Medical student debt and major life choices other than specialty.

BACKGROUND: Median indebtedness at graduation is now more than $170,000 for graduates of US Medical Schools. Debate still exists as to whether higher debt levels influence students to choose high paying non-primary care specialties. Notably, no previous research on the topic has taken into account cost of attendance when constructing a debt model, nor has any research examined the non-career major life decisions that medical students face. METHODS: Medical students were surveyed using an anonymous electronic instrument developed for this study. The survey was delivered through a link included in a study email and students were recruited from school wide listservs and through snowball sampling (students were encouraged to share a link to the survey with other medical students). No incentives were offered for survey completion. RESULTS: Responses were recorded from 102 US Allopathic medical schools (n=3,032), with 22 institutions (11 public, 11 private) meeting inclusion criteria of 10% student body response proportion (n=1,846). Students with higher debt relative to their peers at their home institution reported higher frequencies of feeling callous towards others, were more likely to choose a specialty with a higher average annual income, were less likely to plan to practice in underserved locations, and were less likely to choose primary care specialties. Students with higher aggregate amounts of medical student loan debt were more likely to report high levels of stress from their educational debt, to delay getting married and to report disagreement that they would choose to become a physician again, if given the opportunity to revisit that choice. Increases in both aggregate and relative debt were associated with delaying having children, delaying buying a house, concerns about managing and paying back educational debt, and worrying that educational debt will influence one's specialty choice. CONCLUSIONS: Medical student debt and particularly debt relative to peers at the same institution appears to influence the way that students approach major life choices like when to start a family, when to buy a home, and what specialty to choose. Future research should take into account cost of attendance when looking for the impact of medical student debt on major life choices.

Mannitol infusion within 15 min of cross-clamp improves living donor kidney preservation.

BACKGROUND: Optical coherence tomography (OCT) revealed that cells lining proximal convoluted tubules of living donor kidneys (LDKs) procured by laparoscopic procedures were very swollen in response to the brief period of ischemia experienced between the time of arterial vessel clamping and flushing the excised kidney with cold preservation solution. Damage to the tubules as a result of this cell swelling resulted in varying degrees of acute tubular necrosis (ATN) that slowed the recovery of the donor kidneys during the first 2 weeks after their transplantation. METHODS: To prevent this cell damage during LDK procurement, we changed the protocol for intravenous administration of mannitol (i.e., 12.5 or 25 g) to the donor. Specifically, we reduced the time of mannitol administration from 30 to 15 min or less before clamping the renal artery. RESULT: OCT revealed that this change in the timing of mannitol administration protected the human donor proximal tubules from normothermic-induced cell swelling. An evaluation of posttransplant recovery of renal function showed that patients treated with this modified protocol returned to normal renal function significantly faster than those treated with mannitol 30 min or more before clamping the renal artery. CONCLUSION: Because slow graft recovery in the first weeks after transplantation represents a risk factor for long-term graft function and survival, we believe that this change in pretreatment protocol will improve renal transplants in patients receiving LDK.

Estimating the number of low-income americans exposed to household air pollution from burning solid fuels.

BACKGROUND: Exposure to household air pollution (HAP) from inefficient biomass and coal stoves kills nearly 4 million people every year worldwide. HAP is an environmental risk associated with poverty that affects an estimated 3 billion people mostly in low- and middle-income countries. OBJECTIVES: Our goal was to estimate the number of low-income Americans exposed to potentially health-damaging concentrations of HAP. METHODS: We mapped county-level data for the percentage of households using wood, coal, and/or coke as their primary heating fuel along with percent of the population below the federal poverty level. Using U.S. Census data and the likelihood of fugitive emissions as reported in the literature, we estimated the number of low-income Americans potentially exposed to HAP. RESULTS: Solid fuel is the primary heating source for > 2.5 million U.S. households, or 6.5 million people. The mapping exercise showed several rural areas, primarily in the northern and western regions, that have high levels of solid-fuel use and poverty. We then identified 117 counties with high co-incident poverty and solid-fuel use as high-priority counties for research into potential health risks from HAP. We estimate that between 500,000 and 600,000 low-income people in the United States are likely exposed to HAP from burning solid fuels within their homes. CONCLUSION: HAP occurs within the United States and should be further investigated for adverse health risks, especially among those living in areas with rural poverty.

Household air pollution: a call for studies into biomarkers of exposure and predictors of respiratory disease.

Household air pollution (HAP) from indoor burning of biomass or coal is a leading global cause of morbidity and mortality, mostly due to its association with acute respiratory infection in children and chronic respiratory and cardiovascular diseases in adults. Interventions that have significantly reduced exposure to HAP improve health outcomes and may reduce mortality. However, we lack robust, specific, and field-ready biomarkers to identify populations at greatest risk and to monitor the effectiveness of interventions. New scientific approaches are urgently needed to develop biomarkers of human exposure that accurately reflect exposure or effect. In this Perspective, we describe the global need for such biomarkers, the aims of biomarker development, and the state of development of tests that have the potential for rapid transition from laboratory bench to field use.

Amphimedosides A-C: synthesis, chemoselective glycosylation, and biological evaluation.

The amphimedosides, discovered in 2006, are the first examples of naturally occurring glycosylated alkoxyamines. We report syntheses of amphimedosides A-C that feature a stereoselective oxyamine neoglycosylation and found that these alkaloids display modest cytotoxicity toward seven diverse human cancer cell lines, exhibiting IC(50) values ranging from 3.0 µM to greater than 100 µM.

Synthesis and biological evaluation of RON-neoglycosides as tumor cytotoxins.

Cardenolides such as digitoxin have been shown to inhibit cancer cell growth, to reduce cancer metastasis, and to induce apoptosis in tumor cells. Among the most potent digitoxin-based cytotoxins identified to date are MeON-neoglycosides generated via oxyamine neoglycosylation. Here, we report our studies of oxyamine neoglycosylation aimed at facilitating the elucidation of linkage-diversified digitoxin neoglycoside structure-activity relationships. We identified conditions suitable for the convenient synthesis of digitoxin neoglycosides and found that sugar structure, rather than RON-glycosidic linkage, exerts the strongest influence on neoglycoside yield and stereochemistry. We synthesized a library of digitoxin neoglycosides and assessed their cytotoxicity against eight human cancer cell lines. Consistent with previous findings, our data show that the structure of RON-neoglycosidic linkages influences both the potency and selectivity of digitoxin neoglycosides.

A Direct Comparison of the Anticancer Activities of Digitoxin MeON-Neoglycosides and O-Glycosides: Oligosaccharide Chain Length-Dependent Induction of Caspase-9-Mediated Apoptosis.

Digitoxin is a cardiac glycoside currently being investigated for potential use in oncology. While a number of structure-activity relationship studies have been conducted, an investigation of anticancer activity as a function of oligosaccharide chain length has not yet been performed. We generated mono-, di-, and tri-O-digitoxoside derivatives of digitoxin and compared their activity to the corresponding MeON-neoglycosides. Both classes of cardenolide derivatives display comparable oligosaccharide chain length-dependent cytotoxicity toward human cancer cell lines. Further investigation revealed that both classes of compounds induce caspase-9-mediated apoptosis in non-small cell lung cancer cells (NCI-H460). Since O-glycosides and MeON-neoglycosides share a similar mode of action, the convenience of MeON-neoglycosylation could be exploited in future SAR work to rapidly survey large numbers of carbohydrates to prioritize selected O-glycoside candidates for traditional synthesis.