Burchsaleh1641
The study of differential gene expression in persister cells is compounded by ceasure of conventional cellular metabolic pathways during persistence. There is, hence, a requirement to identify and validate suitable reference genes whose expression remains stable during persistence. We evaluated the suitability of five genes viz. dnaJ, groEL, rpoB, kp751, kp4432 as references to study gene expression using real-time polymerase chain reaction (qPCR) during persister cell formation in Klebsiella pneumoniae. Results obtained showed that while dnaJ and groEL suffered from unstable expression; rpoB, kp751 and kp4432 showed stable expression. Further, it was observed that data normalization using either of the stable genes viz. rpoB, kp751, kp4432 alone, resulted in either too low expression levels or too high variation among replicates. Our study indicates the concurrent use of kp4432 and rpoB as reference genes to be the most suitable for reliable analysis of differential gene expression during antibiotic induced persister formation in K. pneumoniae. kp4432 and rpoB encode NAD-dependant phenylacetaldehyde dehydrogenase and DNA-directed RNA polymerase beta subunit respectively. The outcome of this study will increase the utility of qPCR in studying the temporal changes in gene expression during persistence. The study will also aid in understanding mechanisms underlying persister cell formation particularly in K. pneumoniae.
Chronic kidney disease (CKD) is associated with declining physical function and activity. In the general population, lower physical activity is associated with poorer quality of life and greater all-cause mortality. The aim of this study was to assess if lower physical activity levels are associated with adverse health outcomes in patients with advanced CKD.
A multicenter prospective cohort study.
579 adult patients with CKD glomerular filtration rate categories 4 and 5 (G4-G5) treated at 4 Canadian multidisciplinary kidney health clinics between 2012 and2018.
Patient-reported measures of physical activity using the Physical Activity Scale for the Elderly (PASE) questionnaire and subsequently stratified PASE scores into tertiles.
All-cause mortality, progression to kidney failure, and future falls.
Outcomes were analyzed using time-dependent proportional hazards models and logistic regression models.
In 1,193 days of follow-up observation, 118 patients died, 204 progressed to dialysis, and 129 rKD population. These findings are consistent with a potential benefit from maintained physical activity as patients approach kidney failure.
Center for Medicare Services decreased reimbursement rates for peripheral veno-arterial (VA ECMO) and veno-venous (VV ECMO) extracorporeal membrane oxygenation procedures in October 2018. Limited data are available describing hospital costs and clinical resources required to support ECMO patients.
All patients supported on ECMO at our institution between March 2017 and October 2018 were identified. Exclusion criteria were cannulation at referring hospitals, organ transplant recipients, and temporary right ventricular support. The cohort was stratified by initial cannulation strategy. Outcomes were total hospital cost and clinical resource utilization.
29 patients were supported on central VA, 72 on peripheral VA, and 37 on VV ECMO. AS2863619 solubility dmso Thirty-day survival was 48% for central vs 37% for peripheral vs 51% for VV. Hospital costs were $187,848 for central vs $178,069 for peripheral vs $172,994 for VV, P=0.91. Mean hospital stay was 25.8 days for central vs 21.5 for peripheral vs 26.2 for VV, P=0.49. Mean intensive care unit stay was 14.1 days for central vs 12.8 for peripheral vs 7.7 for VV, P=0.25. Mean length of ECMO support was 6.5 days for central vs 6.2 for peripheral vs 7.8 for VV, P=0.38. Mean ventilator time was 13.0 days for central vs 8.2 for peripheral vs 10.0 for VV P=0.06. Hemodialysis was utilized in 41% central, 47% peripheral, and 41% VV patients, P=0.75. Theoretical ECMO reimbursement losses ranged from $1,970,698 to $5,648,219 annually under 2018 Center for Medicare Services rates.
ECMO cannulation strategy has minimal impact on resource utilization and hospital cost.
ECMO cannulation strategy has minimal impact on resource utilization and hospital cost.
The United Kingdom National Institute for Health and Care Excellence guidelines recommend that patients and professionals make shared decisions between surgery and stereotactic ablative radiotherapy (SABR) when treating early stage non-small cell lung cancer (NSCLC). Variation by centre suggests treatment decisions may be disproportionately influenced by clinician judgment and treatment availability rather than patient preference. This systematic review critically evaluates studies of patient and clinician preferences for treatment of early stage NSCLC.
Primary empirical research up to 30 April 2020 was identified from searches of MEDLINE, EMBASE, PsycInfo and Web of Science databases. Data extracted included study characteristics and methods, preferences for NSCLC treatment and involvement in decision-making and risk of bias using the Mixed Methods Appraisal Tool. Findings were synthesized using descriptive data and narrative synthesis.
23 studies were included in the review; 18 measured patient preferences, 4 clinician preferences and 1 both clinician and patient preferences. Patients and clinicians were both most likely to prefer a collaborative role in treatment decisions. Most patients did not recall there being a choice between surgery or SABR options, and thus experienced minimal decisional conflict.
For professionals to support patients in making informed, value based decisions about NSCLC treatments, better quality evidence is needed of the clinical and quality of life trade offs for both surgery and SABR.
For professionals to support patients in making informed, value based decisions about NSCLC treatments, better quality evidence is needed of the clinical and quality of life trade offs for both surgery and SABR.
Health care personnel (HCP) working in outpatient settings routinely interact with patients with acute respiratory illnesses. Absenteeism following symptom development and lack of staff trained to obtain samples limit efforts to identify pathogens among infected HCP.
The Respiratory Protection Effectiveness Clinical Trial assessed respiratory infection incidence among HCP between 2011 and 2015. Research assistants obtained anterior nasal and oropharyngeal swabs from HCP in the workplace following development of respiratory illness symptoms and randomly while asymptomatic. Participants received take-home kits to self-collect swabs when absent from work. Samples mailed to a central laboratory were tested for respiratory viruses by reverse transcription polymerase chain reaction.
Among 2,862 participants, 3,467 swabs were obtained from symptomatic participants. Among symptomatic HCP, respiratory virus was detected in 904 of 3,467 (26.1%) samples. Self-collected samples by symptomatic HCP at home had higher rates of viral detection (40.3%) compared to 24% obtained by trained research assistants in the workplace (P < .001).
In this randomized clinical trial, take-home kits were an easily implemented, effective method to self-collect samples by HCP. Other studies have previously shown relative equivalence of self-collected samples to those obtained by trained healthcare workers. Take-home kit self-collection could diminish workforce exposures and decrease the demand for personnel protective equipment worn to protect workers who collect respiratory samples.
In this randomized clinical trial, take-home kits were an easily implemented, effective method to self-collect samples by HCP. Other studies have previously shown relative equivalence of self-collected samples to those obtained by trained healthcare workers. Take-home kit self-collection could diminish workforce exposures and decrease the demand for personnel protective equipment worn to protect workers who collect respiratory samples.Antipsychotic drugs are commonly prescribed, mainly for the treatment of schizophrenia and other psychotic disorders. Disproportionality analysis of pharmacovigilance data from national and international databases have been recently utilized to investigate the side-effect profiles of antipsychotics and have provided unique insights of their safety. Among several national and international spontaneous reporting databases the databases of the World Health Organization (VigiBase), of the European Medicines Agency (EudraVigilance) and the US Food and Drug Administration (FAERS) incorporate millions of Individual Case Safety Reports. The aim of our study was to systematically review published disproportionality analyses on antipsychotic drugs, in order to summarize the current state of methodology and potential strengths of this analysis while highlighting safety signal generated for these pharmacological group. PubMed was searched using a search algorithm combining terms for antipsychotic drugs and disproportionality analysis. A total of 39 articles were found to be eligible corresponding to 38 original disproportionality studies. Different measures of disproportionality were used in each study reporting odds ratio (ROR), proportional reporting ratio (PRR), empirical Bayes geometric mean (EBGM) and the information component (IC). Despite the inherent limitations of the pharmacovigilance databases disproportionality analysis provides complemented evidence from RCTs on the safety of antipsychotics, especially regarding participants often excluded from RCTs, such as pregnant and breastfeeding women, children and participants with drug abuse, comorbidities or concomitant medications.There is increasing evidence showing that HDACs regulates BDNF (brain-derived neurotrophic factor) expression through its interaction with the Bdnf gene promoter, a key regulator to consolidate memory. Although the nuclear mechanisms regulated by HDACs that control BDNF expression have been partially described recently, the temporal events for memory consolidation remain unknown. Hence, in this work, we studied the temporal pattern for the activation of the BDNF/TrkB pathway through class I HDAC inhibition to enhance object recognition memory (ORM) consolidation. To this end, we inhibited class I HDAC into the insular cortex (IC) and a weak ORM protocol was used to assess temporal expression and function of the BDNF/TrkB pathway in the IC. We found that cortical class I HDAC inhibition enhanced long-term ORM, coincident with a clear peak of BDNF expression at 4 h after acquisition. Furthermore, the tyrosine kinase B (TrkB) receptor blockade at 4 h, but not at 8 h, impaired the consolidation of ORM. These results suggest that histone acetylation regulates the temporal expression of BDNF in cortical circuits potentiating the long-term recognition memory.Within the hindbrain, serotonin (5-HT) functions as a modulator of the central glucagon-like peptide-1 (GLP-1) system. This interaction between 5-HT and GLP-1 is achieved via 5-HT2C and 5-HT3 receptors and is relevant for GLP-1-mediated feeding behavior. The central GLP-1 system is activated by various stressors, activates the hypothalamic pituitary adrenocortical (HPA) axis, and contributes to stress-related behaviors. Whether 5-HT modulates GLP-1's role in the stress response in unknown. We hypothesized that the serotonergic modulation of GLP-1-producing neurons (i.e., PPG neurons) is stimuli-specific and that stressed-induced PPG activity is one of the modalities in which 5-HT plays a role. In this study, we investigated the roles of 5-HT2C and 5-HT3 receptors in mediating the activation of PPG neurons in the nucleus tractus solitarius (NTS) following exposure to three different acute stressors lithium chloride (LiCl), noncontingent cocaine (Coc), and novel restraint stress (RES). Results showed that increased c-Fos expression in PPG neurons following LiCl and RES-but not Coc-is dependent on hindbrain 5-HT2C and 5-HT3 receptor signaling.
