Development and internal validation of a clinical score to predict neonatal hypoglycaemia in women with gestational diabetes.

INTRODUCTION: Gestational diabetes (GD) is a risk factor for neonatal hypoglycaemia (NH), but other factors can increase this risk. OBJECTIVES: To create a score to predict NH in women with GD. METHODS: Retrospective study of women with GD with a live singleton birth between 2012 and 2017 from the Portuguese GD registry. Pregnancies with and without NH were compared. A logistic regression was used to study NH predictors. Variables independently associated with NH were used to score derivation. The model's internal validation was performed by a bootstrapping. The association between the score and NH was assessed by logistic regression. RESULTS: We studied 10216 pregnancies, 410 (4.0%) with NH. The model's AUC was 0.628 (95%CI: 0.599-0.657). Optimism-corrected c-index: 0.626. Points were assigned to variables associated with NH in proportion to the model's lowest regression coefficient: insulin-treatment 1, preeclampsia 3, preterm delivery 2, male sex 1, and small-for-gestational-age 2, or large-for-gestational-age 3. NH prevalence by score category 0-1, 2, 3, 4, and ≥5 was 2.3%, 3.0%, 4.5%, 6.0%, 7.4%, and 11.5%, respectively. Per point, the OR for NH was 1.35 (95% CI: 1.27-1.42). A score of 2, 3, 4, 5 or ≥6 (versus ≤1) had a OR for NH of 1.67 (1.29-2.15), 2.24 (1.65-3.04), 2.83 (2.02-3.98), 3.08 (1.83-5.16), and 6.84 (4.34-10.77), respectively. CONCLUSION: Per each score point, women with GD had 35% higher risk of NH. Those with ≥6 points had 6.8-fold higher risk of NH compared to a score ≤1. Our score may be useful for identifying women at a higher risk of NH.

Resting-State EEG Signature of Early Consciousness Recovery in Comatose Traumatic Brain Injury Patients.

Background Resting-state electroencephalogram (rsEEG) is usually obtained to assess seizures in comatose patients with traumatic brain injury (TBI) patients. We aim to investigate rsEEG measures and their prediction of early recovery of consciousness in comatose TBI patients. Methods This is a retrospective study of comatose TBI patients who were admitted to a level-1 trauma center (10/2013-1/2022). Demographics, basic clinical data, imaging characteristics, and EEG data were collected. We calculated using 10-minute rsEEGs: power spectral density (PSD), permutation entropy (PE - complexity measure), weighted symbolic-mutual-information (wSMI - global information sharing measure), Kolmogorov complexity (Kolcom - complexity measure), and heart-evoked potentials (HEP - the averaged EEG signal relative to the corresponding QRS complex on electrocardiogram). We evaluated the prediction of consciousness recovery before hospital discharge using clinical, imaging, rsEEG data via Support Vector Machine with a linear kernel (SVM). Results We studied 113 (out of 134, 84%) patients with rsEEGs. A total of 73 (65%) patients recovered consciousness before discharge. Patients who recovered consciousness were younger (40 vs. 50, p .01). Patients who recovered consciousness had higher Kolcom (U = 1688, p = 0.01,), increased beta power (U = 1652 p = 0.003), with higher variability across channels ( U = 1534, p = 0.034), and epochs (U = 1711, p = 0.004), lower delta power (U = 981, p = 0.04) and showed higher connectivity across time and channels as measured by wSMI in the theta band (U = 1636, p = .026, U = 1639, p = 0.024) than those who didn't recover. The ROC-AUC improved from 0.66 (using age, motor response, pupils' reactivity, and CT Marshall classification) to 0.69 (p < 0.001) when adding rsEEG measures. Conclusion We describe the rsEEG EEG signature in recovery of consciousness prior to discharge in comatose TBI patients. Resting-state EEG measures improved prediction beyond the clinical and imaging data.

Covert Tracking to Immersive Stimuli in Traumatic Brain Injury Subjects With Disorders of Consciousness.

Eye tracking assessments are clinician dependent and can contribute to misclassification of coma. We investigated responsiveness to videos with and without audio in traumatic brain injury (TBI) subjects using video eye-tracking (VET). We recruited 20 healthy volunteers and 10 unresponsive TBI subjects. Clinicians were surveyed whether the subject was tracking on their bedside assessment. The Coma Recovery Scale-Revised (CRS-R) was also performed. Eye movements in response to three different 30-second videos with and without sound were recorded using VET. The videos consisted of moving characters (a dancer, a person skateboarding, and Spiderman). Tracking on VET was defined as visual fixation on the character and gaze movement in the same direction of the character on two separate occasions. Subjects were classified as "covert tracking" (tracking using VET only), "overt tracking" (VET and clinical exam by clinicians), and "no tracking". A k-nearest-neighbors model was also used to identify tracking computationally. Thalamocortical connectivity and structural integrity were evaluated with EEG and MRI. The ability to obey commands was evaluated at 6- and 12-month follow-up. The average age was 29 (± 17) years old. Three subjects demonstrated "covert tracking" (CRS-R of 6, 8, 7), two "overt tracking" (CRS-R 22, 11), and five subjects "no tracking" (CRS-R 8, 6, 5, 6, 7). Among the 84 tested trials in all subjects, 11 trials (13%) met the criteria for "covert tracking". Using the k-nearest approach, 14 trials (17%) were classified as "covert tracking". Subjects with "tracking" had higher thalamocortical connectivity, and had fewer structures injured in the eye-tracking network than those without tracking. At follow-up, 2 out of 3 "covert" and all "overt" subjects recovered consciousness versus only 2 subjects in the "no tracking" group. Immersive stimuli may serve as important objective tools to differentiate subtle tracking using VET.

No sonographer, no radiologist: New system for automatic prenatal detection of fetal biometry, fetal presentation, and placental location.

Ultrasound imaging is a vital component of high-quality Obstetric care. In rural and under-resourced communities, the scarcity of ultrasound imaging results in a considerable gap in the healthcare of pregnant mothers. To increase access to ultrasound in these communities, we developed a new automated diagnostic framework operated without an experienced sonographer or interpreting provider for assessment of fetal biometric measurements, fetal presentation, and placental position. This approach involves the use of a standardized volume sweep imaging (VSI) protocol based solely on external body landmarks to obtain imaging without an experienced sonographer and application of a deep learning algorithm (U-Net) for diagnostic assessment without a radiologist. Obstetric VSI ultrasound examinations were performed in Peru by an ultrasound operator with no previous ultrasound experience who underwent 8 hours of training on a standard protocol. The U-Net was trained to automatically segment the fetal head and placental location from the VSI ultrasound acquisitions to subsequently evaluate fetal biometry, fetal presentation, and placental position. In comparison to diagnostic interpretation of VSI acquisitions by a specialist, the U-Net model showed 100% agreement for fetal presentation (Cohen's κ 1 (p<0.0001)) and 76.7% agreement for placental location (Cohen's κ 0.59 (p<0.0001)). This corresponded to 100% sensitivity and specificity for fetal presentation and 87.5% sensitivity and 85.7% specificity for anterior placental location. The method also achieved a low relative error of 5.6% for biparietal diameter and 7.9% for head circumference. Biometry measurements corresponded to estimated gestational age within 2 weeks of those assigned by standard of care examination with up to 89% accuracy. This system could be deployed in rural and underserved areas to provide vital information about a pregnancy without a trained sonographer or interpreting provider. The resulting increased access to ultrasound imaging and diagnosis could improve disparities in healthcare delivery in under-resourced areas.

Motoric Cognitive Risk Syndrome: Prevalence and Cognitive Performance. A cross-sectional study.

Background: Motoric Cognitive Risk Syndrome (MCR) is a predementia stage where slow gait speed and subjective memory complaints are present. The purpose of this study was to estimate the prevalence of MCR and assess its relationship with sociodemographic factors and chronic conditions. Methods: This is a secondary analysis of the SABE Colombia study conducted in 2015. The analytic sample consisted of 17·577 participants. After determining MCR prevalence, logistic regression was performed to examine the correlates of MCR. Findings: The prevalence of MCR was 10·71 %. The median age was 71 years and women composed 74·63 % of the MCR group. After adjusting for confounding variables MCR was associated with increasing age (OR 1·69, CI 1·43 - 1·92), no or low education (OR 1·99, CI 1·67- 2·37), MMSE (OR 0·93, CI 0·91 - 0·95) and chronic conditions such as mental disorders (OR 1·36, CI 1·11-1·67), history of myocardial infarction (OR 1·24, CI 1·04 - 1·47), hypertension (OR 1·23, CI 1·08 - 1·40) and diabetes (OR 1.18, CI 1.01 - 1.37). Interpretation: This study found a prevalence of 10·71 % of MCR in Colombian older adults. Additionally, MCR was associated with chronic conditions and sociodemographic factors identified in prior studies. These results increase the awareness of a novel predementia stage whose identification can be performed by clinicians in the outpatient clinic, minimizing the cost of a full neuropsychologic evaluation performed in a memory clinic. Funding: Funded by the Administrative Department of Science, Technology and Innovation (Colciencias) and the Ministry of Health and Social Protection of Colombia.

Leptin, Both Bad and Good Actor in Cancer.

Leptin is an important regulator of basal metabolism and food intake, with a pivotal role in obesity. Leptin exerts many different actions on various tissues and systems, including cancer, and is considered as a linkage between metabolism and the immune system. During the last decades, obesity and leptin have been associated with the initiation, proliferation and progression of many types of cancer. Obesity is also linked with complications and mortality, irrespective of the therapy used, affecting clinical outcomes. However, some evidence has suggested its beneficial role, called the "obesity paradox", and the possible antitumoral role of leptin. Recent data regarding the immunotherapy of cancer have revealed that overweight leads to a more effective response and leptin may probably be involved in this beneficial process. Since leptin is a positive modulator of both the innate and the adaptive immune system, it may contribute to the increased immune response stimulated by immunotherapy in cancer patients and may be proposed as a good actor in cancer. Our purpose is to review this dual role of leptin in cancer, as well as trying to clarify the future perspectives of this adipokine, which further highlights its importance as a cornerstone of the immunometabolism in oncology.

Methylation of the central transcriptional regulator KLF4 by PRMT5 is required for DNA end resection and recombination.

Cell fitness and survival upon exposure to DNA damage depends on the repair of DNA lesions. Interestingly, cellular identity does affect and finetunes such response, although the molecular basis of such differences between tissues and cell types is not well understood. Thus, a possibility is that DNA repair itself is controlled by the mechanisms that govern cell identity. Here we show that the KLF4, involved in cellular homeostasis, proliferation, cell reprogramming and cancer development, directly regulates resection and homologous recombination proficiency. Indeed, resection efficiency follows KLF4 protein levels, i.e. decreases upon KLF4 downregulation and increases when is overexpressed. Moreover, KLF4 role in resection requires its methylation by the methyl-transferase PRMT5. Thus, PRMT5 depletion not only mimics KLF4 downregulation, but also showed an epistatic genetic relationship. Our data support a model in which the methylation of KLF4 by PRMT5 is a priming event required to license DNA resection and homologous recombination.

[Dyslipidemia Secondary to Hypothyroidism and Cholestasis]. / Dislipidemia Secundária a Hipotiroidismo e Colestase.

In about 28% of patients, dyslipidemia has a secondary cause. Many times, the treatment of these causes can lead to the total correction of dyslipidemia. We describe the case of a 50-year-old female patient with class II obesity and primary biliary cirrhosis, evaluated for mixed dyslipidemia with poor control (statins and fibrates were being administered) as well as abnormal liver tests. The investigation carried out revealed primary auto-immune hypothyroidism. After normalisation of thyroid function by treatment with levothyroxine, as well as suspending the administration of statins and fibrates, there was an improvement in the lipid profile, although hypercholesterolemia continued. During this time, the patient was diagnosed with diabetes and she re-commenced statin therapy (atorvastatin 10 mg), which resulted in a normal lipid profile being achieved. In this case, the authors set out to highlight the importance of excluding secondary causes of dyslipidemia - including hypothyroidism, and then go on to discuss particular aspects of statin therapy for liver disease.

Cerca de 28% dos doentes com dislipidemia apresentam na sua etiologia causas secundárias. A resolução de algumas destas causas pode levar à correção total da dislipidemia. Descreve-se o caso de uma doente do sexo feminino, 50 anos, com obesidade grau II e cirrose biliar primária referenciada por dislipidemia mista com mau controlo (sob estatina e fibrato) e com alterações analíticas hepáticas. No estudo efetuado constatou-se hipotiroidismo primário auto-imune. Após normalização da função tiroideia pelo tratamento com levotiroxina, além da suspensão da estatina e fibrato, verificou-se melhoria do perfil lipídico, embora mantendo hipercolesterolemia. Neste período de tempo foi-lhe diagnosticada diabetes mellitus pelo que se instituiu de novo terapêutica com estatina (atorvastatina 10 mg), com normalização do perfil lipídico. Com este caso pretende-se salientar a importância da exclusão de causas secundárias de dislipidemia, nomeadamente o hipotiroidismo, bem como discutir aspectos particulares do tratamento com estatinas na doença hepática.

Prevalence and Determinants of Painful and Painless Neuropathy in Type 1 Diabetes Mellitus.

Aims: To evaluate (1) the prevalence of diabetic distal symmetrical sensory-motor polyneuropathy (DSPN) and painful DSPN among patients with type 1 diabetes mellitus (DM1) aged over 18 years and (2) the determinant factors of neuropathy and pain in those patients. Materials and Methods: An epidemiological, cross-sectional, observational study was performed; 330,386 people were included, and a total of 444 people were diagnosed with DM1. After exclusion of possible confounders, 360 patients were assessed for painless and painful DSPNs using neurological examination and questionnaires for neuropathy and pain. Odds ratio (OR) and confidence intervals (95% CI) were estimated using multinomial logistic regression models. The analysis was based on a framework with four conceptual levels that consider feasible pathways between several risk factors: (1) socio-demographic factors and diabetes duration, (2) patient habits, (3) co-morbidities, and (4) metabolic factors and disease complications. Results: The prevalence of DSPN and painful DSPN were 42.8 and 18.9%, respectively. Diabetes duration was positively associated with painful (OR = 1.107, 95% CI: 1.107-1.139) and painless DSPN (OR = 1.069, 95% CI: 1.043-1.096). Education level was negatively associated with painful DSPN (OR = 0.889, 95% CI: 0.826-0.957). Sex (female) was positively associated only with painless DSPN (OR = 1.769, 95% CI: 1.007-3.107). Being a current or former smoker was positively associated only with painless DSPN (OR = 1.940, 95% CI: 1.069-3.518). Hypertension was positively associated with painful DSPN (OR = 2.474, 95% CI: 1.110-5.512) and painless DSPN (OR = 2.565, 95% CI: 1.252-5.256). Glycated hemoglobin (HbA1c) was positively associated only with painless DSPN (OR = 1.193, 95% CI: 1.018-1.399). Conclusions: Diabetes duration and hypertension have a direct impact on the development of painful and painless DSPN. However, female sex and HbA1c have a direct effect only on the development of painless DSPN, and education level has an indirect effect on the development of painful DSPN. Therefore, it can be concluded that different etiological factors have different contributions to the development of neuropathy and pain.

Malignant paraganglioma and somatotropinoma in a patient with germline SDHB mutation-genetic and clinical features.

BACKGROUND: Pituitary adenomas and paragangliomas/pheocromocytomas are rare endocrine tumours, which can be sporadic or familial. During many years their coexistence in the same individual was considered a coincidental finding. However, an association between these two entities was recently demonstrated, with the possible involvement of SDHx genes. CASE REPORT: We describe a 57-year-old female patient, who was under surveillance since 1997 for a malignant paraganglioma with vertebral bone metastasis, and harboured a germline frameshift mutation in exon 6 of SDHB gene [c.587-591DelC]. Seventeen years later, she was diagnosed with acromegaly and underwent transesphenoidal endoscopic resection of a somatotropinoma. Three months after surgery she started treatment with lanreotide for residual disease. Despite initial good response, she developed resistance to first generation of somatostatin analogues and treatment had to be switched to pegvisomant. In the immunohistochemical staining, the pituitary adenoma was positive for SDHA expression, while SDHB showed an heterogeneous staining pattern, with areas markedly positive and others with positive and negative cells. CONCLUSIONS: Our findings provide useful data for understanding the link between paragangliomas/pheocromocytomas and somatotropinomas. While we confirm the well-established link between SDHB mutations and paragangliomas/pheocromocytomas, particularly with malignant paragangliomas, the preservation-at least partially-of SDHB expression in the somatotropinoma tissue does not allow drawing definite conclusions about the involvement of the SDHB mutation in pituitary adenoma.

Proteolytic Degradation of Hippocampal STEP61 in LTP and Learning.

Striatal-enriched protein tyrosine phosphatase (STEP) modulates key signaling molecules involved in synaptic plasticity and neuronal function. It is postulated that STEP opposes the development of long-term potentiation (LTP) and that it exerts a restraint on long-term memory (LTM). Here, we examined whether STEP61 levels are regulated during hippocampal LTP and after training in hippocampal-dependent tasks. We found that after inducing LTP by high frequency stimulation or theta-burst stimulation STEP61 levels were significantly reduced, with a concomitant increase of STEP33 levels, a product of calpain cleavage. Importantly, inhibition of STEP with TC-2153 improved LTP in hippocampal slices. Moreover, we observed that after training in the passive avoidance and the T-maze spontaneous alternation task, hippocampal STEP61 levels were significantly reduced, but STEP33 levels were unchanged. Yet, hippocampal BDNF content and TrkB levels were increased in trained mice, and it is known that BDNF promotes STEP degradation through the proteasome. Accordingly, hippocampal pTrkBTyr816, pPLCγTyr783, and protein ubiquitination levels were increased in T-SAT trained mice. Remarkably, injection of the TrkB antagonist ANA-12 (2 mg/Kg, but not 0.5 mg/Kg) elicited LTM deficits and promoted STEP61 accumulation in the hippocampus. Also, STEP knockout mice outperformed wild-type animals in an age- and test-dependent manner. Summarizing, STEP61 undergoes proteolytic degradation in conditions leading to synaptic strengthening and memory formation, thus highlighting its role as a molecular constrain, which is removed to enable the activation of pathways important for plasticity processes.

In vivo estimation of the Young's modulus in normal human dermis.

Skin elastic properties change during a cutaneous disorder or in the aging process. Deep knowledge of skin layers helps monitoring and diagnosing structural changes. High frequency ultrasound (HF-US) has been recently introduced to diagnose and evaluate some dermatological disorders in the clinical practice. US elastography adds elasticity information of the analyzed tissue. In particular, harmonic elastography estimates the speed of shear waves produced by external vibration sources, in order to relate the shear wave speed to the Young's modulus. In the epidermis and dermis layers, shear waves are not generated; in contrast, surface acoustic waves (SAWs) exist as they propagate in the top of the tissue. This study uses crawling wave sonoelastography for the estimation of SAWs in human thigh dermis in vivo. Experiments were performed in ten volunteers in the range of 200 - 500 Hz. As other studies suggest, SAW speed needs to be compensated to reach shear wave speed, for calculating the Young's modulus. Thus, the SAW speed estimated was corrected when it propagates in solidUS gel interface. Specifically, the elasticity modulus found was $18.35 \pm 1.04$ KPa for a vibration frequency of 200 Hz. Results suggest that the elasticity modulus can be estimated in vivo using crawling wave HF-US for skin application and shows potential for future application in skin disorders.

Faculty and student perception of innovative evaluation strategies in a medical programme basic area / Percepción de docentes y estudiantes sobre estrategias innovadoras de evaluación en el área básica de un programa de medicina

ABSTRACT Objective: To understand the on-line knowledge examination, the Interdisciplinary Evaluation and Feedback Seminar (SERI in Spanish) and the Objective Structured Clinical Examination (OSCE) as innovative evaluation strategies, based on the perceptions of faculty and students of an medical programme basic area. Materials and methods: Qualitative, microethnographic research. Five focus groups and seven in-depth interviews were conducted with faculty members and students who gave their informed consent and their permission for recording. The data were analysed using open axial coding and emerging categories. Triangulation of sources, authors and techniques was used, and a final report was prepared before returning the information. Results: The strategies studied have strengths and weaknesses; on-line examination is well accepted by the students but there is a lack coordination. Greater faculty training in the use of the platform is required, and it is important to establish mechanisms to avoid potential fraud. SERI favours feedback but there is a need to reduce the risk of affecting self-esteem and to find ways to improve knowledge assessment. OSCE comes closer to the correlation between basic training and clinical practice, but organisation and physical space for stations need to be improved. Conclusions: Innovative evaluation strategies must be the focus of constant review in terms of their structure and implementation in order to strengthen comprehensive student training.

RESUMEN Objetivo: comprender las estrategias innovadoras de evaluación: examen de conocimientos en la plataforma virtual, Seminario de Evaluación y Retroalimentación Interdisciplinar (SERI) y Examen de Conocimientos por Objetivos Estructurado (ECOE), desde las percepciones de docentes y estudiantes del área básica de un programa de medicina. Materiales y métodos: investigación cualitativa, microetnográfica. Se realizaron cinco grupos focales y siete entrevistas en profundidad a docentes y estudiantes, con grabación autorizada y consentimiento informado; se analizó la información mediante codificación abierta y axial, y generación de categorías emergentes. Se utilizó triangulación de fuentes, autores y técnicas, se elaboró informe final, previa devolución de información. Resultados: las estrategias investigadas tienen fortalezas y debilidades, el examen en plataforma es bien recibido por estudiantes pero le falta coordinación. Se necesita mayor capacitación de docentes en el uso de la plataforma, y es importante establecer mecanismos para evitar posibles fraudes. El SERI favorece la retroalimentación, pero se requiere que disminuya el riesgo de vulnerar la autoestima y permita una mejor valoración de conocimientos. El ECOE los acerca a la correlación básico-clínica, pero falta organización y espacio para las estaciones. Conclusiones: las estrategias innovadoras de evaluación deben someterse a una constante revisión desde su estructura y ejecución, fortaleciendo así la formación integral de los estudiantes.

Huntington's disease: novel therapeutic perspectives hanging in the balance.

INTRODUCTION: Huntington's disease (HD), an autosomal dominant neurodegenerative disorder caused by an expansion of CAG repeats in the huntingtin gene, has long been characterized by the presence of motor symptoms due to the loss of striatal projection neurons. Cognitive dysfunction and neuropsychiatric symptoms are also present and they occur in the absence of cell death in most mouse models, pointing to neuronal dysfunction and abnormal synaptic plasticity as causative mechanisms. Areas covered: Here, we focus on those common mechanisms altered by the presence of mutant huntingtin affecting corticostriatal and hippocampal function as therapeutic targets that could prove beneficial to ameliorate both cognitive and motor function in HD. Specifically, we discuss the importance of reestablishing the balance in (1) synaptic/extrasynaptic N-methyl-D-aspartate receptor signaling, (2) mitochondrial dynamics/trafficking, (3) TrkB/p75NTR signaling, and (4) transcriptional activity. Expert opinion: Mutant huntingtin has a broad impact on multiple cellular processes, which makes it very challenging to design a curative therapeutic strategy. As we point out here, novel therapeutic interventions should look for multi-purpose drugs targeting common and early affected processes leading to corticostriatal and hippocampal dysfunction that additionally operate in a feedforward vicious cycle downstream the activation of extrasynaptic N-methyl-D-aspartate receptor.

Multiple roles of the splicing complex SF3B in DNA end resection and homologous recombination.

The appropriate repair of DNA double strand breaks is critical for genome maintenance. Thus, several cellular pathways collaborate to orchestrate a coordinated response. These include the repair of the breaks, which could be achieved by different mechanisms. A key protein involved in the regulation of the repair of broken chromosomes is CtIP. Here, we have found new partners of CtIP involved in the regulation of DNA break repair through affecting DNA end resection. We focus on the splicing complex SF3B and show that its depletion impairs DNA end resection and hampers homologous recombination. Functionally, SF3B controls CtIP function at, as least, two levels: by affecting CtIP mRNA levels and controlling CtIP recruitment to DNA breaks, in a way that requires ATM-mediated phosphorylation of SF3B2 at serine 289. Indeed, overexpression of CtIP rescues the resection defect caused by SF3B downregulation. Strikingly, other SF3B depletion phenotypes, such as impaired homologous recombination or cellular sensitivity to DNA damaging agents, are independent of CtIP levels, suggesting a more general role of SF3B in controlling the response to chromosome breaks.

Age-related changes in STriatal-Enriched protein tyrosine Phosphatase levels: Regulation by BDNF.

Recent results indicate that STriatal-Enriched protein tyrosine Phosphatase (STEP) levels are regulated by brain-derived neurotrophic factor (BDNF), whose expression changes during postnatal development and aging. Here, we studied STEP ontogeny in mouse brain and changes in STEP with age with emphasis on the possible regulation by BDNF. We found that STEP expression increased during the first weeks of life, reaching adult levels by 2-3weeks of age in the striatum and cortex, and by postnatal day (P) 7 in the hippocampus. STEP protein levels were unaffected in BDNF+/- mice, but were significantly reduced in the striatum and cortex, but not in the hippocampus, of BDNF-/- mice at P7 and P14. In adult wild-type mice there were no changes in cortical and hippocampal STEP61 levels with age. Conversely, striatal STEP levels were reduced from 12months of age, correlating with higher ubiquitination and increased BDNF content and signaling. Lower STEP levels in older mice were paralleled by increased phosphorylation of its substrates. Since altered STEP levels are involved in cellular malfunctioning events, its reduction in the striatum with increasing age should encourage future studies of how this imbalance might participate in the aging process.

Social Memory and Social Patterns Alterations in the Absence of STriatal-Enriched Protein Tyrosine Phosphatase.

STriatal-Enriched protein tyrosine Phosphatase (STEP) is a neural-specific protein that opposes the development of synaptic strengthening and whose levels are altered in several neurodegenerative and psychiatric disorders. Since STEP is expressed in brain regions implicated in social behavior, namely the striatum, the CA2 region of the hippocampus, cortex and amygdala, here we investigated whether social memory and social patterns were altered in STEP knockout (KO) mice. Our data robustly demonstrated that STEP KO mice presented specific social memory impairment as indicated by the three-chamber sociability test, the social discrimination test, the 11-trial habituation/dishabituation social recognition test, and the novel object recognition test (NORT). This affectation was not related to deficiencies in the detection of social olfactory cues, altered sociability or anxiety levels. However, STEP KO mice showed lower exploratory activity, reduced interaction time with an intruder, less dominant behavior and higher immobility time in the tail suspension test than controls, suggesting alterations in motivation. Moreover, the extracellular levels of dopamine (DA), but not serotonin (5-HT), were increased in the dorsal striatum of STEP KO mice. Overall, our results indicate that STEP deficiency disrupts social memory and other social behaviors as well as DA homeostasis in the dorsal striatum.

Gender and Health in Spanish Nurses / Gênero e Saúde em Enfermeiras Espanholas / Género y Salud en Enfermeras Españolas

Abstract gender exercises a powerful effect on determining health status: it may limit different rates of exposure to certain risks, different patterns in the quest for treatment or differential impacts of the social economic determinants of health. The object of this study has been to discover the relationships between gender and health in a special group of the Spanish population, male/female nurses. Spanish male (n = 98) and female (n = 98) nurses completed measures of gender norms, and health behavior variables. The analysis of correlations between health variables and gender norms indicates that registering a higher score in gender norms correlates with lower scores in physical and mental health and lifestyles. The logistical regression equations (self-perceived health, mental health and the number of illnesses suffered) identify differences between male and female nurses, with the only common variable being the level of perceived stress.

Resumo O gênero exerce um efeito poderoso na determinação do estado de saúde. Ele pode limitar diferentes níveis de exposição a certos riscos, diferentes padrões na busca por tratamento ou diferentes impactos de determinantes socioeconômicos na saúde. Este estudo teve por objetivo descobrir as relações entre gênero e saúde em um grupo especial da população espanhola, enfermeiros e enfermeiras. Enfermeiros (n = 98) e enfermeiras (n = 98) completaram medidas de normas de gênero e comportamentos de saúde. A análise das correlações entre variáveis de saúde e normas de gênero indicaram que um alto escore nas normas de gênero se correlaciona com baixos escores de saúde física/mental e estilos de vida. As equações de regressão logística (saúde auto percebida, saúde mental e número de dolências) identificaram diferenças entre enfermeiros e enfermeiras; estresse percebido foi a única variável em comum.

Resumen el género ejerce un efecto poderoso en la determinación del estado de salud y puede limitar diferentes niveles de exposición a ciertos riesgos, diferentes patrones en la búsqueda por tratamiento o diferentes impactos de determinantes socioeconómicos en la salud. El objetivo de este estudio fue descubrir las relaciones entre género y salud en un grupo especial de la población española, enfermeros y enfermeras. Enfermeros (n = 98) y enfermeras (n = 98) completaron medidas de normas de género y comportamientos de salud. El análisis de las correlaciones entre variables de salud y de género indicaron que un alto escore en las normas de género se correlaciona con bajos escores de salud física/mental y estilos de vida. Las ecuaciones de regresión logística (salud autopercibida, salud mental y número de dolencias) identificaron diferencias entre enfermeros y enfermeras; estrés percibido ha sido la única variable en común.

Measurement of surface acoustic waves in high-frequency ultrasound: Preliminary results.

Skin lesions change elastic properties near the surface. In the last decades, several non-invasive elastography techniques have been developed for detecting the mechanical properties of tissue. In particular, harmonic elastography is characterized for inducing shear wave propagation by an external vibrator in order to estimate shear modulus. However, near the boundary region, propagation is governed by surface acoustic waves (SAW). This paper combines crawling waves elastography with a high-frequency ultrasound (HFUS) system for the estimation of the SAW-to-shear compensation factor when ultrasound (US) gel is used as coupling interface. Experiments explore the SAWspeed in a homogeneous phantom with a solid-water interface in order to corroborate theoretical findings. Subsequently, experiments in a solid-US gel interface are conducted in order to find the correct compensation factor. Preliminary results suggest that SAW propagation can be detected using HFUS, and shear velocity maps can be generated by applying the estimated empirical correction factor. This study will potentially avoid the underestimation of shear modulus when using SAW-based HFUS elastography which is promising for the better diagnosis of skin diseases.

Chelerythrine promotes Ca2+-dependent calpain activation in neuronal cells in a PKC-independent manner.

BACKGROUND: Chelerythrine is widely used as a broad range protein kinase C (PKC) inhibitor, but there is controversy about its inhibitory effect. Moreover, it has been shown to exert PKC-independent effects on non-neuronal cells. METHODS: In this study we investigated possible off-target effects of chelerythrine on cultured cortical rodent neurons and a neuronal cell line. RESULTS: We found that 10µM chelerythrine, a commonly used concentration in neuronal cultures, reduces PKC and cAMP-dependent protein kinase substrates phosphorylation in mouse cultured cortical neurons, but not in rat primary cortical neurons or in a striatal cell line. Furthermore, we found that incubation with chelerythrine increases pERK1/2 levels in all models studied. Moreover, our results show that chelerythrine promotes calpain activation as assessed by the cleavage of spectrin, striatal-enriched protein tyrosine phosphatase and calcineurin A. Remarkably, chelerythrine induces a concentration-dependent increase in intracellular Ca2+ levels that mediates calpain activation. In addition, we found that chelerythrine induces ERK1/2- and calpain-independent caspase-3 activation that can be prevented by the Ca2+ chelator BAPTA-AM. CONCLUSIONS: This is the first report showing that chelerythrine promotes Ca2+-dependent calpain activation in neuronal cells, which has consequences for the interpretation of studies using this compound. GENERAL SIGNIFICANCE: Chelerythrine is still marketed as a specific PKC inhibitor and extensively used in signal transduction studies. We believe that the described off-target effects should preclude its use as a PKC inhibitor in future works.