Is There a Risk of Suburban Transmission of Malaria in Selangor,Malaysia?

Background

The suburban transmission of malaria in Selangor, Malaysia’s most developed and populous state still remains a concern for public health in this region. Despite much successful control efforts directed at its reduction, sporadic cases, mostly brought in by foreigners have continued to occur. In addition, cases of simian malaria caused by Plasmodium knowlesi, some with fatal outcome have caused grave concern to health workers. The aim of this study was to investigate the possibility of local malaria transmission in suburban regions of Selangor, which are adjacent to secondary rainforests.

Findings

A malaria survey spanning 7 years (2006 - 2012) was conducted in Selangor. A total of 1623 laboratory confirmed malaria cases were reported from Selangor’s nine districts. While 72.6% of these cases (1178/1623) were attributed to imported malaria (cases originating from other countries), 25.5% (414/1623) were local cases and 1.9% (31/1623) were considered as relapse and unclassified cases combined. In this study, the most prevalent infection was P. vivax (1239 cases, prevalence 76.3%) followed by P. falciparum (211, 13.0%), P. knowlesi (75, 4.6%), P. malariae (71, 4.4%) and P. ovale (1, 0.06%). Mixed infections comprising of P. vivax and P. falciparum were confirmed (26, 1.6%). Entomological surveys targeting the residences of malaria patients’ showed that the most commonly trapped Anopheles species was An. maculatus. No oocysts or sporozoites were found in the An. maculatus collected. Nevertheless, the possibility of An. maculatus being the malaria vector in the investigated locations was high due to its persistent occurrence in these areas.

Conclusions

Malaria cases reported in this study were mostly imported cases. However the co-existence of local cases and potential Plasmodium spp. vectors should be cause for concern. The results of this survey reflect the need of maintaining closely monitored malaria control programs and continuous extensive malaria surveillance in Peninsula Malaysia.     

Chlorophyll composition of Photosystems IIα, IIβ and I in tobacco chloroplasts

The antenna composition of the Photosystems II_α, II_β and I was studied in tobacco chloroplasts. Absorbance spectra, recorded at 4 K, were analyzed for the wild type and the mutants Su/su and Su/su var. Aurea, containing higher concentrations of the photosystems. With chloroplasts of Su/su we measured the action spectra of the three photosystems from 625 to 690 nm. Above 675 nm absorption by Photosystem I dominated. This sytem had a maximum at 678 nm and a shoulder at 660 nm. Of the long-wavelength chlorophyll a forms, absorbing at 690, 697 and 705 nm at 4 K, which are generally assigned to Photosystem I, the 697 nm form occurred in an amount of four molecules per reaction center of Photosystem I in each type of chloroplast. The Photosystem II_α spectrum was characterized by maxima at 650 and 672 nm, showing clearly the participation of the chlorophyll a and b containing light-harvesting complex. In the mutants the light-harvesting complex has a chlorophyll a to chlorophyll b ratio of more than 1; the amount of the 672 nm chlorophyll a was normal, whereas the amount of chlorophyll b was markedly decreased in the mutants relative to the wild type. The Photosystem II_β spectrum mainly consisted of a band at 683 nm.     

Synthesis and biological evaluation of benzyl styrylsulfonyl derivatives as potent anticancer mitotic inhibitors

We herein report the synthesis, biological activity and structure activity relationship of derivatives of benzylstyrylsulfone, benzylstyrylsulfine and benzylsulfonyl-N-phenylacetamide. A lead compound 7 represents a new class of mitotic inhibitors that demonstrates potent anti-proliferative activity and selectively induces cancer cell apoptosis while sparing non-transformed lung fibroblast.     

The mouse seminal vesicle shape mutation is allelic with Fgfr2

The mouse seminal vesicle shape (svs) mutation is a spontaneous recessive mutation that causes branching morphogenesis defects in the prostate gland and seminal vesicles. Unlike many other mutations that reduce prostatic and/or seminal vesicle branching, the svs mutation dramatically reduces branching without reducing organ growth. Using a positional cloning approach, we identified the svs mutant lesion as a 491 bp insertion in the tenth intron of Fgfr2 that results in changes in the pattern of Fgfr2 alternative splicing. An engineered null allele of Fgfr2 failed to complement the svs mutation proving that a partial loss of FGFR2(IIIb) isoforms causes svs phenotypes. Thus, the svs mutation represents a new type of adult viable Fgfr2 allele that can be used to elucidate receptor function during normal development and in the adult. In the developing seminal vesicles, sustained activation of ERK1/2 was associated with branching morphogenesis and this was absent in svs mutant seminal vesicles. This defect appears to be the immediate downstream effect of partial loss of FGFR2(IIIb) because activation of FGFR2(IIIb) by FGF10 rapidly induced ERK1/2 activation, and inhibition of ERK1/2 activation blocked seminal vesicle branching morphogenesis. Partial loss of FGFR2(IIIb) was also associated with down-regulation of several branching morphogenesis regulators including Shh, Ptch1, Gli1, Gli2, Bmp4, and Bmp7. Together with previous studies, these data suggest that peak levels of FGFR2(IIIb) signaling are required to induce branching and sustain ERK1/2 activation, whereas reduced levels support ductal outgrowth in the prostate gland and seminal vesicles.     

Cancer Stage,Comorbidity, and Socioeconomic Differences in the Effect of Cancer on Labour Market Participation: A Danish Register-Based Follow-Up Study

Purpose

Socioeconomic inequality in return to work after cancer treatment and rehabilitation have been documented, but less is known about its causes. This paper investigates the role played by breast cancer stage at diagnosis and comorbidity.

Methods

We used the comprehensive Danish Cancer Registry to follow 7372 women aged 30-60, who were in the labour force when diagnosed with breast cancer in 2000-06 and survived at least three years. Controls were 213,276 women without breast cancer. Inequalities in employment outlook were estimated as interaction effects in linear regression between educational attainment and disease on employment.

Results

There is significant interaction between education and breast cancer, but it is only marginally affected by including stage and comorbidity in the regression models. Education, breast cancer stage, and comorbidity all have strong effects on later employment, and a considerable amount of the educational effect is mediated by comorbidity and pre-cancer labour market participation and income.

Conclusion

The result of the study is negative in the sense that the stronger effect of breast cancer on employment among low-educated compared to highly educated individuals is not explained by cancer stage or comorbidity. The fact that comorbidity has little impact on inequality may be due to a different social patterning of most comorbidity compared to breast cancer.     

Cell Line Derived Multi-Gene Predictor of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer: A Validation Study on US Oncology 02-103 Clinical Trial

Background

Massively-parallel sequencing (MPS) technologies create challenges for informed consent of research participants given the enormous scale of the data and the wide range of potential results.

Discussion

We propose that the consent process in these studies be based on whether they use MPS to test a hypothesis or to generate hypotheses. To demonstrate the differences in these approaches to informed consent, we describe the consent processes for two MPS studies. The purpose of our hypothesis-testing study is to elucidate the etiology of rare phenotypes using MPS. The purpose of our hypothesis-generating study is to test the feasibility of using MPS to generate clinical hypotheses, and to approach the return of results as an experimental manipulation. Issues to consider in both designs include: volume and nature of the potential results, primary versus secondary results, return of individual results, duty to warn, length of interaction, target population, and privacy and confidentiality.

Summary

The categorization of MPS studies as hypothesis-testing versus hypothesis-generating can help to clarify the issue of so-called incidental or secondary results for the consent process, and aid the communication of the research goals to study participants.     

Inhibition of S/G2 phase CDK4 reduces mitotic fidelity

Cyclin-dependent kinase 4 (CDK4)/cyclin D has a key role in regulating progression through late G(1) into S phase of the cell cycle. CDK4-cyclin D complexes then persist through the latter phases of the cell cycle, although little is known about their potential roles. We have developed small molecule inhibitors that are highly selective for CDK4 and have used these to define a role for CDK4-cyclin D in G(2) phase. The addition of the CDK4 inhibitor or small interfering RNA knockdown of cyclin D3, the cyclin D partner, delayed progression through G(2) phase and mitosis. The G(2) phase delay was independent of ATM/ATR and p38 MAPK but associated with elevated Wee1. The mitotic delay was because of failure of chromosomes to migrate to the metaphase plate. However, cells eventually exited mitosis, with a resultant increase in cells with multiple or micronuclei. Inhibiting CDK4 delayed the expression of the chromosomal passenger proteins survivin and borealin, although this was unlikely to account for the mitotic phenotype. These data provide evidence for a novel function for CDK4-cyclin D3 activity in S and G(2) phase that is critical for G(2)/M progression and the fidelity of mitosis.     

Effect of a pulsating anti-gravity suit on peak exercise performance in individual with spinal cord injuries

The aim of this study was to examine effects of a pulsating pressure anti-gravity suit on the peak values of oxygen uptake (VO2) and power during maximal arm exercise in spinal-cord-injured (SCI) individuals. Five well-trained SCI men (with lesions at levels between T6 and L1) and seven well-trained able-bodied men (ABC) performed two incremental (10 W x min(-1)) arm-cranking tests. During one test the pressure in the anti-G suit pulsated between 4.7 kPa (35 mmHg) and 9.3 kPa (70 mmHg) every 2 s (PPG+), during the other test (PPG-) all the subjects wore the anti-G suit in a deflated state. Tests were performed in a counter-balanced order. Peak VO2 in SCI was 1 ml x kg(-1) x min(-1) lower during PPG+ compared to PPG- (P = 0.05). Peak power and peak heart rate were not significantly different during PPG+ compared to PPG-. These results would suggest that no increase in work capacity can be obtained with a pulsating pressure anti-gravity suit in either SCI or ABC.     

All quiet on the western front? Using phenological inference to detect the presence of a latent gypsy moth invasion in Northern Minnesota

Following establishment in a new environment, invasive species expand their range through stratified diffusion, the coupling of local growth and spatial spread with long-distance movement of propagules that found new colonies. Consequently, the stages of arrival and establishment serially repeat until the entire habitat susceptible to invasion is occupied. An empirical example of such a phenomenon is the gypsy moth, Lymantria dispar (L.), invasion of northeastern Minnesota. Under a regional management program, a trapping grid is deployed along the L. dispar leading edge to detect male moth presence and inform management decisions. However, the presence of moths does not always indicate reproducing populations, and moths dispersing from populations behind the front can obscure the presence of latent invasions. We analyzed trapping data during the arrival and establishment of L. dispar in this region (2000–2012), supplemented with sentinel trap data to ascertain the timing of male moth flight (2005–2009), and derived yearly phenological predictions for male moth flight. We also used a male wing morphology metric (2007–2009) to further quantify spatial and temporal patterns associated with the L. dispar invasion. We provide evidence of an established L. dispar population when analyses suggest spatial randomness in trap catch data, and how the presence of phenologically distinct, immigrating adult moths from source populations outside of Minnesota recorded from sentinel traps could lead to the overestimation of the abundance of an established population. This work highlights the complexity of the initial invasion process even in a well-studied system for which a sensitive monitoring program exists.