Spatial and temporal dynamics of corticosterone and corticosterone binding globulin are driven by environmental heterogeneity

The question of whether changes in glucocorticoid concentrations reflect consistent changes in physiology associated with transitions between different stages of reproduction, or whether they reflect responses to environmental conditions, is one the central issues in field endocrinology studies. We examined the temporal and spatial dynamics of corticosterone (CORT, baseline, and acute stress-induced) and corticosterone binding globulin (CBG) concentrations in blood of Black-legged Kittiwakes (Rissa tridactyla) breeding at four major colonies in the Bering Sea, Alaska, during 1999-2005. We found that total CORT, free CORT, and CBG capacity varied inconsistently among reproductive stages, colonies, and years. Total CORT levels were positively correlated with CBG capacity. Variation in free CORT was largely driven by variation in total CORT. Results suggest that the adrenocortical function and CBG in breeding kittiwakes do not vary as a consequence of stage-specific modulation associated with a particular reproductive stage as in some short-lived passerine birds. Rather, in accord with predictions for a long-lived species, the lack of consistent colony, year, and reproductive stage patterns in baseline and maximum CORT, and CBG indicates that environmental factors, probably local dynamics of food availability, drive variation in these factors.     

The flip-flop HuR: part of the problem or the solution in fighting cancer?

Chronic inflammation has long been appreciated to play a critical role in tumor development and maintenance. Among the mechanisms involved in coordinating the initiation and resolution of inflammation are those responsible for modifying mRNA stability and/or translation. Several studies have linked the RNA-binding protein HuR, which increases mRNA stability, with malignant transformation. However, in this issue of the JCI, Yiakouvaki et al. compellingly demonstrate in mice that increased HuR activity in myeloid cells has a protective role in the onset of pathologic intestinal inflammation (i.e., colitis) and colitis-associated cancer (CAC). These observations highlight the need to understand the roles of HuR in distinct cell populations in vivo and suggest that enhancing HuR activity may be of clinical benefit in protecting against pathologic inflammation and cancer.     

Personal Characteristics Associated with Resident Physicians’ Self Perceptions of Preparedness to Deliver Cross-Cultural Care

BACKGROUND  Recent reports from the Institute of Medicine emphasize patient-centered care and cross-cultural training as a means of improving the quality of medical care and eliminating racial and ethnic disparities. OBJECTIVE  To determine whether, controlling for training received in medical school or during residency, resident physician socio-cultural characteristics influence self-perceived preparedness and skill in delivering cross-cultural care. DESIGN  National survey of resident physicians. PARTICIPANTS  A probability sample of residents in seven specialties in their final year of training at US academic health centers. MEASUREMENT  Nine resident characteristics were analyzed. Differences in preparedness and skill were assessed using the χ² statistic and multivariate logistic regression. RESULTS  Fifty-eight percent (2047/3500) of residents responded. The most important factor associated with improved perceived skill level in performing selected tasks or services believed to be useful in treating culturally diverse patients was having received cross-cultural skills training during residency (OR range 1.71–4.22). Compared with white residents, African American physicians felt more prepared to deal with patients with distrust in the US healthcare system (OR 1.63) and with racial or ethnic minorities (OR 1.61), Latinos reported feeling more prepared to deal with new immigrants (OR 1.88) and Asians reported feeling more prepared to deal with patients with health beliefs at odds with Western medicine (1.43). CONCLUSIONS  Cross-cultural care skills training is associated with increased self-perceived preparedness to care for diverse patient populations providing support for the importance of such training in graduate medical education. In addition, selected resident characteristics are associated with being more or less prepared for different aspects of cross-cultural care. This underscores the need to both include medical residents from diverse backgrounds in all training programs and tailor such programs to individual resident needs in order to maximize the chances that such training is likely to have an impact on the quality of care.     

Nucleosomes, linker DNA, and linker histone form a unique structural motif that directs the higher-order folding and compaction of chromatin

The compaction level of arrays of nucleosomes may be understood in terms of the balance between the self-repulsion of DNA (principally linker DNA) and countering factors including the ionic strength and composition of the medium, the highly basic N termini of the core histones, and linker histones. However, the structural principles that come into play during the transition from a loose chain of nucleosomes to a compact 30-nm chromatin fiber have been difficult to establish, and the arrangement of nucleosomes and linker DNA in condensed chromatin fibers has never been fully resolved. Based on images of the solution conformation of native chromatin and fully defined chromatin arrays obtained by electron cryomicroscopy, we report a linker histone-dependent architectural motif beyond the level of the nucleosome core particle that takes the form of a stem-like organization of the entering and exiting linker DNA segments. DNA completes ≈1.7 turns on the histone octamer in the presence and absence of linker histone. When linker histone is present, the two linker DNA segments become juxtaposed ≈8 nm from the nucleosome center and remain apposed for 3–5 nm before diverging. We propose that this stem motif directs the arrangement of nucleosomes and linker DNA within the chromatin fiber, establishing a unique three-dimensional zigzag folding pattern that is conserved during compaction. Such an arrangement with peripherally arranged nucleosomes and internal linker DNA segments is fully consistent with observations in intact nuclei and also allows dramatic changes in compaction level to occur without a concomitant change in topology.     

Engraftment of human HSCs in nonirradiated newborn NOD-scid IL2rγ null mice is enhanced by transgenic expression of membrane-bound human SCF

Immunodeficient mice engrafted with human HSCs support multidisciplinary translational experimentation, including the study of human hematopoiesis. Heightened levels of human HSC engraftment are observed in immunodeficient mice expressing mutations in the IL2-receptor common γ chain (IL2rg) gene, including NOD-scid IL2rγ(null) (NSG) mice. Engraftment of human HSC requires preconditioning of immunodeficient recipients, usually with irradiation. Such preconditioning increases the expression of stem cell factor (SCF), which is critical for HSC engraftment, proliferation, and survival. We hypothesized that transgenic expression of human membrane-bound stem cell factor Tg(hu-mSCF)] would increase levels of human HSC engraftment in nonirradiated NSG mice and eliminate complications associated with irradiation. Surprisingly, detectable levels of human CD45(+) cell chimerism were observed after transplantation of cord blood-derived human HSCs into nonirradiated adult as well as newborn NSG mice. However, transgenic expression of human mSCF enabled heightened levels of human hematopoietic cell chimerism in the absence of irradiation. Moreover, nonirradiated NSG-Tg(hu-mSCF) mice engrafted as newborns with human HSCs rejected human skin grafts from a histoincompatible donor, indicating the development of a functional human immune system. These data provide a new immunodeficient mouse model that does not require irradiation preconditioning for human HSC engraftment and immune system development.     

An interleukin 4 (IL-4)-independent pathway for CD4+ T cell IL-4 production is revealed in IL-4 receptor-deficient mice

IL-4 receptor α chain (IL-4Rα)-deficient mice were generated by gene-targeting in BALB/c embryonic stem cells. Mutant mice showed a loss of IL-4 signal transduction and functional activity. The lack of IL-4Rα resulted in markedly diminished, but not absent, TH2 responses after infection with the helminthic parasite Nippostrongylus brasiliensis. CD4⁺, CD62L-high, and CD62L-low T cell populations from uninfected IL-4Rα^−/− mice were isolated by cell sorting. Upon primary stimulation by T cell receptor cross-linkage, the CD62L-low, but not the CD62L-high, cells secreted considerable amounts of IL-4, which was strikingly enhanced upon 4-day culture with anti-CD3 in the presence or absence of IL-4. CD62L-low cells isolated from IL-4Rα^−/−, β₂-microglobulin^−/− double homozygous mice produced less IL-4 than did either IL-4Rα^−/− or wild-type mice. These results indicate that an IL-4-independent, β₂-microglobulin-dependent pathway exists through which the CD62L-low CD4⁺ population has acquired IL-4-producing capacity in vivo, strongly suggesting that these cells are NK T cells.     

Barriers to nutrition care for nursing home residents

The prevalence of protein-calorie malnutrition (PCM) in nursing home residents has reached 85% in some nursing homes and is linked to increased mortality among residents. Separate survey questionnaires were developed and administered to 99 nursing assistants and 44 nurses (35 RNs, 9 LPNs) from five eastern Washington nursing homes. The purpose was to assess nurse (RN, LPN) and nursing assistant perceived beliefs and views related to nutritional needs of nursing home residents that have a potential impact on PCM of residents. Experienced nursing assistants did not view the nurse as an active participant during mealtime. Specific barriers such as a lack of time and training, too many residents, working short staffed, poor food quality, and a lack of nurse-nursing-assistant teamwork may contribute to residents not getting enough food to eat. An education program addressing staff relationships and nutrition training of nursing assistants could improve the ability of nursing staff to ensure residents' food intake and improve the quality of life for residents in nursing homes.     

Panamanian grandmothers' family relationships and adjustment to having a grandchild with a disability

The purpose of this article was to explore the family relationships and role adjustment of grandmothers in the Republic of Panama who have a grandchild with special needs. Thirty Panamanian grandmothers of children with a disability were interviewed using a standardized format and non-directive probing. Categories of analysis were established only after the data was fully collected and reviewed. The results indicate that for most Panamanian grandmothers, their changes in family relationships are not dramatic when they have a grandchild with a disability; however, 25% clearly report a deteriorated relationship with their son-in-laws. They view their relationship with their grandchild with a disability to be one that provides a mixture of affection, love, acceptance and patience. In the area of role adjustment, they see a need to become more involved in areas that include assisting their grandchildren and/or her family with care-giving and household responsibilities, economic and medical support, or in areas related to school/academic, spiritual or recreational activities. With respect to emotional adjustment, Panamanian grandmothers of children with disabilities distinguish themselves from grandmothers in the United States, by experiencing reduced emotional stress and dwelling less on personal loss, grief, or role stigma. The implications are that there appear to be universal beliefs and adjustment factors that Panamanian grandmothers of grandchildren with disabilities experience. However, culture appears to have a genuine influence that results in subtle but unique differences from their U.S. counterparts.     

Impact of race on prostate-specific antigen outcome after radical prostatectomy for clinically localized adenocarcinoma of the prostate.

PURPOSE: To compare prostate-specific antigen (PSA) outcome after radical prostatectomy (RP) for prostate cancer in African-American and white men using previously established risk groups. PATIENTS AND METHODS: Between 1989 and 2000, 2,036 men (n = 162 African-American men, n = 1,874 white men) underwent RP for clinically localized prostate cancer. Using pretreatment PSA, Gleason score, clinical T stage, and percentage of positive biopsy specimens, patients were stratified into low- and high-risk groups. For each risk group, PSA outcome was estimated using the actuarial method of Kaplan and Meier. Comparisons of PSA outcome between African-American and white men were made using the log-rank test. RESULTS: The median age and PSA level for African-American and white men were 60 and 62 years old and 8.8 and 7.0 ng/mL, respectively. African-Americans had a statistically significant increase in PSA (P =.002), Gleason score (P =.003), clinical T stage (P =.004), and percentage of positive biopsy specimens (P =.04) at presentation. However, there was no statistical difference in the distribution of PSA, clinical T stage, or Gleason score between racial groups in the low- and high-risk groups. The 5-year estimate of PSA outcome was 87% in the low-risk group for all patients (P =.70) and 28% versus 32% in African-American and white patients in the high-risk group (P =.28), respectively. Longer follow-up is required to confirm if these results are maintained at 10 years. CONCLUSION: Even though African-American men presented at a younger age and with more advanced disease compared with white men with prostate cancer, PSA outcome after RP when controlled for known clinical predictive factors was not statistically different. This study supports earlier screening in African-American men.