Ni(2,2':6',2''-terpyridine)2: a high-spin octahedral formal Ni(0) complex.

We have synthesised and characterised the complex Ni(tpy)2 (tpy = 2,2':6',2''-terpyridine). This formally Ni(0) complex is paramagnetic both in the solid state and in solution (S = 2). The crystal structure shows an octahedral geometry, with molecules arranged in independent dimers involving π-stacking between pairs of complexes. Magnetic measurementes and DFT calculations suggest the existence of temperature-dependent intermolecular antiferromagnetic coupling in the solid state.

Gold-catalyzed endo-selective cyclization of alkynylcyclobutanecarboxamides: synthesis of cyclobutane-fused dihydropyridones.

Cyclobutane-fused dihydropyridones can be efficiently synthesized by a completely endo-selective gold-catalyzed cyclization of alkynylcyclobutanes bearing an appended amide, which proceeds under mild conditions. The observed selectivity, which is reversed from that previously observed for the cyclization of related alcohols and acids, is supported by DFT calculations.

Long-term efficacy of percutaneous tibial nerve stimulation for faecal incontinence and a new approach for partial responders.

BACKGROUND: The aim of the present study was to evaluate the long-term efficacy of percutaneous tibial nerve stimulation (PTNS) for patients with faecal incontinence (FI) refractory to conservative treatment. Secondary aims were to identify predictors of response and validate new treatment pathways for partial responders. METHODS: A prospective, interventional study was carried out in a specialist defecatory disorder unit from a university hospital between January 2010 and June 2017 on patients > 18 years old with FI refractory to conservative treatment. Thirty-minute PTNS sessions were performed in three phases (weekly, biweekly and monthly) up to a year, with clinical reassessment at 3, 6, 12 and 36 months. Patients were classified as optimal responders when their pretreatment Wexner score decreased > 50%; partial responders when it decreased 25-50%; and insufficient responders if it decreased < 25%. Only optimal and partial responders progressed into successive phases. RESULTS: Between 2010 and 2017, 139 patients (110 women, median age 63 years [range 22-82 years]) were recruited. After the first phase, 4 patients were optimal responders, 93 were partial responders and 36 were insufficient responders. At 6 and 12 months, 66 and 89 patients respectively were optimal responders, with an optimal response rate of 64% at the end of treatment. A total of 93.3% patients with a partial response initially finally became optimal responders. Furthermore, at 36 months, 71.9% of patients were still optimal responders without supplementary treatment, although their quality of life did not improve significantly. Baseline Wexner scores ≤ 10 and symptom duration < 1 year were identified as predictive factors for positive responses to PTNS. CONCLUSIONS: Patients undergoing PTNS for 1 year following this protocol had optimal long-term responses. PTNS sessions for up to 1 year in patients who were partial responders prevents a high percentage of them from needing more invasive treatments, and maintains long-term continence in patients who were optimal responders.

Adaptación transcultural y validación del cuestionario STOP-bang del inglés al español como herramienta de detección precoz del síndrome de apnea del sueño en el paciente quirúrgico y en la población general / Cross-cultural adaptation and Validation of the STOP-bang Questionnaire from English to Spanish as a tool for the early detection of sleep apnea syndrome in the surgical patient and in the general population

Introduccion: El síndrome de apnea obstructiva del sueño (SAOS) o síndrome de apnea-hipoapnea (SAHS) es uno de los trastornos del sueño más prevalentes en la población general. Está asociado a un aumento en la prevalencia de intubación orotraqueal difícil y de las complicaciones postoperatorias. Se recomienda la aplicación de tests de detección precoz validados como el test en inglés de STOP-bang (STBC); un test de alta calidad metodológica, sensibilidad y especificidad en la detección precoz del SAHS tanto en la población quirúrgica como general. Objetivo: La validación, traducción y adaptación cultural del test STBC a la población española. Material y metodos: Se realizó la adaptación transcultural del STBC al español y un estudio de validación posterior con 77 pacientes consecutivos. El análisis estadístico evaluó la fiabilidad, la validez y la factibilidad de la versión traducida y adaptada culturalmente. Resultados: Se incluyeron el 44% de mujeres y el 56% de varones con una edad media de 53,58±12,88 años. Los resultados en la fiabilidad fueron: un coeficiente alfa de Cronbach de 0,767, una correlación de Pearson r=0,777 (p<0,001) y una correlación de Sperman rho=0,455 (p=0,044). La factibilidad del estudio fue del 100%. La validez de criterio se evaluó mediante el coeficiente Kappa que fué de 0,444. Para una puntuación >3 del cuestionario adaptado al español los resultados de sensibilidad y de especificidad según los distintos niveles de corte del índice apnea hipoapnea (IAH)>5, >15 y >30) fueron: sensibilidad del 87, 91 y 100%, respectivamente, y de especificidad del 50, 31 y 22%, respectivamente.(AU)

Introduction: Obstructive sleep apnea syndrome (OSAS) or apnea-hypoapnea syndrome (SAHS) is one of the most prevalent sleep disorders in the general population. It is associated with an increase in the prevalence of difficult orotracheal intubation and postoperative complications. The application of validated early detection tests,such the STOP-Bang test in English (STBC), is recommended; a test of high methodological quality, sensitivity and specificity in the early detection of SAHS in both surgical and general populations. Objective: The validation, translation, cross-cultural adaptation of the STBC to the Spanish population. Material and methods: The transcultural adaptation of the STBC to Spanish was carried out and a subsequent validation study with 77 consecutive patients was carried out. The statistical analysis evaluated the reliability, validity and feasibility of the translated and culturally adapted version. Results: 44% of women and 56% of men were included,with a mean age of 53.58±12.88 years. The reliability results were: a Cronbach's Alpha Coefficient of 0.767, a Pearson correlation r=.777 (P<.001) and a Sperman correlation rho=.455 (P=.044). The feasibility of the study was 100%. Criterion validity was evaluated using the Kappa coefficient, which was 0.444. For a score >3 of the questionnaire adapted to Spanish, the results of sensitivity, specificity according to the different cut-off levels of the apnea hypopnea index (AHI)>5, >15, >30) were: Sensitivity 87%, 91% and 100% respectively and Specificity of 50%, 31% and 22%. Conclusions: The STBC questionnaire translated, adapted and validated into Spanish, evaluated in the present study, is reliable and valid with respect to the original design of the questionnaire. It is a useful tool that is easy to understand and implement, which can be used rigorously to stratify surgical risk and carry out adequate perioperative planning of those patients at risk of SAHS.(AU)

Cross-cultural adaptation and validation of the STOP-bang Questionnaire from English to Spanish as a tool for the early detection of sleep apnea syndrome in the surgical patient and in the general population.

INTRODUCTION: Obstructive Sleep Apnea Syndrome (OSAS) or Apnea-Hypoapnea Syndrome (SAHS) is one of the most prevalent sleep disorders in the general population. It is associated with an increase in the prevalence of difficult orotracheal intubation and postoperative complications. The application of validated early detection tests, such the STOPbang test in English (STBC), is recommended; a test of high methodological quality, sensitivity and specificity in the early detection of SAHS in both surgical and general populations. OBJECTIVE: The validation, translation, cross-cultural adaptation of the STBC to the Spanish population. MATERIAL AND METHODS: The transcultural adaptation of the STBC to Spanish was carried out and a subsequent validation study with 77 consecutive patients was carried out. The statistical analysis evaluated the reliability, validity and feasibility of the translated and culturally adapted version. RESULTS: 44% of women and 56% of men were included, with a mean age of 53.58 ± 12.88 years. The reliability results were: a Cronbach's Alpha Coefficient of 0.767, a Pearson correlation r = 0.777 (P < .001) and a Sperman correlation rho = 0.455 (P = .044). The feasibility of the study was 100%. Criterion validity was evaluated using the Kappa coefficient, which was 0.444. For a score >3 of the questionnaire adapted to Spanish, the results of sensitivity, specificity according to the different cut-off levels of the apnea hypopnea index (AHI) >5, >15, >30) were: Sensitivity 87%, 91% and 100% respectively and Specificity of 50%, 31% and 22%. CONCLUSIONS: The STBC questionnaire translated, adapted and validated into Spanish, evaluated in the present study, is reliable and valid with respect to the original design of the questionnaire. It is a useful tool that is easy to understand and implement, which can be used rigorously to stratify surgical risk and carry out adequate perioperative planning of those patients at risk of SAHS.

Pd-catalyzed C(sp3)-C(sp) bond formation in iodocyclobutenes.

A synthesis of skipped 1,4-enynes through functionalization of the cyclobutene core with alkynes has been achieved, suggesting an unusual pathway of oxidative addition in tertiary iodoalkanes.

On the mechanism of the formation of alkyl-Ni(I) catalysts.

The formation of catalytically active alkyl-Ni(i) complexes by comproportionation of diorgano-Ni(ii) precursors and Ni(0) species proceeds easily through triplet states by alkyl ligand exchange. The process involves inversion of the configuration at the carbon that is transferred.

Advertising Games of Chance in Adolescents and Young Adults in Spain.

Gambling advertising can influence attitudes and gaming behavior of adolescents and young adults (A&Y). To study the effect of advertising on the attitudes and gaming behavior of a sample of 2887 Spanish A&Y (12-22 years old), by means of a self-report assessment. On average, participants show a weak effect of advertising, however there are great variations, estimating that 11% of A&Y acknowledge being influenced by advertising and 5% recognize being severely affected. Men see themselves more impacted than women, without age differences. Those who play videogames signal a stronger effect of this kind of advertising and although these differences are not substantial in effect size, they reach statistically significance in 12 of the 13 questions assessed. A&Y who showed higher scores indicating problematic use of videogames in the IDGS9-SF, are those who indicate a greater impact of advertising on their attitudes towards gaming, as well as on the way they play or on their intention to play. These results support the idea that videogames can, albeit modestly, predispose engagement in games of chance.

Triflyl-assisted reductive Pd-catalyzed Tsuji-Trost type reaction.

New (triflyl)cyclobutenes have been prepared by palladium-catalyzed hydrodetriflylation reaction using water and deuterium oxide as convenient hydrogen and deuterium sources. In addition, an investigation of the possible mechanism for this Tsuji-Trost type reaction of bis(triflyl)cyclobutenes has been facilitated by labelling studies and density functional theory (DFT) calculations.

Predictors for a dementia gene mutation based on gene-panel next-generation sequencing of a large dementia referral series.

Next-generation genetic sequencing (NGS) technologies facilitate the screening of multiple genes linked to neurodegenerative dementia, but there are few reports about their use in clinical practice. Which patients would most profit from testing, and information on the likelihood of discovery of a causal variant in a clinical syndrome, are conspicuously absent from the literature, mostly for a lack of large-scale studies. We applied a validated NGS dementia panel to 3241 patients with dementia and healthy aged controls; 13,152 variants were classified by likelihood of pathogenicity. We identified 354 deleterious variants (DV, 12.6% of patients); 39 were novel DVs. Age at clinical onset, clinical syndrome and family history each strongly predict the likelihood of finding a DV, but healthcare setting and gender did not. DVs were frequently found in genes not usually associated with the clinical syndrome. Patients recruited from primary referral centres were compared with those seen at higher-level research centres and a national clinical neurogenetic laboratory; rates of discovery were comparable, making selection bias unlikely and the results generalisable to clinical practice. We estimated penetrance of DVs using large-scale online genomic population databases and found 71 with evidence of reduced penetrance. Two DVs in the same patient were found more frequently than expected. These data should provide a basis for more informed counselling and clinical decision making.

Ni-Catalyzed Cyclization of Enynes and Alkynylboronates: Atom-Economical Synthesis of Boryl-1,4-dienes.

We report a novel atom-economical Ni-catalyzed cyclization reaction of enynes with alkynylboronates. The reaction employs a non-expensive Ni salt, a phosphine-based ligand and easy-handling alkynylboronates as boron-carbon source. The reaction provides complex fused-bicyclic compounds containing borylated 1,4-cyclohexadienes in high yields in short reaction times, involving the formation of two C-C bonds in one step. A reasonable reaction mechanism is proposed based on mechanistic experimental results.

Ni-Catalyzed Reductive Dicarbofunctionalization of Nonactivated Alkenes: Scope and Mechanistic Insights.

Olefins devoid of directing or activating groups have been dicarbofunctionalized here with two electrophilic carbon sources under reductive conditions. Simultaneous formation of one C(sp3)-C(sp3) and one C(sp3)-C(sp2) bond across a variety of unbiased π-systems proceeds with exquisite selectivity by the combination of a Ni catalyst with TDAE as sacrificial reductant. Control experiments and computational studies revealed the feasibility of a radical-based mechanism involving, formally, two interconnected Ni(I)/Ni(III) processes and demonstrated the different ability of Ni(I) species (Ni(I)I vs PhNi(I)) to reduce the C(sp3)-I bond. The role of the reductant was also investigated in depth, suggesting that a one-electron reduction of Ni(II) species to Ni(I) is thermodynamically favored. Further, the preferential activation of alkyl vs aryl halides by ArNi(I) complexes as well as the high affinity of ArNi(II) for secondary over tertiary C-centered radicals explains the lack of undesired homo- and direct coupling products (Ar-Ar, Ar-Alk) in these transformations.

Atom-Economical Ni-Catalyzed Diborylative Cyclization of Enynes: Preparation of Unsymmetrical Diboronates.

We report a Ni-catalyzed diborylative cyclization of enynes that affords carbo- and heterocycles containing both alkyl- and alkenylboronates. The reaction is fully atom-economical, shows a broad scope, and employs a powerful and inexpensive catalytic Ni-based system. The reaction mechanism seems to involve activation of the enyne by Ni(0) through oxidative cyclometalation of the enyne prior to diboron reagent activation. An unprecedented dinuclear bis(organometallic) Ni(I) intermediate complex was isolated.

The current prevalence of asthma, allergic rhinitis, and eczema related symptoms in school-aged children in Costa Rica.

OBJECTIVE: Asthma prevalence in Costa Rica is among the highest worldwide. We aimed to determine the prevalence of asthma among school-age children in the Central Highland Area of Costa Rica. METHODS: Cross-sectional study using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was performed. Parents or guardians of children aged 6-13 years completed written questionnaires. RESULTS: Total of 2817 school-aged children returned these questionnaires (74.1% return rate). The prevalence of asthma, rhinitis, and eczema was 21.9%, 42.6%, and 19.2%, respectively. The co-existence of the 3 diseases was seen in 22.6% of children with asthma. Boys had a slightly higher prevalence of these conditions, and younger children had higher prevalence of asthma and eczema, but lower prevalence of rhinitis than older children. The use of acetaminophen and antibiotics in the first 12 months of life showed a significant association with the prevalence of asthma, rhinitis, and eczema. Wheezing with exercise, dry cough at night, and ever rhinitis was highly associated with asthma symptoms in the last 12 months. In contrast, no association was found between children exposed to smoking at home. Frequent traffic next to the house was reported more frequently by the parents of children with asthma, although no significant association was found. CONCLUSION: The prevalence of asthma showed a significant decrease compared to previous studies. However, there was an unexpected high prevalence of rhinitis. Exposure to acetaminophen and antibiotic during the first year of life was highly associated with asthma symptoms.

Ligand-Controlled Electron Structure of Catalytically Active Ni Complexes.

We have performed a systematic study of the electron structure of a series of Ni(I) and Ni(II) iodo and methyl complexes with a variety of di- and tridentate nitrogen ligands to study the influence of these ligands in the structure of catalytically active complexes in cross-coupling reactions. Ni(II) compounds show the expected square-planar configuration typical of complexes of d8 metals, regardless of the kind of coordinating nitrogen atom (sp2 or sp3) found in ligands derived from either trialkylamines or pyridines. In contrast, Ni(I) complexes show different structures. Thus, the absence of orbitals capable of delocalizing the unpaired electron (such as in TMEDA and PMDTA derivatives) leads to nonplanar iodo or methyl tetracoordinate complexes. In contrast, the presence of ligands derived from pyridine allows delocalization of the unpaired electron on the ligand. This delocalization is especially effective for terpyridine species.

Examination of cytological smears and cell blocks of pleural fluid: Complementary diagnostic value for malignant effusions / Examen del frotis citológico y bloque celular del líquido pleural: valor diagnóstico complementario en los derrames malignos

Objectives. To evaluate the independent usefulness of pleural fluid smear and cell block (CB) preparations for the diagnosis of malignant effusions. Patients and methods. A total of 632 cytological smears and 554 CBs from 414 consecutive patients with malignant effusions were retrospectively evaluated. Results. The diagnostic yield of a first specimen was 44% regardless of whether a smear or CB cytologic examination was performed. The use of subsequent separated specimens increased the identification of malignancy to 56%. Overall, 11% of samples found to be negative by cytologic smears showed malignant cells on CBs, whereas 15% of negative CBs were reported as positive on smear slides. Pleural fluid specimens with low red and/or white blood cell counts more frequently resulted in the generation of suboptimal CB preparations. Conclusions. If CBs and smears are prepared and examined, the percentage of positive diagnoses will be greater than if only one method is used (AU)

Objetivos. Evaluar la utilidad independiente de frotis y bloques celulares (BC) del líquido pleural para diagnosticar derrames malignos. Pacientes y métodos. Se evaluaron retrospectivamente un total de 632 frotis citológicos y 554 BC de 414 pacientes consecutivos con derrame pleural maligno. Resultados. La sensibilidad diagnóstica de una primera muestra fue del 44%, tanto en frotis como en BC. El análisis de muestras separadas ulteriores aumentó al 56% la identificación de derrames malignos. Globalmente, el 11% de muestras negativas mediante frotis mostraron células malignas en los BC, mientras que el 15% de BC negativos resultaron positivos en el estudio del frotis. Los líquidos pleurales con recuentos bajos de hematíes o leucocitos produjeron con mayor frecuencia BC insuficientes para diagnóstico. Conclusiones. Si se evalúan frotis y BC, el porcentaje de resultados positivos es superior que si se emplean estas técnicas de forma aislada (AU)

Examination of cytological smears and cell blocks of pleural fluid: Complementary diagnostic value for malignant effusions.

OBJECTIVES: To evaluate the independent usefulness of pleural fluid smear and cell block (CB) preparations for the diagnosis of malignant effusions. PATIENTS AND METHODS: A total of 632 cytological smears and 554 CBs from 414 consecutive patients with malignant effusions were retrospectively evaluated. RESULTS: The diagnostic yield of a first specimen was 44% regardless of whether a smear or CB cytologic examination was performed. The use of subsequent separated specimens increased the identification of malignancy to 56%. Overall, 11% of samples found to be negative by cytologic smears showed malignant cells on CBs, whereas 15% of negative CBs were reported as positive on smear slides. Pleural fluid specimens with low red and/or white blood cell counts more frequently resulted in the generation of suboptimal CB preparations. CONCLUSIONS: If CBs and smears are prepared and examined, the percentage of positive diagnoses will be greater than if only one method is used.

Tunable Metal-Catalyzed Heterocyclization Reactions of Allenic Amino Alcohols: An Experimental and Theoretical Study.

Controlled preparation of 2,5-dihydro-1H-pyrroles, 3,6-dihydro-2H-pyrans, and pyrroles has been achieved through switchable chemo- and regioselectivity in the metal-catalyzed heterocyclization reactions of allenic amino alcohols. The gold-catalyzed cycloisomerization reaction of α-amino-ß-hydroxyallenes was effective as 5-endo cyclization by addition of amino functionality to the distal allene carbon to yield enantiopure 2,5-dihydro-1H-pyrroles, whereas their palladium-catalyzed cyclizative coupling reactions furnished 3,6-dihydro-2H-pyrans through a chemo- and regioselective 6-endo cycloetherification. Conversely, the gold-catalyzed heterocyclization reaction of ß-amino-γ-hydroxyallenes generated exclusively pyrrole derivatives. These results could be explained through a chemo- and regioselective 5-exo aminocyclization to the central allene carbon followed by aromatization. Chemo- and regioselectivity depend on both linker elongation as well as the type of catalyst. This behavior can be justified by means of density functional theory calculations.

The SLE variant Ala71Thr of BLK severely decreases protein abundance and binding to BANK1 through impairment of the SH3 domain function.

The B-lymphocyte kinase (BLK) gene is associated genetically with several human autoimmune diseases including systemic lupus erythematosus. We recently described that the genetic risk is given by two haplotypes: one covering several strongly linked single-nucleotide polymorphisms within the promoter of the gene that correlated with low transcript levels, and a second haplotype that includes a rare nonsynonymous variant (Ala71Thr). Here we show that this variant, located within the BLK SH3 domain, is a major determinant of protein levels. In vitro analyses show that the 71Thr isoform is hyperphosphorylated and promotes kinase activation. As a consequence, BLK is ubiquitinated, its proteasomal degradation enhanced and the average life of the protein is reduced by half. Altogether, these findings suggest that an intrinsic autoregulatory mechanism previously unappreciated in BLK is disrupted by the 71Thr substitution. Because the SH3 domain is also involved in protein interactions, we sought for differences between the two isoforms in trafficking and binding to protein partners. We found that binding of the 71Thr variant to the adaptor protein BANK1 is severely reduced. Our study provides new insights on the intrinsic regulation of BLK activation and highlights the dominant role of its SH3 domain in BANK1 binding.