This study identified Vibrio parahaemolyticus in oyster and seawater samples collected from Delaware Bay from June through October of 2016. Environmental parameters including water temperature, ...salinity, dissolved oxygen, pH, and chlorophyll a were measured per sampling event. Oysters homogenate and seawater samples were 10-fold serially diluted and directly plated on CHROMagarᵀᴹ Vibrio medium. Presumptive V. parahaemolyticus colonies were counted and at least 20% of these colonies were selected for molecular chracterization. V. parahaemolyticus isolates (n = 165) were screened for the presence of the species-specific thermolabile hemolysin (tlh) gene, the pathogenic thermostable direct hemolysin (tdh)/ thermostable related hemolysin (trh) genes, the regulatory transmembrane DNA-binding gene (toxR), and V. parahaemolyticus metalloprotease (vpm) gene using a conventional PCR. The highest mean levels of the presumptive V. parahaemolyticus were 9.63×103 CFU/g and 1.85×103 CFU/mL in the oyster and seawater samples, respectively, during the month of July. V. parahaemolyticus levels in oyster and seawater samples were significantly positively correlated with water temperature. Of the 165 isolates, 137 (83%), 110 (66.7%), and 108 (65%) were tlh+, vpm+, and toxR+, respectively. Among the V. parahaemolyticus (tlh+) isolates, 7 (5.1%) and 15 (10.9%) were tdh+ and trh+, respectively, and 24 (17.5%), only oyster isolates, were positive for both genes. Potential pathogenic strains that possessed tdh and/or trh were notably higher in oyster (39%) than seawater (15.6%) isolates. The occurrence of total V. parahaemolyticus (tlh+) was not necessarily proportional to the potential pathogenic V. parahaemolyticus. Co-occurrence of the five genetic markers were observed only among oyster isolates. The co-occurrence of the gene markers showed a relatedness potential of tdh occurrence with vpm. We believe exploring the role of V. parahaemolyticus metalloprotease and whether it is involved in the toxic activity of the thermostable direct hemolysin (TDH) protein can be of significance. The outcomes of this study will provide some foundation for future studies regarding pathogenic Vibrio dynamics in relation to environmental quality.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The elevation of kynurenic acid (KYNA) observed in schizophrenic patients may contribute to core symptoms arising from glutamate hypofunction, including cognitive impairments. Although increased KYNA ...levels reduce excitatory neurotransmission, KYNA has been proposed to act as an endogenous antagonist at the glycine site of the glutamate NMDA receptor (NMDAR) and as a negative allosteric modulator at the α7 nicotinic acetylcholine receptor. Levels of KYNA are elevated in CSF and the postmortem brain of schizophrenia patients, and these elevated levels of KYNA could contribute to NMDAR hypofunction and the cognitive deficits and negative symptoms associated with this disease. However, the impact of endogenously produced KYNA on brain function and behavior is less well understood due to a paucity of pharmacological tools. To address this issue, we identified PF-04859989, a brain-penetrable inhibitor of kynurenine aminotransferase II (KAT II), the enzyme responsible for most brain KYNA synthesis. In rats, systemic administration of PF-04859989 dose-dependently reduced brain KYNA to as little as 28% of basal levels, and prevented amphetamine- and ketamine-induced disruption of auditory gating and improved performance in a sustained attention task. It also prevented ketamine-induced disruption of performance in a working memory task and a spatial memory task in rodents and nonhuman primates, respectively. Together, these findings support the hypotheses that endogenous KYNA impacts cognitive function and that inhibition of KAT II, and consequent lowering of endogenous brain KYNA levels, improves cognitive performance under conditions considered relevant for schizophrenia.
Most gastrointestinal stromal tumors (GIST) have activating mutations of
, or uncommonly
. Fifteen percent of adult and 85% of pediatric GISTs are wild type (WT), commonly having high expression of ...IGF-1R and loss of succinate dehydrogenase (SDH) complex function. We tested the efficacy of linsitinib, an oral TKI IGF-1R inhibitor, in patients with WT GIST.
A multicenter phase II trial of linsitinib was conducted. The primary endpoint was objective response rate. Secondary endpoints were clinical benefit rate: complete response, partial response, and stable disease (SD) ≥ 9 months, and quantitative 218Ffluoro-2-deoxy-D-glucose (FDG) metabolic response (MR) at week 8. Serum levels for glucose, insulin, IGF-1R ligand IGF1, and binding proteins were obtained to explore correlations to patient outcomes and FDG-PET results.
Twenty patients were accrued in a 6-month period. Grade 3-4 toxicities possibly related to linsitinib were uncommon (8.5%). No objective responses were seen. Clinical benefit rate (CBR) at 9 months was 40%. Intense FDG uptake was observed at baseline, with partial MR of 12% and stable metabolic disease of 65% at week 8; these patients had RECIST 1.1 SD as their best response. Progression-free survival (PFS) and overall survival Kaplan-Meier estimates at 9 months were 52% and 80%, respectively. SDHA/B loss determined by IHC was seen in 35% and 88% of cases, respectively.
Linsitinib is well tolerated in patients with WT GIST. Although the 9-month CBR was 40%, and PFS at 9 months was 52%, no objective responses were observed. Rapid accrual to this study demonstrates that clinical trials of experimental agents in selected subtypes of GIST are feasible.
The health implications related to electronic cigarettes are not fully understood and has created a public health concern. The purpose of this narrative review was to highlight the oral and systemic ...health concerns associated with electronic cigarettes and compare these concerns to those associated with conventional tobacco cigarettes.
The literature was obtained from PubMed, Ovid Medline, CINAHL, and Scopus databases in June 2021 and updated in February 2023. Sources were chosen based on the following inclusion criteria: date of publication between 2011 and 2023 and written in English. Articles were excluded based on irrelevance to the topic, weak study designs, lack of outcome data, low quality randomized control trials, unavailability of the full text article, and non-empirical research designs. The Cochrane tool, ROBINS-I, was used to assess the risk of bias.
A total of 78 studies were included in the review. E-cigarette use was associated with significant adverse effects for cardiovascular, respiratory, immunological, and periodontal health as compared to nonusers; however, impacts were worse with conventional smoked cigarettes. Long term health effects remain unknown with e-cigarettes, but associations have been identified with periodontal and peri-implant disease, oral cancer, and mental health disorders. The heterogeneity of e-cigarette use related to vaping behavior, devices, and liquids limits the ability to generalize results. There is a need for the development of a research standard for exposure methods to establish a consensus with e-cigarette use and support the validity of results among researchers.
According to current research, e-cigarettes may induce less harm than traditional tobacco products, but e-cigarettes do not remove the carcinogenic and toxic risk that has been associated with conventional cigarettes. Further research is needed to make broad conclusions on the safety of e-cigarettes compared to conventional cigarettes and to nonusers.
Matrix-assisted laser desorption ionization–time-of-flight (MALDI-TOF) mass spectrometry is commonly used to identify bacteria and yeasts. Studies indicate that MALDI-TOF is relatively indifferent to ...the medium used for culture. We report on an investigation into high- and low-confidence MALDI-TOF misidentifications of Mycoplasma arginini and Mycoplasma alkalescens from urine specimens plated to CHROMagar™ Orientation medium that appear to be due to the intrinsic mass spectrum of the medium.
•CHROMagar™ Orientation has an intrinsic MALDI-TOF spectrum that can be misidentified as Mycoplasma alkalescens or Mycoplasma arginini.•No other media sampled in the laboratory produced spectra with reliable identifications.•The endogenous spectrum of CHROMagar Orientation may be due to Mycoplasma contamination or 1 of its components or chance similarity between the spectrum of its components and Mycoplasma alkalescens and Mycoplasma arginini spectra.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Selective activation of dopamine D1 receptors remains a promising pro-cognitive therapeutic strategy awaiting robust clinical investigation. PF-6142 is a key example from a recently disclosed novel ...series of non-catechol agonists and partial agonists of the dopamine D1/5 receptors (D1R) that exhibit pharmacokinetic (PK) properties suitable for oral delivery. Given their reported potential for functionally biased signaling compared to known catechol-based selective agonists, and the promising rodent PK profile of PF-6142, we utilized relevant
in vivo
assays in male rodents and male and female non-human primates (NHP) to evaluate the pharmacology of this new series. Studies in rodents showed that PF-6142 increased locomotor activity and prefrontal cortex acetylcholine release, increased time spent in wakefulness, and desynchronized the EEG, like known D1R agonists. D1R selectivity of PF-6142 was supported by lack of effect in D1R knock-out mice and blocked response in the presence of the D1R antagonist SCH-23390. Further, PF-6142 improved performance in rodent models of NMDA receptor antagonist-induced cognitive dysfunction, such as MK-801-disrupted paired-pulse facilitation, and ketamine-disrupted working memory performance in the radial arm maze. Similarly, PF-6142 reversed ketamine-induced deficits in NHP performing the spatial delayed recognition task. Of importance, PF-6142 did not alter the efficacy of risperidone in assays predictive of antipsychotic-like effect in rodents including pre-pulse inhibition and conditioned avoidance responding. These data support the continued development of non-catechol based D1R agonists for the treatment of cognitive impairment associated with brain disorders including schizophrenia.
Eastern oysters (
Crassostrea virginica
) from three locations along the Delaware Bay were surveyed monthly from May to October 2017 for levels of total
Vibrio parahaemolyticus
, pathogenic strains ...of
V. parahaemolyticus
and
Vibrio vulnificus
, and for strain-specific bacteriophages against vibrios (vibriophages). The objectives were to determine (a) whether vibriophages against known strains or serotypes of clinical and environmental vibrios were detectable in oysters from the Delaware Bay and (b) whether vibriophage presence or absence corresponded with
Vibrio
abundances in oysters. Host cells for phage assays included pathogenic
V. parahaemolyticus
serotypes O3:K6, O1:KUT (untypable) and O1:K1, as well as clinical and environmental strains of
V. vulnificus
. Vibriophages against some, but not all, pathogenic
V. parahaemolyticus
serotypes were readily detected in Delaware Bay oysters. In July, abundances of total and pathogenic
V. parahaemolyticus
at one site spiked to levels exceeding regulatory guidelines. Phages against three
V. parahaemolyticus
host serotypes were detected in these same oysters, but also in oysters with low
V. parahaemolyticus
levels. Serotype-specific vibriophage presence or absence did not correspond with abundances of total or pathogenic
V. parahaemolyticus
. Vibriophages were not detected against three
V. vulnificus
host strains, even though
V. vulnificus
were readily detectable in oyster tissues. Selected phage isolates against
V. parahaemolyticus
showed high host specificity. Transmission electron micrographs revealed that most isolates were ~ 60-nm diameter, non-tailed phages. In conclusion, vibriophages were detected against pandemic
V. parahaemolyticus
O3:K6 and O1:KUT, suggesting that phage monitoring in specific host cells may be a useful technique to assess public health risks from oyster consumption.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
PDF
