causes health care-associated opportunistic infections that can be difficult to treat due to a high incidence of antibiotic resistance. One of the many secreted proteins of
is the PhlA phospholipase ...enzyme. Genes involved in the production and secretion of PhlA were identified by screening a transposon insertion library for phospholipase-deficient mutants on phosphatidylcholine-containing medium. Mutations were identified in four genes (
,
,
, and
) that are involved in the flagellum-dependent PhlA secretion pathway. An additional phospholipase-deficient isolate harbored a transposon insertion in the
gene encoding a predicted serine
-acetyltransferase required for cysteine biosynthesis. The
requirement for extracellular phospholipase activity was confirmed using a fluorogenic phospholipase substrate. Phospholipase activity was restored to the
mutant by the addition of exogenous l-cysteine or
-acetylserine to the culture medium and by genetic complementation. Additionally,
transcript levels were decreased 6-fold in bacteria lacking
and were restored with added cysteine, indicating a role for cysteine-dependent transcriptional regulation of
phospholipase activity.
mutants also exhibited a defect in swarming motility that was correlated with reduced levels of
and
flagellar regulator gene transcription. Together, these findings suggest a model in which cysteine is required for the regulation of both extracellular phospholipase activity and surface motility in
is known to secrete multiple extracellular enzymes, but PhlA is unusual in that this protein is thought to be exported by the flagellar transport apparatus. In this study, we demonstrate that both extracellular phospholipase activity and flagellar function are dependent on the cysteine biosynthesis pathway. Furthermore, a disruption of cysteine biosynthesis results in decreased
and flagellar gene transcription, which can be restored by supplying bacteria with exogenous cysteine. These results identify a previously unrecognized role for CysE and cysteine in the secretion of
phospholipase and in bacterial motility.
Clinically significant cognitive impairment is found in a subset of patients undergoing bariatric surgery. These difficulties could contribute to a reduced adherence to postoperative lifestyle ...changes and decreased weight loss. The present study is the first to prospectively examine the independent contribution of cognitive function to weight loss after bariatric surgery. Executive function/attention and verbal memory at baseline were expected to negatively predict the percentage of excess weight loss (%EWL) and body mass index (BMI) at follow-up. Three sites of the Longitudinal Assessment of Bariatric Surgery parent project were used: Columbia (New York, NY), Cornell (Princeton, NJ), and the Neuropsychiatric Research Institute (Fargo, ND).
A total of 84 individuals enrolled in the Longitudinal Assessment of Bariatric Surgery project undergoing bariatric surgery completed a cognitive evaluation at baseline. The BMI and %EWL were calculated at the 12-week and 12-month postoperative follow-up visits.
Clinical impairment in task performance was most prominent in tasks associated with verbal recall and recognition (14.3-15.5% of the sample) and perseverative errors (15.5%). After accounting for demographic and medical variables, the baseline test results of attention/executive function and memory predicted the BMI and %EWL at 12 months but not at 12 weeks.
These results have demonstrated that baseline cognition predicts for greater %EWL and lower BMI 12 months after bariatric surgery. Additional work is needed to clarify the degree to which cognition contributes to adherence and the potential mediation of cognition on the relationship between adherence and weight loss in this group.
Objective
The drug poisoning crisis throughout North America necessitates novel harm reduction approaches. Emerging evidence suggests that cannabidiol (CBD) may have some utility as a harm reduction ...modality for those with problematic substance use. This rapid review aimed to synthesize available evidence on CBD as a potential harm reduction tool for people who use drugs while providing clinical and research insights.
Method
A systematic search in EMBASE, MEDLINE, CENTRAL, and CINAHL was completed in July 2022. For inclusion, studies had to meet the following criteria: (1) drawn from an adult population of people who use drugs; (2) investigates CBD as an intervention for problematic substance use or harm reduction–related outcomes; (3) be published after the year 2000 and in English; and (4) be primary research or a review article. A narrative synthesis was used to group outcomes relevant to harm reduction and provide clinical and research insights.
Results
We screened 3,134 records, of which 27 studies (5 randomized trials) were included. The evidence remains limited, but available studies support the potential utility of CBD to reduce drug-induced craving and anxiety in opioid use disorder. There were low-quality studies suggesting that CBD may improve mood and general well-being of people who use drugs. Evidence suggests that CBD monotherapy may not be an adequate harm reduction strategy for problematic substance use but rather an adjunct to the standard of care.
Conclusion
Low-quality evidence suggests that CBD may reduce drug cravings and other addiction-related symptoms and that CBD may have utility as an adjunct harm reduction strategy for people who use drugs. However, there is a significant need for more research that accurately reflects CBD dosing and administration regimens used in a real-world context.
We assessed students' perception of the impact of the pandemic on their well-being, education, academic achievement, and whether grit and resilience alter students’ ability to mitigate the stress ...associated with disruptions in education. We hypothesized that students would report a negative impact, and those with higher grit and resilience scores would be less impacted.
A multidisciplinary team of educators created and distributed a survey to medical students. Survey results were analyzed using descriptive statistics, ANOVA, and multivariate linear regressions. A p-value <.05 was considered statistically significant.
A total of 195 students were included in the study. Approximately 92% reported that clinical education was negatively affected, including participants with higher grit scores. Students with higher resilience scores were more optimistic about clinical education. Those with higher resilience scores were less likely to report anxiety, insomnia, and tiredness.
More resilient students were able to manage the stress associated with the disruption in their education. Resiliency training should be year-specific, and integrated into the UME curriculum due to the different demands each year presents.
•40% of students reported feeling pessimistic about their education during the COVID-19 pandemic.•Students with higher resilience scores experienced less psychological symptoms, and loss of professional identity.•Students with higher resilience scores reported a more positive outlook on academic achievement compared to those with lower resilience scores.•Resilience was found to be more protective than grit for medical students during the COVID-19 pandemic.
Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We sought to describe prognostic factors, treatment and outcomes for individuals with ...ovarian SLCT.
Individuals with SLCT were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Medical records were systematically abstracted, and pathology was centrally reviewed when available.
In total, 191 participants with ovarian SLCT enrolled, with most (92%, 175/191) presenting with FIGO stage I disease. Germline DICER1 results were available for 156 patients; of these 58% had a pathogenic or likely pathogenic germline variant. Somatic (tumor) DICER1 testing showed RNase IIIb hotspot variants in 97% (88/91) of intermediately and poorly differentiated tumors. Adjuvant chemotherapy was administered in 40% (77/191) of cases, and among these, nearly all patients received platinum-based regimens (95%, 73/77), and 30% (23/77) received regimens that included an alkylating agent. Three-year recurrence-free survival for patients with stage IA tumors was 93.6% (95% CI: 88.2–99.3%) compared to 67.1% (95% CI: 55.2–81.6%) for all stage IC and 60.6% (95% CI: 40.3–91.0%) for stage II-IV (p < .001) tumors. Among patients with FIGO stage I tumors, those with mesenchymal heterologous elements treated with surgery alone were at higher risk for recurrence (HR: 74.18, 95% CI: 17.99–305.85).
Most individuals with SLCT fare well, though specific risk factors such as mesenchymal heterologous elements are associated with poor prognosis. We also highlight the role of DICER1 surveillance in early detection of SLCT, facilitating stage IA resection.
•Most (92%, 175/191) ovarian Sertoli-Leydig cell tumors (SLCTs) present as FIGO stage I disease with a favorable prognosis.•FIGO stage I tumors with mesenchymal heterologous elements are at higher risk for recurrence when not receiving chemotherapy.•Somatic (tumor) DICER1 RNase IIIb hotspot variants were found in 97% of intermediately and poorly differentiated SLCTs.•More than half (58%, 91/156) of individuals were found to have a germline DICER1 pathogenic/likely pathogenic variant.•DICER1 surveillance recommendations facilitated detection of asymptomatic ovarian SLCT with nearly all resected as stage IA.
A compact means to separate microwave and millimeter-wave optical signals by RF frequency in real time is demonstrated. The approach is to employ an integrated optical Bragg grating Fabry-Perot ...(BGFP) device to spatially separate optically modulated microwave signals with high resolution. The compactness is achieved through the use of an integrated optical hybrid diffractive lens beam expander to provide the required optical wavefront to the BGFP. A proof-of-principle measurement was performed from 1 to 23 GHz with peak finesse of 27. The theoretical analysis, fabrication procedure, experimental results, limitations, and improvements are described.
Despite advances in treatment for cystic fibrosis (CF), liver disease remains a major contributor to morbidity and mortality for persons with CF. Therefore, liver transplantation may be considered in ...end-stage CF-related liver disease. We present a young patient with CF who underwent solo liver transplantation and has successfully restarted on elexacaftor/tezacaftor/ivacaftor without significant pulmonary or hepatic complications after transplant.
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