Novel protective mechanism for interleukin-33 at the mucosal barrier during influenza-associated bacterial superinfection.

Influenza A is a highly contagious respiratory virus that causes seasonal epidemics and occasional worldwide pandemics. The primary cause of influenza-related mortality is bacterial superinfection. There are numerous mechanisms by which preceding influenza infection attenuates host defense, allowing for increased susceptibility to bacterial pneumonia. Herein, we demonstrate that influenza inhibits Staphylococcus aureus-induced production of interleukin-33 (IL-33). Restoration of IL-33 during influenza A and methicillin-resistant S. aureus superinfection enhanced bacterial clearance and improved mortality. Innate lymphoid Type 2 cells and alternatively activated macrophages are not required for IL-33-mediated protection during superinfection. We show that IL-33 treatment resulted in neutrophil recruitment to the lung, associated with improved bacterial clearance. These findings identify a novel role for IL-33 in antibacterial host defense at the mucosal barrier.

Socio-demographic factors, comorbidity and diagnostic delay among women diagnosed with cervical, endometrial or ovarian cancer.

This study investigates the association between socio-demographic factors, comorbidity and diagnostic delay among gynaecological cancer patients. A questionnaire was sent to 1052 women diagnosed with cervical, endometrial or ovarian cancer between October 2006 and December 2007 in Denmark. Long patient delays were associated with diagnosis with a greater risk of experiencing long delays among women diagnosed with cervical and endometrial cancer as opposed to ovarian cancer. The risk of experiencing long GP referral delays was associated with residential area, with a greater risk of long delays in rural vs. urban areas. Long gynaecologist appointment delays were associated with younger age, while long secondary care delays were associated with living in a capital area and having comorbidity. Long total delays were associated with diagnosis with greater risk of experiencing long delays among women diagnosed with cervical and endometrial cancer as opposed to ovarian cancer, and with working as opposed to being retired. In conclusion, this study found that socio-demographic factors and comorbidity play a role in the probability of experiencing long delays. If delays in diagnosis are to be reduced, there must be increased recognition of the significance of symptoms among patients and interventions aimed at ensuring timely care by specialists.

The effect of post-injury depression on return to pre-injury function: a prospective cohort study.

BACKGROUND: Millions of people seek emergency department (ED) care for injuries each year, the majority for minor injuries. Little is known about the effect of psychiatric co-morbid disorders that emerge after minor injury on functional recovery. This study examined the effect of post-injury depression on return to pre-injury levels of function. METHOD: This was a longitudinal cohort study with follow-up at 3, 6 and 12 months post-injury: 275 adults were randomly selected from those presenting to the ED with minor injury; 248 were retained over the post-injury year. Function was measured with the Functional Status Questionnaire (FSQ). Psychiatric disorders were diagnosed using the Structured Clinical Interview for DSM-IV-TR disorders (SCID). RESULTS: During the post-injury year, 18.1% [95% confidence interval (CI) 13.3-22.9] were diagnosed with depression. Adjusting for clinical and demographic covariates, the depressed group was less likely to return to pre-injury levels of activities of daily living [odds ratio (OR) 8.37, 95% CI 3.78-18.53] and instrumental activities of daily living (OR 3.25, 95% CI 1.44-7.31), less likely to return to pre-injury work status (OR 2.37, 95% CI 1.04-5.38), and more likely to spend days in bed because of health (OR 2.41, 95% CI 1.15-5.07). CONCLUSIONS: Depression was the most frequent psychiatric diagnosis in the year after minor injury requiring emergency care. Individuals with depression did not return to pre-injury levels of function during the post-injury year.

Cognitive functioning in sporadic amyotrophic lateral sclerosis: a six month longitudinal study.

OBJECTIVE: To observe changes in cognition over six months in subjects with recently diagnosed sporadic amyotrophic lateral sclerosis (ALS). METHODS: The study used a between-group and within-group longitudinal design. Nineteen ALS subjects and eight matched caregivers were recruited to participate in baseline neuropsychological assessments that were repeated six months later. Between group comparisons for these variables were undertaken at baseline and six months later. Within group/across time comparisons for these variables were carried out for both groups. Individual analyses for the neuropsychological variables using z scores were done for the ALS subjects using their baseline performance as the basis for comparison with their six month performance. RESULTS: The between-group and within-group comparisons did not show significant differences in cognitive function over time. In individual analyses, however, seven of 19 ALS subjects (36.84%) developed abnormal neuropsychological performance over six months. CONCLUSIONS: Early in the disease course, over one third of the ALS subjects developed cognitive deficits over six months. These findings support the hypothesis that cognitive deficits in ALS become more prominent over time.

Leaf stomatal and epidermal cell development: identification of putative quantitative trait loci in relation to elevated carbon dioxide concentration in poplar.

Genetic variation in stomatal initiation and density, and epidermal cell size and number were examined in a hybrid pedigree of Populus trichocarpa T. & G. and P. deltoides Marsh in both ambient ([aCO2]) and elevated ([eCO2]) concentrations of CO2. We aimed to link anatomical traits with the underlying genetic map of F2 Family 331, composed of 350 markers across 19 linkage groups. Leaf stomatal and epidermal cell traits showed pronounced differences between the original parents. We considered the following traits in the F2 population: stomatal density (SD), stomatal index (SI), epidermal cell area (ECA) and the number of epidermal cells per leaf (ECN). In [eCO2], adaxial SD and SI were reduced in the F2 population, whereas ECA increased and ECN remained unchanged. In [aCO2], four putative quantitative trait loci (QTL) with logarithm of the odds ratio (LOD) scores greater than 2.9 were found for stomatal traits on linkage group B: adaxial SI (LOD scores of 5.4 and 5.2); abaxial SI (LOD score of 3.3); and SD (LOD score of 3.2). These results imply that QTL for SI and SD share linkage group B and are under genetic control. More moderate LOD scores (LOD scores >/= 2.5) suggest QTL for SI on linkage groups A and B and for SD on linkage groups B, D and X with a probable co-locating quantitative trait locus for SI and SD on linkage group D (position 46.3 cM). The QTL in both [aCO2] and [eCO2] for adaxial SD were co-located on linkage group X (LOD scores of 3.5 and 2.6, respectively) indicating a similar response across both treatments. Putative QTL were located on linkage group A (position 89.2 cM) for both leaf size and ECN in [aCO2] and for ECA at almost the same position. The data provide preliminary evidence that leaf stomatal and cell traits are amenable to QTL analysis.

Problem behaviour, caregiver reactions, and impact among caregivers of persons with Alzheimer's disease.

BACKGROUND: Problem behaviours that occur during Alzheimer's disease (AD) can have major impact on caregivers. How caregivers react to these behaviours may determine the total impact experienced from caregiving. PURPOSE: This study examined the relationships between problematic behaviours and caregiving impact in 30 primary caregivers of persons with AD. The first question explored the relationship between frequency of problem behaviour and impact; the second explored the relationship between caregiver reactions to problem behaviours and impact from caregiving. METHODS: The frequency of problem behaviour and the caregiver reaction was measured using The Revised Memory and Behaviour Problem Checklist (Teri et al. 1992). The impact from caregiving was operationalized using the Cost of Care Index developed by Kosberg and Cairl (1986). RESULTS: Significant associations were found for 11 of the 20 subscales that measured the association between the frequency of problem behaviour in the client and the impact from caregiving experienced by the caregiver. In comparison, the association between caregiver's reaction to problem behaviours and impact from caregiving was even more significant in value with 15 subscales of 20 being significant. Female caregivers experienced a greater reaction to disruptive and depressive behaviour when compared with male caregivers even though both genders reported similar frequencies of problem behaviours. In regard to findings about the impact from caregiving, four of the six indicators were higher for women than for men. CONCLUSIONS: Caregiver reaction to problem behaviours was more highly associated with impact from caregiving than the actual frequency of the behaviours. These findings have great implications for intervention programs. Caregivers, especially females, need to receive individualized, specific education/training on how to understand and manage disruptive and depressive behaviour in persons with AD.

Unsolicited narratives from the Internet: a rich source of qualitative data.

Recently, the Internet has become a forum for informal communication. Many--whose voices may have been unheard--can now express themselves through this medium. Rich narratives are available to the qualitative researcher from bulletin boards, guestbooks, Web pages, and listservs on the Internet. In this article, these data sources are defined and described. Strategies for using these data are discussed. One concern with using unsolicited data from the Internet is the protection of human subjects and the requirement for consent. A proposed model describing the process for deciding when such data are publicly available, as defined by the Office for the Protection of Rights of Research Subjects, and when the use of the data requires consent is presented.

Rehabilitation applications in caring for patients with Pick's disease and frontotemporal dementias.

The basic principles of rehabilitation philosophy relevant to the care of patients with neurodegenerative diseases, specifically Pick's disease and frontotemporal dementias, are briefly defined. These principles are illustrated by the case study of a patient with a clinical diagnosis of Pick's disease.

Respite care--volunteers as providers.

1. Although many studies examine the impact of respite care on caregivers, few studies have examined the impact of such programs on the volunteer respite provider. Results of such formative evaluation studies must be antecedent to the question of whether respite care "works." 2. Fear of persons with Alzheimer's Disease (AD) was a consistent theme verbalized in this study. Educational programs must therefore include more exposure to actual persons with AD. 3. Caregivers with some past experience composed the majority of volunteers in this group (n = 78%). Recruiting former caregivers of deceased persons with AD may be fruitful future areas of study.

Chromatin, TAFs, and a novel multiprotein coactivator are required for synergistic activation by Sp1 and SREBP-1a in vitro.

The promoter selectivity factor Sp1 often cooperates with other enhancer-binding proteins to activate transcription. To study the molecular underpinnings of these regulatory events, we have reconstituted in vitro the synergy observed in vivo between Sp1 and the sterol-regulated factor SREBP-1a at the low density lipoprotein receptor (LDLR) promoter. Using a highly purified human transcription system, we found that chromatin, TAFs, and a novel SREBP-binding coactivator activity, which includes CBP, are all required to mediate full synergistic activation by Sp1 and SREBP-1a. The SREBP-binding domain of CBP inhibits activation by SREBP-1a and Sp1 in a dominant-negative fashion that is both chromatin- and activator-specific. Whereas recombinant CBP alone is not sufficient to mediate activation, a human cellular fraction containing CBP can support high levels of chromatin-dependent synergistic activation. Purification of this activity to near homogeneity resulted in the identification of a multiprotein coactivator, including CBP, that selectively binds to the SREBP-1a activation domain and is capable of mediating high levels of synergistic activation by SREBP/Sp1 on chromatin templates. The development of a reconstituted chromatin transcription system has allowed us to isolate a novel coactivator that is recruited by the SREBP-1a activation domain and that functions in concert with TFIID to coordinate the action of multiple activators at complex promoters in the context of chromatin.

Lexical acquisition in probable Alzheimer's disease.

Patients with probable Alzheimer's disease (pAD) were exposed to a new verb in a naturalistic fashion. We probed their knowledge of the word's semantic and grammatical characteristics for several minutes following this exposure, and compared this with their performance on parallel measures assessing known words. Significant differences were seen between pAD patients and controls in the acquisition of the new verb's semantic meaning and its argument structure, but pAD patients did not differ from controls in the acquisition of the new word's grammatical form class. Individual patient analyses demonstrated parallel deficits restricted to the semantic meaning and argument structure of the new word and known words in several pAD patients, suggesting that a selective language impairment contributed to their word learning deficit. This pattern is consistent with an intimate relationship between semantic meaning and argument structure in semantic memory. Other pAD patients had difficulty learning about all aspects of the new word, despite good performance with known words, suggesting that compromised memory may have limited their lexical acquisition.

Family caregiving: who provides the care, and at what cost?

Today, there are an estimated 1.6 million people over 65 years of age who require assistance with two or more daily activities. This number is projected to rise to 2.1 million by 2001, with fewer family caregivers expected to be available to provide this informal care. Seventy-two percent of unpaid family caregivers are women, the majority of whom are mid-life daughters or daughters in law. Uncompensated care to the frail elderly requires an average of 28 to 39.9 hours per week of custodial care. The financial impact on informal caregivers includes: 9% of family caregivers who leave the labor force to provide care, 29.4% who adjust their work schedules, and 18.1% who take time off without pay. The estimated annual value of uncompensated kin care in 1990 was $18 billion. Thirty-two percent of all family caregivers are categorized as poor or near-poor at incomes that are less than 125% of the federal poverty level.

The family's role in long-term care.

Long-term care provided by family members is the central care of our current health care system. The purpose of this article is to review the family's role in long-term care. Issues such as cost containment and inequities in our current social policy are reviewed. Suggestions for future directions in social policy are presented.

The COQ5 gene encodes a yeast mitochondrial protein necessary for ubiquinone biosynthesis and the assembly of the respiratory chain.

Saccharomyces cerevisiae is a facultative anaerobe capable of meeting its energy requirements by fermentation and is thus an ideal system for studying the biogenesis of respiring mitochondria. We have isolated a respiration-deficient mutant exhibiting a pleiotropic loss of the mitochondrial electron transport chain. The corresponding wild-type gene, COQ5, was cloned, sequenced, and able to restore respiratory growth. Deletion of the chromosomal COQ5 gene results in a respiration deficiency and reduced levels of respiratory protein components. Exogenously added decylubiquinone can partially restore electron transport chain function to mitochondrial membranes from the deletion mutant. The COQ5 nucleotide sequence predicts a polypeptide of 307 amino acids containing a mitochondrial targeting signal. COQ5p is 43% identical to the polypeptide predicted by the Escherichia coli open reading frame, o251 (1). The COQ5 gene, when introduced into E. coli, complements the respiratory deficiency of an ubiE mutant that maps near o251, suggesting that it is the yeast homolog of the ubiE gene product. We conclude that the COQ5 gene encodes the mitochondria-localized 2-hexaprenyl-6-methoxy-1,4-benzoquinone methyltransferase of the yeast ubiquinone biosynthetic pathway.

Hypothesis-Driven Treatment of Naming Deficits.

This article proposes to use information processing models of cognition to guide behaviorally based treatments of language deficits, specifically, single-word object naming. Our approach is illustrated with a clinical case of a transcortical sensory aphasic. Clinical neuropsychological and functional imaging data demonstrate that the components comprising the information processing network that underpins naming can be mapped onto a cerebral neural network in the neurologically intact and that reorganization of function seen in transcortical sensory aphasia can demonstrate plasticity in this neural network. The observed balance of impaired and preserved clinical and physiological components in reorganizing neural networks such as this can be used to design treatment strategies to alleviate naming deficits.

Anomaly judgments of subject-predicate relations in Alzheimer's disease.

Claims that patients with probable Alzheimer's disease (AD) have semantic memory difficulty have received equivocal support. A common assumption has been that defining or core information determines the truth value of word meaning on measures requiring semantic memory such as category membership judgments or confrontation naming, but this assumption may not be valid. In the present study, we assessed the comprehension of subject-predicate sentences independent of their truth value by asking AD patients to judge the coherence of statements such as "The tulip is tall" or "*The tulip is jealous." We found that AD patients are significantly more impaired than controls at judging the coherence of these simple subject-predicate sentences. Moreover, AD patients were more successful at judging the coherence of statements that contain attributes with a narrow scope of reference compared to attributes with a broad scope of reference. These findings support the hypothesis that AD patients have a semantic memory impairment and suggest a specific deficit processing the network of semantic relations underlying word meaning in semantic memory.

Category-specific difficulty naming with verbs in Alzheimer's disease.

We studied 20 patients with Alzheimer's disease (AD) on a picture-naming task consisting of frequency-matched pairs of nouns and verbs that were homophonic and homographic (e.g., paint). Intragroup comparisons revealed that verb naming is significantly more difficult for patients with AD than noun naming. An error analysis demonstrated that patients with AD produce significantly more semantic and descriptive errors for verbs than nouns. We correlated verb naming and noun naming with measures of grammatical comprehension, lexical retrieval, and visuoperceptual processing, but there were no selective effects for verbs compared with nouns. Differences in the mental representation of concepts underlying verbs and nouns may account, in part, for the relative difficulty naming with verbs in AD.