Association between Urinary Sodium Excretion and Body Fat in School-Aged Children: Insights from the ARIA Study.

Childhood obesity has been associated with increased sodium intake. Nonetheless, evidence linking sodium intake to Body Mass Index (BMI) and Body Fat Mass Percentage (%BF) remains limited, especially in the pediatric age group. Therefore, this study aims to investigate whether there is an association between 24 h urinary sodium excretion with BMI and %BF in a sample group of children from the ARIA study. This cross-sectional analysis included 303 children aged 7 to 12 from across 20 public schools in Porto, Portugal. Weight and %BF were assessed using the Tanita™ BC-418 Segmental Body Analyzer. Children's Total Energy Intake (TEI) was estimated through a single 24 h Recall Questionnaire, and urinary sodium and potassium excretion was estimated by a 24 h urine collection. The association of %BF and BMI with 24 h sodium excretion was estimated by a binary logistic regression adjusted for sex, age, physical activity, total energy intake, parental education, and 24 h urinary excreted potassium. There was a significant positive association between higher levels of urinary sodium excretion and higher %BF values, even after adjusting for confounders. However, the same was not observed for BMI. Our findings suggest that higher sodium intake is associated with higher values of %BF among children, regardless of TEI and potassium intake.

Efficacy and safety of guttiferone E in melanoma-bearing mice.

Melanoma, an aggressive and potentially fatal skin cancer, is constrained by immunosuppression, resistance, and high toxicity in its treatment. Consequently, there is an urgent need for innovative antineoplastic agents. Therefore, this study investigated the antimelanoma potential of guttiferone E (GE). In an allogeneic murine B16 melanoma model, GE was administered subcutaneously and intraperitoneally. Antitumor evaluation included tumor volume/weight measurements and histopathological and immunohistochemical analysis. Furthermore, the toxicity of the treatments was evaluated through body/organ weights, biochemical parameters, and genotoxicity. Subcutaneous administration of 20 mg/kg of GE resulted in a significant reduction in both tumor volume and weight, effectively suppressing melanoma cell proliferation as evidenced by a decrease in mitotic figures. The tumor growth inhibition rate was equivalent to 54%. This treatment upregulated cleaved caspase-3, indicating apoptosis induction. On the other hand, intraperitoneal administration of GE showed no antimelanoma effect. Remarkably, GE treatments exhibited no toxicity, evidenced by non-significant differences in body weight gain, as well as organ weight, biochemical parameters of nephrotoxicity and hepatotoxicity, and genotoxic damage. This study revealed, for the first time, the efficacy of subcutaneous administration of GE in reducing melanoma, in the absence of toxicity. Furthermore, it was observed that the apoptotic signaling pathway is involved in the antimelanoma property of GE. These findings offer valuable insights for further exploring GE's therapeutic applications in melanoma treatment.

Comparison between whole-body magnetic resonance imaging and whole-body metaiodobenzylguanidine scintigraphy in the evaluation of primary tumor and metastases in neuroblastoma.

BACKGROUND: Whole-body metaiodobenzylguanidine (131 I-MIBG) scintigraphy is the gold standard method to detect neuroblastoma; however, it depends on radioactive material and is expensive. In contrast, whole-body magnetic resonance imaging (WB-MRI) is affordable in developing countries and has been shown to be effective in the evaluation of solid tumors. This study aimed to compare the sensitivity and specificity of WB-MRI with MIBG in the detection of primary tumors and neuroblastoma metastases. PROCEDURE: This retrospective study enrolled patients with neuroblastoma between 2013 and 2020. All patients underwent WB-MRI and MIBG at intervals of up to 15 days. The results were marked in a table that discriminated anatomical regions for each patient. Two experts evaluated, independently and in anonymity, the WB-MRI images, and two others evaluated MIBG. The results were compared in terms of sensitivity and specificity, for each patient, considering MIBG as the gold standard. This study was approved by the UNIFESP Ethics Committee. RESULTS: Thirty patients with neuroblastoma were enrolled in this study. The age ranged from 1 to 15 years, with a mean of 5.7 years. The interval between exams (WB-MRI and MIBG) ranged from 1 to 13 days, with an average of 6.67 days. Compared to MIBG, WB-MRI presented a sensitivity and specificity greater than or equal to 90% for the detection of primary neuroblastoma in bones and lymph nodes. When we consider the patient without individualizing the anatomical regions, WB-MRI presented sensitivity of 90% and specificity of 73.33%. CONCLUSION: In conclusion, WB-MRI is a sensitive and specific method to detect neuroblastoma in bone and lymph nodes and highly sensible to primary tumor diagnosis, suggesting that this test is a viable alternative in places where MIBG is difficult to access. Studies with a larger number of cases are necessary for definitive conclusions.

Pharmacotherapeutic follow-up of a patient with multimorbities: experience report / Acompanhamento farmacoterapêutico em paciente com multimorbidades: um relato de experiência / Seguimiento farmacoterapéutico en pacientes con multimorbilidad: informe de una experiencia

Chronic non-communicable diseases are growing global health problems. The objective of this study was to promote pharmaceutical care for a patient with multimorbidities in order to improve its quality of life. A pharmacotherapeutic follow-up was performed using the SOAP method, registered in the form of clinical evolution, along with laboratory tests, anthropometric measurements and application of validated instruments to assess pharmacological adherence, mental health and quality of life. The report deals with a female patient, 55 years old, obese and dyslipidemic, sedentary, hypertensive, diabetic and on the control phase of breast cancer. Self-medication with antibiotics and a proton pump inhibitor was identified. Despite the good pharmacological adherence, the patient had decompensated diabetes, accompanied by dyslipidemia without treatment and interruption of supplements. After pharmacological and non- pharmacological interventions, the patient showed a significant improvement in the reduction of anthropometric measurements and in biochemical parameters. At the end of the follow-up, pharmaceutical care proved to be fundamental in identifying the patient's health problems, contributing to obtain a more rational pharmacotherapy.

As doenças crônicas não transmissíveis são problemas de saúde globais crescentes. O objetivo deste estudo foi promover a assistência farmacêutica a um paciente com multimorbidades, a fim de melhorar sua qualidade de vida. Foi realizado acompanhamento farmacoterapêutico pelo método SOAP e aplicação de instrumentos validados para avaliar adesão farmacológica, saúde mental e qualidade de vida. O relato trata de uma paciente do sexo feminino, 55 anos, obesa e dislipidêmica, sedentária, hipertensa, diabética e em fase de controle do câncer de mama. Foi identificada automedicação com antibióticos e inibidor de bomba de prótons. Apesar da boa adesão farmacológica, a paciente apresentava diabetes descompensado, acompanhada de dislipidemia sem tratamento e interrupção das suplementações. Após intervenções farmacológicas e não farmacológicas, a paciente apresentou melhora significativa na redução das medidas antropométricas e nos parâmetros bioquímicos. Ao final do acompanhamento, a assistência farmacêutica mostrou-se fundamental na identificação dos problemas de saúde do paciente.

Las enfermedades crónicas no transmisibles constituyen un creciente problema de salud mundial. El objetivo de este estudio fue promover la asistencia farmacéutica a un paciente con multimorbilidades para mejorar su calidad de vida. Se realizó seguimiento farmacoterapéutico por el método SOAP y aplicación de instrumentos validados para evaluar adherencia farmacológica, salud mental y calidad de vida. O relato trata de uma paciente do sexo feminino, 55 anos, obesa e dislipidêmica, sedentária, hipertensa, diabética e em fase de controle do câncer de mama. Se identificó automedicación con antibióticos e inhibidor de la bomba de protones. A pesar del buen cumplimiento farmacológico, la paciente presentó diabetes descompensada, acompañada de dislipidemia no tratada e interrupción de la suplementación. Tras intervenciones farmacológicas y no farmacológicas, la paciente mostró una mejoría significativa en la reducción de las medidas antropométricas y los parámetros bioquímicos. Al final del seguimiento, la asistencia farmacéutica demostró ser fundamental en la identificación de los problemas de salud del paciente.

Neurodevelopment and Dietary Intake in Toddlers-A Cross-Sectional Study from the Healthy Children 2021 Project.

Little is known about the potential associations between neurodevelopment, dietary diversity and food processing in the toddler period. This study aimed to estimate the association between these dietary quality dimensions and neurodevelopment in toddlers. Data for this cross-sectional analysis came from the Healthy Children 2021 project and included 212 toddlers (51.9% females, aged 12-36 months) from 15 Portuguese childcare centers. Neurodevelopment was assessed through Bayley Scales of Infant and Toddler Development. Dietary intake was gathered by a two-day non-consecutive dietary recall. The food items were categorised with NOVA classification. Dietary diversity was explored through Minimum Dietary Diversity (MDD). Logistic regression models adjusted for potential confounders were performed. Girls with a higher energy contribution of unprocessed/minimally processed foods and with an above median MDD score had higher odds of achieving a higher neurodevelopment score (aOR:1.04; 95%CI 1.01; 1.08 and aOR:2.26; 95%CI 1.01; 5.06, respectively); no significant association was observed in boys. Our findings suggest that these dietary dimensions are associated with a higher neurodevelopment in toddler girls. This should be further studied as a possible early link between dietary factors and neurodevelopment. Promotion of healthy eating can be promising in improving neurocognitive development and might help to introduce public health recommendations for toddlers' nutrition.

Reconstructive surgery and adjuvant radiotherapy for the multimodal approach in oral cancer: a single cancer centre experience.

Introduction and importance: Ablative surgery for oral cancer, irrespective of the histological subtype, causes large tissue defects, functional and aesthetic damage. Microsurgical free flaps have been widely used in reconstruction after resection, with satisfactory success rates in conjunction with adjuvant radiotherapy (RT). This study aims to describe our clinical institutional experience based on the multimodal treatment performed in four cases diagnosed with oral squamous cell carcinoma with the use of different microvascular free flaps and RT. Case series presentation: Four patients underwent reconstructive microsurgery after surgical resection of oral cancer, using three types of free flap: radial forearm fasciocutaneous, osteomyocutaneous fibular, and anterolateral thigh musculocutaneous flaps; RT was performed in Case 2 and Case 3. In the period of 3 years after microsurgical reconstruction and RT, flaps remain clinically stable without failure signs in full patients submitted to multimodal treatment. Clinical discussion: After resection of oral carcinomas, extensive tissue defects can be successfully treated with reconstructive microsurgery using different types of microvascular free flaps. RT for locoregional control is a feasible option and did not seem to interfere with the survival of flaps. Conclusion: An enhance long-term follow-up to assess overall and disease-free survival rates and quality of life must be carried out; however, cohort studies would be necessary for better understanding of the role of each treatment in the multimodal scheme.

Glucose may Contribute to Retrieval and Reconsolidation of Contextual Fear Memory Through Hippocampal Nr4a3 and Bdnf mRNA Expression and May Act Synergically with Adrenaline.

Adrenaline (Ad) and glucose released into the bloodstream during stress may strengthen contextual fear memory. However, no previous studies have detached the effects of glucose from Ad in this paradigm. Using Ad-deficient mice, we aimed to evaluate the effect of glucose on contextual fear memory when endogenous Ad is absent. Fear conditioning was performed in wild-type (WT) and Ad-deficient mice (129 × 1/SvJ) administered with glucose (30 or 10 mg/kg; i.p.) or/and Ad (0.01 mg/kg; i.p.) or vehicle (0.9% NaCl; i.p.). Catecholamines were quantified using HPLC-ED. Real-time qPCR was used to assess mRNA expression of hippocampal genes. WT and Ad-deficient mice display increased contextual fear memory when administered with glucose both in acquisition and context days when compared to vehicle. Also, Nr4a3 and Bdnf mRNA expression increased in glucose-administered Ad-deficient mice. Sub-effective doses of glucose plus Ad administered simultaneously to Ad-deficient mice increased contextual fear memory, contrary to independent sub-effective doses. Concluding, glucose may be an important part of the peripheral to central pathway involved in the retrieval and reconsolidation of fear contextual memories independently of Ad, possibly due to increased hippocampal Nr4a3 and Bdnf gene expression. Furthermore, Ad and glucose may act synergically to strengthen contextual fear memory.

Does the Mediterranean Dietary Pattern Promote Lower Sodium Urinary Excretion in Children?

An adequate sodium intake is related to various health benefits. Parallelly, the Mediterranean diet (MD) is a dietary pattern known for its many positive impacts on health. Nonetheless, the association between adherence to the MD and sodium urinary excretion is scarce, even more in children. This study aimed to assess the association between MD adherence and the excretion of sodium, as a proxy of intake. This cross-sectional analysis comprised 295 children (46.8% females, aged 7-11 years, mean age: 8.53 ± 0.73 years) from 20 schools within Porto, Portugal. MD adherence was evaluated utilizing the alternate Mediterranean score (aMED). Higher scores denote a healthier dietary pattern (0-8). Sodium excretion was estimated by 24-h urine collection. The association between adherence to MD and Na excretion was estimated by logistic regression, adjusting for confounders. Children in the higher sodium excretion group had a higher intake of legumes, a higher body mass index and parents with lower education levels compared to children in the lower sodium excretion group. In logistic regression analysis, sodium urinary excretion was not associated with higher MD adherence, even after adjustment for confounders. High MD adherence could not be associated with lower sodium excretion in children.

Mediterranean Diet and Airway Inflammation in School-Aged Children.

There seems to exist an intricate relationship between airway inflammation, body mass index (BMI), and diet. The intake of specific foods or food groups has been suggested to suppress the oxidative stress and inflammatory processes that characterize airway inflammation, but little is known about dietary patterns and their complex interplay with BMI and airway inflammation. Therefore, this cross-sectional study aimed to explore the association between adherence to the Mediterranean diet (MD), a characteristic European diet, and levels of airway inflammation in school-aged children, taking into account their BMI. This cross-sectional analysis comprised 660 children: 49.1% females, 7-12 years old. Adherence to the MD was assessed through the alternate Mediterranean score (aMED). Higher scores represent a healthier diet (0-8). Airway inflammation was assessed measuring exhaled fractional nitric oxide (eNO). Two categories of BMI were considered: non-overweight/non-obese (p < 85th) and overweight/obese (p ≥ 85th). The associations between diet and airway inflammation were estimated using logistic regression models. Higher scores of the aMED were associated with decreased odds of having eNO ≥ 35 ppb, but only in non-overweight/non-obese children (OR = 0.77; 95% CI, 0.61-0.97). For overweight/obese children, the previous association was not significant (OR = 1.57, 95% CI, 0.88-2.79). Our findings suggest that adherence to the MD is associated with lower levels of airway inflammation among non-overweight/non-obese children.

Insulin enhances contextual fear memory independently of its effect in increasing plasma adrenaline.

AIMS: Adrenaline enhances contextual fear memory consolidation possibly by activating liver ß2-adrenoceptors causing transient hyperglycaemia. Contrastingly, insulin-induced hypoglycaemia may culminate in blood adrenaline increment, hidering the separation of each hormone's action in contextual fear memory. Therefore, an adrenaline-deficient mouse model was used aiming to investigate if contextual fear memory consolidation following insulin administration requires or not subsequent increases in plasma adrenaline, which occurs in response to insulin-induced hypoglycemia. MAIN METHODS: Fear conditioning was performed in wild-type (WT) and adrenaline-deficient (Pnmt-KO) male mice (129 × 1/SvJ) treated with insulin (2 U/kg, intraperitoneal (i.p.)) or vehicle (0.9 % NaCl (i.p.)). Blood glucose was quantified. Catecholamines were quantified using HPLC with electrochemical detection. Quantitative real-time polymerase chain reaction was used to assess mRNA expression of hippocampal Nr4a1, Nr4a2, Nr4a3, and Bdnf genes. KEY FINDINGS: Insulin-treated WT mice showed increased freezing behaviour when compared to vehicle-treated WT mice. Also, plasma dopamine, noradrenaline, and adrenaline increased in this group. Insulin-treated Pnmt-KO animals showed increased freezing behaviour when compared with respective vehicle. However, no changes in plasma or tissue catecholamines were identified in insulin-treated Pnmt-KO mice when compared with respective vehicle. Furthermore, insulin-treated Pnmt-KO mice presented increased Bdnf mRNA expression when compared to vehicle-treated Pnmt-KO mice. SIGNIFICANCE: Concluding, enhanced freezing behaviour after insulin treatment, even in adrenaline absence, may indicate a key role of insulin in contextual fear memory. Insulin may cause central molecular changes promoting contextual fear memory formation and/or retrieval. This work may indicate a further role of insulin in the process of contextual fear memory modulation.

Factors associated with higher quality of clinical practice guidelines and their recommendations for the pharmacological treatment of depression: a systematic review.

OBJECTIVE: The objective of this study was to assess the quality of clinical practice guidelines (CPGs) for the pharmacological treatment of depression along with their recommendations and factors associated with higher quality. DESIGN: We conducted a systematic review that included CPGs for the pharmacological treatment of depression in adults. DATA SOURCES: We searched for publications from 1 January 2011 to 31 December 2021, in MEDLINE, Cochrane Library, Embase, PsycINFO, BVS and 12 other databases and guideline repositories. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included CPGs containing recommendations for the pharmacological treatment of depression in adults at outpatient care setting, regardless of whether it met the U.S. National Academy of Medicine criteria, or not. If a CPG included recommendations for both children and adults, they were considered. No language restriction was applied. DATA EXTRACTION AND SYNTHESIS: Data extraction was also conducted independently and in duplicate, a process that was validated in a previous project. The quality of the CPGs and their recommendations were assessed by three independent reviewers using Appraisal of Guidelines for Research and Evaluation (AGREE II) and Appraisal of Guidelines for Research and Evaluation-Recommendations Excellence (AGREE-REX). A CPG was considered to be of high quality if AGREE II Domain 3 was ≥60%; while their recommendations were considered high if AGREE-REX Domain 1 was ≥60%. RESULTS: Seventeen out of 63 (27%) CPGs were classified as high quality, while 7 (11.1%) had high-quality recommendations. The factors associated with higher-scoring CPGs and recommendations in the multiple linear regression analyses were 'Handling of conflicts of interest', 'Multiprofessional team' and 'Type of institution'. 'Inclusion of patient representative in the team' was also associated with higher-quality recommendations. CONCLUSIONS: The involvement of professionals from diverse backgrounds, the handling of conflicts of interest, and the inclusion of patients' perspectives should be prioritised by developers aiming for high-quality CPGs for the treatment of depression.

Diet Quality and Exhaled Breath Condensate Markers in a Sample of School-Aged Children.

Exhaled breath condensate (EBC) analysis is a recently developed, non-invasive method used to identify and quantify biomarkers, mainly those coming from the lower respiratory tract. It seems that diet can influence the airway's inflammation and change the exhaled breath composition. This study aimed to assess the association between diet quality intake and markers in EBC among school-aged children. A cross-sectional analysis included 150 children (48.3% females, aged 7-12 years, mean age: 8.7 ± 0.8 years) from 20 schools across Porto, Portugal. We assessed diet quality through the Healthy Eating Index (HEI)-2015, which was estimated based on a single 24 h food recall questionnaire. EBC samples were collected, and we assessed their ionic content (Na+, K+) and conductivity. The association between diet quality and Na+, K+, Na+/K+ ratio and conductivity was estimated using logistic regression models adjusted for potential confounders. After adjustment, a higher quality diet score increases the odds of higher conductivity values of the EBC (aOR = 1.04, 95%CI 1.00; 1.08). Our findings suggest that a higher diet quality in school-aged children is associated with higher conductivity levels of the EBC.

Guidelines' recommendations for the treatment-resistant depression: A systematic review of their quality.

INTRODUCTION: Depression is a serious and widespread mental health disorder. A significant proportion of patients with depression fail to remit after two antidepressant treatment trials, a condition named treatment-resistant depression (TRD). Clinical practice guidelines (CPGs) are instruments aimed to improve diagnosis and treatment. This study objective is to systematically appraise the quality and elaborate a comparison of high-quality CPGs with high-quality recommendations aimed at TRD. METHODS AND ANALYSIS: We searched several specialized databases and organizations that develop CPGs. Independent researchers assessed the quality of the CPGs and their recommendations using AGREE II and AGREE-REX instruments, respectively. We selected only high-quality CPGs that included definition and recommendations for TRD. We investigated their divergencies and convergencies as well as weak and strong points. RESULTS: Among seven high-quality CPGs with high-quality recommendations only two (Germany's Nationale Versorgungs Leitlinie-NVL and US Department of Veterans Affairs and Department of Defense-VA/DoD) included specific TRD definition and were selected. We found no convergent therapeutic strategy among these two CPGs. Electroconvulsive therapy is recommended by the NVL but not by the VA/DoD, while repetitive transcranial magnetic stimulation is recommended by the VA/DoD but not by the NVL. While the NVL recommends the use of lithium, and a non-routine use of thyroid or other hormones, psychostimulants, and dopaminergic agents the VA/DoD does not even include these drugs among augmentation strategies. Instead, the VA/DoD recommends ketamine or esketamine as augmentation strategies, while the NVL does not mention these drugs. Other differences between these CPGs include antidepressant combination, psychotherapy as a therapeutic augmentation, and evaluation of the need for hospitalization all of which are only recommended by the NVL. CONCLUSIONS: High-quality CPGs for the treatment of depression diverge regarding the definition and use of the term TRD. There is also no convergent approach to TRD from currently high-quality CPGs.

Molecular pathways underlying sympathetic autonomic overshooting leading to fear and traumatic memories: looking for alternative therapeutic options for post-traumatic stress disorder.

The sympathoadrenal medullary system and the hypothalamic-pituitary-adrenal axis are both activated upon stressful events. The release of catecholamines, such as dopamine, norepinephrine (NE), and epinephrine (EPI), from sympathetic autonomic nerves participate in the adaptive responses to acute stress. Most theories suggest that activation of peripheral ß-adrenoceptors (ß-ARs) mediates catecholamines-induced memory enhancement. These include direct activation of ß-ARs in the vagus nerve, as well as indirect responses to catecholamine-induced glucose changes in the brain. Excessive sympathetic activity is deeply associated with memories experienced during strong emotional stressful conditions, with catecholamines playing relevant roles in fear and traumatic memories consolidation. Recent findings suggest that EPI is implicated in fear and traumatic contextual memories associated with post-traumatic stress disorder (PTSD) by increasing hippocampal gene transcription (e.g., Nr4a) downstream to cAMP response-element protein activation (CREB). Herein, we reviewed the literature focusing on the molecular mechanisms underlying the pathophysiology of memories associated with fear and traumatic experiences to pave new avenues for the treatment of stress and anxiety conditions, such as PTSD.

Radiation-induced Sarcoma in the Head and Neck: Clinical, Imaging, Histopathological, and Therapeutic Characterization.

Radiation-induced head and neck sarcoma (RIHNS) is a rare and serious long-term complication of radiotherapy (RT), with poor prognosis and high morbidity and mortality. Diagnosis is based on immunohistochemistry and molecular biomarker analysis, and therapy is usually surgical. Other adjuvant therapies might be considered. This case report aimed to describe the clinical, imaging, histopathological, and therapeutic characteristics of a rare case of RIHNS in the mandible after 21 years of RT. A 68-year-old male patient underwent a partial left parotidectomy in 1995, was diagnosed with pleomorphic adenoma, and after recurrence of the lesion in 2000, underwent an ipsilateral total parotidectomy with adjuvant RT. In May 2021, he complained of an ulcerated nodular lesion on the tongue that extended toward the lower gingiva, associated with oral bleeding and difficulties with swallowing. After biopsy in the gingival margin and histopathological analysis, the diagnosis of high-grade spindle-cell sarcoma was established. Complete surgical resection with microsurgical reconstruction using a fibular osteomusculocutaneous free flap was performed. RIHNS could appear after a period of almost 20 years after RT. Surgical resection with reconstructive surgery was a reliable and feasible therapeutic option that showed favorable clinical results after an appropriate follow-up.

How can the built environment affect the impact of autonomous vehicles' operational behaviour on air quality?

Autonomous vehicles (AVs) are pointed out as the technology that will reshape the concept of mobility, with significant implications for the economy, the environment, and society. This fact will bring new challenge to cities urban planning. Research to anticipate the AVs impacts, maximizing their benefits and reduce trade-offs are currently crucial. This work investigates the potential challenges and benefits of gradually replace internal combustion engine human driven vehicles with different penetration rates of AVs - 10%, 30%, 50%, 70%, 90%, and 100% - in urban roads of different characteristics, either in terms of traffic singularities or volumes, and its related implications on air quality. For that purpose, two urban areas with distinct features, Porto and Aveiro, were selected as case studies, and a modelling setup composed of a traffic model, an emission model, and a local air quality model was applied. The results revealed that the AVs benefits are directly linked with the urban design and the road characteristics. In the Aveiro case study, the AVs promoted positive changes with average reductions in daily NOx emissions (compared with the baseline scenario, without AVs) ranging between -2.1% (for C10%) and -7.7% (for C100%). In line with the emissions impacts, positive effects were found on air quality, with average reductions of NO2 concentrations up to -4% (for C100%). In Porto urban area, slight differences in NOx emissions were obtained (<2%), which implied no changes in the air quality levels. The distinct impact of AVs in the study areas is mostly explained by the traffic light coordination system and directional split distributions in the main roads. These results provide valuable insights to support decision-makers in the definition of strategies that allow the integration of these new emerging technologies in the road infrastructure, considering the features of the urban design, traffic profile and road characteristics.

Recommendations for the pharmacological treatment of treatment-resistant depression: A systematic review protocol.

INTRODUCTION: Depression is a serious and widespread mental health disorder. Although effective treatment does exist, a significant proportion of patients with depression fail to respond to antidepressant treatment trials, a condition named treatment-resistant depression. Efficient approach should be given this condition in order to revert the burden caused by depression. Clinical practice guidelines (CPGs) are evidence-based health promotion instruments to improve diagnosis and treatment. CPGs recommendations for treatment-resistant depression must be trustworthy. The objective of the proposed study is to systematically identify, appraise the quality of CPGs for the treatment of depression and elaborate a synthesis of recommendations for treatment-resistant depression of CPGs considered to be of high quality and with high quality recommendations. METHODS AND ANALYSIS: We will search the databases of organizations, such as PubMed, Embase, Cochrane Library, PsycInfo, and the Virtual Health Library, and organizations that develop CPGs. Three independent researchers will assess the quality of the CPGs and their recommendations using the AGREE II and AGREE-REX instruments, respectively. Given the identification of divergences and convergences as well as weak and strong points among high quality CPGs, our work may help developers, clinicians and eventually patients. ETHICS AND DISSEMINATION: No ethical approval is required for a systematic review, as no patient data will be used. The research results will be disseminated in conferences and submitted to a peer reviewed journal.

Treatment With Nepicastat Decreases Contextual Traumatic Memories Persistence in Post-traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a common anxiety mental disorder and can be manifested after exposure to a real or perceived life-threatening event. Increased noradrenaline and adrenaline in plasma and urine have been documented in PTSD. Dopamine-ß-hydroxylase (DBH) catalyzes the conversion of dopamine to noradrenaline and consequently, DBH inhibition reduces catecholamines. Our aim was to evaluate if nepicastat treatment decreases PTSD signs in an animal model. Wild-type (129x1/SvJ) female mice were submitted to PTSD induction protocol. DBH-inhibitor nepicastat (30 mg/kg) or vehicle (0.2% HPMC) were administered once daily since day 0 until day 7 or 12. The percentage of freezing was calculated on days 0, 1, 2, and 7, and behavioral tests were performed. Quantification of nepicastat in plasma and DBH activity in the adrenal gland was evaluated. Catecholamines were quantified by HPLC with electrochemical detection. mRNA expression of Npas4 and Bdnf in hippocampus was evaluated by qPCR.Mice in the PTSD-group and treated with nepicastat showed a decrease in freezing, and an increase in the time spent and entries in open arms in elevated plus maze test. In mice treated with nepicastat, adrenal gland DBH activity was decreased, and catecholamines were also decreased in plasma and tissues. On day 7, in mice treated with nepicastat, there was an increase of Npas4 and Bdnf mRNA expression in the hippocampus.In conclusion, DBH inhibitor nepicastat has an effect consistent with a decrease in the persistence of traumatic memories and anxiety-like behavior in this PTSD mice model. The disruption of traumatic memories through interference with the formation, consolidation, retrieval, and/or expression processes may be important to decrease PTSD symptoms and signs. The increase in Npas4 and Bdnf mRNA expression in the hippocampus may be important to develop a weaker traumatic contextual memory after nepicastat treatment.