Gas Sensing and Half-Metallic Materials Design Using Metal Embedded into S Vacancies in WS2 Monolayers: Adsorption of NO, CO, and O2 Molecules.

The adsorption of CO, NO, and O2 molecules onto Cu, Ag, and Au atoms placed in the S vacancies of a WS2 monolayer was elucidated within dispersion-corrected density functional theory. The binding energies computed for embedded defects into S vacancies were 2.99 (AuS), 2.44 (AgS), 3.32 eV (CuS), 3.23 (Au2S2), 2.55 (Ag2S2), and 3.48 eV/atom (Cu2S2), respectively. The calculated diffusion energy barriers from an S vacancy to a nearby site for Cu, Ag, and Au were 2.29, 2.18, and 2.16 eV, respectively. Thus, the substitutional atoms remained firmly fixed at temperatures above 700 K. Similarly, the adsorption energies showed that nitric oxide and carbon oxide molecules exhibited stronger chemisorption than O2 molecules on any of the metal atoms (Au, Cu, or Ag) placed in the S vacancies of the WS2 monolayer. Therefore, the adsorption of O2 did not compete with NO or CO adsorption and did not displace them. The density of states showed that a WS2 monolayer modified with a Cu, Au, or Ag atom could be used to design sensing devices, based on electronic or magnetic properties, for atmospheric pollutants. More interestingly, the adsorption of CO changed only the electronic properties of the MoS2-AuS monolayer, which could be used for sensing applications. In contrast, the O2 molecule was chemisorbed more strongly than CO or NO on Au2S2, Cu2S2, or Ag2S2 placed into di-S vacancies. Thus, if the experimental system is exposed to air, the low quantities of O2 molecules present should result in the oxidation of the metallic atoms. Furthermore, the O2 molecules adsorbed on WS2-Au2S2 and WS2-CuS introduced a half-metallic behavior, making the system suitable for applications in spintronics.

Substitutional Coinage Metals as Promising Defects for Adsorption and Detection of Gases on MoS2 Monolayers: A Computational Approach.

Defective molybdenum disulfide (MoS2) monolayers (MLs) modified with coinage metal atoms (Cu, Ag and Au) embedded in sulfur vacancies are studied at a dispersion-corrected density functional level. Atmospheric constituents (H2, O2 and N2) and air pollutants (CO and NO), known as secondary greenhouse gases, are adsorbed on up to two atoms embedded into sulfur vacancies in MoS2 MLs. The adsorption energies suggest that the NO (1.44 eV) and CO (1.24 eV) are chemisorbed more strongly than O2 (1.07 eV) and N2 (0.66 eV) on the ML with a cooper atom substituting for a sulfur atom. Therefore, the adsorption of N2 and O2 does not compete with NO or CO adsorption. Besides, NO adsorbed on embedded Cu creates a new level in the band gap. In addition, it was found that the CO molecule could directly react with the pre-adsorbed O2 molecule on a Cu atom, forming the complex OOCO, via the Eley-Rideal reaction mechanism. The adsorption energies of CO, NO and O2 on Au2S2, Cu2S2 and Ag2S2 embedded into two sulfur vacancies were competitive. Charge transference occurs from the defective MoS2 ML to the adsorbed molecules, oxidizing the later ones (NO, CO and O2) since they act as acceptors. The total and projected density of states reveal that a MoS2 ML modified with copper, gold and silver dimers could be used to design electronic or magnetic devices for sensing applications in the adsorption of NO, CO and O2 molecules. Moreover, NO and O2 molecules adsorbed on MoS2-Au2s2 and MoS2-Cu2s2 introduce a transition from metallic to half-metallic behavior for applications in spintronics. These modified monolayers are expected to exhibit chemiresistive behavior, meaning their electrical resistance changes in response to the presence of NO molecules. This property makes them suitable for detecting and measuring NO concentrations. Also, modified materials with half-metal behavior could be beneficial for spintronic devices, particularly those that require spin-polarized currents.

The SciQA Scientific Question Answering Benchmark for Scholarly Knowledge.

Knowledge graphs have gained increasing popularity in the last decade in science and technology. However, knowledge graphs are currently relatively simple to moderate semantic structures that are mainly a collection of factual statements. Question answering (QA) benchmarks and systems were so far mainly geared towards encyclopedic knowledge graphs such as DBpedia and Wikidata. We present SciQA a scientific QA benchmark for scholarly knowledge. The benchmark leverages the Open Research Knowledge Graph (ORKG) which includes almost 170,000 resources describing research contributions of almost 15,000 scholarly articles from 709 research fields. Following a bottom-up methodology, we first manually developed a set of 100 complex questions that can be answered using this knowledge graph. Furthermore, we devised eight question templates with which we automatically generated further 2465 questions, that can also be answered with the ORKG. The questions cover a range of research fields and question types and are translated into corresponding SPARQL queries over the ORKG. Based on two preliminary evaluations, we show that the resulting SciQA benchmark represents a challenging task for next-generation QA systems. This task is part of the open competitions at the 22nd International Semantic Web Conference 2023 as the Scholarly Question Answering over Linked Data (QALD) Challenge.

The broad pathogenetic role of TCF7L2 in human diseases beyond type 2 diabetes.

The TCF7L2 protein is a key transcriptional effector of the Wnt/ß-catenin signaling pathway, regulating gene expression. It was initially identified in cancer research and embryologic developmental studies. Later, the TCF7L2 gene was linked to type 2 diabetes (T2D), implicating TCF7L2 and Wnt-signaling in metabolic disorders and homeostasis. In fact, TCF7L2-T2D variants confer the greatest relative risk for T2D, unquestionably predicting conversion to T2D in individuals with impaired glucose tolerance. We aim to describe the relevance of TCF7L2 in other human disorders. The TCF7L2-single nucleotide polymorphisms (SNPs) and T2D-risk association have been replicated in numerous follow-up studies, and research has now been performed in several other diseases. In this article, we discuss common TCF7L2-T2D variants within the framework of their association with human diseases. The TCF7L2 functional regions need to be further investigated because the molecular and cellular mechanisms through which TCF7L2 contributes to risk associations with different diseases are still not fully elucidated. In this review, we show the association of common TCF7L2-T2D variants with many types of diseases. However, the role of rare genetic variations in the TCF7L2 gene in distinct diseases and ethnic groups has not been explored, and understanding their impact on specific phenotypes will be of clinical relevance. This offers an excellent opportunity to gain a clearer picture of the role that the TCF7L2 gene plays in the pathophysiology of human diseases. The potential pleiotropic role of TCF7L2 may underlie a possible pathway for comorbidity in human disorders.

Sustained low-density lipoprotein-cholesterol <70 mg/dl is associated with improved cardiovascular outcomes in the clinical setting.

BACKGROUND AND AIMS: Clinical trials have shown that intensive low-density lipoprotein cholesterol (LDL-C) lowering improves cardiovascular outcomes among patients with atherosclerotic cardiovascular disease (ASCVD), but data are limited in real clinical practice, particularly for patients with ASCVD informing different territories. METHODS: FRENA was a prospective registry of consecutive outpatients with coronary, cerebrovascular or peripheral artery disease. We compared the incidence of recurrent events in patients with sustained LDL-C levels <70 mg/dl compared with those with ≥70 mg/dl. RESULTS: As of December 2018, 1182 patients were eligible for this study. Among them, 172 (14.5%) had mean LDL-C levels ≤70 mg/dl, and 1010 (85.5%) had <70 mg/dl. Their clinical characteristics at baseline were similar. During 5 years of follow-up, 252 patients (21%) suffered major adverse cardiovascular events (MACE). The incidence rates of MACE were 3.42 events per 100 patient-years (95% confidence interval [95% CI] 2.17-5.14) in patients with levels <70 mg/dl and 5.57 (95% CI, 4.87-6.34) in those with ≥70 mg/dl; the rate ratio was 0.61 (95% CI, 0.39-0.92), p = 0.019. On multivariable analysis, patients with LDL-C levels <70 mg/dl were at lower risk for MACE (hazard ratio [HR]: 0.61 [95% CI, 0.39-0.93] p < 0.05). MACE reduction was driven by a decrease in coronary and peripheral events with no significant effect on stroke. CONCLUSIONS: Long-term sustained LDL-C <70 mg/dl in the clinical practice is associated with reduction in cardiovascular and peripheral vascular events with no apparent effect on stroke.

Stroke Outcome Measurements From Electronic Medical Records: Cross-sectional Study on the Effectiveness of Neural and Nonneural Classifiers.

BACKGROUND: With the rapid adoption of electronic medical records (EMRs), there is an ever-increasing opportunity to collect data and extract knowledge from EMRs to support patient-centered stroke management. OBJECTIVE: This study aims to compare the effectiveness of state-of-the-art automatic text classification methods in classifying data to support the prediction of clinical patient outcomes and the extraction of patient characteristics from EMRs. METHODS: Our study addressed the computational problems of information extraction and automatic text classification. We identified essential tasks to be considered in an ischemic stroke value-based program. The 30 selected tasks were classified (manually labeled by specialists) according to the following value agenda: tier 1 (achieved health care status), tier 2 (recovery process), care related (clinical management and risk scores), and baseline characteristics. The analyzed data set was retrospectively extracted from the EMRs of patients with stroke from a private Brazilian hospital between 2018 and 2019. A total of 44,206 sentences from free-text medical records in Portuguese were used to train and develop 10 supervised computational machine learning methods, including state-of-the-art neural and nonneural methods, along with ontological rules. As an experimental protocol, we used a 5-fold cross-validation procedure repeated 6 times, along with subject-wise sampling. A heatmap was used to display comparative result analyses according to the best algorithmic effectiveness (F1 score), supported by statistical significance tests. A feature importance analysis was conducted to provide insights into the results. RESULTS: The top-performing models were support vector machines trained with lexical and semantic textual features, showing the importance of dealing with noise in EMR textual representations. The support vector machine models produced statistically superior results in 71% (17/24) of tasks, with an F1 score >80% regarding care-related tasks (patient treatment location, fall risk, thrombolytic therapy, and pressure ulcer risk), the process of recovery (ability to feed orally or ambulate and communicate), health care status achieved (mortality), and baseline characteristics (diabetes, obesity, dyslipidemia, and smoking status). Neural methods were largely outperformed by more traditional nonneural methods, given the characteristics of the data set. Ontological rules were also effective in tasks such as baseline characteristics (alcoholism, atrial fibrillation, and coronary artery disease) and the Rankin scale. The complementarity in effectiveness among models suggests that a combination of models could enhance the results and cover more tasks in the future. CONCLUSIONS: Advances in information technology capacity are essential for scalability and agility in measuring health status outcomes. This study allowed us to measure effectiveness and identify opportunities for automating the classification of outcomes of specific tasks related to clinical conditions of stroke victims, and thus ultimately assess the possibility of proactively using these machine learning techniques in real-world situations.

Induction of cell death in ovarian cancer cells by doxorubicin and oncolytic vaccinia virus is associated with CREB3L1 activation.

We have demonstrated that oncolytic vaccinia virus synergizes with doxorubicin (DOX) in inducing immunogenic cell death in platinum-resistant ovarian cancer cells and increases survival in syngeneic and xenograft tumor models. However, the mechanisms underlying the virus- and doxorubicin-mediated cancer cell death remain unknown. In this study, we investigated the effect of the oncolytic virus and doxorubicin used alone or in combination on activation of the cytoplasmic transcription factor CREB3L1 (cyclic AMP [cAMP] response element-binding protein 3-like 1) in ovarian cancer cell lines and clinical specimens. We demonstrated that doxorubicin-mediated cell death in ovarian cancer cell lines was associated with nuclear translocation of CREB3L1 and that the effect was augmented by infection with oncolytic vaccinia virus or treatment with recombinant interferon (IFN)-ß used as a viral surrogate. This combination treatment was also effective in mediating nuclear translocation of CREB3L1 in cancer cells isolated from ovarian tumor biopsies at different stages of disease progression. The measurement of CREB3L1 expression in clinical specimens of ovarian cancer revealed lack of correlation with the stage of disease progression, suggesting that understanding the mechanisms of nuclear accumulation of CREB3L1 after doxorubicin treatment alone or in combination with oncolytic virotherapy may lead to the development of more effective treatment strategies against ovarian cancer.

Recurrent Frameshift Neoantigen Vaccine Elicits Protective Immunity With Reduced Tumor Burden and Improved Overall Survival in a Lynch Syndrome Mouse Model.

BACKGROUND & AIMS: DNA mismatch repair deficiency drives microsatellite instability (MSI). Cells with MSI accumulate numerous frameshift mutations. Frameshift mutations affecting cancer-related genes may promote tumorigenesis and, therefore, are shared among independently arising MSI tumors. Consequently, such recurrent frameshift mutations can give rise to shared immunogenic frameshift peptides (FSPs) that represent ideal candidates for a vaccine against MSI cancer. Pathogenic germline variants of mismatch repair genes cause Lynch syndrome (LS), a hereditary cancer syndrome affecting approximately 20-25 million individuals worldwide. Individuals with LS are at high risk of developing MSI cancer. Previously, we demonstrated safety and immunogenicity of an FSP-based vaccine in a phase I/IIa clinical trial in patients with a history of MSI colorectal cancer. However, the cancer-preventive effect of FSP vaccination in the scenario of LS has not yet been demonstrated. METHODS: A genome-wide database of 488,235 mouse coding mononucleotide repeats was established, from which a set of candidates was selected based on repeat length, gene expression, and mutation frequency. In silico prediction, in vivo immunogenicity testing, and epitope mapping was used to identify candidates for FSP vaccination. RESULTS: We identified 4 shared FSP neoantigens (Nacad [FSP-1], Maz [FSP-1], Senp6 [FSP-1], Xirp1 [FSP-1]) that induced CD4/CD8 T cell responses in naïve C57BL/6 mice. Using VCMsh2 mice, which have a conditional knockout of Msh2 in the intestinal tract and develop intestinal cancer, we showed vaccination with a combination of only 4 FSPs significantly increased FSP-specific adaptive immunity, reduced intestinal tumor burden, and prolonged overall survival. Combination of FSP vaccination with daily naproxen treatment potentiated immune response, delayed tumor growth, and prolonged survival even more effectively than FSP vaccination alone. CONCLUSIONS: Our preclinical findings support a clinical strategy of recurrent FSP neoantigen vaccination for LS cancer immunoprevention.

Lower airway bacterial microbiome may influence recurrence after resection of early-stage non-small cell lung cancer.

OBJECTIVE: The lower airway bacterial microbiome influences carcinogenesis and response to immunotherapy in non-small cell lung cancer (NSCLC). We investigated the association of this microbiome with recurrence in early NSCLC. METHODS: Microbiomes of presurgery bronchoalveolar lavage (BAL) and saliva, and resected stage I NSCLC tumor and adjacent lung tissues of 48 patients were examined by 16S gene sequencing. Tumor gene expression was measured by RNA sequencing. RESULTS: Spatial relationships of the different biospecimen types was reflected in their microbiomes, with microbiomes of BAL intermediate to those of saliva and lung tissue. BAL and saliva microbiomes were less dissimilar in patients with high α-amylase levels in BAL, indicating oral aspiration as a source of lower airway microbiota. BAL microbiomes of patients with recurrence within 32 months of surgery differed from those without recurrence during ≥32 months of follow-up (n = 18 each), despite no difference for age, sex, smoking history, and tumor histology and grade. The recurrence-associated BAL microbiome signature was present in 16 of the 18 recurrence cases but in only two of the others. Signature presence was associated with shorter recurrence-free survival (log-rank test P < .001; hazard ratio = 14.5), and greater expression in tumors of genes for cell proliferation and epithelial mesenchymal transition. Immune cellular composition of the tumor microenvironment was not different between patients with and without the signature. CONCLUSIONS: Presurgery composition of lower airway microbiome may be associated with recurrence of early NSCLC. This association may reflect an influence of the microbiome on tumor biology.

Efficient identification of neoantigen-specific T-cell responses in advanced human ovarian cancer.

BACKGROUND: Efficient identification of neoantigen-specific T-cell responses in epithelial ovarian cancer (EOC) remains a challenge. Existing investigations of spontaneous T-cell response to tumor neoepitope in EOC have taken the approach of comprehensive screening all neoantigen candidates, with a validation rate of 0.5-2%. METHODS: Whole-exome and transcriptome sequencing analysis of treatment-naive EOC patients were performed to identify neoantigen candidates, and the immunogenicity of prioritized neoantigens was evaluated by analyzing spontaneous neoantigen-specfic CD4+ and CD8+ T-cell responses in the tumor and/or peripheral blood. The biological relevance of neoantigen-specific T-cell lines and clones were analyzed by evaluating the capacity of autologous ovarian tumor recognition. Genetic transfer of T-cell receptor (TCR) from these neoantigen-specific T-cell clones into peripheral blood T-cells was conducted to generate neoepitope-specific T-cells. The molecular signature associated with positive neoantigen T-cell responses was investigated, and the impacts of expression level and lymphocyte source on neoantigen identification were explored. RESULTS: Using a small subset of prioritized neoantigen candidates, we were able to detect spontaneous CD4+ and/or CD8+ T-cell responses against neoepitopes from autologous lymphocytes in half of treatment-naïve EOC patients, with a significantly improved validation rate of 19%. Tumors from patients exhibiting neoantigen-specific T-cell responses exhibited a signature of upregulated antigen processing and presentation machinery, which was also associated with favorable patient survival in the TCGA ovarian cohort. T-cells specific against two mutated cancer-associated genes, NUP214 and JAK1, recognized autologous tumors. Gene-engineering with TCR from these neoantigen-specific T-cell clones conferred neoantigen-reactivity to peripheral T-cells. CONCLUSIONS: Our study demonstrated the feasibility of efficiently identifying both CD4+ and CD8+ neoantigen-specific T-cells in EOC. Autologous lymphocytes genetically engineered with tumor antigen-specific TCR can be used to generate cells for use in the personalized adoptive T-cell transfer immunotherapy.

Protein Kinase N1 control of androgen-responsive serum response factor action provides rationale for novel prostate cancer treatment strategy.

Sustained reliance on androgen receptor (AR) after failure of AR-targeting androgen deprivation therapy (ADT) prevents effective treatment of castration-recurrent (CR) prostate cancer (CaP). Interfering with the molecular machinery by which AR drives CaP progression may be an alternative therapeutic strategy but its feasibility remains to be tested. Here, we explore targeting the mechanism by which AR, via RhoA, conveys androgen-responsiveness to serum response factor (SRF), which controls aggressive CaP behavior and is maintained in CR-CaP. Following a siRNA screen and candidate gene approach, RNA-Seq studies confirmed that the RhoA effector Protein Kinase N1 (PKN1) transduces androgen-responsiveness to SRF. Androgen treatment induced SRF-PKN1 interaction, and PKN1 knockdown or overexpression severely impaired or stimulated, respectively, androgen regulation of SRF target genes. PKN1 overexpression occurred during clinical CR-CaP progression, and hastened CaP growth and shortened CR-CaP survival in orthotopic CaP xenografts. PKN1's effects on SRF relied on its kinase domain. The multikinase inhibitor lestaurtinib inhibited PKN1 action and preferentially affected androgen regulation of SRF over direct AR target genes. In a CR-CaP patient-derived xenograft, expression of SRF target genes was maintained while AR target gene expression declined and proliferative gene expression increased. PKN1 inhibition decreased viability of CaP cells before and after ADT. In patient-derived CaP explants, lestaurtinib increased AR target gene expression but did not significantly alter SRF target gene or proliferative gene expression. These results provide proof-of-principle for selective forms of ADT that preferentially target different fractions of AR's transcriptional output to inhibit CaP growth.

[Cerebral tuberculosis without meningitis in a immunocompetent child]. / Tuberculosis cerebral sin meningitis en un niño inmunocompetente.

Cerebral tuberculosis TB (tuberculomas) without meningitis is an uncommon disease with a high morbidity and mortality. We report on a case that illustrates the complexity of this clinical presentation. An 11 month old, previously healthy male infant was brought to the clinic due to fever present during the last 1.5 months, associated with loss of neurodevelopmental goals and signs of endocranial hypertension. CT scan of the skull revealed dilatation of the ventricular system with transependimary edema; MRI showed multiple intra- and extra-axial micronodular images and hydrocephalus. Studies of CSF (cyto-chemical analysis, staining, culture for aerobes, fungi, mycobacteria, and molecular tests for TB were negative). Empirical management for subacute meningoencephalitis was prescribed complemented with tetraconjugated treatment for TB and steroids. As there was no microbiological isolation, biopsy of a cerebellar lesion was performed, which revealed chronic necrotizing granulomatous inflammation and acid-alcohol resistant bacilli. The diagnosis of cerebral TB without meningeal involvement was confirmed. The objective of the present report is to emphasize the importance of considering this presentation of TB in children, to remark the need of exhaustive search for the etiologic agent by obtaining samples of the different fluids and tissues even if it implies recurring to invasive methods.

Tuberculosis cerebral sin meningitis en un niño inmunocompetente / Cerebral tuberculosis without meningitis in a immunocompetent child

Resumen La tuberculosis (TBC) cerebral o tuberculoma(s) sin meningitis es una enfermedad poco frecuente y de alta morbimortalidad. Presentamos el caso clínico de un lactante de 11 meses, previamente sano, que consultó por fiebre prolongada y síntomas neurológicos. La RM de encéfalo mostró múltiples imágenes micronodulares e hidrocefalia. El estudio de LCR para bacterias, hongos y micobacterias fue negativo. Se prescribió terapia empírica como una meningoencefalitis subaguda y tratamiento antituberculoso tetraconjugado y corticoesteroides. La confirmación del diagnóstico de TBC cerebral se realizó por biopsia de la lesión, con presencia de inflamación granulomatosa crónica necrosante y bacilos ácido-alcohol resistentes. Se enfatiza la importancia de considerar esta presentación de TBC en niños, y la necesidad de la búsqueda exhaustiva del agente etiológico en diferentes líquidos y tejidos, aun por métodos invasores.

Cerebral tuberculosis TB (tuberculomas) without meningitis is an uncommon disease with a high morbidity and mortality. We report on a case that illustrates the complexity of this clinical presentation. An 11 month old, previously healthy male infant was brought to the clinic due to fever present during the last 1.5 months, associated with loss of neurodevelopmental goals and signs of endocranial hypertension. CT scan of the skull revealed dilatation of the ventricular system with transependimary edema; MRI showed multiple intra- and extra-axial micronodular images and hydrocephalus. Studies of CSF (cyto-chemical analysis, staining, culture for aerobes, fungi, mycobacteria, and molecular tests for TB were negative). Empirical management for subacute meningoencephalitis was prescribed complemented with tetraconjugated treatment for TB and steroids. As there was no microbiological isolation, biopsy of a cerebellar lesion was performed, which revealed chronic necrotizing granulomatous inflammation and acid-alcohol resistant bacilli. The diagnosis of cerebral TB without meningeal involvement was confirmed. The objective of the present report is to emphasize the importance of considering this presentation of TB in children, to remark the need of exhaustive search for the etiologic agent by obtaining samples of the different fluids and tissues even if it implies recurring to invasive methods.

FOXA1 hypermethylation: link between parity and ER-negative breast cancer in African American women?

BACKGROUND: Reproductive factors, particularly parity, have differential effects on breast cancer risk according to estrogen receptor (ER) status, especially among African American (AA) women. One mechanism could be through DNA methylation, leading to altered expression levels of genes important in cell fate decisions. METHODS: Using the Illumina 450K BeadChip, we compared DNA methylation levels in paraffin-archived tumor samples from 383 AA and 350 European American (EA) women in the Women's Circle of Health Study (WCHS). We combined 450K profiles with RNA-seq data and prioritized genes based on differential methylation by race, correlation between methylation and gene expression, and biological function. We measured tumor protein expression and assessed its relationship to DNA methylation. We evaluated associations between reproductive characteristics and DNA methylation using linear regression. RESULTS: 410 loci were differentially methylated by race, with the majority unique to ER- tumors. FOXA1 was hypermethylated in tumors from AA versus EA women with ER- cancer, and increased DNA methylation correlated with reduced RNA and protein expression. Importantly, parity was positively associated with FOXA1 methylation among AA women with ER- tumors (P = 0.022), as was number of births (P = 0.026), particularly among those who did not breastfeed (P = 0.008). These same relationships were not observed among EA women, although statistical power was more limited. CONCLUSIONS: Methylation and expression of FOXA1 is likely impacted by parity and breastfeeding. Because FOXA1 regulates a luminal gene expression signature in progenitor cells and represses the basal phenotype, this could be a mechanism that links these reproductive exposures with ER- breast cancer.

Low serum levels of alpha1 anti-trypsin (α1-AT) and risk of airflow obstruction in non-primary α1-AT-deficient patients with compensated chronic liver disease.

BACKGROUND: Alpha1 anti-trypsin (α1-AT), a serine protease inhibitor synthesized in the liver, is a major circulating antiprotease that provides defense against proteolytic damage in several tissues. Its deficiency is associated with airflow obstruction. The present study aimed to explore the role of α1-AT as a biomarker of airflow performance in chronic liver disease (CLD). MATERIAL/METHODS: Serum α1-AT levels and lung function (spirometry) were evaluated in non-primary α1-AT-deficient, alcoholic CLD patients without evident respiratory limitations. RESULTS: Thirty-four patients with airflow obstruction (n=11), airflow restriction (n=12), and normal airflow (n=11, age-matched controls) were eligible. α1-AT was decreased in the airflow obstruction group. ROC-cutoff α1-AT=24 mg/dL effectively discriminated airflow obstruction (AUC=0.687) and was associated with a 10-fold higher risk (p=0.0007). CONCLUSIONS: Lower α1-AT increased the risk of airflow obstruction in CLD patients without primary α1-AT deficiency.

Deficiencia de micronutrientes y enfermedad celíaca en pediatría / Micronutrient deficiencies and celiac disease in Pediatrics

La enfermedad celíaca (EC) parece estar cambiando en su clínica, desde formas diarreicas con desnutrición hasta aquellas con clínica más silente y más tardía. La enteropatía de la EC ocurre con malabsorción de macro- y micronutrientes, que incluyen Fe, Zn, Cu, folato, Ca, vitaminas E, D, B12 y B6, con mecanismos de transporte alterados. La anemia ferropriva se ha descrito en EC como única manifestación o como la manifestación extraintestinal más frecuente. La deficiencia de Zn es frecuente en EC, asociada a un retraso de crecimiento y alteraciones inmunitarias. La malabsorción intestinal puede comprometer la absorción de vitamina D, aunque su aporte dietario es responsable solo del 20% de las concentraciones séricas, por lo que lo importante es la exposición dérmica al sol. La causa de deficiencia de vitamina B12 en EC es desconocida; debe considerarse ante alteraciones neurológicas y hematológicas. La deficiencia de Cu se ha descrito de preferencia en celíacos adultos. Se concluye que, en el seguimiento de la EC, debiera estudiarse periódicamente la deficiencia de micronutrientes por sus consecuencias a largo plazo; debe sospecharse una EC ante signos clínicos no explicados de deficiencia de micronutrientes.

Celiac disease (CD) is apparently changing in its clinical presentation, from chronic diarrhea and malnutrition to a silent clinic at older ages. The basal enteropathy of CD induces macro-and micronutrient malabsorption. Described micronutrient deficiencies in CD include: Fe, Zn, Cu, folate, Ca, vitamin E, D, B12 and B6, with complex transporter mechanisms altered. Ferropenic anemia has been described in CD as the exclusive sign and the most common extraintestinal sign. Zn deficiency is frequent in CD, associated with growth delay and immune alterations. Even though the main basis for vitamin D metabolic status is the activation of subdermal vitamin precursors by sun-UVB rays, the small bowel compromise may affect activity and vitamin D absorption. Pathophysiology of vitamin B12 deficiency in CD is unknown; it must be suspected in CD patients presenting neurological and haematological alterations. Copper deficiency has been described mainly in adult CD patients. Micronutrient deficiencies should be periodically studied through the CD follow-up; celiac disease must be studied if clinical signs of micronutrient deficiencies are diagnosed.

[Micronutrient deficiencies and celiac disease in Pediatrics]. / Deficiencia de micronutrientes y enfermedad celíaca en pediatría.

Celiac disease (CD) is apparently changing in its clinical presentation, from chronic diarrhea and malnutrition to a silent clinic at older ages. The basal enteropathy of CD induces macro-and micronutrient malabsorption. Described micronutrient deficiencies in CD include: Fe, Zn, Cu, folate, Ca, vitamin E, D, B12 and B6, with complex transporter mechanisms altered. Ferropenic anemia has been described in CD as the exclusive sign and the most common extraintestinal sign. Zn deficiency is frequent in CD, associated with growth delay and immune alterations. Even though the main basis for vitamin D metabolic status is the activation of subdermal vitamin precursors by sun-UVB rays, the small bowel compromise may affect activity and vitamin D absorption. Pathophysiology of vitamin B12 deficiency in CD is unknown; it must be suspected in CD patients presenting neurological and haematological alterations. Copper deficiency has been described mainly in adult CD patients. Micronutrient deficiencies should be periodically studied through the CD follow-up; celiac disease must be studied if clinical signs of micronutrient deficiencies are diagnosed.

Validation of the bladder control self-assessment questionnaire (B-SAQ) in men.

OBJECTIVE: To validate the Bladder Control Self-Assessment Questionnaire (B-SAQ), a short screener to assess lower urinary tract symptoms (LUTS) and overactive bladder (OAB) in men. PATIENTS AND METHODS: This was a prospective, single-centre study including 211 patients in a urology outpatient setting. All patients completed the B-SAQ and Kings Health Questionnaire (KHQ) before consultation, and the consulting urologist made an independent assessment of LUTS and the need for treatment. The psychometric properties of the B-SAQ were analysed. RESULTS: A total of 98% of respondents completed all items correctly in <5 min. The mean B-SAQ scores were 12 and 3.3, respectively for cases (n = 101) and controls (n = 108) (P < 0.001). Good correlation was evident between the B-SAQ and the KHQ. The agreement percentages between the individual B-SAQ items and the KHQ symptom severity scale were 86, 85, 84 and 79% for frequency, urgency, nocturia and urinary incontinence, respectively. Using a B-SAQ symptom score threshold of ≥4 alone had sensitivity, specificity and positive predictive values for detecting LUTS of 75, 86 and 84%, respectively, with an area under the curve of 0.88; however, in combination with a bother score threshold of ≥1 these values changed to 92, 46 and 86%, respectively. CONCLUSIONS: The B-SAQ is an easy and quick valid case-finding tool for LUTS/OAB in men, but appears to be less specific in men than in women. The B-SAQ has the potential to raise awareness of LUTS. Further validation in a community setting is required.

Neurogenic detrusor overactivity in patients with spinal cord injury: evaluation and management.

Lower urinary tract dysfunction can have a significant impact on patients with spinal cord injury. Over the years, many treatment options have become available. This article reviews the assessment and management of neurogenic detrusor overactivity, with a particular focus on articles from the recent literature. Recent guidelines on the subject will be discussed. Management options include antimuscarinics and bladder emptying measures, botulinum toxin A, and neuromodulation in refractory cases and surgery for intractable cases. Recent and relevant publications in these areas will be summarized and discussed.