Access and use of human tissues from the developing world: ethical challenges and a way forward using a tissue trust

Background  

Scientists engaged in global health research are increasingly faced with barriers to access and use of human tissues from the developing world communities where much of their research is targeted. In part, the problem can be traced to distrust of researchers from affluent countries, given the history of 'scientific-imperialism' and 'biocolonialism' reflected in past well publicized cases of exploitation of research participants from low to middle income countries.     

Restructuring the inpatient practice of an academic internal medicine department.

The authors describe the process undertaken by the Department of Medicine at the Mayo Clinic in Rochester, Minnesota to improve inpatient care. The department systematically analyzed its inpatient practice and developed a set of hypotheses that challenged whether new inpatient models with greater physician commitment could improve the quality of care; patient, resident, and staff satisfaction; and financial performance. The new practice model they developed, which includes using more physicians whose time is dedicated to the hospital practice, has led to a more focused hospital experience for learners and has implications for all academic medical centers involved with primary care, subspecialty care, and hospital consultative services.     

Body mass index and physical activity in relation to the incidence of hip fracture in postmenopausal women

Hip fracture risk is known to increase with physical inactivity and decrease with obesity, but there is little information on their combined effects. We report on the separate and combined effects of body mass index (BMI) and physical activity on hospital admissions for hip fracture among postmenopausal women in a large prospective UK study. Baseline information on body size, physical activity, and other relevant factors was collected in 1996–2001, and participants were followed for incident hip fractures by record linkage to National Health Service (NHS) hospital admission data. Cox regression was used to calculate adjusted relative risks of hip fracture. Among 925,345 postmenopausal women followed for an average of 6.2 years, 2582 were admitted to hospital with an incident hip fracture. Hip fracture risk increased with decreasing BMI: Compared with obese women (BMI of 30+ kg/m²), relative risks were 1.71 [95% confidence interval (CI) 1.47–1.97)] for BMI of 25.0 to 29.9 kg/m² and 2.55 (95% CI 2.22–2.94) for BMI of 20.0 to 24.9 kg/m². The increase in fracture risk per unit decrease in BMI was significantly greater among lean women than among overweight women (p < .001). For women in every category of BMI, physical inactivity was associated with an increased risk of hip fracture. There was no significant interaction between the relative effects of BMI and physical activity. For women who reported that they took any exercise versus no exercise, the adjusted relative risk of hip fracture was 0.68 (95% CI 0.62–0.75), with similar results for strenuous exercise. In this large cohort of postmenopausal women, BMI and physical activity had independent effects on hip fracture risk. © 2011 American Society for Bone and Mineral Research.     

Engaging in cognitive activities, aging, and mild cognitive impairment: a population-based study

The authors investigated whether engaging in cognitive activities is associated with aging and mild cognitive impairment (MCI) in a cross-sectional study derived from an ongoing population-based study of normal cognitive aging and MCI in Olmsted County, MN. A random sample of 1,321 study participants ages 70 to 89 (N=1,124 cognitively normal persons, and N=197 subjects with MCI) were interviewed about the frequency of cognitive activities carried out in late life (within 1 year of the date of interview). Computer activities; craft activities, such as knitting, quilting, etc.; playing games; and reading books were associated with decreased odds of having MCI. Social activities, such as traveling, were marginally significant. Even though the point-estimates for reading magazines, playing music, artistic activities, and group activities were associated with reduced odds of having MCI, none of these reached statistical significance. The equally high prevalence of reading newspapers in both groups yielded no significant between-group difference.     

Distribution and metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) in female rats and their pups at dietary doses

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mammary carcinogen in female rats and is present in a wide variety of cooked meats. We address here the excretion of PhIP and its metabolites into the breast-milk of lactating rats and the ability of chlorophyllin, a food product derivative with chemopreventive properties, to affect these levels at low PhIP doses. Lactating female F344 rats with suckling pups were orally administered 50, 500 and 1000 ng [14C]PhIP/kg body weight. The excretion of the [14C]PhIP into milk and its distribution among the mammary tissue, liver and blood of the dam, as well as among stomach contents and liver of their suckling pups was measured using accelerator mass spectrometry (AMS). PhIP, PhIP-4'- sulfate, 4'-hydroxy-PhIP, and N2-hydroxy-PhIP-N3-glucuronide were found in the milk at all doses. The chlorophyllin (500 microg/kg) co- administration with PhIP (500 ng/kg) caused increased levels of [14C]PhIP in the milk (32%) and stomach contents (35%) of the pups relative to the animals not receiving chlorophyllin at these low PhIP doses. In contrast, lower [14C]PhIP levels in the chlorophyllin treated animals were observed in the blood (47%) and mammary tissue (68%) of the dam, as well as the pup's liver tissue (37%) compared to the animals receiving only PhIP. Chlorophyllin co-administration resulted in an increased amount of N2-hydroxy-PhIP-N3-glucuronide (42%), increased PhIP (79%) and decreased levels of PhIP-4'-sulphate (77%) relative to the animals not receiving chlorophyllin. These results suggest that PhIP and PhIP metabolites are present in the breast-milk of lactating rats at human dietary PhIP exposures and that PhIP is absorbed by the newborn. Furthermore, these results suggest that other dietary components can affect the dosimetry of PhIP in breast-feeding offspring.      

In vivo photodynamic inactivation of Candida albicans using chloro‐aluminum phthalocyanine

This study evaluated the photoinactivation of Candida albicans in a murine model of oral candidiasis using chloro‐aluminum phthalocyanine (ClAlP) encapsulated in cationic nanoemulsions (NE) and chloro‐aluminum phthalocyanine (ClAlP) diluted in DMSO (DMSO) as photosensitizer (PS). Seventy‐five 6‐week‐old female Swiss mice were immunosuppressed and inoculated with C. albicans to induce oral candidiasis. PDT was performed on the tongue by the application of the photosensitizers and LED light (100 J cm^?2–660 nm). Twenty‐four hours and 7 days after treatments, microbiological evaluation was carried out by recovering C. albicans from the tongue of animals (CFU ml^?1). Then, mice were sacrificed and the tongues were surgically removed for histological and biomolecular analysis of pro‐ and anti‐inflammatory cytokines. Data were analyzed by ANOVA followed by Tukey's post hoc test. ClAlP‐NE‐mediated PDT reduced 2.26 log₁₀ of C. albicans recovered from the tongue when compared with the control group (P?L?) (P < 0.05). PDT did not promote adverse effects on the tongue tissue. Seven days after treatment, all animals were completely healthy. In summary, PDT mediated by chloro‐aluminum phthalocyanine entrapped in cationic nanoemulsions was effective in reducing C. albicans recovered from the oral lesions of immunocompromised mice.     

A bowel symptom questionnaire for the elderly.

While functional gastrointestinal complaints are common in the elderly, valid instruments for their assessment are lacking. We have developed the elderly bowel symptom questionnaire (EBSQ) and report its feasibility, reliability, and validity in medical outpatients and a larger sample of the community (aged 65-93). Reliability was measured by a test-retest procedure, while concurrent validity was documented by comparing physician interview and self-report data. Reliability (median kappa 0.65, interquartile range 0.49-0.79), and validity (median kappa 0.68, interquartile range 0.51-0.80) were very acceptable. A random sample of 424 independently living elderly persons was obtained; 77% replied to the mail survey. Medical record review showed that no current diagnosis of irritable bowel syndrome was missed by the questionnaire. Our results confirm that the EBSQ was easy to understand and well accepted, and was a reliable and valid measure of gastrointestinal symptoms in older persons; this instrument may have important clinical and research applications.