detect signals from SU in GMSK and OFDM systems. It is concluded that the Rényi-Entropy detector has a higher performance than the conventional energy detector in the Additive White Gaussian Noise (AWGN) and Rayleigh channels. The system increases the detection probability (PD) to over 96% with a Signal to Noise Ratio (SNR) of 10dB and starting 5 dB below energy sensing levels.

Effect of green tea extract on arterial stiffness, lipid profile and sRAGE in patients with type 2 diabetes mellitus: a randomised, double-blind, placebo-controlled trial.

Type 2 diabetes mellitus (T2DM) is associated with premature atherosclerosis and arterial stiffening due to the accumulation of advanced glycation end-products in vessel walls. Green tea polyphenols are considered cardio-protective substances. In this randomised double-blind placebo-controlled trial (NCT02627898), we evaluated the effect of Green tea extract on arterial stiffness parameters, lipids, body composition and sRAGE levels. Twenty normotensive patients with T2DM treated with the standard therapy and statins, mean age 53.2 ± 9.4 years and mean BMI 30.1 ± 4.5 kg/m2, were randomised to receive a daily dose of 400 mg of green tea extract (polyphenols ≥90%, EGCG ≥45%) or placebo for 12 weeks. Compared to placebo, administration of green tea extract decreased central augmentation index (-3.05 ± 10.8% vs. 6.7 ± 0.1%, p = .04). These findings suggest that green tea extract could be used as an adjunct to the standard therapy to improve arterial stiffness in T2DM.

Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide.

The aim was to determine the effects of dulaglutide, a synthetic once-weekly, injectable human glucagon-like peptide 1 analogue that lowers blood glucose, body weight, appetite and blood pressure, on cardiovascular outcomes. People with type 2 diabetes, aged ≥50 years, with glycated haemoglobin (HbA1c) ≤9.5%, and either a previous cardiovascular event, evidence of cardiovascular disease or ≥2 cardiovascular risk factors were randomly allocated to a weekly subcutaneous injection of either dulaglutide (1.5 mg) or placebo and followed within the ongoing Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial every 3 to 6 months. The primary cardiovascular outcome is the first occurrence of the composite of cardiovascular death or non-fatal myocardial infarction or non-fatal stroke. Secondary outcomes include each component of the primary composite cardiovascular outcome, a composite clinical microvascular outcome comprising retinal or renal disease, hospitalization for unstable angina, heart failure requiring hospitalization or an urgent heart failure visit, and all-cause mortality. Follow-up will continue until the accrual of 1200 confirmed primary outcomes. Recruitment of 9901 participants (mean age 66 years, 46% women) occurred in 370 sites located in 24 countries over a period of 2 years. The mean duration of diabetes was 10 years, mean baseline HbA1c was 7.3%, and 31% had prior cardiovascular disease. The REWIND trial's international scope, high proportion of women, high proportion of people without prior cardiovascular disease and inclusion of participants whose mean baseline HbA1c was 7.3% suggests that its cardiovascular and safety findings will be directly relevant to the typical middle-aged patient seen in general practice throughout the world.

[Reliability of an automatic monitor for blood pressure measurement]. / Confiabilidad de un monitor automatizado para la medición de la presión arterial.

Background A correct blood pressure (BP) measurement is essential for the diagnosis and control of high BP. AIM: To evaluate the agreement and repeatability of BP measurements with the OMRON HEM-7320-LA device compared to a mercury sphygmomanometer. MATERIAL AND METHODS: A cross-sectional study comparing BP measurements made by two randomly selected trained nurses and an automatic oscillometric device. The mercurial sphygmomanometer was connected to the automated device via a "T" type connector and a dual-head stethoscope was used, allowing simultaneous measurements. The results were analyzed with one-factor analysis of variance, Bland-Altman's test, repeatability coefficient (RC), and intra-class correlation coefficient (ICC). RESULTS: Forty-nine participants aged 56 ± 19 years were included. Nineteen had hypertension (38%). We did not observe a significant difference in either systolic (SBP) or diastolic blood pressure (DBP) pressure measurements between the observers and the device. The mean difference was -0.09 mmHg (95% confidence intervals (CI)-0.9 to 0.7) for SBP and -0.9 mmHg (95% CI -1.7 to -0.13) for DBP. The RC for SBP (6.2, 5.2 and 5.8 mmHg) and DBP (4.7, 4.2 y 5.2 mmHg) was similar between the observers and the device. The ICC for SBP was 0.990 (95% CI 0.983 to 0.995, p < 0.01) and 0.986 (95% CI 0.977 to 0.991, p < 0.01) for DBP. CONCLUSIONS: There was a high level of agreement and similar measurement repeatability in the measurements performed by the automatic device and the mercurial sphygmomanometer. No differences in BP measurements were observed.

Identification of beta-Lactamases and beta-Lactam-Related Proteins in Human Pathogenic Bacteria using a Computational Search Approach.

A systematic analysis of beta-lactamases based on comparative proteomics has not been performed thus far. In this report, we searched for the presence of beta-lactam-related proteins in 591 bacterial proteomes belonging to 52 species that are pathogenic to humans. The amino acid sequences for 19 different types of beta-lactamases (ACT, CARB, CifA, CMY, CTX, FOX, GES, GOB, IMP, IND, KPC, LEN, OKP, OXA, OXY, SHV, TEM, NDM, and VIM) were obtained from the ARG-ANNOT database and were used to construct 19 HMM profiles, which were used to identify potential beta-lactamases in the completely sequenced bacterial proteomes. A total of 2877 matches that included the word "beta-lactamase" and/or "penicillin" in the functional annotation and/or in any of its regions were obtained. These enzymes were mainly described as "penicillin-binding proteins," "beta-lactamases," and "metallo-beta-lactamases" and were observed in 47 of the 52 species studied. In addition, proteins classified as "beta-lactamases" were observed in 39 of the species included. A positive correlation between the number of beta-lactam-related proteins per species and the proteome size was observed (R 0.78, P < 0.00001). This correlation partially explains the high presence of beta-lactam-related proteins in large proteomes, such as Nocardia brasiliensis, Bacillus anthracis, and Mycobacterium tuberculosis, along with their absence in small proteomes, such as Chlamydia spp. and Mycoplasma spp. We detected only five types of beta-lactamases (TEM, SHV, CTX, IMP, and OXA) and other related proteins in particular species that corresponded with those reported in the literature. We additionally detected other potential species-specific beta-lactamases that have not yet been reported. In the future, better results will be achieved due to more accurate sequence annotations and a greater number of sequenced genomes.

Effect of necrosectomy and vacuum-assisted closure (VAC) on mitochondrial function and oxidative stress markers in severe acute pancreatitis.

BACKGROUND: Severe acute pancreatitis (SAP) is associated with high morbidity and mortality. OBJECTIVE: To evaluate whether necrosectomy, alone or combined with vacuum-assisted closure (VAC), has any additional beneficial effects on mitochondrial function and/or oxidative stress markers in SAP. METHODS: Patients with SAP, APACHE II score > 8, and inadequate response to management in an intensive care unit were included in a prospective observational study. Sixteen underwent necrosectomy and 24 underwent necrosectomy plus VAC every 48 h. Patients were then categorized as survivors or deceased. Submitochondrial membrane fluidity of platelets and F0F1-ATPase hydrolysis were measured to represent mitochondrial function. Oxidative/nitrosative stress was measured using lipoperoxides (LPOs), nitric oxide (NO), erythrocyte membrane fluidity, and total antioxidant capacity (TAC). RESULTS: Membrane fluidity in submitochondrial particles of platelets remained significantly increased throughout the study, and then eventually rised in deceased patients managed with necrosectomy + VAC vs. survivors (p < 0.041). Hydrolysis was significantly increased from baseline to endpoint in all patients, predominating in those who died after management with necrosectomy (p < 0.03). LPO increased in all patients, and necrosectomy was more efficient for the eventual decrease in survivors (p < 0.039). NO was found to be increased for the baseline-endpoint result among both survivors and deceased patients with both management options. Erythrocyte membrane fluidity was increased in survivors managed with necrosectomy + VAC, and eventually returned to normal (p < 0.045). TAC was found to be consumed in all patients for the duration of the study. CONCLUSIONS: Mitochondrial dysfunction and oxidative/ nitrosative stress with significant systemic antioxidant consumption were found. Necrosectomy was more efficient and better cleared LPOs. Necrosectomy + VAC improved erythrocyte membrane fluidity and increased survival.