Too Much Dentistry.

This Viewpoint explores whether all dental procedures are clinically necessary given their expense and the disparate access to treatment among some socioeconomic and racial and ethnic groups.

Water Resistance Therapy in Individuals with Parkinson's Disease: A Session-by-Session Analysis of the Vocal Quality.

OBJECTIVES: Verify session-by-session effects of the water resistance therapy (WRT) on the vocal quality of individuals with Parkinson's disease (PD). METHODS: This is a retrospective analytical study. Then, the samples were acquired from a database composed of 10 men aged between 50 and 90 years old diagnosed with PD. The participants underwent WRT with a resonance tube; then, they were guided to perform the following phonatory tasks: comfortable pitch and loudness, high pitch, low pitch, ascending and descending glissandos, and sentence uttering. Furthermore, tube depth ranged from 2 cm to 9 cm. Finally, WRT was implemented twice per week, totaling eight sessions, each lasting 45 minutes. Participants were assessed before and after each therapy session. Hence, the data were assessed with spectrographic analysis, vocal intensity, cepstral peak prominence-smoothed, alpha ratio, L1-L0, oscillatory frequency, and auditory-perceptual assessment of overall degree, roughness, breathiness, and instability. One-way repeated measures analysis of variance and Friedman tests were applied (P < 0.05). Furthermore, Holm-Sidak and Tukey tests were used as posthoc tests. RESULTS: After the sixth session, the spectrographic analysis revealed that the tracing color intensity of medium frequencies darkened, whereas a better result could be observed after the eighth session. Regarding vocal intensity, the improvement could be observed from the third session. Additionally, L1-L0 followed the same results. The overall degree auditory-perceptual assessment revealed the best results only after the second, third, and fourth sessions; however, after the eighth session, the instability increased. CONCLUSIONS: WRT allowed better results from the third session, with some improvements in the sixth session. However, the instability increased after the eighth session; thus, it is important to review the phonatory tasks and session numbers to avoid an overload in the phonatory system.

High certainty evidence is stable and trustworthy, whereas evidence of moderate or lower certainty may be equally prone to being unstable.

OBJECTIVES: To assess to what extent the overall quality of evidence indicates changes to observe intervention effect estimates when new data become available. METHODS: We conducted a meta-epidemiological study. We obtained evidence from meta-analyses of randomized trials of Cochrane reviews addressing the same health-care question that was updated with inclusion of additional data between January 2016 and May 2021. We extracted the reported effect estimates with 95% confidence intervals (CIs) from meta-analyses and corresponding GRADE (Grading of Recommendations Assessment, Development, and Evaluation) assessments of any intervention comparison for the primary outcome in the first and the last updated review version. We considered the reported overall quality (certainty) of evidence (CoE) and specific evidence limitations (no, serious or very serious for risk of bias, imprecision, inconsistency, and/or indirectness). We assessed the change in pooled effect estimates between the original and updated evidence using the ratio of odds ratio (ROR), absolute ratio of odds ratio (aROR), ratio of standard errors (RoSE), direction of effects, and level of statistical significance. RESULTS: High CoE without limitations characterized 19.3% (n = 29) out of 150 included original Cochrane reviews. The update with additional data did not systematically change the effect estimates (mean ROR 1.00; 95% CI 0.99-1.02), which deviated 1.06-fold from the older estimates (median aROR; interquartile range [IQR]: 1.01-1.15), gained precision (median RoSE 0.87; IQR 0.76-1.00), and maintained the same direction with the same level of statistical significance in 93% (27 of 29) of cases. Lower CoE with limitations characterized 121 original reviews and graded as moderate CoE in 30.0% (45 of 150), low CoE in 32.0% (48 of 150), and very low CoE in 18.7% (28 of 150) reviews. Their update had larger absolute deviations (median aROR 1.12 to 1.33) and larger gains in precision (median RoSE 0.78-0.86) without clear and consistent differences between these categories of CoE. Changes in effect direction or statistical significance were also more common in the lower quality evidence, again with a similar extent across categories (without change in 75.6%, 64.6%, and 75.0% for moderate, low, very low CoE). As limitations increased, effect estimates deviated more (aROR 1.05 with zero, 1.11 with one, 1.25 with two, 1.24 with three limitations) and changes in direction or significance became more frequent (93.2% stable with no limitations, 74.5% with one, 68.2% with two, and 61.5% with three limitations). CONCLUSION: High-quality evidence without methodological deficiencies is trustworthy and stable, providing reliable intervention effect estimates when updated with new data. Evidence of moderate and lower quality may be equally prone to being unstable and cannot indicate if available effect estimates are true, exaggerated, or underestimated.

Risk of bias and methodological critical appraisal in systematic reviews of non- and micro-invasive caries management for primary and permanent teeth.

INTRODUCTION: Paediatric dentistry should rely on evidence-based clinical decisions supported by high-quality, unbiased systematic reviews (SRs). Therefore, the purpose of this study was to systematically evaluate the methodological quality and risk of bias of SRs focused on non- and micro-invasive treatment for caries lesions in primary and permanent teeth. METHODS: A comprehensive search was conducted in multiple databases, including MEDLINE/PubMed, Scopus, Web of Science, EMBASE, Epistemonikos, and ProQuest, up to March 2023 to identify relevant systematic reviews (SRs) focused on non- and micro-invasive caries treatment. Two independent reviewers extracted data from the included SRs and assessed the methodological quality and risk of bias using the AMSTAR 2 and ROBIS tools, respectively. RESULTS: A total of 39 SRs were included in the analysis. Among these, 27 SRs (69.2%) were assessed as having critically low methodological quality, 11 SRs (28.2%) were considered to have low methodological quality and only one SR was rated as high-quality. The primary concern identified was the absence of protocol registration before the commencing the study, observed in 33 SR when using the AMSTAR 2 tool. According to the ROBIS tool, 21 studies (53.8%) were categorised as low risk of bias, 10 (25.6%) as high risk and eight (20.5%) as unclear risk of bias. CONCLUSION: Our analysis revealed that SRs focused on non- and micro-invasive treatment for caries in children and adolescents had critically low methodological quality according to the AMSTAR 2 tool but demonstrated a low risk of bias based on the ROBIS tool. These findings highlight the importance of emphasizing prospective protocol registration, clear reporting of statistical analyses, and addressing potential bias implications within this topic. By addressing these issues, we can enhance the quality of SRs and ensure that clinical decisions rely on unbiased and trustworthy evidence. Registry DOI: 10.17605/OSF.IO/AR4MS.

Hospitalizations for coronavirus disease 2019: an analysis of the occurrence waves.

The pandemic has been characterized by several waves defined by viral strains responsible for the predominance of infections. We aimed to analyze the mean length of hospital stay for patients with COVID-19 during the first three waves of the pandemic and its distribution according to sociodemographic and clinical variables. This retrospective study used the notifications of patients hospitalized for COVID-19 in a Brazilian state during the period of the three waves of the disease as the data source. There were 13,910 hospitalizations for confirmed COVID-19 cases. The first wave was the longest, with 4101 (29.5%) hospitalizations, while the third, although shorter, had a higher number of hospitalized patients (N = 6960). The average length of stay in the hospital in all waves was associated with age groups up to 60 years old., elementary, high school and higher education, residents of the periurban area Regarding the presence of comorbidities, there was a statistically significant difference in the mean number of days of hospitalization among patients with chronic cardiovascular disease and obesity (P < 0.001). In conclusion, the COVID-19 pandemic has been distinctly revealed among the waves.

Health professionals' recommendations on the use of fluoride varnish for caries prevention in preschool children.

BACKGROUND: Fluoride varnish (FV) is widely recommended for caries prevention in preschool children, despite its anticaries benefits being uncertain and modest. Dentists often report using clinical practice guidelines (CPGs) as a source of scientific information. AIM: To identify and analyze recommendations for clinical practice on the use of FV for caries prevention in preschool children and to assess the methodological quality of the CPG on this topic. DESIGN: Two researchers independently used 12 search strategies and searched the first five pages of Google Search™ and three guideline databases for recommendations freely available to health professionals on the use of FV for caries prevention in preschoolers. Then, they retrieved and recorded recommendations that met the eligibility criteria and extracted the data. A third researcher resolved disagreements. Each included CPG was appraised using the AGREE II instrument. RESULTS: Twenty-nine documents were included. Recommendations varied according to age, patients' caries risk, and application frequency. Of the six CPGs, only one scored above 70% in the AGREE II overall assessment. CONCLUSION: Recommendations on the use of FV lacked scientific evidence, and CPGs were of poor quality. Application of FV is widely recommended despite recent evidence showing an uncertain, modest, and possibly not clinically relevant anticaries benefit. Dentists should be aware that it is necessary to critically appraise CPGs since they may be of poor quality.

Low-Frequency TENS in Women With Behavioral Dysphonia: Preliminary Data From a Randomized Clinical Trial.

PURPOSE: To verify the effectiveness of low-frequency transcutaneous electrical nerve stimulation (TENS) simultaneously applied to the performance of vocal exercises in women with behavioral dysphonia. METHODS: This is a randomized, blinded clinical trial (Register Number: RBR-5k95vs). Twelve adult women with vocal nodules, randomly divided into three groups (G1: 4 participants - 12 sessions - application of placebo TENS simultaneously to the execution of vocal exercises; G2: 5 participants - 12 sessions - application of low-frequency TENS (frequency at 10 Hz, 200 µs duration phase, motor threshold, with electrodes placed on the thyroid cartilage lamina, bilaterally); and G3: 3 participants - 12 sessions - application of low-frequency TENS (same condition as G2) simultaneously to the execution of vocal exercises), participated in this study. The therapies were performed for 30 minutes in each session, twice a week. The participants were evaluated regarding vocal quality through acoustic voice analysis (fundamental frequency, Cesptral Peak Prominence-Smoothed (CPPs), alpha ratio, L1-L0, Acoustic Breathiness Index (ABI), and Acoustic Vocal Quality Index (AVQI)), vocal economy through electroglottography, and vocal self-assessment using the Voice-Related Quality of Life (V-RQOL) protocol. Assessments were performed before and immediately after voice therapy. Data were analyzed using the two-way repeated-measures ANOVA (variance analysis) test to compare assessment times and intervention groups. RESULTS: It was observed that G2 presented a reduction in the ABI acoustic parameter after the intervention and an increase in the values of the CPPs and L1-L0 parameter and in the scores of the physical and total V-RQOL domains. There were no differences for the other outcomes in relation to time and group. CONCLUSION: Preliminary results indicate that low-frequency TENS applied alone can reduce ABI parameter values and improve voice-related quality of life in dysphonic women.

Electric hand warmer versus observation to avoid discomfort during scalp cooling for chemotherapy-induced alopecia prevention: a randomized study.

Chemotherapy-induced alopecia (CIA) is a challenge in the management of cancer patients. Scalp cooling (SC) leads to reduction in CIA, however it is associated with significant adverse events, leading to 3-13% discontinuation rates. This pilot study evaluated the role of Electric Hand Warmers (EHW) on thermal (TC), sensorial (SCo) and general comfort (GC) in patients with breast cancer (BC) undergoing chemotherapy and SC to reduce CIA. Patients were randomly assigned to EHW use or observation. TC, SCo and GC were evaluated after each chemotherapy infusion. Favorable outcomes in both TC and SCo defined a positive result on GC. We analysed the impact of age, alopecia, chemotherapy regimen and EHW use in the different comfort scales using a Logistic Regression (LR) model. Forty women with early breast cancer were randomly assigned to EHW (n = 20) or observation (n = 20) during neo(adjuvant) chemotherapy. Median age was 53 years. In the EHW arm, favorable thermal response was reported by 79% versus 50% in the control arm (odds ratio [OR] 3.79, p < 0.001). SCo was satisfactory in 82% in the EHW arm versus 74% in the control arm (OR 1.62, p = 0.1). Overall, 73% in the EHW arm had favorable GC versus 44% in the control arm (OR 3.4, p < 0.001). Age, alopecia, and chemotherapy regimen did not impact on comfort measures. Conclusion: Our study suggests that the use of an EHW has a consistent favorable impact on TC and GC of BC patients under SC technology to prevent CIA.

The Immunomodulatory Activity of Punica granatum L. Peel Extract Increases the Lifespan of Mice with Lethal Sepsis.

Sepsis is an organ dysfunction syndrome associated with high mortality. To date, no effective treatment is available to combat this disease. Punica granatum L. is a potential alternative treatment due to its anti-inflammatory, antimicrobial, and antioxidant properties. Thus, this study aimed to evaluate the effects of a hydroalcoholic crude extract from the peels of P. granatum (HCEPg) in mice with lethal sepsis. Lethal polymicrobial sepsis was induced in female Swiss mice via cecal ligation and puncture (CLP). Initially, the animals were divided into three groups: Sham (false-operated), CLP-control (phosphate-buffered saline), and CLP-HCEPg (single dose, 5 mg/kg, subcutaneous administration). Treatment was initiated immediately after the induction of sepsis, and survival was evaluated every 12 hr for 5 days. Those who survived were euthanized. Serum cytokine levels were measured using a cytometric bead array Mouse Inflammatory Cytokine Kit. The number of colony-forming units, as well as the number of cells in the lymphoid organs and their activation markers, were analyzed. Results showed that treatment with HCEPg increased lifespan and reduced bacterial counts in the peritoneum, bloodstream, and spleen. HCEPg also decreased hydrogen peroxide secretion by phagocytes and augmented serum IL-10 levels, indicating its systemic anti-inflammatory effects. Additionally, treatment with HCEPg attenuated infection-induced lung hemorrhage. Overall, P. granatum extract improved the lifespan of septic mice, possibly due to its antimicrobial, anti-inflammatory, and immunomodulatory effects, thereby regulating bacterial load and translocation, as well as controlling the systemic inflammation induced by sepsis.

Malignancy Associated with Low-Risk HPV6 and HPV11: A Systematic Review and Implications for Cancer Prevention.

High-risk human papillomavirus (HPV) is etiologically related to cervical cancer, other anogenital cancers and oropharyngeal carcinomas. Low-risk HPV, especially HPV6 and HPV11, cause genital warts and laryngeal papillomas. However, the accumulating data suggests that HPV6 and HPV11 may cause malignant lesions at non-cervical anatomic sites. This review aims to estimate the proportions of single and dual HPV6/11 infections in multiple cancers reported in the last 10 years in the Cochrane, Embasa and PubMed databases. Secondly, the genomes of HPV6/11 were compared with the most common high-risk genotype, HPV16, to determine the similarities and differences. A total of 11 articles were selected, including between one and 334 HPV+ cancer patients. The frequencies of single or dual HPV6/11 infections ranged between 0-5.5% for penile and 0-87.5% for laryngeal cancers and were null for vulvar, vaginal and oral cancers. The genomic similarities between HPV6/11 and HPV16 mainly involved the E7 gene, indicating a limited ability to block cell differentiation. The presence of single or dual HPV6/11 infections in variable proportions of penile and laryngeal cancers support the vaccination strategies that cover these genotypes, not only for preventing genital warts but also for cancer prevention. Other risk factors and co-carcinogens are likely to participate in epithelial carcinogenesis associated with low-risk HPV.

The impact of COVID-19 on maternal death and fetal death, a cohort study in Brazil.

OBJECTIVE: The study aimed to evaluate the risk of maternal death and fetal death among pregnant women infected with SARS-CoV-2. METHODS: This is a retrospective cohort study among pregnant women with secondary data from the National Live Births System (Sistema Nacional de Nascidos Vivos), National Mortality System (Sistema Nacional de Mortalidade), and e-SUS Health Surveillance System (Sistema e-SUS Vigilância em Saúde). Pregnant women confirmed for COVID-19 had positive RT-PCR between March 2020 and May 2021, pregnant women without COVID-19 were those without notification for disease. Maternal death, fetal death, and stillbirth were assessed as primary outcomes. RESULTS: We included 68,673 pregnant women not notified as suspected of COVID-19 and 1,386 with a confirmed diagnosis of COVID-19. Among pregnant women with COVID-19, 1013 (73.0%) were aged 20 to 34 years, 655 (47.2%) were brown, 907 (65.4%) had ≥ 8 years of education, in the third trimester of pregnancy (41.5%), undergoing cesarean section (64.5%). In adjusted analyses, COVID-19 in pregnancy had a higher risk of maternal death (relative risk [RR] 18.73-95% confidence interval [95%CI] 11.07-31.69), fetal death/stillbirth (RR 1.96-95%CI 1.18-3.25), preterm birth [RR 1.18-95%CI 1.01-1.39], cesarean delivery (RR 1.07-95%CI 1.02-1.11), and cesarean delivery occurring before the onset of labor (RR 1.33-95%CI 1.23-1.44). CONCLUSION: COVID-19 may contribute to unfavorable pregnancy outcomes. Results showed that pregnant women infected with SARS-CoV-2 had a higher risk of maternal death, fetal death/stillbirth, preterm birth, cesarean delivery, and cesarean section occurring before the onset of labor.

Neutrophil extracellular traps (NETs), transfusion requirements and clinical outcomes in orthotopic liver transplantation.

Inflammatory phenomena have a direct impact on the prognosis of orthotopic liver transplantation (OLT). Neutrophil extracellular traps (NETs) contribute to OLT inflammation and hemostasis imbalance in OLT. The association between NETosis, clinical outcomes and transfusion requirements is not determined. To evaluate NETs release during OLT and the effect of NETosis ontransfusion requirements and adverse outcomes in a prospective cohort of patients submitted to OLT. We quantified citrullinated histones (cit-H3) and circulating-free-DNA (cf-DNA) in ninety-three patients submitted to OLT in three periods: pre-transplant, after graft reperfusion and before discharge. NETs markers were compared between these periods using ANOVA test. The association of NETosis and adverse outcomes was evaluated using regression models adjusted for age, sex and corrected MELD. We observed a peak of circulating NETs following reperfusion, evidenced by a 2.4-fold increase in cit-H3 levels in the post-graft reperfusion period (median levels of cit-H3 pre transplant: 0.5 ng/mL, after reperfusion: 1.2 ng/mL and at discharge 0.5 ng/mL, p < 0.0001). We observed an association between increased levels of cit-H3 and in-hospital death (OR = 1.168, 95% CI 1.021-1.336, p = 0.024). No association was found between NETs markers and transfusion requirements. There is a prompt release of NETs after reperfusion that is associated with poorer outcomes and death. Intraoperative NETs release seems to be independent of transfusion requirements. These findings highlight the relevance of inflammation promoted by NETS and its impact on OLT adverse clinical outcomes.

Evaluation of a gene signature related to thrombotic manifestations in antiphospholipid syndrome.

Thrombotic primary antiphospholipid syndrome (t-PAPS) is an acquired condition characterized by heterogeneous thrombotic manifestations, which is intriguing since venous and arterial thrombosis appear to have distinct pathogenesis. Gene expression analysis may constitute a new approach to evaluate potential similarities or differences between the clinical manifestations of t-PAPS. Recently, dysregulation of the ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 genes has been associated with both arterial and venous thrombosis in the general population. Therefore, the aim of this study was to examine whether ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 expression was associated with t-PAPS. Gene expression was quantified by qPCR of total leukocyte mRNA. In this case-control study, 102 t-PAPS patients, 17 asymptomatic antiphospholipid (aPL) carriers and 100 controls were evaluated. Increased expression of ANXA3 (P = 0.008) and TNFAIP6 (P = 0.001) and decreased expression of the TXK gene (P = 0.0001) were associated with an increased risk of t-PAPS compared to the control. ANXA3 upregulation was more evident in cases of arterial thrombosis and multiple thrombotic events. There was no difference in the expression of these genes between triple and non-triple aPL positivity. ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 expression levels were also similar between aPL carriers and controls (P = 0.77; P = 0.48; P = 0.08; P = 0.73, and P = 0.13, respectively). In conclusion, our results showed that genes related to hemostasis (ANXA3) and immunity (TNFAIP6, TXK) are dysregulated in t-PAPS compared to controls. Gene dysregulation was not detected in aPL carriers and was not related to the aPL profile, suggesting that this gene signature is related to thrombotic manifestations rather than to aPL burden. Our results suggest that innate immunity and hemostasis pathways are associated with t-PAPS at a molecular level and may play a role in disease severity.

Economic evaluation of fluoride varnish application in preschoolers: A systematic review.

BACKGROUND: Fluoride varnish (FV) is a convenient way of professionally applying fluoride in preschoolers. However, its modest anticaries effect highlights the need for economic evaluations. AIM: To assess economic evaluations reporting applications of FV to reduce caries incidence in preschoolers. DESIGN: We included full economic evaluations with preschool participants, in which the intervention was FV and the outcome was related to dentin caries. We searched in CENTRAL; MEDLINE via PubMed; WEB OF SCIENCE; EMBASE; SCOPUS; LILACS; BBO; and BVS Economia em saúde, OpenGrey, and EconoLit. Clinical trial registers, thesis and dissertations, and meeting abstracts were hand searched, as well as 11 dental journals. Risk of bias in the included studies was assessed using the Philips' and Drummond's (full and simplified) tools. RESULTS: Titles and abstracts of 2871 articles were evaluated, and 200 were read in full. Eight cost-effectiveness studies were included: five modeling and three within-trial evaluations. None of the studies gave sufficient information to allow a thorough assessment using the bias tools. We did not combine the results of the studies due to the great heterogeneity among them. Four studies reported that FV in preschool children was a cost-effective measure, but in one of these studies, sealants and fluoride toothpaste were more cost-effective measures than the varnish, and three studies used limited data that compromised the generalizability of their results. The other four studies showed a large increase in costs due to the application of varnish and/or low cost-effectiveness. CONCLUSION: We did not find convincing overall evidence that applying FV in preschoolers is an anticaries cost-effective measure. The protocol of this systematic review is available at Open Science Framework (https://osf.io/xw5va/).

SOX3 duplication in a boy with 46,XX ovotesticular disorder of sex development and his 46,XX sister with atypical genitalia: Probable germline mosaicism.

Ovotesticular disorders of sex development (OT-DSD) are characterized by ovarian follicles and seminiferous tubules in the same individual, with a wide range of atypical genitalia. We report on two sibs with atypical genitalia and SRY-negative 46,XX DSD, OT-DSD was confirmed only in the boy, while the girl had bilateral ovaries. Chromosome microarray analysis (CMA) showed a 737-kb duplication at Xq27.1 including the entire SOX3 gene in both sibs, which was confirmed by quantitative real time PCR. Also, X chromosome inactivation assay showed random inactivation in both sibs. Whole exome sequencing revealed no pathogenic or likely pathogenic variant. CMA of the parents showed normal results for both, suggesting that germline mosaicism could be the reason of recurrence of this duplication in the siblings. Our results support a pathogenic role of SOX3 overexpression in 46,XX subjects leading to variable DSD phenotypes.

Efficacy and safety of hemodialysis strategies for pregnant women with chronic kidney disease: Systematic review.

Pregnancy in chronic kidney disease (CKD) women is relatively rare, and the less risky choice of hemodialysis is unknown. The objective of this systematic review was to identify, systematically evaluate and summarize the available evidence on the efficacy and safety of hemodialysis strategies for pregnant CKD women. Sensitive search strategies were applied to six databases without data or language restrictions. Comparative (randomized and non-randomized) studies were prioritized. Two reviewers independently selected, extracted, and critically evaluated data from studies. The risk of bias assessment was performed using the ROBINS-I tool, considering the study design (non-randomized comparative observational studies). The certainty of the evidence was assessed using the GRADE approach. From 7210 references identified, six retrospective cohort studies were included (576 women). The effects of intensive hemodialysis (over 20 h/week) are uncertain for maternal and neonatal mortality (Peto odds ratio [OR] 0.85; 95% confidence interval [95% CI] 0.26-2.80), miscarriage (Peto OR 0, 38; 95% CI 0.12-1.23), stillbirths (Peto OR 0, 56; 95% CI 0.13-2.31), preterm birth (Peto OR 0.87; 95% CI 0.33-2.28), low birth weight (Peto OR 0.71; 95% CI 0.20-2.50) and congenital anomalies rates. The certainty of the evidence was very low due to studies methodological limitations and effect estimates imprecision. The uncertainty about intensive versus conventional hemodialysis effects for pregnant women with CKD and the imprecision in the estimated effects precludes any recommendation. The strategy choice must consider treatment availability, costs, and maternal social aspects until future studies provide more reliable evidence. PROSPERO CRD42021259237.

The influence of the low-frequency transcutaneous electrical nerve stimulation application moment in vocal quality of dysphonic women.

Objective: to compare the immediate effects of low-frequency TENS employment on vocal quality in women with behavioral dysphonia before and after vocal exercises.Methodology: 30 women (mean = 31.3 years old), diagnosed with behavioral dysphonia received low-frequency TENS before (TENS + VE Group) and after vocal exercises (VE + TENS Group) with a 1-week washout. They had their sustained vowel/a/and running speech recorded before and after each procedure for auditory-perceptual analysis and acoustic measures. The low-frequency TENS parameters applied were symmetrical biphasic quadratic pulse, 200 µs phase, 10 Hz frequency, intensity on the motor threshold, and the electrodes were positioned on the submandibular and superior fibers of the trapezius muscle region. The vocal exercises: tongue trill, humming, finger kazoo, and water resistance therapy were performed totalizing 20 min.Results: intragroup analysis of sustained vowel/a/showed reduction in both groups of strain parameter and increased the breathiness; only VE + TENS Group increased the instability parameter, decreased fundamental frequency, and increased in SPI values; the running speech analysis showed an increase in the overall degree, roughness, and breathiness parameters. However, in VE + TENS Group, there was a statistically significant decrease in the intensity of the strain and an increase in breathiness. The acoustic measures showed that VE + TENS Group had a higher variation than TENS + VE Group regarding NHR.Conclusion: vocal exercises followed by low-frequency TENS have more immediate positive effects on voice quality than the low-frequency TENS followed by vocal exercises. This is a preliminary immediate effects study, and these effects could be verified through long-term assessments.

Sociodemographic and Clinical Factors Associated with Treatment Outcomes for Drug-resistant Tuberculosis.

Drug-resistant tuberculosis (DR-TB) continues to be a serious public health problem. The objective of this study was to evaluate the sociodemographic, radiological, clinical, and outcome characteristics and assess the determinants of unfavorable outcomes in DR-TB. The descriptive-analytical study was carried out in a reference outpatient clinic in Rio de Janeiro, Brazil, among DR-TB cases that received treatment between February 2016 and October 2020, using descriptive statistics, χ2 test, and logistic regression multivariate. Of the 148 cases, 12.2% were resistant to rifampicin, 12.2% were resistant to isoniazid, 18.2% were polyresistant, 56.1% multidrug resistant, and 1.3% were extensively drug resistant. Most of the patients were men, aged up to 44 years, with brown or black skin, having up to 8 years of schooling, unemployed or working in the informal economy, and of low income. Presenting with acquired resistance or positive sputum smear microscopy in the diagnosis, taking more than four drugs, and being unemployed were associated with unfavorable outcomes. Having no income or acquired resistance doubled the chances of unfavorable outcomes. There was a high proportion of unfavorable outcomes, thereby highlighting the need to concentrate efforts on planning and executing public policies that include the severity of DR-TB and its risk factors.

Biallelic frameshift variant in the TBC1D2B gene in two siblings with progressive gingival overgrowth, fibrous dysplasia of face, and mental deterioration.

Biallelic loss-of-function variants in the TBC1D2B gene were recently reported as a cause of a neurodevelopmental disorder with seizures and gingival overgrowth. Here, we report two male siblings with the similar clinical characteristics. They started with gingival overgrowth and bilateral growth of soft tissues in the malar region at 3 years of age, which evolved with significant maxillary hypertrophy and compression of the brainstem due to fibrous dysplasia of facial bones. After disease evolution, they presented with mental deterioration, limb tremors, and gait ataxia. One of them also presented with seizures. Whole exome sequencing revealed a novel biallelic frameshift variant [c.595del; p.(Val199Trpfs*22)] in the TBC1D2B gene in both patients, which was confirmed and found in heterozygous state in each of their parents. There are strong similarities in clinical characteristics, age of onset, and evolution between the patients described here and cases reported in the literature, including cherubism-like phenotype with progressive gingival overgrowth and seizures. This is the fourth family in the world in which a biallelic loss-of-function variant in the TBC1D2B gene is associated with this phenotype. These results support that loss of TBC1D2B is the cause of this rare condition.

Effects of Resonance Tube Voice Therapy on Parkinson's Disease: Clinical Trial.

PURPOSE: To verify the effect of resonance tube voice therapy on the vocal aspects of patients with Parkinson's Disease (PD). METHOD: Intra-subject comparative controlled clinical trial with a single group assignment. Fourteen individuals with PD (10 men, mean age 66.1 years; four women, mean age 73.75 years) received eight 45-minute sessions of voice therapy, twice a week for 4 weeks. The therapy consisted of semi-occluded vocal tract exercises - phonation method in a resonance tube (glass, 27 cm x 9 mm) in water. Tube depth in water ranged from 2 cm to 9 cm, as the difficulty in carrying out the exercises increased (usual pitch, high pitch, low pitch, ascending/descending glissandos), followed by sentence production. The assessments were made three times: at baseline (Time0), after 30 days without intervention (Time1), and 1 day after eight intervention sessions (Time2). The following aspects were assessed: vocal intensity; acoustic parameters (Smoothed Cepstral Peak Prominence - CPPs, alpha ratio, and L1-L0 difference); auditory-perceptual analysis of the overall degree of vocal quality deviation; voice symptoms (Voice Symptom Scale protocol - VoiSS) and voice-related quality of life (Voice-Related Quality of Life Protocol - V-RQOL). The results were compared at the three times of assessment Time0/Time1/Time2 using one-way repeated measures ANOVA test and Tukey test (5% significance). RESULTS: intervention significantly increased: vocal intensity, L1-L0 value of vowel /a/ and counting, CPP value in counting, and decreased: the overall degree of vocal quality deviation in 78% of participants, the total score of VoiSS protocol, the limitation, and emotional subscales. In addition, the intervention increased the score of all the domains of V-RQOL protocol - physical, socio-emotional, and total. CONCLUSION: Resonance tube phonation in voice therapy was effective in increasing vocal intensity and long-term acoustic parameters, the improved overall degree of vocal quality, reducing voice symptoms, and increasing voice-related quality of life in individuals with PD.