Culture Clash: The Medical Encounter as a Source of Health Disparities

In 2002, the Institute of Medicine (IOM) issued its landmark report entitled Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care. The report identified three potential sources of healthcare disparities for minority and other underserved communities - patient-level factors, healthcare system-level factors, and care process-level factors. Care process-level factors included issues such as bias, stereotyping, prejudice and clinical uncertainty on the part of healthcare providers. Recommendations to address these factors included a call for additional research, interventions to enhance patient-provider communication, and integration of cross-cultural education into the training of all current and future health professionals. In this presentation, I will briefly review models of health disparities and the role of provider beliefs in these disparities. I will describe various forms of bias (e.g., stereotypes, prejudice,implicit, explicit) and patient-level outcomes of experiencing bias. I will discuss the current research into provider bias and its limitations. Finally, I will discuss the relationship of cultural competence to bias. Specifically, I will propose a model for Culturally Competent Communication and how the use of the model for assessing and training provider behavior could serve as a framework for addressing provider bias as a cause of health disparities

6'-Methoxy Raloxifene-analog enhances mouse bone properties with reduced estrogen receptor binding

Raloxifene (RAL) is an FDA-approved drug used to treat osteoporosis in postmenopausal women. RAL suppresses bone loss primarily through its role as a selective estrogen receptor modulator (SERM). This hormonal estrogen therapy promotes unintended side effects, such as hot flashes and increased thrombosis risk, and prevents the drug from being used in some patient populations at-risk for fracture, including children with bone disorders. It has recently been demonstrated that RAL can have significant positive effects on overall bone mechanical properties by binding to collagen and increasing bone tissue hydration in a cell-independent manner. A Raloxifene-Analog (RAL-A) was synthesized by replacing the 6-hydroxyl substituent with 6-methoxy in effort to reduce the compound's binding affinity for estrogen receptors (ER) while maintaining its collagen-binding ability. It was hypothesized that RAL-A would improve the mechanical integrity of bone in a manner similar to RAL, but with reduced estrogen receptor binding. Molecular assessment showed that while RAL-A did reduce ER binding, downstream ER signaling was not completely abolished. In-vitro, RAL-A performed similarly to RAL and had an identical concentration threshold on osteocyte cell proliferation, differentiation, and function. To assess treatment effect in-vivo, wildtype (WT) and heterozygous (OIM+/-) female mice from the Osteogenesis Imperfecta (OI) murine model were treated with either RAL or RAL-A from 8 weeks to 16 weeks of age. There was an untreated control group for each genotype as well. Bone microarchitecture was assessed using microCT, and mechanical behavior was assessed using 3-point bending. Results indicate that both compounds produced analogous gains in tibial trabecular and cortical microarchitecture. While WT mechanical properties were not drastically altered with either treatment, OIM+/- mechanical properties were significantly enhanced, most notably, in post-yield properties including bone toughness. This proof-of-concept study shows promising results and warrants the exploration of additional analog iterations to further reduce ER binding and improve fracture resistance

African trypanosomes

Abstract African trypanosomes cause human African trypanosomiasis and animal African trypanosomiasis. They are transmitted by tsetse flies in sub-Saharan Africa. Although most famous for their mechanisms of immune evasion by antigenic variation, there have been recent important studies that illuminate important aspects of the biology of these parasites both in their mammalian host and during passage through their tsetse fly vector. This Primer overviews current research themes focused on these parasites and discusses how these biological insights and the development of new technologies to interrogate gene function are being used in the search for new approaches to control the parasite. The new insights into the biology of trypanosomes in their host and vector highlight that we are in a ‘golden age’ of discovery for these fascinating parasites

Comparison Of Cognitive Performance Following One Hour Of Passive Heating Or Walking In Older Adults: A Preliminary Analysis

Moderate-intensity exercise increases measures of cognitive performance such as working memory and cognitive flexibility. Hyperthermia can result in declines in cognitive performance through reduced motor function and response inhibition. However, these results have been observed during cognitive performance in the heat while core temperatures remain elevated. Heat therapy may promote improvements in cognitive function after treatment similar to exercise training by inducing a stress-related response. The purpose of this study was to compare cognitive performance immediately following one hour of moderate-intensity aerobic exercise or one hour of whole-body passive heating. METHODS: Four adults (age: 67.3 + 3.3 years, BMI: 29.0 + 5.4 kg/m2, 2 female) participated in a randomized repeated measures study. Participants completed either one hour of moderate intensity walking on a treadmill (TM; 65-75% age-predicted maximum heart rate) or one hour of seated passive heating (HEAT) in a controlled environmental heat chamber (32-35 degrees Celsius, \u3c 40% humidity). Cognitive performance was measured using computerized software (Automated Neuropsychological Assessment Metrics, ANAM, Vista LifeSciences, Inc.), which provides objective measures of cognitive performance through a variety of test batteries designed to measure variables such as motor coordination, cognitive flexibility, and response inhibition. Variables were analyzed as a change in score from the familiarization exam (pre- or post-treatment minus – baseline) to minimize the learning effect. RESULTS: No differences between measures of motor coordination (TM: 6 + 12.7 vs. 5 + 12.7; HEAT: 0 + 1.4 vs. -1 + 1.4), cognitive flexibility (TM: -1 + 1.4 vs. 1.5 + 0.7; HEAT: 3.5 + 0.7 vs. 3.5 + 0.7), or response inhibition (TM: 17 + 22.6 vs. 23.5 + 23.3; HEAT: 1.5 + 2.1 vs. 8 + 2.8) were found following either treatment. CONCLUSION: One bout of moderate intensity aerobic exercise or whole-body passive heating does not impair cognitive performance. In addition, one hour of passive heating does not result in decreased cognitive performance in older adults. Post-hyperthermic stress response did not impair cognitive function

Zoledronate and Raloxifene combination therapy enhances material and mechanical properties of diseased mouse bone

Current interventions to reduce skeletal fragility are insufficient at enhancing both the quantity and quality of bone when attempting to improve overall mechanical integrity. Bisphosphonates, such as Zoledronate (ZOL), are used to treat a variety of bone disorders by increasing bone mass to decrease fracture risk, but long-term use has been shown in some settings to compromise bone quality. Alternatively, Raloxifene (RAL) has recently been demonstrated to improve tissue quality and overall mechanical properties in a cell-independent manner by binding to collagen and increasing tissue hydration. We hypothesized that a combination of RAL and ZOL would improve mechanical and material properties of bone more than either monotherapy alone by enhancing both quantity and quality. In this study, wildtype (WT) and heterozygous (OIM+/−) male mice from the Osteogenesis Imperfecta (OI) murine model were treated with either RAL, ZOL, or both from 8 weeks to 16 weeks of age. Using the OIM model allows for investigation of therapeutic effects on a quality-based bone disease. Combination treatment resulted in higher trabecular architecture, cortical mechanical properties, and cortical fracture toughness in diseased mouse bone. Two fracture toughness properties, which are direct measures of the tissue's ability to resist the initiation and propagation of a crack, were significantly improved with combination treatment in OIM+/− compared to control. There was no significant effect on fracture toughness with either monotherapy alone in either genotype. Following the mass-based effects of ZOL, trabecular bone volume fraction was significantly higher with combination treatment in both genotypes. Combination treatment resulted in higher ultimate stress in both genotypes. RAL and combination treatment in OIM+/− also increased resilience compared to the control. In conclusion, this study demonstrates the beneficial effects of using combination drug treatments to increase bone mass while simultaneously improving tissue quality, especially to enhance the mechanical integrity of diseased bone. Combination therapies could be a potential method to improve bone health and combat skeletal fragility on both the microscopic and macroscopic levels

The Impact of Laser Control on The Porosity And Microstructure of Selective Laser Melted Nickel Superalloy 718

Additively manufacturing high performance metals by laser processing represents an exciting opportunity to exploit localized properties by varying input parameters throughout the process. This work explores the solidification and microstructural properties of selectively laser melted (SLM) Inconel 718 (IN718) using unique processing parameters. By employing traditional pulsed laser physics techniques, samples were manufactured with a continuous wave laser to study a potential ubiquitous approach. While the overall power density was controlled, the power, speed, and hatch spacing were varied. The porosity and grain sizes of the samples were characterized by optical and scanning electron microscopes. The influence of processing parameters showed physical differences in the final samples. Sample degradation was observed in higher power processes with porosity up 10%, likely due to increased temperatures and more intense thermal gradients

Anaerobic Performance in Female Collegiate Wrestlers During Ovulation Versus the Mid-luteal Phase of the Menstrual Cycle: A Pilot Study

Anaerobic performance may vary during different phases of the menstrual cycle. The greatest differences occur between the late-follicular phase (i.e., ovulation) and the mid-luteal phase. Optimal anaerobic performance may be observed during the mid-luteal phase. PURPOSE: To explore differences in upper and lower body anaerobic performance during ovulation versus the mid-luteal phase of the menstrual cycle in collegiate female wrestlers. METHODS: Six female collegiate wrestlers (age = 18.6 ± 0.2 yrs; height = 165.0 ± 0.5 cm; body mass = 79.7 ± 9.6 kg; lean body mass = 45.6 ± 2.8 kg; % body fat = 31.4 ± 6.6%) performed both upper and lower body Wingate tests, each lasting 30 seconds, during the ovulation and the mid-luteal phases of the menstrual cycle. Upper and lower body tests were performed 24 hours apart. Menstrual cycle phases were determined by calendar tracking, reverse estimation of ovulation, and administration of a urinary luteinizing hormone test assessed daily until positive results indicated ovulation. Lower body power was measured using a Velotron cycle ergometer, with a resistance of 0.075 kg/kg applied after a 5-second sprint at a resistance of 1 kg (50 W). Peak power (W) and relative power (W/kg) were measured. Upper body power was measured using a Monark hand ergometer with a 0.045 kg/kg resistance applied after a 5-second sprint at a resistance of 0.5 kg (25 W). Peak power (W) and relative power (W/kg) was calculated using rotation count, weight applied, and distance per rotation. Paired t-tests were used to analyze differences in means during the ovulation vs mid-luteal phases with a significance level of 0.05. RESULTS: There were no significant differences between trials for any variables measured. Lower body peak power (W) was 848.3 ± 126.1W vs 855.0 ± 143.9W. Lower body relative power (W/kg) was 11.8 ± 0.7W/kg vs 11.9 ± 0.8W/kg. Upper body peak power (W) was 162.1 ± 29.6 vs 160.2 ± 13.2W. Upper body relative power (W/kg) was 2.3 ± 0.4W/kg vs 2.2 ± 0.2W/kg. CONCLUSION: There may not be an optimal timing of significantly increased anaerobic performance in regard to menstrual phase in these wrestlers

Non-linear hierarchy of the quorum sensing signalling pathway in bloodstream form African trypanosomes.

Trypanosoma brucei, the agents of African trypanosomiasis, undergo density-dependent differentiation in the mammalian bloodstream to prepare for transmission by tsetse flies. This involves the generation of cell-cycle arrested, quiescent, stumpy forms from proliferative slender forms. The signalling pathway responsible for the quorum sensing response has been catalogued using a genome-wide selective screen, providing a compendium of signalling protein kinases phosphatases, RNA binding proteins and hypothetical proteins. However, the ordering of these components is unknown. To piece together these components to provide a description of how stumpy formation arises we have used an extragenic suppression approach. This exploited a combinatorial gene knockout and overexpression strategy to assess whether the loss of developmental competence in null mutants of pathway components could be compensated by ectopic expression of other components. We have created null mutants for three genes in the stumpy induction factor signalling pathway (RBP7, YAK, MEKK1) and evaluated complementation by expression of RBP7, NEK17, PP1-6, or inducible gene silencing of the proposed differentiation inhibitor TbTOR4. This indicated that the signalling pathway is non-linear. Phosphoproteomic analysis focused on one pathway component, a putative MEKK, identified molecules with altered expression and phosphorylation profiles in MEKK1 null mutants, including another component in the pathway, NEK17. Our data provide a first molecular dissection of multiple components in a signal transduction cascade in trypanosomes