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1.
PLoS One ; 15(6): e0234330, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32516331

RESUMO

Presbyopia and myopia research shows a growing interest in ciliary muscle biometry using optical coherence tomography (OCT). Until now, segmentation of the ciliary muscle is often performed manually using either custom-developed programs or image processing software. Here we present a novel software for semi-automatic segmentation of the ciliary muscle. It provides direct import of OCT images in DICOM format, a standardized procedure for segmentation, image distortion correction, the export of anatomical ciliary muscle landmarks, like ciliary muscle apex and scleral spur, as well as a continuous thickness profile of the ciliary muscle as a novel way of analysis. All processing steps are stored as XML files, fostering documentation and reproducibility of research through the possibility of replicating the analysis. Additionally, CilOCT supports batch processing for the automated analysis of large numbers of images and the respective data export to tabulated text files based on the stored XML files. CilOCT was successfully applied in several studies and their results will be summarized in this paper.

2.
Eur J Endocrinol ; 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32567559

RESUMO

OBJECTIVE: Determining the factors associated with new-onset pre-diabetes and type 2 diabetes mellitus (T2D) is important for improving the current prevention strategies and for a better understanding of the disease. DESIGN: To study the factors (clinical, circulating protein and genetic) associated with new onset pre-diabetes and T2D in an initially healthy (without diabetes) populational familial cohort with a long follow-up (STANISLAS cohort). METHODS: 1506 participants that attended both the visit-1 and visit-4, separated by ≈20 years. Over 400 proteins, GWAS and genetic associations were studied using models adjusted for potential confounders. Both prospective (V1 to V4) and cross-sectional (V4) analyses were performed. RESULTS: People who developed pre-diabetes (n =555) and/or T2D (n =73) were older, had higher BMI, blood pressure, glucose, LDL cholesterol, and lower eGFR. After multivariable selection, PAPP-A (pappalysin-1) was the only circulating protein associated with the onset of both pre-diabetes and T2D with associations persisting at visit-4 (i.e., ≈20 years later). FGF-21 (fibroblast growth factor 21) was a strong prognosticator for incident T2D in the longitudinal, but not in the cross-sectional analysis. The heritability of the circulating PAPP-A was estimated at 44%. In GWAS analysis the SNP rs634737 was associated with PAPP-A both at V1 and V4. External replication also showed lower levels of PAPP-A in patients with T2D. CONCLUSIONS: The risk of developing pre-diabetes and T2D increases with age, and with features of the metabolic syndrome. Circulating PAPP-A, which has an important genetic component, was associated with both the development and presence of pre-diabetes and T2D.

3.
Am J Hypertens ; 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32267470

RESUMO

BACKGROUND: Recent studies have shown that hyperuricemia may be associated with incident hypertension (HTN). We examined whether serum uric acid (SUA) is a predictor of HTN and target organ damage (TOD) 20 years later in initially healthy middle-aged individuals. METHODS: Participants from the Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux (STANISLAS) a single-center familial longitudinal cohort study (961 initially healthy adults and 570 children) underwent clinical and laboratory measurements at baseline and after approximately 20 years. Blood pressure (BP: using ambulatory BP measurements), urine albumin-to-creatinine ratio, estimated glomerular filtration rate (eGFR), left ventricular hypertrophy (LVH), diastolic dysfunction, and carotid-femoral pulse wave velocity (PWV) were measured at the end of follow-up. RESULTS: In the parent population, higher baseline or last SUA levels and higher change in SUA (ΔUA) were significantly associated with an increased risk of HTN development, even after adjusting for known HTN risk factors (all P < 0.01). Higher baseline SUA was marginally associated with an increased risk of having high carotid-femoral PWV (P = 0.05). The association of SUA with BP increase was body mass index dependent (the increase in BP being greater in leaner subjects; interactionp < 0.05), and the association of SUA with eGFR decline was age dependent (the decline in eGFR being greater in older subjects; interactionp < 0.05). There was no significant association between SUA and diastolic dysfunction or LVH. In the whole population (i.e. including children), a significant association between SUA at baseline and the risk of HTN and higher carotid-femoral PWV was also found (both P < 0.02). CONCLUSIONS: Increased SUA is associated with the development of HTN and vascular/renal TOD in initially healthy midlife subjects.

4.
Sci Rep ; 10(1): 5018, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193512

RESUMO

Biofeedback training has been used to access autonomically-controlled body functions through visual or acoustic signals to manage conditions like anxiety and hyperactivity. Here we examined the use of auditory biofeedback to improve accommodative responses to near visual stimuli in patients wearing single vision (SV) and multifocal soft contact lenses (MFCL). MFCLs are one evidence-based treatment shown to be effective in slowing myopia progression in children. However, previous research found that the positive addition relaxed accommodation at near, possibly reducing the therapeutic benefit. Accommodation accuracy was examined in 18 emmetropes and 19 myopes while wearing SVCLs and MFCLs (centre-distance). Short periods of auditory biofeedback training to improve the response (reduce the lag of accommodation) was performed and accommodation re-assessed while patients wore the SVCLs and MFCLs. Significantly larger accommodative lags were measured with MFCLs compared to SV. Biofeedback training effectively reduced the lag by ≥0.3D in individuals of both groups with SVCL and MFCL wear. The training was more effective in myopes wearing their habitual SVCLs. This study shows that accommodation can be changed with short biofeedback training independent of the refractive state. With this proof-of-concept, we hypothesize that biofeedback training in myopic children wearing MFCLs might improve the treatment effectiveness.

5.
J Am Heart Assoc ; 9(7): e013836, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32200718

RESUMO

Background The diet impact on cardiovascular diseases has been investigated widely, but the association between dietary patterns (DPs) and subclinical cardiovascular damage remains unclear. More informative DPs could be provided by considering metabolic syndrome components as intermediate markers. This study aimed to identify DPs according to generation and sex using reduced-rank regression (RRR) with metabolic syndrome components as intermediate markers and assess their associations with intima-media thickness, left ventricular mass, and carotid-femoral pulse-wave velocity in an initially healthy population-based family study. Methods and Results This study included 1527 participants from the STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux) cohort fourth examination. DPs were derived using reduced-rank regression according to generation (G1: age ≥50 years; G2: age <50 years) and sex. Associations between DPs and cardiovascular damage were analyzed using multivariable linear regression models. Although identified DPs were correlated between generations and sex, qualitative differences were observed: whereas only unhealthy DPs were found for both men generations, healthy DPs were identified in G2 ("fruity desserts") and G1 ("fiber and w3 oil") women. The "alcohol," "fast food and alcohol," "fried, processed, and dairy products," and "meat, starch, sodas, and fat" DPs in G1 and G2 men and in G1 and G2 women, respectively, were associated with high left ventricular mass (ß [95% CI], 0.23 [0.10-0.36], 0.76 [0.00-1.52], 1.71 [0.16-3.26], and 1.80 [0.45-3.14]). The "alcohol" DP in G1 men was positively associated with carotid-femoral pulse-wave velocity (0.22 [0.09-0.34]). Conclusions The DPs that explain the maximum variation in metabolic syndrome components had different associations with subclinical cardiovascular damage across generation and sex. Our results indicate that dietary recommendations should be tailored according to age and sex. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01391442.

6.
Clin Gerontol ; 43(3): 243-255, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31547777

RESUMO

Objectives: Stimulus preference assessments are a systematic, observation-based approach for identifying preferences among individuals with impaired communication skills. The purpose of this paper is to provide a review of the existing empirical literature that has utilized these methods with persons who have neurocognitive disorder (NCD).Methods: Studies were identified by searching online databases using a variety of search terms. Articles were included in the review if they were peer-reviewed, in English, were empirical in nature, and conducted a stimulus preference assessment with older adults diagnosed with NCD.Results: Eleven articles met the search criteria. Results revealed that data from stimulus preference assessments could increase activity engagement, increase requests for preferred items, identify reinforcers, and reduce behavioral and psychological symptoms.Conclusions: A small body of empirical literature suggests that data derived from stimulus preference assessments can be used to improve the lives of persons with NCD and their caregivers. Additional research is needed, however, to determine how effectively these procedures can be implemented into everyday practice in long-term care facilities.Clinical Implications: Stimulus preference assessments may provide a clinically useful means for efficiently identifying preferences in persons with severe NCD who cannot verbalize their needs.

8.
Vision Res ; 163: 42-51, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401218

RESUMO

Previous work suggested an association between near vision and myopia. We therefore investigated the accommodation process in emmetropes and myopes regarding morphologic changes of the ciliary muscle (CM) and power changes of the lens for different accommodation demands. The temporal CM of 18 emmetropic and 20 myopic students was imaged via anterior segment optical coherence tomography during far and near accommodation (2.5D, 3D, 4D). Additionally, accommodation dynamics to the stimuli pattern far-near-far (15 s each; 2.5D, 3D, 4D) were recorded with eccentric infrared photorefraction. OCT images were processed using custom-developed software facilitating the analysis of selective CM thickness (CMT) readings and CMT profiles. Anterior CMT readings were significantly smaller in myopes. Starting at 1.4 mm posterior to the scleral spur (SP), myopic CM became thicker than emmetropic. Anterior CMT changes (ΔCMT) continuously increased with accommodation demand in myopes while emmetropic ΔCMT only increased from 2.5D to 3D. Compared to emmetropes, myopes showed smaller ΔCMT but increased CM movement relative to SP. There were no significant differences between the groups for accommodation changes from far to near vision and vice versa, velocity, microfluctuations, power spectra or lag of accommodation. At 4 D, larger ΔCMT were associated with lower lens changes for disaccommodation. While CM shape, movement, and thickness showed distinct differences depending on refractive error, emmetropes and myopes did not differ in their dynamic accommodation. Further analysis is necessary to evaluate whether the CM's anatomical shape or predispositions in its intramuscular constituents are causative factors in myopigenesis.

9.
Exp Eye Res ; 186: 107741, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31336108

RESUMO

There is evidence for a possible link between myopia development and near vision. We investigated the effect of prolonged nearwork on ciliary muscle (CM) morphology and accommodation in 18 myopic and 17 emmetropic subjects (age 19 to 25). The CM was imaged during far (0.25 D) and near vision (4 D) using optical coherence tomography (OCT), and accommodation to a step pulse (0.25 D - 4 D - 0.25 D, 15 s each) was assessed by eccentric infrared photorefraction before and after a 30-min reading task at 25 cm. OCT images were analyzed using a custom-developed semi-automatic segmentation algorithm to determine CM thickness (CMT) profiles and selective CMT readings. Accommodation was assessed using a non-linear model. On average, the CM got thinner after nearwork, predominantly at 0.0-1.4 mm posterior to the scleral spur in emmetropes, and at 1.0-1.9 mm in myopes. Selective CMT readings confirmed a significant thinning after nearwork (univariate ANOVA F1,66 = 26.313, p < 0.001), without any influence of the subjects' refractive state (F1,66 = 1.887, p = 0.174) or the target distance (F1,66 = 0.014, p = 0.907). The mean accommodation response for targets at infinity was significantly increased after nearwork (F1,32 = 7.775, p = 0.009), with a larger myopic shift in myopes (F1,32 = 11.310, p = 0.002). No change in velocity of accommodation was found. Sharing properties of striated muscles, the CM was expected to increase its thickness, but the opposite was found. Previous studies suggesting sustained nearwork to result in a CM spasm cannot be confirmed by the data presented here. Further research exploring the possible impact of sympathetic innervation is necessary as it is activated during intense nearwork.


Assuntos
Acomodação Ocular/fisiologia , Corpo Ciliar/patologia , Emetropia/fisiologia , Músculo Liso/patologia , Miopia/fisiopatologia , Trabalho , Adulto , Corpo Ciliar/diagnóstico por imagem , Feminino , Humanos , Masculino , Músculo Liso/diagnóstico por imagem , Refração Ocular , Tomografia de Coerência Óptica , Visão Binocular , Adulto Jovem
10.
Matern Child Nutr ; 15(4): e12872, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31284324

RESUMO

Previous studies have shown a high level of noncompliance with recommendations on breastfeeding duration, especially in France. The objective was to describe the association between breastfeeding initiation and duration and the statutory duration of postnatal maternity leave, the gap between the end of legal maternity leave and the mother's return to work, and maternal working time during the first year post-partum. Analyses were based on 8,009 infants from the French nationwide ELFE cohort. We assessed the association with breastfeeding initiation by using logistic regression and, among breastfeeding women, with categories of breastfeeding duration by using multinomial logistic regression. Among primiparous women, both postponing return to work for at least 3 weeks after statutory postnatal maternity leave (as compared with returning to work at the end of the statutory period) and working less than full-time at 1 year post-partum (as compared with full-time) were related to higher prevalence of breastfeeding initiation. Among women giving birth to their first or second child, postponing the return to work until at least 15 weeks was related to a higher prevalence of long breastfeeding duration (at least 6 months) as compared with intermediate duration (3 to <6 months). Working part-time was also positively related to breastfeeding duration. Among women giving birth to their third child or more, working characteristics were less strongly related to breastfeeding duration. These results support extending maternity leave or working time arrangements to encourage initiation and longer duration of breastfeeding.

11.
Chem Senses ; 44(4): 257-265, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30859182

RESUMO

Infants' olfactory experience begins before birth and extends after birth through milk and complementary foods. Until now, studies on the effects of chemosensory experience in utero and/or through human milk focused on experimentally controlled exposure to only 1 target food bearing a specific odor quality and administered in sizeable amounts. This study aimed to assess whether early olfactory experience effect was measurable in "everyday conditions" of maternal food intake during pregnancy and lactation, and of infant intake at weaning, leading to expose the infant to corresponding odors as fetus, neonate, and infant up to 8 and 12 months of age. Infants' early food exposures were assessed by asking mothers to fill out diaries about their food consumption during pregnancy and breastfeeding, and about their infant's consumption during complementary feeding. To test odor liking, odorants representing a priori pleasant and unpleasant food odors, as well as odorless stimuli, were presented. The infant's exploratory behavior toward odorized bottles and nonodorized control bottles was measured in terms of mouthing duration, which is thought to reflect attraction and/or appetence. At age 8 months only, positive correlations were found between liking of some unpleasant odors and early exposure to these odors through mother's diet. No correlations were found between infants' liking of the pleasant odors and early exposures to the foods bearing these odors. This study highlights that early exposure to unpleasant food odors may increase subsequent liking (or reduce subsequent dislike) of these food odors at least until the age of 8 months.


Assuntos
Queijo , Preferências Alimentares , Odorantes/análise , Olfatometria , Olfato , Verduras , Adulto , Animais , Pré-Escolar , Feminino , Peixes , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez
12.
Am J Kidney Dis ; 73(5): 596-604, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30777634

RESUMO

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) characterized by decreased glomerular filtration rate (GFR) is often accompanied by various degrees of impaired tubular function in the cortex and medulla. Assessment of tubular function may therefore be useful in establishing the severity of kidney disease and identifying those at greater risk for CKD progression. We explored reductions in urinary concentrating ability, a well-known feature of CKD, as a risk factor for GFR decline and end-stage renal disease (ESRD). STUDY DESIGN: Prospective longitudinal cohort study. SETTING & PARTICIPANTS: 2,084 adult patients with CKD stages 1 to 4 from the French NephroTest Cohort Study. PREDICTOR: Fasting urinary osmolality measured using delta cryoscopy. OUTCOMES: ESRD, mortality before ESRD, and measured GFR (mGFR) assessed using 51Cr-EDTA renal clearance. ANALYTICAL APPROACH: Cause-specific hazards models were fit to estimate crude and adjusted associations of urinary osmolality with ESRD and death before ESRD. Linear mixed models with random intercepts were fit to evaluate the association of urinary osmolality with slope of decline in mGFR. RESULTS: At baseline, mean age was 58.7±15.2 (SD) years with a median mGFR of 40.2 (IQR, 29.1-54.5) mL/min/1.73m2 and a median fasting urinary osmolality of 502.7±151.7mOsm/kg H2O. Baseline fasting urinary osmolality was strongly associated with mGFR (R=0.54; P < 0.001). 380 ESRD events and 225 deaths before ESRD occurred during a median follow-up of 5.9 (IQR, 3.8-8.2) years. Patients with lower baseline fasting urinary osmolality had higher adjusted risk for ESRD but not for mortality (HRs of 1.97 [95% CI, 1.26-3.08] and 0.99 [95% CI, 0.68-1.44], respectively, for the lowest vs highest tertile). Based on a mixed linear model adjusted for baseline mGFR and clinical characteristics, patients in the lowest tertile of baseline urinary osmolality had a steeper decline in kidney function (-4.9% ± 0.9% per year; P < 0.001) compared with patients in the highest tertile. LIMITATIONS: Fasting was self-reported. CONCLUSIONS: Fasting urinary osmolality may be a useful tool, in addition to GFR and albuminuria, for assessing nonglomerular damage in patients with CKD who are at higher risk for CKD progression.


Assuntos
Jejum/urina , Taxa de Filtração Glomerular/fisiologia , Biomarcadores/urina , Progressão da Doença , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Prognóstico , Estudos Prospectivos , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/urina , Fatores de Risco , Taxa de Sobrevida/tendências
13.
Biomed Opt Express ; 10(1): 119, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30775087

RESUMO

[This corrects the article on p. 5100 in vol. 9, PMID: 30319924.].

14.
Cancer Res ; 79(5): 905-917, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30674530

RESUMO

Medulloblastoma and central nervous system primitive neuroectodermal tumors (CNS-PNET) are aggressive, poorly differentiated brain tumors with limited effective therapies. Using Sleeping Beauty (SB) transposon mutagenesis, we identified novel genetic drivers of medulloblastoma and CNS-PNET. Cross-species gene expression analyses classified SB-driven tumors into distinct medulloblastoma and CNS-PNET subgroups, indicating they resemble human Sonic hedgehog and group 3 and 4 medulloblastoma and CNS neuroblastoma with FOXR2 activation. This represents the first genetically induced mouse model of CNS-PNET and a rare model of group 3 and 4 medulloblastoma. We identified several putative proto-oncogenes including Arhgap36, Megf10, and Foxr2. Genetic manipulation of these genes demonstrated a robust impact on tumorigenesis in vitro and in vivo. We also determined that FOXR2 interacts with N-MYC, increases C-MYC protein stability, and activates FAK/SRC signaling. Altogether, our study identified several promising therapeutic targets in medulloblastoma and CNS-PNET. SIGNIFICANCE: A transposon-induced mouse model identifies several novel genetic drivers and potential therapeutic targets in medulloblastoma and CNS-PNET.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Cerebelares/genética , Meduloblastoma/genética , Tumores Neuroectodérmicos Primitivos/genética , Animais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Transformação Celular Neoplásica/genética , Neoplasias Cerebelares/metabolismo , Neoplasias Cerebelares/patologia , Elementos de DNA Transponíveis/genética , Feminino , Fatores de Transcrição Forkhead/genética , Proteínas Ativadoras de GTPase/biossíntese , Proteínas Ativadoras de GTPase/genética , Humanos , Masculino , Meduloblastoma/metabolismo , Meduloblastoma/patologia , Proteínas de Membrana/genética , Camundongos , Camundongos Nus , Mutagênese Insercional/métodos , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologia , Tumores Neuroectodérmicos Primitivos/metabolismo , Tumores Neuroectodérmicos Primitivos/patologia , Prognóstico
15.
Midwifery ; 69: 67-75, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30399510

RESUMO

OBJECTIVE: To assess the role of the mother's mother and mothers' previous personal experiences with breastfeeding and childcare in breastfeeding practices. DESIGN AND SETTING: The analysis included 13,774 mother-infant dyads from the French national birth cohort ELFE. Feeding practices were assessed by face-to-face interview in maternity wards in 2011, by phone interviews at months 2 and 12 post-partum and by Internet/paper questionnaires monthly from months 3-10. Sociodemographic, maternal and newborn-related factors were collected in the maternity unit and by postnatal phone interview at month 2. Multivariable logistic and linear regression was used to assess the association of mother's mother and mothers' previous personal experiences with breastfeeding initiation and duration. FINDINGS: Previous breastfeeding experience (i.e., whether mothers had breastfed their previous children) was positively associated with both breastfeeding initiation and duration. Mothers who had been breastfed themselves as infants were more likely to initiate and continue breastfeeding than non-breastfed mothers. Conversely, non-breastfed mothers who had received care advice from their own mother were less likely to start and maintain breastfeeding. The effect of having been breastfed in infancy was especially important for primiparous mothers and to a lesser extent, multiparous mothers with no previous breastfeeding experience. Also, formal experience in childcare, in a professional context, was associated with breastfeeding initiation but not duration. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Mother's mother and mother's previous breastfeeding experience have a strong influence on breastfeeding practices. Breastfeeding interventions should be tailored to the mother's level of experience and should provide extra support for multiparous mothers with no previous breastfeeding experience.


Assuntos
Aleitamento Materno/psicologia , Relação entre Gerações/etnologia , Mães/psicologia , Fatores de Tempo , Adulto , Atitude Frente a Saúde/etnologia , Aleitamento Materno/etnologia , Aleitamento Materno/métodos , Comportamento de Escolha , Estudos de Coortes , Feminino , França/etnologia , Avós/psicologia , Humanos , Modelos Logísticos , Período Pós-Parto/psicologia , Fatores Socioeconômicos , Inquéritos e Questionários
16.
Pigment Cell Melanoma Res ; 32(2): 326-331, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30387922

RESUMO

The incidence of malignant melanoma has increased over the past two decades. A combined BRAF/MEK inhibitor regimen has been shown to lead to prolonged survival and progression-free survival in patients with metastatic BRAF V600-mutant melanoma. Different nephrotoxic effects have been described, among them hyponatremia. The goal of the present narrative review was to understand the pathophysiological mechanisms driving hyponatremia when using selective BRAF inhibitors and/or MEK inhibitors in order to propose potential strategies to prevent or to treat this side effect. Several mechanisms of kidney injury have been suggested including changes in glomerular and tubular function. However, the precise mechanisms of hyponatremia remain unknown. Our hypothesis is that BRAF/MEK inhibitors lead to hyponatremia and water retention (so-called dilution hyponatremia) by activating aquaporin 2 (AQP2) trafficking from its intracellular compartment to the luminal cell membrane, and by activating ENaC channel. Therefore, we recommend treating the hyponatremia related to BRAF/MEK inhibitors with restriction of fluid intake.


Assuntos
Hiponatremia/tratamento farmacológico , Hiponatremia/fisiopatologia , Melanoma/tratamento farmacológico , Melanoma/fisiopatologia , Inibidores de Proteínas Quinases/uso terapêutico , Humanos , Hiponatremia/complicações , Hiponatremia/diagnóstico , Melanoma/complicações , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Modelos Biológicos , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/metabolismo
17.
Biomed Opt Express ; 9(10): 5100-5114, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30319924

RESUMO

The purpose of this study was to provide an in-depth analysis of the ciliary muscle's (CM) morphological changes during accommodation by evaluating CM thickness (CMT) profiles. The CM of 15 near-emmetropic subjects (age 20-39) was imaged via optical coherence tomography (OCT) during far (0 D) and near vision (3 D). A custom-made Java-based program was used for semi-automatic CM segmentation and thickness measurements. CMT profiles were generated to determine regions of the largest shape changes. The results revealed on average a thinning within the first 0.25 mm and a thickening from 0.36 to 1.48 mm posterior to scleral spur when accommodating from 0 to 3 D. In contrast to previous analyses, this method offers pixel-wise reconstruction of CM shapes and quantification of accommodative change across the entire muscle boundary.

18.
J Acquir Immune Defic Syndr ; 79(4): 445-452, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30142140

RESUMO

BACKGROUND: HIV epidemics disproportionately affect transwomen worldwide. Trans-specific guidance, outreach, and interventions to increase pre-exposure prophylaxis (PrEP) use among transwomen are scarce. SETTING: Rio de Janeiro, Brazil. METHODS: We measured awareness and willingness to use PrEP and examined factors associated with those outcomes among transwomen in Rio de Janeiro and estimated how many transwomen would be eligible for PrEP. Data originate from Transcender study, a respondent-driven sampling survey conducted from August 2015 to January 2016. We performed regression models for PrEP awareness and willingness. RESULTS: One hundred thirty-one (38.0%) of 345 participants had heard of PrEP. Among transwomen who self-reported as HIV-negative, 162 (76.4%, N = 212 with available data) reported willingness to use it and 163 (66.8%, N = 244) met PrEP behavioral eligibility criteria. Transwomen with health access in the previous 6 months who reported HIV-infected sexual partner and with 8+ years of schooling had increased odds of PrEP awareness. Lower PrEP awareness was associated with condomless anal intercourse and newly diagnosed HIV infection. Younger age and perceiving themselves at risk of HIV infection increased the odds of PrEP willingness. Lower odds of PrEP willingness were associated with concerns about long-term effects of PrEP and with difficulties in getting access to health care due to transphobia. CONCLUSION: Combination of low awareness, high willingness, and substantial PrEP eligibility corroborates transwomen as a key population for HIV prevention. PrEP is a promising and empowering strategy for HIV prevention among transwomen, but trans-specific recommendations are needed to effectively implement PrEP in this population.


Assuntos
Transmissão de Doença Infecciosa/prevenção & controle , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Profilaxia Pré-Exposição/métodos , Pessoas Transgênero , Adolescente , Adulto , Brasil , Feminino , Acesso aos Serviços de Saúde/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Adulto Jovem
19.
World J Gastroenterol ; 24(48): 5418-5432, 2018 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-30622371

RESUMO

Therapeutic options for the treatment of colorectal cancer (CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hyper-mutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. Substantial improvement in treatment outcome could be achieved by development of efficient patient-individual CRC vaccination strategies. This mini-review summarizes the current knowledge on the two general classes of targets: tumor-associated antigens (TAAs) and tumor-specific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a variety of clinical studies examined the efficacy of different TAA-derived peptide vaccines. Combinations of several TAAs as the next step and the development of personalized TAA-based peptide vaccines are discussed. Improvements of peptide-based vaccines achievable by adjuvants and immune-stimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens - in CRC almost exclusively neoantigens - which revealed promising results; particularly no severe adverse events were reported so far. Critical progress for clinical outcomes can be expected by individualizing neoantigen-based peptide vaccines and combining them with immune-stimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest developments, truly personalized neoantigen-based peptide vaccines can be expected to fulfill modern precision medicine's requirements and will manifest as treatment pillar for routine clinical management of CRC.


Assuntos
Antígenos de Neoplasias/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Neoplasias Colorretais/terapia , Imunoterapia/métodos , Adjuvantes Imunológicos/uso terapêutico , Antígenos de Neoplasias/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Vacinas Anticâncer/imunologia , Neoplasias Colorretais/imunologia , Terapia Combinada/métodos , Humanos , Resultado do Tratamento , Vacinação/métodos , Vacinas de Subunidades/imunologia , Vacinas de Subunidades/uso terapêutico
20.
Matern Child Nutr ; 14(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29265745

RESUMO

Breastfeeding is recommended until 6 months of age, but a wide range of infant formula is available for nonbreastfed or partially breastfed infants. Our aim was to describe infant formula selection and to examine social- and health-related factors associated with this selection. Analyses were based on 13,291 infants from the French national birth cohort Etude Longitudinale Française depuis l'Enfance. Infant diet was assessed at Month 2 by phone interview and monthly from Months 3 to 10 via internet/paper questionnaires. Infant formulas were categorized in 6 groups: extensively or partially hydrolysed, regular with or without prebiotics/probiotics, and thickened with or without prebiotics/probiotics. Associations between type of infant formula used at 2 months and family or infant characteristics were assessed by multinomial logistic regressions. At Month 2, 58.1% of formula-fed infants were fed with formula enriched in prebiotics/probiotics, 31.5% with thickened formula, and 1.4% with extensively hydrolysed formula. The proportion of formula-fed infants increased regularly, but the type of infant formula used was fairly stable between 2 and 10 months. At Month 2, extensively hydrolysed formulas were more likely to be used in infants with diarrhoea or regurgitation problems. Partially hydrolysed formulas were more often used in families with high income, with a history of allergy, or with infants with regurgitation issues. Thickened formulas were used more with boys, preterm infants, infants with regurgitation issues, or in cases of early maternal return to work. The main factors related to the selection of infant formula were family and infant health-related ones.


Assuntos
Desenvolvimento Infantil , Características da Família , Métodos de Alimentação , Intolerância Alimentar/dietoterapia , Fórmulas Infantis , Fenômenos Fisiológicos da Nutrição do Lactente , Hidrolisados de Proteína/uso terapêutico , Adulto , Aleitamento Materno/etnologia , Estudos de Coortes , Escolaridade , Feminino , França , Humanos , Fórmulas Infantis/efeitos adversos , Fórmulas Infantis/química , Fórmulas Infantis/microbiologia , Fenômenos Fisiológicos da Nutrição do Lactente/etnologia , Recém-Nascido , Estudos Longitudinais , Masculino , Inquéritos Nutricionais , Prebióticos/administração & dosagem , Probióticos/química , Probióticos/uso terapêutico , Estudos Prospectivos , Hidrolisados de Proteína/química , Fatores Socioeconômicos , Viscosidade , Mulheres Trabalhadoras
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