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At least 19 recordsLinked to original sources
PubMed2026

Genetic diversity of Collaborative Cross mice implicates FFAR3 as a target for ILC2 anti-inflammatory reprogramming.

Pulmonary group 2 innate lymphoid cells (ILC2s) are key drivers of Type 2 inflammation in diseases like asthma, yet the molecular mechanisms regulating their function are incompletely understood. Using the genetically diverse Collaborative Cross (CC) mouse panel, we mapped a quantitative trait locus (QTL) that governs ILC2 prevalence in the lung after aeroallergen exposure. This QTL induces a large population of ILC2s in the lung that are resistant to activation and have diminished Type 2 effector function. We identified free-fatty acid receptor 3 (Ffar3) as a gene responsible for this effect and demonstrated that FFAR3 signaling reprograms ILC2s to an anti-inflammatory state by promoting their survival, reducing Type 2 cytokine production, and enhancing IL-10 expression. This anti-inflammatory state is dependent on IL-2 signaling, is characterized by decreased ST2 expression, and is distinct from previously described IL-10-producing ILC2 phenotypes. FFAR3-dependent reprogramming is mediated by epidermal growth factor receptor (EGFR) upregulation, and FFAR3's anti-inflammatory effect is partially conserved in human ILC2s.

Animals↗
PubMed2022

A Multitrait Locus Regulates Sarbecovirus Pathogenesis.

Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to severe acute respiratory syndrome coronavirus (SARS-CoV) disease outcomes. We find several loci control differential disease outcome for a variety of traits in the context of SARS-CoV infection. Importantly, we identify a locus on mouse chromosome 9 that shows conserved synteny with a human GWAS locus for SARS-CoV-2 severe disease. We follow-up and confirm a role for this locus, and identify two candidate genes, CCR9 and CXCR6, that both play a key role in regulating the severity of SARS-CoV, SARS-CoV-2, and a distantly related bat sarbecovirus disease outcomes. As such we provide a template for using experimental mouse crosses to identify and characterize multitrait loci that regulate pathogenic infectious outcomes across species. IMPORTANCE Host genetic variation is an important determinant that predicts disease outcomes following infection. In the setting of highly pathogenic coronavirus infections genetic determinants underlying host susceptibility and mortality remain unclear. To elucidate the role of host genetic variation on sarbecovirus pathogenesis and disease outcomes, we utilized the Collaborative Cross (CC) mouse genetic reference population as a model to identify susceptibility alleles to SARS-CoV and SARS-CoV-2 infections. Our findings reveal that a multitrait loci found in chromosome 9 is an important regulator of sarbecovirus pathogenesis in mice. Within this locus, we identified and validated CCR9 and CXCR6 as important regulators of host disease outcomes. Specifically, both CCR9 and CXCR6 are protective against severe SARS-CoV, SARS-CoV-2, and SARS-related HKU3 virus disease in mice. This chromosome 9 multitrait locus may be important to help identify genes that regulate coronavirus disease outcomes in humans.

Animals↗
PubMed1992

Drug treatment of panic disorder. Comparative efficacy of alprazolam, imipramine, and placebo. Cross-National Collaborative Panic Study, Second Phase Investigators.

The Cross-National Collaborative Panic Study, Phase Two, compared alprazolam with imipramine and with placebo in a sample of 1168 randomly assigned subjects. The study, conducted at 12 centres, assessed clinical change over eight weeks of double-blind drug treatment. Improvement occurred with alprazolam by week 1 and 2, and with imipramine by week 4. By the end of week 8, however, the effects of the two active drugs were similar to each other, and both were superior to placebo for most outcome measures.

Adult↗
PubMed1992

Center differences and cross-national invariance in help-seeking for panic disorder. A report from the cross-national collaborative panic study.

Help-seeking behaviour for treatment of panic disorder was investigated in the sample of the Cross-National Collaborative Panic Study Second Phase. A total of 1168 patients were entered into this trial in 14 countries. Although there were significant center differences in prior treatment and utilization of health services there were also similarities. Treatment had been provided mainly by general practitioners. Drug treatment consisted mostly of prescription of classical tranquilizers and had a longer duration than treatment by psychotherapy. Patients with agoraphobic avoidance, past major depression and longer duration of illness used medical and psychiatric treatment facilities more intensely. Older and more severely disabled subjects were more frequently treated by medical health care providers and were more likely to receive psychotropic drugs. The results indicate that general practitioners carry an important load in the treatment of panic disorders but may need more information about recent development in pharmacotherapy for this condition.

Adult↗
PubMed1991

Chronology of panic and avoidance, age of onset in panic disorder, and prediction of treatment response. A report from the Cross-National Collaborative Panic Study.

The relevance of the chronology between panic disorder and avoidance behavior and of an early, medium or late onset of panic disorder was tested. Groups from the sample of the cross-national collaborative panic study (CNCPS) were compared for differences in basic characteristics and for the ability to predict treatment response. Patients who developed avoidance behavior before the full syndrome of panic disorder had less often a full agoraphobia but were not different in their response to treatment. Patients with an early onset of panic disorder suffered more often from agoraphobia. The treatment response was similar in the groups with early, medium or late onset of panic disorder. Neither the chronology between panic disorder and avoidance behavior nor the age of onset of panic disorder predicted outcome in short-term treatment with alprazolam or imipramine.

Adult↗
PubMed2026

IMPROVE kidney care: perspectives from marginalised people with CKD and risk factors for CKD on access to, and experience of, kidney care services: a cross-sector collaborative exploration, employing qualitative approaches.

BACKGROUND: Access to, and experience of, chronic kidney disease (CKD) care is inequitable-with barriers to accessing quality care for marginalised groups. We conducted an exploratory study employing qualitative approaches to understand the factors that influence access to, and experience of, healthcare services for marginalised people with CKD and at risk of CKD. METHODS: An exploratory study employing qualitative approaches was conducted as a cross-sector collaboration between kidney care services and an activist, antiracist community-based research and social justice organisation (Mabadiliko Community Interest Company (CIC)). Two groups were recruited: 1) those with risk factors for CKD or early-stage CKD, and 2) people who presented late to kidney care services. Semi-structured interviews were co-designed with people with lived experience and conducted by Mabadiliko CIC. Thematic analysis was undertaken, with themes refined by participants. RESULTS: Twenty interviews were undertaken with a diverse cohort of participants. Knowledge and awareness of CKD was limited, and compounded by a lack of delivery of accessible, culturally congruent information. Significant barriers to accessing kidney care exist for marginalised people, including people who are from global majority ethnic backgrounds, Disabled people, and/or people experiencing material hardship. These barriers are compounded by interpersonal discrimination and paternalistic power dynamics within healthcare interactions. CONCLUSION: This study captures the experiences of marginalised people at different stages of their journey with CKD, in accessing and engaging with kidney care services. Participants faced a complex array of challenges, highlighting opportunities for multi-level intervention. We outline recommendations to address these issues, co-developed with participants.

chronic kidney disease↗
PubMed1992

The changing rate of major depression. Cross-national comparisons. Cross-National Collaborative Group.

OBJECTIVE: To estimate temporal trends in the rates of major depression cross-nationally. DESIGN: Nine epidemiologic surveys and three family studies. SETTING AND PARTICIPANTS: Approximately 39,000 subjects in population-based samples from nine epidemiologic surveys, and 4000 relatives from three family studies that were conducted independently but using similar methodology in the 1980s in North America, Puerto Rico, Western Europe, the Middle East, Asia, and the Pacific Rim. OUTCOME MEASURES: Age at first onset of major depression by birth cohort and time period. RESULTS: There was an increase in the cumulative lifetime rates of major depression with each successively younger birth cohort at all sites with the exception of the Hispanic samples, in whom the rates in the older cohort (1915 through 1935) were approximately equal to those of the younger cohorts. However, results of fitting statistical models that separate period and cohort effects showed an overall increase in the rates of major depression over time over all countries, although the magnitude of the increase varied by country. The average relative risk of major depression between a particular cohort and the cohort born immediately before varied between 2.6 (95% confidence interval, 1.8 to 3.7) in Florence, Italy, and 1.3 (95% confidence interval, 1.2 to 1.4) in Christchurch, New Zealand. Short-term fluctuations in the rates of major depression during specific time periods and in specific cohorts also varied by country. CONCLUSIONS: Cross-nationally, the more recent birth cohorts are at increased risk for major depression. There are, however, variations in the long- and short-term trends for major depression by country, which suggests that the rates in these countries may have been affected by differing historical, social, economic, or biological environmental events. The linking of demographic, epidemiologic, economic, and social indices by country to these changes may clarify environmental conditions that influence the rates of major depression.

Adult↗
PubMed2025

Cathepsin Z is a conserved susceptibility factor underlying tuberculosis severity.

Tuberculosis (TB) outcomes vary widely, from asymptomatic infection to mortality, yet most animal models do not recapitulate human phenotypic and genotypic variation. The genetically diverse Collaborative Cross mouse panel models distinct facets of TB disease that occur in humans and allows identification of genomic loci underlying clinical outcomes. We previously mapped a TB susceptibility locus on mouse chromosome 2. Here, we identify cathepsin Z (Ctsz) as a lead candidate underlying this TB susceptibility and show that Ctsz ablation leads to increased bacterial burden, pulmonary inflammation and decreased survival in mice. Ctsz disturbance within murine macrophages enhances production of chemokine (C-X-C motif) ligand 1 (CXCL1), a known biomarker of TB severity. From a Ugandan household contact study, we identify significant associations between CTSZ variants and TB disease severity. Finally, we examine patient-derived TB granulomas and report CTSZ localization within granuloma-associated macrophages, placing human CTSZ at the host-pathogen interface. These findings implicate a conserved CTSZ-CXCL1 axis in humans and genetically diverse mice that mediates TB disease severity.

Animals↗
PubMed1991

Transmission of human T-lymphotropic virus types I and II by blood transfusion. A retrospective study of recipients of blood components (1983 through 1988). The American Red Cross HTLV-I/II Collaborative Study Group.

We studied results of a "lookback" program involving laboratory testing and interviews of 133 recipients of prior donations from blood donors seropositive for human T-lymphotropic virus types I and II (HTLV-I/II) identified at 28 American Red Cross blood centers. The study was designed to explore the natural course of posttransfusion HTLV-I/II infection among individuals who received blood components from donors subsequently identified as being HTLV-I/II seropositive. Seventeen recipients were seropositive, an apparent transmission rate of 12.8%. Red blood cells and platelets were the implicated components, and red blood cells that were less than 6 days old had a transmission efficiency of 80%. Virus typing enabled documentation of primary and secondary transfusion transmission of HTLV-I and HTLV-II, including the direct transmission of HTLV-II by a donor with a history of intravenous drug use. We conclude that transfusion transmission of HTLV-I/II to approximately 700 recipients per year occurred in the United States before routine donor testing began in 1988.

Adolescent↗
PubMed2024

A research synthesis of humans, animals, and environmental compartments exposed to PFAS: A systematic evidence map and bibliometric analysis of secondary literature.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a class of widely used anthropogenic chemicals. Concerns regarding their persistence and potential adverse effects have led to multiple secondary research publications. Here, we aim to assess the resulting evidence base in the systematic secondary literature by examining research gaps, evaluating the quality of reviews, and exploring interdisciplinary connections. METHODS: This study employed a systematic evidence-mapping approach to assess the secondary literature on the biological, environmental, and medical aspects of exposure to 35 fluorinated compounds. The inclusion criteria encompassed systematic reviews published in peer-reviewed journals, pre-prints, and theses. Comprehensive searches across electronic databases and grey literature identified relevant reviews. Data extraction and synthesis involved mapping literature content and narrative descriptions. We employed a modified version of the AMSTAR2 checklist to evaluate the methodological rigour of the reviews. A bibliometric data analysis uncovered patterns and trends in the academic literature. A research protocol for this study was previously pre-registered (osf.io/2tpn8) and published (Vendl et al., Environment International 158 (2022) 106973). The database is freely accessible through the interactive and user-friendly web application of this systematic evidence map at https://hi-this-is-lorenzo.shinyapps.io/PFAS_SEM_Shiny_App/. RESULTS: Our map includes a total of 175 systematic reviews. Over the years, there has been a steady increase in the annual number of publications, with a notable surge in 2021. Most reviews focused on human exposure, whereas environmental and animal-related reviews were fewer and often lacked a rigorous systematic approach to literature search and screening. Review outcomes were predominantly associated with human health, particularly with reproductive and children's developmental health. Animal reviews primarily focused on studies conducted in controlled laboratory settings, and wildlife reviews were characterised by an over-representation of birds and fish species. Recent reviews increasingly incorporated quantitative synthesis methodologies. The methodological strengths of the reviews included detailed descriptions of study selection processes and disclosure of potential conflicts of interest. However, weaknesses were observed in the critical lack of detail in reporting methods. A bibliometric analysis revealed that the most productive authors collaborate within their own country, leading to limited and clustered international collaborations. CONCLUSIONS: In this overview of the available systematic secondary literature, we map literature content, assess reviews' methodological quality, highlight data gaps, and draw research network clusters. We aim to facilitate literature reviews, guide future research initiatives, and enhance opportunities for cross-country collaboration. Furthermore, we discuss how this systematic evidence map and its publicly available database benefit scientists, regulatory agencies, and other stakeholders by providing access to current systematic secondary literature on PFAS exposure.

Bibliometrics↗
PubMed1992

Assessing impairment in patients with panic disorder: the Sheehan Disability Scale.

The DSM-III-R incorporates both distress (symptoms) and disability (impairment) in the definition of a psychiatric disorder. In psychiatric research there is a wide array of instruments used to measure symptom severity, but a limited selection for the assessment of impairment. The psychometric properties of one such instrument, The Sheehan Disability Scale (Sheehan 1983), are evaluated in this paper. The data analyzed come from two studies of patients with panic disorder, the Cross National Collaborative Panic Study--Phase I and the Panic Depression Study. In this report both the alpha coefficients and factor analyses indicate that the reliability of the scale is acceptable. The factor structure of the items and the sensitivity to change of their composite demonstrate satisfactory construct validity. The criterion-related validity is substantiated by the significant relationship between symptomatology and impairment. These analyses were limited to patients with panic disorder. Further work is needed to evaluate the instrument in assessing patients with other disorders.

Activities of Daily Living↗
PubMed1990

Consistencies and discrepancies in self- and observer-rated anxiety scales. A comparison between the self- and observer-rated Marks-Sheehan scales.

The Marks-Sheehan anxiety scales are the only scales where self-ratings and observer ratings are perfectly matched by the number, the content and the scaling of the items. Therefore these scales are an excellent tool to investigate the compatibility and to study different structures in self- and observer ratings. This was done by using the data material on the Marks-Sheehan scales of the Cross National Collaborative Panic Study. In this study 1168 outpatients who met the DSM-III criteria for panic disorder were randomly allocated either to alprazolam, imipramine or placebo treatment. Our results show that the Marks-Sheehan scales are highly comparable to other established rating scales. Both scales have a similar stable and consistent factor pattern for somatic symptoms but not for psychic symptoms of anxiety. Our results provide empirical evidence that the low consistencies between self- and observer ratings reported so far can be improved by using a rating scale which matches up item for self- and observer ratings. However, other sources of disagreement can only be solved by more elaborated item descriptions and training of patients as well as raters to obtain a better compatibility between self- and observer rating scales.

Adult↗
PubMed1990

Self- and observer assessment in anxiolytic drug trials: a comparison of their validity.

Self-rating scales are considered to be less useful for comparing different treatments in anxiety patients than observer-rating scales. However, the empirical evidence for this assumption is not adequate. A self-rating inventory of 35 items related to anxiety was perfectly parallel with an observer-rating inventory. Both instruments were used in the Cross National Collaborative Panic Study to compare the efficacy of imipramine, alprazolam and placebo in an 8-week drug trial in a sample of 1168 outpatients. The variance of the self-rating assessments was about two times higher. Both scales were equally sensitive to change; however, the measurement of change by means of the self-rating scale was slightly less consistent. The discriminative power of the observer-rating scale between placebo and active treatment was two to three times higher than that of the self-rating scale; consequently the observer-rating procedure provides a more valid instrument when the efficacies of different anxiolytic treatments are compared between different groups of patients.

Adult↗
PubMed1991

Subtyping panic disorder by major depression and avoidance behaviour and the response to active treatment.

In order to establish the clinical validity of currently used ways of subtyping panic disorder the predictive power of associated current avoidance behaviour and (secondary) major depression for the response to active treatment (alprazolam, imipramine) was tested. The analysis was based on the data from the Cross-National-Collaborative-Panic-Study. Limited support for validity evidenced by predicting drug response was found for grading panic disorder by the severity of avoidance behaviour; patients with panic attacks and agoraphobia are more responsive to imipramine (compared with alprazolam) when using the reduction of the total number of panic attacks (or of spontaneous panic attacks) as the outcome criterion; patients without any avoidance behaviour did better with alprazolam (compared with imipramine).

Adult↗
PubMed1991

Avoidance behaviour: a predictor of the efficacy of pharmacotherapy in panic disorder?

The impact of the avoidance behaviour on the psychopharmacological treatment of panic disorder was explored in the Cross National Collaborative Panic Study (n = 1134 patients); in this double blind randomized trial alprazolam, imipramine and placebo were compared during an 8-week treatment period. Patients with extensive avoidance behaviour (agoraphobia) had the most profit from the active drugs. Counter expectancy these specific drug effects were most pronounced in avoidance behaviour. Active drugs (in particular imipramine) were especially more effective than placebo if the patients presented with associated avoidance behaviour. The results suggest that agoraphobia defines more a particular type of anxiety disorder overlapping with panic disorder than merely a severe state of panic disorder.

Adult↗
PubMed1990

Depression and panic anxiety: the effect of depressive co-morbidity on response to drug treatment of patients with panic disorder and agoraphobia.

Numerous studies have established that there is increased co-morbidity of depressive symptoms among patients with panic disorder with and without agoraphobia, but questions remain as to whether the symptom pattern and clinical course are similar to that of primary depressions. The Cross-National Collaborative Panic Study was initiated to study the effects of alprazolam, a triazolobenzodiazepine, in the treatment of panic disorder. In the first phase, which included more than 500 subjects, alprazolam was compared against placebo. In the second phase, alprazolam was compared with imipramine and placebo in a double-blind, randomized, controlled trial. Results of both the first and second phases will be reviewed as they bear on the issue of drug treatment of secondary depression accompanying panic disorder. The presence of depressive symptoms does not adversely influence anti-panic and anti-phobic response to medication. Equivalent drug-placebo differences occur on multiple measures of anxiety--including the number and intensity of panic attacks, phobias, anticipatory anxiety, and overall anxiety.

Agoraphobia↗