Nanoparticle formation from poly(acrylic acid) and oppositely charged peptides

Cationic peptides self assemble upon interacting with sodium salt of oppositely charged polymer, poly(acrylic acid), PAA, giving rise to water-soluble nanoparticles at very low concentration (0.1 mM of PAA). The morphology of these kinds of nanoparticles is mainly governed by the composition of the complexes, which can be expressed as Z+/-, i.e., the ratio of positively charged units to the concentration of anionic units of the polymers present in the system. In the present study, at lower Z+/-, the particles are elongated in shape but adopt spherical shape of 75-100 nm in diameter at higher Z+/- values. We propose that the nanoparticles containing cationic peptides obtained by this methodology can serve as delivery system to enhance the antinociception effect of the chimeric peptide with previously administered doses.     

Water soluble nanoparticles from PEG-based cationic hyperbranched polymer and RNA that protect RNA from enzymatic degradation

Recent advances in understanding biological systems have proven that RNA is not merely the carrier of genetic information, but also a key molecule in regulation of gene expression and other crucial metabolic processes. Therefore, it is being considered as an ideal therapeutic candidate both for metabolic and genetic disorders. However, research involving RNA molecules faces a practical limitation since RNA is highly labile. We have developed a novel method to protect RNA from cleavage by complexing it with a hyperbranched cationic polymer. It was found that total cellular RNA isolated from yeast spontaneously interacts with the positively charged polymer to form a spherical nanoparticle morphology. This interaction protects the RNA against enzymatic degradation. This methodology can be easily adapted for long-term storage of RNA, long distance transfer of RNA, and genetic engineering using RNA as a building block.     

Mitochondrial DNA Copy Number and Risk of Oral Cancer: A Report from Northeast India

Background

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer globally. Tobacco consumption and HPV infection, both are the major risk factor for the development of oral cancer and causes mitochondrial dysfunction. Genetic polymorphisms in xenobiotic-metabolizing enzymes modify the effect of environmental exposures, thereby playing a significant role in gene–environment interactions and hence contributing to the individual susceptibility to cancer. Here, we have investigated the association of tobacco - betel quid chewing, HPV infection, GSTM1-GSTT1 null genotypes, and tumour stages with mitochondrial DNA (mtDNA) content variation in oral cancer patients.

Methodology/Principal Findings

The study comprised of 124 cases of OSCC and 140 control subjects to PCR based detection was done for high-risk HPV using a consensus primer and multiplex PCR was done for detection of GSTM1-GSTT1 polymorphism. A comparative ΔCt method was used for determination of mtDNA content. The risk of OSCC increased with the ceased mtDNA copy number (P_trend = 0.003). The association between mtDNA copy number and OSCC risk was evident among tobacco – betel quid chewers rather than tobacco – betel quid non chewers; the interaction between mtDNA copy number and tobacco – betel quid was significant (P = 0.0005). Significant difference was observed between GSTM1 - GSTT1 null genotypes (P = 0.04, P = 0.001 respectively) and HPV infection (P<0.001) with mtDNA content variation in cases and controls. Positive correlation was found with decrease in mtDNA content with the increase in tumour stages (P<0.001). We are reporting for the first time the association of HPV infection and GSTM1-GSTT1 null genotypes with mtDNA content in OSCC.

Conclusion

Our results indicate that the mtDNA content in tumour tissues changes with tumour stage and tobacco-betel quid chewing habits while low levels of mtDNA content suggests invasive thereby serving as a biomarker in detection of OSCC.     

Off‐Shoring Clinical Research: Exploitation and the Reciprocity Constraint

The last 20 years have seen a staggering growth in the practice of off‐shoring clinical research to low‐and middle‐income countries (LICs and MICs), a growth that has been matched by the neoliberal policies adopted by host countries towards attracting trials to their shores. A recurring concern in this context is the charge of exploitation, linked to various aspects of off‐shoring. In this paper, I examine Alan Wertheimer's approach and offer an alternative view of understanding exploitation in this context. I will suggest that the justification for the enterprise of research is largely dependent on its integration within a health system from which participants regularly benefit and I argue that an attention to a principle of reciprocity will enable us to better recognize and address exploitation in international research.     

Missed Opportunities: Refusal to Confirm Reactive Rapid HIV Tests in the Emergency Department

Background

HIV infection remains a major US public health concern. While HIV-infected individuals now benefit from earlier diagnosis and improved treatment options, progress is tempered by large numbers of newly diagnosed patients who are lost to follow-up prior to disease confirmation and linkage to care.

Methodology

In the randomized, controlled USHER trial, we offered rapid HIV tests to patients presenting to a Boston, MA emergency department. Separate written informed consent was required for confirmatory testing. In a secondary analysis, we compared participants with reactive results who did and did not complete confirmatory testing to identify factors associated with refusal to complete the confirmation protocol.

Principal Findings

Thirteen of 62 (21.0%, 95% CI (11.7%, 33.2%)) participants with reactive rapid HIV tests refused confirmation; women, younger participants, African Americans, and those with fewer HIV risks, with lower income, and without primary care doctors were more likely to refuse. We projected that up to four true HIV cases were lost at the confirmation stage.

Conclusions

These findings underscore the need to better understand the factors associated with refusal to confirm reactive HIV testing and to identify interventions that will facilitate confirmatory testing and linkage to care among these populations.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00502944","term_id":"NCT00502944"}}NCT00502944; {"type":"clinical-trial","attrs":{"text":"NCT01258582","term_id":"NCT01258582"}}NCT01258582.     

A Novel Copper Chelate Modulates Tumor Associated Macrophages to Promote Anti-Tumor Response of T Cells

BackgroundAt the early stages of carcinogenesis, the induction of tumor specific T cell mediated immunity seems to block the tumor growth and give protective anti-tumor immune response. However, tumor associated macrophages (TAMs) might play an immunosuppressive role and subvert this anti tumor immunity leading to tumor progression and metastasis.Conclusion/SignificanceOur results show the potential usefulness of CuNG in immunotherapy of drug-resistant cancers through reprogramming of TAMs that in turn reprogram the T cells and reeducate the T helper function to elicit proper anti-tumorogenic Th1 response leading to effective reduction in tumor growth.     

A comparison of VO2max and metabolic variables between treadmill running and treadmill skating

The purpose of this study was to determine differences in VO2max and metabolic variables between treadmill running and treadmill skating. This study also examined VO2max responses during a continuous skating treadmill protocol and a discontinuous skating treadmill protocol. Sixteen male high school hockey players, who had a mean age of 16 +/- 1 years and were of an above-average fitness level, participated in this study. All subjects completed 4 exercise trials: a 1-hour skating treadmill familiarization trial, a treadmill running trial, and 2 randomized skating treadmill trials. Minute ventilation (VE), oxygen consumption VO2), carbon dioxide production VCO2), respiratory exchange ratio (RER), and heart rate were averaged every 15 seconds up to VO2max for each exercise test. The results showed that there was a significant difference (P < 0.05) for VO2max (mL.kg.min) and maximal VCO2 (L.min) between the running treadmill protocol and discontinuous skating treadmill protocol. There was also a significant difference for maximal RER between the discontinuous and continuous skating treadmill protocol and between the discontinuous skating treadmill protocol and running treadmill protocol. In conclusion, the running treadmill elicited a greater VO2max (mL.kg.min) than the skating treadmill did, but when it comes to specificity of ice skating, the skating treadmill may be ideal. Also, there was no significant difference between the discontinuous and continuous skating treadmill protocols. Therefore, a continuous protocol is possible on the skating treadmill without compromising correct skating position and physiologic responses. However, the continuous skating treadmill protocol should undergo validation before other scientists, coaches, and strength and conditioning professionals can apply it correctly.