Search

Objective: Patients with bipolar disorder spend most of their clinical lifetime in the depressive phase of their illness. However, antidepressants are discouraged in the treatment of bipolar depression due to concerns over manic induction and drug ineffectiveness. Some reports suggest that monoamine oxidase inhibitors (MAOIs) may be safe and effective compared to other antidepressants in treating bipolar depression. The present study compared the safety and effectiveness of MAOI therapy in patients with bipolar versus unipolar depression. Methods: Data were collected from approximately 2500 clinical research charts of patients treated with MAOI therapy at a university mood disorder clinic between 1983 and 2015. A mixed‐effects model was created with patient entered as the random effect. The model included the primary diagnosis (i.e., either unipolar or bipolar depression) and other clinical covariates as fixed‐effect predictors. Results: Patients with bipolar depression demonstrated lower post‐treatment clinical global impressions/severity scores versus patients with unipolar depression (p = 0.04). Neither group demonstrated a full syndromal manic or hypomanic episode. A higher proportion of patients with bipolar depression reported myoclonic tics and tremors, which may have resulted from concomitant lithium use. Amongst the covariates, only the number of prior antidepressant trials predicted poorer outcomes from MAOI therapy. Conclusion: MAOIs may be more effective—and as safe—for patients with bipolar depression versus unipolar depression. Future studies should explore this possible advantage using a larger sample size. [ABSTRACT FROM AUTHOR]

Objective: An implicit assumption in the use of depressive severity measures to assess change during treatment, such as the Hamilton Rating Scale for Depression (HRSD), is that reductions from pre- to post-treatment that are equal to each other are of equal value. However, stakeholders' valuations of changes might depart substantially from this assumption. Method: Vignettes were constructed that reflected the six possible 1, 2, and 3-point reductions on five cognitive and four somatic symptoms derived from the HRSD. Former or currently depressed patients provided judgments of the importance of the symptom reductions. Mean importance ratings were modeled using symptom category and the pre/post-treatment combination. Differences were explored using the Tukey method. Results: Results indicated that mean ratings, from most to least important, were: Anxiety, Suicide, Depressed Mood, Work, and Guilt (the cognitive symptoms) followed by Somatic, Sleep, Appetite & Weight, and Retardation (the somatic symptoms). Participants valued reductions that resulted in posttreatment scores of zero more than expected, given the magnitude of the reductions. Conclusions: The value of reductions in symptoms captured by the HRSD, as judged by patients, appears to differ as a function of symptom category and the post-treatment score. Similar patterns might characterize other measures of depression severity. [ABSTRACT FROM AUTHOR]

Within mental health, approaches to determine whether a patient experienced "meaningful" change from treatment have predominantly involved imposing thresholds on three types of metrics derived from assessments of symptom severity: end score (posttreatment score), absolute change (pre- minus posttreatment score), and proportion of change. However, none of these approaches have considered input from the consumer. This study examined correspondences between various reductions from pre- to posttreatment symptom severity levels and patients' judgments of satisfaction with change. Former or currently depressed patients were asked to provide judgments of their satisfaction reflected in vignettes that used descriptions from the Hamilton Rating Scale for Depression. Judgments from 108 female participants were fit using four metrics: end score, absolute change, proportion of change, and the combination of end score and absolute change. Akaike information criteria (AICs) and Akaike weights were used to determine the best-fitting model. Cutoffs were calculated for the five levels of satisfaction with change. Proportion of change best accounted for variation in the patients' ratings. For "slightly … ," "somewhat … ," "moderately … ," and "very … ," the proportions of reduction that corresponded with each of these ratings of satisfaction were, respectively: 17%, 39%, 62%, and 84%. Our a priori level of satisfaction (between "somewhat" and "moderately") corresponded to a 50% reduction in pretreatment severity. This study may provide services some insight into their female patients' satisfaction with change from treatment for depression using only the proportion of reduction from pretreatment severity. A similar procedure could be applied to other diagnostic groups, as well as other constructs that attend to the patient's perspective. [ABSTRACT FROM AUTHOR]

The highly strained bowl‐shaped pentacyclic structure of herquline A has rendered it one of the most difficult problems in organic synthesis yet to be solved. The challenges associated with the synthesis of herquline A have been well documented in four Ph.D. dissertations and in multiple reports regarding syntheses of its structurally simpler congeners. Herein, we report the construction of the pentacyclic core of herquline A that contains both N10−C2 and C3−C3′ bonds. The key for success was the development of the tandem aza‐Michael addition/enolate capture protocol that set the stage for subsequent palladium catalyzed C3(sp2)−C3′(sp2) coupling reaction. Ensuing oxidative dearomatization of the left aryl ring allowed the formation of the pentacyclic diketone core of herquline A. [ABSTRACT FROM AUTHOR]

Background: No evidence-based therapy for borderline personality disorder (BPD) exhibits a clear superiority. However, BPD is highly heterogeneous, and different patients may specifically benefit from the interventions of a particular treatment. Methods: From a randomized trial comparing a year of dialectical behavior therapy (DBT) to general psychiatric management (GPM) for BPD, long-term (2-year-post) outcome data and patient baseline variables (n = 156) were used to examine individual and combined patient-level moderators of differential treatment response. A two-step bootstrapped and partially cross-validated moderator identification process was employed for 20 baseline variables. For identified moderators, 10-fold bootstrapped cross-validated models estimated response to each therapy, and long-term outcomes were compared for patients randomized to their model-predicted optimal v. non-optimal treatment. Results: Significant moderators surviving the two-step process included psychiatric symptom severity, BPD impulsivity symptoms (both GPM > DBT), dependent personality traits, childhood emotional abuse, and social adjustment (all DBT > GPM). Patients randomized to their model-predicted optimal treatment had significantly better long-term outcomes (d = 0.36, p = 0.028), especially if the model had a relatively stronger (top 60%) prediction for that patient (d = 0.61, p = 0.004). Among patients with a stronger prediction, this advantage held even when applying a conservative statistical check (d = 0.46, p = 0.043). Conclusions: Patient characteristics influence the degree to which they respond to two treatments for BPD. Combining information from multiple moderators may help inform providers and patients as to which treatment is the most likely to lead to long-term symptom relief. Further research on personalized medicine in BPD is needed. [ABSTRACT FROM AUTHOR]

Objective: We use a new variable selection procedure for treatment selection which generates treatment recommendations based on pre-treatment characteristics for adults with mild-to-moderate depression deciding between cognitive behavioral (CBT) versus psychodynamic therapy (PDT). Method: Data are drawn from a randomized comparison of CBT versus PDT for depression (N = 167, 71% female, mean-age = 39.6). The approach combines four different statistical techniques to identify patient characteristics associated consistently with differential treatment response. Variables are combined to generate predictions indicating each individual's optimal-treatment. The average outcomes for patients who received their indicated treatment versus those who did not were compared retrospectively to estimate model utility. Results: Of 49 predictors examined, depression severity, anxiety sensitivity, extraversion, and psychological treatment-needs were included in the final model. The average post-treatment Hamilton-Depression-Rating-Scale score was 1.6 points lower (95%CI = [0.5:2.8]; d = 0.21) for those who received their indicated-treatment compared to non-indicated. Among the 60% of patients with the strongest treatment recommendations, that advantage grew to 2.6 (95%CI = [1.4:3.7]; d = 0.37). Conclusions: Variable selection procedures differ in their characterization of the importance of predictive variables. Attending to consistently-indicated predictors may be sensible when constructing treatment selection models. The small N and lack of separate validation sample indicate a need for prospective tests before this model is used. [ABSTRACT FROM AUTHOR]

Objectives: Lithium and quetiapine are known to be effective treatments for bipolar disorder. However, little information is available to inform prediction of response to these medications. Machine‐learning methods can identify predictors of response by examining variables simultaneously. Further evaluation of models on a test sample can estimate how well these models would generalize to other samples. Methods: Data (N = 482) were drawn from a randomized clinical trial of outpatients with bipolar I or II disorder who received adjunctive personalized treatment plus either lithium or quetiapine. Elastic net regularization (ENR) was used to generate models for lithium and quetiapine; these models were evaluated on a test set. Results: Predictions from the lithium model explained 17.4% of the variance in actual observed scores of patients who received lithium in the test set, while predictions from the quetiapine model explained 32.1% of the variance of patients that received quetiapine. Of the baseline variables selected, those with the largest parameter estimates were: severity of mania; attention‐deficit/hyperactivity disorder (ADHD) comorbidity; nonsuicidal self‐injurious behavior; employment; and comorbidity with each of two anxiety disorders (social phobia/society anxiety and agoraphobia). Predictive accuracy of the ENR model outperformed the simple and basic theoretical models. Conclusion: ENR is an effective approach for building optimal and generalizable models. Variables identified through this methodology can inform future research on predictors of response to lithium and quetiapine, as well as future modeling efforts of treatment choice in bipolar disorder. [ABSTRACT FROM AUTHOR]

Objectives: Antidepressants may be less effective in treatment-resistant depression (TRD). In this exploratory study, we examined the widely held hypothesis that monoamine oxidase inhibitor (MAOI) therapy may be superior to tricyclic antidepressant (TCA) therapy for TRD. We also examined the influence of the number of prior treatment trials on TCA versus MAOI effectiveness in TRD.Methods: Data were retrospectively extracted from approximately 2,500 treatment charts of patients with TRD who were attending a university mood disorder clinic between 1983 and 2015. Hierarchical linear modeling was used to examine the efficacy of drug class on outcome as well as the interaction between drug class and the number of prior antidepressant trials.Results: 147 treatment outcome observations were made from 94 unipolar, depressed patients who either received TCA (N = 47) or MAOI (N = 100) monotherapy for TRD. For patients unresponsive to at least one prior trial, drug class significantly predicted end-of-treatment CGI/S scores, with TCAs showing worse (i.e., higher) end-of-treatment CGI/S scores relative to MAOI therapy (b = 1.04, t = 4.98, p < 0.0001). When examining the interaction between drug class and the number of prior antidepressant trials, the interaction effect was significant (b = -0.50, t = -2.43, p = 0.02); however, the advantage for MAOI versus TCA therapy decreases with more prior, failed, antidepressant trials.Conclusion: Results suggest that MAOIs may be more effective than TCAs for early stage TRD. This difference in effectiveness between MAOIs and TCAs diminished as the number of prior treatment trials increased. However, the TCA sample size was limited and the analysis was retrospective with non-randomized conditions. [ABSTRACT FROM AUTHOR]

Reformed experimental activities (REActivities) are an innovative approach to the delivery of the traditional material in an undergraduate organic chemistry laboratory. A description of the design and implementation of REActivities at both a four- and two-year institution is discussed. The results obtained using a reformed teaching observational protocol are described and correlated to the transferability of REActivities between different instructors and their transportability between different institutions. [ABSTRACT FROM AUTHOR]

TGF-β1 signaling is a critical driver of collagen accumulation and fibrotic disease but also a vital suppressor of inflammation and epithelial cell proliferation. The nature of this multifunctional cytokine has limited the development of global TGF-β1 signaling inhibitors as therapeutic agents. We conducted phenotypic screens for small molecules that inhibit TGF-β1-induced epithelial-mesenchymal transition without immediate TGF-β1 receptor (TβR) kinase inhibition. We identified trihydroxyphenolic compounds as potent blockers of TGF-β1 responses (IC50 ~50 nM), Snail1 expression, and collagen deposition in vivo in models of pulmonary fibrosis and collagen-dependent lung cancer metastasis. Remarkably, the functional effects of trihydroxyphenolics required the presence of active lysyl oxidase-like 2 (LOXL2), thereby limiting effects to fibroblasts or cancer cells, the major LOXL2 producers. Mechanistic studies revealed that trihydroxyphenolics induce auto-oxidation of a LOXL2/3-specific lysine (K731) in a time-dependent reaction that irreversibly inhibits LOXL2 and converts the trihydrophenolic to a previously undescribed metabolite that directly inhibits TβRI kinase. Combined inhibition of LOXL2 and TβRI activities by trihydrophenolics resulted in potent blockade of pathological collagen accumulation in vivo without the toxicities associated with global inhibitors. These findings elucidate a therapeutic approach to attenuate fibrosis and the disease-promoting effects of tissue stiffness by specifically targeting TβRI kinase in LOXL2-expressing cells. [ABSTRACT FROM AUTHOR]

The development of next-generation sequencing (NGS) technology allows to sequence whole exomes or genome. However, data analysis is still the biggest bottleneck for its wide implementation. Most laboratories still depend on manual procedures for data handling and analyses, which translates into a delay and decreased efficiency in the delivery of NGS results to doctors and patients. Thus, there is high demand for developing an automatic and an easy-to-use NGS data analyses system. We developed comprehensive, automatic genetic analyses controller named Mobile Genome Express (MGE) that works in smartphones or other mobile devices. MGE can handle all the steps for genetic analyses, such as: sample information submission, sequencing run quality check from the sequencer, secured data transfer and results review. We sequenced an Actrometrix control DNA containing multiple proven human mutations using a targeted sequencing panel, and the whole analysis was managed by MGE, and its data reviewing program called ELECTRO. All steps were processed automatically except for the final sequencing review procedure with ELECTRO to confirm mutations. The data analysis process was completed within several hours. We confirmed the mutations that we have identified were consistent with our previous results obtained by using multi-step, manual pipelines. [ABSTRACT FROM AUTHOR]

To examine whether the recent price patterns and transaction costs of Bitcoin represent a general characteristic of decentralized virtual currencies, we analyze virtual currencies in online games that have been voluntarily managed by individuals since 1990s. We find that matured game currencies have price stability similar to that of small size equities or gold, and their transaction costs are sometimes lower than real currencies. Assuming that virtual currencies with a longer history can provide an estimate for Bitcoin’s prospects, we project that Bitcoin will be less influenced by speculative trades and become a low cost alternative to real currencies. [ABSTRACT FROM AUTHOR]

The article discusses potential complications related to blood transfusions in orthpopaedic surgery. It also discusses strategies to reduce the need for transfusion, and review the orthopaedic literature to discuss issues related to postoperative anemia. It is noted that international survey of blood utilization reveal orthopaedics uses 6% to 13.8% of allogeneic and autologous packed red blood cells, total hip arthroplasty uses 4.85% and total knee arthroplasty uses 1.93%.

Simple Summary: We conducted a retrospective cohort study to evaluate the association between broad-spectrum antibiotic use and disease progression in early-stage melanoma patients who underwent surgery. We used healthcare claims data (2008–2018) and identified individuals with melanoma diagnosis and surgery within 90 days of diagnosis. We studied the relationship between melanoma progression (a proxy measure created using cancer therapies, surgery, and metastasis) within 2 years of melanoma surgery and antibiotic use in three time windows separately: (i) 3 months prior to surgery, (ii) 1 month after surgery, and (iii) 3 months after surgery. We found that prescriptions for antibiotics in 3 months prior to surgery were not associated with melanoma progression; in contrast, antibiotic use in post-1- and post-3-months windows was associated with reduced risk of progression. Our study is exploratory and limited to early-stage melanoma patients with surgery. Animal studies and a few clinical studies have reported mixed findings on the association between antibiotics and cancer incidence. Antibiotics may inhibit tumor cell growth, but could also alter the gut-microbiome-modulated immune system and increase the risk of cancer. Studies that assess how antibiotics affect the progression of cancer are limited. We evaluated the association between broad-spectrum antibiotic use and melanoma progression. We conducted a retrospective cohort study using IQVIA PharMetrics® Plus data (2008–2018). We identified patients with malignant melanoma who underwent wide local excision or Mohs micrographic surgery within 90 days of first diagnosis. Surgery date was the index date. Patients were excluded if they had any other cancer diagnosis or autoimmune disorders in 1 year before the index date ("baseline"). Exposure to broad-spectrum antibiotics was identified in three time windows using three cohorts: 3 months prior to the index date, 1 month after the index date, and 3 months after the index date. The covariates were patients' demographic and clinical characteristics identified in the 1-year baseline period. The patients were followed from the index date until cancer progression, loss of enrollment, or the end of 2 years after the index date. Progression was defined as: (i) any hospice care after surgery, (ii) a new round of treatment for melanoma (surgery, chemotherapy, immunotherapy, targeted therapy, or radiotherapy) 180 days after prior treatment, or (iii) a metastasis diagnosis or a diagnosis of a new nonmelanoma primary cancer at least 180 days after first melanoma diagnosis or prior treatment. A high-dimensional propensity score approach with inverse weighting was used to adjust for the patients' baseline differences. Cox proportional hazard regression was used for estimating the association. The final samples included 3930, 3831, and 3587 patients (mean age: 56 years). Exposure to antibiotics was 16% in the prior-3-months, 22% in the post-1-month, and 22% in the post-3-months. In the pre-3-months analysis, 9% of the exposed group and 9% of the unexposed group had progressed. Antibiotic use was not associated with melanoma progression (HR: 0.81; 95% CI: 0.57–1.14). However, antibiotic use in subsequent 1 month and subsequent 3 months was associated with 31% reduction (HR: 0.69; 95% CI: 0.51–0.92) and 32% reduction (HR: 0.68; 95% CI: 0.51–0.91) in progression, respectively. In this cohort of patients with likely early-stage melanoma cancer, antibiotic use in 1 month and 3 months after melanoma surgery was associated with a lower risk of melanoma progression. Future studies are warranted to validate the findings. [ABSTRACT FROM AUTHOR]

• Neurotrophic factors and growth factors enhance adult hippocampal neurogenesis. • VEGF couples angiogenesis and adult hippocampal neurogenesis. • PV/nNOS interneurons induces functional hyperemia through nitric oxide signaling. • Functional hyperemia enhances adult hippocampal neurogenesis. • Neurovascular dysfunction is indicated in Alzheimer's disease. The subgranular zone of the dentate gyrus provides a local microenvironment (niche) for neural stem cells. In the adult brain, it has been established that the vascular compartment of such niches has a significant role in regulating adult hippocampal neurogenesis. More recently, evidence showed that neurovascular coupling, the relationship between blood flow and neuronal activity, also regulates hippocampal neurogenesis. Here, we review the most recent articles on addressing the intricate relationship between neurovasculature and adult hippocampal neurogenesis and a novel pathway where functional hyperemia enhances hippocampal neurogenesis. In the end, we have further reviewed recent research showing that impaired neurovascular coupling may cause declined neurogenesis and contribute to brain damage in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Dropout from psychotherapy is common and can have negative effects for patients, providers, and researchers. A better understanding of when and why patients stop treatment early, as well as actionable factors contributing to dropout, has the potential to prevent it. Here, we examined dropout from a large randomized controlled trial of transdiagnostic versus single-diagnosis cognitive-behavioral treatment (CBT) for patients with anxiety disorders (n = 179; Barlow et al., 2017). We aimed to characterize the timing of and reasons for dropout and test whether participants who dropped out had different symptom trajectories than those who completed treatment. Results indicated that overall, the greatest risk of dropout was prior to the first treatment session. In single-diagnosis CBT, dropout risk was particularly elevated before the first session and after other early sessions, whereas in transdiagnostic CBT, dropout risk was low and stable before and during treatment. Participants most often dropped out due to failure to comply with study procedures or dissatisfaction with or desiring alternative treatment. Results from multilevel models showed that trajectories of anxiety symptoms did not significantly differ between dropouts and completers. These findings suggest that there may be specific time windows for targeted and timely interventions to prevent dropout from CBT. [ABSTRACT FROM AUTHOR]

Background Although engagement of infectious disease physicians has been demonstrated to improve clinical outcomes in a variety of disease states, the extent of infectious disease (ID) physician engagement in quality improvement (QI) or their knowledge of QI has not been assessed. Methods A 12-question, web-based survey was distributed to members of the Infectious Diseases Society of America (IDSA) between August and October 2019 to assess knowledge of and engagement in QI. The survey link was sent to IDSA members who self-identified patient care as their primary professional activity. Results Responses were received from 200 individuals (5.4% response rate, which is just below the standard IDSA survey response rate of 6%), consisting of 175 adult infectious disease physicians (IDPs). Most respondents were employed in a hospital or clinic (41%), private or group practice (25%), or university/medical center (24%). Fifty-eight percent of respondents currently participate in QI projects, while 38% serve on QI oversight committees. Among respondents, 27% reported not being engaged in QI. Infection prevention/hospital epidemiology (77%), stewardship (72%), and antimicrobial resistance (56%) were the most commonly reported measure types. Respondents reported barriers that limited participation in QI, including cost (61%), lack of time (56%), lack of data collection resources (48%), and lack of an ID-specific registry (46%). IDPs report significant interest in additional training in QI and new quality measures. Conclusions Although IDPs participate in QI, there are gaps in QI knowledge and measurement systems. The low response rate of our survey also suggests a lack of engagement in QI among IDPs. Closing these gaps will benefit ID in a value-driven health care economy. [ABSTRACT FROM AUTHOR]

Objective: To compare rates and risk factors of severe COVID-19-related outcomes between American Indian/Alaska Native (AI/AN) and non-Hispanic White people (NHW). Methods: Aggregate Social Vulnerability Index (SVI), COVID-19-related risk factor, hospitalization, and mortality data were obtained from 16 states for January 1, 2020-March 31, 2021. Generalized estimating equation Poisson regression models calculated age-adjusted cumulative incidences, incidence ratios (IR), and 95% confidence intervals (CI) comparing AI/AN and NHW persons by age, sex, and county-level SVI status. Results: Race data were missing for 42.7% of COVID-19 cases, 24.7% of hospitalizations, and 10.1% of deaths. Risk of AI/AN COVID-19 mortality was 2.6 times that of NHW persons (IR 2.6, 95% CI: 1.7 - 3.4); risk of COVID-19-related hospitalization among AI/AN persons was 3.5 times that of NHW (IR: 3.5, 95% CI: 2.7 - 4.3). Severe COVID-19 outcomes were significantly higher for AI/AN persons compared to NHW persons across all age and sex groups. There was no statistically significant difference in COVID-19 outcomes by SVI status. Associations between severe COVID-19 outcomes and co-morbid risk factors were inconsistent. Conclusions: Results describe increased risk of severe COVID-19 outcomes for AI/AN persons compared to NHW persons despite quality issues in public health surveillance data. Data linkages and improved ascertainment reduce race/ethnicity misclassification and improve data quality. COVID-19-related health burdens among AI/AN persons warrant improved access for AI/AN communities to medical countermeasures and healthcare resources. [ABSTRACT FROM AUTHOR]

Natural and synthetic zeolites are microporous hydrated aluminosilicate minerals known for their high thermal stability and their use in various catalytic applications. In this study, the potential of modified Philippine natural zeolite as a cheap alternative to noble metal catalysts in three-way catalytic converters was investigated. The natural zeolite (Z) of the heulandite variety was treated using hydrochloric acid and then ion-exchanged with sodium (NaZ) and copper (CuZ) ions in succession. Energy-dispersive X-ray spectroscopy analysis revealed successful replacement of sodium and other exchangeable cations by copper in the zeolite at 1.19%. Morphological features using scanning electron microscope have shown uniform dispersion of copper as well as uniform particle distribution. In the emission study, a stationary two-stroke 125 cm3 spark-ignition gasoline engine motorcycle at three different speeds of 10 (low), 40 (medium) and 70 (high) kilometers per hour (kph) was used to investigate the catalytic properties of CuZ with the non-catalytic setup as baseline. Using the modified zeolite catalyst, emission test results have shown significant reduction in carbon monoxide (CO) and hydrocarbon (HC) emissions in all speeds, while nitrogen monoxide (NO) emission was significantly reduced from medium to high speeds, suggesting that NO reduction was highly influenced by reaction temperature. Highest reduction in CO emission was 59.61% at medium speed, while highest HC and NO emissions were 66.52% and 76.63%, respectively, at high speed. While further tests are recommended, results show the potential of modified Philippine natural zeolite as a cheap alternative material for three-way catalytic converters. [ABSTRACT FROM AUTHOR]

Histone acetylation is a key component in the consolidation of long-term fear memories. Histone acetylation is fueled by acetyl-coenzyme A (acetyl-CoA), and recently, nuclear-localized metabolic enzymes that produce this metabolite have emerged as direct and local regulators of chromatin. In particular, acetyl-CoA synthetase 2 (ACSS2) mediates histone acetylation in the mouse hippocampus. However, whether ACSS2 regulates long-term fear memory remains to be determined. Here, we show that Acss2 knockout is well tolerated in mice, yet the Acss2-null mouse exhibits reduced acquisition of long-term fear memory. Loss of Acss2 leads to reductions in both histone acetylation and expression of critical learning and memory-related genes in the dorsal hippocampus, specifically following fear conditioning. Furthermore, systemic administration of blood-brain barrier-permeable Acss2 inhibitors during the consolidation window reduces fear-memory formation in mice and rats and reduces anxiety in a predator-scent stress paradigm. Our findings suggest that nuclear acetyl-CoA metabolism via ACSS2 plays a critical, previously unappreciated, role in the formation of fear memories. [ABSTRACT FROM AUTHOR]

Background: Telemedicine use increased during the COVID-19 pandemic due to concerns for patient and provider safety. Given the lack of testing resources initially and the large geographical range served by Augusta University (AU), a telemedicine platform with up-to-date screening guidelines was implemented for COVID-19 testing in March 2020. Our objective was to understand the level of adherence to telemedicine screening guidelines for COVID-19. Methods: The study population included health care providers and population who participated in an encounter in the AU Health Express Care virtual care program from March 22 to May 21, 2020. All encounters were intended to be for COVID-19 screening, free, and available 24 h per day, 7 days per week. Screening guidelines were developed by AU based on information from the Centers for Disease Control and Prevention and the Georgia Department of Public Health. Results: Among 17,801 total encounters, 13,600 were included in the final analysis. Overall adherence to screening guidelines was 71% in the adult population and 57% in the pediatric population. When providers did not follow guidelines, 72% determined that the patient should have a positive screen. Guidelines themselves determined that only 52% of encounters should have a positive screen. Providers' specialty significantly correlated with guideline adherence (p = 0.002). Departments with the highest adherence were psychiatry, neurology, and ophthalmology. No significant correlation was found between guideline adherence and provider degree/position. Conclusions: This study provides proof of concept of a free telehealth screening platform during an ongoing pandemic. Our screening experience was effective and different specialties participated. Our patient population lived in lower than average income zip codes, suggesting that our free telemedicine screening program successfully reached populations with higher financial barriers to health care. Early training and a posteriori knowledge of telemedicine was likely key to screening guideline adherence. [ABSTRACT FROM AUTHOR]

An organic solvent-stable alkaline hydrolase (PA27) from Pseudomonas aeruginosa MH38 was expressed, characterized, and immobilized for biotechnological applications. Recombinant PA27 was expressed in Escherichia coli as a 27 kDa soluble protein and was purified by standard procedures. PA27 was found to be stable at pH 8-11 and below 50 °C. It maintained more than 80% of its activity under alkaline conditions (pH 8.0-11.0). Furthermore, PA27 exhibited remarkable stability in benzene and n-hexane at concentrations of 30% and 50%. Based on these properties, immobilization of PA27 for biotechnological applications was explored. Scanning electron microscopy revealed a very smooth spherical structure with numerous large pores. Interestingly, immobilized PA27 displayed improved thermal/chemical stabilities and high reusability. Specifically, immobilized PA27 has improved thermal stability, maintaining over 90% of initial activity after 1 h of incubation at 80 °C, whereas free PA27 had only 35% residual activity. Furthermore, immobilized PA27 showed higher residual activity than the free enzyme biocatalysts against detergents, urea, and phenol. Immobilized PA27 could be recycled 20 times with retention of ∼60% of its initial activity. Furthermore, macroscopic hydrogel formation of PA27 was also investigated. These characteristics make PA27 a great candidate for an industrial biocatalyst with potential applications. [ABSTRACT FROM AUTHOR]

Purpose: Measurements of breast arterial calcifications (BAC) can offer a personalized, non‐invasive approach to risk‐stratify women for cardiovascular diseases such as heart attack and stroke. We aim to detect and segment breast arterial calcifications in mammograms accurately and suggest novel measurements to quantify detected BAC for future clinical applications. Methods: To separate BAC in mammograms, we propose a lightweight fine vessel segmentation method Simple Context U‐Net (SCU‐Net). Due to the large image size of mammograms, we adopt a patch‐based way to train SCU‐Net and obtain the final whole‐image‐size results by stitching patchwise results together. To further quantify calcifications, we test five quantitative metrics to inspect the progression of BAC for subjects: sum of mask probability metric (PM), sum of mask area metric (AM), sum of mask intensity metric (SIM), sum of mask area with threshold intensity metric TAMX, and sum of mask intensity with threshold X metric TSIMX. Finally, we demonstrate the ability of the metrics to longitudinally measure calcifications in a group of 26 subjects and evaluate our quantification metrics compared with calcified voxels and calcium mass on breast CT for 10 subjects. Results: Our segmentation results are compared with state‐of‐the‐art network architectures based on recall, precision, accuracy, F1 score/Dice score, and Jaccard index evaluation metrics and achieve corresponding values of 0.789, 0.708, 0.997, 0.729, and 0.581 for whole‐image‐size results. The quantification results all show >95% correlation between quantification measures on predicted masks of SCU‐Net as compared to the groundtruth and measurement of calcification on breast CT. For the calcification quantification measurement, our calcification volume (voxels) results yield R2‐correlation values of 0.834, 0.843, 0.832, 0.798, and 0.800 for the PM,AM,SIM,TAM100,TSIM100 metrics, respectively; our calcium mass results yield comparable R2‐correlation values of 0.866, 0.873, 0.840, 0.774, and 0.798 for the same metrics. Conclusions: Simple Context U‐Net is a simple method to accurately segment arterial calcification retrospectively on routine mammograms. Quantification of the calcifications based on this segmentation in the retrospective cohort study has sufficient sensitivity to detect the normal progression over time and should be useful for future research and clinical applications. [ABSTRACT FROM AUTHOR]

Postoperative external beam radiation therapy (EBRT) with superficial X-rays or electrons and high-dose-rate brachytherapy (HDR BT) are both viable options for managing keloid scars. However, complex keloid scars are especially challenging to manage. We aim to compare the benefit and challenges between interstitial HDR BT and electron EBRT in treating the complex keloids. Three patients with 7 complex keloids: 3 jaw lines, 1 postauricular, 1 posterior neck, and 2 chest walls are included in this study. All patients are treated to 6 Gy x 3 fractions with HDR BT using the flexible interstitial catheters, and electron EBRT plans were created retrospectively for dosimetric comparison. The average D 90 is 21.8 ± 8.3 Gy (1 SD) (121%) and 16.9 ± 1.9 Gy (1SD) (94%) in HDR and EBRT plans, respectively. The average treatment time was 7 minutes per patient (range: 6 – 8.5 minutes) for the HDR BT. Dosimetric comparison reveals that HDR plans provide superior coverage to the keloid scars than the EBRT plans. Clinical workflow is streamlined with HDR procedures. The cosmetic outcome with the interstitial HDR BT is satisfactory. [ABSTRACT FROM AUTHOR]

Objective: To determine the predictive value of an aneuploid diagnosis with a targeted next-generation sequencing-based preimplantation genetic testing for aneuploidy (PGT-A) assay in prognosticating the failure of a successful delivery.Design: Prospective, blinded, multicenter, nonselection study. All usable blastocysts were biopsied, and the single best morphologic blastocyst was transferred before genetic analysis. Preimplantation genetic testing for aneuploidy was performed after clinical outcome was determined. Clinical outcomes were compared to PGT-A results to calculate the predictive value of a PGT-A aneuploid diagnosis.Setting: Fertility centers.Patient(s): Couples undergoing their first in vitro fertilization cycle without recurrent pregnancy loss, antral follicle count < 8, or body mass index ≥ 35 kg/m2.Intervention(s): None.Main Outcome Measure(s): The primary outcome was the ability of the analytical result of aneuploid to predict failure to deliver (clinical result). A secondary outcome was the impact of the trophectoderm biopsy on sustained implantation.Result(s): Four hundred two patients underwent 484 single, frozen, blastocyst transfers. The PGT-A aneuploid diagnosis clinical error rate was 0%. There was no difference in sustained implantation between the study group and an age-matched control group, where biopsy was not performed (47.9% vs. 45.8).Conclusion(s): The PGT-A assay evaluated was highly prognostic of failure to deliver when an aneuploid result was obtained. Additionally, the trophectoderm biopsy had no detectable adverse impact on sustained implantation.Clinical Trial Registration Numbers: NCT02032264 and NCT03604107. [ABSTRACT FROM AUTHOR]

Purpose: To compare brachytherapy to external beam radiation therapy (EBRT) with respect to overall survival (OS) and disease-specific survival (DSS) among NSCLC patients undergoing limited surgical resection. Methods: All cases of T1-4 N0 M0 NSCLC undergoing limited resection and either brachytherapy or EBRT diagnosed between 2004 and 2014 were extracted from the Surveillance, Epidemiology, and End Results database. Chi-square test and Fisher's exact analysis were used to analyze categorical variables while Student's t-test was used to analyze continuous variables. Univariate analysis to assess for differences in survival with respect to covariates was performed with the log-rank test. Multivariable analysis was performed with Cox proportional hazards regression models among the entire cohort and after sub-stratification by T stage. Results: Among 543 patients, 471 underwent EBRT and 72 underwent brachytherapy. Brachytherapy demonstrated improved OS and DSS on univariate analysis as compared to EBRT (p < 0.05). Cox regression also demonstrated improved OS and DSS with brachytherapy (HR 0.604; 95% CI [0.380; 0.961] and HR 0.524; 95% CI [0.303; 0.908], respectively). Sub-cohort analysis demonstrated significant improvement in survival only among patients with T1 disease with similar survival between brachytherapy and EBRT among higher stage disease. Conclusions: Patients undergoing brachytherapy for T1-T4, N0, M0 NSCLC demonstrated at least similar survival as compared to those undergoing EBRT among patients undergoing limited resection. Improved survival was demonstrated among patients with T1 disease. [ABSTRACT FROM AUTHOR]

A retrospective analysis of the Surveillance, Epidemiology, and End Results database was performed to evaluate the effect of radiotherapy (RT) on overall survival and disease-specific survival. Patients undergoing RT had improved overall survival and disease-specific survival on multivariate Cox regression and after propensity score matching as compared with patients who did not receive RT. Introduction: The aim of this study was to perform a Surveillance, Epidemiology, and End Results (SEER) analysis on the effect of radiotherapy (RT) on survival among patients with prostate ductal adenocarcinoma (DA), a rare variant of prostate cancer. Patients and Methods: Cases of T1 to 4 N0 M0 prostate DA diagnosed between 2004 and 2013 were extracted from SEER. The association between categorical variables and radiation therapy was assessed for statistical significance using the x² test or Fisher exact test. Difference in continuous variables across the RT groups was assessed for statistical significance using the 2-sample t test or non-parametric test. The distribution of overall survival (OS) and disease-specific survival (DSS) between the RT groups was assessed using the Kaplan-Meier method and the log rank test and after propensity matching. The association between hazards of death (HR) and covariates was examined using Cox proportional hazards model. A 2-sided P-value of .05 was used to determine statistical significance. Results: A total of 205 patients met inclusion criteria. On univariate analysis, RT was associated with significant improvement in OS and DSS. On multivariate Cox regression, RT significantly decreased risk of death for both OS and DSS (HR, 0.516; 95% confidence interval [CI], 0.273-0.978 and HR, 0.232; 95% CI, 0.082-0.658, respectively). After propensity score matching, RT demonstrated a persistent improvement in both OS and DSS. Conclusions: RT decreased risk of death for both OS and DSS in patients with node-negative, nonmetastatic prostate DA on multivariable analysis. RT was also associated with improved OS and DSS after propensity matching. [ABSTRACT FROM AUTHOR]

Purpose: The health care industry has many stakeholders who seek relationships within government to ensure certain interests are considered in the legislative process. This study characterized the federal political contributions of US radiation oncologists (ROs).Methods and Materials: Public finance data from the Federal Election Commission (FEC) containing self-identified ROs' contributions to a federal candidate or committee were obtained from 2003 to 2018. Contribution recipients were classified as a political action committee (PAC) or a presidential, Senate, or House candidate. Political parties of recipients were based on FEC designations. For PACs, political parties of recipients were based on spending patterns to political parties in each 2-year election cycle or, when unavailable, overall spending patterns of greater than 50% to 1 political party, as detailed by the Center for Responsive Politics. Data were analyzed temporally, and Spearman's rho was used to assess trends.Results: From 2003 to 2018, the FEC reported a total of 31,646,000 federal political contributions. Exactly 4617 federal political contributions were made from 1021 unique self-identified ROs, totaling $3,350,747. The number of ROs making contributions ranged from 56 in 2005 to 600 in 2016 (mean, 289 ± 191.4 ROs yearly), with a mean annual contribution of $209,422. Of all RO dollars, 61.5% went to Democrats, 37.5% to Republicans, and 1.0% to third-party candidates. Most RO dollars (81.0%) went to PACs rather than candidates, with the majority of those PAC dollars (50.2%) directed toward the American Society for Radiation Oncology Political Action Committee. There was a positive annual trend in number of donors by year (ρ = 0.83, P < .0001) as well as RO contributions to the House (ρ = 0.58, P < .02), Senate (ρ = 0.58, P < .02), Democrats (ρ = 0.81, P < .001), Republicans (ρ = 0.66, P < .006), third-parties (ρ = 0.87, P < .001), PACs (ρ = 0.85, P < .0001), and overall (ρ = 0.8, P < .001). There was not a significant trend in contributions to presidential candidates (ρ = 0.71, P = .06).Conclusions: ROs' federal political contributions have significantly increased over the last decade and a half. This growth overwhelmingly represents contributions to specialty-focused PACs and both Democratic and Republican congressional candidates. [ABSTRACT FROM AUTHOR]

To characterize inventions and assess trends in brachytherapy innovation based on brachytherapy-related patents awarded across the past 2 decades and provide insights that will help inform future research and entrepreneurship in the field. The United States Patent and Trademark Office database was searched for patents awarded between 1999 and 2018 with a classification code corresponding to the broadest brachytherapy search category. Patent characteristics were stratified and compared by geographic location, affiliation, and theme of invention. There were 202 brachytherapy-related patents awarded from 2009 to 2018, which indicates a 56% increase in patent productivity and brachytherapy innovation compared with the previous decade from 1999 to 2008. Patents had an industry affiliation in 83% of cases from 1999 to 2008 and in 76% of cases from 2009 to 2018. Meanwhile, academic participation in brachytherapy patent innovation rose from 4% to 11% in that time. The focus and theme of inventions evolved across time, with radiation sources being the most common theme from 1999 to 2008 and falling to third place in 2009–2018. Conversely, development of brachytherapy-related patents involving exogenous agents such as drug-conjugates, radiosensitizers, and adjuncts to treatment increased substantially in the subsequent decade. While no collaboration was observed between academia and industry between 1999 and 2008, notable partnerships emerged in the subsequent decade which amounted to almost 5% of all patents awarded between 2009 and 2018. There has been an increase in overall brachytherapy patent production over time, and this has been accompanied by a greater variety of distinct patent themes. Collaboration between industry and academia is rare. Knowledge of brachytherapy patents may inform future research innovation in this field. [ABSTRACT FROM AUTHOR]

Many patients with open-angle glaucoma eventually require >2 medications to lower their intraocular pressure (IOP). Fixed-combination ophthalmic solutions can be advantageous in patients who require multiple medications, but the number of fixed combinations combining 3 complementary IOP-lowering agents remains limited. This study assessed the efficacy and safety of a triple fixed combination (TFC) of bimatoprost 0.01%/brimonidine 0.15%/timolol 0.5% ophthalmic solution in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT), compared with a dual fixed combination (DFC) of brimonidine 0.2%/timolol 0.5%. Patients with a baseline IOP of 23–34 mm Hg in both eyes and no history of IOP-lowering procedures were eligible for participation in this multicenter, double-masked, randomized, Phase III study. After washout of previous treatment (if applicable), patients were randomized to receive TFC or DFC twice daily in each eye for 3 months. The primary efficacy variable was the change from baseline in mean IOP in the worse eye at week 12 in the modified intent-to-treat (mITT) population. TFC was superior to DFC if the treatment difference (TFC – DFC) favored TFC at week 12 (P ≤ 0.05; 2-sample t test). Secondary and sensitivity analyses were also performed. Safety, including adverse events, was assessed at all visits. The mITT/safety population included 185 patients (TFC, n = 90; DFC, n = 95). TFC superiority was demonstrated at all postbaseline visits (all, P < 0.001) through week 12 (week 12 treatment difference: ─2.17 mm Hg; 95% CI, ─3.12 to ─1.22). While treatment-related conjunctival hyperemia was more frequent with TFC than with DFC (47.8% vs 23.2%; P < 0.001), consistent with the additional presence of bimatoprost in TFC, most cases were mild and the numbers of patient discontinuations at week 12 were similar between the TFC and DFC groups (11 [12.2%] vs 7 [7.4%] patients; P = 0.266). No unexpected adverse events were reported. Compared with DFC, TFC provided superior IOP lowering throughout the primary efficacy period. An acceptable tolerability profile was observed through 12 months of use of TFC, offering an effective therapeutic option in patients with POAG or OHT who require multiple medications to control their IOP. Additional studies are required for the assessment of the long-term effects of TFC. ClinicalTrials.gov identifier: NCT01217606. • Bimatoprost can be used twice daily in this novel fixed-combination formulation. • This triple fixed combination significantly lowers intraocular pressure. • The effect was superior to that of a well-established dual fixed combination. • No unexpected adverse events were reported. • A new treatment for control of intraocular pressure requiring multiple medications. [ABSTRACT FROM AUTHOR]

The shift from volume-based to value-based reimbursement has created a need for quantifying clinical performance of infectious diseases (ID) physicians. Nationally recognized ID specialty-specific quality measures will allow stakeholders, such as patients and payers, to determine the value of care provided by ID physicians and will promote clinical quality improvement. Few ID-specific measures have been developed; herein, we provide an overview of the importance of quality measurement for ID, discuss issues in quality measurement specific to ID, and describe standards by which candidate quality measures can be evaluated. If ID specialists recognize the need for quality measurement, then ID specialists can direct ID-related quality improvement, quantify the impact of ID physicians on patient outcomes, compare their performance to that of peers, and convey to stakeholders the value of the specialty. [ABSTRACT FROM AUTHOR]

In this paper, we present a review of machine health managements for the smart factory. As the Industry 4.0 leads current factory automation and intelligent machines, the machine health management for diagnostic and prognostic purposes are essential, and their importance is getting more significant for the realization of the smart factory in the Industry 4.0. After brief introductions to important concepts and definitions composing smart factory and Industry 4.0, the developments in maintenance strategies towards Prognostics and health management (PHM) of machines are summarized. The review of machine health managements is followed, classifying the references by the monitoring components, types of measurements, as well as PHM tools and algorithms. 94 existing articles are reviewed and summarized in this regard. The implementations of machine health managements within the smart factory are discussed in terms of data connectivity, communications, Cyber-physical system (CPS) and virtual factory, relating them to Internet of things (IoT), cloud computing, and big data management. [ABSTRACT FROM AUTHOR]

The Center for Medicare and Medicaid Services adopted the Early Management Bundle, Severe Sepsis/Septic Shock (SEP-1) performance measure to the Hospital Inpatient Quality Reporting Program in July 2015 to help address the high mortality and high cost associated with sepsis. The SEP-1 performance measure requires, among other critical interventions, timely administration of antibiotics to patients with sepsis or septic shock. The multistakeholder workgroup recognizes the need for SEP-1 but strongly believes that multiple antibiotics listed in the antibiotic tables for SEP-1 are not appropriate and the use of these antibiotics, as called for in the SEP-1 measure, is not in alignment with prudent antimicrobial stewardship. To promote the appropriate use of antimicrobials and combat antimicrobial resistance, the workgroup provides recommendations for appropriate antibiotics for the treatment of sepsis. [ABSTRACT FROM AUTHOR]

Accurate target delineation/contouring is essential for radiation treatment planning and the clinical efficacy of radiation therapy. Clinical trial data has demonstrated the importance of quality contouring and treatment planning for optimal survival outcomes. As a result, improving the quality of target delineation is an important goal in the education of radiation oncology residents. However, there is limited quantitative data on the quality of residents' contours. Therefore, it would be beneficial to track performance and improvement in resident target delineation during residency. The purpose of this study was to determine if it was feasible to track the concordance of radiation oncology residents' contours with faculty physicians' contours. Residents were asked to contour target volumes (GTV, CTV, ITV, PTV, etc.) based on patient history, physical exam, clinical stage and fused diagnostic imaging and were allowed to use any available outside resources, including textbooks, review articles, consensus guidelines, and online atlases. Resident contours were saved as separate structures. Finalized, faculty physician-approved contours were also saved. Saved contour structures and data from October 2019 through June 2020 were reviewed for feasibility. In total, 209 structures had both resident and faculty versions saved within Eclipse and were available for analysis. The Boolean Operations Tool in Eclipse (Varian Medical Systems, Palo Alto, CA, USA) was used to create an intersection volume of the resident/faculty contours. Separately, the Boolean Operations Tool was used to create a union volume of the resident/faculty contours. Based on these two volumes, the Jaccard Concordance Index (JCI) was calculated by dividing the intersection volume (in cubic centimeters [cc]) by the union volume (cc). The JCI could be successfully calculated for 203 (97.1%) of the 209 structures. For 6 structures (2.9%), both the intersection and union volumes could not be calculated because the volumes were too small for Eclipse to determine. All 6 of these structures were small brain metastases. Tracking and comparing the concordance of resident contours and faculty physician contours is feasible using available tools in Eclipse. Additional data collection and assessment is necessary before this technique can be more widely utilized. [ABSTRACT FROM AUTHOR]

The triazine antitubercular JSF-2019 was of interest due to its in vitro efficacy and the nitro group shared with the clinically relevant delamanid and pretomanid. JSF-2019 undergoes activation requiring F 420 H 2 and one or more nitroreductases in addition to Ddn. An intrabacterial drug metabolism (IBDM) platform was leveraged to demonstrate the system kinetics, evidencing formation of NO⋅ and a des-nitro metabolite. Structure-activity relationship studies focused on improving the solubility and mouse pharmacokinetic profile of JSF-2019 and culminated in JSF-2513, relying on the key introduction of a morpholine. Mechanistic studies with JSF-2019, JSF-2513, and other triazines stressed the significance of achieving potent in vitro efficacy via release of intrabacterial NO⋅ along with inhibition of InhA and, more generally, the FAS-II pathway. This study highlights the importance of probing IBDM and its potential to clarify mechanism of action, which in this case is a combination of NO⋅ release and InhA inhibition. • Optimization of an antitubercular agent afforded gains in solubility and plasma PK • The triazines release intrabacterial NO⋅ as the predominant mechanism of action • The triazines/their intrabacterial metabolites also inhibit InhA and FAS-II pathway Wang et al. disclose the optimization of a triazine antitubercular agent and probe its mechanism of action. They demonstrate the significance of studying intrabacterial drug metabolism. Through this approach and other methods, they evidence a novel mechanism involving NO⋅ release and inhibition of the cell wall biosynthesis enzyme InhA. [ABSTRACT FROM AUTHOR]

A summary is presented of the article "Deficiency of microRNA miR-34a expands cell fate potential in pluripotent stem cells," published in the online version of the journal. Topics discussed include the generation of embryonic and extraembryonic lineages in teratomas and the role of protein-coding genes, noncoding RNAs, and endogenous retroviruses in stem cell development.

Objective To determine whether endometrial hCG infusion at the time of human blastocyst transfer impacts implantation rates. Design Randomized double-blinded placebo-controlled trial. Setting Academic. Patient(s) Infertile couples with the female partner less than 43 years old (n = 300) undergoing fresh or frozen ET of one or two blastocysts. Intervention(s) Patients undergoing ET were randomized into either a treatment or a control group. The treatment group received an infusion of 500 IU of hCG diluted in ET media. The control group received a sham infusion of ET media. Infusions were done using a separate catheter less than 3 minutes before actual ET. Main Outcome Measure(s) Sustained implantation rate: ongoing viable gestation (primary outcome) and ongoing pregnancy rate (secondary outcome). Result(s) A total of 473 blastocysts were transferred into 300 patients. There were no differences between the two groups in sustained implantation rate (48.1% in the hCG group, 44.2% in the control group) or ongoing pregnancy rate (58.8% in the hCG group, 52.0% in the control group). Conclusion(s) Endometrial infusion of hCG at the time of blastocyst ET does not improve sustained implantation rates. Clinical Trial Registration Number NCT01643993 . [ABSTRACT FROM AUTHOR]