STIM1 regulates pancreatic ß-cell behaviour: A modelling study.

Pancreatic ß-cells are equipped with the molecular machinery allowing them to respond to high glucose levels in the form of electrical activity and Ca2+ oscillations. These oscillations drive insulin secretion. Two key ionic mechanisms involved in this response are the Store-Operated Current and the current through ATP-dependent K+ channels. Both currents have been shown to be regulated by the protein STIM1, but this dual regulation by STIM1 has not been studied before. In this paper, we use mathematical modelling to gain insight into the role of STIM1 in the ß-cell response. We extended a previous ß-cell model to include the dynamics of STIM1 and described the dependence of the ATP-dependent K+ current on STIM1. Our simulations suggest that the total concentration of STIM1 modifies the bursting frequency, the burst duration and the intracellular Ca2+ levels. These results are in good agreement with experimental reports, and the contribution of the studied currents to electrical activity and Ca2+ dynamics is discussed. The model predicts that in the absence of STIM1 the excitability of the plasma membrane increases and that the glucose threshold for electrical activity is shifted to lower concentrations. These computational predictions may be related to impaired insulin secretion under conditions of reduced STIM1 in the diabetic state.

Eletrofiação aplicada a cicatrização de feridas: revisão de literatura / Electrospinning applied to wound healing: literature review / Electroalambre aplicado a la cicatrización de heridas: revisión de la literatura

feridas correspondem a interrupção da continuidade da pele, com a perda de uma ou mais camadas do tecido cutâneo. Curativos tradicionalmente aplicados em feridas cutâneas buscam principalmente fornecer uma barreira de proteção e permitir o desenvolvimento dos eventos celulares e bioquímicos que compreendem a cicatrização. Objetivou-se com este estudo apresentar sob a forma de revisão de literatura narrativa os principais eventos relacionados ao processo de reparo tecidual da pele, bem como abordar a aplicabilidade da técnica de eletrofiação no desenvolvimento de curativos funcionais biocompatíveis. Foram selecionados artigos voltados à caracterização dos eventos chave ocorridos a nível tecidual durante a cicatrização e, na sequência, buscou-se artigos voltados à produção, caracterização e aplicação de filmes nanoeletrofiados com ênfase na utilização de biopolímeros e substâncias bioativas. Observou-se que a maioria dos trabalhos recentes, voltados a pesquisa de base, descrevem a resposta vascular como o principal evento do processo cicatricial, sendo responsável pelas etapas que se desenrolam a seguir, que compreendem as fases inflamatória, proliferativa e de remodelamento, classicamente já descritas. Os curativos funcionais baseados em polímeros eletrofiados apresentam resultados superiores quanto testados in vitro e in vivo. As características morfoestruturais mimetizam a matriz extracelular e podem atuar em tecidos alvo como dispositivos de entrega de substâncias. Conclui-se que a atualização e reorganização de conceitos relativos à cicatrização podem contribuir no desenvolvimento de inovações, como os curativos produzidos por eletrofiação. Embora promissora, as desvantagens da técnica encontram-se principalmente no processo de obtenção e disponibilidade, que limitam a aplicação clínica em escala comercial.

Wounds correspond to the interruption of skin continuity, with the loss of one or more layers of skin tissue. Dressings traditionally applied to cutaneous wounds mainly seek to provide a protective barrier and allow the development of cellular and biochemical events that comprise healing. The objective of this study was to present, in the form of a narrative literature review, the main events related to the skin tissue repair process, as well as to address the applicability of the electrospinning technique in the development of biocompatible functional dressings. Articles focused on the characterization of the key events that occurred at the tissue level during healing were selected and, subsequently, articles focused on the production, characterization and application of nanoelectrospun films with emphasis on the use of biopolymers and bioactive substances were sought. It was observed that most recent works, focused on basic research, describe the vascular response as the main event of the healing process, being responsible for the steps that follow, which include the inflammatory, proliferative and remodeling phases, classically already described. Functional dressings based on electrospun polymers show superior results when tested in vitro and in vivo. The morphostructural features mimic the extracellular matrix and can act in target tissues as substance delivery devices. It is concluded that the updating and reorganization of concepts related to healing can contribute to the development of innovations, such as dressings produced by electrospinning. Although promising, the technique's disadvantages lie mainly in the process of obtaining and availability, which limit clinical application on a commercial scale.

Las heridas corresponden a la interrupción de la continuidad de la piel, con la pérdida de una o más capas de tejido cutáneo. Los apósitos aplicados tradicionalmente a las heridas cutáneas buscan principalmente proporcionar una barrera protectora y permitir el desarrollo de los eventos celulares y bioquímicos que comprenden la curación. El objetivo de este estudio fue presentar en forma de revisión bibliográfica narrativa los principales acontecimientos relacionados con el proceso de reparación tisular de la piel, así como abordar la aplicabilidad de la técnica de electrodeposición en el desarrollo de apósitos funcionales biocompatibles. Se seleccionaron artículos dirigidos a la caracterización de los eventos chave ocurridos a nivel técnico durante la cicatrización y, a continuación, se buscaron artículos dirigidos a la producción, caracterización y aplicación de películas nanoelectrofíricas con énfasis en el uso de biopolímeros y sustancias bioativas. Se observa que la mayoría de los trabajos recientes, realizados en la investigación de base, describen la respuesta vascular como el principal evento del proceso cicatricial, siendo responsable de las etapas que se desarrollan a continuación, que comprenden las fases inflamatoria, proliferativa y de remodelación, clásicamente descritas. Los apósitos funcionales basados en polímeros electro-tejidos presentan resultados superiores cuando se prueban in vitro e in vivo. Las características morfoestruturales mimetizan la matriz extracelular y pueden actuar en tejidos alvos como dispositivos de entrega de sustancias. Se concluye que la actualización y la reorganización de los conceptos relativos a la cicatrización pueden contribuir al desarrollo de innovaciones, como las curativas producidas por la electrofagia. Aunque es prometedora, las desventajas de la técnica radican principalmente en el proceso de obtención y la disponibilidad, que limitan la aplicación clínica a escala comercial.

Reduction of ER-Mitochondria Distance: a Key Feature in Alzheimer's and Parkinson's Disease, and During Cancer Treatment.

One remarkable dynamic cell structure is the region between the endoplasmic reticulum (ER) and the mitochondria, termed the mitochondria-associated membranes (MAM). MAMs carry out different cellular functions such as Ca2+ homeostasis and lipid synthesis, which depend on an adequate distance separating the ER and mitochondria. A decreased distance has been observed in Alzheimer's disease, Parkinson's disease, and during cancer treatment. It is unclear how dysregulation of the spatial characteristics of MAMs can cause abnormal Ca2+ dynamics which could end in cell death. In this work, a computational model was proposed to study the relationship between a decreased ER-mitochondria distance and mitochondria-induced cell death. Our results point towards the mitochondrial permeability transition pore (mPTP) as a key cell death signaling mechanism indirectly regulated by the spatial characteristics of MAMs.Clinical Relevance- The endoplasmic reticulum-mitochondria crosstalk plays an important role in the mPTP-induced apoptosis. This process could be behind neurodegeneration in Alzheimer's and Parkinson's diseases, as well as behind the induced cell death during cancer treatment.

Salivary glands ultrasonography as a diagnostic aid in Sjögren syndrome: A prospective pilot investigation.

OBJECTIVE: The aims of this pilot investigation were to calculate the levels of sensitivity and specificity of salivary glands ultrasonography (SGUS) in diagnosing Sjögren syndrome (SS) and to assess the ultrasonographic findings of parotid and submandibular glands. STUDY DESIGN: Patients diagnosed with SS or dry mouth and healthy controls were enrolled. Bilateral parotid and submandibular glands were assessed for (1) parenchymal inhomogeneity (PIH), (2) median size of the glands, (3) visibility of glandular posterior borders, and (4) size of sialolith, if present. RESULTS: This study included 34 female patients, of whom 12 had SS (35.3%), 12 had dry mouth (35.3%), and 10 were healthy controls (29.4%). Patients with SS showed higher PIH scores in all glands with the median differences being statistically higher in the right and left parotids and left submandibular glands (P < .001, P = .012, and P < .001, respectively). SGUS, with a PIH cutoff ≥2, showed a sensitivity of 100% and a specificity of 81.6% for detecting SS. The majority of SS had invisible glandular posterior borders (P < .001). Median size of the glands and size of the sialolith did not show any statistically significant differences between groups. CONCLUSIONS: SGUS is a noninvasive imaging modality with good sensitivity and specificity that might be valuable as a diagnostic aid for SS.

Influence of zirconia crown artifacts on cone beam computed tomography scans and image superimposition of tomographic image and tooth surface scan: An in vitro study.

STATEMENT OF PROBLEM: Zirconia restorations create significant artifacts on 3D cone beam computed tomography (CBCT) imaging. Static computer-assisted implant surgery (s-CAIS) relies on the accuracy of superimposition between an intraoral surface scan and CBCT imaging. However, how the artifacts from zirconia on the tomographic image might affect the predictability of s-CAIS is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the effect of zirconia crown restorations on the superimposition process for s-CAIS. MATERIAL AND METHODS: Four stone casts generated 4 groups: a control group (CG) with no crowns and 3 experimental groups with 4 (TG4), 7 (TG7), and 13 (TG13) zirconia crowns. A total of 40 CBCT scans were made for the 4 groups (n=10). All CBCTs were imported into a computer planning software program, and the casts from all 4 groups were scanned by using a high-resolution laboratory scanner. The standard tessellation language (STL) files were imported, segmented, and the 3 files superimposed for all groups. The accuracy of the superimposition was assessed, in millimeters, in 3 planes corresponding to anterior-posterior, horizontal, and vertical, as well as the overall measurement, and the results were analyzed statistically (α=.05). RESULTS: The overall analysis demonstrated statistically significant differences between all groups (P<.001), except between CG and TG4. The anterior-posterior dimension demonstrated significant differences between CG and TG7 (P<.001), CG and TG13 (P<.001), TG4 and TG7 (P=.004), and TG4 and TG13 (P=.001). For the vertical dimension analysis, significant differences were found between CG and TG7 (P=.001), CG and TG13 (P<.001), and TG4 and TG13 (P<.001). For the horizontal variable, statistically significant differences were found between CG and TG7 (P=.049), CG and TG13 (P<.001), TG4 and TG13 (P<.001), and TG7 and TG13 (P=.003). CONCLUSIONS: The accuracy of the superimposition of the images was influenced by the number of zirconia crowns, with an increased number reducing the superimposition accuracy.

Iron Absorption from Iron-Biofortified Sweetpotato Is Higher Than Regular Sweetpotato in Malawian Women while Iron Absorption from Regular and Iron-Biofortified Potatoes Is High in Peruvian Women.

BACKGROUND: Sweetpotato and potato are fast-maturing staple crops and widely consumed in low- and middle-income countries. Conventional breeding to biofortify these crops with iron could improve iron intakes. To our knowledge, iron absorption from sweetpotato and potato has not been assessed. OBJECTIVE: The aim was to assess iron absorption from regular and iron-biofortified orange-fleshed sweetpotato in Malawi and yellow-fleshed potato and iron-biofortified purple-fleshed potato in Peru. METHODS: We conducted 2 randomized, multiple-meal studies in generally healthy, iron-depleted women of reproductive age. Malawian women (n = 24) received 400 g regular or biofortified sweetpotato test meals and Peruvian women (n = 35) received 500 g regular or biofortified potato test meals. Women consumed the meals at breakfast for 2 wk and were then crossed over to the other variety. We labeled the test meals with 57Fe or 58Fe and measured cumulative erythrocyte incorporation of the labels 14 d after completion of each test-meal sequence to calculate iron absorption. Iron absorption was compared by paired-sample t tests. RESULTS: The regular and biofortified orange-fleshed sweetpotato test meals contained 0.55 and 0.97 mg Fe/100 g. Geometric mean (95% CI) fractional iron absorption (FIA) was 5.82% (3.79%, 8.95%) and 6.02% (4.51%, 8.05%), respectively (P = 0.81), resulting in 1.9-fold higher total iron absorption (TIA) from biofortified sweetpotato (P < 0.001). The regular and biofortified potato test meals contained 0.33 and 0.69 mg Fe/100 g. FIA was 28.4% (23.5%, 34.2%) from the regular yellow-fleshed and 13.3% (10.6%, 16.6%) from the biofortified purple-fleshed potato meals, respectively (P < 0.001), resulting in no significant difference in TIA (P = 0.88). CONCLUSIONS: FIA from regular yellow-fleshed potato was remarkably high, at 28%. Iron absorbed from both potato test meals covered 33% of the daily absorbed iron requirement for women of reproductive age, while the biofortified orange-fleshed sweetpotato test meal covered 18% of this requirement. High polyphenol concentrations were likely the major inhibitors of iron absorption. These trials were registered at www.clinicaltrials.gov as NCT03840031 (Malawi) and NCT04216030 (Peru).

Sequencing depth and genotype quality: accuracy and breeding operation considerations for genomic selection applications in autopolyploid crops.

KEY MESSAGE: Polypoid crop breeders can balance resources between density and sequencing depth, dosage information and fewer highly informative SNPs recommended, non-additive models and QTL advantages on prediction dependent on trait architecture. The autopolyploid nature of potato and sweetpotato ensures a wide range of meiotic configurations and linkage phases leading to complex gene-action and pose problems in genotype data quality and genomic selection analyses. We used a 315-progeny biparental F1 population of hexaploid sweetpotato and a diversity panel of 380 tetraploid potato, genotyped using different platforms to answer the following questions: (i) do polyploid crop breeders need to invest more for additional sequencing depth? (ii) how many markers are required to make selection decisions? (iii) does considering non-additive genetic effects improve predictive ability (PA)? (iv) does considering dosage or quantitative trait loci (QTL) offer significant improvement to PA? Our results show that only a small number of highly informative single nucleotide polymorphisms (SNPs; ≤ 1000) are adequate for prediction in the type of populations we analyzed. We also show that considering dosage information and models considering only additive effects had the best PA for most traits, while the comparative advantage of considering non-additive genetic effects and including known QTL in the predictive model depended on trait architecture. We conclude that genomic selection can help accelerate the rate of genetic gains in potato and sweetpotato. However, application of genomic selection should be considered as part of optimizing the entire breeding program. Additionally, since the predictions in the current study are based on single populations, further studies on the effects of haplotype structure and inheritance on PA should be studied in actual multi-generation breeding populations.

Second hand smoke (SHS) exposure in children. An evaluation of a preventative measure.

AIMS: To evaluate the effectiveness of the preventative programme "Smoke-free Homes" undertaken in 4th year children and their parents or guardians, aiming to reduce children's exposure to second hand smoke (SHS) in the home. MATERIAL AND METHODS: This was a pre- and post-test pre-experimental study, in students from 32 Braga district primary schools 2007/08. A self-administered and structured questionnaire was given out to 795 students in the classroom before and after the programme. In analysing data, we used the chi-squared test for the categorical variables. RESULTS: The rate of children exposed to regular or occasional SHS due to living with at least one smoker dropped from 42.2% to 32.6% (p=0.001). The percentage of students, children of smokers who stated that their father smoked regularly or occasionally at home, dropped from 68.0% pre-test to 51.6% posttest (p=0.000). No significant reduction was seen in mothers. CONCLUSION: Based on the data, we can conclude that the "Smoke-free Homes" programme was effective in preventing smoking in the home, and therefore reducing the rate of children exposed to SHS by about 10%. However, it appears that about a third of children are still exposed, which highlights the need for further measures in this area. Healthcare professionals, particularly those working in Paediatrics, should advise parents to quit smoking, especially in the home.

[Prevalence and smoking trends in Portugal and Europe]. / Estado actual e evolução da epidemia tabágica em Portugal e na Europa.

UNLABELLED: Tobacco smoking is the cause of more than half million deaths/year in the European Union (EU). Monitoring smoking prevalence is an important tool to evaluate the epidemic and its evolution and to assess the effectiveness of preventive measures. The comparison between countries may help us identify good control practices. OBJECTIVE: To describe the current state and evolution of the smoking epidemic in several EU countries, and to characterize the Portuguese situation in comparison with those countries. METHODS: To characterize smoking habits and their evolution in the population over 15 years old, several Eurobarometer reports from 1995 to 2007 were used. The characterization of School Aged Children's smoking habits was based on the Health Behaviour in School-Aged Children data of 1993-4 and 2002. The Portuguese situation also used the information available from the National Health Surveys of 1987 up to 2005/06. RESULTS: The global prevalence of smoking in adult population in most of the European countries is over 25%. The average prevalence of male and female smokers in School-Aged Children over 15 years of age is approximately 18% if we consider both genders together. In most countries the prevalence of tobacco consumption is higher in girls when compared to boys. In Portugal, the prevalence in the population over 15 years of age has one of the lowest values among European countries (30,6 % for men and 11,6% for women). Despite these crude prevalence rates, high age-sex-specific prevalence rates were found in age groups 25-34 and 35-44 in men (39,9% e 44,6% respectively) and in women (17,6 e 21,2% respectively). In 2002, at the age of 15, the percentage of daily smoking girls in Portugal was 19.5%. This value reveals that Portugal is among the countries with higher prevalence rates of smoking among adolescent girls. Over the last decade (1996-2006), a decrease in tobacco consumption has been observed in most EU countries, both in adult population and in School-Aged Children. In Portugal, this consumption has levelled off in adult men and in youngsters aged 15, but shows a significant increase in female adults and school-aged girls. CONCLUSIONS: Although Portugal presents low global prevalence rates in the European context, the substantial increases observed in the young adult female population are of particular concern because of its impact on women's health and the risk of pre and post-natal associated childhood exposure. These results reveal that current preventive strategies in Portugal are ineffective in reducing smoking prevalence among children and young adults.

Ecología trófica y aspectos reproductivos de Trichomycterus areolatus (Pisces, Trichomycteridae)en ambientes lóticos artificiales / Trophic ecology and reproductive aspects of Trichomycterus areolatus (Pisces, Trichomycteridae) in irrigation canal environments

Twelve of the sixteen species of fishes present in the Itata river basin enter the irrigation canals at least once a year, constituting a habitat that is frequently utilized by the native fish assemblages. However, only Trichomycterus areolatus, a native siluriform, is found in great number throughout the entire year, being the dominant species of such artificial environments. Among the factors that could explain the relative success of T. areolatus are its benthonic habits, adaptation to rithral habitat, an offer of trophic resources that is in line with its feeding habits, and a lower abundance of predators in the canals. In this study, the trophic ecology of this species in 174 individuals inhabiting the Itata river (Octava Región, Chile) and 231 from irrigation canals that arise from this river are analyzed and compared. In addition, the length-weight relationship and seasonal frequencies of reproductive status are analyzed, with the purpose of inferring on the status of these populations and their possible condition of resident in these canals. In canals, its diet includes a greater number of different taxa as well as total number of preys consumed in comparison with the river populations, including items of greater biomass, such as lumbriculides. The selectivity analysis showed that T. areolatus prefer prey items like Chironomidae, Baetidae, Elmidae, Plecoptera and Hyallela. Although both the river as well as canal populations show an isometric type growth, they reach greater body lengths and weights in the latter. According to the reproductive states analysis in different periods of the year, populations inhabiting canal environments reproduce synchronically with those of the river, although these latter tend to show a slight delay in the reproductive activity

Doce de las dieciséis especies de peces presentes en la cuenca del río Itata ingresan al menos en una época del año a los canales de riego, constituyendo un hábitat frecuentemente utilizado por la ictiofauna nativa. Sin embargo sólo el siluriforme Trichomycterus areolatus se encuentra en altas abundancias todo el año, siendo la especie dominante de estos ambientes fluviales artificiales. Entre los factores que pueden dar cuenta de su éxito relativo dentro de los canales están sus hábitos bentónicos y adaptación a ambientes ritrales, una oferta de recursos tróficos concordante con sus hábitos alimentarios y una menor abundancia de depredadores. En este estudio se analiza comparativamente la ecología trófica de esta especie en 174 individuos que habitan en el río Itata (Octava Región de Chile) y 231 de canales de riego que nacen de este sistema fluvial. Además se analizan las relaciones de talla-peso y frecuencia estacional de estados reproductivos, con el fin de inferir acerca del estado de las poblaciones y su condición de residentes en canales de riego. La dieta de las poblaciones de canales incluye una mayor riqueza de táxones y una mayor cantidad de presas consumidas respecto a las del curso natural. El análisis de selectividad muestra que T. areolatus prefiere, tanto en el río como en los canales de riego,presas tales como Chironomidae, Baetidae, Elmidae, Plecoptera y Hyallela. Además, en los canales de riego prefiere presas de mayor biomasa como los lumbricúlidos. Si bien las poblaciones locales de canales presentan, al igual que los ejemplares de río, un crecimiento de tipo isométrico, éstos alcanzan mayores tallas y pesos corporales que los individuos de los cauces naturales. De acuerdo al análisis de estados reproductivos de 345 ejemplares en diferentes períodos del año, las poblaciones de ambientes de canal se reproducen sincrónicamente con las del río, aunque con un leve retardo en la actividad reproductiva

Contaminación de catéteres endovenosos en un servicio pediátrico / Intravenous catheters contamination in a pediatric ward

La contaminación de los catéteres es una complicación común y a menudo inadvertida de la terapia endovenosa. Este estudio se efectuó para conocer la proporción de catéteres contaminados en nuestro medio, los gérmenes causales y algunos factores de riesgo asociados, en el Servicio de Pediatría del Hospital General de León, Gto. Se cultivaron, por rodamiento en agar, 116 catéteres obtenidos por simple disponibilidad (76 cortos y 40 largos). Se encontró una colonizacion global del 31.8 por ciento, con predominio de bacilos gramnegativos, seguidos por cocos grampositivos, La contaminación fue mayor para los catéteres largos que para los cortos (65 vs 14.4 por ciento, P<0.0001). Todos los catéteres cortos se habían aplicado por punción y todos los largos, por venodisección. Como factor asociado con la colonización de los catéteres largos se encontró el tiempo quirúrgico de venodisección mayor de 25 minutos. Para los cortos, los factores relacionados fueron la permanencia mayor de 72 horas y más de tres intentos fallidos en la aplicación. Se concluye en la necesidad de hacer conciencia del riesgo de la contaminación de la cateterización endovenosa, de contar con personal experto en la aplicación de catéteres y de preferir su aplicación por punción