Normocephalic sagittal craniosynostosis in young children is common and unrecognized.

OBJECTIVE: Sagittal craniosynostosis (SC) is usually diagnosed during early childhood by the presence of scaphocephaly. Recently, our group found 3.3% of children under 5 years of age with normocephalic sagittal craniosynostosis (NSC) using computed tomography (CT) scans. This paper aims to validate our preliminary findings using a larger cohort of patients, and analyze factors associated with incidental NSC. METHODS: A retrospective review of head CT scans in patients aged 0 to 71 months who presented to the emergency department of our tertiary care institution between 2008 and 2020 was completed. Patients with syndromes associated with craniosynostosis (CS), history of hydrocephalus, or other brain/cranial abnormalities were excluded. Two craniofacial surgeons reviewed the CT scans to evaluate the presence and extent of CS. Demographic information, gestational age, past medical and family history, medications, and chief complaint were recorded as covariates, and differences between patients with and without CS were analyzed. Furthermore, comparison of the prevalence of CS across age groups was studied. Additional analysis exploring association between independent covariates and the presence of CS was performed in two sub-cohorts: patients ≤ 24 months of age and patients > 24 months of age. RESULTS: A total of 870 scans were reviewed. SC was observed in 41 patients (4.71% - 25 complete, 16 incomplete), all with a normal cranial index (width/length > 0.7). The prevalence of SC increased up to 36 months of age, then plateaued through 72 months of age. Patients under 2 years of age with family history of neurodevelopmental disease had 49.32 (95% CI [4.28, 567.2]) times higher odds of developing CS. Sub-cohort of patients above 24 months of age showed no variable independently predicted developing CS. CONCLUSION: NSC in young children is common. While the impact of this condition is unknown, the correlation with family history of neurodevelopmental disease is concerning.

Secukinumab demonstrates high efficacy and a favourable safety profile in paediatric patients with severe chronic plaque psoriasis: 52-week results from a Phase 3 double-blind randomized, controlled trial.

BACKGROUND: Secukinumab has demonstrated sustained long-term efficacy with a favourable safety profile in various psoriatic disease manifestations in adults. OBJECTIVES: Here, the efficacy and safety of two secukinumab dosing regimens [low dose (LD) and high dose (HD)] in paediatric patients with severe chronic plaque psoriasis over one year are reported. METHODS: In this multicentre, double-blind study (NCT02471144), patients aged 6 to <18 years with severe chronic plaque psoriasis were stratified and randomized by weight (<25 kg, 25 to <50 kg, ≥50 kg) and age (6 to <12 years, 12 to <18 years) to receive low-dose (LD: 75/75/150 mg) or high-dose (HD: 75/150/300 mg) subcutaneous secukinumab or placebo or etanercept 0.8 mg/kg (up to a max of 50 mg). RESULTS: Overall, 162 patients were randomized to receive secukinumab LD (n = 40) or HD (n = 40), etanercept (n = 41) or placebo (n = 41). The co-primary objectives of the study were met with both secukinumab doses (LD and HD) showing superior efficacy compared to placebo (P < 0.0001) with respect to PASI 75 response (80.0%, 77.5% vs. 14.6%) and IGA mod 2011, 0 or 1 response (70%, 60% vs. 4.9%) at Week 12. Both secukinumab doses were superior to placebo (P < 0.0001) with respect to PASI 90 response at Week 12 (72.5%, 67.5% vs. 2.4%). The efficacy of both doses was sustained to Week 52 with secukinumab achieving higher responses vs. etanercept (PASI 75/90/100: LD, 87.5%/75.0%/40.0% and HD, 87.5%/80.0%/47.5.% vs. etanercept, 68.3%/51.2%/22.0% and IGA 0 or 1: LD, 72.5% and HD, 75.0% vs. etanercept, 56.1%). The safety profile of secukinumab was consistent with the adult Phase 3 studies, with no new safety signals identified. CONCLUSIONS: Both doses of secukinumab demonstrated high and sustained efficacy up to Week 52 with a favourable safety profile in paediatric patients with severe chronic plaque psoriasis.

POGLUT1 biallelic mutations cause myopathy with reduced satellite cells, α-dystroglycan hypoglycosylation and a distinctive radiological pattern.

Protein O-glucosyltransferase 1 (POGLUT1) activity is critical for the Notch signaling pathway, being one of the main enzymes responsible for the glycosylation of the extracellular domain of Notch receptors. A biallelic mutation in the POGLUT1 gene has been reported in one family as the cause of an adult-onset limb-girdle muscular dystrophy (LGMD R21; OMIM# 617232). As the result of a collaborative international effort, we have identified the first cohort of 15 patients with LGMD R21, from nine unrelated families coming from different countries, providing a reliable phenotype-genotype and mechanistic insight. Patients carrying novel mutations in POGLUT1 all displayed a clinical picture of limb-girdle muscle weakness. However, the age at onset was broadened from adult to congenital and infantile onset. Moreover, we now report that the unique muscle imaging pattern of "inside-to-outside" fatty degeneration observed in the original cases is indeed a defining feature of POGLUT1 muscular dystrophy. Experiments on muscle biopsies from patients revealed a remarkable and consistent decrease in the level of the NOTCH1 intracellular domain, reduction of the pool of satellite cells (SC), and evidence of α-dystroglycan hypoglycosylation. In vitro biochemical and cell-based assays suggested a pathogenic role of the novel POGLUT1 mutations, leading to reduced enzymatic activity and/or protein stability. The association between the POGLUT1 variants and the muscular phenotype was established by in vivo experiments analyzing the indirect flight muscle development in transgenic Drosophila, showing that the human POGLUT1 mutations reduced its myogenic activity. In line with the well-known role of the Notch pathway in the homeostasis of SC and muscle regeneration, SC-derived myoblasts from patients' muscle samples showed decreased proliferation and facilitated differentiation. Together, these observations suggest that alterations in SC biology caused by reduced Notch1 signaling result in muscular dystrophy in LGMD R21 patients, likely with additional contribution from α-dystroglycan hypoglycosylation. This study settles the muscular clinical phenotype linked to POGLUT1 mutations and establishes the pathogenic mechanism underlying this muscle disorder. The description of a specific imaging pattern of fatty degeneration and muscle pathology with a decrease of α-dystroglycan glycosylation provides excellent tools which will help diagnose and follow up LGMD R21 patients.

Positive influence of a dental anaesthesia simulation model on the perception of learning by Mexican dental students.

INTRODUCTION: This study evaluated the influence of three-repetition training with a dental anaesthesia simulation model (DASM) on the perception of learning by dental students. MATERIALS AND METHODS: Dental students who had never used a dental anaesthesia technique were randomly divided into two groups that were taught the anterior superior alveolar nerve infiltrative anaesthesia technique. Group 1 (G1; N = 10) followed a three-stage learning method: (i) theoretical lecture, (ii) clinical demonstration and (iii) DASM training, including three repetitions of the anaesthesia technique. Group 2 (G2; N = 10) followed only the 1st and 2nd stages. The students in both groups then performed the anaesthesia technique. The perception of the students was evaluated by four learning concepts. Each was evaluated with a 5-point Likert scale questionnaire. The average score of each item of the questionnaire for G1 was compared with that of G2. Statistically significant differences were identified with the Mann-Whitney test. The average working time of each group was timed and compared by Student's t-test to identify possible statistically significant differences. RESULTS: Students in G1 showed higher average scores of perception in controlling the handling of the dental syringe and confidence in performing the injection (P < 0.05) and showed an average working time shorter than that of the students in G2 (P < 0.05). CONCLUSION: The DASM positively influenced the perception learning of the dental students; it increased their confidence and syringe handling ability, as well as skills to perform the injection of anaesthesia more quickly.

Association of polymorphisms in growth hormone and leptin candidate genes with live weight traits of Brahman cattle.

Polymorphisms in candidate genes can produce significant and favorable changes in the phenotype, and therefore are useful for the identification of the best combination of favorable variants for marker-assisted selection. In the present study, an assessment to evaluate the effect of 11 single nucleotide polymorphisms (SNPs) in candidate genes on live weight traits of registered Brahman cattle was performed. Data from purebred bulls were used in this assessment. The dataset included birth (BW), weaning (WW), and yearling (YW) weights. A panel of 11 SNP markers, selected by their formerly reported or apparent direct and indirect association with live weight traits, was included in an assessment previously confirming their minimum allele frequency (<0.05). Live weights were adjusted BW (aBW), WW (aWW), and YW (aYW) using a generalized linear model, which included the fixed effects of herd and season of birth and the random effect of the sire and year of birth. An SNP in a growth hormone gene (GH4.1) was significantly related to aWW (P = 0.035) with an estimate substitution effect of 3.97 kg (P = 0.0210). In addition, a leptin SNP (LEPg.978) was significantly associated with aYW (P = 0.003) with an estimate substitution effect of 9.57 kg (P = 0.0007). The results suggest that markers GH4.1 and LEPg.978 can be considered as candidate loci for assisted genetic improvement programs in Mexican Brahman cattle.

A simple mathematical model that describes the growth of the area and the number of total and viable cells in yeast colonies.

UNLABELLED: We propose a model, based on the Gompertz equation, to describe the growth of yeasts colonies on agar medium. This model presents several advantages: (i) one equation describes the colony growth, which previously needed two separate ones (linear increase of radius and of the squared radius); (ii) a similar equation can be applied to total and viable cells, colony area or colony radius, because the number of total cells in mature colonies is proportional to their area; and (iii) its parameters estimate the cell yield, the cell concentration that triggers growth limitation and the effect of this limitation on the specific growth rate. To elaborate the model, area, total and viable cells of 600 colonies of Saccharomyces cerevisiae, Debaryomyces fabryi, Zygosaccharomyces rouxii and Rhodotorula glutinis have been measured. With low inocula, viable cells showed an initial short exponential phase when colonies were not visible. This phase was shortened with higher inocula. In visible or mature colonies, cell growth displayed Gompertz-type kinetics. It was concluded that the cells growth in colonies is similar to liquid cultures only during the first hours, the rest of the time they grow, with near-zero specific growth rates, at least for 3 weeks. SIGNIFICANCE AND IMPACT OF THE STUDY: Mathematical models used to predict microbial growth are based on liquid cultures data. Models describing growth on solid surfaces, highlighting the differences with liquids cultures, are scarce. In this work, we have demonstrated that a single Gompertz equation describes accurately the increase of the yeast colonies, up to the point where they reach their maximum size. The model can be used to quantify the differences in growth kinetics between solid and liquid media. Moreover, as all its parameters have biological meaning, it could be used to build secondary models predicting yeast growth on solid surfaces under several environmental conditions.

Fermentation adaptability of three probiotic Lactobacillus strains to oat, germinated oat and malted oat substrates.

Functional foods targeting the improvement of gastrointestinal health are widely recognized; of these, dairy-based probiotics are the most popular. Thus, the design of nondairy probiotics applying fruits, vegetables and cereals has raised great interest in the healthy food sector. The objective of this work was to assess the potential of germinated and malted oat substrates to support the growth of the probiotic cultures Lactobacillus acidophilus, Lactobacillus casei and Lactobacillus rhamnosus. Fermentations were carried out with distinctive oat substrates at inoculum levels of 3, 5 and 7% v/v, substrate concentrations of 3, 5 and 7% w/v and with sucrose addition 1·5% w/v. Lag phase profiles, maximum growth rates and maximal growths were evaluated; protein and sugar contents were also quantified. There was no significant effect (P > 0·05) of the inoculum size on the fermentation kinetics; however, oat media significantly affected the growth kinetics. In simple oat media, Lact. acidophilus exhibited biphasic growth patterns. Lactobacillus growth patterns were significantly affected (P < 0·05) by the supplementation with protein sources. The germination and malting processes significantly improved oats nutrient characteristics demonstrating to be adequate substrates for the fermentation with probiotic lactobacilli. Significance and impact of the study: In this work, the effect of oat media composition and fermentation conditions on the growth kinetics of three probiotic lactobacilli was determined. The variation in the inoculum levels did not have a significant effect on the probiotic cultures growth. Results revealed that protein supplemented simple, germinated and malted oat enhanced the cell viability of the probiotic lactobacilli; Lactobacillus casei exhibited better growth adaptability. The results also highlight that different weight in volume oat substrate concentrations has particular effects on Lact. casei growth kinetics. Our results contribute to a better understanding of oat-based media formulations as substrates for probiotic cultures.

Goat milk consumption modulates liver divalent metal transporter 1 (DMT1) expression and serum hepcidin during Fe repletion in Fe-deficiency anemia.

Iron deficiency is the most prevalent micronutrient deficiency worldwide. In spite of the crucial role of hepatocyte divalent metal transporter 1 (DMT1) and hepcidin in Fe metabolism, to date, no studies have directly tested the role of these proteins in liver Fe metabolism during Fe repletion after induced Fe-deficiency anemia. Therefore, the aim of the current study was to assess the effect of goat or cow milk-based diets on Fe metabolism in one of the main body storage organs, the liver, during the course of Fe repletion with goat or cow milk-based diets in anemic rats. Animals were placed on a preexperimental period of 40 d, a control group receiving a normal-Fe diet and the Fe-deficient group receiving a low-Fe diet (5 mg of Fe/kg of diet). Rats were fed for 30 d with goat or cow milk-based diets with normal Fe content (45 mg of Fe/kg of diet). The hematological parameters, serum hepcidin, hepatosomatic index, liver Fe content, and liver DMT1 expression were determined. During the recovery of the anemia with milk-based diets, the restoration of liver Fe content and hematological parameters, especially with goat milk, increased the red blood cell count, favoring the oxygen supply and weight gain. Moreover, goat milk consumption potentiates liver DMT1 expression, enhancing Fe metabolism and storage. In addition, the increase in serum hepcidin in anemic rats observed in the current study also explains and supports the higher liver Fe content after supplying goat milk, because it blocks the liberation of Fe from hepatocytes, increasing its storage in liver.

Impact of single and combined local air pollution mitigation measures in an urban environment.

Urban air pollution is one of the most important environmental problems for human health and several strategies have been developed for its mitigation. The objective of this study is to assess the impact of single and combined mitigation measures on concentrations of air pollutants emitted by traffic at pedestrian level in the same urban environment. The effectiveness of different scenarios of green infrastructure (GI), the implementation of photocatalytic materials and traffic low emission zones (LEZ) are investigated, as well as several combinations of LEZ and GI. A wide set of scenarios is simulated through Computational Fluid Dynamics (CFD) modelling for two different wind directions (perpendicular (0°) and 45° wind directions). Wind flow for the BASE scenario without any measure implemented was previously evaluated using wind-tunnel measurements. Air pollutant concentrations for this scenario are compared with the results obtained from the different mitigation scenarios. Reduction of traffic emissions through LEZ is found to be the most effective single measure to improve local air quality. However, GI enhances the effects of LEZ, which makes the combination of LEZ + GI a very effective measure. The effectiveness of this combination depends on the GI layout, the intensity of emission reduction in the LEZ and the traffic diversion in streets surrounding the LEZ. These findings, in line with previous literature, suggest that the implementation of GI may increase air pollutant concentrations at pedestrian level for some cases. However, this study highlights that this negative effect on air quality can turn into positive when used in combination with reductions of local traffic emissions.

Rationale and study design for an Individualized PeriopeRative Open lung VEntilatory approach in Emergency Abdominal Laparotomy/scopy: study protocol for a prospective international randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPC) are the most frequent postoperative complications, with an estimated prevalence in elective surgery ranging from 20% in observational cohort studies to 40% in randomized clinical trials. However, the prevalence of PPCs in patients undergoing emergency abdominal surgery is not well defined. Lung-protective ventilation aims to minimize ventilator-induced lung injury and reduce PPCs. The open lung approach (OLA), which combines recruitment manoeuvres (RM) and positive end-expiratory pressure (PEEP) titration, aims to minimize areas of atelectasis and the development of PPCs; however, there is no conclusive evidence in the literature that OLA can prevent PPCs. The purpose of this study is to compare an individualized perioperative OLA with conventional standardized lung-protective ventilation in patients undergoing emergency abdominal surgery with clinical signs of intraoperative lung collapse. METHODS: Randomized international clinical trial to compare an individualized perioperative OLA (RM plus individualized PEEP and individualized postoperative respiratory support) with conventional lung-protective ventilation (standard PEEP of 5 cmH2O and conventional postoperative oxygen therapy) in patients undergoing emergency abdominal surgery with clinical signs of lung collapse. Patients will be randomised to open-label parallel groups. The primary outcome is any severe PPC during the first 7 postoperative days, including: acute respiratory failure, pneumothorax, weaning failure, acute respiratory distress syndrome, and pulmonary infection. The estimated sample size is 732 patients (366 per group). The final sample size will be readjusted during the interim analysis. DISCUSSION: The Individualized Perioperative Open-lung Ventilatory Strategy in emergency abdominal laparotomy (iPROVE-EAL) is the first multicentre, randomized, controlled trial to investigate whether an individualized perioperative approach prevents PPCs in patients undergoing emergency surgery.

Using dispersion models at microscale to assess long-term air pollution in urban hot spots: A FAIRMODE joint intercomparison exercise for a case study in Antwerp.

In the framework of the Forum for Air Quality Modelling in Europe (FAIRMODE), a modelling intercomparison exercise for computing NO2 long-term average concentrations in urban districts with a very high spatial resolution was carried out. This exercise was undertaken for a district of Antwerp (Belgium). Air quality data includes data recorded in air quality monitoring stations and 73 passive samplers deployed during one-month period in 2016. The modelling domain was 800 × 800 m2. Nine modelling teams participated in this exercise providing results from fifteen different modelling applications based on different kinds of model approaches (CFD - Computational Fluid Dynamics-, Lagrangian, Gaussian, and Artificial Intelligence). Some approaches consisted of models running the complete one-month period on an hourly basis, but most others used a scenario approach, which relies on simulations of scenarios representative of wind conditions combined with post-processing to retrieve a one-month average of NO2 concentrations. The objective of this study is to evaluate what type of modelling system is better suited to get a good estimate of long-term averages in complex urban districts. This is very important for air quality assessment under the European ambient air quality directives. The time evolution of NO2 hourly concentrations during a day of relative high pollution was rather well estimated by all models. Relative to high resolution spatial distribution of one-month NO2 averaged concentrations, Gaussian models were not able to give detailed information, unless they include building data and street-canyon parameterizations. The models that account for complex urban geometries (i.e. CFD, Lagrangian, and AI models) appear to provide better estimates of the spatial distribution of one-month NO2 averages concentrations in the urban canopy. Approaches based on steady CFD-RANS (Reynolds Averaged Navier Stokes) model simulations of meteorological scenarios seem to provide good results with similar quality to those obtained with an unsteady one-month period CFD-RANS simulations.

First Report of Konjac mosaic virus in Zamioculcas zamiifolia.

Zamioculcas zamiifolia (Lodd.) Engl. ("Zanzibar Gem," "ZZ plant") is the monotypic species of the genus belonging to the family Araceae. It is a stemless perennial plant native to Africa, from Kenya to South Africa, that produces succulent rhizomes at the base of its attractive dark green and glossy foliage. Symptoms of mosaic and foliar distortion were observed on a plant purchased at an ornamental plants shop in São Paulo state, Brazil. In order to identify the causal agent, transmission and serological tests, as well as electron microscopy (EM) observations, reverse transcription (RT)-PCR, and sequencing were carried out. EM observations revealed the presence of elongated, flexuous viral particles in foliar extracts and cytoplasmic lamellar aggregates of type II lamellar inclusions (Edwardson's classification), in thin sections. No symptoms were induced following mechanical inoculation on Chenopodium amaranticolor, C. murale, Gomphrena globosa, Nicotiana megalosiphon, N. debneyii, nor on the aroids Philodendron scandens, P. selloum, Dieffenbachia amoena, Colocasia esculenta, and Z. zamiifolia. Up to 2 months after inoculation, plants were still symptomless, and the virus was not detected by RT-PCR. The indirect ELISA tests were negative with antisera against Dasheen mosaic virus (gift from F. W. Zettler, University of Florida) and Turnip mosaic virus (gift from P. Roggero, IFA, Turin, Italy). RT-PCR performed on the original purchased ornamental plant with potyvirus-specific primers (CI-R = ACICCRTTYTCDATDATRTTIGTIGC and CI-F = GGIVVIGTIGGIWSIGGIAARTCIAC) targeting the cytoplasmic inclusion protein cistron of the potyvirus genome produced a fragment of approximately 650 bp (GenBank Accession No. KC990386). The sequence was similar to those of potyvirus species with nucleotide identity, determined by PAUP v.4.0b10 for Macintosh, ranging from 64% for Pokeweed mosaic virus (JQ609065) to 93% for Konjac mosaic virus KoMV-F (NC007913). KoMV has been detected in aroid species in Taiwan, India, Korea, Japan (1,2), Germany, and The Netherlands (3,4). This is the first report of a viral disease on Z. zamiifolia and of KoMV in the Americas. Such information along with the vegetative propagation of ZZ plants strongly suggests that KoMV is spread worldwide. References: (1) P. Manikonda et al. J. Phytopathol. 159:133, 2011. (2) M. Nishiguchi et al. Arch Virol. 151:1643, 2006. (3) D.-E. Lesemann and S. Winter. Acta Hort. 568:135, 2002. (4) K. Pham et al. Acta Hort. 568:143, 2002.

[Study of the expression of neural stem cell markers in neuroblastoma tumor samples and correlation with prognostic factors]. / Estudio de expresión de marcadores de células madre neurales en neuroblastoma y correlación con factores pronóstico.

INTRODUCTION: The existence of cancer stem cells (CSC) in neuroblastoma (NB) has been associated with the development of metastasis, resistance to chemotherapy and recurrence. Our objective is to analyze the expression of proliferation and differentiation markers of neural progenitor cells in NB samples, and to correlate this expression with clinical variables such as histology, genetics and response to conventional therapy. MATERIAL AND METHODS: We performed a retrospective-experimental study with neuroblastoma samples obtained from biopsies or tumor resections between 2010-2012 in our Hospital. Fluorescence immunohistochemistry was used to analyze the expression of the different markers: CD44, CD74, CD133, tyrosine hydroxylase, endothelin receptors type A (ETA) and B (ETB), p75, nestina y and Phox2b, all of them related to neural stem cell biology. The level of expression of the markers was then correlated with clinical variables. RESULTS: Nestin expression was positive in 72.2% of samples and ETA in 66.7%. PHOX2B and CD74 expression were lower, being positive in less than 30%. The markers CD44, ETB and PHOX2B were expressed in more aggressive tumors. ETA expression correlated significantly with unfavorable histology tumors (p= 0.01), N-myc amplification (p= 0.05) and recurrence/progression (p= 0.05). CONCLUSION: The expression of CD44, ETB and ETA was associated with more aggressive tumors and poor prognostic factors. These markers are in the membrane of neural stem cells and may be useful to identify and isolate by flow cytometry CSCs of NB for the study of new therapeutic targets.

Isolated cardiomyopathy caused by a DMD nonsense mutation in somatic mosaicism: genetic normalization in skeletal muscle.

X-linked dilated cardiomyopathy is a pure cardiac dystrophinopathy phenotype mainly caused by DMD mutations that present a specific transcription effect in cardiac tissue. We report a 26-year-old male who presented with severe dilated cardiomyopathy and high creatine kinase. The patient did not complain of skeletal muscle weakness. A muscle biopsy showed mild dystrophic changes and a low proportion of dystrophin-negative fibres. A molecular study identified a nonsense DMD mutation (p.Arg2098X) in somatic mosaicism. The ratio of mutant versus normal allele in blood and skeletal muscle suggests selective pressure against mutant muscle cells, a process known as genetic normalization. We hypothesize that this process may have mitigated skeletal muscle symptoms in this patient. This is the second report of a DMD somatic mosaic with evidence of genetic normalization in muscle. Somatic DMD mutations should be considered in patients presenting with idiopathic dilated cardiomyopathy.

[Fibreoptic clinical training in anaesthesia. Course design and results based on a self-assessment survey]. / Entrenamiento clínico con fibrobroncoscopio en anestesia. Diseño y resultados del curso según encuesta de autoevaluación.

BACKGROUND AND OBJECTIVE: Fibreoptic intubation is the technique of choice for resolving complications related to a difficult airway. Our aim was to determine whether a clinical-practice-based, individualized course provides sufficient training and confidence to allow anaesthetists to routinely practice fibreoptic intubation. METHODS: Our hospital developed a clinical-practice-based, individualized course on fibreoptic intubation in general anaesthesia that provided practice in sedated spontaneously breathing patients and insertion through supraglottic devices. From 2005 to 2009, we e-mailed participants for response to an anonymous online self-assessment survey. We asked participants about the training outcomes and their overall degree of satisfaction. RESULTS: Seventy-seven participants were sent the questionnaire six months after the course and 61% responded. All respondents considered themselves skilled in handling the bronchoscope at the end of the course and 97% used it in their routine practice in patients with difficult airways. CONCLUSIONS: These results suggest a high success rate can be expected from individually tailored fibreoptic intubation courses that supplement theory and mannequin experience with clinical practice.

Estimates of population exposure to atmospheric pollution and health-related externalities in a real city: The impact of spatial resolution on the accuracy of results.

Health impacts of atmospheric pollution is an important issue in urban environments. Its magnitude depends on population exposure which have been frequently estimated by considering different approaches relating pollutant concentration and population exposed to it. However, the uncertainties due to the spatial resolution of the model used to estimate the pollutant concentration or due to the lack of representativeness of urban air quality monitoring station (AQMS) have not been evaluated in detail. In this context, NO2 annual average concentration at pedestrian level in the whole city of Pamplona (Spain) modelled at high spatial resolution (~1 m) by Computational Fluid Dynamic (CFD) simulations is used to estimate the total population exposure and health-related externalities by using different approaches. Air pollutant concentration and population are aggregated at different spatial resolutions ranging from a horizontal grid cell size of 100 m × 100 m to a coarser resolution where the whole city is covered by only one cell (6 km × 5 km). In addition, concentrations at AQMS locations are also extracted to assess the representativeness of those AQMS. The case with a spatial resolution of 100 m × 100 m for both pollutant-concentration distribution and population data is used as a reference (Base case) and compared with those obtained with the other approaches. This study indicates that the spatial resolution of concentration and population distribution in the city should be 1 km × 1 km or finer to obtain appropriate estimates of total population exposure (underestimations <13%) and health-related externalities (underestimations <37%). For the cases with coarser resolutions, a strong underestimation of total population exposure (>31%) and health-related externalities (>76%) was found. On the other hand, the use of AQMS concentrations can induce important errors due to the limited spatial representativeness, in particular in terms of population exposure.

[An established anesthesia team-care model: over 12000 cases in a digestive endoscopy unit]. / Consolidación de un modelo asistencial basado en un equipo de anestesia: experiencia en más de 12.000 casos en una Unidad de Endoscopia Digestiva.

BACKGROUND AND OBJECTIVE: The growing demand for digestive and other endoscopic procedures outside the operating room, both in terms of type of endoscopy and number of patients, requires reorganization of the anesthesiology department's workload. We describe 2 years of our hospital digestive endoscopy unit's experience with a now well-established care model involving both anesthesiologists and nurse anesthetists. MATERIAL AND METHODS: After previously reviewing the medical records of outpatients and conducting a telephone interview about state of health, nurse anesthetists administered a combination of propofol and remifentanil through a target-controlled infusion system under an anesthesiologist's direct supervision. RESULTS: The ratio of anesthesiologists to nurses ranged from 1:2 to 1:3 according to the complexity of the examination procedure. Over 12000 endoscopies (simple to advanced) in a total of 11853 patients were performed under anesthesia during the study period. Airway management maneuvers were required by 4.9% of the patients; 0.18% required bag ventilation for respiratory depression, and 0.084% required bolus doses of a vasopressor to treat hypotension or atropine to treat bradycardia. The procedure had to be halted early in 9 patients (0.07%). No patient required orotracheal intubation and none died. Nor were any complications related to sedation recorded. CONCLUSION: The results suggest that this care model can safely accommodate a large caseload in anesthesia at an optimum level of quality.

Estimates of pedestrian exposure to atmospheric pollution using high-resolution modelling in a real traffic hot-spot.

Atmospheric pollution is a very relevant risk for the human health, in particular in urban environments, where most people lives and high levels of pollution are found. Population exposure is traditionally estimated through concentration recorded at air quality monitoring stations (AQMS) or modelled at a spatial resolution of the order of 1 km2. However, these methodologies have limitations in urban areas where strong gradients of concentration, even in the same street, exist. In addition, the movements of pedestrians make difficult to compute reliable estimates of pollutant concentration to which people are exposed to. In this context, the main objective of this study is to estimate the exposure of pedestrians to ambient nitrogen oxides (NOx) concentrations with high spatial resolution in a real urban traffic hot-spot under different methodologies. To achieve this objective, a novel methodology which combines high-resolution NOx concentrations from computational fluid dynamic (CFD) simulations with the pedestrian flows obtained by pedestrian mobility microsimulations is applied to an urban area of Madrid, Spain. High-resolution maps show pedestrian exposure peaks, at bus stops and crosswalks, that cannot be captured by the simpler methods based on spatial average concentration (SAC) or concentration measured in an AQMS. Total daily exposure obtained is 1.19 · 109 person s µg m-3, while SAC and AQMS concentration methods yielded 9-23% and 30-40% lower values. In conclusion, the proposed methodology allows to determine the areas with higher exposure in order to design local strategies to reduce the impact on human health. In addition, from a more general point of view, the total exposure in the studied area is better estimated by using spatial average concentration than through concentration recorded by AQMS. The assessment of the spatial representative of AQMS becomes necessary to use AQMS concentration to evaluate air quality and population exposure of an urban area.

Genetic and environmental parameters for milk production, udder health, and fertility traits in Mexican Holstein cows.

Genetic and phenotypic parameters for Mexican Holstein cows were estimated for first- to third-parity cows with records from 1998 to 2003 (n=2,971-15,927) for 305-d mature equivalent milk production (MEM), fat production (MEF), and protein production (MEP), somatic cell score (SCS), subsequent calving interval (CAI), and age at first calving (AFC). Genetic parameters were obtained by average information matrix-REML methodology using 6-trait (first-parity data) and 5-trait (second- and third-parity data) animal models. Heritability estimates for production traits were between 0.17+/-0.02 and 0.23+/-0.02 for first- and second-parity cows and between 0.12+/-0.03 and 0.13+/-0.03 for third-parity cows. Heritability estimates for SCS were similar for all parities (0.10+/-0.02 to 0.11+/-0.03). For CAI, estimates of heritability were 0.01+/-0.05 for third-parity cows and 0.02+/-0.02 for second-parity cows. The heritability for AFC was moderate (0.28+/-0.03). No unfavorable estimates of correlations were found among MEM, MEF, MEP, CAI, and SCS. Estimates of environmental and phenotypic correlations were large and positive among production traits; favorable between SCS and CAI; slightly favorable between MEM, MEF, and MEP and SCS, between AFC and SCS, and between SCS and CAI; and small but unfavorable between production traits and CAI. Estimates of genetic variation and heritability indicate that selection would result in genetic improvement of production traits, AFC, and SCS. Estimates of both heritability and genetic variation for CAI were small, which indicates that genetic improvement would be difficult.

Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert's disease. / Guía clínica para el diagnóstico y seguimiento de la distrofia miotónica tipo 1, DM1 o enfermedad de Steinert.

BACKGROUND AND OBJECTIVES: Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1. MATERIAL AND METHODS: Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide. RECOMMENDATIONS: The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives. CONCLUSION: MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up.