The Effect of a Bidirectional Exchange on Faculty and Institutional Development in a Global Health Collaboration

Purpose

The MUYU Collaboration is a partnership between Mulago Hospital-Makerere University College of Health Sciences (M-MakCHS), in Kampala, Uganda, and the Yale University School of Medicine. The program allows Ugandan junior faculty to receive up to 1 year of subspecialty training within the Yale hospital system. The authors performed a qualitative study to assess the effects of this program on participants, as well as on M-MakCHS as an institution.

Methods

Data was collected via semi-structured interviews with exchange participants. Eight participants (67% of those eligible as of 4/2012) completed interviews. Study authors performed data analysis using standard qualitative data analysis techniques.

Results

Analysis revealed themes addressing the benefits, difficulties, and opportunities for improvement of the program. Interviewees described the main benefit of the program as its effect on their fund of knowledge. Participants also described positive effects on their clinical practice and on medical education at M-MakCHS. Most respondents cited financial issues as the primary difficulty of participation. Post-participation difficulties included resource limitations and confronting longstanding institutional and cultural habits. Suggestions for programmatic improvement included expansion of the program, ensuring appropriate management of pre-departure expectations, and refinement of program mentoring structures. Participants also voiced interest in expanding post-exchange programming to ensure both the use of and the maintenance of new capacity.

Conclusions

The MUYU Collaboration has benefitted both program participants and M-MakCHS, though these benefits remain difficult to quantify. This study supports the assertion that resource-poor to resource-rich exchanges have the potential to provide significant benefits to the resource-poor partner.     

Dietary choice for a balanced nutrient intake increases the mean and reduces the variance in the reproductive performance of male and female cockroaches

Sexual selection may cause dietary requirements for reproduction to diverge across the sexes and promote the evolution of different foraging strategies in males and females. However, our understanding of how the sexes regulate their nutrition and the effects that this has on sex‐specific fitness is limited. We quantified how protein (P) and carbohydrate (C) intakes affect reproductive traits in male (pheromone expression) and female (clutch size and gestation time) cockroaches (Nauphoeta cinerea). We then determined how the sexes regulate their intake of nutrients when restricted to a single diet and when given dietary choice and how this affected expression of these important reproductive traits. Pheromone levels that improve male attractiveness, female clutch size and gestation time all peaked at a high daily intake of P:C in a 1:8 ratio. This is surprising because female insects typically require more P than males to maximize reproduction. The relatively low P requirement of females may reflect the action of cockroach endosymbionts that help recycle stored nitrogen for protein synthesis. When constrained to a single diet, both sexes prioritized regulating their daily intake of P over C, although this prioritization was stronger in females than males. When given the choice between diets, both sexes actively regulated their intake of nutrients at a 1:4.8 P:C ratio. The P:C ratio did not overlap exactly with the intake of nutrients that optimized reproductive trait expression. Despite this, cockroaches of both sexes that were given dietary choice generally improved the mean and reduced the variance in all reproductive traits we measured relative to animals fed a single diet from the diet choice pair. This pattern was not as strong when compared to the single best diet in our geometric array, suggesting that the relationship between nutrient balancing and reproduction is complex in this species.     

Osteoporosis in experimental postmenopausal polyarthritis: the relative contributions of estrogen deficiency and inflammation

Generalized osteoporosis in postmenopausal rheumatoid arthritis (RA) is caused both by estrogen deficiency and by the inflammatory disease. The relative importance of each of these factors is unknown. The aim of this study was to establish a murine model of osteoporosis in postmenopausal RA, and to evaluate the relative importance and mechanisms of menopause and arthritis-related osteoporosis. To mimic postmenopausal RA, DBA/1 mice were ovariectomized, followed by the induction of type II collagen-induced arthritis. After the mice had been killed, paws were collected for histology, one femur for bone mineral density (BMD) and sera for analyses of markers of bone resorption (RatLaps; type I collagen cross-links, bone formation (osteocalcin) and cartilage destruction (cartilage oligomeric matrix protein), and for the evaluation of antigen-specific and innate immune responsiveness. Ovariectomized mice displayed more severe arthritis than sham-operated controls. At termination of the experiment, arthritic control mice and non-arthritic ovariectomized mice displayed trabecular bone losses of 26% and 22%, respectively. Ovariectomized mice with arthritis had as much as 58% decrease in trabecular BMD. Interestingly, cortical BMD was decreased by arthritis but was not affected by hormonal status. In addition, markers of bone resorption and cartilage destruction were increased in arthritic mice, whereas markers of bone formation were increased in ovariectomized mice. This study demonstrates that the loss of endogenous estrogen and inflammation contribute additively and equally to osteoporosis in experimental postmenopausal polyarthritis. Markers of bone remodeling and bone marrow lymphocyte phenotypes indicate different mechanisms for the development of osteoporosis caused by ovariectomy and arthritis in this model.     

Influence of fungi on growth and survival of Onychiurus armatus (Collembola) in a metal polluted soil

Summary The influence of food quantity and quality on growth and survival of Onychiurus armatus (Tullb.) in metal polluted environments has been investigated in laboratory experiments. The Collembola was reared on five species of fungi isolated from a metal polluted soil close to a brass mill in SE Sweden.Survival of O. armatus was improved when fungal biomass was continuously added in a polluted mor (1,300 ppm Zn and 200 ppm Cu), and when specimens were fed metal polluted fungi for 1, 3 and 7 days a week, only those that were starved had increased mortality. Allometric growth, on the other hand, was significantly reduced when Collembola was given surplus of metal polluted fungi, whereas growth losses caused by metals were offset by protein rich food. Hence, sufficient food quantities alone could overcome mortality losses but not growth retardation in a metal polluted environment.Feeding preference of O. armatus was not determined by the protein content of the fungi although this was beneficial for growth. Metals changed the relative palatability of fungal species, but one of the metal tolerant species, Paecilomyces farinosus, which was also protein rich, remained reasonably attractive for O. armatus also when it was metal polluted. The mechanisms by which growth and survival of O. armatus were promoted by a combination of protein and Zn/Cu rich fungi seemed to be crucial in understanding the fate of a population of this species in a metal polluted soil.     

Expression of EGR-1 in a subset of olfactory bulb dopaminergic cells

In the adrenal medulla, binding of the immediate early gene (IEG) proteins, EGR-1 (ZIF-268/KROX-24/NGFI-A) and AP-1, to the tyrosine hydroxylase (Th) proximal promoter mediate inducible Th expression. The current study investigated the potential role of EGR-1 in inducible Th expression in the olfactory bulb (OB) since IEGs bound to the AP-1 site in the Th proximal promoter are also necessary for activity-dependent OB TH expression. Immunohistochemical analysis of a naris-occluded mouse model of odor deprivation revealed weak EGR-1 expression levels in the OB glomerular layer that were activity-dependent. Immunofluorescence analysis indicated that a majority of glomerular cells expressing EGR-1 also co-expressed TH, but only small subset of TH-expressing cells contained EGR-1. By contrast, granule cells, which lack TH, exhibited EGR-1 expression levels that were unchanged by naris closure. Together, these finding suggest that EGR-1 mediates activity-dependent TH expression in a subset of OB dopaminergic neurons, and that there is differential regulation of EGR-1 in periglomerular and granule cells.     

Localization of cytochrome P450 CYP2S1 expression in human tissues by in situ hybridization and immunohistochemistry.

CYP2S1 is a recently discovered dioxin-inducible member of the cytochrome P450 superfamily. It has been shown to be involved in the metabolism of some aromatic hydrocarbons as well as retinoic acid, suggesting a role in biotransformation of both exogenous and endogenous compounds. In this study, we used mRNA in situ hybridization and immunohistochemistry to investigate the cellular localization of CYP2S1 in various human tissues using tissue microarrays. High expression levels were observed mainly in epithelial cell types, especially in the epithelia frequently exposed to xenobiotics. In the respiratory tract, the expression was strong in nasal cavity, bronchi, and bronchioli, whereas it was low in the alveolar lining cells. Similarly, CYP2S1 was highly expressed in the epithelial cells throughout the gastrointestinal tract. Strong epithelial expression was also observed in uterine cervix, urinary bladder, and skin. In many exocrine glands (e.g., adrenal gland and pancreas), secretory epithelial cells showed moderate to strong expression levels. In the liver, the expression was low. CYP2S1 was highly expressed in epithelial cells that are major targets for carcinogen exposure and common progenitor cells to tumor development. Indeed, we found strong CYP2S1 expression in many tumors of epithelial origin.     

Dynamic readjustment of parental methylation patterns of the 5'-flank of the mouse H19 gene during in vitro organogenesis

Gametic marks are stably propagated in order to manifest parent of origin-specific expression patterns of imprinted genes in the developing conceptus. Although the character of the imprint has not yet been fully elucidated, there is compelling evidence that it involves a methylation mark. This is exemplified by a region upstream of the H19 gene, which is not only methylated in a parent of origin-specific manner, but also regulates the silencing of the maternal Igf2 and paternal H19 alleles, respectively. We show here that the parental-specific methylation patterns within the differentially methylated domain (DMD) are perturbed in the soma during in vitro organogenesis. Under these conditions, the paternal DMD allele becomes partially demethylated, whereas the maternal DMD allele gains methylation. Despite these effects, there were no changes in allelic Igf2 or H19 expression patterns in the embryo. Finally, we show that although TSA derepresses the paternal H19 allele in ectoplacental cone when in vitro developed, there is no discernible effect on the methylation status of the paternally inherited 5'-flank in comparison to control samples. Collectively, this data demonstrates that the parental mark is sensitive to a subset of environmental cues and that a certain degree of plasticity of the gametic mark is tolerated without affecting the manifestation of the imprinted state.     

X-ray microanalysis of airway surface liquid in the mouse

The ionic composition of airway surface liquid (ASL) has been debated, and, in particular for the mouse, a wide range of values has been published. Two techniques were developed to measure the elemental composition of the ASL. X-ray microanalysis of ASL was carried out at low temperature on trachea removed from isoflurane-anesthetized animals and shock-frozen. In the second technique, dextran beads were placed on top of the epithelium of the trachea removed from pentobarbital-anesthetized animals, left to equilibrate with the ASL, dried, and subjected to X-ray microanalysis. Both techniques showed that mouse tracheal ASL has significantly lower concentrations of Na and Cl (approximately 60-80 mM) than serum. Differences between the two techniques were due to different sampling of mucus. CFTR(-/-) mice had significantly higher concentrations of Na and Cl in their ASL than age-matched controls. Pilocarpine or isoproterenol stimulation significantly reduced the ion concentrations in tracheal ASL. ASL was also collected with the dextran bead method from the nasal cavity in situ in pentobarbital-anesthetized animals. In control animals, the elemental composition of nasal fluid was similar to that of tracheal ASL. Pilocarpine stimulation caused a significant increase in Na, Cl, and K; stimulation with isoproterenol or phenylephrine caused a significant increase only in K. It is concluded that mouse ASL under unstimulated conditions is hypotonic, which may be related to the relative paucity of submucosal glands in the mouse trachea.     

CTCF shapes chromatin by multiple mechanisms: the impact of 20 years of CTCF research on understanding the workings of chromatin

More than 10⁹ base pairs of the genome in higher eucaryotes are positioned in the interphase nucleus such that gene activation, gene repression, remote gene regulation by enhancer elements, and reading as well as adjusting epigenetic marks are possible. One important structural and functional component of chromatin organization is the zinc finger factor CTCF. Two decades of research has advanced the understanding of the fundamental role that CTCF plays in regulating such a vast expanse of DNA.