DPYD genotyping and 5-fluoropyrimidine toxicity: An overview of systematic reviews protocol / Genotipado del gen DPYD y toxicidad de 5-fluoropirimidinas: Protocolo de una revisión de revisiones sistemáticas

Introduction: The increased risk of severe and life-threatening toxicity in patients with dihydropyridine dehydrogenase (DPD) deficiency, under treatment with fluoropyrimidines, has been widely studied. An up-to-date overview of systematic reviews summarizing existing literature can add value by highlighting most relevant information and supports decision-making regarding treatment in DPD deficient patients. The main objective of this overview of systematic reviews is to identify published systematic reviews on the association between germline variations in the DPYD gene and fluoropyrimidine toxicity.Methods and analysis: This protocol was developed following the Preferred Reported Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) checklist, and the overview of systematic reviews will be reported in accordance with the PRISMA statement. PubMed, Embase, Scopus, and the Cochrane Library will be searched from inception to 2023. Systematic reviews irrespective of study designs that analyze the association between germline variations in the DPYD and fluoropyrimidine toxicity will be considered. Methodological quality will be assessed using AMSTAR2 checklist (Measurement Tool to Assess Systematic Reviews 2). Two independent investigators will perform the study selection, quality assessment, and data collection. Discrepancies will be solved by a third investigator.(AU)

Introducción: El incremento del riesgo de toxicidad grave y potencialmente mortal en pacientes con deficiencia de dihidropiridina deshidrogenasa (DPD) en tratamiento con fluoropirimidinas ha sido ampliamente estudiado. Una revisión actualizada de las revisiones sistemáticas publicadas, que agrupe la literatura existente, puede añadir valor al resaltar la información más relevante y respaldar la toma de decisiones con respecto al tratamiento en pacientes con deficiencia de DPD. El objetivo principal de esta revisión de revisiones sistemáticas es identificar revisiones sistemáticas publicadas sobre la asociación entre variaciones en el linaje germinal del gen DPYD y la toxicidad de las fluoropirimidinas. Métodos y análisis: Este protocolo se ha desarrollado siguiendo la lista de verificación de los Protocolos para Revisiones Sistemáticas y Metaanálisis Preferidos (PRISMA-P), y la revisión de las revisiones sistemáticas se comunicará de acuerdo con la declaración PRISMA. Se realizará una búsqueda en PubMed, Embase, Scopus y la Biblioteca Cochrane desde su inicio hasta 2023. Se considerarán aquellas revisiones sistemáticas, independientemente de los diseños de estudio, que analicen la asociación entre variaciones en el linaje germinal del gen DPYD y la toxicidad de las fluoropirimidinas. La calidad metodológica se evaluará utilizando la lista de verificación AMSTAR2 (Herramienta de Medición para Evaluar Revisiones Sistemáticas 2). Dos investigadores independientes realizarán la selección de estudios, la evaluación de la calidad y la recopilación de datos. Las discrepancias se resolverán mediante un tercer investigador.(AU)

Genotipado del gen DPYD y toxicidad de 5-fluoropirimidinas: Protocolo de una revisión de revisiones sistemáticas / DPYD genotyping and 5-fluoropyrimidine toxicity: An overview of systematic reviews protocol

Introduction: The increased risk of severe and life-threatening toxicity in patients with dihydropyridine dehydrogenase (DPD) deficiency, under treatment with fluoropyrimidines, has been widely studied. An up-to-date overview of systematic reviews summarizing existing literature can add value by highlighting most relevant information and supports decision-making regarding treatment in DPD deficient patients. The main objective of this overview of systematic reviews is to identify published systematic reviews on the association between germline variations in the DPYD gene and fluoropyrimidine toxicity.Methods and analysis: This protocol was developed following the Preferred Reported Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) checklist, and the overview of systematic reviews will be reported in accordance with the PRISMA statement. PubMed, Embase, Scopus, and the Cochrane Library will be searched from inception to 2023. Systematic reviews irrespective of study designs that analyze the association between germline variations in the DPYD and fluoropyrimidine toxicity will be considered. Methodological quality will be assessed using AMSTAR2 checklist (Measurement Tool to Assess Systematic Reviews 2). Two independent investigators will perform the study selection, quality assessment, and data collection. Discrepancies will be solved by a third investigator.(AU)

Introducción: El incremento del riesgo de toxicidad grave y potencialmente mortal en pacientes con deficiencia de dihidropiridina deshidrogenasa (DPD) en tratamiento con fluoropirimidinas ha sido ampliamente estudiado. Una revisión actualizada de las revisiones sistemáticas publicadas, que agrupe la literatura existente, puede añadir valor al resaltar la información más relevante y respaldar la toma de decisiones con respecto al tratamiento en pacientes con deficiencia de DPD. El objetivo principal de esta revisión de revisiones sistemáticas es identificar revisiones sistemáticas publicadas sobre la asociación entre variaciones en el linaje germinal del gen DPYD y la toxicidad de las fluoropirimidinas. Métodos y análisis: Este protocolo se ha desarrollado siguiendo la lista de verificación de los Protocolos para Revisiones Sistemáticas y Metaanálisis Preferidos (PRISMA-P), y la revisión de las revisiones sistemáticas se comunicará de acuerdo con la declaración PRISMA. Se realizará una búsqueda en PubMed, Embase, Scopus y la Biblioteca Cochrane desde su inicio hasta 2023. Se considerarán aquellas revisiones sistemáticas, independientemente de los diseños de estudio, que analicen la asociación entre variaciones en el linaje germinal del gen DPYD y la toxicidad de las fluoropirimidinas. La calidad metodológica se evaluará utilizando la lista de verificación AMSTAR2 (Herramienta de Medición para Evaluar Revisiones Sistemáticas 2). Dos investigadores independientes realizarán la selección de estudios, la evaluación de la calidad y la recopilación de datos. Las discrepancias se resolverán mediante un tercer investigador.(AU)

The error of estimated GFR in predialysis care.

The error of estimated glomerular filtration rate (eGFR) and its consequences in predialysis are unknown. In this prospective multicentre study, 315 predialysis patients underwent measured GFR (mGFR) by the clearance of iohexol and eGFR by 52 formulas. Agreement between eGFR and mGFR was evaluated by concordance correlation coefficient (CCC), total deviation index (TDI) and coverage probability (CP). In a sub-analysis we assessed the impact of eGFR error on decision-making as (i) initiating dialysis, (ii) preparation for renal replacement therapy (RRT) and (iii) continuing clinical follow-up. For this sub-analysis, patients who started RRT due to clinical indications (uremia, fluid overload, etc.) were excluded. eGFR had scarce precision and accuracy in reflecting mGFR (average CCC 0.6, TDI 70% and cp 22%) both in creatinine- and cystatin-based formulas. Variations -larger than 10 ml/min- between mGFR and eGFR were frequent. The error of formulas would have suggested (a) premature preparation for RTT in 14% of stable patients evaluated by mGFR; (b) to continue clinical follow-up in 59% of subjects with indication for RTT preparation due to low GFRm and (c) to delay dialysis in all asymptomatic patients (n = 6) in whom RRT was indicated based on very low mGFR. The error of formulas in predialysis was frequent and large and may have consequences in clinical care.

Online platform for cardiopulmonary resuscitation and automated external defibrillator training in a rural area: a community clinical trial protocol.

INTRODUCTION: Sudden death resulting from cardiorespiratory arrest carries a high mortality rate and frequently occurs out of hospital. Immediate initiation of cardiopulmonary resuscitation (CPR) by witnesses, combined with automated external defibrillator (AED) use, has proven to double survival rates. Recognising the challenges of timely emergency services in rural areas, the implementation of basic CPR training programmes can improve survival outcomes. This study aims to evaluate the effectiveness of online CPR-AED training among residents in a rural area of Tarragona, Spain. METHODS: Quasi-experimental design, comprising two phases. Phase 1 involves assessing the effectiveness of online CPR-AED training in terms of knowledge acquisition. Phase 2 focuses on evaluating participant proficiency in CPR-AED simulation manoeuvres at 1 and 6 months post training. The main variables include the score difference between pre-training and post-training test (phase 1) and the outcomes of the simulated test (pass/fail; phase 2). Continuous variables will be compared using Student's t-test or Mann-Whitney U test, depending on normality. Pearson's χ2 test will be applied for categorical variables. A multivariate analysis will be conducted to identify independent factors influencing the main variable. ETHICS AND DISSEMINATION: This study adheres to the tenets outlined in the Declaration of Helsinki and of Good Clinical Practice. It operated within the Smartwatch project, approved by the Clinical Research Ethics Committee of the Primary Care Research Institute IDIAP Jordi Gol i Gurina Foundation, code 23/081-P. Data confidentiality aligns with Spanish and European Commission laws for the protection of personal data. The study's findings will be published in peer-reviewed journals and presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT05747495.

DPYD genotyping and 5-fluoropyrimidine toxicity: An overview of systematic reviews protocol. / [Artículo traducido] Genotipado del gen DPYD y toxicidad de las 5-fluoropirimidinas: protocolo de un resumen de revisiones sistemáticas.

INTRODUCTION: The increased risk of severe and life-threatening toxicity in patients with dihydropyridine dehydrogenase deficiency, under treatment with fluoropyrimidines, has been widely studied. An up-to-date overview of systematic reviews summarizing existing literature can add value by highlighting most relevant information and supports decision-making regarding treatment in dihydropyridine dehydrogenase deficient patients. The main objective of this overview is to identify published systematic reviews on the association between germline variations in the DPYD gene and fluoropyrimidine toxicity. METHODS AND ANALYSIS: This protocol was developed following the Preferred Reported Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) checklist, and the overview of systematic reviews will be reported in accordance with the PRISMA statement. PubMed, Embase, Scopus and the Cochrane Library will be searched from inception to 2023. Systematic reviews irrespective of study designs that analyze the association between germline variations in the DPYD and fluoropyrimidine toxicity will be considered. Methodological quality will be assessed using AMSTAR2 checklist (Measurement Tool to Assess Systematic Reviews 2). Two independent investigators will perform the study selection, quality assessment and data collection. Discrepancies will be solved by a third investigator.

DPYD genotyping and 5-fluoropyrimidine toxicity: An overview of systematic reviews protocol.

INTRODUCTION: The increased risk of severe and life-threatening toxicity in patients with dihydropyridine dehydrogenase (DPD) deficiency, under treatment with fluoropyrimidines, has been widely studied. An up-to-date overview of systematic reviews summarizing existing literature can add value by highlighting most relevant information and supports decision-making regarding treatment in DPD deficient patients. The main objective of this overview of systematic reviews is to identify published systematic reviews on the association between germline variations in the DPYD gene and fluoropyrimidine toxicity. METHODS AND ANALYSIS: This protocol was developed following the Preferred Reported Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) checklist, and the overview of systematic reviews will be reported in accordance with the PRISMA statement. PubMed, Embase, Scopus, and the Cochrane Library will be searched from inception to 2023. Systematic reviews irrespective of study designs that analyze the association between germline variations in the DPYD and fluoropyrimidine toxicity will be considered. Methodological quality will be assessed using AMSTAR2 checklist (Measurement Tool to Assess Systematic Reviews 2). Two independent investigators will perform the study selection, quality assessment, and data collection. Discrepancies will be solved by a third investigator. REGISTRATION DETAILS: Registration number in PROSPERO: CRD42023401226.

Adverse childhood experiences and stress among oral health students: a descriptive correlational study.

Background: Stress is a challenge to many post-secondary students and, if prolonged and unmanaged, can affect academic success. Understanding factors that contribute to students' stress is important. One possible contributor may be adverse childhood experiences (ACEs); that is, traumatic events that occur during the first 18 years of life. Inverse relationships between the number of ACEs and indicators of poor mental well-being have been proposed. Objective: To describe ACEs in oral health students (OHS) and the associations between the number and types of ACEs and levels of perceived stress, an indicator of mental well-being. Methods: Invitations to participate in an anonymous online cross-sectional survey were sent to all OHS, 19 years and older, attending Dalhousie University in Halifax, Nova Scotia, Canada. Self-reports of ACEs and perceived stress were collected. Zero-order correlations and regression modelling were used to examine associations. Results: Twenty-six percent (26%, n = 66) of OHS completed the survey. Respondents reported an average of 2.20 ACEs; 34.9% reported ≥ 3 ACEs. Emotional abuse (41%) was the most reported ACE. Associations were observed between numbers of ACEs and stress. Levels of stress increased with the number of ACEs (r = 0.23, p < 0.05). Regression modelling determined levels of stress were not affected by ACE type (F (3,62) = 2.24, p = 0.092). Discussion: This was the first study to examine associations between ACEs and perceived stress in OHS. These students reported greater numbers of ACEs than age-matched general populations. Levels of stress were associated with numbers of ACEs. Conclusion: Faculty in dental and dental hygiene programs should recognize the prevalence of ACEs among OHS and the potential impact on their mental well-being.

Contexte: Le stress est un défi pour de nombreux étudiants du postsecondaire : s'il est ressenti sur une longue période et s'il n'est pas géré, il peut nuire à la réussite scolaire. Il est important de comprendre les facteurs qui contribuent au stress des étudiants. Les expériences négatives durant l'enfance (ENE), c.-à-d. les événements traumatiques vécus au cours des 18 premières années de vie, peuvent constituer l'un de ces facteurs. On a suggéré une corrélation inverse entre le nombre d'ENE et les indicateurs d'un mauvais bien-être mental. Objectif: Décrire les ENE chez les étudiants en santé buccodentaire (ESB) et les corrélations entre les types et le nombre d'ENE d'une part et les niveaux de stress perçus, un indicateur du bien-être mental, d'autre part. Méthodes: On a fait parvenir des invitations à participer à un sondage transversal anonyme en ligne à tous les ESB âgés de 19 ans et plus qui fréquentent l'Université Dalhousie à Halifax, en Nouvelle-Écosse (Canada). On a recueilli des données autodéclarées sur les ENE et le stress perçu. Des corrélations d'ordre zéro et la modélisation par régression ont été utilisées pour examiner les relations entre les données. Résultats: Vingt-six pour cent (26 %, n = 66) des ESB ont répondu au sondage. En moyenne, les répondants ont fait mention de 2,20 ENE, et 34,9 % ont déclaré ≥ 3 ENE. La violence psychologique (41 %) était le type d'ENE le plus largement déclaré. On a constaté des corrélations entre le nombre d'ENE et le niveau de stress. Les niveaux de stress augmentaient avec le nombre d'ENE (r = 0,23, p < 0,05). La modélisation par régression a permis d'établir que les types d'ENE n'avaient pas d'incidence sur les niveaux de stress (F [3,62] = 2,24, p = 0,092). Discussion: Il s'agissait de la première étude à examiner les relations entre les ENE et le stress perçu par les ESB. Ces étudiants ont déclaré un plus grand nombre d'ENE que la même classe d'âge dans la population générale. On a constaté une corrélation entre les niveaux de stress et le nombre d'ENE. Conclusion: Les membres du corps professoral des programmes dentaires et d'hygiène dentaire doivent reconnaître la prévalence des ENE parmi les ESB ainsi que les effets éventuels sur leur bien-être mental.

First reported double drug-drug interaction in a cancer renal patient under everolimus treatment: therapeutic drug monitoring and review of literature.

Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) used in both transplantation and cancer treatment (breast, renal and neuroendocrine). In transplantation, therapeutic drug monitoring (TDM) is recommended due to the potential drug-drug interactions with chronic medications, which can affect everolimus pharmacokinetics. In cancer treatment, everolimus is used at higher doses than in transplantation and without a systematic drug monitoring.We present a case report of a 72-year-old woman with epilepsy history to whom everolimus 10 mg QD was prescribed as third line of treatment for renal cell carcinoma (RCC). The potential drug interactions between everolimus and the patient's chronic medications, carbamazepine and phenytoin, are significant as both are known as strong inducers CYP3A4 metabolism, potentially leading to underexposure to everolimus.TDM of everolimus was recommended by the pharmacist. The literature suggests that a minimum plasma concentration (Cminss) of everolimus over 10 ng/ml is associated with better response to treatment and progression-free survival (PFS). The patient's everolimus dose had to be increased until 10 mg BID, and regular monitoring of everolimus levels showed an increase in Cminss from 3.7 ng/ml to 10.8 ng/ml.This case highlights the importance of checking for potential drug interactions and monitoring everolimus levels in patients on chronic medication, especially those with several inducers or inhibitors of CYP3A4 metabolism. TDM can help to ensure that patients are treated with their optimal dose, which can improve the effectiveness of the treatment or minimize the risk of toxicities.

Adhesion of human pathogenic bacteria to endothelial cells is facilitated by fibronectin interaction.

Human pathogenic bacteria circulating in the bloodstream need to find a way to interact with endothelial cells (ECs) lining the blood vessels to infect and colonise the host. The extracellular matrix (ECM) of ECs might represent an attractive initial target for bacterial interaction, as many bacterial adhesins have reported affinities to ECM proteins, in particular to fibronectin (Fn). Here, we analysed the general role of EC-expressed Fn for bacterial adhesion. For this, we evaluated the expression levels of ECM coding genes in different ECs, revealing that Fn is the highest expressed gene and thereby, it is highly abundant in the ECM environment of ECs. The role of Fn as a mediator in bacterial cell-host adhesion was evaluated in adhesion assays of Acinetobacter baumannii, Bartonella henselae, Borrelia burgdorferi, and Staphylococcus aureus to ECs. The assays demonstrated that bacteria colocalised with Fn fibres, as observed by confocal laser scanning microscopy. Fn removal from the ECM environment (FN1 knockout ECs) diminished bacterial adherence to ECs in both static and dynamic adhesion assays to varying extents, as evaluated via absolute quantification using qPCR. Interactions between adhesins and Fn might represent the crucial step for the adhesion of human-pathogenic Gram-negative and Gram-positive bacteria targeting the ECs as a niche of infection.

Injury-induced activation of the endocannabinoid system promotes axon regeneration.

Regeneration after a peripheral nerve injury still remains a challenge, due to the limited regenerative potential of axons after injury. While the endocannabinoid system (ECS) has been widely studied for its neuroprotective and analgesic effects, its role in axonal regeneration and during the conditioning lesion remains unexplored. In this study, we observed that a peripheral nerve injury induces axonal regeneration through an increase in the endocannabinoid tone. We also enhanced the regenerative capacity of dorsal root ganglia (DRG) neurons through the inhibition of endocannabinoid degradative enzyme MAGL or a CB1R agonist. Our results suggest that the ECS, via CB1R and PI3K-pAkt pathway activation, plays an important role in promoting the intrinsic regenerative capacity of sensory neurons after injury.

Therapeutic Drug Monitoring of Lacosamide: Is 10 to 20 mg/L a Suitable Reference Range for Patients With Epilepsy?

OBJECTIVES: The reference range for lacosamide (LCM) has been updated from 1 to 10 mg/L to 10 to 20 mg/L. Historically, LCM range was defined from trough-level measurements, but the newer ranges were obtained from peak-level measurements. The purpose of the study was to evaluate the relationship between LCM plasma levels higher than 10 mg/L and the incidence of adverse effects. METHODS: This was a single-center, retrospective, observational study of adult outpatients with epilepsy who were prescribed LCM and had LCM serum concentrations (LCM-SCs) >10 mg/L on drug-fasting samples, measured from June 2017 to December 2020. RESULTS: A total of 55 LCM-SC samples corresponding to 44 patients (25 women [57%]) were analyzed. The median age was 47 (39-61) years. The median LCM-SC was 13.4 (11.2-17.8) mg/L. Adverse effects were reported in 18 patients (41%). Forty-eight percent (21 of 44) of patients required an LCM dose reduction, with a mean LCM-SC of 16.0 (13.2-18.1) mg/L, whereas, in the remaining patients (23 of 44), LCM dose was not modified, with a mean LCM-SC of 12.2 (10.7-14.2) mg/L ( P = 0.0244). Forty-one percent (18 of 44) of patients reported adverse effects related to LCM, with a mean LCM-SC of 15.6 (12.7-18.4) mg/L, whereas, in the remaining patients (26 of 44), adverse effects did not occur, with a mean LCM-SC of 12.6 (10.7-16.5) mg/L ( P = 0.0495). CONCLUSIONS: The 10 to 20 mg/L reference range clearly increases toxicity in patients treated with LCM. Adjusting the reference range upper limit to 12 mg/L with a routine therapeutic drug monitoring program is suggested, to achieve a reasonable probability of efficacy and decrease toxicity.

Peripheral CB1 receptor blockade acts as a memory enhancer through a noradrenergic mechanism.

Peripheral inputs continuously shape brain function and can influence memory acquisition, but the underlying mechanisms have not been fully understood. Cannabinoid type-1 receptor (CB1R) is a well-recognized player in memory performance, and its systemic modulation significantly influences memory function. By assessing low arousal/non-emotional recognition memory in mice, we found a relevant role of peripheral CB1R in memory persistence. Indeed, the peripherally-restricted CB1R specific antagonist AM6545 showed significant mnemonic effects that were occluded in adrenalectomized mice, and after peripheral adrenergic blockade. AM6545 also transiently impaired contextual fear memory extinction. Vagus nerve chemogenetic inhibition reduced AM6545-induced mnemonic effect. Genetic CB1R deletion in dopamine ß-hydroxylase-expressing cells enhanced recognition memory persistence. These observations support a role of peripheral CB1R modulating adrenergic tone relevant for cognition. Furthermore, AM6545 acutely improved brain connectivity and enhanced extracellular hippocampal norepinephrine. In agreement, intra-hippocampal ß-adrenergic blockade prevented AM6545 mnemonic effects. Altogether, we disclose a novel CB1R-dependent peripheral mechanism with implications relevant for lengthening the duration of non-emotional memory.

Effectiveness of an App for tobacco cessation in pregnant smokers (TOBBGEST): study protocol.

BACKGROUND: Tobacco consumption during pregnancy is one of the most modifiable causes of morbidity and mortality for both pregnant smokers and their foetus. Even though pregnant smokers are conscious about the negative effects of tobacco consumption, they also had barriers for smoking cessation and most of them continue smoking, being a major public health problem. The aim of this study is to determine the effectiveness of an application (App) for mobile devices, designed with a gamification strategy, in order to help pregnant smokers to quit smoking during pregnancy and in the long term. METHODS: This study is a multicentre randomized community intervention trial. It will recruit pregnant smokers (200 participants/group), aged more than 18 years, with sporadically or daily smoking habit in the last 30 days and who follow-up their pregnancy in the Sexual and Reproductive Health Care Services of the Camp de Tarragona and Central Catalonia Primary Care Departments. All the participants will have the usual clinical practice intervention for smoking cessation, whereas the intervention group will also have access to the App. The outcome measure will be prolonged abstinence at 12 months after the intervention, as confirmed by expired-carbon monoxide and urinary cotinine tests. Results will be analysed based on intention to treat. Prolonged abstinence rates will be compared, and the determining factors will be evaluated using multivariate statistical analysis. DISCUSSION: The results of this study will offer evidence about the effectiveness of an intervention using a mobile App in smoking cessation for pregnant smokers, to decrease comorbidity associated with long-term smoking. If this technology is proven effective, it could be readily incorporated into primary care intervention for all pregnant smokers. TRIAL REGISTRATION: Clinicaltrials.gov ID NCT05222958 . Trial registered 3 February 2022.

El pediatre davant un lactant amb dismorfisme cranial / El pediatra ante un lactante con dismorfia craneal / The pediatrician’s approach to an infant with cranial dysmorphism

Fonament. El dismorfisme cranial és una anomalia detectadasovint des de l’atenció primària. Els darrers anys la sevaincidència ha anat en augment a causa de la implantació dela campanya per evitar la mort sobtada dels lactants, en quèes recomana la posició en decúbit supí per dormir. Sovintaquesta troballa exploratòria és fruit de derivacions a especialistes atesa la dificultat que suposa diferenciar els dismorfismes cranials posturals dels d’origen sinostòtic, secundaris a la fusió prematura de les sutures cranials.Objectiu. Descriure la presentació clínica, l’exploració física, els possibles tractaments i el pronòstic dels diferentsdismorfismes cranials, posant un èmfasi especial en donarclaus per diferenciar els dismorfismes cranials posturalsdels sinostòtics.Mètode. Mitjançant revisió bibliogràfica, emprant les paraules clau «craniosynostosis» i «nonsynostotic plagiocephaly»a les bases de dades UpToDate i PubMed.Resultats. El tractament i el pronòstic dels dismorfismescranials varia en funció de l’etiologia i la gravetat. En lesdeformitats posicionals és primordial conèixer les mesurespreventives per evitar-los. D’altra banda, les craniosinostosis s’han de derivar a neurocirurgia i totes es tracten quirúrgicament. Operades a temps, les craniosinostosis solentenir molt bon pronòstic i se n’eviten les seqüeles.Conclusions. Té una importància vital saber diferenciar lesetiologies dels diferents dismorfismes cranials. Cal empoderar els pares de manera que puguin prevenir dismorfismes posturals i, com a pediatres, hem de ser capaços dereconèixer possibles craniosinostosis i derivar-les a la consulta especialitzada per fer un tractament precoç i millorarel pronòstic d’aquests infants. (AU)

Fundamento. Las dismorfias craneales son una anomalía detectadafrecuentemente desde la atención primaria. En los últimos años suincidencia ha ido en aumento debido a la implantación de la campaña para evitar la muerte súbita de los lactantes, donde se recomienda la posición en decúbito supino para dormir. A menudo este hallazgo exploratorio es fruto de derivaciones a especialistas dadala dificultad que supone diferenciar las dismorfias craneales posturales de las de origen sinostótico, secundarias a la fusión prematura de las suturas craneales.Objetivo. Describir la presentación clínica, la exploración física, losposibles tratamientos y el pronóstico de las diferentes dismorfiascraneales, poniendo especial énfasis en dar claves para diferenciarlas dismorfias craneales posturales de las sinostóticas.Método. Mediante revisión bibliográfica, usando las palabras clave«craniosynostosis» y «nonsynostotic plagiocephaly» en las basesde datos UpToDate y PubMed.Resultados. El tratamiento y pronóstico de las dismorfias cranealesvaría en función de su etiología y gravedad. En las deformidadesposicionales es primordial conocer las medidas preventivas paraevitarlas. Por otro lado, las craneosinostosis deben ser derivadas aneurocirugía y todas se tratan quirúrgicamente. Operadas a tiempo,las craneosinostosis suelen tener muy buen pronóstico y se evitanlas secuelas de esta entidad.Conclusiones. Es de vital importancia saber diferenciar las etiologías de las diferentes dismorfias craneales. Hay que empoderar alos padres de forma que puedan prevenir dismorfias posturales y,como pediatras, debemos ser capaces de reconocer posibles craneosinostosis y derivarlas a la consulta especializada para poderhacer un tratamiento precoz y mejorar el pronóstico de estos niños. (AU)

Background. Cranial dysmorphism is a congenital defect usuallydetected in primary care. Over the last few years, its incidence hasincreased due to the implementation of prone position for infantsduring sleep to avoid sudden death. Often, this finding results inreferrals to specialists given the difficulties in distinguishing between positional dysmorphism from those of syntostotic origin,which are secondary to premature fusion of the cranial sutures.Objective. To describe the clinical presentation, physical examination, possible treatments, and prognosis, of the different cranialdysmorphisms, and highlight the differential diagnosis betweenpositional dysmorphism and craniosynostosis.Method. Literature review of the UpToDate and PubMed databasesusing the key words “craniosynostosis” and “nonsynostotic plagiocephaly”. Results. The treatment and prognosis of cranial dysmorphism varies according to its etiology and severity. In positional deformitiesit is key to understand the possible preventive measures. Childrenwith craniosynostosis should be referred for neurosurgicaltreatment. With timely surgical correction, craniosynostosis have avery good prognosis with minimal sequelae.Conclusions. It is important to differentiate between the differentcauses of cranial dysmorphism. Parents should be educated toprevent positional deformities, and pediatricians should be able torecognize possible cases of craniosynostosis and refer them forearly treatment. (AU)

Type 2 Diabetes Mellitus and COVID-19: A Narrative Review.

Type-2 diabetes mellitus (T2DM) is a chronic metabolic disorder. The incidence and prevalence of patients with T2DM are increasing worldwide, even reaching epidemic values in most high- and middle-income countries. T2DM could be a risk factor of developing complications in other diseases. Indeed, some studies suggest a bidirectional interaction between T2DM and COVID-19. A growing body of evidence shows that COVID-19 prognosis in individuals with T2DM is worse compared with those without. Moreover, various studies have reported the emergence of newly diagnosed patients with T2DM after SARS-CoV-2 infection. The most common treatments for T2DM may influence SARS-CoV-2 and their implication in infection is briefly discussed in this review. A better understanding of the link between TD2M and COVID-19 could proactively identify risk factors and, as a result, develop strategies to improve the prognosis for these patients.

Nociception-Dependent CCL21 Induces Dorsal Root Ganglia Axonal Growth via CCR7-ERK Activation.

While chemokines were originally described for their ability to induce cell migration, many studies show how these proteins also take part in many other cell functions, acting as adaptable messengers in the communication between a diversity of cell types. In the nervous system, chemokines participate both in physiological and pathological processes, and while their expression is often described on glial and immune cells, growing evidence describes the expression of chemokines and their receptors in neurons, highlighting their potential in auto- and paracrine signalling. In this study we analysed the role of nociception in the neuronal chemokinome, and in turn their role in axonal growth. We found that stimulating TRPV1+ nociceptors induces a transient increase in CCL21. Interestingly we also found that CCL21 enhances neurite growth of large diameter proprioceptors in vitro. Consistent with this, we show that proprioceptors express the CCL21 receptor CCR7, and a CCR7 neutralizing antibody dose-dependently attenuates CCL21-induced neurite outgrowth. Mechanistically, we found that CCL21 binds locally to its receptor CCR7 at the growth cone, activating the downstream MEK-ERK pathway, that in turn activates N-WASP, triggering actin filament ramification in the growth cone, resulting in increased axonal growth.

Genetic control of neuronal activity enhances axonal growth only on permissive substrates.

BACKGROUND: Neural tissue has limited regenerative ability. To cope with that, in recent years a diverse set of novel tools has been used to tailor neurostimulation therapies and promote functional regeneration after axonal injuries. METHOD: In this report, we explore cell-specific methods to modulate neuronal activity, including opto- and chemogenetics to assess the effect of specific neuronal stimulation in the promotion of axonal regeneration after injury. RESULTS: Opto- and chemogenetic stimulations of neuronal activity elicited increased in vitro neurite outgrowth in both sensory and cortical neurons, as well as in vivo regeneration in the sciatic nerve, but not after spinal cord injury. Mechanistically, inhibitory substrates such as chondroitin sulfate proteoglycans block the activity induced increase in axonal growth. CONCLUSIONS: We found that genetic modulations of neuronal activity on both dorsal root ganglia and corticospinal motor neurons increase their axonal growth capacity but only on permissive environments.

Abordaje multidisciplinar de personas con enfermedad mental y problemas sociales desde Atención Primaria / Multidisciplinary approach to people with mental illness and social problems from Primary Care. A clinical case

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How Are Non-Medical Settlement Service Organizations Supporting Access to Healthcare and Mental Health Services for Immigrants: A Scoping Review.

Following resettlement in high-income countries, many immigrants and refugees experience barriers to accessing primary healthcare. Local non-medical settlement organizations, such as the Local Immigration Partnerships in Canada, that support immigrant integration, may also support access to mental health and healthcare services for immigrant populations. This scoping review aims to identify and map the types and characteristics of approaches and interventions that immigrant settlement organizations undertake to support access to primary healthcare for clients. We systematically searched MEDLINE, Social Services Abstracts, CINAHL, and PsycInfo databases from 1 May 2013 to 31 May 2021 and mapped research findings using the Social-Ecological Model. The search identified 3299 citations; 10 studies met all inclusion criteria. Results suggest these organizations support access to primary healthcare services, often at the individual, relationship and community level, by collaborating with health sector partners in the community, connecting clients to health services and service providers, advocating for immigrant health, providing educational programming, and initiating community development/mobilization and advocacy activities. Further research is needed to better understand the impact of local non-medical immigrant settlement organizations involved in health care planning and service delivery on reducing barriers to access in order for primary care services to reach marginalized, high-need immigrant populations.