Miscellaneous Problems

Contains reports on four research projects

Changes in temperature of heel skin under pressure in hip surgery patients

OBJECTIVE: The aim of the study was to examine the effect of external pressure of the bed surface on heel skin temperature in adults in the first 3 days after hip surgery. DESIGN: A quasi-experimental study in a prospective, within-subjects, repeated-measures design. SETTING: This study was performed at 2 acute-care hospitals. PARTICIPANTS: Eighteen subjects (9 men and 9 women) with a mean age of 58.3 (±16.1) years were recruited after hip surgery at the 2 hospitals. METHODS: Temperature sensors were placed on the plantar surface of each foot, close to the heels. Measures were taken when the heels were (1) suspended above the bed surface for 20 minutes (preload), (2) on the bed surface for 15 minutes (loading), and (3) suspended again above the bed surface for 15 minutes (unloading). MAIN OUTCOME MEASURES: Heel skin temperature and demographic data. RESULTS: Heel temperature increased during loading and unloading in both legs on postoperative days 1 (P = .003) and 3 (P = .04) but not on postoperative day 2. Heel temperature in the nonoperative leg decreased in the first 3 minutes of unloading on postoperative days 2 (P = .02) and 3 (P .01). CONCLUSION: Heel temperature increased with loading and unloading on postoperative days 1 and 3. Upon immediate unloading, hyperemic response was present only in the nonoperative leg. Keeping the heels off the bed surface at all times may avoid heel skin temperature changes and prevent tissue damage. Further research is needed to identify the mechanisms that explain the effect of external pressure on heel temperature

Do bilinguals have different concepts? The case of shape and material in Japanese L2 users of English

An experiment investigated whether Japanese speakers’ categorisation of objects and substances as shape or material is influenced by acquiring English, based on Imai and Gentner (1997). Subjects were presented with an item such as a cork pyramid and asked to choose between two other items that matched it for shape (plastic pyramid) or for material (piece of cork). The hypotheses were that for simple objects the number of shape-based categorisations would increase according to experience of English and that the preference for shape and material-based categorisations of Japanese speakers of English would differ from mono¬lingual speakers of both languages. Subjects were 18 adult Japanese users of English who had lived in English-speaking countries between 6 months and 3 years (short-stay group), and 18 who had lived in English-speaking countries for 3 years or more (long-stay group). Both groups achieved above criterion on an English vocabulary test. Results were: both groups preferred material responses for simple objects and substances but not for complex objects, in line with Japanese mono¬linguals, but the long-stay group showed more shape preference than the short-stay group and also were less different from Americans. These effects of acquiring a second language on categorisation have implications for conceptual representation and methodology

DNA repair biomarkers XPF and phospho-MAPKAP kinase 2 correlate with clinical outcome in advanced head and neck cancer.

BackgroundInduction chemotherapy is a common therapeutic option for patients with locoregionally-advanced head and neck cancer (HNC), but it remains unclear which patients will benefit. In this study, we searched for biomarkers predicting the response of patients with locoregionally-advanced HNC to induction chemotherapy by evaluating the expression pattern of DNA repair proteins.MethodsExpression of a panel of DNA-repair proteins in formalin-fixed paraffin embedded specimens from a cohort of 37 HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation were analyzed using quantitative immunohistochemistry.ResultsWe found that XPF (an ERCC1 binding partner) and phospho-MAPKAP Kinase 2 (pMK2) are novel biomarkers for HNSCC patients undergoing platinum-based induction chemotherapy. Low XPF expression in HNSCC patients is associated with better response to induction chemoradiotherapy, while high XPF expression correlates with a worse response (p = 0.02). Furthermore, low pMK2 expression was found to correlate significantly with overall survival after induction plus chemoradiation therapy (p = 0.01), suggesting that pMK2 may relate to chemoradiation therapy.ConclusionsWe identified XPF and pMK2 as novel DNA-repair biomarkers for locoregionally-advanced HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation. Our study provides insights for the use of DNA repair biomarkers in personalized diagnostics strategies. Further validation in a larger cohort is indicated

Regulation of Brown and White Adipocyte Transcriptome by the Transcriptional Coactivator NT-PGC-1α

The β3-adrenergic receptor (AR) signaling pathway is a major component of adaptive thermogenesis in brown and white adipose tissue during cold acclimation. The β3-AR signaling highly induces the expression of transcriptional coactivator PGC-1α and its splice variant N-terminal (NT)-PGC-1α, which in turn activate the transcription program of adaptive thermogenesis by co-activating a number of transcription factors. We previously reported that NT-PGC-1α is able to increase mitochondrial number and activity in cultured brown adipocytes by promoting the expression of mitochondrial and thermogenic genes. In the present study, we performed genome-wide profiling of NT-PGC-1α-responsive genes in brown adipocytes to identify genes potentially regulated by NT-PGC-1α. Canonical pathway analysis revealed that a number of genes upregulated by NT-PGC-1α are highly enriched in mitochondrial pathways including fatty acid transport and β-oxidation, TCA cycle and electron transport system, thus reinforcing the crucial role of NT-PGC-1α in the enhancement of mitochondrial function. Moreover, canonical pathway analysis of NT-PGC-1α-responsive genes identified several metabolic pathways including glycolysis and fatty acid synthesis. In order to validate the identified genes in vivo, we utilized the FL-PGC-1α-/- mouse that is deficient in full-length PGC-1α (FL-PGC-1α) but expresses a slightly shorter and functionally equivalent form of NT-PGC-1α (NT-PGC-1α254). The β3-AR-induced increase of NT-PGC-1α254 in FL-PGC-1α-/-brown and white adipose tissue was closely associated with elevated expression of genes involved in thermogenesis, mitochondrial oxidative metabolism, glycolysis and fatty acid synthesis. Increased adipose tissue thermogenesis by β3-AR activation resulted in attenuation of adipose tissue expansion in FL-PGC-1α-/- adipose tissue under the high-fat diet condition. Together, the data strengthen our previous findings that NT-PGC-1α regulates mitochondrial genes involved in thermogenesis and oxidative metabolism in brown and white adipocytes and further suggest that NT-PGC-1α regulates a broad spectrum of genes to meet cellular needs for adaptive thermogenesis

Longitudinal patterns of unmet need for contraception among women living with HIV on antiretroviral therapy in South Africa

Objectives: Fertility intentions and contraceptive use are often not assessed in the context of clinical HIV care, representing a possible programming gap if women's family planning needs change over time. We aimed to identify longitudinal patterns of unmet need for contraception over a 12-month period among women living with HIV taking antiretroviral therapy (ART). Study design: 850 non-pregnant, HIV-positive women aged 18-35 on or initiating ART in Johannesburg, South Africa, were enrolled into a prospective cohort study in 2009-2010. Fertility intentions and contraceptive use were assessed during routine HIV care visits via an interviewer-administered questionnaire, and women were referred for on-site contraceptive counseling. We used group-based trajectory modeling to identify patterns of unmet need for contraception over 12 months, first in the entire population and then in a subset of recent ART initiators. Results: In the full population we identified four patterns of unmet need for contraception over one year. Half of the enrolled women were predicted to have a consistently high probability of unmet need, 22.9% a consistently low probability, 16.7% a decreasing probability, and 10.4% an increasing probability over time. Contraceptive method discontinuation and rapidly changing fertility intentions were the primary drivers of changing (increasing or decreasing) unmet need over follow-up. Results were similar in recent ART initiators. Conclusions: Half of women were estimated to have a high probability of unmet need that persisted over time, and more than a quarter were estimated to experience patterns of changing unmet need over 12 months. Family planning needs should be assessed more regularly in HIV-positive women to prevent unintended pregnancies and support safer conception among women trying to conceive

Trajectories of fertility intentions among women living with HIV in South Africa

Fertility intentions are thought to be dynamic among women of reproductive age, yet few studies have assessed fertility intentions over time among women with HIV. We examine temporal patterns of fertility intentions in women with HIV to assess the extent to which fertility intentions–and the corresponding need for safer conception and judicious antiretroviral therapy (ART) regimen selection–vary over time. 850 non-pregnant HIV-positive women aged 18–35 on or being initiated onto ART in Johannesburg, South Africa were enrolled into a prospective cohort study (2009–2010). Fertility intentions were assessed at enrollment and at 30-day intervals via an interviewer-administered questionnaire. We used group-based trajectory modelling to identify longitudinal patterns of fertility intentions over 12 months. We identified four patterns of fertility intentions, which we labelled “consistently low” (representing ∼60% of the population), “low and increasing” (∼23%), “high and increasing” (∼12%), and “high and decreasing” (∼5%). Our findings suggest that a single family-planning assessment at one time point is insufficient to fully identify and meet the reproductive needs of women with HIV. As HIV testing and treatment evolve in South Africa, routine screening for fertility intentions can offer important opportunities to optimize HIV treatment, prevention, and maternal and child health