Hilab System Device in an Oncological Hospital: A New Clinical Approach for Point of Care CBC Test, Supported by the Internet of Things and Machine Learning.

The complete blood count (CBC) is a highly requested test that is generally restricted to centralized laboratories, which are limited by high cost, being maintenance-demanding, and requiring costly equipment. The Hilab System (HS) is a small, handheld hematological platform that uses microscopy and chromatography techniques, combined with machine learning (ML) and artificial intelligence (AI), to perform a CBC test. This platform uses ML and AI techniques to add higher accuracy and reliability to the results besides allowing for faster reporting. For clinical and flagging capability evaluation of the handheld device, the study analyzed 550 blood samples of patients from a reference institution for oncological diseases. The clinical analysis encompassed the data comparison between the Hilab System and a conventional hematological analyzer (Sysmex XE-2100) for all CBC analytes. The flagging capability study compared the microscopic findings from the Hilab System and the standard blood smear evaluation method. The study also assessed the sample collection source (venous or capillary) influences. The Pearson correlation, Student t-test, Bland-Altman, and Passing-Bablok plot of analytes were calculated and are shown. Data from both methodologies were similar (p > 0.05; r ≥ 0.9 for most parameters) for all CBC analytes and flagging parameters. Venous and capillary samples did not differ statistically (p > 0.05). The study indicates that the Hilab System provides humanized blood collection associated with fast and accurate data, essential features for patient wellbeing and quick physician decision making.

Preclinical Evaluation of the Tumorigenic and Immunomodulatory Properties of Human Bone Marrow Mesenchymal Stromal Cell Populations with Clonal Trisomy 5.

Cytogenetic aberrations may emerge in human mesenchymal stromal cells (MSC) during ex vivo expansion for cell therapy. We have detected clonal trisomy 5 in two distinct autologous MSC products expanded from bone marrow which, based on the current quality control criteria, could not be released for clinical use. Although a safety concern, it is still unclear to what extent recurrent aneuploidies detected in MSC products may affect the threshold for neoplastic transformation or the medicinal properties of these cells. We have carried out an exploratory preclinical study to evaluate these MSC products with clonal trisomy 5, regarding their oncogenic and immunomodulatory potential. Cell population growth in vitro was reduced in MSC cultures with clonal trisomy 5 compared with the population growth of their euploid MSC counterparts, based on a lower cumulative population doubling level, reduced cell proliferation index, and increased senescence-associated beta-galactosidase activity. Subcutaneous injection of clinically relevant amount of MSC population, either with or without clonal trisomy 5, did not generate tumors in immunodeficient mice within a follow-up period of six months. Most importantly, MSC population with clonal trisomy 5 kept immunomodulatory properties upon interferon gamma (IFNγ) licensing, displaying overexpression of IDO, CXCL9, CXCL10, and CXCL11, in a similar fashion than that of IFNγ-licensed euploid MSC. Our findings suggest that bone marrow MSC products with clonal trisomy 5 may retain their therapeutic potential, based on poor tumor initiating capability and preserved immunomodulatory potency. This preclinical evidence may further support the definition of release criteria of autologous MSC products for cell therapy under critical clinical scenarios. This trial is registered with Clinical Study registration number: RBR-29x2pr.

Report of a clinical and laboratory management of cell therapy for knee cartilage in the face of mycoplasma contamination.

To describe a case of autologous chondrocyte implantation after cell culture contamination by Mycoplasma pneumoniae and the measures taken to successfully complete cell therapy in a patient with focal chondral lesion. A 45-year-old male patient, complaining of chronic pain on the knee and no history of trauma. He had a chondral lesion in the trochlear region of the femur and clinical tests compatible with pain in the anterior compartment of the knee. Conservative treatment failed to alleviate symptoms. Surgical treatment was indicated, but due to the size of the lesion, membrane-assisted autologous chondrocyte implantation was the technique of choice. Cartilage biopsies were collected from the intercondylar region of the distal femur. After isolation, chondrocytes were expanded ex vivo in a trained laboratory, for three weeks, and seeded onto a commercially available collagen membrane prior to implantation in the knee. Two days before surgery, a cell culture sample tested positive for Mycoplasma pneumoniae. The source of contamination was found to be autologous blood serum, extracted from the patient´s peripheral vein, and used to supplement the cell culture medium. After treating the patient with antibiotics, all procedures were repeated and the new final cell product, free from contaminants, was successfully implanted. We discuss the strategies available to deal with this situation, and describe the results of this particular case, which led to modifications in the autologous chondrocyte implant protocol.

The first gene therapy for RPE65 biallelic dystrophy with voretigene neparvovec-rzyl in Brazil.

PURPOSE: To report the first Brazilian patient with RPE65 deficiency-inherited retinal dystrophy (RPE65-IRD) treated with voretigene neparvovec-rzyl (VN). METHODS: An adult patient with Leber congenital amaurosis-2 with a homozygous mutation in the RPE65 gene (p.Phe83Leu) was treated bilaterally with VN. The clinical and surgical aspects are described. The baseline and 4-month postoperative ophthalmologic examinations included measurement of the best-corrected visual acuity (BCVA), full-field stimulus threshold (FST) test, Octopus 900 semiautomated kinetic visual fields (VFs), and microperimetry. RESULTS: No complications developed in this patient. The BCVA remained stable. The full-field stimulus threshold test (FST) and VFs showed clinically significant improvements bilaterally. The patient reported significant improvements in the ability to perform daily activities, mainly for those requiring the VFs and vision in a low-luminescence environment. CONCLUSIONS: The treatments were beneficial for this patient who was homozygous for RPE65 p.Phe83Leu. The first VN treatments in an adult Brazilian patient in clinical practice showed measurable improvements in visual outcomes that were meaningful for the patient's daily activities. TRANSLATIONAL RELEVANCE: This case reinforces the clinical trial results and proves that the procedure is feasible in countries such as Brazil.

Swallowing disorders and associated factors in older adults living in nursing homes.

PURPOSE: The aim of this study was to identify the frequency of swallowing disorders and the associated factors in older adults living in nursing homes. METHODS: This is a cross-sectional study with a sample of 73 older adults (≥ 60 years; mean age = 80 ± 7.49 years; female = 82.2%) living in five non-profit Brazilian nursing homes. Demographic and clinical data were collected. The frequency of swallowing disorders was determined by the Volume-Viscosity Swallow Test (VVS-T). Covariables with a p-value less than 0.20 according to Pearson's chi-square test or Fisher's exact test were included in the multiple logistic regression analysis model. The level of significance was 5%. RESULTS: The frequency of swallowing disorders was 63%. The multiple logistic regression model revealed that the chance of an older adult living in a nursing home presenting with swallowing disorders increased by 8% with each 1-year increase in age. Decreases in oral intake level improved the chance of a negative result in the VVS-T by approximately four times, and an individual with a FOIS level below seven was almost 11 times more likely to have a swallowing disorder. CONCLUSION: The frequency of swallowing disorders in older adults living in nursing homes is high and is associated with age and oral intake. The management care team should be aware of the early detection of these conditions to prevent complications of oropharyngeal dysphagia.

Matrix-assisted autologous chondrocyte transplantation for treatment of focal chondral lesions in the knee: the Hospital Israelita Albert Einstein experience

ABSTRACT Objective Phase 1 clinical trial to determine feasibility, safety, and efficacy of a new advanced cell therapy product for treatment of knee articular cartilage injuries. Methods Three participants with knee focal chondral lesions were included, with no signs of osteoarthritis. Chondrocytes were obtained through knee arthroscopy, cultured in collagen membrane for 3 weeks at the laboratory, subjected to tests to release the cell therapy product, and implanted. All patients underwent a specific 3-month rehabilitation protocol, followed by assessments using functional and imaging scales. The main outcome was the incidence of severe adverse events. Results Three participants were included and completed the 2-year follow-up. There was one severe adverse event, venous thrombosis of distal leg veins, which was no associated with therapy, was treated and left no sequelae. The clinical and radiological scales showed improvement in the three cases. Conclusion The preliminary results, obtained with the described methodology, allow concluding that this product of advanced cell therapy is safe and feasible. ReBEC platform registration number: RBR-6fgy76

Report of a clinical and laboratory management of cell therapy for knee cartilage in the face of mycoplasma contamination

ABSTRACT To describe a case of autologous chondrocyte implantation after cell culture contamination by Mycoplasma pneumoniae and the measures taken to successfully complete cell therapy in a patient with focal chondral lesion. A 45-year-old male patient, complaining of chronic pain on the knee and no history of trauma. He had a chondral lesion in the trochlear region of the femur and clinical tests compatible with pain in the anterior compartment of the knee. Conservative treatment failed to alleviate symptoms. Surgical treatment was indicated, but due to the size of the lesion, membrane-assisted autologous chondrocyte implantation was the technique of choice. Cartilage biopsies were collected from the intercondylar region of the distal femur. After isolation, chondrocytes were expanded ex vivo in a trained laboratory, for three weeks, and seeded onto a commercially available collagen membrane prior to implantation in the knee. Two days before surgery, a cell culture sample tested positive for Mycoplasma pneumoniae. The source of contamination was found to be autologous blood serum, extracted from the patient´s peripheral vein, and used to supplement the cell culture medium. After treating the patient with antibiotics, all procedures were repeated and the new final cell product, free from contaminants, was successfully implanted. We discuss the strategies available to deal with this situation, and describe the results of this particular case, which led to modifications in the autologous chondrocyte implant protocol.

Tongue measurements and pharyngeal residue in amyotrophic lateral sclerosis.

Aim: We aimed to analyze the relationship between tongue measurements and vallecular residue in patients with amyotrophic lateral sclerosis (ALS). Materials & methods: Twenty-one patients with ALS were assessed for posterior maximum tongue isometric pressure (PMTIP) and posterior tongue isometric endurance (PTIE) by the Iowa Oral Performance Instrument; vallecular residue after 10 ml of moderately thickened consistency by Fiberoptic Endoscopic Evaluation of Swallowing; and tongue thickness (TT) by ultrasonography. Results: PMTIP, PTIE and TT were decreased compared with the reference values for healthy individuals and were not different between patients with and without vallecular residue. Conclusion: In ALS, PMTIP, PTIE and TT are not good predictors of vallecular residue in the tested volume and food consistency.

Lay abstract This study aimed to analyze the relationship of measurable characteristics of the tongue in patients with amyotrophic lateral sclerosis (ALS) and the accumulation of residue after swallowing in an area located just after the tongue. This accumulation of residue provides a sensation of bolus stuck in the throat and increases the risk of weight loss, choking and pulmonary complications. Twenty-one ALS patients were assessed for tongue pressure, tongue endurance, tongue thickness and residue after swallowing of the 10 ml of moderately thickened consistency. This study concluded that all tongue measurements were low in ALS patients with and without residue. Therefore, these tongue measurements are not good predictors of vallecular residue in the tested volume and food consistency.

Characterizing temporal and spatial recruitment of systemically administered RPE65-programmed bone marrow-derived cells to the retina in a mouse model of age-related macular degeneration.

PURPOSE: Previously, we reported that the intravenous injection of bone marrow-derived cells (BMDC) infected with lentivirus expressing the human RPE65 gene resulted in the programming of BMDC to promote visual recovery in a mouse model of age-related macular degeneration (AMD). The aim of this study was to characterize the spatial and temporal recruitment of these programmed BMDC to the retinal pigment epithelial (RPE) layer. METHODS: C57BL/6J female mice received a subretinal injection of AAV1-SOD2 ribozyme to knock down (KD) superoxide dismutase 2 (SOD2) and induce AMD-like pathology. BMDC were isolated from GFP+ mice and infected with a lentivirus expressing RPE65. One month after SOD2 KD, fifty thousand GFP+ RPE65-BMDC were injected in the mouse tail vein. Animals were terminated at different time points up to 60 min following cell administration, and localization of GFP+ cells was determined by fluorescence microscopy of neural retina and RPE flat mounts and tissue sections. RESULTS: GFP+ RPE65- BMDC were observed in SOD2 KD neural retina and RPE as early as 1 min following administration. With increasing time, the number of cells in the neural retina decreased, while those in the RPE increased. While the number of cells in peripheral and central retina remained similar at each time point, the number of BMDC recruited to the central RPE increased in a time-dependent manner up to a maximum by 60 min post administration. Immunohistochemistry of cross-sections of the RPE layer confirmed the incorporation of donor GFP+ BMDC into the RPE layer and that these GFP+ human RPE65 expressing cells co-localized with murine RPE65. No GFP+ cells were observed in the neural retina or RPE layer of normal uninjured control eyes. CONCLUSIONS: Our study shows that systemically administered GFP+ RPE65-BMDC can reach the retina within minutes and that the majority of these BMDC are recruited to the injured RPE layer by 60 min post injection.

Método intensivo de terapia vocal para idosos / Intensive voice therapy for the elderly

RESUMO O objetivo deste relato de caso foi descrever os resultados da terapia fonoaudiológica intensiva, em um caso de presbifonia, e apresentar uma proposta de tratamento vocal para idosos, demonstrando seus resultados na qualidade vocal, qualidade de vida e imagem laríngea de um paciente com presbifonia. O programa Terapia Vocal para Idosos (TVI) é constituído por uma sequência de exercícios, que visam ao aumento da loudness, coordenação pneumofonoarticulatória, melhora na vibração de mucosa e equilíbrio de ressonância, além da variação e controle da frequência. O modelo terapêutico em questão foi aplicado em um indivíduo do gênero feminino, com 87 anos de idade e queixas de voz fraca e dificuldade em ser ouvido. As terapias ocorreram de maneira intensiva em 16 sessões com 30 minutos de duração, quatro vezes por semana e com realização de exercícios em casa. A experiência de aplicação do programa em formato intensivo mostrou efeitos positivos na qualidade vocal, com diminuição do desvio global da voz, soprosidade na emissão sustentada e rugosidade na emissão sustentada e fala. A melhora no desempenho vocal refletiu em aumento nos valores dos domínios físico e global do protocolo de qualidade de vida relacionada à voz. Houve, também, melhora no fechamento glótico. O tratamento vocal com o método TVI intensivo demonstra efeitos positivos no tratamento da presbifonia e tem o potencial de promover benefícios na qualidade vocal, na qualidade de vida relacionada à voz e nos aspectos laríngeos dos idosos.

ABSTRACT The aim of this study is to describe the results of intensive voice therapy in a presbyphonia case and to propose a voice treatment program for the elderly by demonstrating vocal quality, quality of life and laryngeal image results. The Voice Therapy for the Elderly (VTE) program consisted of a sequence of exercises that aimed at increasing intensity, pneumo-articulatory coordination, mucosal vibration and resonance balance, and increasing frequency variation and control. The therapeutic model in question was applied to an 87-year-old female subject with complaints of a weak voice and difficulty to be heard by others. This therapy program was applied with an intensive approach over 16 sessions, 30 minutes each session, four times a week, with assigned homework. The intensive voice therapy format demonstrated positive effects on vocal quality with an overall reduction in voice deviation, breathiness, and roughness on sustained phonation and speech. Vocal performance improvement showed a subsequent increase in the physical and general aspects of voice-related quality of life. There was also improvement in glottic closure. Voice treatment via the VTE method, with an intensive approach revealed to be positive in the treatment of presbyphonia and can potentially promote benefits for the elderly in terms of voice quality, voice-related quality of life, and laryngeal changes.

Clinical Translation of Mesenchymal Stromal Cell Therapy for Graft Versus Host Disease.

Graft versus host disease (GVHD) is a common condition in patients subjected to allogeneic hematopoietic stem cell transplantation (HSCT). The immune cells derived from the grafted stem cells attack recipient's tissues, including those from the skin, liver, eyes, mouth, lungs, gastrointestinal tract, neuromuscular system, and genitourinary tract, may lead to severe morbidity and mortality. Acute GVHD can occur within few weeks after the allogeneic cells have engrafted in the recipient while chronic GVHD may occur any time after transplant, typically within months. Although treatable by systemic corticosteroid administration, effective responses are not achieved for a significant proportion of patients, a condition associated with poor prognosis. The use of multipotent mesenchymal stromal cells (MSCs) as an alternative to treat steroid-refractory GVHD had improved last decade, but the results are still controversial. Some studies have shown improvement in the life quality of patients after MSCs treatment, while others have found no significant benefits. In addition to variations in trial design, discrepancies in protocols for MSCs isolation, characterization, and ex vivo manipulation, account for inconsistent clinical results. In this review, we discuss the immunomodulatory properties supporting the therapeutic use of MSCs in GVHD and contextualize the main clinical findings of recent trials using these cells. Critical parameters for the clinical translation of MSCs, including consistent production of MSCs according to Good Manufacturing Practices (GMPs) and informative potency assays for product quality control (QC), are addressed.

Improving the Transduction of Bone Marrow-Derived Cells with an Integrase-Defective Lentiviral Vector.

In lentiviral vector (LV) applications where transient transgene expression is sufficient, integrase-defective lentiviral vectors (IDLVs) are beneficial for reducing the potential for off-target effects associated with insertional mutagenesis. It was previously demonstrated that human RPE65 mRNA expression from an integrating lentiviral vector (ILV) induces endogenous Rpe65 and Cralbp mRNA expression in murine bone marrow-derived cells (BMDCs), initiating programming of the cells to retinal pigment epithelium (RPE)-like cells. These cells regenerate RPE in retinal degeneration models when injected systemically. As transient expression of RPE65 is sufficient to activate endogenous RPE-associated genes for programming BMDCs, use of an ILV is an unnecessary risk. In this study, an IDLV expressing RPE65 (IDLV3-RPE65) was generated. Transduction with IDLV3-RPE65 is less efficient than the integrating vector (ILV3-RPE65). Therefore, IDLV3-RPE65 transduction was enhanced with a combination of preloading 20 × -concentrated viral supernatant on RetroNectin at a multiplicity of infection of 50 and transduction of BMDCs by low-speed centrifugation. RPE65 mRNA levels increased from ∼12-fold to ∼25-fold (p < 0.05) after modification of the IDLV3-RPE65 transduction protocol, achieving expression similar to the ∼27-fold (p < 0.05) increase observed with ILV3-RPE65. Additionally, the study shows that the same preparation of RetroNectin can be used to coat up to three wells with no reduction in transduction. Critically, IDLV3-RPE65 transduction initiates endogenous Rpe65 mRNA expression in murine BMDCs and Cralbp/CRALBP mRNA in both murine and human BMDCs, similar to expression observed in ILV3-RPE65-transduced cells. Systemic administration of ILV3-RPE65 or IDLV3-RPE65 programmed BMDCs in a mouse model of retinal degeneration is sufficient to retain visual function and reduce retinal degeneration compared to mice receiving no treatment or naïve BMDC. It is concluded that IDLV3-RPE65 is appropriate for programming BMDCs to RPE-like cells.

Efetividade do programa terapia vocal para idosos nas formas convencional e intensiva / Effectiveness of the method vocal therapy for elderly in the conventional and intensive approach

A terapia vocal é a opção inicial de tratamento em casos de alterações vocais decorrentes do envelhecimento. Existem poucas propostas de intervenção específicas para esta situação e as análises dos seus efeitos são limitadas. O tratamento ocorre tradicionalmente na frequência de uma ou duas vezes semanais, no entanto algumas propostas sugerem uma abordagem intensiva, não havendo clareza quanto à melhor forma de aplicação. Sendo assim, este estudo tem o objetivo de verificar os efeitos de um programa de Terapia Vocal para idosos (TVI) e se há diferenças entre a administração do tratamento no formato intensivo e convencional. Foram encaminhados para terapia vocal 27 idosos randomizados em dois grupos, sendo que o Grupo Intensivo (GI) realizou 16 sessões quatro vezes por semana e o Grupo Convencional (GC), 16 sessões duas vezes semanais. Para a comparação dos efeitos da terapia foram avaliados os aspectos de qualidade de vida por meio do protocolo Qualidade de Vida em Voz (QVV), qualidade vocal por meio da avaliação perceptivoauditiva e laríngeos por meio da análise perceptivo-visual dos exames. O profissional que aplicou o tratamento foi cego quanto aos procedimentos de avaliação, realizados na semana anterior ao início dos atendimentos, na semana seguinte ao término do mesmo e um mês após. O programa TVI envolveu exercícios de diversas técnicas com potencial para melhorar os aspectos vocais impactados pelo envelhecimento Finalizaram o tratamento 25 idosos, 13 do GI e 12 do GC. Os resultados evidenciaram melhora quanto a qualidade de vida relacionada a voz e em relação à qualidade vocal, mas não nos aspectos laríngeos. Após um mês foi mantida a melhora no QVV e na qualidade de voz, soprosidade e instabilidade durante emissões sustentadas e qualidade vocal e rugosidade na fala. Não foram observadas diferenças entre a terapia intensiva e convencional à exceção do arqueamento de pregas vocais que diminuiu em 38,46% dos participantes do GI e em nenhum do GC...

The voice therapy is the initial treatment option in cases of vocal changes due to aging. There are few specifics intervention proposals for these cases and the assessments of its effects are limited. The treatment traditionally occurs at the frequency of once or twice a week, however some methods suggests an intensive approach, there is no clarity as to the best way for applying. Therefore, this study aims to verify the effects of the method Vocal Therapy for Elderlies (VTE) and whether there are differences between the treatment administration in the intensive and conventional format. Underwent the vocal therapy 27 elderly randomized into two groups, whereas the Intensive Group (IG) accomplished 16 sessions four times a week and the Conventional Group (CG) 16 sessions twice a week. For the comparison of the effects of therapy were evaluated aspects of quality of life through the voice-related quality of life (V-RQOL) protocol, vocal quality through the auditory perceptual and laryngeal through the visual perceptive analysis of the exams. The professional who administered the treatment was blind as to the assessment procedures, accomplished in the week before the beginning of the sessions in the week following the end of it and one month after. The VTE method involved exercises of various techniques with potential to improve the vocal aspects impacted by aging. Finished the treatment 25 elderly, 13 in IG and 12 of CG. The results showed improvement as the voice related quality of life and in relation to perceptual vocal quality, but not in the laryngeal aspects. After a month was maintained improvement in V-RQOL and general vocal quality, breathiness and instability during sustained vocal emissions and general vocal quality and roughness in speech. No differences were found between the intensive therapy and conventional except the vocal fold bowing that decreased in 38.46% of participants of the IG and in none of the CG...

Efetividade do programa terapia vocal para idosos nas formas convencional e intensiva / Effectiveness of the method vocal therapy for elderly in the conventional and intensive approach

A terapia vocal é a opção inicial de tratamento em casos de alterações vocais decorrentes do envelhecimento. Existem poucas propostas de intervenção específicas para esta situação e as análises dos seus efeitos são limitadas. O tratamento ocorre tradicionalmente na frequência de uma ou duas vezes semanais, no entanto algumas propostas sugerem uma abordagem intensiva, não havendo clareza quanto à melhor forma de aplicação. Sendo assim, este estudo tem o objetivo de verificar os efeitos de um programa de Terapia Vocal para idosos (TVI) e se há diferenças entre a administração do tratamento no formato intensivo e convencional. Foram encaminhados para terapia vocal 27 idosos randomizados em dois grupos, sendo que o Grupo Intensivo (GI) realizou 16 sessões quatro vezes por semana e o Grupo Convencional (GC), 16 sessões duas vezes semanais. Para a comparação dos efeitos da terapia foram avaliados os aspectos de qualidade de vida por meio do protocolo Qualidade de Vida em Voz (QVV), qualidade vocal por meio da avaliação perceptivoauditiva e laríngeos por meio da análise perceptivo-visual dos exames. O profissional que aplicou o tratamento foi cego quanto aos procedimentos de avaliação, realizados na semana anterior ao início dos atendimentos, na semana seguinte ao término do mesmo e um mês após. O programa TVI envolveu exercícios de diversas técnicas com potencial para melhorar os aspectos vocais impactados pelo envelhecimento Finalizaram o tratamento 25 idosos, 13 do GI e 12 do GC. Os resultados evidenciaram melhora quanto a qualidade de vida relacionada a voz e em relação à qualidade vocal, mas não nos aspectos laríngeos. Após um mês foi mantida a melhora no QVV e na qualidade de voz, soprosidade e instabilidade durante emissões sustentadas e qualidade vocal e rugosidade na fala. Não foram observadas diferenças entre a terapia intensiva e convencional à exceção do arqueamento de pregas vocais que diminuiu em 38,46% dos participantes do GI e em nenhum do GC...

The voice therapy is the initial treatment option in cases of vocal changes due to aging. There are few specifics intervention proposals for these cases and the assessments of its effects are limited. The treatment traditionally occurs at the frequency of once or twice a week, however some methods suggests an intensive approach, there is no clarity as to the best way for applying. Therefore, this study aims to verify the effects of the method Vocal Therapy for Elderlies (VTE) and whether there are differences between the treatment administration in the intensive and conventional format. Underwent the vocal therapy 27 elderly randomized into two groups, whereas the Intensive Group (IG) accomplished 16 sessions four times a week and the Conventional Group (CG) 16 sessions twice a week. For the comparison of the effects of therapy were evaluated aspects of quality of life through the voice-related quality of life (V-RQOL) protocol, vocal quality through the auditory perceptual and laryngeal through the visual perceptive analysis of the exams. The professional who administered the treatment was blind as to the assessment procedures, accomplished in the week before the beginning of the sessions in the week following the end of it and one month after. The VTE method involved exercises of various techniques with potential to improve the vocal aspects impacted by aging. Finished the treatment 25 elderly, 13 in IG and 12 of CG. The results showed improvement as the voice related quality of life and in relation to perceptual vocal quality, but not in the laryngeal aspects. After a month was maintained improvement in V-RQOL and general vocal quality, breathiness and instability during sustained vocal emissions and general vocal quality and roughness in speech. No differences were found between the intensive therapy and conventional except the vocal fold bowing that decreased in 38.46% of participants of the IG and in none of the CG...

Combined dermatan sulfate and endothelial progenitor cell treatment: action on the initial inflammatory response after arterial injury in C57BL/6 mice.

BACKGROUND AIMS: Dermatan sulfate (DS), an anticoagulant and antithrombotic glycosaminoglycan, also has anti-inflammatory activity. In this study, we investigated the effect of DS treatment in the presence or absence of bone marrow mononuclear cells (MNCs) or endothelial progenitor cells (EPCs) in the vascular response to carotid artery lesion in C57BL6 mice. METHODS: Thrombus formation, the expression of adhesion molecules and factors involved in vascular remodeling, inflammation or vascular tone were analyzed by histologic examination, Western blotting and enzyme-linked immunoassay 1 and 3 days after vascular injury. RESULTS: DS injections prevented thrombus formation and decreased P-selectin expression after 3 days of the injury. DS treatment also increased plasma SDF-1 levels but failed to rescue endothelial nitric oxide synthase (eNOS) expression, which is responsible for vascular tone. Treatment with MNCs alone failed to prevent thrombus formation 1 day after injury and increased intercellular adhesion molecule-1 expression, likely because of the inflammatory nature of these cells. Treatment with EPCs with DS was the most efficient among all therapies studied. Dual administration of EPCs and DS promoted an increase in the expression of adhesion molecules and, at the same time, induced a higher expression of eNOS at the injury site. Furthermore, it stimulated an elevated number of EPCs to migrate and adhere to the vascular wall. DISCUSSION: Simultaneous treatment with EPCs and DS increased the expression of adhesion molecules, prevented thrombosis, rescued the expression of eNOS and increased migration of EPCs to the site of injury, thereby affecting thrombus remodeling and inflammation and can be involved in vessel hemostasis.

Differentiation of C57/BL6 mice bone marrow mononuclear cells into early endothelial progenitors cells in different culture conditions.

Endothelial progenitor cells (EPCs) can be isolated from bone marrow and characterized by the expression of cellular markers such as CD34, CD133, VEGFR2, CD31, and VE-Cadherin, by the uptake of acetylated low-density lipoprotein and by in vitro tube formation in tridimensional matrices. These cells are able to differentiate into mature endothelial cells and participate in the re-endothelization of damaged vessels. In this work, we tested different cultured media that can promote the proliferation and differentiation of mononuclear cells (MNCs) into early EPCs, with defined concentrations of growth factors and serum in order to establish a composition that may ensure us the reproducibility of our cultures. MNCs from mice bone marrow were cultivated using selective culture media containing DMEM or M199 supplemented with 10% FBS, VEGF, bFGF, and IGF, for 3, 7, and 14 days. Differentiation into early EPCs was analyzed using immunohistochemistry, FACS and western blotting and by functional parameters as uptake of ac-LDL, and formation of vessel-like structures. The cells cultivated with medium DMEM-M1 (DMEM plus VEGF, bFGF and IGF) expressed CD34, CD133, CD31, VEGFR2, and VE-Cadherin at all culture time-points with increased expression of these markers after 7 days. Only EPCs cultured for 30 days were able to form vessel-like structure. The uptake of ac-LDL was observed after 3, 7, 14, and 30 days, confirming the differentiation of mononuclear cells into early EPCs. DMEM-M1 was able to sustain MNCs proliferation and differentiation, increasing the expression of the characteristic EPC markers, allowing the expansion of early EPCs in culture in a similar way to that observed in commercial available media.

A framework for understanding shared substrates of airway protection

Deficits of airway protection can have deleterious effects to health and quality of life. Effective airway protection requires a continuum of behaviors including swallowing and cough. Swallowing prevents material from entering the airway and coughing ejects endogenous material from the airway. There is significant overlap between the control mechanisms for swallowing and cough. In this review we will present the existing literature to support a novel framework for understanding shared substrates of airway protection. This framework was originally adapted from Eccles' model of cough28 (2009) by Hegland, et al.42 (2012). It will serve to provide a basis from which to develop future studies and test specific hypotheses that advance our field and ultimately improve outcomes for people with airway protective deficits.

Neuroradiology and voice findings in stroke / Achados de neurorradiologia e voz no acidente vascular encefálico

Neurological dysphonias are vocal disorders followed by injuries or changes in the nervous system. Stroke is the second leading cause of death worldwide and the brain damage caused by it can affect communication in several aspects. The changes in the vocal features caused by these lesions are poorly described regarding the location and extent of cerebral involvement. The aim of this study was to describe vocal parameters of ten elderly patients affected by stroke according to the topography of the lesion at neuroimaging. We recorded from them: perceptual and auditory evaluation of voice and laryngeal diadochokinesis. Neuroimaging studies were classified according to location, extent, laterality territory of brain injury. The results show a population of extensive middle cerebral artery strokes and strokes with varied location in the brain. The subjects' voices showed predominantly the presence of roughness, breathiness, richeness and instability, and change in laryngeal motor control, demonstrated by reduced speed and instability in laryngeal diadochokinesis. These features presented in patients with extensive middle cerebral artery stroke and in patients with short strokes with varied location in the brain. The results suggest that the vocal features in the assessed cases do not depend only on the topography of the brain damage. Thus, it is important to consider the patient as unique in clinical evaluation.

As disfonias neurológicas são distúrbios vocais que acompanham lesões ou alterações no sistema nervoso. O acidente vascular encefálico (AVE) é a segunda causa de morte no mundo e os danos cerebrais causados podem afetar a comunicação do indivíduo em diversos aspectos. As alterações de voz características dessas lesões são pouco descritas quanto à localização e extensão do acometimento cerebral. O objetivo deste estudo foi descrever as características fonatórias de dez idosos acometidos por AVE, de acordo com a topografia da lesão observada ao exame de neuroimagem. Todos os participantes tiveram amostras de voz gravadas e foi realizada avaliação perceptivo-auditiva da voz e da diadococinesia laríngea. Os exames de neuroimagem foram classificados quanto à localização, extensão, lateralidade e território de vascularização da lesão cerebral. Os resultados mostram uma população de AVEs extensos de artéria cerebral média e AVEs de localização variada no cérebro. As vozes dos sujeitos mostraram predominantemente presença de rugosidade, soprosidade, instabilidade e pastosidade, além de alteração no controle motor laríngeo, demonstrado pela velocidade reduzida e instabilidade na repetição de vogais. Essas características ocorreram tanto no grupo de pacientes com AVE extenso de lesão da artéria cerebral média como em pacientes com AVEs menores de localização variada no cérebro. Os achados sugerem que as manifestações vocais dos casos estudados não dependem apenas da topografia da lesão. Daí a importância de considerar as individualidades de cada paciente no momento da avaliação clínica.

Jaboticaba (Myrciaria jaboticaba (Vell) Berg) peel increased triglycerides excretion and hepatic lipid peroxidation in high-fat-fed rats / Consumo de casca de jabuticaba (Myrciaria jaboticaba (Vell) Berg) melhorou a excreção de triglicerídeos e a peroxidação lipídica hepática de ratos alimentados com dieta hiperlipídica

OBJECTIVE: The aim of this study was to evaluate the influence of high-fat diets with 1%, 2%, and 4% freeze-dried jaboticaba peel on the serum, liver, and fecal lipid profile of obese rats. METHODS: Thirty male Sprague-Dawley rats were divided into 5 groups. Obesity was induced in four groups using a high-fat diet (35% lipids). One group was used as a high-fat diet control (High-fat group - HF). The other three high-fat-diet groups were given 1%, 2%, and 4% freeze-dried jaboticaba peel (High-Fat Jaboticaba - HFJ1, HFJ2, and HFJ4, respectively) in the last 40 experimental days. Blood and the liver were collected after 70 days of treatment and feces were collected in the last experimental week. Total cholesterol, triglycerides, and lipids were measured in the serum, liver, and dried feces. ffer in the experimental groups. HFJ2 group had the highest hepatic and fecal lipid contents compared with the group fed a diet with normal fat content (N), but low hepatic lipid peroxidation. HFJ4 group had the highest mean hepatic and fecal cholesterol levels. Hepatic triglyceride levels did not differ among the groups, and groups HFJ1 and HFJ4 presented the highest fecal triglyceride content. CONCLUSION: The amounts of jaboticaba peel used by this study did not protect against hepatic steatosis or undesired levels of other studied lipids, but it did increase fecal triglycerides. Lipid peroxidation in the liver decreased in the HFJ2 group...

OBJETIVO: O objetivo deste estudo foi avaliar o efeito de dietas hiperlipídicas adicionadas de 1%, 2% e 4% de casca de jabuticaba liofilizada sobre os perfis lipídicos do fígado, soro e fezes de ratos. MÉTODOS: Trinta ratos, machos, Sprague-Dawley, foram divididos em cinco grupos. A obesidade foi induzida em quatro grupos, com dieta hiperlipídica ou High-Fat - HF (35% de lipídeos). Três desses grupos receberam a dieta hiperlipídica adicionada de 1%, 2% e 4% de casca de jabuticaba liofilizada (Jabuticaba - HFJ1, HFJ2 e HFJ4, respectivamente) nos últimos 40 dias de experimento. Sangue e fígado foram coletados após 70 dias de tratamento e as fezes na última semana experimental. Colesterol e triglicerídeos totais foram avaliados no soro, fígado e fezes secas, bem como lipídeos totais. RESULTADOS: No segundo período do experimento, a ingestão dietética e energética dos animais HFJ4 foi maior em relação ao grupo High-Fat. Não houve diferença significativa entre os grupos experimentais para colesterol total e triglicerídeos séricos. O grupo HFJ2 demonstrou maiores níveis de lipídeos hepáticos e fecais em relação a N, apesar de a peroxidação lipídica ter diminuído nesse grupo. O HFJ4 mostrou a maior média de colesterol hepático e fecal. Não houve diferenças significativas para triglicerídeos hepáticos, e os grupos HFJ1 e HFJ4 excretaram mais triglicerídeos pelas fezes. CONCLUSÃO: As doses utilizadas de casca de jabuticaba não mostraram efeitos benéficos contra a esteatose hepática ou outro parâmetro lipídico avaliado, com exceção para a excreção de triglicerídeos. O índice de peroxidação lipídica hepática diminuiu nos ratos alimentados com 2% de casca de jabuticaba liofilizada...

Interference of Dynamic Visual Noise on encoding visual information in working memory / Interferência do Ruído Visual Dinâmico na codificação da informação visual na memória de trabalho

We aimed to compare the effects of the Dynamic Visual Noise (DVN) on visual memory when presented at different times in an item recognition task either during information encoding, retention interval or throughout the trial. Noise had general effect on participants' performance with stronger impairment on stimuli encoding. The data suggest that visual memory is accessed through perception and, therefore, it suffers external interference, as the one caused by the DVN. We consider that the effect occurred while the information was being kept in consciousness by a specific short-term storage subsystem. These results contribute to the understanding of the architecture used by the visual working memory and show that the DVN is an appropriate technique to study the visual memory...

O objetivo deste estudo foi comparar os efeitos do Ruído Visual Dinâmico (RVD) na memória visual quando apresentado em uma tarefa de reconhecimento de item durante a codificação da informação, no intervalo de retenção ou durante toda a prova. O ruído ocasionou maior interferência na memória quando apresentado durante a codificação do estímulo. Os dados sugerem que a memória visual é acessada via percepção, por isto, sofre interferência externa como a causada pelo RVD. Sugere-se que o efeito ocorreu enquanto a informação era mantida na consciência por um subsistema de armazenamento de curto prazo. Estes resultados contribuem para a compreensão da arquitetura da memória de trabalho e mostram que o RVD é uma técnica apropriada para estudar a memória visual...