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Introduction: Recently, cystic fibrosis transmembrane regulator modulator therapy with elexacaftor/tezacaftor/ivacaftor has become available for children with cystic fibrosis (CF) carrying at least one F508del mutation. Objective: To assess the intermediate term effects of elexacaftor/tezacaftor/ivacaftor in children with cystic fibrosis in a real-world setting. Methods: We performed a retrospective analysis of records of children with cystic fibrosis, who started elexacaftor/tezacaftor/ivacaftor between 8/2020 and 10/2022. Pulmonary function tests, nutritional status, sweat chloride and laboratory data were assessed before, 3 and 6 months after the start of elexacaftor/tezacaftor/ivacaftor respectively. Results: Elexacaftor/tezacaftor/ivacaftor was started in 22 children 6–11 years and in 24 children 12–17 years. Twenty-seven (59%) patients were homozygous for F508del (F/F) and 23 (50%) patients were transitioned from ivacaftor/lumacaftor (IVA/LUM) or tezacaftor/ivacaftor (TEZ/IVA) to elexacaftor/tezacaftor/ivacaftor. Overall, mean sweat chloride concentration decreased by 59.3 mmol/L (95% confidence interval: -65.0 to -53.7 mmol/L, p < 0.0001) under elexacaftor/tezacaftor/ivacaftor. Sweat chloride concentration also decreased significantly after transition from IVA/LUM or TEZ/IVA to elexacaftor/tezacaftor/ivacaftor (-47.8 mmol/l; 95% confidence interval: -57.6 to -37.8 mmol/l, n = 14, p < 0.0001). Sweat chloride reduction was more marked in children with the F/F than in those with the F/MF genotype (69.4 vs 45.9 mmol/L, p < 0.0001). At 3 months follow-up, body-mass-index-z-score increased by 0.31 (95% CI, 0.2–0.42, p < 0.0001) with no further increase at 6 months. BMI-for-age-z-score was more markedly improved in the older group. Overall pulmonary function (percent predicted FEV1) at 3 months follow-up increased by 11.4% (95% CI: 8.0–14.9, p < 0.0001) with no further significant change after 6 months. No significant differences were noted between the age groups. Children with the F/MF genotype had a greater benefit regarding nutritional status and pulmonary function tests than those with the F/F genotype. Adverse events led to elexacaftor/tezacaftor/ivacaftor dose reduction in three cases and a temporary interruption of therapy in four cases. Conclusion: In a real-world setting, elexacaftor/tezacaftor/ivacaftor therapy had beneficial clinical effects and a good safety profile in eligible children with cystic fibrosis comparable to previously published data from controlled clinical trials. The positive impact on pulmonary function tests and nutritional status seen after 3 months of elexacaftor/tezacaftor/ivacaftor therapy was sustained at 6 months follow-up. [ABSTRACT FROM AUTHOR]

Objective: to identify the relationship between the use of information and communication technologies (ICTs) and anxiety, alcohol and tobacco consumption in high school adolescents from Puebla, Mexico. Method: descriptive correlational study, carried out with 301 adolescents from a public school in 2018. The New Addictions Detection Questionnaire and Hamilton Anxiety Scale were applied. For statistical analysis, the Kolmogorov Smirnov coefficient and Mann Whitney U, Spearman correlation and multiple linear regression. Results: the mean use of ICTs was 84.36 (SD = 15.1). Internet (M = 16.72, SD = 4.6) and cell phones (M = 15.52, SD = 5.0) were the most used. The use of ICTs and anxiety were statistically significant (F=21.719, p=.001), where the Internet and television predicted anxiety. About the use of ICTs and alcohol consumption (F = 3.745, p =.001) indicates that what this condition predicts is the use of cell phones. In the case of ICTs with tobacco use, there was no statistical significance. Conclusion: there is a relationship with the use of ICTs, anxiety and alcohol consumption in high school students in the state of Puebla. [ABSTRACT FROM AUTHOR]

Background: To determine the effect of threshold inspiratory muscle training (IMT) on functional fitness and respiratory muscle strength (RMS) compared to incentive spirometry (IS) in children/adolescents with obesity. Methods: A total of 60 obese children/adolescents aged 8-15 years were randomized into the threshold IMT group (n = 20), the IS group (n = 20), or the control group (n = 20). The IMT group performed 30 inspiratory breaths with the intensity set at 40% of baseline maximal inspiratory pressure (MIP) twice daily for 8 weeks; the IS group performed 30 breaths with sustained maximum inspiration twice daily for 8 weeks; and, the control group was assigned no training device for 8 weeks. Six-min walk test (6-MWT), RMS, and spirometry were compared between baseline and 8 weeks. Results: Six-MWT distance (528.5 ± 36.2 vs. 561.5 ± 35.2 m, p = 0.002) and MIP (121.2 ± 26.8 vs. 135.3 ± 32.1%Predicted, p = 0.03) were significantly improved after 8 weeks of IMT training. There was no significant difference in any evaluated pulmonary function parameters between baseline and 8 weeks in the IS or control groups; however, 6-MWT distance demonstrated a trend toward significant improvement in the IS group (526.9 ± 59.1 vs.549.0 ± 50.6 m, p = 0.10). No significant difference among groups was found for any variable relative to change from baseline to post-training. Conclusions: Eight weeks of threshold IMT training significantly improved both inspiratory muscle strength (MIP) and functional fitness (6-MWT) in children/adolescents with obesity. Eight weeks of IS training yielded a trend toward significantly improved functional fitness. [ABSTRACT FROM AUTHOR]

Objective: to relate depression and quality of life in hemodialysis patients. Method: descriptive and correlational study, with patients aged between 18 and 65 years on hemodialysis, in a health institution in the state of Puebla, Mexico. The Beck Depression Inventory and the WHOKOL-BREF questionnaire were applied in march 2020. For the analysis, the Spearman correlation and the Mann Whitney U were used. Results: 61% of the population was formed by men, whose age varied from 34 to 49 years old. More than 50% had from 6 to 10 years with a hemodialysis treatment. 41.7% showed mild depression, 20.8 moderate and 37.5 low. The average quality of life was 56.3 (SD=6.3). There is a negative and significant relationship between depression and quality of life (rs = -.530, p =.001). Conclusion: the presence of depression in hemodialysis patients presents changes in social relationships and physical health, and the greater the depression, the lower the quality of life. [ABSTRACT FROM AUTHOR]

Catalytic inhibition of topoisomerase II during G2 phase delays onset of mitosis due to the activation of the so‐called decatenation checkpoint. This checkpoint is less known compared with the extensively studied G2 DNA damage checkpoint and is partially compromised in many tumor cells. We recently identified MCPH1 as a key regulator that confers cells with the capacity to adapt to the decatenation checkpoint. In the present work, we have explored the contributions of checkpoint kinase 1 (Chk1) and polo‐like kinase 1 (Plk1), in order to better understand the molecular basis of decatenation checkpoint. Our results demonstrate that Chk1 function is required to sustain the G2 arrest induced by catalytic inhibition of Topo II. Interestingly, Chk1 loss of function restores adaptation in cells lacking MCPH1. Furthermore, we demonstrate that Plk1 function is required to bypass the decatenation checkpoint arrest in cells following Chk1 inhibition. Taken together, our data suggest that MCPH1 is critical to allow checkpoint adaptation by counteracting Chk1‐mediated inactivation of Plk1. Importantly, we also provide evidence that MCPH1 function is not required to allow recovery from this checkpoint, which lends support to the notion that checkpoint adaptation and recovery are different mechanisms distinguished in part by specific effectors. [ABSTRACT FROM AUTHOR]

Introduction: IFN lambda (type III‐IFN‐λ1) is a molecule primarily produced by epithelial cells that provides an important first‐line defence against viral respiratory infections and has been linked to the pathogenesis of viral‐induced wheezing in early life. The goal of this study was to better understand the regulation of innate IFN‐lambda responses in vitro in primary human infant airway epithelial cells (AECs) and in vivo using nasal aspirates during viral respiratory infections. Methods: IFN‐lambda protein levels were quantified: (a) in human infant AECs exposed to (poly(I:C) dsRNA) under different experimental conditions (n = 8 donors); and (b) in nasal aspirates of young children (≤3 years) hospitalized with viral respiratory infection (n = 138) and in uninfected controls (n = 74). In vivo IFN‐lambda airway levels during viral infections were correlated with individual characteristics and respiratory disease parameters. Results: Our in vitro experiments showed that the poly(I:C)‐induced innate production of IFN lambda in human infant AECs is regulated by (a) p38‐MAPK/NF‐kB dependent mechanism; and (b) exposure to pro‐inflammatory signals such as IL1β. Our in vivo studies demonstrated that (a) infants (<18 months) had higher virus‐induced IFN‐lambda airway secretion; (b) subjects with RSV infection showed the highest IFN‐lambda airway levels; and (c) individuals with the highest virus‐induced IFN‐lambda levels (>90th percentile) had higher viral loads and were more likely to have respiratory sick visits within 12 months of discharge (OR = 5.8). Conclusion: IFN‐lambda responses to dsRNA in the human infant airway epithelium are regulated by p38‐MAPK and NF‐kB signalling. High in vivo IFN‐lambda production is influenced by virus type and associated with recurrent respiratory sick visits in young children. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRs) control gene expression and the development of the immune system and antiviral responses. MiR-155 is an evolutionarily-conserved molecule consistently induced during viral infections in different cell systems. Notably, there is still an unresolved paradox for the role of miR-155 during viral respiratory infections. Despite being essential for host antiviral TH1 immunity, miR-155 may also contribute to respiratory disease by enhancing allergic TH2 responses and NFkB-mediated inflammation. The central goal of this study was to define how airway miR-155 production is related to TH1, TH2, and pro-inflammatory cytokine responses during naturally occurring viral respiratory infections in young children. Methods: Normalized nasal airway levels of miR-155 and nasal protein levels of IFN-γ, TNF-α, IL-1β, IL-13, IL-4 were quantified in young children (≤2 years) hospitalized with viral respiratory infections and uninfected controls. These data were linked to individual characteristics and respiratory disease parameters. Results: A total of 151 subjects were included. Increased miR-155 levels were observed in nasal samples from patients with rhinovirus, RSV and all respiratory viruses analyzed. High miR-155 levels were strongly associated with high IFN-γ production, increased airway TH1 cytokine polarization (IFN-γ/IL-4 ratios) and increased pro-inflammatory responses. High airway miR-155 levels were linked to decreased respiratory disease severity in individuals with high airway TH1 antiviral responses. Conclusions: The airway secretion of miR-155 during viral respiratory infections in young children is associated with enhanced antiviral immunity (TH1 polarization). Further studies are needed to define additional physiological roles of miR-155 in the respiratory tract of human infants and young children during health and disease. [ABSTRACT FROM AUTHOR]

Objective: to compare the risk factors, the stages of acquisition and the consumption of alcohol and tobacco as the relationship that exists between the risk factors and the consumption of alcohol and tobacco, in high school students of urban complements of the north and south of Nuevo Leon, Mexico Method: comparative, correlational study, cluster sampling and a sample of 374 in the period from 2016 to 2017. POSIT and EASJ were used as instruments and for the analysis the chi-square test, Friedman, Kruskal Wallis H, Spearman correlation and a regression model. Results: 31.6% of adolescents were in the stage of maintenance of alcohol consumption and 63.6% in the stage of precontemplation of tobacco consumption. The school risk factors (H = 15.19, p = .004) and individual risk factors (H = 22.0, p = .001) have more presence in the preparation stage (= 62.74; Mdn = 64.70) and maintenance of alcohol consumption (= 50.45; Mdn = 51.35). In tobacco use, individual risk factors in the preparation phase and family risk factors in maintenance stand out (p<.001). There is a relationship between risk factors and alcohol consumption (rs = .376, p< .001) and tobacco (rs = .345, p < .001). Conclusion: risk factors intervene in traffic through the stages of acquisition of licit drug use. [ABSTRACT FROM AUTHOR]

Objective: to analyze undergraduate nursing students' perception of biological risk and its relationship with their prior practical training. Method: a descriptive cross-sectional study was conducted among undergraduate nursing students enrolled in clinical practice courses in the academic year 2013-2014 at the School of Nursing at the University of Barcelona. Variables: sociodemographic variables, employment, training, clinical experience and other variables related to the assessment of perceived biological risk were collected. Both a newly developed tool and the Dimensional Assessment of Risk Perception at the worker level scale (Escala de Evaluación Dimensional del Riesgo Percibido por el Trabajador, EDRP-T) were used. Statistical analysis: descriptive and univariate analysis were used to identify differences between the perception of biological risk of the EDRP-T scale items and sociodemographic variables. Results: students without prior practical training had weaker perceptions of biological risk compared to students with prior practical training (p = 0.05 and p=0.04, respectively). Weaker perceptions of biological risk were found among students with prior work experience. Conclusion: practical training and work experience influence the perception of biological risk among nursing students. [ABSTRACT FROM AUTHOR]

The reaction of fac-[ReBr(CO)3(NCMe)2] (1) with either pyrazole (Hpz) or 3,5-dimethylpyrazole (Hdmpz) in a 1:2 Re/pyrazole ratio affords the known complexes fac-[ReBr(CO)3(Hpz)2] (2) and [ReBr(CO)3(Hdmpz)2] (3). Using a 1:1 ratio, MeCN as solvent, and longer reaction times led to a mixture in which the major components are the pyrazolylamidino complexes fac-[ReBr(CO)3(HNC(CH3)pz-κ²N,N] (4) and fac-[ReBr(CO)3(HNC(CH3)dmpz-κ²N,N] (5). The complexes fac-[ReBr(CO)3(Hpz)(NCMe)] (6) and fac-[ReBr(CO)3(Hdmpz)(NCMe)] (7) (along with 2 and 3) were found to be minor components of these reactions. Analogous reactions of fac-[Re(OClO3)(CO)3(NCMe)2] yielded fac-[Re(NCCH3)(CO)3(HNC(CH3)pz-κ²N,N]ClO4 (8), fac-[Re(NCCH3)(CO)3(HNC(CH3)dmpz-κ²N,N]ClO4 (9), fac-[Re(Hpz)(CO)3(HNC(CH3)pz-κ²N,N]ClO4 (10), and fac-[Re(Hdmpz)(CO)3(HNC(CH3)dmpz-κ²N,N]ClO4 (11). The X-ray structure of 11 showed the perchlorate anion to be hydrogen-bonded by the N-H groups of the pyrazole and pyrazolylamidino ligands. The behavior of the compound fac-[Re(Hdmpz)(CO)3(HNC(CH3)dmpz-κ²N,N]BAr′4 (13) (synthesized by reaction of [ReBr(CO)3(Hdmpz)2] (3) with (i) AgOTf and (ii) NaBAr′4IMeCN) as an anion receptor has been studied in CD3CN solution. In addition, the structure of the supramolecular adduct fac-[Re(CO)3(Hdmpz)(HNC(CH3)dmpz-κ²N,N]·Cl (14), featuring chloride binding by the two N-H groups, was determined by X-ray diffraction. [ABSTRACT FROM AUTHOR]

Explores the political and social dimensions of Latino community-based advocacy in New Jersey. Discussion on how major actors assess the effectiveness of Latino nonprofit advocacy; Linkages between the advocacy organization and state policymakers; Negotiation and decision-making in matters related to community advocacy.

Abstract. A female child with Weaver syndrome is described. She did not show the excessive growth characteristic of this syndrome until after adequate caloric intake was achieved by feeding through a gastric feeding tube. Her inadequate nutrition was a result of feeding difficulties during infancy. In addition, she had recurrent pulmonary infections, apneic spells, and severe developmental delay. She died at 16 months of sepsis, congestive heart failure, and respiratory arrest. The autopsy revealed marked atrophy of the brain and cardiac ventricular hypertrophy. Most of the brain changes were thought to be from hypoxia. [ABSTRACT FROM AUTHOR]

The global rise in type 2 diabetes results from a combination of genetic predisposition with environmental assaults that negatively affect insulin action in peripheral tissues and impair pancreatic β-cell function and survival. Nongenetic heritability of metabolic traits may be an important contributor to the diabetes epidemic. Transfer RNAs (tRNAs) are noncoding RNA molecules that play a crucial role in protein synthesis. tRNAs also have noncanonical functions through which they control a variety of biological processes. Genetic and environmental effects on tRNAs have emerged as novel contributors to the pathogenesis of diabetes. Indeed, altered tRNA aminoacylation, modification, and fragmentation are associated with β-cell failure, obesity, and insulin resistance. Moreover, diet-induced tRNA fragments have been linked with intergenerational inheritance of metabolic traits. Here, we provide a comprehensive review of how perturbations in tRNA biology play a role in the pathogenesis of monogenic and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Streptococcus suis is a coccus Gram positive, anaerobic optional. Human infection by this microorganism is a zoonotic disease that usually presents as purulent meningitis. Mortality is low but is common sequelae. A case of meningitis by S. suis secondary to contact with pigs is presented here. A 35-year-old male patient was admitted to the hospital complaining of high fever, malaise, vomiting and headache. A physical examination revealed decreased level of consciousness, with adequate response to painful stimulus and his eyes with deconjugated gaze. S. suis was isolated in blood culture. He was treated with cefotaxime, vancomycin and acyclovir in the intensive care unit. He experienced progressive improvement. He was discharged with severe deafness and a minimally unstable gait as sequellae. [ABSTRACT FROM AUTHOR]

Communication is the key to understanding the emotional vulnerability of patients in critical condition. A sudden change in health experienced by these individuals due to an accident or illness can lead to serious psycho-emotional outcomes. Main objective: To conduct and evaluate an augmentative alternative communication training program (CONCETEM) for pre-hospital nurses and determine its utility and the satisfaction of the nurses. Methods: The study has an observational-descriptive design. The sample was 12 pre-hospital nurses selected by inclusion criteria. Post-training evaluation was conducted by the research team to learn whether nurses could perform the communicative intervention. Results: 100% of the nurses who underwent CONECTEM training were prepared to implement communicative intervention in the ambulance. 60% of the nurses considered that the training was very useful for improving the quality of care for critically ill patients transferred by ambulance. The nurses' satisfaction with the communication training was 'very good' for 42.4% and 'good' for 58.3%. Conclusions: The results support the importance of Augmentative Alternative Communication training to improve outcomes in critically ill patients and reveal that nurses feel that more training is needed. [ABSTRACT FROM AUTHOR]

Background: Since the World Health Organization recommended single low-dose (0.25 mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant Plasmodium falciparum, several single-site studies have been conducted to assess efficacy.Methods: An individual patient meta-analysis to assess gametocytocidal and transmission-blocking efficacy of PQ in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (1) gametocyte carriage in the first 2 weeks post treatment; and (2) the probability of infecting at least 1 mosquito or of a mosquito becoming infected.Results: In 2574 participants from 14 studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytemia on day 0 (odds ratio [OR], 0.22; 95% confidence interval [CI], .17-.28 and OR, 0.12; 95% CI, .08-.16, respectively). Rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (P = .010 for day 7). Addition of 0.25 mg/kg PQ was associated with near complete prevention of transmission to mosquitoes.Conclusions: Transmission blocking is achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP. [ABSTRACT FROM AUTHOR]

The transcription factor EGR2 is expressed in Schwann cells, where it controls peripheral nerve myelination. Mutations of EGR2 have been found in patients with congenital hypomyelinating neuropathy or Charcot-Marie-Tooth disease type 1D. In a patient with congenital amyelinating neuropathy, we observed pathological abnormalities recapitulating the peripheral nervous system phenotype of homozygous Egr2-null mice. This patient, born from consanguineous parents, showed no EGR2 immunoreactivity in Schwann cells and harbored a homozygous 10.7-kilobase-long deletion encompassing a myelin-specific enhancer of EGR2. This regulatory mutation is the first genetic abnormality associated with congenital amyelinating neuropathy in humans. ANN NEUROL 2012; [ABSTRACT FROM AUTHOR]

OBJECTIVES: After the withdrawal of some cyclooxygenase-2 (COX-2) selective inhibitors, traditional nonsteroidal anti-inflammatory drug (NSAID) use has increased, but without additional prevention strategies against upper gastrointestinal (GI) complications in many cases. Here, we report the effect of antisecretory drugs and nitrates on the risk of upper GI peptic ulcer bleeding (UGIB) associated with nonselective NSAIDs, aspirin, antiplatelet agents, and anticoagulants. METHODS: This case–control study matched 2,777 consecutive patients with UGIB (confirmed by endoscopy) with 5,532 controls (2:1). Adjusted relative risks (RR) of UGIB are reported. RESULTS: Proton pump inhibitors (PPIs) (RR 0.33, 95% confidence interval [CI] 0.27–0.39), H2-receptor antagonists (H2-RAs) (RR 0.65, 95% CI 0.50–0.85), and nitrates (RR 0.52, 95% CI 0.38–0.70) reduced UGIB risk. PPI use was associated with greater reductions among both traditional NSAID (RR 0.13, 95% CI 0.09–0.19 vs RR 0.30, 95% CI 0.17–0.53 with H2-RAs; RR 0.48, 95% CI 0.19–1.24 with nitrates) and low-dose aspirin users (RR 0.32, 95% CI 0.22–0.51 vs RR 0.40, 95% CI 0.19–0.73 with H2-RA; RR 0.69, 95% CI 0.36–1.04 with nitrates), and among patients taking clopidogrel (RR 0.19, 95% CI 0.07–0.49). For patients taking anticoagulants, use of nitrates, H2-RA, or PPIs was not associated with a significant effect on UGIB risk. CONCLUSION: Antisecretory agent or nitrate treatment is associated with reduced UGIB RR in patients taking NSAID or aspirin. Only PPI therapy was associated with a marked, consistent risk reduction among patients receiving all types of agents (including nonaspirin antiplatelet agents). Protection was not apparent in patients taking anticoagulants. [ABSTRACT FROM AUTHOR]

Objective: to verify if there are significant changes in the perception of human care by nursing professionals in hospitalized patients throughout the days of hospitalization. Method: longitudinal and comparative study, in a sample of 166 patients admitted to the emergency departments observation, internal medicine, general surgery and infectiology, from June to September 2019. A sociodemographic data card and the perception scale of Humanized Nursing Care Behaviors, third version, were applied. Results: 51.8% of hospitalized patients were male, with a mean age of 38.8 years. In the perception of humanized nursing care, there was an increase of 13.3% in the usual category on the fifth day of hospitalization compared to the first day of hospitalization. Conclusion: the patient perceives better humanized care over the days of his hospitalization. In this way, with the length of the interaction, the humanized care of the nursing professional becomes more visible to hospitalized patients, meeting basic needs and relieving pain with the awareness of intentional care. [ABSTRACT FROM AUTHOR]

Phosphoglycerate kinase (PGK)1 deficiency is an X-linked inherited disease associated with different clinical presentations, sometimes as myopathic affectation without hemolytic anemia. We present a 40-year-old male with a mild psychomotor delay and mild mental retardation, who developed progressive exercise intolerance, cramps and sporadic episodes of rhabdomyolysis but no hematological features. A genetic study was carried out by a next-generation sequencing (NGS) panel of 32 genes associated with inherited metabolic myopathies. We identified a missense variant in the PGK1 gene c.1114G > A (p.Gly372Ser) located in the last nucleotide of exon 9. cDNA studies demonstrated abnormalities in mRNA splicing because this change abolishes the exon 9 donor site. This novel variant is the first variant associated with a myopathic form of PGK1 deficiency in the Spanish population. [ABSTRACT FROM AUTHOR]

Objective: identify the relationship between the terminal and instrumental values and the consumption of tobacco in the health professionals of a primary care level of a public institution. Method: correlational descriptive design. The population was 165 participants. The instruments were a personal data and a prevalence of licit drug consumption survey and Schwartz and Bilsky value questionnaire. Results: 22% of the health professionals consume tobacco, starting at 13 years old, consuming one cigarette in a typical day with higher intake of male. The prevalence reports are: global 73.3%, lapsic 3%, current 4.7% and instant 2.4%. The most important instrumental value of the health professionals was to be able and the in terminal values was an exciting life. No relationship was found between the values and the tobacco consumption of the health professionals (r = -.157, p = 0.44), for the instrumental values there is no relation (r = - .050, p = .591). Conclusion: the tobacco consumption of health professionals is minimal and the values obtained are in conditions to provide guidance to reduce consumption. [ABSTRACT FROM AUTHOR]

The sibling species Microtus thomasi and M. atticus represent probably the highest karyotypic diversity within the genus Microtus and are an interesting model for chromosomal evolution studies. In addition to variation in autosomes, they show a high intraspecific variation in the size and morphology of both sex chromosomes. We analyzed individuals with different sex chromosome constitutions using 3 painting probes, 2 from Y chromosome variants and 1 from the small arm of the submetacentric X chromosome. Our comparative painting approach uncovered 12 variants of Y and 14 variants of X chromosomes, which demonstrates that the polymorphism of sex chromosomes is substantially larger than previously reported. We suggest that 2 main processes are responsible for this sex chromosome polymorphism: change of morphology from acrocentric to submetacentric or metacentric chromosomes and increase in size due to accumulation of repetitive DNA sequences, generating heterochromatic blocks. Strong genetic drift in small and fragmented populations of these 2 species could be related to the origin and maintenance of the large polymorphism of sex chromosomes. We proposed that a similar polymorphism variation combined with random drift fixing the biggest sex chromosomes could have occurred in the origin of some of the actual Microtus species with giant sex chromosomes. [ABSTRACT FROM AUTHOR]

Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original results from 121 laboratories across 15 countries. We report on 1326 duplicate results; a discrepancy in reporting the upper allele occurred in 51% of cases, this reduced to 13.3% and 9.7% when we applied acceptable measurement errors proposed by the American College of Medical Genetics and the Draft European Best Practice Guidelines, respectively. Duplicate results were available for 1250 lower alleles; discrepancies occurred in 40% of cases. Clinically significant discrepancies occurred in 4.0% of cases with a potential unexplained misdiagnosis rate of 0.3%. There was considerable variation in the discrepancy rate among 10 of the countries participating in this study. Out of 1326 samples, 348 were re-analysed by an accredited diagnostic laboratory, based in Germany, with concordance rates of 93% and 94% for the upper and lower alleles, respectively. This became 100% if the acceptable measurement errors were applied. The central laboratory correctly reported allele sizes for six standard reference samples, blind to the known result. Our study differs from external quality assessment (EQA) schemes in that these are duplicate results obtained from a large sample of patients across the whole diagnostic range. We strongly recommend that laboratories state an error rate for their measurement on the report, participate in EQA schemes and use reference materials regularly to adjust their own internal standards. [ABSTRACT FROM AUTHOR]

Abstract: Myofibrillar myopathies (MFM) are a group of disorders associated with mutations in DES, CRYAB, MYOT, ZASP, FLNC, or BAG3 genes and characterized by disintegration of myofibrils and accumulation of degradation products into intracellular inclusions. We retrospectively evaluated 53 MFM patients from 35 Spanish families. Studies included neurologic exam, muscle imaging, light and electron microscopic analysis of muscle biopsy, respiratory function testing and cardiologic work-up. Search for pathogenic mutations was accomplished by sequencing of coding regions of the six genes known to cause MFM. Mutations in MYOT were the predominant cause of MFM in Spain affecting 18 of 35 families, followed by DES in 11 and ZASP in 3; in 3 families the cause of MFM remains undetermined. Comparative analysis of DES, MYOT and ZASP associated phenotypes demonstrates substantial phenotypic distinctions that should be considered in studies of disease pathogenesis, for optimization of subtype-specific treatments and management, and directing molecular analysis. [Copyright &y& Elsevier]

Quench initiation in homogeneous YBa2Cu3O7-δ (YBCO) coated conductors in nitrogen vapor has been analyzed using Digital Speckle Pattern Interferometry (DSPI) and measurements of the temporal evolution of the electric field along the conductor. These optical experiments can detect sample surface displacements smaller than 100 nm in the perpendicular direction. In these quench experiments, displacements are caused by dilatation effects associated with heat generation during the transition to the normal state. DSPI detects a multispot origin of quench initiation in these homogeneous materials. This confirms that, in addition to Ic distributions, there are other factors as inhomogeneities in thermal stabilizations that strongly determine sample quench behavior. The knowledge of the origin of this behavior is important for the design of different applications. The technique has been improved in order to characterize samples immersed in liquid nitrogen. The first results in 0.025 mm-thick Cu foils immersed in liquid nitrogen are presented. In addition to sample heating, DSPI allows the visualization of liquid nitrogen convention movements. [ABSTRACT FROM AUTHOR]

Abstract: Giant axonal neuropathy (GAN, MIM: 256850) is a devastating autosomal recessive disorder characterized by an early onset severe peripheral neuropathy, varying central nervous system involvement and strikingly frizzly hair. Giant axonal neuropathy is usually caused by mutations in the gigaxonin gene (GAN) but genetic heterogeneity has been demonstrated for a milder variant of this disease. Here, we report ten patients referred to us for molecular genetic diagnosis. All patients had typical clinical signs suggestive of giant axonal neuropathy. In seven affected individuals, we found disease causing mutations in the gigaxonin gene affecting both alleles: two splice-site and four missense mutations, not reported previously. Gigaxonin binds N-terminally to ubiquitin activating enzyme E1 and C-terminally to various microtubule associated proteins causing their ubiquitin mediated degradation. It was shown for a number of gigaxonin mutations that they impede this process leading to accumulation of microtubule associated proteins and there by impairing cellular functions. [Copyright &y& Elsevier]

Following publication of the original article [1], the authors reported an error in Figure 2, where the color code of the text boxes is reversed. Figure 2-amended shows the correct color association between the text boxes and the different areas in the map: Navarra, neighbouring communities and other Spanish communities. [ABSTRACT FROM AUTHOR]

Toxic oil syndrome (TOS) resulted from consumption of rapeseed oil denatured with 2% aniline and affected more than 20,000 persons. Eighteen years after the epidemic, many patients continue to report neurologic symptoms that are difficult to evaluate using conventional techniques. We conducted an epidemiologic study to determine whether an exposure to toxic oil 18 years ago was associated with current adverse neurobehavioral effects. We studied a case group of 80 adults exposed to toxic oil 18 years ago and a referent group of 79 adult age- and sex-frequency-matched unexposed subjects. We interviewed subjects for demographics, health status, exposures to neurotoxicants, and responses to the Kaufman Brief Intelligence Test (K-BIT), Programa Integrado de Exploracion Neuropsicologica (PIEN), and Goldberg depression questionnaires and administered quantitative neurobehavioral and neurophysiologic tests by computer or trained nurses. The groups did not differ with respect to educational background or other critical variables. We examined associations between case and referent groups and the neurobehavioral and neurophysiologic outcomes of interest. Decreased distal strength of the dominant and nondominant hands and increased vibrotactile thresholds of the fingers and toes were significantly associated with exposure to toxic oil. Finger tapping, simple reaction time latency, sequence B latency, symbol digit latency, and auditory digit span were also significantly associated with exposure. Case subjects also had statistically significantly more neuropsychologic symptoms compared with referents. Using quantitative neurologic tests, we found significant adverse central and peripheral neurologic effects in a group of TOS patients 18 years after exposure to toxic oil when compared with a nonexposed referent group. These effects were not documented by standard clinical examination and were found more frequently in women. [ABSTRACT FROM AUTHOR]

Background: Genetic testing for BRCA1/2 genes is widely used as a strategy to reduce incidence and morbidity of hereditary breast and ovarian cancer (HBOC). The purpose of this study is to analyse the demographic and molecular characteristics of BRCA germline mutations in Navarra, Spain, and to investigate the clinical profile of hereditary and sporadic breast cancer (BC) and ovarian cancer (OC) in the Community.Methods: The study includes 1246 individuals assessed for BRCA1/2 genetic testing in Navarra, during 2000-2016, and a cohort of BC (n = 4384) and OC (n = 561) from the population-based Navarra Cancer Registry. Distribution and molecular characteristics of BRCA1/2 mutations, as well as, comparative analysis of the clinical course, pathologic features and overall survival (OS) of patients in different risk groups were investigated.Results: BRCA mutation detection rate was 16%, with higher proportion (63%) of BRCA2 families. Nineteen per cent of mutations were recurrent, one of which, BRCA2 c.6024dupG, showed high association to OC. BRCA carriers had double risk (95% CI = 1.04-4.33) of developing multiple malignancies than low risk families and were diagnosed at a much earlier age (16.6 and 11.7 years difference for BC and OC, respectively) when compared to the general population. For BC, BRCA carriers showed a more advanced histological stage, higher risk of bilateral neoplasms (OR = 4.3; 95% CI = 1.3-11.4, for BRCA2 carriers) and worse OS rate at 5-, 10- and 15- years, than women with sporadic tumors. For OC, over 70% of patients of all risk groups showed advanced stages at diagnosis, with the highest among BRCA1 carriers (91%). Furthermore, they also had higher probability of developing ovarian bilateral tumors (OR = 7.8, 95% CI = 1.7-55.7, for BRCA1 carriers) than the general population. Five-year OS rate was worse among women with sporadic OC than BRCA carriers, but it levelled out over the 15-year period.Conclusions: In addition to national similarities in the HBOC-BRCA1/2 associated mutational spectrum, we identified a recurrent BRCA2 pathogenic variant (c.6024dupG), highly associated to OC in Navarra. Carriers of BRCA1/2 mutations showed a more severe BC and OC phenotype and had a worse overall prognosis when compared to a large cohort of women with sporadic counterpart tumors. [ABSTRACT FROM AUTHOR]

Background: Rubinstein‐Taybi syndrome (RSTS) is a rare congenital disorder characterized by broad thumbs and halluces, intellectual disability, distinctive facial features, and growth retardation. Clinical manifestations of RSTS are varied and overlap with other syndromes' phenotype, which makes clinical diagnosis challenging. CREBBP is the major causative gene (55%–60% of the cases), whereas pathogenic variants found in EP300 represent the molecular cause in 8% of RSTS patients. A wide range of CREBBP pathogenic variants have been reported so far, including point mutations (30%–50%) and large deletions (10%). Methods: The aim of this study was to characterize the CREBBP genetic variant spectrum in 39 RSTS patients using Multiplex Ligation‐dependent Probe Amplification and DNA sequencing techniques (Sanger and Trio‐based whole‐exome sequencing). Results: We identified 15 intragenic deletions/duplications, ranging from one exon to the entire gene. As a whole, 25 de novo point variants were detected: 4 missense, 12 nonsense, 5 frameshift, and 4 splicing pathogenic variants. Three of them were classified as of uncertain significance and one of the patients carried two different variants. Conclusion: Seventeen of the 40 genetic variants detected were reported for the first time in this work contributing, thus, to expand the molecular knowledge of this complex disorder. [ABSTRACT FROM AUTHOR]

Background: Management of Helicobacter pylori infection has been expanded from the gastroenterology specialist (GS) to primary care physicians (PCPs), with a large increase in requests for urea breath tests (UBT). Due to the lack of evidence at this level, we evaluated the appropriateness of UBT indications and treatment for H pylori infections between PCPs and GSs and the effect of introducing specific counseling to PCPs. Materials and Methods: This was a quasi‐experimental study. Phase I included 650 consecutive UBT requested by PCPs (400) and GSs (250). Indications and treatments were classified as appropriate or inappropriate based on national guidelines. Data on eradication rates were also collected. In phase II, 240 UBT and patients' treatment outcomes were analyzed after individually counseling PCPs on both aspects. Results: Of 1049 UBT, inappropriate indications in phase I were significantly higher in tests requested by PCP compared with GS (35.9% vs 7.2%; P < 0.001). Inappropriate treatment regimens were significantly higher for PCPs in phase I (65.8% vs 26.4%; P < 0.001). Consequently, eradication rates were significantly lower in patients treated by PCPs compared with those treated by GS (63.7% vs 81.4%; P = 0.004). A significant increase in adherence to appropriate treatment regimens (75.8% vs 34.2%; P < 0.001) and eradication rates (79.2% vs 63.7%; P = 0.002) were observed in the PCP group after counseling; however, the appropriateness of indications did not improve. Conclusions: Patients infected with H pylori managed at the primary care level had poorer outcomes. The introduction of specific counseling for PCPs significantly improved treatment management, but not indications. [ABSTRACT FROM AUTHOR]