Development of an Epstein-Barr virus-associated lymphoproliferative disorder in a patient treated with azacitidine for chronic myelomonocytic leukaemia.

Some chemotherapeutic agents can cause iatrogenic lymphoproliferative disorders. In analogy to what has been observed with other nucleoside analogues such as cladribine and fludarabine, we document the first case of an Epstein-Barr virus-positive, iatrogenic immunodeficiency-associated, lymphoproliferative disease, formally resembling polymorphic post-transplant lymphoproliferative disease in a patient treated with azacitidine (Vidaza) for chronic myelomonocytic leukaemia (CMML). A 78-year-old female patient was diagnosed with CMML in January 2012, and treatment with azacitidine was initiated, which lasted for five cycles from February until June 2012. The patient was hospitalized in June 2012 under the suspicion of pneumonia. Transformation of the CMML was suspected at that time too. During hospitalization, a generalized enlargement of the lymph nodes and the spleen was noticed. The patient rapidly deteriorated and finally died of respiratory insufficiency. At autopsy, an Epstein-Barr virus-associated lymphoproliferative disorder, resembling polymorphic post-transplant lymphoproliferative disease with involvement of the lymph nodes, the spleen and the lung and causing necrotizing pneumonia, was diagnosed. Diagnostic criteria for diffuse large B-cell lymphoma or infectious mononucleosis-like lymphoproliferative disease were not met. This is the first documented case of an azacitidine-associated lymphoproliferative disease, raising awareness for possible not yet known side effects of this drug, which should be kept in mind by oncologists and pathologists.

Integrative multi-omics analyses of date palm (Phoenix dactylifera) roots and leaves reveal how the halophyte land plant copes with sea water.

Date palm (Phoenix dactylifera L.) is able to grow and complete its life cycle while being rooted in highly saline soils. Which of the many well-known salt-tolerance strategies are combined to fine-tune this remarkable resilience is unknown. The precise location, whether in the shoot or the root, where these strategies are employed remains uncertain, leaving us unaware of how the various known salt-tolerance mechanisms are integrated to fine-tune this remarkable resilience. To address this shortcoming, we exposed date palm to a salt stress dose equivalent to seawater for up to 4 weeks and applied integrative multi-omics analyses followed by targeted metabolomics, hormone, and ion analyses. Integration of proteomic into transcriptomic data allowed a view beyond simple correlation, revealing a remarkably high degree of convergence between gene expression and protein abundance. This sheds a clear light on the acclimatization mechanisms employed, which depend on reprogramming of protein biosynthesis. For growth in highly saline habitats, date palm effectively combines various salt-tolerance mechanisms found in both halophytes and glycophytes: "avoidance" by efficient sodium and chloride exclusion at the roots, and "acclimation" by osmotic adjustment, reactive oxygen species scavenging in leaves, and remodeling of the ribosome-associated proteome in salt-exposed root cells. Combined efficiently as in P. dactylifera L., these sets of mechanisms seem to explain the palm's excellent salt stress tolerance.

Learning from Fifteen Years of Genome-Wide Association Studies in Age-Related Macular Degeneration.

Over the last 15 years, genome-wide association studies (GWAS) have greatly advanced our understanding of the genetic landscape of complex phenotypes. Nevertheless, causal interpretations of GWAS data are challenging but crucial to understand underlying mechanisms and pathologies. In this review, we explore to what extend the research community follows up on GWAS data. We have traced the scientific activities responding to the two largest GWAS conducted on age-related macular degeneration (AMD) so far. Altogether 703 articles were manually categorized according to their study type. This demonstrates that follow-up studies mainly involve "Review articles" (33%) or "Genetic association studies" (33%), while 19% of publications report on findings from experimental work. It is striking to note that only three of 16 AMD-associated loci described de novo in 2016 were examined in the four-year follow-up period after publication. A comparative analysis of five studies on gene expression regulation in AMD-associated loci revealed consistent gene candidates for 15 of these loci. Our random survey highlights the fact that functional follow-up studies on GWAS results are still in its early stages hampering a significant refinement of the vast association data and thus a more accurate insight into mechanisms and pathways.

Tenascin-C expression controls the maturation of articular cartilage in mice.

OBJECTIVE: Expression of the de-adhesive extracellular matrix protein tenascin-C (TNC) is associated with the early postnatal development of articular cartilage which is both load-dependent and associated with chondrocyte differentiation. We assessed morphological changes in the articular cartilage of TNC deficient mice at postnatal ages of 1, 4 and 8 weeks compared to age-matched wildtype mice. RESULTS: Cartilage integrity was assessed based on hematoxylin and eosin stained-sections from the tibial bone using a modified Mankin score. Chondrocyte density and cartilage thickness were assessed morphometrically. TNC expression was localized based on immunostaining. At 8 weeks of age, the formed tangential/transitional zone of the articular cartilage was 27% thicker and the density of chondrocytes in the articular cartilage was 55% lower in wildtype than the TNC-deficient mice. TNC protein expression was associated with chondrocytes. No relevant changes were found in mice at 1 and 4 weeks of age. The findings indicate a role of tenascin-C in the post-natal maturation of the extracellular matrix in articular cartilage. This might be a compensatory mechanism to strengthen resilience against mechanical stress.

Shoot chloride translocation as a determinant for NaCl tolerance in Vicia faba L.

Faba bean (Vicia faba L.) is sensitive to salinity. While toxic effects of sodium (Na+) are well studied, toxicity aspects of chloride (Cl-) and the underlying tolerance mechanisms to Cl- are not well understood. For this reason, shoot Cl- translocation and its effect as potential determinant for tolerance was tested. Diverse V. faba varieties were grown hydroponically and stressed with 100 mM NaCl until necrotic leaf spots appeared. At this point, biomass formation, oxidative damage of membranes as well as Na+, Cl- and potassium concentrations were measured. The V. faba varieties contrasted in the length of the period they could withstand the NaCl stress treatment. More tolerant varieties survived longer without evolving necrosis and were less affected by inhibitory effects on photosynthesis. The concentration of Cl- at the time point of developing leaf necrosis was in the same range irrespective of the variety, while that of Na+ varied. This indicates that Cl- concentrations, and not Na+ concentrations are critical for the formation of salt necrosis in faba bean. Tolerant varieties profited from lower Cl- translocation to leaves. Therefore, photosynthesis was less affected in those varieties with lower Cl-. This mechanism is a new trait of interest for salt tolerance in V. faba.

Is short term intraoperative application of disinfectants harmful to breast implants in breast reconstruction? An experimental study and literature survey.

OBJECTIVES: Bacterial contamination of breast implants and biofilm formation has been discussed as a major reason for implant loss and capsular contraction. Intra- and perioperative treatment of breast implants with disinfectants to prevent bacterial contamination has been frequently reported. Given the increasing awareness of concerns about product liability the question of whether short-time irrigation of implants with antimicrobial substances during the operative procedure would potentially alter the integrity of the implant shell has attracted legal and medical interest. In this study we therefore investigated whether irrigating breast implants with antimicrobials commonly used in clinical practice with a clinically relevant application time would affect the physical integrity of the implant shell. MATERIALS AND METHODS: Samples, which were previously punched from the shell of explanted standard silicone gel filled breast implants in a defined way, were exposed to different disinfectant solutions for two minutes. Multiple defined specimens from 5 different explants from 4 different producers (including PIP) were tested. The testing included tensile strength and disruption tests. RESULTS: In our prospective test series we could not find a significant influence of a single distinct disinfectant on silicone shell implant surfaces. CONCLUSION: Despite the potential legal implications that might be considered when a surgeon manipulates an implant with disinfectants intraoperatively, we find it worthwhile to state that from a material and surgical standpoint there is no evidence that short-time treatment of alloplastic materials would be detrimental to the physical properties of the implant shell.

Immunocytochemistry and laser capture microdissection for real-time quantitative PCR identify hindbrain neurons activated by interaction between leptin and cholecystokinin.

Current evidence suggests that leptin reduces food intake in part by enhancing the hindbrain neuronal response to meal-related gastrointestinal signals, including cholecystokinin (CCK), but the phenotypes of the relevant cells are not known. To identify neurons that participate in this interaction in the rat nucleus of the solitary tract (NTS), we induced c-Fos gene expression in NTS neurons with leptin and CCK. We focused on NTS catecholamine neurons because these cells have been implicated in the feeding response to CCK. Hindbrain sections from rats that received CCK with or without leptin pretreatment were immunostained for c-Fos and tyrosine hydroxylase (TH) by a double immunofluorescence procedure. Leptin pretreatment increased the number of NTS cells expressing c-Fos-like immunoreactivity (cFLI) 3-fold relative to CCK alone, but the number of TH-positive cells with cFLI was increased 6-fold. Next, cells detected by immunofluorescence for TH were collected by laser capture microdissection and pooled for real-time quantitative PCR of c-Fos mRNA. Here, neither le0ptin nor CCK alone affected the relative amount of mRNA in the TH cell-enriched samples, but leptin plus CCK substantially increased c-Fos mRNA content. These histochemical findings identify hindbrain catecholamine cells as potential mediators of the interaction between leptin and CCK.

Silencing of GATA3 defines a novel stem cell-like subgroup of ETP-ALL.

BACKGROUND: GATA3 is pivotal for the development of T lymphocytes. While its effects in later stages of T cell differentiation are well recognized, the role of GATA3 in the generation of early T cell precursors (ETP) has only recently been explored. As aberrant GATA3 mRNA expression has been linked to cancerogenesis, we investigated the role of GATA3 in early T cell precursor acute lymphoblastic leukemia (ETP-ALL). METHODS: We analyzed GATA3 mRNA expression by RT-PCR (n = 182) in adult patients with T-ALL. Of these, we identified 70 of 182 patients with ETP-ALL by immunophenotyping. DNA methylation was assessed genome wide (Illumina Infinium® HumanMethylation450 BeadChip platform) in 12 patients and GATA3-specifically by pyrosequencing in 70 patients with ETP-ALL. The mutational landscape of ETP-ALL with respect to GATA3 expression was investigated in 18 patients and validated by Sanger sequencing in 65 patients with ETP-ALL. Gene expression profiles (Affymetrix Human genome U133 Plus 2.0) of an independent cohort of adult T-ALL (n = 83) were used to identify ETP-ALL and investigate GATA3low and GATA3high expressing T-ALL patients. In addition, the ETP-ALL cell line PER-117 was investigated for cytotoxicity, apoptosis, GATA3 mRNA expression, DNA methylation, and global gene expression before and after treatment with decitabine. RESULTS: In our cohort of 70 ETP-ALL patients, 33 % (23/70) lacked GATA3 expression and were thus defined as GATA3low. DNA methylation analysis revealed a high degree of GATA3 CpG island methylation in GATA3low compared with GATA3high ETP-ALL patients (mean 46 vs. 21 %, p < 0.0001). Genome-wide expression profiling of GATA3low ETP-ALL exhibited enrichment of myeloid/lymphoid progenitor (MLP) and granulocyte/monocyte progenitor (GMP) genes, while T cell-specific signatures were downregulated compared to GATA3high ETP-ALL. Among others, FLT3 expression was upregulated and mutational analyses demonstrated a high rate (79 %) of FLT3 mutations. Hypomethylating agents induced reversal of GATA3 silencing, and gene expression profiling revealed downregulation of hematopoietic stem cell genes and upregulation of T cell differentiation. CONCLUSIONS: We propose GATA3low ETP-ALL as a novel stem cell-like leukemia with implications for the use of myeloid-derived therapies.

Dnmt3a regulates myeloproliferation and liver-specific expansion of hematopoietic stem and progenitor cells.

DNA methyltransferase 3A (DNMT3A) mutations are observed in myeloid malignancies, including myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Transplantation studies have elucidated an important role for Dnmt3a in stem cell self-renewal and in myeloid differentiation. Here, we investigated the impact of conditional hematopoietic Dnmt3a loss on disease phenotype in primary mice. Mx1-Cre-mediated Dnmt3a ablation led to the development of a lethal, fully penetrant MPN with myelodysplasia (MDS/MPN) characterized by peripheral cytopenias and by marked, progressive hepatomegaly. We detected expanded stem/progenitor populations in the liver of Dnmt3a-ablated mice. The MDS/MPN induced by Dnmt3a ablation was transplantable, including the marked hepatomegaly. Homing studies showed that Dnmt3a-deleted bone marrow cells preferentially migrated to the liver. Gene expression and DNA methylation analyses of progenitor cell populations identified differential regulation of hematopoietic regulatory pathways, including fetal liver hematopoiesis transcriptional programs. These data demonstrate that Dnmt3a ablation in the hematopoietic system leads to myeloid transformation in vivo, with cell-autonomous aberrant tissue tropism and marked extramedullary hematopoiesis (EMH) with liver involvement. Hence, in addition to the established role of Dnmt3a in regulating self-renewal, Dnmt3a regulates tissue tropism and limits myeloid progenitor expansion in vivo.

Concerted stimulation of transcription by glucocorticoid receptors and basal transcription factors: limited transcriptional synergism suggests mediation by coactivators/adaptors.

Steroid receptors have been reported to stimulate transcription in a manner synergistic with other transcription factors. We have examined this synergism or functional cooperativity between glucocorticoid receptors and basal transcription factors in a variety of promoter and reporter gene contexts. A fragment containing a hormone response element from mouse mammary tumor virus was fused to well characterized promoters from the herpes virus thymidine kinase and mouse beta-globin genes and to related mutant promoters altered by inactivation of transcription factor-binding sites through point mutagenesis or deletion. These constructs were transfected into glucocorticoid-sensitive fibroblasts, and reporter gene activity was assessed with or without hormonal stimulation. In contrast to previous studies, we found little indication of synergistic interaction between elements mediating a hormone response and adjacent basal promoters. In fact, we observed that inactivating basal factor-binding sites, thereby decreasing promoter strength, actually increased hormone inducibility. We suggest that the inverse relationship between basal promoter strength and the induction ratio attained upon hormonal stimulation may be due to limitation of a common factor, an "adaptor" through which glucocorticoid receptor and basal transcription factors interact with the components of the RNA polymerase II complex to stimulate rates of transcription.

Women's interest in chemoprevention for breast cancer.

BACKGROUND: Chemoprevention is the use of pharmacologic or natural agents to inhibit the development of cancer. Tamoxifen citrate is the only approved chemopreventive agent for breast cancer. We sought to determine whether women are interested in taking a drug to prevent breast cancer and to assess the relationship between objective and subjective breast cancer risk and interest in chemoprevention. METHODS: We conducted telephone interviews (November 3, 1997, to May 6, 1998) among a community sample of women aged 40 to 45 and 50 to 55 years enrolled in a randomized controlled trial to evaluate the efficacy of a tailored mammography decision aid. Objective breast cancer risk was measured using the 5-year Gail score. Subjective breast cancer risk was measured using perceptions of absolute risk, perceptions of comparative risk, and worry about getting breast cancer. At 12-month follow-up (November 2, 1998, to July 20, 1999), we measured interest in taking a drug to prevent breast cancer. RESULTS: Among the 1273 women surveyed, 23% were interested in taking a drug to prevent breast cancer; 8% were potentially eligible for tamoxifen therapy (5-year Gail score > or = 1.66%). Eligibility for chemoprevention, based on the 5-year Gail score, was not associated with interest in taking a drug to prevent breast cancer. Women who were worried about breast cancer were 3 times more likely to be interested in taking a drug to prevent breast cancer than those who were not worried. CONCLUSION: Women's interest in chemoprevention might arise more from worries about getting breast cancer than from their objective risk factors.

[Ankylosing spondylitis. Therapy and complications of 34 spine fractures]. / Ankylosierende Spondylitis. Therapie und Komplikationen von 34 Wirbelsäulenfrakturen.

BACKGROUND: Spine fractures in ankylosing spondylitis (AS) are extremely unstable and associated with a high complication rate. The aim of this retrospective study was to evaluate the therapy and complications of these fractures in AS for a better understanding and management. PATIENTS AND METHODS: A total of 32 patients with 34 traumatic spine fractures were treated from 1981 to 2002. Cause of trauma, fracture site, and neurological examination were assessed. Analyses of the management of the treatment and complications were performed. RESULTS: Banal traumas resulted mostly in spinal fractures at the C 5/6 and C 6/7 level. Two patients were treated conservatively, while the others were stabilized operatively. Before therapy was undertaken, six patients suffered from a cervical radiculopathy, ten patients had an incomplete and two a complete paraplegia. After therapy, neurological status improved in eight patients, but one had a deterioration of neurological symptoms. CONCLUSIONS: Dorsal or combined dorsoventral stabilization of these fractures is necessary for better mobilization of these patients and to avoid further complications.

Differences between men and women with HIV-related Pneumocystis carinii pneumonia: experience from 3,070 cases in New York City in 1987.

Although women make up the fastest growing group of persons with AIDS, studies of human immunodeficiency virus (HIV)-infected persons reported to date have included predominantly or exclusively men. We evaluated sex differences in sociodemographic characteristics, hospital characteristics, in-hospital resource use, and short-term mortality rates for 2,526 men and 544 women admitted for their first-episode of HIV-related Pneumocystis carinii pneumonia (PCP) in New York City in 1987. Compared with men, women were significantly less likely to be white (81% vs. 54%, p < or = 0.001) or have private health insurance (80% vs. 58%, p < or = 0.001), and more likely to be admitted through an emergency room (79% vs. 71%, p < or = 0.001) and receive care at hospitals that had less experience treating PCP (p < or = 0.001). Women were more likely than men to die in the hospital [33% vs. 24%; crude odds ratio = 1.56, confidence interval (CI) = 1.28-1.91, p < or = 0.001]. In a logistic regression model, the risk of death in the hospital was associated with age 60-65 years [adjusted odds ratio (AOR) = 4.19, CI = 2.13-8.21], not having private health insurance (AOR = 1.37, CI = 1.08-1.75), admission through the emergency room (AOR = 1.54, CI = 1.21-1.96), and receiving care at hospitals with less experience treating PCP (AOR = 1.63, CI = 1.15-2.30), but women were not significantly more likely to die in the hospital than men (AOR = 1.18, CI = 0.93-1.50). Poorer access to medical care as well as higher use of hospitals with less experience treating AIDS may account for the difference in mortality rates observed in women with HIV-related PCP.

Hormone replacement therapy and reduced cognitive decline in older women: the Cache County Study.

OBJECTIVE: To examine the association between postmenopausal hormone replacement therapy (HRT) and the trajectory of global cognitive change with age. METHODS: The Modified Mini-Mental State Examination (MMSE) was administered to a population sample of 2,073 nondemented, community-dwelling female residents of Cache County, UT, aged 65 and older. Current and past HRT and other medications at a baseline interview and at follow-up 3 years later were assessed. Between interviews, a telephone Women's Health Questionnaire was administered to assess initial exposure, duration, and recency of HRT. Generalized estimating equation marginal models were used to evaluate the cross-sectional and longitudinal relations of HRT and modified MMSE score. Also assessed were effects with multivitamins and calcium supplements as exposures likely to reflect a "healthy lifestyle" among HRT users. Model covariates included the presence of APOE epsilon4 alleles, age, education, concurrent depression, several chronic diseases, and self-perceived general health. RESULTS: Age, lower education, depression, and APOE epsilon4 were all associated with lower baseline modified MMSE scores. With these covariates in the model, lifetime HRT use was associated with better baseline modified MMSE scores and a slower rate of decline. Stratification by APOE genotype did not alter these effects. Apparent benefits with HRT were attenuated but remained significant after elimination of scores from participants with incident dementia. A significant interaction between age and HRT indicated the strongest effects in women aged 85 and older. Measures of age at initial use of HRT, duration, and recency of exposure did not improve the models. No effects were seen with the "healthy lifestyle" control exposures. CONCLUSIONS: In a population cohort of older women, lifetime HRT exposure was associated with improved global cognition and attenuated decline over a 3-year interval. Improvements were greatest in the oldest old.

Sleep in the laboratory and sleep at home II: comparisons of middle-aged insomnia sufferers and normal sleepers.

STUDY OBJECTIVES: The study compared adaptation responses and sleep pattern differences shown by normal sleepers and insomnia sufferers during lab (LPSG) and home (HPSG) polysomnography. DESIGN: A counter-balanced, matched-group design was used. Participants underwent 3 consecutive nocturnal LPSG's and 3 consecutive nocturnal PSG's in their homes (HPSG's). SETTING: The sleep disorders laboratories at affiliated VA and university medical centers. PARTICIPANTS: Thirty-five (18 women) middle-aged (40 to 59 years) noncomplaining normal sleepers and an age-matched sample of 33 (17 women) individuals who met structured interview criteria for persistent primary insomnia were the study participants. MEASUREMENTS AND RESULTS: A series of multivariate and univariate analyses were conducted with 9 common sleep parameters to address study objectives. Bed partner influences were controlled by conducting separate sets of analyses for those with and without routine home bed partners. The interaction of participant type (normal vs. insomnia), sleep setting, and PSG sequence (HPSG 1st vs. LPSG 1st) affected first night values of sleep efficiency and stage 2 sleep among those without routine bed partners, and REM latency and sleep efficiency among those with routine bed partners. Analyses which controlled for first night and sequencing effects showed a significant participant type x sleep setting interaction among those with bed partners. These latter analyses suggested that LPSG's may underestimate the home sleep time of insomnia sufferers and overestimate the sleep continuity of normal sleepers, at least among those who routinely sleep with a bed partner. CONCLUSIONS: The nocturnal recording site may influence adaptation effects and sleep pattern differences noted between insomnia sufferers and normal sleepers.

Hormone replacement therapy and the risk of colorectal cancer: a meta-analysis.

OBJECTIVE: To review systematically the association between hormone replacement therapy (HRT) and the risk of developing or dying from colorectal cancer. DATA SOURCES: We searched the English-language literature using MEDLINE, Current Contents, CancerLit, and bibliographies of selected studies. METHODS OF STUDY SELECTION: We included studies that specifically addressed the association of HRT with colorectal cancer, had adequate controls, and had retrievable risk estimates. We excluded letters, reviews, and multiple publications of the same data. TABULATION, INTEGRATION, AND RESULTS: Studies were evaluated independently by two of the authors. The exposures of interest were ever, recent, or former use of HRT, and the main outcome measures were colon and rectal cancer incidence and mortality. To reduce the risk of a "healthy estrogen user" bias, we defined recent HRT use as either at time of assessment or within the previous year. The most adjusted risk estimates were extracted. We used a random-effects model to calculate summary relative risks (RRs) and confidence intervals (CIs). Recent use of HRT was associated with a 33% reduction in the risk of colon cancer (RR = 0.67; 95% CI 0.59, 0.77). Protection was limited to recent users; the risk of colon cancer with ever use of HRT was 0.92 (95% CI 0.79, 1.08). Duration of use was not significant. Three studies addressed the risk of fatal colon cancer; the summary RR for death from colon cancer in HRT users was 0.72 (95% CI 0.64, 0.81) compared with nonusers. Rectal cancer incidence was not associated with HRT. CONCLUSION: The risk of colon cancer may be decreased among recent postmenopausal HRT users. Although data are limited, the risk of fatal colon cancer also may be lower in HRT users.

Insomnia and the eye of the beholder: are there clinical markers of objective sleep disturbances among adults with and without insomnia complaints?

Previous findings suggest that some who report insomnia sleep well, whereas some noncomplaining individuals sleep rather poorly. This study was conducted to determine if mood, anxiety, and sleep-related beliefs might relate to perceived sleep disturbance. Thirty-two women and 32 men (aged 40-79 years) with primary insomnia and an aged-matched sample of 61 normal sleepers (31 women, 30 men) completed 6 nocturnal sleep recordings, as well as the Beck Depression Inventory (BDI), the Trait portion of the State-Trait Anxiety Inventory (STAI-2), and the Dysfunctional Beliefs and Attitudes About Sleep Questionnaire. Sleep and interview data were used to subdivide the majority of the sample (n = 108) into objective normal sleepers and subjective insomnia sufferers who seemingly slept well and subjective normal sleepers and objective insomnia sufferers who slept poorly. The 2 subjective subgroups showed the most marked differences on most of the psychometric measures. The findings suggest that the psychological factors scrutinized in this study may mediate sleep satisfaction and/or predict objective sleep difficulties.

Slow-wave sleep and waking cognitive performance II: Findings among middle-aged adults with and without insomnia complaints.

Previous studies showing a relationship between nocturnal slow-wave sleep (SWS) and subsequent diurnal performance among young normal sleepers and older insomnia sufferers have provided limited support for the notion that this sleep stage serves a restorative role for neurocognitive functioning. The current study, which examined the relationship between SWS and reaction time performance among middle-aged adults with and without insomnia complaints, was conducted to further explore this possibility. A sample of 31 noncomplaining middle-aged (ages 40 to 59 years) normal sleepers and a like-aged sample of 27 insomnia sufferers, provided data for the current investigation. All participants underwent nocturnal sleep monitoring immediately prior to undergoing a battery of daytime tests that measured simple reaction time, vigilance/signal detection, and complex reaction time. Results showed relationships between reaction time performances on some tasks and some SWS measures among both the normal sleepers and insomnia sufferers. Findings supported our prediction that the presence of sleep pathology (e.g., insomnia) alters the SWS-performance relationship observed, but the results failed to show a consistent relationship between SWS and subsequent performance within either sample. The findings suggest that the specific performance demands of the task in question as well as physiological parameters other than SWS may determine performance as well. Findings for this and previous studies do provide some support for the contention that the neurocognitive restorative value of SWS may change across the lifespan. Possible implications of the study's findings are discussed and directions for future research are considered.

Influence of arginine, omega-3 fatty acids and nucleotide-supplemented enteral support on systemic inflammatory response syndrome and multiple organ failure in patients after severe trauma.

This study investigated the influence of an enteral diet supplemented with arginine, omega-3 fatty acids, and nucleotides (Impact, Sandoz Nutrition, Berne, Switzerland) on the incidence of systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF) in patients after severe trauma. Thirty-two patients with an injury-severity score > 20 were included in this prospective, randomized, double-blind, controlled study. Primary endpoints were the incidence of SIRS and MOF. Secondary endpoints were parameters of acute phase and immune response as well as infection rate, mortality, and hospital stay. For statistical analysis 29 patients (test group n = 16, control n = 13) were eligible. In the test group, significantly fewer SIRS days per patient were found during 28 d. The difference was highly significant between d 8-14 (P < 0.001). MOF score was significantly lower in the test group on d 3 and d 8-11 (P < 0.05). Acute phase parameters showed lower C-reactive protein serum levels (significant on D day 4) and fibrinogen plasma levels (significant on d 12 and 14; P < 0.05). HLA-DR expression on monocytes showed significantly higher fluorescence activity on d 7. No significant difference was found for T-lymphocyte CD4/CD8 ratio, interleukin-2 receptor expression, infection rate, mortality (2/16 vs. 4/13), and hospital stay. The results of the study provide further support for beneficial effects of arginine, omega-3-fatty acids and nucleotide-supplemented enteral diet in critically ill patients.

Cigarette smoking in veteran women: the impact of job strain.

To evaluate the health effects of role overload, the relationship between multiple role (i.e., worker, spouse, caretaker) strain and current cigarette smoking was examined. A cross-sectional survey of women veterans, aged 36-85 years, was performed measuring home and job strain and health behaviors. Of the 275 women who rated both their work and home strains, 25% (n = 69) currently smoke cigarettes. Higher work strain, but not higher home strain, was associated with smoking adjusting for age, education, income, weight, and marital status. A stressful work environment may trigger persistent smoking and should be addressed during smoking cessation counseling.