A genome-wide association study identifies novel gene associations with facial skin wrinkling and mole count in Latin Americans.

BACKGROUND: Genome-wide association studies (GWASs) have identified genes influencing skin ageing and mole count in Europeans, but little is known about the relevance of these (or other genes) in non-Europeans. OBJECTIVES: To conduct a GWAS for facial skin ageing and mole count in adults < 40 years old, of mixed European, Native American and African ancestry, recruited in Latin America. METHODS: Skin ageing and mole count scores were obtained from facial photographs of over 6000 individuals. After quality control checks, three wrinkling traits and mole count were retained for genetic analyses. DNA samples were genotyped with Illumina's HumanOmniExpress chip. Association testing was performed on around 8 703 729 single-nucleotide polymorphisms (SNPs) across the autosomal genome. RESULTS: Genome-wide significant association was observed at four genome regions: two were associated with wrinkling (in 1p13·3 and 21q21·2), one with mole count (in 1q32·3) and one with both wrinkling and mole count (in 5p13·2). Associated SNPs in 5p13·2 and in 1p13·3 are intronic within SLC45A2 and VAV3, respectively, while SNPs in 1q32·3 are near the SLC30A1 gene, and those in 21q21·2 occur in a gene desert. Analyses of SNPs in IRF4 and MC1R are consistent with a role of these genes in skin ageing. CONCLUSIONS: We replicate the association of wrinkling with variants in SLC45A2, IRF4 and MC1R reported in Europeans. We identify VAV3 and SLC30A1 as two novel candidate genes impacting on wrinkling and mole count, respectively. We provide the first evidence that SLC45A2 influences mole count, in addition to variants in this gene affecting melanoma risk in Europeans.

A Computational Study on the Role of Parameters for Identification of Thyroid Nodules by Infrared Images (and Comparison with Real Data).

According to experts and medical literature, healthy thyroids and thyroids containing benign nodules tend to be less inflamed and less active than those with malignant nodules. It seems to be a consensus that malignant nodules have more blood veins and more blood circulation. This may be related to the maintenance of the nodule's heat at a higher level compared with neighboring tissues. If the internal heat modifies the skin radiation, then it could be detected by infrared sensors. The goal of this work is the investigation of the factors that allow this detection, and the possible relation with any pattern referent to nodule malignancy. We aim to consider a wide range of factors, so a great number of numerical simulations of the heat transfer in the region under analysis, based on the Finite Element method, are performed to study the influence of each nodule and patient characteristics on the infrared sensor acquisition. To do so, the protocol for infrared thyroid examination used in our university's hospital is simulated in the numerical study. This protocol presents two phases. In the first one, the body under observation is in steady state. In the second one, it is submitted to thermal stress (transient state). Both are simulated in order to verify if it is possible (by infrared sensors) to identify different behavior referent to malignant nodules. Moreover, when the simulation indicates possible important aspects, patients with and without similar characteristics are examined to confirm such influences. The results show that the tissues between skin and thyroid, as well as the nodule size, have an influence on superficial temperatures. Other thermal parameters of thyroid nodules show little influence on surface infrared emissions, for instance, those related to the vascularization of the nodule. All details of the physical parameters used in the simulations, characteristics of the real nodules and thermal examinations are publicly available, allowing these simulations to be compared with other types of heat transfer solutions and infrared examination protocols. Among the main contributions of this work, we highlight the simulation of the possible range of parameters, and definition of the simulation approach for mapping the used infrared protocol, promoting the investigation of a possible relation between the heat transfer process and the data obtained by infrared acquisitions.

Nasal airflow simulations suggest convergent adaptation in Neanderthals and modern humans.

Both modern humans (MHs) and Neanderthals successfully settled across western Eurasian cold-climate landscapes. Among the many adaptations considered as essential to survival in such landscapes, changes in the nasal morphology and/or function aimed to humidify and warm the air before it reaches the lungs are of key importance. Unfortunately, the lack of soft-tissue evidence in the fossil record turns difficult any comparative study of respiratory performance. Here, we reconstruct the internal nasal cavity of a Neanderthal plus two representatives of climatically divergent MH populations (southwestern Europeans and northeastern Asians). The reconstruction includes mucosa distribution enabling a realistic simulation of the breathing cycle in different climatic conditions via computational fluid dynamics. Striking across-specimens differences in fluid residence times affecting humidification and warming performance at the anterior tract were found under cold/dry climate simulations. Specifically, the Asian model achieves a rapid air conditioning, followed by the Neanderthals, whereas the European model attains a proper conditioning only around the medium-posterior tract. In addition, quantitative-genetic evolutionary analyses of nasal morphology provided signals of stabilizing selection for MH populations, with the removal of Arctic populations turning covariation patterns compatible with evolution by genetic drift. Both results indicate that, departing from important craniofacial differences existing among Neanderthals and MHs, an advantageous species-specific respiratory performance in cold climates may have occurred in both species. Fluid dynamics and evolutionary biology independently provided evidence of nasal evolution, suggesting that adaptive explanations regarding complex functional phenotypes require interdisciplinary approaches aimed to quantify both performance and evolutionary signals on covariation patterns.

Normative Data for Sweat Rate and Whole-Body Sodium Concentration in Athletes Indigenous to Tropical Climate.

This study determined normative data for sweat rate (SR) and whole-body (WB) sweat sodium concentration [Na+] in athletes indigenous to a tropical climate, categorized by age, gender, and sport classification. We analyzed data from 556 athletes (386 adult and 170 young) in endurance (END), team/ball (TBA), and combat (COM) sports exercising in tropical environments (wet bulb globe temperature = 29.4 ± 2.1 °C). SR was calculated from change in body weight corrected for urine output and fluid/food intake. Sweat was collected using absorbent patches, and regional [Na+] was determined using an ion selective analyzer and normalized to WB sweat [Na+]. Data are expressed as mean ± SD. SR was higher in males compared with females in both young (24.2 ± 7.7 ml·kg-1·hr-1 vs. 16.7 ± 5.7 ml·kg-1·hr-1) and adult (22.8 ± 7.4 ml·kg-1·hr-1 vs. 18.6 ± 7.0 ml·kg-1·hr-1) athletes, in END sports in girls (END = 19.1 ± 6.0 ml·kg-1·hr-1; TBA = 14.6 ± 4.5 ml·kg-1·hr-1), and in adult males (END = 25.2 ± 6.3 ml·kg-1·hr-1; TBA = 19.1 ± 7.2 ml·kg-1·hr-1; COM = 18.4 ± 8.5 ml·kg-1·hr-1) and females (END = 23.5 ± 5.6 ml·kg-1·hr-1; TBA = 14.2 ± 5.2 ml·kg-1·hr-1; COM = 15.3 ± 5.2 ml·kg-1·hr-1); p < .05. WB sweat [Na+] was higher in adult athletes than in young athletes (43 ± 10 mmol/L vs. 40 ± 9 mmol/L, p < .05). These norms provide a reference range for low, low average, average high, and high SR and WB sweat [Na+], which serve as a guide for fluid replacement for athletes who live and train in the tropics.

A fractal-like electrode based on double-wall nanotubes of anatase exhibiting improved electrochemical behaviour in both lithium and sodium batteries.

An anatase nanotube array has been prepared with a special morphology: two concentric walls and a very small central cavity. The method used here to achieve the double-wall structure is a single-step anodization process under a voltage ramp. Thanks to this nanostructure, which is equivalent to a fractal electrode, the electrochemical behaviour is improved, and the specific capacity is higher in both lithium and sodium cells due to pseudocapacitance. The double-wall structure of the nanotube enhances the surface of TiO2 being in contact with the electrolyte solution, thus allowing an easy penetration of the alkali ions into the electrode active material. The occurrence of sodium titanate in the electrode material after electrochemical reaction with sodium is studied by using EPR, HRTEM and NMR experiments.

Biological effect of nutritional recovery on serum concentrations of inflammation cytokines in the malnourished child. / Efecto biológico de la recuperación nutricional en las concentraciones séricas de citocinas inflamatorias en el niño desnutrido grave.

Children with severe malnutrition have a dysfunction of the immune response that can significantly increase morbidity and mortality from infections. The aim of this investigation was to evaluate the effect of nutritional recovery in serum measurements of inflammatory cytokines; such as interleukin 12 (IL-12), interleukin 17 (IL-17), interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). In a prospective and longitudinal study, 24 severe malnourished children aged between 1 and 2 years-old, who were part of a program of nutritional recovery, were selected based on clinical and anthropometric criteria. Serum measurements of cytokines were determined before and after dietary treatment, using the technique of sandwich Enzyme-Linked ImmunoSorbent Assay (ELISA). For comparisons, Student's t test was used, considered p <0.05 as statistically significant. A difference was observed in the concentrations of IL-12, IL-17, IFN-γ and TNF-α before and after treatment (p <0.05), which suggests that malnutrition provokes an inflammatory state and two months of intensive nutritional support, not only promotes the clinical recovery of severe malnourished children, but also the recovery of the immune response with regard to the production of soluble mediators, such as cytokines.

[Posterior nutcracker syndrome: retroaortic renal vein associated with arteriovenous fistula and renal cancinoma. Report of a case and review of literature]. / Síndrome del cascanueces posterior: vena renal retroaórtica asociada a fístula arteriovenosa y carcinoma renal. A propósito de un caso y revisión de la literatura.

Vascular retroperitoneal alterations are little frequent and nevertheless, more diagnosed. We presented a case of association very little frequents in which a vascular congenital malformation is related to the presence of a renal arteriovenous fistula and a left renal carcinoma in a patient who only presented hematuria. These vascular variations must be considered at the moment for planning a surgery with the purpose of making it safer and to avoid complications. The case is discussed and literature is reviewed.

Etanercept therapy for psoriasis in a patient with concomitant hepatitis C and liver transplant.

We report a case of a 49 year-old male who had undergone liver transplant due to hepatitis C, Laennec's cirrhosis, and hepatocellular carcinoma, and was treated with etanercept for recalcitrant generalized psoriasis. Clearance of psoriasis was achieved without any adverse effects or complications of his current conditions.

Disease evolution of patients with mycosis fungoides--a report of 30 cases.

Mycosis fungoides is the most common disease of the primary cutaneous T-cell lymphoma group. This is a retrospective study to evaluate the outcome of 30 patients with mycosis fungoides who were followed up for at least 3 years, 18 of them followed for 5 years and 9 of them followed for 7 years. A total of 10 patients achieved a sustained remission, 2 patients achieved a remission but then relapsed and three patients died from lymphoma-related death. It is concluded that the majority of the patients with T1 or T2 stage MF usually have a good prognosis. As a rule, those who do progress further in the disease have advanced stages at the moment of the diagnosis; the disease progression occurring during the first 3-5 years after diagnosis.

An Infrared Thermal Images Database and a New Technique for Thyroid Nodules Analysis.

Thyroid nodules diseases are a common health problem and thyroidal cancer is becoming increasingly prevalent. They appear in the neck and bottom neck region, superficially over the trachea. Cancer tissues are characterized by higher temperatures than surrounding tissues. Thermography is a diagnostic tool increasingly used to detect cancer and abnormalities. Artificial intelligence is an approach which can be applied to thyroid nodules classification, but is necessary to have a proper number of cases with proven diagnosis. In this paper, a new database that contain infrared thermal images, clinical and physiological data is presented. The description of each nodule per patient, and the acquisition protocol (based on Dynamic Infrared Thermography approach) is considered as well. A semi-automatic method for image registration was implemented to pre-process the thermograms and a new method for the Region of Interest (ROI) extraction is proposed. Moreover, the obtained ROI results are confirmed by medical specialists and turned available for future comparison with other works.

Are patients who call a primary care office referred to the emergency department by non-healthcare personnel without the input of a physician?

Objective. We hypothesized that a significant percentage of patients who are referred to the Emergency Department (ED) after calling their primary care physician's (PCP) office receive such instructions without the input of a physician. Methods. We enrolled a convenience sample of stable adults at an inner-city ED. Patients provided written answers to structured questions regarding PCP contact prior to the ED visit. Continuous data are presented as means ± standard deviation; categorical data as frequency of occurrence. 95% confidence intervals were calculated. Results. The study group of 660 patients had a mean age of 41.7 ± 14.7 years and 72.6% had income below $20,000/year. 472 patients (71.51%; 67.9%-74.8%) indicated that they had a PCP. A total of 155 patients (23.0%; 19.9%-26.4%) called to contact their PCP prior to ED visit. For patients who called their PCP office and were directed by phone to the ED, the referral pattern was observed as follows: 31/98 (31.63%; 23.2%-41.4%) by a non-health care provider without physician input, 11/98 (11.2%; 6.2%-19.1%) by a non-healthcare provider after consultation with a physician, 12/98 (12.3%; 7.7%-20.3%) by a nurse without physician input, and 14/98 (14.3%; 8.6%-22.7%) by a nurse after consultation with physician. An additional 11/98, 11.2%; 6.2-19.1%) only listened to a recorded message and felt the message was directing them to the ED. Conclusion. A relatively small percentage of patients were referred to the ED without the consultation of a physician in our overall population. However, over half of those that contacted their PCP's office felt directed to the ED by non-health care staff.

High-intensity ultrasonication as a way to prepare graphene/amorphous iron oxyhydroxide hybrid electrode with high capacity in lithium battery.

The preparation of graphene/iron oxyhydroxide hybrid electrode material with very homogeneous distribution and close contact of graphene and amorphous iron oxyhydroxide nanoparticles has been achieved by using high-intensity ultrasonication. Due to the negative charge of the graphene surface, iron ions are attracted toward the surface of dispersed graphene, according to the zeta potential measurements. The anchoring of the FeO(OH) particles to the graphene layers has been revealed by using mainly TEM, XPS and EPR. TEM observations show that the size of the iron oxide particles is about 4 nm. The ultrasonication treatment is the key parameter to achieve small particle size in these graphene/iron oxyhydroxide hybrid materials. The electrochemical behavior of composite graphene/amorphous iron oxyhydroxide prepared by using high-intensity ultrasonication is outstanding in terms of gravimetric capacity and cycling stability, particularly when metallic foam is used as both the substrate and current collector. The XRD-amorphous character of iron oxyhydroxide in the hybrid electrode material and the small particle size contribute to achieve the improved electrochemical performance.

[Assessment of the effectiveness and safety of Sativex® in compassionate use]. / Evaluación de eficacia y tolerabilidad de Sativex® en uso compasivo.

INTRODUCTION: Sativex® is a drug approved for use in the treatment of spasticity in multiple sclerosis. We sought to study the tolerability and effectiveness of this drug product in pathologies beyond the scope of the indications of the product data sheet, by means of its compassionate use. AIM: To evaluate the effectiveness and safety of Sativex in pathologies that are not included on the product data sheet, using a compassionate use protocol. PATIENTS AND METHODS: A six-month observational study was conducted to evaluate the effectiveness and safety of Sativex in neuropathic pain and in spasticity from causes other than multiple sclerosis. RESULTS: A total of 10 patients were included: six females and four males. Side effects appeared in only two of them and the drug product was withdrawn in one case. After starting treatment with Sativex by means of a compassionate use protocol, the consumption of concomitant drugs was reduced by 34.2% (p=0.004), and administration of botulinum toxin was suspended in seven patients (70%). The improvement on the Ashworth spasticity scale was 65.6% (p=0.004) and the score on the analogical visual scale dropped by 49.2% (p=0.026). CONCLUSIONS: Sativex may be an interesting therapeutic alternative in patients with spasticity and pain when the treatments that are usually available have been employed but patients' quality of life continues to be significantly compromised.

TITLE: Evaluacion de eficacia y tolerabilidad de Sativex ® en uso compasivo.Introduccion. Sativex ® es un farmaco aprobado para el tratamiento de la espasticidad en la esclerosis multiple. Hemos querido estudiar la tolerabilidad y eficacia de este farmaco en patologias fuera de indicacion de ficha tecnica, mediante su uso compasivo. Objetivo. Valorar la eficacia y tolerabilidad de Sativex en patologias no incluidas en la ficha tecnica, mediante un protocolo de uso compasivo. Pacientes y metodos. Se realizo un estudio observacional, de seis meses de duracion, para evaluar la eficacia y tolerabilidad de Sativex en el dolor neuropatico y en la espasticidad de causa diferente a la esclerosis multiple. Resultados. Se incluyo un total de 10 pacientes, seis mujeres y cuatro hombres. Solo hubo efectos adversos en dos de ellos, y el farmaco se suspendio en un caso. Tras el inicio del tratamiento con Sativex mediante protocolo de uso compasivo, el consumo de farmacos concomitantes se redujo un 34,2% (p = 0,004), y se suspendio la administracion de toxina botulinica en siete pacientes (70%). La mejoria de la escala de espasticidad de Ashworth fue del 65,6% (p = 0,004) y la escala visual analogica disminuyo su puntuacion un 49,2% (p = 0,026). Conclusion. Sativex puede ser una alternativa terapeutica interesante en pacientes con espasticidad y dolor cuando se han utilizado los tratamientos habituales disponibles, pero los pacientes continuan con afectacion significativa de su calidad de vida.

Mitral homograft in the tricuspid position, aortic homograft and mitral plasty in a drug addict with multiple valve endocarditis.

The case is reported of multiple valve surgery using as little prosthetic material as possible in a drug addict with recurrent right and left bacterial endocarditis. The patient underwent aortic valve replacement with a cryopreserved aortic homograft, mitral repair and tricuspid valve replacement with a mitral homograft, using a modified technique. The indications and surgical options for tricuspid valve endocarditis in this patient group are discussed, with particular focus on technical aspects of using mitral homografts in the tricuspid position.

Improving the performance of titania nanotube battery materials by surface modification with lithium phosphate.

Self-organized TiO2 nanotubes ranging from amorphous to anatase structures were obtained by anodization procedures and thermal treatments at 500°C. Then electrolytic Li3PO4 films were successfully deposited on the nanotube array by an electrochemical procedure consisting in proton reduction with subsequent increase in pH, hydrogen phosphate dissociation and Li3PO4 deposition on the surface of the cathode. The Li3PO4 polymorph (γ or ß) in the deposit could be tailored by modifying the electrodeposition parameters, such as time or current density, as determined by X-ray patterns. The morphological analysis evidenced the formation of a 3D nanostructure consisting of Li3PO4 coating the TiO2 nanotube array. The anode-solid electrolyte stacking was tested in lithium half cells. Interestingly, the electrochemical performances revealed a better cycling stability for samples containing low amount of lithium phosphate, which is deposited for short times and low current densities. These results suggested the possibility of fabricating 3D Li-ion batteries. nt-TiO2/γ-Li3PO4/LiFePO4 full cells were cycled at different rates in the C/5-5C range. This cathode-limited microbattery delivered a reversible gravimetric capacity of 110 mA h g(-1) and a capacity retention of 75 % after 190 cycles at 5C.

Development of a proof of concept immunochromatographic lateral flow assay for point of care diagnosis of Mycobacterium tuberculosis.

BACKGROUND: Despite major public health initiatives and the existence of efficacious treatment regimes, tuberculosis (TB) remains a threat, particularly in resource-limited settings. A significant part of the problem is the difficulty of rapidly identifying infected individuals, and as a result, there has been renewed interest in developing better diagnostics for infection or disease caused by Mycobacterium tuberculosis. Many of the existing tools, however, have limitations such as poor sensitivity or specificity, or the need for well-equipped laboratories to function effectively. Serodiagnostic approaches in particular have long drawn attention, due to their potential utility in large field studies, particularly in resource-poor settings. Unfortunately none of the serodiagnostic approaches have so far proven useful under field conditions. RESULTS: We screened a large panel of antigens with serodiagnostic potential by ELISA and selected a subpanel that was strongly and broadly recognised by TB patients, but not by controls. These antigens were then formulated into a simple immuno-chromatographic lateral flow assay format, suitable for field use, and tested against panels of plasma and blood samples from individuals with different clinical status (confirmed TB patients, household contacts, and apparently healthy community controls), recruited from Ethiopia (a highly TB-endemic country) and Turkey (a TB meso-endemic country). While specificity was good (97-100% in non TB-endemic controls), the sensitivity was not as high as expected (46-54% in pulmonary TB, 25-29% in extra-pulmonary TB). CONCLUSIONS: Though below the level of sensitivity the consortium had set for commercial development, the assay specifically identified M. tuberculosis-infected individuals, and provides a valuable proof of concept.

Nanocrystalline CoSn2-carbon composite electrode prepared by using sonochemistry.

A sonochemical method has been used to prepare negative electrode materials containing intermetallic nanoparticles and polyacrylonitrile (PAN). The ultrasound irradiation is applied to achieve small particle size. After annealing at 490 °C under Ar-flow, the polymer PAN is partially carbonized and the metallic nanoparticles are surrounded by a carbonaceous matrix. The main metallic phase is CoSn(2). The carbonaceous coating and the surface oxides have been explored by using XPS. The resulting CoSn(2)-carbonaceous phase electrode (CoSn(2)@C) shows improved electrochemical behavior (ca. 450 mAh/g after 50 cycles) in comparison with previous reports on pure crystalline CoSn(2). The reaction between CoSn(2)@C and Li has been studied by using XRD and (119)Sn Mössbauer spectroscopy. The formation of large grains of crystalline Li(x)Sn phases after the first discharge is discarded. The small particle size which is achieved by using ultrasonication and the carbonaceous matrix contribute to maintain the Co-Sn interactions during the electrochemical cycling. The aggregation of the nanosized metallic particles upon electrochemical cycling can be suppressed by the carbonaceous matrix (pyrolytic PAN).

Efecto biológico de la recuperación nutricional en las concentraciones séricas de citocinas inflamatorias en el niño desnutrido grave / Biological effect of nutritional recovery on serum concentrations of inflammation cytokines in the malnourished child

El niño con desnutrición grave tiene una disfunción de la respuesta inmune que puede aumentar de manera significativa la morbilidad y la mortalidad por infecciones. El objetivo de la presente investigación fue evaluar el efecto de la recuperación nutricional en las concentraciones séricas de citocinas inflamatorias; tales como: interleucina 12 (IL-12), interleucina 17 (IL-17), interferón gamma (IFN-γ) y factor de necrosis tumoral alfa (TNF-α). En un estudio de tipo prospectivo y longitudinal, se seleccionó la población con base a criterios clínicos y antropométricos, constituida por 24 niños desnutridos graves en edades comprendidas entre 1 y 2 años, quienes formaban parte de un programa de recuperación nutricional. La concentración sérica de las citocinas investigadas se determinó antes y después del tratamiento nutricional, empleando la técnica de Inmunoanálisis Enzimático (ELISA) de doble anticuerpo. Para establecer comparaciones se utilizó la t de Student, y se consideró una p<0,05 como estadísticamente significante. Se observó una diferencia en las concentraciones de IL-12, IL-17, IFN-γ y TNF-α antes y después del tratamiento (p<0,05), lo cual parece indicar que la desnutrición per se provoca un estado inflamatorio y que 2 meses de apoyo nutricional intensivo, favorecen no solo la recuperación clínica del niño desnutrido grave, sino también la recuperación de su respuesta inmunitaria en cuanto a la producción de mediadores solubles como son las citocinas.

Children with severe malnutrition have a dysfunction of the immune response that can significantly increase morbidity and mortality from infections. The aim of this investigation was to evaluate the effect of nutritional recovery in serum measurements of inflammatory cytokines; such as interleukin 12 (IL-12), interleukin 17 (IL-17), interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). In a prospective and longitudinal study, 24 severe malnourished children aged between 1 and 2 years-old, who were part of a program of nutritional recovery, were selected based on clinical and anthropometric criteria. Serum measurements of cytokines were determined before and after dietary treatment, using the technique of sandwich Enzyme-Linked ImmunoSorbent Assay (ELISA). For comparisons, Student’s t test was used, considered p <0.05 as statistically significant. A difference was observed in the concentrations of IL-12, IL-17, IFN-γ and TNF-α before and after treatment (p <0.05), which suggests that malnutrition provokes an inflammatory state and two months of intensive nutritional support, not only promotes the clinical recovery of severe malnourished children, but also the recovery of the immune response with regard to the production of soluble mediators, such as cytokines.

[Leber's optic neuropathy, ten years on: Harding's syndrome]. / Neuropatía óptica de Leber, diez años después: síndrome de Harding.

TITLE: Neuropatia optica de Leber, diez años despues: sindrome de Harding.