Exploring Inflammatory Asthma Phenotypes: Proteomic Signatures in Serum and Induced Sputum.

Asthma drug responses may differ due to inflammatory mechanisms triggered by the immune cells in the pulmonary microenvironment. Thus, asthma phenotyping based on the local inflammatory profile may aid in treatment definition and the identification of new therapeutic targets. Here, we investigated protein profiles of induced sputum and serum from asthma patients classified into eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic asthma, according to inflammatory phenotypes. Proteomic analyses were performed using an ultra-performance liquid chromatography (ultra-HPLC) system coupled to the Q Exactive Hybrid Quadrupole Orbitrap Mass Spectrometer. Fifty-two (52) proteins showed significant differences in induced sputum among the groups, while only 12 were altered in patients' sera. Five proteins in the induced sputum were able to discriminate all phenotypic groups, while four proteins in the serum could differentiate all except the neutrophilic from the paucigranulocytic inflammatory pattern. This is the first report on comparative proteomics of inflammatory asthma phenotypes in both sputum and serum samples. We have identified a potential five-biomarker panel that may be able to discriminate all four inflammatory phenotypes in sputum. These findings not only provide insights into potential therapeutic targets but also emphasize the potential for personalized treatment approaches in asthma management.

Salivary SARS-CoV-2 RNA for diagnosis of COVID-19 patients: a systematic revisew and meta-analysis of diagnostic accuracy.

Accurate, self-collected, and non-invasive diagnostics are critical to perform mass-screening diagnostic tests for COVID-19. This systematic review with meta-analysis evaluated the accuracy, sensitivity, and specificity of salivary diagnostics for COVID-19 based on SARS-CoV-2 RNA compared with the current reference tests using a nasopharyngeal swab (NPS) and/or oropharyngeal swab (OPS). An electronic search was performed in seven databases to find COVID-19 diagnostic studies simultaneously using saliva and NPS/OPS tests to detect SARS-CoV-2 by RT-PCR. The search resulted in 10,902 records, of which 44 studies were considered eligible. The total sample consisted of 14,043 participants from 21 countries. The accuracy, specificity, and sensitivity for saliva compared with the NPS/OPS was 94.3% (95%CI= 92.1;95.9), 96.4% (95%CI= 96.1;96.7), and 89.2% (95%CI= 85.5;92.0), respectively. Besides, the sensitivity of NPS/OPS was 90.3% (95%CI= 86.4;93.2) and saliva was 86.4% (95%CI= 82.1;89.8) compared to the combination of saliva and NPS/OPS as the gold standard. These findings suggest a similarity in SARS-CoV-2 RNA detection between NPS/OPS swabs and saliva, and the association of both testing approaches as a reference standard can increase by 3.6% the SARS-CoV-2 detection compared with NPS/OPS alone. This study supports saliva as an attractive alternative for diagnostic platforms to provide a non-invasive detection of SARS-CoV-2.

Salivary ATR-FTIR Spectroscopy Coupled with Support Vector Machine Classification for Screening of Type 2 Diabetes Mellitus.

The blood diagnosis of diabetes mellitus (DM) is highly accurate; however, it is an invasive, high-cost, and painful procedure. In this context, the combination of ATR-FTIR spectroscopy and machine learning techniques in other biological samples has been used as an alternative tool to develop a non-invasive, fast, inexpensive, and label-free diagnostic or screening platform for several diseases, including DM. In this study, we used the ATR-FTIR tool associated with linear discriminant analysis (LDA) and a support vector machine (SVM) classifier in order to identify changes in salivary components to be used as alternative biomarkers for the diagnosis of type 2 DM. The band area values of 2962 cm-1, 1641 cm-1, and 1073 cm-1 were higher in type 2 diabetic patients than in non-diabetic subjects. The best classification of salivary infrared spectra was by SVM, showing a sensitivity of 93.3% (42/45), specificity of 74% (17/23), and accuracy of 87% between non-diabetic subjects and uncontrolled type 2 DM patients. The SHAP features of infrared spectra indicate the main salivary vibrational modes of lipids and proteins that are responsible for discriminating DM patients. In summary, these data highlight the potential of ATR-FTIR platforms coupled with machine learning as a reagent-free, non-invasive, and highly sensitive tool for screening and monitoring diabetic patients.

Salivary Detection of Zika Virus Infection Using ATR-FTIR Spectroscopy Coupled with Machine Learning Algorithms and Univariate Analysis: A Proof-of-Concept Animal Study.

Zika virus (ZIKV) diagnosis is currently performed through an invasive, painful, and costly procedure using molecular biology. Consequently, the search for a non-invasive, more cost-effective, reagent-free, and sustainable method for ZIKV diagnosis is of great relevance. It is critical to prepare a global strategy for the next ZIKV outbreak given its devastating consequences, particularly in pregnant women. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy has been used to discriminate systemic diseases using saliva; however, the salivary diagnostic application in viral diseases is unknown. To test this hypothesis, we intradermally challenged interferon-gamma gene knockout C57/BL6 mice with ZIKV (50 µL,105 FFU, n = 7) or vehicle (50 µL, n = 8). Saliva samples were collected on day three (due to the peak of viremia) and the spleen was also harvested. Changes in the salivary spectral profile were analyzed by Student's t test (p < 0.05), multivariate analysis, and the diagnostic capacity by ROC curve. ZIKV infection was confirmed by real-time PCR of the spleen sample. The infrared spectroscopy coupled with univariate analysis suggested the vibrational mode at 1547 cm-1 as a potential candidate to discriminate ZIKV and control salivary samples. Three PCs explained 93.2% of the cumulative variance in PCA analysis and the spectrochemical analysis with LDA achieved an accuracy of 93.3%, with a specificity of 87.5% and sensitivity of 100%. The LDA-SVM analysis showed 100% discrimination between both classes. Our results suggest that ATR-FTIR applied to saliva might have high accuracy in ZIKV diagnosis with potential as a non-invasive and cost-effective diagnostic tool.

One-Year Update on Salivary Diagnostic of COVID-19.

Background: Coronavirus disease 2019 (COVID-19) is a global health problem, which is challenging healthcare worldwide. In this critical review, we discussed the advantages and limitations in the implementation of salivary diagnostic platforms of COVID-19. The diagnostic test of COVID-19 by invasive nasopharyngeal collection is uncomfortable for patients and requires specialized training of healthcare professionals in order to obtain an appropriate collection of samples. Additionally, these professionals are in close contact with infected patients or suspected cases of COVID-19, leading to an increased contamination risk for frontline healthcare workers. Although there is a colossal demand for novel diagnostic platforms with non-invasive and self-collection samples of COVID-19, the implementation of the salivary platforms has not been implemented for extensive scale testing. Up to date, several cross-section and clinical trial studies published in the last 12 months support the potential of detecting SARS-CoV-2 RNA in saliva as a biomarker for COVID-19, providing a self-collection, non-invasive, safe, and comfortable procedure. Therefore, the salivary diagnosis is suitable to protect healthcare professionals and other frontline workers and may encourage patients to get tested due to its advantages over the current invasive methods. The detection of SARS-CoV-2 in saliva was substantial also in patients with a negative nasopharyngeal swab, indicating the presence of false negative results. Furthermore, we expect that salivary diagnostic devices for COVID-19 will continue to be used with austerity without excluding traditional gold standard specimens to detect SARS-CoV-2.

Effectiveness of a resistance exercise program for lower limbs in chronic renal patients on hemodialysis: A randomized controlled trial.

INTRODUCTION: Physical inactivity in hemodialysis patients is associated with increased mortality. The objective of this study was evaluated the effect of an intradialytic resistance exercise program on chronic kidney disease (CKD) patients on hemodialysis. METHODS: One hundred seven patients were included in the study. They were aged 18-60 years, of both sexes, had undergone hemodialysis treatment for at least 1 year, sedentary. Patients were randomly divided into two groups: stretching (STG) and resistance exercise (REG). Intervention programs were performed for 8 weeks, three times a week. The evaluations were performed before and after the training programs. The primary outcome was functional capacity using the 6-minute walk test (6MWT). Secondary outcomes were peripheral muscle strength, respiratory muscle strength, spirometric respiratory function, and laboratory data. FINDINGS: Comparisons between groups revealed the following clinically relevant results in favor of REG: lower limb muscle strength (mean difference [MD] = -1.99, 95% confidence interval [CI] = -2.77 to -1.21; d = -0.53), distance walked in the 6MWT (MD = -26.27, 95% CI = -45.40 to -7.14; d = -0.46), creatinine (MD = -1.52, 95% CI = -2.49 to -0.54; d = -0.66), and calcium (MD = -0.44, 95% CI = -0.78 to -0.10; d = -0.49). DISCUSSION: CKD patients on hemodialysis have reduced functional capacity compared to healthy sedentary individuals. In turn, this reduction appears to be associated with a lower survival rate and affects the performance of their daily living activities. Thus, resistance exercise performed in the intradialytic phase is an effective therapeutic strategy for CKD patients, mainly because it increases functional capacity and lower limb muscle strength.

Hydroelectrolytic Disorder in COVID-19 patients: Evidence Supporting the Involvement of Subfornical Organ and Paraventricular Nucleus of the Hypothalamus.

Multiple neurological problems have been reported in coronavirus disease-2019 (COVID-19) patients because severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) likely spreads to the central nervous system (CNS) via olfactory nerves or through the subarachnoid space along olfactory nerves into the brain's cerebrospinal fluid and then into the brain's interstitial space. We hypothesize that SARS-CoV-2 enters the subfornical organ (SFO) through the above routes and the circulating blood since circumventricular organs (CVOs) such as the SFO lack the blood-brain barrier, and infection of the SFO causes dysfunction of the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON), leading to hydroelectrolytic disorder. SARS-CoV-2 can readily enter SFO-PVN-SON neurons because these neurons express angiotensin-converting enzyme-2 receptors and proteolytic viral activators, which likely leads to neurodegeneration or neuroinflammation in these regions. Considering the pivotal role of SFO-PVN-SON circuitry in modulating hydroelectrolyte balance, SARS-CoV-2 infection in these regions could disrupt the neuroendocrine control of hydromineral homeostasis. This review proposes mechanisms by which SARS-CoV-2 infection of the SFO-PVN-SON pathway leads to hydroelectrolytic disorder in COVID-19 patients.

COVID-19 - The clinical consequences of social isolation and the relation with sleep bruxism and comorbidities.

SARS-COV-2 is a highly pathogenic coronavirus that causes the disease known as COVID-19, which has infected more than 100 million people worldwide. The main form of containment of the pandemic is social isolation. However the isolation, the severity of the COVID-19 disease, the uncertainty of the future and the economic impact are the possible causes of anxiety as an adverse effect of the pandemic. The literature describes the possible association between anxiety with poor sleep quality, exacerbation of painful conditions, gastroesophageal reflux disease, increased consumption of drugs and the possibility of developing or enhancing sleep bruxism. Health professionals should keep in mind the possibility of overlapping with the different clinical conditions mentioned and the need for a multi-professional team to manage these patients.

Pathophysiology of SARS-CoV-2 in Lung of Diabetic Patients.

Novel coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its impact on patients with comorbidities is clearly related to fatality cases, and diabetes has been linked to one of the most important causes of severity and mortality in SARS-CoV-2 infected patients. Substantial research progress has been made on COVID-19 therapeutics; however, effective treatments remain unsatisfactory. This unmet clinical need is robustly associated with the complexity of pathophysiological mechanisms described for COVID-19. Several key lung pathophysiological mechanisms promoted by SARS-CoV-2 have driven the response in normoglycemic and hyperglycemic subjects. There is sufficient evidence that glucose metabolism pathways in the lung are closely tied to bacterial proliferation, inflammation, oxidative stress, and pro-thrombotic responses, which lead to severe clinical outcomes. It is also likely that SARS-CoV-2 proliferation is affected by glucose metabolism of type I and type II cells. This review summarizes the current understanding of pathophysiology of SARS-CoV-2 in the lung of diabetic patients and highlights the changes in clinical outcomes of COVID-19 in normoglycemic and hyperglycemic conditions.

Acute and chronic effects of combined exercise on ambulatory blood pressure and its variability in hypertensive postmenopausal women.

The aim of this study was to investigate the acute and chronic effects, and their correlation, after combined aerobic and resistance exercises in blood pressure (BP) and its variability (BPV) in hypertensive postmenopausal women. Fourteen hypertensive postmenopausal women monitored BP at rest and during 24 h by ambulatory BP monitoring in a control day without exercise performance a pretraining (baseline), after an acute exercise session (acute), and after a chronic exercise training for 10 weeks (chronic). After exercise training, systolic BP (SBP, Δ = -150 mmHg.24 h), diastolic BP (DBP, Δ = -96 mmHg.24 h), and mean BP (MBP, Δ = -95 mmHg.24 h) area under the curve were smaller than baseline measurements (P < 0.05) with no difference between acute and baseline measurements. The SBP (ΔSD24 = -2, ΔSDdn = -1.7, and ΔARV24 = -1.9 mmHg), DBP (ΔSD24 = -0.9, ΔSDdn = -0.8, and ΔARV24 = -0.9 mmHg), and MBP (ΔSD24 = -1.5, ΔSDdn = -1.3, and ΔARV24 = -1.2 mmHg) variability reduced in acute session in relation to baseline, with no chronic effects. There are moderate correlations between acute and chronic responses in wake SBP, sleep DBP, and SD24. In conclusion, combined exercise reduces ambulatory BP chronically but not acutely. In contrast, BPV decreases after an acute session but not chronically. Awake SBP, sleep DBP, and SD24indices are promising candidates to predict individual cardiovascular responses to exercise.

Effect of consuming a late-night high-protein/moderate-carbohydrate vs. low-protein/high-carbohydrate meal by night workers on their food perceptions later during the day: a randomized crossover study.

It is typical of night workers to consume a large dinner meal before their work shift, even though this practice may increase the risk for metabolic disorders. Night workers usually eat at night to socialize with colleagues as well as to stay alert and to avoid upset stomach during the night shift. However, little is known if and how the composition of the nighttime meal by night shift workers influences their food perceptions and eating behavior later during the day. The aim of this study was to analyze the effect of a high-protein/moderate-carbohydrate (HP/MCHO) meal vs. low-protein/high-carbohydrate (LP/HCHO) meal eaten at night by night-shift workers on their food consumption and perceptions later during the day. Fourteen male night shift workers were followed-up for 7 days for their eating and sleep habits. Then, participants underwent two isocaloric dietary events - one event a HP/MCHO meal containing 45% carbohydrate, 35% protein, and 20% fat and the other event a LP/HCHO meal containing 65% carbohydrate, 15% protein, and 20% fat, with a 6-day washout period between them - at 01:00 h during their night shift. Thereafter throughout the day, participants filled a food register of all the food consumed and perceptions, including hunger before meals, enjoyment of meals, and satiety. Generalized estimating equation analyses were used to examine the effect of both conditions on food consumption and food perceptions. Appetite for salty food snacks was greater after the HP/MCHO condition than after the LP/HCHO condition (p = .041). During the day following consumption of the nighttime HP/MCHO vs. LP/HCHO meal, there was higher percentage of carbohydrate consumption during lunch and a lower percentage of fat consumption during dinner (48.14% vs. 36.98% and 27.34% vs. 40.39%, respectively). These findings suggest the composition in terms of carbohydrates, protein, and fats of the meal consumed for the night shift by night workers may affect later during the day both food consumption and perceptions.

The erythrocyte membrane stability is associated with sleep time and social jetlag in shift workers.

The osmotic stability of the erythrocyte membrane (OSEM) has been associated with changes in lipid profile, blood glucose and blood pressure. Changes in these parameters are very frequent in shift workers, possibly because of the lack of synchronization of biological rhythms, which results in the social jetlag. However, the existence of association between OSEM and circadian misalignment has not been investigated in this population. Therefore, this study investigated whether shift work, sleep time and social jetlag (SJL) are associated with biochemical and hematological variables. A population consisting of 79 men working at night (n = 37) or during the day (n = 42), aged between 21 and 65 years and with a mean BMI of 27.56 ± 4.0 kg/m2, was investigated cross-sectionally in relation to sleep time, SJL, anthropometric (height, weight and waist circumference) and blood variables, with emphasis on the OSEM. SJL was calculated by the absolute difference between the midpoint of sleep on work and rest days. The Generalized Linear Model (GzLM) was used to investigate the existence of associations between SJL and average sleep time in relation to the analyzed variables. Workers without SJL presented lower baseline lysis values of erythrocytes in isotonic medium in relation to workers with SJL. In addition, workers who slept on average less than 6 hours had higher OSEM, and higher total and LDL-cholesterol in relation to those who slept more than 6 hours, regardless of the shift. It is possible that the association of sleep deprivation and SJL with erythrocyte membrane stability is mediated through changes in the lipid profile.

Effects of salbutamol and phlorizin on acute pulmonary inflammation and disease severity in experimental sepsis.

Respiratory infection can be exacerbated by the high glucose concentration in the airway surface liquid (ASL). We investigated the effects of salbutamol and phlorizin on the pulmonary function, oxidative stress levels and SGLT1 activity in lung, pulmonary histopathological damages and survival rates of rats with sepsis. Sepsis was induced by cecal ligation and puncture surgery (CLP). Twenty-four hours after surgery, CLP rats were intranasally treated with saline, salbutamol or phlorizin. After 2 hours, animals were anesthetized and sacrificed. Sepsis promoted atelectasis and bronchial inflammation, and led to increased expression of SGLT1 on cytoplasm of pneumocytes. Salbutamol treatment reduced bronchial inflammation and promoted hyperinsuflation in CLP rats. The interferon-ɤ and Interleucin-1ß concentrations in bronchoalveolar lavage (BAL) were closely related to the bronchial inflammation regulation. Salbutamol stimulated SGLT1 in plasma membrane; whereas, phlorizin promoted the increase of SGLT1 in cytoplasm. Phlorizin reduced catalase activity and induced a significant decrease in the survival rate of CLP rats. Taken together, sepsis promoted atelectasis and lung inflammation, which can be associated with SGLT1 inhibition. The loss of function of SGLT1 by phlorizin are related to the augmented disease severity, increased atelectasis, bronchial inflammation and a significant reduction of survival rate of CLP rats. Alternatively salbutamol reduced BAL inflammatory cytokines, bronchial inflammation, atelectasis, and airway damage in sepsis. These data suggest that this selective ß2-adrenergic agonist may protect lung of septic acute effects.

Predictors of success for mandibular repositioning appliance in obstructive sleep apnea syndrome.

The characteristics of non-obese patients with mild to moderate Obstructive Sleep Apnea Syndrome (OSAS) who will present with a good response to Mandibular Repositioning Appliance (MRA) treatment have not yet been well established in the literature. The aim of this study is to assess whether polysomnographic (PSG), demographic, anthropometric, cephalometric, and otorhinolaryngological parameters predict MRA success in the treatment of OSAS. Forty (40) males with mild and moderate OSAS were assessed pretreatment and 2-months post-treatment after wearing an MRA. Demographic, anthropometric, otorhinolaryngological (ENT), cephalometric, and polysomnographic parameters, including continuous positive airway pressure (CPAP) titrated pressure, dental models, Epworth Sleepiness Scale, quality of life (Short Form SF-36), and mood state (Profile of Mood States - POMS), were assessed. The responders exhibited fewer oropharyngeal alterations, increased upper pharyngeal space, reduced lower airway space, and increased mandibular intercanine width, and they had milder disease. Nevertheless, no predictive factors of MRA success could be found. MRA was more successful among men with a more pervious airway, a larger interdental width and milder OSAS. However, a combined [1] functional and structural assessment is needed to successfully predict the [2] effectiveness of MRA treatment of OSA.

Predictors of success for mandibular repositioning appliance in obstructive sleep apnea syndrome

Abstract The characteristics of non-obese patients with mild to moderate Obstructive Sleep Apnea Syndrome (OSAS) who will present with a good response to Mandibular Repositioning Appliance (MRA) treatment have not yet been well established in the literature. The aim of this study is to assess whether polysomnographic (PSG), demographic, anthropometric, cephalometric, and otorhinolaryngological parameters predict MRA success in the treatment of OSAS. Forty (40) males with mild and moderate OSAS were assessed pretreatment and 2-months post-treatment after wearing an MRA. Demographic, anthropometric, otorhinolaryngological (ENT), cephalometric, and polysomnographic parameters, including continuous positive airway pressure (CPAP) titrated pressure, dental models, Epworth Sleepiness Scale, quality of life (Short Form SF-36), and mood state (Profile of Mood States – POMS), were assessed. The responders exhibited fewer oropharyngeal alterations, increased upper pharyngeal space, reduced lower airway space, and increased mandibular intercanine width, and they had milder disease. Nevertheless, no predictive factors of MRA success could be found. MRA was more successful among men with a more pervious airway, a larger interdental width and milder OSAS. However, a combined [1] functional and structural assessment is needed to successfully predict the [2] effectiveness of MRA treatment of OSA.

Ventilator-associated pneumonia: the influence of bacterial resistance, prescription errors, and de-escalation of antimicrobial therapy on mortality rates

Abstract Ventilator-associated pneumonia is the most prevalent nosocomial infection in intensive care units and is associated with high mortality rates (14–70%). Aim This study evaluated factors influencing mortality of patients with Ventilator-associated pneumonia (VAP), including bacterial resistance, prescription errors, and de-escalation of antibiotic therapy. Methods This retrospective study included 120 cases of Ventilator-associated pneumonia admitted to the adult adult intensive care unit of the Federal University of Uberlândia. The chi-square test was used to compare qualitative variables. Student's t-test was used for quantitative variables and multiple logistic regression analysis to identify independent predictors of mortality. Findings De-escalation of antibiotic therapy and resistant bacteria did not influence mortality. Mortality was 4 times and 3 times higher, respectively, in patients who received an inappropriate antibiotic loading dose and in patients whose antibiotic dose was not adjusted for renal function. Multiple logistic regression analysis revealed the incorrect adjustment for renal function was the only independent factor associated with increased mortality. Conclusion Prescription errors influenced mortality of patients with Ventilator-associated pneumonia, underscoring the challenge of proper Ventilator-associated pneumonia treatment, which requires continuous reevaluation to ensure that clinical response to therapy meets expectations.

Ventilator-associated pneumonia: the influence of bacterial resistance, prescription errors, and de-escalation of antimicrobial therapy on mortality rates.

UNLABELLED: Ventilator-associated pneumonia is the most prevalent nosocomial infection in intensive care units and is associated with high mortality rates (14-70%). AIM: This study evaluated factors influencing mortality of patients with Ventilator-associated pneumonia (VAP), including bacterial resistance, prescription errors, and de-escalation of antibiotic therapy. METHODS: This retrospective study included 120 cases of Ventilator-associated pneumonia admitted to the adult adult intensive care unit of the Federal University of Uberlândia. The chi-square test was used to compare qualitative variables. Student's t-test was used for quantitative variables and multiple logistic regression analysis to identify independent predictors of mortality. FINDINGS: De-escalation of antibiotic therapy and resistant bacteria did not influence mortality. Mortality was 4 times and 3 times higher, respectively, in patients who received an inappropriate antibiotic loading dose and in patients whose antibiotic dose was not adjusted for renal function. Multiple logistic regression analysis revealed the incorrect adjustment for renal function was the only independent factor associated with increased mortality. CONCLUSION: Prescription errors influenced mortality of patients with Ventilator-associated pneumonia, underscoring the challenge of proper Ventilator-associated pneumonia treatment, which requires continuous reevaluation to ensure that clinical response to therapy meets expectations.

Exercise capacity in polycystic kidney disease.

BACKGROUND: Reports about exercise performance in autosomal dominant polycystic kidney disease (ADPKD) are scarce. We aimed to evaluate exercise capacity and levels of nitric oxide and asymmetric dimethylarginine (ADMA) in normotensive patients with ADPKD. STUDY DESIGN: Prospective controlled cohort study. SETTING & PARTICIPANTS: 26 patients with ADPKD and 30 non-ADPKD control participants (estimated glomerular filtration rate>60 mL/min/1.73 m2, aged 19-39 years, and blood pressure [BP]<140/85 mmHg). We excluded smokers, obese people, and individuals with associated diseases. PREDICTOR: ADPKD versus control. OUTCOMES: Exercise capacity and nitric oxide and ADMA levels in response to exercise. MEASUREMENTS: Cardiopulmonary exercise testing and serum and urinary nitric oxide, plasma ADMA, and BP levels before and after exercise. RESULTS: Mean basal systolic and diastolic BP, estimated glomerular filtration rate, and age did not differ between the ADPKD and control groups (116±12 vs. 110±11 mmHg, 76±11 vs 71±9 mmHg, 113±17 vs. 112±9.6 mL/min/1.73 m2, and 30±8 vs. 28.9±7.3 years, respectively). Peak oxygen uptake and anaerobic threshold were significantly lower in the ADPKD group than in controls (22.2±3.3 vs. 31±4.8 mL/kg/min [P<0.001] and 743.6±221 vs. 957.4±301 L/min [P=0.01], respectively). Postexercise serum and urinary nitric oxide levels in patients with ADPKD were not significantly different from baseline (45±5.1 vs. 48.3±4.6 µmol/L and 34.7±6.5 vs. 39.8±6.8 µmol/mg of creatinine, respectively), contrasting with increased postexercise values in controls (63.1±1.9 vs. 53.9±3.1 µmol/L [P=0.01] and 61.4±10.6 vs. 38.7±5.6 µmol/mg of creatinine [P=0.01], respectively). Similarly, whereas postexercise ADMA level did not change in the ADPKD group compared to those at rest (0.47±0.04 vs. 0.45±0.02 µmol/L [P=0.6]), it decreased in controls (0.39±0.02 vs. 0.47±0.02 µmol/L [P=0.006]), as expected. A negative correlation between nitric oxide and ADMA levels after exercise was found in only the control group (r = -0.60; P<0.01). LIMITATIONS: Absence of measurements of flow-mediated dilatation and oxidative status. CONCLUSIONS: We found lower aerobic capacity in young normotensive patients with ADPKD with preserved kidney function and inadequate responses of nitric oxide and ADMA levels to acute exercise, suggesting the presence of early endothelial dysfunction in this disease.

Not telling the truth in the patient-physician relationship.

The presence of truth and honesty is a permanent demand, and becomes vital the more committed and intimate a relationship is. Medical practice is relevant to this discussion when one questions whether or not a physician should always tell their patient the truth in the face of a progressive or potentially fatal disease, regarding their diagnosis, outcome, therapy and evolution of the specific disease. From this discussion we aim, with the present report, to look at the truth applicable to the patient-physician relationship, and its ethical and moral implications; and also to look at where the Brazilian Code of Medical Ethics (BCME) and the medical literature stand regarding this issue. One concludes that there are only two moments not to tell a patient the truth: when the patient does not want to be informed, and when the truth could be iatrogenic. The question now is, when would the truth be iatrogenic? Physicians, in our opinion, would not be able to judge solitarily when the truth might be deleterious to their patient. Alternatively, we proposed the appointment of a multidisciplinary commission to help the doctor with such a decision.