Occurrence of area postrema syndrome during follow-up: phenotype and influence over NMOSD activity in LATAM in real-world settings.

INTRODUCTION: We aimed to assess the frequency, duration, and severity of area postrema syndrome (APS) during follow-up in neuromyelitis optica spectrum disorder (NMOSD) patients, as well as its association with inflammatory activity and prognostic factors of APS severity in a real-world setting. METHODS: We conducted a retrospective study on a cohort of Latin American (LATAM) NMOSD patients who had experienced APS during their follow-up. Patients from Mexico, Peru, Brazil, Colombia, Panama, Chile and Argentina patients who met 2015 NMOSD criteria were included. We evaluated data on symptom type (nausea, vomiting and/or hiccups), frequency, duration, severity (measured by APS severity scale), association with other NMOSD core relapses, and acute treatments (symptomatic and immunotherapy or plasmapheresis). Logistic regression was conducted to evaluate factors associated with APS severity (vs. mild-moderate). RESULTS: Out of 631 NMOSD patients, 116 (18.3%) developed APS during their follow-up. The most common APS phenotype was severe. Inflammatory activity (i.e., relapses) significantly decreased after the onset of APS. Half of the patients experienced isolated APS with a median duration of 10 days, and the most frequently used acute treatment was IV steroids. All three symptoms were present in 44.6% of the patients. APS symptoms resolved following immunotherapy. Logistic regression did not identify independent factors associated with the severity of APS. CONCLUSIONS: Our findings indicate that 18.3% of NMOSD patients developed APS during the follow-up period, with most patients fulfilling criteria for severe APS. The inflammatory activity decreased after the onset of APS compared to the previous year.

Evaluation of critical parameters in the hollow-fibre system for tuberculosis: A case study of moxifloxacin.

AIMS: The hollow­fibre system for tuberculosis (HFS­TB) is a preclinical model qualified by the European Medicines Agency to underpin the anti­TB drug development process. It can mimic in vivo pharmacokinetic (PK)­pharmacodynamic (PD) attributes of selected antimicrobials, which could feed into in silico models to inform the design of clinical trials. However, historical data and published protocols are insufficient and omit key information to allow experiments to be reproducible. Therefore, in this work, we aim to optimize and standardize various HFS­TB operational procedures. METHODS: First, we characterized bacterial growth dynamics with different types of hollow­fibre cartridges, Mycobacterium tuberculosis strains and media. Second, we mimicked a moxifloxacin PK profile within hollow­fibre cartridges, in order to check drug­fibres compatibility. Lastly, we mimicked the moxifloxacin total plasma PK profile in human after once daily oral dose of 400 mg to assess PK­PD after different sampling methods, strains, cartridge size and bacterial adaptation periods before drug infusion into the system. RESULTS: We found that final bacterial load inside the HFS­TB was contingent on the studied variables. Besides, we demonstrated that drug­fibres compatibility tests are critical preliminary HFS­TB assays, which need to be properly reported. Lastly, we uncovered that the sampling method and bacterial adaptation period before drug infusion significantly impact actual experimental conclusions. CONCLUSION: Our data contribute to the necessary standardization of HFS­TB experiments, draw attention to multiple aspects of this preclinical model that should be considered when reporting novel results and warn about critical parameters in the HFS­TB currently overlooked.

Implementation of an Ecological Momentary Assessment (EMA) in Naturalistic Psychotherapy Settings: Qualitative Insights from Patients, Therapists, and Supervisors Perspectives.

Ecological momentary assessment (EMA) allows measuring intra-individual processes moment by moment, identifying and modeling, in a naturalistic way, individual levels and changes in different psychological processes. However, active EMA requires a high degree of adherence, as it implies a significant burden for patients. Moreover, there is still no consensus on standardized procedures for implementation. There have been few results in detecting desirable characteristics for the design and implementation of an EMA device. Studies that address these issues from the perspectives of participants in psychotherapeutic processes are needed. To analyze the perspectives of patients, therapists and supervisors on the implementation of an EMA device in a psychotherapeutic treatment for depression. The sample will include eight patients, eleven therapists and five supervisors, taken from a research project that implemented an EMA system for monitoring the dynamics of affectivity at the beginning of psychotherapies for depression. Semi-structured interviews specific to each group are being conducted and analyzed from a qualitative approach based on consensual qualitative research (CQR). Participants reported having a positive evaluation of the study's informational resources and implementation. Difficulties were expressed in responding in the morning hours and the importance of having a customized EMA that is tailored to the needs of the patients was expressed. Furthermore, patients and therapists agreed that the impact of the use of the monitoring system on treatment was neutral or positive. In contrast, patients considered the EMA to be positive for their daily life.

Reliable prediction of difficult airway for tracheal intubation from patient preoperative photographs by machine learning methods.

BACKGROUND: Estimating the risk of a difficult tracheal intubation should help clinicians in better anaesthesia planning, to maximize patient safety. Routine bedside screenings suffer from low sensitivity. OBJECTIVE: To develop and evaluate machine learning (ML) and deep learning (DL) algorithms for the reliable prediction of intubation risk, using information about airway morphology. METHODS: Observational, prospective cohort study enrolling n=623 patients who underwent tracheal intubation: 53/623 difficult cases (prevalence 8.51%). First, we used our previously validated deep convolutional neural network (DCNN) to extract 2D image coordinates for 27 + 13 relevant anatomical landmarks in two preoperative photos (frontal and lateral views). Here we propose a method to determine the 3D pose of the camera with respect to the patient and to obtain the 3D world coordinates of these landmarks. Then we compute a novel set of dM=59 morphological features (distances, areas, angles and ratios), engineered with our anaesthesiologists to characterize each individual's airway anatomy towards prediction. Subsequently, here we propose four ad hoc ML pipelines for difficult intubation prognosis, each with four stages: feature scaling, imputation, resampling for imbalanced learning, and binary classification (Logistic Regression, Support Vector Machines, Random Forests and eXtreme Gradient Boosting). These compound ML pipelines were fed with the dM=59 morphological features, alongside dD=7 demographic variables. Here we trained them with automatic hyperparameter tuning (Bayesian search) and probability calibration (Platt scaling). In addition, we developed an ad hoc multi-input DCNN to estimate the intubation risk directly from each pair of photographs, i.e. without any intermediate morphological description. Performance was evaluated using optimal Bayesian decision theory. It was compared against experts' judgement and against state-of-the-art methods (three clinical formulae, four ML, four DL models). RESULTS: Our four ad hoc ML pipelines with engineered morphological features achieved similar discrimination capabilities: median AUCs between 0.746 and 0.766. They significantly outperformed both expert judgement and all state-of-the-art methods (highest AUC at 0.716). Conversely, our multi-input DCNN yielded low performance due to overfitting. This same behaviour occurred for the state-of-the-art DL algorithms. Overall, the best method was our XGB pipeline, with the fewest false negatives at the optimal Bayesian decision threshold. CONCLUSIONS: We proposed and validated ML models to assist clinicians in anaesthesia planning, providing a reliable calibrated estimate of airway intubation risk, which outperformed expert assessments and state-of-the-art methods. Our novel set of engineered features succeeded in providing informative descriptions for prognosis.

Adjusting and validating a procedure for parenteral anaesthesia in neonatal mice.

For neonatal pups, parenteral anaesthesia is said to be not reliable as low doses induce no anaesthesia whereas high doses render high mortality rates. In this work we have adapted parenteral anaesthesia procedures approved for pups >7 days of age, to anaesthetize neonatal animals (postnatal days 3-4; P3-P4) for keeping them immobile for a long period. In our first experiment we analysed the behaviour of P3-P4 mouse pups for 70 min after intraperitoneal administration of low (37.5/3.75 mg/kg) or high (50/5) doses of a ketamine/xylazine anaesthetic mixture, both in the low range as compared with dosages employed in adults. Pups became immobile in ≈7 min and remained immobile for ≈45 min, irrespective of the age and dose of anaesthesia, younger pups (P3) being apparently more sensitive to the dosage. In the second experiment, we studied the response of P3 pups to mildly nociceptive stimulations, performed with a 4.0 g von Frey filament applied to the dorsal aspect of their paws. These stimuli elicited reaction in 100% of the cases in non-anaesthetized pups. The results indicate that the high dose significantly reduced responses as compared with the low dose of anaesthesia. With the low dose, <40% of the pups were unresponsive to nociceptive stimulation, whereas the high dose resulted in 50-60% of the animals not responding. Mortality was low irrespective of age or dose, suggesting that doses can be further increased if needed for invasive experimental procedures.

RhoA downregulation in the murine intestinal epithelium results in chronic Wnt activation and increased tumorigenesis.

Rho GTPases are molecular switches regulating multiple cellular processes. To investigate the role of RhoA in normal intestinal physiology, we used a conditional mouse model overexpressing a dominant negative RhoA mutant (RhoAT19N) in the intestinal epithelium. Although RhoA inhibition did not cause an overt phenotype, increased levels of nuclear ß-catenin were observed in the small intestinal epithelium of RhoAT19N mice, and the overexpression of multiple Wnt target genes revealed a chronic activation of Wnt signaling. Elevated Wnt signaling in RhoAT19N mice and intestinal organoids did not affect the proliferation of intestinal epithelial cells but significantly interfered with their differentiation. Importantly, 17-month-old RhoAT19N mice showed a significant increase in the number of spontaneous intestinal tumors. Altogether, our results indicate that RhoA regulates the differentiation of intestinal epithelial cells and inhibits tumor initiation, likely through the control of Wnt signaling, a key regulator of proliferation and differentiation in the intestine.

Metabolic Rewiring and Altered Glial Differentiation in an iPSC-Derived Astrocyte Model Derived from a Nonketotic Hyperglycinemia Patient.

The pathophysiology of nonketotic hyperglycinemia (NKH), a rare neuro-metabolic disorder associated with severe brain malformations and life-threatening neurological manifestations, remains incompletely understood. Therefore, a valid human neural model is essential. We aimed to investigate the impact of GLDC gene variants, which cause NKH, on cellular fitness during the differentiation process of human induced pluripotent stem cells (iPSCs) into iPSC-derived astrocytes and to identify sustainable mechanisms capable of overcoming GLDC deficiency. We developed the GLDC27-FiPS4F-1 line and performed metabolomic, mRNA abundance, and protein analyses. This study showed that although GLDC27-FiPS4F-1 maintained the parental genetic profile, it underwent a metabolic switch to an altered serine-glycine-one-carbon metabolism with a coordinated cell growth and cell cycle proliferation response. We then differentiated the iPSCs into neural progenitor cells (NPCs) and astrocyte-lineage cells. Our analysis showed that GLDC-deficient NPCs had shifted towards a more heterogeneous astrocyte lineage with increased expression of the radial glial markers GFAP and GLAST and the neuronal markers MAP2 and NeuN. In addition, we detected changes in other genes related to serine and glycine metabolism and transport, all consistent with the need to maintain glycine at physiological levels. These findings improve our understanding of the pathology of nonketotic hyperglycinemia and offer new perspectives for therapeutic options.

Hepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver.

The metabolic functions of the liver are spatially organized in a phenomenon called zonation, linked to the differential exposure of portal and central hepatocytes to nutrient-rich blood. The mTORC1 signaling pathway controls cellular metabolism in response to nutrients and insulin fluctuations. Here we show that simultaneous genetic activation of nutrient and hormone signaling to mTORC1 in hepatocytes results in impaired establishment of postnatal metabolic and zonal identity of hepatocytes. Mutant hepatocytes fail to upregulate postnatally the expression of Frizzled receptors 1 and 8, and show reduced Wnt/ß-catenin activation. This defect, alongside diminished paracrine Wnt2 ligand expression by endothelial cells, underlies impaired postnatal maturation. Impaired zonation is recapitulated in a model of constant supply of nutrients by parenteral nutrition to piglets. Our work shows the role of hepatocyte sensing of fluctuations in nutrients and hormones for triggering a latent metabolic zonation program.

Cost-sensitive ordinal classification methods to predict SARS-CoV-2 pneumonia severity.

OBJECTIVE: To study the suitability of costsensitive ordinal artificial intelligence-machine learning (AIML) strategies in the prognosis of SARS-CoV-2 pneumonia severity. MATERIALS & METHODS: Observational, retrospective, longitudinal, cohort study in 4 hospitals in Spain. Information regarding demographic and clinical status was supplemented by socioeconomic data and air pollution exposures. We proposed AI-ML algorithms for ordinal classification via ordinal decomposition and for cost-sensitive learning via resampling techniques. For performance-based model selection, we defined a custom score including per-class sensitivities and asymmetric misprognosis costs. 260 distinct AI-ML models were evaluated via 10 repetitions of 5×5 nested cross-validation with hyperparameter tuning. Model selection was followed by the calibration of predicted probabilities. Final overall performance was compared against five well-established clinical severity scores and against a 'standard' (non-cost sensitive, non-ordinal) AI-ML baseline. In our best model, we also evaluated its explainability with respect to each of the input variables. RESULTS: The study enrolled n = 1548 patients: 712 experienced low, 238 medium, and 598 high clinical severity. d = 131 variables were collected, becoming d ' = 148 features after categorical encoding. Model selection resulted in our best-performing AI-ML pipeline having: a) no imputation of missing data, b) no feature selection (i.e. using the full set of d ' features), c) 'Ordered Partitions' ordinal decomposition, d) cost-based reimbalance, and e) a Histogram-based Gradient Boosting classifier. This best model (calibrated) obtained a median accuracy of 68.1% [67.3%, 68.8%] (95% confidence interval), a balanced accuracy of 57.0% [55.6%, 57.9%], and an overall area under the curve (AUC) 0.802 [0.795, 0.808]. In our dataset, it outperformed all five clinical severity scores and the 'standard' AI-ML baseline. DISCUSSION & CONCLUSION: We conducted an exhaustive exploration of AI-ML methods designed for both ordinal and cost-sensitive classification, motivated by a real-world application domain (clinical severity prognosis) in which these topics arise naturally. Our model with the best classification performance exploited successfully the ordering information of ground truth classes, coping with imbalance and asymmetric costs. However, these ordinal and cost-sensitive aspects are seldom explored in the literature.

BPTF cooperates with MYCN and MYC to link neuroblastoma cell cycle control to epigenetic cellular states.

The nucleosome remodeling factor BPTF is required for the deployment of the MYC-driven transcriptional program. Deletion of one Bptf allele delays tumor progression in mouse models of pancreatic cancer and lymphoma. In neuroblastoma, MYCN cooperates with the transcriptional core regulatory circuitry (CRC). High BPTF levels are associated with high-risk features and decreased survival. BPTF depletion results in a dramatic decrease of cell proliferation. Bulk RNA-seq, single-cell sequencing, and tissue microarrays reveal a positive correlation of BPTF and CRC transcription factor expression. Immunoprecipitation/mass spectrometry shows that BPTF interacts with MYCN and the CRC proteins. Genome-wide distribution analysis of BPTF and CRC in neuroblastoma reveals a dual role for BPTF: 1) it co-localizes with MYCN/MYC at the promoter of genes involved in cell cycle and 2) it co-localizes with the CRC at super-enhancers to regulate cell identity. The critical role of BPTF across neuroblastoma subtypes supports its relevance as a therapeutic target.

Neuroendocrine Tumor Presented With Axillary Mass: A Case Report.

ABSTRACT: A 79-year-old man presented with a palpable left axillary mass and ultrasonography findings of conglomerate lymph nodes. The initial clinical suspicion was a lymphoproliferative disorder, but histopathological results revealed a grade 3 neuroendocrine tumor. The mass showed somatostatin receptor overexpression in 99m Tc-HYNIC-TOC scintigraphy and high uptake in 18 F-FDG PET/CT. Bilateral hypermetabolic adrenal nodes suggestive of metastases were also detected. The patient was treated with chemotherapy and immunotherapy, and PET/CT scan showed a partial metabolic response after 4 cycles. According to this case, neuroendocrine tumor should be considered in the differential diagnosis of axillary masses.

Donors with repeated blood product discards for filtration problems, clots or hemolysis: Causes and follow-up.

INTRODUCTION: Sanquin donor medicine department is informed when donations or their components are rejected. This can occur isolated or frequently. It is undesirable because the donations cannot be used and there may be an underlying medical cause. Based on regional approaches, a uniform procedure was developed. METHODS: Information about whole blood, plasma- plateletpheresis donations from which one or more components were rejected for filtration time (>2 h), hemolysis or clots were extracted from blood bank information system. After rejection of two successive components or donations or total ≥3 the donor is contacted. Depending on the medical history and investigation by the family doctor, the donor carrier is re-evaluated. We looked for the causes of the discarded products and performed a survey among blood services regarding polices with discarded products. RESULTS: One or more components from 1742 of about 2.2 million successful donations (0.08%) were rejected. The highest percentage of rejection was seen in plateletpheresis (1.5%), all for clots. No underlying medical causes were found. 24 whole blood donors were found to have sickle cell trait (SCT) and were permanently deferred. The policies for follow-up after discarded products or acceptance of SCT donors vary between the 16 blood banks. Six organizations do not follow-up donors and seven accept SCT for blood or plasma donation. CONCLUSION: Informing donors with repeated discarded products avoids the non-use of donations. Causes of repeated discarded products can be found by follow-up of donors. The results of the survey indicate a large discrepancy in policies applied worldwide.

Plasmid-encoded toxin of Escherichia coli cleaves complement system proteins and inhibits complement-mediated lysis in vitro.

Plasmid-encoded toxin (Pet) is an autotransporter protein of the serine protease autotransporters of Enterobacteriaceae (SPATE) family, important in the pathogenicity of Escherichia coli. The pet gene was initially found in the enteroaggregative E. coli (EAEC) virulence plasmid, pAA2. Although this virulence factor was initially described in EAEC, an intestinal E. coli pathotype, pet may also be present in other pathotypes, including extraintestinal pathogenic strains (ExPEC). The complement system is an important defense mechanism of the immune system that can be activated by invading pathogens. Proteases produced by pathogenic bacteria, such as SPATEs, have proteolytic activity and can cleave components of the complement system, promoting bacterial resistance to human serum. Considering these factors, the proteolytic activity of Pet and its role in evading the complement system were investigated. Proteolytic assays were performed by incubating purified components of the complement system with Pet and Pet S260I (a catalytic site mutant) proteins. Pet, but not Pet S260I, could cleave C3, C5 and C9 components, and also inhibited the natural formation of C9 polymers. Furthermore, a dose-dependent inhibition of ZnCl2-induced C9 polymerization in vitro was observed. E. coli DH5α survived incubation with human serum pre-treated with Pet. Therefore, Pet can potentially interfere with the alternative and the terminal pathways of the complement system. In addition, by cleaving C9, Pet may inhibit membrane attack complex (MAC) formation on the bacterial outer membrane. Thus, our data are suggestive of a role of Pet in resistance of E. coli to human serum.

Gene editing: a near future for the treatment of genetic kidney diseases.

The study by Chen et al. is the first to apply the revolutionary genetic engineering tool, base editing, in a rat model for the treatment of primary hyperoxaluria type 1, a disease that originates in the liver but in which the kidney is the main organ affected. This commentary contextualizes and describes the gene-editing technology applied by the authors, provides an interpretation and opinion of their results, and indicates possible future applications.

Brain MRI features of postdural puncture headache.

BACKGROUND: Postdural puncture headache (PDPH) is a relatively common acute complication that occurs following regional anesthesia and is among the clinical features of secondary intracranial hypotension syndrome (IHS).The aim of this study was to document the radiological findings specific to PDPH with brain MRI and to determine whether these findings differed from those described in the third edition of the International Headache Society's International Classification of Headache Disorders (ICHD-3). METHODS: Thirty patients who were diagnosed with PDPH based on the ICHD-3 clinical criteria were enrolled in the study and signed the informed consent form approved by our hospital ethics committee. Their symptoms were recorded and they underwent brain MRI before and after the administration of a gadolinium-based contrast agent within 48-72 hours after the onset of their orthostatic headache. RESULTS: All patients with PDPH presented with MRI features of pachymeningeal enhancement. The thickness of the pachymeningeal enhancement varied from 0.6 mm to 4.1 mm, with a mean of 1.6 mm+0.8.No cases of brain sagging were observed. 4 of the 30 patients presented with intracranial subdural fluid collections, 7 presented with pneumocephalus and 7 pituitary gland enlargement. CONCLUSIONS: The radiological characteristics of IHS and PDPH are most likely the result of compensatory mechanisms in response to decreased cerebrospinal fluid pressure. The acute nature of PDPH probably causes its radiological MRI characteristics to differ from those of IHS, given that no brain sagging could be demonstrated.

Early Family Experiences, Drug Use, and Psychosocial Adjustment across the Life Span: Is Parental Strictness Always a Protective Factor?

Objective: This study analyzes whether parental strictness, which is shared by authoritative parenting (strictness and warmth) and authoritarian parenting (strictness without warmth) styles, always acts as a main protective factor against drug use and psychosocial maladjustment in children. This conclusion has already been stated in numerous classic studies, though emergent research suggests that there are benefits to parental warmth regardless of whether strictness is present or not. Method: Sample were 2,095 Spanish participants (1,227 females, 58.6%), 581 adolescent children (aged 12-18 years, 27.7%) and 1,514 adult children (72.3%). The measures were the main parenting style dimensions (warmth and strictness), drug use, and a set of indicators of psychosocial adjustment. A 4 × 2 × 4 MANOVA was applied for all outcomes with parenting style, sex, and age as independent variables. Results: Indulgent parenting (warmth without strictness) was related to less drug use than parenting without warmth (authoritarian and neglectful). Additionally, indulgent and authoritative parenting styles were related to better scores on psychosocial adjustment than authoritarian and neglectful styles, although the indulgent parenting was the only style related to the optimal scores being equal or even more effective than the authoritative style. Conclusion: Contrary to classical studies, present findings suggest that it is the parental warmth instead of the parental strictness that seems to be effective in protecting against drug use and psychosocial maladjustment.

Objetivo: En este estudio se analiza si, como asumen numerosos estudios clásicos, el componente de severidad que comparte el estilo parental autorizativo (severidad y afecto) con el estilo autoritario (severidad sin afecto) actúan siempre como el principal factor protector del consumo de drogas y el desajuste psicosocial de los hijos. Sin embargo, la investigación emergente sugiere los beneficios del afecto parental independientemente de la severidad. Método: Los participantes fueron 2,095 hijos españoles (1,227 mujeres, 58.6%), 581 adolescentes (de 12 a 18 años, 27.7%) y 1,514 adultos (72.3%). Las medidas fueron de las principales dimensiones del estilo parental (afecto y severidad), del consumo de drogas y un conjunto de indicadores del ajuste psicosocial. Se aplicó un MANOVA 4 × 2 × 4 con todos los criterios evaluados analizando el estilo parental, el sexo y la edad como variables independientes. Resultados: El estilo indulgente (afecto sin severidad) se relacionó con un menor consumo de drogas que los estilos sin afecto (autoritario y negligente). Además, los estilos indulgente y autorizativo se relacionaron con mejores puntuaciones en ajuste psicosocial, aunque el indulgente fue el único estilo relacionado con las puntuaciones óptimas siendo igual o incluso más eficaz que el estilo autorizativo. Conclusión: A diferencia de los estudios clásicos, los presentes resultados sugieren que el afecto parental, en vez de la severidad, parece ser eficaz como protección frente al consumo de drogas y el desajuste psicosocial.

Underlying and proximate drivers of biodiversity changes in Mesoamerican biosphere reserves.

Protected areas are of paramount relevance to conserving wildlife and ecosystem contributions to people. Yet, their conservation success is increasingly threatened by human activities including habitat loss, climate change, pollution, and species overexploitation. Thus, understanding the underlying and proximate drivers of anthropogenic threats is urgently needed to improve protected areas' effectiveness, especially in the biodiversity-rich tropics. We addressed this issue by analyzing expert-provided data on long-term biodiversity change (last three decades) over 14 biosphere reserves from the Mesoamerican Biodiversity Hotspot. Using multivariate analyses and structural equation modeling, we tested the influence of major socioeconomic drivers (demographic, economic, and political factors), spatial indicators of human activities (agriculture expansion and road extension), and forest landscape modifications (forest loss and isolation) as drivers of biodiversity change. We uncovered a significant proliferation of disturbance-tolerant guilds and the loss or decline of disturbance-sensitive guilds within reserves causing a "winner and loser" species replacement over time. Guild change was directly related to forest spatial changes promoted by the expansion of agriculture and roads within reserves. High human population density and low nonfarming occupation were identified as the main underlying drivers of biodiversity change. Our findings suggest that to mitigate anthropogenic threats to biodiversity within biosphere reserves, fostering human population well-being via sustainable, nonfarming livelihood opportunities around reserves is imperative.

Do We Know Enough about Negative Parenting? Recent Evidence on Parenting Styles and Child Maladjustment / ¿Sabemos suficiente sobre el estilo parental negativo? Pruebas recientes sobre los estilos parentales y la inadaptación de los hijos

Background: There are serious doubts as to whether parental strictness, one of the two main dimensions of parental style, can be a negative or positive component of parenting in traditional societies. Method: Parenting style (authoritarian, authoritative, indulgent, and neglectful) was captured from strictness and warmth dimensions and child maladjustment was assessed with problems of self-esteem and self-concept (academic, social, emotional, family, and physical) studied worldwide. The sample was composed of 1,282 Chinese participants (676 females, 52.7%), 581 adolescent children (age ranging from 12-18 years, 45.3%), and 701 young adult children (age ranging from 19-31 years, 54.7%). A 4 × 2 × 2 factorial MANOVA was applied for all outcomes using parenting style, sex, and age as the independent variables. Results: The statistical analysis plainly indicated that authoritarian (strictness but not warmth) and neglectful (neither strictness nor warmth) parenting styles were associated with higher maladjustment in terms of lower self-esteem and self-concept scores. Indulgent (not strictness but warmth) and authoritative (strictness and warmth) parenting were positive parenting styles acting as protective factors against self-esteem and self-concept problems. The authoritative style (strictness and warmth), but not the authoritarian parenting style (strictness but not warmth), was the most positive parenting for academic self-concept, but only among adolescents. Conclusions: Interestingly, completely contrary to expectations that authoritarian parenting might be a positive parenting in traditional societies, present findings suggest that the authoritarian style might be a negative parenting related to child maladjustment. (AU)

Antecedentes: Existen serias dudas sobre si la severidad parental, una de las dos dimensiones principales del estilo parental, puede ser un componente negativo o positivo de la socialización en las sociedades tradicionales. Método: El estilo parental (autoritario, autorizativo, indulgente y negligente) se evaluó a partir de las dimensiones de severidad y afecto, y el desajuste de los hijos por medio de problemas de autoestima y autoconcepto (académicos, sociales, emocionales, familiares y físicos) estudiados en todo el mundo. La muestra estaba compuesta por 1,282 participantes chinos (676 mujeres, 52.7%), 581 hijos adolescentes (de 12 a 18 años, 45.3%) y 701 hijos adultos jóvenes (de 19 a 31 años, 54.7%). Se aplicó un MANOVA factorial 4 × 2 × 2 para todos los criterios utilizando el estilo parental, el sexo y la edad como variables independientes. Resultados: El análisis estadístico indicó claramente que el estilo parental autoritario (severidad sin afecto) y el negligente (ni severidad ni afecto) estaban relacionados con un mayor desajuste, como indican las menores puntuaciones de autoestima y autoconcepto. El estilo indulgente (afecto sin severidad) y el autorizativo (severidad y afecto) fueron estilos parentales positivos que actuaron como factores protectores contra los problemas de autoestima y autoconcepto. El estilo autorizativo (severidad y afecto), pero no el autoritario (severidad sin afecto), fue el más positivo para el autoconcepto académico, pero sólo en los adolescentes. Conclusiones: En contra de las expectativas de que el estilo parental autoritario podría ser positivo para la socialización en las sociedades tradicionales, los presentes resultados sugieren que la socialización autoritaria es un estilo parental negativo relacionado con problemas de desajuste de los hijos. (AU)

Early Family Experiences, Drug Use, and Psychosocial Adjustment across the Life Span: Is Parental Strictness Always a Protective Factor? / [Las experiencias tempranas en la familia, el uso de drogas y el ajuste psicosocial: ¿es siempre la severidad parental un factor de protección?]

Objective: This study analyzes whether parental strictness, which is shared by authoritative parenting (strictness and warmth) and authoritarian parenting (strictness without warmth) styles, always acts as a main protective factor against drug use and psychosocial maladjustment in children. This conclusion has already been stated in numerous classic studies, though emergent research suggests that there are benefits to parental warmth regardless of whether strictness is present or not. Method: Sample were 2,095 Spanish participants (1,227 females, 58.6%), 581 adolescent children (aged 12-18 years, 27.7%) and 1,514 adult children (72.3%). The measures were the main parenting style dimensions (warmth and strictness), drug use, and a set of indicators of psychosocial adjustment. A 4 × 2 × 4 MANOVA was applied for all outcomes with parenting style, sex, and age as independent variables. Results: Indulgent parenting (warmth without strictness) was related to less drug use than parenting without warmth (authoritarian and neglectful). Additionally, indulgent and authoritative parenting styles were related to better scores on psychosocial adjustment than authoritarian and neglectful styles, although the indulgent parenting was the only style related to the optimal scores being equal or even more effective than the authoritative style. Conclusion: Contrary to classical studies, present findings suggest that it is the parental warmth instead of the parental strictness that seems to be effective in protecting against drug use and psychosocial maladjustment.(AU)

Objetivo: En este estudio se analiza si, como asumen numerosos estudios clásicos, el componente de severidad que comparte el estilo parental autorizativo (severidad y afecto) con el estilo autoritario (severidad sin afecto) actúan siempre como el principal factor protector del consumo de drogas y el desajuste psicosocial de los hijos. Sin embargo, la investigación emergente sugiere los beneficios del afecto parental independientemente de la severidad. Método: Los participantes fueron 2,095 hijos españoles (1,227 mujeres, 58.6%), 581 adolescentes (de 12 a 18 años, 27.7%) y 1,514 adultos (72.3%). Las medidas fueron de las principales dimensiones del estilo parental (afecto y severidad), del consumo de drogas y un conjunto de indicadores del ajuste psicosocial. Se aplicó un MANOVA 4 × 2 × 4 con todos los criterios evaluados analizando el estilo parental, el sexo y la edad como variables independientes. Resultados: El estilo indulgente (afecto sin severidad) se relacionó con un menor consumo de drogas que los estilos sin afecto (autoritario y negligente). Además, los estilos indulgente y autorizativo se relacionaron con mejores puntuaciones en ajuste psicosocial, aunque el indulgente fue el único estilo relacionado con las puntuaciones óptimas siendo igual o incluso más eficaz que el estilo autorizativo. Conclusión: A diferencia de los estudios clásicos, los presentes resultados sugieren que el afecto parental, en vez de la severidad, parece ser eficaz como protección frente al consumo de drogas y el desajuste psicosocial.(AU)

HSP70 binds to specific non-coding RNA and regulates human RNA polymerase III.

Molecular chaperones are critical for protein homeostasis and are implicated in several human pathologies such as neurodegeneration and cancer. While the binding of chaperones to nascent and misfolded proteins has been studied in great detail, the direct interaction between chaperones and RNA has not been systematically investigated. Here, we provide the evidence for widespread interaction between chaperones and RNA in human cells. We show that the major chaperone heat shock protein 70 (HSP70) binds to non-coding RNA transcribed by RNA polymerase III (RNA Pol III) such as tRNA and 5S rRNA. Global chromatin profiling revealed that HSP70 binds genomic sites of transcription by RNA Pol III. Detailed biochemical analyses showed that HSP70 alleviates the inhibitory effect of cognate tRNA transcript on tRNA gene transcription. Thus, our study uncovers an unexpected role of HSP70-RNA interaction in the biogenesis of a specific class of non-coding RNA with wider implications in cancer therapeutics.