Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) sample preparation methods, including the direct, on-plate formic acid, and ethanol/formic acid tube extraction methods, were evaluated for their ability to render highly pathogenic organisms nonviable and safe for handling in a biosafety level 2 laboratory. Of these, the tube extraction procedure was the most successful, with none of the tested strains surviving this sample preparation method. Tube extracts from several agents of bioterrorism and their near neighbors were analyzed in an eight-laboratory study to examine the utility of the Bruker Biotyper and Vitek MS MALDI-TOF MS systems and their in vitro diagnostic (IVD), research-use-only, and Security-Relevant databases, as applicable, to accurately identify these agents. Forty-six distinct strains of Bacillus anthracis, Yersinia pestis, Francisella tularensis, Burkholderia mallei, Burkholderia pseudomallei, Clostridium botulinum, Brucella melitensis, Brucella abortus, Brucella suis, and Brucella canis were extracted and distributed to participating laboratories for analysis. A total of 35 near-neighbor isolates were also analyzed.

Background: Diabetes and periodontitis have a bi-directional relationship. And yet, collaborations between primary healthcare practitioners in diabetes and oral health care are minimal. This study explored the views of general practice and oral health professionals on the link between diabetes and periodontitis, and interprofessional diabetes and oral health management. Methods: A sequential mixed-methods exploratory research design was used. General practice and oral health professionals were recruited from four community health centres in Melbourne. Quantitative surveys explored participants' experiences, attitudes and knowledge of diabetes and oral health management and interprofessional collaboration; qualitative follow-up interviews explored survey responses with selected participants. Results: 58 participants completed the online surveys; 22 then participated in semi-structured interviews. Participants generally had strong intentions to collaborate interprofessionally in diabetes and oral health management. Most general practice and oral health professional participants were willing to perform simple screening for periodontitis or diabetes respectively. Themes from the interviews were grouped under three domains: 'a ttitude towards diabetes and oral health management', 'subjective norms' and 'perceived behavioural control'; and an overarching domain to describe participants' 'current practice'. Existing siloed primary healthcare practices and lack of formal referral pathways contribute to poor interprofessional collaboration. Most participants were unsure of each other's responsibilities and roles. Their lack of training in the relationship between general and oral health, compounded by systemic barriers including time constraint, high dental costs, long public dental waiting list and unintegrated health information systems, also impeded interprofessional care. Conclusions: The diabetes and oral health link is not properly recognised or managed collaboratively by relevant primary healthcare professionals in Australia. There is, nonetheless, strong intentions to engage in interprofessional diabetes and oral health care to contribute to improved patient outcomes. Primary healthcare professionals need dedicated and accredited interprofessional training and competencies, formal referral systems and sustainable health policies to facilitate collaboration.

Phosphotyrosine Interaction Domain containing 1 (PID1; NYGGF4) inhibits growth of medulloblastoma, glioblastoma and atypical teratoid rhabdoid tumor cell lines. PID1 tumor mRNA levels are highly correlated with longer survival in medulloblastoma and glioma patients, suggesting their tumors may have been more sensitive to therapy. We hypothesized that PID1 sensitizes brain tumors to therapy. We found that PID1 increased the apoptosis induced by cisplatin and etoposide in medulloblastoma and glioblastoma cell lines. PID1 siRNA diminished cisplatin-induced apoptosis, suggesting that PID1 is required for cisplatin-induced apoptosis. Etoposide and cisplatin increased NFκB promoter reporter activity and etoposide induced nuclear translocation of NFκB. Etoposide also increased PID1 promoter reporter activity, PID1 mRNA, and PID1 protein, which were diminished by NFκB inhibitors JSH-23 and Bay117082. However, while cisplatin increased PID1 mRNA, it decreased PID1 protein. This decrease in PID1 protein was mitigated by the proteasome inhibitor, bortezomib, suggesting that cisplatin induced proteasome dependent degradation of PID1. These data demonstrate for the first time that etoposide- and cisplatin-induced apoptosis in medulloblastoma and glioblastoma cell lines is mediated in part by PID1, involves NFκB, and may be regulated by proteasomal degradation. This suggests that PID1 may contribute to responsiveness to chemotherapy.

Quantitative ultrasound (QUS) techniques such as pixel intensity, ultrasound strain, and shear wave elastography have made it possible to identify the echogenicity (brightness) and mechanical properties (stiffness) of normal and pathological tissues. These techniques can be utilized as an alternative diagnosis tool to assess post stroke spasticity. Current clinical assessment methods include the Modified Ashworth Scale (MAS) and the Modified Tardieu Scale (MTS), which can result in inconsistencies due to their subjective nature. QUS provides robust approaches to assessing muscle stiffness associated with post stroke spasticity. Computer-aided pixel count quantifies tissue echogenicity in grayscale image. A strain ratio in ultrasound strain imaging compares the stiffness and movement (lengthening or shortening) of a spastic muscle with nonspecific muscle. In addition, shear wave elastography provides the shear wave velocity of an affected muscle that directly associated with the muscle stiffness before and after treatment for spasticity. This article reviews the theory behind these aforementioned concepts and discuss the relations between QUS and skeletal muscles in post stroke spasticity.

Recombinant protein production in the methylotrophic yeast Pichia pastoris largely relies on integrative vectors. Although the stability of integrated expression cassettes is well appreciated for most applications, the availability of reliable episomal vectors for this host would represent a useful tool to expedite cloning and high-throughput screening, ameliorating also the relatively high clonal variability reported in transformants from integrative vectors caused by off-target integration in the P. pastoris genome. Recently, heterologous and endogenous autonomously replicating sequences (ARS) were identified in P. pastoris by genome mining, opening the possibility of expanding the available toolbox to include efficient episomal plasmids. The aim of this technical report is to validate a 452-bp sequence ("panARS") in context of P. pastoris expression vectors, and to compare their performance to classical integrative plasmids. Moreover, we aimed to test if such episomal vectors would be suitable to sustain in vivo recombination, using fragments for transformation, directly in P. pastoris cells.

We reviewed relevant syphilis diagnostic literature and conducted a meta-analysis to address the question, "What is the sensitivity and specificity of the Syphilis Health Check, a rapid qualitative test for the detection of human antibodies to Treponema pallidum." The Syphilis Health Check is the only rapid syphilis test currently cleared by the Food and Drug Administration (FDA). We conducted a systematic review and a meta-analysis using Bayesian bivariate random-effects and fixed-effect models to create pooled estimates of sensitivity and specificity of the Syphilis Health Check. We identified 5 test evaluations published in the literature and 10 studies submitted to the FDA and for a Clinical Laboratory Improvement Amendments waiver application. The pooled sensitivity (95% CI) from the laboratory evaluations (n = 5) was 98.5% (92.1-100%), while pooled specificity was 95.9% (81.5-100.0%). The pooled sensitivity for prospective studies (n = 10) was 87.7% ( 71.8-97.2%), while pooled specificity was 96.7% (91.9-99.2%). Using nontreponemal supplemental testing, the sensitivity improved to a pooled sensitivity of 97.0% (94.8-98.6%). The Syphilis Health Check may provide accurate detection of treponemal antibody.

We conducted a systematic review of relevant syphilis diagnostic literature to address the question, "What is the sensitivity and specificity of the treponemal tests currently approved by the Food and Drug Administration (FDA) for the diagnosis of syphilis (by stage)?" There were 16 treponemal assays evaluated: 13 immunoassays and 3 manual assays (fluorescent treponemal antibody absorbed test [FTA-ABS], microhemagglutination assay for Treponema pallidum antibodies [MHA-TP], Treponema pallidum particle agglutination assay [TP-PA]). MHA-TP and FTA-ABS were less sensitive in primary and secondary syphilis than TP-PA; TP-PA is the most specific manual treponemal assay. There is insufficient evidence to recommend one particular treponemal immunoassay (eg, enzyme immunoassays, chemiluminescence immunoassays, microbead immunoassays) over another based on published performance data. For diagnosis of neurosyphilis, cerebrospinal fluid (CSF) TP-PA has similar performance to CSF FTA-ABS in studies with patients with definitive or presumptive neurosyphilis. However, CSF treponemal testing has limitations in its sensitivity and specificity and should be interpreted within the context of the clinical scenario, additional CSF test results and syphilis prevalence.

Interleukin 17 producing CD4 T cells contribute to control of Mycobacterium tuberculosis (Mtb) infection in humans; whether infection with Human Immunodeficiency Virus (HIV) disproportionately affects distinct Th17 cell subsets that respond to Mtb are incompletely defined.

Recent exome sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several human intellectual disabilities and cognitive disorders. However, it is currently unknown how mutations in BAF complexes result in impaired cognitive function. Postmitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Mice harboring selective genetic manipulations of BAF53b have severe defects in long-term memory and long-lasting forms of hippocampal synaptic plasticity. We rescued memory impairments in BAF53b mutant mice by reintroducing BAF53b in the adult hippocampus, which suggests a role for BAF53b beyond neuronal development. The defects in BAF53b mutant mice appeared to derive from alterations in gene expression that produce abnormal postsynaptic components, such as spine structure and function, and ultimately lead to deficits in synaptic plasticity. Our results provide new insight into the role of dominant mutations in subunits of BAF complexes in human intellectual and cognitive disorders.

During the summer of 2015, New York, New York, USA, had one of the largest and deadliest outbreaks of Legionnaires' disease in the history of the United States. A total of 138 cases and 16 deaths were linked to a single cooling tower in the South Bronx. Analysis of environmental samples and clinical isolates showed that sporadic cases of legionellosis before, during, and after the outbreak could be traced to a slowly evolving, single-ancestor strain. Detection of an ostensibly virulent Legionella strain endemic to the Bronx community suggests potential risk for future cases of legionellosis in the area. The genetic homogeneity of the Legionella population in this area might complicate investigations and interpretations of future outbreaks of Legionnaires' disease.

The emergence of a novel coronavirus, namely, SARS-CoV-2, necessitated the use of rapid, accurate diagnostics to quickly diagnose COVID-19. This need has increased with the emergence of new variants and continued waves of COVID-19 cases. The ID NOW COVID-19 assay is a rapid nucleic acid amplification test (NAAT) that is used by hospitals, urgent care facilities, medical clinics, and public health laboratories for rapid molecular SARS-CoV-2 testing at the point of care. The District of Columbia Department of Forensic Sciences Public Health Laboratory Division (DC DFS PHL) implemented ID NOW COVID-19 testing in nontraditional laboratory settings, including a mobile testing unit, health clinic, and emergency department, to assist with rapid identification and isolation for populations at high risk of SARS-CoV-2 transmission in the District of Columbia. The DC DFS PHL provided these nontraditional laboratories with safety risk assessment, assay training, competency assessment, and quality control monitoring as parts of a comprehensive quality management system (QMS). We assessed the accuracy of the ID NOW COVID-19 assay when operated in the context of these trainings and systems. This was done by comparing results from 9,518 paired tests, and strong agreement (κ = 0.88, OPA = 98.3%) was found between the ID NOW COVID-19 assay and laboratory-based NAATs. These findings indicate that the ID NOW COVID-19 assay can be used to detect SARS-CoV-2 in nontraditional laboratory settings when used within the context of a comprehensive QMS.