Age-matched Case-control Study Research Articles

CD4+ T cell surface alpha enolase is lower in older adults

To identify novel cell ageing markers in order to gain insight into ageing mechanisms, we adopted membrane enrichment and comparison of the CD4+ T cell membrane proteome (purified by cell surface labelling using Sulfo-NHS-SS-Biotin reagent) between healthy young (n=9, 20–25 years) and older (n=10; 50–70 years) male adults. Following two-dimensional gel electrophoresis (2DE) to separate pooled membrane proteins in triplicates, the identity of protein spots with age-dependent differences (p<0.05 and >1.4 fold difference) was determined using liquid chromatography–mass spectrometry (LC–MS/MS). Seventeen protein spot density differences (ten increased and seven decreased in the older adult group) were observed between young and older adults. From spot intensity analysis, CD4+ T cell surface α-enolase was decreased in expression by 1.5 fold in the older age group; this was verified by flow cytometry (n=22) and qPCR with significantly lower expression of cellular α-enolase mRNA and protein compared to young adult CD4+ T cells (p<0.05). In an independent age-matched case-control study, lower CD4+ T cell surface α-enolase expression was observed in age-matched patients with cardiovascular disease (p<0.05). An immune-modulatory role has been proposed for surface α-enolase and our findings of decreased expression suggest that deficits in surface α-enolase merit investigation in the context of immune dysfunction during ageing and vascular disease.

Association of Wilms' tumor 1 gene single-nucleotide polymorphism rs16754 with colorectal cancer.

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Our recent study demonstrated that the expression of Wilms' tumor 1 gene (WT1) is associated with surgical outcome in CRC patients. The present study aimed to investigate the genetic association of the single-nucleotide polymorphism rs16754 in the WT1 gene with the occurrence of CRC, using an age-matched case-control study design. In addition, the correlation between genotype and WT1 expression was investigated. Genomic DNA samples from 104 CRC cases, aged 15-65 years, and 208 healthy controls, were genotyped for rs16754 using the TaqMan genotyping method. The genotype distribution conformed to the Hardy-Weinberg equilibrium (P=0.80). The overall minor allele frequency (MAF) of rs16754 (allele A) was 0.33. The MAF among CRC cases was significantly higher compared with that in controls (0.39 vs. 0.31, respectively; P=0.03). The AA genotype was significantly associated with the disease (odds ratio = 2.51, 95% confidence interval: 1.24-5.07, P=0.01). Cases with the AA genotype exhibited a significantly poorer 3-year overall survival (60%), compared with those with the GG or GA genotypes (80%) (log-rank test, P<0.01). Reverse transcription quantitative polymerase chain reaction analysis demonstrated that the expression of WT1 in tumor tissues was higher compared with that in normal tissue; however, there were no significant differences in its expression among different genotypes. Therefore, rs16754 was found to be associated with the occurrence and prognosis of CRC in our subjects.

Factors Associated with Non-typhoidal Salmonella Bacteremia versus Typhoidal Salmonella Bacteremia in Patients Presenting for Care in an Urban Diarrheal Disease Hospital in Bangladesh.

BackgroundNon-typhoidal Salmonella (NTS) and Salmonella enterica serovar Typhi bacteremia are the causes of significant morbidity and mortality worldwide. There is a paucity of data regarding NTS bacteremia in South Asia, a region with a high incidence of typhoidal bacteremia. We sought to determine clinical predictors and outcomes associated with NTS bacteremia compared with typhoidal bacteremia.MethodologyWe performed a retrospective age-matched case-control study of patients admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, between February 2009 and March 2013. We compared demographic, clinical, microbiological, and outcome variables of NTS bacteremic patients with age-matched S. Typhi bacteremic patients, and a separate comparison of patients with NTS bacteremia and patients with NTS gastroenteritis.Principal FindingsOf 20 patients with NTS bacteremia, 5 died (25% case fatality), compared to none of 60 age-matched cases of S. Typhi bacteremia. In univariate analysis, we found that compared with S. Typhi bacteremia, cases of NTS bacteremia had more severe acute malnutrition (SAM) in children under five years of age, less often presented with a duration of fever ≥ 5 days, and were more likely to have co-morbidities on admission such as pneumonia and clinical signs of sepsis (p<0.05 in all cases). In multivariable logistic regression, SAM, clinical sepsis, and pneumonia were independent risk factors for NTS bacteremia compared with S. Typhi bacteremia (p<0.05 in all cases). Notably, we found marked differences in antibiotic susceptibilities, including NTS strains resistant to antibiotics commonly used for empiric therapy of patients suspected to have typhoid fever.Conclusions/SignificanceDiarrheal patients with NTS bacteremia more often presented with co-morbidities and had a higher case fatality rate compared to those with typhoidal bacteremia. Clinicians in regions where both typhoid and NTS bacteremia are prevalent need to be vigilant about the possibility of both entities, especially given notable differences in antibiotic susceptibility patterns.

Abstract 2364: CD68+ immune cells show different infiltration patterns in tissue samples from women with no clinical breast disease and those who have benign breast disease

Abstract Introduction: The role of macrophages in the tumor microenvironment is of increasing interest for tumor progression and invasion. Here we investigated the difference in CD68+ cell density in tissue samples from women with Benign Breast Disease (BBD) and women with no clinical breast disease from the Komen Tissue Bank (KTB) at Indiana University. Method: Archived breast tissue samples from women with BBD and no clinical breast disease were obtained for this age-matched case-control study. BBD samples included cases [later got Breast Cancer (BC)] and controls (did not get BC). Samples were characterized via H&amp;E stain for epithelial proliferation [normal (N), fibrocystic non-proliferative (NP), proliferative (P), or atypia (A)]. CD68+ cell density was obtained by digital image quantitation on a per lobule basis (Total CD68+ cells/mm2). Statistical analysis was performed with mixed effects regression. Results: Among 276 women (median age 53, range 35-79) comprising 92 age-matched triplets, 2508 lobules were evaluated [789 KTB, 839 BBD case, 880 BBD control]. 1407 (56%) lobules were normal and 1101 (44%) were fibrocystic {NP [613 (56%)], P [448 (41%)] and A [40 (4%)]}. Out of 2508 lobules analyzed, 2362 (94%) had CD68+ cells, while 146 (6%) showed zero CD68+ cells [19 (2%) BBD cases, 20 (2%) BBD controls, 107 (14%) KTB, p&amp;lt;0.0001]. KTB samples showed significantly lower (p&amp;lt;0.0001) CD68+ density (median 136 cells/mm2) as compared to BBD cases (median 313 cells/mm2) and BBD controls (median 299 cells/mm2). (See Table) For each lobule type, KTB samples had lower CD68+ density compared with the same lobule type in BBD samples (p&amp;lt;0.0001). Conclusion: CD68+ cells are more frequent in breast lobules from women with BBD compared to normal donors. This finding in premalignant breast tissues is consistent with inflammation as a driver of tumorigenesis. BBD case (n = 92 patients)BBD control (n = 92 patients)KTB(n = 92 patients)n lobulesMedian (IQR)n lobulesMedian (IQR)n lobulesMedian (IQR)Overall839313 (165 - 538)880299 (164 - 527)789136 (55 - 272)By Lobule TypeNormal344310 (177 - 557)434331 (177 - 567)629128 (55 - 255)All non-normal/fibrocystic lobules combined495314 (157 - 527)446274 (152 - 478)160159 (58 - 393)Fibrocystic non-proliferative231319 (153 - 543)263274 (140 - 496)119163 (71 - 359)Fibrocystic proliferative246295 (153 - 496)169277 (153 - 478)33128 (30 - 385)Atypia18484 (313 - 739)14260 (223 - 375)8216 (0 - 493)IQR - Interquartile range (25th percentile - 75th percentile) Citation Format: Muhammad A. Arshad, Daniel W. Visscher, Tanya L. Hoskin, Rushin D. Brahmbhatt, Alvaro Pena Jimenez, Melody L. Stallings Mann, Erin E. Miller, Linda M. Murphy, Jodi M. Carter, Stacey J. Winham, Keith L. Knutson, Derek C. Radisky, Amy C. Degnim. CD68+ immune cells show different infiltration patterns in tissue samples from women with no clinical breast disease and those who have benign breast disease. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2364. doi:10.1158/1538-7445.AM2015-2364

Association of Polymorphism of Neuronal Nitric Oxide Synthase Gene with Risk to Parkinson's Disease.

Environmental factors are implicated in aging as well as genetic predisposition-induced Parkinson's disease (PD) pathogenesis. Wrongdoers increase oxidative stress and nitrosative burden, which eventually degenerate the nigrostriatal dopaminergic neurons. Inhibition of the expression of nitric oxide synthase (NOS), an enzyme responsible for nitric oxide (NO) biosynthesis, prevents the demise of the nigrostriatal dopaminergic neurons. Polymorphism of NOS is thus expected to alter PD susceptibility. The study therefore aimed to examine an association of neuronal NOS (nNOS) gene polymorphism with nitrite, an indicator of nitrosative load; lipid peroxidation, an index of oxidative stress and PD susceptibility. An age-matched case-control study was performed in the north Indian residents enrolled at the Neurology Department of the King George's Medical University, Lucknow, India. While nNOS exon 29 TT variant genotype [odds ratio (OR) = 2.20, 95% CI = 1.08-5.34, P = 0.040], combined TT and CT variants [OR = 1.68, 95% CI = 1.05-2.69, P = 0.031] and T allele [OR = 1.58, 95% CI = 1.10-2.28, P = 0.014] were found to be significantly associated with PD susceptibility, no association between nNOS exon 18 [OR for TT carriers = 1.97, 95% CI = 0.89-4.20, P = 0.09 and OR for T allele = 1.35, 95% CI = 0.94-1.93, P = 0.098] and PD risk was observed. Lipid peroxidation was augmented in all patients irrespective of their genotype. While genotype independent increase in nitrite content was observed in PD patients of exon 29 polymorphic groups, only heterozygous variant genotype of exon 18 was associated with augmentation in nitrite level as compared with respective control. The results obtained thus demonstrate that selected nNOS polymorphisms do not significantly contribute to PD risk in north Indian population.

Clinical epidemiological study of peri-conceptional multiple risk factors and congenital heart diseases

To evaluate the associations between the occurrence of congenital heart diseases (CHDs) in children and exposures to peri-conceptional multiple nongenetic risk factors. For this age-matched case-control study, standardized data were collected from 435 families of children with CHD and 574 families of non-malformed children. The questionnaires were conducted on multiple nongenetic risk factors including paternal characteristics and conditions, maternal therapeutic drug exposure, housing renovation, hair perming and dyeing and parental occupational exposure. The CHD infants weighed less than control group (P < 0.01). However two groups had no significant differences in age, height, parental age or heart rate. Educational levels of parents had a negative correlation with CHD. Conotruncal defect and simple ventricular septum defect were the most common cardiac abnormalities. Therapeutic drug exposure, viral infection and occupational exposure all had a high level of correlation with conotruncal defect (OR = 6.74, OR = 3.73, OR = 2.82 respectively). And ventricular septum defect was associated with therapeutic drug exposure, home decoration, hair perming and dyeing and parental exposure of work environment (OR = 2.77, OR = 1.76, OR = 1.89 respectively). Multiple nongenetic risk factors may contribute to the occurrence of CHD.

Pseudoexfoliation syndrome in chronic kidney disease patients

This study was performed to determine whether chronic kidney disease (CKD) is associated with an increased risk of pseudoexfoliation (PEX) syndrome. This is an age-matched case control study evaluating frequency of PEX in patients over age 40 with the diagnosis of stage 1–4 CKD and those undergoing hemodialysis (HD). Subjects over age 40 with hypertension and/or diabetes mellitus (DM) and normal kidney functions were studied as a control group. CKD was diagnosed as decreased glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m2 for at least 3 months. Study groups were arranged as group 1 consisting of HD receiving CKD patients, group 2 consisting of CKD patients who do not need HD and group 3 as a control. Demographic properties and the prevalence of PEX were evaluated and compared between groups. Because of the effect of DM on PEX occurrence, it was also evaluated after exclusion of diabetic patients. A total of 101 cases in group 1, 106 cases in group 2 and 117 cases in group 3 were included in the study. Pseudoexfoliation was found in 7 (6.9%) patients in group 1, 5 (4.7%) patients in group 2 and 7 (5.9%) patients in group 3 (p > 0.05). After exclusion of diabetic patients the prevalence of PEX changed as 4 (5.6%) in group 1, 2 (4.4%) in group 2 and 1 (1.8%) in group 3 (p > 0.05). In conclusion, CKD was not associated with increased prevalence of PEX in this study.

Do maternal interactive behaviors correlate with developmental outcomes and mastery motivation in toddlers with and without motor delay?

Maternal interactive behaviors theoretically affect developmental outcomes and mastery motivation in young children. However, these associations are inconsistent in the literature. The purposes of this study were: (1) to examine the differences in maternal behaviors between toddlers with motor delay (MD) and those with typical development (TD), (2) to investigate the correlation of maternal behaviors and developmental quotients (DQs) in toddlers with MD and TD, and (3) to examine the correlation of maternal behaviors and mastery motivation in toddlers with MD and TD. This was a sex- and mental age-matched case-control study. Twenty-two mother-child dyads of toddlers with MD (ages 23-47 months) and 22 dyads of sex- and mental age-matched toddlers with TD (ages 15-29 months) were recruited. Maternal scores from the Nursing Child Assessment Teaching Scale, 2 indicators of motivation (persistence and mastery pleasure) from individualized mastery tasks and the Dimensions of Mastery Questionnaire, and DQs from the Comprehensive Developmental Inventory for Infants and Children were assessed. Mothers of children in the MD group showed significantly lower cognitive growth fostering scores than mothers of children in the TD group. Maternal total scores were significantly correlated with whole DQs in both groups. In the MD group, maternal total scores correlated significantly with DMQ mastery pleasure but not with mastery task motivation. The study design makes it impossible to know the causal relationships between maternal behaviors and children's DQs and motivation. Mothers of toddlers with MD exhibited less adequate interactive behaviors than mothers of toddlers with TD. Because higher-quality maternal behaviors correlated with higher DQs in the MD group, clinicians should encourage parents to participate in early intervention programs and model high-quality parenting behavior to enhance parents' and children's outcomes.

Risk factors associated with rural and urban epidemics of leptospirosis in Tiruchirappalli District of Tamilnadu, India

The study sought to determine the risk factors involved in Leptospira infection in rural settings and the relative severity of the disease in comparison with the urban environment in Tiruchirappalli district, Tamil Nadu, India. During an upsurge of leptospirosis, 621 suspected blood samples were obtained from patients and screened by MAT and IgM ELISA. To set up an age-matched case control study, 1,230 seronegative control samples were also included in the study. The case-control analysis was carried out using unconditional logistic regression and all P-values were two-sided. From 621 suspected cases, 214 (74 %) from rural and 196 (59 %) from urban settings had a laboratory-confirmed diagnosis of leptospirosis. The highest antibody titres were identified against Leptospira interrogans serovar Canicola both in rural (35 %) and urban (38 %) settings. Increased infection risk was observed for cases in the age group of 20–40 years and 10–40 years in rural and urban settings respectively. In rural settings, the risk of leptospiral infection was found to be significantly (P < 0.0001) associated with people having cattle at their house and those involved in wet cultivation. Among urban cases, building workers and people living in house dwelling near water bodies were significantly (P < 0.0001) associated with leptospiral infection. The findings of the present study identified ideal niches for the transmission of leptospires in the rural and urban settings. Identification and understanding the potential risk factors in different environments would help to identify the source of contamination. This also identifies the need for more public health assistance.

Endothelial nitric oxide synthase gene polymorphisms and the risk of hypertension in an Indian population.

Genetic variants of eNOS gene play a significant role in the pathogenesis of hypertension. Many environmental factors have, also, been implicated in the aetiology of hypertension. We carried out an age-matched case-control study among adults. Hypertension was defined according to JNC-VII criteria and eNOS gene polymorphisms were determined by PCR and PCR followed by PCR-RFLP. eNOS intron 4 aa genotype (adjusted OR 6.81; 95% CI 2.29–20.25) and eNOS 894TT genotype (adjusted OR 7.84; 95% CI 2.57–23.96) were associated with the risk of hypertension. Tobacco users (either smoking/chewing or both) with eNOS intron 4 aa genotype (OR 14.00: 95% CI 1.20–163.37), eNOS 894GG genotype (OR 5.56: 95% CI 3.72–8.31), and eNOS T-786C CC genotype (OR 9.00: 95% CI 1.14–71.04) were at an increased risk of hypertension. Similarly a significant gene-environment interaction was observed between individuals consuming alcohol with eNOS intron 4 aa genotype (OR 12.00: 95% CI 1.20–143.73) and eNOS 894GG genotype (OR 1.95: 95% CI 1.35–2.81). The present study identified few susceptible genotypes of the eNOS gene with the risk of hypertension. Moreover, the interactive effects between the environmental factors and the risk of hypertension were dependent on the eNOS genotypes.

Decreased serum anti-Mullerian hormone levels in girls with newly diagnosed cancer

Are anti-Müllerian hormone (AMH) levels reduced in girls with newly diagnosed cancer before the start of treatment? AMH levels are already compromised in girls at the time of cancer diagnosis compared with healthy girls. In women diagnosed with cancer, evidence of reduced ovarian function has been described even before treatment has started. In girls with newly diagnosed cancer, no data are available. We performed an age-matched case-control study in girls with newly diagnosed cancer. We determined serum AMH levels in a cohort of 208 girls with newly diagnosed cancer, up to 18 years of age at diagnosis, and compared them with AMH levels of 250 age-matched healthy girls. The diagnoses included were acute lymphoblastic leukaemia, acute myeloid leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma, nephroblastoma, sarcoma and neuroblastoma. The median age was 6.6 years (range 0.0-17.4), comparable with that in the control group (median 6.3 years, range 0.3-18.0). Girls with childhood cancer presented with significantly lower serum AMH levels compared with healthy age-matched controls (standard deviation scores (SDS) -0.8, P < 0.001). Median AMH level in patients was 1.4 μg/l (0.1-10.2) versus 3.0 μg/l (0.1-18.3) in controls. Specifically, 84% of all patients had AMH levels below the 50th percentile of normal AMH levels, and 19% below the 10th percentile. Surrogate markers of general health status (temperature, C-reactive protein and haemoglobin levels at diagnosis) were significantly correlated with AMH SDS. Some caution is warranted because AMH levels increase with age in healthy children but the cases and controls were age-matched in our study. Although our sample size was large, additional studies are still required in an independent cohort. Our study shows that AMH levels are reduced in girls with newly diagnosed cancer even before the cancer treatment has started. AMH levels correlate with impairment of general health status in girls. Therefore, besides (pre) antral follicle number, other factors may influence serum AMH levels. Longitudinal studies during and after childhood cancer are currently being performed in order to evaluate possible ovarian recovery after discontinuation of treatment. W.v.D. is supported by the Paediatric Oncology Centre Society for Research (KOCR), Rotterdam, The Netherlands. J.S.E.L. has received grants from the following companies (in alphabetical order): Ferring, Genovum, Merck Serono, Merck Sharp and Dome, Organon, Serono, Shering Plough and Shering. All other authors have nothing to disclose.

Diagnosing paediatric myocarditis: what really matters

ObjectivePaediatric myocarditis has remained a diagnostic challenge. We aim to identify distinct characteristics and derive a scoring system that will trigger further investigations to be performed among paediatric patients presenting...

The Relationship Between Cord Blood Cytokine Levels and Perinatal Factors and Retinopathy of Prematurity: A Gestational Age-Matched Case-Control Study

To investigate the relationship between cytokine levels in cord blood and perinatal factors and retinopathy of prematurity (ROP) in gestational age-matched, preterm, newborn infants. Each of 20 premature singleton infants with ROP (gestational age < 32 weeks) was matched for gestational age, birth weight, and sex with two control infants without ROP. The concentration of 10 cytokines in cord blood extracted at birth was measured using a multiplex bead array assay. Data on maternal factors, labor and delivery characteristics, and neonatal parameters were also collected from both groups. The variables obtained were compared using the conditional logistic regression model. No differences in the levels of inflammatory cytokines (IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, interferon-γ, and TNF-α) and growth factors (insulin-like growth factor-1 and VEGF) were detected between the two groups. Multivariate conditional logistic regression analysis indicated that elevated maternal leukocyte count on admission and low Apgar scores at 5 minutes were significantly associated with an increased risk of ROP. Cytokine levels in cord blood are not associated with the risk of ROP, whereas elevated maternal blood leukocyte count and low Apgar score are associated with ROP. These data suggest that the determination of cytokine levels in cord blood samples in premature infants may be of little value for predicting ROP.

Anxiety is associated with impaired tolerance of colonoscopy preparation in inflammatory bowel disease and controls

Background and aimPain and nausea are often reported during bowel cleansing (BC) for ileocolonoscopy (IC). We aimed to explore putative mechanisms associated with impaired tolerance to BC. MethodsA 1:1 (100 IBD and 100 controls) sex and age matched case–control study was performed. Patients completed the hospital anxiety and depression scale (HADS-A/HADS-D), visceral sensitivity index (VSI) and state-trait anxiety inventory, state scale (STAI-S), in addition to self-assessment of BC and abdominal pain and nausea ratings during BC. Endoscopists reported the Mayo score, Harvey Bradshaw index (HBI), simple endoscopic score for Crohn's disease, and Boston bowel preparation scale (BBPS). ResultsHigher VSI and depression scores were observed in IBD patients. VSI (P<0.0001) and age (P=0.008) showed a positive and negative association with abdominal pain during BC, respectively. HADS-A (P=0.009) and female sex (P=0.02) were positively associated with nausea during BC, while age (P=0.02) showed a negative association. Disease activity was not associated with worse BBPS or nausea during BC, while a higher HBI was associated with more pain during BC (P=0.0006). Nausea (P=0.007) and abdominal pain (P=0.003) during BC, and less previous ICs (P=0.03) were independently associated with anxiety prior to IC (STAI-S). Significant correlations were found between VSI and STAI-S and disease activity. ConclusionHigher gastrointestinal-specific anxiety and co-morbid anxiety are associated with increased pain and nausea during BC, respectively. Pain and nausea during BC were in turn associated with higher anxiety levels at the moment of IC, potentially creating a “vicious circle”. Measures taken to reduce anxiety could improve BC and IC tolerance.

Clinical and Molecular Characteristics of Pyometra in Female Dogs

Pyometra is a common disease of female dogs. In Sweden, where approximately 90% of the dog population is intact (not neutered), nearly 25% of all female dogs are diagnosed with the disease before 10 years of age. In certain high-risk breeds, this risk of developing pyometra exceeds 50%. Various clinical signs associated with the genital tract as well as with systemic disease are present in dogs with pyometra. A frequent and serious consequence of the uterine infection is endotoxaemia and progression into the systemic inflammatory response syndrome (SIRS), or sepsis, and the disease is then regarded as a medical emergency. Acute phase proteins and inflammatory markers associated with SIRS and with the outcome as measured by length of hospitalization have been identified in blood samples. Recently, the inflammatory response in infected uterine tissue during pyometra has been more closely explored. The expression of many genes associated with chemokines, cytokines, inflammatory cell extravasation, anti-bacterial action, the complement system and innate immune responses and also a large panel of proteases are upregulated in the uterine tissue in pyometra. Products of certain upregulated genes may be detected systemically and used for diagnostic or prognostic purposes provided that tests are developed in the future. More knowledge of the complex local and systemic inflammatory response in pyometra may allow identification of novel disease biomarkers or future targets for treatment. In this article, clinical as well as molecular characteristics of the disease are reviewed.

Hypertension and the Risk of Breast Cancer in Chilean Women: a Case-control Study

Breast cancer is the most common cancer in women worldwide. Although different metabolic factors have been implicated in breast cancer development, the relationship between hypertension and breast cancer has not been elucidated. To evaluate hypertension as a risk factor for breast cancer in Chilean women of low and middle socio-economic status. We conducted an age-matched (1:1) case-control study in 3 hospitals in Santiago, Chile. Breast cancer cases (n=170) were histopathologically confirmed. Controls had been classified as Breast Imaging Reporting and Data System I (negative) or II (benign findings) within 6 months of recruitment. Blood pressure was measured using a mercury sphygmomanometer and standardized procedures. We used 2 hypertension cut-off points: blood pressures of ≥140/90 mmHg and ≥130/85 mmHg. Fasting insulin and glucose levels were assessed, and anthropometric, sociodemographic, and behavioral information were collected. Odds ratios and 95% confidence intervals were estimated for the entire sample and restricted to postmenopausal women using multivariable conditional logistic regression models. Hypertension (≥140/90 mmHg) was significantly higher in cases (37.1%) than controls (17.1%) for the entire sample and in postmenopausal pairs (44.0% compared to 23.8%). In crude and adjusted models, hypertensive women had a 4-fold increased risk of breast cancer (adjusted odds ratio: 4.2; 95% confidence interval: 1.8; 9.6) compared to non-hypertensive women in the entire sample. We found a similar association in the postmenopausal group (adjusted odds ratio: 2.8; 95% confidence interval: 1.1; 7.4). A significant effect was also observed when hypertension was defined as blood pressure of ≥130/85 mmHg. A significant association was found between hypertension and breast cancer over the entire sample and when restricted to postmenopausal women. Hypertension is highly prevalent in Latin America and may be a modifiable risk factor for breast cancer; therefore, a small association between hypertension and breast cancer may have broad implications.

Behavioral feeding problems and parenting stress in eosinophilic gastrointestinal disorders in children.

Children with eosinophilic gastrointestinal disorders (EGID) and their families are asked to adhere to dietary restrictions which can present significant daily challenges. However, little is known about child and family functioning and adaptation and the impact of psychosocial functioning (e.g., behavioral feeding problems) on adherence to dietary restrictions in this pediatric population. We conducted a gender- and age-matched case-control study wherein parents of children with EGID and healthy control children completed measures of behavioral feeding problems, parenting stress, and adherence to prescribed dietary restrictions. Children with EGID (n = 92) have significantly higher levels of behavioral feeding problems than healthy controls (n = 89; t = 5.7, p < 0.001; t = 7.9, p < 0.001). In particular, younger children demonstrated higher levels of behavioral feeding problems than older children. While behavioral feeding problems were not predictive of adherence to dietary restriction recommendations, they were positively associated with parenting stress. The study results indicate that, for families caring for a child with EGID, higher levels of behavioral feeding problems are associated with parent maladjustment or dysfunction. A multidisciplinary treatment team is needed to provide comprehensive psychosocial and feeding evaluations and treatment in EGID families.

Low antibodies against Plasmodium falciparum and imbalanced pro-inflammatory cytokines are associated with severe malaria in Mozambican children: a case–control study

BackgroundThe factors involved in the progression from Plasmodium falciparum infection to severe malaria (SM) are still incompletely understood. Altered antibody and cellular immunity against P. falciparum might contribute to increase the risk of developing SM.MethodsTo identify immune responses associated with SM, a sex- and age-matched case–control study was carried out in 134 Mozambican children with SM (cerebral malaria, severe anaemia, acidosis and/or respiratory distress, prostration, hypoglycaemia, multiple seizures) or uncomplicated malaria (UM). IgG and IgM against P. falciparum lysate, merozoite antigens (MSP-119, AMA-1 and EBA-175), a Duffy binding like (DBL)-α rosetting domain and antigens on the surface of infected erythrocytes were measured by ELISA or flow cytometry. Plasma concentrations of IL-12p70, IL-2, IFN-γ, IL-4, IL-5, IL-10, IL-8, IL-6, IL-1β, TNF, TNF-β and TGF-β1 were measured using fluorescent bead immunoassays. Data was analysed using McNemar’s and Signtest.ResultsCompared to UM, matched children with SM had reduced levels of IgG against DBLα (P < 0.001), IgM against MSP-119 (P = 0.050) and AMA-1 (P = 0.047), TGF-β1 (P <0.001) and IL-12 (P = 0.039). In addition, levels of IgG against P. falciparum lysate and IL-6 concentrations were increased (P = 0.004 and P = 0.047, respectively). Anti-DBLα IgG was the only antibody response associated to reduced parasite densities in a multivariate regression model (P = 0.026).ConclusionsThe lower levels of antibodies found in children with SM compared to children with UM were not attributable to lower exposure to P. falciparum in the SM group. IgM against P. falciparum and specific IgG against a rosetting PfEMP1 domain may play a role in the control of SM, whereas an imbalanced pro-inflammatory cytokine response may exacerbate the severity of infection. A high overlap in symptoms together with a limited sample size of different SM clinical groups reduced the power to identify immunological correlates for particular forms of SM.

Lean Muscle Mass in Classic or Ovulatory PCOS: Association with Central Obesity and Insulin Resistance

This age-matched case-control study assessed total and segmental lean muscle mass in classic or ovulatory polycystic ovary syndrome (PCOS) patients and investigated whether lean mass is associated with hormone and metabolic features. Participants underwent anthropometric and clinical evaluation. Habitual physical activity was assessed with a digital pedometer, and body composition by dual-energy X-ray absorptiometry. Laboratory measurements included total cholesterol, cholesterol fractions, triglycerides, glucose, total serum testosterone, serum insulin, estradiol, luteinizing hormone, and SHBG. Energy intake was calculated using a food frequency questionnaire. Classic PCOS patients had higher body mass index (BMI), waist circumference, testosterone and lipid accumulation product values than ovulatory PCOS and controls. Energy consumption, homeostasis model assessment index, SHBG, free androgen index and triglycerides, total and trunk lean mass were higher only in classic PCOS women vs. controls. Arm, leg, trunk, total or limb lean masses were not correlated with hormone levels in any of the groups. However, in PCOS women lipid accumulation product was positively correlated with total (r=0.56, p=0.001), trunk (r=0.59, p=0.001), arm (r=0.54, p=0.001), leg (r=0.44, p=0.03) and limb (r=0.48, p=0.001) lean masses. BMI was positively correlated with all lean mass segments and independently associated with total lean mass. Lipid accumulation product and BMI were independently associated with trunk lean mass variation. The increase in lean mass in classic PCOS appears to be associated with insulin resistance and central obesity rather than with energy intake, physical activity or androgens.

Congenital heart defects and parental occupational exposure to chemicals

Congenital heart defects (CHDs) are the most common major malformations in newborns. In this study we examined the associations between the occurrence of CHDs in children and periconceptional occupational parental exposures to chemicals. In an age-matched case-control study with standardized data collection at c. 15 months after birth, 424 mothers and 421 fathers of a child with CHD and 480 mothers and 477 fathers of a non-malformed child, filled out questionnaires on periconceptional general and job characteristics. A job exposure matrix, which links the information on job title and a description of work tasks to an expert judgement on exposure to chemicals in the workplace, was used. The overall prevalence of occupational exposure to chemicals was 5.0 in cases and 6.2% in controls for mothers [odds ratio (OR) adjusted = 0.92; 95% confidence interval (CI): 0.26-3.25], while 22.3 and 15.9% for fathers, respectively (OR adjusted = 1.23; 95% CI: 0.39-3.91). No association of maternal occupational exposure to chemicals with risk of CHDs was found. Paternal exposure to phthalates was associated with a higher incidence of CHDs in general (OR adjusted = 2.08; 95% CI: 1.27-3.40). Paternal exposure to phthalates was associated with perimembranous ventricular septal defect (OR adjusted = 2.84; 95% CI: 1.37-5.92), to polychlorinated compounds with atrioventricular septal defect (OR adjusted = 4.22; 95% CI: 1.23-14.42) and to alkylphenolic compounds with coarctation of the aorta (OR adjusted = 3.85; 95% CI: 1.17-12.67). Periconceptional paternal (but not maternal) occupational exposure to certain chemicals is associated with an increased risk of CHDs in children. The results, however, must be interpreted cautiously as exposure probabilities are a crude measure of exposure.