Identifying biologically implausible values in big longitudinal data: an example applied to child growth data from the Brazilian food and nutrition surveillance system.

BACKGROUND: Several strategies for identifying biologically implausible values in longitudinal anthropometric data have recently been proposed, but the suitability of these strategies for large population datasets needs to be better understood. This study evaluated the impact of removing population outliers and the additional value of identifying and removing longitudinal outliers on the trajectories of length/height and weight and on the prevalence of child growth indicators in a large longitudinal dataset of child growth data. METHODS: Length/height and weight measurements of children aged 0 to 59 months from the Brazilian Food and Nutrition Surveillance System were analyzed. Population outliers were identified using z-scores from the World Health Organization (WHO) growth charts. After identifying and removing population outliers, residuals from linear mixed-effects models were used to flag longitudinal outliers. The following cutoffs for residuals were tested to flag those: -3/+3, -4/+4, -5/+5, -6/+6. The selected child growth indicators included length/height-for-age z-scores and weight-for-age z-scores, classified according to the WHO charts. RESULTS: The dataset included 50,154,738 records from 10,775,496 children. Boys and girls had 5.74% and 5.31% of length/height and 5.19% and 4.74% of weight values flagged as population outliers, respectively. After removing those, the percentage of longitudinal outliers varied from 0.02% (<-6/>+6) to 1.47% (<-3/>+3) for length/height and from 0.07 to 1.44% for weight in boys. In girls, the percentage of longitudinal outliers varied from 0.01 to 1.50% for length/height and from 0.08 to 1.45% for weight. The initial removal of population outliers played the most substantial role in the growth trajectories as it was the first step in the cleaning process, while the additional removal of longitudinal outliers had lower influence on those, regardless of the cutoff adopted. The prevalence of the selected indicators were also affected by both population and longitudinal (to a lesser extent) outliers. CONCLUSIONS: Although both population and longitudinal outliers can detect biologically implausible values in child growth data, removing population outliers seemed more relevant in this large administrative dataset, especially in calculating summary statistics. However, both types of outliers need to be identified and removed for the proper evaluation of trajectories.

Ethnoracial disparities in childhood growth trajectories in Brazil: a longitudinal nationwide study of four million children.

BACKGROUND: The literature contains scarce data on inequalities in growth trajectories among children born to mothers of diverse ethnoracial background in the first 5 years of life. OBJECTIVE: We aimed to investigate child growth according to maternal ethnoracial group using a nationwide Brazilian database. METHODS: A population-based retrospective cohort study employed linked data from the CIDACS Birth Cohort and the Brazilian Food and Nutrition Surveillance System (SISVAN). Children born at term, aged 5 years or younger who presented two or more measurements of length/height (cm) and weight (kg) were followed up between 2008 and 2017. Prevalence of stunting, underweight, wasting, and thinness were estimated. Nonlinear mixed effect models were used to estimate childhood growth trajectories, among different maternal ethnoracial groups (White, Asian descent, Black, Pardo, and Indigenous), using the raw measures of weight (kg) and height (cm) and the length/height-for-age (L/HAZ) and weight-for-age z-scores (WAZ). The analyses were also adjusted for mother's age, educational level, and marital status. RESULTS: A total of 4,090,271 children were included in the study. Children of Indigenous mothers exhibited higher rates of stunting (26.74%) and underweight (5.90%). Wasting and thinness were more prevalent among children of Pardo, Asian, Black, and Indigenous mothers than those of White mothers. Regarding children's weight (kg) and length/height (cm), those of Indigenous, Pardo, Black, and Asian descent mothers were on average shorter and weighted less than White ones. Regarding WAZ and L/HAZ growth trajectories, a sharp decline in average z-scores was evidenced in the first weeks of life, followed by a period of recovery. Over time, z-scores for most of the subgroups analyzed trended below zero. Children of mother in greater social vulnerability showed less favorable growth. CONCLUSION: We observed racial disparities in nutritional status and childhood growth trajectories, with children of Indigenous mothers presenting less favorable outcomes compared to their White counterparts. The strengthening of policies aimed at protecting Indigenous children should be urgently undertaken to address systematic ethnoracial health inequalities.

Mental Health and Emotional Disorders During the COVID-19 Pandemics: Prevalence and Extent in PICU Staff.

OBJECTIVES: To assess the prevalence of burnout, anxiety and depression symptoms, and posttraumatic stress disorder (PTSD) in PICU workers in Brazil during the first peak of the COVID-19 pandemic. To compare the results of subgroups stratified by age, gender, professional category, health system, and previous mental health disorders. DESIGN: Multicenter, cross-sectional study using an electronic survey. SETTING: Twenty-nine public and private Brazilian PICUs. SUBJECTS: Multidisciplinary PICU workers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Self-reported questionnaires were used to measure burnout (Maslach Burnout Inventory), anxiety and depression (Hospital Anxiety and Depression Scale), and PTSD (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [PCL-5]) in 1,084 respondents. Subjects were mainly young (37.1 ± 8.4 yr old) and females (85%), with a median workload of 50 hours per week. The prevalence of anxiety and depression was 33% and 19%, respectively, whereas PTSD was 13%. The overall median burnout scores were high in the emotional exhaustion and personal accomplishment dimensions (16 [interquartile range (IQR), 8-24] and 40 [IQR, 33-44], respectively) whereas low in the depersonalization one (2 [IQR, 0-5]), suggesting a profile of overextended professionals, with a burnout prevalence of 24%. Professionals reporting prior mental health disorders had higher prevalence of burnout (30% vs 22%; p = 0.02), anxiety (51% vs 29%; p < 0.001), and depression symptoms (32.5% vs 15%; p < 0.001), with superior PCL-5 scores for PTSD ( p < 0.001). Public hospital workers presented more burnout (29% vs 18.6%, p < 0.001) and more PTSD levels (14.8% vs 10%, p = 0.03). Younger professionals were also more burned out ( p < 0.05 in all three dimensions). CONCLUSIONS: The prevalence of mental health disorders in Brazilian PICU workers during the first 2020 peak of COVID-19 was as high as those described in adult ICU workers. Some subgroups, particularly those reporting previous mental disorders and younger professionals, should receive special attention to prevent future crises.

Risk Perception and Decision Making about Early-Onset Sepsis among Neonatologists: A National Survey.

OBJECTIVE: Many newborns are investigated and empirically treated for suspected early-onset sepsis (EOS). This study aimed to describe neonatologists' self-identified risk thresholds for investigating and treating EOS and assess the consistency of these thresholds with clinical decisions. STUDY DESIGN: Voluntary online survey, available in two randomized versions, sent to neonatologists from 20 centers of the Brazilian Network on Neonatal Research. The surveys included questions about thresholds for investigating and treating EOS and presented four clinical scenarios with varying calculated risks. In survey version A, only the scenarios were presented, and participants were asked if they would order a blood test or start antibiotics. Survey version B presented the same scenarios and the risk of sepsis. Clinical decisions were compared between survey versions using chi-square tests and agreement between thresholds and clinical decisions were investigated using Kappa coefficients. RESULTS: In total, 293 surveys were completed (145 survey version A and 148 survey version B). The median risk thresholds for blood test and antibiotic treatment were 1:100 and 1:25, respectively. In the high-risk scenario, there was no difference in the proportion choosing antibiotic therapy between the groups. In the moderate-risk scenarios, both tests and antibiotics were chosen more frequently when the calculated risks were included (survey version B). In the low-risk scenario, there was no difference between survey versions. There was poor agreement between the self-described thresholds and clinical decisions. CONCLUSION: Neonatologists overestimate the risk of EOS and underestimate their risk thresholds. Knowledge of calculated risk may increase laboratory investigation and antibiotic use in infants at moderate risk for EOS. KEY POINTS: · Neonatologists overestimate the risk of EOS.. · There is wide variation in diagnostic/treatment thresholds for EOS.. · Clinical decision on EOS is not consistent with risk thresholds.. · Knowledge of risk may increase investigation and treatment of EOS..

Unexpected findings of hepatitis B and delta infection in northeastern Brazil: A public health alert.

INTRODUCTION AND OBJECTIVES: Research has shown that hepatitis B (HBV) and Delta virus (HDV) are a worldwide public health problem. This study aims to estimate the prevalence rates of HBV and HDV infection in five municipalities of Maranhão, Northeastern Brazil. MATERIALS AND METHODS: A total sample between 3856 and 4000 individuals. Questionnaires were used to register sociodemographic characteristics and factors associated with transmission. Patients were tested for hepatitis B virus surface antigen (HBsAg), anti-hepatitis B core antigen (anti-HBc), and antibodies against hepatitis Delta virus (anti-HDV). Factors associated with HBV were detected by means of multivariate Poisson regression. RESULTS: Overall, 3983 subjects were included. Ninety-two of the participants were HBsAg-positive (2.30%, 95% CI 1.80-2.80), and anti-HBc was detected in 1535 (38.50%, 95% CI 37-40). The factors associated with the presence of anti-HBc were: (1) Municipality (P<0.001); Age (P<0.001); School education (P<0.001); Illicit drug use (P=0.001); non-HBV vaccine (P=0.041). Among the HBsAg carriers, eight were anti-HDV-positive (8.69%, 95% CI 2.90-14.40). The most frequent HBV genotype was D4. The only HDV genotype was HDV-8. CONCLUSION: HBV exhibited intermediate endemicity in the studied region. Traditional factors were associated with exposure to the virus. The presence of the HDV was confirmed. The most frequent HBV and HDV genotypes were unlike the ones currently described in Brazil.

DNA-Based Electrodes and Computational Approaches on the Intercalation Study of Antitumoral Drugs.

The binding between anticancer drugs and double-stranded DNA (dsDNA) is a key issue to understand their mechanism of action, and many chemical methods have been explored on this task. Molecular docking techniques successfully predict the affinity of small molecules into the DNA binding sites. In turn, various DNA-targeted drugs are electroactive; in this regard, their electrochemical behavior may change according to the nature and strength of interaction with DNA. A carbon paste electrode (CPE) modified with calf thymus ds-DNA (CPDE) and computational methods were used to evaluate the drug-DNA intercalation of doxorubicin (DOX), daunorubicin (DAU), idarubicin (IDA), dacarbazine (DAR), mitoxantrone (MIT), and methotrexate (MTX), aiming to evaluate eventual correlations. CPE and CPDE were immersed in pH 7 0.1 mM solutions of each drug with different incubation times. As expected, the CPDE response for all DNA-targeted drugs was higher than that of CPE, evidencing the drug-DNA interaction. A peak current increase of up to 10-fold was observed; the lowest increase was seen for MTX, and the highest increase for MIT. Although this increase in the sensitivity is certainly tied to preconcentration effects of DNA, the data did not agree entirely with docking studies, evidencing the participation of other factors, such as viscosity, interfacial electrostatic interactions, and coefficient of diffusion.

Hippocampal HECT E3 ligase inhibition facilitates consolidation, retrieval, and reconsolidation, and inhibits extinction of contextual fear memory.

Ubiquitination is involved in synaptic plasticity and memory, but the involvement of HECT E3 ligases in these processes has not yet been established. Here, we bilaterally infused heclin, a specific inhibitor of some of these ligases, into the dorsal hippocampus of male Wistar rats that were trained in a contextual fear conditioning. Heclin improved short-term memory, consolidation, retrieval, and reconsolidation when administered immediately post training, prior to testing, or after memory reactivation, respectively. In addition, it impaired memory extinction when administered prior to a long reactivation session. Heclin infusion was also tested for locomotor activity and anxiety-like behavior in a circular arena, but no effect was seen. Taken together, these results indicate that HECT E3 ligases are involved in the modulation of fear memory.

Different methods of cell quantification can lead to different results: a comparison of digital methods using a pilot study of dendritic cells in HIV-positive patients.

BACKGROUND: Although new digital pathology tools have improved the positive cell quantification, there is a heterogeneity of the quantification methods in the literature. The aim of this study was to evaluate and propose a novel dendritic cells quantification method in squamous cell carcinoma comparing it with a conventional quantification method. MATERIAL AND METHODS: Twenty-six squamous cell carcinomas HIV-positive cases affecting the oropharynx, lips and oral cavity were selected. Immunohistochemistry for CD1a, CD83, and CD207 was performed. The immunohistochemical stains were evaluated by automated examination using a positive pixel count algorithm. A conventional quantification method (unspecific area method; UA) and a novel method (specific area method; SA) were performed obtaining the corresponding density of positive dendritic cells for the intratumoral and peritumoral regions. The Mann-Whitney U test was used to verify the influence of the quantification methods on the positive cell counting according to the evaluated regions. Data were subjected to the ANOVA and Student's t-test to verify the influence of the tumour location, stage, histological grade, and amount of inflammation on the dendritic cells density counting. RESULTS: The cell quantification method affected the dendritic cells counting independently of the evaluated region (P-value <0.05). Significant differences between methods were also observed according to the tumour features evaluations. CONCLUSIONS: The positive cell quantification method influences the dendritic cells density results. Unlike the conventional method (UA method), the novel SA method avoids non-target areas included in the hotspots improving the reliability and reproducibility of the density cell quantification.

Calcium intake improvement after nutritional intervention in paediatric patients with osteogenesis imperfecta.

BACKGROUND: In several bone disorders, adequate calcium intake is a coadjuvant intervention to regular treatment. Osteogenesis imperfecta (OI) is a collagen disorder with a range of symptoms, ranging from fractures to minimum trauma, and it is typically treated with bisphosphonates. In the present study, we evaluate the impact of a nutritional intervention (NI) on dietary calcium intake and bone mineral density (BMD) in paediatric patients with OI. METHODS: A nonrandomised clinical trial was designed with a NI. Dietary calcium intake, anthropometry and clinical features were assessed at baseline, including anthropometry, basal metabolic rate (BMR), BMD. In addition, a food guidance form was developed and sent to patients by mail. After 12 months, clinical features of patients were reassessed and compared with the baseline data. RESULTS: Fifty-two children and adolescents were enrolled. Significant increases in total calcium intake (mg day-1 ), percentage of adequate calcium intake (%) and number of cups of milk ingested were observed after NI. We detected a positive correlation between the variation of BMD and milk consumption in patients treated with bisphosphonate. CONCLUSIONS: We observed an increase in calcium intake in patients with OI. This finding demonstrates the importance of nutrition therapy as part of a multidisciplinary treatment approach for bone health.

Mental health symptoms and disorders in elite athletes: a systematic review on cultural influencers and barriers to athletes seeking treatment.

OBJECTIVE: To summarise the literature on the barriers to athletes seeking mental health treatment and cultural influencers of mental health in elite athletes. DESIGN: Systematic review DATA SOURCES: PubMed, Cochrane, Scopus, SportDiscus (Ebsco), and PsycINFO (ProQuest) up to November 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Qualitative and quantitative original studies of elite athletes (those who competed at the professional, Olympic, or collegiate/university levels), published in any language. RESULTS: Stigma, low mental health literacy, negative past experiences with mental health treatment-seeking, busy schedules, and hypermasculinity are barriers to elite athletes seeking mental health treatment. Cultural influencers of mental health in elite athletes include: (1) the lack of acceptance of women as athletes; (2) lower acceptability of mental health symptoms and disorders among non-white athletes; (3) non-disclosure of religious beliefs; and (4) higher dependence on economic benefits. Coaches have an important role in supporting elite athletes in obtaining treatment for mental illness. Brief anti-stigma interventions in elite athletes decrease stigma and improve literary about mental health. CONCLUSION: There is a need for various actors to provide more effective strategies to overcome the stigma that surrounds mental illness, increase mental health literacy in the athlete/coach community, and address athlete-specific barriers to seeking treatment for mental illness. In this systematic review, we identified strategies that, if implemented, can overcome the cultural factors that may otherwise limit athletes seeking treatment. Coaches are critical for promoting a culture within elite athletes' environments that encourages athletes to seek treatment.

Influence of sleep bruxism severity on masticatory efficiency: electromyographic analysis.

The objective of the present study was to ascertain masticatory efficiency by evaluating electromyographic activity in the masseter and temporalis muscles in subjects with sleep bruxism of varying severity, as determined by BiteStrip. Thirty-four subjects with sleep bruxism were divided into two groups: a mild sleep bruxism group with a mean (± standard deviation) age of 31.3 ± 6.2 years (n = 15) and a severe sleep bruxism group with a mean age of 29.8 ± 7.1 years (n = 19). Full-night polysomnography (PSG) was performed in eligible subjects. The linear envelope integral was used to determine masticatory efficiency on the basis of the electromyographic signal of the masseter and temporalis muscles during habitual and non-habitual chewing. There was significantly higher (p .05) electromyographic activity in the severe bruxism group than in the mild bruxism group during both peanut chewing in the right (p = .03) and left (p = .03) temporalis muscles and raisin chewing in the right (p = .01) and left (p = .05) temporalis muscles. Furthermore, Parafilm M chewing showed similar results in the right (p = .008) and left (p = .02) temporalis muscles. These results suggested that subjects with severe sleep bruxism had lower masticatory efficiency.

One-level step section histological analysis is insufficient to confirm complete pathological response after neoadjuvant chemoradiation for rectal cancer.

BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) for rectal cancer may lead to cure. As we currently lack reliable methods to clinically confirm the absence of disease, some patients undergo radical resection and have pathological complete response (pCR) still undergo surgery. Furthermore, it is uncertain if conventional one-level histopathological analysis is accurate enough to determine complete response. Confirming pCR is essential to determine the prognosis and to consider the patient's inclusion in trials of adjuvant therapy. The aim of this study was to determine whether the current 1-level approach is sufficient to confirm pCR. METHODS: Four hundred and thirty-five patients with rectal cancer who received nCRT followed by radical resection were analyzed. All cases identified as pCR by 1-level step section histological evaluation were reassessed with 3-level step sections and immunohistochemical analysis to verify the presence of residual disease. RESULTS: Out of 435 patients, 75 (17.2%) were staged as ypT0. Of these, 6 had lymph node involvement and 1 had distant metastasis, leaving 68 (15.6%) who had pCR. After the additional step sections, residual tumor was detected in 12 (17.6%) of these 68. The final pCR rate was 12.9%. Distant recurrence was detected in 7.1% of real-pCR patients compared to 16.7% in the false-pCR group (p = 0.291). Sensitivity of clinical assessment for detecting pCR was 35.7%, and the accuracy of 1-section histological evaluation to identify pCR was 82.4%. CONCLUSIONS: Histopathological analysis with 1-level step section is insufficient to determine complete tumor eradication. The 3-level sections methodology revealed residual tumor cells in patients initially classified as ypT0. Further studies with larger sample size are required to verify the clinical relevance of these residual tumor cells. Caution should continue to be applied to watch and wait strategies following nCRT.

Erratum to: One-level step section histological analysis is insufficient to confirm complete pathological response after neoadjuvant chemoradiation for rectal cancer.

Unfortunately, one of the author name was wrongly published in the original publication. The complete correct name should read as follows "Beatriz Camargo Azevedo". The original article was updated.

Teaching in higher education in nursing and identity construction: entry, career and permanence. / Docência no ensino superior em enfermagem e constituição identitária: ingresso, trajetória e permanência.

OBJECTIVE: To identify and analyze the relation between biographical and relational processes in constituting the professional identity of the nursing course faculty in higher education institutions in the state of Goiás, Brazil. METHOD: This study is a qualitative research, data were collected in 2014, attended by 11 teachers from four nursing courses. A semi-structured interview was used. Data analysis was guided by the thematic content analysis modality and discussions used the theoretical-philosophical framework of Dubar. RESULTS: Three thematic categories were identified: The entry into higher education teaching in nursing; The identity construction process of teaching in nursing and; Identity, career and permanence in the teaching profession. FINAL CONSIDERATIONS: The constitution of the teaching professional identity required a complex negotiation between the biographic and relational aspects, highlighting the search for professional faculty development mechanisms.

Prevalence and correlates of cannabis use among athletes-A systematic review.

BACKGROUND AND OBJECTIVES: Despite scientific evidence that marijuana impairs performance and mental health, there is evidence that some athletes are at higher risk for use. This review aims to identify possible risk factors associated with marijuana use in athletes. METHODS: A search was conducted in the PubMed database with the keywords: (marijuana OR cannabis OR tetrahydrocannabinol OR delta-9-tetrahydrocannabinol OR THC) AND (sports OR sport OR athlete OR athletes). We retrieved 186 studies. After applying the inclusion/exclusion criteria, 15 studies remained for review. RESULTS: The review revealed a number of potential risk factors for marijuana use among adult athletes, including being male, Caucasian, using sport performance-enhancing drugs, using marijuana to enhance recreation or non-sport performance, and practicing specific types of sports including skeleton, bobsleding, and ice hockey. Contrary to use patterns in the general population, among athletes marijuana appears to take the place of tobacco as the second most widely used drug, after alcohol. Many elite athletes denied the use of marijuana, which suggests that toxicological testing is an important tool for identifying users, because it is more accurate than self-report. Geography appears important, as in areas of high consumption, prevalence among athletes appears to be greater as well. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Contrary to the image that athletes do not use psychoactive drugs, this review suggests that a number of athletic subgroups are at increased risk for marijuana use. Surprisingly, a common rationale for use appears to be to enhance sports performance. As in the general population, experimentation starts early-in pre-adolescence-at an age that prevention and guidance programs could have positive influences. (Am J Addict 2016;25:518-528).

Current practice in identifying and treating cardiovascular risk, with a focus on residual risk associated with atherogenic dyslipidaemia.

A panel of European experts on lipids and cardiovascular disease discussed clinical approaches to managing cardiovascular risk in clinical practice, including residual cardiovascular risk associated with lipid abnormalities, such as atherogenic dyslipidaemia (AD). A simplified definition of AD was proposed to enhance understanding of this condition, its prevalence, and its impact on cardiovascular risk. Atherogenic dyslipidaemia can be defined by high fasting triglyceride levels (≥2.3 mmol/L) and low high-density lipoprotein cholesterol (HDL-c) levels (≤1.0 and ≤1.3 mmol/L in men and women, respectively) in statin-treated patients at high cardiovascular risk. The use of a single marker for the diagnosis and treatment of AD, such as non-HDL-c, was advocated. Interventions including lifestyle optimization and low-density lipoprotein (LDL)-lowering therapy with statins (±ezetimibe) are implemented by all experts. Treatment of residual AD can be performed with the addition of fenofibrate, since it can improve the complete lipoprotein profile and reduce the risk of cardiovascular events in patients with AD. Specific clinical scenarios in which fenofibrate may be prescribed are discussed, and include patients with very high triglycerides (≥5.6 mmol/L), patients who are intolerant or resistant to statins, and patients with AD and at high cardiovascular risk. The fenofibrate-statin combination was considered by the experts to benefit from a favourable benefit-risk profile. Cardiovascular experts adopt a multifaceted approach to the prevention of atherosclerotic cardiovascular disease, with lifestyle optimization, LDL-lowering therapy, and treatment of AD with fenofibrate routinely used to help reduce a patient's overall cardiovascular risk.

Neonatal handling causes impulsive behavior and decreased pharmacological response to methylphenidate in male adult wistar rats.

Neonatal handling has an impact on adult behavior of experimental animals and is associated with rapid and increased palatable food ingestion, impaired behavioral flexibility, and fearless behavior to novel environments. These symptoms are characteristic features of impulsive trait, being controlled by the medial prefrontal cortex (mPFC). Impulsive behavior is a key component of many psychiatric disorders such as attention deficit hyperactivity disorder (ADHD), manic behavior, and schizophrenia. Others have reported a methylphenidate (MPH)-induced enhancement of mPFC functioning and improvements in behavioral core symptoms of ADHD patients. The aims of the present study were: (i) to find in vivo evidence for an association between neonatal handling and the development of impulsive behavior in adult Wistar rats and (ii) to test whether neonatal handling could have an impact on monoamine levels in the mPFC and the pharmacological response to MPH in vivo. Therefore, experimental animals (litters) were classified as: "non-handled" and "handled" (10[Formula: see text]min/day, postnatal days 1-10). After puberty, they were exposed to either a larger and delayed or smaller and immediate reward (tolerance to delay of reward task). Acute MPH (3[Formula: see text]mg/Kg. i.p.) was used to suppress and/or regulate impulsive behavior. Our results show that only neonatally handled male adult Wistar rats exhibit impulsive behavior with no significant differences in monoamine levels in the medial prefrontal cortex, together with a decreased response to MPH. On this basis, we postulate that early life interventions may have long-term effects on inhibitory control mechanisms and affect the later response to pharmacological agents during adulthood.

The cannabinoid system in the retrosplenial cortex modulates fear memory consolidation, reconsolidation, and extinction.

Despite the fact that the cannabinoid receptor type 1 (CB1R) plays a pivotal role in emotional memory processing in different regions of the brain, its function in the retrosplenial cortex (RSC) remains unknown. Here, using contextual fear conditioning in rats, we showed that a post-training intra-RSC infusion of the CB1R antagonist AM251 impaired, and the agonist CP55940 improved, long-term memory consolidation. Additionally, a post-reactivation infusion of AM251 enhanced memory reconsolidation, while CP55940 had the opposite effect. Finally, AM251 blocked extinction, whereas CP55940 facilitated it and maintained memory extinguished over time. Altogether, our data strongly suggest that the cannabinoid system of the RSC modulates emotional memory.

Repair of critical-size bone defects using bone marrow stromal cells: a histomorphometric study in rabbit calvaria. Part I: use of fresh bone marrow or bone marrow mononuclear fraction.

OBJECTIVES: The aim of this study was to compare the bone healing observed after the use of (1) a scaffold enriched with fresh bone marrow, (2) a scaffold enriched with bone marrow mononuclear fraction, and (3) a scaffold alone. MATERIAL AND METHODS: Twenty one rabbits were randomly divided into three groups of six animals and 1 group of 3 animals. Bilateral 12-mm diameter defects were created in the animals' parietal bones. In Control Group, the defects were filled with a xenograft alone (n = 6); in Group 1, with a xenograft enriched with fresh bone marrow (n = 6); in Group 2, with a xenograft enriched with bone marrow mononuclear fraction (n = 6) and in Unfilled Group, nothing was grafted (n = 3). In Groups 1, 2, and Control, one of the calvarial defects was randomly covered with a barrier membrane. The rabbits were sacrificed 8 weeks after surgery, and their parietal bones were harvested and analyzed histomorphometrically. RESULTS: The histomorphometric analysis showed no difference between Group 1 and the Control Group regarding non-vital mineralized tissue area, but Group 2 showed a statistically significant higher percentage than the Control Group (P < 0.05) for both situations, with membrane (21.24 ± 3.78% and 13.52 ± 3.00%, respectively) and without membrane (20.91 ± 2.01% and 13.08 ± 1.72%, respectively). Group 2 showed the highest percentage of vital mineralized tissue area, followed by Group 1 and the Control Group (P < 0.05) for both situations, with membrane (28.17 ± 3.19%; 21.14 ± 7.38% and 13.06 ± 5.24%, respectively) and without membrane (21.13 ± 0.55%; 12.45 ± 6.34% and 6.56 ± 1.20%, respectively). Group 2 showed the lowest percentage of non-mineralized tissue area, followed by Group 1 and Control Group (P < 0.05) for both situations, with membrane (50.59 ± 6.64%; 58.75 ± 7.14% and 73.41 ± 6.87%, respectively) and without membrane (57.97 ± 1.91%; 71.74 ± 6.63% and 80.37 ± 2.67%, respectively). The sides in which the defects were covered with the barrier membrane showed better bone healing compared with the uncovered sides, in all groups (intragroup comparison, P < 0.05). The Unfilled Group specimens showed no bone formation. CONCLUSIONS: Both methods using bone marrow stromal cells contributed to enhancing bone healing, especially that using the bone marrow mononuclear fraction. The use of a barrier membrane seemed to have a synergistic effect.