High-dimensional profiling reveals Tc17 cell enrichment in active Crohn's disease and identifies a potentially targetable signature.

The immune-pathology in Crohn's disease is linked to dysregulated CD4+ T cell responses biased towards pathogenic TH17 cells. However, the role of CD8+ T cells able to produce IL-17 (Tc17 cells) remains unclear. Here we characterize the peripheral blood and intestinal tissue of Crohn's disease patients (n = 61) with flow and mass cytometry and reveal a strong increase of Tc17 cells in active disease, mainly due to induction of conventional T cells. Mass cytometry shows that Tc17 cells express a distinct immune signature (CD6high, CD39, CD69, PD-1, CD27low) which was validated in an independent patient cohort. This signature stratifies patients into groups with distinct flare-free survival associated with differential CD6 expression. Targeting of CD6 in vitro reduces IL-17, IFN-γ and TNF production. These results identify a distinct Tc17 cell population in Crohn's disease with proinflammatory features linked to disease activity. The Tc17 signature informs clinical outcomes and may guide personalized treatment decisions.

Benzopyrone coumarin leads to an inhibition of ochratoxin biosynthesis in representatives of Aspergillus and Penicillium spp. via a type of feedback response mechanism.

Growth and mycotoxin biosynthesis of the ochratoxin-producing fungal strains Aspergillus carbonarius, Aspergillus steynii, Penicillium verrucosum, and Penicillium nordium were analyzed on standard laboratory growth medium supplemented with different amounts of coumarin, an organic compound of the benzopyrone class. Neither the growth nor the phenotypic morphology of the filamentous fungi analyzed was affected by using coumarin concentrations equivalent to 2.5 to 25 µg/ml of medium. In contrast, the ochratoxin biosynthesis was strongly inhibited in both strains of the Aspergillus species and nearly completely inhibited in both Penicillium strains at coumarin concentrations above 8.75 µg/ml. Analyzing the transcriptional activity of the otapksPN polyketide synthase gene in P. nordicum using real-time PCR revealed a strong concentration-dependent decrease in gene expression. Taken together, the data show that ochratoxin biosynthesis in representative strains of the genera Aspergillus and Penicillium could be effectively inhibited by coumarin in a concentration-dependent manner. It could be suggested that the molecular background behind this inhibition is some kind of feedback response mechanism, based on the structural similarity of coumarin to the benzopyrone moiety of the ochratoxin molecule.

Factors associated with no surgery or radiation therapy for invasive cervical cancer in Black and White women.

This paper identifies the proportion of invasive cervical cancer cases that do not receive cancer-directed surgery or radiation; assesses the influence of race, stage, age, grade, nodal status, histology, and co-morbid cancer primaries on receipt of treatment; and considers reasons why cancer-directed therapy is not received. We analyzed data for 8,119 patients with invasive cervical cancer from eleven population-based tumor registries in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, 1992-96. Approximately 8.03% of Whites and 11.64% of Blacks did not receive surgery or radiation therapy (no therapy). The percentage of cases receiving no therapy were greatest for unstaged cases, and for cases with unknown grade or unknown lymph node status. Adjusted odds of no therapy significantly increased with distant and unstaged disease (vs local stage) and older age (vs 0-39) at diagnosis; unknown grade (vs well differentiated); or unknown lymph node (vs no lymph node) status. Black cases were more likely to be unstaged and unstaged cases are more likely to not receive therapy. Blacks were more likely than Whites not to receive surgery because it was not recommended, contraindicated due to other conditions, or refused. Of cases refusing radiation, 53.85% of Whites and 83.33% of Blacks refused surgery, and of women refusing surgery, 22.58% of Whites and 50% of Blacks refused radiation. Stage, age, grade, and lymph node status directly influence receipt of treatment. Race influences receipt of treatment indirectly through stage. Reasons why therapy was not received (eg, not recommended, refused) differ according to race and stage at diagnosis.

Continuous positive airway pressure: patients' and caregivers' learning needs and barriers to use.

OBJECTIVE: To identify learning needs and factors related to postdischarge use of continuous positive airway pressure (CPAP) ventilation. DESIGN: Exploratory descriptive correlational. SETTING: Metropolitan and rural clinics. SUBJECTS: Adult patients (N = 21) and family caregivers, one half 60 years or older. INSTRUMENTS: Family interviews, life satisfaction and quality, family function and relationship, depression and learning preparedness. RESULTS: There were numerous learning needs related to CPAP machine management, monitoring illness severity, and recognizing depressive symptomology, oxygen deficits, and cardiovascular sequelae. Family members are involved in overcoming barriers interfering with nightly CPAP use. Interview and questionnaire data clearly indicate life satisfaction improves after CPAP treatment. CONCLUSION: Predischarge and teaching programs coordinated by expert nurses are needed to address families' learning needs and support habitual long-term CPAP use. Family problem solving and depression interventions, instruction on recognizing symptoms of cardiovascular complications, and long-term follow-up programs are currently being studied.

Effect of concentration problems on the malleability of children's aggressive and shy behaviors.

OBJECTIVE: Previous research has demonstrated the central role of early childhood concentration problems in the development of aggression and other maladaptive behaviors. The present study investigated the moderating effect of concentration problems on the impact of a classroom-based preventive intervention directed at aggressive and shy behaviors in an epidemiologically defined sample of 1,084 urban first-grade children. METHOD: Concentration problems, aggressive behavior, and shy behavior were assessed by a structured teacher interview (the Teacher Observation of Classroom Adaptation-Revised) in the fall and spring of first grade. RESULTS: Children with high ratings on concentration problems in the fall had higher levels of teacher-rated aggressive and shy behavior in the spring than did children without such problems. The intervention reduced aggressive and shy behavior in children regardless of fall concentration level. Boys, but not girls, in the intervention condition with high concentration problems had higher levels of spring aggression than those without such problems, but they also showed the greatest reductions in aggressive behavior from fall to spring. CONCLUSIONS: These results suggest that aggressive behavior is malleable in children with concentration problems, provide further evidence on the etiological significance of concentration problems for the development of maladaptive behavior, and highlight the importance of directly targeting concentration problems to maximize preventive intervention impact.

Caregiver learning needs and reactions to managing home mechanical ventilation.

OBJECTIVE: To identify caregivers' learning needs and reactions to providing care for adult patients receiving mechanical ventilation in the home. This report originated from a study that was undertaken to describe family function and reactions of family members. DESIGN: Prospective, descriptive. SETTING: Data collected at clients' homes in a midwestern city. SUBJECTS: Twenty caregivers and adult patients who are dependent on mechanical ventilation at home. INSTRUMENTS: Patients and their caregivers completed family coping and family function instruments. Caregivers also completed a Learning Needs Checklist and a caregiving inventory. RESULTS: The results indicate that caregivers, all relatives, provided an average of 7.3 hours per day direct care with little assistance from extended family or professionals. More disrupted schedules, financial strain, increased burden, and negative reaction to caregiving was associated with increasing ventilator hours per day. Family function was perceived as satisfactory by both patients and caregivers. Survival knowledge and skills were being taught, but additional information was needed by caregivers. There were no differences by gender in perceived learning needs, family function, or tasks of daily caregiving. CONCLUSIONS: Preferences for types of information suggest the use of a three-phase teaching program that should be sensitive to individual learning needs. A variety of coping strategies were used by families to manage home mechanical ventilation including problem-solving and mobilizing help from friends, extended family, community, or church.

The course and malleability of aggressive behavior from early first grade into middle school: results of a developmental epidemiologically-based preventive trial.

The course and malleability of aggressive behavior from beginning elementary school through transition into middle school was investigated. In a developmental epidemiologically defined population of 1000 urban first graders, a two year classroom-based randomized preventive trial was aimed at reducing aggressive behavior, an antecedent of delinquency, violent behavior, and heavy drug use in adolescence and adulthood. Earlier we reported impact in first grade on teacher and peer ratings and on classroom observations. We report here on the course and on sixth grade teacher ratings of aggressive behavior. Improvement was observable during transition times, in first grade and in middle school, among the males in the preventive intervention who were more aggressive in first grade.

Developmental epidemiologically based preventive trials: baseline modeling of early target behaviors and depressive symptoms.

Describes a conceptual framework for identifying and targeting developmental antecedents in early childhood that have been shown in previous work to predict delinquency and violent behavior, heavy drug use, depression, and other psychiatric symptoms and possibly disorders in late adolescence and into adulthood. Criteria are described that guided choices of targets for two epidemiologically based, randomized preventive trials carried out in 19 elementary schools in the eastern half of Baltimore, involving more than 2,400 first-grade children over the course of first and second grades. Baseline models derived from the first of two cohorts show the evolving patterns of concurrence among the target antecedents. The central role of concentration problems emerged. From Fall to Spring in first grade, concentration problems led to shy and aggressive behavior and poor achievement in both genders and to depressive symptoms among girls. There was evidence for reciprocal relationships in girls. For example, depressive symptoms led to poor achievement in both girls and boys, whereas poor achievement led to depressive symptoms in girls but not boys, at least over the first-grade year. These results provide important epidemiological data relevant to the developmental paths leading to the problem outcomes and suggest preventive trials.

Adaptation in families with a member requiring mechanical ventilation at home.

Current health care trends indicate that ventilator-dependent patients increasingly will be discharged to home after shorter hospitalizations. The purpose of this study was to determine how care givers adapt to having ventilator-dependent adults at home. Twenty families were interviewed in their homes by using an eight-question semistructured interview guide. The Roy model was used as a framework to analyze these data. Two instruments, the Family Coping Scale (F-COPES) and the Family APGAR, were administered to measure family coping and function. Patients, aged 18 to 74 years, required 24-hour (n = 9), 12- to 15-hour (n = 5), or 8- to 12-hour (n = 6) home ventilatory support and had neuromuscular or trauma-related diagnoses. Months receiving ventilation ranged from 2 to 312. Care givers, aged 20 to 74 years, were all relatives. Six care givers reported using support services outside their extended family. F-COPES scores fell within national norms whether the patient required 24-hour or less ventilation. Family APGAR results revealed satisfaction with overall family function although scores decreased over time. Interview data indicated that essential knowledge and skills are taught but additional information is desired. Both positive and negative responses to care giving were identified, with the majority of responses being concerned with role mastery, self-concept, and dependency issues. Positive themes in the interviews reflected confidence in ventilator care, satisfaction with the decision to care for their family member at home, and improved quality of life. Negative themes in the interviews reflected the burden of care giving, the dependence of the patient on the care giver, resentment, and hopelessness.(ABSTRACT TRUNCATED AT 250 WORDS)

Nocturnal positive pressure ventilation via nasal mask.

Five patients with chronic respiratory failure from neuromuscular disease and symptomatic worsening nocturnal hypoventilation were treated with nocturnal ventilation. Home ventilation at night was provided by a volume-cycled positive pressure ventilator attached to a nasal mask originally designed to administer nasal continuous positive airway pressure (CPAP) for obstructive sleep apnea. The device was well tolerated. Symptoms of headache, insomnia/somnolence, and impaired intellectual capacity rapidly disappeared with nocturnal ventilatory support. Daytime arterial PO2 and PCO2 improved after therapy. There are several advantages over commonly used, negative pressure devices for nocturnal ventilation. These include patient synchronization of tidal volume, ease of application, less cumbersome apparatus, more nocturnal patient mobility, and absence of production of upper airway obstruction.