Evaluation of Meibomian gland dysfunction using meibography in patients with xeroderma pigmentosum.

PURPOSE: To assess Meibomian gland dysfunction using meibography in patients with xeroderma pigmentosum and correlate with ocular surface changes. METHODS: This cross-sectional study evaluated patients with xeroderma pigmentosum. All patients underwent a comprehensive and standardized interview. The best-corrected visual acuity of each eye was determined. Detailed ophthalmic examination was conducted, including biomicroscopy examination of the ocular surface, Schirmer test type I, and meibography, and fundus examination was also performed when possible. Meibomian gland dysfunction was assessed by non-contact meibography using Oculus Keratograph® 5M (OCULUS Inc., Arlington, WA, USA). Saliva samples were collected using the Oragene DNA Self-collection kit (DNA Genotek Inc., Ottawa, Canada), and DNA was extracted as recommended by the manufacturer. Factors associated with abnormal meiboscores were assessed using generalized estimating equation models. RESULTS: A total of 42 participants were enrolled, and 27 patients underwent meibography. The meiboscore was abnormal in the upper eyelid in 8 (29.6%) patients and in the lower eyelid in 17 (62.9%). The likelihood of having abnormal meiboscores in the lower eyelid was 16.3 times greater than that in the upper eyelid. In the final multivariate model, age (p=0.001), mutation profile (p=0.006), and presence of ocular surface malignant tumor (OSMT) (p=0.014) remained significant for abnormal meiboscores. For a 1-year increase in age, the likelihood of abnormal meiboscores increased by 12%. Eyes with OSMT were 58.8 times more likely to have abnormal meiboscores than eyes without ocular surface malignant tumor. CONCLUSION: In the final model, age, xeroderma pigmentosum profile, previous cancer, and clinical alterations on the eyelid correlated with a meiboscore of ≥2. Meibomian gland dysfunction was common in patients with xeroderma pigmentosum, mainly in the lower eyelid. The severity of Meibomian gland dysfunction increases with age and is associated with severe eyelid changes.

Evaluation of Meibomian gland dysfunction using meibography in patients with xeroderma pigmentosum

ABSTRACT Purpose: To assess Meibomian gland dysfunction using meibography in patients with xeroderma pigmentosum and correlate with ocular surface changes. Methods: This cross-sectional study evaluated patients with xeroderma pigmentosum. All patients underwent a comprehensive and standardized interview. The best-corrected visual acuity of each eye was determined. Detailed ophthalmic examination was conducted, including biomicroscopy examination of the ocular surface, Schirmer test type I, and meibography, and fundus examination was also performed when possible. Meibomian gland dysfunction was assessed by non-contact meibography using Oculus Keratograph® 5M (OCULUS Inc., Arlington, WA, USA). Saliva samples were collected using the Oragene DNA Self-collection kit (DNA Genotek Inc., Ottawa, Canada), and DNA was extracted as recommended by the manufacturer. Factors associated with abnormal meiboscores were assessed using generalized estimating equation models. Results: A total of 42 participants were enrolled, and 27 patients underwent meibography. The meiboscore was abnormal in the upper eyelid in 8 (29.6%) patients and in the lower eyelid in 17 (62.9%). The likelihood of having abnormal meiboscores in the lower eyelid was 16.3 times greater than that in the upper eyelid. In the final multivariate model, age (p=0.001), mutation profile (p=0.006), and presence of ocular surface malignant tumor (OSMT) (p=0.014) remained significant for abnormal meiboscores. For a 1-year increase in age, the likelihood of abnormal meiboscores increased by 12%. Eyes with OSMT were 58.8 times more likely to have abnormal meiboscores than eyes without ocular surface malignant tumor. Conclusion: In the final model, age, xeroderma pigmentosum profile, previous cancer, and clinical alterations on the eyelid correlated with a meiboscore of ≥2. Meibomian gland dysfunction was common in patients with xeroderma pigmentosum, mainly in the lower eyelid. The severity of Meibomian gland dysfunction increases with age and is associated with severe eyelid changes.

Serum from patients with asthma potentiates macrophage phagocytosis and human mesenchymal stromal cell therapy in experimental allergic asthma.

BACKGROUND/AIMS: Although several studies have demonstrated that mesenchymal stromal cells (MSCs) exhibit beneficial immunomodulatory properties in preclinical models of allergic asthma, effects on airway remodeling have been controversial. Recent evidence has shown that MSCs modify their in vivo immunomodulatory actions depending on the specific inflammatory environment encountered. Accordingly, we assessed whether the therapeutic properties of human mesenchymal stromal cells (hMSCs) could be potentiated by conditioning these cells with serum (hMSC-serum) obtained from patients with asthma and then transplanted in an experimental model of house dust mite (HDM)-induced allergic asthma. METHODS: hMSC and hMSC-serum were administered intratracheally 24 h after the final HDM challenge. hMSC viability and inflammatory mediator production, lung mechanics and histology, bronchoalveolar lavage fluid (BALF) cellularity and biomarker levels, mitochondrial structure and function as well as macrophage polarization and phagocytic capacity were assessed. RESULTS: Serum preconditioning led to: (i) increased hMSC apoptosis and expression of transforming growth factor-ß, interleukin (IL)-10, tumor necrosis factor-α-stimulated gene 6 protein and indoleamine 2,3-dioxygenase-1; (ii) fission and reduction of the intrinsic respiratory capacity of mitochondria; and (iii) polarization of macrophages to M2 phenotype, which may be associated with a greater percentage of hMSCs phagocytosed by macrophages. Compared with mice receiving hMSCs, administration of hMSC-serum led to further reduction of collagen fiber content, eotaxin levels, total and differential cellularity and increased IL-10 levels in BALF, improving lung mechanics. hMSC-serum promoted greater M2 macrophage polarization as well as macrophage phagocytosis, mainly of apoptotic hMSCs. CONCLUSIONS: Serum from patients with asthma led to a greater percentage of hMSCs phagocytosed by macrophages and triggered immunomodulatory responses, resulting in further reductions in both inflammation and remodeling compared with non-preconditioned hMSCs.

Extracellular Vesicles from Different Sources of Mesenchymal Stromal Cells Have Distinct Effects on Lung and Distal Organs in Experimental Sepsis.

The effects of the administration of mesenchymal stromal cells (MSC) may vary according to the source. We hypothesized that MSC-derived extracellular vesicles (EVs) obtained from bone marrow (BM), adipose (AD), or lung (L) tissues may also lead to different effects in sepsis. We profiled the proteome from EVs as a first step toward understanding their mechanisms of action. Polymicrobial sepsis was induced in C57BL/6 mice by cecal ligation and puncture (SEPSIS) and SHAM (control) animals only underwent laparotomy. Twenty-four hours after surgery, animals in the SEPSIS group were randomized to receive saline or 3 × 106 MSC-derived EVs from BM, AD, or L. The diffuse alveolar damage was decreased with EVs from all three sources. In kidneys, BM-, AD-, and L-EVs reduced edema and expression of interleukin-18. Kidney injury molecule-1 expression decreased only in BM- and L-EVs groups. In the liver, only BM-EVs reduced congestion and cell infiltration. The size and number of EVs from different sources were not different, but the proteome of the EVs differed. BM-EVs were enriched for anti-inflammatory proteins compared with AD-EVs and L-EVs. In conclusion, BM-EVs were associated with less organ damage compared with the other sources of EVs, which may be related to differences detected in their proteome.

Mutational signatures and increased retrotransposon insertions in xeroderma pigmentosum variant skin tumors.

Xeroderma pigmentosum variant (XP-V) is an autosomal recessive disease with an increased risk of developing cutaneous neoplasms in sunlight-exposed regions. These cells are deficient in the translesion synthesis (TLS) DNA polymerase eta, responsible for bypassing different types of DNA lesions. From the exome sequencing of 11 skin tumors of a genetic XP-V patients' cluster, classical mutational signatures related to sunlight exposure, such as C>T transitions targeted to pyrimidine dimers, were identified. However, basal cell carcinomas also showed distinct C>A mutation spectra reflecting a mutational signature possibly related to sunlight-induced oxidative stress. Moreover, four samples carry different mutational signatures, with C>A mutations associated with tobacco chewing or smoking usage. Thus, XP-V patients should be warned of the risk of these habits. Surprisingly, higher levels of retrotransposon somatic insertions were also detected when the tumors were compared with non-XP skin tumors, revealing other possible causes for XP-V tumors and novel functions for the TLS polymerase eta in suppressing retrotransposition. Finally, the expected high mutation burden found in most of these tumors renders these XP patients good candidates for checkpoint blockade immunotherapy.

Persistencia académica en estudiantes universitarios: ¿cómo se manifiesta la autoeficacia emocional? / Academic persistence in university students: how is emotional self-efficacy manifested? / Persistência acadêmica em estudantes universitários: como se manifesta a autoeficácia emocional?

Resumen (analítico) Los índices de deserción presentes en la educación superior ameritan el desarrollo de acciones que posibiliten la transformación de tal realidad; por lo que comprender cómo se manifiesta la autoeficacia emocional en estudiantes que persisten en su formación universitaria constituye un punto de partida para lograr tal propósito. En ese sentido, se realizó un estudio cualitativo, de corte fenomenológico-hermenéutico, en el cual participaron siete estudiantes universitarios de Santa Marta, Colombia, seleccionados de manera intencional, a quienes se les realizó una entrevista semiestructurada y cuyos datos fueron analizados mediante el análisis temático. Los resultados indican que la autoeficacia emocional se manifiesta en los estudiantes que persisten en su formación universitaria a través de cinco formas o mecanismos: la autodeterminación, la autoconfianza, el optimismo, la autoafirmación y la perseverancia.

Abstract (analytical) The dropout rates for higher education require the implementation of actions to transform this reality. Understanding how emotional self-efficacy manifests itself in students who persist with their university education represents a starting point for this process. A qualitative study was carried out using a phenomenological-hermeneutical approach with the participation of 7 university students from Santa Marta, Colombia who were intentionally selected. The students responded to a semi-structured interview and the data collected through this tool was analyzed using a thematic analysis. The results show that emotional self-efficacy is manifested in students who persist with their university education through 5 mechanisms: self-determination, self-confidence, optimism, self-assertion and perseverance.

Resumo (analítico) Os índices de evasão presentes no ensino superior merecem o desenvolvimento de ações que possibilitem a transformação dessa realidade, portanto, compreender como a autoeficácia emocional se manifesta nos alunos que persistem na formação universitária constitui um ponto de partida para atingir esse propósito. Nesse sentido, foi realizado um estudo qualitativo, de natureza fenomenoló-gicohermenêutica, do qual participaram 7 estudantes universitários de Santa Marta, Colômbia, selecionados intencionalmente, os quais foram submetidos a uma entrevista semiestruturada e cujos dados foram analisados através da análise temática. Os resultados indicam que a autoeficácia emocional se manifesta nos alunos que persistem na formação universitária por meio de 5 formas ou mecanismos: autodeterminação, autoconfiança, otimismo, autoafirmação e perseverança.

Behavioral manifestations in rodent models of autism spectrum disorder: protocol for a systematic review and network meta-analysis.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with severe social communication, interaction, and sensory processing impairments. Efforts to understand its etiology and pathophysiology are crucial for improving treatment and prevention measures. Preclinical models of ASD are essential for investigating the biological mechanisms and should present translatability potential. We aim to evaluate the consistency of the most commonly used rodent models of ASD in displaying autistic-like behavior through a systematic review and meta-analysis. METHODS: This review will focus on the most frequently used autism models, surveying studies of six genetic (Ube3a, Pten, Nlgn3, Shank3, Mecp2, and Fmr1), three chemically induced (valproic acid (VPA), lipopolysaccharide (LPS), and polyinosinic:polycytidylic acid (poly(I:C))), and one inbred model (BTBR T+ Itpr3tf/J mouse strain). Two independent reviewers will screen the records. Data extraction of behavioral outcomes and risk of bias evaluation will be performed. We will conduct a meta-analysis whenever at least five studies investigate the same model and behavioral outcome. We will also explore the heterogeneity and publication bias. Network meta-analyses are planned to compare different models. DISCUSSION: By shortening the gap between animal behavior and human endophenotypes or specific clinical symptoms, we expect to help researchers on which rodent models are adequate for research of specific behavioral manifestations of autism, which potentially require a combination of them depending on the research interest. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021226299 .

Mutagenicity Profile Induced by UVB Light in Human Xeroderma Pigmentosum Group C Cells.

Nucleotide excision repair (NER) is one of the main pathways for genome protection against structural DNA damage caused by sunlight, which in turn is extensively related to skin cancer development. The mutation spectra induced by UVB were investigated by whole-exome sequencing of randomly selected clones of NER-proficient and XP-C-deficient human skin fibroblasts. As a model, a cell line unable to recognize and remove lesions (XP-C) was used and compared to the complemented isogenic control (COMP). As expected, a significant increase of mutagenesis was observed in irradiated XP-C cells, mainly C>T transitions, but also CC>TT and C>A base substitutions. Remarkably, the C>T mutations occur mainly at the second base of dipyrimidine sites in pyrimidine-rich sequence contexts, with 5'TC sequence the most mutated. Although T>N mutations were also significantly increased, they were not directly related to pyrimidine dimers. Moreover, the large-scale study of a single UVB irradiation on XP-C cells allowed recovering the typical mutation spectrum found in human skin cancer tumors. Eventually, the data may be used for comparison with the mutational profiles of skin tumors obtained from XP-C patients and may help to understand the mutational process in nonaffected individuals.

Mesenchymal Stromal Cells From Emphysematous Donors and Their Extracellular Vesicles Are Unable to Reverse Cardiorespiratory Dysfunction in Experimental Severe Emphysema.

Although bone marrow-derived mesenchymal stromal cells (BM-MSCs) from patients with chronic obstructive pulmonary disease (COPD) appear to be phenotypically and functionally similar to BM-MSCs from healthy sources in vitro, the impact of COPD on MSC metabolism and mitochondrial function has not been evaluated. In this study, we aimed to comparatively characterize MSCs from healthy and emphysematous donors (H-MSCs and E-MSCs) in vitro and to assess the therapeutic potential of these MSCs and their extracellular vesicles (H-EVs and E-EVs) in an in vivo model of severe emphysema. For this purpose, C57BL/6 mice received intratracheal porcine pancreatic elastase once weekly for 4 weeks to induce emphysema; control animals received saline under the same protocol. Twenty-four hours after the last instillation, animals received saline, H-MSCs, E-MSCs, H-EVs, or E-EVs intravenously. In vitro characterization demonstrated that E-MSCs present downregulation of anti-inflammatory (TSG-6, VEGF, TGF-ß, and HGF) and anti-oxidant (CAT, SOD, Nrf2, and GSH) genes, and their EVs had larger median diameter and lower average concentration. Compared with H-MSC, E-MSC mitochondria also exhibited a higher respiration rate, were morphologically elongated, expressed less dynamin-related protein-1, and produced more superoxide. When co-cultured with alveolar macrophages, both H-MSCs and E-MSCs induced an increase in iNOS and arginase-1 levels, but only H-MSCs and their EVs were able to enhance IL-10 levels. In vivo, emphysematous mice treated with E-MSCs or E-EVs demonstrated no amelioration in cardiorespiratory dysfunction. On the other hand, H-EVs, but not H-MSCs, were able to reduce the neutrophil count, the mean linear intercept, and IL-1ß and TGF-ß levels in lung tissue, as well as reduce pulmonary arterial hypertension and increase the right ventricular area in a murine model of elastase-induced severe emphysema. In conclusion, E-MSCs and E-EVs were unable to reverse cardiorespiratory dysfunction, whereas H-EVs administration was associated with a reduction in cardiovascular and respiratory damage in experimental severe emphysema.

Xeroderma pigmentosum variant: squamous cell carcinoma of the lower lip harboring exon 11 mutation of POLH.

Xeroderma pigmentosum (XP) is a rare inherited disease caused by deficiencies in DNA damage repair, which mainly results from the failure of nucleotide excision repair or defects in translesion DNA synthesis. The development of multiple malignancies is one of the most prominent features of this condition, which is clinically characterized by the occurrence of hyperpigmentation and lesions associated with sunlight exposure. Lip squamous cell carcinoma in patients with XP has rarely been reported, and information regarding the genetic analysis of these patients is limited. In this report, a case of a 20-year-old patient who developed squamous cell carcinoma in the lower lip is described. Although the tumor was surgically excised, the patient presented with recurrence a few months later. Targeted sequencing using a customized panel of DNA repair genes revealed a mutation in POLH, the gene encoding DNA polymerase eta. Therefore, molecular characterization is important to further improve the understanding of possible phenotype-genotype correlations and mechanisms involved in the pathogenesis of XP.

Mitochondria-Rich Fraction Isolated From Mesenchymal Stromal Cells Reduces Lung and Distal Organ Injury in Experimental Sepsis.

OBJECTIVES: To ascertain whether systemic administration of mitochondria-rich fraction isolated from mesenchymal stromal cells would reduce lung, kidney, and liver injury in experimental sepsis. DESIGN: Animal study. SETTING: Laboratory investigation. SUBJECTS: Sixty C57BL/6 male mice. INTERVENTIONS: Sepsis was induced by cecal ligation and puncture; sham-operated animals were used as control. At 24 hours after surgery, cecal ligation and puncture and Sham animals were further randomized to receive saline or mitochondria-rich fraction isolated from mesenchymal stromal cells (3 × 106) IV. At 48 hours, survival, peritoneal bacterial load, lung, kidney, and liver injury were analyzed. Furthermore, the effects of mitochondria on oxygen consumption rate and reactive oxygen species production of lung epithelial and endothelial cells were evaluated in vitro. MEASUREMENTS AND MAIN RESULTS: In vitro exposure of lung epithelial and endothelial cells from cecal ligation and puncture animals to mitochondria-rich fraction isolated from mesenchymal stromal cells restored oxygen consumption rate and reduced total reactive oxygen species production. Infusion of exogenous mitochondria-rich fraction from mesenchymal stromal cells (mitotherapy) reduced peritoneal bacterial load, improved lung mechanics and histology, and decreased the expression of interleukin-1ß, keratinocyte chemoattractant, indoleamine 2,3-dioxygenase-2, and programmed cell death protein 1 in lung tissue, while increasing keratinocyte growth factor expression and survival rate in cecal ligation and puncture-induced sepsis. Mitotherapy also reduced kidney and liver injury, plasma creatinine levels, and messenger RNA expressions of interleukin-18 in kidney, interleukin-6, indoleamine 2,3-dioxygenase-2, and programmed cell death protein 1 in liver, while increasing nuclear factor erythroid 2-related factor-2 and superoxide dismutase-2 in kidney and interleukin-10 in liver. CONCLUSIONS: Mitotherapy decreased lung, liver, and kidney injury and increased survival rate in cecal ligation and puncture-induced sepsis.

Dynamic arterial elastance measured with pressure recording analytical method, and mean arterial pressure responsiveness in hypotensive preload dependent patients undergoing cardiac surgery: A prospective cohort study.

BACKGROUND: Organ perfusion is a factor of cardiac output and perfusion pressure. Recent evidence shows that dynamic arterial elastance is a reliable index of the interaction between the left ventricle and the arterial system and, in turn, of left ventricular mechanical efficiency. A practical approach to the assessment of dynamic arterial elastance at the bedside is the ratio between pulse pressure variation and stroke volume variation, which might predict the effect of a fluid challenge on the arterial pressure in patients undergoing cardiac surgery. OBJECTIVE: To evaluate the ability of dynamic arterial elastance, measured by the pressure recording analytical method (PRAM), to predict the response of mean arterial pressure (MAP) to a fluid challenge. DESIGN: Prospective observational study. SETTING: Cardiac surgery patients in a university hospital. PATIENTS: Preload-dependent (pulse pressure variation ≥13%), hypotensive (MAP ≤65 mmHg) patients, without right ventricular dysfunction, at the end of cardiac surgery. INTERVENTIONS: A 250 ml fluid challenge infused over 3 min. MAIN OUTCOME MEASURES: A receiver-operating characteristic curve was generated to test the ability of the baseline (before fluid challenge) dynamic arterial elastance (primary endpoint) and all other haemodynamic variables (secondary endpoint) to predict MAP responsiveness (≥10% increase in MAP) after a fluid challenge. RESULTS: Of 270 patients undergoing cardiac surgery, 97 (35.9%) were preload-dependent, hypotensive and received a fluid challenge. Of these 97 patients, 50 (51%) were MAP responders (≥10% increase in MAP) and 47 (48%) were MAP nonresponders (<10% increase in MAP). Baseline dynamic arterial elastance (mean ±â€ŠSD) had an area under the curve of 0.64 ±â€Š0.06 [95% confidence interval (CI), 0.53 to 0.73; P = 0.017]. A dynamic arterial elastance at least 1.07 with a grey zone ranging between 0.9 and 1.5 had 86% sensitivity (95% CI, 73 to 94) and 45% specificity (95% CI, 30 to 60) in predicting MAP increase. CONCLUSION: In a hypotensive preload-dependent cardiac surgery cohort without right ventricular dysfunction, dynamic arterial elastance measured by PRAM can predict pressure response for values greater than 1.5 or less than 0.9.

XPC and POLH/XPV Genes Mutated in a Genetic Cluster of Xeroderma Pigmentosum Patients in Northeast Brazil.

Xeroderma pigmentosum (XP) is a rare genetic condition in which exposure to sunlight leads to a high tumor incidence due to defective DNA repair machinery. Herein, we investigated seven patients clinically diagnosed with XP living in a small city, Montanhas (Rio Grande do Norte), in the Northeast region of Brazil. We performed high-throughput sequencing and, surprisingly, identified two different mutated genes. Six patients carry a novel homozygote mutation in the POLH/XPV gene, c.672_673insT (p.Leu225Serfs*33), while one patient carries a homozygote mutation in the XPC gene, c.2251-1G>C. This latter mutation was previously described in Southeastern Africa (Comoro Island and Mozambique), Pakistan, and in a high incidence in Brazil. The XP-C patient had the first symptoms before the first year of life with aggressive ophthalmologic tumor progression and a melanoma onset at 7 years of age. The XP-V patients presented a milder phenotype with later onset of the disorder (mean age of 16 years old), and one of the six XP-V patients developed melanoma at 72 years. The photoprotection is minimal among them, mainly for the XP-V patients. The differences in the disease severity between XP-C (more aggressive) and XP-V (milder) patients are obvious and point to the major role of photoprotection in the XPs. We estimate that the incidence of XP patients at Montanhas can be higher, but with no diagnosis, due to poor health assistance. Patients still suffer from the stigmatization of the condition, impairing diagnosis, education for sun protection, and medical care.

Large deletions in immunoglobulin genes are associated with a sustained absence of DNA Polymerase η.

Somatic hypermutation of immunoglobulin genes is a highly mutagenic process that is B cell-specific and occurs during antigen-driven responses leading to antigen specificity and antibody affinity maturation. Mutations at the Ig locus are initiated by Activation-Induced cytidine Deaminase and are equally distributed at G/C and A/T bases. This requires the establishment of error-prone repair pathways involving the activity of several low fidelity DNA polymerases. In the physiological context, the G/C base pair mutations involve multiple error-prone DNA polymerases, while the generation of mutations at A/T base pairs depends exclusively on the activity of DNA polymerase η. Using two large cohorts of individuals with xeroderma pigmentosum variant (XP-V), we report that the pattern of mutations at Ig genes becomes highly enriched with large deletions. This observation is more striking for patients older than 50 years. We propose that the absence of Pol η allows the recruitment of other DNA polymerases that profoundly affect the Ig genomic landscape.

Whole-exome sequencing reveals the impact of UVA light mutagenesis in xeroderma pigmentosum variant human cells.

UVA-induced mutagenesis was investigated in human pol eta-deficient (XP-V) cells through whole-exome sequencing. In UVA-irradiated cells, the increase in the mutation frequency in deficient cells included a remarkable contribution of C>T transitions, mainly at potential pyrimidine dimer sites. A strong contribution of C>A transversions, potentially due to oxidized bases, was also observed in non-irradiated XP-V cells, indicating that basal mutagenesis caused by oxidative stress may be related to internal tumours in XP-V patients. The low levels of mutations involving T induced by UVA indicate that pol eta is not responsible for correctly replicating T-containing pyrimidine dimers, a phenomenon known as the 'A-rule'. Moreover, the mutation signature profile of UVA-irradiated XP-V cells is highly similar to the human skin cancer profile, revealing how studies involving cells deficient in DNA damage processing may be useful to understand the mechanisms of environmentally induced carcinogenesis.

Multiple doses of adipose tissue-derived mesenchymal stromal cells induce immunosuppression in experimental asthma.

In experimental house dust mite (HDM)-induced allergic asthma, therapeutic administration of a single dose of adipose tissue-derived mesenchymal stromal cells (MSCs) ameliorates lung inflammation but is unable to reverse remodeling. We hypothesized that multiple doses of MSCs might exert better therapeutic effects by reducing lung inflammation and remodeling but might also result in immunosuppressive effects in experimental asthma. HDM was administered intranasally in C57BL/6 mice. After the last HDM challenge, mice received two or three doses of MSCs (105 cells per day) or saline intravenously. An additional cohort of mice received dexamethasone as a positive control for immunosuppression. Two and three doses of MSCs reduced lung inflammation, levels of interleukin (IL)-4, IL-13, and eotaxin; total leukocyte, CD4+ T-cell, and eosinophil counts in bronchoalveolar lavage fluid; and total leukocyte counts in bone marrow, spleen, and mediastinal lymph nodes. Two and three doses of MSCs also reduced collagen fiber content and transforming growth factor-ß levels in lung tissue; however, the three-dose regimen was more effective, and reduced these parameters to control levels, while also decreasing α-actin content in lung tissue. Two and three doses of MSCs improved lung mechanics. Dexamethasone, two and three doses of MSCs similarly increased galectin levels, but only the three-dose regimen increased CD39 levels in the thymus. Dexamethasone and the three-dose, but not the two-dose regimen, also increased levels of programmed death receptor-1 and IL-10, while reducing CD4+ CD8low cell percentage in the thymus. In conclusion, multiple doses of MSCs reduced lung inflammation and remodeling while causing immunosuppression in HDM-induced allergic asthma.

Assistência pré-natal segundo registros profissionais presentes na caderneta da gestante / Asistencia pre-natal segundo registro profesional presentes en la caderneta de la gestante / Prenatal care according to professional records present in the pregnant's book

Objetivo: descrever a assistência pré-natal segundo registros profissionais presentes na caderneta da gestante. Método: estudo quantitativo, realizado com puérperas de uma maternidade filantrópica, localizada em um município do interior do Estado do Ceará. Os dados sociodemográficos foram coletados em entrevista e as informações do pré-natal por meio da caderneta da gestante. Os dados foram analisados com base na estatística descritiva. Resultados: participaram 52 puérperas que possuíam de 15 a 40 anos. Observaram-se falhas no registro de informações do pré-natal, sendo as mais graves no que diz respeito aos exames laboratoriais e à avaliação nutricional da gestante. Considerações Finais: faz-se necessário uma mudança na conduta dos profissionais, por meio de qualificação acerca da assistência pré-natal e acompanhamento frequente por parte dos gestores de saúde do município, pois por meio do registro correto das informações obtidas durante a consulta é possível realizar acompanhamento adequado durante o parto e puerpério.

Objective: to describe the prenatal care according to the professional records present in the pregnant's book. Method: a quantitative study carried out with puerperal women of a philanthropic maternity located in a municipality in the interior of the State of Ceará. The sociodemographic data were collected in an interview and prenatal information through the pregnant's book. Data were analyzed by descriptive statistics. Results: 52 women between 15 and 40 years old participated of study. There were flaws in the recording of information, the most serious being related to laboratory tests and nutritional evaluation of the pregnant woman. Final Considerations: a change in professional conduct is necessary, through qualification about prenatal care and frequent follow-up by the municipal health managers, since by recording the information obtained during the consultation it is possible to carry out adequate follow-up during childbirth and puerperium.

Objetivo: describir la asistencia prenatal según registros profesionales presentes en la caderneta de la gestante. Método: estudio cuantitativo, realizado con puérperas de una maternidad filantrópica ubicada en un municipio del interior de Ceará. Los datos sociodemográficos fueron recolectados en entrevista y las informaciones del prenatal por medio de la caderneta de la gestante. Los datos fueron analizados por estadística descriptiva. Resultados: participaron 52 puérperas entre 15 y 40 años. Se observaron fallas en el registro de información, siendo las más graves relacionadas con los exámenes de laboratorio y la evaluación nutricional de la gestante. Consideraciones finales: se hace necesario un cambio en la conducta profesional, por medio de cualificación acerca de la asistencia prenatal y acompañamiento frecuente por parte de los gestores municipales de salud, pues por medio del registro de las informaciones obtenidas durante la consulta es posible realizar un seguimiento adecuado durante el parto y el puerperio.

Identificação de fatores de risco à saúde entre mulheres usuárias de métodos contraceptivos hormonais / Identification of health risk factors among women using hormonal contraceptive methods / Identificación de factores de riesgo a la salud entre mujeres usuarias de métodos anticonceptivos hormonales

Objetivo: Identificar fatores de risco para uso de anticoncepcionais hormonais em usuárias desses métodos. Método: Estudo descritivo de abordagem quantitativa realizado entre janeiro e abril de 2016 em Redenção, Ceará, Brasil. As mulheres foram convidadas a responder um formulário estruturado. Os princípios éticos desta pesquisa foram assegurados. Os dados foram tabelados e analisados por estatística descritiva através do SPSS 20.0. Resultados: Participaram 100 mulheres. Média de idade = 26,91 anos. 75% haviam realizado Planejamento Reprodutivo. O fator de risco mais prevalente foi a enxaqueca (59%). No histórico familiar, a doença mais relatada foi Hipertensão Arterial Sistêmica (75%). Conclusão: Doenças antes relacionadas a pacientes com idades elevadas estão cada vez mais presentes em mulheres jovens, que necessitam de maior assistência no planejamento reprodutivo, com foco na anamnese e exame físico geral, responsáveis por revelar achados significantes para a elegibilidade de métodos contraceptivos, visando a redução de riscos à saúde

Objective: To identify risk factors for the use of hormonal contraceptives in users of these methods. Method: Descriptive study of a quantitative approach carried out between January and April 2016 in Redenção, Ceará, Brazil. The women were invited to respond to a structured form. The ethical principles of this research have been secured. The data were tabulated and analyzed by descriptive statistics through SPSS 20.0. Results: 100 women participated. Mean age = 26.91 years. 75% had performed Reproductive Planning. The most prevalent risk factor was migraine (59%). In the family history, the most frequently reported disease was systemic arterial hypertension (75%). Conclusions: Previously related diseases of patients with high ages are increasingly present in young women, who need more assistance in reproductive planning, focusing on anamnesis and general physical examination, responsible for revealing significant findings for the eligibility of contraceptive methods, aiming to the reduction of health risks

Objetivo: Identificar factores de riesgo para el uso de anticonceptivos hormonales en las usuarias de estos métodos. Método: Estudio descriptivo de abordaje cuantitativo realizado entre enero y abril de 2016 en Redención, Ceará, Brasil. Las mujeres fueron invitadas a responder a un formulario estructurado. Los principios éticos de esta investigación fueron asegurados. Los datos fueron tabulados y analizados por estadística descriptiva a través del SPSS 20.0. Resultados: Participaron 100 mujeres. Media de edad = 26,91 años. El 75% habían realizado Planificación Reproductiva. El factor de riesgo más prevalente fue la migraña (59%). En el historial familiar, la enfermedad más relatada fue Hipertensión Arterial Sistémica (75%). Conclusión: Las enfermedades antes relacionadas con los pacientes con edades elevadas están cada vez más presentes en mujeres jóvenes, que necesitan una mayor asistencia en la planificación reproductiva, con foco en la anamnesis y examen físico general, responsables de revelar hallazgos significantes para la elegibilidad de métodos anticonceptivos, visando la reducción de los riesgos para la salud