Prevalence of depressive symptoms and correlates among individuals who self-reported SARS-CoV-2 infection after optimizing the COVID-19 response in China.

Background: The burden of depression symptoms has increased among individuals infected with SARS-CoV-2 during COVID-19 pandemic. However, the prevalence and associated factors of depressive symptoms among individuals infected with SARS-CoV-2 remain uncertain after optimizing the COVID-19 response in China. Methods: An online cross-sectional survey was conducted among the public from January 6 to 30, 2023, using a convenience sampling method. Sociodemographic and COVID-19 pandemic-related factors were collected. The depression symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Logistic regression analysis was performed to explore the associated factors with depressive symptoms. Results: A total of 2,726 participants completed the survey. The prevalence of depression symptoms was 35.3%. About 58% of the participants reported experiencing insufficient drug supply. More than 40% of participants reported that they had missed healthcare appointments or delayed treatment. One-third of participants responded experiencing a shortage of healthcare staff and a long waiting time during medical treatment. Logistic regression analysis revealed several factors that were associated with depression symptoms, including sleep difficulties (OR, 2.84; 95% CI, 2.34-3.44), chronic diseases (OR, 2.15; 95% CI, 1.64-2.82), inpatient treatment for COVID-19 (OR, 3.24; 95% CI, 2.19-4.77), with COVID-19 symptoms more than 13 days (OR, 1.30, 95% CI 1.04-1.63), re-infection with SARS-CoV-2 (OR, 1.52; 95% CI, 1.07-2.15), and the increased in demand for healthcare services (OR, 1.32; 95% CI, 1.08-1.61). Conclusion: This study reveals a moderate prevalence of depression symptoms among individuals infected with SARS-CoV-2. The findings underscore the importance of continued focus on depressive symptoms among vulnerable individuals, including those with sleeping difficulties, chronic diseases, and inpatient treatment for COVID-19. It is necessary to provide mental health services and psychological interventions for these vulnerable groups during the COVID-19 epidemic.

Centile curves and reference values for height, body mass, body mass index and waist circumference of Peruvian children and adolescents.

This study aimed to provide height, body mass, BMI and waist circumference (WC) growth centile charts for school-children, aged 4-17 years, from central Peru, and to compare Peruvian data with North-American and Argentinean references. The sample consisted of 8753 children and adolescents (4130 boys and 4623 girls) aged 4 to 17 years, from four Peruvian cities: Barranco, La Merced, San Ramón and Junín. Height, body mass and WC were measured according to standardized techniques. Centile curves for height, body mass, BMI and WC were obtained separately for boys and girls using the LMS method. Student t-tests were used to compare mean values. Overall boys have higher median heights than girls, and the 50th percentile for body mass increases curvilinearly from 4 years of age onwards. In boys, the BMI and WC 50th percentiles increase linearly and in girls, the increase presents a curvilinear pattern. Peruvian children are shorter, lighter and have higher BMI than their counterparts in the U.S. and Argentina; in contrast, age and sex-specific WC values are lower. Height, body mass and WC of Peruvian children increased with age and variability was higher at older ages. The growth patterns for height, body mass, BMI and WC among Peruvian children were similar to those observed in North-American and Argentinean peers.

Birth weight and longitudinal growth in infants born below 32 weeks' gestation: a UK population study.

OBJECTIVE: To describe birth weight and postnatal weight gain in a contemporaneous population of babies born <32 weeks' gestation, using routinely captured electronic clinical data. DESIGN: Anonymised longitudinal weight data from 2006 to 2011. SETTING: National Health Service neonatal units in England. METHODS: Birth weight centiles were constructed using the LMS method, and longitudinal weight gain was summarised as mean growth curves for each week of gestation until discharge, using SITAR (Superimposition by Translation and Rotation) growth curve analysis. RESULTS: Data on 103 194 weights of 5009 babies born from 22-31 weeks' gestation were received from 40 neonatal units. At birth, girls weighed 6.6% (SE 0.4%) less than boys (p<0.0001). For babies born at 31 weeks' gestation, weight fell after birth by an average of 258 g, with the nadir on the 8th postnatal day. The rate of weight gain then increased to a maximum of 28.4 g/d or 16.0 g/kg/d after 3 weeks. Conversely for babies of 22 to 28 weeks' gestation, there was on average no weight loss after birth. At all gestations, babies tended to cross weight centiles downwards for at least 2 weeks. CONCLUSIONS: In very preterm infants, mean weight crosses centiles downwards by at least two centile channel widths. Postnatal weight loss is generally absent in those born before 29 weeks, but marked in those born later. Assigning an infant's target centile at birth is potentially harmful as it requires rapid weight gain and should only be done once weight gain has stabilised. The use of electronic data reflects contemporary medical management.

Distal NF-kB binding motif functions as an enhancer for nontypeable H. influenzae-induced DEFB4 regulation in epithelial cells.

Among the antimicrobial molecules produced by epithelial cells, DEFB4 is inducible in response to proinflammatory signals such as cytokines and bacterial molecules. Nontypeable Haemophilus influenzae (NTHi) is an important human pathogen that exacerbates chronic obstructive pulmonary disease in adult and causes otitis media and sinusitis in children. Previously, we have demonstrated that DEFB4 effectively kills NTHi and is induced by NTHi via TLR2 signaling. The 5'-flanking region of DEFB4 contains several NF-κB binding motifs, but their NTHi-specific activity remains unclear. In this study, we aimed to elucidate molecular mechanism involved in DEFB4 regulation, focusing on the role of the distal NF-κB binding motif of DEFB4 responding to NTHi. Here, we show that the human middle ear epithelial cells up-regulate DEFB4 expression in response to NTHi via NF-κB activation mediated by IκKα/ß-IκBα signaling. Deletion of the distal NF-κB binding motif led to a significant reduction in NTHi-induced DEFB4 up-regulation. A heterologous construct containing the distal NF-κB binding motif was found to increase the promoter activity in response to NTHi, indicating a NTHi-responding enhancer activity of the distal NF-κB binding motif. Furthermore, electrophoretic mobility shift assays and chromatin immunoprecipitation assays showed that the p65 domain of NF-κB binds to the distal NF-κB binding motif in response to NTHi. Taken together, our results suggest that NTHi-induced binding of p65 NF-κB to the distal NF-κB binding motif of DEFB4 enhances NTHi-induced DEFB4 regulation in epithelial cells.

Oscillometric blood pressure percentiles for Polish normal-weight school-aged children and adolescents.

OBJECTIVE: The objective of this study was to construct blood pressure (BP) references with the use of a validated oscillometric device for normal-weight, school-aged children and adolescents and to study BP predictors. METHODS: BP was measured in 14 266 randomly selected, normal-weight Polish children and adolescents aged 7-18 years, who were free of chronic disease, using a validated oscillometric device (Datascope Accutor Plus). Height, weight and waist circumference were measured. BP percentiles were constructed for age and height simultaneously with the use of a polynomial regression model. The normative values of BP were compared with the US normal-weight reference, German oscillometric reference, and Polish auscultatory reference. RESULTS: Reference BP percentiles by sex, age and height are presented. At median height, the age-specific differences in the 90th BP percentiles compared with German oscillometric reference ranged in the case of boys from -3 to 2  mmHg and from -5 to -1  mmHg, SBP and DBP, respectively, and in the case of girls from 0 to 3  mmHg and from -5 to -1  mmHg, SBP and DBP, respectively. As compared to weight, waist circumference was stronger SBP predictor in low birth weight boys. CONCLUSION: The study provides BP references for oscillmetric device, based on a current, nationally representative sample of normal-weight Polish children and adolescents. The normative values of BP were compared taking into consideration the height and BMI differences, the pubertal spurt, the methods of BP measurement and percentile construction.

Population-based centile curves for triceps, subscapular, and abdominal skinfold thicknesses in Polish children and adolescents--the OLAF study.

UNLABELLED: Skinfold thicknesses are used as valid anthropometric indicators of regional body fatness. Actual population-based values for skinfold thicknesses for Polish children are not available. The purpose of this study was to provide population-based values for triceps, subscapular, and abdominal skinfold thicknesses in healthy children and adolescents. A total number of 17,416 boys and girls aged 6.5-18.5 years, randomly selected from whole Polish population of children and adolescents, were enrolled in the study. Skinfold thicknesses (triceps, subscapular, and abdominal) were measured using Harpenden skinfold caliper. All measurements were taken after the training of participating investigators. The LMS method was used to fit percentile curves across age for each skinfold. Q tests for fit were used to assess the global goodness of fit of our final models. The study shows for the first time smoothed population-based values of body fat distribution indices for Polish children and adolescents 7-18 years of age. Reported skinfold centiles are higher compared to previously established for Warsaw children and very close to the actual US data. CONCLUSION: Our study provided for the first time population-based values for skinfold thicknesses evaluation in a way allowing to calculate reliable Z scores. The early detection of abnormal fat stores, using our population-based values and respective Z scores, may be now implemented for practice.

Growth references for Brazilian children and adolescents: healthy growth in Cariri study.

AIM: To construct reference values for height, body mass and BMI of children and adolescents from the Cariri region, Brazil; to compare the growth of Cariri children with those from CDC (Centers for Disease Control and Prevention) and with references from other Brazilian regions; to verify the associations between socioeconomic status and height, body mass and BMI in children and youth from both sexes. SUBJECTS AND METHODS: The sample comprised 3311 girls and 3280 boys aged 7-17 years, participating in the study 'Healthy Growth in Cariri'. Socioeconomic status was defined according to school attendance: private and public. Centile curves for height, body mass and BMI were constructed using the LMS method. RESULTS: Significant differences between children and adolescents from Cariri and those from other Brazilian regions and the CDC references were found for height and body mass. In girls from private schools, average differences in height compared to the CDC references ranged from 0.79-5.9 cm and in boys from 2.9-8.6 cm. CONCLUSION: Children from Cariri show a growth pattern in height, body mass and BMI that closely resembles the patterns observed in developed countries, but the absolute values in height and body mass are markedly lower than CDC references and growth references for other regions in Brazil.

Polish 2010 growth references for school-aged children and adolescents.

Growth references are useful in monitoring a child's growth, which is an essential part of child care. The aim of this paper was to provide updated growth references for Polish school-aged children and adolescents and show the prevalence of overweight and obesity among them. Growth references for height, weight, and body mass index (BMI) were constructed with the lambda, mu, sigma (LMS) method using data from a recent, large, population-representative sample of school-aged children and adolescents in Poland (n = 17,573). The prevalence of overweight and obesity according to the International Obesity Taskforce definition was determined with the use of LMSGrowth software. Updated growth references for Polish school-aged children and adolescents were compared with Polish growth references from the 1980s, the Warsaw 1996-1999 reference, German, and 2000 CDC references. A positive secular trend in height was observed in children and adolescents from 7 to 15 years of age. A significant shift of the upper tail of the BMI distribution occurred, especially in Polish boys at younger ages. The prevalence of overweight or obesity was 18.7% and 14.1% in school-aged boys and girls, respectively. The presented height, weight, and BMI references are based on a current, nationally representative sample of Polish children and adolescents without known disorders affecting growth. Changes in the body size of children and adolescents over the last three decades suggest an influence of the changing economical situation on anthropometric indices.

Spiral ligament fibrocyte-derived MCP-1/CCL2 contributes to inner ear inflammation secondary to nontypeable H. influenzae-induced otitis media.

BACKGROUND: Otitis media (OM), one of the most common pediatric infectious diseases, causes inner ear inflammation resulting in vertigo and sensorineural hearing loss. Previously, we showed that spiral ligament fibrocytes (SLFs) recognize OM pathogens and up-regulate chemokines. Here, we aim to determine a key molecule derived from SLFs, contributing to OM-induced inner ear inflammation. METHODS: Live NTHI was injected into the murine middle ear through the tympanic membrane, and histological analysis was performed after harvesting the temporal bones. Migration assays were conducted using the conditioned medium of NTHI-exposed SLFs with and without inhibition of MCP-1/CCL2 and CCR2. qRT-PCR analysis was performed to demonstrate a compensatory up-regulation of alternative genes induced by the targeting of MCP-1/CCL2 or CCR2. RESULTS: Transtympanic inoculation of live NTHI developed serous and purulent labyrinthitis after clearance of OM. THP-1 cells actively migrated and invaded the extracellular matrix in response to the conditioned medium of NTHI-exposed SLFs. This migratory activity was markedly inhibited by the viral CC chemokine inhibitor and the deficiency of MCP-1/CCL2, indicating that MCP-1/CCL2 is a main attractant of THP-1 cells among the SLF-derived molecules. We further demonstrated that CCR2 deficiency inhibits migration of monocyte-like cells in response to NTHI-induced SLF-derived molecules. Immunolabeling showed an increase in MCP-1/CCL2 expression in the cochlear lateral wall of the NTHI-inoculated group. Contrary to the in vitro data, deficiency of MCP-1/CCL2 or CCR2 did not inhibit OM-induced inner ear inflammation in vivo. We demonstrated that targeting MCP-1/CCL2 enhances NTHI-induced up-regulation of MCP-2/CCL8 in SLFs and up-regulates the basal expression of CCR2 in the splenocytes. We also found that targeting CCR2 enhances NTHI-induced up-regulation of MCP-1/CCL2 in SLFs. CONCLUSIONS: Taken together, we suggest that NTHI-induced SLF-derived MCP-1/CCL2 is a key molecule contributing to inner ear inflammation through CCR2-mediated recruitment of monocytes. However, deficiency of MCP-1/CCL2 or CCR2 alone was limited to inhibit OM-induced inner ear inflammation due to compensation of alternative genes.

The height-, weight-, and BMI-for-age of Polish school-aged children and adolescents relative to international and local growth references.

BACKGROUND: The growth of children is an indicator of health and society's wellbeing. Growth references are useful in monitoring a child's growth, which is a very important part of child care. Poland's growth references are not updated regularly. Although several growth reference ranges have been developed in Poland over recent years, sampling was restricted to urban populations of major cities. The aim of this study was to assess how well Polish children match with, or diverge from, regional charts and to compare them with international growth references. METHODS: Four Polish and two international (WHO 2007 and USCDC2000) growth references were used to calculate the height, weight and BMI z-scores in a recent, large, population-representative sample of school-aged children and adolescents in Poland. The distributions of z-scores were analysed with descriptive and inferential statistical methods. RESULTS: Mean height z-scores calculated with the use of the WHO 2007 and USCDC2000 references were positive and significantly different from zero over the entire age range. The mean height z-score was closest to zero in the Poznan reference for boys (0.05) and Warszawa reference for girls (0.01). Median weight z-scores were positive under all weight references over the entire age range with only the exception of 18-year-old girls' weight z-score calculated relative to USCDC2000. Median BMI z-scores were positive in males in early childhood, decreasing with age. In the case of girls, the median BMI z-score calculated using WHO 2007 and USCDC2000 was close to zero in early childhood, decreased in adolescents and reached minimum values at age 18 years. Median BMI z-scores calculated with the use of the Lodz reference fluctuated between 0.05 and 0.2 over the studied age range. CONCLUSIONS: In this contemporary sample of Polish school-aged children, distributions of height, weight and BMI differed from those of children from the international growth references. These differences should be considered when using the references. There exist certain limitations to the analysis of height, weight, and BMI z-scores when Polish regional references are used.

Child body mass index in four cities of East China compared to Western references.

BACKGROUND: The rising trends in child obesity worldwide are poorly documented in China. AIM: The present study compared the distribution of body mass index (BMI) by age in children from four cities in East China with Western references. SUBJECTS AND METHODS: 94 370 boys and 90 048 girls aged 0-19 years from Shanghai, Jinan, Xuzhou and Hefei were measured in 1999-2004 for length/height and weight. The LMS method was used to construct BMI centiles for each city. Shanghai children aged 0-6 years in 1986 and US and UK BMI references were used for comparison. RESULTS: The median BMI curves for the four cities differed in shape from those for the USA and UK. Chinese boys were fatter than US boys in early to mid-childhood but less so in adolescence, and US boys were fatter at age 18. Within China the adiposity rebound was earlier in boys than girls. Shanghai children were appreciably fatter in 2000 than in 1986, and boys more so than girls. CONCLUSIONS: The roots of child obesity lie in early life, particularly in boys, and are linked to economic development, which has important implications for both the aetiology of child obesity and the health of current and future Chinese children.

Lysozyme M deficiency leads to an increased susceptibility to Streptococcus pneumoniae-induced otitis media.

BACKGROUND: Lysozyme is an antimicrobial innate immune molecule degrading peptidoglycan of the bacterial cell wall. Lysozyme shows the ubiquitous expression in wide varieties of species and tissues including the tubotympanum of mammals. We aim to investigate the effects of lysozyme depletion on pneumococcal clearance from the middle ear cavity. METHODS: Immunohistochemistry was performed to localize lysozyme in the Eustachian tube. Lysozyme expression was compared between the wild type and the lysozyme M-/- mice using real time quantitative RT-PCR and western blotting. Muramidase activity and bactericidal activity of lysozyme was measured using a lysoplate radial diffusion assay and a liquid broth assay, respectively. To determine if depletion of lysozyme M increases a susceptibility to pneumococal otitis media, 50 CFU of S. pneumoniae 6B were transtympanically inoculated to the middle ear and viable bacteria were counted at day 3 and 7 with clinical grading of middle ear inflammation. RESULTS: Immunolabeling revealed that localization of lysozyme M and lysozyme P is specific to some/particular cell types of the Eustachian tube. Lysozyme P of lysozyme M-/- mice was mainly expressed in the submucosal gland but not in the tubal epithelium. Although lysozyme M-/- mice showed compensatory up-regulation of lysozyme P, lysozyme M depletion resulted in a decrease in both muramidase and antimicrobial activities. Deficiency in lysozyme M led to an increased susceptibility to middle ear infection with S. pneumoniae 6B and resulted in severe middle ear inflammation, compared to wild type mice. CONCLUSION: The results suggest that lysozyme M plays an important role in protecting the middle ear from invading pathogens, particularly in the early phase. We suggest a possibility of the exogenous lysozyme as an adjuvant therapeutic agent for otitis media, but further studies are necessary.

Induction of beta defensin 2 by NTHi requires TLR2 mediated MyD88 and IRAK-TRAF6-p38MAPK signaling pathway in human middle ear epithelial cells.

BACKGROUND: All mucosal epithelia, including those of the tubotympanium, are secreting a variety of antimicrobial innate immune molecules (AIIMs). In our previous study, we showed the bactericidal/bacteriostatic functions of AIIMs against various otitis media pathogens. Among the AIIMs, human beta-defensin 2 is the most potent molecule and is inducible by exposure to inflammatory stimuli such as bacterial components or proinflammatory cytokines. Even though the beta-defensin 2 is an important AIIM, the induction mechanism of this molecule has not been clearly established. We believe that this report is the first attempt to elucidate NTHi induced beta-defensin expression in airway mucosa, which includes the middle ear. METHODS: Monoclonal antibody blocking method was employed in monitoring the TLR-dependent NTHi response. Two gene knock down methods - dominant negative (DN) plasmid and small interfering RNA (siRNA) - were employed to detect and confirm the involvement of several key genes in the signaling cascade resulting from the NTHi stimulated beta-defensin 2 expression in human middle ear epithelial cell (HMEEC-1). The student's t-test was used for the statistical analysis of the data. RESULTS: The experimental results showed that the major NTHi-specific receptor in HMEEC-1 is the Toll-like receptor 2 (TLR2). Furthermore, recognition of NTHi component(s)/ligand(s) by TLR2, activated the Toll/IL-1 receptor (TIR)-MyD88-IRAK1-TRAF6-MKK3/6-p38 MAPK signal transduction pathway, ultimately leading to the induction of beta-defensin 2. CONCLUSION: This study found that the induction of beta-defensin 2 is highest in whole cell lysate (WCL) preparations of NTHi, suggesting that the ligand(s) responsible for this up-regulation may be soluble macromolecule(s). We also found that this induction takes place through the TLR2 dependent MyD88-IRAK1-TRAF6-p38 MAPK pathway, with the primary response occurring within the first hour of stimulation. In combination with our previous studies showing that IL-1alpha-induced beta-defensin 2 expression takes place through a MyD88-independent Raf-MEK1/2-ERK MAPK pathway, we found that both signaling cascades act synergistically to up-regulate beta-defensin 2 levels. We propose that this confers an essential evolutionary advantage to the cells in coping with infections and may serve to amplify the innate immune response through paracrine signaling.

Nonlinear growth generates age changes in the moments of the frequency distribution: the example of height in puberty.

Higher moments of the frequency distribution of child height and weight change with age, particularly during puberty, though why is not known. Our aims were to confirm that height skewness and kurtosis change with age during puberty, to devise a model to explain why, and to test the model by analyzing the data longitudinally. Heights of 3245 Christ's Hospital School boys born during 1927-1956 were measured twice termly from 9 to 20 years (n=129508). Treating the data as independent, the mean, standard deviation (SD), skewness, and kurtosis were calculated in 40 age groups and plotted as functions of age t. The data were also analyzed longitudinally using the nonlinear random-effects growth model H(t)=h(t-epsilon )+alpha, with H(t) the cross-sectional data, h(t) the individual mean curve, and epsilon and alpha subject-specific random effects reflecting variability in age and height at peak height velocity (PHV). Mean height increased monotonically with age, while the SD, skewness, and kurtosis changed cyclically with, respectively, 1, 2, and 3 turning points. Surprisingly, their age curves corresponded closely in shape to the first, second, and third derivatives of the mean height curve. The growth model expanded as a Taylor series in epsilon predicted such a pattern, and the longitudinal analysis showed that adjusting for age at PHV on a multiplicative scale largely removed the trends in the higher moments. A nonlinear growth process where subjects grow at different rates, such as in puberty, generates cyclical changes in the higher moments of the frequency distribution.

Reference ranges for spirometry across all ages: a new approach.

RATIONALE: The Third National Health and Nutrition Examination Survey (NHANES III) reference is currently recommended for interpreting spirometry results, but it is limited by the lack of subjects younger than 8 years and does not continuously model spirometry across all ages. OBJECTIVES: By collating pediatric data from other large-population surveys, we have investigated ways of developing reference ranges that more accurately describe the relationship between spirometric lung function and height and age within the pediatric age range, and allow a seamless transition to adulthood. METHODS: Data were obtained from four surveys and included 3,598 subjects aged 4-80 years. The original analyses were sex specific and limited to non-Hispanic white subjects. An extension of the LMS (lambda, mu, sigma) method, widely used to construct growth reference charts, was applied. MEASUREMENTS AND MAIN RESULTS: The extended models have four important advantages over the original NHANES III analysis as follows: (1) they extend the reference data down to 4 years of age, (2) they incorporate the relationship between height and age in a way that is biologically plausible, (3) they provide smoothly changing curves to describe the transition between childhood and adulthood, and (4) they highlight the fact that the range of normal values is highly dependent on age. CONCLUSIONS: The modeling technique provides an elegant solution to a complex and longstanding problem. Furthermore, it provides a biologically plausible and statistically robust means of developing continuous reference ranges from early childhood to old age. These dynamic models provide a platform from which future studies can be developed to continue to improve the accuracy of reference data for pulmonary function tests.

Toll-like receptor 2-dependent NF-kappaB activation is involved in nontypeable Haemophilus influenzae-induced monocyte chemotactic protein 1 up-regulation in the spiral ligament fibrocytes of the inner ear.

Inner ear dysfunction secondary to chronic otitis media (OM), including high-frequency sensorineural hearing loss or vertigo, is not uncommon. Although chronic middle ear inflammation is believed to cause inner ear dysfunction by entry of OM pathogen components or cytokines from the middle ear into the inner ear, the underlying mechanisms are not well understood. Previously, we demonstrated that the spiral ligament fibrocyte (SLF) cell line up-regulates monocyte chemotactic protein 1 (MCP-1) expression after treatment with nontypeable Haemophilus influenzae (NTHI), one of the most common OM pathogens. We hypothesized that the SLF-derived MCP-1 plays a role in inner ear inflammation secondary to OM that is responsible for hearing loss and dizziness. The purpose of this study was to investigate the signaling pathway involved in NTHI-induced MCP-1 up-regulation in SLFs. Here we show for the first time that NTHI induces MCP-1 up-regulation in the SLFs via Toll-like receptor 2 (TLR2)-dependent activation of NF-kappaB. TLR2(-/-)- and MyD88(-/-)-derived SLFs revealed involvement of TLR2 and MyD88 in NTHI-induced MCP-1 up-regulation. Studies using chemical inhibitors and dominant-negative constructs demonstrated that it is mediated by the IkappaKbeta-dependent IkappaBalpha phosphorylation and NTHI-induced NF-kappaB nuclear translocation. Furthermore, we demonstrated that the binding of NF-kappaB to the enhancer region of MCP-1 is involved in this up-regulation. In addition, we have identified a potential NF-kappaB motif that is responsive and specific to certain NTHI molecules or ligands. Further studies are necessary to reveal specific ligands of NTHI that activate host receptors. These results may provide us with new therapeutic strategies for prevention of inner ear dysfunction secondary to chronic middle ear inflammation.

An investigation of minimisation criteria.

BACKGROUND: Minimisation can be used within treatment trials to ensure that prognostic factors are evenly distributed between treatment groups. The technique is relatively straightforward to apply but does require running tallies of patient recruitments to be made and some simple calculations to be performed prior to each allocation. As computing facilities have become more widely available, minimisation has become a more feasible option for many. Although the technique has increased in popularity, the mode of application is often poorly reported and the choice of input parameters not justified in any logical way. METHODS: We developed an automated package for patient allocation which incorporated a simulation arm. We here demonstrate how simulation of data can help to determine the input parameters to be used in a subsequent application of minimisation. RESULTS: Several scenarios were simulated. Within the selected scenarios, increasing the number of factors did not substantially adversely affect the extent to which the treatment groups were balanced with respect to the prognostic factors. Weighting of the factors tended to improve the balance when factors had many categories with only a slight negative effect on the factors with fewer categories. When interactions between factors were included as minimisation factors, there was no major reduction in the balance overall. CONCLUSION: With the advent of widely available computing facilities, researchers can be better equipped to implement minimisation as a means of patient allocation. Simulations prior to study commencement can assist in the choice of minimisation parameters and can be used to justify those selections.

Synergistic effect of interleukin 1 alpha on nontypeable Haemophilus influenzae-induced up-regulation of human beta-defensin 2 in middle ear epithelial cells.

BACKGROUND: We recently showed that beta-defensins have antimicrobial activity against nontypeable Haemophilus influenzae (NTHi) and that interleukin 1 alpha (IL-1 alpha) up-regulates the transcription of beta-defensin 2 (DEFB4 according to new nomenclature of the Human Genome Organization) in human middle ear epithelial cells via a Src-dependent Raf-MEK1/2-ERK signaling pathway. Based on these observations, we investigated if human middle ear epithelial cells could release IL-1 alpha upon exposure to a lysate of NTHi and if this cytokine could have a synergistic effect on beta-defensin 2 up-regulation by the bacterial components. METHODS: The studies described herein were carried out using epithelial cell lines as well as a murine model of acute otitis media (OM). Human cytokine macroarray analysis was performed to detect the released cytokines in response to NTHi exposure. Real time quantitative PCR was done to compare the induction of IL-1 alpha or beta-defensin 2 mRNAs and to identify the signaling pathways involved. Direct activation of the beta-defensin 2 promoter was monitored using a beta-defensin 2 promoter-Luciferase construct. An IL-1 alpha blocking antibody was used to demonstrate the direct involvement of this cytokine on DEFB4 induction. RESULTS: Middle ear epithelial cells released IL-1 alpha when stimulated by NTHi components and this cytokine acted in an autocrine/paracrine synergistic manner with NTHi to up-regulate beta-defensin 2. This synergistic effect of IL-1 alpha on NTHi-induced beta-defensin 2 up-regulation appeared to be mediated by the p38 MAP kinase pathway. CONCLUSION: We demonstrate that IL-1 alpha is secreted by middle ear epithelial cells upon exposure to NTHi components and that it can synergistically act with certain of these molecules to up-regulate beta-defensin 2 via the p38 MAP kinase pathway.

Multilevel generalized linear models for modelling age-related gender difference in violent behaviour and associated factors in the general household population.

It is preferable to use longitudinal data when studying patterns of violence and antisocial behaviour over the lifespan together with the associated risk factors in the general population. From the statistical modelling perspective, random samples of cross-sectional data, representative of the population, can be a reliable alternative. Sampling, weighting, and possible geographical clustering of the behaviour must be considered in the analysis together with correct choice of model as a function of age, although cohort effects and age effects are not separated from the analysis. This paper demonstrates the use of multilevel generalized linear models in the British National Survey of Psychiatric Morbidity in 2000. A multilevel logistic model as a special case of a generalized linear model with individual weightings was adapted for a dichotomous measure of violence and extended to Poisson and negative binomial outcomes. Three types of age function, discrete age effects, continuous age effects, and piecewise polynomial function of age intervals were evaluated for goodness of fit, and for their practical advantages and disadvantages. Models were developed for possible risk factors in relation to specific age groups of interest.

Overexpression of the NF2 gene inhibits schwannoma cell proliferation through promoting PDGFR degradation.

The loss of NF2 gene function leads to vestibular nerve schwannoma formation in humans. The NF2 gene product, Merlin/Schwannomin, has recently been found to interact with the two PDZ domains containing protein EBP50/NHE-RF, which is itself known to interact with the PDGF receptor (PDGFR) in several cell types. In this study, an up-regulation of both PDGFR and EBP50/NHE-RF, and an interaction of both proteins were found in primary human schwannoma tissue. Furthermore, using an adenoviral vector mediated gene transfer technique, changes in the phenotypic characteristics after NF2 gene restoration in a newly established NF2 gene-mutated human schwannoma cell line (HEI 193) were investigated. The overexpression of Merlin/Schwannomin in HEI 193 led to an inhibition of cell proliferation under serum-free conditions. Upon PDGF stimulation in culture, Merlin/Schwannomin appeared to inhibit the activation of the MAPK and PI3K signaling pathways, impinging on the phosphorylation of Erk 1/2 and Akt, respectively. The data also show that PDGFR is more rapidly internalized by the schwannoma cells overexpressing NF2. Therefore, this process is suggested as a model for a mechanism of Merlin/Schwannomin tumor suppressor function, which intermediates acceleration of the cell surface growth factor degradation.