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1.
medRxiv ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38947098

ABSTRACT

Despite their importance, little is known about how social drivers of health shape communicative outcomes in autism. Even less is known when considering the intersection of race and language impairment. An understanding of factors in communicative outcomes is key for characterizing developmental trajectories and informing supports. This cross-sectional observational study examined the role of social drivers of health in communicative outcomes of racially and ethnically minoritized autistic adolescents and adults. Participants ages 13 to 30 (N = 73) completed a behavioral assessment protocol, including language and nonverbal cognitive skills, as well as social drivers of health (sense of community, unmet services, barriers to services). Correlational analyses revealed associations between social drivers of health on social communication impairment and real-world communication. Generalized linear mixed-effects modeling revealed that language predicted real-world communication, but sense of community predicted social communication impairment. Findings point to the importance of assessing both individual differences and social drivers of health in outcomes in autism research. Future work should focus on social drivers of health in larger-scale analyses of outcomes in minoritized autistic individuals during the transition to adulthood, considering supports that align with service eligibility and person-centered outcomes.

2.
medRxiv ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38746405

ABSTRACT

Self-determination plays an important role in outcomes in autism and shows intersectional disparities. Yet, little is known about the role of individual differences or social drivers of health in the development of self-determination. Understanding these factors is key for developing effective supports. This mixed-methods convergent study examined self-determination in racially and ethnically minoritized autistic individuals and caregivers. Participants ages 13 to 30 ( N = 73) varying widely in language and cognitive ability and caregivers ( n =52) completed the Self-Determination Inventory. Autism traits and sense of community predicted caregiver report of self-determination, and autism traits and language predicted self-report of self-determination, consistent with DisCrit and Diversity Science. Self-Determination Inventory interviews of a subset of participants ( n = 13) and caregivers ( n = 9) were analyzed using inductive thematic analysis. Themes pointed to the role of the intersection of race and disability in shaping self-determination. Altogether, findings point to the importance of these frameworks, environmental influences, and multi-informant perspectives in characterizing self-determination. Future work should focus on the impact of environmental factors in self-determination in minoritized autistic individuals during the transition to adulthood.

3.
Lang Speech Hear Serv Sch ; 54(2): 379-386, 2023 04 03.
Article in English | MEDLINE | ID: mdl-36649542

ABSTRACT

PURPOSE: Meeting the needs of Maya children in U.S. schools requires extensive training. Research is lacking in best practices to support students with intersectional identities. This article provides a roadmap centralized on Maya children's experiences, acknowledging the linguistic diversity of Maya immigrants, their language and cultural practices, and their integration into or exclusion from minoritized and White neighborhoods in the United States to provide a starting point for culturally responsive service delivery. CONCLUSIONS: Supporting the needs of Maya children requires an approach that values and recognizes their intersectional identities while developing collaborative relationships with students, families, and educators. Application of the roadmap will support to (a) identify educational obstacles faced by Maya children, (b) integrate translanguaging to support best practices for educational success, and (c) determine service delivery considerations for bilingual/trilingual, multicultural children. More research on the topic is needed to establish evidence-based practice guidelines to utilize a translanguaging pedagogy within speech-language pathology.


Subject(s)
Multilingualism , Child , Humans , United States , Language , Schools , Linguistics , Cultural Diversity
4.
Animals (Basel) ; 12(24)2022 Dec 19.
Article in English | MEDLINE | ID: mdl-36552505

ABSTRACT

Understanding how cows respond to heat stress has helped to provide effective herd management practices to tackle this environmental challenge. The possibility of selecting animals that are genetically more heat tolerant may provide additional means to maintain or even improve the productivity of the Canadian dairy industry, which is facing a shifting environment due to climate changes. The objective of this study was to estimate the genetic parameters for heat tolerance of milk, fat, and protein yields in Canadian Holstein cows. A total of 1.3 million test-day records from 195,448 first-parity cows were available. A repeatability test-day model fitting a reaction norm on the temperature-humidity index (THI) was used to estimate the genetic parameters. The estimated genetic correlations between additive genetic effect for production and for heat tolerance ranged from -0.13 to -0.21, indicating an antagonistic relationship between the level of production and heat tolerance. Heritability increased marginally as THI increased above its threshold for milk yield (0.20 to 0.23) and protein yield (0.14 to 0.16) and remained constant for fat yield (0.17). A Spearman rank correlation between the estimated breeding values under thermal comfort and under heat stress showed a potential genotype by environmental interaction. The existence of a genetic variability for heat tolerance allows for the selection of more heat tolerant cows.

5.
Perspect ASHA Spec Interest Groups ; 7(4): 981-994, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36105373

ABSTRACT

Purpose: The ultimate aim of an assessment is to help examiners make valid conclusions about an individual's skill given their performance on a particular measure. Yet, assessing the language abilities of culturally and linguistically diverse individuals requires researchers and practitioners to carefully consider the appropriateness of traditional parameters of test psychometrics (e.g., reliability, or consistency of assessments as measurement) plus the intersectional identities that inform the generalizability of these parameters. The purpose of this clinical focus article is to provide clinicians and researchers with resources to interpret and use common standardized language assessments in English for culturally and linguistically diverse school-age youth. We present theories from psychometrics, legal studies, and education relevant to language assessment of diverse individuals, review standardized language assessments in English, and provide theory-to-practice applications of language assessment scenarios. Conclusions: Implementing intersectional approaches in working with diverse children and using assessment scores as just one piece of evidence amid a broader evidence base will contribute to a more accurate evaluation of culturally and linguistically diverse children's language abilities. A comprehensive approach involving multiple stakeholders across the field of communication sciences and disorders may support achieving such implementation.

6.
Front Public Health ; 10: 928174, 2022.
Article in English | MEDLINE | ID: mdl-35875036

ABSTRACT

Old people residing in nursing homes have been a vulnerable group to the coronavirus disease 2019 (COVID-19) pandemic, with high rates of infection and death. Our objective was to describe the profile of institutionalized patients with a confirmed COVID-19 infection and the socioeconomic and morbidity factors associated with hospitalization and death. We conducted a retrospective cohort study including data from subjects aged 65 years or older residing in a nursing home with a confirmed COVID-19 infection from March 2020 to March 2021 (4,632 individuals) in Aragón (Spain). We analyzed their sociodemographic and clinical profiles and factors related to hospitalization and mortality at 7, 30, and 90 days of COVID-19 diagnosis using logistic regression analyses. We found that the risk of hospitalization and mortality varied according to sociodemographic and morbidity profile. There were inequalities in hospitalization by socioeconomic status and gender. Patients with low contributory pensions and women had a lower risk of hospitalization. Diabetes mellitus, heart failure, and chronic kidney disease were associated with a higher risk of hospitalization. On the contrary, people with dementia showed the highest risk of mortality with no hospitalization. Patient-specific factors must be considered to develop equitable and effective measures in nursing homes to be prepared for future health threats.


Subject(s)
COVID-19 , Pandemics , COVID-19/epidemiology , COVID-19 Testing , Female , Humans , Nursing Homes , Retrospective Studies , Spain/epidemiology
7.
Food Chem X ; 13: 100259, 2022 Mar 30.
Article in English | MEDLINE | ID: mdl-35498981

ABSTRACT

Aiming to understand the impact of hardening on the biological potential of bean protein and peptides, we evaluated the antioxidant and vasorelaxant properties of common beans after and before hardening. It was also evaluated the effect of extrusion and autoclaving in the biological potential of hardened beans. In general, hardening caused a reduction from 13.5 to 39.6% on the antioxidant activity of the peptide-rich fractions. On the other hand, hardening did not strongly interfere with the vascular reactivity in thoracic aorta rings, being observed maximal relation varying from 801% to 84.7%. The thermal treatment caused a general increase in the antioxidant and vasorelaxant potential of these fractions, being observed EC50 values ranging from 0.22 mg mL-1 to 0.26 mg mL-1. We can conclude that hardening did not seem to affect definitively the bioactivity of the obtained peptide-rich fractions. Finally, this study allows suggesting practical applications of extrusion as a thermal process in the production of functional food ingredients, and as ready-to-eat products presenting nutraceutical potential. In addition, autoclaving can be used as a pre-treatment of the hardened grains aiming to use them as whole grains with potentialized benefits for human health.

8.
Colloids Surf B Biointerfaces ; 209(Pt 1): 112213, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34801977

ABSTRACT

In this study, a nanocomposite produced with a blend of polyvinyl alcohol and partially hydrolyzed starch from Solanum lycocarpum was used as a matrix to entrap natural bioactive peptides from Phaseolus vulgaris. The nanocomposites were characterized by dynamic light scattering, scanning electron microscopy, and field emission gun scanning electron microscopy. The nanocomposites were then orally administered to Wistar rats, and their absorption was determined using morphometric, histopathological, cytochemistry, transmission electron microscopy, and biochemical analysis. Results showed that despite some aggregates being formed, the nanocomposites efficiently entrapped the natural peptides, with a loading capacity of 303.62 mg (45.7%) and an entrapment efficiency of 85.3% (267.02 µmol). Histochemical and morphological analysis revealed the absence of tissue injury and cellular changes, indicating the absence of deleterious and toxic effects. Transmission electron microscopy showed the internalization of the nanocomposites in the enterocytes, and biochemical analysis indicated that natural peptides were absorbed reaching the bloodstream.


Subject(s)
Nanocomposites , Phaseolus , Animals , Peptides , Polyvinyl Alcohol , Rats , Rats, Wistar , Starch
9.
Am J Speech Lang Pathol ; 30(5): 1990-2002, 2021 09 23.
Article in English | MEDLINE | ID: mdl-34432987

ABSTRACT

Purpose Microaggressions and how they affect underrepresented college students have been frequently documented. However, there is a lack of literature on the experiences of underrepresented communication sciences and disorders (CSD) students. The purpose of this study is to understand how underrepresented post baccalaureate, undergraduate, and graduate students in CSD experience microaggressions in their academic programs. Method A 19-item electronic survey was developed by American Speech-Language-Hearing Association's Multicultural Issues Board and distributed via multiple online platforms. A diverse group of 155 underrepresented CSD students completed the survey. A multistage qualitative thematic analysis was used to analyze students' experiences. Results Students (64.51%) who completed the survey have experienced microaggressions in their academic programs. Prominent themes of students' descriptions of microaggressions included feelings of otherness, damaging generalization, maltreatment from faculty, and maltreatment from peers. Students reported various responses to microaggressions including identity management strategies, disengaging, and working hard to exceed expectations and to prove themselves. Conclusions This study illustrates the ways that underrepresented CSD students experience symbolic violence from clients, peers, and faculty. It has implications for the need to cultivate more inclusive learning and social environments in CSD programs. Further research is needed to explore the ramifications of microaggressions and ways to effectively reduce and eventually eradicate them. Supplemental Material https://doi.org/10.23641/asha.15240723.


Subject(s)
Communication , Students , Faculty , Humans , Peer Group , Surveys and Questionnaires , United States
10.
Article in English | MEDLINE | ID: mdl-34205348

ABSTRACT

It is essential to understand the impact of social inequalities on the risk of COVID-19 infection in order to mitigate the social consequences of the pandemic. With this aim, the objective of our study was to analyze the effect of socioeconomic inequalities, both at the individual and area of residence levels, on the probability of COVID-19 confirmed infection, and its variations across three pandemic waves. We conducted a retrospective cohort study and included data from all individuals tested for COVID-19 during the three waves of the pandemic, from March to December 2020 (357,989 individuals) in Aragón (Spain). We studied the effect of inequalities on the risk of having a COVID-19 confirmed diagnosis after being tested using multilevel analyses with two levels of aggregation: individuals and basic healthcare area of residence (deprivation level and type of zone). Inequalities in the risk of COVID-19 confirmed infection were observed at both the individual and area level. There was a predominance of low-paid employees living in deprived areas. Workers with low salaries, unemployed and people on minimum integration income or who no longer receive the unemployment allowance, had a higher probability of COVID-19 infection than workers with salaries ≥ €18,000 per year. Inequalities were greater in women and in the second wave. The deprivation level of areas of residence influenced the risk of COVID-19 infection, especially in the second wave. It is necessary to develop individual and area coordinated measures by areas in the control, diagnosis and treatment of the epidemic, in order to avoid an increase in the already existing inequalities.


Subject(s)
COVID-19 , Female , Humans , Retrospective Studies , SARS-CoV-2 , Socioeconomic Factors , Spain/epidemiology
11.
J Comp Physiol B ; 191(2): 427-438, 2021 03.
Article in English | MEDLINE | ID: mdl-33570665

ABSTRACT

Bats are unique among mammals in that they have evolved the capacity to fly. This has generated strong selective pressure on the morphology and function of their digestive system. Given that in bats intestinal length and nominal surface-area are proportional to body mass, this trait importantly relates to explaining some of their digestive characteristics. We described the relationship between digestive traits and body mass of four species of bats of the family Vespertilionidae living in a montane ecosystem in central Mexico. We calculated food transit time, apparent dry matter digestibility, and defecation rate in feeding trials under captive conditions. We also: (1) built a model of the relationship between digestive traits and body mass to determine if this association was consistent within the members of the family Vespertilionidae, and (2) mapped these traits along the phylogeny to explore how digestive characteristics may have evolved. In our feeding trials, body mass was positively related to transit time and negatively related to apparent dry matter digestibility. The model predicted accurately the transit time in bats with body mass < 20 g. The phylogenetic approach suggested that over the evolutionary history of the family, transit time decreased as digestibility increased. Because of the results obtained here, it is likely that for most bats of the family Vespertilionidae, adaptations in digestive traits to process food have followed evolutionary changes in their body mass. We discuss these findings in a physiological and ecological context.


Subject(s)
Chiroptera , Animals , Digestion , Ecosystem , Mammals , Phylogeny
12.
Biotechnol Prog ; 36(2): e2934, 2020 03.
Article in English | MEDLINE | ID: mdl-31642208

ABSTRACT

Lignocellulosic wastes can be potentially converted into several bioproducts such as glucose, xylo-oligosaccharides, and bioethanol. Certain processes, such as enzymatic hydrolysis, are generally needed to convert biomass into bioproducts. The present study investigated the production of xylanases and cellulases by Streptomyces thermocerradoensis I3 under solid-state fermentation (SSF), using wheat bran as a low-cost medium. The activities of xylanase and carboxymethyl cellulase (CMCase) were evaluated until 96 hr of incubation. The highest enzyme activity was observed after 72 hr of incubation. The crude enzyme extract was sequentially filtered, first using a 50 kDa filter, followed by a 30 kDa filter. Fraction 3 (F3) exhibited activities of both xylanase and CMCase. Xylanase and CMCase showed optimum activity at 70°C and pH 6.0 and 55°C and pH 6.0, respectively. The zymogram analysis showed a single activity band with a molecular mass of approximately 17 kDa. These findings provide strong evidence that the enzyme is a bifunctional xylanase/endoglucanase. This enzyme improved the saccharification of sugarcane bagasse by 1.76 times that of commercial cellulase. This enzyme has potential applications in various biotechnological procedures.


Subject(s)
Cellulase/metabolism , Fermentation , Streptomyces/metabolism , Xylosidases/metabolism , Hydrogen-Ion Concentration , Temperature
13.
PLoS One ; 14(12): e0212727, 2019.
Article in English | MEDLINE | ID: mdl-31805054

ABSTRACT

Passive acoustic monitoring (PAM) coupled with automated species identification is a promising tool for species monitoring and conservation worldwide. However, high false indications of presence are still an important limitation and a crucial factor for acceptance of these techniques in wildlife surveys. Here we present the Assemblage of Focal Species Recognizers-AFSR, a novel approach for decreasing false positives and increasing models' precision in multispecies contexts. AFSR focusses on decreasing false positives by excluding unreliable sound file segments that are prone to misidentification. We used MatlabHTK, a hidden Markov models interface for bioacoustics analyses, for illustrating AFSR technique by comparing two approaches, 1) a multispecies recognizer where all species are identified simultaneously, and 2) an assemblage of focal species recognizers (AFSR), where several recognizers that each prioritise a single focal species are then summarised into a single output, according to a set of rules designed to exclude unreliable segments. Both approaches (the multispecies recognizer and AFSR) used the same sound files training dataset, but different processing workflow. We applied these recognisers to PAM recordings from a remote island colony with five seabird species and compared their outputs with manual species identifications. False positives and precision improved for all the five species when using AFSR, achieving remarkable 0% false positives and 100% precision for three of five seabird species, and < 6% false positives, and >90% precision for the other two species. AFSR' output was also used to generate daily calling activity patterns for each species. Instead of attempting to withdraw useful information from every fragment in a sound recording, AFSR prioritises more trustworthy information from sections with better quality data. AFSR can be applied to automated species identification from multispecies PAM recordings worldwide.


Subject(s)
Acoustics , Biological Monitoring/methods , Birds/classification , Animals , Automation , New Zealand , Species Specificity
14.
Alzheimers Res Ther ; 10(1): 12, 2018 01 29.
Article in English | MEDLINE | ID: mdl-29378651

ABSTRACT

BACKGROUND: Immunotherapy targeting the amyloid-ß (Aß) peptide is a promising strategy for the treatment of Alzheimer's disease (AD); however, none of the active or passive vaccines tested have been demonstrated to be effective to date. We have developed the first active vaccine against the C-terminal end of Aß40, ABvac40, and assessed its safety and tolerability in a phase I clinical trial. METHODS: A randomised, double-blind, placebo-controlled, parallel-group, phase I study of ABvac40 was conducted with patients aged 50-85 years with mild to moderate AD. Participants were entered into three separate groups according to time of study entry and were randomly allocated to receive ABvac40 or placebo (overall ratio 2:1). The first group received two half-doses of ABvac40 or placebo, whereas the second and third groups received two and three full doses, respectively. All treatments were administered subcutaneously at 4-week intervals. Patients, carers and investigators were blind to treatment allocation throughout the study. The primary objective was to assess the safety and tolerability of ABvac40 by registering all adverse events (AEs). All patients who received at least one dose of treatment were included in the safety analysis. The secondary objective was to evaluate the immunogenicity of ABvac40 by titration of specific anti-Aß40 antibodies in plasma. RESULTS: Twenty-four patients were randomly allocated: 16 patients to the ABvac40 group and 8 patients to the placebo group. All randomised patients completed the study, therefore the intention-to-treat and safety populations were identical. Overall, 71 AEs affecting 18 patients were recorded: 11 (69%) in the ABvac40 group and 7 (88%) in the placebo group (p = 0.6214). Neither incident vasogenic oedema nor sulcal effusion (amyloid-related imaging abnormalities corresponding to vasogenic oedema and sulcal effusions) nor microhaemorrhages (amyloid-related imaging abnormalities corresponding to microhaemorrhages and hemosiderin deposits) were detected throughout the study period in the ABvac40-treated patients. Eleven of 12 (~92%) individuals receiving three injections of ABvac40 developed specific anti-Aß40 antibodies. CONCLUSIONS: ABvac40 showed a favourable safety and tolerability profile while eliciting a consistent and specific immune response. An ongoing phase II clinical trial is needed to confirm these results and to explore the clinical efficacy of ABvac40. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03113812 . Retrospectively registered on 14 April 2017.


Subject(s)
Alzheimer Disease/immunology , Alzheimer Disease/therapy , Alzheimer Vaccines/therapeutic use , Amyloid beta-Peptides/immunology , Immunogenicity, Vaccine , Peptide Fragments/immunology , Aged , Aged, 80 and over , Alzheimer Disease/blood , Alzheimer Vaccines/adverse effects , Double-Blind Method , Female , Follow-Up Studies , Humans , Male , Middle Aged , Protein Domains , Severity of Illness Index , Treatment Outcome
15.
An Bras Dermatol ; 92(4): 492-498, 2017.
Article in English | MEDLINE | ID: mdl-28954097

ABSTRACT

BACKGROUND:: Many factors are currently being identified as potential inductors of skin cancer in patients after a liver transplant, among them, immunosuppressive regimen. OBJECTIVE:: To study the factors that influence the incidence of skin cancer in patients after liver transplant. METHODS:: We have carried out a retrospective and observational study with 170 transplanted patients who had undergone transplantation from 1997 to 2010. We have adjusted the multiple logistic regression model (saturated model) to the ensemble of collected data using skin cancer as dependent variable, indicated in anatomopathological analysis between 1997 and 2014. RESULTS:: Incidence of skin cancer was 9.4%. Predictors were incidence of diabetes in the third year after the transplantation (p=0.047), not using tacrolimus in the first year after the transplantation (p=0.025) and actinic keratosis (p=0.003). STUDY LIMITATIONS:: An important limitation is that the interpretation of the results was based on information collected of patients undergoing transplantation at a single center. Future research, multicentric and involving larger and more diverse populations, are needed. CONCLUSIONS:: Factors found might contribute to Brazilian surveillance programs associated with decreased incidence of skin cancer.


Subject(s)
Carcinoma, Basal Cell/epidemiology , Carcinoma, Squamous Cell/epidemiology , Immunosuppression Therapy/adverse effects , Liver Transplantation/adverse effects , Skin Neoplasms/epidemiology , Adult , Age Factors , Brazil/epidemiology , Carcinoma, Basal Cell/etiology , Carcinoma, Basal Cell/pathology , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/pathology , Diabetes Mellitus/epidemiology , Female , Humans , Immunosuppressive Agents/therapeutic use , Incidence , Logistic Models , Male , Middle Aged , Retrospective Studies , Risk Factors , Skin Neoplasms/etiology , Skin Neoplasms/pathology
16.
Sci Rep ; 6: 19348, 2016 Jan 19.
Article in English | MEDLINE | ID: mdl-26783107

ABSTRACT

Aldehydes accumulate in inflammation, during myocardial infarction and have been associated with pain symptoms. One pathway of aldehyde detoxification is the conjugation with carnosine. A 3-methylpyridinium carnosine adduct from the reaction of carnosine and acrolein was characterized using extensive spectroscopic measurements. The adduct with urinary concentrations of 1.82 ± 0.68 nmol/mg of creatinine is one of the most abundant acrolein metabolites in urine and opens promising therapeutic strategies for carnosine.


Subject(s)
Acrolein/chemistry , Acrolein/urine , Carnosine/chemistry , Carnosine/urine , Chromatography, High Pressure Liquid , Humans , Nuclear Magnetic Resonance, Biomolecular , Spectrometry, Mass, Electrospray Ionization
17.
Res Vet Sci ; 101: 34-7, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26267086

ABSTRACT

The selected dodecapeptide (1)DRALYGPTVIDH(12) from a phage-displayed peptide library and the crystal structure of the envelope glycoprotein B (Env gB) from Herpes Simplex Virus type 1 (HSV-1) led us to the identification of a new discontinuous epitope on the Bovine herpesvirus type 1 (BoHV-1) Env gB. In silico analysis revealed a short BoHV-1 gB motif ((338)YKRD(341)) within a epitope region, with a high similarity to the motifs shared by the dodecapeptide N-terminal region ((5)YxARD(1)) and HSV-1 Env gB ((326)YARD(329)), in which the (328)Arg residue is described to be a neutralizing antibody target. Besides the characterization of an antibody-binding site of the BoHV-1 Env gB, we have demonstrated that the phage-fused peptide has the potential to be used as a reagent for virus diagnosis by phage-ELISA assay, which discriminated BoHV-1 infected serum samples from negative ones.


Subject(s)
Epitopes/genetics , Herpesvirus 1, Bovine/genetics , Models, Molecular , Viral Proteins/genetics , Animals , Antibodies, Neutralizing/immunology , Binding Sites/genetics , Cattle , Enzyme-Linked Immunosorbent Assay/veterinary , Oligonucleotides/genetics , Peptide Library , Protein Conformation
18.
Stem Cell Rev Rep ; 11(2): 228-41, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25618295

ABSTRACT

Derivation of articular chondrocytes from human stem cells would advance our current understanding of chondrogenesis, and accelerate development of new stem cell therapies for cartilage repair. Chondrogenic differentiation of human embryonic stem cells (hESCs) has been studied using supplemental and cell-secreted morphogenetic factors. The use of bioreactors enabled insights into the effects of physical forces and controlled oxygen tension. In this study, we investigated the interactive effects of controlled variation of oxygen tension and chondrocyte-secreted morphogenetic factors on chondrogenic differentiation of hESCs in the embryoid body format (hESC-EB). Transient hypoxic culture (2 weeks at 5 % O2 followed by 1 week at 21 % O2) of hESC-EBs in medium conditioned with primary chondrocytes up-regulated the expression of SOX9 and suppressed pluripotent markers OCT4 and NANOG. Pellets derived from these cells showed significant up-regulation of chondrogenic genes (SOX9, COL2A1, ACAN) and enhanced production of cartilaginous matrix (collagen type II and proteoglycan) as compared to the pellets from hESC-EBs cultured under normoxic conditions. Gene expression profiles corresponded to those associated with native cartilage development, with early expression of N-cadherin (indicator of cell condensation) and late expression of aggrecan (ACAN, indicator of proteoglycan production). When implanted into highly vascularized subcutaneous area in immunocompromised mice for 4 weeks, pellets remained phenotypically stable and consisted of cartilaginous extracellular matrix (ECM), without evidence of dedifferentiation or teratoma formation. Based on these results, we propose that chondrogenesis in hESC can be synergistically enhanced by a control of oxygen tension and morphogenetic factors secreted by chondrocytes.


Subject(s)
Cell Hypoxia/genetics , Cell- and Tissue-Based Therapy , Chondrogenesis , Embryoid Bodies/metabolism , Human Embryonic Stem Cells/metabolism , Animals , Cartilage/growth & development , Cartilage/metabolism , Cell Differentiation/genetics , Chondrocytes/metabolism , Embryoid Bodies/cytology , Gene Expression Regulation, Developmental , Homeodomain Proteins/biosynthesis , Human Embryonic Stem Cells/cytology , Humans , Mice , Nanog Homeobox Protein , Octamer Transcription Factor-3/biosynthesis , Oxygen/metabolism , SOX9 Transcription Factor/biosynthesis
19.
Sci Rep ; 4: 5359, 2014 Jun 19.
Article in English | MEDLINE | ID: mdl-24942522

ABSTRACT

Light sticks (LS) are sources of chemiluminescence commonly used in pelagic fishery, where hundreds are discarded and reach the shores. Residents from fishing villages report an improper use of LS contents on the skin. Given the scarce information regarding LS toxicity, the effects of LS solutions in cell cultures were evaluated herein. Loss of viability, cell cycle changes and DNA fragmentation were observed in HepG2 cell line and skin fibroblasts. A non-cytotoxic LS concentration increased the occurrence of the mutagenic lesion 1,N(6)-εdAdo in HepG2 DNA by three-fold. Additionally, in vitro incubations of spent LS contents with DNA generated dGuo-LS adducts, whose structure elucidation revealed the presence of a reactive chlorinated product. In conclusion, the LS contents were found to be highly cyto- and genotoxic. Our data indicate an urgent need for LS waste management guidelines and for adequate information regarding toxic outcomes that may arise from human exposure.


Subject(s)
Fisheries/instrumentation , Light , Luminescence , Organic Chemicals/pharmacology , Anthracenes/chemistry , Anthracenes/pharmacology , Cell Survival/drug effects , Cells, Cultured , Chromatography, High Pressure Liquid , DNA Adducts/chemistry , DNA Adducts/drug effects , Dibutyl Phthalate/chemistry , Dibutyl Phthalate/pharmacology , Fibroblasts/drug effects , Fibroblasts/metabolism , Fisheries/methods , Hep G2 Cells , Humans , Mass Spectrometry/methods , Molecular Structure , Mutagens/chemistry , Mutagens/pharmacology , Organic Chemicals/chemistry , Oxalates/chemistry , Oxalates/pharmacology , Phthalic Acids/chemistry , Phthalic Acids/pharmacology , Skin/cytology , Waste Management/methods
20.
Proc Natl Acad Sci U S A ; 110(21): 8680-5, 2013 May 21.
Article in English | MEDLINE | ID: mdl-23653480

ABSTRACT

Congenital defects, trauma, and disease can compromise the integrity and functionality of the skeletal system to the extent requiring implantation of bone grafts. Engineering of viable bone substitutes that can be personalized to meet specific clinical needs represents a promising therapeutic alternative. The aim of our study was to evaluate the utility of human-induced pluripotent stem cells (hiPSCs) for bone tissue engineering. We first induced three hiPSC lines with different tissue and reprogramming backgrounds into the mesenchymal lineages and used a combination of differentiation assays, surface antigen profiling, and global gene expression analysis to identify the lines exhibiting strong osteogenic differentiation potential. We then engineered functional bone substitutes by culturing hiPSC-derived mesenchymal progenitors on osteoconductive scaffolds in perfusion bioreactors and confirmed their phenotype stability in a subcutaneous implantation model for 12 wk. Molecular analysis confirmed that the maturation of bone substitutes in perfusion bioreactors results in global repression of cell proliferation and an increased expression of lineage-specific genes. These results pave the way for growing patient-specific bone substitutes for reconstructive treatments of the skeletal system and for constructing qualified experimental models of development and disease.


Subject(s)
Bone Regeneration , Bone Substitutes , Cell Differentiation , Induced Pluripotent Stem Cells , Tissue Engineering , Tissue Scaffolds , Animals , Bioreactors , Cells, Cultured , Female , Gene Expression Regulation , Humans , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Mice , Mice, SCID , Organ Specificity
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