Milk intake and incident stroke and CHD in populations of European descent: a Mendelian randomisation study.

Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (ß = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.

Super large cardiac hemangioma in right atrium and inferior vena cava: case report.

BACKGROUND: Cardiac hemangiomas are rare cardiac neoplasia usually diagnosed in autopsies, from being asymptomatic to debuting with sudden death. The largest hemangioma published in the literature is of 130 mm size, we present the following case of a successful cardiac hemangioma excision of 280 × 35 mm in size, diagnosed due to recurrent cardiac symptoms. CASE PRESENTATION: A 48-year-old female patient, Jehovah's Witness, with no previous diagnoses, is admitted due to recurrent syncopal episodes in the previous months. A transthoracic echocardiogram diagnosed a tumor in the right atrium and inferior vena cava producing a diastolic right ventricular, with preservation of the left ventricular ejection fraction at 55%. Given the high mortality risk, a surgical intervention was performed immediately. Successful excision was completed confirming a 280 × 35 mm mass without any complications, consistent with hemangioma on histopathology. Postoperative recovery showed no recurrence or complications. CONCLUSIONS: Cardiac hemangiomas are rare and its clinical course can be varied from patient to patient. We present excision of a large cardiac mass with a high mortality risk due to its size and the patient's spiritual beliefs.

Breakdown of the coherence effects and Fermi liquid behavior in YbAl3 nanoparticles.

A change in the Kondo lattice behavior of bulk YbAl3 has been observed when the alloy is shaped into nanoparticles (≈12 nm). Measurements of the electrical resistivity show inhibited coherence effects and deviation from the standard Fermi liquid behavior (T 2-dependence). These results are interpreted as being due to the effect of the disruption of the periodicity of the array of Kondo ions provoked by the size reduction process. Additionally, the ensemble of randomly placed nanoparticles also triggers an extra source of electronic scattering at very low temperatures (≈15 K) due to quantum interference effects.

Meal patterns across ten European countries - results from the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study.

OBJECTIVE: To characterize meal patterns across ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study. DESIGN: Cross-sectional study utilizing dietary data collected through a standardized 24 h diet recall during 1995-2000. Eleven predefined intake occasions across a 24 h period were assessed during the interview. In the present descriptive report, meal patterns were analysed in terms of daily number of intake occasions, the proportion reporting each intake occasion and the energy contributions from each intake occasion. SETTING: Twenty-seven centres across ten European countries. SUBJECTS: Women (64 %) and men (36 %) aged 35-74 years (n 36 020). RESULTS: Pronounced differences in meal patterns emerged both across centres within the same country and across different countries, with a trend for fewer intake occasions per day in Mediterranean countries compared with central and northern Europe. Differences were also found for daily energy intake provided by lunch, with 38-43 % for women and 41-45 % for men within Mediterranean countries compared with 16-27 % for women and 20-26 % for men in central and northern European countries. Likewise, a south-north gradient was found for daily energy intake from snacks, with 13-20 % (women) and 10-17 % (men) in Mediterranean countries compared with 24-34 % (women) and 23-35 % (men) in central/northern Europe. CONCLUSIONS: We found distinct differences in meal patterns with marked diversity for intake frequency and lunch and snack consumption between Mediterranean and central/northern European countries. Monitoring of meal patterns across various cultures and populations could provide critical context to the research efforts to characterize relationships between dietary intake and health.

Magnetic phase diagram of superantiferromagnetic TbCu2 nanoparticles.

The structural state and static and dynamic magnetic properties of TbCu2 nanoparticles are reported to be produced by mechanical milling under inert atmosphere. The randomly dispersed nanoparticles as detected by TEM retain the bulk symmetry with an orthorhombic Imma lattice and Tb and Cu in the 4e and 8h positions, respectively. Rietveld refinements confirm that the milling produces a controlled reduction of particle sizes reaching ≃6 nm and an increase of the microstrain up to ≃0.6%. The electrical resistivity indicates a metallic behavior and the presence of a magnetic contribution to the electronic scattering which decreases with milling times. The dc-susceptibility shows a reduction of the Néel transition (from 49 K to 43 K) and a progressive increase of a peak (from 9 K to 15 K) in the zero-field-cooled magnetization with size reduction. The exchange anisotropy is very weak (a bias field of ≃30 Oe) and is due to the presence of a disordered (thin) shell coupled to the antiferromagnetic core. The dynamic susceptibility evidences a critical slowing down in the spin-disordered state for the lowest temperature peak associated with a spin glass-like freezing with a tendency of zv and ß exponents to increase when the size becomes 6 nm (zv ≃ 6.6 and ß ≃ 0.85). A Rietveld analysis of the neutron diffraction patterns 1.8 ≤ T ≤ 60 K, including the magnetic structure determination, reveals that there is a reduction of the expected moment (≃80%), which must be connected to the presence of the disordered particle shell. The core magnetic structure retains the bulk antiferromagnetic arrangement. The overall interpretation is based on a superantiferromagnetic behavior which at low temperatures coexists with a canting of surface moments and a mismatch of the antiferromagnetic sublattices of the nanoparticles. We propose a novel magnetic phase diagram where changes are provoked by a combination of the decrease of size and the increase of microstrain.

Effects of stray capacitance to ground in three electrode monopolar needle bioimpedance measurements.

Positive phase angle is documented and analyzed in a three electrode monopolar needle measurement. Inductance equivalent behavior of the stray capacitance to ground is described as error source in a non-inductive sample measurement.

Magnetic properties of TbAl2 nanometric alloys.

The magnetic properties of nanometric TbAI2 alloys have been investigated. The Curie temperature (T(c)) of these nanometric alloys is strongly size dependent and decreases from 103 K for the bulk alloy down to 98 K for the 14 nm alloy, as the particle volume is reduced. This reduction of T(c) has been explained by a finite-size scaling law of type [T(c)(D) -T(c)(infinity)]/T(c)(infinity) = -(D/D0)-(1/vp), with v = 0.7 and D0 = 2.2a (a, the lattice parameter), in agreement with the three-dimensional Heisenberg model. The size dependence of the coercivity has also been established. An increase of the coercivity from 0.08 kOe (bulk) to 1 kOe for 10 h milled alloy, indicates the crossover from multidomain to single domain behavior around 85 nm, as expected from the estimate of the critical size of monodomain particles. The field dependence of the magnetization indicates a faster thermal reduction of the magnetization of the nanosized alloys (17% in 300 h milled alloy with mean particle size of 14 nm) related to the bulk (3%), in the temperature range between 5 K and 30 K. The results can be explained as a direct consequence of the competing effects of the surface and the purely finite-size effects, in an ensemble of nanometric particles suffering interactions.

Essential role of microphthalmia transcription factor for DNA replication, mitosis and genomic stability in melanoma.

Malignant melanoma is an aggressive cancer known for its notorious resistance to most current therapies. The basic helix-loop-helix microphthalmia transcription factor (MITF) is the master regulator determining the identity and properties of the melanocyte lineage, and is regarded as a lineage-specific 'oncogene' that has a critical role in the pathogenesis of melanoma. MITF promotes melanoma cell proliferation, whereas sustained supression of MITF expression leads to senescence. By combining chromatin immunoprecipitation coupled to high throughput sequencing (ChIP-seq) and RNA sequencing analyses, we show that MITF directly regulates a set of genes required for DNA replication, repair and mitosis. Our results reveal how loss of MITF regulates mitotic fidelity, and through defective replication and repair induces DNA damage, ultimately ending in cellular senescence. These findings reveal a lineage-specific control of DNA replication and mitosis by MITF, providing new avenues for therapeutic intervention in melanoma. The identification of MITF-binding sites and gene-regulatory networks establish a framework for understanding oncogenic basic helix-loop-helix factors such as N-myc or TFE3 in other cancers.

Rapid formation and high diffusibility of actin-cofilin cofilaments at low pH.

Cofilin is a small actin-binding protein that is known to bind both F-actin and G-actin, severing the former. The interaction of cofilin with actin is pH-sensitive, F-actin being preferentially bound at low pH and G-actin at higher pH, within the physiological range. Diffusion coefficients of F-actin with cofilin were measured by the fluorescence recovery after photobleaching (FRAP) technique. This has the potential for simultaneous and direct measurement of average polymer length via the average diffusion coefficient of the polymers (DLM) as well as the fraction of polymerized actin, fLM, present in solution. In the range of cofilin-actin ratios up to 1 : 1 and at both pH 6.5 and pH 8.0, the diffusion coefficients of the polymers increased with the amount of cofilin present in the complex, in a co-operative manner to a plateau. We interpret this as indicating co-operative binding/severing and that filaments less than a certain length cannot be severed further. Under the conditions used here, filaments were found to be more motile at pH 6.5 than at pH 8.0. At pH 8.0, some actin is expected to be sequestered as ADP-actin-cofilin complexes, with the remaining actin being present as long slowly diffusing filaments. At pH 6.5, however, cofilin binds to F-actin to form short rapidly diffusing cofilaments. These filaments form very rapidly from cofilin-actin monomeric complexes, possibly indicating that this complex is able to polymerize without dissociation. These findings may be relevant to the nuclear import of actin-cofilin complexes.

Benzyl derivatives of 2,1,3-benzo- and benzothieno[3,2-a]thiadiazine 2,2-dioxides: first phosphodiesterase 7 inhibitors.

The synthesis of a new family of benzyl derivatives of 2,1,3-benzo- and benzothieno[3,2-a]thiadiazine 2,2-dioxides was achieved. The biological data revealed the first heterocyclic family of compounds with PDE 7 inhibitory properties appearing to be a new objective for the treatment of T-cell-dependent disorders. The IC(50) values or percent inhibition values of the compounds against PDE 7 were calculated by testing them against human recombinant PDE 7 expressed in S. cerevisiae. In this expression system the only cyclic nucleotide hydrolyzing activity present in cell extracts corresponded to human PDE 7. Isoenzyme selectivity PDE 7 versus PDE 4 and PDE 3 was also measured. Considering simultaneously inhibition of the three different isoenzymes, monobenzyl derivatives 15 and 23 showed interesting PDE 7 potency (around 10 microM); although not statistically significant, a trend toward selectivity with respect to PDE 3 and PDE 4 was obtained. Benzothiadiazine 16, although less potent at PDE 7 (IC(50) = 25 microM), also showed a trend of selectivity toward PDE 3 and PDE 4. These compounds are considered the best leads for further optimization.

[A basic health care center. Care oriented at the community]. / Examen de salud de un área básica. Enfermería orientada a la comunidad.

Principle problems of a basic health care area (Lérida) are identified. This area, which has a patient case load of 22,244 people, was studied during the winter of 1993-94 by using information from various sources. Results indicate that the population of this community are basically young, urban, have a high cultural and social level, and are mostly employed. The principle causes of mortality are the same as in the rest of Cataluña. Diseases that cause the most working days lost to illness are: respiratory, mental and bone-joint problems. The most frequent diseases seen in the clinic are: hypertension, respiratory infections, endocrine and mental. An overall look at the state of health of these patients show that the principle problems are: tobacco use, high blood pressure, arthritis, lumbago, depression, stroke, diabetes and breast cancer.

[A multicenter primary care study on alcohol consumption]. / Estudio multicéntrico sobre el abordaje del consumo de alcohol en atención primaria.

OBJECTIVES: To find records of alcoholic drink consumption in general medical records and actions taken when at-risk drinkers were identified. DESIGN: A descriptive study using clinical auditing at 4 Health Centres. PARTICIPANTS: 399 Primary Care (PC) clinical records. MEASUREMENTS AND MAIN RESULTS: Only 24.8% of the clinical records included alcoholic drink consumption over the last two years. Only 11 (2.8%)-all for men-of the records examined fulfilled the criteria for the drinker being considered at-risk. Low recording of alcohol might be for different reasons: some related to the professionals, others to the internal organisation of the PC team, yet others due to the external support structure. Causes related to internal organisation and the professionals were considered priority, as it was harder to intervene from the team into external causes. CONCLUSIONS: The results show low recording of alcohol consumption and justify the design of specific interventions. The methodology of continual quality improvement helps us identify the causes, the possible solutions and to design the strategy for change.

Chromosomal and in vitro culture studies in a case of primary plasma cell leukemia.

We present a cytogenetic study of a case of primary plasma cell leukemia (PCL) whose plasma cells were cultured in vitro with different mitogens. Cytogenetic studies demonstrated a reduction of the genome, monosomy of chromosomes 8, 13, and 22 being the most frequent. Neither structural changes nor marker chromosomes were observed. The hypodiploid karyotype was confirmed and confined to the neoplastic clone (lambda positive cells) by the MAC (Morphology, Antibody, Chromosome) method, which allows a simultaneous study of chromosomes, cell morphology, and immunologic phenotype. Stimulating the culture of plasmocytes in vitro with IL-6 + PHA, only normal metaphases could be obtained; on the other hand, a large number of abnormal metaphases were observed with the use of LPS as a mitogen. A surprisingly high yield of metaphases was obtained in this case, contrary to the rule in the in vitro growth of plasmocytic proliferations. Possible explanations of this fact are considered.

[Smoking habits in nursing students: prevalence, attitudes and knowledge]. / El tabaquismo en los estudiantes de enfermería: prevalencia, actitudes y conocimientos.

The purpose of this study has been to evaluate the prevalence of smoking habit, knowledge on the adverse health effects and attitudes towards it among nurses students in their three years of study (University School of Girona). A self-administrated questionnaire was used. A total of 135 questionnaires were answered (88%) from an estimated available population of 154 students (94% females with 21 years old of mean age). The prevalence of current smoking was 34.3%; ex smokers 23.3% and non smokers 42.5%. The mean of tobacco consumption was 367.6 cigarettes/month. 92% no smokers, 91% ex smokers and 76% smokers thought that smoking has adverse health effects (p less than 0.001). They consider the health protection like the first reason to give up smoking. 38% will advise their healthy smokers patients about the risk of their habit. We conclude: 1.-Low prevalence of smoking habit; 2.-Nurses should know methods aimed at lowering smoking rates, assuming that they have determined influence on the population behavior.

[Tobaccoism in medical students]. / El tabaquismo en los estudiantes de medicina.

AIM: To evaluate medical students' understanding of the harmfulness of tobacco; their attitude to it; and the spread of tobacco addiction among them. DESIGN: This was a crossover study, using information collected through a self-answer questionnaire. SITE. It was carried out in the Faculty of Medicine in the Autonomous University of Barcelona. PARTICIPANTS: The people under study were the 490 students registered in the first year of Medicine and doing the Biostatistics course. MAIN MEASUREMENTS AND RESULTS: The information was collected by means of a voluntary self-answer questionnaire, which was distributed during class-hours of the Biostatistics course. 68% of those registered answered. This broke down into: 25.7% smokers; 25.1% ex-smokers; and 49.2% non-smokers. 88% of students expressed total agreement as to the harmfulness of tobacco, though there were important differences between smokers and non-smokers (p < 0.01). The illness which they related most closely to tobacco addiction was Lung Cancer; and the least closely related was Bladder Cancer. Only 30% would warn healthy smokers about the risks attached to their addiction. 50% believe it is the doctor's responsibility to convince the general population to give up smoking. CONCLUSIONS: The spread of tobacco addiction is lower among medical students than among the general population of the same age and than among health professionals. We think it is essential to integrate an action programme against tobacco addiction into the overall study plan.