Non-functional alternative splicing caused by a Latino pathogenic variant in a case of PMM2-CDG.

We report on a Mexican mestizo with a multisystemic syndrome including neurological involvement and a type I serum transferrin isoelectric focusing (Tf IEF) pattern. Diagnosis of PMM2-CDG was obtained by clinical exome sequencing (CES) that revealed compound heterozygous variants in PMM2, the encoding gene for the phosphomannomutase 2 (PMM2). This enzyme catalyzes the conversion of mannose-6-P to mannose-1-P required for the synthesis of GDP-Man and Dol-P-Man, donor substrates for glycosylation reactions. The identified variants were c.422G>A (R141H) and c.178G>T, the former being the most frequent PMM2 pathogenic mutation and the latter a previously uncharacterized variant restricted to the Latino population with conflicting interpretations of pathogenicity and that we here report causes leaky non-functional alternative splicing (p.V60Cfs*3).

Identification through exome sequencing of the first PMM2-CDG individual of Mexican mestizo origin.

Congenital Disorders of Glycosylation (CDG) are scarcely reported from Latin America. We here report on a Mexican mestizo with a multi-systemic syndrome including neurological involvement and a type I transferrin (Tf) isoelectric focusing (IEF) pattern. Clinical exome sequencing (CES) showed known compound missense variants in PMM2 c.422G > A (p.R141H) and c.395 T > C (p.I132T), coding for the phosphomanomutase 2 (PMM2). PMM2 catalyzes the conversion of mannose-6-P to mannose-1-P required for the synthesis of GDP-Man and Dol-P-Man, donor substrates for glycosylation reactions. This is the third reported Mexican CDG patient and the first with PMM2-CDG. PMM2 has been recently identified as one of the top 10 genes carrying pathogenic variants in a Mexican population cohort.

What´s new in intraabdominal candidiasis in critically ill patients, a review.

A high prevalence of invasive candidiasis has been reported in recent years. Patients admitted to an intensive care unit are at the highest risk for invasive candidiasis, mostly due to the severity of their disease, immune-suppressive states, prolonged length of stay, broad-spectrum antibiotics, septic shock, and Candida colonization. Intraabdominal candidiasis comprises a range of clinical manifestations, from just the suspicion based on clinical scenario to fever, leukocytosis, increase in biomarkers to the isolation of the responsible microorganism. In critically ill patients with IAC prompt treatment and adequate source control remains the ultimate goal.

Assessing prediction accuracy for outcomes of ventilator-associated events and infections in critically ill children: a prospective cohort study.

OBJECTIVES: To assess the prediction accuracy of the 2008 US Centers for Disease Control and Prevention (CDC) definitions for ventilator-associated pneumonia (VAP)/ventilator-associated tracheobronchitis (VAT), 2013 CDC definitions for ventilator-associated events (VAE) and a new VAE algorithm in the paediatric (Ped) population, the Ped-VAE. METHODS: We performed a prospective 13-month cohort study at a multidisciplinary paediatric intensive care unit (PICU). Primary endpoints were duration of ventilation episode, PICU or hospitalization length of stay from episode and episode mortality. Episodes without VAE (or VAP/VAT) served as comparison groups. RESULTS: One hundred eight episodes of ventilation (99 children) with 2554 ventilator-days were assessed. In episodes not meeting 2008 CDC definitions, a median of 6 ventilator-days (PICU stay 11 days) was documented (with eight deaths), not significantly different from episodes not meeting VAE or Ped-VAE definitions. Using 2008 CDC criteria, 11 (10.2%) respiratory infections (eight tracheobronchitis) were identified, seven VAEs using 2013 CDC criteria (6.4%) and 29 (26.8%) using Ped-VAE criteria (relative risk vs. 2008 CDC criteria 2.58; 95% confidence interval 1.36-4.91). In contrast with their comparison groups, episodes meeting 2008 CDC criteria did not significantly predict outcomes, whereas VAEs (only four possible VAPs) were associated with significantly more ventilation and PICU length of stay (12-day/8-day increase) and sevenfold increase in mortality. Ped-VAE did not increase mortality, but it was associated with 4-day increase in ventilation and PICU length of stay, with ten possible VAPs, and atelectasis (9/12) as the main paediatric ventilator-associated condition. CONCLUSIONS: The 2008 CDC criteria did not predict outcomes, whereas VAE only identified very severe events. The Ped-VAE algorithm had more accuracy predicting outcomes by characterizing lower oxygenation changes and identifying hypoxaemia severity, a major driver of management.

[Workplace bullying during specialty training in a pediatric hospital in Mexico: a little-noticed phenomenon]. / Acoso laboral durante la formación como especialista en un hospital de pediatría en México: un fenómeno poco percibido.

BACKGROUND: Workplace bullying (WB) is a hostile or intimidating behavior that is practiced against workers and has a negative impact on health, job performance, and the learning process. The objective was to research WB magnitude and its associated factors in Mexico. METHODS: Mixed method study. A survey was designed and administered to all the residents in a pediatric hospital in Mexico who agreed to participate. The survey was divided in two sections: a) resident self-reported events of workplace bullying and associated factors, b) situations and factors of abuse were interrogated in a targeted manner. RESULTS: 137 residents participated in the survey, out of which 32% spontaneously reported have been bullied, and 82.4% harassing behaviors in the targeted section. Personal factors that cause WB in this population were: gender, mental skills and physical appearance. Situations that predispose to harassment were: hierarchy, and lack of supervision. Teachers were more frequently the perpetrators. Factors identified as significant for WB were: being female, younger than 29, studying pediatrics, being unmarried, and having reported harassment spontaneously. CONCLUSIONS: The frequency of WB and associated factors are similar to those reported by other authors. Half of the residents did not report spontaneously harassing events, but identified them in the targeted section, which suggests that they consider them as part of the "costumes and habits" during their medical training, or they consider them irrelevant.

Introducción: el acoso laboral es una conducta intimidatoria que se practica contra el trabajador e impacta negativamente en el estado de salud, el desempeño laboral y el aprendizaje. El presente trabajo investiga su magnitud y sus factores asociados en México. Métodos: metodología mixta. Se diseñó y aplicó una encuesta a los residentes de un hospital pediátrico de México que aceptaron participar. Se dividió en dos secciones: a) el residente reportó eventos de mobbing y factores asociados, b) se exploraron de manera dirigida situaciones de abuso documentadas en la literatura. Resultados: participaron 137 residentes. De ellos, 32% reportó espontáneamente haber sufrido acoso, mientras que 82.4% lo refirió en el cuestionario dirigido. Los factores personales precipitantes fueron: sexo, habilidades mentales y apariencia física. Las situaciones que predispusieron al acoso fueron jerarquía y falta de supervisión. Los profesores fueron los principales perpetradores, ocurrió más comúnmente en hospitalización. Se identificaron como factores significativos el sexo femenino, tener menos de 29 años, estudiar pediatría, ser solteros y haber reportado acoso de manera espontánea. Conclusiones: la frecuencia de acoso es similar a la reportada por otros autores. La mitad de los residentes no reportaron espontáneamente eventos de acoso pero los identificaron en el cuestionamiento dirigido, lo que sugiere que consideran estos eventos como parte de "los usos y costumbres" durante su entrenamiento médico, o los consideran irrelevantes.

Infections in intensive care unit adult patients harboring multidrug-resistant Pseudomonas aeruginosa: implications for prevention and therapy.

The purpose of this paper was to report the burden and characteristics of infection by multidrug-resistant Pseudomonas aeruginosa (MDR-PA) in clinical samples from intensive care unit (ICU) adults, and to identify predictors. This was a retrospective observational study at four medical-surgical ICUs. The case cohort comprised adults with documented isolation of an MDR-PA strain from a clinical specimen during ICU stay. Multivariate analysis was performed to identify predictors for MDR-PA infection. During the study period, 5667 patients were admitted to the ICU and P. aeruginosa was isolated in 504 (8.8%). MDR-PA was identified in 142 clinical samples from 104 patients (20.6%); 62 (43.6%) of these samples appeared to be true infections. One hundred and eighteen (83.1%) isolates were susceptible only to amikacin and colistin, and 13 (9.2%) were susceptible only to colistin. Overall, the MIC50 to meropenem was 16 µg/mL and the MIC90 was >32 µg/mL, with 60.4% of respiratory samples being MIC >32 µg/mL to meropenem. Independent predictors for MDR-PA infection were fever/hypothermia [odds ratio (OR) 9.09], recent antipseudomonal cephalosporin therapy (OR 6.31), vasopressors at infection onset (OR 4.40), and PIRO (predisposition, infection, response, and organ dysfunction) score >2 (OR 2.06). This study provides novel information that may be of use for the clinical management of patients harboring MDR-PA and for the control of the spread of this organism.

Association between source control and mortality in 258 patients with intra-abdominal candidiasis: a retrospective multi-centric analysis comparing intensive care versus surgical wards in Spain.

Early empiric therapy and adequate resuscitation have been identified as main predictors of outcome in patients with candidemia or bacteremia. Moreover, source control is a major determinant in infectious sites when feasible, as a main technique to reduce microbiological burden. A retrospective, multicenter, cohort study was performed at surgical wards and intensive care units (ICU) of three University Hospitals in Spain between 2010 and 2014, with the aim of improving understanding of the interaction between source control, early antifungal therapy, and use of vasoactives in patients with intra-abdominal candidiasis (IAC). Source control was defined as all physical actions taken to control a focus of infection and reduce the favorable conditions that promote microorganism growth or that maintain the impairment of host defenses. Two hundred and fifty-eight patients with IAC were identified. Sixty-one patients were at ICU for diagnosis. Mortality was higher in the ICU group compared to what was documented for the non-ICU group (35 % vs 19.5 %, p = 0011). Adequate source control within 48 h of diagnosis was achieved in 60 % of the cohort. In multivariate analysis, inadequate source control was identified as the only common risk factor for 30-day mortality in both groups (ICU group OR: 13.78 (95% CI: 2.60-72.9, p = 0.002) and non-ICU group OR: 6.53 (95% CI: 2.56-16.61, p = <0.001). The population receiving both adequate source control and adequate antifungal treatment was the one associated with a higher survival rate, in both the ICU and surgical groups. Source control remains a key element in IAC, inside and outside the intensive care unit. Early antifungal treatment among ICU patients was associated with lower mortality.

Construcción y validación de una escala de asertividad en la relación paciente-médico / Construction and validation of a scale of assertivity of patients-medical personnel

Resumen: El objetivo de este estudio fue la construcción y validación de un instrumento que evalúe la asertividad de pacientes con el personal médico. Participaron 216 pacientes con enfermedades crónico-degenerativas (Medad = 42.74, DE = 8.76) de un hospital público de la Ciudad de México, seleccionados mediante un muestreo no probabilístico accidental. Para validar el instrumento se llevó a cabo un análisis evaluando el poder discriminativo de los reactivos, se obtuvo la confiabilidad y la estructura factorial. La escala final contiene 21 reactivos que explican el 44.29% de la varianza total y la coherencia teórica de la estructura distribuida en 4 factores: No asertividad-pasividad, No asertividad-inseguridad, Asertividad-positiva y Agresividad; el instrumento tiene un nivel de confiabilidad de α = 0.816, por lo que se concluye que esta escala cumple con los criterios de confiabilidad y validez para medir asertividad en la práctica clínica e investigación, con la limitante de que este instrumento se validó únicamente con población hospitalaria de la Cd. de México.

Abstract: The objective of this study was the construction and validation of an instrument to evaluate patients' assertiveness with the medical personnel. Two hundred and sixteen patients with chronic degenerative diseases (Mage = 42.74, SD = 8.76), from a public hospital in Mexico City participated in this study, selected through a non probability haphazard sampling. In order to validate this instrument, an analysis was carried out evaluating the discriminative power of the items, the reliability and the factorial structure were obtained. The final scale contains 21 items, that explain 44.29% of the total variance and the theoretical coherence of the structure distributed on 4 factors: Non Assertiveness-Passivity, Non Assertiveness-Insecurity, Positive-Assertiveness and Aggressiveness, this instrument has a reliability level of α = .816, so it is concluded that this scale complies with the reliability and validity criteria to measure the assertiveness on clinic practice and investigation, with the limitation regarding its validation in the hospital population of Mexico City.

Predictors of choice of initial antifungal treatment in intraabdominal candidiasis.

Intraabdominal candidiasis (IAC) is the second most frequent form of invasive candidiasis, and is associated with high mortality rates. This study aims to identify current practices in initial antifungal treatment (IAT) in a real-world scenario and to define the predictors of the choice of echinocandins or azoles in IAC episodes. Secondary analysis was performed of a multinational retrospective cohort at 13 teaching hospitals in four countries (Italy, Greece, Spain and Brazil), over a 3-year period (2011-2013). IAC was identified in 481 patients, 323 of whom received antifungal therapy (classified as the treatment group). After excluding 13 patients given amphotericin B, the treatment group was further divided into the echinocandin group (209 patients; 64.7%) and the azole group (101 patients; 32.3%). Median APACHE II scores were significantly higher in the echinocandin group (p 0.013), but IAT did not differ significantly with regard to the Candida species involved. Logistic multivariate stepwise regression analysis, adjusted for centre effect, identified septic shock (adjusted OR (aOR) 1.54), APACHE II >15 (aOR 1.16) and presence in surgical ward at diagnosis (aOR 1.16) as the top three independent variables associated with an empirical echinocandin regimen. No differences in 30-day mortality were observed between groups. Echinocandin regimen was the first choice for IAT in patients with IAC. No statistical differences in mortality were observed between regimens, but echinocandins were administered to patients with more severe disease. Some disagreements were identified between current clinical guidelines and prescription of antifungals for IAC at the bedside, so further educational measures are required to optimize therapies.

Invasive candidiasis: from mycobiome to infection, therapy, and prevention.

Candida spp. are commonly found in humans, colonizing most healthy individuals. A high prevalence of invasive candidiasis has been reported in recent years. Here, we assess the relation between Candida spp. as part of the human mycobiome, the host defense mechanisms, and the pathophysiology of invasive disease in critically ill patients. Many hypotheses have been proposed to explain the different immune responses to the process where Candida goes through healthy mycobiome to colonization to invasion; the involvement of other microbiota inhabitants, changes in temperature, low nitrogen levels, and the caspase system activation have been described. Patients admitted to an intensive care unit (ICU) are at the highest risk for invasive candidiasis, mostly due to the severity of their disease, immune-suppressive states, prolonged length of stay, broad-spectrum antibiotics, septic shock, and Candida colonization. The first approach should be using predictive scores as screening, followed by the determination of biomarkers (when available), and, in the near future, probably immune-genomics and analysis of the clinical background in order to initiate prompt and correct treatment. Regarding treatment, the initiation with an echinocandin is strongly recommended in critically ill patients. In conclusion, prompt treatment and adequate source control in the more severe patients remains the ultimate goal, as well as restoration of a healthy microbiota.

The T963C mutation of TP53 gene does not participate in the clonal origin of canine TVT.

In dogs, the canine transmissible venereal tumor (CTVT) is the only neoplasm which is not produced by neoplastic transformation of normal cells; the tumor is transmitted from the affected dog to healthy dogs by implantation of one or various clones of cancer cells. Thus, the CTVT of dogs analyzed in various countries reveals similar genetic characteristics and consequently CTVT is considered to have a clonal origin. The CTVTs obtained from dogs in Korea showed the T963C mutation on TP53 gene; this mutation was thought to be a molecular alteration which participates in the origin of the ancestral clone, CTVT. Nonetheless, this supposed mutation has not been identified in other studies which were carried out for the purpose of clarifying the clonal origin of CTVT. Thus we have considered it important to identify the role of the T963C mutation of the TP53 gene in the clonal origin of CTVT in dogs. Consequently the region which includes the mutation of the TP53 gene in twenty samples of CTVT obtained from various canine breeds was PCR amplified and afterwards its sequence of nucleotides was determined. We conclude that this mutation did not participate in the clonal origin of the tumor, but was acquired at a later stage.

Effect of exogenous ethylene on ACC content and ACC oxidase activity during ripening of Manila mangoes subjected to hot water treatment.

Mangoes (Mangifera indica L.) 'Manila' were subjected to the USDA-approved hot water treatment and then exposed to synthetic air mixtures containing 0.5, 0.75 or 1 ml l(-1) of ethylene for 6, 12 or 18 h at 25 degrees C, to induce accelerated ripening. After treatment the mangoes were allowed to ripen in air at 24-25 degrees C. The content of 1-aminocyclopropane-1-carboxylic acid (ACC) and ACC oxidase (ACO) activity increased in fruit treated with 0.5 and 0.75 ml l(-1) of ethylene for 6 or 12 h. Ethylene production was reduced in fruit treated with 1 ml l(-1) of ethylene. This was due to the decreased of ACC synthesis rather than to lower ACC oxidase activity. Treatment with 0.5 ml l(-1) of ethylene for 12 h was found best for accelerate ripening; fruits were fully ripened and edible 3 days after treatment, compared to 6-7 days for untreated mangoes.