Adults with Treacher Collins Syndrome Share Comparable 3D Upper Airway Dimensions with Nonsyndromic Individuals.

Purpose: Sleep apnea symptoms, such as snoring and daytime somnolence, are commonly observed in individuals with Treacher Collins Syndrome (TCS) and may be related to airway obstruction due to micro- and retro-gnathia. This study aims to three-dimensionally evaluate the upper airway using cone-beam computed tomography (CBCT) exams of adolescents (TCS-ADOL) and adults (TCS-ADUL) with TCS compared to a nonsyndromic group (CON). Materials and Methods: Twenty-six CBCT exams were divided into three groups: TCS-ADOL (n = 7) (13.14 ± 1.67 years): CBCT exams of TCS adolescents; TCS-ADUL (n = 10) (21.80 ± 4.39 years): CBCT exams of TCS adults; and CON (n = 9) (25.33 ± 8.57 years): CBCT exams of adult nonsyndromic individuals with Class II skeletal pattern. The variables analyzed were (1) total upper airway volume; (2) nasal cavity volume; (3) total pharyngeal volume; (4) nasopharyngeal volume; (5) oropharyngeal volume; (6) pharyngeal minimal cross-sectional area; (7) pharyngeal length; and (8) pharyngeal depth. Scans were analyzed by two examiners, and intra- and inter-rater agreement was calculated. A p-value of ≤0.05 was considered significant. Results: Although not statistically significant, the TCS-ADUL group showed decreased airway volume and minimal cross-sectional areas compared to the CON group. There were also significant differences between TCS-ADOL and TCS-ADUL, with significantly lower airway volumes in the TCS-ADOL group. Strong positive correlations were found between certain airway measurements in the TCS-ADOL group, which were not observed in adults. Conclusions: The upper airways of adults with TCS are dimensionally similar to those of nonsyndromic individuals, despite absolute value reductions found in the syndromic group. The reduced airway in the adolescent population suggests significant potential for growth, mainly in pharyngeal dimensions.

Contractility assessment using aligned human iPSC-derived cardiomyocytes.

INTRODUCTION: Cardiac safety assessment, such as lethal arrhythmias and contractility dysfunction, is critical during drug development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been shown to be useful in predicting drug-induced proarrhythmic risk through international validation studies. Although cardiac contractility is another key function, fit-for-purpose hiPSC-CMs in evaluating drug-induced contractile dysfunction remain poorly understood. In this study, we investigated whether alignment of hiPSC-CMs on nanopatterned culture plates can assess drug-induced contractile changes more efficiently than non-aligned monolayer culture. METHODS: Aligned hiPSC-CMs were obtained by culturing on 96-well culture plates with a ridge-groove-ridge nanopattern on the bottom surface, while non-aligned hiPSC-CMs were cultured on regular 96-well plates. Next-generation sequencing and qPCR experiments were performed for gene expression analysis. Contractility of the hiPSC-CMs was assessed using an imaging-based motion analysis system. RESULTS: When cultured on nanopatterned plates, hiPSC-CMs exhibited an aligned morphology and enhanced expression of genes encoding proteins that regulate contractility, including myosin heavy chain, calcium channel, and ryanodine receptor. Compared to cultures on regular plates, the aligned hiPSC-CMs also showed both enhanced contraction and relaxation velocity. In addition, the aligned hiPSC-CMs showed a more physiological response to positive and negative inotropic agents, such as isoproterenol and verapamil. DISCUSSION: Taken together, the aligned hiPSC-CMs exhibited enhanced structural and functional properties, leading to an improved capacity for contractility assessment compared to the non-aligned cells. These findings suggest that the aligned hiPSC-CMs can be used to evaluate drug-induced cardiac contractile changes.

Give heart cells a beat: An interactive museum exhibit that synchronizes stem cell-derived cardiomyocytes to visitors' heartbeat.

Science museums play an important role in science education, engaging the public with science concepts and building support for scientific research. Here, we describe Give Heart Cells a Beat, an interactive exhibit that lets museum visitors synchronize the beating of live stem cell-derived cardiomyocytes to their own heart rate in real time. The beat rate of cells accurately matched the beat rate of visitors and responded dynamically to changes such as exercise. Visitor evaluation revealed that engagement with the specimen prompted curiosity in heart biology and stem cells. Give Heart Cells a Beat is the product of a close collaboration between a museum and an academic research laboratory, and to our knowledge, it is the first interactive exhibit to use live human heart cells. We hope this exhibit serves as an example for the implementation of stem cell technology in informal science education and inspires future relationships between academia and public science venues.

Effects of blood flow restriction therapy in patients with knee osteoarthritis: protocol for an overview of systematic reviews.

Background: Osteoarthritis (OA) is the most common and prevalent musculoskeletal disease associated with population aging, negatively impacting function and quality of life. A consequence of knee OA is quadriceps muscle weakness. Musculoskeletal rehabilitation using low load exercises, associated with Blood Flow Restriction (BFR) may be a useful alternative to high load exercises when those cannot be tolerated. Several systematic reviews have reported inconclusive results due to discrepancies in study findings, heterogeneity of results, evaluated time points, and research questions explored. Objective: To perform an overview of systematic reviews with meta-analyses, synthesizing the most recent evidence on the effects of muscle strength training with BFR for knee OA. Methodology: Systematic reviews that include primary controlled and randomized clinical trials will be considered for inclusion. Articles will be considered only if they present a clear and reproducible methodological structure, and when they clearly demonstrate that a critical analysis of the evidence was carried out using instrumented analysis. Narrative reviews, other types of review, overviews of systematic reviews, and diagnostic, prognostic and economic evaluation studies will be excluded. Studies must include adults aged 40 years and older with a diagnosis of knee OA. Two authors will perform an electronic search with guidance from an experienced librarian. The following databases will be searched: PubMed via MEDLINE, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), PEDro, Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCO host, Web of Science, and the gray literature. The search strategy used in the databases will follow the acronym PICOS (population, intervention, comparison, outcome, and study design). Screening (i.e., titles and abstracts) of studies identified by the search strategy will be selected using Rayyan (http://rayyan.qcri.org). The quality assessment will be performed using the "Assessment of Multiple Systematic Reviews" (AMSTAR-2) tool. Systematic Review Registration: PROSPERO, CRD42022367209.

Effects of topical ketorolac tromethamine on tear parameters, meibography, goblet cell density, and conjunctival oxidative stress in healthy dogs.

OBJECTIVES: The objective of the study was to evaluate whether a twice-daily instillation of 0.45% preservative-free ketorolac tromethamine (FKT) or 0.4% benzalkonium chloride-preserved ketorolac tromethamine (BACKT), every 12 h for 30 days may affect tear film parameters and the meibography in healthy dogs. Additionally, we assessed whether the same treatments irritated the ocular surface, affected goblet cell density (GCD), and the levels of oxidative stress biomarkers (OSB) in the conjunctiva of the same dogs. PROCEDURES: Experimental and masked comparison study. In 11 healthy dogs baseline values of the lipid layer thickness, tear meniscus height, non-invasive tear breakup time (NI-TFBT), and the meibomian gland (MG) loss were assessed by OSAvet®. For each dog, one eye received 40 µL of BACKT, while the other received 40 µL FKT, every 12 h for 30 consecutive days. Tear parameters and meibography were repeated 15, 30, and 60 days post-treatments. Conjunctival hyperemia and blepharospasm were monitored at the same time points. At baseline and Day 30, a conjunctival biopsy was collected for GCD and OSB determination. RESULTS: Conjunctival hyperemia and blepharospasm were not observed. At Day 15, the MG loss increased only in FKT-treated eyes (p < .001). On Day 30, both treatment groups showed increased MG loss, shortened NI-TFBT, and reduced GCD and catalase (p < .05). At Day 30, BACKT-treated eyes showed lower levels of superoxide dismutase (SOD) (p = .006) and higher levels of malondialdehyde (MDA) (p = .02). Differences between treatments were not observed for any parameter at any time point (p > .05). 60 days after treatment, OSAvet® parameters tended to return to values assessed at baseline; however, significant differences remained for MG loss (p < .05). CONCLUSIONS: Twice-daily instillation of KT, containing or not BAC, for 30 consecutive days shortened NI-TFBT, decreased GCD, and increased the MG loss in healthy dogs. KT should be used with caution when prescribed for long periods, particularly in patients with tear film abnormalities. However, future controlled studies using KT, BAC, and other topical NSAIDs are indicated to further support this finding.

Demineralized dentin matrix technique - a comparison of different demineralizing solutions.

This study aimed to evaluate the microstructure formed after the chemical treatment of teeth, for the development of autogenous grafts from the demineralized dentin matrix (DDM) technique, in order to identify the most efficient demineralizing solution. The specimens, originating from the root and coronal portion, were submitted to ultrasonic cleaning and drying in an oven for 1h at 100 ºC. Then, the density was determined by Archimedes' principle for each specimen, using distilled water as immersion liquid. The samples were separated into five groups: Control group: negative control, Distilled water;EDTA group: positive control, trisodium EDTA; NaOCl group: 2.5% sodium hypochlorite; HCl-0.6M group: 0.6M hydrochloric acid; and H2O2/H2SO4 group: hydrogen peroxide and sulfuric acid. Each specimen was immersed for 1h in the corresponding group descaling solution at 60 ºC. Subsequently, the mass loss and density of the treated specimens were determined by Archimedes' principle. Ultimately, the specimens of each group were characterized by microtomography, Scanning Electron Microscopy, and Energy Dispersive Spectrometry X-ray (SEM-EDS). The results demonstrated that the H2O2/H2SO4 solution allowed the formation of interconnected micropores, suggesting better pore structures for application in scaffolds, when compared to the other studied solutions.

Demineralized dentin matrix technique - a comparison of different demineralizing solutions

Abstract This study aimed to evaluate the microstructure formed after the chemical treatment of teeth, for the development of autogenous grafts from the demineralized dentin matrix (DDM) technique, in order to identify the most efficient demineralizing solution. The specimens, originating from the root and coronal portion, were submitted to ultrasonic cleaning and drying in an oven for 1h at 100 ºC. Then, the density was determined by Archimedes' principle for each specimen, using distilled water as immersion liquid. The samples were separated into five groups: Control group: negative control, Distilled water;EDTA group: positive control, trisodium EDTA; NaOCl group: 2.5% sodium hypochlorite; HCl-0.6M group: 0.6M hydrochloric acid; and H2O2/H2SO4 group: hydrogen peroxide and sulfuric acid. Each specimen was immersed for 1h in the corresponding group descaling solution at 60 ºC. Subsequently, the mass loss and density of the treated specimens were determined by Archimedes' principle. Ultimately, the specimens of each group were characterized by microtomography, Scanning Electron Microscopy, and Energy Dispersive Spectrometry X-ray (SEM-EDS). The results demonstrated that the H2O2/H2SO4 solution allowed the formation of interconnected micropores, suggesting better pore structures for application in scaffolds, when compared to the other studied solutions.

Resumo Este estudo teve como objetivo avaliar a microestrutura formada após o tratamento químico em dentes, para o desenvolvimento de enxertos autógenos a partir da técnica de matriz de dentina desmineralizada (DDM), a fim de identificar a solução desmineralizante mais eficiente. Os espécimes, provenientes da raiz e porção coronal, foram submetidos à limpeza ultrassônica e secagem em estufa por 1h a 100 ºC. Em seguida, a densidade foi determinada pelo princípio de Arquimedes para cada espécime, utilizando água destilada como líquido de imersão. As amostras foram separadas em cinco grupos: Controle: controle negativo, Água destilada; EDTA: controle positivo, EDTA trissódico; NaOCl: hipoclorito de sódio 2,5%; HCl-0.6M: ácido clorídrico 0,6M; e H2O2/H2SO4: peróxido de hidrogênio e ácido sulfúrico. Cada espécime foi imerso por 1h na solução descalcificante de grupo correspondente a 60 ºC. Posteriormente, a perda de massa e a densidade dos espécimes tratados foram determinadas pelo princípio de Arquimedes. Por fim, os espécimes de cada grupo foram caracterizados por microtomografia, microscopia eletrônica de varredura e espectrometria de energia dispersiva de raios-X (SEM-EDS). Os resultados demonstraram que a solução H2O2/H2SO4 permitiu a formação de microporos interligados, sugerindo melhores estruturas de poros para aplicação em scaffolds, quando comparada às demais soluções estudadas.

Reproducibility of drug-induced effects on the contractility of an engineered heart tissue derived from human pluripotent stem cells.

Introduction: Engineered heart tissues (EHTs) are three-dimensional culture platforms with cardiomyocytes differentiated from human pluripotent stem cells (hPSCs) and were designed for assaying cardiac contractility. For drug development applications, EHTs must have a stable function and provide reproducible results. We investigated these properties with EHTs made with different tissue casting batches and lines of differentiated hPSC-cardiomyocytes and analyzed them at different times after being fabricated. Methods: A video-optical assay was used for measuring EHT contractile outputs, and these results were compared with results from motion traction analysis of beating hPSC-cardiomyocytes cultured as monolayers in two-dimensional cultures. The reproducibility of induced contractile variations was tested using compounds with known mechanistic cardiac effects (isoproterenol, EMD-57033, omecamtiv mecarbil, verapamil, ranolazine, and mavacamten), or known to be clinically cardiotoxic (doxorubicin, sunitinib). These drug-induced variations were characterized at different electrical pacing rates and variations in intracellular calcium transients were also assessed in EHTs. Results: To ensure reproducibility in experiments, we established EHT quality control criteria based on excitation-contraction coupling and contractile sensitivity to extracellular calcium concentration. In summary, a baseline contractile force of 0.2 mN and excitation-contraction coupling of EHTs were used as quality control criteria to select suitable EHTs for analysis. Overall, drug-induced contractile responses were similar between monolayers and EHTs, where a close relationship was observed between contractile output and calcium kinetics. Contractile variations at multiple time points after adding cardiotoxic compounds were also detectable in EHTs. Discussion: Reproducibility of drug-induced effects in EHTs between experiments and relative to published work on these cellular models was generally observed. Future applications for EHTs may require additional mechanistic criteria related to drug effects and cardiac functional outputs to be measured in regard to specific contexts of use.

Evaluation of Functional and Joint Health and Associated Factors in Adults With Hemophilia From a Developing Country With Government-Backed Efforts to Improve Hemophilia Care.

Introduction Hemophilic arthropathy affects people with hemophilia (PwH) and causes joint dysfunction and disability. Brazil has a unique situation and implemented policies to improve health care for PwH. The aim of this study was to evaluate the Functional Independence Score in Hemophilia (FISH), Hemophilia Joint Health Score (HJHS), and associated factors among adult PwH attending a Hemophilia Comprehensive Care Center in Brazil. Methods A post hoc analysis was conducted, including 31 patients who had submitted to a physical evaluation during a previously published cross-sectional study performed from June 2015 to May 2016 at the Brasília Blood Center Foundation, Brazil. Results The mean age was 30.8±9.4 years, and 80.6% had severe hemophilia. FISH was 27.0±3.8, and HJHS 18.0±10.8. The ankle was the most often affected joint (25/31, 80.6%). There were significant correlations between FISH and HJHS scores and the Hemophilia Quality of Life Questionnaire for Adults. Patients with severe hemophilia (P = 0.029) and PwH aged ≥ 30 years (P = 0.049) had lower FISH scores. Monthly household income > 2 Brazilian minimum wages was independently associated with improved HJHS (P = 0.033). The factors simultaneously associated with better HJHS and FISH were age < 30 years (P = 0.021) and monthly household income < 2 minimum wages (P = 0.013). Conclusion FISH and HJHS showed favorable scores despite being performed in a country with unfavorable socioeconomic conditions. In addition to hemophilia severity and age, monthly household income was independently associated with functional and articular state of PwH. The results highlight the importance of the free provision of coagulation factors in Brazil.

Is Santaniella a ranunculid? Reassessment of this enigmatic fossil angiosperm from the Lower Cretaceous (Aptian, Crato Konservat-Lagerstätte, Brazil) provides a new interpretation.

PREMISE: The Lower Cretaceous Crato Konservat-Lagerstätte (CKL) preserves a rich flora that includes early angiosperms from northern Gondwana. From this area, the recently described fossil genus Santaniella was interpreted as a ranunculid (presumably Ranunculaceae). However, based on our examination of an additional specimen and a new phylogenetic analysis, we offer an alternative interpretation. METHODS: The new fossil was collected from an active quarry for paving stones in the state of Ceará, northeastern Brazil. We assessed support for alternative phylogenetic hypotheses using a combined analysis of morphological data and DNA sequence data using Bayesian inference. We used a consensus network to visualize the posterior distribution of trees, and we used RoguePlot to illustrate the support for alternative positions on a scaffold tree. RESULTS: The new material includes a flower-like structure not present in the original material and also includes follicles preserved at early stages of development. The flower-like structure is a compact terminal cluster of elliptical sterile laminar organs surrounding internal filamentous structures that occur on flexuous axes. Phylogenetic analyses did not support the fossil placement among eudicots. Instead, Santaniella appears to belong in the magnoliid clade. CONCLUSIONS: The presence of seeds in a marginal-linear placentation and enclosed in a follicle supports the fossil as an angiosperm. However, even though most characters are clearly recognizable, its combination of characters does not provide strong support for a close relationship to any extant order of flowering plants. Its position in the magnoliid clade is intriguing and, based on plicate carpels, it is definitely a mesangiosperm.

Biofeedback interventions for short term upper limb function following stroke: A systematic review with meta-analysis.

BACKGROUND: Biofeedback has been used by rehabilitation professionals in the treatment of poststroke function impairments. PURPOSE: Investigate the efficacy of any type of biofeedback intervention for the treatment of upper limb function in individuals following stroke. STUDY DESIGN: Systematic review of literature with meta-analysis. METHODS: Literature searches were conducted using MESH terms and text words in PubMed, Lilacs, Scielo, Scopus, PEDro, and Web of Science databases. The main outcome was improvement in upper limb's motor function and motor function in activities of daily living. We calculated the Mean Difference and Standardized Mean Difference for the assessment scales reported as primary outcome. The methodological quality of included studies was assessed using PEDro scale. The overall quality of the evidence was assessed using GRADE system. RESULTS: From 1360 articles identified, 16 were included in the review (09 in the meta-analysis). Three forest plots of hemiparesis and one of hemiplegia showed that biofeedback therapy associated with conventional therapy has a greater improvement in participants upper limb motor function when compared to isolated conventional therapy. Two forest plots of hemiparesis and one of hemiplegia showed no superiority in participants improvement for biofeedback associated with conventional therapy when compared to isolated conventional therapy. CONCLUSION: Biofeedback therapy associated with conventional therapy showed a small clinical effect when associated to conventional therapy and very low quality of evidence. Although further research with higher quality evidence is needed.

Effect of 0.15% sodium hyaluronate on tear film breakup time in healthy anesthetized cats.

OBJECTIVES: This study aimed to evaluate the effect of 0.15% sodium hyaluronate (SH) on tear film breakup time (TFBT) in healthy anesthetized cats. PROCEDURES: Forty cats undergoing elective surgery were enrolled. TFBT was assessed before anesthesia to obtain baseline values. As a preanesthetic medication, cats received midazolam, tramadol, and cetamine combined in the same syringe. For anesthetic induction and maintenance, propofol and isoflurane were used. After a 15 min stabilization period to achieve the surgical anesthetic plane, one eye was treated with one drop of SH, while the other eye received saline and served as a control. TFBT was measured at the end of the general anesthesia (T40) and 35 (T75) and 80 min (T120) after the termination of the anesthesia. TFBT values were compared between the control and SH-treated eyes; both values were also compared with the baseline values (p < .05). RESULTS: In the control eyes, TFBT significantly decreased from baseline at all time points (p < .001), while in SH-treated eyes, TFBT significantly increased from baseline only at T40 (p < .0001). In SH-treated eyes, TFBT was significantly higher than that in the control eyes at all time points (p < .001). CONCLUSIONS: In healthy cats, TFBT decreases significantly after 40 min of general anesthesia, and one drop of 0.15% sodium hyaluronate was able to maintain the stability of the tear film for up to 75 min in treated eyes. However, the isolated effect of each drug used in our anesthetic protocol on TFBT should be executed in further studies.

Effects of commercial amniotic membrane extract on the re-epithelialization time and the early expression of matrix metalloproteinase-9 in cats with experimentally induced corneal ulcers.

OBJECTIVES: To investigate whether a commercially available amniotic membrane extract (AME) can accelerate corneal wound healing and suppress the early expression of MMP-9 in the tears of cats with experimentally induced superficial ulcerative keratitis. PROCEDURES: A total number of 16 cats were included. At the end of keratectomy, cats in the treatment group (TG, n = 8) received 40 µl of AME (EyeQ® Amniotic Eye Drops, Vetrix®) four times daily, while cats in the control group (CG, n = 8) received 40 µl of saline at the same time points. Tears were collected 24 and 48 h after keratectomy, and the total MMP-9 was quantified by ELISA. RESULTS: The corneal re-epithelialization rate did not differ between groups (p = .26), being 0.48 ± 0.05 mm2 /h in the CG and 0.41 ± 0.03 mm2 /h in the TG. Similarly, the average time to achieve corneal wound healing did not differ between groups (p = .25) and was 61.50 ± 3.54 h in the CG and 70.50 ± 6.71 h in the TG. The dimensions of the ulcerated areas also did not differ at any time point between the groups (p > .05). In both groups, corneas healed without scarring, pigmentation, or vascularization. The expression of MMP-9 in the tears was similar in both groups at 24 h post-keratectomy, with a slight decrease at 48 h (p > .05). CONCLUSIONS: The instillation of a commercial AME (EyeQ®) is safe, but it did not decrease the corneal re-epithelialization time or the early expression of MMP-9 in the tears of cats with experimentally induced superficial ulcerative keratitis in this study.

Small-sided games in volleyball: A systematic review of the state of the art.

Studies on small-sided games (SSG) in team sports have increased in recent decades. However, the literature concerning this training strategy in volleyball is sparse. This study aims to summarize and analyse the scientific evidence on SSG in volleyball. For this purpose, electronic searches were conducted in August 2021 in PubMed, Scielo, ScienceDirect, Scopus, SPORTDiscus, and Web of Science databases. As result, a total of 22 studies (3 cross-sectional, 7 quasi-experimental, and 12 randomized controlled trial) that used SSG in volleyball were included in the qualitative synthesis after applying the eligibility criteria. Despite the few studies available for each outcome, our results suggest that the SSG can be used as a methodological resource for volleyball teaching and training of educational, recreational, and high-performance character. In conclusion, the use of SSG in volleyball is a pedagogical and training alternative with positive effects on populations with different levels of training (school and university students, recreational adult players, and athletes) considering instructional approaches, sport knowledge, participation in Physical Education classes, health markers, physical fitness, and physiological, psychological, and tactical-technical variables. However, more studies need to be carried out using SSG in volleyball in different contexts, with different manipulations and variables.

Potato waste as feedstock to produce biohydrogen and organic acids: A comparison of acid and alkaline pretreatments using response surface methodology.

The effects of physicochemical pre-treatment were evaluated on hydrogen (H2) production and organic acids from hydrolyzed potato peel. Central composite design (CCD) and response surface methodology (RSM) were used to evaluate the effects of different substrate concentrations on a wet basis (38.8-81.2 g.L-1) and hydrolyser ratios (6M NaOH and 30% HCl: 1.6-4.4% v.v-1; and H2SO4: 2.2-7.8% v.v-1). The experiments were conducted in batch reactors at 37 °C, using a heat-treated microbial consortium. The maximum H2 production potential (P), lag phase (λ), and maximum H2 production rate (Rm) were evaluated for untreated and pre-treated potato peel waste. H2 production was positively influenced under hydrolyzed substrate concentrations ≥75 g.L-1 in the three CCDs performed. Only the increase in the H2SO4 proportions (≥5% v.v-1) had a negative influence on H2 production. Increasing the 30% HCl and 6M NaOH proportions did not significantly influence the cumulative H2 production. The highest hydrogen production was obtained after alkaline pre-treatment by dark fermentation (P: 762.09 mL H2.L-1; λ: 14.56 h; Rm: 38.39 mL H2.L-1.h-1). Based on the CCD and RSM, the highest H2 production (1060.10 mL H2.L-1) was observed with 81.2 g.L-1 hydrolyzed potato peel with 3.0% v.v-1 of 6M NaOH. The highest yield liquid metabolites were acetic (513.70 mg. g-1 COD) and butyric acids (491.90 mg. g-1 COD).

Use of Human iPSC-CMs in Nonclinical Regulatory Studies for Cardiac Safety Assessment.

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide a human-relevant platform for cardiac function assessment. Alternative assays using hiPSC-CMs are increasingly being employed for regulatory decision-making. A retrospective review revealed steady use of hiPSC-CM-based in vitro assays in nonclinical studies of drug-induced cardiotoxicity in regulatory submissions to the U.S. Food and Drug Administration (FDA). Most of the hiPSC-CMs data were obtained in exploratory studies and submitted as supportive evidence in concordance with other nonclinical data. Some of those studies were used to inform clinical trial design. This article provides an overview of the use of hiPSC-CMs in regulatory applications to FDA, with a focus on the integration of human-relevant in vitro data into proarrhythmic and non-proarrhythmic risk assessment. By identifying the regulatory submissions including hiPSC-CMs data, we explore their utility and discuss their limitations for predicting human cardiac safety in clinical trials. An important take-home message is that regulatory acceptance of hiPSC-CMs data is dependent on both the context of use and accurate data interpretation.

Balance Exercise Circuit for fall prevention in older adults: a randomized controlled crossover trial.

Objectives: This study aimed to assess the immediate and short-term effects of the Balance Exercise Circuit (BEC) on muscle strength, postural balance, and quality of life, with the aim of preventing falls in older adults. Methods: Twenty-two volunteers participated in this randomized controlled crossover study. Group A performed BEC training in the initial 3 months and received no intervention in the following 3 months. Group B received no intervention during the first 3 months and then participated in BEC training for the next 3 months. In addition, participants were followed for an additional 3 months. Muscle strength, postural balance, functional mobility, and quality of life were assessed, respectively, using an isokinetic dynamometer, force platform, TUG test, and the WHOQOL. Results: After 3 months of training, Group A presented improved balance and rate of force development (RFD), while Group B presented improvements in RFD, TUG performance, and WHOQOL physical and psychological domains. Regarding the short-term effects, the participants maintained the training effects in WHOQOL balance, RFD, and the social domain. In addition, the number of falls decreased during follow-up. Conclusion: The BEC intervention improved muscle strength, postural balance, and quality of life in older adults, in addition to reducing the risk of falls. Trial registration: Brazilian Registry of Clinical Trials (ReBEC) - RBR-5nvrwm.

Muscle strength in Brazilian firefighters with non-specific chronic low back pain: A cross-sectional study.

BACKGROUND: Imbalance between flexor and extensor muscles of the trunk could negatively influence spinal stability. OBJECTIVES: Investigate the strength balance between flexor and extensor muscles of the trunk in military firefighters with non-specific chronic low back pain (NSCLBP). METHODS: One hundred and two male firefighters were assessed in an isokinetic dynamometer at 120°/s and 60°/s to investigate the balance ratio between flexor and extensor (F/E) muscles. RESULTS: An F/E ratio of 0.72 (SD: 0.22; 95% CI: 0.67-0.76; SEM: 0.02) was observed at 60°/s and 0.94 (SD: 0.41; 95% CI: 0.85-1.03; SEM: 0.04) at 120°/s. The mean peak torque of the extensor muscles was 343.1 N.m/Kg (SD: 94.87; 95% CI: 322.8-363.5; SEM: 10.23) at 60°/s and 270.5 N.m/Kg (SD: 113; 95% CI 246.3-294.8; SEM: 12.18) at 120°/s. The mean peak torque of the flexor muscles was 232.4 N.m/Kg (SD: 53.86; 95% CI 220.8-243.9; SEM: 5.81) at 60°/s and 223.8 N.m/Kg (SD: 66.34; 95% CI 209.6-238.1; SEM: 7.15) at 120°/s. All torques generated by the extensor muscles were higher than the flexor muscles (p < 0.05). CONCLUSIONS: Firefighters with NSCLBP presented a normal F/E balance ratio and higher strength of extensor muscles of the trunk.

IVIVE: Facilitating the Use of In Vitro Toxicity Data in Risk Assessment and Decision Making.

During the past few decades, the science of toxicology has been undergoing a transformation from observational to predictive science. New approach methodologies (NAMs), including in vitro assays, in silico models, read-across, and in vitro to in vivo extrapolation (IVIVE), are being developed to reduce, refine, or replace whole animal testing, encouraging the judicious use of time and resources. Some of these methods have advanced past the exploratory research stage and are beginning to gain acceptance for the risk assessment of chemicals. A review of the recent literature reveals a burst of IVIVE publications over the past decade. In this review, we propose operational definitions for IVIVE, present literature examples for several common toxicity endpoints, and highlight their implications in decision-making processes across various federal agencies, as well as international organizations, including those in the European Union (EU). The current challenges and future needs are also summarized for IVIVE. In addition to refining and reducing the number of animals in traditional toxicity testing protocols and being used for prioritizing chemical testing, the goal to use IVIVE to facilitate the replacement of animal models can be achieved through their continued evolution and development, including a strategic plan to qualify IVIVE methods for regulatory acceptance.