Properties of the H-4-II-E tumor cell system. I. Growth and cell proliferation kinetics of an experimental hepatoma.

Growth and cell proliferation kinetics of hepatoma H-4-II-E and its tissue culture derivative have been studied to establish the characteristics of an in vivo--in vitro solid tumor model. The H-4-II-E line, originating from the Reuber H-35 hepatoma, can be maintained and studied either in cell culture or as a transplantable solid tumor in ACI male rats. In addition it allows for the in vitro assay of cell survival following treatment of animal tumors in situ. In vivo, hepatoma H-4-II-E is rapidly growing tumor with a mean doubling time of 49-2 hr. The cell cyle time is 39-1 hr with a cell loss factor of 0-32. Retrospective examination of tumor specimens obtained during the establishment of the H-4-II-E tumor system demonstrates that both structural as well as cell population changes have occurred. The biological characteristics of the primary tumor (H-35) and an early intermediate stage (H-35tc2) are compared with H-4-II-E and the histopathological, growth and cell kinetic changes are discussed.     

Changes in serum trace element levels following local irradiation of a solid tumor.

The changes in concentrations of a number of trace elements have been determined by neutron activation analysis in tumor, liver, and blood serum of host animals, following local irradiation of a solid tumor (3924A Morris hepatoma). These trace element changes are compared to the changes observed in a parallel study of the effects of the chemotherapeutic agent 5-fluorouracil on the same tumor. Since the changes in some of the trace elements parallel the changes in pathological and biochemical factors resulting from the insult of radiation on the tumor, these trace elements may be valuable markers in the clinical evaluation of therapeutic response and as monitors of the long term effects of cancer therapy.     

A stereochemical model for phospholipids. II: Conformational analysis and molecular packing of phosphatidylethanolamine (PE)

A partition energy method procedure was applied to select the energetically favoured conformations of phosphatidylethanolamine (PE) as polar constituents of phospholipid molecules. The result indicated a large degree of freedom for the two torsion angles of the ester bond of the phosphate and a gauche, gauche star conformation for the ethane bond.A packing process of the molecule was carried out through a potential energy calculation by considering the conformers selected above, using previously published procedure and conventions. All the arrangements which possess the best packing energy values were characterised by an orientation of the PN dipolar segment parallel to the lattice plain. Rotation of the internal torsion angles and rotation in the eulerian space of the molecule produced differences in the charged groups that interact. An additional minimum was present in the energy packing process of those conformers which have the first torsion angle of the phosphate in a trans conformation. This minimum, which corresponds to an orientation of the molecule orthogonal to the lattice plane, requires a complete neutralisation of the point charges on the system.The results of the calculation underline the importance of changes in the behaviour of the polar group of the phospholipids in the packing process.     

Performance bonuses and the quality of primary health care delivered by family health teams in Brazil: A difference-in-differences analysis

BackgroundPay-for-performance (P4P) programmes to incentivise health providers to improve quality of care have been widely implemented globally. Despite intuitive appeal, evidence on the effectiveness of P4P is mixed, potentially due to differences in how schemes are designed. We exploited municipality variation in the design features of Brazil’s National Programme for Improving Primary Care Access and Quality (PMAQ) to examine whether performance bonuses given to family health team workers were associated with changes in the quality of care and whether the size of bonus mattered.Methods and findingsFor this quasi-experimental study, we used a difference-in-differences approach combined with matching. We compared changes over time in the quality of care delivered by family health teams between (bonus) municipalities that chose to use some or all of the PMAQ money to provide performance-related bonuses to team workers with (nonbonus) municipalities that invested the funds using traditional input-based budgets. The primary outcome was the PMAQ score, a quality of care index on a scale of 0 to 100, based on several hundred indicators (ranging from 598 to 660) of health care delivery. We did one-to-one matching of bonus municipalities to nonbonus municipalities based on baseline demographic and economic characteristics. On the matched sample, we used ordinary least squares regression to estimate the association of any bonus and size of bonus with the prepost change over time (between November 2011 and October 2015) in the PMAQ score. We performed subgroup analyses with respect to the local area income of the family health team. The matched analytical sample comprised 2,346 municipalities (1,173 nonbonus municipalities; 1,173 bonus municipalities), containing 10,275 family health teams that participated in PMAQ from the outset. Bonus municipalities were associated with a 4.6 (95% CI: 2.7 to 6.4; p < 0.001) percentage point increase in the PMAQ score compared with nonbonus municipalities. The association with quality of care increased with the size of bonus: the largest bonus group saw an improvement of 8.2 percentage points (95% CI: 6.2 to 10.2; p < 0.001) compared with the control. The subgroup analysis showed that the observed improvement in performance was most pronounced in the poorest two-fifths of localities. The limitations of the study include the potential for bias from unmeasured time-varying confounding and the fact that the PMAQ score has not been validated as a measure of quality of care.ConclusionsPerformance bonuses to family health team workers compared with traditional input-based budgets were associated with an improvement in the quality of care.

Nasser Fardousi and colleagues investigate the association between performance bonuses and the quality of primary health care delivered by family health teams in Brazil.     

Determination of phosphorus in cereal lipids

The effect of digestion methods on the determination of phosphorus in cereal lipids was reinvestigated. Samples were either digested with sulfuric acid or ashed in a muffle furnace at 600 degrees C. The standard deviation and the coefficient of variation were significantly higher for the acid-digested samples. Ashing gave more reliable results, especially when large amounts of lipid material had to be oxidized.     

Altered Antibody Profiles against Common Infectious Agents in Chronic Disease

Despite the important diagnostic value of evaluating antibody responses to individual human pathogens, antibody profiles against multiple infectious agents have not been used to explore health and disease mainly for technical reasons.  We hypothesized that the interplay between infection and chronic disease might be revealed by profiling antibodies against multiple agents. Here, the levels of antibodies against a panel of 13 common infectious agents were evaluated with the quantitative Luciferase Immunoprecipitation Systems (LIPS) in patients from three disease cohorts including those with pathogenic anti-interferon-γ autoantibodies (IFN-γ AAB), HIV and Sjögren’s syndrome (SjS) to determine if their antibody profiles differed from control subjects.  The IFN-γ AAB patients compared to controls demonstrated statistically higher levels of antibodies against VZV (p=0.0003), EBV (p=0.002), CMV (p=0.003), and C. albicans (p=0.03), but lower antibody levels against poliovirus (p=0.04). Comparison of HIV patients with blood donor controls revealed that the patients had higher levels of antibodies against CMV (p=0.0008), HSV-2 (p=0.0008), EBV (p=0.001), and C. albicans (p=0.01), but showed decreased levels of antibodies against coxsackievirus B4 (p=0.0008), poliovirus (p=0.0005),   and HHV-6B (p=0.002). Lastly, SjS patients had higher levels of anti-EBV antibodies (p=0.03), but lower antibody levels against several enteroviruses including a newly identified picornavirus, HCoSV-A (p=0.004), coxsackievirus B4 (p=0.04), and poliovirus (p=0.02). For the IFN-γ AAB and HIV cohorts, principal component analysis revealed unique antibody clusters that showed the potential to discriminate patients from controls.  The results suggest that antibody profiles against these and likely other common infectious agents may yield insight into the interplay between exposure to infectious agents, dysbiosis, adaptive immunity and disease activity.     

Variability in the Effect of 5-HTTLPR on Depression in a Large European Population: The Role of Age,Symptom Profile,Type and Intensity of Life Stressors

Background

Although 5-HTTLPR has been shown to influence the risk of life stress-induced depression in the majority of studies, others have produced contradictory results, possibly due to weak effects and/or sample heterogeneity.

Methods

In the present study we investigated how age, type and intensity of life-stressors modulate the effect of 5-HTTLPR on depression and anxiety in a European population cohort of over 2300 subjects. Recent negative life events (RLE), childhood adversity (CHA), lifetime depression, Brief Symptoms Inventory (BSI) depression and anxiety scores were determined in each subject. Besides traditional statistical analysis we calculated Bayesian effect strength and relevance of 5-HTTLPR genotypes in specified models.

Results

The short (s) low expressing allele showed association with increased risk of depression related phenotypes, but all nominally significant effects would turn to non-significant after correction for multiple testing in the traditional analysis. Bayesian effect strength and relevance analysis, however, confirmed the role of 5-HTTLPR. Regarding current (BSI) and lifetime depression 5-HTTLPR-by-RLE interactions were confirmed. Main effect, with other words direct association, was supported with BSI anxiety. With more frequent RLE the prevalence or symptoms of depression increased in ss carriers. Although CHA failed to show an interaction with 5-HTTLPR, in young subjects CHA sensitized towards the depression promoting effect of even mild RLE. Furthermore, the direct association of anxiety with the s allele was driven by young (≤30) individuals.

Limitations

Our study is cross-sectional and applies self-report questionnaires.

Conclusions

Albeit 5-HTTLPR has only weak/moderate effects, the s allele is directly associated with anxiety and modulates development of depression in homogeneous subgroups.