Physicians’ Experiences and Opinions Regarding Strategies to Improve Care for Minority Patients

Objective: To assess the views and experiences of a select group of physicians interested in minority health issues regarding promising strategies to improve minority care. Methods: Physicians were asked to respond to a 17-item survey assessing the level of agreement, frequency of implementation of and interest in learning more about 7 promising strategies for alleviating disparities. Results: Most physicians (75-95%) agreed that the 7 proposed strategies could be useful to improve the quality of care provided to minority patients, but only 40-66% of physicians had implemented the strategies sometimes or often in their practices. Between 22 and 29% of physicians were interested in learning more about 6 of the 7 strategies, preferably by CME, seminars and newsletters. Conclusion: Physicians concerned with minority health issues agree that commonly suggested strategies for eliminating racial and ethnic disparities in health care could be useful, but have difficulty implementing such approaches

A Fatal Twist: Volvulus of the Small Intestine in a 46-Year-Old Woman

A 46-year-old woman presented to two emergency departments within 12 hours because of acute abdominal pain. Physical exam demonstrated tenderness and epigastric guarding. An ultrasound was interpreted as negative; she was discharged home. Later that evening, she was found dead. Postmortem exam revealed acute hemorrhagic necrosis of a segment of jejunum secondary to volvulus. Clinical clues suggesting presentations of small bowel volvulus are usually nonspecific; the diagnosis is typically confirmed at surgery. Her unremitting abdominal pain, persistent vomiting, and absolute neutrophilia were consistent with an acute process. The etiology of this volvulus was caused by an elastic fibrous band at the root of the jejunal mesentery. While congenital fibrous bands are rare in adults, this interpretation is favored for two reasons. First, the band was located 20 cm superior to postsurgical adhesions in the lower abdomen and pelvis. Second, there was no history of trauma or previous surgery involving the site of volvulus

Stimulation of cannabinoid receptor 2 (CB(2)) suppresses microglial activation

BACKGROUND: Activated microglial cells have been implicated in a number of neurodegenerative disorders, including Alzheimer's disease (AD), multiple sclerosis (MS), and HIV dementia. It is well known that inflammatory mediators such as nitric oxide (NO), cytokines, and chemokines play an important role in microglial cell-associated neuron cell damage. Our previous studies have shown that CD40 signaling is involved in pathological activation of microglial cells. Many data reveal that cannabinoids mediate suppression of inflammation in vitro and in vivo through stimulation of cannabinoid receptor 2 (CB(2)). METHODS: In this study, we investigated the effects of a cannabinoid agonist on CD40 expression and function by cultured microglial cells activated by IFN-γ using RT-PCR, Western immunoblotting, flow cytometry, and anti-CB(2 )small interfering RNA (siRNA) analyses. Furthermore, we examined if the stimulation of CB(2 )could modulate the capacity of microglial cells to phagocytise Aβ(1–42 )peptide using a phagocytosis assay. RESULTS: We found that the selective stimulation of cannabinoid receptor CB(2 )by JWH-015 suppressed IFN-γ-induced CD40 expression. In addition, this CB(2 )agonist markedly inhibited IFN-γ-induced phosphorylation of JAK/STAT1. Further, this stimulation was also able to suppress microglial TNF-α and nitric oxide production induced either by IFN-γ or Aβ peptide challenge in the presence of CD40 ligation. Finally, we showed that CB(2 )activation by JWH-015 markedly attenuated CD40-mediated inhibition of microglial phagocytosis of Aβ(1–42 )peptide. Taken together, these results provide mechanistic insight into beneficial effects provided by cannabinoid receptor CB(2 )modulation in neurodegenerative diseases, particularly AD

Zfp296 Is a Novel, Pluripotent-Specific Reprogramming Factor

Expression of the four transcription factors Oct4, Sox2, Klf4, and c-Myc (OSKM) is sufficient to reprogram somatic cells into induced pluripotent stem (iPSCs). However, this process is slow and inefficient compared with the fusion of somatic cells with embryonic stem cells (ESCs), indicating that ESCs express additional factors that can enhance the efficiency of reprogramming. We had previously developed a method to detect and isolate early neural induction intermediates during the differentiation of mouse ESCs. Using the gene expression profiles of these intermediates, we identified 23 ESC-specific transcripts and tested each for the ability to enhance iPSC formation. Of the tested factors, zinc finger protein 296 (Zfp296) led to the largest increase in mouse iPSC formation. We confirmed that Zfp296 was specifically expressed in pluripotent stem cells and germ cells. Zfp296 in combination with OSKM induced iPSC formation earlier and more efficiently than OSKM alone. Through mouse chimera and teratoma formation, we demonstrated that the resultant iPSCs were pluripotent. We showed that Zfp296 activates transcription of the Oct4 gene via the germ cell–specific conserved region 4 (CR4), and when overexpressed in mouse ESCs leads to upregulation of Nanog expression and downregulation of the expression of differentiation markers, including Sox17, Eomes, and T, which is consistent with the observation that Zfp296 enhances the efficiency of reprogramming. In contrast, knockdown of Zfp296 in ESCs leads to the expression of differentiation markers. Finally, we demonstrated that expression of Zfp296 in ESCs inhibits, but does not block, differentiation into neural cells

Comparison of Pittsburgh compound B and florbetapir in cross-sectional and longitudinal studies.

IntroductionQuantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B-based and florbetapir-based amyloid imaging in the same participants from two independent cohorts using a crossover design.MethodsPittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter-individual variability of the two tracers were compared using multivariate linear models both cross-sectionally and longitudinally.ResultsGlobal amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers.DiscussionAlthough the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers

I Don\u27t Have a Diagnosis for You: Preparing Medical Students to Communicate Diagnostic Uncertainty in the Emergency Department

Introduction: Diagnostic uncertainty abounds in medicine, and communication of that uncertainty is critical to the delivery of high-quality patient care. While there has been training in communicating diagnostic uncertainty directed towards residents, a gap remains in preparing medical students to understand and communicate diagnostic uncertainty. We developed a session to introduce medical students to diagnostic uncertainty and to practice communicating uncertainty using a checklist during role-play patient conversations. Methods: This virtual session was conducted for third-year medical students at the conclusion of their core clerkships. It consisted of prework, didactic lecture, peer role-play, and debriefing. The prework included reflection prompts and an interactive online module. The role-play featured a patient complaining of abdominal pain being discharged from the emergency department without a confirmed diagnosis. Students participated in the role of patient, provider, or observer. Results: Data from an anonymous postsession survey (76% response rate; 202 of 265 students) indicated that most students (82%; 152 of 185) felt more comfortable communicating diagnostic uncertainty after the session. A majority (83%; 166 of 201) indicated the session was useful, and most (81%; 149 of 184) indicated it should be included in the curriculum. Discussion: This virtual session requires few facilitators; has peer role-play, eliminating the need for standardized patients; and is adaptable for in-person teaching. As its goal was to introduce an approach to communicating diagnostic uncertainty, not achieve mastery, students were not individually assessed for proficiency using the Uncertainty Communication Checklist. Students felt the session intervention was valuable

Genomic and molecular characterization of preterm birth.

Preterm birth (PTB) complications are the leading cause of long-term morbidity and mortality in children. By using whole blood samples, we integrated whole-genome sequencing (WGS), RNA sequencing (RNA-seq), and DNA methylation data for 270 PTB and 521 control families. We analyzed this combined dataset to identify genomic variants associated with PTB and secondary analyses to identify variants associated with very early PTB (VEPTB) as well as other subcategories of disease that may contribute to PTB. We identified differentially expressed genes (DEGs) and methylated genomic loci and performed expression and methylation quantitative trait loci analyses to link genomic variants to these expression and methylation changes. We performed enrichment tests to identify overlaps between new and known PTB candidate gene systems. We identified 160 significant genomic variants associated with PTB-related phenotypes. The most significant variants, DEGs, and differentially methylated loci were associated with VEPTB. Integration of all data types identified a set of 72 candidate biomarker genes for VEPTB, encompassing genes and those previously associated with PTB. Notably, PTB-associated genes RAB31 and RBPJ were identified by all three data types (WGS, RNA-seq, and methylation). Pathways associated with VEPTB include EGFR and prolactin signaling pathways, inflammation- and immunity-related pathways, chemokine signaling, IFN-γ signaling, and Notch1 signaling. Progress in identifying molecular components of a complex disease is aided by integrated analyses of multiple molecular data types and clinical data. With these data, and by stratifying PTB by subphenotype, we have identified associations between VEPTB and the underlying biology

Identification of Replication Competent Murine Gammaretroviruses in Commonly Used Prostate Cancer Cell Lines

A newly discovered gammaretrovirus, termed XMRV, was recently reported to be present in the prostate cancer cell line CWR22Rv1. Using a combination of both immunohistochemistry with broadly-reactive murine leukemia virus (MLV) anti-sera and PCR, we determined if additional prostate cancer or other cell lines contain XMRV or MLV-related viruses. Our study included a total of 72 cell lines, which included 58 of the 60 human cancer cell lines used in anticancer drug screens and maintained at the NCI-Frederick (NCI-60). We have identified gammaretroviruses in two additional prostate cancer cell lines: LAPC4 and VCaP, and show that these viruses are replication competent. Viral genome sequencing identified the virus in LAPC4 and VCaP as nearly identical to another known xenotropic MLV, Bxv-1. We also identified a gammaretrovirus in the non-small-cell lung carcinoma cell line EKVX. Prostate cancer cell lines appear to have a propensity for infection with murine gammaretroviruses, and we propose that this may be in part due to cell line establishment by xenograft passage in immunocompromised mice. It is unclear if infection with these viruses is necessary for cell line establishment, or what confounding role they may play in experiments performed with these commonly used lines. Importantly, our results suggest a need for regular screening of cancer cell lines for retroviral “contamination”, much like routine mycoplasma testing

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT