Evaluating the efficacy of combination and single-agent immunotherapies in real-world patterns of disease progression and survival of metastatic melanoma patients.

The objective of this study is to describe survival outcomes in patients with metastatic melanoma in a real-world setting receiving combination and single-agent immunotherapy outside the clinical trial context. We conducted a retrospective single-institution study of patients with metastatic melanoma in a real-world setting. Survival was calculated using log-rank test. Contingency tables were analyzed using Fisher's Exact test. CD8 + T-cell densities were measured using quantitative immunofluorescence and analyzed using Mann-Whitney U test. The median overall survival (OS) for 132 patients was 45.3 months. Brain metastasis did not confer a higher risk of death relative to liver and/or bone disease (39.53 versus 30.00 months, respectively; P  = 0.687). Anti-PD-1 monotherapy was the most common first-line treatment, received by 49.2% of patients. There was no significant difference in OS between patients receiving single-agent anti-PD-1 and combination anti-PD-1 plus CTLA-4 (39.4 months versus undefined; P  = 0.643). Patients treated with combination therapy were more likely to be alive without progression at the last follow-up than those who received monotherapy (70.4% versus 49.2%; P  = 0.0408). Median OS was 21.8 months after initiation of second-line therapy after anti-PD-1 monotherapy. CD8+ T-cell densities were higher in patients who achieved disease control on first-line immunotherapy ( P  = 0.013). In a real-world setting, patients with metastatic melanoma have excellent survival rates, and treatment benefit can be achieved even after progression on first-line therapy. Combination immunotherapy may produce more favorable long-term outcomes in a real-world setting. High pretreatment CD8+ T-cell infiltration correlates with immunotherapy efficacy.

A 3D-Printed Customizable Platform for Multiplex Dynamic Biofilm Studies.

Biofilms are communities of microbes that colonize surfaces. While several biofilm experimental models exist, they often have limited replications of spatiotemporal dynamics surrounding biofilms. For a better understanding dynamic and complex biofilm development, this manuscript presents a customizable platform compatible with off-the-shelf well plates that can monitor microbial adhesion, growth, and associated parameters under various relevant scenarios by taking advantage of 3D printing. The system i) holds any substrate in a stable, vertical position, ii) subjects samples to flow at different angles, iii) switches between static and dynamic modes during an experiment, and iv) allows multiplexing and real-time monitoring of biofilm parameters. Simulated fluid dynamics is employed to estimate flow patterns around discs and shear stresses at disc surfaces. A 3D printed peristaltic pump and a customized pH measurement system for real-time tracking of spent biofilm culture media are equipped with a graphical user interface that grants control over all experimental parameters. The system is tested under static and dynamic conditions with Streptococcus mutans using different carbon sources. By monitoring the effluent pH and characterizing biochemical, microbiological, and morphological properties of cultured biofilms, distinct properties are demonstrated. This novel platform liberates designing experimental strategies for investigations of biofilms under various conditions.

Minority stress, depression, and cigarette smoking among Chinese gay versus bisexual men: a two-group structural equation model analyses.

BACKGROUND: Literature in the West suggested that bisexual men have a higher smoking rate compared to gay men. Data on patterns of smoking among gay and bisexual men are limited in Eastern Asian countries like China. This study examined the cigarette smoking prevalence for gay versus bisexual men in China and their unique minority stress - smoking pathways. METHODS: Between September 2017 and November 2018, we surveyed a convenience sample of 538 gay men and 138 bisexual men recruited from local sexual minority organizations in four metropolitan cities in China (i.e., Beijing, Wuhan, Nanchang, and Changsha). Measures included sexual orientation, sociodemographics, theory-based minority stressors, depressive symptoms, and past 30-day cigarette smoking. Two-group (gay men vs. bisexual men) structural equation modeling (SEM) was used to test possible distinct mechanisms between theory-based stressors, depressive symptoms, and cigarette smoking among gay men and bisexual men, respectively. RESULTS: The mean age of participants was 26.51 (SD = 8.41) years old and 76.3% of them had at least a college degree. Bisexual men reported a higher rate of cigarette smoking compared to gay men (39.9% vs. 27.3%). Two-group SEM indicated that the pathways for cigarette smoking were not different between gay and bisexual men. Higher rejection anticipation was associated with greater depressive symptoms (standardized ß = 0.32, p < .001), and depressive symptoms were not associated with cigarette smoking. CONCLUSIONS: Minority stress, specifically rejection anticipation, may be critical considerations in addressing depressive symptoms, but not smoking, among both gay and bisexual men in China.

Nationally representative prevalence estimates of gay, bisexual, and other men who have sex with men who have served in the U.S. military.

OBJECTIVES: To estimate the number of men in the U.S. military who are gay, bisexual, or other men who have sex with men (MSM) to inform the development of military and other federal policies. STUDY DESIGN: We analyzed data from the National Surveys of Family Growth to estimate the number of U.S. men who were gay, bisexual, or MSM, and who had served in the military, compared to those who did not serve. We stratified using hierarchical categories of gay, bisexual, and other MSM to compare proportions in the military and general population. RESULTS: We found that 4.23% of men self-reported as gay, bisexual, or other MSM among men who served in the military, compared to 4.14% among men who had not served (p = 0.93). When stratified, we found that 0.78% self-reported as gay among men who served in the military, compared to 2.12% among men who had not served (p<0.001). CONCLUSIONS: The proportion of men who identified as a gay was lower in the military than in the general population. This finding might have been influenced by historical military policies related to sexual orientation.

A Survey of Staff Perceptions of an Emergency Medicine Pharmacist Program in a Community Hospital: A Brief Report.

STUDY OBJECTIVE: For an emergency medicine pharmacist to become a well-integrated multidisciplinary team member, his or her services need to be accepted by the emergency department (ED) staff. There have been 2 published studies attesting the value of the emergency medicine pharmacist by ED staff: at an academic medical and trauma center in 2007 and a large academic medical center in 2011. The aim of this study is to determine whether the emergency medicine pharmacist's value, as perceived by ED staff, would be similarly accepted at a smaller community hospital with limited clinical pharmacist services. METHODS: This prospective, descriptive survey examined the perceptions of ED providers and nurses in regard to the emergency medicine pharmacist at a 26-bed Level II trauma center with 65,135 annual visits. RESULTS: Of the 90 participants polled, 50% (45) responded. Overall, the ED staff's perceptions of an emergency medicine pharmacist were positive. Eighty-six percent of all participants surveyed had consulted the emergency medicine pharmacist at least once in their last 5 shifts. Thirty-one percent answered that being available for consultation was the most important aspect of the emergency medicine pharmacist's role, whereas attending codes (22%) and patient education (20%) were the next most important activities. Providers consulted with the emergency medicine pharmacist most for antibiotic stewardship (including guided empiric therapy and culture callbacks) drug-drug and drug-disease state interactions, and dosing of pediatric medications. Nurses referred to the emergency medicine pharmacist most for compatibility consultations, medication retrieval, and high-risk medication verification. CONCLUSION: As was previously found in academic settings, an emergency medicine pharmacist is an invaluable addition to the health care team and can be incorporated into an existing pharmacy staffing model at a small, community hospital.

A pocket-sized metabolic analyzer for assessment of resting energy expenditure.

BACKGROUND & AIMS: The assessment of metabolic parameters related to energy expenditure has a proven value for weight management; however these measurements remain too difficult and costly for monitoring individuals at home. The objective of this study is to evaluate the accuracy of a new pocket-sized metabolic analyzer device for assessing energy expenditure at rest (REE) and during sedentary activities (EE). The new device performs indirect calorimetry by measuring an individual's oxygen consumption (VO2) and carbon dioxide production (VCO2) rates, which allows the determination of resting- and sedentary activity-related energy expenditure. METHODS: VO2 and VCO2 values of 17 volunteer adult subjects were measured during resting and sedentary activities in order to compare the metabolic analyzer with the Douglas bag method. The Douglas bag method is considered the Gold Standard method for indirect calorimetry. Metabolic parameters of VO2, VCO2, and energy expenditure were compared using linear regression analysis, paired t-tests, and Bland-Altman plots. RESULTS: Linear regression analysis of measured VO2 and VCO2 values, as well as calculated energy expenditure assessed with the new analyzer and Douglas bag method, had the following linear regression parameters (linear regression slope LRS0, and R-squared coefficient, r(2)) with p = 0: LRS0 (SD) = 1.00 (0.01), r(2) = 0.9933 for VO2; LRS0 (SD) = 1.00 (0.01), r(2) = 0.9929 for VCO2; and LRS0 (SD) = 1.00 (0.01), r(2) = 0.9942 for energy expenditure. In addition, results from paired t-tests did not show statistical significant difference between the methods with a significance level of α = 0.05 for VO2, VCO2, REE, and EE. Furthermore, the Bland-Altman plot for REE showed good agreement between methods with 100% of the results within ±2SD, which was equivalent to ≤10% error. CONCLUSION: The findings demonstrate that the new pocket-sized metabolic analyzer device is accurate for determining VO2, VCO2, and energy expenditure.

Solubilization of therapeutic agents in micellar nanomedicines.

We use atomistic molecular dynamics simulations to reveal the binding mechanisms of therapeutic agents in PEG-ylated micellar nanocarriers (SSM). In our experiments, SSM in buffer solutions can solubilize either ≈11 small bexarotene molecules or ≈6 (2 in low ionic strength buffer) human vasoactive intestinal peptide (VIP) molecules. Free energy calculations reveal that molecules of the poorly water-soluble drug bexarotene can reside at the micellar ionic interface of the PEG corona, with their polar ends pointing out. Alternatively, they can reside in the alkane core center, where several bexarotene molecules can self-stabilize by forming a cluster held together by a network of hydrogen bonds. We also show that highly charged molecules, such as VIP, can be stabilized at the SSM ionic interface by Coulombic coupling between their positively charged residues and the negatively charged phosphate headgroups of the lipids. The obtained results illustrate that atomistic simulations can reveal drug solubilization character in nanocarriers and be used in efficient optimization of novel nanomedicines.

COMBREX: a project to accelerate the functional annotation of prokaryotic genomes.

COMBREX (http://combrex.bu.edu) is a project to increase the speed of the functional annotation of new bacterial and archaeal genomes. It consists of a database of functional predictions produced by computational biologists and a mechanism for experimental biochemists to bid for the validation of those predictions. Small grants are available to support successful bids.

Deep venous thromboembolism in a triathlete.

BACKGROUND: Demanding athletic events can contribute multiple risk factors to the development of deep venous thrombosis (DVT) in athletes. OBJECTIVES: To discuss risk factors for the development of DVT in athletes participating in athletic events. CASE REPORT: We present the case of a young female athlete who had a DVT, complicated by pulmonary embolism, after participating in a half-Ironman triathlon. CONCLUSION: Our patient developed a DVT complicated by pulmonary embolism as a result of many factors relating to participation in a triathlon. Demanding athletic events can contribute different risk factors to the development of DVT in athletes. The diagnosis of DVT should be considered in any athlete presenting with leg pain, especially after a strenuous athletic event.

Statistical pattern matching facilitates the design of polyvalent inhibitors of anthrax and cholera toxins.

Numerous biological processes involve the recognition of a specific pattern of binding sites on a target protein or surface. Although ligands displayed by disordered scaffolds form stochastic rather than specific patterns, theoretical models predict that recognition will occur between patterns that are characterized by similar or "matched" statistics. Endowing synthetic biomimetic structures with statistical pattern matching capabilities may improve the specificity of sensors and resolution of separation processes. We demonstrate that statistical pattern matching enhances the potency of polyvalent therapeutics. We functionalized liposomes with an inhibitory peptide at different densities and observed a transition in potency at an interpeptide separation that matches the distance between ligand-binding sites on the heptameric component of anthrax toxin. Pattern-matched polyvalent liposomes inhibited anthrax toxin in vitro at concentrations four orders of magnitude lower than the corresponding monovalent peptide, and neutralized this toxin in vivo. Statistical pattern matching also enhanced the potency of polyvalent inhibitors of cholera toxin. This facile strategy should be broadly applicable to the detection and neutralization of toxins and pathogens.