Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer.

Familial clustering studies indicate that breast cancer risk has a substantial genetic component. To identify new breast cancer risk variants, we genotyped approximately 300,000 SNPs in 1,600 Icelandic individuals with breast cancer and 11,563 controls using the Illumina Hap300 platform. We then tested selected SNPs in five replication sample sets. Overall, we studied 4,554 affected individuals and 17,577 controls. Two SNPs consistently associated with breast cancer: approximately 25% of individuals of European descent are homozygous for allele A of rs13387042 on chromosome 2q35 and have an estimated 1.44-fold greater risk than noncarriers, and for allele T of rs3803662 on 16q12, about 7% are homozygous and have a 1.64-fold greater risk. Risk from both alleles was confined to estrogen receptor-positive tumors. At present, no genes have been identified in the linkage disequilibrium block containing rs13387042. rs3803662 is near the 5' end of TNRC9 , a high mobility group chromatin-associated protein whose expression is implicated in breast cancer metastasis to bone.

[Assaults on professionals in healthcare settings]. / Agresiones hacia profesionales en el ámbito de la salud.

OBJECTIVE: Determine the frequency of assaults on health workers and characterize aspects that deepen understanding and development of prevention strategies. METHODS: A voluntary and confidential electronic survey was conducted through the IntraMed website, a social network of health professionals. Frequency of verbal and physical assaults was analyzed along with their association with demographic variables, occupation, career, specialty, potential consequences, perception of insecurity in the workplace, and proposals to reduce them. RESULTS: A total of 19 967 surveys were analyzed, of which 13 323 (66.7%) described assaults. Assaults were physical in 11.3% of cases, and 73.4% occurred in public institutions, mainly in emergency areas. Delay in care and lack of resources were the most frequent triggers. Alcohol or drug intoxication was reported in 13.8% of aggressors, altered mental status from another cause or psychiatric illness in 13.9%, and no detected impairment of mental faculties in 63%. Of professionals attacked, 16.9% reported sequelae, 7.9% of which were physical, and 28% were temporarily unable to work. Insecurity in the workplace was described by 46.6% of respondents, who suggested various measures to reduce it, chief among them, community education CONCLUSIONS: Verbal and physical violence toward health workers was frequent, resulting in work-related, mental, and even physical sequelae. This study contributes information that could be used to develop strategies aimed at prevention and control of assaults.

Consensus report of the XI Congress of the Spanish Society of Odontology for the handicapped and special patients.

This article summarizes the findings of consensus of the XI congress of the SEOEME. All of these conclusions are referring to the review articles responsible to the general rapporteurs in order to bringing up to date knowledge with regard to the use of implants in patients medically compromised and with special needs and, in the dental management of autism and cerebral palsy, in the dental treatment of patients with genetic and adquired haematological disorders, the dental implications of cardiovascular disease and hospital dentistry.

European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene.

Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.

Ancestry-shift refinement mapping of the C6orf97-ESR1 breast cancer susceptibility locus.

We used an approach that we term ancestry-shift refinement mapping to investigate an association, originally discovered in a GWAS of a Chinese population, between rs2046210[T] and breast cancer susceptibility. The locus is on 6q25.1 in proximity to the C6orf97 and estrogen receptor alpha (ESR1) genes. We identified a panel of SNPs that are correlated with rs2046210 in Chinese, but not necessarily so in other ancestral populations, and genotyped them in breast cancer case:control samples of Asian, European, and African origin, a total of 10,176 cases and 13,286 controls. We found that rs2046210[T] does not confer substantial risk of breast cancer in Europeans and Africans (OR = 1.04, P = 0.099, and OR = 0.98, P = 0.77, respectively). Rather, in those ancestries, an association signal arises from a group of less common SNPs typified by rs9397435. The rs9397435[G] allele was found to confer risk of breast cancer in European (OR = 1.15, P = 1.2 x 10(-3)), African (OR = 1.35, P = 0.014), and Asian (OR = 1.23, P = 2.9 x 10(-4)) population samples. Combined over all ancestries, the OR was 1.19 (P = 3.9 x 10(-7)), was without significant heterogeneity between ancestries (P(het) = 0.36) and the SNP fully accounted for the association signal in each ancestry. Haplotypes bearing rs9397435[G] are well tagged by rs2046210[T] only in Asians. The rs9397435[G] allele showed associations with both estrogen receptor positive and estrogen receptor negative breast cancer. Using early-draft data from the 1,000 Genomes project, we found that the risk allele of a novel SNP (rs77275268), which is closely correlated with rs9397435, disrupts a partially methylated CpG sequence within a known CTCF binding site. These studies demonstrate that shifting the analysis among ancestral populations can provide valuable resolution in association mapping.

Transanal irrigation as a therapeutic option for patients with incontinence and severe chronic constipation refractory to first-line treatment.

INTRODUCTION: The aim is to evaluate the utility of transanal irrigation such as treatment of incontinence and severe chronic constipation which is refractory to first-line therapy, and to assess its impact into the symptomatology and quality of life. METHODS: Observational retrospective study of patients with incontinence and chronic constipation that had initiated transanal irrigation in two hospitals of the region. We collect sociodemographic variables, comorbidity, previous treatments, tests, parameters and incidences during the irrigation, and punctuation in the Cleveland Clinic Incontinence and Constipation Scores and EuroQol-5D Quality Of Life Scale before and after the treatment. RESULTS: 40 patients, 20 with incontinence and 20 with chronic constipation. After an average period of 9 months of treatment, in 14 patients with incontinence we have observed a mean clinical improvement of 7,45 points before-after treatment measured with Cleveland Clinic Incontinence Score, and a mean improvement of 23 points in their quality of life before-after treatment measured with EQ5D Scale (P < .001); and in 16 patients with constipation a mean clinical improvement of 7,6 points before-after treatment measured with Cleveland Clinic Constipation Score, and a mean improvement of 31,5 points in their quality of life before-after treatment measured with EQ5D Scale (P < .001). CONCLUSIONS: Transanal irrigation is an effective therapy for patients with incontinence and chronic constipation that are refractory to first-line therapies. It's an easy, self-administered and safe procedure. When the patient learns how to use it, the symptomatology and quality of life are improved.

Redefining monetary policy rules: A threshold approach.

In this paper, we try to analyse the extent to which a redefinition of the monetary policy rule would help to avoid the zero-lower bound, as well as to explore the conditions needed to avoid that constraint. To that aim, we estimate the threshold values of the key variables of the policy rule: the inflation gap and the output gap. The threshold model allows us to know which are the turning points from which the relationship between the key variables and the interest rate revert. In the Eurozone countries, we have found that the inflation gap always contributes to increasing the nominal interest rate. On the contrary, the output gap works differently when it reaches values above or below the threshold value, which would favour the reduction of the interest rates towards the zero level.

Aqueous humor neutrophil gelatinase-associated lipocalin levels in patients with idiopathic acute anterior uveitis.

PURPOSE: The purpose of this study was to evaluate the levels of neutrophil gelatinase-associated lipocalin (NGAL) in the aqueous humor in eyes with idiopathic acute anterior uveitis (AAU). METHODS: A comparative control study. Aqueous humor was collected from 20 eyes of 20 patients with idiopathic AAU. The control group included 20 aqueous samples from 20 patients about to undergo cataract surgery and without any other ocular or systemic diseases. The level of NGAL was determined with a commercially available ELISA kit. RESULTS: The concentration of NGAL in aqueous humor was markedly higher in patients with idiopathic AAU than in control subjects (Mann-Whitney U test, p<0.001). The level of NGAL was 139,197.38+/-183,426.36 (mean+/-SD) pg/ml in eyes with AAU and 3,169.96+/-1,595.78 pg/ml in the eyes of the control group. CONCLUSIONS: The aqueous humor NGAL level is increased in eyes with idiopathic AAU. These results imply that NGAL is associated with the regulation of inflammation in patients with AAU and could be used as a biomarker of ocular inflammation and immunomodulatory treatment response.

[Influence of personal, professional and cross-national factors in burnout syndrome in Hispanic Americans and Spanish health workers (2007)]. / Influencia de factores personales, profesionales y transnacionales en el síndrome de burnout en personal sanitario hispanoamericano y Español (2007).

BACKGROUND: Burnout syndrome is related to cultural and individual factors. The aim of this study was to compare the frequency of burnout and the scores for its three components with the perceptions and the demographic and professional characteristics of the workers. METHODS: Burnout syndrome was studied in 11,530 Hispanic Americans and Spanish healthcare professionals (51% male, mean age 41.7 years). The Maslach Burnout Inventory and a previously drawn up questionnaire were administered online from the Intramed website from December 2006 to September 2007. Associations were tested using multiple logistic regression. RESULTS: The frequency of burnout in professionals resident in Spain was 14.9%, in Argentina 14.4%, and in Uruguay 7.9% whereas professionals in Mexico, Ecuador, Peru, Columbia, Uruguay, Guatemala and El Salvador presented frequencies of burnout of between 2.5% and 5.9%. By professions, doctors had a prevalence of burnout of 12.1%, nurses 7.2%, and dentists, psychologists and nutritionists of <6%. Amongst doctors, burnout predominated amongst doctors working in emergency departments (17%) and internal medicine departments (15.5%) whereas anaesthetists and dermatologists had the lowest prevalence (5% and 5.3%, respectively). Older age (OR=0.96), having children (OR=0.93), the perception of feeling valued (OR=0.53), optimism (OR=0.80), job satisfaction (OR=0.80), and satisfaction with salary (OR=0.91) are variables which protect against burnout. CONCLUSIONS: The expression of burnout varies among nations and professions. Age (older age), having children, the perception of feeling valued, optimism, job satisfaction and satisfaction with salary are protective variables of burnout.

[Detection of specific T cells for 264-272 and 149-157 peptides of p53 protein in peripheral blood of patients with breast cancer]. / Detección de linfocitos T citotóxicos contra los epítopos 264-272 y 149-157 de la proteína p53 en sangre periférica de pacientes con cáncer de mama.

BACKGROUND AND OBJECTIVE: p53 protein is overexpressed in nearly half of all human tumours. An HLA-A2.1-restricted immunological response mediated by anti-p53 CD8+ T cells directed against the wild type p53 264-272 epitope has been demonstrated in patients with head and neck squamous carcinomas. The existence of such a response in patients with other cancer types could be determinant for the development of specific antitumour vaccines targeting the p53 protein. We aimed to determine the presence of anti-p53 specific CD8+ T cells in peripheral blood of breast cancer patients in vivo. PATIENTS AND METHOD: p53 264-272-specific CD8+ T cells were directly enumerated in the peripheral circulation of patients with breast cancer using tetrameric p53 264-272/HLA-A2.1 complexes by multicolor flow cytometry. The same procedure was used to enumerate T cells specific for another HLA-A2.1 restricted wild type p53 epitope, p53 (149-157). RESULTS: The 99th percentile of the concentration of anti-p53 cells in 6 HLA A2- breast cancer patients was 1/5634 (cut-off point). The median counts of anti-p53264-272 and anti-p53149-157 lymphocytes in 14 HLA A2.1+ patients were 1/2383 and 1/2335 respectively. All of the HLA A2+ patients had concentrations of anti-p53 lymphocytes above the cut-off point for at least one of the epitopes: 13/14 (93%) for p53(264-272) and 11/12 (92%) for p53(149-157). CONCLUSIONS: A specific immunological response mediated by anti-p53 CD8+ T cells has been detected in patients with breast carcinoma. More studies are needed to confirm these results and to determine its usefulness for the development of p53-based vaccines.

Veteran Patient Perspectives and Experiences During Implementation of a Patient-Centered Medical Home Model.

BACKGROUND: The Veterans Health Administration (VA) has implemented the largest shift to a patient-centered medical home (PCMH) model of care in the United States to date. OBJECTIVE: We interviewed veterans about their experiences of primary care to understand whether they observed changes in care during this period as well as to learn which characteristics of care mattered most to their experiences. METHOD: Qualitative interviews were conducted with 32 veterans receiving primary care at 1 of 8 VA clinics in the northwest United States. Interviews were analyzed using an inductive-deductive hybrid approach by an interdisciplinary team that included a veteran patient. RESULT: Participants noticed recent positive changes, including improved communications and shorter waits in clinic, but rarely were aware of VA's PCMH initiative; a strong relationship with the primary care provider and feeling cared for/respected by everyone involved in care delivery were key components of quality care. The needs of the veteran community as a whole also shaped discussion of care expectations. CONCLUSION: The PCMH model may provide benefits even when invisible to patients. Veteran awareness of population needs suggests a promising role for veteran involvement in further PCMH transformation efforts.

Results of a pilot trial of immunotherapy with dendritic cells pulsed with autologous tumor lysates in patients with advanced cancer.

AIMS AND BACKGROUND: The purpose of the study was to test the immunological and clinical effects of infusions of dendritic cells pulsed with autologous tumor lysate in patients with advanced cancer. PATIENTS AND METHODS: Peripheral blood mononuclear cells from 15 patients with metastatic cancer (melanoma in 10, lung cancer in 2, renal cell carcinoma in 1, sarcoma in 1, breast cancer in 1) were harvested by leukapheresis after mobilization with GM-CSF (5 microg/kg/day s.c. for 4 days). Mononuclear cells were separated and cultured in GM-CSF (1000 U/ml) and interleukin-4 (1000 U/ml) for 7 days. Phenotype was assessed by 2-color flow cytometry and immunocytochemistry. On day 6, dendritic cells were pulsed with 1 g of fresh autologous tumor lysate for 24 h and infused intravenously. Interleukin-2 (6 million IU), interferon a (4 million IU) and GM-CSF (400 microg) were injected s.c. daily for 10 days beginning on the day of dendritic cell infusion. Treatment was repeated every 21 days for 3 courses. RESULTS: The morphology, immunocytochemistry and phenotype of cultured cells was consistent with dendritic cells: intense positivity for HLA-DR and CD86, with negativity for markers of other lineages, including CD3, CD4, CD8 and CD14. More than 5 x 10(7) dendritic cells were injected in all patients. Nine patients developed >5 mm delayed type cutaneous hypersensitivity reactions to tumor lysate+/-GM-CSF after the first immunization (larger than GM-CSF in all cases). Median delayed type cutaneous hypersensitivity to lysate +/- GM-CSF was 3 cm after the third immunization. One melanoma patient with skin, liver, lung and bone metastases had a partial response lasting 8 months (followed by progression in the brain). Seven patients had stable disease for >3 months, and 7 had progression. CONCLUSIONS: Infusion of tumor lysate-pulsed dendritic cells induces a strong cell-mediated antitumor immune reaction in patients with advanced cancer and has some clinical activity.

Clear cell carcinoma of the ovary diagnosed in ascitic fluid. A case report.

BACKGROUND: Clear cell carcinoma of the ovary (CCC) is a rare variety of ovarian cancer. CASE: A case of CCC in a 49-year-old woman was diagnosed in asciticfluid on thin-layer preparations. Peritoneal fluid cytology revealed papillary clusters of cells with clear cytoplasm and extracellular hyaline material generally without neoplastic cells. The tumor was excised, and the histologic sections confirmed the cytologic diagnosis. CONCLUSION: CCC has a distinctive cytomorphologic appearance, and the entity may be diagnosed on ascitic fluid cytology.

Cornelia de Lange syndrome: a case report.

Cornelia de Lange is a genetic syndrome which affects between 1/10.000 and 1/60.000 neonates, but its genetic bases are still not clear. Its principal clinical characteristics are the delay in growth and development, hirsute, structural anomalies in the limbs and distinctive facial characteristic. Dental problems are frequent and include: ogival palate, micrognathia, dental malalignment, delayed teething, microdontic teeth, periodontal disease and dental erosion produced by gastric reflux. Discussed is the case of a 29 year old patient affected by the syndrome in question, which presents the principal clinical characteristics. The patient's general state of health is acceptable, without cardiac or respiratory alterations. The intraoral exploration shows policaries, periodontal disease, persistence of the temporal teeth and ectopic molars. After completing the necessary pre-operatory preparations, the entire odontological treatment was carried out under general aesthesia, due to the patient's total lack of collaboration.

Epidemiología de la Infección Maxilofacial, tratada quirúrgicamente en el Hospital de Urgencia Asistencia Pública: 5 años de revisión / Epidemiology of Maxillofacial Infection, surgically treated in the Public Assistance Emergency Hospital: 5 years of review

Introducción: Infecciones moderadas, severas y/o profundas del territorio maxilofacial (ITM) constituyen un desafío de gran relevancia en los centros hospitalarios de alta complejidad. Objetivo: Actualizar esta epidemiología de resolución quirúrgica bajo anestesia general, en pabellón central tratado en el Hospital de Urgencia Asistencia Pública (HUAP) durante el período comprendido entre diciembre de 2014 a diciembre de 2019 y compararla con la realidad de otros centros hospitalarios de alta complejidad en Chile y en el extranjero. Materiales y Método: Estudio retrospectivo que analizó los protocolos operatorios de los pacientes intervenidos quirúrgicamente por ITM, en pabellón central, bajo anestesia general, en un período de 60 meses. Las variables analizadas fueron edad, género, espacio anatómico comprometido y presentación clínica. Resultados: Se realizaron 291 procedimientos quirúrgicos, para 452 infecciones. La edad promedio de los pacientes fue 38 años, con predominio del sexo masculino (57,3%); el rango de edad más afectado fue entre los 30-39 años (26,1%); el espacio submandibular fue el más comprometido (29,5%). Discusión: Los resultados expuestos concuerdan con estudios a nivel nacional e internacional. Conclusión: Resulta necesario continuar la investigación epidemiológica para establecer políticas de prevención y tratamiento eficientes en relación a cada servicio y en conjunto a nivel de salud pública.

Introduction: Moderate, severe or deep infections of the maxillofacial territory (IMT) are a relevant problem in hospital centres. Objective: To demonstrate and update the epidemiology of IMT´s with surgical resolution under general Anesthesia in mayor operating rooms at the Public Assistance Emergency Hospital (HUAP) during the period from December 2014 to December 2019, and to compare it with the epidemiological reality of other hospital centres in Chile and abroad. Materials and Method: A retrospective study analyzed the operative protocols of patients for 60 months. Studied variables were age, sex, compromised anatomical space and clinical presentation. Results: 291 surgical procedures were performed to resolve 452 infections. The average age of the operated patients was 38 years, with a slight predominance of the male gender (57.3%); the most affected age range was between 30 and 39 years (26.1%); the submandibular space was the most compromised (29.5%). Discussion: The exposed results agree with studies carried out at national and international level. Conclusion: It is necessary to continue an epidemiological investigation in order to establish efficient prevention and treatment policies for each service and altogether to unify public health statistics.

Men, women who cares? A population-based study on sex differences and gender roles in empathy and moral cognition.

Research on sex differences in empathy has revealed mixed findings. Whereas experimental and neuropsychological measures show no consistent sex effect, self-report data consistently indicates greater empathy in women. However, available results mainly come from separate populations with relatively small samples, which may inflate effect sizes and hinder comparability between both empirical corpora. To elucidate the issue, we conducted two large-scale studies. First, we examined whether sex differences emerge in a large population-based sample (n = 10,802) when empathy is measured with an experimental empathy-for-pain paradigm. Moreover, we investigated the relationship between empathy and moral judgment. In the second study, a subsample (n = 334) completed a self-report empathy questionnaire. Results showed some sex differences in the experimental paradigm, but with minuscule effect sizes. Conversely, women did portray themselves as more empathic through self-reports. In addition, utilitarian responses to moral dilemmas were less frequent in women, although these differences also had small effect sizes. These findings suggest that sex differences in empathy are highly driven by the assessment measure. In particular, self-reports may induce biases leading individuals to assume gender-role stereotypes. Awareness of the role of measurement instruments in this field may hone our understanding of the links between empathy, sex differences, and gender roles.

Empathy for others' suffering and its mediators in mental health professionals.

Empathy is a complex cognitive and affective process that allows humans to experience concern for others, comprehend their emotions, and eventually help them. In addition to studies with healthy subjects and various neuropsychiatric populations, a few reports have examined this domain focusing on mental health workers, whose daily work requires the development of a saliently empathic character. Building on this research line, the present population-based study aimed to (a) assess different dimensions of empathy for pain in mental health workers relative to general-physicians and non-medical workers; and (b) evaluate their relationship with relevant factors, such as moral profile, age, gender, years of experience, and workplace type. Relative to both control groups, mental health workers exhibited higher empathic concern and discomfort for others' suffering, and they favored harsher punishment to harmful actions. Furthermore, this was the only group in which empathy variability was explained by moral judgments, years of experience, and workplace type. Taken together, these results indicate that empathy is continuously at stake in mental health care scenarios, as it can be affected by contextual factors and social contingencies. More generally, they highlight the importance of studying this domain in populations characterized by extreme empathic demands.

Primary pulmonary botryomycosis diagnosed by fine needle aspiration cytology: a case report.

BACKGROUND: Primary pulmonary botryomycosis is an uncommon suppurative bacterial infection of the lung. Cytologic findings by conventional methods and thin-layer preparations in1 case are presented. CASE: A 45-year-old man had primary pulmonary botryomycosis diagnosed by fine needle aspiration cytology (FNAC). Aspiration smears were characterized by densely packed microorganisms surrounded by polymorphonuclear leukocytes. Microbiologic analysis of cytologic material revealed colonies of Streptococcus constellatus. CONCLUSION: FNAC diagnosis of pulmonary botryomycosis offers the opportunity to distinguish this bacterial infection from lung cancer and avoid unnecessary surgery.