Widespread kidney anomalies in children with Down syndrome.

BACKGROUND: Rare autopsy studies have described smaller kidneys as well as urinary tract anomalies in Down syndrome. This observation has never been investigated in vivo and little is known about the possible consequences upon kidney function. Here we wish to confirm whether children with Down syndrome have smaller kidneys and to evaluate their kidney function in vivo. METHODS: This retrospective cohort study enrolled 49 children with Down syndrome, as well as 49 age- and sex-matched controls at the Queen Fabiola Children's University Hospital in Brussels, Belgium. Doppler and kidney ultrasonography, spot urine albumin to creatinine ratio, estimated glomerular filtration rate (eGFR), and anthropometric data were recorded. RESULTS: Kidney size in children with Down syndrome was smaller than age- and sex-matched controls in terms of length (p < 0.001) and volume (p < 0.001). Kidney function based on eGFR was also decreased in Down syndrome compared to historical normal. Twenty-one of the children with Down syndrome (42%) had eGFR < 90 mL/min/1.73 m2, with 5 of these (10%) having an eGFR < 75 mL/min/1.73 m2. In addition, 7 of the children with Down syndrome (14%) had anomalies of the kidney and/or urinary tract that had previously been undiagnosed. CONCLUSIONS: Children with Down syndrome have significantly smaller kidneys than age-matched controls as well as evidence of decreased kidney function. These findings, in addition to well-noted increased kidney and urologic anomalies, highlight the need for universal anatomical and functional assessment of all individuals with Down syndrome. A higher resolution version of the Graphical abstract is available as Supplementary information.

Progressive Control of Streptococcus agalactiae-Induced Innate Inflammatory Response Is Associated with Time Course Expression of MicroRNA-223 by Neutrophils.

Group B streptococcus (GBS) is a human-pathogenic bacterium inducing a strong inflammatory response that may be detrimental for host tissues if not finely regulated. The inflammatory response can be modulated by different molecular mechanisms, among which growing evidence points toward the crucial role of microRNAs (miRNAs). Regarding innate inflammatory response, studies have reported that miR-223 is essential for the control of granulocyte proliferation and activation. Moreover, a number of investigations on miRNA expression profiling performed in various inflammatory settings have revealed that miR-223 is among the top differentially expressed miRNAs. Yet the dynamic pattern of expression of miR-223 in vivo with respect to the evolution of the inflammatory process, especially in microbial infection, remains elusive. In this study, we analyzed the kinetic expression of miR-223 in an inflammatory model of GBS-induced murine pneumonia and looked for correlates with inflammatory markers, including innate cell infiltrates. We found that miR-223 expression is rapidly induced at very early time points (3 to 6 h postinfection [p.i.]) mainly by lung-infiltrating neutrophils. Interestingly, the level of miR-223 accumulating in the lungs remains higher at later stages of infection (24 h and 48 h p.i.), and this correlates with reduced expression of primary inflammatory cytokines and chemokines and with a shift in infiltrating monocyte and macrophage subtypes toward a regulatory phenotype. Transient inhibition of miR-223 by an antagomir resulted in significant increase of CXCL2 expression and partial enhancement of infiltrating neutrophils in GBS-infected lung tissues. This suggests the potential contribution of miR-223 to the resolution phase of GBS-induced acute inflammation.

FGFR1 mutations cause Hartsfield syndrome, the unique association of holoprosencephaly and ectrodactyly.

BACKGROUND: Harstfield syndrome is the rare and unique association of holoprosencephaly (HPE) and ectrodactyly, with or without cleft lip and palate, and variable additional features. All the reported cases occurred sporadically. Although several causal genes of HPE and ectrodactyly have been identified, the genetic cause of Hartsfield syndrome remains unknown. We hypothesised that a single key developmental gene may underlie the co-occurrence of HPE and ectrodactyly. METHODS: We used whole exome sequencing in four isolated cases including one case-parents trio, and direct Sanger sequencing of three additional cases, to investigate the causative variants in Hartsfield syndrome. RESULTS: We identified a novel FGFR1 mutation in six out of seven patients. Affected residues are highly conserved and are located in the extracellular binding domain of the receptor (two homozygous mutations) or the intracellular tyrosine kinase domain (four heterozygous de novo variants). Strikingly, among the six novel mutations, three are located in close proximity to the ATP's phosphates or the coordinating magnesium, with one position required for kinase activity, and three are adjacent to known mutations involved in Kallmann syndrome plus other developmental anomalies. CONCLUSIONS: Dominant or recessive FGFR1 mutations are responsible for Hartsfield syndrome, consistent with the known roles of FGFR1 in vertebrate ontogeny and conditional Fgfr1-deficient mice. Our study shows that, in humans, lack of accurate FGFR1 activation can disrupt both brain and hand/foot midline development, and that FGFR1 loss-of-function mutations are responsible for a wider spectrum of clinical anomalies than previously thought, ranging in severity from seemingly isolated hypogonadotropic hypogonadism, through Kallmann syndrome with or without additional features, to Hartsfield syndrome at its most severe end.

Sex-related immunity: could Toll-like receptors be the answer in acute inflammatory response?

An increasing number of studies have highlighted the existence of a sex-specific immune response, wherein men experience a worse prognosis in cases of acute inflammatory diseases. Initially, this sex-dependent inflammatory response was attributed to the influence of sex hormones. However, a growing body of evidence has shifted the focus toward the influence of chromosomes rather than sex hormones in shaping these inflammatory sex disparities. Notably, certain pattern recognition receptors, such as Toll-like receptors (TLRs), and their associated immune pathways have been implicated in driving the sex-specific immune response. These receptors are encoded by genes located on the X chromosome. TLRs are pivotal components of the innate immune system, playing crucial roles in responding to infectious diseases, including bacterial and viral pathogens, as well as trauma-related conditions. Importantly, the TLR-mediated inflammatory responses, as indicated by the production of specific proteins and cytokines, exhibit discernible sex-dependent patterns. In this review, we delve into the subject of sex bias in TLR activation and explore its clinical implications relatively to both the X chromosome and the hormonal environment. The overarching objective is to enhance our understanding of the fundamental mechanisms underlying these sex differences.

Sex-biased expression of selected chromosome x-linked microRNAs with potent regulatory effect on the inflammatory response in children with cystic fibrosis: A preliminary pilot investigation.

Previous studies have reported sex disparity in cystic fibrosis (CF) disease, with females experiencing more pulmonary exacerbations and frequent microbial infections resulting in shorter survival expectancy. This concerns both pubertal and prepubertal females, which is in support to the prominent role of gene dosage rather than the hormonal status. The underlying mechanisms are still poorly understood. The X chromosome codes for a large number of micro-RNAs (miRNAs) that play a crucial role in the post-transcriptional regulation of several genes involved in various biological processes, including inflammation. However, their level of expression in CF males and females has not been sufficiently explored. In this study, we compared in male and female CF patients the expression of selected X-linked miRNAs involved in inflammatory processes. Cytokine and chemokine profiles were also evaluated at both protein and transcript levels and cross-analyzed with the miRNA expression levels. We observed increased expression of miR-223-3p, miR-106a-5p, miR-221-3p and miR-502-5p in CF patients compared to healthy controls. Interestingly, the overexpression of miR-221-3p was found to be significantly higher in CF girls than in CF boys and this correlates positively with IL-1ß. Moreover, we found a trend toward lower expression in CF girls than in CF boys of suppressor of cytokine signaling 1 (SOCS1) and the ubiquitin-editing enzyme PDLIM2, two mRNA targets of miR-221-3p that are known to inhibit the NF-κB pathway. Collectively, this clinical study highlights a sex-bias in X-linked miR-221-3p expression in blood cells and its potential contribution to sustaining a higher inflammatory response in CF girls.

Hereditary Tyrosinemia Type 1 Mice under Continuous Nitisinone Treatment Display Remnants of an Uncorrected Liver Disease Phenotype.

Hereditary tyrosinemia type 1 (HT1) is a genetic disorder of the tyrosine degradation pathway (TIMD) with unmet therapeutic needs. HT1 patients are unable to fully break down the amino acid tyrosine due to a deficient fumarylacetoacetate hydrolase (FAH) enzyme and, therefore, accumulate toxic tyrosine intermediates. If left untreated, they experience hepatic failure with comorbidities involving the renal and neurological system and the development of hepatocellular carcinoma (HCC). Nitisinone (NTBC), a potent inhibitor of the 4-hydroxyphenylpyruvate dioxygenase (HPD) enzyme, rescues HT1 patients from severe illness and death. However, despite its demonstrated benefits, HT1 patients under continuous NTBC therapy are at risk to develop HCC and adverse reactions in the eye, blood and lymphatic system, the mechanism of which is poorly understood. Moreover, NTBC does not restore the enzymatic defects inflicted by the disease nor does it cure HT1. Here, the changes in molecular pathways associated to the development and progression of HT1-driven liver disease that remains uncorrected under NTBC therapy were investigated using whole transcriptome analyses on the livers of Fah- and Hgd-deficient mice under continuous NTBC therapy and after seven days of NTBC therapy discontinuation. Alkaptonuria (AKU) was used as a tyrosine-inherited metabolic disorder reference disease with non-hepatic manifestations. The differentially expressed genes were enriched in toxicological gene classes related to liver disease, liver damage, liver regeneration and liver cancer, in particular HCC. Most importantly, a set of 25 genes related to liver disease and HCC development was identified that was differentially regulated in HT1 vs. AKU mouse livers under NTBC therapy. Some of those were further modulated upon NTBC therapy discontinuation in HT1 but not in AKU livers. Altogether, our data indicate that NTBC therapy does not completely resolves HT1-driven liver disease and supports the sustained risk to develop HCC over time as different HCC markers, including Moxd1, Saa, Mt, Dbp and Cxcl1, were significantly increased under NTBC.

A medication adherence-enhancing simulation intervention in pediatric cystic fibrosis.

Adherence to chronic pulmonary drugs in cystic fibrosis (CF) is suboptimal. We studied the feasibility and effectiveness of a multistep medication adherence-enhancing simulation intervention for pediatric CF, which was embedded in motivational interviewing and education. Product simulation experiments were performed by the children themselves, and they addressed adherence to mucolytics/hydrators and antibiotics. Dornase alfa-treated patients aged 7-13 years were included. We invited each patient and their parents to attend an interview. PowerPoint slides were presented and discussed. The final slide invited the patient to perform the simulation experiments, and, in so doing, they experienced what happens when they either do or do not take their medication. An educational film was applied as a summary tool. A patient-centered empathic counseling style was used. Two months later, the child and their parents each completed a different anonymous questionnaire. Overall, 21 patients were included. Parents rated the means of communication and improvement in their child's motivation as very satisfactory. Children highly appreciated the experiments they performed. They often answered two questions on dornase alfa correctly and associated knowledge with adherence. Our results suggest that experiential simulation-based learning is extremely appropriate, and that this multistep intervention is feasible and effective in pediatric CF.

Sex difference in innate inflammatory response and macrophage polarization in Streptococcus agalactiae-induced pneumonia and potential role of microRNA-223-3p.

While number of studies have shown that biological sex is a risk factor in the incidence and severity of infection-induced inflammatory diseases, the underlying mechanisms are still poorly understood. In this study, we compared the innate inflammatory response in male and female mice with group B streptococcal (GBS)-induced pneumoniae. Although male and female mice displayed similar bacterial burdens, males exhibited more innate inflammatory cytokines and chemokines and a higher proportion of infiltrating monocytes/macrophages. The analysis of the distribution of macrophage subtypes M1 (pro-inflammatory) versus M2 (anti-inflammatory) yielded a higher M1/M2 ratio in infected males compared with females. Given the importance of the chromosome X-linked microRNA-223-3p (miR-223-3p) in modulating the inflammatory process and macrophage polarization, we investigated its potential contribution in sex bias of GBS-induced innate inflammatory response. Knock-down of miR-223-3p with specific antagomiR resulted in increased inflammatory response and higher M1/M2 ratio following GBS infection. Notably, compared to male mice, we detected higher amount of miR-223-3p in macrophages from females that correlated negatively with M1 phenotype. These results suggest that differential expression of miR-233-3p may impact macrophage polarization, thereby contributing to fine-tune sex differences in inflammatory response.

Ataluren (PTC124) induces cystic fibrosis transmembrane conductance regulator protein expression and activity in children with nonsense mutation cystic fibrosis.

RATIONALE: Nonsense (premature stop codon) mutations in mRNA for the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF) in approximately 10% of patients. Ataluren (PTC124) is an oral drug that permits ribosomes to readthrough premature stop codons in mRNA to produce functional protein. OBJECTIVES: To evaluate ataluren activity, safety, and pharmacokinetics in children with nonsense mutation CF. METHODS: Patients were assessed in two 28-day cycles, comprising 14 days on and 14 days off ataluren. Patients took ataluren three times per day (morning, midday, and evening) with randomization to the order of receiving a lower dose (4, 4, and 8 mg/kg) and a higher dose (10, 10, and 20 mg/kg) in the two cycles. MEASUREMENTS AND MAIN RESULTS: The study enrolled 30 patients (16 male and 14 female, ages 6 through 18 yr) with a nonsense mutation in at least one allele of the CFTR gene, a classical CF phenotype, and abnormal baseline nasal epithelial chloride transport. Ataluren induced a nasal chloride transport response (at least a -5-mV improvement) or hyperpolarization (value more electrically negative than -5 mV) in 50% and 47% of patients, respectively, with more hyperpolarizations at the higher dose. Improvements were seen in seven of nine nonsense mutation genotypes represented. Ataluren significantly increased the proportion of nasal epithelial cells expressing apical full-length CFTR protein. Adverse events and laboratory abnormalities were infrequent and usually mild. Ataluren pharmacokinetics were similar to those in adults. CONCLUSIONS: In children with nonsense mutation CF, ataluren can induce functional CFTR production and is well tolerated.

CFTR Protein: Not Just a Chloride Channel?

Cystic fibrosis (CF) is a recessive genetic disease caused by mutations in a gene encoding a protein called Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). The CFTR protein is known to acts as a chloride (Cl-) channel expressed in the exocrine glands of several body systems where it also regulates other ion channels, including the epithelial sodium (Na+) channel (ENaC) that plays a key role in salt absorption. This function is crucial to the osmotic balance of the mucus and its viscosity. However, the pathophysiology of CF is more challenging than a mere dysregulation of epithelial ion transport, mainly resulting in impaired mucociliary clearance (MCC) with consecutive bronchiectasis and in exocrine pancreatic insufficiency. This review shows that the CFTR protein is not just a chloride channel. For a long time, research in CF has focused on abnormal Cl- and Na+ transport. Yet, the CFTR protein also regulates numerous other pathways, such as the transport of HCO3-, glutathione and thiocyanate, immune cells, and the metabolism of lipids. It influences the pH homeostasis of airway surface liquid and thus the MCC as well as innate immunity leading to chronic infection and inflammation, all of which are considered as key pathophysiological characteristics of CF.

Immunoglobulin G: A useful outcome marker in the follow-up of cystic fibrosis patients?

BACKGROUND AND METHODS: Hypergammaglobulinemia (hyper-IgG) and hypogammaglobulinemia (hypo-IgG) have been reported in patients with cystic fibrosis (CF). Although the clinical respiratory course is paradoxically different, depending on the IgG status, this association remains elusive. Therefore, we performed a longitudinal study to assess the annual evolution of IgG profiles in a cohort of pediatric patients with CF, from their diagnosis until 2016. We then compared clinical findings with the patients' IgG status to determine whether IgG status could reflect the respiratory clinical course of patients with CF. RESULTS: Among the 66 patients with CF that were aged between 12 months and 18 years in 2016 (mean age: 9.3 years [SD: 5.2]), hypo-IgG was observed in 15.2% and no hyper-IgG was identified. Longitudinal assessment since diagnosis revealed no hyper-IgG but 33.3% of patients had at least one sample showing hypo-IgG, among which two patients displayed persistent hypo-IgG. The number of pulmonary exacerbations, duration of antibiotic therapy, and erythrocyte sedimentation rate were all lower in hypo-IgG patients. No difference was observed for the genotype, chronic Pseudomonas aeruginosa or Staphylococcus aureus infection, and in the parameters of lung function. CONCLUSION: The IgG profile of pediatric patients with CF has changed over recent decades, particularly with regard to hyper-IgG. In a significant portion of the pediatric CF population, hypo-IgG is transient and only identifiable in longitudinal assessments. This study reinforces that hypo-IgG patients paradoxically present a more favorable course of clinical status. Therefore, IgG levels could be a useful outcome marker in the follow-up of patients with CF.

Comparison of culture and qPCR for the detection of Pseudomonas aeruginosa in not chronically infected cystic fibrosis patients.

BACKGROUND: Pseudomonas aeruginosa is the major respiratory pathogen causing severe lung infections among CF patients, leading to high morbidity and mortality. Once infection is established, early antibiotic treatment is able to postpone the transition to chronic lung infection. In order to optimize the early detection, we compared the sensitivity of microbiological culture and quantitative PCR (qPCR) for the detection of P. aeruginosa in respiratory samples of not chronically infected CF patients. RESULTS: In this national study, we followed CF patients during periods between 1 to 15 months. For a total of 852 samples, 729 (86%) remained P. aeruginosa negative by both culture and qPCR, whereas 89 samples (10%) were positive by both culture and qPCR.Twenty-six samples were negative by culture but positive by qPCR, and 10 samples were positive by culture but remained negative by qPCR. Five of the 26 patients with a culture negative, qPCR positive sample became later P. aeruginosa positive both by culture and qPCR. CONCLUSION: Based on the results of this study, it can be concluded that qPCR may have a predictive value for impending P. aeruginosa infection for only a limited number of patients.

Effect of systemic inflammation on inspiratory and limb muscle strength and bulk in cystic fibrosis.

RATIONALE: Diaphragm thickness is increased in cystic fibrosis (CF), but it shows a marked variability between patients. The variable response of the diaphragm to loading may reflect the combined and opposite effects of training by the respiratory disease and systemic inflammation. OBJECTIVES: To assess the impact of systemic inflammation on diaphragm and limb muscle strength and bulk in adult patients with CF. METHODS: In 38 stable patients with CF and 20 matched control subjects, we measured fat-free mass (FFM), inspiratory muscle strength, diaphragm thickness, quadriceps and biceps strength and cross-sectional area, and circulating levels of leukocytes, C-reactive protein, IL-6, IL-8, IL-17, tumor necrosis factor-alpha, tumor necrosis factor-alpha soluble receptors, and immunoglobulin G. MEASUREMENTS AND MAIN RESULTS: Patients had increases in several inflammatory markers that correlated with the severity of lung disease and nutritional depletion. Compared with control subjects, patients with CF had increased diaphragm thickness and inspiratory muscle strength and showed a trend toward a reduction in limb muscle strength and bulk. Multiple regression analyses identified FFM and airway resistance as independent predictors of diaphragm thickness, but systemic inflammation had no (or only a minor) predictive effect on FFM, inspiratory muscle strength, diaphragm thickness, and limb muscle strength and bulk. CONCLUSIONS: In patients with CF, the intensity of systemic inflammation does not account significantly for the variance of FFM and diaphragm or limb muscle strength and bulk. Training of the diaphragm in CF occurs despite the presence of systemic inflammation.

Illustration of tessellation in Down syndrome.

Background: Tessellated fundus refers to a specific change in the appearance of the internal layers of the eye in which the choroidal large vessels became visible through polygonal hypopigmented areas. Such hypopigmented areas alternate with hyperpigmented zones in a tigroid pattern. Fundus tessellation is often associated with myopia and choroidal thinning.Materials and Methods: We analyzed fundus images from 50 children with Down syndrome and 52 controls.Results: Tessellation was present in 64% of children with Down syndrome, compared with only 13.5% of controls (p < .0001). In most cases, tessellation was located peripapillary, and no difference was observed in tessellation localization between children with Down syndrome and controls (p = .60). Although more prevalent in myopic children with and without Down syndrome, tessellation was present in almost half (48%) of children with Down syndrome with hyperopia versus only 5% of controls with the same refractive status.Conclusions: Mechanical stretching of the choroid could explain the high rate of tessellation in myopes. Other factors must contribute to the higher prevalence of tessellated fundus in children with Down syndrome without myopia. We discuss potentially relevant factors and propose vascular involvement as a contributor to tessellation in our population with Down syndrome. Further studies assessing choroidal vasculature in individuals with Down syndrome are needed to confirm this theory.

Oxidative Stress, Glutathione Metabolism, and Liver Regeneration Pathways Are Activated in Hereditary Tyrosinemia Type 1 Mice upon Short-Term Nitisinone Discontinuation.

Hereditary tyrosinemia type 1 (HT1) is an inherited condition in which the body is unable to break down the amino acid tyrosine due to mutations in the fumarylacetoacetate hydrolase (FAH) gene, coding for the final enzyme of the tyrosine degradation pathway. As a consequence, HT1 patients accumulate toxic tyrosine derivatives causing severe liver damage. Since its introduction, the drug nitisinone (NTBC) has offered a life-saving treatment that inhibits the upstream enzyme 4-hydroxyphenylpyruvate dioxygenase (HPD), thereby preventing production of downstream toxic metabolites. However, HT1 patients under NTBC therapy remain unable to degrade tyrosine. To control the disease and side-effects of the drug, HT1 patients need to take NTBC as an adjunct to a lifelong tyrosine and phenylalanine restricted diet. As a consequence of this strict therapeutic regime, drug compliance issues can arise with significant influence on patient health. In this study, we investigated the molecular impact of short-term NTBC therapy discontinuation on liver tissue of Fah-deficient mice. We found that after seven days of NTBC withdrawal, molecular pathways related to oxidative stress, glutathione metabolism, and liver regeneration were mostly affected. More specifically, NRF2-mediated oxidative stress response and several toxicological gene classes related to reactive oxygen species metabolism were significantly modulated. We observed that the expression of several key glutathione metabolism related genes including Slc7a11 and Ggt1 was highly increased after short-term NTBC therapy deprivation. This stress response was associated with the transcriptional activation of several markers of liver progenitor cells including Atf3, Cyr61, Ddr1, Epcam, Elovl7, and Glis3, indicating a concreted activation of liver regeneration early after NTBC withdrawal.

Cancer worry and insomnia complaints among American women.

One-third of women worrying about breast cancer report impaired ability to function daily. It is unclear whether women who worry about breast cancer would experience more sleep problems than those who do not. Data were obtained from a cross-sectional study of black and white women to investigate the association between breast cancer worry and insomnia complaints. Several questionnaires were administered during face-to-face interviews to elicit health and sociodemographic data. The present analyses focused on black and white women (n = 1,038; age range = 50-70 years) with no cancer antecedents or history. Overall, 62% of the women worried about breast cancer, and 49% reported insomnia complaints. Logistic regression analyses, adjusting for effects of age, ethnicity, family history, and perceived risk of developing breast cancer, yielded an odds ratio for insomnia complaints of 1.52 (95% CI: 1.15-2.02, p < .001) among women reporting breast cancer worry. More than one half of the women worrying about breast cancer were likely to report insomnia complaints, notwithstanding the fact that those women did not have a history of cancer. Although fewer black women reported breast cancer worry and insomnia complaints, they were as affected as white women by the impact of worry on mood and daily activities.

Why Children's Hospitals Are Unique and So Essential.

Children's hospitals were created in the nineteenth century, first in France and then in England. They were designed to provide optimal care to infants, children, and adolescents in a specific environment where parents were admitted and where the special needs of children were catered for. No other system currently offers so many advantages as the multidisciplinary teams with their pediatricians, surgeons, anesthetists, intensive care specialists, and all the allied health professionals who can add their knowledge to the quality of care. From the beginning, they played a major role in caring for socially disadvantaged children. They brought together more than 95% of tertiary care, including cancer care and organ transplantations. They represent the best blend for the study of pediatric medicine and physiology, for high-level preventive medicine, and for research in all fields of pediatrics. This probably explains why they have developed everywhere around the world. This article explains the paramount importance of children's hospitals for providing safe and effective multidisciplinary pediatric care.

The Number of X Chromosomes Influences Inflammatory Cytokine Production Following Toll-Like Receptor Stimulation.

Sex differences are observed in the evolution of numerous inflammatory conditions. Women exhibit better clinical courses compared to men in acute inflammatory processes, yet worse prognosis in several chronic inflammatory diseases. Inflammatory markers are significantly different between prepubertal boys and girls, whose sex steroid levels are very low, suggesting genetics play a role. To evaluate the potential influence of the X chromosome, we studied cytokine production and protein phosphorylation following Toll-like receptor (TLR) activation in whole blood and purified neutrophils and monocytes of healthy adults of both sexes as well as subjects with Klinefelter syndrome. We recorded higher levels of inflammatory cytokines in men compared to both women and patients with Klinefelter syndrome following whole blood stimulation. In purified monocytes, production of inflammatory cytokines was also higher in men compared to women, while Klinefelter subjects expressed the same pattern of cytokine production as males, in contrast with whole blood analyses. These differences remained after adjusting for sex steroid levels. Our study revealed higher cytokine inflammatory responses in men than women, yet also compared to subjects with Klinefelter syndrome, who carry two copies of the X chromosome, like women, and thus potentially benefit from the cellular mosaicism of X-linked genes.

Insomnia symptoms in a multiethnic sample of American women.

BACKGROUND: Ethnic disparities in socioeconomic factors, risk markers, and coping styles affect health status. This study examined whether those factors influence insomnia symptoms in a multiethnic sample of urban American women. METHODS: Women (n = 1440, average age = 59.5 +/- 6.45 years) participating in the study were recruited using a stratified, cluster sampling technique. The sample comprises African Americans (22%), English-speaking Caribbeans (22%), Haitians (22%), Dominicans (12%), Eastern Europeans (11%), and European Americans (11%). Trained staff conducted face-to-face interviews lasting 1.5 hours acquiring demographic, health, and sleep data. RESULTS: Analysis indicated significant ethnic differences in socioeconomics, risk markers, and health characteristics. The prevalence of insomnia symptoms (defined as either difficulty initiating sleep, difficulty maintaining sleep, or early morning awakening) among African Americans was 71%, English-speaking Caribbeans 34%, Haitians 33%, Dominicans 73%, Eastern Europeans 77%, and European Americans 70%. Hierarchical regression results showed that ethnicity explained 20% of the variance in the insomnia variable. Sociodemographic factors explained 5% of the variance, risk markers explained 5%, medical factors 20%, and coping styles 1%. Goodness-of-fit test indicated the model was reliable [chi-square = 276, p < 0.001], explaining 51% of the variance. CONCLUSIONS: Findings show interethnic heterogeneity in insomnia symptoms, even among groups previously assumed to be homogeneous. Different factors seemingly influence rates of insomnia symptoms within each ethnic group examined. These findings have direct relevance in the management of sleep problems among women of different ethnic backgrounds. Understanding of ethnic/cultural factors affecting the sleep experience is important in interpreting subjective sleep data.

Racial differences in suicidality in an older urban population.

PURPOSE: This study used epidemiological data of older African Americans and Caucasians living in an urban community to compare those factors associated with active or passive suicidal ideation in each racial group. DESIGN AND METHODS: Using 1990 census data for Brooklyn, New York, we attempted to interview all cognitively intact adults aged 55 or older in randomly selected block groups. The sample consisted of 214 Whites and 860 Blacks. We adapted George's social antecedent model to examine 19 independent variables; the dependent variable was based on lifetime history of passive or active suicidal ideation (hereafter, suicidality). We weighted the sample by race and gender. To control for sampling design effects, we used SUDAAN for data analysis. RESULTS: Whites reported higher prevalence than Blacks for current suicidality (5.8% vs 2.3%) and lifetime suicidality (14.8% vs 10.2%). None of the differences were significant. In logistic regression analysis conducted for each race, four variables were associated with suicidality within both races: higher depressive symptom scores, higher anxiety symptom scores, copes by using medications, and lower religiosity. Two variables were associated with suicidality only among Whites: higher use of spiritualists and copes by keeping calm. One variable, greater use of doctors for mental health problems, was significant only among Blacks. IMPLICATIONS: There were no racial differences in the prevalence of suicidality. Virtually all of the factors associated with suicidality are potentially ameliorable. Among both racial groups, suicidality is likely to be impacted by addressing depressive and anxiety symptoms and, when appropriate, by encouraging various coping strategies, especially religiosity.