Successful treatment of bacterial infections requires the timely administration of appropriate antimicrobial therapy. The failure to initiate the correct therapy in a timely fashion results in poor ...clinical outcomes, longer hospital stays, and higher medical costs. Current approaches to antibiotic susceptibility testing of cultured pathogens have key limitations ranging from long run times to dependence on prior knowledge of genetic mechanisms of resistance. We have developed a rapid antimicrobial susceptibility assay for Staphylococcus aureus based on bacterial cytological profiling (BCP), which uses quantitative fluorescence microscopy to measure antibiotic induced changes in cellular architecture. BCP discriminated between methicillin-susceptible (MSSA) and -resistant (MRSA) clinical isolates of S. aureus (n=71) within 1–2h with 100% accuracy. Similarly, BCP correctly distinguished daptomycin susceptible (DS) from daptomycin non-susceptible (DNS) S. aureus strains (n=20) within 30min. Among MRSA isolates, BCP further identified two classes of strains that differ in their susceptibility to specific combinations of beta-lactam antibiotics. BCP provides a rapid and flexible alternative to gene-based susceptibility testing methods for S. aureus, and should be readily adaptable to different antibiotics and bacterial species as new mechanisms of resistance or multidrug-resistant pathogens evolve and appear in mainstream clinical practice.
•Bacterial cytological profiling identifies antibiotic resistant S. aureus.•BCP predicts best treatment options for multidrug resistant MRSA.•Resistant strains are correctly identified within 1h.•BCP does not require prior knowledge of resistance mechanism.
There is a great need for rapid antimicrobial susceptibility testing (AST) as it can dramatically improve clinical outcome for bacterial infections. Most currently proposed ASTs are dependent on knowledge of known resistance genes or based solely on growth/lysis. We have developed a new diagnostic method for rapidly determining antibiotic susceptibility of Staphylococcus aureus using quantitative fluorescence microscopy to measure antibiotic induced changes in cellular architecture. Our test has the potential to change the way antibiotic susceptibility testing is done in the future and is readily adaptable to different antibiotics and bacterial species regardless of the mechanisms of resistance.
Abstract
Background
A stronger safety climate in nursing homes may reduce avoidable adverse events. Yet efforts to strengthen safety climate may fail if nursing homes are not ready to change. To ...inform improvement efforts, we examined the link between organizational readiness to change and safety climate.
Methods
Seven safety climate domains and organizational readiness to change were measured with validated Community Living Center/CLC Employee Survey of Attitudes about Resident Safety and Organizational Readiness to Change Assessment. Safety climate domains comprised of safety priorities, supervisor commitment to safety, senior management commitment to safety, safety attitudes, environmental safety, coworker interactions around safety, and global rating of CLC. We specified models with and without readiness to change to explain CLC- and person-level variance in safety climate domains.
Results
One thousand three hundred ninety seven workers (frontline staff and managers) responded from 56 US Veterans Health Administration CLCs located throughout the US. Adding readiness to change reduced baseline CLC-level variance of outcomes (2.3–9.3%) by > 70% for interpersonal domains (co-workers, supervisors, and senior management). Readiness to change explained person-level variance of every safety climate domain (
P
< 0.05), especially for interpersonal domains.
Conclusions
Organizational readiness to change predicted safety climate. Safety climate initiatives that address readiness to change among frontline staff and managers may be more likely to succeed and eventually increase resident safety.
Purpose
Occult hernias, hernias seen on radiologic imaging but not felt on physical exam, are common. Despite their high prevalence, little is known about the natural history of this finding. Our aim ...was to determine and report on the natural history of patients with occult hernias including the impact on abdominal wall quality of life (AW-QOL), need for surgery, and risk of acute incarceration/strangulation.
Methods
This was a prospective cohort study of patients who underwent a computed tomography (CT) abdomen/pelvis scan from 2016 to 2018. Primary outcome was change in AW-QOL using the modified Activities Assessment Scale (mAAS), a hernia-specific, validated survey (1 = poor, 100 = perfect). Secondary outcomes included elective and emergent hernia repairs.
Results
A total of 131 (65.8%) patients with occult hernias completed follow-up with a median (IQR) of 15.4 (22.5) months. Nearly half of these patients (42.8%) experienced a decrease in their AW-QOL, 26.0% were unchanged, and 31.3% reported improvement. One-fourth of patients (27.5%) underwent abdominal surgery during the study period: 9.9% were abdominal procedures without hernia repair, 16.0% involved elective hernia repairs, and 1.5% were emergent hernia repairs. AW-QOL improved for patients who underwent hernia repair (+ 11.2 ± 39.7,
p
= 0.043) while those who did not undergo hernia repair experienced no change in AW-QOL (− 3.0 ± 35.1).
Conclusion
When untreated, patients with occult hernias on average experience no change in their AW-QOL. However, many patients experience improvement in AW-QOL after hernia repair. Additionally, occult hernias have a small but real risk of incarceration requiring emergent repair. Further research is needed to develop tailored treatment strategies.
Immobilization of bioactive molecules on the surface of magnetic nanoparticles is of great interest, because the magnetic properties of these bioconjugates promise to greatly improve the delivery and ...recovery of biomolecules in biomedical applications. Here we present the preparation and functionalization of magnetite (Fe3O4) nanoparticles 20 nm in diameter and the successful covalent conjugation of the enzyme glucose oxidase to the amino-modified nanoparticle surface. Functionalization of the magnetic nanoparticle surface with amino groups greatly increased the amount and activity of the immobilized enzyme compared with immobilization procedures involving physical adsorption. The enzymatic activity of the glucose oxidase-coated magnetic nanoparticles was investigated by monitoring oxygen consumption during the enzymatic oxidation of glucose using a ruthenium phenanthroline fluorescent complex for oxygen sensing. The glucose oxidase-coated magnetite nanoparticles could function as nanometric glucose sensors in glucose solutions of concentrations up to 20 mmol L(-1). Immobilization of glucose oxidase on the nanoparticles also increased the stability of the enzyme. When stored at 4 degrees C the nanoparticle suspensions maintained their bioactivity for up to 3 months.
A ligandless and base-free Cu-catalyzed protocol for the cross-coupling of arylboronic acids and potassium aryltrifluoroborate salts with primary and secondary aliphatic amines and anilines is ...described. The process utilizes catalytic copper(II) acetate monohydrate and 4 Å molecular sieves in dichloromethane at slightly elevated temperatures under an atmosphere of oxygen. A broad range of functional groups are tolerated on both of the cross-coupling partners.
Phospholipase A2 (PLA2) cleave phospholipids preferentially at the sn-2 position, liberating free fatty acids and lysophospholipids. They are classified into six main groups based on size, location, ...function, substrate specificity and calcium requirement. These classes include secretory PLA2 (sPLA2), cytosolic (cPLA2), Ca2+-independent (iPLA2), platelet activating factor acetylhydrolases (PAF-AH), lysosomal PLA2 (LyPLA2) and adipose specific PLA2 (AdPLA2). It is hypothesized that PLA2 can serve as pharmacological targets for the therapeutic treatment of several diseases, including cardiovascular diseases, atherosclerosis, immune disorders and cancer. Special emphasis has been placed on inhibitors of sPLA2 isoforms as pharmacological moieties, mostly due to the fact that these enzymes are activated during inflammatory events and because their expression is increased in several diseases. This review focuses on understanding how sPLA2 isoform expression is altered during disease progression and the possible therapeutic interventions to specifically target sPLA2 isoforms, including new approaches using nano-particulate-based strategies.
Aims. Mitochondrial dysfunction contributes to many forms of peripheral and central nervous system degeneration. Therapies that protect mitochondrial number and function have the potential to impact ...the progression of conditions such as diabetic neuropathy. We therefore assessed indices of mitochondrial function in dorsal root ganglia (DRG) and brain cortex of the Zucker diabetic fatty (ZDF) rat model of type 2 diabetes and tested the therapeutic impact of a neurogenic compound, NSI-189, on both mitochondrial function and indices of peripheral and central neurological dysfunction. Materials and Methods. ZDF rats were maintained for 16 weeks of untreated diabetes before the start of oral treatment with NSI-189 for an additional 16 weeks. Nerve conduction velocity, sensitivity to tactile and thermal stimuli, and behavioral assays of cognitive function were assessed monthly. AMP-activated protein kinase (AMPK) phosphorylation, mitochondrial protein levels, and respiratory complex activities were assessed in the DRG and brain cortex after 16 weeks of treatment with NSI-189. Results. Treatment with NSI-189 selectively elevated the expression of protein subunits of complexes III and V and activities of respiratory complexes I and IV in the brain cortex, and this was accompanied by amelioration of impaired memory function and plasticity. In the sensory ganglia of ZDF rats, loss of AMPK activity was ameliorated by NSI-189, and this was accompanied by reversal of multiple indices of peripheral neuropathy. Conclusions. Efficacy of NSI-189 against dysfunction of the CNS and PNS function in type 2 diabetic rats was accompanied by improvement of mitochondrial function. NSI-189 exhibited actions at different levels of mitochondrial regulation in central and peripheral tissues.
Purpose: Depression is more prevalent in patients with gastroesophageal reflux disease (GERD) than in controls. The disorder can worsen the quality of life of GERD patients and is also associated ...with poor treatment response. However, there are limited data on its prevalence and risk factors in GERD patients in Southeast Asia. We aimed to assess the prevalence and severity of depression and its associated factors in Vietnamese patients with GERD. Patients and methods: A cross-sectional study was conducted on GERD patients. GERD was defined as troublesome typical reflux symptoms at least twice a week or having endoscopic erosive reflux disease. The revised Beck’s Depression Inventory (BDI-IA), which has been locally validated, was used to evaluate depression (BDI-IA < 10: none, 10– 18: mild to moderate, 19– 29: moderate to severe, and ≥ 30: severe depression). Multiple logistic regression analysis was used to identify independent factors associated with depression. Results: A total of 194 patients were recruited. The mean age was 44.1 ± 12.0 years, and the male-to-female ratio was 1:1.2. The depression rate was 47.9% (mild to moderate: 30.9%, moderate to severe: 16.0%, and severe: 1.0%). In multivariate analysis, sex and duration of reflux symptoms were the only two risk factors for depression. Compared to males, females were more likely to suffer from depression: odds ratio (OR) = 3.941 (95% confidence interval CI, 1.386– 11.205), p = 0.010. Compared to patients with a duration of reflux symptoms < 1 year, those with a duration of 1– 10 years and > 10 years were more likely to suffer from depression with a dose‒response: OR = 3.520 (95% CI, 1.057– 11.717), p = 0.040; and OR = 5.605 (1.046– 30.019), p = 0.044, respectively. Conclusion: Depression was prevalent, and a long duration of reflux symptoms was its predominant risk factor in Vietnamese patients with GERD.
The M-type phospholipase A2 receptor (PLA2R1) is a member of the C-type lectin superfamily and can internalize secreted phospholipase A2 (sPLA2) via endocytosis in non-cancer cells. sPLA2 itself was ...recently shown to be overexpressed in prostate tumors and to be a possible mediator of metastasis; however, little is known about the expression of PLA2R1 or its function in prostate cancers. Thus, we examined PLA2R1 expression in primary prostate cells (PCS-440-010) and human prostate cancer cells (LNCaP, DU-145, and PC-3), and we determined the effect of PLA2R1 knockdown on cytotoxicity induced by free or liposome-encapsulated chemotherapeutics. Immunoblot analysis demonstrated that the expression of PLA2R1 was higher in prostate cancer cells compared to that in primary prostate cells. Knockdown of PLA2R1 expression in PC-3 cells using shRNA increased cell proliferation and did not affect the toxicity of cisplatin, doxorubicin (Dox), and docetaxel. In contrast, PLA2R1 knockdown increased the in vitro toxicity of Dox encapsulated in sPLA2 responsive liposomes (SPRL) and correlated with increased Dox and SPRL uptake. Knockdown of PLA2R1 also increased the expression of Group IIA and X sPLA2. These data show the novel findings that PLA2R1 is expressed in prostate cancer cells, that PLA2R1 expression alters cell proliferation, and that PLA2R1 modulates the behavior of liposome-based nanoparticles. Furthermore, these studies suggest that PLA2R1 may represent a novel molecular target for controlling tumor growth or modulating delivery of lipid-based nanomedicines.
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