Seasonal Variations in Sleep of Free-Ranging Arabian oryx (Oryx leucoryx) under Natural Hyper-Arid Conditions.
Sleep. 2018 Feb 21;:
Authors: Davimes JG, Alagaili AN, Bhagwandin A, Bertelsen MF, Mohammed OB, Bennett NC, Manger PR, Gravett N
Study objectives: The Arabian oryx lives under hyper-arid conditions in the Arabian Desert and exhibits temporal niche switching of activity patterns at a seasonal level. The objective of the current study was to provide a polysomnographic-based study of sleep in free-roaming Arabian oryx in their natural habitat to determine whether extreme seasonal climate variations resulted in changes in sleep patterns and physiology associated with the seasonal switching of temporal niches.
Methods: Electroencephalography, nuchal electromyography, actigraphy and subcutaneous temperature were recorded in free-roaming Arabian oryx in the Mahazat as-Sayd Protected Area, Kingdom of Saudi Arabia during winter and summer.
Results: Total daily sleep time in winter was 6.69 h and 3.77 h in summer. In winter, oryx exhibited nocturnal sleep typical of artiodactyls of around 60 kg body mass. In summer oryx, slept mostly during the day and subcutaneous temperature was seen to rise during sleep, but not as rapidly as the rises observed in ambient air temperature. REM sleep formed a very small percentage of total sleep time, especially so in the summer.
Conclusions: The unusual sleep patterns and physiology during summer appears to be related to high ambient air temperatures that affect both intrinsic and extrinsic factors necessary for survival. The Arabian oryx appears to use sleep physiology as an adaptive thermoregulatory mechanism in the hot summer months.
PMID: 29474674 [PubMed - as supplied by publisher]
Identification of new chromenone derivatives as cholinesterase inhibitors and molecular docking studies.
Med Chem. 2018 Feb 21;:
Authors: Iqbal J, Abbasi MSA, Zaib S, Afridi S, Furtmann N, Bajorath J, Langer P
BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia among aging population. This devastating disorder is generally associated with the gradual memory loss, specified by decrease of acetylcholine level in the cortex hippocampus of the brain due to hyper-activation of cholinesterases (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)).
OBJECTIVE: Therefore, inactivation of AChE and BChE by inhibitors can increase the acetylcholine level and hence may be an encouraging strategy for the treatment of AD and related neurological problems.
METHOD: In this contribution, two series of chromenone-based derivatives were tested by Ellmann's calorimetric method for AChE and BChE inhibition.
RESULTS: All the compounds showed inhibitory activity against cholinesterases and some of them exhibited dual inhibition of AChE as well as BChE. The most potent inhibitor of AChE was 2l having an IC50 value of 0.08±0.03 µM, while 3q inhibited the BChE with an IC50 value of 0.04±0.01 µM. In case of dual inhibition, 3h showed an inhibitory concentration of 0.15±0.01 µM for AChE, and 0.09±0.01 µM for BChE. Molecular docking studies were performed to explore the probable binding modes of the most potent dual inhibitors.
CONCLUSION: It can be hypothesized that the inhibitors are able to target cholinesterase pathways and may emerge as a suitable outset for the further development process.
PMID: 29473519 [PubMed - as supplied by publisher]
Primary aldosteronism and thyroid disorders in atrial fibrillation: A Swedish nationwide case-control study.
Eur J Prev Cardiol. 2018 Jan 01;:2047487318759853
Authors: Mourtzinis G, Adamsson Eryd S, Rosengren A, Björck L, Adiels M, Johannsson G, Manhem K
Background Atrial fibrillation is associated with hyperthyroidism. Patients with primary aldosteronism have an increased prevalence of atrial fibrillation. However, the prevalence of primary aldosteronism in the atrial fibrillation population is unknown. Aim This nationwide case-control study aimed to compare the prevalence of primary aldosteronism and thyroid disorders in patients with atrial fibrillation with that of age- and sex-matched controls. Methods We identified all atrial fibrillation cases in Sweden between 1987 and 2013 ( n = 713,569) by using the Swedish National Patient Register. A control cohort without atrial fibrillation was randomly selected from the Swedish Total Population Register with a case to control ratio of 1:2. This control cohort was matched for age, sex and place of birth ( n = 1,393,953). Results The prevalence of primary aldosteronism in December 2013 was 0.056% in the atrial fibrillation cohort and 0.024% in controls. At the same time, the prevalence of hypothyroidism was 5.9% in the atrial fibrillation cohort and 3.7% in controls. The prevalence of hyperthyroidism was 2.3% in the atrial fibrillation cohort and 0.8% in controls. Conclusion This study shows, for the first time, a doubled prevalence of primary aldosteronism in a large cohort of patients with atrial fibrillation compared with the general population. There is also an increased prevalence of hypo- and hyper-thyroidism in patients with atrial fibrillation compared with the general population.
PMID: 29473461 [PubMed - as supplied by publisher]
Severe Blood-Brain Barrier Disruption in Cardioembolic Stroke.
Front Neurol. 2018;9:55
Authors: Liu C, Shi F, Chen Z, Yan S, Ding X, Lou M
Background: Previous studies demonstrated that cardioembolism (CE) was prone to develop hemorrhagic transformation (HT), whereas hyper-permeability of blood-brain barrier (BBB) might be one reason for the development of HT. We, thus, aimed to investigate whether the BBB permeability (BBBP) was higher in CE stroke than other stroke subtypes in acute ischemic stroke (AIS) patients.
Methods: This study was a retrospective review of prospectively collected clinical and imaging database of AIS patients who underwent CT perfusion. Hypoperfusion was defined as Tmax >6 s. The average relative permeability-surface area product (rPS), reflecting the BBBP, was calculated within the hypoperfusion region (rPShypo). CE was diagnosed according to the international Trial of Org 10172 in Acute Stroke Treatment criteria. Receiver operating characteristics (ROC) curve analysis was used to determine predictive value of rPShypo for CE. Logistic regression was used to identify independent predictors for CE.
Results: A total of 187 patients were included in the final analysis [median age, 73 (61-80) years; 75 (40.1%) females; median baseline National Institutes of Health Stroke Scale score, 12 (7-16)]. Median rPShypo was 65.5 (35.8-110.1)%. Ninety-seven (51.9%) patients were diagnosed as CE. ROC analysis revealed that the optimal rPShypo threshold for CE was 86.71%. The value of rPShypo and the rate of rPShypo>86.71% were significantly higher in patients with CE than other stroke subtypes (p < 0.05), after adjusting for the potential confounds.
Conclusion: The extent of BBB disruption is more severe in CE stroke than other stroke subtypes during the hyperacute stage.
PMID: 29472890 [PubMed]
Oncogene-induced senescence mediated by c-Myc requires USP10 dependent deubiquitination and stabilization of p14ARF.
Cell Death Differ. 2018 Feb 22;:
Authors: Ko A, Han SY, Choi CH, Cho H, Lee MS, Kim SY, Song JS, Hong KM, Lee HW, Hewitt SM, Chung JY, Song J
Oncogene-induced senescence (OIS) is a critical tumor-suppressor mechanism, which prevents hyper-proliferation and transformation of cells. c-Myc promotes OIS through the transcriptional activation of p14ARF followed by p53 activation. Although the oncogene-mediated transcriptional regulation of p14ARF has been well addressed, the post-translational modification of p14ARF regulated by oncogenic stress has yet to be investigated. Here, we found that c-Myc increased p14ARF protein stability by inducing the transcription of ubiquitin-specific protease 10 (USP10). USP10, in turn, mediated the deubiquitination of p14ARF, preventing its proteasome-dependent degradation. USP10-null mouse embryonic fibroblasts and human primary cells depleted of USP10 bypassed c-Myc-induced senescence via the destabilization of p14ARF, and these cells displayed accelerated hyper-proliferation and transformation. Clinically the c-Myc-USP10-p14ARF axis was disrupted in non-small cell lung cancer patients, resulting in significantly worse overall survival. Our studies indicate that USP10 induced by c-Myc has a crucial role in OIS by maintaining the stability of key tumor suppressor p14ARF.
PMID: 29472714 [PubMed - as supplied by publisher]
Cholesterol-enriched membrane microdomains are needed for insulin signaling and proliferation in hepatic cells.
Am J Physiol Gastrointest Liver Physiol. 2018 Feb 22;:
Authors: Fonseca MC, França A, Florentino RM, Fonseca RC, Melo AC, Vidigal PTV, Oliveira AG, Dubuquoy L, Nathanson MH, Leite MF
Hepatocyte proliferation during liver regeneration is a well-coordinated process regulated by the activation of several growth factor receptors, including the insulin receptor (IR). The IR can be localized in part to cholesterol-enriched membrane microdomains, but the role of such domains in insulin-mediated events in hepatocytes is not known. We investigated whether partitioning of IRs into cholesterol-enriched membrane rafts is important for the mitogenic effects of insulin in the hepatic cells. IR and lipid rafts were labeled in HepG2 cells and primary rat hepatocytes. Membrane cholesterol was depleted in vitro with Metyl-beta-cyclodextrin (MβCD) and in vivo with lovastatin. Insulin-induced calcium (Ca2+) signals studies were examined in HepG2 cells and in freshly isolated rat hepatocytes as well as in whole liver in vivo by intravital confocal imaging. Liver regeneration was studied by 70% partial hepatectomy (PH), and hepatocyte proliferation was assessed by PCNA staining. A subpopulation of IR was found in membrane microdomains enriched in cholesterol. Depletion of cholesterol from plasma membrane resulted in redistribution of the IR along the cells, which was associated with impaired insulin-induced nuclear Ca2+ signals, a signaling event that regulates hepatocyte proliferation. Cholesterol depletion also led to ERK 1/2 hyper-phosphorylation. Lovastatin administration to rats decreased hepatic cholesterol content, disrupted lipid rafts and decreased insulin-induced Ca2+ signaling in hepatocytes, and delayed liver regeneration after PH. Therefore, membrane cholesterol content and lipid rafts integrity showed to be important for the proliferative effects of insulin in hepatic cells.
PMID: 29471671 [PubMed - as supplied by publisher]
Comparative Survey of Holding Positions for Reducing Vaccination Pain in Young Infants.
Pain Res Manag. 2017;2017:3273171
Authors: Yin HC, Cheng SW, Yang CY, Chiu YW, Weng YH
Background. Infant holding position may reduce vaccination pain. However, the optimal position for young infants remains controversial. Objectives. To compare the effectiveness of holding infants in the supine position and the effectiveness of holding infants in upright position for relieving acute pain from vaccine injection. Methods. This prospective cohort study enrolled 6-12-week-old healthy infants. We examined infant pain responses by evaluating the following three categories: (1) crying, (2) irritability, and (3) facial expression. Results. In total, 282 infants were enrolled, with 103 and 179 held in the supine and upright positions, respectively. At 30 s after vaccination, the infants in the supine position showed a larger decrease in crying (p < 0.001), irritability (p = 0.002), and pained facial expression (p = 0.001) than did those in the upright position. However, there was no significant difference in pain response between two groups at 180 s after intervention. Conclusion. In 2-month-old infants, the supine position may reduce acute pain more effectively than does the upright position. Our findings provide a clinical strategy for relieving vaccination pain in young infants.
PMID: 28246489 [PubMed - indexed for MEDLINE]