The Biological Standard of Living in the two Germanies.

Physical stature is used as a proxy for the biological standard of living in the two Germanies before and after unification in an analysis of a cross-sectional sample (1998) of adult heights, as well as among military recruits of the 1990s. West Germans tended to be taller than East Germans throughout the period under consideration. Contrary to official proclamations of a classless society, there were substantial social differences in physical stature in East-Germany. Social differences in height were greater in the East among females, and less among males than in the West. The difficulties experienced by the East-German population after 1961 is evident in the increase in social inequality of physical stature thereafter, as well as in the increasing gap relative to the height of the West-German population. After unification, however, there is a tendency for East-German males, but not of females, to catch up with their West-German counterparts

Changes in undergraduate student alcohol consumption as they progress through university

BACKGROUND: Unhealthy alcohol use amongst university students is a major public health concern. Although previous studies suggest a raised level of consumption amongst the UK student population there is little consistent information available about the pattern of alcohol consumption as they progress through university. The aim of the current research was to describe drinking patterns of UK full-time undergraduate students as they progress through their degree course. METHOD: Data were collected over three years from 5895 undergraduate students who began their studies in either 2000 or 2001. Longitudinal data (i.e. Years 1–3) were available from 225 students. The remaining 5670 students all responded to at least one of the three surveys (Year 1 n = 2843; Year 2 n = 2219; Year 3 n = 1805). Results: Students reported consuming significantly more units of alcohol per week at Year 1 than at Years 2 or 3 of their degree. Male students reported a higher consumption of units of alcohol than their female peers. When alcohol intake was classified using the Royal College of Physicians guidelines [1] there was no difference between male and females students in terms of the percentage exceeding recommended limits. Compared to those who were low level consumers students who reported drinking above low levels at Year 1 had at least 10 times the odds of continuing to consume above low levels at year 3. Students who reported higher levels of drinking were more likely to report that alcohol had a negative impact on their studies, finances and physical health. Consistent with the reduction in units over time students reported lower levels of negative impact during Year 3 when compared to Year 1. CONCLUSION: The current findings suggest that student alcohol consumption declines over their undergraduate studies; however weekly levels of consumption at Year 3 remain high for a substantial number of students. The persistence of high levels of consumption in a large population of students suggests the need for effective preventative and treatment interventions for all year groups

Clinical subtype, treatment response, and survival in De Novo and recurrent metastatic breast cancer

Purpose: This study evaluated whether patients with de novo metastatic breast cancer (MBC) have superior outcomes compared to those with recurrent MBC in a contemporary treatment era and examined factors related to outcome differentials. Methods: Using an institutional database, we examined patient and tumor characteristics, treatment response, and outcome among 232 patients with de novo and 612 patients with recurrent MBC diagnosed between 2011 and 2017. Results: De novo MBC had 9-month (m) longer overall survival (OS) than recurrent MBC (36.4 vs 27.4 m, p < 0.001). Contributions to this difference included nearly twofold more HER2-positive (29.3% vs 15.2%) and significantly fewer triple-negative breast cancers (20.3% vs 32.4%, both p < 0.001) in de novo compared with recurrent MBC cohorts. Stratified by clinical subtype, progression-free survival (PFS) on first-line therapy was significantly longer in de novo MBC in all but the triple-negative subtype, 25.5 vs 11.6 m (p < 0.001) among 390 patients with hormone receptor-positive, HER2-negative, 11.4 vs 5.4 m (p = 0.002) among 142 patients with HER2-positive, and 4.0 vs 3.0 m (p = 0.121) among 162 with triple-negative MBC. In multivariable analysis, de novo status remained independently associated with improved OS (hazard ratio 0.63, 95% CI 0.49–0.80), regardless of subtype and other features. Conclusion: Patients with de novo MBC have better outcomes than those with recurrent MBC. Differences in clinical subtype and response to therapy in the metastatic setting contribute to, but do not fully explain, this difference. Longer PFS to first-line therapy in de novo MBC suggests biologic differences compared to recurrent MBC, which may be intrinsic or due to acquired resistance from treatment for prior localized breast cancer in recurrent disease

Differential activation of inflammatory pathways in A549 type II pneumocytes by Streptococcus pneumoniae strains with different adherence properties

BACKGROUND: Adherence of Streptococcus pneumoniae bacteria to lung cells is a first step in the progression from asymptomatic carriage to pneumonia. Adherence abilities vary widely among S. pneumoniae patient isolates. In this study, the binding properties of S. pneumoniae isolates and the effects of binding on activation of the Nuclear Factor-Kappa-B (NFκB) pathway and cytokine secretion by type II pneumocytes were measured. METHODS: Mechanisms of high- and low-binding S. pneumoniae adherence to A549 cells were investigated by blocking putative receptors on bacteria and host cells with antibody and by eluting choline-binding proteins off of bacterial surfaces. NFκB activation was measured by western blot and immunocytochemistry and cytokine secretion was detected by a protein array. RESULTS: This study shows that S. pneumoniae isolates from pneumonia patients (n = 298) can vary by as much as 1000-fold in their ability to bind to human lung epithelial cells. This difference resulted in differential activation of the NFκB pathway. High-, but not low-binding S. pneumoniae used Choline-binding protein A (CbpA) to bind to complement component C3 on epithelial cell surfaces. Interleukin-8 (IL-8) was the only cytokine secreted by cells treated with either low- or high-binding S. pneumoniae. CONCLUSION: These results indicate that S. pneumoniae clinical isolates are not homogeneous in their interaction with host epithelial cells. The differential activation of host cells by high- and low-binding S. pneumoniae strains could have implications for the treatment of pneumococcal pneumonia and for vaccine development

Net Efficacy Adjusted for Risk (NEAR): A Simple Procedure for Measuring Risk:Benefit Balance

BACKGROUND: Although several mathematical models have been proposed to assess the risk:benefit of drugs in one measure, their use in practice has been rather limited. Our objective was to design a simple, easily applicable model. In this respect, measuring the proportion of patients who respond favorably to treatment without being affected by adverse drug reactions (ADR) could be a suitable endpoint. However, remarkably few published clinical trials report the data required to calculate this proportion. As an approach to the problem, we calculated the expected proportion of this type of patients. METHODOLOGY/PRINCIPAL FINDINGS: Theoretically, responders without ADR may be obtained by multiplying the total number of responders by the total number of subjects that did not suffer ADR, and dividing the product by the total number of subjects studied. When two drugs are studied, the same calculation may be repeated for the second drug. Then, by constructing a 2 x 2 table with the expected frequencies of responders with and without ADR, and non-responders with and without ADR, the odds ratio and relative risk with their confidence intervals may be easily calculated and graphically represented on a logarithmic scale. Such measures represent "net efficacy adjusted for risk" (NEAR). We assayed the model with results extracted from several published clinical trials or meta-analyses. On comparing our results with those originally reported by the authors, marked differences were found in some cases, with ADR arising as a relevant factor to balance the clinical benefit obtained. The particular features of the adverse reaction that must be weighed against benefit is discussed in the paper. CONCLUSION: NEAR representing overall risk-benefit may contribute to improving knowledge of drug clinical usefulness. As most published clinical trials tend to overestimate benefits and underestimate toxicity, our measure represents an effort to change this trend

Measurement of complement receptor 1 on neutrophils in bacterial and viral pneumonia

BACKGROUND: A reliable prediction of the causative agent of community-acquired pneumonia (CAP) is not possible based on clinical features. Our aim was to test, whether the measurement of the expression of complement receptors or Fcγ receptors on neutrophils and monocytes would be a useful preliminary test to differentiate between bacterial and viral pneumonia. METHODS: Sixty-eight patients with CAP were studied prospectively. Thirteen patients had pneumococcal pneumonia; 13 patients, influenza A pneumonia; 5 patients, atypical pneumonia, and 37 patients, aetiologically undefined pneumonia. Leukocyte receptor expression was measured within 2 days of hospital admission. RESULTS: The mean expression of complement receptor 1 (CR1) on neutrophils was significantly higher in the patients with pneumococcal pneumonia than in those with influenza A pneumonia. The mean expression of CR1 was also significantly higher in aetiologically undefined pneumonia than in influenza A pneumonia, but there was no difference between pneumococcal and undefined pneumonia. CONCLUSION: Our results suggest that the expression of CR1 is higher in classical bacterial pneumonia than in viral pneumonia. Determination of the expression of CR1 may be of value as an additional rapid tool in the aetiological diagnosis, bacterial or viral infection, of CAP. These results are preliminary and more research is needed to assess the utility of this new method in the diagnostics of pneumonia

Genetic Mapping of Social Interaction Behavior in B6/MSM Consomic Mouse Strains

Genetic studies are indispensable for understanding the mechanisms by which individuals develop differences in social behavior. We report genetic mapping of social interaction behavior using inter-subspecific consomic strains established from MSM/Ms (MSM) and C57BL/6J (B6) mice. Two animals of the same strain and sex, aged 10 weeks, were introduced into a novel open-field for 10 min. Social contact was detected by an automated system when the distance between the centers of the two animals became less than ~12 cm. In addition, detailed behavioral observations were made of the males. The wild-derived mouse strain MSM showed significantly longer social contact as compared to B6. Analysis of the consomic panel identified two chromosomes (Chr 6 and Chr 17) with quantitative trait loci (QTL) responsible for lengthened social contact in MSM mice and two chromosomes (Chr 9 and Chr X) with QTL that inhibited social contact. Detailed behavioral analysis of males identified four additional chromosomes associated with social interaction behavior. B6 mice that contained Chr 13 from MSM showed more genital grooming and following than the parental B6 strain, whereas the presence of Chr 8 and Chr 12 from MSM resulted in a reduction of those behaviors. Longer social sniffing was observed in Chr 4 consomic strain than in B6 mice. Although the frequency was low, aggressive behavior was observed in a few pairs from consomic strains for Chrs 4, 13, 15 and 17, as well as from MSM. The social interaction test has been used as a model to measure anxiety, but genetic correlation analysis suggested that social interaction involves different aspects of anxiety than are measured by open-field test

Abnormal behavior in mice mutant for the Disc1 binding partner, Dixdc1

Disrupted-in-Schizophrenia-1 (DISC1) is a genetic susceptibility locus for major mental illness, including schizophrenia and depression. The Disc1 protein was recently shown to interact with the Wnt signaling protein, DIX domain containing 1 (Dixdc1). Both proteins participate in neural progenitor proliferation dependent on Wnt signaling, and in neural migration independently of Wnt signaling. Interestingly, their effect on neural progenitor proliferation is additive. By analogy to Disc1, mutations in Dixdc1 may lead to abnormal behavior in mice, and to schizophrenia or depression in humans. To explore this hypothesis further, we generated mice mutant at the Dixdc1 locus and analyzed their behavior. Dixdc1−/− mice had normal prepulse inhibition, but displayed decreased spontaneous locomotor activity, abnormal behavior in the elevated plus maze and deficits in startle reactivity. Our results suggest that Dixdc1−/− mice will be a useful tool to elucidate molecular pathophysiology involving Disc1 in major mental illnesses