Role of Tris-CaEDTA as an adjuvant with nebulised tobramycin in cystic fibrosis patients with Pseudomonas aeruginosa lung infections: A randomised controlled trial

BackgroundWe tested if disrupting iron utilisation by P. aeruginosa by adding the Tris-buffered chelating agent CaEDTA to nebulised tobramycin would enhance bacterial clearance and improve lung function in CF patients.MethodsIn this double-blind, randomised controlled trial, 26 episodes (25 patients) with P. aeruginosa infection admitted to two CF centres for treatment of an acute pulmonary exacerbation were randomly assigned to receive either 75 mg CaEDTA in Tris-buffered saline or placebo (Tris-buffered saline) nebulised in combination with 250 mg tobramycin twice daily for six weeks followed with four week safety follow-up. Primary endpoints were safety, tolerability, and bacterial density of P. aeruginosa. A secondary endpoint was lung function.ResultsThe study drug was well tolerated with adverse events comparable in both groups. The mean (SD) reduction in sputum P. aeruginosa count (log₁₀ CFU/g) in the CaEDTA vs placebo group was 2·05 (2·57) vs 0·82 (2·71) at two weeks relative to admission (p = 0·39). The mean improvement in ppFEV₁ was 16 vs 5 (p = 0·16); 11 vs 2 (p = 0·28); and 6 vs 2 percentage points (p = 0·47) at two, six, and ten weeks in CaEDTA and placebo groups, respectively.ConclusionsIn this pilot study in CF patients, an increase in the reduction of sputum density of P. aeruginosa and an increase in ppFEV₁ was observed in the group of patients who received Tris-CaEDTA added to inhaled tobramycin compared to the group who received inhaled tobramycin alone, although these differences were not statistically significant. The treatment was also shown to be safe.     

The Empirical Status of the Preparation Hypothesis: Explicating Women’s Genital Responses to Sexual Stimuli in the Laboratory

Research conducted in our laboratory and in other laboratories has revealed that (1) women’s genital responses to visual and auditory stimuli are strongly affected by the presence of sexual cues, but that (2) specific sexual cues (e.g., gender of actors, the presence of sexual violence) often have little impact on the magnitude of the responses—that is, similar genital responses are observed to very different sexual stimuli. In addition, (3) women’s genital responses do not strongly correspond with self-reported sexual partner and activity preferences, or (4) with self-reported sexual arousal during the presentation of sexual stimuli. Taken together, these facts represent a puzzle, especially considering that men’s genital responses are highly affected by specific sexual cues and strongly correspond to stated preferences and self-reported sexual arousal. One hypothesis to explain female low cue-specificity and low concordance (relative to men) is the preparation hypothesis: Women’s indiscriminate genital responses serve a protective function. That is, they do not indicate or necessarily promote sexual interest and motivation, but rather prepare the vaginal lumen for possible sexual activity and therefore prevent injuries that may occur as a result of penetration. We review evidence for and against this hypothesis. We conclude that the evidence is favorable but not entirely convincing, and more work is required to reach a firm conclusion. We offer directions for future research.

     

A Scoping Review of Empirical Asexuality Research in Social Science Literature

Archives of Sexual Behavior - Research on asexuality as a part of the experience of human sexuality has increased over the last two decades. However, there has not yet been a systematic review of...     

An Investigation of Sexual and Relationship Adjustment During COVID-19

The COVID-19 pandemic and the mitigation measures put in place have resulted in universal disruption in the usual ways of life for individuals. The current study sought to investigate how aspects of sexual health (well-being and functioning) and relationship satisfaction changed or remained stable during the pandemic. During two separate time points (Time 1 including Time 1 and a retrospective baseline, Time 2), participants completed online measures of sexual well-being (sexual pleasure, partnered and solitary orgasm frequency, sexual distress), sexual functioning, and relationship satisfaction. Participants reported slight declines in sexual pleasure, frequency of orgasms with a partner, and frequency of solitary orgasms from pre-COVID-19 (retrospective baseline) to Time 1, with no significant differences in sexual distress and relationship satisfaction. For individuals with vulvas, sexual functioning improved from Time 1 to Time 2, whereas no significant differences in sexual functioning were observed for individuals with penises. Aspects of sexual health and relational satisfaction did not sufficiently change across time points to be considered meaningful health outcome changes. Given that minimal disruptions were noted in pre-COVID-19 to COVID-19 sexuality, these results highlight the potential resiliency of individuals’ sexuality when facing sudden changes in their daily lives. Implications of COVID-19’s effects on sexual well-being and relationship satisfaction research are broadly discussed.

     

A Descriptive Analysis of the Epidemiology and Motivations for Laser Tattoo Removal in an Underserved Population

Journal of Community Health - Tattoos of formerly gang-involved and incarcerated individuals can negatively impact their ability to reintegrate into society. Laser tattoo removal is essential to...     

Inhibitory effects of ginseng total saponins on hypoxia-induced dysfunction and injuries of cultured astrocytes

The effects of ginseng total saponins (GTS) on hypoxic damage of primary cultures of astrocytes were studied. Hypoxia was created by placing cultures in an air tight chamber that was flushed with 95% N(2)/5% CO(2) for 15 min before being sealed. Cultures showed evidence of significant cell injury after 24 h of hypoxia (increased lactate dehydrogenase (LDH) content in the culture medium, cell swelling and decreased glutamate uptake and protein content). Addition of GTS (0.1, 0.3 mg/ml) to the cultures during the exposure to hypoxic conditions produced dose-dependent inhibition of the LDH efflux. GTS (0.1, 0.3 mg/ml) also produced significant inhibition of the increased cell volume of astrocytes measured by [(3)H]O-methyl-D-glucose uptake under the hypoxic conditions. Decreased glutamate uptake and protein content was inhibited by GTS. These data suggest that GTS prevents astrocytic cell injury induced by severe hypoxiain vitro.     

Isolation of the ERG2 gene,encoding sterol Δ8Δ→7 isomerase,from the rice blast fungus Magnaporthe grisea and its expression in the maize smut pathogen Ustilago maydis

The Magnaporthe grisea ERG2 gene, encoding ⁸⁷ sterol isomerase, was isolated from a genomic library by heterologous hybridization to a fragment of the Ustilago maydis ERG2 gene. The isolated gene contained a reading frame of 745 bp which encoded a protein of 221 amino acids. The coding region was interrupted by a single putative 79-bp-long intron. The deduced amino-acid sequence exhibited similarity to the ERG2 gene products of U. maydis and of Saccharomyces cerevisiae, particularly in the central region of the proteins. The NH₂-terminal of all three proteins contained a long stretch of amino acids that were strongly hydrophobic, suggesting that they may function by anchoring the protein to a membrane surface. The M. grisea ERG2 gene complemented a U. maydis deletion mutant in which the ERG2 gene had been removed using a one-step gene replacement procedure. The ⁸⁷ sterol isomerase produced by the M. grisea ERG2 gene exhibited a level of sensitivity to the sterol biosynthesis inhibitor, tridemorph, similar to that of the enzyme derived from the U. maydis ERG2 gene.     

Inhibitory effect of the root ofCoptis japonica on catecholamine biosynthesis in PC12 cells

The effect of the root ofCoptis japonica (COPT), both the dichloromethane soluble (CH₂Cl₂) and insoluble (H₂O) fractions, on catecholamine contents and tyrosine hydroxylase (TH) activity in PC12 cells was investigated. CH₂Cl₂ and H₂O fractions showed 21 and 53% inhibitions on dopamine content, respectively, at a concentration of 40 μg/ml in medium: the H₂O fraction provided a greater inhibitory effect. The TH activity was reduced by the treatment of COPT (H₂O fraction). These results suggest that COPT has an inhibitory effect on the catecholamine biosynthesis by the reduction of TH activity in PC12 cells.     

Cytokines associated with amyloid plaques in Alzheimer's disease brain stimulate human glial and neuronal cell cultures to secrete early complement proteins, but not C1-inhibitor

Complement activation products C1q, C4c/d, and C3c/d in amyloid plaques in Alzheimer's disease probably result from direct binding and activation of C1 by amyloid beta peptides. RT-PCR and in situ hybridization studies have shown that several complement factors are produced in the brain parenchyma. In the present study, cytokines that can be detected in amyloid plaques (i.e., interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-alpha) were found to differentially stimulate the expression of C1 subcomponents, C1-Inhibitor (C1-Inh), C4, and C3, by astrocyte and microglial cell cultures derived from postmortem adult, human brain specimens and by neuroblastoma cell lines in culture. C1r and C1s were secreted at low levels by astrocytes and neuroblastoma cell lines. Exposure of cells to IL-1 alpha, IL-1 beta, TNF-alpha and to a far lesser extent IL-6, markedly upregulated C1r, C1s, and C3 production. C4 synthesis increased in response to interferon (IFN)-gamma and IL-6, whereas that of C1-Inh could be stimulated only by IFN-gamma. Thus, C1-Inh production is refractory to stimulation by plaque-associated cytokines, whereas these cytokines do stimulate C1r, C1s, and also C4 and C3 secretion by astrocytes and neuronal cells in culture. In contrast to the amyloid plaque associated cytokines IL-1 beta, IL-1 alpha, and TNF-alpha, the amyloid peptide A beta 1-42 itself did not stimulate C1r and C1s synthesis by astrocytes, microglial cells, or neuroblastoma cell lines. Microglial cells were the only cell type that constitutively expressed C1q. The ability of C1q to reassociate with newly formed C1r and C1s upon activation of C1 and subsequent inactivation by C1-Inh, may enable ongoing complement activation at sites of amyloid deposition, especially when C1-Inh is consumed and not replaced.     

Severe symptoms following a massive intentional L-thyroxine ingestion.

L-Thyroxine (T4) is commonly prescribed medication for hypothyroidism in humans and animals. Overdose has generally resulted in limited symptomatology managed with sedatives and beta-adrenergic receptor antagonists. We describe the largest acute T4 ingestion ever reported, which resulted in a profound thyrotoxicosis, resistant to treatment. A 34-y-old man ingested 900 (0.8 mg) tablets of veterinary T4 (720 mg) and was given 60 g of activated charcoal. He became lethargic on post-ingestion days 2 and 3; had vomiting, diaphoresis and insomnia on day 4; on day 5 he "looked like he had too much coffee", began "using a lot of words" and became agitated, assaultive and stopped speaking intelligibly; and on day 6 returned to the hospital combative and confused. He was diaphoretic, mydriatic, hyperreflexic, tremulous, with clear lungs and active bowel sounds, and received activated charcoal, haloperidol, diazepam, and phenobarbital, and was tracheally intubated. During hospitalization he was rehydrated, treated with propranolol and diazepam, but remained continuously tachycardic. On day 12 he became afebrile and his tachycardia resolved. Free T4 levels ranged from > 13 mcg/dL on day 6 to 1.2 mcg/dL on day 12. By discharge (day 15) he had lost 20 kilograms of body weight, but was clinically euthyroid 2 w later. This case suggests that large intentional T4 ingestions should be managed differently than current T4 overdose protocol.