Ethyl 4-hydr­oxy-1-(2-morpholinopro­pano­yl)-2,6-diphenyl-1,2,5,6-tetra­hydro­pyridin-3-carboxyl­ate

In the title compound, C27H32N2O5, the morpholine ring adopts a chair conformation with two C atoms deviating by −0.656 (4) and 0.679 (3) Å from the least-squares plane defined by the rest of atoms in the ring. The tetra­hydro­pyridine ring adopts a half-chair conformation. The mol­ecular structure is stabilized by a strong intra­molecular O—H⋯O inter­action, generating an S(6) motif. The crystal packing is stabilized by inter­molecular C—H⋯O inter­actions, generating a C(7) chain along the a axis, and R 2 2(20) and R 4 4(20) graph-set motifs

Performance Analysis On A Variable Capacity Swash Plate Compressor

A numerical study on the performance of a variable capacity swash plate compressor for an automotive air-conditioning system was carried out. The compressor under investigation had six cylinders and capacity regulation was made by changing the swash plate inclination angle. A numerical simulation program was made based on mathematical modelings on the swash plate dynamics, refrigerant states in various control volumes such as cylinders and crank room, and flows in the opening passages of electric control valve for crank room pressure control. The simulation results such as mass flow rate, compressor power consumption, cooling capacity and COP were compared with measurements within ±5% deviation over various operating conditions except at low operating speed such as idling condition. By using the simulation program, the effect of the crank room pressure on the swash plate inclination angle and the determination of the crank room pressure level by the electric control valve openings could be investigated

2,4-Bis(2-chloro­phen­yl)-3-aza­bicyclo­[3.3.1]nonan-9-one

The mol­ecular structure of the title compound, C20H19Cl2NO, reveals chair conformations for both six-membered rings of the bicyclic system. Both 2-chloro­phenyl groups adopt equatorial dispositions with the chloro substituents oriented towards the carbonyl group; the aryl groups are orientated at an angle of 28.64 (3)° with respect to each other

Effects of Tamsulosin, Solifenacin, and Combination Therapy for the Treatment of Ureteral Stent Related Discomforts

Purpose: To evaluate the effect of tamsulosin, solifenacin, and combination therapy of two agents in improving the lower urinary tract symptoms of patients with indwelling double-J ureteral stents. Materials and Methods: A total of 168 patients underwent placement of a double-J ureteral stent after retrograde ureteroscopy for urinary stone disease. All patients received polyurethane double-J ureteral stents (6 Fr, 24 or 26 cm), which were removed a mean of 14 days postoperatively. A total of 48 patients were given no medication (Group 1), 43 patients were given tamsulosin 0.2 mg once daily (Group 2), 45 patients were given solifenacin 5 mg once daily (Group 3), and 32 patients were given a combination of two agents postoperatively (Group 4). International Prostate Symptom Score/quality of life (IPSS/QoL) and visual analogue pain scale (VAPS) questionnaires were completed by each patient at 1 day postoperatively and on the day of stent removal. Results: In the total group of patients, the mean age was 50.24±12.90 years. There was a significant difference in the IPSS total score between group 1 and groups 3 and 4. Group 4 also differed significantly from group 1 in the irritative subscore. The obstructive subscore differed between groups 2 and 4 and group 1. There was a statistically significant difference between group 1 and group 4 in the QoL score. There were no significant differences in the VAPS. Conclusions: Combination therapy with tamsulosin and solifenacin improved both irritative and obstructive symptoms more than in the other groups. Combination therapy should be strongly considered for patients who complain of stent-related symptoms. Key Words: Pain; Stents; Ureter This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licens

Induced neural stem cells from distinct genetic backgrounds exhibit different reprogramming status

Somatic cells could be directly converted into induced neural stem cells (iNSCs) by ectopic expression of defined transcription factors. However, the underlying mechanism of direct lineage transition into iNSCs is largely unknown. In this study, we examined the effect of genetic background on the direct conversion process into an iNSC state. The iNSCs from two different mouse strains exhibited the distinct efficiency of lineage conversion as well as clonal expansion. Furthermore, the expression levels of endogenous NSC markers, silencing of transgenes, and in vitro differentiation potential were also different between iNSC lines from different strains. Therefore, our data suggest that the genetic background of starting cells influences the conversion efficiency as well as reprogramming status of directly converted iNSCs.ope

Multivariate analysis of prognostic factors in patients with pulmonary actinomycosis

BACKGROUND: There have been few studies of pulmonary actinomycosis, which is an uncommon anaerobic infection. Consequently, the optimal therapeutic regimen, appropriate duration of treatment, long-term prognosis, and factors predicting prognosis are not well established. METHODS: We retrospectively reviewed the medical records of histopathologically confirmed cases of pulmonary actinomycosis seen between November 2003 and December 2012. RESULTS: The study included 68 patients with a mean age of 58.4 ± 11.6 years. Of the 68, initial surgery was performed in 15 patients (22.1%), while the remaining 53 (77.9%) received antibiotic therapy initially. In the initial antibiotic group, 45/53 (84.9%) were cured without relapse (median antibiotic duration 5.3 months). 5/53 (9.4%) patients were refractory medically (median antibiotic duration 9.7 months), and 3/53 (5.7%) experienced a recurrence (median time to relapse 35.3 months). In the initial surgery group, 14/15 (93.3%) were cured and treatment failure occurred in one (6.7%). In the multivariate analysis, the absence of an antibiotic response at 1 month was the only independent factor associated with a poor treatment outcome, with an adjusted odds ratio of 49.2 (95% CI, 3.34–724.30). There was no significant difference in treatment outcome based on the size of the parenchymal lesion, comorbidities, whether intravenous antibiotics were used, antibiotic therapy duration, or whether the initial treatment was surgical. CONCLUSIONS: Antibiotic treatment with or without surgery was effective for treatment of pulmonary actinomycosis. Nevertheless, treatment failure or recurrence occurred in a considerable proportion of patients, especially those resistant to the initial antibiotic treatment

Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine

Despite growing interest and a recent surge in papers, the role of autophagy in glucose and lipid metabolism is unclear. We produced mice with skeletal muscle–specific deletion of Atg7 (encoding autophagy-related 7). Unexpectedly, these mice showed decreased fat mass and were protected from diet-induced obesity and insulin resistance; this phenotype was accompanied by increased fatty acid oxidation and browning of white adipose tissue (WAT) owing to induction of fibroblast growth factor 21 (Fgf21). Mitochondrial dysfunction induced by autophagy deficiency increased Fgf21 expression through induction of Atf4, a master regulator of the integrated stress response. Mitochondrial respiratory chain inhibitors also induced Fgf21 in an Atf4-dependent manner. We also observed induction of Fgf21, resistance to diet-induced obesity and amelioration of insulin resistance in mice with autophagy deficiency in the liver, another insulin target tissue. These findings suggest that autophagy deficiency and subsequent mitochondrial dysfunction promote Fgf21 expression, a hormone we consequently term a 'mitokine', and together these processes promote protection from diet-induced obesity and insulin resistance

Transcriptional regulatory networks of tumor-associated macrophages that drive malignancy in mesenchymal glioblastoma.

BACKGROUND: Glioblastoma (GBM) is a complex disease with extensive molecular and transcriptional heterogeneity. GBM can be subcategorized into four distinct subtypes; tumors that shift towards the mesenchymal phenotype upon recurrence are generally associated with treatment resistance, unfavorable prognosis, and the infiltration of pro-tumorigenic macrophages. RESULTS: We explore the transcriptional regulatory networks of mesenchymal-associated tumor-associated macrophages (MA-TAMs), which drive the malignant phenotypic state of GBM, and identify macrophage receptor with collagenous structure (MARCO) as the most highly differentially expressed gene. MARCO CONCLUSIONS: Collectively, our study characterizes the global transcriptional profile of TAMs driving mesenchymal GBM pathogenesis, providing potential therapeutic targets for improving the effectiveness of GBM immunotherapy