Senescent accelerated prone 8 (SAMP8) mice as a model of age dependent neuroinflammation.

BACKGROUND: Aging and age-related diseases are strong risk factors for the development of neurodegenerative diseases. Neuroinflammation (NIF), as the brain's immune response, plays an important role in aged associated degeneration of central nervous system (CNS). There is a need for well characterized animal models that will allow the scientific community to understand and modulate this process. METHODS: We have analyzed aging-phenotypical and inflammatory changes of brain myeloid cells (bMyC) in a senescent accelerated prone aged (SAMP8) mouse model, and compared with their senescence resistant control mice (SAMR1). We have performed morphometric methods to evaluate the architecture of cellular prolongations and determined the appearance of Iba1+ clustered cells with aging. To analyze specific constant brain areas, we have performed stereology measurements of Iba1+ cells in the hippocampal formation. We have isolated bMyC from brain parenchyma (BP) and choroid plexus plus meningeal membranes (m/Ch), and analyzed their response to systemic lipopolysaccharide (LPS)-driven inflammation. RESULTS: Aged 10 months old SAMP8 mice present many of the hallmarks of aging-dependent neuroinflammation when compared with their SAMR1 control, i.e., increase of protein aggregates, presence of Iba1+ clusters, but not an increase in the number of Iba1+ cells. We have further observed an increase of main inflammatory mediator IL-1ß, and an augment of border MHCII+Iba1+ cells. Isolated CD45+ bMyC from brain parenchyma (BP) and choroid plexus plus meningeal membranes (m/Ch) have been analyzed, showing that there is not a significant increase of CD45+ cells from the periphery. Our data support that aged-driven pro-inflammatory cytokine interleukin 1 beta (IL-1ß) transcription is enhanced in CD45+BP cells. Furthermore, LPS-driven systemic inflammation produces inflammatory cytokines mainly in border bMyC, sensed to a lesser extent by the BP bMyC, showing that IL-1ß expression is further augmented in aged SAMP8 compared to control SAMR1. CONCLUSION: Our data validate the SAMP8 model to study age-associated neuroinflammatory events, but careful controls for age and strain are required. These animals show morphological changes in their bMyC cell repertoires associated to age, corresponding to an increase in the production of pro-inflammatory cytokines such as IL-1ß, which predispose the brain to an enhanced inflammatory response after LPS-systemic challenge.

DNGR-1(+) dendritic cells are located in meningeal membrane and choroid plexus of the noninjured brain.

The role and different origin of brain myeloid cells in the brain is central to understanding how the central nervous system (CNS) responds to injury. C-type lectin receptor family 9, member A (DNGR-1/CLEC9A) is a marker of specific DC subsets that share functional similarities, such as CD8α(+) DCs in lymphoid tissues and CD103(+) CD11b(low) DCs in peripheral tissues. Here, we analyzed the presence of DNGR-1 in DCs present in the mouse brain (bDCs). Dngr-1/Clec9a mRNA is expressed mainly in the meningeal membranes and choroid plexus (m/Ch), and its expression is enhanced by fms-like tyrosine kinase 3 ligand (Flt3L), a cytokine involved in DC homeostasis. Using Clec9a(egfp/egfp) mice, we show that Flt3L induces accumulation of DNGR-1-EGFP(+) cells in the brain m/Ch. Most of these cells also express major histocompatibility complex class II (MHCII) molecules. We also observed an increase in specific markers of cDC CD8α+ cells such as Batf-3 and Irf-8, but not of costimulatory molecules such as Cd80 and Cd86, indicating an immature phenotype for these bDCs in the noninjured brain. The presence of DNGR-1 in the brain provides a potential marker for the study of this specific brain cell subset. Knowledge and targeting of brain antigen presenting cells (APCs) has implications for the fight against brain diseases such as neuroinflammation-based neurodegenerative diseases, microbe-induced encephalitis, and brain tumors such as gliomas.

Community monitoring for youth violence surveillance: testing a prediction model.

Predictive epidemiology is an embryonic field that involves developing informative signatures for disorder and tracking them using surveillance methods. Through such efforts assistance can be provided to the planning and implementation of preventive interventions. Believing that certain minor crimes indicative of gang activity are informative signatures for the emergence of serious youth violence in communities, in this study we aim to predict outbreaks of violence in neighborhoods from pre-existing levels and changes in reports of minor offenses. We develop a prediction equation that uses publicly available neighborhood-level data on disorderly conduct, vandalism, and weapons violations to predict neighborhoods likely to have increases in serious violent crime. Data for this study were taken from the Chicago Police Department ClearMap reporting system, which provided data on index and non-index crimes for each of the 844 Chicago census tracts. Data were available in three month segments for a single year (fall 2009, winter, spring, and summer 2010). Predicted change in aggravated battery and overall violent crime correlated significantly with actual change. The model was evaluated by comparing alternative models using randomly selected training and test samples, producing favorable results with reference to overfitting, seasonal variation, and spatial autocorrelation. A prediction equation based on winter and spring levels of the predictors had area under the curve ranging from .65 to .71 for aggravated battery, and .58 to .69 for overall violent crime. We discuss future development of such a model and its potential usefulness in violence prevention and community policing.

Vaccination status and outcomes in critical COVID-19 patients.

OBJECTIVE: To analyze the clinical characteristics and outcomes of patients with COVID-19-related acute respiratory failure on the basis of their vaccination status at the time of ICU admission. METHODS: We conducted a retrospective observational study using a prospective database of patients admitted to the ICU of a university hospital in the city of Murcia, in Spain, between January 1, 2021 and September 1, 2022. Clinical, analytical, and sociodemographic data were collected and analyzed on the basis of patient vaccination status. We adjusted for confounding variables using propensity score matching and calculated adjusted ORs and 95% CIs. RESULTS: A total of 276 patients were included in the study. Of those, 8.3% were fully vaccinated, 12% were partially vaccinated, and 79.7% were unvaccinated. Although fully vaccinated patients had more comorbidities, partially vaccinated patients had higher disease severity. The proportion of patients with severe acute respiratory failure was higher in the unvaccinated group, followed by the partially vaccinated group. No significant differences were found among the different groups regarding complications, duration of ventilatory support, or length of ICU/hospital stay. In the sample selected by propensity score matching, the number of patients with severe complications and the in-hospital mortality rate were higher in unvaccinated patients, but the differences were not significant. CONCLUSIONS: This study failed to show a significant improvement in outcomes in critically ill COVID-19 patients vaccinated against SARS-CoV-2. However, the CIs were wide and the mortality point estimates favored patients who received at least one dose of COVID-19 vaccine.

Violence Prevention Programs Are Effective When Initiated During the Initial Workup of Patients in an Urban Level I Trauma Center.

This study represents the first attempt at evaluating the ability of the CureViolence Hospital-Response Intervention Program (previously CeaseFire) to disrupt the pattern of violent reinjury. The clinical data points of 300 African American men who presented to our trauma center with a gunshot wound and received intervention at the bedside between 2005 and 2007 (with a 48-month follow-up) were collected. This cohort was matched with a post hoc historical control group using hospital records from 2003 to 2005. The mean age for both groups was 23.9 years. Odds ratios and 95% confidence intervals were obtained. Using a binary logistical regression model, we assessed the performance of three variables of interest: age at the time of the initial injury, treatment group, and initial disposition group to predict recidivism. We utilized the Nagelkerke R square method, which described the proportion of the variance of the reinjury rate and validated our findings using the Hosmer-Lemeshow test (for goodness-of-fit). Six percent (n = 18) of subjects in the treatment group and 11% (n = 33) in the control group returned with a new injury, yielding a total reinjury rate of 8.5%. Most patients returned only once with another violent injury. Individuals who did not receive CureViolence services were nearly twice as likely (odds ratio = 1.94; 95% confidence interval = 1.065, 3.522) to return with a violent reinjury. This finding suggests that Hospital-Response Intervention Programs (HRIP) have a protective effect in violently injured patients. We therefore conclude our HRIP positively affected at-risk patients and prevented violent reinjury.

Vaccination status and outcomes in critical COVID-19 patients / Situação vacinal e desfechos em pacientes com COVID-19 em estado crítico

ABSTRACT Objective: To analyze the clinical characteristics and outcomes of patients with COVID-19-related acute respiratory failure on the basis of their vaccination status at the time of ICU admission. Methods: We conducted a retrospective observational study using a prospective database of patients admitted to the ICU of a university hospital in the city of Murcia, in Spain, between January 1, 2021 and September 1, 2022. Clinical, analytical, and sociodemographic data were collected and analyzed on the basis of patient vaccination status. We adjusted for confounding variables using propensity score matching and calculated adjusted ORs and 95% CIs. Results: A total of 276 patients were included in the study. Of those, 8.3% were fully vaccinated, 12% were partially vaccinated, and 79.7% were unvaccinated. Although fully vaccinated patients had more comorbidities, partially vaccinated patients had higher disease severity. The proportion of patients with severe acute respiratory failure was higher in the unvaccinated group, followed by the partially vaccinated group. No significant differences were found among the different groups regarding complications, duration of ventilatory support, or length of ICU/hospital stay. In the sample selected by propensity score matching, the number of patients with severe complications and the in-hospital mortality rate were higher in unvaccinated patients, but the differences were not significant. Conclusions: This study failed to show a significant improvement in outcomes in critically ill COVID-19 patients vaccinated against SARS-CoV-2. However, the CIs were wide and the mortality point estimates favored patients who received at least one dose of COVID-19 vaccine.

RESUMO Objetivo: Analisar as características clínicas e desfechos de pacientes com insuficiência respiratória aguda por COVID-19 com base na situação vacinal no momento da admissão na UTI. Métodos: Estudo observacional retrospectivo com um banco de dados prospectivo de pacientes admitidos na UTI de um hospital universitário em Múrcia, na Espanha, entre 1º de janeiro de 2021 e 1º de setembro de 2022. Dados clínicos, analíticos e sociodemográficos foram coletados e analisados com base na situação vacinal dos pacientes. Por meio de pareamento por escore de propensão, foram realizados ajustes de modo a levar em conta as variáveis de confusão. Além disso, foram calculadas as OR ajustadas e IC95%. Resultados: Foram incluídos no estudo 276 pacientes. Destes, 8,3% apresentavam vacinação completa, 12% apresentavam vacinação incompleta e 79,7% não haviam sido vacinados. Embora os pacientes com vacinação completa apresentassem mais comorbidades, os com vacinação incompleta apresentavam doença mais grave. A proporção de pacientes com insuficiência respiratória aguda grave foi maior nos não vacinados, seguidos daqueles com vacinação incompleta. Não foram observadas diferenças significativas entre os diferentes grupos quanto a complicações, tempo de suporte ventilatório ou tempo de internação na UTI/hospital. Na amostra selecionada pelo pareamento por escore de propensão, o número de pacientes com complicações graves e a taxa de mortalidade hospitalar foram maiores em pacientes não vacinados, mas as diferenças não foram significativas. Conclusões: Este estudo não conseguiu demonstrar uma melhoria significativa dos desfechos em pacientes com COVID-19 em estado crítico e vacinados contra o SARS-CoV-2. No entanto, os IC foram amplos e as estimativas pontuais de mortalidade favoreceram os pacientes que receberam pelo menos uma dose de vacina contra a COVID-19.

Caregiving attitudes and at-risk maternal behavior among mothers with major mental illness.

In an effort to improve parenting assessments for mothers with mental illness, this study examined the relationship between caregiving attitudes and maternal behavior. Participants included 44 mothers with major mental illness who were involved with the child welfare system and their young children. The Parenting Opinion Questionnaire (POQ) was administered to assess caregiving attitudes. Maternal behavior was assessed directly in a videotaped observation. Unrealistic maternal caregiving attitudes, especially attitudes that a child should provide a parent with support and comfort, were associated with at-risk maternal behavior. The findings support the application of the POQ for use in multimeasure, multimethod parenting evaluations.

Multiple-family groups for urban children with conduct difficulties and their families.

The authors present the results of two studies designed to improve treatment engagement among urban youths with conduct and oppositional behavioral difficulties. In the first study, information on attitudes about mental health treatment was obtained from 159 adult caregivers of children who were referred to an urban child mental health clinic because of disruptive behavioral difficulties. The caregivers listed insufficient time, lack of transportation, the child's not wanting to attend treatment, and the caregiver's concern that treatment might not help as barriers to service use. The data from study 1 were used to design a multiple-family group intervention to be tested in study 2. The families who participated in these groups attended an average of seven sessions during the 16-week study, compared with four sessions for families who participated in family therapy and three for families who participated in individual psychotherapy.

Predictors of participation in a family-focused preventive intervention for substance use.

This study reports patterns of involvement in a family-focused preventive intervention, Schools and Families Educating (SAFE) Children, targeting early predictors of risk for delinquency and drug use among 175 African American and Latino first-grade children living in economically disadvantaged inner-city neighborhoods. Three empirically derived patterns emerged: joiners, responders, and minimal responders. Joiners were immediately responsive and enthusiastic and participated fully. Responders attended fully only after extensive effort was made to recruit and retain them. However, once engaged, they attended fully and participated with enthusiasm. Minimal responders attended a few sessions sporadically even with extensive, ongoing effort to engage them. Ethnicity, marital status, parental antisocial behavior, economic and loss stressors, monitoring, and child's depression and hyperactivity were significant discriminators of group membership.