Apramycin resistance in epidemic carbapenem-resistant Klebsiella pneumoniae ST258 strains.

Background: Recent studies indicated that the monosubstituted deoxystreptamine aminoglycoside apramycin is a potent antibiotic against a wide range of MDR Gram-negative pathogens.

Objectives: To evaluate the in vitro activity of apramycin against carbapenem-resistant Klebsiella pneumoniae (CRKp) isolates from New York and New Jersey, and to explore mechanisms of apramycin resistance.

Methods: Apramycin MICs were determined by broth microdilution for 155 CRKp bloodstream isolates collected from 2013 to 2018.

IS-Mediated Mobilization of the Colistin Resistance Gene in Escherichia coli.

The mobile colistin resistance gene has globally disseminated since it was first reported in 2017 in mobilization assays in this study demonstrate the functionality of the composite transposon structure IS-IS in wild-type and strains. These transpositions generated 4-bp duplications at the target sites. This is the first report demonstrating the mobility of the gene by transposition.

A Novel, Drug Resistance-Independent, Fluorescence-Based Approach To Measure Mutation Rates in Microbial Pathogens.

All evolutionary processes are underpinned by a cellular capacity to mutate DNA. To identify factors affecting mutagenesis, it is necessary to compare mutation rates between different strains and conditions. Drug resistance-based mutation reporters are used extensively to measure mutation rates, but they are suitable only when the compared strains have identical drug tolerance levels-a condition that is not satisfied under many "real-world" circumstances, e.

Gardnerella vaginalis population dynamics in bacterial vaginosis.

Bacterial vaginosis (BV) is the leading cause of vaginal discharge and is associated with the facultative Gram-variable bacterium Gardnerella vaginalis, whose population structure consists of four clades. Our goal was to determine if these clades differ with regard to abundance during BV. We performed a short-term longitudinal study of BV.

Approved Glycopeptide Antibacterial Drugs: Mechanism of Action and Resistance.

The glycopeptide antimicrobials are a group of natural product and semisynthetic glycosylated peptides that show antibacterial activity against Gram-positive organisms through inhibition of cell-wall synthesis. This is achieved primarily through binding to the d-alanyl-d-alanine terminus of the lipid II bacterial cell-wall precursor, preventing cross-linking of the peptidoglycan layer. Vancomycin is the foundational member of the class, showing both clinical longevity and a still preferential role in the therapy of methicillin-resistant Staphylococcus aureus and of susceptible Enterococcus spp.

Draft Genome Sequence of a Metronidazole-Resistant Derivative of Gardnerella vaginalis Strain ATCC 14019.

We report the genome sequence of a metronidazole-resistant derivative of Gardnerella vaginalis ATCC 14019. This strain was obtained after serial selection to increase the MIC from 4 to ≥500 µg/ml. Two coding changes, in genes encoding a response regulator and an NAD(+) synthetase, arose during selection.

Identification of intrinsically metronidazole-resistant clades of Gardnerella vaginalis.

Gardnerella vaginalis is associated with bacterial vaginosis (BV), the most common cause of vaginal discharge. Metronidazole is a front-line therapy for BV, and treatment failure and recurrent disease are common problems. Whole-genome sequencing studies have revealed that G.

Draft Genome Sequence of a Metronidazole-Resistant Gardnerella vaginalis Isolate.

We report the draft genome sequence of a Gardnerella vaginalis strain (3549624) isolated from a vaginal specimen. G. vaginalis is associated with bacterial vaginosis, the most common cause of vaginal discharge, which is often treated with metronidazole.

Draft Genome Sequence of a Metronidazole-Susceptible Atopobium vaginae Isolate.

We report the draft genome sequence of a vaginal isolate of Atopobium vaginae vaginae (strain 44061), an organism linked to bacterial vaginosis (BV), the most common gynecological infection in the United States. This species is often highly resistant to metronidazole, which is a front-line therapy for BV. Strain 44061 is a metronidazole-susceptible isolate (MIC, 16 µg/ml), and its genome sequence will be useful for comparative studies to elucidate the molecular basis of metronidazole resistance in this species.

Trichomonas vaginalis metronidazole resistance is associated with single nucleotide polymorphisms in the nitroreductase genes ntr4Tv and ntr6Tv.

Metronidazole resistance in the sexually transmitted parasite Trichomonas vaginalis is a problematic public health issue. We have identified single nucleotide polymorphisms (SNPs) in two nitroreductase genes (ntr4Tv and ntr6Tv) associated with resistance. These SNPs were associated with one of two distinct T.

X-Plate Technology: a new method for detecting fluconazole resistance in Candida species.

Candida species are responsible for many opportunistic fungal infections. Fluconazole is a well-tolerated antifungal drug, commonly used in the treatment of candidiasis. However, with fluconazole resistance ever increasing, rapid detection and antifungal susceptibility testing of Candida is imperative for proper patient treatment.

Cardiac atria are the primary source of ANP release in hypoxia-adapted rats.

Aims: atrial natriuretic peptide (ANP) is released from the heart in response to hypoxia and helps mitigate the development of pulmonary hypertension. However, the mechanism of hypoxia-induced ANP release is not clear. The cardiac atria are the primary source of ANP secretion under normal conditions, but right ventricular ANP expression is markedly up-regulated during adaptation to hypoxia.

Detection of erythromycin and clindamycin resistance genes in Group B Streptococcal clinical isolates and cervicovaginal-rectal swabs.

A multiplex PCR assay was used to detect the erythromycin (EM) and clindamycin (CM) antibiotic resistance genes, ermB, ermTR, and mefA/E, in Group B Streptococcal (GBS) clinical isolates and in DNA extracted from the corresponding cervicovaginal-rectal (CVR) swabs. We compared these results to the standard EM/CM double disk diffusion assay of 46 isolates. Given that these genes are present in other CVR flora and are found on mobile genetic elements, the PCR assay was unable to predict GBS resistance directly from the swabs.

Erythromycin and clindamycin resistance in group B streptococcal clinical isolates.

Erythromycin (EM) and clindamycin (CM) susceptibility testing was performed on 222 clinical isolates of group B Streptococcus. A multiplex PCR assay was used to detect the ermB, ermTR, and mefA/E antibiotic resistance genes. These results were compared to the phenotypes as determined by the standard EM/CM double disk diffusion assay.

Isoflurane neuroprotection in hypoxic hippocampal slice cultures involves increases in intracellular Ca2+ and mitogen-activated protein kinases.

Background: The volatile anesthetic isoflurane reduces acute and delayed neuron death in vitro models of brain ischemia, an action that the authors hypothesize is related to moderate increases in intracellular calcium concentration ([Ca2+]i). Specifically, the authors propose that during hypoxia, moderate increases in [Ca2+]i in the presence of isoflurane stimulates the Ca2+-dependent phosphorylation of members of the mitogen-activated protein kinase (MAP) kinase Ras-Raf-MEK-ERK pathway that are critical for neuroprotective signaling and suppression of apoptosis.

Methods: Death of CA1, CA3, and dentate neurons in rat hippocampal slice cultures was assessed by propidium iodide fluorescence 48-72 h after 60-75 min of hypoxia.

Protective effects of TASK-3 (KCNK9) and related 2P K channels during cellular stress.

Tandem pore domain (or 2P) K channels form a recently isolated family of channels that are responsible for background K currents in excitable tissues. Previous studies have indicated that 2P K channel activity produces membrane hyperpolarization, which may offer protection from cellular insults. To study the effect of these channels in neuroprotection, we overexpressed pH-sensitive 2P K channels by transfecting the partially transformed C8 cell line with these channels.

Mild hypothermia, but not propofol, is neuroprotective in organotypic hippocampal cultures.

The neuroprotective potency of anesthetics such as propofol compared to mild hypothermia remains undefined. Therefore, we determined whether propofol at two clinically relevant concentrations is as effective as mild hypothermia in preventing delayed neuron death in hippocampal slice cultures (HSC). Survival of neurons was assessed 2 and 3 days after 1 h oxygen and glucose deprivation (OGD) either at 37 degrees C (with or without 10 or 100 microM propofol) or at an average temperature of 35 degrees C during OGD (mild hypothermia).

Impact of changing foot progression angle on foot pressure measurement in children with neuromuscular diseases.

To analyze the effect of lower-limb rotation on foot pressure distribution, 16 patients (23 feet) with neuromuscular diseases who received derotation osteotomy of lower limbs without concomitant foot-ankle procedures were included in this retrospective study. The cross-correlation analysis showed that the interval change of the foot progression angle was correlated with the interval change of the medial-lateral foot pressure impulse distribution. The externally rotated foot progression angle tends to introduce higher loading on the medial foot, and the internally rotated foot progression angle shifts the loading to lateral side of the foot.

Distal hamstring lengthening in ambulatory children with cerebral palsy: primary versus revision procedures.

To document the benefits and limitations of distal hamstring lengthening (HL), 61 children (105 limbs) with cerebral palsy treated by distal HL with complete preoperative and postoperative evaluations were reviewed. There was significant improvement in popliteal angle, fixed knee flexion contracture, knee angle at foot contact (FC), and mid-stance knee extension after HL. On the other hand, the hip power generation peak decreased, and the anterior pelvic tilt increased.

gamma-Aminobutyric acid-A receptors contribute to isoflurane neuroprotection in organotypic hippocampal cultures.

Unlabelled: The mechanisms by which anesthetics such as isoflurane reduce cell death in rodent models of cerebral ischemia remain incompletely defined. Reduction in glutamate excitotoxicity explains some but not all of isoflurane's neuroprotection. Because isoflurane potentiates gamma-aminobutyric acid (GABA) receptor-mediated ion fluxes and GABA(A) receptor agonists have neuroprotective effects, we hypothesized that GABA(A) receptors contribute to isoflurane neuroprotection.

Dynamic pedobarograph in evaluation of varus and valgus foot deformities.

Objective documentation of dynamic varus and valgus deformities of the hindfoot is still a clinical dilemma. In a review of spastic foot deformities, clinical, radiographic, and foot pressure data were collected in 108 children with cerebral palsy. According to the clinical assessment, five categories of foot deformities were defined: severe varus, varus, neutral, valgus, and severe valgus.

Assessing human-robotic performance for vocational placement.

This paper describes the results of an exploratory study of the use of standard occupational therapy assessment tests to measure the effective manipulation ability of individuals with disabilities using a robotic aid. Robotic manipulators have been explored for use as a vocational accommodation to support the job placement of individuals with severe manipulation disabilities. One of the factors that has impeded the transfer of this work is the lack of practical information that is relevant to the vocational placement process.

Lithium has no direct effect on cardiac function in the isolated, perfused rat heart.

To determine if lithium exerts direct cardiac toxicity, using an isolated, perfused rat heart model, paced and unpaced beating rat hearts were perfused with Krebs-Henseleit bicarbonate solution and left ventricular pressures were measured via a balloon-tipped catheter positioned in the left ventricle via the mitral valve. Following a stabilization period, hearts were then perfused with Krebs-Henseleit bicarbonate solution containing 1, 10, and 100 mM ionized lithium chloride or lithium carbonate in an antecedent dose-response protocol and perfused for 10 min. at each dose.

The Medical Academic Advancement Program at the University of Virginia School of Medicine.

Since 1984 the University of Virginia School of Medicine has conducted the Medical Academic Advancement Program for minority and disadvantaged students interested in careers in medicine. The program is a six-week residential program for approximately 130 undergraduate and post-baccalaureate students per year. It emphasizes academic course work--biology, chemistry, physics, and essay writing--to prepare the participants for the Medical College Admission Test.

Mitochondrial distribution within the terminal neurite of the pacinian corpuscle.

Electron-microscopic analyses of the mitochondrial organization within the neurite innervating the Pacinian corpuscle (PC) were performed to test the hypothesis that the sites of mechanotransduction are the filopodia projecting from the neurite's surface. Since high concentrations of mitochondria imply the need for metabolic energy, and since transduction mechanisms are heavily dependent on such energy, it was reasoned that the greatest concentration of mitochondria should occur near the filopodia if they are involved in mechanotransduction. The analysis that the mitochondria lie close to the terminal neurite's membrane, on average within 0.