Anxiety among children a year after the onset of the COVID-19 pandemic: a Brazilian cross-sectional online survey.

Aim: This study seeks to build upon a prior investigation into the impact of the COVID-19 pandemic and to evaluate the prevalence of anxiety among Brazilian children, along with its associated factors, one year after the commencement of the pandemic. Design: A cross-sectional study. Methods: A survey was conducted from April­May 2021 in Brazil. Children aged 6­12 and their guardians from five Brazilian regions were included. The Children's Anxiety Questionnaire (CAQ; scores 4­12) and Numerical Rating Scale (NRS; scores 0­10) were used to measure anxiety. Results: Of the 906 children, 53.3% were girls (average age = 8.79 ± 2.05 years). Mothers responded for 87.1% of the children, and 70.9% were from the Southeast region. Based on a CAQ score of ≥9 and an NRS score of ≥8, the anxiety prevalence was 24.9 and 34.9%, respectively. Using logistic regression, a CAQ ≥9 score was associated with older children and children with chronic disease or disability. An NRS score of ≥8 was associated with reduced family income during the pandemic, the person caring for the children, and with children with chronic disease or disability. Conclusion: These findings suggest the need to implement public health actions aimed at children with chronic diseases and disabilities and their parents to guide them regarding the warning signs and negative emotions. This study contributes to characterizing the evolution of the pandemic in Brazil and provides a basis for comparison with the literature from other countries.

Integrating health promotion with and for older people - eHealth (IHOPe) - evaluating remote integrated person-centred care : Protocol of a randomised controlled trial with effectiveness, health economic, and process evaluation.

BACKGROUND: Healthcare and welfare systems worldwide are unprepared to accommodate the growing population of older people. Simultaneously, the cost of reactive care for older people is increasing. However, healthcare systems in many countries are reforming towards integrated and person-centred care with a focus on health promotion and proactive actions. The Integrating Health Promotion with and for Older People - eHealth (IHOPe) project aims to describe and evaluate a person-centred e-support intervention that promotes a sustainable partnership between community-dwelling frail older people and health and social care professionals. METHODS: The IHOPe project is designed as a randomised controlled trial comparing a control group receiving standard care with an intervention group receiving standard care and add-on person-centred care through telephone support and a digital platform. The primary outcome measure is a composite score of changes in general self-efficacy and the need for unscheduled hospital care. The project is conducted in Gothenburg, Sweden. At least 220 participants aged ≥ 75 years will be included after being screened using a frailty instrument. The study design, intervention components, digital platform, and questionnaires were developed in close collaboration with an advisory group of inter-professional researchers, stakeholders, clinicians, and older representatives. Data will mainly be collected through questionnaires at baseline and 3, 6, and 12 months after inclusion in the study. Recruitment is ongoing and should be completed during 2023. Data will be analysed using quantitative and qualitative methods. The evaluation will include effectiveness, process, and health economics. The study was approved by the Regional Ethical Review Board in Gothenburg, Sweden (Dnr 2019-05364, Dnr 2020-03550, Dnr 2021-03255). DISCUSSION: The findings will expand our knowledge of remotely integrated person-centred care for frail older people. Thereby, the IHOPe project is expected to fill highlighted knowledge gaps on intervention evaluations including the triad of person-centred, digital, and integrated care elements, as well as economic evaluations of remote health services for frail older people. The study is ongoing, and the results are not completed but if they turn out to be positive, implementation is not limited to time or location. TRIAL REGISTRATION: ClinicalTrial.gov: NCT04416815. Registered 07/06/2021.

Older adults' provision of informal care and support to their peers - A cornerstone of swedish society: Demographic characteristics and experiences of social isolation.

BACKGROUND: Family members provide the majority of informal care for older adults in Sweden. Nevertheless, by providing a range of assistance, peers often emerge as a central to counter social isolation among older adults. Therefore, there is a need to know more about what informal care provision by older adults to their peers means for different groups of older adults. AIM: This study investigated the types of informal care and support that older adults provide to their peers in Sweden, and how these types of care and support are associated with demographic characteristics and social isolation. We also compared older adults who provide informal care and support with those who do not. METHOD: For this purpose, we used a national online survey named "Involuntary loneliness among senior citizens" answered by 10,044 older adults enrolled in the Swedish Citizen Panel. We adopted a mixed-method design to analyse the survey data, including free-text options (n = 2155) and numerical data. Social isolation was assessed using a score built from the social loneliness items of the UCLA Loneliness Scale. RESULTS: In our population, 21.5% of the older adults were providing informal care and support to their peers. Practical/instrumental help was frequently offered by younger participants (<75 years), men and respondents who were less socially isolated. On a general level, the factors that were positively associated with giving informal care and support to peers were older age, being male, retired, married/living in a relationship, living in an urban area/big city and exhibiting greater isolation. Focusing specifically on social support shows that older participants (>80) and those experiencing less social isolation (score < 24) were more engaged in social activities.  CONCLUSION: This paper is unique in exploring the informal peer-caregiver's perceptions of isolation. Data were collected during the COVID-19 pandemic; this highlights the need to recognise informal care and support between older adults and to acknowledge their contributions as an essential component of Swedish civil society, especially during a societal crisis.

Person-centred care: looking back, looking forward.

An interdisciplinary group of clinical and non-clinical academics in Sweden created a research centre for the study of person-centred care (PCC) in long-term illness: the University of Gothenburg Centre for Person-Centred Care (GPCC). The GPCC steering committee formulated a position paper with three 'simple routines' to initiate, implement, and safeguard PCC in daily clinical practice. The EJCN accepted this position paper for publication in 2011. This brief review seeks to present how PCC, as defined in the position paper, has been used in research and published in EJCN during the past 5 years (2016-20). Clinical implications and future research in PCC are also suggested.

A systematic review on implementation of person-centered care interventions for older people in out-of-hospital settings.

THE PURPOSE: of this study was to explore the content and essential components of implemented person-centered care in the out-of-hospital context for older people (65+). METHOD: A systematic review was conducted, searching for published research in electronic databases: PubMed, CINAHL, Scopus, PsycInfo, Web of Science and Embase between 2017 and 2019. Original studies with both qualitative and quantitative methods were included and assessed according to the quality assessment tools EPHPP and CASP. The review was limited to studies published in English, Swedish, Danish, Norwegian and Spanish. RESULTS: In total, 63 original articles were included from 1772 hits. The results of the final synthesis revealed the following four interrelated themes, which are crucial for implementing person-centered care: (1) Knowing and confirming the patient as a whole person; (2) Co-creating a tailored personal health plan; (3) Inter-professional teamwork and collaboration with and for the older person and his/her relatives; and (4) Building a person-centered foundation. CONCLUSION: Approaching an interpersonal and inter-professional teamwork and consultation with focus on preventive and health promoting actions is a crucial prerequisite to co-create optimal health care practice with and for older people and their relatives in their unique context.

Children's Anxiety and Factors Related to the COVID-19 Pandemic: An Exploratory Study Using the Children's Anxiety Questionnaire and the Numerical Rating Scale.

The repercussions of the COVID-19 pandemic on children's lives deserve attention. This study aimed to assess the prevalence of anxiety among Brazilian children and its associated factors during social distancing during COVID-19. We used a cross-sectional design with an online survey from April to May 2020 in Brazil. We included children aged 6-12 years and their guardians. The Children's Anxiety Questionnaire (CAQ; scores 4-12) and the Numerical Rating Scale (NRS; scores 0-10) were used to measure anxiety. We enrolled 157 girls and 132 boys, with a mean age of 8.84 (±2.05) years; 88.9% of respondents were mothers. Based on CAQ ≥ 9, the prevalence of anxiety was 19.4% (n = 56), and higher among children with parents with essential jobs and those who were social distancing without parents. In logistic regression, the following variables were associated with higher CAQ scores: social distancing without parents; more persons living together in home; and education level of guardians. Based on NRS > 7, the prevalence of anxiety was 21.8% (n = 63); however, no associations with NRS scores were found with the investigated variables. These findings suggest the necessity of implementing public health actions targeting these parents and their children at the population level.

[Ethical guides, criteria for admission in intensive care, palliative care. Multi-society recommendations for allocation of resources during the COVID-19 pandemic]. / Guías éticas para la atención durante la pandemia COVID-19. Recomendaciones multisocietarias para asignación de recursos.

Guidelines on resource allocation, ethics, triage processes with admission and discharge criteria from critical care and palliative care units during the pandemia are here presented. The interdisciplinary and multi-society panel that prepared these guidelines represented by bioethicists and specialists linked to the end of life: clinicians, geriatricians, emergentologists, intensivists, and experts in palliative care and cardiopulmonary resuscitation. The available information indicates that approximately 80% of people with COVID-19 will develop mild symptoms and will not require hospital care, while 15% will require intermediate or general room care, and the remaining 5% will require assistance in intensive care units. The need to think about justice and establish ethical criteria for allocation patients arise in conditions of exceeding available resources, such as outbreaks of diseases and pandemics, with transparency being the main criterion for allocation. These guides recommend general criteria for the allocation of resources relies on bioethical considerations, rooted in Human Rights and based on the value of the dignity of the human person and substantial principles such as solidarity, justice and equity. The guides are recommendations of general scope and their usefulness is to accompany and sustain the technical and scientific decisions made by the different specialists in the care of critically ill patients, but given the dynamic nature of the pandemic, a process of permanent revision and adaptation of recommendations must be ensured.

Se presentan las guías sobre ética de asignación de recursos, procesos de triaje con criterios de ingreso y egreso de unidades de cuidados críticos y atención paliativa durante la pandemia. El panel interdisciplinario y multisocietario que las preparó estuvo representado por bioeticistas y por especialistas vinculados al fin de la vida: clínicos, geriatras, emergentólogos, intensivistas, expertos en cuidados paliativos y en reanimación cardiopulmonar. La información disponible indica que aproximadamente 80% de las personas con COVID-19 desarrollarán síntomas leves y no requerirán asistencia hospitalaria, mientras que 15% precisará cuidados intermedios o en salas generales, y el 5% restante requerirá de asistencia en unidades de cuidados intensivos. La necesidad de pensar en justicia y establecer criterios éticos de asignación surgen en condiciones de superación de los recursos disponibles, como en brotes de enfermedades y pandemias, siendo la transparencia el principal criterio para la asignación. Estas guías recomiendan criterios generales de asignación de recursos en base a consideraciones bioéticas, enraizadas en los Derechos Humanos y sustentadas en el valor de la dignidad de la persona humana y principios sustanciales como la solidaridad, la justicia y la equidad. Las guías son recomendaciones de alcance general y su utilidad consiste en acompañar y sostener las decisiones técnicas y científicas que tomen los distintos especialistas en la atención del paciente crítico, pero dado el carácter dinámico de la pandemia, debe asegurarse un proceso de revisión y readaptación permanente de las recomendaciones.

Guías éticas para la atención durante la pandemia COVID-19: Recomendaciones multisocietarias para asignación de recursos / Ethical guides, criteria for admission in intensive care, palliative care. Multi-society recommendations for allocation of resources during the COVID-19 pandemic

Se presentan las guías sobre ética de asignación de recursos, procesos de triaje con criterios de ingreso y egreso de unidades de cuidados críticos y atención paliativa durante la pandemia. El panel interdisciplinario y multisocietario que las preparó estuvo representado por bioeticistas y por especialistas vinculados al fin de la vida: clínicos, geriatras, emergentólogos, intensivistas, expertos en cuidados paliativos y en reanimación cardiopulmonar. La información disponible indica que aproximadamente 80% de las personas con COVID-19 desarrollarán síntomas leves y no requerirán asistencia hospitalaria, mientras que 15% precisará cuidados intermedios o en salas generales, y el 5% restante requerirá de asistencia en unidades de cuidados intensivos. La necesidad de pensar en justicia y establecer criterios éticos de asignación surgen en condiciones de superación de los recursos disponibles, como en brotes de enfermedades y pandemias, siendo la transparencia el principal criterio para la asignación. Estas guías recomiendan criterios generales de asignación de recursos en base a consideraciones bioéticas, enraizadas en los Derechos Humanos y sustentadas en el valor de la dignidad de la persona humana y principios sustanciales como la solidaridad, la justicia y la equidad. Las guías son recomendaciones de alcance general y su utilidad consiste en acompañar y sostener las decisiones técnicas y científicas que tomen los distintos especialistas en la atención del paciente crítico, pero dado el carácter dinámico de la pandemia, debe asegurarse un proceso de revisión y readaptación permanente de las recomendaciones.

Guidelines on resource allocation, ethics, triage processes with admission and discharge criteria from critical care and palliative care units during the pandemia are here presented. The interdisciplinary and multi-society panel that prepared these guidelines represented by bioethicists and specialists linked to the end of life: clinicians, geriatricians, emergentologists, intensivists, and experts in palliative care and cardiopulmonary resuscitation. The available information indicates that approximately 80% of people with COVID-19 will develop mild symptoms and will not require hospital care, while 15% will require intermediate or general room care, and the remaining 5% will require assistance in intensive care units. The need to think about justice and establish ethical criteria for allocation patients arise in conditions of exceeding available resources, such as outbreaks of diseases and pandemics, with transparency being the main criterion for allocation. These guides recommend general criteria for the allocation of resources relies on bioethical considerations, rooted in Human Rights and based on the value of the dignity of the human person and substantial principles such as solidarity, justice and equity. The guides are recommendations of general scope and their usefulness is to accompany and sustain the technical and scientific decisions made by the different specialists in the care of critically ill patients, but given the dynamic nature of the pandemic, a process of permanent revision and adaptation of recommendations must be ensured.

Perceptions, experiences and barriers to lifestyle modifications in first-generation Middle Eastern immigrants to Sweden: a qualitative study.

OBJECTIVE: The prevalence of type 2 diabetes (T2D) among Iraqi immigrants to Sweden is high and partly related to sedentary physical activity and calorie dense food. The aim of the present study was to explore perceptions, experiences and barriers concerning lifestyle modifications (LSM) in Iraqi immigrants to Sweden at risk for T2D. DESIGN: A qualitative thematic analysis was conducted on data collected from gender-specific focus group interviews which took place during a culturally adapted randomised controlled intervention study addressing motivation to lifestyle change, self-empowerment, behavioural modifications and sociocultural barriers to LSM. Seven focus groups were held, with an interval of 1-4 weeks between January and May of 2015; each session lasted approximately 1.5 hours. SETTING: The city of Malmö, Sweden. PARTICIPANTS: Out of 27 women and 23 men assigned to the intervention group, 19 women and 14 men who attended at least one focus group session were included in the study. RESULTS: Participants expressed awareness of the content of healthy lifestyle practices. They also expressed numerous social and cultural barriers to LSM connected to irregular meals, overeating, food and drinking preferences and family expectations. Overeating was described as a consequence of social and cultural norms and expectations and of poor mental well-being. Facilitators for reaching successful LSM were connected to family involvement and support. CONCLUSION: Our study reports that facilitators for LSM are connected to presence of family support. Preventive actions addressing family involvement may benefit Middle Eastern immigrants at high risk for T2D to consider healthier lifestyles practices. Identification of sociocultural barriers and facilitators for LSM are crucial for successful health promotion in minority populations at risk for T2D. TRIAL REGISTRATION: Trial registration number: NCT01420198 for the MEDIM-study; Pre-results.

Emricasan Ameliorates Portal Hypertension and Liver Fibrosis in Cirrhotic Rats Through a Hepatocyte-Mediated Paracrine Mechanism.

In cirrhosis, liver microvascular dysfunction is a key factor increasing hepatic vascular resistance to portal blood flow, which leads to portal hypertension. De-regulated inflammatory and pro-apoptotic processes due to chronic injury play important roles in the dysfunction of liver sinusoidal cells. The present study aimed at characterizing the effects of the pan-caspase inhibitor emricasan on systemic and hepatic hemodynamics, hepatic cells phenotype, and underlying mechanisms in preclinical models of advanced chronic liver disease. We investigated the effects of 7-day emricasan on hepatic and systemic hemodynamics, liver function, hepatic microcirculatory function, inflammation, fibrosis, hepatic cells phenotype, and paracrine interactions in rats with advanced cirrhosis due to chronic CCl4 administration. The hepato-protective effects of emricasan were additionally investigated in cells isolated from human cirrhotic livers. Cirrhotic rats receiving emricasan showed significantly lower portal pressure than vehicle-treated animals with no changes in portal blood flow, indicating improved vascular resistance. Hemodynamic improvement was associated with significantly better liver function, reduced hepatic inflammation, improved phenotype of hepatocytes, liver sinusoidal endothelial cells, hepatic stellate cells and macrophages, and reduced fibrosis. In vitro experiments demonstrated that emricasan exerted its benefits directly improving hepatocytes' expression of specific markers and synthetic capacity, and ameliorated nonparenchymal cells through a paracrine mechanism mediated by small extracellular vesicles released by hepatocytes. Conclusion: This study demonstrates that emricasan improves liver sinusoidal microvascular dysfunction in cirrhosis, which leads to marked amelioration in fibrosis, portal hypertension and liver function, and therefore encourages its clinical evaluation in the treatment of advanced chronic liver disease.

Establishing a Core Outcome Measure for Life Participation: A Standardized Outcomes in Nephrology-kidney Transplantation Consensus Workshop Report.

BACKGROUND: Kidney transplantation confers substantial survival and quality of life benefits for many patients with end-stage kidney disease compared with dialysis, but complications and side effects of immunosuppression can impair participation in daily life activities. Life participation is a critically important patient-reported outcome for kidney transplant recipients but is infrequently and inconsistently measured in trials. We convened a consensus workshop on establishing an outcome measure for life participation for use in all trials in kidney transplantation. METHODS: Twenty-five (43%) kidney transplant recipients/caregivers and 33 (57%) health professionals from 8 countries participated in 6 facilitated breakout group discussions. Transcripts were analyzed thematically. RESULTS: Four themes were identified. Returning to normality conveyed the patients' goals to fulfill their roles (ie, in their family, work, and community) and reestablish a normal lifestyle after transplant. Recognizing the diverse meaning and activities of "life" explicitly acknowledged life participation as a subjective concept that could refer to different activities (eg, employment, recreation, family duties) for each individual patient. Capturing vulnerability and fluctuations posttransplant (eg, due to complications and side-effects) distinguished between experiences in the first year posttransplant and the long-term impact of transplantation. Having a scientifically rigorous, feasible, and meaningful measure was expected to enable consistent and frequent assessment of life participation in trials in kidney transplantation. CONCLUSIONS: A feasible and validated core outcome measure for life participation is needed so that this critically important patient-reported outcome can be consistently and meaningfully assessed in trials in kidney transplantation to inform decision making and care of recipients.

Emricasan, a pan-caspase inhibitor, improves survival and portal hypertension in a murine model of common bile-duct ligation.

Development of portal hypertension (PHT) is a central prognostic factor in patients with cirrhosis. Circulating microparticles (MPs) are released by hepatocytes in a caspase-dependent manner, are increased in circulation of patients with cirrhosis, and contribute to PHT via induction of impaired vasoconstrictor responses. Here, we tested the hypothesis that emricasan, a pan-caspase inhibitor, ameliorates PHT and reduction in release of MPs. We used a short-term and long-term protocol following common bile-duct ligation (BDL) in C57BL/6 mice (10 and 20 days, respectively). Mice were treated daily via intraperitoneal injection with 10 mg/kg/day of emricasan or placebo. Circulating MP levels were analyzed using flow cytometry and function via ex vivo angiogenesis assays. In contrast to BDL-placebo group, nearly all BDL-emricasan-treated mice survived after long-term BDL. Assessment of portal pressure showed a significant increase in BDL-placebo mice compared to sham-placebo mice. In contrast, BDL-emricasan mice had significantly lower levels of portal pressure compared to BDL-placebo mice. Although emricasan treatment resulted in a decrease in fibrosis, the changes did not reach statistical significance, suggesting that the effects on PHT are at least in part independent of the anti-fibrotic effects of the drug. Following short-term BDL, hepatocellular cell death as well as liver fibrosis had improved and circulating MPs were significantly reduced in BDL-emricasan mice compared to BDL-placebo. Circulating MPs from BDL-placebo mice induced endothelial cell activation, and this was significantly reduced in MPs from BDL-emricasan mice. Our results indicate that emricasan treatment improves survival and PHT in a murine model of long-term BDL. Emricasan is a promising agent for the treatment of PHT. KEY MESSAGE: Emricasan, a pan-caspase inhibitor, improves survival and portal hypertension induced by long-term bile-duct ligation (BDL) in mice Emricasan reduces liver damage, hepatocyte death, and fibrosis, following short-term BDL in mice, and these changes are associated with a decrease in circulating microparticle (MPs) Circulating MPs from BDL-placebo but not from BDL-emiricasan-treated mice activate endothelial cells ex vivo.

Caspase Inhibition Reduces Hepatic Tissue Factor-Driven Coagulation In Vitro and In Vivo.

Tissue factor (TF) is the primary activator of the blood coagulation cascade. Liver parenchymal cells (ie, hepatocytes) express TF in a molecular state that lacks procoagulant activity. Hepatocyte apoptosis is an important feature of acute and chronic liver diseases, and Fas-induced apoptosis increases hepatocyte TF procoagulant activity in vitro. We determined the impact of a pan-caspase inhibitor, IDN-7314, on hepatocyte TF activity in vitro and TF-mediated coagulation in vivo. Treatment of primary mouse hepatocytes with the Fas death receptor ligand (Jo2, 0.5 µg/ml) for 8 h increased hepatocyte TF procoagulant activity and caused release of TF-positive microvesicles. Pretreatment with 100 nM IDN-7314 abolished Jo2-induced caspase-3/7 activity and significantly reduced hepatocyte TF procoagulant activity and release of TF-positive microvesicles. Treatment of wild-type C57BL/6 mice with a sublethal dose of Jo2 (0.35 mg/kg) for 4.5 h increased coagulation, measured by a significant increase in plasma thrombin-antithrombin and TF-positive microvesicles. Total plasma microvesicle-associated TF activity was reduced in mice lacking hepatocyte TF; suggesting TF-positive microvesicles are released from the apoptotic liver. Fibrin(ogen) deposition increased in livers of Jo2-treated wild-type mice and colocalized primarily with cleaved caspase-3-positive hepatocytes. Pretreatment with IDN-7314 reduced caspase-3 activation, prevented the procoagulant changes in Jo2-treated mice, and reduced hepatocellular injury. Overall, the results indicate a central role for caspase activity in TF-mediated activation of coagulation following apoptotic liver injury. Moreover, the results suggest that liver-selective caspase inhibition may be a putative strategy to limit procoagulant and prothrombotic changes in patients with chronic liver disease.

Caffeine combined with sedative/anesthetic drugs triggers widespread neuroapoptosis in a mouse model of prematurity.

OBJECTIVES: Caffeine (CAF) and sedative/anesthetic drugs (SADs) are often coadministered to premature infants in the neonatal intensive care unit (NICU). While SAD neurotoxicity in the developing brain is well established, it is not fully clear whether CAF interacts with SADs and whether this interaction is detrimental. Using a mouse model of prematurity, we hypothesized that CAF would increase apoptotic neurotoxicity when coadministered with SADs. METHODS: Postnatal day 3 mice were treated with vehicle or 80 mg/kg CAF prior to challenge with 6 mg/kg midazolam, 40 mg/kg ketamine, or 40 µg/kg fentanyl. Six hours later, pups were sacrificed for activated caspase 3 (AC3) immunohistochemistry, and number of AC3 positive cells per mm3 throughout neocortex, hippocampus, caudate, thalamus, and colliculi was analyzed. RESULTS: CAF caused a statistically significant increase in AC3 positive cells when coadministered with midazolam (p = 0.002), ketamine (p = 0.014), or fentanyl (p < 0.001). Our composite dataset suggests that the addition of CAF to these SADs has a supra-additive effect, causing more neurotoxicity than expected. CONCLUSIONS: CAF may augment the neurotoxic action of SADs indicated for neonatal sedation/anesthesia in the NICU by triggering widespread apoptosis in the developing brains of premature infants.

Dexmedetomidine protects against glucocorticoid induced progenitor cell apoptosis in neonatal mouse cerebellum.

OBJECTIVES: Glucocorticoids (GCs) are used to improve respiratory mechanics in preterm infants despite clinical evidence linking neonatal GC therapy to cerebellar pathology. In developing mouse cerebellum, the GC dexamethasone (DEX) causes rapid GC-induced neural progenitor cell apoptosis (GINA). Focusing on pharmacological neuroprotection strategies, we investigated whether dexmedetomidine (DMT) protects against GINA. METHODS: Neonatal mice were pretreated with DMT prior to DEX challenge. Additionally, we tested clonidine and yohimbine in vivo to determine mechanism of DMT neuroprotection. For in vitro studies, cerebellar neural progenitor cells were pretreated with DMT before DEX challenge. RESULTS: In vivo, DMT attenuated GINA at 1 µg/kg and above, p < 0.0001. Clonidine significantly attenuated GINA, p < 0.0001, while yohimbine reversed DMT neuroprotection, p < 0.0001, suggesting DMT neuroprotection is likely mediated via adrenergic signaling. In vitro, DMT neuroprotection was achieved at 10 µM and above, p < 0.001, indicating DMT rescue is cell autonomous. CONCLUSIONS: DMT affords dose-dependent neuroprotection from GINA at clinically relevant doses, an effect that is cell autonomous and likely mediated by α2 adrenergic receptor agonism. DMT co-administration with GCs may be an effective strategy to protect the neonatal brain from GINA while retaining the beneficial effects of GCs on respiratory mechanics.

Calidad de vida relacionada con la salud en escolares de 10 a 14 años con sobrepeso y obesidad en la ciudad de Medellín, Colombia / Health Related-quality of Life in Schoolchildren with Obesity and Overweight in Medellin, Colombia

El exceso de peso a tempranas edades afecta la salud física y mental de niños y niñas y puede repercutir en su calidad de vida. Objetivo: evaluar la calidad de vida relacionada con salud (CVRS) en escolares con y sin sobrepeso y obesidad de una institución educativa de Medellín (Colombia). Población y Métodos: Se realizó un estudio transversal de tipo descriptivo-comparativo. La muestra fue probabilística con 679 escolares participantes de ambos sexos, con edades entre los 10 y 14 años de edad. El instrumento usado para determinar el estado nutricional fue el ANTHRO-PLUS y para medir CVRS utilizó el KIDSCREEN-27. Resultados: el 24 % de los participantes tenían exceso de peso, 19.9 % de ellos con sobrepeso y el 4.1 % con obesidad. En relación con la CVRS, los escolares con sobrepeso y obesidad se perciben con más problemas de actividad física y salud (AF) y menos aceptación social (AS). Para los hombres, el exceso de peso afecta las posibilidades de realizar la misma actividad física que sus pares, convirtiéndose fácilmente en objeto de burla e intimidación. Para las mujeres, la percepción de su CVRS no varió significativamente tuvieran normo o sobrepeso. Conclusiones: la percepción de CVRS de los escolares no es homogénea, está afectada por la edad, el sexo y los condicionantes culturales alrededor de la construcción de la imagen corporal.

Excess weight affects the physical and mental health of children and can affect their quality of life. Objetive: Evaluate the quality of life related to health (HRQOL) in schoolchildren with and without overweight and obesity of an educational institution of Medellin (Colombia). Methods: A descriptive crosssectional study was conducted comparative type. The sample was probabilistic school with 679 participants of both sexes aged between 10 and 14 years old. The instrument used to determine the nutritional status was ANTHRO-PLUS and measure HRQOL used the KIDSCREEN-27. Results: Participants were overweight 24%; overweight children were 19% and 4% of them were obese. Regarding school HRQOL overweight and obesity are perceived more problems physical activity and health (AF) and less social acceptance (AS). For men being overweight it affects the chances of performing the same physical activity as their peers and becoming easily mocked and intimidation. For women, the perception of HRQOL did not differ significantly had normal or overweight. Conclusions: The perception of HRQOL of school is not homogeneous, is affected by age, sex and cultural conditions around the construction of body image.

Alcohol stimulates macrophage activation through caspase-dependent hepatocyte derived release of CD40L containing extracellular vesicles.

BACKGROUND & AIMS: The mechanisms by which hepatocyte exposure to alcohol activates inflammatory cells such as macrophages in alcoholic liver disease (ALD) are unclear. The role of released nano-sized membrane vesicles, termed extracellular vesicles (EV), in cell-to-cell communication has become increasingly recognized. We tested the hypothesis that hepatocytes exposed to alcohol may increase EV release to elicit macrophage activation. METHODS: Primary hepatocytes or HepG2 hepatocyte cell lines overexpressing ethanol-metabolizing enzymes alcohol dehydrogenase (HepG2(ADH)) or cytochrome P450 2E1 (HepG2(Cyp2E1)) were treated with ethanol and EV release was quantified with nanoparticle tracking analysis. EV mediated macrophage activation was monitored by analysing inflammatory cytokines and macrophage associated mRNA expression, immunohistochemistry, biochemical serum alanine aminotransferase and triglycerides analysis in our in vitro macrophage activation and in vivo murine ethanol feeding studies. RESULTS: Ethanol significantly increased EV release by 3.3-fold from HepG2(Cyp2E1) cells and was associated with activation of caspase-3. Blockade of caspase activation with pharmacological or genetic approaches abrogated alcohol-induced EV release. EV stimulated macrophage activation and inflammatory cytokine induction. An unbiased microarray-based approach and antibody neutralization experiments demonstrated a critical role of CD40 ligand (CD40L) in EV mediated macrophage activation. In vivo, wild-type mice receiving a pan-caspase, Rho kinase inhibitor or with genetic deletion of CD40 (CD40(-/-)) or the caspase-activating TRAIL receptor (TR(-/-)), were protected from alcohol-induced injury and associated macrophage infiltration. Moreover, serum from patients with alcoholic hepatitis showed increased levels of CD40L enriched EV. CONCLUSION: In conclusion, hepatocytes release CD40L containing EV in a caspase-dependent manner in response to alcohol exposure which promotes macrophage activation, contributing to inflammation in ALD.

Perceptions and Practices of Physical Activity Among Colombian Overweight/Obese Schoolchildren.

The purpose of this study was to explore the contexts that shape obese children's engagement in physical activity (PA) focusing on children's perceptions. The qualitative design consisted of non-participant observations, and unstructured and semi-structured focus group and individual interviews. Data were analyzed by use of conventional content analysis. Participants were overweight/obese children from a public school in Colombia. The findings show that the main context where PA took place was during physical education (PE) classes at school and in the children's neighborhoods. The participants perceived the PE classes to be too competitive and demotivating. PA taking place outside school was associated with fun, but occurred only on an infrequent basis and was challenged by living in insecure neighborhoods. Adapting a health promotion approach that emphasizes participation and social environments might motivate obese children to become physically active at school as well as during leisure time.

The effect of the stay active advice on physical activity and on the course of acute severe low back pain.

BACKGROUND: Disability due to acute low back pain (ALBP) runs parallel with distress and physical inactivity. If low back pain persists, this may lead to long-term sick leave and chronic back pain. This prospective randomized study evaluated the effect on physical activity and on the course of ALBP of two different treatment advices provided in routine care. METHODS: Ninety-nine patients with acute severe LBP examined within 48 h after pain onset were randomized to the treatment advices "Stay active in spite of pain" (stay active group) or "Adjust activity to the pain" (adjust activity group). Pedometer step count and pain intensity (Numeric Rating Scale, NRS, 0-10) were followed daily during seven days. Linear mixed modeling were employed for statistical analyses. RESULTS: The step count change trajectory showed a curvilinear shape with a steep initial increase reaching a plateau after day 3 in both groups, followed by an additional increase to day 7 in the stay active group only. At day 1, the step count was 4560 in the stay active group compared to 4317 in adjust activity group (p = 0.76). Although there were no statistical differences between the two groups in the parameters describing the change trajectory for step count, the increase in step count was larger in the stay active group. At day 7 the step count was 9865 in the stay active group compared to 6609 in the adjust activity group (p = 0.008). The pain intensity (NRS) trajectory was similar in the two groups. Between day 1 and day 7 it decreased linearly from 5.0 to 2.8 in the stay active group (p < 0.001), and from 4.8 to 2.3 in the adjust activity group (p < 0.001). CONCLUSIONS: Patients with acute severe LBP advised to stay active in spite of the pain exhibited a considerable more active behavior compared to patients adjusting their activity to pain. This result confirms compliance to the treatment advice as well as the utility of the stay active advice to promote additional physical activity for more health benefits in patients with ALBP. There was minimal effect of the treatment advice on the course of ALBP. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02517762).

Hedgehog regulates cerebellar progenitor cell and medulloblastoma apoptosis.

The external granule layer (EGL) is a proliferative region that produces over 90% of the neurons in the cerebellum but can also malignantly transform into a cerebellar tumor called the medulloblastoma (the most common malignant brain tumor in children). Current dogma considers Hedgehog stimulation a potent proliferative signal for EGL neural progenitor cells (NPCs) and medulloblastomas. However, the Hedgehog pathway also acts as a survival signal in the neural tube where it regulates dorsoventral patterning by controlling NPC apoptosis. Here we show that Hedgehog stimulation is also a potent survival signal in the EGL and medulloblastomas that produces a massive apoptotic response within hours of signal loss in mice. This toxicity can be produced by numerous Hedgehog antagonists (vismodegib, cyclopamine, and jervine) and is Bax/Bak dependent but p53 independent. Finally, since glucocorticoids can also induce EGL and medulloblastoma apoptosis, we show that Hedgehog's effects on apoptosis can occur independent of glucocorticoid stimulation. This effect may play a major role in cerebellar development by directing where EGL proliferation occurs thereby morphologically sculpting growth. It may also be a previously unknown major therapeutic effect of Hedgehog antagonists during medulloblastoma therapy. Results are discussed in terms of their implications for both cerebellar development and medulloblastoma treatment.