The potential health impacts of climate change: An overview

Climate change would have a range of impacts on human health. Health impacts would be caused by the direct effect of climatic factors on human health, such as heat stress, and possible changes in the frequency and intensity of extreme weather events such as storms, floods and droughts. Impacts on health would also be mediated by the indirect effects of climate change, such as changes in availability of food and water and the distribution of vector‐borne diseases. The majority of health impacts would be adverse and would depend greatly on the vulnerability of populations.     

Genetically determined lean mass and dietary response

Weight loss attenuates many obesity-related co-morbidities, but is difficult to sustain with dietary change. Dietary adherence, not macronutrient composition, is a better predictor of weight loss. Weight loss-induced endocrine changes promote food intake and increase energy efficiency, contributing to the difficulty with dietary adherence and weight regain. Macronutrient preference is partly genetically determined, suggesting that personalized dietary interventions might be more successful. In this issue, Li et al. report that a genetic risk score comprising the cumulative weighted effects of variants previously associated with increased lean mass is associated with increased satiety and weight loss 6 months after initiating a low- but not a high-fat diet. The effects were attenuated by 2 years. These findings suggest that genetic variants may influence response to specific diet. Further studies are necessary to assess whether genetically determined lean mass is causally associated with dietary response. Significant progress has recently been made in identifying additional genetic determinants of lean mass, which will enable such investigations and potentially inform future nutritional studies.     

Global gene expression in pseudomyxoma peritonei,with parallel development of two immortalized cell lines

Pseudomyxoma peritonei (PMP) is a rare tumor of appendiceal origin. Treatment is major cytoreductive surgery but morbidity is high. PMP is considered chemo-resistant; its molecular biology is understudied; and presently, there is no platform for pre-clinical drug testing. Here, we performed exon array analysis from laser micro-dissected PMP tissue and normal colonic epithelia. The array analysis identified 27 up-regulated and 34 down-regulated genes: candidate up-regulated genes included SLC16A4, DSC3, Aldolase B, EPHX4, and ARHGAP24; candidate down-regulated genes were MS4A12, TMIGD1 and Caspase-5. We confirmed differential expression of the candidate genes and their protein products using in-situ hybridization and immuno-histochemistry. In parallel, we established two primary PMP cell lines, N14A and N15A, and immortalized with an SV40 T-antigen lentiviral vector. We cross-checked for expression of the candidate genes (from the array analyses) using qPCR in the cell lines and demonstrated that the gene profiles were distinct from those of colorectal tumor libraries and commonly used colon cell lines. N14A and N15A were responsiveness to mitomycin and oxaliplatin. This study characterizes global gene expression in PMP, and the parallel development of the first immortalized PMP cell lines; fit for pre-clinical testing and PMP oncogene discovery.     

Antigen‐specific B lymphocytes acquire proteoglycan aggrecan from cartilage extracellular matrix resulting in antigen presentation and CD4+ T‐cell activation

The majority of studies examining antigen‐presenting cell (APC) function have focused on the capture and presentation of antigens released from pathogens or damaged cells. However, antigen‐specific B cells are also capable of efficiently extracting antigens that are either tethered to, or integrally part of the plasma membrane of various target cells. In this study we show that B cells are also highly efficient at extracting integral components of the extracellular matrix (ECM) for subsequent presentation. In particular we demonstrate that B cells specific for aggrecan, an integral component of cartilage ECM, acquire this rheumatoid arthritis candidate autoantigen in both a B‐cell‐receptor‐dependent and a contact‐dependent manner. We also demonstrate that the subsequent presentation of aggregan from ECM leads to CD4⁺ T‐cell activation and effector cell formation. Recent studies have identified B‐cell‐mediated antigen presentation as essential for the development of autoimmunity, but a unique role for B cells compared with other APC has yet to be defined. Our findings lead us to propose that the acquisition of ECM‐derived autoantigens represents a mechanism that defines the APC requirement for B cells in the development of autoimmunity.     

Basis of selection of first and second line highly active antiretroviral therapy for HIV/AIDS on genetic barrier to resistance: a literature review

The effectiveness of combination antiretroviral therapy (cART) continues to improve as treatment choices expand with the development of new antiretroviral agents and regimens. However, the successful long-term treatment of HIV/AIDS is under threat from the emergence of drug-resistant strains to multiple agents and entire drug classes.     

Research priorities to address polypharmacy in older adults with cancer

Polypharmacy poses a significant public health problem that disproportionately affects older adults (≥65 years) since this population represents the largest consumers of medications. Clinicians caring for older adults with cancer must rely on evidence to understand polypharmacy and its implications, not only to communicate with patients and other healthcare providers, but also because of the significant interplay between polypharmacy, cancer, cancer-related treatment, and clinical outcomes. Interest in polypharmacy is rising because of its prevalence, the origins and facilitating factors behind it, and the direct and indirect clinical outcomes associated with it. The growing body of publications focused on polypharmacy in older adults with cancer demonstrates that this is a significant area of research; however, limited evidence exists to guide medication use (e.g., prescribing, administration) in this population. Currently, research priorities aimed at polypharmacy in the field of geriatric oncology lack clarity. We identified current gaps in the literature in order to establish research priorities for polypharmacy in older adults with cancer. The five research priorities—Polypharmacy Methodology and Definitions, Suboptimal Medication Use, Comorbidities and Geriatric Syndromes, Underrepresented Groups, and Polypharmacy Interventions—highlight critical areas for future research to improve outcomes for older adults with cancer.     

Effectiveness of different molecular forms of C. histolyticum class I collagenase to recover islets

One factor that may contribute to variability between different lots of purified collagenase to recover islets is the molecular form of C. histolyticum class I (C1) collagenase used in the isolation procedure. Two different enzyme mixtures containing C1, class II (C2) collagenase and BP Protease were compared for their effectiveness to recover islets from split adult porcine pancreas. The same enzyme activities per g trimmed tissue were used for all isolations with the only difference being the mass of C1 required to achieve 25,000 collagen degradation activity U/g tissue. The results show no differences in performance of the two enzyme mixtures. The only significant difference is 19 fold more truncated C1 was required to achieve the same result as intact C1.