A screen for cell envelope stress uncovers an inhibitor of prolipoprotein diacylglyceryl transferase, Lgt, in .

The increasing prevalence of antibiotic resistance demands the discovery of antibacterial chemical scaffolds with unique mechanisms of action. Phenotypic screening approaches, such as the use of reporters for bacterial cell stress, offer promise to identify compounds while providing strong hypotheses for follow-on mechanism of action studies. From a collection of ∼1,800 GFP transcriptional reporter strains, we identified a reporter that is highly induced by cell envelope stress-pProm -GFP.

Behavioral assessment and treatment of pica: a brief report.

Pica is a life-threatening behavior that is relatively common among individuals with intellectual and developmental disabilities. Pica can be conceptualized as a response chain in which the pica item acts as a discriminative stimulus for the next response (i.e.

Improving Access and Quality of Behavioral Health Services for Health Care Employees.

To describe key features and the initial implementation of an employer-sponsored program designed to increase access to quality mental health treatment for employees of a large health care system. Methods: Retrospective data were collected on employer's efforts to develop a programmatic solution to address barriers to accessing quality mental health treatment among its employees and on initial program implementation. Results: Data from the initial cohort ( N = 1049) of program participants support the use of low threshold digital tools to enhance access to care, the importance of care navigation and a robust curated provider network in matching employees to appropriate care options, and the value of providing online, evidence-based psychotherapy to facilitate high rates of treatment engagement.

Impacts of COVID-19 on alcohol use among help-seeking adults.

The coronavirus (COVID-19) pandemic has been associated with both increased and decreased alcohol use. Authors explored reasons for increased and decreased alcohol use since the COVID-19 lockdown (March 2020) in a sample of help-seeking adults (HSA) participating in a remote-based alcohol reduction text-messaging intervention in the USA. At the time of recruitment, the HSA in this study were interested in reducing rather than stopping their alcohol consumption.

A mobile CRISPRi collection enables genetic interaction studies for the essential genes of Escherichia coli.

Advances in gene editing, in particular CRISPR interference (CRISPRi), have enabled depletion of essential cellular machinery to study the downstream effects on bacterial physiology. Here, we describe the construction of an ordered E. coli CRISPRi collection, designed to knock down the expression of 356 essential genes with the induction of a catalytically inactive Cas9, harbored on the conjugative plasmid pFD152.

Automated, tailored adaptive mobile messaging to reduce alcohol consumption in help-seeking adults: A randomized controlled trial.

Aims: To test differential outcomes between three 6-month text-messaging interventions to reduce at-risk drinking in help-seeking adults.

Design: A three-arm single-blind randomized controlled trial with 1-, 3-, 6- and 12-month follow-ups.

Setting: United States.

Smoked Cannabis Effects in Cannabis Users at Clinical High-Risk for Psychosis: A Further Investigation of Cognition and Reward.

Objective: Some adverse cannabis effects are greater in individuals on the psychosis spectrum compared to healthy individuals. We have previously reported that smoked cannabis acutely worsened psychotic- like states and reduced cognitive performance selectively in cannabis users at clinical high-risk (CHR) for psychosis. The objective of the present study was to further investigate the acute effects of cannabis on cognition and reward processing in CHR cannabis users.

Robust quantitative assessment of collagen fibers with picrosirius red stain and linearly polarized light as demonstrated on atherosclerotic plaque samples.

Collagen is an important component in maintaining structural integrity and functionality of tissues and is modulated in various biological processes. Its visualization and possible quantification using histopathological stains can be important for understanding disease progression or therapeutic response. Visualization of collagen fiber with the histological stain picrosirius red (PSR) is enhanced with polarized light and quantitative analysis is possible using circular polarizers.

Lipid plaque burden in NSTE-ACS patients with or without COPD: insights from the SCAP Trial.

Background: Chronic obstructive pulmonary disease (COPD) patients have higher recurrence of adverse events and worse prognosis after acute coronary syndrome (ACS). The underlying pathophysiological mechanism is not fully elucidated.

Methods: In screening for COPD in ACS (SCAP) Trial (NCT02324660), ACS patients with smoking habit underwent a predischarge screening procedure to detect undiagnosed chronic obstructive pulmonary disease (UCOPD) confirmed with spirometry at 60 days.

Reliable in vivo intravascular imaging plaque characterization: A challenge unmet.

Intravascular imaging has enabled in vivo assessment of coronary artery pathology and detection of plaque characteristics that are associated with increased vulnerability. Prospective invasive imaging studies of coronary atherosclerosis have demonstrated that invasive imaging modalities can detect lesions that are likely to progress and cause cardiovascular events and provided unique insights about atherosclerotic evolution. However, despite the undoubted value of the existing imaging techniques in clinical and research arenas, all the available modalities have significant limitations in assessing plaque characteristics when compared with histology.

Integrated Lipidomics and Proteomics Point to Early Blood-Based Changes in Childhood Preceding Later Development of Psychotic Experiences: Evidence From the Avon Longitudinal Study of Parents and Children.

Background: The identification of early biomarkers of psychotic experiences (PEs) is of interest because early diagnosis and treatment of those at risk of future disorder is associated with improved outcomes. The current study investigated early lipidomic and coagulation pathway protein signatures of later PEs in subjects from the Avon Longitudinal Study of Parents and Children cohort.

Methods: Plasma of 115 children (12 years of age) who were first identified as experiencing PEs at 18 years of age (48 cases and 67 controls) were assessed through integrated and targeted lipidomics and semitargeted proteomics approaches.

The lack of meaningful association between depression severity measures and neurocognitive performance.

Background: Neurocognitive deficits are common in depression, but most prior studies have not found strong associations between standard measures of symptom severity and the extent of these neurocognitive deficits. Diagnostic heterogeneity, or the lack of specific questions about neurocognition in these measures, may be undermining these associations.

Method: Neuropsychological performance was assessed via 10 tasks in a sample of 262 unmedicated patients with Major Depressive Disorder (MDD) and compared to that in healthy volunteers (n = 140), then correlated with (1) standard measures of depression severity including the Hamilton Depression Rating Scale and Beck Depression Inventory, (2) previously established, factor-analytically derived symptom factors that characterize the heterogeneity of these scales, and (3) a separate measure of cognitive complaint (Cognitive Failures Questionnaire) that was included to address the absence of specific questions about cognition in standard rating scales.

Large-scale variation in density of an aquatic ecosystem indicator species.

Monitoring indicator species is a pragmatic approach to natural resource assessments, especially when the link between the indicator species and ecosystem state is well justified. However, conducting ecosystem assessments over representative spatial scales that are insensitive to local heterogeneity is challenging. We examine the link between polychlorinated biphenyl (PCB) contamination and population density of an aquatic habitat specialist over a large spatial scale using non-invasive genetic spatial capture-recapture.

The Lipid-Rich Plaque Study of vulnerable plaques and vulnerable patients: Study design and rationale.

Background: It has been hypothesized that the outcome post-PCI could be improved by the detection and subsequent treatment of vulnerable patients and lipid-rich vulnerable coronary plaques (LRP). A near-infrared spectroscopy (NIRS) catheter capable of detecting LRP is being evaluated in The Lipid-Rich Plaque Study.

Study Design: The LRP Study is an international, multicenter, prospective cohort study conducted in patients with suspected coronary artery disease (CAD) who underwent cardiac catheterization with possible ad hoc PCI for an index event.

Intravascular ultrasound and near-infrared spectroscopic features of coronary lesions with intraplaque haemorrhage.

Aims: Intraplaque haemorrhage is considered a major contributor to lesion progression. We assessed coronary lesions with intraplaque haemorrhage using intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS).

Methods And Results: We evaluated coronary arteries from autopsy hearts using 40MHz IVUS and NIRS and compared the imaging findings to histopathology.

Polychlorinated biphenyls (PCBs) in adult and juvenile mallards (Anas platyrhynchos) from the Hudson River, New York, USA.

The Hudson River, NY, USA is contaminated for over 300 km with polychlorinated biphenyls (PCBs) released from two General Electric (GE) capacitor plants. We collected adult and juvenile mallards (Anas platyrhynchos) from four different areas of the river; an area upstream of the GE plants (n = 38), two areas directly downstream of the GE plants (n = 41, n = 38), and an area more than 100 km downstream in the freshwater tidal river (n = 20). Collections occurred during July and August (2008) when ducks were flightless to ensure ducks were "resident" and exposures were local.

Hybrid intravascular imaging: recent advances, technical considerations, and current applications in the study of plaque pathophysiology.

Cumulative evidence from histology-based studies demonstrate that the currently available intravascular imaging techniques have fundamental limitations that do not allow complete and detailed evaluation of plaque morphology and pathobiology, limiting the ability to accurately identify high-risk plaques. To overcome these drawbacks, new efforts are developing for data fusion methodologies and the design of hybrid, dual-probe catheters to enable accurate assessment of plaque characteristics, and reliable identification of high-risk lesions. Today several dual-probe catheters have been introduced including combined near infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), that is already commercially available, IVUS-optical coherence tomography (OCT), the OCT-NIRS, the OCT-near infrared fluorescence (NIRF) molecular imaging, IVUS-NIRF, IVUS intravascular photoacoustic imaging and combined fluorescence lifetime-IVUS imaging.

The vulnerable artery: early and rapid deposition of lipid in coronary arteries is associated with subsequent development of thin-cap fibroatheromas.

Aims: We aimed to determine whether intravascular ultrasound (IVUS) and near infrared spectroscopy (NIRS) could identify arteries which would subsequently develop a thin-cap fibroatheroma (TCFA).

Methods And Results: Three-vessel angiography, IVUS and NIRS evaluations were performed at three, six and nine months after induction of diabetes mellitus and hypercholesterolaemia in 13 Yorkshire pigs (n=37 arteries). In vivo total arterial plaque plus media (P+M) area, echo-attenuated plaque (AP) area by IVUS, and lipid core burden index (LCBI) by NIRS were compared to histology at nine months.

Confirmation of the Intracoronary Near-Infrared Spectroscopy Threshold of Lipid-Rich Plaques That Underlie ST-Segment-Elevation Myocardial Infarction.

Objective: In a previous exploratory analysis, intracoronary near-infrared spectroscopy (NIRS) found the majority of culprit lesions in ST-segment-elevation myocardial infarction (STEMI) to contain a maximum lipid core burden index in 4 mm (maxLCBI4mm) of >400. This initial study was limited by a small sample size, enrollment at a single center, and post hoc selection of the maxLCBI4mm ≥400 threshold. This study was designed a priori to substantiate the ability of NIRS to discriminate STEMI culprit from nonculprit segments and to confirm the performance of the maxLCBI4mm ≥400 threshold.

Large lipid-rich coronary plaques detected by near-infrared spectroscopy at non-stented sites in the target artery identify patients likely to experience future major adverse cardiovascular events.

Aims: A recent study demonstrated that intracoronary near-infrared spectroscopy (NIRS) findings in non-target vessels are associated with major adverse cardiovascular and cerebrovascular events (MACCE). It is unknown whether NIRS findings at non-stented sites in target vessels are similarly associated with future MACCE. This study evaluated the association between large lipid-rich plaques (LRP) detected by NIRS at non-stented sites in a target artery and subsequent MACCE.

Near-infrared spectroscopy-intravascular ultrasound: scientific basis and clinical applications.

Coronary angiography underestimates the magnitude of the atherosclerotic burden and cannot detect the presence of disease in the early phases. Recognition of these inherent limitations of angiography has been an impetus for the development of other coronary imaging techniques. The novel near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) catheters can detect and quantify the presence of lipid core in the atherosclerotic plaque and associate it with other features such as lumen size and plaque architecture.