Caspase-11–dependent cell death is controlled by carboxypeptidase B1 by inducing the cleavage of C3 and activation of C3aR.
, one of ∼600 bacterial species in the human oral cavity, is among the most acidogenic constituents of the plaque biofilm. Considered to be the primary causative agent of dental caries, harbors a 25kDa SloR metalloregulatory protein which controls metal ion transport across the bacterial cell membrane to maintain essential metal ion homeostasis. The expression of SloR derives, in part, from transcriptional readthrough of the operon which encodes a Mn/Fe ABC transport system. Herein, we describe the details of the promoter that drives this transcription, as well as a novel independent promoter in an intergenic region (IGR) that contributes to downstream expression. RT-PCR studies support transcription that is independent of expression, and the results of 5' RACE revealed a transcription start site in the IGR from which the -10 and -35 promoter regions were predicted. The results of gel mobility shift assays support direct SloR binding to the IGR, albeit with lower affinity than SloR binding to the promoter. Function of the promoter was validated in qRT-PCR experiments. Interestingly, expression was not significantly impacted when grown in the presence of high manganese, whereas expression of the operon was repressed under these conditions. The results of transcription studies support SloR-mediated transcriptional-activation of and -repression of Taken together, these findings implicate SloR as a bifunctional regulator that represses promoter activity and encourages transcription from an independent promoter. Tooth decay is a ubiquitous infectious disease that is especially pervasive in underserved communities worldwide. -induced carious lesions cause functional, physical, and/or aesthetic impairment in the vast majority of adults, and in 60-90% of schoolchildren in industrialized countries. Billions of dollars are spent annually on caries treatment, and productivity losses due to absenteeism from the workplace are significant. Research aimed at alleviating-induced tooth decay is important because it can address the socioeconomic disparity that is associated with dental cavities and improve overall general health which is inextricably linked to oral health. Research focused on the SloR metalloregulatory protein can guide the development of novel therapeutics and so alleviate the burden of dental cavities.
Clinicians have evaluated motion measurement technologies in older adults with depression, dementia, anxiety, and schizophrenia. Results from studies in dementia populations suggest that motion measurement technologies can assist clinicians in diagnosing dementia earlier through the evaluation of gait, balance, and postural kinematics. Motion detection technologies can also be used to identify mood episodes at an earlier stage by detecting subtle behavioral changes. Clinicians may use the objective data provided by technologies such as accelerometers to identify illnesses earlier, which may inform treatment decisions. The data may be used as a suitable surrogate marker for detecting depression in older adults, predicting the likelihood of falls, or quantifying physical activity in older adults with chronic mental illnesses or anxiety. Motion-based technologies also have the potential to detect physical activity for older adults residing in nursing homes. Wearable technologies are generally well tolerated in older adults, although the use of new technology and electronic health data could involve privacy and security concerns among this vulnerable population.
Background Obtaining collateral information from a patient is an essential component of providing effective psychiatric and psychotherapeutic care. Research indicates that patients’ social and electronic media contains information relevant to their psychotherapy and clinical care. However, it remains unclear to what degree this content is being actively utilized by clinicians as a part of diagnosis or therapy. Moreover, clinicians’ attitudes around this practice have not been well characterized. Objective This survey aimed to establish the current attitudes and behaviors of outpatient clinicians regarding the incorporation of patients’ social and electronic media into psychotherapy. Methods A Web-based survey was sent to outpatient psychotherapists associated with McLean Hospital in Belmont, Massachusetts. The survey asked clinicians to indicate to what extent and with which patients they reviewed patients’ social and electronic media content as part of their clinical practice, as well as their reasons for or against doing so. Results Of the total 115 respondents, 71 (61.7%) indicated that they had viewed at least one patient’s social or electronic media as part of psychotherapy, and 65 of those 71 (92%) endorsed being able to provide more effective treatment as a result of this information. The use of either short message service text messages or email was significantly greater than the use of other electronic media platforms (χ 2 1 =24.1, n=115, P <.001). Moreover, the analysis of survey responses found patterns of use associated with clinicians’ years of experience and patient demographics, including age and primary diagnosis. Conclusions The incorporation of patients’ social and electronic media into therapy is currently common practice among clinicians at a large psychiatric teaching hospital. The results of this survey have informed further questions about whether reviewing patient’s media impacts the quality and efficacy of clinical care.
Background Psychiatry has long needed a better and more scalable way to capture the dynamics of behavior and its disturbances, quantitatively across multiple data channels, at high temporal resolution in real time. By combining 24/7 data—on location, movement, email and text communications, and social media—with brain scans, genetics, genomics, neuropsychological batteries, and clinical interviews, researchers will have an unprecedented amount of objective, individual-level data. Analyzing these data with ever-evolving artificial intelligence could one day include bringing interventions to patients where they are in the real world in a convenient, efficient, effective, and timely way. Yet, the road to this innovative future is fraught with ethical dilemmas as well as ethical, legal, and social implications (ELSI). Objective The goal of the Ethics Checklist is to promote careful design and execution of research. It is not meant to mandate particular research designs; indeed, at this early stage and without consensus guidance, there are a range of reasonable choices researchers may make. However, the checklist is meant to make those ethical choices explicit, and to require researchers to give reasons for their decisions related to ELSI issues. The Ethics Checklist is primarily focused on procedural safeguards, such as consulting with experts outside the research group and documenting standard operating procedures for clearly actionable data (eg, expressed suicidality) within written research protocols. Methods We explored the ELSI of digital health research in psychiatry, with a particular focus on what we label “deep phenotyping” psychiatric research, which combines the potential for virtually boundless data collection and increasingly sophisticated techniques to analyze those data. We convened an interdisciplinary expert stakeholder workshop in May 2020, and this checklist emerges out of that dialogue. Results Consistent with recent ELSI analyses, we find that existing ethical guidance and legal regulations are not sufficient for deep phenotyping research in psychiatry. At present, there are regulatory gaps, inconsistencies across research teams in ethics protocols, and a lack of consensus among institutional review boards on when and how deep phenotyping research should proceed. We thus developed a new instrument, an Ethics Checklist for Digital Health Research in Psychiatry (“the Ethics Checklist”). The Ethics Checklist is composed of 20 key questions, subdivided into 6 interrelated domains: (1) informed consent; (2) equity, diversity, and access; (3) privacy and partnerships; (4) regulation and law; (5) return of results; and (6) duty to warn and duty to report. Conclusions Deep phenotyping research offers a vision for vastly more effective care for people with, or at risk for, psychiatric disease. The potential perils en route to realizing this vision are significant; however, and researchers must be willing to address the questions in the Ethics Checklist before embarking on each leg of the journey.
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