Cytochrome b5 reductase 3 overexpression and dietary nicotinamide riboside supplementation promote distinctive mitochondrial alterations in distal convoluted tubules of mouse kidneys during aging.

The kidney undergoes structural and physiological changes with age, predominantly studied in glomeruli and proximal tubules. However, limited knowledge is available about the impact of aging and anti-aging interventions on distal tubules. In this study, we investigated the effects of cytochrome b5 reductase 3 (CYB5R3) overexpression and/or dietary nicotinamide riboside (NR) supplementation on distal tubule mitochondria. Initially, transcriptomic data were analyzed to evaluate key genes related with distal tubules, CYB5R3, and NAD+ metabolism, showing significant differences between males and females in adult and old mice. Subsequently, our emphasis focused on assessing how these interventions, that have demonstrated the anti-aging potential, influenced structural parameters of distal tubule mitochondria, such as morphology and mass, as well as abundance, distance, and length of mitochondria-endoplasmic reticulum contact sites, employing an electron microscopy approach. Our findings indicate that both interventions have differential effects depending on the age and sex of the mice. Aging resulted in an increase in mitochondrial size and a decrease in mitochondrial abundance in males, while a reduction in abundance, size, and mitochondrial mass was observed in old females when compared with their adult counterparts. Combining both the interventions, CYB5R3 overexpression and dietary NR supplementation mitigated age-related changes; however, these effects were mainly accounted by NR in males and by transgenesis in females. In conclusion, the influence of CYB5R3 overexpression and dietary NR supplementation on distal tubule mitochondria depends on sex, genotype, and diet. This underscores the importance of incorporating these variables in subsequent studies to comprehensively address the multifaceted aspects of aging.

Domain wall propagation and pinning induced by current pulses in cylindrical modulated nanowires.

The future developments in 3D magnetic nanotechnology require the control of domain wall dynamics by means of current pulses. While this has been extensively studied in 2D magnetic strips (planar nanowires), few reports on this exist in cylindrical geometry, where Bloch point domain walls are expected to have intriguing properties. Here, we report an investigation on cylindrical magnetic Ni nanowires with geometrical notches. An experimental work based on synchrotron X-ray magnetic circular dichroism (XMCD) combined with photoemission electron microscopy (PEEM) indicates that large current densities induce domain wall nucleation, while smaller currents move domain walls preferably antiparallel to the current direction. In the region where no pinning centers are present, we found a domain wall velocity of about 1 km s-1. Thermal modelling indicates that large current densities temporarily raise the temperature in the nanowire above the Curie temperature, leading to nucleation of domain walls during the system cooling. Micromagnetic modelling with a spin-torque effect shows that for intermediate current densities, Bloch point domain walls with chirality parallel to the Oersted field propagate antiparallel to the current direction. In other cases, domain walls can be bounced from the notches and/or get pinned outside their positions. We thus found that current is not only responsible for domain wall propagation, but also is a source of pinning due to the Oersted field action.

Increased frequency of CD14+HLA-DR-/low cells in type 2 diabetes patients with poor glycemic control.

AIMS: Type 2 diabetes (T2DM) is associated with alterations of the immune response and T2DM patients have an increased risk for infections and certain sorts of cancers. Although CD14+HLA-DR-/low cells have emerged as important mediators of immunosuppression in several pathologies, including cancer and non-malignant diseases, the presence of these cells in T2DM is not fully characterized. METHODS: In this study, we evaluated the frequency of CD14+HLA-DR-/low cells in non-obese T2DM patients and their association with glycemic control. Peripheral blood mononuclear cells were isolated from healthy controls (HC, n = 24) and non-obese T2DM patients (n = 25), the population was evaluated by flow cytometry, and an analysis of correlation between cell frequencies and clinical variables was performed. RESULTS: CD14+HLA-DR-/low monocytes were expanded in patients with T2DM compared to HC regardless of weight. Among the subjects with T2DM, the frequency of CD14+HLA-DR-/low was higher in patients with poor glycemic control (HbA1c > 9%) compared to those with better glycemic control (HbA1c < 9%) and, positively correlated with the years since the diagnosis of T2DM, the age of the patients and the glycemic index. CONCLUSIONS: An increased frequency of CD14+HLA-DR-/low cells in the blood of T2DM patients was recorded. The influence of hyperglycemia seems to be independent of obesity, but related to glycemic control and age.

Gut microbiota and voluntary alcohol consumption.

Alcohol is part of the usual diet of millions of individuals worldwide. However, not all individuals who drink alcohol experience the same effects, nor will everyone develop an alcohol use disorder. Here we propose that the intestinal microbiota (IMB) helps explain the different consumption patterns of alcohol among individuals. 507 humans participated in this study and alcohol consumption and IMB composition were analyzed. On the other hand, in 80 adult male Wistar rats, behavioral tests, alcohol intoxication, fecal transplantation, administration of antibiotics and collection of fecal samples were performed. For identification and relative quantification of bacterial taxa was used the bacterial 16 S ribosomal RNA gene. In humans, we found that heavy episodic drinking is associated with a specific stool type phenotype (type 1, according to Bristol Stool Scale; p < 0.05) and with an increase in the abundance of Actinobacteria (p < 0.05). Next, using rats, we demonstrate that the transfer of IMB from alcohol-intoxicated animals causes an increase in voluntary alcohol consumption in transplant-recipient animals (p < 0.001). The relative quantification data indicate that the genus Porphyromonas could be associated with the effect on voluntary alcohol consumption. We also show that gut microbiota depletion by antibiotics administration causes a reduction in alcohol consumption (p < 0.001) and altered the relative abundance of relevant phyla such as Firmicutes, Bacteroidetes or Cyanobacteria (p < 0.05), among others. Benjamini-Hochberg false discovery rate (FDR) correction was performed for multiple comparisons. These studies reveal some of the consequences of alcohol on the IMB and provide evidence that manipulation of IMB may alter voluntary alcohol consumption.

Repair of Traumatic Urethral Strictures: La Paz University Hospital Experience.

INTRODUCTION: The management of traumatic urethral strictures remains a challenge for urologists. Alteration of the pelvic anatomy and the significant fibrosis generated by the trauma make surgical repair complex. In most cases, the existing defect between the urethral ends is small, and the ideal treatment is end-to-end perineal urethroplasty. Cases of extensive strictures that are left with long gap defects may require the use of different sequential maneuvers to achieve a tension-free anastomosis. OBJECTIVE: To describe the experience at our center with urethral strictures induced by closed perineal trauma. MATERIALS AND METHODS: A retrospective analysis of 116 patients who underwent urethroplasty for urethral stricture after blunt perineal trauma at our center between 1965 and 2020 was conducted. Demographic data, date, mechanism of action of the trauma, emergency management, previous urethral interventions, surgical technique carried out in our center, complications, presence of erectile dysfunction, and urinary incontinence were collected. RESULTS: 82 patients (70.7%) presented with pelvic fractures. The most frequent etiology of trauma was traffic accidents (68%), followed by crushing injuries (24%). Suprapubic cystostomy was placed in 50.2% of patients, and urethral realignment was performed in 25.3%. The mean stricture length was 2.2 cm, affecting mostly the membranous urethra (67%). During surgery, it was necessary to perform crural separation in 61.5% and partial pubectomy in 18.8% of the cases. Erectile dysfunction developed after trauma in 40.5% of cases, while new erectile dysfunction was noted in 4.3% of patients after surgery. Surgery was successful in 91.3% of cases, with a median follow-up of 16 (6-47) months. CONCLUSION: Delayed anastomotic urethroplasty offers a high success rate in traumatic urethral strictures.

Identification of genetic risk factors associated with ischaemic stroke in young Mexican patients.

BACKGROUND: Numerous polymorphisms in candidate genes coding for haemostatic system proteins have been proposed as risk factors for thrombosis. METHODS: We performed a case-control study of consecutive ischaemic stroke survivors aged ≤45 years, treated at our neurology department from 2006 to 2014. Polymerase chain reaction-restriction fragment length polymorphism identified the following polymorphisms: Thr325Ile and Ala147Thr in TAFI, 4G/5G in PAI-1, PLA1/A2 in platelet glycoprotein IIb/IIIa, Glu298Asp in eNOS, and C677T in 5,10-MTHFR. A multivariate logistic regression analysis was performed to evaluate the independent risk of stroke. RESULTS: 204 cases and 204 age- and sex-matched controls were included in the study. Clinical and genetic variables associated with ischaemic stroke were hypertension (P=.03), tobacco use (P=.02), and the polymorphisms Glu298Asp (genotype: P=.001, allele frequency: P=.001) and C677T (genotype: P=.01); the Ala147Thr, Thr325IIe, 4G/5G, and PLA1/A2 mutations were not associated with ischaemic stroke. The 298Asp (P=.03) and T (P=.01) alleles, hypertension (P=.03), tobacco use (P=.01) and family history of stroke (P=.04) were identified as independent risk factors. CONCLUSION: The polymorphisms Glu298Asp and C677T, affecting the eNOS and 5,10-MTHFR enzymes, respectively, and smoking, hypertension, and family history of stroke were associated with ischaemic stroke in young Mexican patients; this was not the case for the Thr325Ile, Ala147Thr, 4G/5G, and PLA1/A2 polymorphisms of the genes coding for fibrinolytic proteins and platelet receptors.

Hepatocarcinoma: diagnóstico y resección con radiofrecuencia quirúrgica / HEPATOCARCINOMA: DIAGNOSIS AND RESECTION WITH SURGICAL RADIO FREQUENCY

Objetivo: Presentar metodología diagnostica y resección atípica, con fines curativos de hepatocarcinoma. Caso clínico: Femenina de 82 años, con múltiples antecedentes entre el que se destaca, hepatitis a virus C de 15 años de evolución, que presenta por estudios complementarios alta sospecha de hepatocarcinoma, se realiza laparotomía exploradora con resección atípica de tumor en segmento 5 y 6 con radiofrecuencia quirúrgica y colecistectomía con colangiografía intraoperatoria. Cursa post operatorio sin complicaciones con alta sanatorial al 8vo dia. Conclusion: Hay que sospechar esta patología en pacientes con antecedentes de hepatopatía viral, plantear screening adecuado para un diagnóstico temprano y la mejor resolución adaptada a cada paciente. Dentro de las opciones terapéuticas encontramos la radiofrecuencia quirúrgica como una buena herramienta, con índice bajo de complicaciones

Objective: To present diagnostic methodology and atypical resection, for curative purposes of hepatocarcinoma. Clinical case: An 82-year-old female, with multiple history factors, among them, hepatitis C virus of 15 years of evolution, which presents high suspicion of hepatocarcinoma due to complementary studies, exploratory laparotomy is performed with atypical resection of tumor in segments 5 and 6 with surgical radiofrequency and cholecystectomy with intraoperative cholangiography. Post-operative course without complications with sanatorial discharge on the 8th day. Conclusion: This pathology must be suspected in patients with history of viral liver disease. We suggest an adequate screening for an early diagnosis and the best resolution adapted to each patient. Among the therapeutic options we find surgical radiofrequency as a good tool, with a low rate of complications

Identificación de factores de riesgo genéticos asociados a la enfermedad vascular cerebral de tipo isquémico en jóvenes mexicanos / Identification of genetic risk factors associated with ischaemic stroke in young Mexican patients

Introducción: Diversos polimorfismos en genes candidatos que codifican proteínas del sistema hemostático se han propuesto como factores de riesgo para el desarrollo de trombosis.MétodosCasos y controles, sobrevivientes de enfermedad vascular cerebral (EVC) isquémica idiopática ≤ 45 años de edad del servicio de neurología incluidos de manera consecutiva de 2006 a 2014. Por PCR-RFLP se identificaron los polimorfismos: Thr325Ile y Ala147Thr del gen de TAFI, 4G/5G del gen de PAI-1, PLA1/A2 del gen de la glucoproteína plaquetaria IIb/IIIa, Glu298Asp del gen de eNOS, y C677T del gen de la 5,10 MTHFR. Se realizó un análisis multivariado de regresión logística para calcular el riesgo independiente de EVC.ResultadosDoscientos cuatro casos y 204 controles pareados por edad y sexo. Se asoció al polimorfismo Glu298Asp (genotipo p = 0,001 y frecuencia alélica p = 0,001), C677T (genotipo p = 0,01), hipertensión (p = 0,03) y tabaquismo (p = 0,02) con la presencia de EVC isquémico, no así para los polimorfismos Ala147Thr, Thr325IIe, 4G/5G y PLA1/A2. Se identificó como factor de riesgo independiente al alelo 298Asp (p = 0,03), T (p = 0,01), hipertensión (p = 0,03), tabaquismo (p = 0,01) y AHFEAT (p = 0,04).ConclusionesLos polimorfismos Glu298Asp y C677T de los genes que codifican a la enzima eNOS y 5,10 MTHFR, tabaquismo, hipertensión y AHFEAT se asociaron a la presencia de EVC isquémico en jóvenes mexicanos, no así el Thr325Ile, Ala147Thr, 4G/5G, PLA1/A2 en genes que codifican proteínas del sistema de fibrinólisis y receptores plaquetarios. (AU)

Introduction: Numerous polymorphisms in candidate genes coding for haemostatic system proteins have been proposed as risk factors for thrombosis.MethodsWe performed a case-control study of consecutive ischaemic stroke survivors aged ≤ 45 years, treated at our neurology department from 2006 to 2014. Polymerase chain reaction–restriction fragment length polymorphism identified the following polymorphisms: Thr325Ile and Ala147Thr in TAFI, 4G/5G in PAI-1, PLA1/A2 in platelet glycoprotein IIb/IIIa, Glu298Asp in eNOS, and C677T in 5,10-MTHFR. A multivariate logistic regression analysis was performed to evaluate the independent risk of stroke.Results204 cases and 204 age- and sex-matched controls were included in the study. Clinical and genetic variables associated with ischaemic stroke were hypertension (P = .03), tobacco use (P = .02), and the polymorphisms Glu298Asp (genotype: P = .001, allele frequency: P = .001) and C677T (genotype: P = .01); the Ala147Thr, Thr325IIe, 4G/5G, and PLA1/A2 mutations were not associated with ischaemic stroke. The 298Asp (P = .03) and T (P = .01) alleles, hypertension (P = .03), tobacco use (P = .01) and family history of stroke (P = .04) were identified as independent risk factors.ConclusionsThe polymorphisms Glu298Asp and C677T, affecting the eNOS and 5,10-MTHFR enzymes, respectively, and smoking, hypertension, and family history of stroke were associated with ischaemic stroke in young Mexican patients; this was not the case for the Thr325Ile, Ala147Thr, 4G/5G, and PLA1/A2 polymorphisms of the genes coding for fibrinolytic proteins and platelet receptors. (AU)

B regulatory cells associated with changes in biochemical and inflammatory parameters in normal-glycemic individuals, pre-diabetes and T2DM patients.

AIM: To determine the percentages of (CD19 + CD24 + CD38+, CD19 + CD24 + CD27+, CD19 + IL-10+)-Breg cells, IL-17 single and IL-17+/IFN-γ double producers T cells and IFN-γ+ T cells, in normal-glycemic individuals, prediabetes and T2DM patients, and to analyze the association of Breg cells with metabolic parameters of T2DM. METHODS: percentages of Breg cells, IL-17+ and IL-17 + IFN-γ+ T cells, IFN-γ+ T cells and IL-10 were determined by flow cytometry. IL-6 levels were evaluated by ELISA assay. RESULTS: increased IL-6 levels, IL-17+ and IL-17 + IFN-γ+ T cells and a diminution of IL-10 levels and CD19 + IL-10+ cells in T2DM patients were observed. We found that CD19 + CD24 + CD27+ cells and CD19 + CD24 + CD38+ cells were increased in T2DM patients. The percentages of CD19 + CD24 + CD38+ cells were associated with HOMA-B, TyG index, HDL and cholesterol values. In normal-glycemic individuals, CD19 + CD24 + CD27+ cells were inversely associated to triglycerides and TyG index. In prediabetes patients, CD19 + CD24 + CD38+ cells were inversely related with cholesterol and LDL. Finally, CD19 + CD24 + CD38+ cells were inversely related with HDL values in T2DM patients. CONCLUSION: Our results suggest that increased percentages of IL-17 single and IL-17/IFN-γ double producers T cells in T2DM patients may be a consequence of the initial CD19 + IL-10+ cells reduction. Furthermore, dyslipidemia could play an important role in percentages and activity of B regulatory cells.

Genealogical data of Boer and Nubian goats in Mexico.

The pedigree file of the Boer and Nubian goat breeds in Mexico was constructed using the national database provided by the Asociación Mexicana de Criadores de Ganado Caprino de Registro. Field technicians routinely updated the goat national database by recording information from flocks participating in the performance-recording system. Information on animal identification number, parents, birth date, sex, breed, and farm of origin were used to undertake pedigree analyses using the ENDOG program (version 4.8). This paper presents a pedigree data file, tables and figures of characteristics of pedigree data, pedigree analyses, pedigree integrity, effective population size and genetic conservation index. The data can be used to estimate other population parameters, to monitor the genetic diversity of the Boer and Nubian goat breeds in Mexico, and also to design balanced breeding programs, maintaining genetic variation at reasonable levels and maximizing genetic progress in these populations.

Molecular mechanisms of cell death induced in glioblastoma by experimental and antineoplastic drugs: New and old drugs induce apoptosis in glioblastoma.

Glioblastoma multiforme (GBM) is one of the most aggressive astrocytic tumors; it is resistant to most chemotherapeutic agents currently available and is associated with a poor patient survival. Thus, the development of new anticancer compounds is urgently required. Herein, we studied the molecular mechanisms of cell death induced by the experimental drugs resveratrol and MG132 or the antineoplastic drugs cisplatin and etoposide on a human GBM cell line (D54) and on primary cultured mouse astrocytes (PCMAs). Caspases, Bcl-2, inhibitors of apoptosis proteins (IAP) family members, and p53 were identified as potential molecular targets for these drugs. All drugs had a cytotoxic effect on D54 cells and PCMAs, with a similar inhibitory concentration (IC50) after 24 h. However, MG132 and cisplatin were more effective to induce apoptosis and autophagy than resveratrol and etoposide. Cell death by apoptosis involved the activation of caspases-3/7, -8, and -9, increased lysosomal permeability, LC3 lipidation, poly-(ADP-ribose) polymerase (PARP)-1 fragmentation, and a differential expression of genes related with apoptosis and autophagy like Mcl-1, Survivin, Noxa, LC3, and Beclin. In addition, apoptosis activation was partially dependent on p53 activation. Since experimental and antineoplastic drugs yielded similar results, further work is required to justify their use in clinical protocols.

The influence of dopaminergic polymorphisms on selective stopping.

Although the genetic influence on global stopping has been extensively investigated, little is known about the genetic contribution to other more complex forms of inhibitory control such as selective stopping. The selectivity of inhibitory control can be assessed by using the stimulus-selective stop-signal task. Notably, recent behavioural and neural evidence indicates that individuals can adopt selective but also non-selective stopping strategies to solve it. This study aimed to investigate for the first time the influence of two relevant dopaminergic polymorphisms (in COMT and DRD2 genes) on stimulus-selective stopping in a sample of 529 adults. Results showed that although none of these polymorphisms (neither individually nor in combination) modulate the latency of the stop process in each strategy (the stop-signal reaction time), the choice of strategy was influenced by their interaction. These results suggest that dopaminergic polymorphisms might influence strategy adoption in selective stopping paradigms, which constitutes a novel finding.

Nicotine modulates molecules of the innate immune response in epithelial cells and macrophages during infection with M. tuberculosis.

Smoking increases susceptibility to becoming infected with and developing tuberculosis. Among the components of cigarette smoke, nicotine has been identified as the main immunomodulatory molecule; however, its effect on the innate immune system is unknown. In the present study, the effect of nicotine on molecules of the innate immune system was evaluated. Lung epithelial cells and macrophages were infected with Mycobacterium tuberculosis (Mtb) and/or treated with nicotine. The results show that nicotine alone decreases the expression of the Toll-like receptors (TLR)-2, TLR-4 and NOD-2 in all three cell types, as well as the production of the SP-D surfactant protein in type II pneumocytes. Moreover, it was observed that nicotine decreases the production of interleukin (IL)-6 and C-C chemokine ligand (CCL)5 during Mtb infection in epithelial cells (EpCs), whereas in macrophages derived from human monocytes (MDMs) there is a decrease in IL-8, IL-6, tumor necrosis factor (TNF)-α, IL-10, CCL2, C-X-C chemokine ligand (CXCL)9 and CXCL10 only during infection with Mtb. Although modulation of the expression of cytokines and chemokines appears to be partially mediated by the nicotinic acetylcholine receptor α7, blocking this receptor found no effect on the expression of receptors and SP-D. In summary, it was found that nicotine modulates the expression of innate immunity molecules necessary for the defense against tuberculosis.

Identification of putative miRNA biomarkers in early rheumatoid arthritis by genome-wide microarray profiling: A pilot study.

Despite the existing research, the etiology of rheumatoid arthritis (RA), an autoimmune disease remains poorly understood with early and accurate diagnosis difficult to achieve. MicroRNAs (miRNAs) play an important role in biological processes as modulators of transcription and translation. Previous studies have demonstrated a downregulation of several genes in early RA stages and in addition, miRNAs may serve as early biomarkers of subclinical changes in early RA. When comparing the four groups (ANOVA P < 0.01, fold change > 4), we found 253 differentially expressed miRNAs. Of these, 97 miRNAs were identified as overexpressed in early rheumatoid arthritis. The validation of miRNA microarray expression was performed in a set by RT-qPCR and showed strong agreement with microarray expression data. The putative targets of overexpressed microRNAs in early RA were significantly enriched in apoptosis, tolerance loss and Wnt pathways. Moreover, ROC analysis showed values of AUC 0.76 and P < 0.05 for miR 361-5p, identifying this miRNA as a potential biomarker of disease. We identified specific microRNAs associated with early rheumatoid arthritis and proposed them as early biomarkers of disease. Our results provide novel insight into immune disease physiopathology and describe unreported microRNAs in RA with potential for clinical use.

Dataset on growth curves of Boer goats fitted by ten non-linear functions.

Data on the description of growth of female Boer goats from the Mexican national breeding flock are presented. Goat meat is highly appreciated for the preparation of traditional dishes of Mexican cuisine, and its demand is on the rise. Boer goats are of relatively recent arrival in Mexico and the size of the performance-recorded flock has been increasing steadily in the last ten years. Repeated measures of body weight at different ages from birth to adulthood of Boer goats are scarce. When available, such data can be used to describe the growth pattern and the meat production potential of goat meat breeds such as the Boer. This paper presents data on estimators of growth curve parameters, plots of average predicted growth curves, plots of residuals on age, and data on goodness of fit statistics of ten non-linear functions fitted to describe the growth curve of Boer goats.

Adult-onset hypothyroidism increases ethanol consumption.

RATIONALE: Only in Europe it can be estimated that more than 20 million of people would be affected by hypothyroidism in some moment of their life. Given that ethanol consumption is so frequent, it would be reasonable to ask what the consequences of ethanol consumption in those individuals affected by hypothyroidism are. OBJECTIVES: To study the interaction between hypothyroidism and ethanol consumption. METHODS: We study ethanol consumption in a rat model of methyl-mercaptoimidazole-induced-adult-onset hypothyroidism and thyroid T4/T3 hormone supplementation. Also, we studied the effects of ethanol on motor activity, memory, and anxiety. RESULTS: We found that hypothyroidism increased the voluntary ethanol consumption and that this was enhanced by thyroid hormone supplementation. Hypothyroidism was associated with motor hyperactivity which was prevented either by T4/T3 supplementation or ethanol. The relationship between hypothyroidism, ethanol, and anxiety was more complex. In an anxiogenic context, hypothyroidism and T4/T3 supplementation would increase immobility, an anxiety-like behavior, while in a less anxiogenic context would decrease rearing, a behavior related to anxiety. Regarding memory, acute ethanol administration did not alter episodic-like memory in hypothyroid rats. Gene expression of enzymes involved in the metabolism of ethanol, i.e., Adh1 and Aldh2, were altered by hypothyroidism and T4/T3 supplementation. CONCLUSIONS: Our results suggest that hypothyroid patients would need personalized attention in terms of ethanol consumption. In addition, they point that it would be useful to embrace the thyroid axis in the study of ethanol addiction, including as a possible therapeutic target for the treatment of alcoholism and its comorbid disorders.

Prevención de extubación no programada en pacientes con ventilación mecánica invasiva / Prevention of non-programed tube-extractions among patients with invasive mechanical ventilation / Prevenção de extubação não programada em pacientes com ventilação mecânica invasiva

Introducción Las extubaciones no programadas constituyen un evento adverso frecuente y de alto impacto, en la mayoría de los casos la presencia de este evento se relaciona con factores como la vía aérea, ventilación mecánica, nivel de sedación, estado y actividad mental del paciente, entre otros también prevenibles. Por ello, se establece un indicador de calidad para prevenir extubaciones no programadas en pacientes con ventilación mecánica invasiva y tubo endotraqueal. Objetivo Realizar la validación de contenido del indicador y describir el nivel de cumplimiento para la prevención de extubaciones no programadas en pacientes con ventilación mecánica invasiva en un hospital de tercer nivel de la Ciudad de México, con el propósito de dar a conocer nuevos aportes en materia de prevención. Metodología Estudio cuantitativo y descriptivo, con una muestra no probabilística a conveniencia conformada por 46 procesos observados durante el turno matutino en tres servicios de hospitalización. Resultados Se encontró que el 96% de los procesos observados arrojaron un nivel de prevención medio para las extubaciones no programadas. Al evaluar el índice de eficiencia global del indicador, se obtuvo un resultado del 59.8%, lo cual muestra que las acciones para prevenir una extubación no programada se cumplen en un porcentaje muy bajo. Conclusiones Se detectó una omisión de funciones por los profesionales de la salud en la prevención de este evento, por lo que se propuso un plan de mejora para la institución con el propósito de disminuir los eventos relacionados a las extubaciones.

Introduction Non-programed extubation, constitute a frequent high impact adverse event involving issues on the airway, mechanical ventilation, sedation level, patient´s mental activity, among others. Because of this, a quality indicator is established in order to help prevent non-programed extubation among patients with invasive mechanical ventilation and endotracheal tube. Objective To perform a validation of content on this indicator in a third level hospital of the City of Mexico, and describe the level of adherence to its components in order to prevent non-programed extubation among patients with invasive mechanical ventilation and endotracheal tube, and share the resulting contributions in the area of prevention. Methodology This is a quantitative and descriptive study with a non-probabilistic sample by convenience of 46 processes which were observed during the morning shifts in three hospitalization services. Results It was found that 96% of the processes observed showed an insufficient level of prevention of non-programed extubation. The assessment of the efficiency related to indicator´s components showed a 59.8% compliance, suggesting that the actions to prevent non-programed extubation are not sufficiently taken. Conclusions An important related omission by health professionals regarding the prevention of this kind of adverse events was detected, and thus, a corresponding improvement plan for the institution was proposed.

Introdução As extubaçãos não programadas constituem um evento adverso frequente e de alto impacto, na maioria dos casos, a presença deste evento relaciona-se com fatores como a via aérea, ventilação mecânica, nível de sedação, estado e atividade mental do paciente, entre outros, também preveníeis. Por isso, estabelece-se um indicador de qualidade para prevenir extubaçãos não programadas em pacientes com ventilação mecânica invasiva e tubo endotraqueal. Objetivo Realizar a validação de conteúdo do indicador e descrever o nível de cumprimento para a prevenção de extubaçãos não programadas em pacientes com ventilação mecânica invasiva em um hospital de terceiro nível da Cidade do México, com o propósito de dar a conhecer novas contribuições em matéria de prevenção. Metodologia Estudo quantitativo e descritivo, com uma amostra não probabilística a conveniência, conformada por 46 processos observados durante o turno matutino em três serviços de hospitalização. Resultados Encontrou-se que o 96% dos processos observados revelaram um nível de prevenção médio para as extubaçãos não programadas. Avaliando o índice de eficiência global do indicador, obteve-se um resultado do 59.8%, o qual mostra que as ações para prevenir uma extubação não programada cumprem-se em uma porcentagem muito baixa. Conclusões Identificou-se uma omissão de funções pelos profissionais da saúde na prevenção deste evento, pelo que se propus um plano de melhora para a instituição com o propósito de diminuir os eventos relacionados às extubaçãos.

Transcriptional signature associated with early rheumatoid arthritis and healthy individuals at high risk to develop the disease.

BACKGROUND: Little is known regarding the mechanisms underlying the loss of tolerance in the early and preclinical stages of autoimmune diseases. The aim of this work was to identify the transcriptional profile and signaling pathways associated to non-treated early rheumatoid arthritis (RA) and subjects at high risk. Several biomarker candidates for early RA are proposed. METHODS: Whole blood total RNA was obtained from non-treated early RA patients with <1 year of evolution as well as from healthy first-degree relatives of patients with RA (FDR) classified as ACCP+ and ACCP- according to their antibodies serum levels against cyclic citrullinated peptides. Complementary RNA (cRNA) was synthetized and hybridized to high-density microarrays. Data was analyzed in Genespring Software and functional categories were assigned to a specific transcriptome identified in subjects with RA and FDR ACCP positive. Specific signaling pathways for genes associated to RA were identified. Gene expression was evaluated by qPCR. Receiver operating characteristic (ROC) analysis was used to evaluate these genes as biomarkers. RESULTS: A characteristic transcriptome of 551 induced genes and 4,402 repressed genes were identified in early RA patients. Bioinformatics analysis of the data identified a specific transcriptome in RA patients. Moreover, some overlapped transcriptional profiles between patients with RA and ACCP+ were identified, suggesting an up-regulated distinctive transcriptome from the preclinical stages up to progression to an early RA state. A total of 203 pathways have up-regulated genes that are shared between RA and ACCP+. Some of these genes show potential to be used as progression biomarkers for early RA with area under the curve of ROC > 0.92. These genes come from several functional categories associated to inflammation, Wnt signaling and type I interferon pathways. CONCLUSION: The presence of a specific transcriptome in whole blood of RA patients suggests the activation of a specific inflammatory transcriptional signature in early RA development. The set of overexpressed genes in early RA patients that are shared with ACCP+ subjects but not with ACCP- subjects, can represent a transcriptional signature involved with the transition of a preclinical to a clinical RA stage. Some of these particular up-regulated and down-regulated genes are related to inflammatory processes and could be considered as biomarker candidates for disease progression in subjects at risk to develop RA.

Parathyroid hormone, calcidiol, calcitriol and adverse events in the acute coronary syndrome. / Hormona paratiroidea, calcidiol, calcitriol y riesgo de eventos adversos en pacientes con síndrome coronario agudo.

OBJECTIVE: To know the clinical profile as well as the prognostic significance of elevated levels of parathyroid hormone (PTH) in patients admitted for acute coronary syndrome (ACS). DESIGN AND SETTING: Observational and prospective study of patients admitted for ACS in a single Spanish center during a period of six months. INTERVENTION AND VARIABLES OF INTEREST: The circulating concentrations of PTH, calcidiol, calcitriol, NT-proBNP, C-reactive protein, cystatinC and fibrinogen were determined within the first 48h at admission. We performed adjusted models to predict death or re-entry for ACS after hospital discharge. RESULTS: A total of 161 patients were recruited (age 67±14 years, 75.2% were men). Forty-one (25.5%) patients had elevated PTH values. During follow-up for a period of 275 person-years, 50 adverse events were recorded. Patients with elevated PTH levels were proportionally more women (21.2 vs. 39.0%) and older (63.3 vs. 77.8 years, both P<.05). Likewise, they presented significantly more cardiovascular risk and a worse prognosis during follow-up (incidence rate ratio 2.64 CI 95%: 1.5-4.6). However, in an adjusted model by the GRACE score, PTH levels were not shown to be an independent risk factor (hazard ratio=1.1; 95% CI: 0.6-2.2), neither other components of the panel. CONCLUSIONS: The proportion of patients with elevated levels of PTH admitted for ACS was high. The presence of high PTH levels was associated with an unfavorable clinical profile and a worse outcome during the follow-up, although it was not an independent predictor of poor prognosis.