Multi-center atrial fibrillation electrocardiogram (ECG) classification using Fourier space convolutional neural networks (FD-CNN) and transfer learning.

There has been a proliferation of machine learning (ML) electrocardiogram (ECG) classification algorithms reaching >85% accuracy for various cardiac pathologies. Despite the high accuracy at individual institutions, challenges remain when it comes to multi-center deployment. Transfer learning (TL) is a technique in which a model trained for a specific task is repurposed for another related task, in this case ECG ML model trained at one institution is fine-tuned to be utilized to classify ECGs at another institution. Models trained at one institution, however, might not be generalizable for accurate classification when deployed broadly due to differences in type, time, and sampling rate of traditional ECG acquisition. In this study, we evaluate the performance of time domain (TD) and frequency domain (FD) convolutional neural network (CNN) classification models in an inter-institutional scenario leveraging three different publicly available datasets. The larger PTB-XL ECG dataset was used to initially train TD and FD CNN models for atrial fibrillation (AFIB) classification. The models were then tested on two different data sets, Lobachevsky University Electrocardiography Database (LUDB) and Korea University Medical Center database (KURIAS). The FD model was able to retain most of its performance (>0.81 F1-score), whereas TD was highly affected (<0.53 F1-score) by the dataset variations, even with TL applied. The FD CNN showed superior robustness to cross-institutional variability and has potential for widespread application with no compromise to ECG classification performance.

Fourier space approach for convolutional neural network (CNN) electrocardiogram (ECG) classification: A proof-of-concept study.

There has been a proliferation of machine learning (ML) electrocardiogram (ECG) classification algorithms reaching > 85% accuracy for various cardiac pathologies. Although the accuracy within institutions might be high, models trained at one institution might not be generalizable enough for accurate detection when deployed in other institutions due to differences in type of signal acquisition, sampling frequency, time of acquisition, device noise characteristics and number of leads. In this proof-of-concept study, we leverage the publicly available PTB-XL dataset to investigate the use of time-domain (TD) and frequency-domain (FD) convolutional neural networks (CNN) to detect myocardial infarction (MI), ST/T-wave changes (STTC), atrial fibrillation (AFIB) and sinus arrhythmia (SARRH). To simulate interinstitutional deployment, the TD and FD implementations were also compared on adapted test sets using different sampling frequencies 50 Hz, 100 Hz and 250 Hz, and acquisition times of 5 s and 10s at 100 Hz sampling frequency from the training dataset. When tested on the original sampling frequency and duration, the FD approach showed comparable results to TD for MI (0.92 FD - 0.93 TD AUROC) and STTC (0.94 FD - 0.95 TD AUROC), and better performance for AFIB (0.99 FD - 0.86 TD AUROC) and SARRH (0.91 FD - 0.65 TD AUROC). Although both methods were robust to changes in sampling frequency, changes in acquisition time were detrimental to the TD MI and STTC AUROCs, at 0.72 and 0.58 respectively. Alternatively, the FD approach was able to maintain the same level of performance, and, therefore, showed better potential for interinstitutional deployment.

Supplementation with Spirulina platensis Prevents Damage to Rat Erections in a Model of Erectile Dysfunction Promoted by Hypercaloric Diet-Induced Obesity.

Erectile dysfunction (ED) is the inability to achieve and/or maintain a penile erection sufficient for sexual satisfaction. Currently, many patients do not respond to the pharmacotherapy. The effects of a supplementation with Spirulina platensis, were evaluated in a model of ED induced by hypercaloric diet consumption. Wistar rats were divided into groups fed with standard diet (SD) or hypercaloric diet (HD) and supplemented with this alga at doses of 25, 50 or 100 mg/kg. Experimental adiposity parameters and erectile function were analyzed. In SD groups, Spirulina platensis reduced food intake, final body mass and adiposity index, and increased the total antioxidant capacity (TAC) of adipose tissue. However, no change was observed in erectile function. In the HD group, without Spirulina supplementation, a decrease in food intake was observed, in addition to an increase of final body mass, weight gain, adipose reserves, and adiposity index. Additionally, reduction in the number and increase in the latency of penile erection and adipose malondialdehyde levels, as well as a reduction in TCA was noted. Furthermore, cavernous contractility was increased, and the relaxing response was decreased. Interestingly, these deleterious effects were prevented by the algae at doses of 25, 50 and/or 100 mg/kg. Therefore, the supplementation with S. platensis prevents damages associated to a hypercaloric diet consumption and emerges as an adjuvant the prevention of ED.

Spirulina Platensis Supplementation Coupled to Strength Exercise Improves Redox Balance and Reduces Intestinal Contractile Reactivity in Rat Ileum.

The blue alga Spirulina platensis has presented several pharmacological activities, highlighting its actions as an anti-inflammatory and antioxidant. In addition, there are few studies with the influence of strength training on physiological parameters, as intestinal contractility and oxidative cell damage. We evaluated the influence of S. platensis supplementation, strength training, and its association on contractile reactivity of rat ileum, as well as the balance of oxidative stress/antioxidant defenses. Methods: Male Wistar rats were divided into; sedentary (S); S + supplemented with algae at 50 (S50), 150 (S150), and 500 mg/kg (S500); trained (T); and T + supplemented (T50, T150, and T500). Contractile reactivity was analyzed by kymographs; oxidative stress on ileum by the malondialdehyde (MDA) formation; and the antioxidant capacity by 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. S. platensis supplementation reduced the reactivity of rat ileum to carbachol (CCh) and KCl, while training reduced only the CCh efficacy. In addition, association potentiated the reduction on contractile reactivity. Supplementation reduced the oxidative stress and increased oxidation inhibition; training alone did not alter this parameter, however association potentiated this beneficial effect. Therefore, this study demonstrated that both supplementation and its association with strength training promote beneficial effects regarding intestinal contractile reactivity and oxidative stress, providing new insights for intestinal disorders management.

Tocolytic action and underlying mechanism of galetin 3,6-dimethyl ether on rat uterus.

BACKGROUND: Galetin 3,6-dimethyl ether (FGAL) is a flavonoid isolated from aerial parts of Piptadenia stipulacea. Previously, FGAL was shown to inhibit both carbachol- and oxytocin-induced phasic contractions in the rat uterus, which was more potent with oxytocin. Thus, in this study, we aimed to investigate the tocolytic action mechanism of FGAL on the rat uterus. METHODS: Segments of rat uterus ileum were suspended in organ bath containing modified Locke-Ringer solution at 32 °C, bubbled with carbogen mixture under a resting tension of 1 g. Isotonic contractions were registered using kymographs and isometric contractions using force transducer. RESULTS: FGAL was more potent in relaxing uterus pre-contracted with oxytocin than with KCl. Additionally, FGAL shifted oxytocin-induced cumulative contractions curves to the right in a non-parallel manner, with Emax reduction, indicating a pseudo-irreversible noncompetitive antagonism of oxytocin receptors (OTR) or a downstream pathway target. Moreover, FGAL shifted CaCl2-induced cumulative contraction curves to the right in a non-parallel manner in depolarizing medium, nominally without Ca2+, with Emax reduction, suggesting the inhibition of Ca2+ influx through CaV. The relaxant potency of FGAL was reduced by CsCl, a non-selective K+ channel blocker, suggesting positive modulation of these channels. Furthermore, in presence of apamin, 4-aminopyridine, glibenclamide or 1 mM TEA+, the relaxant potency of FGAL was attenuated, indicating the participation of SKCa, KV, KATP and highlighting BKCa. Aminophylline, a non-selective phosphodiesterase (PDE) blocker, did not affect the FGAL relaxant potency, excluding the modulation of cyclic nucleotide PDEs pathway by FGAL. CONCLUSION: Tocolytic effect of FGAL on rat uterus occurs by pseudo-irreversible noncompetitive antagonism of OTR and activation of K+ channels, primarily BKCa, leading to calcium influx reduction through CaV.

Toxicological, Antidiarrheal and Spasmolytic Activities of Solanum paniculatum.

Solanum paniculatum is popularly known as "jurubeba-verdadeira". In folk medicine, its roots, stems, and leaves are used as tonics, anti-inflammatories, carminatives, diuretics, and for gastrointestinal disorders. This species is listed in the Brazilian Pharmacopoeia and belongs to the "Relação Nacional de Plantas Medicinais de Interesse ao SUS". Based on folk medicine data of the Solanum genus, we decided to investigate whether the crude ethanol extract from S. paniculatum aerial parts presents toxicological, antidiarrheal, and spasmolytic activities. The crude ethanol extract from S. paniculatum aerial parts did not produce in vitro or in vivo toxicity and showed dose-dependent antidiarrheal activity, inhibiting equipotently both the defecation frequency (ED50 = 340.3 ± 35.1 mg/kg) and liquid stool formation (ED50 = 370.1 ± 19.4 mg/kg) in mice. Conversely, the crude ethanol extract from S. paniculatum aerial parts did not inhibit normal intestinal transit, even though it has shown a dose-dependent reduction of both the castor oil-induced intestinal transit (Emax = 36.9 ± 1.3 %, ED50 = 242.0 ± 8.6 mg/kg) and intestinal fluid content (Emax = 74.8 ± 2.4 %, ED50 = 328.9 ± 15.9 mg/kg). Additionally, the crude ethanol extract from S. paniculatum aerial parts was approximately 2-fold more potent in antagonizing the phasic contractions induced with histamine (IC50 = 63.7 ± 3.5 µg/mL) than carbachol 10(-6) M (IC50 = 129.3 ± 14.1 µg/mL). Therefore, we concluded that the crude ethanol extract from S. paniculatum aerial parts presents antidiarrheal activity in mice related to the inhibition of small intestinal motility and secretion as well as nonselective spasmolytic activity on the guinea pig ileum.

Essential oil from Xylopia frutescens Aubl. reduces cytosolic calcium levels on guinea pig ileum: mechanism underlying its spasmolytic potential.

BACKGROUND: Xylopia frutescens Aubl. (embira, semente-de-embira or embira-vermelha), is used in folk medicine as antidiarrheal. The essential oil from its leaves (XF-EO) has been found to cause smooth muscle relaxation. Thus, the aim of this study was to investigate the spasmolytic action by which XF-EO acts on guinea pig ileum. METHODS: The components of the XF-EO were identified by gas chromatography-mass spectrometry. Segments of guinea pig ileum were suspended in organ bath containing modified Krebs solution at 37 °C, bubbled with carbogen mixture under a resting tension of 1 g. Isotonic contractions were registered using kymographs and isometric contractions using force transducer coupled to an amplifier and computer. Fluorescence measurements were obtained with a microplate reader using Fluo-4. RESULTS: Forty-three constituents were identified in XF-EO, mostly mono- and sesquiterpenes. XF-EO has been found to cause relaxation on guinea pig ileum. The essential oil inhibited in a concentration-dependent manner both CCh- and histamine-induced phasic contractions, being more potent on histamine-induced contractions as well as antagonized histamine-induced cumulative contractions in a non-competitive antagonism profile. XF-EO relaxed in a concentration-dependent manner the ileum pre-contracted with KCl and histamine. Since the potency was smaller in organ pre-contracted with KCl, it was hypothesized that XF-OE would be acting as a K(+) channel positive modulator. In the presence of CsCl (non-selective K(+) channel blocker), the relaxant potency of XF-OE was not altered, indicating a non-participation of these channels. Moreover, XF-EO inhibited CaCl2-induced cumulative contractions in a depolarizing medium nominally without Ca(2+) and relaxed the ileum pre-contracted with S-(-)-Bay K8644 in a concentration-dependent manner, thus, was confirmed the inhibition of Ca(2+) influx through Cav1 by XF-EO. In cellular experiments, the viability of longitudinal layer myocytes from guinea pig ileum was not altered in the presence of XF-OE and the Fluo-4-associated fluorescence intensity in these intestinal myocytes stimulated by histamine was reduced by the essential oil, indicating a [Ca(2+)]c reduction. CONCLUSION: Spasmolytic action mechanism of XF-EO on guinea pig ileum can involve histaminergic receptor antagonism and Ca(2+) influx blockade, which results in [Ca(2+)]c reduction leading to smooth muscle relaxation.

Decreasing fall risk in spinocerebellar ataxia.

[Purpose] Spinocerebellar ataxia consists of a group of autosomal dominant disorders that cause progressive degeneration, mainly in the cerebellum and its connections. Falls, which are a significant concern of this condition, reduce patients' mobility, deteriorate their health and have physical and social consequences. The aim of this study was to test the effectiveness of a modified protocol for improving balance and diminishing the fall risk of spinocerebellar ataxia patients exclusively. [Subjects and Methods] Exercises aiming to improve static and dynamic balance, whole body movements, measures to prevent falls and falling strategies were performed twice per week for four weeks by 11 spinocerebellar ataxia patients. Balance was evaluated using the Berg Balance Scale. [Results] The results show that there was a significant increase in Berg Balance Scale scores after the interventions (Wilcoxon p=0.0034). [Conclusion] This study demonstrated that the modified protocol is effective at reducing the fall risk of spinocerebellar ataxia patients. This protocol may be a useful option for appropriately coping with falls caused by spinocerebellar ataxia.

Mechanisms underlying the relaxant effect of Galetin 3,6- dimethyl ether, from Piptadenia stipulacea (Benth.) Ducke, on guinea-pig trachea.

Galetin 3,6-dimethyl ether (FGAL), a flavonoid from the aerial parts of Piptadenia stipulacea (Benth.) Ducke, was found to exert a relaxant effect on carbachol (CCh)-pre-contracted guinea-pig trachea. Based on cumulative concentration-response curves to CCh, FGAL antagonized muscarinic receptors pseudo-irreversibly and noncompetitively, since it inhibited and shifted these curves towards higher concentrations in a nonparallel manner. In addition, FGAL was more potent in relaxing contractions induced by 18 mM as compared to 60 mM KCl (pD2 = 5:50 ±0:36 and 4.80 ±0.07, respectively), indicating the participation of K+ channels. In the presence of 10 mM tetraethylammonium (TEA+) chloride, a nonselective K+ channel blocker, the relaxant potency of FGAL was reduced (from pD2 = 5:12 ±0:07 to 4.87 ±0.02). Among several selective blockers of K+ channel subtypes, only apamin, an SKCa (small-conductance Ca2+-activated K+ channels) blocker, attenuated the relaxant potency of FGAL (pD2 = 4:85±0:06), suggesting SKCa activation. FGAL was equipotent in relaxing trachea contracted by 60 mM KCl (pD2 =4:80 ±0:07) or 10-6 M CCh (pD2 = 5:02 ±0:07), suggesting CaV (voltage-gated calcium channel), but not ROCs (receptor-operated calcium channels) participation. Furthermore, aminophylline-induced relaxation (pD2 = 4:12 ±0:06) was potentiated around 4-fold (pD2 = 4:80 ±0:44) in the presence of FGAL. Moreover, forskolininduced relaxation (pD2 = 6:51 ±0:06) was potentiated around 2.5-fold (pD2 = 6:90 ±0:05) by FGAL. Conversely, sodium nitroprusside-induced relaxation was unaffected, indicating that the AC/cAMP/PKA pathway, but not the NO pathway, may be modulated by the flavonoid. These results suggest that, in guinea-pig trachea, FGAL induces relaxation by pseudo-irreversible noncompetitive antagonism on muscarinic receptors, modulation of K+ and Ca2+ channels, as well as activation of the AC/cAMP/PKA pathway.

Mechanisms underlying vasorelaxation induced in rat aorta by galetin 3,6-dimethyl ether, a flavonoid from Piptadenia stipulacea (Benth.) Ducke.

In this study, we investigated the relaxant action of galetin 3,6-dimethyl ether (FGAL) on rat aorta. The flavonoid relaxed both PMA­ and phenylephrine (Phe)-induced contractions (pD2 = 5.36 ± 0.11 and 4.17 ± 0.10, respectively), suggesting the involvement of PKC and Phe pathways or α1 adrenergic receptor blockade. FGAL inhibited and rightward shifted Phe-induced cumulative contraction­response curves, indicating a noncompetitive antagonism of α1 adrenergic receptors. The flavonoid was more potent in relaxing 30 mM KCl- than 80 mM KCl-induced contractions (pD2 = 5.50 ± 0.22 and 4.37 ± 0.12). The vasorelaxant potency of FGAL on Phe-induced contraction was reduced in the presence of 10 mM TEA+. Furthermore, in the presence of apamin, glibenclamide, BaCl2 or 4-AP, FGAL-induced relaxation was attenuated, indicating the participation of small conductance calcium-activated K+ channels (SKCa), ATP-sensitive K+ channels (KATP), inward rectifier K+ channels (Kir) and voltage-dependent K+ channels (KV), respectively. FGAL inhibited and rightward shifted CaCl2-induced cumulative contraction-response curves in both depolarizing medium (high K+) and in the presence of verapamil and phenylephrine, suggesting inhibition of Ca2+ influx through voltage-gated calcium channels (CaV) and receptor operated channels (ROCs), respectively. Likewise, FGAL inhibited Phe-induced contractions in Ca2+-free medium, indicating inhibition of Ca2+ release from the sarcoplasmic reticulum (SR). FGAL potentiated the relaxant effect of aminophylline and sildenafil but not milrinone, suggesting the involvement of phosphodiesterase V (PDE V). Thus, the FGAL vasorelaxant mechanism involves noncompetitive antagonism of α1 adrenergic receptors, the non-selective opening of K+ channels, inhibition of Ca2+ influx through CaV or ROCs and the inhibition of intracellular Ca2+ release. Additionally, there is the involvement of cyclic nucleotide pathway, particularly through PDE V inhibition.

Evaluation of Robustness of S-Transform Based Phase Velocity Estimation in Viscoelastic Phantoms and Renal Transplants.

Ultrasound shear wave elastography (SWE) methods are being used to differentiate healthy versus diseased tissue on the basis of their viscoelastic mechanical properties. Tissue viscoelasticity is often studied by analyzing shear wave phase velocity dispersion curves, which is the variation of phase velocity with frequency or wavelength. Recently, a unique approach using a generalized Stockwell transformation (GST-SFK) was proposed for the calculation of dispersion curves in viscoelastic media over expanded frequency band. In this work, the method's robustness was evaluated on data from five custom-made viscoelastic tissue-mimicking phantoms and sixty in vivo renal transplants. For each phantom, 15 shear wave motion data acquisitions were taken, while 10-13 acquisitions were acquired for renal transplants measured in the renal cortex. For each data-set mean and standard deviation (SD) of estimated phase velocity dispersion curves were studied. In addition, the viscoelastic parameters of the Zener model were examined, which were preceded by a convergence analysis. For viscoelastic phantoms scanned with a research ultrasound scanner, and for the in vivo renal transplants scanned with a clinical scanner, the decisive advantage of the GST-SFK method over the standard two-dimensional Fourier transform (2D-FT) method was shown. The GST-SFK method provided dispersion curve estimates with lower SD over a wider frequency band in comparison to the 2D-FT method. These advantages are relevant to the analysis of the mechanical properties of tissues in clinical practice to discriminate healthy from diseased tissue.

Kidney cortex shear wave motion simulations based on segmented biopsy histology.

BACKGROUND AND OBJECTIVE: Biopsy stands as the gold standard for kidney transplant assessment, yet its invasive nature restricts frequent use. Shear wave elastography (SWE) is emerging as a promising alternative for kidney transplant monitoring. A parametric study involving 12 biopsy data sets categorized by standard biopsy scores (3 with normal histology, 3 with interstitial inflammation (i), 3 with interstitial fibrosis (ci), and 3 with tubular atrophy (ct)), was conducted to evaluate the interdependence between microstructural variations triggered by chronic allograft rejection and corresponding alterations in SWE measurements. METHODS: Heterogeneous shear wave motion simulations from segmented kidney cortex sections were performed employing the staggered-grid finite difference (SGFD) method. The SGFD method allows the mechanical properties to be defined on a pixel-basis for shear wave motion simulation. Segmentation techniques enabled the isolation of four histological constituents: glomeruli, tubules, interstitium, and fluid. Baseline ex vivo Kelvin-Voigt mechanical properties for each constituent were drawn from established literature. The parametric evaluation was then performed by altering the baseline values individually. Shear wave velocity dispersion curves were measured with the generalized Stockwell transform in conjunction with slant frequency-wavenumber analysis (GST-SFK) algorithm. By fitting the curve within the 100-400 Hz range to the Kelvin-Voigt model, the rheological parameters, shear elasticity (µ1) and viscosity (µ2), were estimated. A time-to-peak algorithm was used to estimate the group velocity. The resultant in silico models emulated the heterogeneity of kidney cortex within the shear wave speed (SWS) reconstructions. RESULTS: The presence of inflammation showed considerable spatial composition disparities compared to normal cases, featuring a 23 % increase in interstitial area and a 19 % increase in glomerular area. Concomitantly, there was a reduction of 12 % and 47 % in tubular and fluid areas, respectively. Consequently, mechanical changes induced by inflammation predominate in terms of rheological differentiation, evidenced by increased elasticity and viscosity. Mild tubular atrophy showed significant elevation in group velocity and µ1. Conversely, mild and moderate fibrosis exhibited negligible alterations across all parameters, compatible with relatively limited morphological impact. CONCLUSIONS: This proposed model holds promise in enabling patient-specific simulations of the kidney cortex, thus facilitating exploration into how pathologies altering cortical morphology correlates to modifications in SWE-derived rheological measurements. We demonstrated that inflammation caused substantial changes in measured mechanical properties.

New phosphodiesterase-4 inhibitors present airways relaxant activity in a guinea pig acute asthma model.

Asthma is a disease characterized by chronic inflammation and hyper responsiveness of airways. We aimed to assess the relaxant potential of phosphodiesterase-4 (PDE4) inhibitors N-sulfonilhidrazonic derivatives on non-asthmatic and asthmatic guinea pig trachea. Firstly, guinea pigs were sensitized and challenged with ovalbumin, and then morphological, and contractile changes were evaluated resulting from asthma, followed by evaluation of relaxant effect of derivatives on guinea pig trachea and the cAMP levels measurement by ELISA. It has been evidenced hypertrophy of airway smooth muscle, inflammatory infiltrate, and vascular abnormalities. Moreover, only sensitized tracheal rings were responsive to OVA. Contractile response to histamine, but not to carbachol, was greater in sensitized animals, however the relaxant response to aminophylline and isoprenaline were the same in non-asthmatics and asthmatics. N-sulfonilhidrazonic derivatives presented equipotent relaxant action independent of epithelium, with exception of LASSBio-1850 that presented a low efficacy (< 50%) and LASSBio-1847 with a 4-fold higher potency on asthmatics. LASSBio-1847 relaxant curve was impaired in the presence of propranolol and potentiated by isoprenaline in both groups. Furthermore, relaxation was potentiated 54- and 4-fold by forskolin in non-asthmatics and asthmatics, respectively. Likewise, LASSBio-1847 potentiated relaxant curve of aminophylline 147- and 4-fold in both groups. The PKA inhibitor H-89 impaired the relaxant potency of the derivative. Finally, LASSBio-1847 increased tracheal intracellular cAMP levels similarly to rolipram, selective PDE4 inhibitor, in both animals. LASSBio-1847 showed to be promising to relax guinea pig trachea from non-sensitized and sensitized guinea pigs by activation of ß2-adrenergic receptors/AC/cAMP pathway.

Robotic Ultrasound and Novel Collagen Analyses for Polycystic Kidney Disease Research Using Mice.

BACKGROUND: 3D imaging and histology are critical tools for assessing polycystic kidney disease ( PKD ) in patients and animal models. Magnetic resonance ( MR ) imaging provides micron resolution, but is time consuming, expensive, and access to equipment and expertise is limiting. Robotic ultrasound ( US ) imaging has lower spatial resolution but is faster, more cost effective, and accessible. Similarly, Picrosirius red ( PSR ) staining and brightfield microscopy is commonly used to assess fibrosis; however, alternative methods have been shown in non-kidney tissues to provide greater sensitivity and more detailed structural characterization. METHODS: In this study, we evaluated the utility of robotic US and alternative methods of quantifying PSR staining for PKD research. We compared longitudinal total kidney volume ( TKV ) measurements using US and MR. We additionally compared PSR imaging and quantification using standard brightfield with that by circularly polarized light with hue analysis, and fluorescence imaging analyzed using CT-FIRE software for automatic detection of individual collagen fibers. RESULTS: Increased TKV was detected by US in Pkd1RC/RC vs wild type ( WT ) at timepoints spanning early to established disease. US inter-observer variability was greater but allowed scanning in 2-5 minutes/mouse while MR required 20-30 minutes/mouse. While no change in fibrotic index was detected in this cohort of relatively mild disease using brightfield, polarized light showed fibers skewed thinner in Pkd1RC/RC vs WT. Fluorescence imaging showed a higher density of collagen fibers in Pkd1RC/RC vs WT, and fibers were thinner and curvier with no change in length. Additionally, fiber density was higher in both glomeruli and tubules in Pkd1RC/RC , and glomeruli had a higher fiber density than tubules in Pkd1RC/RC , and trended higher in WT. CONCLUSIONS: These studies show robotic ultrasound is a rigorous imaging tool for pre-clinical PKD research. Additionally, they demonstrate the increased sensitivity of polarized and fluorescence analysis of PSR-stained collagen.

A review of the pathophysiology and the role of ion channels on bronchial asthma.

Asthma is one of the main non-communicable chronic diseases and affects a huge portion of the population. It is a multifactorial disease, classified into several phenotypes, being the allergic the most frequent. The pathophysiological mechanism of asthma involves a Th2-type immune response, with high concentrations of allergen-specific immunoglobulin E, eosinophilia, hyperreactivity and airway remodeling. These mechanisms are orchestrated by intracellular signaling from effector cells, such as lymphocytes and eosinophils. Ion channels play a fundamental role in maintaining the inflammatory response on asthma. In particular, transient receptor potential (TRP), stock-operated Ca2+ channels (SOCs), Ca2+-activated K+ channels (IKCa and BKCa), calcium-activated chloride channel (TMEM16A), cystic fibrosis transmembrane conductance regulator (CFTR), piezo-type mechanosensitive ion channel component 1 (PIEZO1) and purinergic P2X receptor (P2X). The recognition of the participation of these channels in the pathological process of asthma is important, as they become pharmacological targets for the discovery of new drugs and/or pharmacological tools that effectively help the pharmacotherapeutic follow-up of this disease, as well as the more specific mechanisms involved in worsening asthma.

Prevalence and burden of headaches as assessed by the health family program.

BACKGROUND: Unified health systems often have Family Health Programs (FHPs) as a core component of their preventive and early curative strategies. In Brazil, the FHP is established to proactively identify diseases such as diabetes and hypertension. OBJECTIVE: To use the FHP in order to assess the prevalence of primary headaches, as per the Second Edition of the International Classification of Headache Disorders in a Brazilian city covered by the program, and to document the burden of migraine and tension-type headache (TTH) in this population. METHODS: FHP agents were trained on how to apply questionnaires that screened for the occurrence of headaches in the past year. Screening method had been previously validated. Respondents that screened positively were interviewed by a headache specialist, and all their headache types were classified. Additionally, disability (Migraine Disability Assessment Scale and Headache Impact Test) and health-related quality of life were assessed. RESULTS: The 1-year prevalence of migraine was 18.2% [95% confidence interval = 13.7; 23.5]. TTH occurred in 22.9% [18.0%; 28.6%]. Other primary headaches occurred in 10.8% of the participants. Idiopathic stabbing headache was significantly more common in individuals with migraine relative to those without migraine (44.7% vs 10.3%, P < .001). Contrasting with TTH, migraineurs had a mean of 3.1 headache types vs 1.9 in TTH (P < .001). Secondary headaches occurred in 21.7% of the participants over a 1-year period [16.9%; 27.3%]. Most cases were headaches attributed to infection (mostly respiratory). The impact of migraine was bimodal. Most sufferers had little impact, but a sizable minority was severely impaired. CONCLUSIONS: The FHP can be effectively used to bring individuals with headache to the attention of providers. Future investigations should assess whether this increased attention translates into improved outcomes.

The different facets of heme-oxygenase 1 in innate and adaptive immunity.

Heme oxygenase (HO) enzymes are responsible for the main oxidative step in heme degradation, generating equimolar amounts of free iron, biliverdin and carbon monoxide. HO-1 is induced as a crucial stress response protein, playing protective roles in physiologic and pathological conditions, due to its antioxidant, anti-apoptotic and anti-inflammatory effects. The mechanisms behind HO-1-mediated protection are being explored by different studies, affecting cell fate through multiple ways, such as reduction in intracellular levels of heme and ROS, transcriptional regulation, and through its byproducts generation. In this review we focus on the interplay between HO-1 and immune-related signaling pathways, which culminate in the activation of transcription factors important in immune responses and inflammation. We also discuss the dual interaction of HO-1 and inflammatory mediators that govern resolution and tissue damage. We highlight the dichotomy of HO-1 in innate and adaptive immune cells development and activation in different disease contexts. Finally, we address different known anti-inflammatory pharmaceuticals that are now being described to modulate HO-1, and the possible contribution of HO-1 in their anti-inflammatory effects.

Erectile Dysfunction: Key Role of Cavernous Smooth Muscle Cells.

Erectile dysfunction is increasingly affecting men, from the elderly to young adults, being a sexual disorder related to the inability to generate or maintain a penile erection. This disorder is related to psychosocial factors such as anxiety, depression, and low self-esteem, to organic factors such as the presence of preexisting conditions like hypertension, diabetes and dyslipidemia. The pathophysiology of the disease is related to changes in the neurotransmission of the autonomic or the non-cholinergic non-adrenergic nervous system, as well as the release of local mediators, such as thromboxane A2 and endothelin, and hormonal action. These changes lead to impaired relaxation of cavernous smooth muscle, which reduces local blood flow and impairs penile erection. Currently, therapy is based on oral vasodilation, such as sildenafil, tadalafil, vardenafil and iodenafil, or by direct administration of these agents into the corpus cavernosum or by intraurethral route, such as alprostadil and papaverine. Despite this, studies that consolidate the understanding of its pathophysiological process contribute to the discovery of new more efficient drugs for the treatment of erectile dysfunction. In this sense, in the present work an extensive survey was carried out of the mechanisms already consolidated and the most recent ones related to the development of erectile dysfunction.

[Controversy in estimating glomerular filtration rate through traditional equations in transgender people: discussion through a case report].

Introduction: Chronic kidney disease (CKD) and the number of transgender people is on the rise. Hormone replacement therapy may be associated with the development of adverse effects, including kidney disease. Objective: To report the case of a transgender patient using hormone therapy who developed CKD. Case Report: Male transgender patient, 28 years old, using testosterone cypionate every 15 days, without any comorbidity. Evolved with hypertensive peaks of 160-150/110 mmHg and loss of kidney function (Ur 102 mg/dl, Cr 3.5 mg/dl, estimated Glomerular Filtration Rate (eGFR) of 22 ml/min/1.73m2 considering male gender and 16.6 ml/min/1.73m2 considering female gender). Abdominal ultrasound showed chronic parenchymal nephropathy. Due to the significant reduction in eGFR, the patient was referred for kidney transplantation, but he was not included in the list because he had a creatinine clearance of 23 ml/min/1.73m2 for males and 21.5 ml/min/1.73m2 for females in the most recent tests. Conclusion: Hormone replacement may have contributed to the increase in the patient's blood pressure and, consequently, to the development of CKD. There is still no well-established consensus on the best way to estimate the GFR in transgender people, and it seems to be more appropriate to consider the gender to which the person self-identifies or to perform the calculation for both genders, obtaining an estimate of the range in which the patient's GFR lies.

Functional and morphologic dysfunctions in the airways of rats submitted to an experimental model of obesity-exacerbated asthma.

The obesity-exacerbated asthma phenotype is characterized by more severe asthma symptoms and glucocorticoid resistance. The aim of this study was to standardize an obesity-exacerbated asthma model by a high glycemic level index (HGLI) diet and ovalbumin (OVA) sensitization and challenges in Wistar rats. Animals were divided into groups: control (Ctrl), obese (Ob), asthmatic (Asth), obese asthmatic (Ob + Asth) and obese asthmatic treated with dexamethasone (Ob + Asth + Dexa), and in vivo and in vitro functional and morphological parameters were measured. After HGLI consumption, there was an increase in body weight, fasting blood glucose, abdominal circumferences, body mass index and adiposity index. Respiratory function showed a reduction in pulmonary tidal volume and ventilation. In isolated tracheas, carbachol showed an increase in contractile efficacy in the Ob, Ob + Asth and Ob + Asth + Dexa, but mostly on Ob + Asth. Histological analysis of lungs showed peribronchovascular inflammation and smooth muscle hypertrophy and extracellular remodeling on Ob + Asth and Ob + Asth + Dexa. An obesity-exacerbated asthma model was successfully established. Therefore, this model allows further molecular investigations and the search for new therapies for the treatment and relief of symptoms of patients with obesity-induced resistant asthma.