Previous investigations have shown that interleukin-6, a member of the JAK-STAT activating family of cytokines, plays an important role in prostate carcinoma. Here we demonstrate the co-expression of ...another member of this cytokine family, interleukin-11 (IL-11), and components of its receptor (interleukin-11 receptor; IL-11R), ie, IL-11Rα (involved in ligand recognition), and gp130 (involved in signal transduction) in cultured normal and malignant prostate-derived epithelial cell lines. In the DU-145 prostate carcinoma cell line, rhIL-11 stimulates a transient and dose-dependent increase in the tyrosine 705-phosphorylated, active form of STAT3 (STAT3 P-Tyr705), involved in the downstream signaling of IL-11R and other members of the gp130-dependent receptors. The ability of IL-11 to activate STAT3 in prostate-derived cells may be mechanistically important, given recent data suggesting that constitutively activated STAT3 may be associated with the malignant phenotype. In 51 human primary tissues derived from normal prostate, benign prostatic hyperplasia, and prostate carcinomas, IL-11Rα and gp130 were commonly expressed, with a statistically significant elevation in the expression of IL-11Rα in prostate carcinoma. Also, the tyrosine-phosphorylated, activated form of STAT3 was observed more prominently in the nuclei of cells residing in malignant glands compared to those in nonmalignant samples. Thus, the IL-11 receptor system is up-regulated in prostate carcinoma, and may be one part of a cytokine network that maintains STAT3 in its activated form in these tissues.
Although a split regimen of bowel preparation has been associated with higher levels of bowel cleansing, it is still uncertain whether it has a favourable effect on the adenoma detection rate (ADR). ...The present study was aimed at evaluating whether a split regimen was superior to the traditional 'full-dose, day-before' regimen in terms of ADR.
In a multicentre, randomised, endoscopist-blinded study, 50-69-year-old subjects undergoing first colonoscopy after positive-faecal immunochemical test within an organised colorectal cancer organised screening programmes were 1:1 randomised to receive low-volume 2-L polyethylene glycol (PEG)-ascorbate solution in a 'split-dose' (Split-Dose Group, SDG) or 'day-before' regimen (Day-Before Group, DBG). The primary endpoint was the proportion of subjects with at least one adenoma. Secondary endpoints were the detection rates of advanced adenomas and serrated lesions at per-patient analysis and the total number of lesions.
690 subjects were included in the study. At per-patient analysis, the proportion of subjects with at least one adenoma was significantly higher in the SDG than in the DBG (183/345, 53.0% vs 141/345, 40.9%, relative risk (RR) 1.22, 95% CI 1.03 to 1.46); corresponding figures for advanced adenomas were 26.4% (91/345) versus 20.0% (69/345, RR 1.35, 95% CI 1.06 to 1.73). At per-polyp analysis, the total numbers of both adenomas and advanced adenomas per subject were significantly higher in the SDG (1.15 vs 0.8, p <0.001; 0.36 vs 0.22, p<0.001).
In an organised screening setting, the adoption of a split regimen resulted into a higher detection rate of clinically relevant neoplastic lesions, thus improving the effectiveness of colonoscopy. Based on such evidence, the adoption of a split regimen for colonoscopy should be strongly recommended.
NCT02178033.
In this case, we explore physician conflict with performing surgery (tracheostomy) for long-term ventilation in a term infant with trisomy 18 and respiratory failure. Experts in neonatal-perinatal ...medicine, pediatric bioethics, and pediatric palliative care have provided comments on this case. An additional commentary was written by the parent of another infant with trisomy 18, who is also a medical provider (physical therapist).
Geospatial data were used to analyze changes to geomorphology of barrier islands and beaches in Southwest Florida resulting from Hurricane Ian in late September 2022. The hurricane generated high ...intensity winds and storm surge causing more than $112 billion in damages, along with massive sediment mobilization due to erosion and deposition. This study quantified net sediment loss and gain on specific barrier islands by storm surge (Sanibel, Naples, Fort Myers Beach, others, though this paper focuses exclusively on Sanibel) by comparing pre- and post-Ian topography generated by a drone-flown LiDAR sensor; changes in elevation were used to quantify spatial variation in sediment volume. Data were collected immediately after Hurricane Ian and compared against topographic data collected by NOAA in 2018. Digital elevation models (DEMs) were used to compare topography, shoreline positions (relative to Mean High Water), foredune position, and volumetric changes using GIS technology. In general, the shoreline position after Ian changed little, indicating that the incoming surge had little influence on the beach. The foredunes, however, were deflated and set back by surge overwash. The outgoing surge created a much more dramatic geomorphologic change. Erosional surge channels cut through the foredunes and upper beach berm along many regions of the coastline. The ebb erosion also caused extensive damage to physical structures when located immediately behind the foredune. Lastly, this work demonstrates the value of employing GIS and remote sensing technology to problems of beach and dune management, the restoration of coastal ecosystems, the enhancement of resilience capacity of both natural and developed infrastructure, and the development of new policy needed to contend with the effects of climate change.
•Vasomotor symptoms in postmenopausal women correlate with insomnia and depression.•Postmenopausal insomnia is best managed with menopausal hormone therapy and cognitive behavioral therapy.•Selective ...serotonin (SSRIs) and dual (SNRIs) reuptake inhibitors are also indicated for postmenopausal insomnia with vasomotor symptoms.•Continuous positive airway pressure and mandibular advancement devices improve cardiovascular outcome in postmenopausal women.
Insomnia, vasomotor symptoms (VMS) and depression often co-occur after the menopause, with consequent health problems and reductions in quality of life. The aim of this position statement is to provide evidence-based advice on the management of postmenopausal sleep disorders derived from a systematic review of the literature. The latter yielded results on VMS, insomnia, circadian rhythm disorders, obstructive sleep apnea (OSA) and restless leg syndrome (RLS). Overall, the studies show that menopausal hormone therapy (MHT) improves VMS, insomnia, and mood.
Several antidepressants can improve insomnia, either on their own or in association with MHT; these include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Long-term benefits for postmenopausal insomnia may also be achieved with non-drug strategies such as cognitive behavioral therapy (CBT) and aerobic exercise. Continuous positive airway pressure (CPAP) and mandibular advancement devices (MADs) both reduce blood pressure and cortisol levels in postmenopausal women suffering from OSA. However, the data regarding MHT on postmenopausal restless legs syndrome are conflicting.
Olives are a potential source of natural anti-oxidants; unfortunately, a complete characterization of olive fruit phenolic profile is still to be achieved, as it is characterized by great complexity ...and variability.
In this study, electrospray ionization mass spectrometry (ESI-MS) was used to characterize phenolic extracts from olive fruits, establishing the most suitable conditions of analysis in order to detect phenolic derivatives. This technique proved to be very useful in the identification and in the structure elucidation of olive phenolic compounds. The olive pulp phenolic fraction proved to be dominated by phenolic glucosides, mainly hexose derivatives of phenolic alcohols, flavonoids, secoiridoids and oleosides. Several oleuropein derivatives were detected, proving that they are already present in olive pulp and not, as previously suggested, originated during oil extraction.
With this study an effective method to characterize olive phenolic compounds was offered and it was possible to confirm the presence of several biophenols in olive extracts, thus giving a contribution to the characterization of olive pulp phenolic fraction.
The PBE-QIDH and SOS1-PBE-QIDH double-hybrid density functionals are merged with a pair of dispersion corrections, namely the pairwise additive D3(BJ) and the non-local correlation functional VV10, ...leading to the corresponding dispersion-corrected models. The parameters adjusting each of the dispersion corrections to the functionals are obtained by fitting to well-established energy datasets (
e.g.
S130) used as a benchmark, giving rise to functionals spanning covalent and non-covalent binding forces. The application of the models to challenging systems out of the training set, like those comprising the L7 database of large supramolecular complexes, or the S66x8 dataset of stretched and elongated intermolecular distances, reveals the high accuracy of the coupling.
The PBE-QIDH and SOS1-PBE-QIDH double-hybrid density functionals are merged with a pair of dispersion corrections, namely the pairwise additive D3(BJ) and the non-local correlation functional VV10, leading to the corresponding dispersion-corrected models.
Background and purpose
The aim was to identify potential genetic risk factors associated with sporadic inclusion body myositis (sIBM).
Methods
An association based case−control approach was utilized ...on whole exome sequencing data of 30 Finnish sIBM patients and a control cohort (n = 193). A separate Italian cohort of sIBM patients (n = 12) was used for evaluation of the results.
Results
Seven single nucleotide polymorphisms were identified in five genes that have a considerably higher observed frequency in Finnish sIBM patients compared to the control population, and the previous association of the genetic human leukocyte antigen region was confirmed.
Conclusions
All seven identified variants could individually or in combination increase the susceptibility for sIBM.
The High Drinking in the Dark (HDID-1) line of mice has been selectively bred for achieving high blood alcohol levels (BALs) in the Drinking in the Dark task, a model of binge-like drinking. ...Recently, we determined that glucocorticoid receptor (GR) antagonism with either mifepristone or CORT113176 (a selective GR antagonist) reduced binge-like ethanol intake in the HDID-1 mice, but not in their founder line, HS/NPT. Here, we examined whether the selection process may have altered glucocorticoid functioning by measuring (1) plasma corticosterone levels and (2) expression of the genes encoding GR (
) and two of its chaperone proteins FKBP51 and FKBP52 (
and
) in the brains (nucleus accumbens, NAc) of HDID-1 and HS/NPT mice. We observed no genotype differences in baseline circulating corticosterone levels. However, HDID-1 mice exhibited a greater stimulated peak corticosterone response to an IP injection (of either ethanol or saline) relative to their founder line. We further observed reduced basal expression of
and
in the NAc of HDID-1 mice relative to HS/NPT mice. Finally, HDID-1 mice exhibited reduced
expression in the NAc relative to HS/NPT mice following an injection of 2 g/kg ethanol. Together, these data suggest that selective breeding for high BALs may have altered stress signaling in the HDID-1 mice, which may contribute to the observed selective efficacy of GR antagonism in reducing binge-like ethanol intake in HDID-1, but not HS/NPT mice. These data have important implications for the role that stress signaling plays in the genetic risk for binge drinking.
We assess here the reliability of orbital optimization for modern double-hybrid density functionals such as the parameter-free PBE-QIDH model. We select for that purpose a set of closed- and ...open-shell strongly and weakly bound systems, including some standard and widely used data sets, to show that orbital optimization improves the results with respect to standard models, notably for electronically complicated systems, and through first-order properties obtained as derivatives of the energy.
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