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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%.

Objective: The Gulf Coast continues to struggle with service need far outpacing available resources. Since 2005, the Regional Coordinating Center for Hurricane Response (RCC) at Morehouse School of Medicine, Atlanta, GA, has supported telehealth solutions designed to meet high service needs (e.g., psychiatry) within primary care and other healthcare organizations. The overall RCC vision is to support autonomous, useful, and sustainable telehealth programs towards mitigating unmet disaster-related needs. Subjects and Methods: To assess Gulf Coast telehealth experiences, we conducted semistructured interviews with both regional key informants and national organizations with Gulf Coast recovery interests. Using qualitative-descriptive analysis, interview transcripts were analyzed to identify shared development themes. Results: Thirty-eight key informants were interviewed, representing a 77.6% participation rate among organizations engaged by the RCC. Seven elements critical to telehealth success were identified: Funding, Regulatory, Workflow, Attitudes, Personnel, Technology, and Evaluation. These key informant accounts reveal shared insights with telehealth regarding successes, challenges, and recommendations. Conclusions: The seven elements critical to telehealth success both confirm and organize development principles from a diverse collective of healthcare stakeholders. The structured nature of these insights suggests a generalizable framework upon which other organizations might develop telehealth strategies toward addressing high service needs with limited resources. [ABSTRACT FROM AUTHOR]

Abstract: A fast, sensitive and selective liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the determination of alfentanil and midazolam in human plasma has been developed and validated. Alfentanil and midazolam were extracted from plasma using a mixed-mode cation exchange solid phase extraction method, with recoveries of both compounds greater than 80% at 3 different concentrations (1, 10 and 100ng/ml). Compounds were analyzed on a C18 column with a water and methanol mobile phase gradient with acetic acid as an additive, at a flow rate of 0.3ml/min. The working assay range was linear from 0.25 to 100ng/ml for each compound. The signal to noise ratio was 80 and 40 for alfentanil and midazolam, respectively, at the lowest concentration calibration standard, with less than 10% matrix suppression by human plasma at this concentration. Alfentanil and midazolam were stable in human plasma during storage at −80°C, processing, and analysis. The procedure was validated and applied to the analysis of plasma samples from healthy human subjects administered oral and intravenous alfentanil and midazolam. [Copyright &y& Elsevier]

Objective: To report a birth of a healthy boy after long-term cryopreservation of oocytes by vitrification. Design: Clinical application. Setting: IVF Center. Patient: A 17 year-old female with secondary pulmonary hypertension caused by transposition of great vessels visited our center in 2002, and she wished oocytes cryopreservation to avoid possible sterility after the following category X medication treatment. Intervention(s): Vitrified oocytes on Electron Microscope (EM) grids were warmed after 5 years of storage. Surviving MII oocytes were microinjected for fertilization and two embryos were transferred into a gestational carrier day 5 after microinjection. Main Outcome Measure(s): Survival, fertilization, cleavage, clinical pregnancy and delivery. Result(s): Eleven out of fourteen oocytes (78.6%) survived warming. Eight Metaphase II (MII) oocytes and 3 in vitro matured oocytes were microinjected; all 11 oocytes (100%) fertilized and 2 embryos were transferred on day 5. A healthy baby boy weighing 3,600 g was delivered at 38 weeks of gestation. Live-birth rates per warmed oocyte and per injected oocyte were 7.1% and 9.1% respectively. Conclusion(s): Cryopreservation after vitrification with EM grids maintained the developmental competence of oocytes after long-term storage and resulted in a successful live birth. [ABSTRACT FROM AUTHOR]

Three acute cardiovascular events within a 4-month period among drivers at an indoor go-kart arena prompted a visit to assess the magnitude of potentially hazardous air pollutant levels within the facility and help identify control measures. Carbon monoxide (CO) and particulate matter with aerodynamic diameters < 2.5 μ m (PM2.5) were measured with personal, continuous-reading instruments to capture their spatial and temporal variability. Average driver and track CO levels during the sampling visit were comparable to state standards for worker exposures and exceeded some health-based guidelines. Average PM2.5 levels were low compared with regulatory standards, but transient PM2.5 peaks of unknown health impact were observed. Driver exposures were modestly but significantly higher than track concentrations measured by stationary monitors and substantially higher than outdoor concentrations. Driver exposures were partitioned into three components, attributed to (1) outdoor pollutants that were drawn unfiltered into the facility, (2) the persistent track cloud from previous races, and (3) proximity to the exhausts of other go-karts while driving in a race. Track cloud and tailpipe proximity components were the dominant contributors to driver CO exposure. The track cloud component lagged the number of go-karts on the track by 10-15 min. The dominant contributor to driver PM2.5 exposure was either the track cloud or outdoor component, depending on how many go-karts were racing simultaneously on the track. Transient spikes in PM2.5 were caused by proximity to other karts' tailpipes during passing events. Recommended methods for decreasing the track cloud component include modifying the ventilation system, race schedules, and number of go-karts racing simultaneously. The tailpipe proximity component can be reduced only by modifying go-kart exhausts or engines. This work represents a brief, limited sampling visit to a single facility, but it demonstrates the levels that are possible on a fairly high-usage afternoon. Future studies should be conducted to assess representative go-kart facility exposures at multiple facilities on multiple days. [ABSTRACT FROM AUTHOR]

Objective: To determine the efficiency of our vitrification technique when applied in young fertile women. Design: Clinical research and application. Setting: In vitro fertilization center. Patient(s): Twenty-one women were recruited from the navy community with 19 patients finishing the study. Intervention(s): Vitrified oocytes with use of the electron microscopic grid method were warmed 6 months after vitrification. Surviving metaphase II oocytes were microinjected for fertilization, and clinical results were evaluated. Main Outcome Measure(s): Survival, fertilization, and cleavage rate. Pregnancy and implantation rate. Result(s): Three hundred ninety-five oocytes were warmed, of which 320 oocytes (81.0%) survived. Two hundred eighty-five metaphase II oocytes were microinjected for fertilization; 206 of them (72.3%) fertilized, and 53 embryos were transferred to 19 patients (in 20 warming cycles). Twenty-four of 53 transferred embryos (45.3%) implanted as confirmed by ultrasound examination. Of the 20 transfers, 16 resulted in clinical pregnancy (80%), 3 miscarried (15%), and 13 (65%) went on to produce 20 live births, respectively. This is much higher in comparison with our previous data using supernumerary oocytes where the rates of implantation and pregnancy were 6% and 21%. Live-birth rates per warmed oocyte and per injected oocyte were 5.1% and 7.2%, respectively. Conclusion(s): High pregnancy and implantation rates were observed after 6 months of cryopreservation by vitrification when oocytes from fertile woman were used. Proper screening of candidates for oocyte cryopreservation is of crucial importance to assure a favorable pregnancy outcome. [Copyright &y& Elsevier]

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]

The Ig superfamily (lgSF) intercellular adhesion molecule-1 (ICAM-1) equilibrates between monomeric and dimeric forms on the cell surface, and dimerization enhances cell adhesion. A crystal structure of ICAM-1 lgSF domains (D) 3–5 revealed a unique dimerization interface in which D4s of two protomers fuse through edge β-strands to form a single super β-sandwich domain. Here, we describe a crystal structure at 2.7-Å resolution of monomeric ICAM-1 D3–D5, stabilized by the monomer-specific Fab CA7. CA7 binds to D5 in a region that is buried in the dimeric interface and is distal from the dimerization site in D4. In monomeric ICAM-1 D3–D5, a 16-residue loop in D4 that is disordered in the dimeric structure could clearly be traced as a BC loop, a short C strand, and a CE meander with a cis-Pro followed by a solvent-exposed, flexible four-residue region. Deletions of 6 or 10 residues showed that the C-strand is essential for monomer stability, whereas a distinct six-residue deletion showed little contribution of the CE meander. Mutation of two inward-pointing Leu residues in edge β-strand E to Lys increased monomer stability, confirming the hypothesis that inward-pointing charged side chains on edge β-strands are an important design feature to prevent β-supersheet formation. Overall, the studies reveal that monomer-dimer transition is associated with a surprisingly large, physiologically relevant, lgSF domain rearrangement. [ABSTRACT FROM AUTHOR]

This essay traces the historical link between the presence of the Orient in the U.S. and the aspects of modern consumption. It looks into the agendas behind the presentation of aesthetic principles and productions of the Far East closer to the American consumer and explores the penetration of the Orient-as-object in aesthetic ethnography. The author ends by asserting the crystallization of consumption, capitalism, and questions of modernity in the figure of the modern Oriental.

Abstract: Protein phosphatase inhibitor-1 (PPI-1) is a major inhibitor of protein phosphatase 1 (PP1), which regulates signal transduction in many eukaryotic cellular processes. Biophysical studies have shown that PPI-1 has a large Stokes radius and is heat stable, suggesting that it lacks extensive secondary structures. The unfolded structure of PPI-1 may enable it to interact with many proteins or ligands during stress conditions. Here we show that PPI-1 can act as a protective molecule, inhibiting protein aggregation and guarding E. coli cells against various stresses. Therefore, PPI-1 seems to have a physiological function as a protective molecule as well as regulator of protein serine/threonine phosphatases. [Copyright &y& Elsevier]

The achievement gap between minority youth and the majority population in the United States is well documented (Johnston & Viadero, 2000). In order to reduce this gap and avail children of poverty of the most effective educational techniques, Project Follow Through was conducted in the 1960's. The research that compared a variety of educational approaches found Direct Instruction techniques to be the most effective along all measures. Since that time there have been numerous studies that have demonstrated the great benefit of Direct Instruction procedures for the education of minority youth. Yet, few school systems use the procedures. The article discusses arguments for and against the adoption of Direct Instruction techniques and makes a plea for minority educators to lead a movement that will lead to widespread espousal of the procedures. [ABSTRACT FROM AUTHOR]

The aggregation and fibrillization of α-synuclein, a major component of Lewy bodies, is a key event in Parkinson’s disease. Although the mechanisms of fibrils formation are largely investigated, physiological function of α-synuclein is not yet clearly elucidated. Here, we showed that C-terminal region of α-synuclein is similar to α-crystalline domain of small heat shock proteins. In our experiments, α-synuclein, like small heat shock proteins, protected cellular proteins from denaturation, and confer Escherichia coli cellular tolerances against thermal- and oxidative-stresses. [Copyright &y& Elsevier]

More than one million copies of the ∼300-bp Alu element are interspersed throughout the human genome, with up to 75% of all known genes having Alu insertions within their introns and/or UTRs. Transcribed Alu sequences can alter splicing patterns by generating new exons, but other impacts of intragenic Alu elements on their host RNA are largely unexplored. Recently, repeat elements present in the introns or 3′-UTRs of 15 human brain RNAs have been shown to be targets for multiple adenosine to inosine (A-to-I) editing. Using a statistical approach, we find that editing of transcripts with embedded Alu sequences is a global phenomenon in the human transcriptome, observed in 2674 (∼2%) of all publicly available full-length human cDNAs (n = 128,406), from >250 libraries and >30 tissue sources. In the vast majority of edited RNAs, A-to-I substitutions are clustered within transcribed sense or antisense Alu sequences. Edited bases are primarily associated with retained introns, extended UTRs, or with transcripts that have no corresponding known gene. Therefore, Alu-associated RNA editing may be a mechanism for marking nonstandard transcripts, not destined for translation. [ABSTRACT FROM AUTHOR]

A new dynamic measurement system has been developed to investigate damping in thin metal films. This system includes a vacuum chamber, in which a free-standing bilayer cantilever sample is vibrated using an electrostatic force, and a laser interferometer to measure the displacement and velocity of the sample. With this equipment, internal friction as low as 10-5 in micrometer thick metal films in a temperature range from 300 to 750 K can be measured. Free-standing cantilevers with different frequencies have been fabricated using well-established integrated circuit (IC) fabrication processes. The cantilevers consist of thin metal films on thicker Si substrates, which exhibit low damping. From measurements of internal friction of Al thin films at various temperatures and frequencies, it is possible to study relaxation processes associated with grain boundary diffusion. The activation energy calculated from the damping data is 0.57 eV, which is consistent with previous research. This value suggests that the mechanism of internal friction in pure Al films involves grain boundary diffusion controlled grain boundary sliding. A model to describe these damping effects has been developed. By deriving an expression for the diffusional strain rate using a two-dimensional (2-D) Coble creep model, and modifying the conventional standard linear solid model for the case of bending, it is possible to give a good account of the observed damping. [ABSTRACT FROM AUTHOR]

: ObjectiveTo assess the usefulness of the vitrification method in clinical practice.: DesignClinical study of vitrification of human oocytes.: SettingA university-affiliated hospital.: Patient(s)Thirty-four patients who agreed to undergo additional IVF-ET after the failed fresh cycle using the previously vitrified/thawed oocytes.: Intervention(s)Surplus oocytes from the IVF-ET patients were vitrified for the next cycle.: Main outcome measure(s)Morphologic normality of post-thawed oocytes, fertilization, cleavage, pregnancy, and implantation rate.: Result(s)Overall morphological survival and fertilization rates of vitrified/liquefied oocytes were 68.6% (325/474) and 71.7% (142/198), respectively. Pregnancy rate and implantation rate per embryo transfer were 21.4% (6/28) and 6.4% (8/125), respectively. All pregnancies resulted in the delivery of healthy babies (1 twin and 5 singletons/6 pregnancies).: Conclusion(s)The feasibility of the vitrification method for human oocytes was confirmed by our clinical results. Subsequent studies on vitrification and thawing procedures should be undertaken for further optimizing the vitrification method. [Copyright &y& Elsevier]

Objective.--To investigate the relationship between various histopathologic features and the results of the tuberculosis (TB)-polymerase chain reaction (PCR) method in routinely submitted histologic specimens for the histopathologic diagnosis of TB. Design.--We used 95 formalin-fixed, paraffin-embedded tissue blocks from 81 patients who were clinically suspected of having TB. We assessed the presence of histopathologic features including well-formed granuloma, poorly formed granuloma, caseous necrosis, and Langhans-type giant cells. We performed nested PCR for IS6110 and Ziehl-Neelsen staining for acid-fast bacilli (AFB). Results.--Of the 81 patients studied, 53 patients had chronic granulomatous inflammation, whereas 28 patients had only chronic inflammation without definite granulomatous inflammation. Of the 53 cases with chronic granulomatous inflammation, 17 (32%) were AFB positive and 36 (68%) were TB-PCR positive. Among cases with chronic granulomatous inflammation, the percentage that were positive and negative by TB-PCR differed significantly with the presence of various histopathologic features. All of the 13 cases with well-formed granuloma, caseous necrosis, and Langhans-type giant cells were TB-PCR positive; how-ever, 10 (36%) of the 28 cases with chronic inflammation without granulomatous lesions were also TB-PCR positive. Conclusions.--TB-PCR is a rapid, sensitive method for the diagnosis of TB in routinely processed formalin-fixed, paraffin-embedded histologic specimens and is readily available in histopathology laboratories. We recommend use of TB-PCR when TB is suspected clinically, especially in cases of chronic inflammation without definite evidence of granulomatous inflammation. [ABSTRACT FROM AUTHOR]

Aggregation of ct-synuclein is thought to play a major role in the pathogenesis of Parkinson's disease (PD), which is characterized by the presence of intracytoplasmic Lewy bodies (LB) in the brain. α-Synuclein and its deletion mutants are largely unfolded proteins with random coil structures as revealed by CD spectra, fluorescence spectra, gel filtration chromatography, and ultracentrifugation. On the basis of its highly unfolded and flexible conformation, we have investigated the chaperone-like activity of α-synuclein in vitro. In our experiments, α-synuclein inhibited the aggregation of model substrates and protected the catalytic activity of alcohol dehydrogenase and rhodanese during heat stress. In addition, α-synuclein inhibited the initial aggregation of reduced/denatured lysozyme on the refolding pathway. Interestingly, deletion of the C-terminal regions led to the abolishment of chaperone activity, although largely unstructured conformations are maintained. Moreover, α-synuclein could inhibit the aggregation of various Escherichia coli cellular proteins during heat stress, and C-terminal deletion mutants could not provide any protection to these cellular proteins. Results with synthetic C-terminal peptides and C-terminal deletion mutants suggest that the second acidic repeat, [sup 125]YEMPSEEGYQDYEPEA[sup 140], is important for the chaperone activity of α-synuclein, and C-terminal deletion leads to the facilitated aggregation with the elimination of chaperone activity. [ABSTRACT FROM AUTHOR]

Investigates the thermal behavior of proteins by purifying and characterizing heat-resistant proteins (HRP) that are not aggregated upon heat treatment. Types of thermal behavior of proteins; Identification of HRP from Jurkat cells; Features and heat stabilities of HRP.

This paper investigated reliability of a postbuckled composite isogrid stiffened shell structure under a compression load. The outside diameter of the isogrid cylinder was 624.8 mm, the length was 368.3 mm and the total weight of the cylinder was 3.24 kg. A finite element buckling analysis result was compared with the axial compression experimental data. The average critical buckling load of 186.56 kN was obtained by using the Patran finite element analysis (FEA). The isogrid shell was modeled using 3-node triangular elements and the stiffeners were modeled using 4-node quad elements with a total of 504 nodes and 900 elements. The postbuckled isogrid cylinder was compression tested to the failure load of 177.35 kN. The postbuckled cylinder continued to resist compression loading even after one or more stiffeners had fractured. The testing evaluation revealed that the stiffener buckling was the critical failure mode and it has been demonstrated to be tolerant to structural damage due to the multiplicity of load paths. The lower experimental bucking load was due to the small imperfections in the cylinder but this problem can be overcome by advancement in the manufacturing methods. [ABSTRACT FROM AUTHOR]

This paper describes the analyses performed to determine why nominally flat composite isogrid panels designed for the Clementine I satellite were warping during the autoclave cure cycle. Analytical models indicated that the largest factor was the mismatch in the coefficient of thermal expansion of different parts of the tooling. The next most important factor was the coefficient of thermal expansion mismatch between the skin and rib materials of the composite isogrid itself. A new tooling design eliminated the first factor, producing a rib-only panel with no warping. An analytical model was developed, which predicted that warping caused by the rib/skin mismatch would be 3.31 mm over a length of 147.32 cm. A panel with the skin was manufactured and found to have a warp of 3.80 mm. Further improvements in producing flat panels will depend on finding appropriate materials for the rib and skin. [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]

Examines explanation that emphasize voter intention. Ability of the House candidates to separate themselves in the eyes of constituents from the national party image; Role of political elites in influencing the behavior of split-ticket voters; Analysis of the personality of voters.

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]