Is there pandemic vitamin D deficiency in the black population? A review of evidence

Although 1,25-dihydroxyvitamin D [1,25(OH)2D] is the biologically active form of vitamin D, measurement of the total serum 25-hydroxyvitamin D [25(OH)D] level is the gold standard used to define vitamin D status. Currently, it is widely accepted that serum 25 (OH) D levels below 20 ng/ml defines vitamin D deficiency. According to this definition, there appears to be pandemic vitamin D deficiency in the Black population. However, there is no evidence of higher-thannormal rates of common complications and symptomology of true vitamin D deficiency in the Black population. What is going on? We researched the MEDLINE databases to find studies, from 1967 to present, that directly compare between Blacks and Caucasians the following: serum vitamin D level, serum calcium level, serum parathyroid hormone level, bone mineral density and health, and non-skeletal risks associated with vitamin D deficiency. The available studies consistently show that Blacks tend to have serum 25(OH)D levels in the deficient range while their serum 1,25(OH)2D level is similar to, if not even slightly higher than that of Caucasians, and that the serum Ca2+ level in Blacks is virtually identical to that in Caucasians. Therefore, it appears that the serum 25(OH)D level is not the best marker of vitamin D sufficiency or deficiency in Blacks. In the future, clinical evaluation of the vitamin D status in the Black population needs to consider other serum biomarkers such as 1,25(OH)2D and/or bioavailable 25(OH)

Nonlinear Response Time-Dependent Density Functional Theory Combined with the Effective Fragment Potential Method

This work presents an extension of the linear response TDDFT/EFP method to the nonlinear-response regime together with the implementation of nonlinear-response TDDFT/EFP in the quantum-chemistry computer package GAMESS. Included in the new method is the ability to calculate the two-photon absorption cross section and to incorporate solvent effects via the EFP method. The nonlinear-response TDDFT/EFP method is able to make correct qualitative predictions for both gas phase values and aqueous solvent shifts of several important nonlinear properties

Nutrition in Medical Education: Where do we stand and what needs to be explored?

Introduction: Dietary interventions and nutrition care improve patient outcomes and reduce healthcare costs. Despite status as a necessary topic in medical school education, many U.S. medical schools do not adequately prepare future physicians for everyday nutritional challenges in clinical practice. There is immense research behind the necessity of nutrition education but little concerning the methods of implementing this change. The purpose of this work was to review the current innovations of nutrition curriculum in the literature and discuss future directions for our medical school. Method: A systematic search of scientific literature databases was performed to examine existing literature about the current state of nutrition curriculum and identify current methods of improving nutrition curriculum. A database search of the undergraduate GW SMHS curricula helped us map where nutrition is currently taught and look into ways to expand and integrate it. Results: Shortcomings in sufficient nutrition education result from lack of proficient faculty, low funding, and lack of established core curricula with guidelines and protocols. Additionally, international medical schools have recognized their deficiency in nutrition education compared to U.S. standards. U.S. institutions making headway in new nutrition education programs include The University of North Carolina, Chapel Hill, Boston University School of Medicine, Southern Illinois School of Medicine, University of Nevada School of Medicine, Northwestern University Feinberg School of Medicine, University of Colorado School of Medicine, Mercer University School of Medicine, and various institutions introducing “culinary medicine”. Successful nutrition integration should be spread longitudinally across all years with an emphasis on active-learning techniques over rote memorization. Creativity, chief support, an established taskforce, trained faculty, and evaluation methods are essential tools to enhance medical curriculum. Looking at GW SMHS curricula, nutrition is concentrated in the Pre-Clinical years with very little emphasis in the Clinical years, a common trend across most medical schools. Medical students may be more confident incorporating nutrition into patient care if nutrition were spread proportionally across all years to combine basic foundations with clinical application. Conclusion: Expanding nutrition curriculum at The George Washington University School of Medicine could involve utilizing the Nutrition in Medicine project developed by The University of North Carolina, Chapel Hill or bringing in internationally renowned chef José Andrés to expand on his previous culinary courses and incorporate nutrition fundamentals into the medical curriculum. Future directions need to evaluate existing programs, current initiatives, and their effectiveness in order to be able to improve programs across the continuum

Unexpectedly high prevalence of sarcoidosis in a representative U.S. Metropolitan population

SummaryThe prevalence of sarcoidosis in the United States is unknown, with estimates ranging widely from 1 to 40 per 100,000. We sought to determine the prevalence of sarcoidosis in our health system compared to other rare lung diseases and to further establish if the prevalence was changing over time. We interrogated the electronic medical records of all patients treated in our health system from 1995 to 2010 (1.48 million patients) using the common ICD9 codes for sarcoidosis (135), lung cancer (162), and several other lung diseases characterized, like sarcoidosis, as “rare lung diseases”. The patient demographic information (race, gender, age) was further analyzed to identify signature data patterns. The prevalence of sarcoidosis in our health system increased steadily from 164/100,000 in 1995 to 330/100,000 in 2010, and this trend could not be ascribed simply to changes in patient demographics or patient referral patterns. We further estimate that the prevalence of sarcoidosis exceeds 48 per 100,000 in Franklin County, Ohio, the demographic profile of which is nearly identical to that of the U.S. Sarcoidosis prevalence increased over time relative to lung cancer, a benchmark disease with stable disease prevalence, and exceeded that of other rare lung diseases. We postulate that the observed 2-fold increase in sarcoidosis disease prevalence in our health system is primarily related to improved detection and diagnostic approaches, and we conclude that the actual prevalence of sarcoidosis in central Ohio greatly exceeds current U.S. estimates

Mucin binding reduces colistin antimicrobial activity

Colistin has found increasing use in treating drug-resistant bacterial lung infections, but potential interactions with pulmonary biomolecules have not been investigated. We postulated that colistin, like aminoglycoside antibiotics, may bind to secretory mucin in sputum or epithelial mucin that lines airways, reducing free drug levels. To test this hypothesis, we measured binding of colistin and other antibiotics to porcine mucin, a family of densely glycosylated proteins used as a surrogate for human sputum and airway mucin. Antibiotics were incubated in dialysis tubing with or without mucin, and concentrations of unbound antibiotics able to penetrate the dialysis tubing were measured over time using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The percentage of antibiotic measured in the dialysate after 4 h in the presence of mucin, relative to the amount without mucin, was 15% for colistin, 16% for polymyxin B, 19% for tobramycin, 52% for ciprofloxacin, and 78% for daptomycin. Antibiotics with the strongest mucin binding had an overall polybasic positive charge, whereas those with comparatively little binding were less basic. When comparing MICs measured with or without added mucin, colistin and polymyxin B showed >100-fold increases in MICs for multiple Gram-negative bacteria. Preclinical evaluation of mucin binding should become a standard procedure when considering the potential pulmonary use of new or existing antibiotics, particularly those with a polybasic overall charge. In the airways, mucin binding may reduce the antibacterial efficacy of inhaled or intravenously administered colistin, and the presence of sub-MIC effective antibiotic concentrations could result in the development of antibiotic resistance

THE SPRING MIGRATION OF ADULT NORTH AMERICAN OSPREYS

Most North American Ospreys (Pandion haliaetus) are migratory, breeding in northern latitudes and migrating long distances to and from their wintering grounds in the tropics. Although fall migration patterns of North American Ospreys have been described and studied, very little has been published about the spring migration of these birds. We used satellite telemetry to: (1) determine the characteristics (timing, duration, migratory routes) of spring migrations of Ospreys; (2) determine if differences in spring migration patterns existed between sexes and among three breeding populations (east coast, midwestern, and western); and (3) compare consecutive fall and spring migrations of individual Ospreys. The median dates for departure from the wintering grounds and arrival on the breeding grounds did not differ significantly between adult male and female Ospreys. Compared to their fall migrations, all male and all east coast Ospreys spent fewer days on migration, fewer days in stopover periods along the migration route, traveled shorter distances overall, and traveled farther (on average) each day during spring. In contrast, fall and spring migration characteristics of all female and western Ospreys were similar. Our findings suggest that, although sex and breeding location might influence the spring migration strategy used by individual Ospreys, both males and females minimize the time spent on migration to ensure a timely arrival on the breeding grounds to establish or defend a nesting territory

Widespread recombination, reassortment, and transmission of unbalanced compound viral genotypes in natural arenavirus infections.

Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential

The effect of distance on reaction time in aiming movements

Target distance affects movement duration in aiming tasks but its effect on reaction time (RT) is poorly documented. RT is a function of both preparation and initiation. Experiment 1 pre-cued movement (allowing advanced preparation) and found no influence of distance on RT. Thus, target distance does not affect initiation time. Experiment 2 removed pre-cue information and found that preparing a movement of increased distance lengthens RT. Experiment 3 explored movements to targets of cued size at non-cued distances and found size altered peak speed and movement duration but RT was influenced by distance alone. Thus, amplitude influences preparation time (for reasons other than altered duration) but not initiation time. We hypothesise that the RT distance effect might be due to the increased number of possible trajectories associated with further targets: a hypothesis that can be tested in future experiments

The combination of temozolomide-irinotecan regresses a doxorubicin-resistant patient-derived orthotopic xenograft (PDOX) nude-mouse model of recurrent Ewing's sarcoma with a FUS-ERG fusion and CDKN2A deletion: Direction for third-line patient therapy.

The aim of the present study was to determine the usefulness of a patient-derived orthotopic xenograft (PDOX) nude-mouse model of a doxorubicin-resistant metastatic Ewing's sarcoma, with a unique combination of a FUS-ERG fusion and CDKN2A deletion, to identify effective drugs for third-line chemotherapy of the patient. Our previous study showed that cyclin-dependent kinase 4/6 (CDK4/6) and insulin-like growth factor-1 receptor (IGF-1R) inhibitors were effective on the Ewing's sarcoma PDOX, but not doxorubicin, similar to the patient's resistance to doxorubicin. The results of the previous PDOX study were successfully used for second-line therapy of the patiend. In the present study, the PDOX mice established with the Ewing's sarcoma in the right chest wall were randomized into 5 groups when the tumor volume reached 60 mm3: untreated control; gemcitabine combined with docetaxel (intraperitoneal [i.p.] injection, weekly, for 2 weeks); irinotecan combined with temozolomide (irinotecan: i.p. injection; temozolomide: oral administration, daily, for 2 weeks); pazopanib (oral administration, daily, for 2 weeks); yondelis (intravenous injection, weekly, for 2 weeks). All mice were sacrificed on day 15. Body weight and tumor volume were assessed 2 times per week. Tumor weight was measured after sacrifice. Irinotecan combined with temozolomide was the most effective regimen compared to the untreated control group (p=0.022). Gemcitabine combined with docetaxel was also effective (p=0.026). Pazopanib and yondelis did not have significant efficacy compared to the untreated control (p=0.130, p=0.818). These results could be obtained within two months after the physician's request and were used for third-line therapy of the patient