Neuroregeneration and immune response after neurorrhaphy are improved with the use of heterologous fibrin biopolymer in addition to suture repair alone.

INTRODUCTION/AIMS: Peripheral nerve injuries result in impaired neuromuscular interactions, leading to morphological and functional alterations. Adjuvant suture repair methods have been used to improve nerve regeneration and modulate the immune response. Heterologous fibrin biopolymer (HFB), a scaffold with adhesive properties, plays a critical role in tissue repair. The aim of this study is to evaluate neuroregeneration and immune response focusing on neuromuscular recovery, using suture-associated HFB for sciatic nerve repair. METHODS: Forty adult male Wistar rats were distributed into four groups (n = 10): C (control), only sciatic nerve location; D (denervated), neurotmesis and 6-mm gap removal and fixation stumps in subcutaneous tissue; S (suture), neurotmesis followed by suture; and SB (suture + HFB), neurotmesis followed by suture and HFB. Analysis of M2 macrophages (CD206+ ), as well as the morphology and morphometry of nerves, soleus muscle, and neuromuscular junctions (NMJs), were performed at 7 and 30 days after surgery. RESULTS: The SB group had the highest M2 macrophage area in both periods. After 7 days, SB was the only group similar to the C group regarding the number of axons; furthermore, after 30 days, the SB group was closer to the C group concerning blood vessel and central myonuclear numbers, NMJ angle, and connective tissue volume. After 7 days, increases in nerve area, as well as the number and area of blood vessels, were also observed in SB. DISCUSSION: HFB potentiates the immune response, increases axonal regeneration, induces angiogenesis, prevents severe muscle degeneration, and assists in NMJ recovery. In conclusion, suture-associated HFB has major implications for improved peripheral nerve repair.

Effects of Nandrolone Decanoate on Skeletal Muscle and Neuromuscular Junction of Sedentary and Exercised Rats.

Background and Objectives: Nandrolone decanoate (ND) is the most widely used among the anabolic androgenic steroids (AAS), synthetic substances derived from testosterone, to improve muscular and health gains associated with exercises. The AAS leads to physical performance enhancement and presents anti-aging properties, but its abuse is associated with several adverse effects. Supraphysiological doses of AAS with or without physical exercise can cause morphological and functional alterations in neuromuscular interactions. This study aims to investigate the effects of ND supraphysiological doses in neuromuscular interactions, focusing on the soleus muscle and its neuromuscular junctions (NMJs) in rats, associated or not with physical exercise. Materials and Methods: Forty male Sprague Dawley rats were divided into four groups: sedentary and exercised groups, with or without ND at the dose of 10 mg/kg/week. The animals were treated for eight weeks, with intramuscular injections, and the soleus muscle was collected for morphological analyses. Results: The supraphysiological doses of ND in the sedentary group caused muscle degeneration, evidenced by splitting fibers, clusters of small fibers, irregular myofibrils, altered sarcomeres, an increase in collagen deposition and in the number of type I muscle fibers (slow-twitch) and central nuclei, as well as a decrease in fibers with peripheral nuclei. On the other hand, in the ND exercise group, there was an increase in the NMJs diameter with scattering of its acetylcholine receptors, although no major morphological changes were found in the skeletal muscle. Thus, the alterations caused by ND in sedentary rats were partially reversed by physical exercise. Conclusions: The supraphysiological ND exposure in the sedentary rats promoted an increase in muscle oxidative pattern and adverse morphological alterations in skeletal muscle, resulting from damage or post-injury regeneration. In the ND-exercised rats, no major morphological changes were found. Thus, the physical exercise partially reversed the alterations caused by ND in sedentary rats.

Angiotensin II and AT1a Receptors in the Proximal Tubules of the Kidney: New Roles in Blood Pressure Control and Hypertension.

Contrary to public perception, hypertension remains one of the most important public health problems in the United States, affecting 46% of adults with increased risk for heart attack, stroke, and kidney diseases. The mechanisms underlying poorly controlled hypertension remain incompletely understood. Recent development in the Cre/LoxP approach to study gain or loss of function of a particular gene has significantly helped advance our new insights into the role of proximal tubule angiotensin II (Ang II) and its AT1 (AT1a) receptors in basal blood pressure control and the development of Ang II-induced hypertension. This novel approach has provided us and others with an important tool to generate novel mouse models with proximal tubule-specific loss (deletion) or gain of the function (overexpression). The objective of this invited review article is to review and discuss recent findings using novel genetically modifying proximal tubule-specific mouse models. These new studies have consistently demonstrated that deletion of AT1 (AT1a) receptors or its direct downstream target Na+/H+ exchanger 3 (NHE3) selectively in the proximal tubules of the kidney lowers basal blood pressure, increases the pressure-natriuresis response, and induces natriuretic responses, whereas overexpression of an intracellular Ang II fusion protein or AT1 (AT1a) receptors selectively in the proximal tubules increases proximal tubule Na+ reabsorption, impairs the pressure-natriuresis response, and elevates blood pressure. Furthermore, the development of Ang II-induced hypertension by systemic Ang II infusion or by proximal tubule-specific overexpression of an intracellular Ang II fusion protein was attenuated in mutant mice with proximal tubule-specific deletion of AT1 (AT1a) receptors or NHE3. Thus, these recent studies provide evidence for and new insights into the important roles of intratubular Ang II via AT1 (AT1a) receptors and NHE3 in the proximal tubules in maintaining basal blood pressure homeostasis and the development of Ang II-induced hypertension.

Genetic Deletion of AT1a Receptor or Na+/H+ Exchanger 3 Selectively in the Proximal Tubules of the Kidney Attenuates Two-Kidney, One-Clip Goldblatt Hypertension in Mice.

The roles of angiotensin II (Ang II) AT1 (AT1a) receptors and its downstream target Na+/H+ exchanger 3 (NHE3) in the proximal tubules in the development of two-kidney, 1-clip (2K1C) Goldblatt hypertension have not been investigated previously. The present study tested the hypothesis that deletion of the AT1a receptor or NHE3 selectively in the proximal tubules of the kidney attenuates the development of 2K1C hypertension using novel mouse models with proximal tubule-specific deletion of AT1a receptors or NHE3. 2K1C Goldblatt hypertension was induced by placing a silver clip (0.12 mm) on the left renal artery for 4 weeks in adult male wild-type (WT), global Agtr1a−/−, proximal tubule (PT)-specific PT-Agtr1a−/− or PT-Nhe3−/− mice, respectively. As expected, telemetry blood pressure increased in a time-dependent manner in WT mice, reaching a maximal response by Week 3 (p < 0.01). 2K1C hypertension in WT mice was associated with increases in renin expression in the clipped kidney and decreases in the nonclipped kidney (p < 0.05). Plasma and kidney Ang II were significantly increased in WT mice with 2K1C hypertension (p < 0.05). Tubulointerstitial fibrotic responses were significantly increased in the clipped kidney (p < 0.01). Whole-body deletion of AT1a receptors completely blocked the development of 2K1C hypertension in Agtr1a−/− mice (p < 0.01 vs. WT). Likewise, proximal tubule-specific deletion of Agtr1a in PT-Agtr1a−/− mice or NHE3 in PT-Nhe3−/− mice also blocked the development of 2K1C hypertension (p < 0.01 vs. WT). Taken together, the present study provides new evidence for a critical role of proximal tubule Ang II/AT1 (AT1a)/NHE3 axis in the development of 2K1C Goldblatt hypertension.

Sex differences in angiotensin II-induced hypertension and kidney injury: role of AT1a receptors in the proximal tubule of the kidney.

In the present study, we tested the hypothesis that there are significant sex differences in angiotensin II (Ang II)-induced hypertension and kidney injury using male and female wildtype (WT) and proximal tubule-specific AT1a receptor knockout mice (PT-Agtr1a-/-). Twelve groups (n=8-12 per group) of adult male and female WT and PT-Agtr1a-/- mice were infused with a pressor dose of Ang II via osmotic minipump for 2 weeks (1.5 mg/kg/day, i.p.) and simultaneously treated with or without losartan (20 mg/kg/day, p.o.) to determine the respective roles of AT1a receptors in the proximal tubules versus systemic tissues. Basal systolic, diastolic, and mean arterial pressure were approximately 13 ± 3 mmHg lower (P<0.01), while basal 24-h urinary Na+, K+, and Cl- excretion were significantly higher in both male and female PT-Agtr1a-/- mice than WT controls (P<0.01) without significant sex differences between different strains. Both male and female WT and PT-Agtr1a-/- mice developed hypertension (P<0.01), and the magnitudes of the pressor responses to Ang II were similar between male and female WT and PT-Agtr1a-/- mice (n.s.). Likewise, Ang II-induced hypertension was significantly attenuated in both male and female PT-Agtr1a-/- mice (P<0.01). Furthermore, losartan attenuated the hypertensive responses to Ang II to similar extents in both male and female WT and PT-Agtr1a-/- mice. Finally, Ang II-induced kidney injury was attenuated in PT-Agtr1a-/- mice (P<0.01). In conclusion, the present study demonstrates that deletion of AT1a receptors in the proximal tubules of the kidney attenuates Ang II-induced hypertension and kidney injury without revealing significant sex differences.

Comparison of Sensitivity and Specificity of Structured and Narrative Reports of Transvaginal Ultrasonogaphy for Adenomyosis.

STUDY OBJECTIVE: To compare the sensitivity and specificity of the transvaginal ultrasonography (TVUS) narrative report with those of the structured report for the diagnosis of adenomyosis. DESIGN: Retrospective study. SETTING: A tertiary teaching hospital. PATIENTS: One hundred ninety-two patients (45 with adenomyosis and 147 controls) who underwent hysterectomy between 2012 and 2016 and were aged 30 years to 55 years, with available preoperative TVUS images, were included. INTERVENTIONS: To compare preoperative TVUS with histologic analysis of the uterus after hysterectomy for the diagnostic of adenomyosis. MEASUREMENTS AND MAIN RESULTS: Data regarding the presence of the ultrasonographic characteristics previously described for the diagnosis of adenomyosis were obtained from the original TVUS report (narrative report) and the structured report from 2 blinded radiologists (R1 and R2). Histologic analysis is defined as the gold standard for the diagnosis of adenomyosis. The mean age (45.4 ± 5.3 years vs 44.9 ± 4.8 years; p = .496) and clinical symptoms were similar between the adenomyosis and control groups, except for dyspareunia, which was more frequently reported in the patients with adenomyosis (25.6% vs 9.4%; p = .006). Most of TVUS characteristics were more frequently observed in the structured reports than in the narrative reports. The structured report presented higher sensitivity (R1: 84.4%, R2: 69.1%; narrative report: 31.1%; p <.05) and lower specificity (R1: 28.0%, R2: 31.2%; narrative report: 90.5%; p <.05) for adenomyosis. The structured report presented higher sensitivity and lower specificity for most of sonographic characteristics evaluated. After logistic regression analysis, no sonographic characteristics presented with statistical significance for the diagnosis of adenomyosis on R1's structured report, while globular uterus (odds ratio [OR] 0.276; p = .006; 95% CI, 0.11-0.697) and poorly defined junctional zone (OR 3.6; p = .007; 95% CI, 1.4-9.2) were significantly associated with adenomyosis. In the narrative report, a myometrial cyst was associated with a higher risk of adenomyosis (odds ratio 9.486, p =.002; CI, 2.359-38.149). CONCLUSION: The narrative reports were more specific, whereas the structured reports were more sensitive for the diagnosis of adenomyosis. In addition, the sensitivity of most of sonographic feature of adenomyosis was higher and the specificity was lower in the structured report. Future prospective studies comparing both reports are needed to validate the current findings.

Separation of benign and malignant breast lesions using dynamic contrast enhanced MRI in a biopsy cohort.

PURPOSE: To assess the diagnostic utility of contrast kinetic analysis for breast lesions and background parenchyma of women undergoing MRI-guided biopsies, for whom standard clinical analysis had failed to separate benign and malignant lesions. MATERIALS AND METHODS: This study included 115 women who had indeterminate lesions based on routine diagnostic breast MRI exams and underwent an MRI (3 Tesla) -guided biopsy of one or more lesions suspicious for breast cancer. Breast dynamic contrast-enhanced (DCE)-MRI was performed using a radial stack-of-stars three-dimensional spoiled gradient echo pulse sequence and modified k-space weighted image contrast image reconstruction. Contrast kinetic model analysis was conducted to characterize the contrast enhancement patterns measured in lesions and background parenchyma (BP). The transfer rate (Ktrans ), interstitial volume fraction (ve ), and vascular volume fraction (vp ) estimated from the lesion and BP were used to separate malignant from benign lesions. RESULTS: The patients with malignant lesions had significantly (P < 0.05) higher median lesion-Ktrans (0.081 min-1 ), higher median BP-Ktrans (0.032 min-1 ), and BP-vp (0.020) than those without malignant lesions (0.056 min-1 , 0.017 min-1 and 0.012, respectively). The area under the receiver operating characteristic curve (AUC) of the BP-Ktrans (0.687) was highest among the single parameters and higher than that of the lesion-Ktrans (0.664). The combined logistic regression model of lesion-Ktrans , lesion-ve , BP-Ktrans , BP-ve , and BP-vp had the highest AUC of 0.730. CONCLUSION: Our results suggest that the contrast kinetic analysis of DCE-MRI data can be used to differentiate the malignant lesions from the benign and high-risk lesions among the indeterminate breast lesions recommended for MRI-guided biopsy exams. LEVEL OF EVIDENCE: 3 J. MAGN. RESON. IMAGING 2017;45:1385-1393.

Obstructive sleep apnea is independently associated with subclinical coronary atherosclerosis among middle-aged women.

PURPOSE: Obstructive sleep apnea (OSA) is associated with coronary disease among men. However, this association is not clear for women. In this study, we evaluate the association between OSA and presence of subclinical atherosclerosis assessed by tomographic coronary calcium score in middle-aged women. METHODS: We evaluated consecutive women aged between 45 and 65 years in perimenopause or postmenopause period (with menstrual irregularity-amenorrhea > 60 days), without manifest cardiovascular disease (heart failure, coronary disease, and stroke), from two gynecologic clinics. All patients underwent clinical evaluation, computed tomographic examination for coronary artery calcium (CAC > 100 Agatston units), and portable sleep study. Multiple logistic regression models were used to evaluate the association between OSA and CAC, controlling for traditional risk factors including Framingham Risk Score (FRS), body mass index (BMI), and diabetes. RESULTS: We studied 214 women (age 56 years (52-61); BMI 28 kg/m2 (25-31), 25 % diabetes, 62 % hypertension). OSA (apnea-hypopnea index (AHI) ≥5 events/h) was diagnosed in 82 women (38.3 %). CAC was more prevalent in patients with moderate/severe OSA (AHI ≥15 events/h) than in patients without or with mild OSA, 19 % vs 4.5 and 1.6 %, respectively (p < 0.01). Moderate to severe OSA was associated with CAC in unadjusted (odds ratio = 6.25, 95 % CI 1.66-23.52; p < 0.01) and adjusted (odds ratio = 8.19, 95 % CI 1.66-40.32; p = 0.01) logistic regression analysis. CONCLUSION: Moderate to severe OSA is independently associated with the presence of CAC in middle-aged women. These results reinforce the concept that women are also susceptible to the cardiovascular consequences of OSA.

Breast MRI at 7 Tesla with a bilateral coil and robust fat suppression.

PURPOSE: To develop a bilateral coil and fat suppressed T1-weighted sequence for 7 Tesla (T) breast MRI. MATERIALS AND METHODS: A dual-solenoid coil and three-dimensional (3D) T1w gradient echo sequence with B1+ insensitive fat suppression (FS) were developed. T1w FS image quality was characterized through image uniformity and fat-water contrast measurements in 11 subjects. Signal-to-noise ratio (SNR) and flip angle maps were acquired to assess the coil performance. Bilateral contrast-enhanced and unilateral high resolution (0.6 mm isotropic, 6.5 min acquisition time) imaging highlighted the 7T SNR advantage. RESULTS: Reliable and effective FS and high image quality was observed in all subjects at 7T, indicating that the custom coil and pulse sequence were insensitive to high-field obstacles such as variable tissue loading. 7T and 3T image uniformity was similar (P=0.24), indicating adequate 7T B1+ uniformity. High 7T SNR and fat-water contrast enabled 0.6 mm isotropic imaging and visualization of a high level of fibroglandular tissue detail. CONCLUSION: 7T T1w FS bilateral breast imaging is feasible with a custom radiofrequency (RF) coil and pulse sequence. Similar image uniformity was achieved at 7T and 3T, despite different RF field behavior and variable coil-tissue interaction due to anatomic differences that might be expected to alter magnetic field patterns.

Dimethyl Fumarate Mediates Sustained Vascular Smooth Muscle Cell Remodeling in a Mouse Model of Cerebral Aneurysm.

Cerebral aneurysms (CA) are a type of vascular disease that causes significant morbidity and mortality with rupture. Dysfunction of the vascular smooth muscle cells (VSMCs) from circle of Willis (CoW) vessels mediates CA formation, as they are the major cell type of the arterial wall and play a role in maintaining vessel integrity. Dimethyl fumarate (DMF), a first-line oral treatment for relapsing-remitting multiple sclerosis, has been shown to inhibit VSMC proliferation and reduce CA formation in a mouse model. Potential unwanted side effects of DMF on VSMC function have not been investigated yet. The present study characterizes the impact of DMF on VSMC using single-cell RNA-sequencing (scRNA-seq) in CoW vessels following CA induction and further explores its role in mitochondrial function using in vitro VSMC cultures. Two weeks of DMF treatment following CA induction impaired the transcription of the glutathione redox system and downregulated mitochondrial respiration genes in VSMCs. In vitro, DMF treatment increased lactate formation and enhanced the mitochondrial production of reactive oxygen species (ROS). These effects rendered VSMCs vulnerable to oxidative stress and led to mitochondrial dysfunction and enhancement of apoptosis. Taken together, our data support the concept that the DMF-mediated antiproliferative effect on VSMCs is linked to disturbed antioxidative functions resulting in altered mitochondrial metabolism. This negative impact of DMF treatment on VSMCs may be linked to preexisting alterations of cerebrovascular function due to renal hypertension. Therefore, before severe adverse effects emerge, it would be clinically relevant to develop indices or biomarkers linked to this disturbed antioxidative function to monitor patients undergoing DMF treatment.

Cepstral Peak Prominence Smoothed - CPPS and Acoustic Voice Quality Index - AVQI in healthy and altered children's voices: comparation, relationship with auditory-perceptual judgment and cut-off points. / Cepstral Peak Prominence Smoothed - CPPS e Acoustic Voice Quality Index - AVQI em vozes infantis saudáveis e alteradas: comparação, relação com julgamento perceptivo-auditivo e pontos de corte.

PURPOSE: To compare the acoustic measurements of Cepstral Peak Prominence Smoothed (CPPS) and Acoustic Voice Quality Index (AVQI) of children with normal and altered voices, to relationship with auditory-perceptual judgment (APJ) and to establish cut-off points. METHODS: Vocal recordings of the sustained vowel and number counting tasks of 185 children were selected from a database and submitted to acoustic analysis with extraction of CPPS and AVQI measurements, and to APJ. The APJ was performed individually for each task, classified as normal or altered, and for the tasks together defining whether the child would pass or fail in a situation of vocal screening. RESULTS: Children with altered APJ and who failed the screening had lower CPPS values and higher AVQI values, than those with normal APJ and who passed the screening. The APJ of the sustained vowel task was related to CPPS and AVQI, and APJ of the number counting task was related only to AVQI and CPPS numbers. The cut-off points that differentiate children with and without vocal deviation are 14.07 for the vowel CPPS, 7.62 for the CPPS numbers and 2.01 for the AVQI. CONCLUSION: Children with altered voices, have higher AVQI values and lower CPPS values, when detected in children with voices within the normal range. The acoustic measurements were related to the auditory perceptual judgment of vocal quality in the sustained vowel task, however, the number counting task was related only to the AVQI and CPPS. The cut-off points that differentiate children with and without vocal deviation are 14.07 for the CPPS vowel, 7.62 for the CPPS numbers and 2.01 for the AVQI. The three measures were similar in identifying voices without deviation and dysphonic voices.

OBJETIVO: Comparar as medidas acústicas de Cepstral Peak Prominence Smoothed (CPPS) e Acoustic Voice Quality Index (AVQI) de crianças com vozes normais e alteradas, relacionar com o julgamento perceptivo-auditivo (JPA) da voz e estabelecer pontos de corte. MÉTODO: Gravações vocais das tarefas de vogal sustentada e contagem de números de 185 crianças foram selecionadas em um banco de dados e submetidas a análise acústica com extração das medidas de CPPS e AVQI, e ao JPA. O JPA foi realizado individualmente para cada tarefa e as amostras foram classificadas posteriormente como normal ou alterada, e para as tarefas em conjunto definindo-se se a criança passaria ou falharia em uma situação de triagem vocal. RESULTADOS: Crianças com JPA alterado e que falharam na triagem apresentaram valores menores de CPPS e maiores de AVQI, do que as com JPA normal e que passaram na triagem. O JPA da tarefa de vogal sustentada se relacionou ao CPPS e AVQI, e da tarefa de contagem de números relacionou-se apenas ao AVQI e CPPS números. Os pontos de corte que diferenciam crianças com e sem desvio vocal são 14,07 para o CPPS vogal, 7,62 para o CPPS números e 2,01 para o AVQI. CONCLUSÃO: Crianças com JPA alterado apresentaram maiores valores de AVQI e menores valores de CPPs. O JPA da tarefa de vogal previu todas as medidas acústicas, porém, de contagem previu apenas as medidas extraídas dela. As três medidas foram semelhantes na identificação de vozes sem desvio e vozes disfônicas.

Immediate effect of inspiratory exercise with exerciser and respiratory encourager in women without vocal complaints. / Efeito imediato de exercício inspiratório com exercitador e incentivador respiratório em mulheres sem queixas vocais.

PURPOSE: To evaluate the immediate effect of the inspiratory exercise with a booster and a respiratory exerciser on the voice of women without vocal complaints. METHODS: 25 women with no vocal complaints, between 18 and 34 years old, with a score of 1 on the Vocal Disorder Screening Index (ITDV) participated. Data collection was performed before and after performing the inspiratory exercise and consisted of recording the sustained vowel /a/, connected speech and maximum phonatory times (MPT) of vowels, fricative phonemes and counting numbers. In the auditory-perceptual judgment, the Vocal Deviation Scale (VSD) was used to verify the general degree of vocal deviation. Acoustic evaluation was performed using the PRAAT software and the parameters fundamental frequency (f0), jitter, shimmer, harmonium-to-noise ratio (HNR), Cepstral Peak Prominence Smoothed (CPPS), Acoustic Voice Quality Index (AVQI) and Acoustic Breathiness Index (ABI). To measure the aerodynamic measurements, the time of each emission was extracted in the Audacity program. Data were statistically analyzed using the Statistica for Windows software and normality was tested using the Shapiro-Wilk test. To compare the results, Student's and Wilcoxon's t tests were applied, adopting a significance level of 5%. RESULTS: There were no significant differences between the results of the JPA and the acoustic measures, in the pre and post inspiratory exercise moments. As for the aerodynamic measures, it was possible to observe a significant increase in the value of the TMF /s/ (p=0.008). CONCLUSION: There was no change in vocal quality after the inspiratory exercise with stimulator and respiratory exerciser, but an increase in the MPT of the phoneme /s/ was observed after the exercise.

OBJETIVO: Avaliar o efeito imediato do exercício inspiratório com incentivador e exercitador respiratório na voz de mulheres sem queixas vocais. MÉTODO: Participaram 25 mulheres sem queixas vocais, entre 18 e 34 anos, com pontuação 1 no Índice de Triagem para Distúrbio Vocal (ITDV). A coleta de dados foi realizada nos momentos antes e após realização de exercício inspiratório e consistiu na gravação de vogal sustentada /a/, fala encadeada e tempos máximos fonatórios (TMF) de vogais, fonemas fricativos e contagem de números. No julgamento perceptivo-auditivo foi utilizada a Escala de Desvio Vocal (EDV) para verificar o grau geral do desvio vocal. Avaliação acústica foi feita no software PRAAT e foram extraídos os parâmetros frequência fundamental (f0), jitter, shimmer, proporção harmônico -ruído (HNR), Cepstral Peak Prominence Smoothed (CPPS), Acoustic Voice Quality Index (AVQI) e Acoustic Breathiness Index (ABI). Para mensuração das medidas aerodinâmicas, o tempo de emissão foi extraído no programa Audacity. Para comparar os resultados utilizou-se o teste paramétrico t de Student para amostras dependentes na análise das variáveis com distribuição normal e o teste de Wilcoxon para variáveis com distribuição não normal. RESULTADOS: Não houve diferenças entre os resultados do JPA e das medidas acústicas, nos momentos pré e pós exercício inspiratório. Quanto às medidas aerodinâmicas foi possível observar aumento significativo no valor do TMF /s/ (p=0,008). CONCLUSÃO: Não houve modificação na qualidade vocal após o exercício inspiratório com incentivador e exercitador respiratório, porém foi observado aumento do TMF do fonema /s/ após a realização do exercício.

Evaluation of the kinetic properties of background parenchymal enhancement throughout the phases of the menstrual cycle.

PURPOSE: To develop and apply a semiautomatic method of segmenting fibroglandular tissue to quantify magnetic resonance (MR) imaging contrast material-enhancement kinetics of breast background parenchyma (BP) and lesions throughout the phases of the menstrual cycle in women with benign and malignant lesions. MATERIALS AND METHODS: The institutional review board approved this retrospective HIPAA-compliant study, and informed consent was waived. From December 2008 to August 2011, 58 premenopausal women who had undergone contrast material-enhanced MR imaging and MR imaging-guided biopsy were identified. The longest time from the start of the last known period was 34 days. One lesion per patient (37 benign and 21 malignant) was analyzed. The patient groups were stratified according to the week of the menstrual cycle when MR imaging was performed. A method based on principal component analysis (PCA) was applied for quantitative analysis of signal enhancement in the BP and lesions by using the percentage of slope and percentage of enhancement. Linear regression and the Mann-Whitney U test were used to assess the association between the kinetic parameters and the week of the menstrual cycle. RESULTS: In the women with benign lesions, percentages of slope and enhancement for both BP and lesions during week 2 were significantly (P < .05) lower than those in week 4. Percentage of enhancement in the lesion in week 2 was lower than that in week 3 (P < .05). The MR images of women with malignant lesions showed no significant difference between the weeks for any of the parameters. There was a strong positive correlation between lesion and BP percentage of slope (r = 0.72) and between lesion and BP percentage of enhancement (r = 0.67) in the benign group. There was also a significant (P = .03) difference in lesion percentage of slope between the benign and malignant groups at week 2. CONCLUSION: The PCA-based method can quantify contrast enhancement kinetics of BP semiautomatically, and kinetics of BP and lesions vary according to the week of the menstrual cycle in benign but not in malignant lesions.

Breast MRI at 7 Tesla with a bilateral coil and T1-weighted acquisition with robust fat suppression: image evaluation and comparison with 3 Tesla.

OBJECTIVES: To evaluate the image quality of T1-weighted fat-suppressed breast MRI at 7 T and to compare 7-T and 3-T images. METHODS: Seventeen subjects were imaged using a 7-T bilateral transmit-receive coil and 3D gradient echo sequence with adiabatic inversion-based fat suppression (FS). Images were graded on a five-point scale and quantitatively assessed through signal-to-noise ratio (SNR), fibroglandular/fat contrast and signal uniformity measurements. RESULTS: Image scores at 7 and 3 T were similar on standard-resolution images (1.1 × 1.1 × 1.1-1.6 mm(3)), indicating that high-quality breast imaging with clinical parameters can be performed at 7 T. The 7-T SNR advantage was underscored on 0.6-mm isotropic images, where image quality was significantly greater than at 3 T (4.2 versus 3.1, P ≤ 0.0001). Fibroglandular/fat contrast was more than two times higher at 7 T than at 3 T, owing to effective adiabatic inversion-based FS and the inherent 7-T signal advantage. Signal uniformity was comparable at 7 and 3 T (P < 0.05). Similar 7-T image quality was observed in all subjects, indicating robustness against anatomical variation. CONCLUSION: The 7-T bilateral transmit-receive coil and adiabatic inversion-based FS technique produce image quality that is as good as or better than at 3 T. KEY POINTS: • High image quality bilateral breast MRI is achievable with clinical parameters at 7 T. • 7-T high-resolution imaging improves delineation of subtle soft tissue structures. • Adiabatic-based fat suppression provides excellent fibroglandular/fat contrast at 7 T. • 7- and 3-T 3D T1-weighted gradient-echo images have similar signal uniformity. • The 7-T dual solenoid coil enables bilateral imaging without compromising uniformity.

Auditory-perceptual evaluation of voice: comparing different speech tasks to identify children with and without laryngeal lesions. / Avaliação perceptivo-auditiva da voz: comparação de diferentes tarefas de fala na identificação de crianças com e sem lesões laríngeas.

PURPOSE: To compare the vowel emission and number counting tasks in perceptual-auditory differentiation among children with and without laryngeal lesions. METHODS: Observational, analytical, and cross-sectional methods were used. Medical records of 44 children were selected from a database of an otorhinolaryngology service at a University Hospital and they were divided into groups: without laryngeal lesion (WOLL), and with laryngeal lesion (WLL), with 33 and 11 children. For the auditory-perceptual evaluation, the vocal samples were separated according to the type of task. They were analyzed separately by a judge who analyzed the general degree of vocal deviation and assessed whether the child would pass or fail in the face of a screening situation. RESULTS: There was a difference between the WOLL and WLL groups in terms of the overall degree of vocal deviation for the task of number counting, with a predominance of mild deviations in WOLL and moderate in WLL. In the screening, there was a difference between the groups during the number counting task, with more failures in the WLL. The groups were similar in the sustained vowel task, both in terms of the overall degree of vocal deviation and the vocal screening. Most children in the WLL failed in both tasks during vocal screening compared to the children in the WOLL who, in general, failed in only one task. CONCLUSION: The task of number counting contributes to the auditory differentiation in children with and without laryngeal lesion, by identifying deviations of greater intensity in children with laryngeal lesion.

OBJETIVO: comparar as tarefas de emissão de vogal e de contagem de números na diferenciação perceptivo-auditiva de crianças com e sem lesão laríngea. MÉTODO: Estudo observacional, analítico, transversal. Utilizou-se banco de dados de uma pesquisa de doutorado, com resultados de avaliações laringológicas e gravação de amostras vocais de 44 crianças que se dividiram em: Grupo sem lesão laríngea (GSLL), com 33 crianças; e grupo com lesão laríngea (GCLL), com 11 crianças. Para a avaliação perceptivo-auditiva, as amostras vocais foram separadas de acordo com o tipo de tarefa e analisadas separadamente por uma juíza, que analisou o grau geral do desvio vocal e informou se, diante de uma situação de triagem, a criança passaria ou falharia. RESULTADOS: Houve diferença entre os grupos GSLL e GCLL quanto ao grau geral do desvio vocal para tarefa de emissão de números, com predomínio de desvios discretos no GSLL e moderados no GCLL. Quanto à triagem, houve diferença entre os grupos para a tarefa de contagem, com mais falhas no GCLL. Os grupos foram semelhantes na tarefa de vogal, tanto no que se refere à intensidade do desvio quanto ao resultado da triagem. A maior parte das crianças do GCLL falhou em ambas as tarefas na situação de triagem vocal, com diferença em relação às crianças do GSLL que, em geral, falharam em apenas uma tarefa. CONCLUSÃO: A tarefa de contagem de números contribui para a diferenciação auditiva de crianças com e sem lesão laríngea, por identificar desvios de maior intensidade em crianças com lesão.

Sex differences in the renin-angiotensin-aldosterone system and its roles in hypertension, cardiovascular, and kidney diseases.

Cardiovascular disease is a pathology that exhibits well-researched biological sex differences, making it possible for physicians to tailor preventative and therapeutic approaches for various diseases. Hypertension, which is defined as blood pressure greater than 130/80 mmHg, is the primary risk factor for developing coronary artery disease, stroke, and renal failure. Approximately 48% of American men and 43% of American women suffer from hypertension. Epidemiological data suggests that during reproductive years, women have much lower rates of hypertension than men. However, this protective effect disappears after the onset of menopause. Treatment-resistant hypertension affects approximately 10.3 million US adults and is unable to be controlled even after implementing ≥3 antihypertensives with complementary mechanisms. This indicates that other mechanisms responsible for modulating blood pressure are still unclear. Understanding the differences in genetic and hormonal mechanisms that lead to hypertension would allow for sex-specific treatment and an opportunity to improve patient outcomes. Therefore, this invited review will review and discuss recent advances in studying the sex-specific physiological mechanisms that affect the renin-angiotensin system and contribute to blood pressure control. It will also discuss research on sex differences in hypertension management, treatment, and outcomes.

Future teachers and the self-perception of vocal symptoms and knowledge about vocal health and hygiene. / Futuros professores e a autopercepção de sintomas vocais e conhecimento em saúde e higiene vocal.

PURPOSE: To analyze responses of future teachers regarding the self-perception of vocal symptoms and knowledge about vocal health and vocal hygiene, relating them to sociodemographic and occupational variables and previous knowledge about voice. METHODS: Observational, analytical and cross-sectional study. A total of 264 undergraduate students participated and the Vocal Health and Hygiene Questionnaire (QSHV), Vocal Symptoms Scale (ESV) and a questionnaire with sociodemographic, occupational and vocal questions were applied. Data were statistically analyzed considering a 5% significance level. RESULTS: QSHV of future teachers had a total mean score of 21.89, suggestive of lack of knowledge about vocal health and hygiene. The results of the ESV are above the instrument's cutoff score, in each of the three domains and in the total score, there was greater symptomatology in first-year students when compared to other students, in the emotional, limitation and total domains. There was a difference when comparing the QSHV with the year of graduation (p=0.001), in which third and fourth year students obtained higher scores. A positive correlation was observed between the total QSHV score and the age variable (p=0.019). CONCLUSION: Future teachers present important vocal symptomatology, compatible with dysphonic individuals, and have insufficient knowledge about vocal health and hygiene. Knowledge is even lower among students in the early undergraduate years and at a younger age. Older future teachers demonstrate more knowledge about vocal health and hygiene. It is necessary to propose preventive actions with this population, even during the graduation period, aiming to reduce the risks of developing vocal problems in the medium or long term during teaching.

OBJETIVO: Analisar respostas de futuros professores quanto à autopercepção de sintomas vocais e conhecimento sobre saúde vocal e higiene vocal, relacionando-os às variáveis sociodemográficas, ocupacionais e conhecimento prévio sobre voz. MÉTODO: Estudo observacional, analítico e transversal. Participaram 264 alunos de licenciatura, foram aplicados Questionário de Saúde e Higiene Vocal (QSHV), Escala de Sintomas Vocais (ESV) e questionário com perguntas sociodemográficas, ocupacionais e vocais. Os dados foram analisados estatisticamente considerando nível de significância 5%. RESULTADOS: QSHV de futuros professores apresentou escore médio total de 21,89, sugestivo de conhecimento insuficiente sobre saúde e higiene vocal. Resultados da ESV estão acima da nota de corte do instrumento, nos três domínios e no escore total, observou-se maior sintomatologia em estudantes do primeiro ano quando comparados aos demais estudantes, nos domínios emocional, limitação e total. Houve diferença na comparação do QSHV com o ano da graduação (p=0,001), em que alunos dos terceiros e quartos anos obtiveram pontuações maiores. Observou-se correlação positiva entre escore total do QSHV e variável idade (p=0,019). CONCLUSÃO: Futuros professores apresentam sintomatologia vocal importante, compatível aos indivíduos disfônicos, e possuem conhecimento insuficiente sobre saúde e higiene vocal. O conhecimento é ainda menor em alunos dos anos de graduação iniciais e com menor idade. Futuros professores com mais idade demonstram ter mais conhecimento sobre saúde e higiene vocal. Faz-se necessária a proposição de ações preventivas à essa população, ainda no período da graduação, visando à diminuição dos riscos ao desenvolvimento de problemas vocais em médio ou longo prazo durante a docência.

Acoustic measurements of CPPS and AVQI pre and post speech therapy. / Medidas acústicas de CPPS e AVQI pré e pós terapia fonoaudiológica.

PURPOSE: To compare the acoustic measurements of Cepstral Peak Prominence-Smoothed (CPPS) and Acoustic Voice Quality Index (AVQI) at pre- and post-voice therapy times. METHODS: This is a before and after intervention study, with retrospective data collection. Twenty-two subjects with a mean age of 49.9 years participated in the study. The vocal therapy occurred between the years 2016 to 2019 in a teaching clinic, and the subjects had vocal samples collected before and after the therapeutic processes. CPPS and AVQI data extractions were performed during pre- and post-therapy. In order to characterize the sample, auditory-perceptual evaluation (APE) regarding the overall degree of vocal deviation at pre- and post-therapy moments was performed. The data were analyzed statistically. RESULTS: The APE data indicated a decrease in the median values of overall vocal deviation degree at the post-therapy stage for both the vowel (p=0.00) and number (p=0.00) samples. The average CPPS for the vowel was 14.53 pre-therapy and 16.37 post-therapy (p=0.01); for the number emission, it was 8.22 pre-therapy and 9.06 post-therapy (p=0.02), there was a difference in the CPPS of the vowel and numbers indicating vocal improvement at post-therapy. The average AVQI was 2.27 pre-therapy and 1.54 post-therapy (p=0.05). There was an improvement in the AVQI results, with borderline p-value. CONCLUSION: Vocal therapy produced changes in the general degree of vocal deviation, as well as in CPPS and AVQI measurements, and the results at the post-therapy moment are similar to those of vocally healthy individuals.

OBJETIVO: Comparar as medidas acústicas de Proeminência do Pico Cepstral Suavizado (CPPS) e Acoustic Voice Quality Index (AVQI) nos momentos pré e pós-terapia Vocal. MÉTODO: Trata-se de estudo de intervenção antes e após, com coleta de dados retrospectiva. Participaram do estudo 22 sujeitos com média de idade de 49,9 anos. A terapia vocal ocorreu entre os anos de 2016 a 2019 em uma clínica-escola, sendo que antes e após os processos terapêuticos, os sujeitos tiveram amostras vocais coletadas. Foram realizadas as extrações dos dados de CPPS e AVQI nos momentos pré e pós-terapia. A fim de caracterizar a amostra, foi realizado julgamento perceptivo-auditivo (JPA) referente ao grau geral do desvio vocal nos momentos pré e pós-terapia. Os dados foram analisados estatisticamente. RESULTADOS: Os dados do JPA indicaram diminuição nos valores medianos de grau geral do desvio vocal no momento pós-terapia, tanto para a amostra de vogal (p=0,00) quanto de números (p=0,00). A média do CPPS para a vogal foi de 14,53 pré-terapia e 16,37 pós-terapia (p= 0,01) e na emissão dos números foi de 8,22 pré-terapia e 9,06 pós-terapia (p=0,02), houve diferença no CPPS da vogal e dos números indicando melhora vocal pós-terapia. A média do AVQI foi de 2,27 pré-terapia e 1,54 pós-terapia (p= 0,05), houve melhora nos resultados do AVQI, com valor de p limítrofe. CONCLUSÃO: A terapia vocal produziu modificações no grau geral do desvio vocal e nas medidas de CPPS e AVQI, sendo que no momento pós terapia os resultados são semelhantes aos apresentados por indivíduos vocalmente saudáveis.

Acetylcholine receptors of the neuromuscular junctions present normal distribution after peripheral nerve injury and repair through nerve guidance associated with fibrin biopolymer.

Peripheral nerve injuries (PNI) lead to alterations in the Agrin-LRP4-MuSK pathway. This results in disaggregation of AChRs and change from epsilon (mature, innervated) to gamma (immature, denervated) subunit. Tubulization technique has been shown to be effective for PNI repair and it also allows the use of adjuvants, such as fibrin biopolymer (FB). This study evaluated the effect of the association of tubulization with FB after PNI on AChRs and associated proteins. Fifty-two adults male Wistar rats were used, distributed in 4 experimental groups: Sham Control (S), Denervated Control (D); Tubulization (TB) and Tubulization + Fibrin Biopolymer (TB+FB). Catwalk was performed every 15 days. Ninety days after surgery the right soleus muscles and ischiatic nerves were submitted to the following analyses: (a) morphological and morphometric analysis of AChRs by confocal microscopy; (b) morphological and morphometric analysis of the ischiatic nerve; (c) protein quantification of AChRs: alpha, gama, and epsilon, of Schwann cells, agrin, LRP4, MuSK, rapsyn, MMP3, MyoD, myogenin, MURF1 and atrogin-1. The main results were about the NMJs that in the TB+FB group presented morphological and morphometric approximation (compactness index; area of the AChRs and motor plate) to the S group. In addition, there were also an increase of S100 and AChRε protein expression and a decrease of MyoD. These positive association resulted in AChRs stabilization that potentiate the neuromuscular regeneration, which strengthens the use of TB for severe injuries repair and the beneficial effect of FB, along with tubulization technique.

The Na+/H+ Exchanger 3 in the Intestines and the Proximal Tubule of the Kidney: Localization, Physiological Function, and Key Roles in Angiotensin II-Induced Hypertension.

The sodium (Na+)/hydrogen (H+) exchanger 3 (NHE3) is one of the most important Na+/H+ antiporters in the small intestines of the gastrointestinal tract and the proximal tubules of the kidney. The roles of NHE3 in the regulation of intracellular pH and acid-base balance have been well established in cellular physiology using in vitro techniques. Localized primarily on the apical membranes in small intestines and proximal tubules, the key action of NHE3 is to facilitate the entry of luminal Na+ and the extrusion of intracellular H+ from intestinal and proximal tubule tubular epithelial cells. NHE3 is, directly and indirectly, responsible for absorbing the majority of ingested Na+ from small and large intestines and reabsorbing >50% of filtered Na+ in the proximal tubules of the kidney. However, the roles of NHE3 in the regulation of proximal tubular Na+ transport in the integrative physiological settings and its contributions to the basal blood pressure regulation and angiotensin II (Ang II)-induced hypertension have not been well studied previously due to the lack of suitable animal models. Recently, novel genetically modified mouse models with whole-body, kidney-specific, or proximal tubule-specific deletion of NHE3 have been generated by us and others to determine the critical roles and underlying mechanisms of NHE3 in maintaining basal body salt and fluid balance, blood pressure homeostasis, and the development of Ang II-induced hypertension at the whole-body, kidney, or proximal tubule levels. The objective of this invited article is to review, update, and discuss recent findings on the critical roles of intestinal and proximal tubule NHE3 in maintaining basal blood pressure homeostasis and their potential therapeutic implications in the development of angiotensin II (Ang II)-dependent hypertension.