Disparities in the risk of the ER/PR/HER2 breast cancer subtypes among Asian Americans in California

BackgroundPopulation-based studies of breast cancer often aggregate all Asians into a single category termed Asian/Pacific Islander (API).Purpose(1) Describe the demographic and clinicopathologic features of early breast cancer utilizing all eight ER/PR/HER2 subtypes among white, black, Hispanic, American Indian, seven Asian ethnicities, and the aggregate API category; (2) ascertain the risk of the ER+/PR+/HER2+, ER−/PR−/HER2−, and ER−/PR−/HER2+ subtypes when compared with the ER+/PR+/HER2− subtype, among seven Asian ethnicities versus non-Hispanic white women and (3) contrast the results with the risk of these same subtypes when using the aggregate API category.MethodsUsing the California Cancer Registry, we identified 225,441 cases of stages 1–4 first primary female invasive breast cancer. Logistic regression was used to assess the association of race with the ER+/PR+/HER2+, ER−/PR−/HER2− (triple-negative), and the ER−/PR−/HER2+ subtypes versus the ER+/PR+/HER2− when adjusted for stage, age, tumor grade, and socioeconomic status. Models were fit separately for each subtype. Odds ratios for the seven Asian ethnicities and the aggregate API category using non-Hispanic white women as the reference category were computed.ResultsThere was an increased risk of the ER+/PR+/HER2+ subtype for the combined API category (OR = 1.16; 95% CI = 1.09–1.23). But only Southeast Asians (OR = 1.17; 95% CI = 1.04–1.31), Filipino (OR = 1.23; 95% CI = 1.12–1.36), and Korean (OR = 1.63; 95% CI = 1.38–1.99) women had an increased risk of this subtype. The reduced risk of the triple-negative subtype seen in APIs (OR = 0.84; 95% CI = 0.79–0.90) was only noted in Chinese (OR = 0.80; 95% CI = 0.70–0.91) and Filipino (OR = 0.65; 95% CI = 0.58–0.73) women whereas Indian Continent (OR = 1.25; 95% CI = 1.01–1.53) women had an increased risk of the triple-negative subtype.The race × stage interaction was statistically significant for the ER−/PR−/HER2+ subtype (p < 0.05). When stratified by stage, there was no statistically significant association of race with subtype in stages 3 and 4. APIs had an increased risk of the ER−/PR−/HER2+ subtype in stage 1 (OR = 1.59; 95% CI = 1.37–1.75) and stage 2 (OR = 1.42; 95% CI = 1.28–1.58) but this risk was not seen in Pacific Islander, Indian Continent, and Japanese women for either stage.ConclusionsAmong the Asian ethnicities, there is marked variability in the demographic and clinicopathologic features of breast cancer. Use of the ER/PR/HER2 subtypes reveals that the risk of the ER−/PR−/HER2−, ER+/PR+/HER2+, and ER−/PR−/HER2+ subtypes varies among the Asian population. The API category, is sometimes, but not always reflective of all Asian women.     

STK15 rs2273535 polymorphism and cancer risk: A meta-analysis of 74,896 subjects

Background: It has been suggested that the serine/threonine kinase 15 (STK15) T91A rs2273535 polymorphism is associated with susceptibility to cancer. However, the results are conflicting. We performed this meta-analysis to derive a more precise estimation of the relationship. Methods: PubMed was searched to select studies. Case–control studies containing available genotype frequencies of the STK15 rs2273535 polymorphism were chosen, and the odds ratio (OR) with its 95% confidence interval (CI) was utilized to assess the strength of association. Results: 52 studies – including 34,057 cases and 40,839 controls – were identified. A significant effect of the STK15 rs2273535 polymorphism on cancer risk was found (AA vs. TT: OR = 1.13, 95%CI = 1.01–1.26, P_{heterogeneity} < 0.001; AA vs. TA/TT: OR = 1.12, 95%CI = 1.02–1.22, P_{heterogeneity} < 0.001; TA/AA vs. TT: OR = 1.06, 95%CI = 1.01–1.12, P_{heterogeneity} < 0.001). Stratified analysis by cancer type revealed that the STK rs2273535 polymorphism may contribute to the risk of breast cancer (AA vs. TT: OR = 1.21, 95%CI = 1.01–1.44, P_{heterogeneity} = 0.002), colorectal cancer (AA vs. TA/TT: OR = 1.24, 95%CI = 1.05–1.47, P_{heterogeneity} = 0.124), and esophageal cancer (AA vs. TA/TT: OR = 1.19, 95%CI = 1.02–1.39, P_{heterogeneity} = 0.148). Further subgroup analysis by ethnicity indicated that there was a statistically increased cancer risk in Asians (AA vs. TA/TT: OR = 1.20, 95%CI = 1.05–1.37, P_{heterogeneity} = 0.004). Conclusion: This meta-analysis suggests that the STK15 rs2273535 polymorphism is a candidate gene polymorphism for cancer susceptibility, especially in Asian populations.     

Association of TP53 codon 72 and CDH1 genetic polymorphisms with colorectal cancer risk in Bangladeshi population

Till now no pharmacogenetic study of TP53 codon 72 (Arg72Pro) and CDH1 rs16260 (-160C<A) genes has been reported on Bangladeshi population relating those with colorectal cancer. So the aim of the study is to determine whether there is an elevated risk of colorectal cancer development with TP53 codon 72 and CDH1 rs16260 genetic polymorphism in Bangladeshi population for the first time. To investigate the association of these two SNPs, we conducted a case-control study with 288 colorectal cancer patients and 295 healthy volunteers by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. We found an increased risk of association between Arg/Pro heterozygosity (adjusted OR = 2.58, 95% CI = 1.77–3.77, p < 0.05) and Pro/Pro mutant homozygosity (adjusted OR = 2.92, 95% CI = 1.78–4.78, p < 0.05) along with the combined genotype (Arg/Pro + Pro/Pro) (adjusted OR = 2.70, 95% CI = 1.90–3.82, p < 0.05) and colorectal cancer predisposition. In case of CDH1 rs16260 polymorphism, C/A heterozygous and A/A mutant homozygous are significantly (p < 0.05) found to be associated with colorectal cancer risk with adjusted OR of 1.94 and 2.63, respectively. The combined genotype of C/A and A/A was also found to be strongly associated with colorectal cancer risk compared to C/C genotype (adjusted OR = 2.02, 95% CI = 1.42–2.87, p < 0.05). In conclusion, heterozygosity and mutant homozygosity as well as the combination of both TP53 Arg72Pro and CDH1 rs16260 polymorphisms are responsible to increase the risk of colorectal cancer development in Bangladeshi population.     

Associations of body mass index with cancer incidence among populations,genders, and menopausal status: A systematic review and meta-analysis

In order to further reveal the differences of association between body mass index (BMI) and cancer incidence across populations, genders, and menopausal status, we performed comprehensive meta-analysis with eligible citations. The risk ratio (RR) of incidence at 10 different cancer sites (per 5 kg/m² increase in BMI) were quantified separately by employing generalized least-squares to estimate trends, and combined by meta-analyses. We observed significantly stronger association between increased BMI and breast cancer incidence in the Asia⿿Pacific group (RR 1.18:1.11⿿1.26) than in European⿿Australian (1.05:1.00⿿1.09) and North-American group (1.06:1.03⿿1.08) (meta-regression p < 0.05). No association between increased BMI and pancreatic cancer incidence (0.94:0.71⿿1.24) was shown in the Asia⿿Pacific group (meta-regression p < 0.05), whereas positive associations were found in other two groups. A significantly higher RR in men was found for colorectal cancer in comparison with women (meta-regression p < 0.05). Compared with postmenopausal women, premenopausal women displayed significantly higher RR for ovarian cancer (pre- vs. post- = 1.10 vs. 1.01, meta-regression p < 0.05), but lower RR for breast cancer (pre- vs. post- = 0.99 vs. 1.11, meta-regression p < 0.0001). Our results indicate that overweight or obesity is a strong risk factor of cancer incidence at several cancer sites. Genders, populations, and menopausal status are important factors effecting the association between obesity and cancer incidence for certain cancer types.     

Urban–rural disparities of child health and nutritional status in China from 1989 to 2006

This paper analyzes urban–rural disparities of China's child health and nutritional status using the China Health and Nutrition Survey data from 1989 to 2006. We investigate degrees of health and nutritional disparities between urban and rural children in China as well as how such disparities have changed during the period 1989–2006. The results show that on average urban children have 0.29 higher height-for-age z-scores and 0.19 greater weight-for-age z-scores than rural children. Urban children are approximately 40% less likely to be stunted (OR = 0.62; p < 0.01) or underweight (OR = 0.62; p < 0.05) during the period 1989–2006. We also find that the urban–rural health and nutritional disparities have been declining significantly from 1989 to 2006. Both urban and rural children have increased consumption of high protein and fat foods from 1989 to 2006, but the urban–rural difference decreased over time. Moreover, the urban–rural gap in child preventive health care access was also reduced during this period.     

Body mass index,iron absorption and iron status in childbearing age women

BackgroundThe prevalence of obesity has increased at an alarming rate worldwide. Some studies have observed an association between iron (Fe) deficiency (ID) and obesity, however more research is needed.ObjectiveTo assess whether body mass index (BMI) is associated with both Fe absorption and Fe status.MethodsA cross sectional sample of 318 Chilean childbearing age women was studied. The women received either a single dose of 0.5 mg of Fe (n = 137, group 1) or 3 mg of Fe plus ascorbic acid (1:2 molar ratio) (n = 181, group 2), both as FeSO₄ with labeled radioisotopes. Fe absorption was assessed through radio Fe erythrocyte incorporation. Fe status was determined by hemoglobin (Hb), mean corpuscular volume, serum Fe, total iron binding capacity, transferrin saturation, erythrocyte Zn protoporphyrin and serum ferritin (SF).Results29%, 47% and 24% of the women were classified as normal, overweight or obese, respectively. Fe absorption was significantly lower in obese women (p < 0.05). In group 1, the geometric mean and range ±1 SD of the percentage of Fe absorption for normal-weight women was 32.9% vs. 19.7% in obese. For group 2, this percentage was 36% vs. 30%, respectively (2-way ANOVA: BMI classification and Fe dose p < 0.05; interaction p = 0.34). Although Fe absorption was lower in obese women, they had higher SF (p < 0.01) and Hb (p < 0.05) concentrations.ConclusionAlthough we did not observe a relationship between BMI and Fe status, obese women displayed lower Fe absorption compared with overweight and normal weight women, possibly due to subclinical inflammation associated with obesity.     

A study on ectoparasites of sheep and goats in eastern part of Amhara region,northeast Ethiopia

A study on ectoparasites of small ruminants was carried out in three districts (woredas) of the eastern part of Amhara Regional State, Ethiopia, from November 2003 to March 2004, with the objectives of determining the prevalence of ectoparasites and identifying the potential risk factors associated with the problem. Out of 752 sheep and 752 goats examined, 50.5% of sheep and 56.4% of goats were infested with one or more ectoparasites. The ectoparasites identified in sheep were Damalina ovis (38.5%), Melophagus ovinus (12.5%), tick infestations (3.4%) and Linognathus spp. (2.4%). In goats, parasites such as Linognathus spp. (28.3%), ticks (22.2%), sarcoptic mites (6.1%) and Ctenocephalides spp. (8.1%) were identified. The prevalence of M. ovinus and D. ovis infestations in sheep were significantly (p < 0.05) higher in the highlands than both lowlands and midlands, which were almost similar. In goats, the risk of sarcoptic mange infestation in lowland and midland was 4.6 and 5.0 times higher than the highlands, respectively. The prevalence of Linognathus spp. in goats was significantly (p < 0.05) higher in the highlands than the lowlands. Both in sheep and goats, no significant difference between young and adult age groups was observed for any ectoparasites except for D. ovis in sheep in which adults (42.2%) were more affected than young animals (29.9%). The goats with poor body condition were 4.3 times at risk for sarcoptic mange (OR = 4.3, p < 0.05), Linognathus spp. (OR = 2.1, p < 0.05) and tick (OR = 1.6, p < 0.05) infestation than goats of good body condition. On the contrary, no significant variation (p > 0.05) in ectoparasite infestation of sheep was observed in relation to body condition. Favorable climates, poor management, poor awareness of farmers and poor animal health extension services are believed to have contributed for the widespread occurrence of ectoparasites.     

A study on the association of TNF-α-308, IL-6-174, IL-10-1082 and IL-1RaVNTR gene polymorphisms with rheumatic heart disease in Pakistani patients

Inflammation is an important contributor to the pathogenesis of rheumatic heart disease (RHD), a disorder of heart valves caused by a combination of immune, genetic and environmental factors. Cytokines are important mediators of inflammatory and immune responses. The aim of this study was to investigate the role of cytokine gene polymorphisms and their potential usefulness as biomarkers in RHD patients from Pakistan. We screened 150 RHD patients and 204 ethnically matched controls for tumor necrosis factor (TNF)-α^-308G/A, interleukin (IL)-10^?1082 G/A, interleukin (IL)-6^-174 G/C and a variable number of tandem repeats (VNTRs) polymorphism of the IL-1Ra gene using polymerase chain reaction. The results showed that TNF-α^-308 A and IL-6^-174 G alleles were associated with susceptibility to RHD (p = 0.000; OR = 2.81; CI = 1.5–5.14 and p = 0.025; OR = 1.50; CI = 1.04–2.16 respectively). The TNF-α^-308 AA and GA genotypes were associated with susceptibility to RHD (p = 0.012; OR = 9.94; CI; 1.21–217.3 and p = 0.046; OR = 1.97; CI = 0.98–3.97 respectively) while the GG genotype seemed to confer resistance (p = 0.003; OR = 0.39; CI = 0.20–0.76). The GG genotype for IL-6^-174 was significantly associated with predisposition to RHD (p = 0.015; OR = 2.6; CI = 1.17–5.85). The A1 (four repeats) and A2 (two repeats) alleles at the IL-1Ra VNTR polymorphism were associated with resistance and susceptibility to RHD respectively. However, this polymorphism deviated from Hardy–Weinberg equilibrium in both patients and controls in our population. TNF-α^-308 and IL-6^-174 polymorphisms may be useful markers for the identification of individuals susceptible to RHD in Pakistan. These individuals could be provided aggressive prophylactic intervention to prevent the morbidity and mortality associated with RHD.     

Tumor characteristics and family history in relation to mammographic density and breast cancer: The French E3N cohort

BackgroundMammographic density is a known heritable risk factor for breast cancer, but reports how tumor characteristics and family history may modify this association are inconsistent.MethodsDense and total breast areas were assessed using Cumulus™ from pre-diagnostic mammograms for 820 invasive breast cancer cases and 820 matched controls nested within the French E3N cohort study. To allow comparisons across models, percent mammographic density (PMD) was standardized to the distribution of the controls. Odds ratios (OR) and 95% confidence intervals (CI) of breast cancer risk for mammographic density were estimated by conditional logistic regression while adjusting for age and body mass index. Heterogeneity according to tumor characteristic and family history was assessed using stratified analyses.ResultsOverall, the OR per 1 SD for PMD was 1.50 (95% CI, 1.33–1.69). No evidence for significant heterogeneity by tumor size, lymph node status, grade, and hormone receptor status (estrogen, progesterone, and HER2) was detected. However, the association of PMD was stronger for women reporting a family history of breast cancer (OR_1SD = 2.25; 95% CI, 1.67–3.04) than in women reporting none (OR_1SD = 1.41; 95% CI, 1.24–1.60; p_{heterogeneity} = 0.002). Similarly, effect modification by FHBC was observed using categories of PMD (p_{heterogeneity} = 0.02) with respective ORs of 15.16 (95% CI, 4.23–54.28) vs. 3.14 (95% CI, 1.89–5.22) for ≥50% vs. <10% PMD.ConclusionsThe stronger association between mammographic density and breast cancer risk with a family history supports the hypothesis of shared genetic factors responsible for familial aggregation of breast cancer and the heritable component of mammographic density.     

Biological costs of economic transition: Stress levels during the transition from communism to capitalism in Poland

At the end of the 1980s, Poland began the transformation from an essentially one-party communist system to a politically pluralistic democratic system. These political and economic changes had major social consequences, among others unemployment and a sharp decrease in real personal income. The aim of the study was to investigate the possible relationship between stress in adult men, measured by the Allostatic Load, and the socio-economic deterioration during the first part of the economic transition. The Allostatic Load included eleven markers assessing adverse nutritional intake, cardiovascular activity, inflammatory processes, and lung, hepatic and renal functions. The results indicate a significantly higher risk of metabolic dysregulation in men examined after 1990, compared to men from previous years. After adjustment for socioeconomic variables and lifestyle variables, men examined in 1991 had a 31% greater risk of higher Allostatic Load compared with men examined in 1985 (OR = 1.31; p = 0.0541), in 1992, this risk was 50% greater (OR = 1.50; p < 0.01), and in 1993, the risk was 66% greater (OR = 1.66; p < 0.05). The conclusion is drawn that significantly more stressogenic factors for men were those directly connected with the financial situation of their families, than a sudden but short increase of prices for goods and services.     

Gender-specific fatty acid profiles in platelet phosphatidyl-choline and -ethanolamine

Previous studies suggested that women synthesise docosahexaenoic acid (DHA) more efficiently from their precursors than men. This study investigated the relationship between diet, platelet phospholipids fatty acids and gender. Dietary intake and platelet phosphatidyl-choline (PC) and phosphatidylethanolamine (PE) fatty acids were determined in Caucasian 40 men and 34 women. Absolute and %energy intakes of arachidonic acid (AA), eicosapentaenoic acid (EPA), and DHA, and the ratios of total n-6/n-3 PUFA and linoleic/alpha-linolenic acids did not differ between the sexes. However, women had higher DHA in PC (1.19 vs 1.05 wt%, p<0.05) and PE (3.62 vs 3.21 wt%, p<0.05) than men. Also EPA (1.10 vs 0.93 wt%, p<0.05) was higher in women's PE. Conversely, men had elevated AA and total n-6 fatty acids in PC. The higher platelet DHA levels and lower platelet AA/EPA and AA/DHA ratios in women of child-bearing age compared with men, may lead to less platelet aggregation and vaso-occlusion.     

Concentration of vascular endothelial growth factor in patients with acute coronary syndrome

Vascular endothelial growth factor (VEGF) is a regulator of vascular formation in physiological and pathological conditions. The aim of our study was to evaluate the value of VEGF as a surrogate marker of myocardial injury in acute ischemic conditions.Materials and methodsIn 104 consecutive patients with acute coronary syndrome (ACS) with and without ST segment elevation (STEMI and NSTEMI) the plasma and serum human VEGF (hVEGF) concentration was measured two times i.e. immediately after admission due to ACS and 24 h later. According to ECG findings and coronary angiography results, patients were divided into three groups. Group A represented major myocardial injury due to ST-segment elevation in precordial leads and/or in I and aVL leads and with left anterior descending (LAD) artery responsible for STEMI symptoms or additionally with significant atherosclerotic lesions (lumen vessel narrowed >50%) in other than LAD coronary arteries. Group B (medium myocardial injury) consisted of patients with ST-segment elevation in II, III and aVF leads and/or ST-segment depression in V2-V3 leads with one-vessel disease and the culprit artery was not LAD. Group C included patients with changes in ECG other than ST-segment elevation independently of the site of atherosclerotic lesions in coronary arteries.ResultsIn all 104 patients with ACS the highest values of serum hVEGF were observed in second measurement (357.9 ± 346 pg/ml, p < 0.01). Although in the first measurement, plasma and serum hVEGF concentration did not differentiate groups, the difference between deltas for serum hVEGF was observed (p < 0.05). Increased number of neutrophils in the first measurement increased the OR of the high serum hVEGF concentration in the first measurement (OR = 1.155; 95%CI: 1.011; 1.32) (p < 0.05). The number of neutrophils in the second measurement also revealed significant relationship with high serum hVEGF in the first assessment (OR = 1.318, 95%CI: 1.097; 1.583) (p < 0.01). Increased values of triglycerides (exceeding the upper limit) were connected with decreased OR of high serum hVEGF concentrations in the first measurement (OR = 0.152, 95%CI: 0.033; 0.695, p < 0.05).ConclusionsIn acute coronary syndrome, serum VEGF concentrations are elevated and can serve as a surrogate marker of myocardial injury. The elevated number of neutrophils increases odds ratio of high VEGF concentrations in ACS. In patients with high concentrations of triglycerides, odds ratio of low level of hVEGF is expected.     

Genetic polymorphism of epidermal growth factor 61A>G and cancer risk: A meta-analysis

Background: Numerous studies have investigated the risk of cancer associated with the polymorphism of epidermal growth factor (EGF) 61A>G, but the results have been inconsistent. We performed this meta-analysis to drive a more precise estimation of association between this polymorphism and risk of cancer. Methods: Electronic searches of PubMed and EMBASE were conducted to select studies. Case-control studies containing available genotype frequencies of EGF 61A>G were chose, and Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association. Results: 23 case-control studies including 5578 cases and 7306 controls were identified. This meta-analysis showed significant effect of EGF 61A>G on cancer risk (GG vs. AA: OR = 1.34, 95%CI = 1.05–1.72; GG vs. GA + AA: OR = 1.23, 95%CI = 1.03–1.47; GG + GA vs. AA: OR = 1.18, 95%CI = 1.02–1.38). In subgroup analysis, significant increased risk was found in gastric cancer and glioma in additive model (OR = 1.54, 95%CI = 1.13–2.12; OR = 1.69, 95%CI = 1.21–2.37) and in recessive model (OR = 1.29, 95%CI = 1.10–1.52; OR = 1.54, 95%CI = 1.16–2.04). Conclusion: This meta-analysis suggested that the EGF 61G allele is a risk factor of cancer, especially for gastric cancer and glioma.     

The influence of a TNF gene polymorphism on the severity of rheumatoid arthritis in the Brazilian Amazon

PurposeThe aim of this study was to investigate the influence of the TNF -308 G/A polymorphism in the promoter region of the tumor necrosis factor-α gene on the susceptibility and severity of rheumatoid arthritis (RA) in individuals from the Brazilian Amazon.MethodsA total of 323 individuals—192 healthy controls without arthritis and 131 individuals suffering from arthritis—were genotyped for this polymorphism using a methodology based on PCR-RFLP.ResultsThe frequency of the A allele (TNF2) in rheumatoid arthritis sufferers was not significantly higher than in the controls (p = 0.926; OR = 0.97; confidence interval 0.54–1.76). However, using a logistic regression model, when the patients were stratified according to whether the manifestations were preponderantly articular or systemic, there was a strong association between the TNF2 allele and systemic arthritis (p = 0.001; OR = 5.89; confidence interval = 1.98–17.5) as well as the use of anti-TNF immunotherapy (p = 0.023; OR = 1.10; confidence interval = 1.00–1.14). The main factors that were found to influence the risk of extra-articular disease were age greater than or equal to 60 years (p = 0.008; OR = 4.06; confidence interval = 1.45–11.38), disease duration greater than 10 years (p = 0.031; OR = 3.10; confidence interval = 1.11–8.63) and positive rheumatoid factor (p = 0.035; OR = 2.07; confidence interval = 1.05–4.09).ConclusionsThese results suggest that the TNF2 allele is associated with the more serious forms of the disease in individuals from the Brazilian Amazon but not with a risk for developing RA.     

Clinical characteristics of tumors derived from colorectal cancer patients who harbor the Tumor Necrosis Factor α-1031T/T and NOD2 3020insC polymorphism

Background: Genetic predispositions to disease have focused on highly penetrant causative changes in tumor suppressor genes or genes associated with DNA mismatch repair. New investigations are revealing new genetic associations with disease that are more subtle in their association with disease and require characterization. Methods: In this report we have examined the tumor characteristics in a group of patients who have been shown to harbor two polymorphisms in two genes that are associated with the immune system NOD2 and TNFα. Results: Colorectal cancers from patients with NOD2 3020insC and TNFα-1031T/T constitutional changes are mostly right-sided disease (OR = 2.21, p = 0.03) with a tendency to higher stages (OR = 2.41, p = 0.06), increased number of associated polyps (OR = 1.77, p = 0.16) and later age of average age of disease onset (p = 0.039). Conclusion: The results reveal that there appear to be specific characteristics associated with the tumors that may aid in determining management strategies to reduce the risk of disease.     

Neutrophil CD64 expression and serum IL-8: Sensitive early markers of severity and outcome in sepsis

The aim of the present study was to investigate which biomarker/s reliably assess severity and mortality early in the sepsis process. In 47 critically-ill patients within the 24 h of septic onset, Interleukins (IL)-8, -1β, -6, -10, and -12p70, tumor necrosis factor-α (TNF-α), procalcitonin (PCT) and C-reactive protein (CRP) were measured in serum. Additionally, CD64 expression was measured in neutrophils. In early sepsis, neutrophil CD64 expression and IL-8 levels are the only biomarkers that increased with sepsis severity, differentiating disease stages: sepsis, severe sepsis and septic shock (p < 0.001). The biomarkers that best evaluate the severity of sepsis (via APACHE II) were CD64, IL-8 and IL-6 (p < 0.01), and the severity of organ failure (via SOFA) were CD64 and IL-8 (p < 0.01). CD64 expression and IL-8 levels were associated with mortality within 28-days (OR = 1.3, p = 0.01 for CD64 and OR = 1.26, p = 0.024 for IL-8 by logistic regression analysis) and ROC curve analysis showed high sensitivity and specificity for predicting sepsis stages and the 28 day mortality. We conclude that there is an early increase of neutrophil CD64 expression and IL-8 levels during sepsis. Based on this single measurement it is possible to reliably assess the stage, detect the severity and predict the 28-day mortality of sepsis.     

Risk factors associated with human papillomavirus prevalence and cervical neoplasia among Cameroonian women

BackgroundThis study used community-based cervical cancer screening for high-risk human-papillomavirus (HPV) to determine demographic and lifestyle factors associated with HPV prevalence and cervical intraepithelial neoplasia grade 2 or worse (CIN2+).MethodsWomen (n = 838) aged 25–65 years were recruited in two sequential studies in Cameroon. Demographic and historical data were obtained from participants and specimens were self-collected for HPV-testing using real-time PCR. HPV-positive women underwent biopsy and endocervical curettage. Associations were determined using bivariate analysis and logistic regression.ResultsHPV and self-reported HIV prevalence were 39.0% and 9.2%, respectively. Eighteen (9.3%) CIN2+ lesions were found among HPV-positive women. Housewives had a higher risk of being HPV infected (OR = 1.60, p = 0.010). HIV co-infection (aOR = 3.44, p < 0.001) and hormonal contraception (aOR = 1.97, p = 0.007) were associated with increased HPV prevalence. HPV-positive women who used condoms during sexual intercourse were at lower risk of CIN2+ (aOR = 0.15, p = 0.029). CIN2–3 lesions were found in women younger than 50 years, with a median age of 36 years (31–44). HPV-16/18-positive women had a 4.65-fold increased risk of CIN2+ (p = 0.015).ConclusionsYoung, single women and housewives were at higher risk of HPV infection. Preventive strategies for cervical cancer in low-resource settings should target women aged 30–50 years for HPV screening, and should focus treatment and follow-up on HPV-16/18-positive women. Further studies are needed to clarify if other risk factors require attention.     

Interleukin-1 receptor antagonist gene (IL1RN) polymorphism possibly associated to severity of rheumatic carditis in a Brazilian cohort

Aims: To evaluate the IL1RN polymorphism as a possible marker for Rheumatic Fever (RF) susceptibility or disease severity. Methods: The genotypes of 84 RF patients (Jones criteria) and 84 normal race-matched controls were determined through the analysis of the number of 86-bp tandem repeats in the second intron of IL1RN. The DNA was extracted from peripheral-blood leukocytes and amplified with specific primers. Clinical manifestations of RF were obtained through a standardized questionnaire and an extensive chart review. Carditis was defined as new onset cardiac murmur that was perceived by a trained physician with corresponding valvae regurgitation or stenosis on echocardiogram. Carditis was classified as severe in the presence of congestive heart failure or upon the indication for cardiac surgery. The statistical association among the genotypes, RF and its clinical variations was determined. Results: The presence of allele 1 and the genotype A1/A1 were found less frequently among patients with severe carditis when compared to patients without this manifestation (OR = 0.11, p = 0.031; OR = 0.092, p = 0.017). Neither allele 1 nor allele 2 were associated with the presence of RF (p = 0.188 and p = 0.106), overall carditis (p = 0.578 and p = 0.767), polyarthritis (p = 0.343 and p = 0.313) and chorea (p = 0.654 and p = 0.633). Conclusion: In the Brazilian population, the polymorphism of the IL-1ra gene is a relevant factor for rheumatic heart disease severity.     

Prevalence of genital HPV infections and HPV serology in adolescent girls,prior to vaccination

Introduction: Monitoring the prevalence of type-specific HPV-DNA infections before and shortly after introduction of routine HPV vaccination offers the opportunity to evaluate early effects of the vaccination program. With this aim a cohort study was set up of 14- to 16-year-old girls eligible for HPV vaccination in the Netherlands. Annually, HPV-DNA and antibody status in vaginal self-samples and in serum respectively, will be studied among vaccinated (58%) and unvaccinated girls (42%). Here we present baseline data on vaginal HPV-DNA status in relation to serum antibodies. Methods: The 1800 enrolled girls filled out an internet-based questionnaire and provided a vaginal self-sample for genotype specific HPV-DNA detection using SPF₁₀ PCR amplification and reverse line probe hybridization. Furthermore, 64% of the girls provided a blood sample for HPV antibody analysis. IgG antibodies against virus-like particles were determined for 7 HPV genotypes. Results: At baseline, type-specific HPV-DNA was detected in 4.4% (n = 79) of the 1800 girls: 2.7% (n = 49) concerned a high risk HPV type (hrHPV-DNA). The three most common types were HPV type 16, 18 and 51 (40%). Out of the hrHPV-DNA positive girls, 32% was seropositive vs. 12% in HPV-DNA negative girls (p < 0.001). Risk factors independently associated with hrHPV-DNA infection among the sexually active girls were age >15 years vs. 14–15 years (OR = 2.6 (1.2–5.9)), age of sexual debut <14 vs. above 14 years (OR = 3.0 (1.1–8.2)), total number of lifetime partners above two vs. less than two partners (OR = 3.2 (1.3–8.0)) and age of partner >17 vs. under 17 years (OR = 4.2 (1.5–13.0)). Conclusion: A low hrHPV-DNA prevalence was found in the adolescent girls. The observed vs. expected age-related increase in HPV-DNA prevalence in this cohort in the coming years (with increased sexual activity) will provide understanding of the effect of HPV vaccination. Furthermore, this cohort study will offer the opportunity to improve knowledge of antibody responses following natural infection and vaccination.     

Placental antiangiogenic prolactin fragments are increased in human and rat maternal diabetes

Introduction/objectivesThe role of the placenta in diabetic mothers on fetal development and programming is unknown. Prolactin (PRL) produced by decidual endometrial cells may have an impact. Although full-length PRL is angiogenic, the processed form by bone morphogenetic protein-1 (BMP-1) and/or cathepsin D (CTSD) is antiangiogenic.The objectives were to investigate the involvement of decidual PRL and its antiangiogenic fragments in placentas from type-1 diabetic women (T1D) and from pregnant diabetic rats with lower offspring weights than controls.MethodsPRL, BMP-1, and CTSD gene expressions and PRL protein level were assessed in T1D placentas (n = 8) at delivery and compared to controls (n = 5). Wistar rats received, at day 7 of pregnancy, streptozotocin (STZ) (n = 5) or nicotinamide (NCT) plus STZ (n = 9) or vehicle (n = 9). Placental whole-genome gene expression and PRL western blots were performed at birth.ResultsIn human placentas, PRL (p < 0.05) and BMP-1 (p < 0.01) gene expressions were increased with a higher amount of cleaved PRL (p < 0.05) in T1D than controls. In rats, diabetes was more pronounced in STZ than in NCT–STZ group with intra-uterine growth restriction. Decidual prolactin-related protein (Dprp) (p < 0.01) and Bmp-1 (p < 0.001) genes were up-regulated in both diabetic groups, with an increased cleaved PRL amount in the STZ (p < 0.05) and NCT–STZ (p < 0.05) groups compared to controls. No difference in CTSD gene expression was observed in rats or women.ConclusionsAlterations in the levels of the PRL family are associated with maternal diabetes in both rats and T1D women suggesting that placental changes in these hormones impact on fetal development.