Experience using high-dose glucose-insulin-potassium (GIK) in critically ill patients

Purpose To audit the use of GIK in terms of safety, haemodynamic effects, and impact on catecholamine dosage. Materials and methods A retrospective, descriptive, evaluative audit of GIK use within the adult ICU of a London teaching hospital was conducted. Rescue therapy of GIK (up to 1.0 Units insulin/kg/h) was administered to improve cardiac function. Outcomes were ICU survival, change in cardiac index (CI) and blood lactate levels, events of hypoglycaemia, hyperglycaemia, hypokalaemia and hyperkalaemia, and discontinuation time of catecholamine inotropes. Results Of 85 patients treated with GIK, 13 (15.3%) survived their ICU stay and 9 (10.5%) were discharged home. In patients surviving until 72 h, a trend of improved CI and lactate levels was seen, often with reductions in catecholamine dosing. Inotropes were discontinued in 35 (54%) patients. Severe hypoglycaemia ( 20 mmol/l), hypokalaemia ( 7 mmol/l) during GIK affected 1, 6, 8 and 1 patients, respectively. These abnormalities were quickly identified. No measurable harm was noted. Conclusions High-dose GIK can be safely used in critically ill patients, though blood glucose and potassium levels must be monitored frequently. GIK was associated with improved CI and blood lactate levels. Impact on survival requires prospective evaluation

Menstrual cycle phase and sexual arousability in women

__Abstract__ Sexual arousability of women has not been consistently found to vary significantly over phases of the menstrual cycle. We studied changes in the temperature of a labium minus and subjective sexual and genital arousal recorded on semantic scales while watching erotic video in 12 women with natural menstrual cycles and 12 women using low-dose estrogen oral contraceptive pills. Natural cycle phase was ascertained by blood progesterone. Subjects were tested twice, with an interval of about 2 weeks. Half of each group had their first test during their luteal phase, the others during their follicular phase. Women tested for the first time in their follicular phase were sexually more aroused than women tested for the first time during their luteal phase. This was true for both objective (i.e., a labium minus change in temperature) and subjective genital arousal. When these women were retested in their alternative phase of the menstrual cycle, those who were then follicular did not score higher than those who were then luteal. On the contrary, the latter group scored as high as when tested during their follicular phase. This phenomenon was observed both in women with and without oral contraception. The nature of the menstrual phase (i.e., natural or pill-induced) seems irrelevant in this respect. Sexual arousal achieved during the first session appeared to be correlated with an increase in desire for making love during the rest of the day and night. Only 1 of 12 women tested during their luteal phase indicated an increase in desire to make love, while 6 of 12 women tested during their follicular phase indicated an increase. Apparently the menstrual cycle phase during the first test determines the immediate response and indirectly affects the response during the second test approximately 10 days later. In a random block design the difference in sexual response between follicular and luteal phase of the menstrual cycle disappears

Heterosexual interactions of pairs of laboratory-housed stumptail macaques (Macaca arctoides) under continuous observation with closed-circuit video recording

Female-male interaction of heterosexual pairs of stumptail macaques, housed together continuously, was studied 24 hr per day using closed-circuit video recording. Two pairs were studied for approximately 2 months each. Although no generalizations can be made from such a small sample, no aspect of behavioral interaction varied significantly with the stage of the menstrual cycle of the female partner. Copulation occurred regularly but only during the daylight hours. Both pairs showed several peak ejaculation days (5-21 ejaculations/day), which were distributed throughout the entire menstrual cycle. In general, the highest number of ejaculations was observed to occur when the animals were put together either for the first time or following a separation of a few days. In one pair the female became pregnant, and from the fifth week of pregnancy onward there was a gradual increase in male aggression, coinciding with a decrease in male sexual and grooming behavior. In a second study eight different pairs were observed during the first day together and male copulatory behavior was studied. Two patterns of copulatory behavior could be discerned: pairs displaying a high number of ejaculations (19-38) and pairs displaying a low number of ejaculations (4-8). With regard to the interejaculatory interval (IEI), the male stumptail appeared to be unique. In contrast to what has been reported for other mammals, i.e., a steady increase in IEI with subsequent ejaculations, the stumptail showed increasing IEIs only during the first three to four, as well as between the last, ejaculations; in between, the IEI remained relatively constant. The maximum number of consecutive ejaculations observed was 38, displayed during a 10-hr time period (mean (± SEM)IEI, 12.9 ± 3.5 min)

Genotoxic mixtures and dissimilar action: Concepts for prediction and assessment

This article has been made available through the Brunel Open Access Publishing Fund. This article is distributed under the terms of the creative commons Attribution license which permits any use, distribution, and reproduction in any medium, provided the original author(s)and the source are credited.Combinations of genotoxic agents have frequently been assessed without clear assumptions regarding their expected (additive) mixture effects, often leading to claims of synergisms that might in fact be compatible with additivity. We have shown earlier that the combined effects of chemicals, which induce micronuclei (MN) in the cytokinesis-block micronucleus assay in Chinese hamster ovary-K1 cells by a similar mechanism, were additive according to the concept of concentration addition (CA). Here, we extended these studies and investigated for the first time whether valid additivity expectations can be formulated for MN-inducing chemicals that operate through a variety of mechanisms, including aneugens and clastogens (DNA cross-linkers, topoisomerase II inhibitors, minor groove binders). We expected that their effects should follow the additivity principles of independent action (IA). With two mixtures, one composed of various aneugens (colchicine, flubendazole, vinblastine sulphate, griseofulvin, paclitaxel), and another composed of aneugens and clastogens (flubendazole, doxorubicin, etoposide, melphalan and mitomycin C), we observed mixture effects that fell between the additivity predictions derived from CA and IA. We achieved better agreement between observation and prediction by grouping the chemicals into common assessment groups and using hybrid CA/IA prediction models. The combined effects of four dissimilarly acting compounds (flubendazole, paclitaxel, doxorubicin and melphalan) also fell within CA and IA. Two binary mixtures (flubendazole/paclitaxel and flubendazole/doxorubicin) showed effects in reasonable agreement with IA additivity. Our studies provide a systematic basis for the investigation of mixtures that affect endpoints of relevance to genotoxicity and show that their effects are largely additive.UK Food Standards Agenc

Extragalactic Peaked-Spectrum Radio Sources at Low-Frequencies are Young Radio Galaxies

© 2022 Dementia and Geriatric Cognitive Disorders. All rights reserved. This is an Open Access article, published by EDP Sciences, under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0).We present a sample of 373 peaked-spectrum (PS) sources with spectral peaks around 150 MHz, selected using a subset of the two LOw Frequency ARray (LOFAR) all-sky surveys, the LOFAR Two Meter Sky Survey and the LOFAR LBA Sky Survey. These LOFAR surveys are the most sensitive low-frequency widefield surveys to date, allowing us to select low-luminosity peaked-spectrum sources. Our sample increases the number of known PS sources in our survey area by a factor 50. The 5 GHz luminosity distribution of our PS sample shows we sample the lowest luminosity PS sources to date by nearly an order of magnitude. Since high-frequency gigahertz-peaked spectrum sources and compact steep-spectrum sources are hypothesised to be the precursors to large radio galaxies, we investigate whether this is also the case for our sample of low-frequency PS sources. Using optical line emission criteria, we find that our PS sources are predominately high-excitation radio galaxies instead of low-excitation radio galaxies, corresponding to a quickly evolving population. We compute the radio source counts of our PS sample, and find they are scaled down by a factor of ≈40 compared to a general sample of radio-loud active galactic nuclei (AGN). This implies that the lifetimes of PS sources are 40 times shorter than large-scale radio galaxies if their luminosity functions are identical. To investigate this, we compute the first radio luminosity function for a homogeneously selected PS sample. We find that for 144 MHz luminosities ≳1025 W Hz-1, the PS luminosity function has the same shape as an unresolved radio-loud AGN population, but shifted down by a factor of ≈-pagination10. We interpret this as strong evidence that these high-luminosity PS sources evolve into large-scale radio-loud AGN. For local low-luminosity PS sources, there is a surplus of PS sources, which we hypothesise to be the addition of frustrated PS sources that do not evolve into large-scale AGN.Peer reviewe

Birth weight influences cardiac structure, function and disease risk: evidence of a causal association

Background and Aims Low birth weight is a common pregnancy complication, which has been associated with higher risk of cardiometabolic disease in later life. Prior Mendelian randomization (MR) studies exploring this question do not distinguish the mechanistic contributions of variants that directly influence birth weight through the foetal genome (direct foetal effects), vs. variants influencing birth weight indirectly by causing an adverse intrauterine environment (indirect maternal effects). In this study, MR was used to assess whether birth weight, independent of intrauterine influences, is associated with cardiovascular disease risk and measures of adverse cardiac structure and function. Methods Uncorrelated (r2 < .001), genome-wide significant (P < 5 × 10−8) single nucleotide polymorphisms were extracted from genome-wide association studies summary statistics for birth weight overall, and after isolating direct foetal effects only. Inverse-variance weighted MR was utilized for analyses on outcomes of atrial fibrillation, coronary artery disease, heart failure, ischaemic stroke, and 16 measures of cardiac structure and function. Multiple comparisons were accounted for by Benjamini–Hochberg correction. Results Lower genetically-predicted birth weight, isolating direct foetal effects only, was associated with an increased risk of coronary artery disease (odds ratio 1.21, 95% confidence interval 1.06–1.37; P = .031), smaller chamber volumes, and lower stroke volume, but higher contractility. Conclusions The results of this study support a causal role of low birth weight in cardiovascular disease, even after accounting for the influence of the intrauterine environment. This suggests that individuals with a low birth weight may benefit from early targeted cardiovascular disease prevention strategies, independent of whether this was linked to an adverse intrauterine environment during gestation

SDN-POA volume, sexual behavior, and partner preference of male rats affected by perinatal treatment with ATD

The present study investigated 1) the importance of the aromatization process during the perinatal period for the development of the sexually dimorphic nucleus in the preoptic area of the hypothalamus (SDN-POA) of male rats, and 2) the relationship between SDN-POA volume and parameters of masculinization in male rats that were treated perinatally with the aromatase-inhibitor ATD. Males were treated with ATD either prenatally or pre- and neonatally, or with the vehicle. Masculine sexual behavior and partner preference were investigated in adulthood. Thereafter, animals were sacrificed and SDN-POA volume was measured. The SDN-POA volume was reduced in both the prenatally and the pre- and neonatally treated group, with a larger reduction in the latter than in the former group. Combined pre- and neonatal ATD treatment resulted in reduced frequency of mounts, intromissions, and ejaculations, as well as a reduced preference for a female over a male. The SDN-POA size was significantly and positively correlated with frequency of masculine sexual behavior, as well as preference for a female over a male

Circulating MicroRNAs as Non-invasive Biomarkers for Canine Cushing's Syndrome

Canine Cushing's syndrome (hypercortisolism) can be caused by a pituitary tumor (pituitary-dependent hypercortisolism; PDH) or a cortisol-secreting adrenocortical tumor (csACT). For both cases, non-invasive biomarkers that could pre-operatively predict the risk of recurrence after surgery would greatly impact clinical decision making. The aim of this study was to determine whether circulating microRNAs (miRNAs) can be used as diagnostic (presence of PDH or csACT) and/or prognostic (disease recurrence, histological grade) non-invasive biomarkers for canine Cushing's syndrome. After a pilot study with 40 miRNAs in blood samples of healthy dogs (n = 3), dogs with PDH (n = 3) and dogs with a csACT (n = 4), we selected a total of 20 miRNAs for the definitive study. In the definitive study, these 20 miRNAs were analyzed in blood samples of healthy dogs (n = 6), dogs with PDH (n = 19, pre- and post-operative samples) and dogs with a csACT (n = 26, pre-operative samples). In dogs with PDH, six miRNAs (miR-122-5p, miR-126-5p, miR-141-3p, miR-222-3p, miR-375-3p and miR-483-3p) were differentially expressed compared to healthy dogs. Of one miRNA, miR-122-5p, the expression levels did not overlap between healthy dogs and dogs with PDH (p = 2.9x10−4), significantly decreased after hypophysectomy (p = 0.013), and were significantly higher (p = 0.017) in dogs with recurrence (n = 3) than in dogs without recurrence for at least one year after hypophysectomy (n = 7). In dogs with csACTs, two miRNAs (miR-483-3p and miR-223-3p) were differentially expressed compared to healthy dogs. Additionally, miR-141-3p was expressed significantly lower (p = 0.009) in dogs with csACTs that had a histopathological Utrecht score of ≥ 11 compared to those with a score of &lt;11. These results indicate that circulating miRNAs have the potential to be non-invasive biomarkers in dogs with Cushing's syndrome that may contribute to clinical decision making