Increased Incidence of TdT-negative Pre-B Acute Lymphoblastic Leukemia Associated With Poor Prognostic Features Among Mexican Children in Central Mexico.

Mexican and Hispanic children in Mexico and the United States, respectively, have the highest incidence and worst outcomes of pre-B acute lymphoblastic leukemia (ALL) compared with other racial/ethnic groups. Terminal deoxynucleotidyl transferase (TdT) is an intranuclear DNA polymerase normally present on immature lymphocytes (TdT-positive) and distinguishes ALL from mature lymphoid malignancies. We performed a multisite retrospective study to determine the incidence of TdT-negative precursor B-cell acute lymphoblastic leukemia (pre-B ALL) among Mexican, Caucasian, and US-born Hispanic children to correlate TdT expression with patient characteristics and known prognostic factors. Fisher exact test was performed for categorical variables and the Wilcoxon rank-sum test was used for continuous variables. TdT-negative pre-B ALL was most frequently identified in patients with National Cancer Institute high-risk disease ( P =0.014). TdT-negative expression was also most frequently associated with hypodiploid pre-B ALL ( P =0.001) and KMT2A gene rearrangement ( P =0.0012). Mexican children had the highest incidence of TdT-negative ALL compared with Caucasians and US Hispanics ( P <0.001), with an increased incidence of poor prognostic features as well. This study demonstrates significant differences in TdT-negative expression, genomic alterations, and leukemic ploidy based on race and ethnicity.

The Existence of the StartReact Effect Implies Reticulospinal, Not Corticospinal, Inputs Dominate Drive to Motoneurons during Voluntary Movement.

Reaction time is accelerated if a loud (startling) sound accompanies the cue-the "StartReact" effect. Animal studies revealed a reticulospinal substrate for the startle reflex; StartReact may similarly involve the reticulospinal tract, but this is currently uncertain. Here we trained two female macaque monkeys to perform elbow flexion/extension movements following a visual cue. The cue was sometimes accompanied by a loud sound, generating a StartReact effect in electromyogram response latency, as seen in humans. Extracellular recordings were made from antidromically identified corticospinal neurons in primary motor cortex (M1), from the reticular formation (RF), and from the spinal cord (SC; C5-C8 segments). After loud sound, task-related activity was suppressed in M1 (latency, 70-200 ms after cue), but was initially enhanced (70-80 ms) and then suppressed (140-210 ms) in RF. SC activity was unchanged. In a computational model, we simulated a motoneuron pool receiving input from different proportions of the average M1 and RF activity recorded experimentally. Motoneuron firing generated simulated electromyogram, allowing reaction time measurements. Only if ≥60% of motoneuron drive came from RF (≤40% from M1) did loud sound shorten reaction time. The extent of shortening increased as more drive came from RF. If RF provided <60% of drive, loud sound lengthened the reaction time-the opposite of experimental findings. The majority of the drive for voluntary movements is thus likely to originate from the brainstem, not the cortex; changes in the magnitude of the StartReact effect can measure a shift in the relative importance of descending systems.SIGNIFICANCE STATEMENT Our results reveal that a loud sound has opposite effects on neural spiking in corticospinal cells from primary motor cortex, and in the reticular formation. We show that this fortuitously allows changes in reaction time produced by a loud sound to be used to assess the relative importance of reticulospinal versus corticospinal control of movement, validating previous noninvasive measurements in humans. Our findings suggest that the majority of the descending drive to motoneurons producing voluntary movement in primates comes from the reticulospinal tract, not the corticospinal tract.

Identification of a cytotoxic factor from a non-pigmented entomopathogenic Serratia marcescens isolate toxic towards human carcinoma cell lines.

It has been reported that cell-free culture broths and some proteins from pigmented and non-pigmented Serratia spp. are cytotoxic towards cancerous and non-cancerous human cell lines. Looking for new molecules toxic against human cancerous cells but harmless towards normal human cells, the aim of this work was (a) to determine whether cell-free broths from the entomopathogenic non-pigmented S. marcescens 81 (Sm81), S. marcescens 89 (Sm89) and S. entomophila (SeMor4.1) presented cytotoxic activity towards human carcinoma cell lines; (b) to identify and purify the associated cytotoxic factor(s) and (c) to evaluate whether the cytotoxic factor(s) was cytotoxic towards non-cancerous human cells. This research was focussed on the observed morphology changes and the proportion of remaining viable cells after incubation in the presence of cell-free culture broths from the Serratia spp isolates to evaluate cytotoxic activity. The results showed that broths from both S. marcescens isolates presented cytotoxic activity and induced cytopathic-like effects on the human neuroblastoma CHP-212 and the breast cancer MDA-MB-231 cells. Slight cytotoxicity was observed in the SeMor4.1 broth. A serralysin-like protein of 50 kDa was identified in Sm81 broth as responsible for cytotoxic activity after purification by ammonium sulphate precipitation and ion-exchange chromatography followed by tandem-mass spectrometry (LC-MS/MS). The serralysin-like protein was toxic against CHP-212 (neuroblastoma), SiHa (human cervical carcinoma) and D-54 (human glioblastoma) cell lines in a dose-dependent manner and showed no cytotoxic activity in primary cultures of normal non-cancerous human keratinocytes and fibroblasts. Therefore, this protein should be evaluated for a potential use as an anticancer agent.

Data envelopment analysis efficiency in the public sector using provider and customer opinion: An application to the Spanish health system.

Measuring the relative efficiency of a finite fixed set of service-producing units (hospitals, state services, libraries, banks,...) is an important purpose of Data Envelopment Analysis (DEA). We illustrate an innovative way to measure this efficiency using stochastic indexes of the quality from these services. The indexes obtained from the opinion-satisfaction of the customers are estimators, from the statistical view point, of the quality of the service received (outputs); while, the quality of the offered service is estimated with opinion-satisfaction indexes of service providers (inputs). The estimation of these indicators is only possible by asking a customer and provider sample, in each service, through surveys. The technical efficiency score, obtained using the classic DEA models and estimated quality indicators, is an estimator of the unknown population efficiency that would be obtained if in each one of the services, interviews from all their customers and all their providers were available. With the object of achieving the best precision in the estimate, we propose results to determine the sample size of customers and providers needed so that with their answers can achieve a fixed accuracy in the estimation of the population efficiency of these service-producing units through the use of a novel one bootstrap confidence interval. Using this bootstrap methodology and quality opinion indexes obtained from two surveys, one of doctors and another of patients, we analyze the efficiency in the health care system of Spain.

Thermogravimetric Analysis and Mass Spectrometry Allow for Determination of Chemisorbed Reaction Products on Metal Organic Frameworks.

Thermogravimetric analysis (TGA) is a technique which can probe chemisorption of substrates onto metal organic frameworks. A TGA method was developed to examine the catalytic oxidation of S-nitrosoglutathione (GSNO) by the MOF H3[(Cu4Cl)3(BTTri)8] (abbr. Cu-BTTri; H3BTTri = 1,3,5-tris(1H-1,2,3-triazol-5-yl)benzene), yielding glutathione disulfide (GSSG) and nitric oxide (NO). Thermal analysis of reduced glutathione (GSH), GSSG, GSNO, and Cu-BTTri revealed thermal resolution of all four analytes through different thermal onset temperatures and weight percent changes. Two reaction systems were probed: an aerobic column flow reaction and an anaerobic solution batch reaction with gas agitation. In both systems, Cu-BTTri was reacted with a 1 mM GSH, GSSG, or GSNO solution, copiously rinsed with distilled-deionized water (dd-H2O), dried (25 °C, < 1 Torr), and assessed by TGA. Additionally, stock, effluent or supernatant, and rinse solutions for each glutathione derivative within each reaction system were assessed by mass spectrometry (MS) to inform on chemical transformations promoted by Cu-BTTri as well as relative analyte concentrations. Both reaction systems exhibited chemisorption of glutathione derivatives to the MOF by TGA. Mass spectrometry analyses revealed that in both systems, GSH was oxidized to GSSG, which chemisorbed to the MOF whereas GSSG remained unchanged during chemisorption. For GSNO, chemisorption to the MOF without reaction was observed in the aerobic column setup, whereas conversion to GSSG and subsequent chemisorption was observed in the anaerobic batch setup. These findings suggest that within this reaction system, GSSG is the primary adsorbent of concern with regards to strong binding to Cu-BTTri. Development of similar thermal methods could allow for the probing of MOF reactivity for a wide range of systems, informing on important considerations such as reduced catalytic efficiency from poisoning, recyclability, and loading capacities of contaminants or toxins with MOFs.

Predictors of anxiety and depression among newly diagnosed people living with HIV: A longitudinal study.

This longitudinal study examined whether past resilience and internalized stigma predicted anxiety and depression among newly diagnosed Spanish-speaking people living with HIV (PLWH). We also analyzed whether coping strategies mediated this relationship. Data were collected at two time points from 119 PLWH. Approximately a third of participants had scores indicative of anxiety symptoms, the same result was found for depressive symptoms. Structural equations modeling revealed that 61% of the variance of anxiety and 48% of the variance of depression 8 months after diagnosis was explained by the proposed model, which yielded a good fit to data. Anxiety and depressive symptoms were significantly and negatively predicted by positive thinking, thinking avoidance, and past resilience, and positively predicted by self-blame. Additionally, anxiety was positively predicted by internalized stigma. Past resilience negatively predicted internalized stigma, self-blame, and thinking avoidance and it positively predicted positive thinking. Internalized stigma positively predicted self-blame. Moreover, internalized stigma had a significant indirect effect on anxiety symptoms through self-blame, and past resilience had significant indirect effects on anxiety symptoms and depressive symptoms through internalized stigma and coping. The results point to the need for clinicians and policy makers to conduct systematic assessments and implement interventions to reduce internalized stigma and train people living with HIV to identify and use certain coping behaviors.

Homochiral Metal-Organic Frameworks for Enantioselective Separations in Liquid Chromatography.

Selective separation of enantiomers is a substantial challenge for the pharmaceutical industry. Chromatography on chiral stationary phases is the standard method, but at a very high cost for industrial-scale purification due to the high cost of the chiral stationary phases. Typically, these materials are poorly robust, expensive to manufacture, and often too specific for a single desired substrate, lacking desirable versatility across different chiral analytes. Here, we disclose a porous, robust homochiral metal-organic framework (MOF), TAMOF-1, built from copper(II) and an affordable linker prepared from natural l-histidine. TAMOF-1 has shown to be able to separate a variety of model racemic mixtures, including drugs, in a wide range of solvents of different polarity, outperforming several commercial chiral columns for HPLC separations. Although not exploited in the present article, it is worthy to mention that the preparation of this new material is scalable to the multikilogram scale, opening unprecedented possibilities for low-energy chiral separation at the industrial scale.

Are Pediatric Critical Personnel Satisfied With Their Lives? Prediction of Satisfaction With Life From Burnout, Posttraumatic Stress, and Posttraumatic Growth, and Comparison With Noncritical Pediatric Staff.

OBJECTIVES: Staff in PICUs shows high burnout, posttraumatic stress disorder symptoms, and posttraumatic growth levels. However, their levels of satisfaction with life and how positive and negative posttrauma outcomes relate to each other and contribute to predict satisfaction with life remain unknown. Thus, we attempted to explore these aspects and to compare the findings with data from pediatric professionals working in noncritical units. DESIGN: This is an observational multicentric, cross-sectional study. SETTING: The PICU of nine hospitals in Spain, and other pediatric units in the same hospitals. SUBJECTS: Two hundred ninety-eight PICU workers (57 physicians, 177 nurses, and 64 nursing assistants) and 189 professionals working in noncritical pediatric units (53 physicians, 104 nurses, and 32 nursing assistants). INTERVENTION: Participants completed the Maslach Burnout Inventory, the Trauma Screening Questionnaire, the Posttraumatic Growth Inventory, and the Satisfaction With Life Scale. MEASUREMENTS AND MAIN RESULTS: Of PICU staff, 16.4% were very satisfied with their lives, 34.2% were satisfied, 34.6% showed average satisfaction with life, and 14.8% were below average. No differences were found between PICU and non-PICU workers. Women reported lower satisfaction with life than men, and physicians reported higher satisfaction with life than other professional groups. The correlation between posttraumatic stress disorder and posttraumatic growth was low, but significant and positive. According to the path analysis with latent variables, 20% of the variance satisfaction with life could be predicted from burnout, posttraumatic stress disorder symptoms, and posttraumatic growth. Higher distress was inversely associated to satisfaction with life, whereas posttraumatic growth contributed to higher satisfaction with life. CONCLUSIONS: Posttraumatic growth can moderate the negative effect of traumatic work-related experiences in satisfaction with life. PICU and non-PICU workers were equally satisfied with their lives. Positive and negative impact of work-related potentially traumatic events can coexist in the same person. Interventions aimed at reducing distress and fostering posttraumatic growth could impact in an improvement in pediatric health professionals' satisfaction with life.

Predicting Posttraumatic Growth in Mothers and Fathers of Critically Ill Children: A Longitudinal Study.

Research on parental psychological effects related to a child's critical illness has focused on studying negative outcomes, while the possibility of posttraumatic growth (PTG), defined as the perception of positive changes after a traumatic event, has been overlooked. This study explores the degree of parental PTG after a child's hospitalization in a pediatric intensive care unit (PICU) and the role of resilience, emotions, perceived severity of the child's condition and stress in predicting PTG. In the first 48 h after their child's discharge from a PICU, N = 196 parents were assessed for resilience, emotions, perceived stress, and the degree to which they perceived their child's condition as severe. 6 months later N = 143 parents were assessed PTG. 6 months post discharge, 37.1% of parents reported PTG at least to a medium degree. Path analyses with latent variables showed that the psychological variables assessed at discharge predicted between 20 and 21% of the total variance in PTG. Resilience affected PTG indirectly, through the bias of positive emotions. PTG is a frequent phenomenon. Psychological interventions aimed at encouraging parental PTG after a child's critical admission should focus on boosting resilience and positive emotions.

Burnout and posttraumatic stress in paediatric critical care personnel: Prediction from resilience and coping styles.

INTRODUCTION: Our aims were (1) to explore the prevalence of burnout syndrome (BOS) and posttraumatic stress disorder (PTSD) in a sample of Spanish staff working in the paediatric intensive care unit (PICU) and compare these rates with a sample of general paediatric staff and (2) to explore how resilience, coping strategies, and professional and demographic variables influence BOS and PTSD. MATERIALS AND METHODS: This is a multicentre, cross-sectional study. Data were collected in the PICU and in other paediatric wards of nine hospitals. Participants consisted of 298 PICU staff members (57 physicians, 177 nurses, and 64 nursing assistants) and 189 professionals working in non-critical paediatric units (53 physicians, 104 nurses, and 32 nursing assistants). They completed the Brief Resilience Scale, the Coping Strategies Questionnaire for healthcare providers, the Maslach Burnout Inventory, and the Trauma Screening Questionnaire. RESULTS: Fifty-six percent of PICU working staff reported burnout in at least one dimension (36.20% scored over the cut-off for emotional exhaustion, 27.20% for depersonalisation, and 20.10% for low personal accomplishment), and 20.1% reported PTSD. There were no differences in burnout and PTSD scores between PICU and non-PICU staff members, either among physicians, nurses, or nursing assistants. Higher burnout and PTSD rates emerged after the death of a child and/or conflicts with patients/families or colleagues. Around 30% of the variance in BOS and PTSD is predicted by a frequent usage of the emotion-focused coping style and an infrequent usage of the problem-focused coping style. DISCUSSION AND CONCLUSIONS: Interventions to prevent and treat distress among paediatric staff members are needed and should be focused on: (i) promoting active emotional processing of traumatic events and encouraging positive thinking; (ii) developing a sense of detached concern; (iii) improving the ability to solve interpersonal conflicts, and (iv) providing adequate training in end-of-life care.

Small Molecule Interferences in Resazurin and MTT-Based Metabolic Assays in the Absence of Cells.

In vitro assays (such as resazurin and MTT) provide an opportunity to determine the cytotoxicity of novel therapeutics before moving forward with expensive and resource-intensive in vivo studies. A concern with using these assays, however, is the production of false responses in the presence of particular chemical functionalities. To better understand this phenomenon, 19 small molecules at 6 concentrations (1 µM-100 mM) were tested in the presence of resazurin and MTT reagents to highlight potential interfering species. Through the use of absorbance measurements (using well-plate assays and UV-vis spectroscopy) with parallel MS analysis, we have shown that significant conversion of the assay reagents readily occurs in the presence of many tested interfering species without the need for any cellular activity. The most attributable sources of interference seem to arise from the presence of thiol and carboxylic acid moieties. Interestingly, the detectable interferences were more prevalent and larger in the presence of MTT (19 species with some deviations >3000%) compared to resazurin (16 species with largest deviation of ∼150%). Additionally, those deviations in the presence of resazurin were only substantial at high concentrations, while MTT showed deviations across the tested concentrations. This comprehensive study gives insight into chemical functional groups (thiols, amines, amides, carboxylic acids) that may interfere with resazurin and MTT assays in the absence of metabolic activity and indicates that proper control studies must be performed to obtain accurate data from these in vitro assays.

Internalized HIV Stigma and Disclosure Concerns: Development and Validation of Two Scales in Spanish-Speaking Populations.

Internalized stigma and disclosure concerns are key elements for the study of mental health in people living with HIV. Since no measures of these constructs were available for Spanish population, this study sought to develop such instruments, to analyze their reliability and validity and to provide a short version. A heterogeneous sample of 458 adults from different Spanish-speaking countries completed the HIV-Internalized Stigma Scale and the HIV-Disclosure Concerns Scale, along with the Hospital Anxiety and Depression Scale, Rosenberg's Self-esteem Scale and other socio-demographic variables. Reliability and correlation analyses, exploratory factor analyses, path analyses with latent variables, and ANOVAs were conducted to test the scales' psychometric properties. The scales showed good reliability in terms of internal consistency and temporal stability, as well as good sensitivity and factorial and criterion validity. The HIV-Internalized Stigma Scale and the HIV-Disclosure Concerns Scale are reliable and valid means to assess these variables in several contexts.

Predictors of Resilience and Posttraumatic Growth Among People Living with HIV: A Longitudinal Study.

This longitudinal study investigated the predictors of HIV-related resilience (HR) and posttraumatic growth (PTG) among Spanish-speaking HIV-positive people. Perceived past resilience, internalised stigma, and coping strategies were hypothesised as possible predictors. Data were collected at two time points from 119 HIV-positive people. Path analyses with latent variables revealed that half of HR 8 months after diagnosis was predicted by rumination, emotional expression, positive thinking, internalised stigma, and perceived past resilience. The latter three, along with isolation, self-blame, thinking avoidance, and help seeking predicted some PTG dimensions 8 months after diagnosis. The results highlight the importance of internalised stigma associated with HIV infection and of the differential use of coping strategies, and point to the need for clinicians and policy makers to implement stigma reduction and appropriate coping strategies interventions.

Posttraumatic growth inventory: factor structure in Spanish-speaking people living with HIV.

This cross-sectional study analyzed the factorial structure of the Posttraumatic Growth Inventory (PTGI) in a sample of 304 Spanish-speaking HIV-positive adults. Participants completed the PTGI and a socio-demographic questionnaire. Exploratory factor analysis (EFA) was carried out through structural equations modeling, with a Varimax rotation. Factors with eigenvalues greater than 1 were extracted, and items with loadings higher than .5 on a factor and lower than .4 on the rest were retained. Two confirmatory factor analyses (CFA) were performed to test a hierarchical model and a bifactor model. Reliability analyses were conducted. EFA suggested a three-factor model keeping 11 of the original 21 items. The three factors that emerged were changes in philosophy of life, in the self and in interpersonal relationships. CFAs suggested that only the bifactor model fitted the data. The three factors as well as the global scale showed good reliability. The factor structure of PTGI's scores in our data is consistent with the three dimensions theorized by Tedeschi and Calhoun, which speaks in favor of the construct validity of this measure.

Development of a screening measure of stress for parents of children hospitalised in a Paediatric Intensive Care Unit.

BACKGROUND: Having a child admitted to intensive care is a highly stressful experience for parents; however there is a lack of screening instruments of parental stress in that context, which would be useful for both, research and clinical purposes. OBJECTIVES: (1) To validate a brief measure of parental stress based on the Parental Stressor Scale: Paediatric Intensive Care Unit (PSS:PICU), (2) to study which environmental factors of the PICU are more stressful in a sample of Spanish parents, and (3) to study which variables are related to higher levels of stress among this group. METHOD: 196 Spanish parents completed the Abbreviated PSS: PICU (A-PSS:PICU) and a general stress scale (the Perceived Stress Scale) upon their child's discharge to test the convergent validity of the tool. Three months later, they were assessed anxiety and depression using the Hospital Anxiety and Depression Scale, and posttraumatic stress with the Davidson Trauma Scale in order to test the predictive validity of the A-PSS:PICU. RESULTS: Two factors emerged from Confirmatory Factor Analyses, (1) stress due to child's condition and (2) stress related to PICU's staff. The A-PSS:PICU showed adequate reliability and convergent and predictive validity. The most stressful aspects were the behaviours and emotional responses of their child and the loss of their parental role. Age, gender, child's condition, length of admission, spiritual beliefs, and mechanical ventilation were associated to parental stress scores. CONCLUSION: The A-PSS:PICU is a reliable and valid measure. Parental stress should be screened during a child's PICU admission to identify parents at risk of post-discharge distress.

Cervidae antlers exploited to manufacture prehistoric tools and hunting implements as a reliable source of ancient DNA.

Antler is one of the primary animal raw materials exploited for technical purposes by the hunter-gatherer groups of the Eurasian Upper Palaeolithic (UP) all over the ecological range of deers, and beyond. It was exhaustively employed to produce one of the most critical tools for the survival of the UP societies: hunting weapons. However, antler implements can be made from diverse deer taxa, with different ecological requirements and ethological behaviours. Identifying the antler's origin at a taxonomic level is thus essential in improving our knowledge of humans' functional, practical and symbolic choices, as well as the human-animal interface during Prehistoric times. Nevertheless, palaeogenetics analyses have focused mainly on bone and teeth, with genetic studies of antler generally focused on modern deer conservation. Here we present the results of the first whole mitochondrial genome ancient DNA (aDNA) analysis by means of in-solution hybridisation capture of antlers from pre-Holocene archaeological contexts. We analysed a set of 50 Palaeolithic and Neolithic (c. 34-8ka) antler and osseous objects from South-Western Europe, Central Europe, South-Western Asia and the Caucasus. We successfully obtained aDNA, allowing us to identify the exploited taxa and demonstrate the archaeological relevance of those finds. Moreover, as most of the antlers were sampled using a minimally-invasive method, further analyses (morphometric, technical, genetic, radiometric and more) remain possible on these objects.

Improved sensorimotor performance via stochastic resonance.

Several studies about noise-enhanced balance control in humans support the hypothesis that stochastic resonance can enhance the detection and transmission in sensorimotor system during a motor task. The purpose of the present study was to extend these findings in a simpler and controlled task. We explored whether a particular level of a mechanical Gaussian noise (0-15 Hz) applied on the index finger can improve the performance during compensation for a static force generated by a manipulandum. The finger position was displayed on a monitor as a small white point in the center of a gray circle. We considered a good performance when the subjects exhibited a low deviation from the center of this circle and when the performance had less variation over time. Several levels of mechanical noise were applied on the manipulandum. We compared the performance between zero noise (ZN), optimal noise (ON), and high noise (HN). In all subjects (8 of 8) the data disclosed an inverted U-like graph between the inverse of the mean variation in position and the input noise level. In other words, the mean variation was significantly smaller during ON than during ZN or HN. The findings suggest that the application of a tactile-proprioceptive noise can improve the stability in sensorimotor performance via stochastic resonance. Possible explanations for this improvement in motor precision are an increase of the peripheral receptors sensitivity and of the internal stochastic resonance, causing a better sensorimotor integration and an increase in corticomuscular synchronization.

Respiratory magnetogram detected with a MEMS device.

Magnetic fields generated by the brain or the heart are very useful in clinical diagnostics. Therefore, magnetic signals produced by other organs are also of considerable interest. Here we show first evidence that thoracic muscles can produce a strong magnetic flux density during respiratory activity, that we name respiratory magnetogram. We used a small magnetometer based on microelectromechanical systems (MEMS), which was positioned inside the open thoracic cage of anaesthetized and ventilated rats. With this new MEMS sensor of about 20 nT resolution, we recorded a strong and rhythmic respiratory magnetogram of about 600 nT.