STAT3 Activates the Pentraxin 3 Gene in Chronic Lymphocytic Leukemia Cells.

Pentraxin-related protein 3 (PTX3), commonly produced by myeloid and endothelial cells, is a humoral pattern recognition protein of the innate immune system. Because PTX3 plasma levels of patients with chronic lymphocytic leukemia (CLL) are high and most circulating cells in patients with CLL are CLL cells, we reasoned that CLL cells produce PTX3. Western immunoblotting revealed that low-density cells from seven of seven patients with CLL produce high levels of PTX3, flow cytometry analysis revealed that the PTX3-producing cells are B lymphocytes coexpressing CD19 and CD5, and confocal microscopy showed that PTX3 is present in the cytoplasm of CLL cells. Because STAT3 is constitutively activated in CLL cells, and because we identified putative STAT3 binding sites within the PTX3 gene promoter, we postulated that phosphorylated STAT3 triggers transcriptional activation of PTX3. Immunoprecipitation analysis of CLL cells' chromatin fragments showed that STAT3 Abs precipitated PTX3 DNA. STAT3 knockdown induced a marked reduction in PTX3 expression, indicating a STAT3-induced transcriptional activation of the PTX3 gene in CLL cells. Using an EMSA, we established and used a dual-reporter luciferase assay to confirm that STAT3 binds the PTX3 gene promoter. Downregulation of PTX3 enhanced apoptosis of CLL cells, suggesting that inhibition of PTX3 might benefit patients with CLL.

Using a boundary crossing lens to understand basic science educator and clinical educator collaboration in instructional design.

PURPOSE: Collaborations between basic science educators (BE) and clinical educators (CE) in medical education are common and necessary to create integrated learning materials. However, few studies describe experiences of or processes used by educators engaged in interdisciplinary teamwork. We use the lens of boundary crossing to explore processes described by BE and CE that support the co-creation of integrated learning materials, and the impact that this work has on them. MATERIALS AND METHODS: We conducted qualitative content analysis on program evaluation data from 27 BE and CE who worked on 12 teams as part of a multi-institutional instructional design project. RESULTS: BE and CE productively engaged in collaboration using boundary crossing mechanisms. These included respecting diverse perspectives and expertise and finding efficient processes for completing shared work that allow BE and CE to build on each other's contributions. BE and CE developed confidence in connecting clinical concepts with causal explanations, and willingness to engage in and support such collaborations at their own institutions. CONCLUSIONS: BE and CE report the use of boundary crossing mechanisms that support collaboration in instructional design. Such practices could be harnessed in future collaborations between BE and CE.

A metacognitive confidence calibration (MCC) tool to help medical students scaffold diagnostic reasoning in decision-making during high-fidelity patient simulations.

The purpose of this study was to 1) help novice students scaffold problem-solving and engage safely in the deliberate practice of diagnostic reasoning and medical decision-making in real time; 2) assess how accurately students gather and apply data in medical reasoning and treatment during high-fidelity patient simulations (HFPSs); 3) identify students' scientific misconceptions related to the case; 4) promote student metacognitive processing, self-assessment, and self-efficacy; and 5) facilitate the explicit calibration of student confidence in deliberate reasoning with patient outcomes. In a mixed-method design, a metacognitive calibration self-assessing (MCC) survey tool was applied to HFPS (n = 80, 20 teams of 6 medical students) and semistructured interviews were conducted with faculty (n = 5). When scored by faculty with a rubric, the mean student accuracy ranged from 23% to 74%, whereas their self-assessment of confidence ranged from 71% to 86%. This result revealed overconfidence bias in novice students regarding the correctness of their wrong responses. The most common misconception identified was inverting cause and effect: metabolic acidosis was pointed to as the cause of the patient's problems rather than a consequence of untreated diabetes mellitus. The most common treatment error was overtreatment, with unnecessary added medication. Interviews with faculty suggested that the MCC tool improved the team process by slowing students down, requiring them to think through their answers, and that overall the tool improved their critical thinking. This study demonstrated the feasibility of using a metacognitive confidence calibration tool to assist novice students in learning safely to make deliberate diagnostic reasoning and decisions on patient care in real time during complex simulations while observing objectively their levels of psychological confidence against patient outcomes.NEW & NOTEWORTHY This study demonstrates the feasibility of a metacognitive confidence calibration tool (MCC) to assess and promote novices in the learning of diagnostic reasoning and treatment decisions on patient care in real time during high-fidelity patient simulations while comparing confidence and accuracy data and identifying students' scientific misconceptions. Results revealed the presence of overconfidence bias, overtreatment, and the misconception of metabolic acidosis as the cause of the patient's problems rather than a consequence of untreated diabetes mellitus.

Exploring students' [pre-pandemic] use and the impact of commercial-off-the-shelf learning platforms on students' national licensing exam performance: A focused review - BEME Guide No. 72.

BACKGROUND: Commercial-off-the-shelf learning platforms developed for medical education (herein referred to as MedED-COTS) have emerged as a resource used by a majority of medical students to prepare for licensing examinations. As MedED-COTS proliferate and include more functions and features, there is a need for an up-to-date review to inform medical educators on (a) students' use of MedED-COTS outside the formal medical school curriculum, (b) the integration of MedED-COTS into the formal curriculum, and (c) the potential effects of MedED-COTS usage on students' national licensing exam scores in the USA. METHODS: Due to the limited number of studies published on either the use or integration of MedED-COTS, a focused review of literature was conducted to guide future research and practice. Data extraction and quality appraisal were conducted independently by three reviewers; with disagreements resolved by a fourth reviewer. A narrative synthesis was completed to answer research questions, contextualize results, and identify trends and issues in the findings reported by the studies included in the review. RESULTS: Results revealed consistent positive correlations between students' use of question banks and their licensing exam performance. The limited number of integration studies, combined with a number of methodological issues, makes it impossible to isolate specific effects or associations of integrated commercial resources on standardized test or course outcomes. However, consistent positive correlations, along with students' pervasive use and strong theoretical foundations explaining the results, provide evidence for integrating MedED-COTS into medical school curricula and highlight the need for further research. CONCLUSIONS: Based on findings, we conclude that students use exam preparation materials broadly and they have a positive impact on exam results; the literature on integration of MedED-COTS into formal curriculum and the use by students of resources outside of exam preparation is scant.

STAT3-Induced Wnt5a Provides Chronic Lymphocytic Leukemia Cells with Survival Advantage.

The wingless and integration site growth factor-5a (Wnt5a) is a ligand of the receptor tyrosine kinase-like orphan receptor-1 (ROR1). Because both Wnt5a and ROR1 are expressed in circulating chronic lymphocytic leukemia (CLL) cells, and because in other cell types, STAT3, which is constitutively activated in CLL, induces Wnt5a signaling, we wondered whether STAT3 induces the expression of Wnt5a in CLL cells. Sequence analysis detected four putative STAT3 binding sites in close proximity to the Wnt5a gene promoter's start codon. Chromatin immunoprecipitation and EMSA revealed that STAT3 binds to the Wnt5a gene promoter, and a luciferase assay showed that STAT3 activates the Wnt5a gene. Additionally, transfection of peripheral blood CLL cells with STAT3 short hairpin RNA downregulated Wnt5a mRNA and protein levels, suggesting that STAT3 binds to the Wnt5a gene promoter and induces the expression of Wnt5a in CLL cells. Flow cytometry and confocal microscopy determined that both Wnt5a and its receptor ROR1 are coexpressed on the surface of CLL cells, and Western immunoblotting showed an inverse correlation between Wnt5a and ROR1 protein levels, implying that, regardless of CLL cells' ROR1 levels, blocking the interaction between Wnt5a and ROR1 might be beneficial to patients with CLL. Indeed, transfection of CLL cells with Wnt5a small interfering RNA reduced Wnt5a mRNA and protein levels and significantly increased the spontaneous apoptotic rate of CLL cells. Taken together, our data unravel an autonomous STAT3-driven prosurvival circuit that provides circulating CLL cells with a microenvironment-independent survival advantage.

Comparison of transvalvular flow rate in aortic stenosis subtypes.

OBJECTIVES: Evaluate ET and TVFR in normal patients, PLFLGAS, LGLFAS, and classic pre and post TAVR. BACKGROUND: Severe aortic stenosis (AS) is defined echocardiographically. Generating a pressure gradient to meet diagnostic criteria is dependent on left ventricular contractility, stroke volume, and ejection time.  Abnormalities in these decrease the mean pressure gradient across the valve creating pathology termed low flow, low gradient AS. This occurs in two subtypes, low ejection fraction LFLGAS and paradoxical LFLGAS (PLFLGAS), in which EF is normal but stroke volume is < 35 ml/m2 . Paradoxical LFLGAS is difficult to diagnose and does not have a confirmatory echocardiographic parameter. Transvalvular flow rate (TVFR), which is defined as stroke volume divided by the ejection time, provides a direct measure of flow across the aortic valve. METHODS: A retrospective study of patients who underwent transcatheter aortic valve replacement (TAVR) at the University of Cincinnati Medical Center between 2016 and 2019 was performed. Patients were classified by AS subtype. ET and TVFR were measured pre and post TAVR and statistically compared using SPSS statistics software and ANOVA analysis. RESULTS: Pre TAVR TVFR in the normal population, severe AS population, and LFLGAS were not significantly different. The pre TAVR TVFR in paradoxical LFLGAS patients was significantly lower than other groups. TVFR improved to the greatest degree post TAVR in PLFLGAS but did not meet statistical significance. CONCLUSIONS: The significantly lower TVFR demonstrated in PLFLGAS provides a comprehensive, direct measurement of aortic valve hemodynamics and PLFLGAS pathology and can aid in diagnosis.

Laser-assisted treatment of peri-implantitis: a retrospective cohort study.

The intent of this study was to provide a retrospective analysis of the clinical outcomes of 222 consecutive patients with 437 implants diagnosed with peri-implantitis and treated with the LAPIP protocol. All patients treated with LAPIP therapy at this practice were included. The primary outcome variable studied was probing depth (PD), and secondary variables were erythema, bleeding on probing, and suppuration. The significance of reductions in PD and clinical signs was assessed using repeated-measures analysis of variance. Complete data for both baseline and follow-up visits were available for 116 patients with a total of 224 treated implants. The rate of successful treatments-defined as follow-up PD ≤ 4.0 mm and elimination of clinical signs-was 90%. The reduction in PD from 5.4 mm at baseline to 3.4 mm at a median of 7.6 months was statistically significant (P ≤ 0.001). The reduction in the frequency of clinical signs was also statistically significant (P ≤ 0.001). Among 138 patients who had follow-up visits but not necessarily complete PD data, 15 implants were recorded as failed and 249 were recorded as intact at the median longest follow-up time of 13.1 months, resulting in a survival rate of 94%. In this single clinical practice, use of the minimally invasive LAPIP protocol for the treatment of peri-implantitis provided effective and predictable clinical outcomes. Future randomized controlled trials are indicated.

Anticoagulation and stress-induced cardiomyopathy.

Stress-induced cardiomyopathy (SCM), is a reversible cardiomyopathy characterized by transient systolic dysfunction following an acute physiologic stress. Thromboembolism occurs at a high frequency in patients with intracardiac thrombus secondary to SCM, with one systematic review reporting a rate of 33.3%. The risk of thrombus formation following SCM has been associated with left-ventricular (LV) contraction abnormalities, catecholaminergic surge, and other associated comorbidities. However, established guidelines for screening and management of intracardiac thrombus in the setting of SCM do not exist at present due to a lack of sufficient clinical trial data. The purpose of this article is to discuss the pathophysiological theory and previously documented evidence from cases of LV thrombus secondary to SCM, and to present our recommendations for management of intracardiac thrombus secondary to SCM.

At High Levels, Constitutively Activated STAT3 Induces Apoptosis of Chronic Lymphocytic Leukemia Cells.

In chronic lymphocytic leukemia (CLL), the increment in PBLs is slower than the expected increment calculated from the cells' proliferation rate, suggesting that cellular proliferation and apoptosis are concurrent. Exploring this phenomenon, we found overexpression of caspase-3, higher cleaved poly (ADP-ribose) polymerase levels (p < 0.007), and a higher apoptosis rate in cells from patients with high counts compared with cells from patients with low counts. Although we previously found that STAT3 protects CLL cells from apoptosis, STAT3 levels were significantly higher in cells from patients with high counts than in cells from patients with low counts. Furthermore, overexpression of STAT3 did not protect the cells. Rather, it upregulated caspase-3 and induced apoptosis. Remarkably, putative STAT3 binding sites were identified in the caspase-3 promoter, and a luciferase assay, chromatin immunoprecipitation, and an EMSA revealed that STAT3 activated caspase-3 However, caspase-3 levels increased only when STAT3 levels were sufficiently high. Using chromatin immunoprecipitation and EMSA, we found that STAT3 binds with low affinity to the caspase-3 promoter, suggesting that at high levels, STAT3 activates proapoptotic mechanisms and induces apoptosis in CLL cells.

Comparison of knowledge retention between high-fidelity patient simulation and read-only participants in undergraduate biomedical science education.

High-fidelity patient simulation (HFPS) is expensive in money and faculty resources. There has been a recent push to increase the use of HFPS for undergraduates to teach basic science. However, it is still unclear if HFPS is superior to other cost-effective modalities for learning, and there have been limited studies comparing HFPS directly with other methods. The purpose of this study was to compare learning between three groups: 1) students who participated in a HFPS after reading material (RS); 2) students who reread material (RR) individually; and 3) students who had no intervention or reading (CON). Quizzes (10 true/false questions) were given presimulation, immediately after the simulation (post-sim 1), and 1 wk later to all groups (post-sim 2). Ninety-seven undergraduate students consented to include their data in the study. All groups scored the same on the presimulation quiz (median of 6). The RR and RS scored significantly higher than the CON group on post-sim 1 (medians 8 vs. 6). All groups performed similarly on post-sim 2. A questionnaire also showed that students had increased perceived confidence about pathophysiology. These data suggest that a single-time use of HFPS for knowledge learning for undergraduate students is not more effective than other methods. Future studies need to determine whether increasing the number of HFPS and developing social learning networks could make HFPS more effective for undergraduates. Additionally, future studies should focus on soft skill development, such as confidence, critical thinking, and teamwork/communication skills, as opposed to knowledge acquisition.

Activation of the B-cell receptor successively activates NF-κB and STAT3 in chronic lymphocytic leukemia cells.

In chronic lymphocytic leukemia (CLL) cells, both interleukin-6 (IL-6) and the B-cell receptor (BCR) activate Janus kinase 2 (JAK2) and induce the phosphorylation of signal transduction and activator of transcription 3 (STAT3) on tyrosine 705 residues. However, whereas IL-6 phosphorylates STAT3 within 15 min, stimulation of the BCR with anti-immunoglobulin M (IgM) antibodies phosphorylates STAT3 in 2-4 hr. Here, we show that this process takes longer because it requires transcriptional activity of NF-κB. Using an electromobility shift assay, we found that incubation with IgM antibodies for 4 or 18 hr, but not 15 min, increased NF-κB DNA-binding of CLL cells and increased binding was translated to increased transcriptional activity. Hence, 42% of the 83 NF-κB target genes were constitutively expressed in all CLL cells prior to any inducible stimuli. However, activation of the BCR increased the number of NF-κB target genes with detectable expression by 23%. Remarkably, prolonged incubation with anti-IgM antibodies induced a time-dependent transcription, production and secretion of IL-6 protein. The IgM-induced production of IL-6 prompted the phosphorylation of STAT3 on tyrosine residues. This effect was inhibited by the JAK1/2 inhibitor of the JAK/STAT3 pathway ruxolitinib. Taken together, these results suggest that in CLL cells, constitutive tonic activation of NF-κB can be further enhanced by the BCR and that the BCR-induced activation of the JAK/STAT3 pathway depends on the NF-κB induced production of IL-6.

CT Measures of Bone Mineral Density and Muscle Mass Can Be Used to Predict Noncancer Death in Men with Prostate Cancer.

Purpose To determine if computed tomographic (CT) metrics of bone mineral density and muscle mass can improve the prediction of noncancer death in men with localized prostate cancer. Materials and Methods Institutional review board approval was obtained, with waiver of informed consent. All patients who underwent radiation therapy for localized prostate cancer between 2001 and 2012 with height, weight, and past medical history documented and who underwent CT that included the L4-5 vertebral interspace were included. On a single axial CT section obtained at the mid-L5 level, the mean CT attenuation of the trabecular bone of the L5 vertebral body (L5HU) was measured. The height-normalized psoas cross-sectional area (PsoasL4-5) was measured on a single CT section obtained at the L4-5 vertebral interface. Multivariable Cox proportional hazards models were used to assess effects on noncancer death. By using parameter estimates from an adjusted model, a prognostic index for prediction of noncancer death was generated and compared with age-adjusted Charlson Comorbidity Index (CCI) by using the Harrell c statistic. Results Six hundred fifty-three men met the inclusion criteria. Prostate cancer risk grouping, androgen deprivation, race, age-adjusted CCI, L5HU, and PsoasL4-5 were included in a multivariable model. Age-adjusted CCI (hazard ratio [HR] = 1.36, P < .001), L5HU (HR = 2.88 for L5HU < 105 HU, HR = 1.42 for 105 HU ≤ L5HU ≤ 150 HU, P < .001), PsoasL4-5 (HR = 1.95 for PsoasL4-5 < 7.5 cm2/m2, P = .003), and race (HR = 1.68 for African American race, HR = 1.77 for other nonwhite race, P = .019) were independent predictors of noncancer death. The prognostic index yielded a c value of 0.747 for the prediction of noncancer death versus 0.718 for age-adjusted CCI alone. Conclusion L5HU and PsoasL4-5, which are surrogates for bone mineral density and muscle mass, respectively, were independent predictors of noncancer death. The prognostic index that incorporated these measures with the CCI was associated with improved accuracy for prediction of noncancer death. © RSNA, 2016 Online supplemental material is available for this article.

Developing a tool for observing group critical thinking skills in first-year medical students: a pilot study using physiology-based, high-fidelity patient simulations.

Most assessments of physiology in medical school use multiple choice tests that may not provide information about a student's critical thinking (CT) process. There are limited performance assessments, but high-fidelity patient simulations (HFPS) may be a feasible platform. The purpose of this pilot study was to determine whether a group's CT process could be observed over a series of HFPS. An instrument [Critical Thinking Skills Rating Instrument CTSRI)] was designed with the IDEAS framework. Fifteen groups of students participated in three HFPS that consisted of a basic knowledge quiz and introduction, HFPS session, and debriefing. HFPS were video recorded, and two raters reviewed and scored all HFPS encounters with the CTSRI independently. Interrater analysis suggested good reliability. There was a correlation between basic knowledge scores and three of the six observations on the CTSRI providing support for construct validity. The median CT ratings significantly increased for all observations between the groups' first and last simulation. However, there were still large percentages of video ratings that indicated students needed substantial prompting during the HFPS. The data from this pilot study suggest that it is feasible to observe CT skills in HFPS using the CTSRI. Based on the findings from this study, we strongly recommend that first-year medical students be competent in basic knowledge of the relevant physiology of the HFPS before participating, to minimize the risk of a poor learning experience.

Persistent increases in Ca(2+) influx through Cav1.2 shortens action potential and causes Ca(2+) overload-induced afterdepolarizations and arrhythmias.

Persistent elevation of Ca(2+) influx due to prolongation of the action potential (AP), chronic activation of the ß-adrenergic system and molecular remodeling occurs in stressed and diseased hearts. Increases in Ca(2+) influx are usually linked to prolonged myocyte action potentials and arrhythmias. However, the contribution of chronic enhancement of Cav1.2 activity on cardiac electrical remodeling and arrhythmogenicity has not been completely defined and is the subject of this study. Chronically increased Cav1.2 activity was produced with a cardiac specific, inducible double transgenic (DTG) mouse system overexpressing the ß2a subunit of Cav (Cavß2a). DTG myocytes had increased L-type Ca(2+) current (ICa-L), myocyte shortening, and Ca(2+) transients. DTG mice had enhanced cardiac performance, but died suddenly and prematurely. Telemetric electrocardiograms revealed shortened QT intervals in DTG mice. The action potential duration (APD) was shortened in DTG myocytes due to significant increases of potassium currents and channel abundance. However, shortened AP in DTG myocytes did not fully limit excess Ca(2+) influx and increased the peak and tail ICa-L. Enhanced ICa promoted sarcoplasmic reticulum (SR) Ca(2+) overload, diastolic Ca(2+) sparks and waves, and increased NCX activity, causing increased occurrence of early and delayed afterdepolarizations (EADs and DADs) that may contribute to premature ventricular beats and ventricular tachycardia. AV blocks that could be related to fibrosis of the AV node were also observed. Our study suggests that increasing ICa-L does not necessarily result in AP prolongation but causes SR Ca(2+) overload and fibrosis of AV node and myocardium to induce cellular arrhythmogenicity, arrhythmias, and conduction abnormalities.

Stimulation of the B-cell receptor activates the JAK2/STAT3 signaling pathway in chronic lymphocytic leukemia cells.

In chronic lymphocytic leukemia (CLL), stimulation of the B-cell receptor (BCR) triggers survival signals. Because in various cells activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway provides cells with survival advantage, we wondered whether BCR stimulation activates the JAK/STAT pathway in CLL cells. To stimulate the BCR we incubated CLL cells with anti-IgM antibodies. Anti-IgM antibodies induced transient tyrosine phosphorylation and nuclear localization of phosphorylated (p) STAT3. Immunoprecipitation studies revealed that anti-JAK2 antibodies coimmunoprecipitated pSTAT3 and pJAK2 in IgM-stimulated but not unstimulated CLL cells, suggesting that activation of the BCR induces activation of JAK2, which phosphorylates STAT3. Incubation of CLL cells with the JAK1/2 inhibitor ruxolitinib inhibited IgM-induced STAT3 phosphorylation and induced apoptosis of IgM-stimulated but not unstimulated CLL cells in a dose- and time-dependent manner. Whether ruxolitinib treatment would benefit patients with CLL remains to be determined.

Cardiac Tamponade Physiology Secondary to Tense Ascites.

Cardiac tamponade is a common and often life-threatening process, which is typically associated with a pericardial effusion or, in rare cases, with a large pleural effusion. Theoretically, as reported in only a single prior case, it can be caused by extrinsic compression from tense ascites. We present a case in which dynamic inferior wall collapse was secondary to increased abdominal pressure from tense ascites. This phenomenon may be more common than previously diagnosed, especially in patients with liver disease. These patients often develop frequent ascites and present with clinical signs and symptoms similar to cardiac tamponade (tachycardia, hypotension and dyspnea). Presently, no formal practice guidelines exist regarding cardiac imaging for these patients. A high index of suspicion is required for timely diagnosis and management.

Selective photoantisepsis.

BACKGROUND AND OBJECTIVE: Selective killing of pathogens by laser is possible due to the difference in absorption of photon energy by pathogens and host tissues. The optical properties of pathogenic microorganisms are used along with the known optical properties of soft tissues in calculations of the laser-induced thermal response of pathogen colonies embedded in a tissue model. The objective is to define the laser parameters that optimize pathogen destruction and depth of the bactericidal effect. MATERIALS AND METHODS: The virtual periodontium is a computational model of the optical and time-dependent thermal properties of infected periodontal tissues. The model simulates the periodontal procedure: Laser Sulcular Debridement.1 Virtual pathogen colonies are placed at different depths in the virtual periodontium to determine the depth for effective bactericidal effects given various laser parameters (wavelength, peak power, pulse duration, scan rate, fluence rate) and differences in pathogen sensitivities. RESULTS: Accumulated background heat from multiple passes increases the depth of the bactericidal effect. In visible and near-IR wavelengths the large difference in absorption between normal soft tissue and Porphyromonas gingivalis (Pg) and Prevotella intermedia (Pi) results in selective destruction. Diode laser (810 nm) efficacy and depth of the bactericidal effect are variable and dependent on hemin availability. Both pulsed-Nd:YAG and the 810 nm diode lasers achieve a 2-3 mm deep damage zone for pigmented Pg and Pi in soft tissue without surface damage (selective photoantisepsis). The model predicts no selectivity for the Er:YAG laser (2,940 nm). Depth of the bactericidal effect is highly dependent on pathogen absorption coefficient. Highly sensitive pathogens may be destroyed as deep as 5-6 mm in soft tissue. Short pulse durations enable confinement of the thermal event to the target. Temporal selectivity is achieved by adjusting pulse duration based on target size. CONCLUSION: The scatter-limited phototherapy model of the infected periodontium is applied to develop a proper dosimetry for selective photoantisepsis. Dosimetry planning is essential to the development of a new treatment modality. Lasers Surg. Med. 48:763-773, 2016. © 2016 Wiley Periodicals, Inc.

The Black Bug Myth: Selective photodestruction of pigmented pathogens.

BACKGROUND AND OBJECTIVE: It is commonly believed that pigmented pathogens are selectively targeted by dental lasers. To test this notion optical diffuse reflection spectroscopy (DRS) was used to obtain absorption spectra for the periodontal pathogens, Porphyromonas gingivalis (Pg) and Prevotella intermedia (Pi). MATERIALS AND METHODS: Spectra from 400 to 1,100 nm wavelengths of Pg colonies cultured with different concentrations of hemin were obtained to test the hypothesis that "visual pigmentation" predicts absorption of near-infrared (IR) dental laser energy. Ablation threshold at 1,064 nm [1] was measured for the pathogenic fungus, Candida albicans (Ca). RESULTS: The hypothesis was demonstrated to be true at 810 nm, it was false at 1,064 nm. Diode laser (810 nm) efficacy and "depth of kill" is dependent on hemin availability from 400 to about 900 nm. Pg and Pi absorption at 1,064 nm (µa = 7.7 ± 2.6 cm(-1) ) is independent of hemin availability but is determined by another unknown chromophore. Ca is non-pigmented but very sensitive to 1,064 nm irradiation. CONCLUSIONS: The amount of visual pigmentation does not necessarily predict sensitivity to dental laser irradiation. Spectra in visible and near-IR wavelengths demonstrate a large difference in absorption between soft tissue and Pg or Pi. This difference represents a host/pathogen differential sensitivity to laser irradiation, the basis for selective photoantisepsis. Lasers Surg. Med. 48:706-714, 2016. © 2016 Wiley Periodicals, Inc.

Faculty and second-year medical student perceptions of active learning in an integrated curriculum.

Patients expect physicians to be lifelong learners who are able to interpret and evaluate diagnostic tests, and most medical schools list the development of lifelong learning in their program objectives. However, lecture is the most often utilized form of teaching in the first two years and is considered passive learning. The current generation of medical students has many characteristics that should support active learning pedagogies. The purpose of this study was to analyze student and faculty perceptions of active learning in an integrated medical curriculum at the second-year mark, where students have been exposed to multiple educational pedagogies. The first hypothesis of the study was that faculty would favor active learning methods. The second hypothesis was that Millennial medical students would favor active learning due to their characteristics. Primary faculty for years 1 and 2 and second-year medical students were recruited for an e-mail survey consisting of 12 questions about active learning and lecture. Students perceived that lecture and passive pedagogies were more effective for learning, whereas faculty felt active and collaborative learning was more effective. Students believed that more content should be covered by lecture than faculty. There were also significant differences in perceptions of what makes a good teacher. Students and faculty both felt that lack of time in the curriculum and preparation time were barriers for faculty. The data suggest that students are not familiar with the process of learning and that more time may be needed to help students develop lifelong learning skills.

Cardiac-specific disruption of Bin1 in mice enables a model of stress- and age-associated dilated cardiomyopathy.

Non-compensated dilated cardiomyopathy (DCM) leading to death from heart failure is rising rapidly in developed countries due to aging demographics, and there is a need for informative preclinical models to guide the development of effective therapeutic strategies to prevent or delay disease onset. In this study, we describe a novel model of heart failure based on cardiac-specific deletion of the prototypical mammalian BAR adapter-encoding gene Bin1, a modifier of age-associated disease. Bin1 deletion during embryonic development causes hypertrophic cardiomyopathy and neonatal lethality, but there is little information on how Bin1 affects cardiac function in adult animals. Here we report that cardiomyocyte-specific loss of Bin1 causes age-associated dilated cardiomyopathy (DCM) beginning by 8-10 months of age. Echocardiographic analysis showed that Bin1 loss caused a 45% reduction in ejection fraction during aging. Younger animals rapidly developed DCM if cardiac pressure overload was created by transverse aortic constriction. Heterozygotes exhibited an intermediate phenotype indicating Bin1 is haplo-insufficient to sustain normal heart function. Bin1 loss increased left ventricle (LV) volume and diameter during aging, but it did not alter LV volume or diameter in hearts from heterozygous mice nor did it affect LV mass. Bin1 loss increased interstitial fibrosis and mislocalization of the voltage-dependent calcium channel Cav 1.2, and the lipid raft scaffold protein caveolin-3, which normally complexes with Bin1 and Cav 1.2 in cardiomyocyte membranes. Our findings show how cardiac deficiency in Bin1 function causes age- and stress-associated heart failure, and they establish a new preclinical model of this terminal cardiac disease.