Dissemination of evidence-based standards of care.

Standards of care pertain to crafting and implementing patient-centered treatment interventions. Standards of care must take into consideration the patient's gender, ethnicity, medical and dental history, insurance coverage (or socioeconomic level, if a private patient), and the timeliness of the targeted scientific evidence. This resolves into a process by which clinical decision-making about the optimal patient-centered treatment relies on the best available research evidence, and all other necessary inputs and factors to provide the best possible treatment. Standards of care must be evidence-based, and not merely based on the evidence - the dichotomy being critical in contemporary health services research and practice. Evidence-based standards of care must rest on the best available evidence that emerges from a concerted hypothesis-driven process of research synthesis and meta-analysis. Health information technology needs to become an every-day reality in health services research and practice to ensure evidence-based standards of care. Current trends indicate that user-friendly methodologies, for the dissemination of evidence-based standards of care, must be developed, tested and distributed. They should include approaches for the quantification and analysis of the textual content of systematic reviews and of their summaries in the form of critical reviews and lay-language summaries

Epigenetic regulation of osteogenesis: human embryonic palatal mesenchymal cells.

Mesenchymal stem cells (MSCs) provide an appropriate model to study epigenetic changes during osteogenesis and bone regeneration due to their differentiation potential. Since there are no unique markers for MSCs, methods of identification are limited. The complex morphology of human embryonic palatal mesenchyme stem cell (HEPM) requires analysis of fractal dimensions to provide an objective quantification of self-similarity, a statistical transformation of cellular shape and border complexity. We propose the hypothesis of a study to compare and contrast sequential steps of osteogenic differentiation in HEPMs both phenotypically using immunocytochemistry, and morphometrically using fractal analysis from undifferentiated passage 1 (P1) to passage 7 (P7) cells. The proof-of-concept is provided by results we present here that identify and compare the modulation of expression of certain epigenetic biomarkers (alkaline phosphatase, ALP; stromal interaction molecule-1, STRO-1; runt-related transcription factor-2, RUNX2), which are established markers of osteogenesis in bone marrow studies, of osteoblastic/skeletal morphogenesis, and of osteoblast maturation. We show that Osteoinductive medium (OIM) modulates the rate of differentiation of HEPM into Run-2+ cells, the most differentiated subpopulation, followed by ALP+ and STRO-1+ cells. Taken together, our phenotypical and morphometric data demonstrate the feasibility of using HEPM to assess osteogenic differentiation from an early undifferentiated to a differentiated stage. This research model may lay the foundation for future studies aimed at characterizing the epigenetic characteristics of osteoimmunological disorders and dysfunctions (e.g., osteoarthritis, temporomandibular joint disorders), so that proteomic profiling can aid the diagnosis and monitor the prognosis of these and other osteoimmunopathologies

Immune surveillance of nasopharyngeal carcinoma (NpC)

In the U.S., nasopharyngeal carcinoma (NpC) kills >7,600 each year. Deaths are predominantly among adult men, and in most cases, early detection and treatment can save lives. Despite the annual spending of approximately 3.2 billion dollars on head and neck cancer research, NpC remains a neglected disease since its fatality rates are among the lowest nation wide. The relative survival rates from NpC have not improved in the U.S. in the last 20 years. Infection with Epstein Barr Virus (EBV) is an important co-factor in the etiology of NpC. In other regions of the word (e.g., South-East Asia, Latin America), EBV infection and NpCrelated prevalence and mortality are substantially higher and more alarming. Epidemiological data indicate high prevalence of EBV infection and increased risk for NpC among Central and South American and Asian immigrants in the U.S., and also predict a sharp increase in NpC incidence in the next decade. To face this emerging threat, it is important to develop and validate novel modes of detection and intervention for NpC. To this end, we characterized the proteomic signature of NpC, and of the tumor infiltrating lymphocytes of the CD8+, activated (CD38+, mTOR+) and regulatory immune cell (FoxP3+) phenotype. Paraffinized biopsies were processed, and tissue microarrays constructed and tested by immunohistochemistry and triimmunohistofluorescence for a battery of signaling markers, including AKT and PI3K, in conjunction with EBV status and ANKRD11, an NpC susceptibility biomarker. Microphotographs, analyzed and quantified by confocal microscopy and fractal analysis, suggest new avenues for immunotherapies of NpC

Deficiencies in Natural Killer Cell Numbers, Expansion, and Function at the Pre-Neoplastic Stage of Pancreatic Cancer by KRAS Mutation in the Pancreas of Obese Mice

The combined/synergistic effect of genetic mutation of KRAS in the pancreas and obesity, a life-style factor on suppression of natural killer (NK) cells at the pre-neoplastic stage of pancreatic cancer has not been investigated and is the subject of this report. Obese mice with KRAS (KC) mutation in the pancreas fed with high-fat calorie diet (HFCD) exhibit severe deficiencies in the NK cell expansion and function at the pre-neoplastic stage of pancreatic cancer. Decreased NK cell-mediated cytotoxicity is observed in the peripheral blood, spleen, pancreas, and peri-pancreatic adipose tissue in obese KC mice, whereas in bone marrow an increased NK cell-mediated cytotoxicity is observed when compared to lean WT mice fed with control diet (CD). Obese KC mice on HFCD demonstrated the least ability to expand NK cells or induce NK cell-mediated cytotoxicity when compared to the other groups of mice. Indeed, the following profile WT/CD > WT/HFCD > KC/CD > KC/HFCD was seen for the ability to expand NK cells or mediate cytotoxicity among four groups of mice in spleen, peripheral blood, pancreas, and peri-pancreatic adipose tissue. Sorted NK cells from the splenocytes of four groups of mice also exhibited the same profiles for the cytotoxicity as the unsorted splenocytes, and a decreased IFN-γ secretion could be seen in cultures of NK cells from KC mice fed with either CD or HFCD. Cultures of NK cells with autologous monocytes from obese KC mice fed with HFCD exhibited decreased cytotoxicity and IFN-γ secretion, whereas cultures of allogeneic NK cells from WT mice fed with CD with osteoclasts of obese mice fed with HFCD demonstrated decreased cytotoxicity but augmented IFN-γ secretion. Increased IL-6 along with decreased IFN-γ and cell-mediated cytotoxicity by the NK cells, within NK-adipose tissue of KC/HFCD mice, may provide safe microenvironment for the expansion of pancreatic tumors

Expanding the Grading of Recommendations Assessment, Development, and Evaluation (Ex-GRADE) for Evidence-Based Clinical Recommendations: Validation Study

Clinicians use general practice guidelines as a source of support for their intervention, but how much confidence should they place on these recommendations? How much confidence should patients place on these recommendations? Various instruments are available to assess the quality of evidence of research, such as the revised Wong scale (R-Wong) which examines the quality of research design, methodology and data analysis, and the revision of the assessment of multiple systematic reviews (R-AMSTAR), which examines the quality of systematic reviews

Ebola: translational science considerations

We are currently in the midst of the most aggressive and fulminating outbreak of Ebola-related disease, commonly referred to as “Ebola”, ever recorded. In less than a year, the Ebola virus (EBOV, Zaire ebolavirus species) has infected over 10,000 people, indiscriminately of gender or age, with a fatality rate of about 50%. Whereas at its onset this Ebola outbreak was limited to three countries in West Africa (Guinea, where it was first reported in late March 2014, Liberia, where it has been most rampant in its capital city, Monrovia and other metropolitan cities, and Sierra Leone), cases were later reported in Nigeria, Mali and Senegal, as well as in Western Europe (i.e., Madrid, Spain) and the US (i.e., Dallas, Texas; New York City) by late October 2014. World and US health agencies declared that the current Ebola virus disease (EVD) outbreak has a strong likelihood of growing exponentially across the world before an effective vaccine, treatment or cure can be developed, tested, validated and distributed widely. In the meantime, the spread of the disease may rapidly evolve from an epidemics to a full-blown pandemic. The scientific and healthcare communities actively research and define an emerging kaleidoscope of knowledge about critical translational research parameters, including the virology of EBOV, the molecular biomarkers of the pathological manifestations of EVD, putative central nervous system involvement in EVD, and the cellular immune surveillance to EBOV, patient-centered anthropological and societal parameters of EVD, as well as translational effectiveness about novel putative patient-targeted vaccine and pharmaceutical interventions, which hold strong promise, if not hope, to curb this and future Ebola outbreaks. This work reviews and discusses the principal known facts about EBOV and EVD, and certain among the most interesting ongoing or future avenues of research in the field, including vaccination programs for the wild animal vectors of the virus and the disease from global translational science perspective