Recently, studies have investigated the significance of the Wnt/β-catenin pathway in prostate cancer. The transcriptional activity of the androgen receptor (AR) is modulated by interaction with ...coregulators, one of which is β-catenin. Curcumin, a dietary yellow pigment of Curcuma longa, has emerged as having a chemopreventive role. Although curcumin has been shown to inhibit AR expression, its molecular mechanism has not been fully elucidated. In this study, whether curcumin mediates the Wnt/β-catenin signaling pathway with regard to AR/β-catenin interactions was studied. Curcumin was shown to induce significant inhibition of AR expression in a dose-dependent manner. Marked curcumin-induced suppression of β-catenin was shown in the nuclear and cytoplasmic extracts as well as whole cell lysates. Further analysis revealed that phosphorylation of Akt and glycogen synthase kinase-3β were attenuated, but phosphorylated β-catenin was increased after curcumin treatment. Finally, cyclin D1 and c-myc, the target gene of the β-catenin/T-cell factor transcriptional complex, were also decreased. These findings suggest that curcumin modulates the Wnt/β-catenin signaling pathway and might have a significant role in mediating inhibitory effects on LNCaP prostate cancer cells.
Theories that extend the Standard Model of particle physics often introduce new interactions that violate charge-parity (CP) symmetry. Charge-parity-violating effects within an atomic nucleus can be ...probed by measuring its nuclear magnetic quadrupole moment (MQM). The sensitivity of such a measurement is enhanced when using a heavy polar molecule containing a nucleus with quadrupole deformation. We determine how the energy levels of a molecule are shifted by the magnetic quadrupole moment and how those shifts can be measured. The measurement scheme requires molecules in a superposition of magnetic sub-levels that differ by many units of angular momentum. We develop a generic scheme for preparing these states. Finally, we consider the sensitivity that can be reached, showing that this method can reduce the current uncertainties on several charge-parity-violating parameters.
Abstract
Spectral responsivity calibrating of Fourier Transform Spectrometer (FTS) is essential for eliminating its systematic error in a ground-based solar observation system. Conventionally the ...calibration is being done by the three-temperature blackbody method, which gives a spectral responsivity curve of the FTS under calibration in addition to the respective temperatures of the blackbody. It is an advantage that the method does not require pre-information on the blackbody temperatures. However, a combination of three temperatures remains a question in terms of the calibration accuracy. In this paper, the method is applied to a high level of radiance calibration at a wavenumber range from 2000 cm-1 to 8000 cm-1. We propose a technique which determines an optimal combination of the three temperatures in the blackbodies to improve the calibration accuracy of the FTS. Experiments were carried out using four arbitrary combinations of blackbody temperatures settings and an optimal combination of the temperature settings. The result deviation of the optimal combination is less than 0.5% and 3% for measured temperature and spectral radiance respectively, which is better than the arbitrary temperature combinations.
There remains uncertainty regarding optimal definitive management for malignant posterior circulation infarcts (MPCI). While guidelines recommend neurosurgery for malignant cerebellar infarcts that ...are refractory to medical therapy, concerns exist about the functional outcome and quality of life after decompressive surgery.
This study aims to evaluate the outcomes of surgical intervention compared to medical therapy in MPCI.
In this systematic review, MEDLINE, Embase and Cochrane databases were searched from inception until 2 April 2021. Studies were included if they involved posterior circulation strokes treated with neurosurgical intervention and reported mortality and functional outcome data. Data were collected according to PRISMA guidelines.
The search yielded 6677 studies, of which 31 studies (comprising 723 patients) were included for analysis. From the included studies, we found that surgical therapy led to significant differences in mortality and functional outcomes in patients with severe disease. Neurological decline and radiological criteria were often used to decide the timing for surgical intervention, as there is currently limited evidence for preventative neurosurgery. There is also limited evidence for the superiority of one surgical modality over another.
For patients with MPCI who are clinically stable at the time of presentation, in terms of mortality and functional outcome, surgical therapy appears to be equivocal to medical therapy. Reliable evidence is lacking, and further prospective studies are rendered.
Solid catalysts of chromium–tungsten–manganese oxides were prepared and used to synthesize fatty acid methyl ester (FAME) through esterification of palm fatty acid distillate (PFAD). Experiments were ...conducted in a batch reactor at a temperature range of 130–190 °C. The physical and chemical properties of the catalysts were characterized by Brunauer–Emmet–Teller, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and thermal gravimetric analysis. The treatment conditions during catalyst preparation, effect of reaction parameters, and catalyst stability were investigated. The catalyst (CrWMnO2) was the most active with maximum FAME content of 85% at optimal reaction conditions of 170 °C reaction temperature for 3 h, methanol-to-PFAD molar ratio of 3:1, catalyst dosage of 1.5 wt.%, and reusability of catalyst for several cycles. Results showed that CrWMnO2 is a potential catalyst for FAME synthesis from feedstock containing high free fatty acid.
•Chromium–tungsten–manganese mixed oxides are used as solid catalyst.•Catalyst is used for esterification of palm fatty acid distillate to methyl esters.•The maximum methyl ester content is 85%.•The catalyst is stable with activity of more than 80% up to the third run.
It has been generally believed that the four main causes of melasma are pregnancy, hormonal contraception, family history and sun exposure; however, there are few published comprehensive studies that ...confirm these assertions. The Pigmentary Disorders Academy - an international group of experts in pigmentary disorders - designed and conducted a global survey of women to investigate the effect of these factors on onset and chronicity of melasma and the course of the disease in order to gain a better understanding of the causative factors associated with this disorder, with a particular focus on hormonal factors and UV exposure in females.
A 40-item largely self-administered questionnaire was completed by 324 women being treated for melasma in nine clinics worldwide.
The mean age at onset of melasma was 34 years, and 48% of subjects questioned had a family history of melasma (97% in a first-degree relative). Subjects with family history of melasma tended to have darker skin (90% types III-VI) compared to those without (77% types III-VI). The most common time of onset was after pregnancy (42%), often years after the last pregnancy, with 29% appearing pre-pregnancy and 26% during pregnancy. Onset was related to darker skin type post-pregnancy (P = 0.002). Risk of onset during pregnancy was associated with having spent more time outdoors (an extra 10 h per week spent working outside increases the odds of onset of melasma during pregnancy by approximately 27%) and an increased maternal age at pregnancy (increased by approximately 8% for each year of age at first pregnancy; P = 0.02). The odds of melasma occurring for the first time during a pregnancy were also increased with multiple pregnancies (twice the odds if 2 vs. 1 pregnancies, three times higher if 3 or more vs. 1 pregnancy). Of the women, 25% who had used hormonal contraception claimed that melasma appeared for the first time after its use, the rate being higher for those without vs. with a family history.
The results suggest that, whilst accepted causes do affect onset of melasma, a combination of these factors often triggers this disorder. These factors may provide further insights into how physicians can manage individual melasma cases, support recommendation of preventative measures and even anticipate treatment results and recurrence.
During laparoscopic-assisted gastrectomy, it is impossible to identify early gastric cancer (EGC) lesions; therefore, a precise localization technique is needed. In this study, we used laparoscopic ...ultrasonography (LUS) after endoscopic clipping as a method of localizing EGC and evaluated the effectiveness of this method.
A prospective study of 17 patients who had undergone laparoscopic-assisted gastrectomy was performed. Three endoscopic clips were applied just proximal to the tumor during the preoperative endoscopy. The applied clips were detected from the serosal side of the stomach using LUS. The serosal surface of the lesion was marked with dye.
In all patients, endoscopic clips were applied proximal to the lesion without complications, and the applied clips were confirmed by plain abdominal radiography. The clips were successfully detected by LUS in all patients. In the resected specimen, the serosal surface, marked with dye, was always just above the clips in the anterior wall or on the anterior wall opposite the clips applied in the posterior wall. The mean detection time was 4.7 min (range, 2-8). With this procedure, two patients underwent total gastrectomy and 15 patients underwent distal subtotal gastrectomy with gastroduodenostomy or gastrojejunostomy. Histological examination confirmed that the resection margins were tumor free in all patients. There was no operative morbidity related to the LUS procedure.
Using LUS to detect endoscopic clips is an easy, safe, and accurate method to localize EGC lesions in laparoscopic-assisted gastrectomy.
We describe a new service model, the Orthopaedic Assessment Unit (OAU), designed to provide care for trauma patients during the COVID-19 pandemic. Patients without COVID-19 symptoms and isolated ...musculoskeletal injuries were redirected to the OAU.
We prospectively reviewed patients throughput during the peak of the global pandemic (7 May 2020 to 7 June 2020) and compared with our historic service provision (7 May 2019 to 7 June 2019). The Mann-Whitney and Fisher Exact tests were used to test the statistical significance of data.
A total of 1,147 patients were seen, with peak attendances between 11am and 2pm; 96% of all referrals were seen within 4h. The majority of patients were seen by orthopaedic registrars (52%) and nurse practitioners (44%). The majority of patients suffered from sprains and strains (39%), followed by fractures (22%) and wounds (20%); 73% of patients were discharged on the same day, 15% given follow up, 8% underwent surgery and 3% were admitted but did not undergo surgery. Our volume of trauma admissions and theatre cases decreased by 22% and 17%, respectively (
=0.058; 0.139). There was a significant reduction of virtual fracture clinic referrals after reconfiguration of services (
<0.001).
Rapid implementation of a specialist OAU during a pandemic can provide early definitive trauma care while exceeding national waiting time standards. The fall in trauma attendances was lower than anticipated. The retention of orthopaedic staff in the department to staff the unit and maintain a high standard of care is imperative.
Posaconazole is an antifungal with a wide-spectrum of activity against common and emerging fungal pathogens. In this randomised, open-label, two-way crossover study, the potential for drug ...interactions with posaconazole via the cytochrome P450 (CYP450) enzyme pathway was evaluated. Thirteen subjects received posaconazole tablets (2×100
mg) once daily for 10 days or no treatment; following a 14-day washout period, subjects were crossed over to the alternate treatment. The inhibition spectra of posaconazole were examined using a cocktail of the following probe substrates: caffeine (CYP1A2), tolbutamide (CYP2C8/9), dextromethorphan (CYP2D6 and total CYP3A4), chlorzoxazone (CYP2E1), and midazolam (hepatic CYP3A4). Except for midazolam, which was intravenously infused on Day 10, the cocktail probes were administered simultaneously on Day 9 during both treatment periods. Blood and urine samples were collected at specified times to quantitate probe substrates and/or metabolites. Based on insignificant differences in mean probe ratios, posaconazole did not inhibit CYP1A2, 2C8/9, 2D6, or 2E1. However, the midazolam AUC
(tf) was higher in the posaconazole than no-treatment group (93.4
ng
h/ml versus 51.4
ng
h/ml,
P<0.01), indicating inhibition of hepatic CYP3A4. Drug interactions mediated by various CYP450 are common with the currently available triazole antifungals, however these results suggest that posaconazole may have an improved and more narrow drug interaction profile (CYP3A4 only) compared with other triazoles.
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