Polymorphisms in the growth hormone receptor: a case-control study in breast cancer

The human growth hormone receptor (GHR) mediates the effects of growth hormone (GH1), starting a signalling cascade that is involved in the regulation of proliferation, differentiation and apoptosis. Recently, an isoform of the GHR gene lacking exon 3 (GHRd3) was associated with accelerated responsiveness to growth hormone. In this study, we investigated the association of the GHRd3 polymorphism with breast cancer risk and performed a haplotype analysis with 3 additional single nucleotide polymorphisms (SNPs) (Gly186Gly, Cys440Phe and Ile544Leu) in the GHR coding region in a Polish cohort. We did not observe any effect of the 4 polymorphisms on breast cancer risk. Neither did the 3 most common haplotypes influence breast cancer risk. However, a rare haplotype (dGGC), containing the GHRd3 allele, was associated with a decreased breast cancer risk (OR 0.30, 95% CI 0.11-0.80).     

The insulin-like growth factor-1 pathway mediator genes: SHC1 Met300Val shows a protective effect in breast cancer

The insulin-like growth factor 1 (IGF-1) pathway plays an important role in regulating cell proliferation, differentiation and apoptosis. IRS1, IRS2 and SHC1 are the key mediators for the downstream pathway processes. Genetic variation within these genes may lead to altered signalling. We screened IRS1, IRS2 and SHC1 for published coding region polymorphisms and choose five of them, IRS1 Ala804Ala and Gly972Arg, IRS2 Cys816Cys and Gly1057Asp and SHC1 Met300Val, for further analysis. We studied the association of the polymorphisms with breast cancer risk using a case-control design with Polish familial breast cancer cases and respective controls. For the polymorphisms in IRS1 and IRS2 no differences in the allele, genotype or haplotype distributions could be detected between the case and control subjects. Carriers of the variant allele of the SHC1 polymorphism were at decreased risk of breast cancer (OR 0.54, 95% CI 0.32-0.90, P = 0.016). A non-significant trend for a protective effect of the SHC1 Val300 allele was also seen in an independent population consisting of German familial breast cancer cases and matched controls. The joint analysis after Mantel-Haenzsel adjustment of the two populations gave an OR of 0.62 (95% CI 0.41-0.93, P = 0.02) for the SHC1 Val300 carriers. A stronger effect was detected in women diagnosed below the age of 50 (OR 0.54, 95% CI 0.32-0.89, P = 0.01). A genotype combination analysis of the non-synonymous polymorphisms in the IRS1, IRS2 and SHC1 genes did not show any effect on breast cancer risk.     

Single nucleotide polymorphisms in breast cancer

A limited number of genes have been identified that explain heritable risks of breast cancer (BC). We searched for low-penetrant genes in an association study using two populations: 223 Finnish unselected patients and 172 Polish familial cases, both with locally collected healthy controls. Candidate genes included DNA repair genes, methylenetetrahydrofolate reductase (MTHFR) and cyclin D1 genes. The frequencies for single nucleotide polymorphisms (SNPs) were measured in the following genes: NBS1, XPC, XPD, XRCC1, XRCC3, MTHFR, and cyclin D1. Odds ratios (ORs) were calculated to the wild-type genotype. The positive findings in the Finnish series were repeated in the Polish series. Significant findings among Finns were associations to XPC exon 15, XPD exon 10 and XRCC3 exon 7, the latter of borderline significance. None of these results could be repeated in the Polish series. The XPC result among Finns was probably an artifact of the control group deviating from the Hardy-Weinberg Equilibrium (HWE). The attempt to repeat the result for the XPD polymorphism among Poles was probably not valid because the control group deviated from the HWE. We conclude that within statistical power of the present study, none of the tested polymorphisms associated with BC, with the probable exception of XPD.     

Gender disparities in the receipt of home care for elderly people with disability in the United States

Context  Projected demographic shifts in the US population over the next 50 years will cause families, health care practitioners, and policymakers to confront a marked increase in the number of people with disabilities living in the community. Concerns about the adequacy of community support are particularly salient to women, who make up a disproportionate number of disabled elderly people and who may be particularly vulnerable because they are more likely to live alone with limited financial resources. Objective  To address gender differences in receipt of informal and formal home care. Design, Setting, and Participants  Nationally representative survey conducted in 1993 among 7443 noninstitutionalized people (4538 women and 2905 men) aged 70 years or older. Main Outcome Measure  Number of hours per week of informal (generally unpaid) and formal (generally paid) home care received by survey participants who reported any activity of daily living (ADL) or instrumental activity of daily living (IADL) impairment (n = 3109) compared by gender and living arrangement and controlling for other factors. Results  Compared with disabled men, disabled women were much more likely to be living alone (45.4% vs 16.8%, P<.001) and much less likely to be living with a spouse (27.8% vs 73.6%, P<.001). Overall, women received fewer hours of informal care per week than men (15.7 hours; 95% confidence interval [CI], 14.5-16.9 vs 21.2 hours; 95% CI, 19.7-22.8). Married disabled women received many fewer hours per week of informal home care than married disabled men (14.8 hours; 95% CI, 13.7-15.8 vs 26.2 hours; 95% CI, 24.6-27.9). Children (>80% women) were the dominant caregivers for disabled women while wives were the dominant caregivers of disabled men. Gender differences in formal home care were small (2.8 hours for women; 95% CI, 2.5-3.1 vs 2.1 hours for men; 95% CI, 1.7-2.4). Conclusion  Large gender disparities appear to exist in the receipt of informal home care for disabled elderly people in the United States, even within married households. Programs providing home care support for disabled elderly people need to consider these large gender disparities and the burden they impose on families when developing intervention strategies in the community.      

On the Calibration of a Numerical Model for Concrete-to-Concrete Interface

The study was devoted to the numerical modelling of concrete-to-concrete interfaces. Such an interface can be found in many modern composite structures, so proper characterisation of its behaviour is of great importance. A strategy for calibration of a model based on cohesive finite elements and the elastic-damage traction–separation constitutive law available by default in the Abaqus code was proposed. Moreover, the default interface material model was enhanced with the user-field-variables subroutine to include a real strength envelope for such interfaces. Afterwards, the modelling approach was validated with numerical simulation of the most popular tests for determining the strength characteristics of concrete-to-concrete interfaces: three-point bending beam with a notch, splitting bi-material cubic specimens, and slant-shear tests. The results of own pilot studies were used as well as those reported by other researchers. The performed simulations proved the accuracy of the proposed modelling strategy (the mean ratio of ultimate forces obtained with numerical models and from experiments was equal to 1.01). Furthermore, the presented examples allowed us to better understand the basic test methods for concrete interfaces and the observed mechanisms of failure during them.     

Antibodies from patients with melioidosis recognize Burkholderia mallei but not Burkholderia thailandensis antigens in the indirect hemagglutination assay

The indirect hemagglutination assay routinely used to detect antibodies to Burkholderia pseudomallei was modified to detect cross-reactivity of antibodies to B. pseudomallei, B. mallei, and B. thailandensis antigens. We demonstrate a lack of cross-reactivity between B. pseudomallei and B. thailandensis but marked cross-reactivity between B. pseudomallei and B. mallei.     

Influence of spinal anesthesia on corrected QT interval

BACKGROUND AND OBJECTIVES: Prolongation of the QT interval may result in grave cardiac arrhythmias, polymorphic ventricular tachycardia ("torsades de pointes"), and ventricular fibrillation. We assessed the influence of spinal anesthesia on the QTc interval and the potential arrhythmogenicity of this method of anesthesia. METHODS: Assessment was performed in 20 male unpremedicated patients, I or II American Society of Anesthesiologists physical status, who underwent spinal anesthesia for elective surgical procedures. Values of the QTc interval, heart rate, and arterial pressure were measured before spinal anesthesia as well as after 1, 3, 5, and 15 minutes of adequate blockade. RESULTS: Statistically significant lengthening of the QTc interval (compared with initial values) was observed in the first minute after blockade and in subsequent measurements. No differences were observed between mean values of the QTc interval after the onset of blockade. No significant changes in heart rate were noted. From the third minute on, significant decreases of the systolic, diastolic, and mean arterial blood pressure were observed as compared with baseline. These decreases in systolic, diastolic, and mean arterial blood pressure persisted for the entire study duration. No one patient developed clinically important cardiac arrhythmias. CONCLUSIONS: Spinal anesthesia provokes significant QTc interval prolongation in patients without cardiovascular disorders.     

The Influence of desflurane on QTc interval

Volatile anesthetics may prolong the QTc interval and this may result in grave cardiac arrhythmias. We assessed the effect of desflurane on the QTc interval in 40 ASA physical status I or II patients. Volatile anesthetic induction with desflurane was performed, and after obtaining adequate level of anesthesia, QTc interval, heart rate, and noninvasive arterial blood pressure were measured. Prolongation of the QTc interval was observed within the first minute of anesthesia. There were no differences in QTc interval changes between sexes at any time. We conclude that desflurane prolongs the QTc interval, but that there are no differences between genders in sensitivity to this action. IMPLICATIONS: We assessed the effect of desflurane on QTc interval in patients without cardiac diseases. Prolongation of the interval was evident by the first minute of desflurane anesthesia. There were no differences between female and male patients.