Increased neuron density in the midbrain of a foveate bird, pigeon, results from profound change in tissue morphogenesis.

The increase of brain neuron number in relation with brain size is currently considered to be the major evolutionary path to high cognitive power in amniotes. However, how changes in neuron density did contribute to the evolution of the information-processing capacity of the brain remains unanswered. High neuron densities are seen as the main reason why the fovea located at the visual center of the retina is responsible for sharp vision in birds and primates. The emergence of foveal vision is considered as a breakthrough innovation in visual system evolution. We found that neuron densities in the largest visual center of the midbrain - i.e., the optic tectum - are two to four times higher in modern birds with one or two foveae compared to birds deprived of this specialty. Interspecies comparisons enabled us to identify elements of a hitherto unknown developmental process set up by foveate birds for increasing neuron density in the upper layers of their optic tectum. The late progenitor cells that generate these neurons proliferate in a ventricular zone that can expand only radially. In this particular context, the number of cells in ontogenetic columns increases, thereby setting the conditions for higher cell densities in the upper layers once neurons did migrate.

Loss of RAS Mutations in Liquid Biopsies of Patients With Multi-Treated Metastatic Colorectal Cancer.

BACKGROUND: Liquid biopsy (LB) is a non-invasive tool to evaluate the heterogeneity of tumors. Since RAS mutations (RAS-mut) play a major role in resistance to antiepidermal growth factor receptor inhibitors (EGFR) monoclonal antibodies (Mabs), serial monitoring of RAS-mut with LB may be useful to guide treatment. The main aim of this study was to evaluate the prognostic value of the loss of RAS-mut (NeoRAS-wt) in LB, during the treatment of metastatic colorectal cancer (mCRC). METHODS: A retrospective study was conducted on patients with mCRC between January 2018 and December 2021. RAS-mut were examined in tissue biopsy, at mCRC diagnosis, and with LB, during treatment. RESULTS: Thirty-nine patients with RAS-mut mCRC were studied. LB was performed after a median of 3 lines (0-7) of systemic treatment including anti-vascular endothelial growth factor (anti-VEGF) Mabs. NeoRAS-wt was detected in 13 patients (33.3%); 9 (69.2%) of them received further treatment with anti-EGFR Mabs with a disease control rate of 44.4%. Median overall survival (OS), from the date of LB testing, was 20 months in the NeoRAS-wt group and 9 months in the persistent RAS-mut group (log-rank 2.985; P = .08), with a 12-month OS of 84.6% and 57.7%, respectively. NeoRAS-wt was identified as a predictor of survival (HR = 0.29; P = .007), with an 11-month improvement in median OS and a 71% decrease in risk of death, in heavily pretreated patients. CONCLUSIONS: In conclusion, monitoring clonal evolution in mCRC by LB may provide an additional treatment line for patients with NeoRAS-wt in advanced disease.

Blockage of the adenosine A2B receptor prevents cardiac fibroblasts overgrowth in rats with pulmonary arterial hypertension.

Sustained pressure overload and fibrosis of the right ventricle (RV) are the leading causes of mortality in pulmonary arterial hypertension (PAH). Although the role of adenosine in PAH has been attributed to the control of pulmonary vascular tone, cardiac reserve, and inflammatory processes, the involvement of the nucleoside in RV remodelling remains poorly understood. Conflicting results exist on targeting the low-affinity adenosine A2B receptor (A2BAR) for the treatment of PAH mostly because it displays dual roles in acute vs. chronic lung diseases. Herein, we investigated the role of the A2BAR in the viability/proliferation and collagen production by cardiac fibroblasts (CFs) isolated from RVs of rats with monocrotaline (MCT)-induced PAH. CFs from MCT-treated rats display higher cell viability/proliferation capacity and overexpress A2BAR compared to the cells from healthy littermates. The enzymatically stable adenosine analogue, 5'-N-ethylcarboxamidoadenosine (NECA, 1-30 µM), concentration-dependently increased growth, and type I collagen production by CFs originated from control and PAH rats, but its effects were more prominent in cells from rats with PAH. Blockage of the A2BAR with PSB603 (100 nM), but not of the A2AAR with SCH442416 (100 nM), attenuated the proliferative effect of NECA in CFs from PAH rats. The A2AAR agonist, CGS21680 (3 and 10 nM), was virtually devoid of effect. Overall, data suggest that adenosine signalling via A2BAR may contribute to RV overgrowth secondary to PAH. Therefore, blockage of the A2AAR may be a valuable therapeutic alternative to mitigate cardiac remodelling and prevent right heart failure in PAH patients.

Exploring the relationship between emotion regulation, inhibitory control, and eating psychopathology in a non-clinical sample.

OBJECTIVE: The present study aimed to explore the relationship between difficulties in emotion regulation and deficits in inhibitory control, and the role of these processes in eating psychopathology in a non-clinical sample. We also explored the specificity in which deficits in inhibitory control may underlie eating psychopathology, namely whether they can be conceptualised as context specific or more extensive in nature. METHOD: Participants were 107 healthy individuals recruited at a major Portuguese university, aged between 18 and 43 years-old (M = 21.23, SD = 4.79). Two computerised neuropsychological tasks (i.e., emotional go/no-go and food go/no-go tasks) were used to assess response inhibition in the presence of general versus context-specific stimuli. A set of self-report measures was used to assess variables of interest such as emotion regulation and eating psychopathology. RESULTS: Results indicated higher response inhibition deficits among participants with higher difficulties in emotion regulation comparing to those with lower difficulties in emotion regulation, particularly in the context of food-related stimuli. In addition, the relationship between difficulties in emotion regulation and eating psychopathology was moderated by inhibitory control deficits in both the context of food and pleasant stimuli. CONCLUSIONS: The present findings highlight inhibitory control as an important process underlying the relationship between difficulties in emotion regulation and eating psychopathology in non-clinical samples. Findings have important implications for clinical practice and the prevention of eating psychopathology in healthy individuals and individuals with eating disorders.

Predicting the future: introducing business analytics to endoscopy units.

BACKGROUND AND AIMS: currently, most endoscopy software only provides limited statistics of past procedures, while none allows patterns to be extrapolated. To overcome this need, the authors applied business analytic models to predict future demand and the need for endoscopists in a tertiary hospital Endoscopy Unit. METHODS: a query to the endoscopy database was performed to retrieve demand from 2015 to 2021. The graphical inspection allowed inferring of trends and seasonality, perceiving the impact of the COVID-19 pandemic, and selecting the best forecasting models. Considering COVID-19's impact in the second quarter of 2020, data for esophagogastroduodenoscopy (EGD) and colonoscopy was estimated using linear regression of historical data. The actual demand in the first two quarters of 2022 was used to validate the models. RESULTS: during the study period, 53,886 procedures were requested. The best forecasting models were: a) simple seasonal exponential smoothing for EGD, colonoscopy and percutaneous endoscopic gastrostomy (PEG); b) double exponential smoothing for capsule endoscopy and deep enteroscopy; and c) simple exponential smoothing for endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS). The mean average percentage error ranged from 6.1 % (EGD) to 33.5 % (deep enteroscopy). Overall, 8,788 procedures were predicted for 2022. The actual demand in the first two quarters of 2022 was within the predicted range. Considering the usual time allocation for each technique, 3.2 full-time equivalent endoscopists (40 hours-dedication to endoscopy) will be required to perform all procedures in 2022. CONCLUSIONS: the incorporation of business analytics into the endoscopy software and clinical practice may enhance resource allocation, improving patient-focused decision-making and healthcare quality.

Forecast models to predict the demand for endoscopic procedures in a tertiary unit: a prospective validation.

Over the past few decades, there has been an exponential increase in the utilization of endoscopic procedures. Accurately predicting the demand is crucial for effective capacity planning and resource allocation in the endoscopic unit. However, predictive models are not integrated into current endoscopy software. To overcome this limitation, our group used data on the demand in our tertiary unit from 2015 to 2021 (83 months) to develop forecast models using exponential smoothing techniques adjusted for trend and seasonality (derivation phase). These models were recently published at the Revista Española de Enfermedades Digestivas.

A transient decrease in mitochondrial activity contributes to establish the ganglion cell fate in retina adapted for high acuity vision.

Although the plan of the retina is well conserved in vertebrates, there are considerable variations in cell type diversity and number, as well as in the organization and properties of the tissue. The high ratios of retinal ganglion cells (RGCs) to cones in primate fovea and bird retinas favor neural circuits essential for high visual acuity and color vision. The role that cell metabolism could play in cell fate decision during embryonic development of the nervous system is still largely unknown. Here, we describe how subtle changes of mitochondrial activity along the pathway converting uncommitted progenitors into newborn RGCs increase the recruitment of RGC-fated progenitors. ATOH7, a proneural protein dedicated to the production of RGCs in vertebrates, activates transcription of the Hes5.3 gene in pre-committed progenitors. The HES5.3 protein, in turn, regulates a transient decrease in mitochondrial activity via the retinoic acid signaling pathway few hours before cell commitment. This metabolic shift lengthens the progression of the ultimate cell cycle and is a necessary step for upregulating Atoh7 and promoting RGC differentiation.

Total lipid concentration of hairs increases after successful attenuation of extrahepatic portosystemic shunts in dogs.

BACKGROUND: Skin and coat quality can reflect nutritional deficiencies in humans and dogs with liver diseases. HYPOTHESIS/OBJECTIVES: Determine skin and coat quality based on a scoring protocol and skin biopsies in dogs with an extrahepatic portosystemic shunt (EHPSS), and determine total lipid concentrations in hairs of dogs at time of surgery and 3 months after successful shunt closure. ANIMALS: Ten client-owned dogs that underwent successful gradual attenuation of EHPSS, as defined by transsplenic portal scintigraphy, were included. MATERIALS AND METHODS: A prospective cohort study was performed. All dogs underwent gradual attenuation of the EHPSS. Skin and coat scoring was performed at diagnosis, surgery, and 1 and 3 months postoperatively. Hair was plucked from the lumbar region for total lipid analysis and an 8 mm punch skin biopsy was taken at time of surgery and 3 months postoperatively, when the dogs underwent transsplenic portal scintigraphy to determine EHPSS closure. RESULTS: No significant differences were observed in skin and coat scoring over time. Total lipid concentrations of hairs increased significantly from surgery to 3 months postoperatively [30 µg/mg hair (13-56 µg/mg hair) to 47 µg/mg hair (25-63 µg/mg hair); p = 0.005]. Skin biopsies showed the presence of significantly more scales 3 months postoperatively (p = 0.018). CONCLUSIONS AND CLINICAL RELEVANCE: A significant increase in total lipid concentrations in hairs suggests that successful surgical attenuation of EHPSS improves either intestinal absorption of lipids, fat metabolism in the liver, or a combination of both.

Contexte - La qualité de la peau et du pelage peut refléter des carences nutritionnelles chez les humains et les chiens atteints de maladies du foie. Hypothèse/Objectifs - Déterminer la qualité de la peau et du pelage sur la base d'un protocole de notation et de biopsies cutanées chez les chiens avec un shunt portosystémique extrahépatique (EHPSS), et déterminer les concentrations totales de lipides dans les poils des chiens au moment de la chirurgie et trois mois après la fermeture réussie du shunt. Animaux - Dix chiens appartenant à des clients qui ont subi une atténuation progressive réussie de l'EHPSS, telle que définie par la scintigraphie portale trans-splénique, ont été inclus. Matériels et méthodes - Une étude de cohorte prospective a été réalisée. Tous les chiens ont subi une atténuation progressive de l'EHPSS. Une notation de la peau et du pelage a été réalisée au moment du diagnostic, de la chirurgie et un et trois mois après l'opération. Les cheveux ont été prélevés dans la région lombaire pour une analyse des lipides totaux et une biopsie cutanée à l'emporte-pièce de 8 mm a été effectuée au moment de la chirurgie et trois mois après l'opération, lorsque les chiens ont subi une scintigraphie portale trans-splénique pour déterminer la fermeture de l'EHPSS. Résultats - Aucune différence significative n'a été observée dans la notation de la peau et du pelage au fil du temps. Les concentrations totales de lipides dans les poils ont augmenté de manière significative entre la chirurgie et trois mois après l'opération [30 µg/mg de poils (13-56 µg/mg de poils) à 47 µg/mg de poils (25-63 µg/mg de poils) ; P = 0,005]. Les biopsies cutanées ont montré la présence de significativement plus d'écailles trois mois après l'opération (P = 0,018). Conclusions et pertinence clinique - Une augmentation significative des concentrations totales de lipides dans les cheveux suggère qu'une atténuation chirurgicale réussie de l'EHPSS améliore soit l'absorption intestinale des lipides, soit le métabolisme des graisses dans le foie, soit une combinaison des deux.

Introducción- la calidad de la piel y el pelaje puede reflejar deficiencias nutricionales en humanos y perros con enfermedades hepáticas. Hipótesis/Objetivos- determinar la calidad de la piel y el pelaje según un protocolo de valoración y en biopsias de piel en perros con shunt portosistémico extrahepática (EHPSS) y determinar las concentraciones totales de lípidos en el pelo de los perros en el momento de la cirugía y tres meses después del tratamiento exitoso del shunt. Animales- se incluyeron diez perros de propietarios particulares que se sometieron a una atenuación gradual exitosa de EHPSS, según se identificó mediante por gammagrafía portal transesplénica. Materiales y métodos - Se realizó un estudio de cohorte prospectivo. A todos los perros se les realizó una atenuación gradual del EHPSS. La valoración de la piel y el pelaje se realizó en el momento del diagnóstico, la cirugía y uno y tres meses después de la operación. Se arrancó el pelo de la región lumbar para el análisis de lípidos totales y se tomó una biopsia de piel con sacabocados (punch) de 8 mm en el momento de la cirugía y tres meses después de la operación, cuando los perros se sometieron a una gammagrafía portal transesplénica para determinar el cierre de EHPSS. Resultados- no se observaron diferencias significativas en la valoración de la piel y el pelaje a lo largo del tiempo. Las concentraciones de lípidos totales del pelo aumentó significativamente desde la cirugía hasta los tres meses posteriores a la operación [30 µg/mg de pelo (13-56 µg/mg de pelo) a 47 µg/mg de cabello (25-63 µg/mg de pelo); P = 0,005]. Las biopsias de piel mostraron la presencia de mayor cantidad de escamas de forma significativa tres meses después de la operación (P = 0,018). Conclusiones y relevancia clínica- un aumento significativo en las concentraciones de lípidos totales en el pelo sugiere que la atenuación quirúrgica exitosa de EHPSS mejora la absorción intestinal de lípidos, el metabolismo de las grasas en el hígado o una combinación de ambos.

Contexto - A qualidade da pele e dos pelos pode refletir deficiências nutricionais em humanos e cães com hepatopatias. Hipótese/Objetivos - Determinar a qualidade da pele e pelos baseada em um protocolo de escore e biópsias cutâneas em cães com shunt portossistêmico extra-hepático (EHPSS) e determinar as concentrações lipídicas totais nos pelos de cães no momento da cirurgia e três meses após o fechamento bem-sucedido do shunt. Animais - Foram incluídos dez cães de proprietários submetidos à atenuação gradual do EHPSS bem-sucedida, confirmada por cintilografia portal transesplênica. Materiais e métodos - Realizou-se um estudo de coorte prospectivo. Todos os cães foram submetidos à atenuação gradual do EHPSS. A classificação de pele e pelos em escores foi realizada no diagnóstico, cirurgia, e com um e três meses de pós-operatório. Os pelos foram arrancados da região lombar para análise lipídica total e uma biópsia com punch de 8mm foi coletada no momento da cirurgia e com três meses de pós-operatório, quando os cães foram submetidos à cintilografia portal transesplênica para determinar o fechamento do EHPSS. Resultados - Não foram observadas diferenças significativas nos escores de pele e pelos ao longo do tempo. As concentrações de lipídicas totais aumentaram significativamente da cirurgia aos três meses de pós-operatório [30 µg/mg de pelo (13-56 µg/mg pelo) para 47 µg/mg de pelo (25-63 µg/mg de pelo); P = 0,005]. As biópsias cutâneas revelaram a presença de significativamente mais escamas com três meses de pós-operatório (P = 0,018). Conclusões e relevância clínica - O aumento significativo de concentrações lipídicas totais nos pelos sugere que a atenuação cirúrgica de EHPSS bem-sucedida melhora tanto a absorção intestinal de lipídeos quanto o metabolismo de gordura no fígado, ou uma combinação dos dois.

The mediating role of self-criticism, experiential avoidance and negative urgency on the relationship between ED-related symptoms and difficulties in emotion regulation.

OBJECTIVE: Difficulties in emotion regulation are thought to play a transdiagnostic role across eating disorders (ED). In the current study, we explored with a path analysis the mediating role of self-criticism, experiential avoidance and negative urgency on the relationship between ED-related symptoms and dimensions of difficulties in emotion regulation. METHOD: Participants were 103 female outpatients recruited at a Portuguese ED hospital unit, diagnosed with an ED, aged 14-60 years old (M = 28.0, SD = 10.5), body mass index (BMI) ranging from 11.72 to 39.44 (M = 20.1, SD = 5.4). RESULTS: The path analysis resulted in a model with an adequate fit to the data (SRMR = 0.05; RMSEA = 0.07 [0.00, 0.12], PCLOSE = 0.269; TLI = 0.97; IFI = 0.99; GFI = 0.95). A final model in which the relationship between ED-related symptoms and dimensions of difficulties in emotion regulation was mediated by self-criticism, experiential avoidance and negative urgency, accounted for a variance of 71% for strategies, 57% for non-acceptance, 62% for impulses, 56% for goals and 20% for clarity. CONCLUSION: Results suggest that self-criticism, experiential avoidance and negative urgency, combined, are relevant in the relationship between ED-related symptoms and difficulties in emotion regulation. ED treatment and emotion regulation skills may be enhanced through the inclusion of specific components that target self-criticism, experiential avoidance and negative urgency, as they become prominent during the therapeutic process.

Control of the Two-photon Visual Process in ex vivo Retinas and in Living Mice.

Palcewska et al. first demonstrated near infrared (NIR) visual response in human volunteers upon two-photon absorption (TPA), in a seminal work of 2014, and assessed the process in terms of wavelength- and power-dependence on murine ex-vivo retinas. In the present study, ex-vivo electroretinography (ERG) is further developed to perform a complete characterization of the effect of NIR pulse duration, energy, and focal spot size on the response. The same set of measurements is successively tested on living mice. We discuss how the nonlinear intensity dependence of the photon absorption process is transferred to the amplitude of the visual response acquired by ERG. Finally, we show that the manipulation of the spectral phase of NIR pulses can be translated to predictable change in the two-photon induced response under physiological excitation conditions.

The factorial structure and psychometric properties of the Committed Action Questionnaire (CAQ-8) in a Portuguese clinical sample with eating disorders.

The Committed Action Questionnaire (CAQ-8) is an instrument developed to measure committed action, an adaptive psychological process. The main goal in the current study was to confirm the factorial structure of the Portuguese version of the CAQ-8 in a transdiagnostic clinical sample of participants diagnosed with an eating disorder (ED). Participants were 102 female outpatients (Mage = 28.1, SD = 10.6; MBMI = 20.0, SD = 5.5) recruited from a clinical setting specialized in the treatment of ED. Confirmatory factor analysis (CFA) was used to confirm the CAQ-8's factorial structure. Both first- and second-order models revealed adequate goodness-of-fit indices (e.g. χ2 /df = 1.545, p = .06; SRMR = 0.049; RMSEA = 0.073; CFI/TLI > 0.95). A moderation model revealed that the conditional effect of weight, shape and eating concerns on experiential avoidance was significantly moderated by increased levels of committed action, F(3, 97) = 23.79, p < .001, accounting for 42% of the final variance. The present study supports the usefulness of the CAQ-8 as a measure of levels of committed action with patients diagnosed with an ED.

Pilot study of dogs with suppurative and non-suppurative Malassezia otitis: A case series.

BACKGROUND: Rarely, Malassezia otitis presents as a painful, erosive otitis with an otic discharge containing Malassezia and neutrophils on cytology. There are no published reports of this type of suppurative Malassezia otitis (SMO). The role of Malassezia hypersensitivity in otitis is still unknown, and no association has been demonstrated with SMO. We compared Malassezia IgE levels, intradermal test and histology changes in SMO dogs with the more conventional Malassezia otitis (MO) presentation. RESULTS: Three dogs (case 1, case 2 and case 3) were diagnosed with SMO, one dog (case 4) was diagnosed with unilateral MO and unilateral SMO, and one dog (case 5) was diagnosed with MO. Only one case (case 4) with SMO/MO had a positive Intradermal Allergy Test (IDAT) and elevated IgE levels for Malassezia. Histopathology findings from SMO revealed: interface dermatitis (case 1 and 3), lymphocytic dermatitis (case 2) and chronic hyperplastic eosinophilic and lymphoplasmacytic dermatitis (case 4). Histopathology findings from MO showed perivascular dermatitis (case 4 and 5). All the cases were treated successfully. CONCLUSIONS: SMO presents with a distinct clinical phenotype in comparison with conventional MO. No consistent aetiology could be isolated. In these clinical cases it is possible that previous treatments could have influenced the results. More research is needed to understand the possible aetiologies and the pathogenesis of SMO.

Nonsuicidal self-injury, difficulties in emotion regulation, negative urgency, and childhood invalidation: A study with outpatients with eating disorders.

OBJECTIVES: Among outpatients with eating disorders (ED), we compared participants without nonsuicidal self-injury (non-NSSI group), with NSSI over a year ago (past NSSI group) and with NSSI in the previous year (current NSSI group) regarding different variables, and examined whether difficulties in emotion regulation and negative urgency moderated the relationship between maternal/paternal invalidation and NSSI. METHOD: The sample included 171 outpatients (94.2% female; Mage = 28.78, SDage = 11.19). RESULTS: Fifty-four participants (31.6%) had NSSI in the previous year. This group showed higher eating pathology, difficulties in emotion regulation, negative urgency, and maternal/paternal invalidation than the non-NSSI group. Analyses revealed an adequate fit to the data for the model that included moderating effects of emotional awareness and negative urgency in the relationship between maternal/paternal invalidation and increased likelihood of NSSI in the previous year. CONCLUSIONS: Interventions for NSSI and ED should include emotion regulation, impulse control, and validation strategies.

Outcomes of Patients with Central Precocious Puberty Due to Loss-of-Function Mutations in the MKRN3 Gene after Treatment with Gonadotropin-Releasing Hormone Analog.

INTRODUCTION: Loss-of-function mutation of MKRN3 represents the most frequent genetic cause of familial central precocious puberty (CPP). The outcomes of gonadotropin-releasing hormone analog (GnRHa) treatment in CPP patients with MKRN3 defects are unknown. OBJECTIVE: To describe the clinical and hormonal features of patients with CPP with or without MKRN3 mutations after GnRHa treatment. Anthropometric, metabolic and reproductive parameters were evaluated. PATIENTS AND METHODS: Twenty-nine female patients with CPP due to loss-of-function mutations in the MKRN3 and 43 female patients with idiopathic CPP were included. Their medical records were retrospectively evaluated for clinical, laboratory, and imaging study, before, during, and after GnRHa treatment. All patients with idiopathic CPP and 11 patients with CPP due to MKRN3 defects reached final height (FH). RESULTS: At the diagnosis, there were no significant differences between clinical and laboratory features of patients with CPP with or without MKRN3 mutations. A high prevalence of overweight and obesity was observed in patients with CPP with or without MKRN3 mutations (47.3 and 50%, respectively), followed by a significant reduction after GnRHa treatment. No significant differences in the values of mean FH and target height were found between the 2 CPP groups after GnRHa treatment. Menarche occurred at the expected age in patients with or without CPP due to MKRN3 mutations (11.5 ± 1.3 and 12 ± 0.6 years, respectively). The prevalence of polycystic ovarian syndrome was 9.1% in patients with CPP due to MKRN3 mutations and 5.9% in those with idiopathic CPP. CONCLUSION: Anthropometric, metabolic, and reproductive outcomes after GnRHa treatment were comparable in CPP patients, with or without MKRN3 mutations, suggesting the absence of deleterious effects of MKRN3 defects in young female adults' life.

Eating Disorder Examination - Questionnaire short forms: A comparison.

OBJECTIVE: The Eating Disorder Examination - Questionnaire (EDE-Q) is a widely used self-report measure of eating-disordered behaviors and attitudes. Recent studies utilizing confirmatory factor analyses (CFA) have proposed alternative and shorter forms. The aim of this study was to compare the full-length version of the EDE-Q and several proposed short forms (7-item, 8-item, and 18-item) in terms of their psychometric properties, including concurrent, convergent and discriminant validity, factor structure, and sensitivity to change. METHODS: Participants from two eating-disorder clinical samples (N = 175 and 38) and from a nonclinical sample (N = 3,413) completed a battery of measures, including the Portuguese version of the EDE-Q. Analyses compared psychometric properties of the available short forms of the EDE-Q among each other. RESULTS: All forms of the EDE-Q showed good internal consistency values, correlated highly among each other (r > .90) and with different measures of eating psychopathology (r > .80). All EDE-Q forms were able to distinguish between cases and controls with moderate-to-high accuracy and were sensitive to change. CFA failed to support the proposed factor structure for all the EDE-Q forms, except for the 7-item form. DISCUSSION: The present study provides empirical background for choosing between different forms of the EDE-Q. Findings indicate that for nonclinical and for clinical research, including studies of treatment change and outcome, the short forms of the EDE-Q can be used. A shorter version is a viable alternative when less time-consuming alternatives are needed, such to quickly screen for eating-disorder psychopathology or to perform session-by-session treatment monitoring.

Psychometric properties of the Portuguese version of the Invalidating Childhood Environment Scale.

PURPOSE: The current study aimed to examine the psychometric properties of the Portuguese version of the invalidating childhood environment scale (ICES) in a non-clinical and clinical sample of eating disorder (ED) patients. This study also investigated the between-sample differences regarding invalidating parental behaviors and family styles and explored the associations between invalidating childhood environments and eating pathology. METHODS: A sample of 410 high school and college students and 101 patients with a diagnosis of ED completed self-report measures. Principal component analyses and confirmatory factor analyses were conducted to examine the factor structure of the ICES. The internal consistency and the between-sample differences and associations between invalidating childhood environments and eating pathology were also tested. RESULTS: Principal component analyses and confirmatory factor analyses indicated a two-factor solution for each parent. The ICES demonstrated high internal consistency and was able to differentiate between non-clinical and clinical samples. The perception of parental invalidation was higher in ED patients, and the clinical sample presented higher scores in the chaotic and perfect family styles and lower scores in the validating family style, in comparison with the non-clinical sample. Both maternal invalidation and invalidating styles were significantly associated with a higher ED symptomatology. CONCLUSIONS: The Portuguese version of the ICES revealed adequate psychometric properties. Considering the relationship between invalidation in family and eating pathology, the ICES may be useful in clinical practice, especially among ED patients. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Delayed neurogenesis with respect to eye growth shapes the pigeon retina for high visual acuity.

The macula and fovea located at the optical centre of the retina make primate visual perception unique among mammals. Our current understanding of retina ontogenesis is primarily based on animal models having no macula and no fovea. However, the pigeon retina and the human macula share a number of structural and functional properties that justify introducing the former as a new model system for retina development. Comparative transcriptome analysis of pigeon and chicken retinas at different embryonic stages reveals that the genetic programmes underlying cell differentiation are postponed in the pigeon until the end of the period of cell proliferation. We show that the late onset of neurogenesis has a profound effect on the developmental patterning of the pigeon retina, which is at odds with the current models of retina development. The uncoupling of tissue growth and neurogenesis is shown to result from the fact that the pigeon retinal epithelium is inhibitory to cell differentiation. The sum of these developmental features allows the pigeon to build a retina that displays the structural and functional traits typical of primate macula and fovea.

Assessment and clinical relevance of the dynamic parameters of ventricular repolarization in patients with grade I left ventricular diastolic dysfunction 1.

Imbalance in ventricular repolarization parameters are related to increased risk of severe arrhythmia and sudden cardiac death. There is limited research regarding markers to detect patients at risk in this early stage. We aimed to assess the influence of grade I left ventricular diastolic dysfunction on repolarization parameters in asymptomatic patients. Ambulatory patients with grade I left ventricular diastolic dysfunction were studied and compared with a control group. We assessed the QT dispersion circadian variation, heart rate variability in the time and frequency domains, and dynamics of QT using a 12-lead Holter. In the diastolic dysfunction group, 8 (30%) patients had QT dispersion > 80 ms. One (3.8%) patient presented premature ventricular complex > 10/h. The comparison between the 2 groups showed that the difference between the standard deviation of normal-to-normal intervals and low frequency power in both groups was statistically significant. We therefore conclude that increased parameters of ventricular repolarization and depressed heart rate variability reflect an imbalance in autonomic responses in patients with grade I left ventricular diastolic dysfunction without cardiovascular symptoms, enabling the identification of patients that are at a higher risk for cardiovascular events.

Eating Disorder-15 (ED-15): Factor structure, psychometric properties, and clinical validation.

OBJECTIVE: The purpose of the current study was to explore the factor structure and psychometric properties of the Portuguese version of the Eating Disorder-15 (ED-15), as well as to establish cutoff scores and normative data for the Portuguese version. METHODS: Participants from a nonclinical sample (N = 860) and an eating disorders clinical sample (N = 260) were invited to complete a set of questionnaires, including the Portuguese version of the ED-15. RESULTS: The first-order two-factor structure originally proposed by the ED-15 authors was endorsed through a confirmatory factor analysis (χ2 /df = 2.610; standardized root-mean-square residual = 0.0325; root-mean-square error of approximation = 0.079; Tucker-Lewis index/goodness-of-fit index/incremental fit index > 0.95). Items revealed adequate construct validity (λ = .54-.90; R2  = .29-.81). The ED-15 revealed excellent internal consistency (α = .91) and temporal stability (intraclass correlation coefficient = .92; 95% CI [.84-.95]). Normative data for the ED-15 were provided. The ED-15 demonstrated acceptable concurrent and convergent validity. Receiver operating characteristic analysis revealed that the ED-15 total score accurately discriminates between participants with and without an eating disorder (area under de curve = .80; SE = .017; p ≤ .001; 95% CI [.766-.834]). A cutoff score for clinical significance and a reliable change index were computed. CONCLUSIONS: The Portuguese version of the ED-15 is a reliable and valid measure of eating psychopathology and symptoms, whenever a brief measure is needed, as in session-by-session assessment of therapy progress and outcome.

Central precocious puberty caused by mutations in the imprinted gene MKRN3.

BACKGROUND: The onset of puberty is first detected as an increase in pulsatile secretion of gonadotropin-releasing hormone (GnRH). Early activation of the hypothalamic-pituitary-gonadal axis results in central precocious puberty. The timing of pubertal development is driven in part by genetic factors, but only a few, rare molecular defects associated with central precocious puberty have been identified. METHODS: We performed whole-exome sequencing in 40 members of 15 families with central precocious puberty. Candidate variants were confirmed with Sanger sequencing. We also performed quantitative real-time polymerase-chain-reaction assays to determine levels of messenger RNA (mRNA) in the hypothalami of mice at different ages. RESULTS: We identified four novel heterozygous mutations in MKRN3, the gene encoding makorin RING-finger protein 3, in 5 of the 15 families; both sexes were affected. The mutations included three frameshift mutations, predicted to encode truncated proteins, and one missense mutation, predicted to disrupt protein function. MKRN3 is a paternally expressed, imprinted gene located in the Prader-Willi syndrome critical region (chromosome 15q11-q13). All affected persons inherited the mutations from their fathers, a finding that indicates perfect segregation with the mode of inheritance expected for an imprinted gene. Levels of Mkrn3 mRNA were high in the arcuate nucleus of prepubertal mice, decreased immediately before puberty, and remained low after puberty. CONCLUSIONS: Deficiency of MKRN3 causes central precocious puberty in humans. (Funded by the National Institutes of Health and others.).