RESUMEN
OBJECTIVE: To assess the impact of caries, Molar Incisor Hypomineralization (MIH), and fluorosis on the Oral Health-Related Quality of Life (OHRQoL) of schoolchildren aged 8-10 years living in area with different fluoride levels in the drinking water. SUBJECT AND METHODS: The prevalence of caries and fluorosis were assessed among 663 Mexican schoolchildren using the International Caries Detection and Assessment System (ICDAS II) and the Thylstrup and Fejerskov Index (TFI), respectively. MIH was recorded using the European Academy of Pediatric Dentistry (EAPD) criteria and OHRQoL using the Child Perceptions Questionnaire (CPQ8-10). Poisson regression models were used in data analysis. RESULTS: Schoolchildren presenting two of the three conditions (cavitated lesions and TFI≥4, cavitated lesions and MIH or TFI≥4 and MIH) experienced worse quality of life than children who did not [RR=4.18; (95% CI 3.83, 4.56)]. Children with all three conditions had worse quality of life than children who did not [RR=5.64; (95% CI 5.13, 6.20)]. CONCLUSIONS: Fluorosis, MIH, and caries have a negative impact on the OHRQoL of schoolchildren living in area with a high concentration of fluoride in their drinking water.
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Caries Dental , Hipoplasia del Esmalte Dental , Agua Potable , Fluorosis Dental , Niño , Humanos , Fluoruros/análisis , Calidad de Vida , Agua Potable/análisis , Estudios Transversales , Fluorosis Dental/epidemiología , Caries Dental/epidemiología , PrevalenciaRESUMEN
Melatonin has been shown to have an antinociceptive effect and its administration could enhance the antinociceptive effect of other drugs. This study assessed the antinociceptive effects of melatonin in combination with paracetamol and N-palmitoylethanolamide (PEA) using the formalin test in mice. Melatonin, paracetamol, and PEA were administered intraplantarly (paw) alone or combined to mice. A concentration-response curve was generated to determine the concentration needed to reach 30% of the maximal antinociceptive effect (EC30). Melatonin, paracetamol and PEA induced a concentration-dependent antinociceptive effect in both phases of the formalin test, being PEA more potent (EC30 = 7.4±0.2 mg/paw) than melatonin (EC30 = 20.5±3.1 mg/paw) or paracetamol (EC30 = 41.8±2.6 mg/paw). Combinations of melatonin with paracetamol or PEA also induced a concentration-dependent antinociceptive effect in the formalin test. Isobolographic analysis showed that melatonin interacts synergistically with either paracetamol or PEA to reduce formalin-induced inflammatory pain. However, the experimental values of EC30 were significantly smaller than those calculated theoretically.
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Acetaminofén , Melatonina , Acetaminofén/farmacología , Amidas , Analgésicos/farmacología , Animales , Relación Dosis-Respuesta a Droga , Etanolaminas , Formaldehído , Melatonina/farmacología , Ratones , Ácidos PalmíticosRESUMEN
The present study evaluates the influence of spirituality/religiosity (S/R) on the coping strategies used by people with cancer (breast and prostate) compared with those without cancer, in a sample of 445 Spanish participants (160 with cancer and 285 without). Significant interactions between the presence of cancer and S/R are observed in the use of coping strategies such as religion, humor and disconnection. Spirituality as a predictor variable through the use of religion as a strategy, increased the explanatory capacity of age by 58.9% (ß = .794) while praying/talking to God predicts the use of this strategy with a ß = .383. In people with cancer, active coping was predicted by spirituality (ß = .327). However, spirituality was a negative predictor of maladaptive coping, with a beta coefficient equal to .383. The data suggest that patients' beliefs need to be considered by health care professionals when designing interventions.
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Neoplasias , Terapias Espirituales , Adaptación Psicológica , Humanos , Masculino , Religión , EspiritualidadRESUMEN
OBJECTIVE: Determining genetic and paracrine mechanisms behind endometrial regeneration in Asherman's syndrome and endometrial atrophy (AS/EA) patients after autologous CD133+ bone marrow-derived stem cell (CD133+ BMDSC) transplantation. DESIGN: Retrospective study using human endometrial biopsies and mouse models. SETTING: Fundación-IVI, IIS-La Fe, Valencia, Spain. SAMPLES: Endometrial biopsies collected before and after CD133+ BMDSC therapy, from eight women with AS/EA (NCT02144987) from the uterus of five mice with only left horns receiving CD133+ BMDSC therapy. METHODS: In human samples, haematoxylin and eosin (H&E) staining, RNA arrays, PCR validation, and neutrophil elastase (NE) immunohistochemistry (IHQ). In mouse samples, PCR validation and protein immunoarrays. MAIN OUTCOME MEASURES: H&E microscopic evaluation, RNA expression levels, PCR, and growth/angiogenic factors quantification, NE IHQ signal. RESULTS: Treatment improved endometrial morphology and thickness for all patients. In human samples, Jun, Serpine1, and Il4 were up-regulated whereas Ccnd1 and Cxcl8 were down-regulated after treatment. The significant decrease of NE signal corroborated Cxcl8 expression. Animal model analysis confirmed human results and revealed a higher expression of pro-angiogenic cytokines (IL18, HGF, MCP-1, MIP2) in treated uterine horns. CONCLUSIONS: CD133+ BMDSC seems to activate several factors through a paracrine mechanism to help tissue regeneration, modifying endometrial behaviour through an immunomodulatory milieu that precedes proliferation and angiogenic processes. Insight into these processes could bring us one step closer to a non-invasive treatment for AS/EA patients. TWEETABLE ABSTRACT: CD133+ BMDSC therapy regenerates endometrium, modifying the immunological milieu that precedes proliferation and angiogenesis.
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Atrofia/terapia , Endometrio/patología , Endometrio/fisiología , Ginatresia/terapia , Regeneración , Trasplante de Células Madre , Antígeno AC133/metabolismo , Animales , Ciclina D1/metabolismo , Citocinas/metabolismo , Regulación hacia Abajo , Femenino , Humanos , Interleucina-8/metabolismo , Elastasa de Leucocito/metabolismo , Modelos Animales , Inhibidor 1 de Activador Plasminogénico/metabolismo , Proteínas Proto-Oncogénicas c-jun/metabolismo , Estudios Retrospectivos , Trasplante Autólogo , Regulación hacia Arriba , Útero/metabolismoRESUMEN
Acacia farnesiana pods are rich in secondary metabolites and their biological activities have been recorded as antibacterial, antioxidant and anthelmintic. Previously, an in vitro bioguided study showed the important ovicidal and larvicidal effects of an organic fraction (EtOAc-F) from a hydroalcoholic extract of A. farnesiana pods against Haemonchus contortus. The present study aimed to assess the in vivo anthelmintic effect of EtOAc-F from A. farnesiana pods on the H. contortus faecal egg elimination in female lambs and on the infective larvae (L3) population reduction in coprocultures. The EtOAc-F was obtained from a hydroalcoholic extract from A. farnesiana pods through chromatographic procedures; additionally, some secondary compounds were identified using high-performance liquid chromatography (HPLC). Twenty-one 'Katahdin' crossbred female lambs ranging from three to four months of age, with body weights 21.9 ± 0.39 kg were used. Animals were orally infected with H. contortus (L3) by a single dose of 350 L3/kg BW. Three experimental groups (n = 7) were assigned as follows: 1) Control (untreated), 2) Albendazole, as a positive control (at 7.5 mg/kg BW, unique dose) and 3) EtOAc-F (at 100 mg/kg BW, once every third day, with three applications in total). Individual faecal samples were collected once a week for 5 weeks (at days 38, 45, 52, 59 and 66) post-treatment, to measure the faecal egg counts (FEC) and to obtain the H. contortus (L3) population from faecal cultures. The highest FEC reduction caused by EtOAc-F was 67.7%; meanwhile, albendazole showed a total FEC reduction after the second week post-treatment (day 45). On the other hand, the fraction caused an important reduction in the larval population in coprocultures (54.3-68.5%). The phytochemical analysis revealed the presence of galloyl derivatives and flavonoids as major compounds. The A. farnesiana pods could serve as a natural anthelmintic for the control of H. contortus, and perhaps for controlling other parasites of veterinary importance.
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Acacia/química , Antihelmínticos/uso terapéutico , Hemoncosis/veterinaria , Extractos Vegetales/uso terapéutico , Enfermedades de las Ovejas/tratamiento farmacológico , Animales , Antihelmínticos/aislamiento & purificación , Antihelmínticos/farmacología , Heces/parasitología , Femenino , Flavonoides/química , Ácido Gálico/química , Hemoncosis/tratamiento farmacológico , Hemoncosis/parasitología , Haemonchus/efectos de los fármacos , Haemonchus/aislamiento & purificación , Hematócrito/veterinaria , Recuento de Huevos de Parásitos/veterinaria , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Distribución Aleatoria , Ovinos , Enfermedades de las Ovejas/parasitologíaRESUMEN
OBJECTIVE: The aim of the study was to examine the relationship between caries experience and obesity in Mexican schoolchildren aged 8-12 years. STUDY DESIGN: This is a cross-sectional study. METHODS: This study was conducted on 522 schoolchildren selected from public schools. The prevalence of caries was evaluated by applying the decayed, missing and filled teeth (DMFT) index and ascertaining the subjects' dental caries experience from the mean DMFT value. Socio-economic data were collected from the parents, with data on the children's characteristics collected from them via a questionnaire. Their weight and height were then measured and used to calculate their body mass index (BMI)-for-age Z-score, which was then adjusted by age and sex. RESULTS: The prevalence of caries was 79.9% (DMFT≥1) in permanent dentition. Of all children, 47.5% of them brushed their teeth two or more times per day, and the prevalence of overweight and obesity was 20.1% and 17.6%, respectively. The logistic regression model showed that children with obesity (a >2 Z-score on the BMI-for-age growth chart) were less likely to have dental caries (odds ratio [OR] = 0.53 [95% confidence interval {CI}: 0.31-0.89]; P = 0.017) than children without obesity, with schoolchildren who consume more sweets per day (OR = 1.65 [95% CI: 1.03-2.62]; P = 0.035) more likely to present caries than schoolchildren who consume fewer sweets per day. CONCLUSION: Children with obesity are less likely to present dental caries. Comprehensive strategies aimed at risk factors can be useful in controlling nutritional status and improving oral health.
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Caries Dental/epidemiología , Obesidad Infantil/epidemiología , Estudiantes/estadística & datos numéricos , Niño , Estudios Transversales , Femenino , Humanos , Masculino , México/epidemiología , Prevalencia , Factores de Riesgo , Instituciones Académicas , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Examine the association between marginalization and fluorosis with caries experience in Mexican rural children aged 8-12, in Oaxaca, Mexico. METHODS: Cross-sectional study of 283 rural schoolchildren selected from two locations with high and medium levels of marginalization where the water fluoride concentration ranged from 2.0 to 2.5 ppm/F. Caries was evaluated using the DMFT index and dental fluorosis with the Thylstrup-Fejerskov Index (TFI). Socioeconomic data were collected from participants' parents, with data on the children's characteristics collected from them via a questionnaire. RESULTS: The prevalence of caries was 72.4% (DMFT ≥1) in the permanent dentition. The prevalence of fluorosis was 98.0% (TFI ≥4=71.4%). 54.8% of the children brushed their teeth two or more times daily. In logistic regression children living in high levels of marginalization were more likely to present caries (OR=2.11, 95% CI 1.13 - 3.93) than children living in medium levels. Children with severe fluorosis (TFI ≥4) (OR=1.93, 95% CI 1.06 - 3.53) were more likely have caries than those with TFI ⟨3. CONCLUSION: Rural children with a high level of marginalization and fluorosis (TFI ≥4) were more likely to present caries. Poor oral hygiene and low dental service levels were found in both marginalized areas. Populations with medium/high marginalization are more susceptible to caries.
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Caries Dental , Fluorosis Dental , Niño , Estudios Transversales , Índice CPO , Fluoruros/análisis , Humanos , México , PrevalenciaRESUMEN
A significant proportion of rhinitis patients without systemic IgE-sensitisation tested by skin prick test and serum allergen-specific IgE (sIgE) display nasal reactivity upon nasal allergen provocation test (NAPT). This disease phenotype has been termed local allergic rhinitis (LAR). LAR is an underdiagnosed entity affecting children and adults from different parts of the world, with moderate-to-severe symptoms, impairment of quality of life and rapid progression to symptom worsening. LAR is a stable phenotype and not merely an initial state of AR. Allergic rhinitis and LAR share many clinical features including a positive NAPT response, markers of type 2 nasal inflammation including sIgE in nasal secretions and a significant rate of asthma development. LAR should be considered as a differential diagnosis in those subjects of any age with symptoms suggestive of AR but no evidence of systemic atopy. Although LAR pathophysiology is partially unknown, in some patients sIgE can be demonstrated directly in the nasal secretions and/or indirectly via positive responses in basophil activation test (BAT). LAR can coexist with other rhinitis phenotypes, especially AR. The diagnosis currently relies on the positivity of NAPT to a single or multiple allergens. NAPT has high sensitivity, specificity and reproducibility, and it is considered the gold standard. BAT and the measurement of nasal sIgE can also contribute to LAR diagnosis. LAR patients benefit from the same therapeutic strategies than AR individuals, including the avoidance of allergen exposure and the pharmacotherapy. Moreover, several recent studies support the effectiveness and safety of allergen immunotherapy for LAR, which opens a window of treatment opportunity in these patients.
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Alérgenos/inmunología , Desensibilización Inmunológica , Inmunoglobulina E/inmunología , Rinitis Alérgica , Humanos , Rinitis Alérgica/diagnóstico , Rinitis Alérgica/inmunología , Rinitis Alérgica/patología , Rinitis Alérgica/terapia , Pruebas CutáneasRESUMEN
BACKGROUND AND OBJECTIVE: Suspicion of an acute allergic reaction is a common reason for attending the emergency department (ED). However, there are few comparisons between the initial diagnosis of suspected allergic reaction made in the ED with the definitive diagnosis made subsequently in the allergy department (AD). Objective: To compare details of the initial diagnosis made in the ED relating to allergy with the final diagnosis made in the AD. METHODS: Patients attending the ED of 2 hospitals with suspected allergic reactions were prospectively enrolled based on key words. A certified allergy specialist reviewed the ED records of these patients and, if these were suggestive of an allergic reaction, the patients were scheduled for further evaluation at the allergy clinic. RESULTS: In total, 2000 patients were enrolled between April 2013 and October 2015. Of these, 1333 passed the initial assessment and underwent further evaluation. Of the 1333 patients, 528 underwent an allergological study, and 206 were confirmed as being allergic. With respect to drug allergy, nonsteroidal anti-inflammatory drugs were the most common triggers, followed by ß-lactams; in food allergy, plant-based foods were the most common. Only 16.4% of patients confirmed as having anaphylaxis in the AD were initially diagnosed with the condition in the ED. CONCLUSION: Of the 528 patients who finally underwent the full allergological study, fewer than half were confirmed as allergic. Moreover, anaphylaxis appears to be underdiagnosed in the ED. Better communication between the ED and the AD is necessary to improve the diagnosis and management of these patients.
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Errores Diagnósticos/estadística & datos numéricos , Servicios Médicos de Urgencia/estadística & datos numéricos , Hipersensibilidad/diagnóstico , Adulto , Alérgenos/inmunología , Servicio de Urgencia en Hospital , Femenino , Humanos , Inmunización , Inmunoglobulina E/sangre , Masculino , Estudios Prospectivos , Reproducibilidad de los Resultados , Pruebas Cutáneas , EspañaRESUMEN
BACKGROUND: Frontal fibrosing alopecia (FFA) is a chronic cicatricial alopecia with an increasing incidence and unknown aetiology. AIM: To identify possible environmental and hormonal factors related to FFA. METHODS: We conducted a multicentre case-control study paired by sex and age, and recruited 664 women (335 cases and 329 controls) and 106 men (20 cases and 86 controls). Study subjects completed an exhaustive questionnaire enquiring about pharmacological, environmental, hormonal, social, job exposure, lifestyle, drugs and diet factors to which they were exposed at least 5 years prior to the onset of the disease. RESULTS: For women, there was a statistical association between alopecia and history of pregnancy (OR = 1.6; 95% CI 1.06-2.41), use of facial sunscreen (OR = 1.6; 95% CI 1.06-2.41) and hormone replacement therapy (HRT) (OR = 1.76; 95% CI 1.11-2.8) or raloxifene (no controls exposed therefore OR was not calculated), exposure to alkylphenolic compounds (OR = 1.48; 95% CI 1.05-2.08), and presence of rosacea (OR = 1.91; 95% CI 1.07-3.39), lichen planus pigmentosus (LPP) (OR = 5.14; 95% CI 1.11-23.6) or hypothyroidism (OR = 1.73; 95% CI 1.11-2.69). For men, there was a statistical association between alopecia and use of facial sunscreens (OR = 11.6; 95% CI 1.7-80.9) or antiageing creams (OR = 1.84; 95% CI 1.04-3.23). CONCLUSIONS: FFA seems to be associated with hormonal exposure (pregnancy, HRT and raloxifene), comorbidities (hypothyroidism, LPP and rosacea) and environmental factors (facial sunscreens, antiageing creams and occupational exposure). Further research is required to analyse the exact mechanism in which these environmental factors participate in the development of this alopecia.
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Alopecia/patología , Fibrosis/patología , Frente/patología , Protectores Solares/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Alopecia/inducido químicamente , Alopecia/etiología , Estudios de Casos y Controles , Comorbilidad , Antagonistas de Estrógenos/efectos adversos , Femenino , Fibrosis/etiología , Terapia de Reemplazo de Hormonas/efectos adversos , Humanos , Liquen Plano/complicaciones , Masculino , Persona de Mediana Edad , Exposición Profesional/efectos adversos , Clorhidrato de Raloxifeno/efectos adversos , Factores de RiesgoRESUMEN
BACKGROUND: Limited data are available regarding the ability of biomarkers to predict complete pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Complete response translates to better patient survival. DEK is a transcription factor involved not only in development and progression of different types of cancer, but is also associated with treatment response. This study aims to analyze the role of DEK in complete pathological response following chemoradiotherapy for locally advanced rectal cancer. METHODS: Pre-treated tumour samples from 74 locally advanced rectal-cancer patients who received chemoradiation therapy prior to total mesorectal excision were recruited for construction of a tissue microarray. DEK immunoreactivity from all samples was quantified by immunohistochemistry. Then, association between positive stained tumour cells and pathologic response to neoadjuvant treatment was measured to determine optimal predictive power. RESULTS: DEK expression was limited to tumour cells located in the rectum. Interestingly, high percentage of tumour cells with DEK positiveness was statistically associated with complete pathological response to neoadjuvant treatment based on radiotherapy and fluoropyrimidine-based chemotherapy and a marked trend toward significance between DEK positiveness and absence of treatment toxicity. Further analysis revealed an association between DEK and the pro-apoptotic factor P38 in the pre-treated rectal cancer biopsies. CONCLUSIONS: These data suggest DEK as a potential biomarker of complete pathological response to treatment in locally advanced rectal cancer.
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Biomarcadores de Tumor/biosíntesis , Proteínas Cromosómicas no Histona/biosíntesis , Proteínas Oncogénicas/biosíntesis , Proteínas de Unión a Poli-ADP-Ribosa/biosíntesis , Neoplasias del Recto/metabolismo , Neoplasias del Recto/terapia , Anciano , Anciano de 80 o más Años , Quimioradioterapia , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Valor Predictivo de las Pruebas , Pronóstico , Neoplasias del Recto/patología , Resultado del TratamientoRESUMEN
BACKGROUND: With the availability of high-quality asthma guidelines worldwide, one possible approach of developing a valid guideline, without re-working the evidence, already analysed by major guidelines, is the ADAPTE approach, as was used for the development of National Guidelines on asthma. METHODS: The guidelines development group (GDG) covered a broad range of experts from medical specialities, primary care physicians and methodologists. The core group of the GDG searched the literature for asthma guidelines 2005 onward, and analysed the 11 best guidelines with AGREE-II to select three mother guidelines. Key clinical questions were formulated covering each step of the asthma management. RESULTS: The selected mother guidelines are British Thoracic Society (BTS), GINA and GEMA 2015. Responses to the questions were formulated according to the evidence in the mother guidelines. Recommendations or suggestions were made for asthma treatment in Mexico by the core group, and adjusted during several rounds of a Delphi process, taking into account: 1. Evidence; 2. Safety; 3. Cost; 4. Patient preference - all these set against the background of the local reality. Here the detailed analysis of the evidence present in BTS/GINA/GEMA sections on prevention and diagnosis in paediatric asthma are presented for three age-groups: children with asthma ≤5 years, 6-11 years and ≥12 years. CONCLUSIONS: For the prevention and diagnosis sections, applying the AGREE-II method is useful to develop a scientifically-sustained document, adjusted to the local reality per country, as is the Mexican Guideline on Asthma.
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Asma/diagnóstico , Asma/prevención & control , Niño , Preescolar , Femenino , Humanos , Masculino , MéxicoRESUMEN
The performance of passive biochemical reactors in acid mine drainage (AMD) treatment could be enhanced by using fine organic substrates in new reactor designs, such as diffusive exchange reactors. This work evaluated the effect of fine cellulosic components in organic mixtures and of enrichment with inoculum, on sulfate and metals removal in discontinuous cultures for three types of synthetic AMD. The cellulosic substrates evaluated were sawdust, microcrystalline cellulose, and forestry cellulose fibers, supplemented with cow manure and leaf compost. Using microcrystalline cellulose and forestry cellulose fibers with the less concentrated AMD, high sulfate reduction rates (73 mg/L-d and 58.2 mg/L-d, respectively) were achieved. Correspondingly, iron concentrations were reduced by 69% and 86.6%. Based on their higher sulfate reducing capacity, cellulose fibers obtained as fiber boards from a local kraft pulp mill were selected for treating a synthetic AMD with a high copper concentration (273 mg/L) and pH 4.94. In batch culture, low sulfate reducing activity (13.10 mg/L-d) was only observed at the highest substrate/AMD ratio (0.5:10) tested. Results show that the use of forestry cellulose fibers in reactive mixtures supplemented with inoculum could be an alternative for optimization of diffusive exchange reactors for AMD treatment.
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Reactores Biológicos , Minería , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/análisis , Concentración de Iones de Hidrógeno , SulfatosRESUMEN
OBJECTIVES: Maraviroc (MVC) is a suitable drug for aviraemic subjects on antiretroviral treatment (ART) developing toxicity. Its prescription requires prior tropism testing. It is unknown if proviral DNA genotypic tropism testing is reliable for guiding MVC initiation in aviraemic subjects, so this study was carried out to address this issue. METHODS: PROTEST was a phase 4, prospective, single-arm clinical trial carried out in 24 HIV care centres in Spain. MVC-naïve HIV-1-infected patients with HIV-1 RNA < 50 copies/mL on stable ART during the previous 6 months who required an ART change because of toxicity and who had R5 HIV, as determined by proviral DNA genotypic tropism testing, initiated MVC with two nucleoside reverse transcriptase inhibitors (NRTIs) and were followed for 48 weeks. Virological failure was defined as two consecutive viral load measurements > 50 copies/mL. RESULTS: Tropism results were available for 141 of 175 (80.6%) subjects screened: 60% had R5 and 85% of these (n = 74) were finally included in the study. Previous ART included protease inhibitors (PIs) in 62% of subjects, nonnucleoside reverse transcriptase inhibitors (NNRTIs) in 36%, and integrase inhibitors (INIs) in 2%. Main reasons for treatment change were dyslipidaemia (42%), gastrointestinal symptoms (22%) and liver toxicity (15%). MVC was given alongside tenofovir (TDF)/emtricitabine (FTC) (54%) and abacavir (ABC)/lamivudine (3TC) (40%) in most patients. Eighty-four per cent of patients maintained a viral load < 50 copies/mL to week 48, whereas 16% discontinued treatment: two withdrew informed consent, one had an R5 to X4 shift between screening and baseline, one was lost to follow-up, one developed an adverse event (rash), two died from non-study-related causes, and five developed protocol-defined virological failure. CONCLUSIONS: Initiation of MVC plus two NRTIs in aviraemic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure for up to 1 year.
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ADN Viral/genética , Genotipo , VIH-1/fisiología , Provirus/genética , Tropismo Viral , Adulto , Antagonistas de los Receptores CCR5/uso terapéutico , Ciclohexanos/uso terapéutico , Femenino , Técnicas de Genotipaje , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Quimioterapia de Mantención/métodos , Masculino , Maraviroc , Persona de Mediana Edad , Estudios Prospectivos , España , Resultado del Tratamiento , Triazoles/uso terapéuticoRESUMEN
BACKGROUND: Histamine is a key immunoregulatory mediator and can dampen proinflammatory responses via activation of histamine receptor 2 (H2 R). The aim of this study was to determine the role of H2 R in modulating lung inflammatory responses. METHODS: H2 R was blocked using famotidine or activated using dimaprit in both the ovalbumin (OVA) and house dust mite extract (HDM) murine models of respiratory inflammation. H2 R-deficient animals and CD1d/H2 R-deficient animals were utilized to examine the CD1d presentation of lipid antigens (αGalCer or OCH) to invariant natural killer T (iNKT) cells. RESULTS: Famotidine treatment resulted in more severe airway disease in the OVA model, while dimaprit treatment significantly reduced disease severity. Both OVA and HDM-induced airway diseases were more severe in H2 R-deficient animals. Flow cytometric analysis of lung tissue from H2 R-deficient animals revealed increased numbers of CD1d+ dendritic cells and increased numbers of iNKT cells. In vitro, αGalCer-stimulated iNKT cells from H2 R-deficient mice secreted higher levels of IL-4, IL-5, and GM-CSF. In vivo, αGalCer or OCH administration to the lung resulted in enhanced mucus secretion, inflammatory cell recruitment, and cytokine production in H2 R-deficient or famotidine-treated animals, while dimaprit dampened the lung iNKT cell response to αGalCer. Removal of iNKT cells in H2 R-deficient (CD1d-/- H2 R-/- ) animals normalized the lung response to HDM. CONCLUSION: The deliberate activation of H2 R, or its downstream signaling molecules, may represent a novel therapeutic target for chronic lung inflammatory diseases, especially when CD1d-mediated presentation of lipid antigens to iNKT cells is contributing to the pathology.
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Células T Asesinas Naturales/inmunología , Células T Asesinas Naturales/metabolismo , Neumonía/inmunología , Neumonía/metabolismo , Receptores Histamínicos H2/metabolismo , Animales , Antígenos CD1d/metabolismo , Biomarcadores , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Inmunofenotipificación , Mediadores de Inflamación , Activación de Linfocitos/inmunología , Recuento de Linfocitos , Ratones , Ratones Noqueados , Fenotipo , Neumonía/genética , Neumonía/patología , Receptores Histamínicos H2/genética , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismoRESUMEN
BACKGROUND: Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. METHODS: Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity were evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity. RESULTS: The serum desaturation index (an indirect measure of SCD) was significantly reduced in nonobese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyper-responsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers. CONCLUSIONS: This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyper-responsiveness and reduced antiviral defense. SCD may represent a new target for therapeutic intervention in asthma patients.
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Asma/metabolismo , Ácidos Grasos/metabolismo , Estearoil-CoA Desaturasa/metabolismo , Animales , Asma/enzimología , Bronquios/citología , Células Cultivadas , Células Epiteliales/enzimología , Ácidos Grasos/sangre , Humanos , Metabolismo de los Lípidos , Ratones , Obesidad , Hipersensibilidad Respiratoria/enzimologíaRESUMEN
BACKGROUND: The success rates and related complications of various techniques for intubation in children with difficult airways remain unknown. The primary aim of this study is to compare the success rates of fiber-optic intubation via supraglottic airway to videolaryngoscopy in children with difficult airways. Our secondary aim is to compare the complication rates of these techniques. METHODS: Observational data were collected from 14 sites after management of difficult pediatric airways. Patient age, intubation technique, success per attempt, use of continuous ventilation, and complications were recorded for each case. First-attempt success and complications were compared in subjects managed with fiber-optic intubation via supraglottic airway and videolaryngoscopy. RESULTS: Fiber-optic intubation via supraglottic airway and videolaryngoscopy had similar first-attempt success rates (67 of 114, 59% vs. 404 of 786, 51%; odds ratio 1.35; 95% CI, 0.91 to 2.00; P = 0.16). In subjects less than 1 yr old, fiber-optic intubation via supraglottic airway was more successful on the first attempt than videolaryngoscopy (19 of 35, 54% vs. 79 of 220, 36%; odds ratio, 2.12; 95% CI, 1.04 to 4.31; P = 0.042). Complication rates were similar in the two groups (20 vs. 13%; P = 0.096). The incidence of hypoxemia was lower when continuous ventilation through the supraglottic airway was used throughout the fiber-optic intubation attempt. CONCLUSIONS: In this nonrandomized study, first-attempt success rates were similar for fiber-optic intubation via supraglottic airway and videolaryngoscopy. Fiber-optic intubation via supraglottic airway is associated with higher first-attempt success than videolaryngoscopy in infants with difficult airways. Continuous ventilation through the supraglottic airway during fiber-optic intubation attempts may lower the incidence of hypoxemia.
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Tecnología de Fibra Óptica , Intubación Intratraqueal/instrumentación , Intubación Intratraqueal/métodos , Laringoscopía/instrumentación , Laringoscopía/métodos , Grabación de Cinta de Video , Niño , Preescolar , Diseño de Equipo , Femenino , Humanos , Lactante , Laringoscopios , Masculino , Sistema de Registros/estadística & datos numéricosRESUMEN
BACKGROUND AND OBJECTIVE: Lipid transfer protein (LTP) sensitization is the most common cause of food allergy in the Mediterranean area, with peach allergy acting as the primary sensitizer in most cases. Lettuce has been described as a common offending food in patients with LTP syndrome. The aim of the study was to investigate the frequency and clinical expression of LTP syndrome in a sample of lettuceallergic patients. METHODS: We determined specific IgE to Pru p 3 and lettuce in a sample of 30 patients with a diagnosis of lettuce allergy. Symptoms elicited by other LTP-containing plant-derived foods and the presence of cofactors were assessed. RESULTS: The clinical symptoms of lettuce allergy were frequently severe, with 18 of the 30 patients experiencing anaphylaxis. All the patients had allergic reactions to other plant foods. Cofactors were involved in the clinical reactions of 13 of the 30 patients. Sensitization to pollens was found in 90% of patients. CONCLUSIONS: Lettuce allergy is found not as an isolated condition but in the context of LTP syndrome and it is characterized by severe reactions and frequent cofactor association.
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Anafilaxia/inmunología , Antígenos de Plantas/efectos adversos , Proteínas Portadoras/efectos adversos , Hipersensibilidad a los Alimentos/inmunología , Lactuca/efectos adversos , Hojas de la Planta/efectos adversos , Proteínas de Plantas/efectos adversos , Adolescente , Adulto , Anafilaxia/sangre , Anafilaxia/diagnóstico , Antígenos de Plantas/administración & dosificación , Antígenos de Plantas/inmunología , Biomarcadores/sangre , Proteínas Portadoras/inmunología , Femenino , Hipersensibilidad a los Alimentos/sangre , Hipersensibilidad a los Alimentos/diagnóstico , Frutas/efectos adversos , Frutas/inmunología , Humanos , Inmunoglobulina E/sangre , Pruebas Inmunológicas , Lactuca/inmunología , Masculino , Persona de Mediana Edad , Hojas de la Planta/inmunología , Proteínas de Plantas/administración & dosificación , Proteínas de Plantas/inmunología , Valor Predictivo de las Pruebas , Prunus persica/efectos adversos , Prunus persica/inmunología , Rinitis Alérgica Estacional/diagnóstico , Rinitis Alérgica Estacional/inmunología , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
OBJECTIVE: To assess the association between dental fluorosis and maternal education in schoolchildren of medium and low socioeconomic status in a low income region of Mexico. DESIGN: Cross-sectional study. SETTINGS: Public schools in the south-central region of Oaxaca, Mexico where the mean fluoride water concentration was 1.01 mg/L (SD 0.21; range 0.71-1.40). Fluoridated salt (200mgF/kg) was available in the region. PARTICIPANTS: 794 schoolchildren. METHODS: To identify the socioeconomic status of the participants, the Bronfman index was used. Dental fluorosis was assessed applying the Thysltrup-Fejerskov Index, (TF). RESULTS: The children's mean age was 10.4 (SD1.2) years. The prevalence of dental fluorosis (TF⟩0) was high 95.7% and 45.2% of the children showed dental fluorosis of TF≥4. The percentage of children showing TF≥4 was 48.8% where their mothers' education was ⟨6 years of schooling compared to 36.7% among other children (p⟨0.001). The multinomial logistic regression model using as base outcome category TF≤2 showed that severe forms of fluorosis (TF≥4) were associated with the consumption of boiled water, (OR= 1.65, p=0.039) of fluoridated salt (OR= 2.61 p=0.001), high brushing frequency (OR=3.12, p=0.001) and lower maternal education (OR=1.71, p=0.007). CONCLUSIONS: A high prevalence of dental fluorosis was observed in the study region. An unequal burden of fluorosis in aesthetically objectionable categories was found in children exposed to several sources of fluoride and whose mother had lower educational level.
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Fluorosis Dental/epidemiología , Niño , Estudios Transversales , Femenino , Fluoruración , Fluoruros , Humanos , Masculino , México/epidemiología , Fosfatos , Pobreza , Prevalencia , Factores de Riesgo , Factores Socioeconómicos , Cloruro de Sodio DietéticoRESUMEN
OBJECTIVES: To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD. DESIGN: A cross-sectional study with a two-step cluster analysis. SETTINGS: A tertiary referral multicenter study. PARTICIPANTS: Nine hundred and eighty-eight adult patients with unilateral MD. MAIN OUTCOME MEASURES: best predictors to define clinical subgroups with potential different aetiologies. RESULTS: We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni- and bilateral MD. CONCLUSIONS: Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials.