Impaired hospitalized patient mobility is associated with nurse injuries.

BACKGROUND: Staff injuries adversely affect the health of staff members as well the ability of health care teams to effectively care for patients. Identifying patients who pose an increased risk of injury may allow for the planning of risk mitigation strategies, but few studies have examined patient factors associated with staff injury risk. AIMS: Examine the relationship between staff injury and patient mobility, which has been linked to other key hospital outcomes. METHODS: Linking occupational health and electronic medical record data, we examined documented patient mobility levels, based on the Activity Measure for Post-Acute Care (AM-PAC) and the Johns Hopkins Highest Level of Mobility (JH-HLM) Scale, on the day prior to injury. In addition, we created a matched cohort of control patients not associated with staff injury to examine the influence of patient mobility on the odds of staff injury. RESULTS: We identified 199 staff injuries associated with 181 patients with 1063 matched controls. Patients had median scores of 11 and 3 on the AM-PAC and JH-HLM, respectively, indicating moderate-severe mobility impairments. In addition, scores in the lowest AM-PAC tertile (6-15) and lowest JH-HLM tertile (1-4) were associated with a 4.46-fold and 2.90-fold increase in the odds of nurse injury, respectively. CONCLUSIONS: These results indicate that moderate-severe mobility impairments are associated with increased risk of nurse injury. Hospitals and clinical care teams should consider documenting mobility routinely and utilizing these values to identify patients who pose an increased risk of nurse injury.

Mouse Parthenogenetic Embryonic Stem Cells with Biparental-Like Expression of Imprinted Genes Generate Cortical-Like Neurons That Integrate into the Injured Adult Cerebral Cortex.

One strategy for stem cell-based therapy of the cerebral cortex involves the generation and transplantation of functional, histocompatible cortical-like neurons from embryonic stem cells (ESCs). Diploid parthenogenetic Pg-ESCs have recently emerged as a promising source of histocompatible ESC derivatives for organ regeneration but their utility for cerebral cortex therapy is unknown. A major concern with Pg-ESCs is genomic imprinting. In contrast with biparental Bp-ESCs derived from fertilized oocytes, Pg-ESCs harbor two maternal genomes but no sperm-derived genome. Pg-ESCs are therefore expected to have aberrant expression levels of maternally expressed (MEGs) and paternally expressed (PEGs) imprinted genes. Given the roles of imprinted genes in brain development, tissue homeostasis and cancer, their deregulation in Pg-ESCs might be incompatible with therapy. Here, we report that, unexpectedly, only one gene out of 7 MEGs and 12 PEGs was differentially expressed between Pg-ESCs and Bp-ESCs while 13 were differentially expressed between androgenetic Ag-ESCs and Bp-ESCs, indicating that Pg-ESCs but not Ag-ESCs, have a Bp-like imprinting compatible with therapy. In vitro, Pg-ESCs generated cortical-like progenitors and electrophysiologically active glutamatergic neurons that maintained the Bp-like expression levels for most imprinted genes. In vivo, Pg-ESCs participated to the cortical lineage in fetal chimeras. Finally, transplanted Pg-ESC derivatives integrated into the injured adult cortex and sent axonal projections in the host brain. In conclusion, mouse Pg-ESCs generate functional cortical-like neurons with Bp-like imprinting and their derivatives properly integrate into both the embryonic cortex and the injured adult cortex. Collectively, our data support the utility of Pg-ESCs for cortical therapy. Stem Cells 2018;36:192-205.

The association between childhood adversities and subsequent first onset of psychotic experiences: a cross-national analysis of 23 998 respondents from 17 countries.

BACKGROUND: Although there is robust evidence linking childhood adversities (CAs) and an increased risk for psychotic experiences (PEs), little is known about whether these associations vary across the life-course and whether mental disorders that emerge prior to PEs explain these associations. METHOD: We assessed CAs, PEs and DSM-IV mental disorders in 23 998 adults in the WHO World Mental Health Surveys. Discrete-time survival analysis was used to investigate the associations between CAs and PEs, and the influence of mental disorders on these associations using multivariate logistic models. RESULTS: Exposure to CAs was common, and those who experienced any CAs had increased odds of later PEs [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.9-2.6]. CAs reflecting maladaptive family functioning (MFF), including abuse, neglect, and parent maladjustment, exhibited the strongest associations with PE onset in all life-course stages. Sexual abuse exhibited a strong association with PE onset during childhood (OR 8.5, 95% CI 3.6-20.2), whereas Other CA types were associated with PE onset in adolescence. Associations of other CAs with PEs disappeared in adolescence after adjustment for prior-onset mental disorders. The population attributable risk proportion (PARP) for PEs associated with all CAs was 31% (24% for MFF). CONCLUSIONS: Exposure to CAs is associated with PE onset throughout the life-course, although sexual abuse is most strongly associated with childhood-onset PEs. The presence of mental disorders prior to the onset of PEs does not fully explain these associations. The large PARPs suggest that preventing CAs could lead to a meaningful reduction in PEs in the population.

Posttraumatic stress disorder in the World Mental Health Surveys.

BACKGROUND: Traumatic events are common globally; however, comprehensive population-based cross-national data on the epidemiology of posttraumatic stress disorder (PTSD), the paradigmatic trauma-related mental disorder, are lacking. METHODS: Data were analyzed from 26 population surveys in the World Health Organization World Mental Health Surveys. A total of 71 083 respondents ages 18+ participated. The Composite International Diagnostic Interview assessed exposure to traumatic events as well as 30-day, 12-month, and lifetime PTSD. Respondents were also assessed for treatment in the 12 months preceding the survey. Age of onset distributions were examined by country income level. Associations of PTSD were examined with country income, world region, and respondent demographics. RESULTS: The cross-national lifetime prevalence of PTSD was 3.9% in the total sample and 5.6% among the trauma exposed. Half of respondents with PTSD reported persistent symptoms. Treatment seeking in high-income countries (53.5%) was roughly double that in low-lower middle income (22.8%) and upper-middle income (28.7%) countries. Social disadvantage, including younger age, female sex, being unmarried, being less educated, having lower household income, and being unemployed, was associated with increased risk of lifetime PTSD among the trauma exposed. CONCLUSIONS: PTSD is prevalent cross-nationally, with half of all global cases being persistent. Only half of those with severe PTSD report receiving any treatment and only a minority receive specialty mental health care. Striking disparities in PTSD treatment exist by country income level. Increasing access to effective treatment, especially in low- and middle-income countries, remains critical for reducing the population burden of PTSD.

Disruptions of working memory and inhibition mediate the association between exposure to institutionalization and symptoms of attention deficit hyperactivity disorder.

BACKGROUND: Young children raised in institutions are exposed to extreme psychosocial deprivation that is associated with elevated risk for psychopathology and other adverse developmental outcomes. The prevalence of attention deficit hyperactivity disorder (ADHD) is particularly high in previously institutionalized children, yet the mechanisms underlying this association are poorly understood. We investigated whether deficits in executive functioning (EF) explain the link between institutionalization and ADHD. METHOD: A sample of 136 children (aged 6-30 months) was recruited from institutions in Bucharest, Romania, and 72 never institutionalized community children matched for age and gender were recruited through general practitioners' offices. At 8 years of age, children's performance on a number of EF components (working memory, response inhibition and planning) was evaluated. Teachers completed the Health and Behavior Questionnaire, which assesses two core features of ADHD, inattention and impulsivity. RESULTS: Children with history of institutionalization had higher inattention and impulsivity than community controls, and exhibited worse performance on working memory, response inhibition and planning tasks. Lower performances on working memory and response inhibition, but not planning, partially mediated the association between early institutionalization and inattention and impulsivity symptom scales at age 8 years. CONCLUSIONS: Institutionalization was associated with decreased EF performance and increased ADHD symptoms. Deficits in working memory and response inhibition were specific mechanisms leading to ADHD in previously institutionalized children. These findings suggest that interventions that foster the development of EF might reduce risk for psychiatric problems in children exposed to early deprivation.

The epidemiology of traumatic event exposure worldwide: results from the World Mental Health Survey Consortium.

BACKGROUND: Considerable research has documented that exposure to traumatic events has negative effects on physical and mental health. Much less research has examined the predictors of traumatic event exposure. Increased understanding of risk factors for exposure to traumatic events could be of considerable value in targeting preventive interventions and anticipating service needs. METHOD: General population surveys in 24 countries with a combined sample of 68 894 adult respondents across six continents assessed exposure to 29 traumatic event types. Differences in prevalence were examined with cross-tabulations. Exploratory factor analysis was conducted to determine whether traumatic event types clustered into interpretable factors. Survival analysis was carried out to examine associations of sociodemographic characteristics and prior traumatic events with subsequent exposure. RESULTS: Over 70% of respondents reported a traumatic event; 30.5% were exposed to four or more. Five types - witnessing death or serious injury, the unexpected death of a loved one, being mugged, being in a life-threatening automobile accident, and experiencing a life-threatening illness or injury - accounted for over half of all exposures. Exposure varied by country, sociodemographics and history of prior traumatic events. Being married was the most consistent protective factor. Exposure to interpersonal violence had the strongest associations with subsequent traumatic events. CONCLUSIONS: Given the near ubiquity of exposure, limited resources may best be dedicated to those that are more likely to be further exposed such as victims of interpersonal violence. Identifying mechanisms that account for the associations of prior interpersonal violence with subsequent trauma is critical to develop interventions to prevent revictimization.

Contributions of the social environment to first-onset and recurrent mania.

In treated cohorts, individuals with bipolar disorder are more likely to report childhood adversities and recent stressors than individuals without bipolar disorder; similarly, in registry-based studies, childhood adversities are more common among individuals who later become hospitalized for bipolar disorder. Because these types of studies rely on treatment-seeking samples or hospital diagnoses, they leave unresolved the question of whether or not social experiences are involved in the etiology of bipolar disorder. We investigated the role of childhood adversities and adulthood stressors in liability for bipolar disorder using data from the National Epidemiologic Survey on Alcohol and Related Conditions (n=33 375). We analyzed risk for initial-onset and recurrent DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) manic episodes during the study's 3-year follow-up period. Childhood physical abuse and sexual maltreatment were associated with significantly higher risks of both first-onset mania (odds ratio (OR) for abuse: 2.23; 95% confidence interval (CI)=1.71, 2.91; OR for maltreatment: 2.10; CI=1.55, 2.83) and recurrent mania (OR for abuse: 1.55; CI=1.00, 2.40; OR for maltreatment: 1.60; CI=1.00, 2.55). In addition, past-year stressors in the domains of interpersonal instability and financial hardship were associated with a significantly higher risk of incident and recurrent mania. Exposure to childhood adversity potentiated the effects of recent stressors on adult mania. Our findings demonstrate a role of social experiences in the initial onset of bipolar disorder, as well as in its prospective course, and are consistent with etiologic models of bipolar disorder that implicate deficits in developmentally established stress-response pathways.

National needs assessment of patients treated at the United States Federally-Funded Hemophilia Treatment Centers.

AIM: The National Hemophilia Program Coordinating Center, with the U.S. Regional Hemophilia Network conducted a national needs assessment of U.S. Hemophilia Treatment Center (HTC) patients. The objectives were to determine: (i) To what extent do patients report that they receive needed services and education; (ii) How well do the services provided meet their needs; and (iii) What are the patients' perspectives about their care. METHODS: A survey was mailed to active patients of 129 HTCs. Respondents completed the anonymous surveys on line or returned them by mail. Questions focused on management and information, access and barriers to care, coping, resources, and transition. RESULTS: Of 24 308 questionnaires mailed, 4004 (16.5%) were returned. Most respondents reported very few gaps in needed services or information and reported that services and information met their needs. Over 90% agreed or strongly agreed that care was patient-centred and rated HTC care as important or very important. Identified gaps included dietary advice, genetic testing, information on ageing, sexual health and basic needs resources. Minority respondents reported more barriers. CONCLUSION: This survey is the largest assessment of the HTC population. Respondents reported that the services and information provided by the HTCs met their needs. Quality improvement opportunities include transition and services related to ageing and sexual health. Further investigation of barriers to care for minorities is underway. Results will help develop national priorities to better serve all patients in the US. HTCs.

Severe hyperkalemia following adrenalectomy for aldosteronoma: prediction, pathogenesis and approach to clinical management- a case series.

BACKGROUND: As the field of Primary Aldosteronism (PA) becomes ever expanded, diagnosis of PA is increasingly diagnosed by endocrinologists. With increased PA screening, many of the cases are now found in patients with complex co-morbidities in addition to their hypertension. Post adrenalectomy renal impairment with hyperkalemia is now increasingly seen in these complex patients, as evidenced by the numerous reports on this issue that have appeared within the past 3 years. We present a small case series to illustrate the breadth of the problem, along with a discussion about how such CKD/hyperkalemic events may be predicted. CASE PRESENTATION: We present three cases of primary aldosteronism with long standing hypertension (more than 10 years) hypokalemia (2.0-3.0 mmol/l). Serum aldosterone was high with low renin activity leading to high aldosterone to renin ratio (ARR). They underwent abdominal CT scan revealing adrenal mass and adrenal vein sample confirmed lateralization. None of the patients had evidence of renal disease before surgery (as evident by normal eGFR and serum creatinine). Post adrenalectomy they had reduction in the blood pressure and became eukalemic. Serum aldosterone and renin activity were low leading to a low ARR. Case 1 developed hyperkalemia and increased serum creatinine 6 weeks post operatively which resolved with initiation of fludrocortisone and every attempt to discontinue fludrocortisone resulted in hyperkalemia and rising creatinine. Her hyperkalemia is under control with oral sodium bicarbonate. Case 2 developed hyperkalemia and increasing creatinine 2 months post operatively transiently requiring fludrocortisone and later on managed with furosemide for hyperkalemia. Case 3 developed renal impairment and hyperkalemia 2 weeks post operatively requiring fludrocortisone. CONCLUSION: Post APA resection severe hyperkalemia may be a common entity and screening should be actively considered in high risk patients. Older age, longer duration of hypertension, impaired pre-op and post-op GFR and higher levels of pre-op aldosterone and are all risk factors which predict the likelihood of developing post-operative hyperkalemia. Fludrocortisone, sodium bicarbonate, loop diuretics and potassium binders can be used for treatment. Treatment choice should be tailored to patient characteristics including fluid status, blood pressure and serum creatinine. Potassium binders should be avoided in patients with history of recent abdominal surgery, opioid use and constipation. Serum electrolytes and creatinine should be monitored every 1-2 weeks after starting treatment to ensure an adequate response. Prolonged management may be necessary in some cases and at-risk patients should be counselled as to the meaning and importance of post-operative changes in measured renal function and potassium.

Human Parthenogenetic Embryonic Stem Cell-Derived Neural Stem Cells Express HLA-G and Show Unique Resistance to NK Cell-Mediated Killing.

Parent-of-origin imprints have been implicated in the regulation of neural differentiation and brain development. Previously we have shown that, despite the lack of a paternal genome, human parthenogenetic (PG) embryonic stem cells (hESCs) can form proliferating neural stem cells (NSCs) that are capable of differentiation into physiologically functional neurons while maintaining allele-specific expression of imprinted genes. Since biparental ("normal") hESC-derived NSCs (N NSCs) are targeted by immune cells, we characterized the immunogenicity of PG NSCs. Flow cytometry and immunocytochemistry revealed that both N NSCs and PG NSCs exhibited surface expression of human leukocyte antigen (HLA) class I but not HLA-DR molecules. Functional analyses using an in vitro mixed lymphocyte reaction assay resulted in less proliferation of peripheral blood mononuclear cells (PBMC) with PG compared with N NSCs. In addition, natural killer (NK) cells cytolyzed PG less than N NSCs. At a molecular level, expression analyses of immune regulatory factors revealed higher HLA-G levels in PG compared with N NSCs. In line with this finding, MIR152, which represses HLA-G expression, is less transcribed in PG compared with N cells. Blockage of HLA-G receptors ILT2 and KIR2DL4 on natural killer cell leukemia (NKL) cells increased cytolysis of PG NSCs. Together this indicates that PG NSCs have unique immunological properties due to elevated HLA-G expression.

Brief report: Parthenogenetic embryonic stem cells are an effective cell source for therapeutic liver repopulation.

Parthenogenesis is the development of an oocyte without fertilization. Mammalian parthenogenetic (PG) embryos are not viable, but can develop into blastocysts from which embryonic stem cells (ESCs) have been derived in mouse and human. PG ESCs are frequently homozygous for alleles encoding major histocompatibility complex (MHC) molecules. MHC homozygosity permits much more efficient immune matching than MHC heterozygosity found in conventional ESCs, making PG ESCs a promising cell source for cell therapies requiring no or little immune suppression. However, findings of restricted differentiation and proliferation of PG cells in developmental chimeras have cast doubt on the potential of PG ESC derivatives for organ regeneration. To address this uncertainty, we determined whether PG ESC derivatives are effective in rescuing mice with lethal liver failure due to deficiency of fumarylacetoacetate hydrolase (Fah). In developmental chimeras generated by injecting wild-type PG ESCs into Fah-deficient blastocysts, PG ESCs differentiated into hepatocytes that could repopulate the liver, provide normal liver function, and facilitate long-term survival of adult mice. Moreover, after transplantation into adult Fah-deficient mice, PG ESC-derived hepatocytes efficiently engrafted and proliferated, leading to high-level liver repopulation. Our results show that--despite the absence of a paternal genome--PG ESCs can form therapeutically effective hepatocytes.

Predicting the minimum liquid surface tension activity of pseudomonads expressing biosurfactants.

UNLABELLED: Bacteria produce a variety of biosurfactants capable of significantly reducing liquid (aqueous) surface tension (γ) with a range of biological roles and biotechnological uses. To determine the lowest achievable surface tension (γMin ), we tested a diverse collection of Pseudomonas-like isolates from contaminated soil and activated sludge and identified those expressing biosurfactants by drop-collapse assay. Liquid surface tension-reducing ability was quantitatively determined by tensiometry, with 57 isolates found to significantly lower culture supernatant surface tensions to 24·5-49·1 mN m(-1) . Differences in biosurfactant behaviour determined by foaming, emulsion and oil-displacement assays were also observed amongst isolates producing surface tensions of 25-27 mN m(-1) , suggesting that a range of structurally diverse biosurfactants were being expressed. Individual distribution identification (IDI) analysis was used to identify the theoretical probability distribution that best fitted the surface tension data, which predicted a γMin of 24·24 mN m(-1) . This was in agreement with predictions based on earlier work of published mixed bacterial spp. data, suggesting a fundamental limit to the ability of bacterial biosurfactants to reduce surface tensions in aqueous systems. This implies a biological restriction on the synthesis and export of these agents or a physical-chemical restriction on their functioning once produced. SIGNIFICANCE AND IMPACT OF THE STUDY: Numerous surveys of biosurfactant-producing bacteria have been conducted, but only recently has an attempt been made to predict the minimum liquid surface tension these surface-active agents can achieve. Here, we determine a theoretical minimum of 24 mN m(-1) by statistical analysis of tensiometry data, suggesting a fundamental limit for biosurfactant activity in bacterial cultures incubated under standard growth conditions. This raises a challenge to our understanding of biosurfactant expression, secretion and function, as well as being of interest to biotechnology where they are used in an increasingly wide range of applications.

The effects of temporally secondary co-morbid mental disorders on the associations of DSM-IV ADHD with adverse outcomes in the US National Comorbidity Survey Replication Adolescent Supplement (NCS-A).

BACKGROUND: Although DSM-IV attention deficit hyperactivity disorder (ADHD) is known to be associated with numerous adverse outcomes, uncertainties exist about how much these associations are mediated temporally by secondary co-morbid disorders. METHOD: The US National Comorbidity Survey Replication Adolescent Supplement (NCS-A), a national survey of adolescents aged 13-17 years (n = 6483 adolescent-parent pairs), assessed DSM-IV disorders with the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI). Statistical decomposition was used to compare direct effects of ADHD with indirect effects of ADHD through temporally secondary mental disorders (anxiety, mood, disruptive behavior, substance disorders) in predicting poor educational performance (suspension, repeating a grade, below-average grades), suicidality (ideation, plans, attempts) and parent perceptions of adolescent functioning (physical and mental health, interference with role functioning and distress due to emotional problems). RESULTS: ADHD had significant gross associations with all outcomes. Direct effects of ADHD explained most (51.9-67.6%) of these associations with repeating a grade in school, perceived physical and mental health (only girls), interference with role functioning and distress, and significant components (34.5-44.6%) of the associations with school suspension and perceived mental health (only boys). Indirect effects of ADHD on educational outcomes were predominantly through disruptive behavior disorders (26.9-52.5%) whereas indirect effects on suicidality were predominantly through mood disorders (42.8-59.1%). Indirect effects on most other outcomes were through both mood (19.8-31.2%) and disruptive behavior (20.1-24.5%) disorders, with anxiety and substance disorders less consistently important. Most associations were comparable for girls and boys. CONCLUSIONS: Interventions aimed at reducing the adverse effects of ADHD might profitably target prevention or treatment of temporally secondary co-morbid disorders.

Intergenerational effects of racism on amygdala and hippocampus resting state functional connectivity.

Racism is an insidious problem with far-reaching effects on the lives of Black, Indigenous, and People of Color (BIPOC). The pervasive negative impact of racism on mental health is well documented. However, less is known about the potential downstream impacts of maternal experiences of racism on offspring neurodevelopment. This study sought to examine evidence for a biological pathway of intergenerational transmission of racism-related trauma. This study examined the effects of self-reported maternal experiences of racism on resting state functional connectivity (rsFC) in n = 25 neonates (13 female, 12 male) birthed by BIPOC mothers. Amygdala and hippocampus are brain regions involved in fear, memory, and anxiety, and are central nodes in brain networks associated with trauma-related change. We used average scores on the Experiences of Racism Scale as a continuous, voxel-wise regressor in seed-based, whole-brain connectivity analysis of anatomically defined amygdala and hippocampus seed regions of interest. All analyses controlled for infant sex and gestational age at the 2-week scanning session. More maternal racism-related experiences were associated with (1) stronger right amygdala rsFC with visual cortex and thalamus; and (2) stronger hippocampus rsFC with visual cortex and a temporo-parietal network, in neonates. The results of this research have implications for understanding how maternal experiences of racism may alter neurodevelopment, and for related social policy.

Mouse MOV10L1 associates with Piwi proteins and is an essential component of the Piwi-interacting RNA (piRNA) pathway.

Piwi-interacting RNAs (piRNAs) are essential for silencing of transposable elements in the germline, but their biogenesis is poorly understood. Here we demonstrate that MOV10L1, a germ cell-specific putative RNA helicase, is associated with Piwi proteins. Genetic disruption of the MOV10L1 RNA helicase domain in mice renders both MILI and MIWI2 devoid of piRNAs. Absence of a functional piRNA pathway in Mov10l1 mutant testes causes loss of DNA methylation and subsequent derepression of retrotransposons in germ cells. The Mov10l1 mutant males are sterile owing to complete meiotic arrest. This mouse mutant expresses Piwi proteins but lacks piRNAs, suggesting that MOV10L1 is required for piRNA biogenesis and/or loading to Piwi proteins.

On-site treatment of avalanche victims: Scoping review and 2023 recommendations of the international commission for mountain emergency medicine (ICAR MedCom).

INTRODUCTION: The International Commission for Mountain Emergency Medicine (ICAR MedCom) developed updated recommendations for the management of avalanche victims. METHODS: ICAR MedCom created Population Intervention Comparator Outcome (PICO) questions and conducted a scoping review of the literature. We evaluated and graded the evidence using the American College of Chest Physicians system. RESULTS: We included 120 studies including original data in the qualitative synthesis. There were 45 retrospective studies (38%), 44 case reports or case series (37%), and 18 prospective studies on volunteers (15%). The main cause of death from avalanche burial was asphyxia (range of all studies 65-100%). Trauma was the second most common cause of death (5-29%). Hypothermia accounted for few deaths (0-4%). CONCLUSIONS AND RECOMMENDATIONS: For a victim with a burial time ≤ 60 minutes without signs of life, presume asphyxia and provide rescue breaths as soon as possible, regardless of airway patency. For a victim with a burial time > 60 minutes, no signs of life but a patent airway or airway with unknown patency, presume that a primary hypothermic CA has occurred and initiate cardiopulmonary resuscitation (CPR) unless temperature can be measured to rule out hypothermic cardiac arrest. For a victim buried > 60 minutes without signs of life and with an obstructed airway, if core temperature cannot be measured, rescuers can presume asphyxia-induced CA, and should not initiate CPR. If core temperature can be measured, for a victim without signs of life, with a patent airway, and with a core temperature < 30 °C attempt resuscitation, regardless of burial duration.

Foot-and-mouth disease virus exhibits an altered tropism in the presence of specific immunoglobulins, enabling productive infection and killing of dendritic cells.

Foot-and-mouth disease virus (FMDV) causes an acute vesicular disease of farm animals. The development of successful control strategies is limited by an incomplete understanding of the immune response to FMDV. Dendritic cells (DC) mediate the induction of immunity to pathogens, but their role in FMDV infection of cattle is uncharacterized. Bovine monocyte-derived DC (moDC) were exposed to integrin-binding and cell culture-adapted strains of FMDV in vitro. MoDC were not largely susceptible to infection by integrin-binding FMDV but were susceptible to culture-adapted virus. Binding specific antibodies to integrin-binding FMDV at neutralizing or subneutralizing IgG concentrations significantly enhanced infection via CD32 (FcγR). Monocytes also expressed CD32 but were nonsusceptible to FMDV immune complex (IC) infection, indicating a requirement for additional factors involved in cellular susceptibility. Infection of moDC by the FMDV IC was productive and associated with high levels of cell death. Infected moDC were unable to efficiently stimulate FMDV-specific CD4(+) memory T cells, but exposing moDC to IC containing inactivated FMDV resulted in significantly increased T cell stimulation. Thus, neutralized FMDV concurrently loses its ability to infect susceptible cells while gaining the capacity to infect immune cells. This represents a change in the tropism of FMDV that could occur after the onset of the antibody response. We propose that IC could dynamically influence the anti-FMDV immune response and that this may explain why the early immune response to FMDV has evolved toward T cell independence in vivo. Moreover, we propose that DC targeting could prove useful in the development of effective vaccines against FMDV.

Home foreclosure and risk of psychiatric morbidity during the recent financial crisis.

BACKGROUND: A defining feature of the US economic downturn of 2008-2010 was the alarming rate of home foreclosure. Although a substantial number of US households have experienced foreclosure since 2008, the effects of foreclosure on mental health are unknown. We examined the effects of foreclosure on psychiatric symptomatology in a prospective, population-based community survey. METHOD: Data were drawn from the Detroit Neighborhoods and Health Study (DNHS), waves 1 and 2 (2008-2010). A probability sample of predominantly African-American adults in Detroit, Michigan participated (n=1547). We examined the association between home foreclosure between waves 1 and 2 and increases in symptoms of DSM-IV major depression and generalized anxiety disorder (GAD). RESULTS: The most common reasons for foreclosure were an increase in monthly payments, an increase in non-medical expenses and a reduction in family income. Exposure to foreclosure between waves 1 and 2 predicted symptoms of major depression and GAD at wave 2, controlling for symptoms at wave 1. Even after adjusting for wave 1 symptoms, sociodemographics, lifetime history of psychiatric disorder at wave 1 and exposure to other financial stressors between waves 1 and 2, foreclosure was associated with an increased rate of symptoms of major depression [incidence density ratio (IDR) 2.4, 95% confidence interval (CI) 1.6-3.6] and GAD (IDR 1.9, 95% CI 1.4-2.6). CONCLUSIONS: We provide the first prospective evidence linking foreclosure to the onset of mental health problems. These results, combined with the high rate of home foreclosure since 2008, suggest that the foreclosure crisis may have adverse effects on the mental health of the US population.

Lifetime co-morbidity of DSM-IV disorders in the US National Comorbidity Survey Replication Adolescent Supplement (NCS-A).

BACKGROUND: Research on the structure of co-morbidity among common mental disorders has largely focused on current prevalence rather than on the development of co-morbidity. This report presents preliminary results of the latter type of analysis based on the US National Comorbidity Survey Replication Adolescent Supplement (NCS-A). METHOD: A national survey was carried out of adolescent mental disorders. DSM-IV diagnoses were based on the Composite International Diagnostic Interview (CIDI) administered to adolescents and questionnaires self-administered to parents. Factor analysis examined co-morbidity among 15 lifetime DSM-IV disorders. Discrete-time survival analysis was used to predict first onset of each disorder from information about prior history of the other 14 disorders. RESULTS: Factor analysis found four factors representing fear, distress, behavior and substance disorders. Associations of temporally primary disorders with the subsequent onset of other disorders, dated using retrospective age-of-onset (AOO) reports, were almost entirely positive. Within-class associations (e.g. distress disorders predicting subsequent onset of other distress disorders) were more consistently significant (63.2%) than between-class associations (33.0%). Strength of associations decreased as co-morbidity among disorders increased. The percentage of lifetime disorders explained (in a predictive rather than a causal sense) by temporally prior disorders was in the range 3.7-6.9% for earliest-onset disorders [specific phobia and attention deficit hyperactivity disorder (ADHD)] and much higher (23.1-64.3%) for later-onset disorders. Fear disorders were the strongest predictors of most other subsequent disorders. CONCLUSIONS: Adolescent mental disorders are highly co-morbid. The strong associations of temporally primary fear disorders with many other later-onset disorders suggest that fear disorders might be promising targets for early interventions.