Decreased mass specific respiration under experimental warming is robust to the microbial biomass method employed

Hartley et al. question whether reduction in Rmass, under experimental warming, arises because of the biomass method. We show the method they treat as independent yields the same result. We describe why the substrate-depletion hypothesis may not solely explain observed responses, and urge caution in interpretation of the seasonal data. © 2009 Blackwell Publishing Ltd/CNRS

The pestivirus N terminal protease N(pro) redistributes to mitochondria and peroxisomes suggesting new sites for regulation of IRF3 by N(pro.)

The N-terminal protease of pestiviruses, N(pro) is a unique viral protein, both because it is a distinct autoprotease that cleaves itself from the following polyprotein chain, and also because it binds and inactivates IRF3, a central regulator of interferon production. An important question remains the role of N(pro) in the inhibition of apoptosis. In this study, apoptotic signals induced by staurosporine, interferon, double stranded RNA, sodium arsenate and hydrogen peroxide were inhibited by expression of wild type N(pro), but not by mutant protein N(pro) C112R, which we show is less efficient at promoting degradation of IRF3, and led to the conclusion that N(pro) inhibits the stress-induced intrinsic mitochondrial pathway through inhibition of IRF3-dependent Bax activation. Both expression of N(pro) and infection with Bovine Viral Diarrhea Virus (BVDV) prevented Bax redistribution and mitochondrial fragmentation. Given the role played by signaling platforms during IRF3 activation, we have studied the subcellular distribution of N(pro) and we show that, in common with many other viral proteins, N(pro) targets mitochondria to inhibit apoptosis in response to cell stress. N(pro) itself not only relocated to mitochondria but in addition, both N(pro) and IRF3 associated with peroxisomes, with over 85% of N(pro) puncta co-distributing with PMP70, a marker for peroxisomes. In addition, peroxisomes containing N(pro) and IRF3 associated with ubiquitin. IRF3 was degraded, whereas N(pro) accumulated in response to cell stress. These results implicate mitochondria and peroxisomes as new sites for IRF3 regulation by N(pro), and highlight the role of these organelles in the anti-viral pathway

Transcultural Diabetes Nutrition Therapy Algorithm: The Asian Indian Application

India and other countries in Asia are experiencing rapidly escalating epidemics of type 2 diabetes (T2D) and cardiovascular disease. The dramatic rise in the prevalence of these illnesses has been attributed to rapid changes in demographic, socioeconomic, and nutritional factors. The rapid transition in dietary patterns in India—coupled with a sedentary lifestyle and specific socioeconomic pressures—has led to an increase in obesity and other diet-related noncommunicable diseases. Studies have shown that nutritional interventions significantly enhance metabolic control and weight loss. Current clinical practice guidelines (CPGs) are not portable to diverse cultures, constraining the applicability of this type of practical educational instrument. Therefore, a transcultural Diabetes Nutrition Algorithm (tDNA) was developed and then customized per regional variations in India. The resultant India-specific tDNA reflects differences in epidemiologic, physiologic, and nutritional aspects of disease, anthropometric cutoff points, and lifestyle interventions unique to this region of the world. Specific features of this transculturalization process for India include characteristics of a transitional economy with a persistently high poverty rate in a majority of people; higher percentage of body fat and lower muscle mass for a given body mass index; higher rate of sedentary lifestyle; elements of the thrifty phenotype; impact of festivals and holidays on adherence with clinic appointments; and the role of a systems or holistic approach to the problem that must involve politics, policy, and government. This Asian Indian tDNA promises to help guide physicians in the management of prediabetes and T2D in India in a more structured, systematic, and effective way compared with previous methods and currently available CPGs

Variation of health-related quality of life assessed by caregivers and patients affected by severe childhood infections.

BACKGROUND: The agreement between self-reported and proxy measures of health status in ill children is not well established. This study aimed to quantify the variation in health-related quality of life (HRQOL) derived from young patients and their carers using different instruments. METHODS: A hospital-based cross-sectional survey was conducted between August 2010 and March 2011. Children with meningitis, bacteremia, pneumonia, acute otitis media, hearing loss, chronic lung disease, epilepsy, mild mental retardation, severe mental retardation, and mental retardation combined with epilepsy, aged between five to 14 years in seven tertiary hospitals were selected for participation in this study. The Health Utilities Index Mark 2 (HUI2), and Mark 3 (HUI3), and the EuroQoL Descriptive System (EQ-5D) and Visual Analogue Scale (EQ-VAS) were applied to both paediatric patients (self-assessment) and caregivers (proxy-assessment). RESULTS: The EQ-5D scores were lowest for acute conditions such as meningitis, bacteremia, and pneumonia, whereas the HUI3 scores were lowest for most chronic conditions such as hearing loss and severe mental retardation. Comparing patient and proxy scores (n = 74), the EQ-5D exhibited high correlation (r = 0.77) while in the HUI2 and HUI3 patient and caregiver scores were moderately correlated (r = 0.58 and 0.67 respectively). The mean difference between self and proxy-assessment using the HUI2, HUI3, EQ-5D and EQ-VAS scores were 0.03, 0.05, -0.03 and -0.02, respectively. In hearing-impaired and chronic lung patients the self-rated HRQOL differed significantly from their caregivers. CONCLUSIONS: The use of caregivers as proxies for measuring HRQOL in young patients affected by pneumococcal infection and its sequelae should be employed with caution. Given the high correlation between instruments, each of the HRQOL instruments appears acceptable apart from the EQ-VAS which exhibited low correlation with the others

Cost of Dry Eye Treatment in an Asian Clinic Setting

10.1371/journal.pone.0037711PLoS ONE76

Withaferin A Alters Intermediate Filament Organization, Cell Shape and Behavior

Withaferin A (WFA) is a steroidal lactone present in Withania somnifera which has been shown in vitro to bind to the intermediate filament protein, vimentin. Based upon its affinity for vimentin, it has been proposed that WFA can be used as an anti-tumor agent to target metastatic cells which up-regulate vimentin expression. We show that WFA treatment of human fibroblasts rapidly reorganizes vimentin intermediate filaments (VIF) into a perinuclear aggregate. This reorganization is dose dependent and is accompanied by a change in cell shape, decreased motility and an increase in vimentin phosphorylation at serine-38. Furthermore, vimentin lacking cysteine-328, the proposed WFA binding site, remains sensitive to WFA demonstrating that this site is not required for its cellular effects. Using analytical ultracentrifugation, viscometry, electron microscopy and sedimentation assays we show that WFA has no effect on VIF assembly in vitro. Furthermore, WFA is not specific for vimentin as it disrupts the cellular organization and induces perinuclear aggregates of several other IF networks comprised of peripherin, neurofilament-triplet protein, and keratin. In cells co-expressing keratin IF and VIF, the former are significantly less sensitive to WFA with respect to inducing perinuclear aggregates. The organization of microtubules and actin/microfilaments is also affected by WFA. Microtubules become wavier and sparser and the number of stress fibers appears to increase. Following 24 hrs of exposure to doses of WFA that alter VIF organization and motility, cells undergo apoptosis. Lower doses of the drug do not kill cells but cause them to senesce. In light of our findings that WFA affects multiple IF systems, which are expressed in many tissues of the body, caution is warranted in its use as an anti-cancer agent, since it may have debilitating organism-wide effects

Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya

Abstract Background: Malarial anaemia is characterized by destruction of malaria infected red blood cells and suppression of erythropoiesis. Interleukin 12 (IL12) significantly boosts erythropoietic responses in murine models of malarial anaemia and decreased IL12 levels are associated with severe malarial anaemia (SMA) in children. Based on the biological relevance of IL12 in malaria anaemia, the relationship between genetic polymorphisms of IL12 and its receptors and SMA was examined. Methods: Fifty-five tagging single nucleotide polymorphisms covering genes encoding two IL12 subunits, IL12A and IL12B, and its receptors, IL12RB1 and IL12RB2, were examined in a cohort of 913 children residing in Asembo Bay region of western Kenya. Results: An increasing copy number of minor variant (C) in IL12A (rs2243140) was significantly associated with a decreased risk of SMA (P = 0.006; risk ratio, 0.52 for carrying one copy of allele C and 0.28 for two copies). Individuals possessing two copies of a rare variant (C) in IL12RB1 (rs429774) also appeared to be strongly protective against SMA (P = 0.00005; risk ratio, 0.18). In addition, children homozygous for another rare allele (T) in IL12A (rs22431348) were associated with reduced risk of severe anaemia (SA) (P = 0.004; risk ratio, 0.69) and of severe anaemia with any parasitaemia (SAP) (P = 0.004; risk ratio, 0.66). In contrast, AG genotype for another variant in IL12RB1 (rs383483) was associated with susceptibility to high-density parasitaemia (HDP) (P = 0.003; risk ratio, 1.21). Conclusions: This study has shown strong associations between polymorphisms in the genes of IL12A and IL12RB1 and protection from SMA in Kenyan children, suggesting that human genetic variants of IL12 related genes may significantly contribute to the development of anaemia in malaria patients

Cure or control: complying with biomedical regime of diabetes in Cameroon

<p>Abstract</p> <p>Background</p> <p>The objective of the study was to explore the cultural aspect of compliance, its underlying principles and how these cultural aspects can be used to improve patient centred care for diabetes in Cameroon.</p> <p>Methods</p> <p>We used participant observation to collect data from a rural and an urban health district of Cameroon from June 2001 to June 2003. Patients were studied in their natural settings through daily interactions with them. The analysis was inductive and a continuous process from the early stages of fieldwork.</p> <p>Results</p> <p>The ethnography revealed a lack of basic knowledge about diabetes and diabetes risk factors amongst people with diabetes. The issue of compliance was identified as one of the main themes in the process of treating diabetes. Compliance emerged as part of the discourse of healthcare providers in clinics and filtered into the daily discourses of people with diabetes. The clinical encounters offered treatment packages that were socially inappropriate therefore rejected or modified for most of the time by people with diabetes. Compliance to biomedical therapy suffered a setback for four main reasons: dealing with competing regimes of treatment; coming to terms with biomedical treatment of diabetes; the cost of biomedical therapy; and the impact of AIDS on accepting weight loss as a lifestyle measure in prescription packages. People with diabetes had fears about and negative opinions of accepting certain prescriptions that they thought could interfere with their accustomed social image especially that which had to do with bridging their relationship with ancestors and losing weight in the era of HIV/AIDS.</p> <p>Conclusion</p> <p>The cultural pressures on patients are responsible for patients' partial acceptance of and adherence to prescriptions. Understanding the self-image of patients and their background cultures are vital ingredients to improve diabetes care in low-income countries of Sub-Sahara Africa like Cameroon.</p