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1.
BMC Med Educ ; 23(1): 403, 2023 Jun 03.
Article in English | MEDLINE | ID: mdl-37268934

ABSTRACT

BACKGROUND: The number of ophthalmologists trained in Brazil has increased, but their satisfaction with the medical residency curriculum is unclear. The purpose of this study is to evaluate the satisfaction and self-confidence of graduates of a reference ophthalmology residency program in Brazil and to analyze whether there is a difference in these parameters among those who graduated in different decades. METHODS: This is a cross-sectional web-based study conducted in 2022 with 379 ophthalmologists who graduated from the Faculty of Medical Sciences of the State University of Campinas (UNICAMP), Brazil. We aim to obtain data on satisfaction and self-confidence in clinical and surgical practices. RESULTS: In total, 158 questionnaires were completed (41.68% response rate); 104 respondents completed their medical residency between 2010 and 2022, 34 between 2000 and 2009, and only 20 before 2000. Most respondents were satisfied or very satisfied with their programs (98.7%). Respondents reported insufficient exposure to low vision rehabilitation (62.7%), toric intraocular implants (60.8%), refractive surgery (55.7%), and orbital trauma surgery (84.8%), particularly among graduates before 2010. They also reported insufficient training in certain non-clinical areas, such as office management (61.4%), health insurance management (88.6%), and personnel and administration skills (74.1%). We found that respondents who graduated a long time ago had higher confidence in clinical and surgical practices. CONCLUSIONS: Brazilian ophthalmology residents and UNICAMP graduates expressed high levels of satisfaction with their residency training programs. Those who completed the program a long time ago appear to have more confidence in clinical and surgical practices. There were clinical and non-clinical areas with insufficient training identified for improvement.


Subject(s)
Internship and Residency , Ophthalmology , Humans , Ophthalmology/education , Education, Medical, Graduate , Cross-Sectional Studies , Curriculum , Surveys and Questionnaires , Personal Satisfaction , Clinical Competence
4.
Mol Cell Biochem ; 471(1-2): 63-69, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32472323

ABSTRACT

Posterior tibial tendon (PTT) dysfunction is three times more common in females, and some patients may have a predisposition without a clinically evident cause, suggesting that individual characteristics play an important role in tendinopathy. The present study investigated the association of rs4986938 (+ 1730G > A; AluI RFLP) and rs1256049 (- 1082G > A; RsaI RFLP) single nucleotide polymorphisms (SNPs) of estrogen receptor-beta (ER-ß) gene with PTT dysfunction. A total of 400 participants were recruited. The PTT dysfunction group: these patients underwent surgery, with PTT tendinopathy confirmed by histopathology and magnetic resonance image (MRI). The control group was composed of participants with no clinical or MRI evidence of PTT dysfunction. Each group was composed of 100 postmenopausal women, 50 premenopausal women, and 50 men. Genomic DNA was extracted from saliva samples, and genotypes were obtained by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Concerning the ER-ß SNP rs4986938, there were significant differences in the frequencies of alleles between test and control groups of all the cases, only postmenopausal women and only men (p < 0.0001, p = 0.0016 and p = 0.0001). Considering the PTT dysfunction group and comparing postmenopausal women versus premenopausal women adding men, the analysis showed significant differences in the allelic distribution (p = 0.0450): the allele A in postmenopausal women is a risk factor. The ER-ß SNP rs1256049 did not show differences in the frequencies of alleles and genotypes between groups. The ER-ß SNP rs4986938, but not ER -ß SNPs rs1256049, may contribute to PTT insufficiency in the Brazilian population, with additional risk in postmenopausal women. Addition, in men the genetic factor could be more determinant.


Subject(s)
Estrogen Receptor beta/genetics , Posterior Tibial Tendon Dysfunction/genetics , Tendinopathy/genetics , Adult , Alleles , Case-Control Studies , Cross-Sectional Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Posterior Tibial Tendon Dysfunction/pathology , Postmenopause , Tendinopathy/pathology
5.
Qual Life Res ; 29(7): 1731-1745, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32246433

ABSTRACT

PURPOSE: Individuals with epidermolysis bullosa (EB) present with various clinical manifestations of different severities that affect quality of life (QoL). This systematic review synthesizes the current evidence about the QoL of individuals with EB. METHODS: We included observational studies with people of all age groups, both sexes, and any EB type. Studies with qualitative methodology, chapters of books, meeting proceedings, and abstracts were excluded. RESULTS: In this study, 12 articles comprising 745 individuals were included. More than half of the articles observed lower QoL in individuals with recessive dystrophic EB (RDEB) or junctional EB (JEB). Three articles indicated that EB affected QoL more in women than in men, and one article identified that children with EB suffered more than adults with the disease. Pain was frequently reported. Seven articles identified difficulty in sports, two identified a need for bathing assistance, and three identified eating difficulties. Additionally, participants reported that family relationships and friendships were affected, and they experienced feelings of anxiety and depression. Some of the instruments used evaluated QoL in general dermatologic conditions, and one was specific to EB. CONCLUSION: QoL is more affected in people who have RDEB and JEB. Regarding sex and age, women and children need special care in their monitoring. It is necessary that guidelines on pain management be more disseminated and put into practice. Future studies should use standardized specific instruments to assess the QoL in EB individuals, while considering the particularities of the different age groups.


Subject(s)
Epidermolysis Bullosa/psychology , Quality of Life/psychology , Cross-Sectional Studies , Female , Humans , Male
6.
Ecotoxicol Environ Saf ; 183: 109553, 2019 Nov 15.
Article in English | MEDLINE | ID: mdl-31416012

ABSTRACT

In the present work, the production of bioemulsifier (BE) by a lactic acid bacterium (LAB) grown at 25 °C in lactic whey-based media for 24 h was evaluated. Maximum production was detected in a medium containing yeast extract, peptone and lactic whey (LAPLW medium), with a yield of 270 mg L-1. The BE proved to be more innocuous for Caco-2 cells, used as a toxicological indicator, than the non-ionic surfactant Triton X-100. In addition, the microbial product presented higher stability to changes in temperature (37 °C to 100 °C), pH (2-10), and salt concentration (5% and 20%, w/v) than the synthetic surfactant. Regarding emulsifying capacity tested against different hydrophobic substrates (kerosene, motor oil, diesel, sunflower oil, and grape oil), the BE displayed E24 values similar to or even better than those of Triton X-100. Finally, Triton X-100 caused irreversible modifications on the giant unilamellar vesicles (used as model membrane system), promoting the solubilization of the lipid bilayers. Nevertheless, BE induced temporary modifications of the membrane, which is associated with incorporation of the bioproduct in the outer layer. These results demonstrate the role of BE in biological processes, including reversible changes in microbial membranes to enhance the access to hydrophobic substrates.


Subject(s)
Biotechnology/methods , Emulsifying Agents/isolation & purification , Enterococcus/metabolism , Lactic Acid/metabolism , Whey/metabolism , Caco-2 Cells , Cell Survival/drug effects , Emulsifying Agents/metabolism , Emulsifying Agents/toxicity , Emulsions , Humans , Hydrophobic and Hydrophilic Interactions , Octoxynol/chemistry , Petroleum/metabolism , Plant Oils/metabolism , Temperature
7.
Osteoporos Int ; 30(5): 1015-1023, 2019 May.
Article in English | MEDLINE | ID: mdl-30693381

ABSTRACT

Although chronic kidney disease is associated with other bone disorders, osteoporosis can be found in this context, and it is defined based on bone mineral density (BMD), measured by dual-energy X-ray absorptiometry. As CKD progresses, the percentage of normal BMD decreases, whereas that of osteopenia/osteoporosis increases, mostly due to hip involvement, particularly in patients with reduced renal function. INTRODUCTION: Osteoporosis is a highly prevalent disease in patients with chronic kidney disease (CKD). We investigated the features of bone mineral density (BMD) in patients with assorted kidney diseases and hypothesized that low BMD, as measured by dual-energy X-ray absorptiometry (DXA), would be more prevalent as kidney function decreased and would correlate with biomarkers of mineral and bone disease. METHODS: DXA obtained from January 1, 2008, to December 31, 2017, clinical, demographic, and biochemical data at the time of image acquisition were recorded. Data from 1172 patients were included in this study (81.3% women, 79.9% white, and 8.1% diabetic). RESULTS: Osteopenia and osteoporosis in at least one site (total hip or spine) were found in 32.7% and 20.0% of patients, respectively. As CKD progressed, the percentage of patients with normal BMD decreased, whereas the percentage of osteopenia and osteoporosis increased, which was mostly due to the total hip involvement, particularly in patients with estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. Older age and hyperparathyroidism were independent risk factors for osteopenia/osteoporosis at the total hip; female gender, older age, and higher iCa were independently associated with the risk of osteopenia/osteoporosis at the spine. With eGFR > 90 ml/min as reference, the odds ratios for osteoporosis/osteopenia at the hip were 1.51 (95% CI 1.01-2.24) and 1.91 (95% CI 1.13-3.20) for patients with eGFR 30-60 and 15-30 ml/min/1.73 m2, respectively. No CKD stage was significantly associated with the risk of osteoporosis/osteopenia at the spine. CONCLUSION: Our results highlighted that low BMD in patients with CKD is associated with age and hyperparathyroidism, and affects predominantly the hip.


Subject(s)
Bone Diseases, Metabolic/etiology , Hip Joint/physiopathology , Lumbar Vertebrae/physiopathology , Renal Insufficiency, Chronic/complications , Absorptiometry, Photon , Adult , Aged , Bone Density/physiology , Bone Diseases, Metabolic/epidemiology , Bone Diseases, Metabolic/physiopathology , Brazil/epidemiology , Disease Progression , Female , Glomerular Filtration Rate/physiology , Humans , Male , Middle Aged , Osteoporosis/epidemiology , Osteoporosis/etiology , Osteoporosis/physiopathology , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/physiopathology , Retrospective Studies , Severity of Illness Index
8.
Environ Technol ; 40(1): 11-18, 2019 Jan.
Article in English | MEDLINE | ID: mdl-28891384

ABSTRACT

The role of Eichhornia crassipes for removing pollutants from low strength sewage was evaluated in three pilot-scale constructed wetlands (CW): CW 1, planted with E. crassipes in a filter media; CW 2, unplanted, composed by filter media; and CW 3, composed by E. crassipes floating on the sewage. The operation was divided into three stages by varying the nominal hydraulic retention time into: (I) 24 h; (II) 48 h; (III) 72 h. Temporal sampling profiles were carried out with collection of the influent and effluent samples to determine temperature, pH, chemical oxygen demand (COD), TKN and TP. Contents of TP and TN were analyzed in the plant tissue of the macrophyte. The best removal efficiency rates for phosphorus (38%) and TKN (47%) were obtained in CW 3 for 72 h. The highest COD removal was observed in the CW 2 (80%) for 48 h. The macrophyte E. crassipes contributed to the absorption process with uptake rate percentages of 8.3% (CW 1) and 9.0% (CW 3) for TN and 0.78% (CW 1) and 1.56% (CW 3) for TP on the dry matter of the plant. The chosen species planted in the systems contributed to the achievement of higher nutrient removal.


Subject(s)
Sewage , Wetlands , Biodegradation, Environmental , Nitrogen , Nutrients , Phosphorus , Waste Disposal, Fluid
9.
J Orthop Surg Res ; 13(1): 316, 2018 Dec 11.
Article in English | MEDLINE | ID: mdl-30537990

ABSTRACT

BACKGROUND: Posterior tibial tendon (PTT) insufficiency is considered as the main cause of adult acquired flat foot and is three times more frequent in females. High estrogen levels exert a positive effect on the overall collagen synthesis in tendons. We have previously demonstrated the association between some genetic single-nucleotide polymorphism (SNP) and tendinopathy. In the present study, we investigated the association of PvuII c454-397T>C (NCBI ID: rs2234693) and XbaI c454-351A>G (NCBI ID: rs9340799) SNPs in estrogen receptor alfa (ER-α) gene with PPT dysfunction. METHODS: A total of 92 female subjects with PTT dysfunction, with histopathological examination of the tendon and magnetic resonance image (MRI) evidence of tendinopathy, were compared to 92 asymptomatic females who presented an intact PPT at MRI for PvuII and XbaI SNPs in the ER-α gene. Genomic DNA was extracted from saliva and genotypes were obtained by polymerase chain reaction restriction fragment length polymorphism. RESULTS: The analysis of PvuII SNPs showed no significant differences in the frequency of alleles and genotypes between control and PTT dysfunction groups. The XbaI SNPs in the ER-α gene showed significant differences in the frequency of genotypes between control and test groups (p = 0.01; OR 95% 1.14 (0.55-2.33). CONCLUSIONS: The XbaI SNP in the ERα gene may contribute to tendinopathy, and the A/A genotype could be a risk factor for PTT tendinopathy in this population. The PvuII SNP studied was not associated with PTT tendinopathy.


Subject(s)
Estrogen Receptor alpha/genetics , Genetic Association Studies/methods , Polymorphism, Single Nucleotide/genetics , Posterior Tibial Tendon Dysfunction/genetics , Postmenopause/physiology , Adult , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Middle Aged , Posterior Tibial Tendon Dysfunction/diagnosis
10.
Sci Total Environ ; 630: 1365-1373, 2018 Jul 15.
Article in English | MEDLINE | ID: mdl-29554756

ABSTRACT

The present study aimed to assess removal potential of chemical oxygen demand (COD), total Kjeldahl nitrogen (TKN), total ammonia nitrogen (TAN), total phosphorus (TP) and acetylsalicylic acid (ASA) in synthetic wastewater simulating low-strength sewage by sequencing-batch mode constructed wetlands (CWs). Six CWs with three substrates (gravel, light expanded clay and clay bricks) and one CW of each substrate was planted with E. crassipes to verify the feasibility of using a floating macrophyte in CWs and verify the best optimized substrate. Results showed that the presence of E. crassipes enhanced the removal of COD for systems with gravel, increasing the removal efficiency from 37% in the unplanted system (CWG-U) to 60% in the planted system (CWG-P). The vegetated CW with clay bricks (CWB-P) presented the best performance for both TKN and TAN removal, with maximum removal efficiencies of 68% and 35%, respectively. Phosphorus was observed to be efficiently removed in systems with clay bricks, both planted (CWB-U) and unplanted (CWB-P), with mean removal efficiencies of 82% and 87%, respectively, probably via adsorption. It was also observed that after 296days of operation, no desorption or increase on phosphorus in effluent samples were observed, thus indicating that the material was not yet saturated and phosphorus probably presents a strong binding to the media. ASA removal efficiency varied from 34% to 92% in CWs, probably due to plant uptake through roots and microbial biodegradation. Plant direct uptake varied from 4 to 74% of the total nitrogen and from 26 to 71% of the total phosphorus removed in CWG-P, CWC-P and CWB-P. E. crassipes was able to uptake up to 4.19g of phosphorus in CWC-P and 11.84g of nitrogen in CWB-P. The findings on this study suggest that E. crassipes could be used in CWs and clay bricks could significantly enhance phosphorus removal capacity in CWs.


Subject(s)
Plants/metabolism , Waste Disposal, Fluid/methods , Water Pollutants, Chemical/metabolism , Wetlands , Biodegradation, Environmental , Biological Oxygen Demand Analysis , Nitrogen , Phosphorus/analysis , Wastewater , Water Pollutants, Chemical/analysis
11.
Br J Dermatol ; 179(1): 42-49, 2018 07.
Article in English | MEDLINE | ID: mdl-29168183

ABSTRACT

Individuals with epidermolysis bullosa (EB) may present with a broad spectrum of growth impairment and multiorgan disorders, with compromised nutritional status and quality of life. The provision of nutrients through a gastrostomy tube may minimize EB-related malnourishment but may also result in skin injuries and infections. In this systematic review we consider the current evidence about the effectiveness of gastrostomy in restoring nutritional status and improving quality of life in patients with EB. Seven studies (n = 146) met selection criteria and patients ranged in age from 6 weeks to 33 years of age. Although it is not a risk-free procedure, the placement of a gastrostomy tube is a feasible and safe alternative to provide nutritional support and to improve the quality of life of patients.


Subject(s)
Epidermolysis Bullosa Dystrophica/surgery , Gastrostomy , Nutritional Status , Quality of Life , Adolescent , Adult , Child , Child, Preschool , Enteral Nutrition/methods , Epidemiologic Methods , Epidermolysis Bullosa Dystrophica/psychology , Female , Humans , Infant , Male , Malnutrition/prevention & control , Malnutrition/psychology , Young Adult
12.
Lett Appl Microbiol ; 66(2): 104-109, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29193183

ABSTRACT

The purpose of this study was to identify and analyse the micro-organisms present in the conjunctival secretion in anophthalmic cavities of wearers of ocular prostheses, as well as on the prostheses used by them, correlating them with the microbiota of the contralateral eye. Nine patients with maxillofacial abnormalities, wearers of an acrylic resin ocular prosthesis participated in the study. Collections of conjunctival secretions and biofilm were performed on the prosthesis, anophthalmic cavity and contralateral eye for the mycological and bacterial analyses. The data were submitted to statistical analysis, performing a Kendall correlation test to identify the correlation between the collection site and the identified micro-organism (P < 0·05). It was verified that the most prevalent micro-organisms were the Staphylococcus aureus and Staphylococcus epidermidis, independent of the collection site, and that negative cultures for fungi were encountered in 85·2% of collections, independent of the region. It was not possible to establish a correlation among the types of micro-organisms and the collection sites. SIGNIFICANCE AND IMPACT OF THE STUDY: Some evidence suggests that the surface roughness of ocular prostheses can influence interactions with micro-organisms, with greater prejudicial consequences, such as the establishment of biofilms, which could lead to infections. Thus, it becomes extremely important to identify the micro-organisms present on the acrylic surfaces of ocular prostheses, as well as the microbiota of the anophthalmic cavity and contralateral eye of wearers of the same, so that subsequent control measures promote the homeostatic maintenance of the ocular region.


Subject(s)
Conjunctiva/microbiology , Eye, Artificial/microbiology , Staphylococcus aureus/isolation & purification , Staphylococcus epidermidis/isolation & purification , Adolescent , Adult , Aged , Anophthalmos/microbiology , Biofilms/growth & development , Child , Child, Preschool , Female , Humans , Infant , Male , Maxillofacial Abnormalities , Microbiota/genetics , Middle Aged , Young Adult
13.
Eur J Clin Nutr ; 71(10): 1206-1211, 2017 10.
Article in English | MEDLINE | ID: mdl-28537577

ABSTRACT

BACKGROUND/OBJECTIVES: C-reactive protein (CRP) is a marker of inflammation that has been shown to be predictive of cardiovascular diseases in adults. To evaluate the distribution of CRP as well as its association with metabolic syndrome and its components. SUBJECTS/METHODS: This is a cross-sectional study on adolescents aged 12-17, participants in the Study of Cardiovascular Risk in Adolescents (ERICA). Anthropometric, biochemical and blood pressure data were collected from 6316 adolescents, selected from a random sample of students in the cities of Brasilia, Fortaleza, João Pessoa, Manaus, Porto Alegre and Rio de Janeiro. Metabolic syndrome was defined by the criteria proposed by International Diabetes Federation for adolescent. Poisson regression model with robust variance, taking into consideration the study's complex sampling design, was used to determine multivariate-adjusted prevalence rate ratios expressing the relationship of metabolic syndrome with CRP. RESULTS: In adolescents with metabolic syndrome, CRP concentrations were five times higher (1.01 mg/l; interquartile range (IQR): 0.54-3.47) compared with those without metabolic syndrome (0.19 mg/l; IQR: 0.10-0.78). In multivariate Poisson regression analysis adjusted by sex, age and skin color, the prevalence of elevated CRP (>3.0 mg/l) was almost three times higher in adolescents with metabolic syndrome than in those without this condition (prevalence ratio (PR): 2.9; 95%CI: 2.0-4.3; P<0.001). Of the metabolic syndrome components, elevated waist circumference, low high-density lipoprotein-cholesterol and high triglycerides were significantly related to CRP in a graded (dose-response) manner. CONCLUSIONS: The association of CRP with metabolic syndrome and its components suggests that inflammation may be useful in assessing cardiovascular risk in adolescents.


Subject(s)
C-Reactive Protein/metabolism , Metabolic Syndrome/epidemiology , Pediatric Obesity/complications , Adolescent , Adolescent Health Services , Anthropometry , Brazil/epidemiology , Child , Cross-Sectional Studies , Female , Humans , Male , Metabolic Syndrome/blood , Metabolic Syndrome/complications , Prevalence , Risk Factors , Surveys and Questionnaires
14.
J Med Entomol ; 54(4): 985-993, 2017 07 01.
Article in English | MEDLINE | ID: mdl-28132021

ABSTRACT

Plant-derived essential oils can be used as insecticides for vector control. However, to establish their safety, it is necessary to perform toxicological studies. Herein, we evaluated the chemical composition and insecticidal activity of the essential oil from the leaves of Croton argyrophyllus on the third- and fourth-instar larvae and adult Aedes aegypti (L., 1762). We also evaluated the acute toxicity of the essential oil in adult female Mus musculus. The lethal concentration 50 (LC50) and 90 (LC90) of C. argyrophyllus essential oil on larvae of Ae. aegypti were 0.31 and 0.70 mg ml-1, respectively, and 5.92 and 8.94 mg ml-1, respectively, on Ae. aegypti adults. The major components of the essential oil were spathulenol (22.80%), (E)-caryophyllene (15.41%), α-pinene (14.07%), and bicyclogermacrene (10.43%). It also displayed acute toxicity in adults of Mus musculus; the intraperitoneal and oral lethal dose 50 (LD50) were 2,000 mg kg-1 and 2,500 mg kg-1, respectively. The results showed that the essential oil from C. argyrophyllus leaves has insecticidal activity on Ae. aegypti larvae and adults at an average lethal concentration below the median lethal dose needed to cause acute toxicity in the common mouse.


Subject(s)
Aedes/drug effects , Croton/chemistry , Insecticides/pharmacology , Insecticides/toxicity , Oils, Volatile/pharmacology , Oils, Volatile/toxicity , Aedes/growth & development , Animals , Female , Larva/drug effects , Larva/growth & development , Lethal Dose 50 , Mice , Mosquito Control , Plant Leaves/chemistry
15.
Braz J Med Biol Res ; 50(1): e5630, 2017 Jan 05.
Article in English | MEDLINE | ID: mdl-28076453

ABSTRACT

Previous studies have reported on the glucose and lipid-lowering effects of ferulic acid (FA) but its anti-obesity potential has not yet been firmly established. This study investigated the possible anti-obesitogenic effects of FA in mice fed a high-fat diet (HFD) for 15 weeks. To assess the antiobesity potential of FA, 32 male Swiss mice, weighing 20-25 g (n=6-8 per group) were fed a normal diet (ND) or HFD, treated orally or not with either FA (10 mg/kg) or sibutramine (10 mg/kg) for 15 weeks and at the end of this period, the body weights of animals, visceral fat accumulation, plasma levels of glucose and insulin hormone, amylase and lipase activities, the satiety hormones ghrelin and leptin, and tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCH-1) were analyzed. Results revealed that FA could effectively suppress the HFD-associated increase in visceral fat accumulation, adipocyte size and body weight gain, similar to sibutramine, the positive control. FA also significantly (P<0.05) decreased the HFD-induced elevations in serum lipid profiles, amylase and lipase activities, and the levels of blood glucose and insulin hormone. The markedly elevated leptin and decreased ghrelin levels seen in HFD-fed control mice were significantly (P<0.05) reversed by FA treatment, almost reaching the values seen in ND-fed mice. Furthermore, FA demonstrated significant (P<0.05) inhibition of serum levels of inflammatory mediators TNF-α, and MCH-1. These results suggest that FA could be beneficial in lowering the risk of HFD-induced obesity via modulation of enzymatic, hormonal and inflammatory responses.


Subject(s)
Anti-Obesity Agents/pharmacology , Coumaric Acids/pharmacology , Cyclobutanes/pharmacology , Intra-Abdominal Fat/drug effects , Obesity/drug therapy , Adipose Tissue/pathology , Animals , Diet, High-Fat , Disease Models, Animal , Male , Mice , Obesity/pathology
16.
Clin Genet ; 91(5): 725-738, 2017 May.
Article in English | MEDLINE | ID: mdl-27807845

ABSTRACT

Microtubule dynamics play a crucial role in neuronal development and function, and several neurodevelopmental disorders have been linked to mutations in genes encoding tubulins and functionally related proteins. Most recently, variants in the tubulin cofactor D (TBCD) gene, which encodes one of the five co-chaperones required for assembly and disassembly of α/ß-tubulin heterodimer, were reported to underlie a recessive neurodevelopmental/neurodegenerative disorder. We report on five patients from three unrelated families, who presented with microcephaly, intellectual disability, intractable seizures, optic nerve pallor/atrophy, and cortical atrophy with delayed myelination and thinned corpus callosum on brain imaging. Exome sequencing allowed the identification of biallelic variants in TBCD segregating with the disease in the three families. TBCD protein level was significantly reduced in cultured fibroblasts from one patient, supporting defective TBCD function as the event underlying the disorder. Such reduced expression was associated with accelerated microtubule re-polymerization. Morpholino-mediated TBCD knockdown in zebrafish recapitulated several key pathological features of the human disease, and TBCD overexpression in the same model confirmed previous studies documenting an obligate dependency on proper TBCD levels during development. Our findings confirm the link between inactivating TBCD variants and this newly described chaperone-associated tubulinopathy, and provide insights into the phenotype of this disorder.


Subject(s)
Developmental Disabilities/genetics , Microcephaly/genetics , Microtubule-Associated Proteins/chemistry , Microtubule-Associated Proteins/genetics , Seizures/genetics , Animals , Child, Preschool , Embryo, Nonmammalian , Epilepsy/genetics , Female , Humans , Infant , Intellectual Disability/genetics , Magnetic Resonance Imaging , Male , Microtubule-Associated Proteins/metabolism , Microtubules/genetics , Microtubules/pathology , Seizures/diagnostic imaging , Zebrafish/embryology , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism
17.
Transplant Proc ; 48(8): 2845-2849, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27788828

ABSTRACT

BACKGROUND: In the development of new biomaterials for pericardium substitute, acellular amniotic membrane (AAM) presents potential for new applications in regenerative medicine. We studied an AAM as a pericardial substitute to achieve a suitable, cost effective, abundant matrix for the purpose of using it as graft for tissue repair. METHODS: Twenty Wistar rats were randomly divided into 2 groups (n = 10/group) and had their pericardiums excised. In the experimental group, the excised pericardium segment was substituted by a 7-mm-diameter patch of decellularized AAM sutured to the lesion area. After 4 weeks, the heart's outer layer of both groups was evaluated. The structure and component characteristics of the scaffold were determined with the use of hematoxylin and eosi, Alizarin Red S, and immumohistochemical staining and scanning electron microscopy. RESULTS: Histopathologic examination of the AAM patches revealed that the integrity of the AAM was preserved, and no calcification was observed on the surface of the myocardium. We also observed thicker pericardium repair tissue in the AAM group compared with the control group. AAM patches, by virtue of their low immunogenicity, evoked minimal host-versus-graft reaction. CONCLUSIONS: We conclude that AAM appears to be an ideal substitute for pericardium lesions, because it is integrated into the biologic tissue owing to its low immunogenicity and its ability to diminish the occurrence of adhesions and scarring, increasing the pericardium thickness.


Subject(s)
Amnion/transplantation , Pericardium/surgery , Tissue Scaffolds , Animals , Biocompatible Materials/pharmacology , Calcinosis/prevention & control , Cicatrix/prevention & control , Male , Random Allocation , Rats , Rats, Wistar , Tissue Adhesions/prevention & control , Wound Healing/physiology
18.
Soft Matter ; 12(29): 6223-31, 2016 Jul 20.
Article in English | MEDLINE | ID: mdl-27378156

ABSTRACT

Cells modulate their shape to fulfill specific functions, mediated by the cell cortex, a thin actin shell bound to the plasma membrane. Myosin motor activity, together with actin dynamics, contributes to cortical tension. Here, we examine the individual contributions of actin polymerization and myosin activity to tension increase with a non-invasive method. Cell-sized liposome doublets are covered with either a stabilized actin cortex of preformed actin filaments, or a dynamic branched actin network polymerizing at the membrane. The addition of myosin II minifilaments in both cases triggers a change in doublet shape that is unambiguously related to a tension increase. Preformed actin filaments allow us to evaluate the effect of myosin alone while, with dynamic actin cortices, we examine the synergy of actin polymerization and myosin motors in driving shape changes. Our assay paves the way for a quantification of tension changes triggered by various actin-associated proteins in a cell-sized system.


Subject(s)
Actins/chemistry , Liposomes/chemistry , Myosins/chemistry , Actin Cytoskeleton , Myosin Type II
19.
Mediators Inflamm ; 2016: 7068287, 2016.
Article in English | MEDLINE | ID: mdl-27073297

ABSTRACT

Leishmania (L.) amazonensis (La) and L. (V.) braziliensis (Lb) are responsible for a large clinical and immunopathological spectrum in human disease; while La may be responsible for anergic disease, Lb infection leads to cellular hypersensitivity. To better understand the dichotomy in the immune response caused by these Leishmania species, we evaluated subsets of dendritic cells (DCs) and T lymphocyte in draining lymph nodes during the course of La and Lb infection in BALB/c mice. Our results demonstrated a high involvement of DCs in La infection, which was characterized by the greater accumulation of Langerhans cells (LCs); conversely, Lb infection led to an increase in dermal DCs (dDCs) throughout the infection. Considering the T lymphocyte response, an increase of effector, activated, and memory CD4(+) T-cells was observed in Lb infection. Interleukin- (IL-) 4- and IL-10-producing CD4(+)and CD8(+) T-cells were present in both La and Lb infection; however, interferon- (IFN-) γ-producing CD4(+)and CD8(+) T-cells were detected only in Lb infection. The results suggest that during Lb infection, the dDCs were the predominant subset of DCs that in turn was associated with the development of Th1 immune response; in contrast La infection was associated with a preferential accumulation of LCs and total blockage of the development of Th1 immune response.


Subject(s)
Dendritic Cells/metabolism , Leishmania braziliensis/pathogenicity , Leishmania/pathogenicity , Lymph Nodes/metabolism , Animals , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , Dendritic Cells/immunology , Flow Cytometry , Interferon-gamma/metabolism , Interleukin-10/metabolism , Interleukin-4/metabolism , Leishmania/immunology , Leishmania braziliensis/immunology , Lymph Nodes/immunology , Male , Mice , Mice, Inbred BALB C
20.
Genes Immun ; 17(1): 13-8, 2016.
Article in English | MEDLINE | ID: mdl-26492519

ABSTRACT

Type 1 diabetes (T1D) is a multifactorial disease that has a strong genetic component. The HLA-G is a nonclassical HLA class I locus that is associated with immunomodulatory functions, including downregulation of innate and adaptive immune responses and induction of immune tolerance. However, there is currently limited information about the involvement of HLA-G in T1D susceptibility. This case-control study aims to investigate the T1D susceptibility association of alleles and genotypes of a widely investigated 14-bp insertion/deletion polymorphism in the HLA-G and to provide further evidence of the frequency distribution of class II HLA-DR-DQ-risk genotypes in T1D children and adolescents in the Brazilian population. The deletion allele and the homozygous deletion genotype are associated with susceptibility to T1D and the insertion allele and the heterozygous deletion/insertion genotype are associated with protection from T1D. We also confirm that genetic susceptibility to T1D is associated with the DRB1*03:01-DQA1*05:01-DQB1*02:01 and DRB1*04-DQA1*03:01-DQB1*03:02 haplotypes in Brazilian northeast region. The DR3-DQ2/DR4-DQ8 genotype conferred the highest detected risk for T1D. Our results identify a novel association of the 14-bp deletion allele and the homozygous deletion genotype with T1D development and provide additional evidence of the importance of HLA class II heterozygous DR3-DQ2/DR4-DQ8 genotype in T1D susceptibility.


Subject(s)
Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/immunology , Genetic Predisposition to Disease , HLA-G Antigens/genetics , Adolescent , Brazil , Case-Control Studies , Child , Female , HLA-D Antigens/genetics , HLA-D Antigens/immunology , HLA-G Antigens/immunology , Haplotypes , Humans , Male , Polymorphism, Genetic
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