Test Characteristics of Cardiac Point-of-Care Ultrasound in Children With Preexisting Cardiac Conditions.

OBJECTIVE: The aim of the study is to assess diagnostic performance of cardiac point-of-care ultrasound (POCUS) performed by pediatric emergency medicine (PEM) physicians in children with preexisting cardiac disease. METHODS: We evaluated the use of cardiac POCUS performed by PEM physicians among a convenience sample of children with preexisting cardiac disease presenting to a tertiary care pediatric ED. We assessed patient characteristics and the indication for POCUS. The test characteristics of the sonologist interpretation for the assessment of both pericardial effusion as well as left ventricular systolic dysfunction were compared with expert POCUS review by PEM physicians with POCUS fellowship training. RESULTS: A total of 104 children with preexisting cardiac disease underwent cardiac POCUS examinations between July 2015 and December 2017. Among children with preexisting cardiac disease, structural defects were present in 72%, acquired conditions in 22%, and arrhythmias in 13% of patients. Cardiac POCUS was most frequently obtained because of chest pain (55%), dyspnea (18%), tachycardia (17%), and syncope (10%). Cardiac POCUS interpretation compared with expert review had a sensitivity of 100% (95% confidence interval [CI], 85.7-100) for pericardial effusion and 100% (95% CI, 71.5-100) for left ventricular systolic dysfunction; specificity was 97.5% (95% CI, 91.3.1-99.7) for pericardial effusion and 98.9% (95% CI, 93.8-99.8) for left ventricular systolic dysfunction. CONCLUSIONS: Cardiac POCUS demonstrates good sensitivity and specificity in diagnosing pericardial effusion and left ventricular systolic dysfunction in children with preexisting cardiac conditions when technically adequate studies are obtained. These findings support future studies of cardiac POCUS in children with preexisting cardiac conditions presenting to the ED.

Ultrasound Assessment of Quadriceps Femoris Muscle Thickness in Critically Ill Children.

OBJECTIVES: Evaluate the reliability of ultrasound to measure quadriceps femoris muscle thickness in critically ill children and to describe serial changes in quadriceps femoris muscle thickness in relation to fluid balance and nutritional intake. DESIGN: Prospective observational study. SETTING: Tertiary care children's hospital. PATIENTS: Inpatients age 3 months to 18 years recently admitted to the ICU who were sedated and mechanically ventilated at the time of the first ultrasound scan. METHODS: Prospective observational study to examine the reliability of averaged ultrasound measurements of quadriceps femoris muscle thickness. Change in average quadriceps femoris muscle thickness over time was correlated with fluid balance and nutritional intake. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Averaged quadriceps femoris muscle thickness demonstrated good to excellent reliability when comparing pediatric critical care providers to pediatric radiologists and when comparing between different pediatric critical care providers. We found no significant association between fluid balance over 1 or 3 days and change in quadriceps femoris muscle thickness over the same time frame. However, there was a significant association between percent of goal calories (p < 0.001) or percent of goal protein (p < 0.001) over 6 days and change in quadriceps femoris muscle thickness over the same time frame. CONCLUSIONS: Averaged ultrasound measurements of quadriceps femoris muscle thickness demonstrate good to excellent reliability, are not confounded by fluid balance, and are useful for tracking changes in muscle thickness that are associated with nutritional intake. Ultrasound-based assessment of quadriceps femoris is a clinically useful tool for evaluating muscle mass and may be a proxy for nutritional status.

Serology- and PCR-based cumulative incidence of SARS-CoV-2 infection in adults in a successfully contained early hotspot (CoMoLo study), Germany, May to June 2020.

Three months after a coronavirus disease (COVID-19) outbreak in Kupferzell, Germany, a population-based study (n = 2,203) found no RT-PCR-positives. IgG-ELISA seropositivity with positive virus neutralisation tests was 7.7% (95% confidence interval (CI): 6.5-9.1) and 4.3% with negative neutralisation tests. We estimate 12.0% (95% CI: 10.4-14.0%) infected adults (24.5% asymptomatic), six times more than notified. Full hotspot containment confirms the effectiveness of prompt protection measures. However, 88% naïve adults are still at high COVID-19 risk.

Effects of slow-wave activity on mood disturbance in major depressive disorder.

BACKGROUND: Studies have demonstrated that decreases in slow-wave activity (SWA) predict decreases in depressive symptoms in those with major depressive disorder (MDD), suggesting that there may be a link between SWA and mood. The aim of the present study was to determine if the consequent change in SWA regulation following a mild homeostatic sleep challenge would predict mood disturbance. METHODS: Thirty-seven depressed and fifty-nine healthy adults spent three consecutive nights in the sleep laboratory. On the third night, bedtime was delayed by 3 h, as this procedure has been shown to provoke SWA. The Profile of Mood States questionnaire was administered on the morning following the baseline and sleep delay nights to measure mood disturbance. RESULTS: Results revealed that following sleep delay, a lower delta sleep ratio, indicative of inadequate dissipation of SWA from the first to the second non-rapid eye movement period, predicted increased mood disturbance in only those with MDD. CONCLUSIONS: These data demonstrate that in the first half of the night, individuals with MDD who have less SWA dissipation as a consequence of impaired SWA regulation have greater mood disturbance, and may suggest that appropriate homeostatic regulation of sleep is an important factor in the disorder.

Roles of plasma membrane proton ATPases AHA2 and AHA7 in normal growth of roots and root hairs in Arabidopsis thaliana.

Plasma membrane H+ -ATPase pumps build up the electrochemical H+ gradients that energize most other transport processes into and out of plant cells through channel proteins and secondary active carriers. In Arabidopsis thaliana, the AUTOINHIBITED PLASMA MEMBRANE H+ -ATPases AHA1, AHA2 and AHA7 are predominant in root epidermal cells. In contrast to other H+ -ATPases, we find that AHA7 is autoinhibited by a sequence present in the extracellular loop between transmembrane segments 7 and 8. Autoinhibition of pump activity was regulated by extracellular pH, suggesting negative feedback regulation of AHA7 during establishment of an H+ gradient. Due to genetic redundancy, it has proven difficult to test the role of AHA2 and AHA7, and mutant phenotypes have previously only been observed under nutrient stress conditions. Here, we investigated root and root hair growth under normal conditions in single and double mutants of AHA2 and AHA7. We find that AHA2 drives root cell expansion during growth but that, unexpectedly, restriction of root hair elongation is dependent on AHA2 and AHA7, with each having different roles in this process.

Insomnia as a Moderator of Response to Time in Bed Restriction for Augmenting Antidepressant Treatment: A Preliminary Investigation.

BACKGROUND: There are complex, bidirectional associations between major depressive disorder and insomnia. In the present study, we evaluated insomnia as a moderator of response to antidepressant therapy in the context of a sleep manipulation (time in bed restriction) for major depressive disorder. METHODS: Fifty-eight adults with major depressive disorder received 8 weeks of fluoxetine 20-40 mgs and were randomized to 8 hr time in bed (8h TIB) or 6 hr time in bed (6h TIB) for the first 2 weeks (participants in the 6h TIB condition were further randomized to a delayed bedtime (Late Bedtime) or advanced rise time (Early Rise Time) group). Insomnia was assessed at baseline using the Insomnia Severity Index. Depression symptom severity was determined by the clinician-rated 17-item Hamilton Rating Scale for Depression (HAMD-17), completed weekly. RESULTS: A group by time interaction was observed whereby HAMD-17 scores were higher for participants assigned to the 6h TIB group (without insomnia, weeks 3 through 7; with insomnia from week 3 through 6, ps < .05) relative to participants without insomnia assigned to the 8h TIB group. There were no differences in HAMD-17 scores for participants with insomnia in the 6h TIB group relative to the 8h TIB group. CONCLUSION: These preliminary findings suggest that response to fluoxetine may be hindered by TIB restriction in individuals without insomnia. Individuals with insomnia respond similarly to fluoxetine regardless of whether their TIB is restricted. Limitations include exclusive use of self-report measures to categorize insomnia, and small sample sizes in several of the subgroups.

Mode Equivalence of Health Indicators Between Data Collection Modes and Mixed-Mode Survey Designs in Population-Based Health Interview Surveys for Children and Adolescents: Methodological Study.

BACKGROUND: The implementation of an Internet option in an existing public health interview survey using a mixed-mode design is attractive because of lower costs and faster data availability. Additionally, mixed-mode surveys can increase response rates and improve sample composition. However, mixed-mode designs can increase the risk of measurement error (mode effects). OBJECTIVE: This study aimed to determine whether the prevalence rates or mean values of self- and parent-reported health indicators for children and adolescents aged 0-17 years differ between self-administered paper-based questionnaires (SAQ-paper) and self-administered Web-based questionnaires (SAQ-Web), as well as between a single-mode control group and different mixed-mode groups. METHODS: Data were collected for a methodological pilot of the third wave of the "German Health Interview and Examination Survey for Children and Adolescents". Questionnaires were completed by parents or adolescents. A population-based sample of 11,140 children and adolescents aged 0-17 years was randomly allocated to 4 survey designs-a single-mode control group with paper-and-pencil questionnaires only (n=970 parents, n=343 adolescents)-and 3 mixed-mode designs, all of which offered Web-based questionnaire options. In the concurrent mixed-mode design, both questionnaires were offered at the same time (n=946 parents, n=290 adolescents); in the sequential mixed-mode design, the SAQ-Web was sent first, followed by the paper questionnaire along with a reminder (n=854 parents, n=269 adolescents); and in the preselect mixed-mode design, both options were offered and the respondents were asked to request the desired type of questionnaire (n=698 parents, n=292 adolescents). In total, 3468 questionnaires of parents of children aged 0-17 years (SAQ-Web: n=708; SAQ-paper: n=2760) and 1194 questionnaires of adolescents aged 11-17 years (SAQ-Web: n=299; SAQ-paper: n=895) were analyzed. Sociodemographic characteristics and a broad range of health indicators for children and adolescents were compared by survey design and data collection mode by calculating predictive margins from regression models. RESULTS: There were no statistically significant differences in sociodemographic characteristics or health indicators between the single-mode control group and any of the mixed-mode survey designs. Differences in sociodemographic characteristics between SAQ-Web and SAQ-paper were found. Web respondents were more likely to be male, have higher levels of education, and higher household income compared with paper respondents. After adjusting for sociodemographic characteristics, only one of the 38 analyzed health indicators showed different prevalence rates between the data collection modes, with a higher prevalence rate for lifetime alcohol consumption among the online-responding adolescents (P<.001). CONCLUSIONS: These results suggest that mode bias is limited in health interview surveys for children and adolescents using a mixed-mode design with Web-based and paper questionnaires.

A wiki for the life sciences where authorship matters.

WikiGenes is the first wiki system to combine the collaborative and largely altruistic possibilities of wikis with explicit authorship. In view of the extraordinary success of Wikipedia there remains no doubt about the potential of collaborative publishing, yet its adoption in science has been limited. Here I discuss a dynamic collaborative knowledge base for the life sciences that provides authors with due credit and that can evolve via continual revision and traditional peer review into a rigorous scientific tool.

Purifying selection acts on coding and non-coding sequences of paralogous genes in Arabidopsis thaliana.

BACKGROUND: Whole-genome duplications in the ancestors of many diverse species provided the genetic material for evolutionary novelty. Several models explain the retention of paralogous genes. However, how these models are reflected in the evolution of coding and non-coding sequences of paralogous genes is unknown. RESULTS: Here, we analyzed the coding and non-coding sequences of paralogous genes in Arabidopsis thaliana and compared these sequences with those of orthologous genes in Arabidopsis lyrata. Paralogs with lower expression than their duplicate had more nonsynonymous substitutions, were more likely to fractionate, and exhibited less similar expression patterns with their orthologs in the other species. Also, lower-expressed genes had greater tissue specificity. Orthologous conserved non-coding sequences in the promoters, introns, and 3' untranslated regions were less abundant at lower-expressed genes compared to their higher-expressed paralogs. A gene ontology (GO) term enrichment analysis showed that paralogs with similar expression levels were enriched in GO terms related to ribosomes, whereas paralogs with different expression levels were enriched in terms associated with stress responses. CONCLUSIONS: Loss of conserved non-coding sequences in one gene of a paralogous gene pair correlates with reduced expression levels that are more tissue specific. Together with increased mutation rates in the coding sequences, this suggests that similar forces of purifying selection act on coding and non-coding sequences. We propose that coding and non-coding sequences evolve concurrently following gene duplication.

Sleep-disordered breathing in major depressive disorder.

Individuals with major depressive disorder often experience obstructive sleep apnea. However, the relationship between depression and less severe sleep-disordered breathing is unclear. This study examined the rate of sleep-disordered breathing in depression after excluding those who had clinically significant sleep apnea (>5 apneas∙h⁻¹). Archival data collected between 1991 and 2005 were used to assess the prevalence of sleep-disordered breathing events in 60 (31 depressed; 29 healthy controls) unmedicated participants. Respiratory events were automatically detected using a program developed in-house measuring thermal nasal air-flow and chest pressure. Results show that even after excluding participants with clinically significant sleep-disordered breathing, individuals with depression continue to exhibit higher rates of sleep-disordered breathing compared with healthy controls (depressed group: apnea-hypopnea index mean = 0.524, SE = 0.105; healthy group: apnea-hypopnea index mean = 0.179, SE = 0.108). Exploratory analyses were also conducted to assess for rates of exclusion in depression studies due to sleep-disordered breathing. Study exclusion of sleep-disordered breathing was quantified based on self-report during telephone screening, and via first night polysomnography. Results from phone screening data reveal that individuals reporting depression were 5.86 times more likely to report a diagnosis of obstructive sleep apnea than presumptive control participants. Furthermore, all of the participants excluded for severe sleep-disordered breathing detected on the first night were participants with depression. These findings illustrate the importance of understanding the relationship between sleep-disordered breathing and depression, and suggest that screening and quantification of sleep-disordered breathing should be considered in depression research.

A review of the 2020 update of the Pediatric Advanced Life Support guidelines.

Pediatric cardiac arrest presents an infrequent but high-stakes event for emergency clinicians, who need to maintain expertise in this area. Evidence regarding pediatric resuscitations has been accumulating substantially over the past decade and highlights the unique considerations and challenges when resuscitating children. This issue reviews resuscitation principles of children in cardiac arrest while addressing the newest evidence-based and best-practice recommendations by the American Heart Association.

Levosimendan increases the phosphorylation state of phospholamban in the isolated human atrium.

Levosimendan (up to 10 µM) given alone failed to increase force of contraction in isolated electrically stimulated (1 Hz) left atrial (LA) preparations from wild-type mice. Only in the additional presence of 0.1 µM rolipram, an inhibitor of the activity of phosphodiesterase IV, levosimendan increased force of contraction in LA and increased the phosphorylation state of phospholamban at amino acid serine 16. Levosimendan alone increased the beating rate in isolated spontaneously beating right atrial preparations from mice and this effect was potentiated by rolipram. The positive inotropic and the positive chronotropic effects of levosimendan in mouse atrial preparations were attenuated by 10 µM propranolol. Finally, we studied the contractile effects of levosimendan in isolated electrically stimulated (1 Hz) right atrial preparations from the human atrium (HAP), obtained during cardiac surgery. We detected concentration-dependent positive inotropic effects of levosimendan alone that reached plateau at 1 µM levosimendan in HAP (n = 11). Levosimendan shortened time of tension relaxation in HAP. Cilostamide (1 µM), an inhibitor of phosphodiesterase III, or propranolol (10 µM) blocked the positive inotropic effect of levosimendan in HAP. Levosimendan (1 µM) alone increased in HAP the phosphorylation state of phospholamban. In conclusion, we present evidence that levosimendan acts via phosphodiesterase III inhibition in the human atrium leading to phospholamban phosphorylation and thus explaining the positive inotropic effects of levosimendan in HAP.

Temperature alters the inotropic, chronotropic and proarrhythmic effects of histamine in atrial muscle preparations from humans and H2-receptor overexpressing mice.

We investigated whether hypothermia and hyperthermia can alter the efficacy and potency of histamine at increasing the force of cardiac contractions in mice that overexpress the human H2 receptor only in their cardiac myocytes (labelled H2-TG). Contractile studies were performed in an organ bath on isolated, electrically driven (1 Hz) left atrial preparations and spontaneously beating right atrial preparations from H2-TG mice and wild-type (WT) littermate control mice. The basal beating rate in the right atrial preparations from H2-TG mice was lowered by hypothermia (23 °C) and elevated by hyperthermia (42 °C). Furthermore, the efficacy of histamine (0.01-100 µM) at exerting positive inotropic effects was more severely attenuated in the left and right H2-TG mouse atria under hypothermia and hyperthermia than under normothermia (37 °C). Similarly, the inotropic response to histamine was attenuated under hypothermia and hyperthermia in isolated electrically stimulated (1 Hz) right atrial preparations obtained from humans undergoing cardiac surgery. The phosphorylation state of phospholamban at serine 16 at 23 °C was inferior to that at 37 °C in left atrial preparations from H2-TG mice in the presence of 10 µM histamine. In contrast, in human atrial preparations, the phosphorylation state of phospholamban at serine 16 in the presence of 100 µM histamine was lower at 42 °C than at 37 °C. Finally, under hyperthermia, we recorded more and longer lasting arrhythmias in right atrial preparations from H2-TG mice than in those from WT mice. We conclude that the inotropic effects of histamine in H2-TG mice and in human atrial preparations, as well as the chronotropic effects of histamine in H2-TG mice, are temperature dependent. Furthermore, we observed that, even without stimulation of the H2 receptors by exogenous agonists, temperature elevation can increase arrhythmias in isolated right atrial preparations from H2-TG mice. We propose that H2 receptors play a role in hyperthermia-induced supraventricular arrhythmias in human patients.

German Health Update Fokus (GEDA Fokus) among Residents with Croatian, Italian, Polish, Syrian, or Turkish Citizenship in Germany: Protocol for a Multilingual Mixed-Mode Interview Survey.

BACKGROUND: Germany has a long history of migration. In 2020, more than 1 person in every 4 people had a statistically defined, so-called migration background in Germany, meaning that the person or at least one of their parents was born with a citizenship other than German citizenship. People with a history of migration are not represented proportionately to the population within public health monitoring at the Robert Koch Institute, thus impeding differentiated analyses of migration and health. To develop strategies for improving the inclusion of people with a history of migration in health surveys, we conducted a feasibility study in 2018. The lessons learned were implemented in the health interview survey German Health Update (Gesundheit in Deutschland aktuell [GEDA]) Fokus, which was conducted among people with selected citizenships representing the major migrant groups in Germany. OBJECTIVE: GEDA Fokus aimed to collect comprehensive data on the health status and social, migration-related, and structural factors among people with selected citizenships to enable differentiated explanations of the associations between migration-related aspects and their impact on migrant health. METHODS: GEDA Fokus is an interview survey among people with Croatian, Italian, Polish, Syrian, or Turkish citizenship living in Germany aged 18-79 years, with a targeted sample size of 1200 participants per group. The gross sample of 33,436 people was drawn from the residents' registration offices of 99 German municipalities based on citizenship. Sequentially, multiple modes of administration were offered. The questionnaire was available for self-administration (web-based and paper-based); in larger municipalities, personal or phone interviews were possible later on. Study documents and the questionnaire were bilingual-in German and the respective translation language depending on the citizenship. Data were collected from November 2021 to May 2022. RESULTS: Overall, 6038 respondents participated in the survey, of whom 2983 (49.4%) were female. The median age was 39 years; the median duration of residence in Germany was 10 years, with 19.69% (1189/6038) of the sample being born in Germany. The overall response rate was 18.4% (American Association for Public Opinion Research [AAPOR] response rate 1) and was 6.8% higher in the municipalities where personal interviews were offered (19.3% vs 12.5%). Overall, 78.12% (4717/6038) of the participants self-administered the questionnaire, whereas 21.88% (1321/6038) took part in personal interviews. In total, 41.85% (2527/6038) of the participants answered the questionnaire in the German language only, 16.69% (1008/6038) exclusively used the translation. CONCLUSIONS: Offering different modes of administration, as well as multiple study languages, enabled us to recruit a heterogeneous sample of people with a history of migration. The data collected will allow differentiated analyses of the role and interplay of migration-related and social determinants of health and their impact on the health status of people with selected citizenships. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43503.

Race, Ethnicity, and Ancestry in Clinical Pathways: A Framework for Evaluation.

Clinical algorithms, or "pathways," promote the delivery of medical care that is consistent and equitable. Race, ethnicity, and/or ancestry terms are sometimes included in these types of guidelines, but it is unclear if this is appropriate for clinical decision-making. At our institution, we developed and applied a structured framework to determine whether race, ethnicity, or ancestry terms identified in our clinical pathways library should be retained, modified, or removed. First, we reviewed all text and associated reference documents for 132 institutionally-developed clinical pathways and identified 8 pathways that included race, ethnicity, or ancestry terms. Five pathways had clear evidence or a change in institutional policy that supported removal of the term. Multispecialty teams conducted additional in-depth evaluation of the 3 remaining pathways (Acute Viral Illness, Hyperbilirubinemia, and Weight Management) by applying the framework. In total, based on these reviews, race, ethnicity, or ancestry terms were removed (n = 6) or modified (n = 2) in all 8 pathways. Application of the framework established several recommended practices, including: (1) define race, ethnicity, and ancestry rigorously; (2) assess the most likely mechanisms underlying epidemiologic associations; (3) consider whether inclusion of the term is likely to mitigate or exacerbate existing inequities; and (4) exercise caution when applying population-level data to individual patient encounters. This process and framework may be useful to other institutional programs and national organizations in evaluating the inclusion of race, ethnicity, and ancestry in clinical guidelines.

Feasibility of bioimpedance spectroscopy and long-term functional assessment in critically ill children.

BACKGROUND & AIMS: Lean body mass loss due to critical illness in childhood could be detrimental to long term outcomes, including functional status and quality of life. We describe the feasibility of body composition assessment by bioimpedance spectroscopy (BIS) in the pediatric intensive care unit (PICU), and functional status and quality of life assessments up to 6 months following admission in a cohort of mechanically ventilated, critically ill children. METHODS: We conducted a prospective, observational pilot study in a multidisciplinary PICU. Children aged 1 month to 18 years who required mechanical ventilation, with expected stay in the PICU of at least 5 days were included. We examined the feasibility of consenting, enrolling, and completing baseline and 6-month assessments of BIS variables, Functional Status Scale (FSS), and Pediatric Quality of Life (Peds QL), in eligible patients. RESULTS: Of 32 patients approached, 23 (72%) completed baseline assessments [median (IQR) age 3.4 (1.0, 7.8) years, 14 (61%) male]; 6-month assessments were completed in 15 (65%) enrolled patients. Mean (SD) phase angle at study enrollment was 2.95 (0.93) and the impedance ratio was 0.90 (0.03). Phase angle (rs = -0.58, p = 0.03) and impedance ratio (rs = 0.61, p = 0.02) by BIS were significantly correlated with total FSS at PICU discharge. Median total FSS and FSS tech (feeding and respiratory domains of FSS) scores improved from enrollment [16 (13, 26) and 8 (7, 10)] to 6 months [6 (6, 9) and 2 (2, 4), respectively, p < 0.001]. Median Peds QL total, physical summary and psychosocial summary scores were not significantly different between PICU discharge and 6 months after PICU admission. Correlations between the total 6-month FSS and a) phase angle (-0.45, p = 0.197) and b) impedance ratio (0.56, p = 0.096) at PICU discharge were not significant. CONCLUSIONS: We have demonstrated the feasibility of obtaining bedside BIS measurements in the PICU, and functional and quality of life assessments remotely following PICU discharge. Body composition and long-term assessment of functional outcomes and quality of life must be incorporated in nutrition trials in critically ill children.

Sleep homeostasis in alcohol-dependent, depressed and healthy control men.

Visually scored and power spectral analyses (PSA) of polysomnography (PSG) recordings reveal abnormalities in alcohol dependence (AD) and major depressive disorder (MDD), including deficiencies in slow wave activity (SWA) during non-rapid eye movement (NREM) sleep. SWA parameters reflect the integrity of the homeostatic sleep drive, which have not been compared in those with AD or MDD. Ten men with AD were compared with 10 men with MDD and 10 healthy controls (HCs), all aged 20-40 years. They maintained an 11 pm to 6 am sleep schedule for 5-7 days, followed by 3 consecutive nights of PSG in the laboratory: night 1 for adaptation/screening; night 2 for baseline recordings; and night 3 as the challenge night, delaying sleep until 2 am. SWA was quantified with PSA across 4 NREM periods. Men with AD generated the least SWA at baseline. In response to sleep delay, HC men showed the expected SWA enhancement and a sharper exponential decline across NREM periods. Both the MDD and the AD groups showed a significantly blunted SWA response to sleep delay. Men with MDD had the least SWA in the first NREM period (impaired accumulation of sleep drive), whereas men with AD had the slowest SWA decay rate (impaired dissipation of sleep drive). These results suggest that both SWA generation and its homeostatic regulation are impaired in men with either AD or MDD. Finding interventions that selectively improve these different components of sleep homeostasis should be a goal of treatment for AD and MDD.

Response network analysis of differential gene expression in human epithelial lung cells during avian influenza infections.

BACKGROUND: The recent emergence of the H5N1 influenza virus from avian reservoirs has raised concern about future influenza strains of high virulence emerging that could easily infect humans. We analyzed differential gene expression of lung epithelial cells to compare the response to H5N1 infection with a more benign infection with Respiratory Syncytial Virus (RSV). These gene expression data are then used as seeds to find important nodes by using a novel combination of the Gene Ontology database and the Human Network of gene interactions. Additional analysis of the data is conducted by training support vector machines (SVM) with the data and examining the orientations of the optimal hyperplanes generated. RESULTS: Analysis of gene clustering in the Gene Ontology shows no significant clustering of genes unique to H5N1 response at 8 hours post infection. At 24 hours post infection, however, a number of significant gene clusters are found for nodes representing "immune response" and "response to virus" terms. There were no significant clusters of genes in the Gene Ontology for the control (Mock) or RSV experiments that were unique relative to the H5N1 response. The genes found to be most important in distinguishing H5N1 infected cells from the controls using SVM showed a large degree of overlap with the list of significantly regulated genes. However, though none of these genes were members of the GO clusters found to be significant. CONCLUSIONS: Characteristics of H5N1 infection compared to RSV infection show several immune response factors that are specific for each of these infections. These include faster timescales within the cell as well as a more focused activation of immunity factors. Many of the genes that are found to be significantly expressed in H5N1 response relative to the control experiments are not found to cluster significantly in the Gene Ontology. These genes are, however, often closely linked to the clustered genes through the Human Network. This may suggest the need for more diverse annotations of these genes and verification of their action in immune response.