Identification of Smith-Magenis syndrome cases through an experimental evaluation of machine learning methods.

This research work introduces a novel, nonintrusive method for the automatic identification of Smith-Magenis syndrome, traditionally studied through genetic markers. The method utilizes cepstral peak prominence and various machine learning techniques, relying on a single metric computed by the research group. The performance of these techniques is evaluated across two case studies, each employing a unique data preprocessing approach. A proprietary data "windowing" technique is also developed to derive a more representative dataset. To address class imbalance in the dataset, the synthetic minority oversampling technique (SMOTE) is applied for data augmentation. The application of these preprocessing techniques has yielded promising results from a limited initial dataset. The study concludes that the k-nearest neighbors and linear discriminant analysis perform best, and that cepstral peak prominence is a promising measure for identifying Smith-Magenis syndrome.

MAIT and Vδ2 unconventional T cells are supported by a diverse intestinal microbiome and correlate with favorable patient outcome after allogeneic HCT.

Microbial diversity is associated with improved outcomes in recipients of allogeneic hematopoietic cell transplantation (allo-HCT), but the mechanism underlying this observation is unclear. In a cohort of 174 patients who underwent allo-HCT, we demonstrate that a diverse intestinal microbiome early after allo-HCT is associated with an increased number of innate-like mucosal-associated invariant T (MAIT) cells, which are in turn associated with improved overall survival and less acute graft-versus-host disease (aGVHD). Immune profiling of conventional and unconventional immune cell subsets revealed that the prevalence of Vδ2 cells, the major circulating subpopulation of γδ T cells, closely correlated with the frequency of MAIT cells and was associated with less aGVHD. Analysis of these populations using both single-cell transcriptomics and flow cytometry suggested a shift toward activated phenotypes and a gain of cytotoxic and effector functions after transplantation. A diverse intestinal microbiome with the capacity to produce activating ligands for MAIT and Vδ2 cells appeared to be necessary for the maintenance of these populations after allo-HCT. These data suggest an immunological link between intestinal microbial diversity, microbe-derived ligands, and maintenance of unconventional T cells.

Validation of the Spanish Version of the Pain Assessment in Advanced Dementia Scale (PAINAD-Sp) in Hospitalized Patients with Neurologic Disorders and Oncologic Patients Unable to Self-Report Their Pain.

BACKGROUND: Pain has a significant impact on hospitalized patients and is a quality indicator for nursing care. The Pain Assessment in Advanced Dementia (PAINAD) scale measures pain in people with communication disorders and advanced dementia, but it has not been validated in any other population. AIMS: The aim of this study was to validate the Spanish version (PAINAD-Sp) in hospitalized patients with neurologic disorders and in end-of-life cancer patients with difficulty self-reporting. DESIGN: The study had two phases: (1) analysis of the content by a committee of experts and (2) a cross-sectional study. SETTINGS: We collected phase 2 data from January 2017 to December 2017 in four hospitals in Barcelona: Hospital Germans Trias i Pujol, Institut Català d'Oncologia, Hospital Vall d'Hebron, and Hospital de Bellvitge. PARTICIPANTS/SUBJECTS: We included all adults who had either a neurological disorder affecting language or an oncological disease with an end-of-life prognosis and difficulty self-reporting pain. We excluded patients with a diagnosis of dementia. METHODS: The cross-sectional study included 325 patients who were simultaneously evaluated by two observers both at rest and in movement. We analyzed psychometric properties in terms of construct validity, reliability, and sensitivity to change. RESULTS: We obtained Cronbach α > .70 in both situations and an inter-rater reliability of 0.80. Confirmatory factor analysis indicated that the model adjusted adequately to a unidimensional structure. In terms of sensitivity to change, the mean difference was greater in movement than at rest (difference in means was 1.15). CONCLUSIONS: The PAINAD-Sp_Hosp scale had good psychometric qualities in terms of validity and reliability in neurology and oncology patients unable to self-report pain.

Expression inactivation of SMARCA4 by microRNAs in lung tumors.

SMARCA4 is the catalytic subunit of the SWI/SNF chromatin-remodeling complex, which alters the interactions between DNA and histones and modifies the availability of the DNA for transcription. The latest deep sequencing of tumor genomes has reinforced the important and ubiquitous tumor suppressor role of the SWI/SNF complex in cancer. However, although SWI/SNF complex plays a key role in gene expression, the regulation of this complex itself is poorly understood. Significantly, an understanding of the regulation of SMARCA4 expression has gained in importance due to recent proposals incorporating it in therapeutic strategies that use synthetic lethal interactions between SMARCA4-MAX and SMARCA4-SMARCA2. In this report, we found that the loss of expression of SMARCA4 observed in some primary lung tumors, whose mechanism was largely unknown, can be explained, at least partially by the activity of microRNAs (miRNAs). We reveal that SMARCA4 expression is regulated by miR-101, miR-199 and especially miR-155 through their binding to two alternative 3'UTRs. Importantly, our experiments suggest that the oncogenic properties of miR-155 in lung cancer can be largely explained by its role inhibiting SMARCA4. This new discovered functional relationship could explain the poor prognosis displayed by patients that independently have high miR-155 and low SMARCA4 expression levels. In addition, these results could lead to application of incipient miRNA technology to the aforementioned synthetic lethal therapeutic strategies.

Periodontopathogen and Epstein-Barr virus-associated periapical periodontitis may be the source of retrograde infectious peri-implantitis.

BACKGROUND: Herpesviral-bacterial synergism may play a role in periodontitis and peri-implantitis etiopathogenesis. Periapical periodontitis (PP) lesions can predict future apical peri-implantitis complications. PURPOSE: This pilot study aimed to substantiate herpesviral-bacterial coinfection in symptomatic (SP) and asymptomatic (AP) PP and assess associations with periodontopathogen salivary contamination in patients receiving implants. MATERIALS AND METHODS: Polymerase chain reaction (PCR)-based identification was performed on PP granulation tissue (GT) from 33 SP and AP patients and compared with unstimulated whole saliva. Quantitative PCR evaluated Epstein-Barr virus (EBV) and cytomegalovirus copy counts. RESULTS: SP GT had higher proportions of periodontopathogens. Symptomatic patients were 3.7 times more likely to be infected with EBV than AP (p = .07; 95% CI: 0.8-16.2). SP were 2.9, 2.1, 3.6, and 1.6 times more likely to be infected with Treponema denticola, Prevotella intermedia, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis, respectively. The odds ratio of EBV infecting PP lesions was two times higher in those positive for the virus in saliva. Saliva Tannerella forsythia-positive patients were 15 times more likely to present this pathogen in PP lesions (p = .038). Saliva EBV-positive individuals were 7 and 3.5 times more likely to yield GT contamination with T. forsythia and T. denticola, respectively. EBV copy counts were significantly higher in SP (p < .01). CONCLUSIONS: A causal association between EBV, specific bacterial anaerobic infection, and symptomatic PP is likely. EBV high prevalence underscores the viral etiological importance. Salivary EBV contamination is likely to be associated with viral and bacterial GT infection. Saliva PCR analysis can be a good predictor of GT specific infection and help establish antimicrobial therapy. If confirmed by prospective longitudinal clinical trials, antiviral therapy could possibly benefit SP and nonresponsive to treatment individuals and help prevent potential peri-implant infectious complications.

Influence of CYP2D6 polymorphisms on serum levels of tamoxifen metabolites in Spanish women with breast cancer.

BACKGROUND: Estrogen receptor-positive breast cancer tumors depend on estrogen signaling for their growth and replication and can be treated by anti-estrogen therapy with tamoxifen. Polymorphisms of the CYP2D6 and CYP2C19 genes are associated with an impaired response to tamoxifen. The study objective was to investigate the impact of genetic polymorphisms in CYP2D6 and CYP2C19 on the pharmacokinetics of tamoxifen and its metabolites in Spanish women with estrogen receptor-positive breast cancer who were candidates for tamoxifen therapy. METHODS: We studied 90 women with estrogen receptor-positive breast cancer, using the AmpliChip CYP450 test to determine CYP2D6 and CYP2C19 gene variants. Plasma levels of tamoxifen and its metabolites were quantified by high-performance liquid chromatography. RESULTS: The CYP2D6 phenotype was extensive metabolizer in 80%, intermediate metabolizer in 12.2%, ultra-rapid metabolizer in 2.2%, and poor metabolizer in 5.6% of patients, and the allele frequency was 35.0% for allele (*)1, 21.0% for *2, and 18.9% for *4. All poor metabolizers in this series were *4/*4, and their endoxifen and 4-hydroxy tamoxifen levels were 25% lower than those of extensive metabolizers. CYP2C19*2 allele, which has been related to breast cancer outcomes, was detected in 15.6% of the studied alleles. CONCLUSION: CYP2D6*4/*4 genotype was inversely associated with 4-hydroxy tamoxifen and endoxifen levels. According to these results, CYP2D6 and CYP2C19 genotyping appears advisable before the prescription of tamoxifen therapy.

Multiplex primer extension reaction and capillary electrophoresis to study the frequency of thrombophilia-related mutations in a spanish population.

BACKGROUND: Thrombophilia is defined as an inherited or acquired abnormality of hemostasis predisposing to thrombosis. While the most common thrombophilia has a genetic origin and is manifested by elevated circulating antiphospholipid antibodies, about 40% of cases presenting with thrombosis are acquired. Factor V Leiden G1691A, prothrombin G20210A, MTHFR C677T, and Factor XII C46T mutations are associated with the risk of developing thrombophilia. METHODS: In this study, a method using single base extension assay coupled with fluorescent detection and capillary electrophoresis was applied to simultaneously detect G1691A, G20210A, C677T and C46T mutations in 1499 patients from Spain with suspicion of thrombotic disease. RESULTS: Out of these individuals, 5.4% were heterozygous for G20210A mutation, 9.21% were heterozygous and 0.20% homozygous for G1691A mutation, 46.36% were heterozygous and 20.71% homozygous for MTHFR mutation, and 30.41% were heterozygous and 3.4% homozygous for C46T mutation. CONCLUSION: We applied an accurate, simple, semi-automatic, and cost-effective method to simultaneously detect the main thrombophilia-related mutations, allowing us to determine the frequency of these mutations in a Spanish population.

Rifampicina isoniazida intermitente en el tratamiento de la tuberculosis pulmonar infantil / Pulmonary infant tuberculosis intermitent in the treatment with rifampin and isoniacid

Se trataron 38 pacientes que tenian tuberculosis pulmonar progresiva, con rifampicina e isoniazida intermitente, despues de una fase inicial diaria; treinta ninos terminaron el tratamiento. Diez tenian neumonia, once bronconeumonia, ocho tuberculosis miliar y uno una caverna. Los resultados fueron muy satisfactorios, pues todos los pacientes curaron clinica y bacteriologicamente. Clinicamente presentaron franca mejoria el 86.2% de los pacientes en el primer mes y el 13,8% a los 4 meses. La curacion bacteriologica fue del 76.4% en el primer mes y del 23.6% entre los dos y los cuatro meses. La mejoria radiologica tuvo lugar en el 73.4% de los casos en los primeros cuatro meses y en el 100% de los casos a los 9 meses. Por estos resultados creemos que el tratamiento quimioterapeutico intermitente con rifampicina e isoniazida es tan efectivo como el regimen de administracion diaria, de facil administracion y acorta el tiempo de tratamiento. Como reacciones toxicas observamos: eosinofilia en el 80% de los casos, la cual persistio generalmente elevada durante todo el tratamiento con algunas fluctuaciones; elevacion de las transaminasas en 18 pacientes en forma transitoria sin necesidad de suspender el...