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PubMed1993

Microscopic spiral waves reveal positive feedback in subcellular calcium signaling.

The regenerative Ca(2+)-induced Ca2+ release mechanism is an important amplifier of signal transduction in diverse cells. In heart muscle cells, this mechanism contributes to the Ca2+ transient activating the mechanical contraction, but it is also believed to drive Ca2+ waves propagating within the cytosol. We investigated the subcellular Ca2+ distribution in heart muscle cells during spontaneous Ca2+ release using laser scanning confocal microscopy with a ratiometric fluorescent indicator technique. Besides planar Ca2+ waves with linear propagation, sequences of confocal optical sections also revealed spiral Ca2+ waves spinning around a subcellular core at approximately 1 Hz. Although the Ca2+ spirals were continuous processes they frequently exhibited an apparently oscillatory output function into the elongated cell body. These oscillatory waves emanating from the spiral at regular intervals were formally considered to be short outer segments of the spiral but could not be distinguished from planar Ca2+ waves propagating along the longitudinal cell axis. The complex spatiotemporal pattern of spiral Ca2+ waves implies the participation of an active process exhibiting a large degree of positive feedback, most likely the Ca(2+)-induced Ca2+ release mechanism.

Aniline Compounds↗

PubMed2006

Trends in physical activity and sedentary behaviour in adolescence: ethnic and socioeconomic differences.

OBJECTIVE: To assess developmental trends in physical activity and sedentary behaviour in British adolescents in relation to sex, ethnicity and socioeconomic status (SES). DESIGN: A 5-year longitudinal study of a diverse cohort of students aged 11-12 years at baseline in 1999. SETTING: 36 London schools sampled using a stratified random sampling procedure. PARTICIPANTS: A total of 5863 students categorised as white, black or Asian, and stratified for SES using the Townsend Index. MAIN OUTCOME MEASURES: Number of days per week of vigorous activity leading to sweating and breathing hard. Hours of sedentary behaviour, including watching television and playing video games. Data were analysed using multilevel, linear, mixed models. RESULTS: Marked reductions in physical activity and increases in sedentary behaviour were noticed between ages 11-12 and 15-16 years. Boys were more active than girls, and the decline in physical activity was greater in girls (46% reduction) than in boys (23%). Asian students were less active than whites, and this was also true of black girls but not boys. Black students were more sedentary than white students. Levels of sedentary behaviour were greater in respondents from lower SES. Most differences between ethnic and SES groups were present at age 11 years, and did not evolve over the teenage years. CONCLUSIONS: Physical activity declines and sedentary behaviour becomes more common during adolescence. Ethnic and SES differences are observed in physical activity and sedentary behaviour in British youth that anticipate adult variations in adiposity and cardiovascular disease risk. These are largely established by age 11-12 years, so reversing these patterns requires earlier intervention.

Adolescent↗

PubMed2026

The COVID-19 pandemic influenced the temporal dynamics of antimicrobial resistance markers and bacterial community across urban wastewater treatment plants.

Urban wastewater systems represent important interfaces between human activity and the environmental occurrence of antimicrobial resistance (AMR) markers. We assessed the temporal dynamics of intI1, ermB, and the 16 S rRNA gene by quantitative PCR across three wastewater systems (EPC, CJC, and JW) in Fortaleza, Brazil, from November 2021 to November 2023. Bacterial communities were additionally characterized by 16 S rRNA gene metabarcoding in 18 samples collected in December 2021 and January 2022. A synchronized decline in 16 S rRNA gene and intI1 concentrations beginning in late 2022 was observed across all three wastewater systems, suggesting a shift toward lower microbial abundance. The ermB gene showed higher and more variable concentrations during part of the pandemic period, followed by convergence toward lower levels; however, the absence of antimicrobial-consumption data precluded attribution of this pattern to changes in macrolide selective pressure. Normalized antimicrobial resistance marker abundances were comparatively stable at EPC and JW but more variable at CJC. EPC exhibited the highest ASV richness, whereas CJC and JW showed greater diversity according to Shannon and inverse Simpson indices. Beta-diversity analyses identified wastewater system as the principal factor associated with bacterial community structure, while the effect of sampling period was smaller and metric-dependent. Neither ermB nor intI1 was individually associated with community composition, although intI1 showed a limited effect after adjustment for wastewater system in one model. Physicochemical parameters were not significantly associated with normalized marker abundances in the exploratory paired analysis. Arcobacter, Acinetobacter, and other potentially relevant genera were detected, but no direct associations between these taxa and the monitored AMR markers could be established. These findings highlight the value of integrating longitudinal qPCR, microbiome profiling, and environmental characterization to improve the interpretation of targeted AMR markers in One Health wastewater surveillance.

Wastewater↗

PubMed2005

The neurodevelopmental model of schizophrenia: update 2005.

Neurodevelopmental models of schizophrenia that identify longitudinal precursors of illness have been of great heuristic importance focusing most etiologic research over the past two decades. These models have varied considerably with respect to specificity and timing of hypothesized genetic and environmental 'hits', but have largely focused on insults to prenatal brain development. With heritability around 80%, nongenetic factors impairing development must also be part of the model, and any model must also account for the wide range of age of onset. In recent years, longitudinal brain imaging studies of both early and adult (to distinguish from late ie elderly) onset populations indicate that progressive brain changes are more dynamic than previously thought, with gray matter volume loss particularly striking in adolescence and appearing to be an exaggeration of the normal developmental pattern. This supports an extended time period of abnormal neurodevelopment in schizophrenia in addition to earlier 'lesions'. Many subtle cognitive, motor, and behavioral deviations are seen years before illness onset, and these are more prominent in early onset cases. Moreover, schizophrenia susceptibility genes and chromosomal abnormalities, particularly as examined for early onset populations (ie GAD1, 22q11DS), are associated with premorbid neurodevelopmental abnormalities. Several candidate genes for schizophrenia (eg dysbindin) are associated with lower cognitive abilities in both schizophrenic and other pediatric populations more generally. Postmortem human brain and developmental animal studies document multiple and diverse effects of developmental genes (including schizophrenia susceptibility genes), at sequential stages of brain development. These may underlie the broad array of premorbid cognitive and behavioral abnormalities seen in schizophrenia, and neurodevelopmental disorders more generally. Increased specificity for the most relevant environmental risk factors such as exposure to prenatal infection, and their interaction with susceptibility genes and/or action through phase-specific altered gene expression now both strengthen and modify the neurodevelopmental theory of schizophrenia.

Adult↗

PubMed2001

Dissection of the humoral immune response toward an immunodominant epitope of HIV: a model for the analysis of antibody diversity in HIV+ individuals.

Understanding the dynamics of the humoral immune response to HIV epitopes in the presence of genetic drift and antigenic variation of the virus may reveal critical elements of protective immunity against HIV. Analysis of antibody maturation and diversity is difficult to study at the molecular level in humans. We used a combinatorial phage display peptide library to elucidate antibody diversity in HIV-infected individuals to a single immunodominant epitope in gp41. A serum sample derived from an HIV+ individual was used to screen a phage display a 12 mer cysteine-constrained loop peptide library. In doing so, we isolated mimotope-presenting phages corresponding to the immunodominant gp41 epitope CSGKLIC (residues 603-609). The mimotopes and control phages expressing epitope variants were reacted with a panel of 30 HIV+ sera. The patients showed distinct and variable recognition patterns compared with one another. Subfractions of the polyclonal sera were affinity purified and analyzed for epitope specificities. These analyses illustrated that epitope variants can be used to decipher antibody diversity. Elucidation of the plasticity of the humoral response and its polyclonality toward discrete epitopes contributes to our understanding of the antibody maturation process in individuals infected with viruses such as HIV.

Amino Acid Sequence↗

PubMed1997

Vacuolar reticulum in oomycete hyphal tips: An additional component of the Ca2+Regulatory system?

Cultures of Achlya sp., Phytophthora cinnamomi, Saprolegnia diclina, S. ferax, and S. parasitica, treated with 6-carboxyfluorescein diacetate solution, accumulate 6-carboxyfluorescein in a reticulate system of fine tubules. The network shows longitudinal polarity within the hyphae, tubules being finest toward the hyphal tips. In more mature subapical regions the network is connected with large vacuoles that also accumulate 6-carboxyfluorescein. A morphologically similar system has also been identified in freeze-substituted hyphae of S. ferax. The network is considered to be vacuolar, but differs from the tubular vacuole system of true fungi in that tubules are less motile, more frequently branched, and do not alternate with clusters of spherical vacuoles. The appearance of the network resembles patterns of calcium-sensitive dye staining and it is suggested that the vacuolar reticulum in the tip region of oomycete hyphae may act as a Ca2+ sink. The tubular reticulum in oomycetes is very fragile and can be shown with 6-carboxyfluorescein in only those hyphal tips with a motility and organelle distribution characteristic of growing hyphae with normal morphology. Diverse abnormal hyphae show a range of other fluorochrome localizations. These include large irregular compartments filled with fluorochrome, and fluorescent cytoplasm with organelles and vacuoles standing out in negative contrast. These localizations in abnormal hyphae are correlated with other structural changes indicative of damage. Special care is required in experiments with oomycetes to avoid such artefacts of localization. Copyright 1997 Academic Press. Copyright 1997 Academic Press

Journal Article↗

PubMed1998

Hypoxia and hypothermia enhance spatial heterogeneities of repolarization in guinea pig hearts: analysis of spatial autocorrelation of optically recorded action potential durations.

INTRODUCTION: Regional dispersions of repolarization (DOR) are arrhythmogenic perturbations that are closely associated with reentry. However, the characteristics of DOR have not been well defined or adequately analyzed because previous algorithms did not take into account spatial heterogeneities of action potential durations (APDs). Earlier simulations proposed that pathologic conditions enhance DOR by decreasing electrical coupling between cells, thereby unmasking differences in cellular repolarization between neighboring cells. Optical mapping indicated that gradients of APD and DOR are associated with fiber structure and are largely independent of activation. We developed an approach to quantitatively characterize APD gradients and DOR to determine how they are influenced by tissue anisotropy and cell coupling during diverse arrhythmogenic insults such as hypoxia and hypothermia. METHODS AND RESULTS: Voltage-sensitive dyes were used to map APs from 124 sites on the epicardium of Langendorff-perfused guinea pig hearts during (1) cycles of hypoxia and reoxygenation and (2) after 30 minutes of hypothermia (32 degrees to 25 degrees C). We introduce an approach to quantitate DOR by analyzing two-dimensional spatial autocorrelation of APDs along directions perpendicular and parallel to the longitudinal axis of epicardial fibers. A spatial correlation length L was derived as a statistical measure of DOR. It corresponds to the distance over which APDs had comparable values, where L is inversely related to DOR. Hypoxia (30 min) caused a negligible decrease in longitudinal thetaL (from 0.530 +/- 0.138 to 0.478 +/- 0.052 m/sec) and transverse thetaT (from 0.225 +/- 0.034 to 0.204 +/- 0.021 m/sec) conduction velocities and did not alter thetaL/thetaT or activation patterns. In paced hearts (cycle length [CL] = 300 msec), hypoxia decreased APDs (123 +/- 18.2 to 46 +/- 0.6 msec; P < 0.001) within 10 to 15 minutes and enhanced DOR, as indicated by reductions of L from 1.8 +/- 0.9 to 1.1 +/- 0.5 mm (P < 0.005). Hypothermia caused marked reductions of thetaL (0.53 +/- 0.138 to 0.298 +/- 0.104 m/sec) and thetaT (0.225 +/- 0.034 to 0.138 +/- 0.027 m/sec), increased APDs (128 +/- 4.4 to 148 +/- 14.5 msec), and reduced L from 2.0 +/- 0.3 to 1.3 +/- 0.6 mm (P < 0.05). L decreased with increased time of hypoxia and recovered upon reoxygenation. Hypoxia and hypothermia reduced L measured along the longitudinal (L(L)) and transverse (L(T)) axes of cardiac fibers while the ratio of L(L)/L(T) remained constant. CONCLUSION: Conventional indexes of DOR (i.e., APD "range" or "standard deviation," evaluated with extracellular electrodes) did not convey the spatial inhomogeneities of repolarization revealed by L. Spatial autocorrelation analysis provides a statistically significant measurement of DOR, which can take into account intrinsic heterogeneities of APDs and fiber orientation. The data show that hypoxia and hypothermia produce reductions of L, even though they have different effects on mean APD and conduction velocity. The preservation of a constant L(L)/L(T) ratio during hypoxia and hypothermia, despite large reductions in L, is consistent with a mechanism in which reduced cell-to-cell coupling unmasks intrinsic dispersions of APD and reduces L(L) and L(T) by the same factor. Thus, the spatial autocorrelation of APDs provides a sensitive index of DOR under normal and arrhythmogenic conditions. It incorporates the anisotropic nature of the myocardium and therefore is preferable to conventional indexes of DOR.

Action Potentials↗

PubMed1999

Genotypes of merozoite surface protein 2 of Plasmodium falciparum in Tanzania.

The merozoite surface protein 2 (MSP2) of Plasmodium falciparum is extremely polymorphic: 82 different msp2 alleles were found in 4 studies of molecular epidemiology conducted in Tanzania. This diversity renders msp2 suitable as a marker gene for the genotyping of P. falciparum infections. Amplification of msp2 by the polymerase chain reaction (PCR), and subsequent restriction digests of the PCR product (PCR-restriction fragment length polymorphism genotyping), has proved to be an informative tool for enumerating multiple concurrent infections in a blood sample, and distinguishing individual alleles. Depending on the specific questions asked in a genotyping study, analytical techniques of different degrees of complexity are employed. The restriction fragments resulting from a single HinfI digest generally allow the enumeration of multiple concurrent infections and the determination of their allelic families. When a restriction pattern is too complex to be resolved, owing to the high number of concurrent infections, or due to the appearance of previously undescribed alleles, one or more additional digests (DdeI, RsaI, ScrfI) may be necessary. To determine individual alleles unequivocally, in particular in longitudinal studies, when several consecutive samples need to be compared with each other, a more detailed analysis involving all 3 additional digests is applied. The methodological experience and results gained in 4 epidemiological field studies involving msp2 genotyping are summarized. We also provide the HinfI restriction patterns and some nucleotide sequences of the alleles found so far in our studies in Tanzania.

Alleles↗

PubMed2000

Use of hydrofluoroalkane propellant delivery system for inhaled albuterol in patients receiving asthma medications.

OBJECTIVE: This study was undertaken to assess drug-use patterns associated with albuterol delivery via a new propellant device compared with conventional chlorofluorocarbon (CFC) metered-dose inhalers (MDIs) in patients taking asthma medications in a population with pharmacy benefits. BACKGROUND: In addition to their ozone-depleting properties, conventional CFC inhalers often deliver inconsistent doses because of loss of prime and temperature instability. A new propellant, hydrofluoroalkane (HFA), incorporates a re-engineered delivery system associated with dosing reproducibility throughout the life of the canister. METHODS: Drug markers associated with management of asthma were used to identify a study cohort of new users of inhaled albuterol from a geographically diverse pharmacyclaims database from July 1, 1997, through December 31, 1997. A population of 282,879 members was identified over the 20-month follow-up period. In addition, a subset of chronic albuterol inhaler users (> or = 12 months; n = 96,879) was also identified to support a longitudinal analysis. Disease severity was controlled for by use of inhaled corticosteroids (ICS). To control for canisters received via physician office samples, HFA patient use was corrected by a physician-based canister adjustment based on HFA sample data. RESULTS: A total of 53.1% of participants were women and 46.1% were men; most of the population (72.5%) was <65 years of age. Canister use for HFA patients was consistently lower (2.7+/-3.2 vs 5.4+/-6.7) than for CFC MDIs for the entire cohort over the 20-month assessment period. This difference was consistently observed for albuterol canister use in patients with and without concomitant ICS use (3.3+/-3.8 HFA vs 7.2+/-7.5 CFC for ICS users and 2.1+/-2.1 HFA vs 4.1+/-5.7 CFC for non-ICS users). Time to next prescription also was longer for HFA patients than for CFC patients (61.6+/-50.9 days HFA vs 47.3+/-40.8 days CFC). When duration of therapy and physician samples associated with product launch were controlled for, similar differences were consistently observed. CFC patients used, on average, 1.3 more canisters per year than did HFA patients (P < 0.001), averaging 10.7 canisters (95% CI, 10.6 to 10.7), compared with 9.4 canisters used by HFA patients (95% CI, 8.9 to 9.9). Further analyses indicated that this finding was consistent when ICS use was controlled for (CFC plus ICS mean, 11.9 canisters vs HFA plus ICS mean, 10.4 canisters; P < 0.001). CONCLUSION: This study provides useful information about the effect of use of a new albuterol delivery system on asthma inhaler management. These data suggest that CFC patients use an average of 1.3 more canisters per year compared with HFA patients independent of asthma severity as measured by ICS use. This improvement in dosing characteristics has the potential to translate into enhanced economic outcomes.

Administration, Inhalation↗

PubMed2026

Evolution of tumor subclones and T-cell dynamics underlie variable ibrutinib responses in Waldenström macroglobulinemia.

To elucidate the molecular basis underlying differential responses and resistance to ibrutinib in Waldenström macroglobulinemia (WM), we conducted a prospective phase 2 trial of ibrutinib monotherapy in treatment-naïve patients. A total of 74 sequential bone marrow (BM) aspirates from 17 patients, collected from baseline through 48 treatment cycles, were profiled using single-cell multiomics. BM cells were segregated primarily into B-cell/plasma cell and T-cell compartments. Longitudinal clonal tracking of malignant B cells/plasma cells identified 3 distinct evolutionary patterns: evolution (early clone contraction with late clone expansion and increasing genomic complexity), devolution (early clone expansion with late clone contraction and genomic simplification), and no evolution (stable clonal architecture). The evolution pattern was strongly associated with disease progression, whereas devolution correlated with durable clinical response. Transcriptomic profiling of resistant clones enabled development and validation of the Waldenström ibrutinib prediction (WIP) score, which predicted treatment response at baseline. Within the WIP signature, LYN emerged as a key regulator; LYN knockdown or inhibition significantly increased WM cell sensitivity to ibrutinib, suggesting a rational combination strategy. In parallel, GZMB+ CD8+ effector-memory T cells expanded after treatment in patients with progressive disease and coexisted with tumor evolution. These cells exhibited persistently impaired cytotoxic programs (eg, GNLY), a dedifferentiated memory-like state, elevated PDCD1 expression, and reduced T-cell receptor diversity. Together, this study provides, to our knowledge, the first single-cell framework of tumor clonal evolution and T-cell dysfunction under ibrutinib in WM, introduces the WIP score as a predictive biomarker for treatment response, and identifies actionable tumor-intrinsic and immune mechanisms driving resistance. This trial was registered at www.ClinicalTrials.gov as NCT02604511.

Aged↗

PubMed1995

Access to paid in-home assistance among disabled elderly people: do Latinos differ from non-Latino whites?

OBJECTIVES: The purpose of this study was to compare the national prevalences and predictors of paid in-home functional assistance among disabled Latino and non-Latino elderly people who receive such assistance. METHODS: Data were derived from the 1988 wave of the National Center for Health Statistics Longitudinal Study on Aging and the 1988 Commonwealth Fund Commission Survey of Elderly Hispanics. Logistic regression was used to model paid care use and to calculate estimated probabilities of such use. RESULTS: Among Latino and non-Latino Whites 74 years of age and older who received functional assistance, similar proportions used paid assistance. Predictors of paid care coincided with established models for non-Latino Whites only. Disabled Latinos had a lower estimated probability of using paid assistance when they were highly disabled and socially isolated but had a higher estimated probability when their children lived nearby. CONCLUSIONS: The effects of disability and social support differ among non-Latino White and Latino elderly people. Latino elderly people with high anticipated needs obtain less paid assistance than similar non-Latino Whites. In addition to a reduction in financial barriers, improving access to long-term care services requires addressing this diversity in service use patterns.

Activities of Daily Living↗

PubMed2025

Host clustering of Campylobacter species and enteric pathogens in a longitudinal cohort of infants, family members and livestock in rural Eastern Ethiopia.

BACKGROUND: Livestock are recognized as major reservoirs for Campylobacter species and other enteric pathogens, posing infection risks to humans. High prevalence of Campylobacter during early childhood has been linked to environmental enteric dysfunction and stunting, particularly in low-resource settings. METHODS: A total of 280 samples from Campylobacter positive households with complete metadata were analyzed by shotgun metagenomic sequencing followed by bioinformatic analysis via the CZ-ID metagenomic pipeline (Illumina mNGS Pipeline v7.1). Further statistical analyses in JMP PRO 16 explored the microbiome, emphasizing Campylobacter and other enteric pathogens. Two-way hierarchical clustering and split k-mer analysis examined host structuring, patterns of co-infections and genetic relationships. Principal component analysis was used to characterize microbiome composition across the seven sample types. RESULTS: The study identified that microbiome composition was strongly host-driven, with more than 3844 genera detected, and two principal components explaining 62% of the total variation. Twenty-one dominant (based on relative abundance) Campylobacter species showed distinct clustering patterns for humans, ruminants, and broad hosts. The broad-host cluster included the most prevalent species, C. jejuni, C. concisus, and C. coli, present across sample types and a sub-cluster within C. jejuni involving humans, chickens, and ruminants. Campylobacter species from chickens showed strong positive correlations with mothers (r = 0.76), siblings (r = 0.61) and infants (r = 0.54), while co-occurrence analysis found a higher likelihood (Pr > 0.5) of pairs such as C. jejuni with C. coli, C. concisus, and C. showae. Analysis of the top 50 most abundant microbial taxa showed a distinct cluster uniquely present in human stool and absent in all livestock. The study also found frequent co-occurrence of C. jejuni with other enteric pathogens such as Salmonella, and Shigella, particularly in human and chicken. Additionally, instances of Candidatus Campylobacter infans (C. infans) were identified co-occurring with Salmonella and Shigella species in stool samples from infants, mothers, and siblings. CONCLUSIONS: A comprehensive analysis of Campylobacter diversity in humans and livestock in a low-resource setting revealed that infants can be exposed to multiple Campylobacter species early in life. C. jejuni is the dominant species with a propensity for co-occurrence with other notable enteric bacterial pathogens, including Salmonella, and Shigella, especially among infants. Video Abstract.

Animals↗

PubMed2006

Do antiviral CD8+ T cells select hepatitis C virus escape mutants? Analysis in diverse epitopes targeted by human intrahepatic CD8+ T lymphocytes.

Hepatitis C virus (HCV) is a variable RNA virus that can readily establish persistent infection. Cellular immune responses are important in the early control of the virus. Evidence from animal models suggests that mutation in epitopes recognized by CD8+ T lymphocytes may play an important role in the establishment of persistence but in human persistent infection, equivalent evidence is lacking. We investigated this by analysing a unique resource: viruses from a set of chronically HCV-infected individuals in whom the CD8+ T-cell responses in liver had previously been accurately mapped. Virus was sequenced in seven individuals at 10 epitopes restricted by 10 human leucocyte antigen (HLA) molecules. Two main patterns emerged: in the majority of epitopes sequenced, no variation was seen. In three epitopes, mutations were identified which were compatible with immune escape as assessed using phylogenetic and/or functional studies. These data suggest that - even where specific intrahepatic T cells are detectable - many epitopes do not undergo mutation in chronic human infection. On the contrary, virus may escape from intrahepatic CD8+ T-cell responses in a 'patchy' manner in certain specific epitopes. Furthermore, longitudinal studies to identify the differences between 'selecting' and 'nonselecting' intrahepatic CD8+ T-cell responses are needed in HCV infection.

CD8-Positive T-Lymphocytes↗

PubMed1998

Women HIV sexual risk takers: related behaviors, interpersonal issues, and attitudes.

HIV and AIDS is a growing health risk for heterosexual women, particularly women of color (Centers for Disease Control and Prevention, 1997). Our research identified 5 types of HIV sexual risk taking in 3 independent samples of adult women from a New England Community: Group A women were noted by low to moderate levels of the 4 risk markers (i.e., unprotected vaginal sex, perceived partner-related risk, number of sexual partners, and unprotected anal sex); Group B women reported very high frequency of unprotected vaginal sex; Group C women were characterized by unprotected anal sex; Group D women had high perceived partner risk; and Group E women reported extremely high levels on all 4 HIV risk markers. Sexual risk groups were validated by demonstrating significant differences among groups on relevant behaviors, interpersonal experiences, and attitudes. Compared to other women, higher risk types reported greater behavioral risk practices (substance use, prostitution, diverse sexual experience), interpersonal risk experiences (sexual abuse, violence), initiation sexual assertiveness, and attitudinal risks (psychosocial distress). They reported less interpersonal assurance (surety of own and partner's HIV status), sexual assertiveness (for condom use and partner communication), psychosocial strengths (sexual self-acceptance), and transtheoretical readiness for change (condom use efficacy, readiness to consider condoms). Results provide additional support for the multifaceted model of HIV risk and the transtheoretical model. Suggestions for specifically focused interventions are given, depending on the pattern of sexual risk taking.

Adolescent↗

PubMed1997

Work and disability status of persons with fibromyalgia.

OBJECTIVE: To determine the prevalence and determinants of self-reported work disability in persons with fibromyalgia (FM). METHODS: A longitudinal, multicenter survey of 1604 patients with FM from 6 centers with diverse socioeconomic characteristics was begun in 1988. Assessments were by self-report questionnaire and telephone contact, and included work and disability events that occurred before and after 1988. Comparative analyses were performed on the entire data set and, separately, on the Wichita data set. RESULTS: More than 16% of patients reported receiving US Social Security disability (SSD) payments (highest center rate 35.7%; lowest center rate 6.3%) compared to 2.2% of the US population (US Social Security Administration data) and 28.9% of patients with rheumatoid arthritis seen at the Wichita outpatient rheumatology clinic. Overall, 26.5% reported receiving at least one form of disability payment when SSD and other sources of disability payments were considered. In Wichita, less than 25% of SSD awards were made specifically for FM, but after 1988 that figure increased to 46.4%. Work disability was greatest at the San Antonio and Los Angeles centers. Multivariate predictors (correlates) included pain, Health Assessment Questionnaire disability, and unmarried status. In addition, more than 70% of patients reporting being disabled did receive disability payments. On the other hand, 64% reported being able to work all or most days, and more than 70% were employed or were homemakers. CONCLUSION: Although most patients (64%) report being able to work, we found high rates of self-reported work disability awards among persons with FM followed in 6 rheumatology centers. But we also found great variability among centers as to awards and as to self-reported work ability. Center differences in work disability might reflect clinic referral patterns, physician beliefs, or socioeconomic status.

Aged↗

PubMed1995

Six-year predictors of problems in a national sample of children and youth: I. Cross-informant syndromes.

OBJECTIVE: To illuminate the development of psychopathology by tracing 6-year predictive paths to outcomes assessed in terms of empirically based syndromes. METHOD: A national sample assessed at ages 4 through 12 years via parent reports was reassessed 3 and 6 years later via parent, teacher, and self-reports. RESULTS: For syndromes having the clearest DSM counterparts, cross-informant predictive paths revealed similar traitlike patterns for Aggressive Behavior in both sexes; Delinquent Behavior was less traitlike, with greater sex differences in predictive paths; the Attention Problems syndrome was developmentally stable, but, surprisingly, it was associated with more diverse difficulties among girls than boys; conversely, Anxious/Depressed was associated with more diverse difficulties among boys than girls. CONCLUSIONS: Quantification of problems via empirically based syndromes can detect important sex, age, and developmental variations that may be masked by uniform diagnostic cutoff points for both sexes and diverse ages. This may be especially true for diagnostic cutoff points derived mainly from clinical cases of one sex, such as depression for girls versus attention and conduct disorders for boys.

Adolescent↗

PubMed2001

Physicians' prevention practices and incidence of neonatal group B streptococcal disease in 2 Canadian regions.

BACKGROUND: The impact of expert guidelines on the prevention of neonatal group B streptococcal (GBS) disease has not been studied in Canada. Our aim was to determine physician practices with regard to this condition before and after publication of Canadian guidelines and to monitor concurrent trends in the incidence of neonatal GBS disease. METHODS: We used repeat cross-sectional surveys, distributed by mail to all family practitioners and obstetricians attending deliveries in Alberta and in the Metropolitan Toronto and Peel region, Ontario, in 1994, 1995 and 1997, to document prevention practices. Audits were conducted for a subset of respondents to confirm reported practices. Population-based surveillance involving all microbiology laboratories in both regions for 1995-1998 was used to document rates of neonatal disease. RESULTS: The overall survey response rates were as follows: for 1994, 1128/1458 (77%); for 1995, 1054/1450 (73%); and for 1997, 1030/1421 (72%). During 1995 and 1997, significantly more obstetric care providers were screening at least 75% of pregnant women in their practices than had been the case in 1994 (747/916 [82%] and 693/812 [85%] v. 754/981 [77%]; p < 0.001). The percentage of obstetric care providers who reported practice that conformed completely with any of 3 consensus prevention strategies increased from 10% in 1994 to 29% in 1997 (p < 0.001). There was a concurrent overall significant decrease in incidence of neonatal GBS disease during the same period. INTERPRETATION: The adoption by Canadian obstetric care providers of neonatal GBS prevention practices recommended by expert groups was slow but improved significantly over time. These findings highlight the difficulties associated with achieving compliance with diverse and frequently changing recommendations. However, the associated incidence of neonatal GBS disease, which was low or declining, suggests that efforts to disseminate current GBS prevention guidelines have been moderately successful.

Alberta↗

PubMed1987

Longitudinal differentiation of metaphase chromosomes of Indian muntjac as studied by restriction enzyme digestion, in situ hybridization with cloned DNA probes and distamycin A plus DAPI fluorescence staining.

The longitudinal differentiation of metaphase chromosomes of the Indian muntjac was studied by digestion with restriction enzymes, in situ hybridization with cloned DNA probes and distamycin A plus DAPI (4'-6-diamidino-2-phenylindole) fluorescence staining. The centromeric regions of chromosomes 3 and 3 + X of a male Indian muntjac cell line were distinct from each other and different from those of other chromosomes. Digestion with a combination of EcoRI and Sau3A revealed a pattern corresponding to that of C-banding. Digestion with AluI, EcoRII or RsaI yielded a band specific to the centromeric region only in chromosomes 3 and 3 + X. Furthermore, HinfI digestion yielded only a band at the centromeric region of chromosome 3, whereas DA-DAPI staining revealed a single band limited to the extreme end of the C-band heterochromatin of the short arm of 3 + X. These results suggest that centromeres of Indian muntjac chromosomes contain at least four different types of repetitive DNA. Such diversity in heterochromatin was also confirmed by in situ hybridization using specific DNA probes isolated and cloned from highly repetitive DNA families. Heterozygosity between chromosome homologs was revealed by restriction enzyme banding. Evidence is presented for the presence of nucleolus organizer regions (NORs) on the long arm of chromosome 1 as well as on the secondary constrictions of 3 and 3 + X.

Animals↗