The lincRNA HOTAIRM1, located in the HOXA genomic region, is expressed in acute myeloid leukemia, impacts prognosis in patients in the intermediate-risk cytogenetic category, and is associated with a distinctive microRNA signature.

Long non-coding RNAs (lncRNAs) are deregulated in several tumors, although their role in acute myeloid leukemia (AML) is mostly unknown.We have examined the expression of the lncRNA HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) in 241 AML patients. We have correlated HOTAIRM1 expression with a miRNA expression profile. We have also analyzed the prognostic value of HOTAIRM1 expression in 215 intermediate-risk AML (IR-AML) patients.The lowest expression level was observed in acute promyelocytic leukemia (P < 0.001) and the highest in t(6;9) AML (P = 0.005). In 215 IR-AML patients, high HOTAIRM1 expression was independently associated with shorter overall survival (OR:2.04;P = 0.001), shorter leukemia-free survival (OR:2.56; P < 0.001) and a higher cumulative incidence of relapse (OR:1.67; P = 0.046). Moreover, HOTAIRM1 maintained its independent prognostic value within the favorable molecular subgroup (OR: 3.43; P = 0.009). Interestingly, HOTAIRM1 was overexpressed in NPM1-mutated AML (P < 0.001) and within this group retained its prognostic value (OR: 2.21; P = 0.01). Moreover, HOTAIRM1 expression was associated with a specific 33-microRNA signature that included miR-196b (P < 0.001). miR-196b is located in the HOX genomic region and has previously been reported to have an independent prognostic value in AML. miR-196b and HOTAIRM1 in combination as a prognostic factor can classify patients as high-, intermediate-, or low-risk (5-year OS: 24% vs 42% vs 70%; P = 0.004).Determination of HOTAIRM1 level at diagnosis provided relevant prognostic information in IR-AML and allowed refinement of risk stratification based on common molecular markers. The prognostic information provided by HOTAIRM1 was strengthened when combined with miR-196b expression. Furthermore, HOTAIRM1 correlated with a 33-miRNA signature.

Role of Age and Sex in the Diagnosis of Early-stage Malignant Melanoma: A Cross-Sectional study.

Age and sex have been identified as predictors of outcome in malignant melanoma (MM). This aim of this multicentre, cross-sectional study was to analyse the role of age and sex as explanatory variables for the diagnosis of thin MM. A total of 2430 patients with MM were recruited. Cases of in situ-T1 MM were more frequent than T2-T4 MM (56.26% vs. 43.74%). Breslow thickness increased throughout decades of life (analysis of variance (ANOVA) p < 0.001), with a weak correlation between Breslow thickness and patient's age (r   = 0.202, p < 0.001). Breslow thickness was significantly less in women (1.79 vs. 2.38 mm, p = 0.0001). Binary logistic regression showed a significant (p < 0.001) odds ratio for age 0-29 years (1.18), and 30-59 years (1.16), and for women (1.09). Age and sex explained 3.64% of the variation observed in Tis-T1 frequency (R2 = 0.0364). Age and sex appear to explain a low percentage of the variation in the early detection of MM.

Tapia's syndrome: pathogenetic mechanisms, diagnostic management, and proper treatment: a case series.

BACKGROUND Tapia's syndrome is an uncommon disease described in 1904 by Antonio Garcia Tapia, a Spanish otolaryngologist. It is characterized by concomitant paralysis of the hypoglossal (XIIth) and pneumogastric (Xth) nerves. Only 69 cases have been described in the literature. Typically, the reported patients presented with a history of orotracheal intubation. Common symptoms are dysphonia, tongue deviation toward the affected side, lingual motility disturbance, and swallowing difficulty. CASE PRESENTATION In the report, we describe three cases of Tapia's syndrome in three Caucasian patients who underwent surgery with general anesthesia. Two of these patients underwent neck abscess drainage, and the third had an open reduction of a shoulder fracture. The clinical symptoms of Tapia's syndrome appeared after extubation. All three of our patients recovered their lost function at 3 months after diagnosis. CONCLUSIONS We underline the importance of performing airway endoscopy and a specific program of swallowing rehabilitation for the proper management of Tapia's syndrome.

Expression of smoothelin and smooth muscle actin in the skin.

INTRODUCTION: Smoothelin is a cytoskeletal protein of differentiated smooth muscle cells with contractile capacity, distinguishing it from other smooth muscle proteins, such as smooth muscle actin (SMA). OBJECTIVE: To evaluate the expression of smoothelin and SMA in the skin in order to establish specific localizations of smoothelin in smooth muscle cells with high contractile capacity and in the epithelial component of cutaneous adnexal structures. Methods: Immunohistochemical analysis (smoothelin and SMA) was performed in 18 patients with normal skin. RESULTS: SMA was expressed by the vascular structures of superficial, deep, intermediate and adventitial plexuses, whereas smoothelin was specifically expressed in the cytoplasm of smooth muscle cells of the deepest vascular plexus and in no other plexus of the dermis. The hair erector muscle showed intense expression of smoothelin and SMA. Cells with nuclear expression of smoothelin and cytoplasmic expression of SMA were observed in the outer root sheath of the inferior portion of the hair follicles and intense cytoplasmic expression in cells of the dermal sheath to SMA. CONCLUSIONS: We report the first study of smoothelin expression in normal skin, which differentiates the superficial vascular plexus from the deep. The deep plexus comprises vessels with high contractile capacity, which is important for understanding dermal hemodynamics in normal skin and pathological processes. We suggest that the function of smoothelin in the outer root sheath may be to enhance the function of SMA, which has been related to mechanical stress. Smoothelin has not been studied in cutaneous pathology; however we believe it may be a marker specific for the diagnosis of leiomyomas and leiomyosarcomas of the skin. Also, smoothelin could differentiate arteriovenous malformations of cavernous hemangioma of the skin

Added Value of Deep Sequencing Relative to Population Sequencing in Heavily Pre-Treated HIV-1-Infected Subjects.

OBJECTIVE: To explore the potential of deep HIV-1 sequencing for adding clinically relevant information relative to viral population sequencing in heavily pre-treated HIV-1-infected subjects. METHODS: In a proof-of-concept study, deep sequencing was compared to population sequencing in HIV-1-infected individuals with previous triple-class virological failure who also developed virologic failure to deep salvage therapy including, at least, darunavir, tipranavir, etravirine or raltegravir. Viral susceptibility was inferred before salvage therapy initiation and at virological failure using deep and population sequencing genotypes interpreted with the HIVdb, Rega and ANRS algorithms. The threshold level for mutant detection with deep sequencing was 1%. RESULTS: 7 subjects with previous exposure to a median of 15 antiretrovirals during a median of 13 years were included. Deep salvage therapy included darunavir, tipranavir, etravirine or raltegravir in 4, 2, 2 and 5 subjects, respectively. Self-reported treatment adherence was adequate in 4 and partial in 2; one individual underwent treatment interruption during follow-up. Deep sequencing detected all mutations found by population sequencing and identified additional resistance mutations in all but one individual, predominantly after virological failure to deep salvage therapy. Additional genotypic information led to consistent decreases in predicted susceptibility to etravirine, efavirenz, nucleoside reverse transcriptase inhibitors and indinavir in 2, 1, 2 and 1 subject, respectively. Deep sequencing data did not consistently modify the susceptibility predictions achieved with population sequencing for darunavir, tipranavir or raltegravir. CONCLUSIONS: In this subset of heavily pre-treated individuals, deep sequencing improved the assessment of genotypic resistance to etravirine, but did not consistently provide additional information on darunavir, tipranavir or raltegravir susceptibility. These data may inform the design of future studies addressing the clinical value of minority drug-resistant variants in treatment-experienced subjects.

Sociodemographic and occupational risk factors associated with the development of different burnout types: the cross-sectional University of Zaragoza study

BACKGROUND: Three different burnout types have been described: The "frenetic" type describes involved and ambitious subjects who sacrifice their health and personal lives for their jobs; the "underchallenged" type describes indifferent and bored workers who fail to find personal development in their jobs, and the "worn-out" in type describes neglectful subjects who feel they have little control over results and whose efforts go unacknowledged. The study aimed to describe the possible associations between burnout types and general sociodemographic and occupational characteristics. METHODS: A cross-sectional study was carried out on a multi-occupational sample of randomly selected university employees (n = 409). The presence of burnout types was assessed by means of the "Burnout Clinical Subtype Questionnaire (BCSQ-36)", and the degree of association between variables was assessed using an adjusted odds ratio (OR) obtained from multivariate logistic regression models. RESULTS: Individuals working more than 40 hours per week presented with the greatest risk for "frenetic" burnout compared to those working fewer than 35 hours (adjusted OR = 5.69; 95% CI = 2.52-12.82; p < 0.001). Administration and service personnel presented the greatest risk of "underchallenged" burnout compared to teaching and research staff (adjusted OR = 2.85; 95% CI = 1.16-7.01; p = 0.023). Employees with more than sixteen years of service in the organisation presented the greatest risk of "worn-out" burnout compared to those with less than four years of service (adjusted OR = 4.56; 95% CI = 1.47-14.16; p = 0.009). CONCLUSIONS: This study is the first to our knowledge that suggests the existence of associations between the different burnout subtypes (classified according to the degree of dedication to work) and the different sociodemographic and occupational characteristics that are congruent with the definition of each of the subtypes. These results are consistent with the clinical profile definitions of burnout syndrome. In addition, they assist the recognition of distinct profiles and reinforce the idea of differential characterisation of the syndrome for more effective treatment.

Polymorphisms of CD16A and CD32 Fcgamma receptors and circulating immune complexes in Meniere's disease: a case-control study.

BACKGROUND: Autoimmune diseases with elevated circulating autoantibodies drive tissue damage and the onset of disease. The Fcγ receptors bind IgG subtypes modulating the clearance of circulating immune complexes (CIC). The inner ear damage in Ménière's disease (MD) could be mediated by an immune response driven by CIC. We examined single-nucleotide polymorphism (SNPs) in the CD16A and CD32 genes in patients with MD which may determine a Fcγ receptor with lower binding to CIC. METHODS: The functional CD16A (FcγRIIIa*559A > C, rs396991) and CD32A (FcγRIIa*519A > G, rs1801274) SNPs were analyzed using PCR-based TaqMan Genotyping Assay in two cohorts of 156 mediterranean and 112 Galicia patients in a case-control study. Data were analyzed by χ2 with Fisher's exact test and Cochran-Armitage trend test (CATT). CIC were measured by ELISA for C1q-binding CIC. RESULTS: Elevated CIC were found in 7% of patients with MD during the intercrisis period. No differences were found in the allelic frequency for rs396991 or rs1801274 in controls subjects when they were compared with patients with MD from the same geographic area. However, the frequency of AA and AC genotypes of CD16A (rs396991) differed among mediterranean and Galicia controls (Fisher's test, corrected p = 6.9 × 10-4 for AA; corrected p = 0.02 for AC). Although genotype AC of the CD16A receptor was significantly more frequent in mediterranean controls than in patients, [Fisher's test corrected p = 0.02; OR = 0.63 (0.44-0.91)], a genetic additive effect for the allele C was not observed (CATT, p = 0.23). Moreover, no differences were found in genotype frequencies for rs396991 between patients with MD and controls from Galicia (CATT, p = 0.14). The allelic frequency of CD32 (rs1801274) was not different between patients and controls either in mediterranean (p = 0.51) or Galicia population (p = 0.11). CONCLUSIONS: Elevated CIC are not found in most of patients with MD. Functional polymorphisms of CD16A and CD32 genes are not associated with onset of MD.

Area deprivation and mortality in the provincial capital cities of Andalusia and Catalonia (Spain)

Objective: To study the linkage between material deprivation and mortality from all causes, for men and women separately, in the capital cities of the provinces in Andalusia and Catalonia (Spain). Methods: A small-area ecological study was devised using the census section as the unit for analysis. 188 983 Deaths occurring in the capital cities of the Andalusian provinces and 109 478 deaths recorded in the Catalan capital cities were examined. Principal components factorial analysis was used to devise a material deprivation index comprising the percentage of manual labourers, unemployment and illiteracy. A hierarchical Bayesian model was used to study the relationship between mortality and area deprivation. Main results: In most cities, results show an increased male mortality risk in the most deprived areas in relation to the least depressed. In Andalusia, the relative risks between the highest and lowest deprivation decile ranged from 1.24 (Malaga) to 1.40 (Granada), with 95% credibility intervals showing a significant excess risk. In Catalonia, relative risks ranged between 1.08 (Girona) and 1.50 (Tarragona). No evidence was found for an excess of female mortality in most deprived areas in either of the autonomous communities. Conclusions: Within cities, gender-related differences were revealed when deprivation was correlated geographically with mortality rates. These differences were found from an ecological perspective. Further research is needed in order to validate these results from an individual approach. The idea to be analysed is to identify those factors that explain these differences at an individual level.

A comparative study of dyslipidaemia in men and woman with androgenic alopecia

Several studies have analyzed the relationship between androgenetic alopecia and cardiovascular disease (mainly heart disease). However few studies have analyzed lipid values in men and women separately. This case-control study included 300 patients consecutively admitted to an outpatient clinic, 150 with early onset androgenetic alopecia (80 males and 70 females) and 150 controls (80 males and 70 females) with other skin diseases. Female patients with androgenic alopecia showed significant higher triglycerides values (123.8 vs 89.43 mg/dl, p = 0.006), total cholesterol values (196.1 vs 182.3 mg/dl, p = 0.014), LDL-C values (114.1 vs 98.8 mg/dl, p = 0.0006) and lower HDL-C values (56.8 vs 67.7 mg/dl, p <0.0001) versus controls respectively. Men with androgenic alopecia showed significant higher triglycerides values (159.7 vs 128.7 mg/dl, p = 0.04) total cholesterol values (198.3 vs 181.4 mg/dl, p = 0.006) and LDL-C values (124.3 vs 106.2, p = 0.0013) versus non-alopecic men. A higher prevalence of dyslipidemia in women and men with androgenic alopecia has been found. The elevated lipid values in these patients may contribute, alongside other mechanisms, to the development of cardiovascular disease in patient with androgenic alopecia.

Is hospital discharge administrative data an appropriate source of information for cancer registries purposes? Some insights from four Spanish registries

Background. The use of hospital discharge administrative data (HDAD) has been recommended for automating, improving, even substituting, population-based cancer registries. The frequency of false positive and false negative cases recommends local validation. Methods. The aim of this study was to detect newly diagnosed, false positive and false negative cases of cancer from hospital discharge claims, using four Spanish population-based cancer registries as the gold standard. Prostate cancer was used as a case study. Results. A total of 2286 incident cases of prostate cancer registered in 2000 were used for validation. In the most sensitive algorithm (that using five diagnostic codes), estimates for Sensitivity ranged from 14.5% (CI95% 10.3-19.6) to 45.7% (CI95% 41.4-50.1). In the most predictive algorithm (that using five diagnostic and five surgical codes) Positive Predictive Value estimates ranged from 55.9% (CI95% 42.4-68.8) to 74.3% (CI95% 67.0-80.6). The most frequent reason for false positive cases was the number of prevalent cases inadequately considered as newly diagnosed cancers, ranging from 61.1% to 82.3% of false positive cases. The most frequent reason for false negative cases was related to the number of cases not attended in hospital settings. In this case, figures ranged from 34.4% to 69.7% of false negative cases, in the most predictive algorithm. Conclusions. HDAD might be a helpful tool for cancer registries to reach their goals. The findings suggest that, for automating cancer registries, algorithms combining diagnoses and procedures are the best option. However, for cancer surveillance purposes, in those cancers like prostate cancer in which care is not only hospital-based, combining inpatient and outpatient information will be required.

Paternity and health services. Qualitative research on men's experiences during pregnancy, delivery and postpartum of theirs partners

Background: Little research has been carried out with regards to the inclusion of men during the birth process. The objective of this paper involves exploring the needs and expectations of the health services manifested by a group of fathers as a result of their experience during the birth process. Methods: Qualitative research was carried out in Granada in 2004 via individual interviews with fathers who showed shared responsibility in the upbringing. The profile is: employment, medium-high educational level, one or more child: 0-6 months of age. The transcript was subsequently submitted to hermeneutic analysis. Results: Some semantic constructs are: 1) Health Services do not concede the women as protagonists, 2) Birth process is depending on the body. Fathers can only support and fight for the relevance of men, 3) Men seem like “invisible”, 4) Health services inhibit their participation, and 5) have dealings with fathers according to their gender roles. The participants address the relationship between expectations of care during the birth process and unsatisfied demands, and the manner in which they employ the obstacles encountered within health services that inhibit their participation as arguments that confirm their separation from the process. Conclusions: This paper draws attention to the limited scope of the provision of healthcare during the birth process in terms of protagonism afforded to fathers. Indeed, despite their requisitory discourse, the interviewees manifest contradictory attitudes in the face of changes that require them to make commitments. We identify elements that could be improved to adapt services to the needs of fathers and vice versa.

Comprehensive analysis of RET common and rare variant patientsin a series of Spanish Hirschsprung patients confirms a synergistic effect of both kinds of events

Background. RET is the major gene associated to Hirschsprung disease (HSCR) with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology. In the present study, we have performed a comprehensive study of our HSCR series evaluating the involvement of both RET rare variants (RVs) and common variants (CVs) in the context of the disease. Methods. RET mutational screening was performed by dHPLC and direct sequencing for the identification of RVs. In addition Taqman technology was applied for the genotyping of 3 RET CVs previously associated to HSCR, including a variant lying in an enhancer domain within RET intron 1 (rs2435357). Statistical analyses were performed using the SPSS v.17.0 to analyze the distribution of the variants. Results. Our results confirm the strongest association to HSCR for the "enhancer" variant, and demonstrate a significantly higher impact of it in male versus female patients. Integration of the RET RVs and CVs analysis showed that in 91.66% of cases with both kinds of mutational events, the enhancer allele is in trans with the allele bearing the RET RV. Conclusions. A gender effect exists on both the transmission and distribution of rare coding and common HSCR causing mutations. In addition, these RET CVs and RVs seem to act in a synergistic way leading to HSCR phenotype.

Baseline characteristics of patients with chronic kidney disease stage 3 and stage 4 in Spain: the MERENA observational cohort study.

To obtain information on cardiovascular morbidity, hypertension control, anemia and mineral metabolism based on the analysis of the baseline characteristics of a large cohort of Spanish patients enrolled in an ongoing prospective, observational, multicenter study of patients with stages 3 and 4 chronic kidney diseases (CKD)

Cluster analysis of behavioural and event-related potentials during a contingent negative variation paradigm in remitting-relapsing and benign forms of multiple sclerosis

Background: Event-related potentials (ERPs) may be used as a highly sensitive way of detecting subtle degrees of cognitive dysfunction. On the other hand, impairment of cognitive skills is increasingly recognised as a hallmark of patients suffering from multiple sclerosis (MS). We sought to determine the psychophysiological pattern of information processing among MS patients with the relapsing-remitting form of the disease and low physical disability considered as two subtypes: 'typical relapsing-remitting' (RRMS) and 'benign MS' (BMS). Furthermore, we subjected our data to a cluster analysis to determine whether MS patients and healthy controls could be differentiated in terms of their psychophysiological profile.Methods: We investigated MS patients with RRMS and BMS subtypes using event-related potentials (ERPs) acquired in the context of a Posner visual-spatial cueing paradigm. Specifically, our study aimed to assess ERP brain activity in response preparation (contingent negative variation -CNV) and stimuli processing in MS patients. Latency and amplitude of different ERP components (P1, eN1, N1, P2, N2, P3 and late negativity -LN) as well as behavioural responses (reaction time -RT; correct responses -CRs; and number of errors) were analyzed and then subjected to cluster analysis. Results: Both MS groups showed delayed behavioural responses and enhanced latency for long-latency ERP components (P2, N2, P3) as well as relatively preserved ERP amplitude, but BMS patients obtained more important performance deficits (lower CRs and higher RTs) and abnormalities related to the latency (N1, P3) and amplitude of ERPs (eCNV, eN1, LN). However, RRMS patients also demonstrated abnormally high amplitudes related to the preparation performance period of CNV (cCNV) and post-processing phase (LN). Cluster analyses revealed that RRMS patients appear to make up a relatively homogeneous group with moderate deficits mainly related to ERP latencies, whereas BMS patients appear to make up a rather more heterogeneous group with more severe information processing and attentional deficits. Conclusions: Our findings are suggestive of a slowing of information processing for MS patients that may be a consequence of demyelination and axonal degeneration, which also seems to occur in MS patients that show little or no progression in the physical severity of the disease over time.

A large study of androgen receptor germline variants and their relation to sex hormone levels and prostate cancer risk. Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

Background: Androgens are key regulators of prostate gland maintenance and prostate cancer growth, and androgen deprivation therapy has been the mainstay of treatment for advanced prostate cancer for many years. A long-standing hypothesis has been that inherited variation in the androgen receptor (AR) gene plays a role in prostate cancer initiation. However, studies to date have been inconclusive and often suffered from small sample sizes. Objective and Methods: We investigated the association of AR sequence variants with circulating sex hormone levels and prostate cancer risk in 6058 prostate cancer cases and 6725 controls of Caucasian origin within the Breast and Prostate Cancer Cohort Consortium. We genotyped a highly polymorphic CAG microsatellite in exon 1 and six haplotype tagging single nucleotide polymorphisms and tested each genetic variant for association with prostate cancer risk and with sex steroid levels. Results: We observed no association between AR genetic variants and prostate cancer risk. However, there was a strong association between longer CAG repeats and higher levels of testosterone (P = 4.73 × 10−5) and estradiol (P = 0.0002), although the amount of variance explained was small (0.4 and 0.7%, respectively). Conclusions: This study is the largest to date investigating AR sequence variants, sex steroid levels, and prostate cancer risk. Although we observed no association between AR sequence variants and prostate cancer risk, our results support earlier findings of a relation between the number of CAG repeats and circulating levels of testosterone and estradiol.