Notes

Procedures, supply types, and training discovered via developing psychological health and substance abuse providers in to principal health care within Ethiopia.
Contemporary breast cancer surgery often requires hospital stays of 1 day or less, presenting challenges to delivery of high-quality care. Without sufficient time for proper education and guidance, patients may delay seeking care, experience anxiety, or seek unnecessary care, leading to poorer outcomes and increased costs. To address this, we evaluated the feasibility of a planning-, outcomes-, and analytics-based mobile health application called Manage My Surgery (MMS) for patients undergoing elective breast cancer surgery.

Patients undergoing breast cancer surgery at an academic health center were invited to use MMS. Those who used the application received pre- and postoperative surveys, which recorded and reported patient satisfaction and outcomes related to the application.

Thirty-three female patients undergoing elective breast cancer surgery used MMS. The median age was 58 years. Nineteen patients underwent lumpectomy, and 14 underwent mastectomy. Users logged on to the application an average of 3.5 times. The median number of questions viewed was 12 (range 2-35). Of 17 patients who completed the feedback survey, 100% said that MMS was helpful during preparation for surgery, 82.3% said that MMS was helpful postoperatively, and 94.1% would recommend MMS to others. Preliminary data on patient-reported outcomes collected by MMS suggest improvements in anxiety and depression over time.

Implementation of a digital care navigation tool in breast cancer surgery patients is feasible. Patients found the tool helpful in both the pre- and postoperative period. Additional ongoing work will focus on patients' self-management skills, long-term outcomes, and health system costs.
Implementation of a digital care navigation tool in breast cancer surgery patients is feasible. Patients found the tool helpful in both the pre- and postoperative period. Additional ongoing work will focus on patients' self-management skills, long-term outcomes, and health system costs.West, John B. High altitude limits of living things. High Alt Med Biol 00000-000, 2021.-The tolerance of animals to high altitude is generally limited by the low partial pressure of oxygen (PO2) in the air. Plant growth at high altitude is also limited but by different mechanisms. This article is a brief survey of the limiting factors of all living things. By a curious coincidence, the highest point on earth, that is Mt. Everest at 8,848 m, appears to be right at the limit of human tolerance to hypoxia. The altitude of the highest permanent human habitation, that is a town, is 5,100 m. This altitude is partly determined by the hypoxia, but also by economic factors. For other terrestrial mammals, birds, and insects, the highest altitudes for permanent habitation apparently belong to field mice (Phyllotis xanthopygus rupestris) and jumping spiders (Euophrys omnisuperstes) at about 6,700 m. Birds have been known to fly as high as 11,000 m although how much they are elevated by atmospheric updrafts is not clear. The record for animals for survival in extreme hypoxia is arguably held by the primitive invertebrate, the tardigrade (Hypsibius dujardini). This has been shown to tolerate the hard vacuum of space where the PO2 is essentially zero for many days. Less is known about the tolerance of plants to extreme altitude. However, vascular plants have been collected at >6,000 m in the Himalayas, and moss grows even higher. Lichens are very tolerant of severe hypoxia. There is evidence that global warming is increasing the highest altitudes at which plants can survive.Macrolide resistance is always a concern when treating Mycobacterium abscessus infections. MAB_2355c was identified previously as a possible new factor that confers the intrinsic resistance of 194 clinical M. abscessus isolates to clarithromycin. Herein, the potential mechanism by which MAB_2355c exerts macrolide resistance was explored by bioinformatics analysis, MAB_2355c cloning and protein purification, ATP hydrolysis assay, gene knockout and complementation, antibiotic sensitivity, and transcription-translation assays. MAB_2355c is a putative ATP-binding cassette F (ABC-F) family protein. Purified MAB_2355c protein exhibits ATP hydrolysis activity, which can be inhibited by ribosome-targeting antibiotics. MAB_2355c mRNA expression is upregulated more significantly after exposure to macrolides than after exposure to other ribosome-targeting antibiotics. MAB_2355c deleted strains showed increased sensitivity to macrolides, which was reduced by MAB_2355c complementation. Finally, MAB_2355c rescued the transcription and translation activities affected by macrolides in vitro. These findings suggest that MAB_2355c confers the resistance of M. abscessus to macrolides by ribosome protection, thus complementing other known resistance mechanisms.Here, we characterized a carbapenem-resistant Vibrio diabolicus strain of shrimp origin with various experiments and bioinformatics analysis. A novel metallo-β-lactamase (MBL) gene, blaVMB-2, that confers resistance to β-lactams, including meropenem and cephalosporins, was identified on a plasmid-borne composite transposon, ISShfr9-ISCR1-blaVMB-2-blaCARB-12-aadA1-ISShfr9, which is capable of generating a blaVMB-2-bearing circular intermediate. ISShfr9 was found to be disseminated in multidrug-resistant (MDR) pathogens, arousing the concern of further transmission of a blaVMB-2-bearing circular intermediate to clinical Enterobacterales strains via such insertion sequences, which warrants further investigations.We investigated the molecular epidemiology of 21 carbapenem-resistant Acinetobacter baumannii isolates from Libya and assessed their relative fitness. Core genome multilocus sequence typing (MLST) revealed five interhospital transmission clusters. Three clusters were associated with the international clones (IC) IC1, IC2, and IC7. Carbapenem-resistance was associated with blaOXA-23, blaGES-11, or blaNDM-1. Compared to that of A. baumannii DSM 30008, the doubling time was similar over 10 h, but after 16 h, half the isolates grew to higher densities, suggesting a fitness advantage.Antibiotic collateral sensitivity, in which acquired resistance to one drug leads to decreased resistance to a different drug, occurs in Burkholderia multivorans. Here, we observed that treatment of extensively drug-resistant variants evolved from a cystic fibrosis (CF) sputum sample isolate with either meropenem or sulfamethoxazole-trimethoprim, depending on past resistance phenotypes, resulted in increased sensitivity to five different classes of antibiotics. We further identified mutations, including putative resistance-nodulation-division efflux pump regulators and uncharacterized pumps, that may be involved in this phenotype in B. multivorans.Anti-infective drug discovery is greatly facilitated by the availability of in vitro assays that are more proficient at predicting the preclinical success of screening hits. Tuberculosis (TB) drug discovery is hindered by the relatively slow growth rate of Mycobacterium tuberculosis and the use of whole-cell-based in vitro assays that are inherently time-consuming, and for these reasons, rapid, noninvasive bioluminescence-based assays have been widely used in anti-TB drug discovery and development. In this study, in vitro assays that employ autoluminescent M. tuberculosis were optimized to determine MIC, minimum bactericidal concentration (MBC), time-kill curves, activity against macrophage internalized M. tuberculosis (90% effective concentration [EC90]), and postantibiotic effect (PAE) to provide rapid and dynamic biological information. Standardization of the luminescence-based MIC, MBC, time-kill, EC90, and PAE assays was accomplished by comparing results of established TB drugs and two ClpC1-targeting TB leads, ecumicin and rufomycin, to those obtained from conventional assays and/or to previous studies. Cumulatively, the use of the various streamlined luminescence-based in vitro assays has reduced the time for comprehensive in vitro profiling (MIC, MBC, time-kill, EC90, and PAE) by 2 months. The luminescence-based in vitro MBC and EC90 assays yield time and concentration-dependent kill information that can be used for pharmacokinetic-pharmacodynamic (PK-PD) modeling. The MBC and EC90 time-kill graphs revealed a significantly more rapid bactericidal activity for ecumicin than rufomycin. The PAEs of both ecumicin and rufomycin were comparable to that of the first-line TB drug rifampin. The optimization of several nondestructive, luminescence-based TB assays facilitates the in vitro profiling of TB drug leads in an efficient manner.Bacteria have a repertoire of strategies to overcome antibiotics in clinical use, complicating our ability to treat and cure infectious diseases. In addition to evolving resistance, bacteria within genetically clonal cultures can undergo transient phenotypic changes and tolerate high doses of antibiotics. These cells, termed persisters, exhibit heterogeneous phenotypes; the strategies that a bacterial population deploys to overcome one class of antibiotics can be distinct from those needed to survive treatment with drugs with another mode of action. It was previously reported that fluoroquinolones, which target DNA topoisomerases, retain the capacity to kill nongrowing bacteria that tolerate other classes of antibiotics. Here, we show that in Escherichia coli stationary-phase cultures and colony biofilms, persisters that survive treatment with the anionic fluoroquinolone delafloxacin depend on the AcrAB-TolC efflux pump. In contrast, we did not detect this dependence on AcrAB-TolC in E. TBOPP coli persisters that survive treatment with three other fluoroquinolone compounds. We found that the loss of AcrAB-TolC activity via genetic mutations or chemical inhibition not only reduces delafloxacin persistence in nongrowing E. coli MG1655 or EDL933 (an E. coli O157H7 strain), but it limits resistance development in progenies derived from delafloxacin persisters that were given the opportunity to recover in nutritive medium following antibiotic treatment. Our findings highlight the heterogeneity in defense mechanisms that persisters use to overcome different compounds within the same class of antibiotics. They further indicate that efflux pump inhibitors can potentiate the activity of delafloxacin against stationary-phase E. coli and block resistance development in delafloxacin persister progenies.We utilized the rabbit model of aortic valve infective endocarditis to examine the combined efficacy of the lysin LSVT-1701 plus daptomycin. The combination of LSVT-1701 plus daptomycin was highly effective at reducing methicillin-resistant Staphylococcus aureus (MRSA) counts in target tissue. When given for four daily doses, both lysin dose regimens in combination with daptomycin sterilized all target tissues. These findings suggest that LSVT-1701 warrants further clinical evaluation as an adjunctive therapy for the treatment of invasive MRSA infections.Meropenem-vaborbactam is a broad-spectrum carbapenem-beta-lactamase inhibitor combination approved in the USA and Europe to treat patients with complicated urinary tract infections and in Europe, other serious bacterial infections, including hospital- acquired and ventilator-associated pneumonia. Population pharmacokinetic (PK) models were developed to characterize the time-course of meropenem and vaborbactam using pooled data from two Phase 1 and two Phase 3 studies. Multi-compartment disposition model structures with linear elimination processes were fit to the data using NONMEM 7.2. Since both drugs are cleared primarily by the kidneys, estimated glomerular filtration rate (eGFR) was evaluated as part of the base structural models. For both agents, a two-compartment model with zero-order input and first-order elimination best described the pharmacokinetic PK data and a sigmoidal Hill-type equation best described the relationship between renal clearance and eGFR. For meropenem, the following significant covariate relationships were identified clearance (CL) decreased with increasing age, CL was systematically different in subjects with end stage renal disease, and all PK parameters increased with increasing weight.
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