Taking control of gene expression with light-activated oligonucleotides.
The recent development of caged oligonucletides that are efficiently activated by ultraviolet (UV) light creates opportunities for regulating gene expression with very high spatial and temporal resolution. By selectively modulating gene activity, these photochemical tools will facilitate efforts to elucidate gene function and may eventually serve therapeutic aims. We demonstrate how the incorporation of a photocleavable blocking group within a DNA duplex can transiently arrest DNA polymerase activity. Indeed, caged oligonucleotides make it possible to control many different protein-oligonucleotide interactions. In related experiments, hybridization of a reverse complementary (antisense) oligodeoxynucleotide to target mRNA can inhibit translation by recruiting endogenous RNases or sterically blocking the ribosome. Our laboratory recently synthesized caged antisense oligonucleotides composed of phosphorothioated DNA or peptide nucleic acid (PNA). The antisense oligonucleotide, which was attached to a complementary blocking oligonucleotide strand by a photocleavable linker, was blocked from binding target mRNA. This provided a useful method for photomodulating hybridization of the antisense strand to target mRNA. Caged DNA and PNA oligonucleotides have proven effective at photoregulating gene expression in cells and zebrafish embryos.


Survival of the aligned: ordering of the plant cortical microtubule array.
The cortical array is a structure consisting of highly aligned microtubules which plays a crucial role in the characteristic uniaxial expansion of all growing plant cells. Recent experiments have shown polymerization-driven collisions between the membrane-bound cortical microtubules, suggesting a possible mechanism for their alignment. We present both a coarse-grained theoretical model and stochastic particle-based simulations of this mechanism, and we compare the results from these complementary approaches. Our results indicate that collisions that induce depolymerization are sufficient to generate the alignment of microtubules in the cortical array.


Charge Transfer in Single Chains of a Donor-Acceptor Conjugated Tri-Block Copolymer.
The photophysics of a conjugated triblock copolymer comprising poly(9,9-dioctylfluorene-co-bis-N,N'-(4-methylphenyl)-bis-N,N'-phenyl-1,4-phenylenediamine) (PFM) electron donor and poly(4-(9,9-dioctyl-9H-fluoren-2-yl)benzo[c][1,2,5]-thiadiazole) (F8BT) electron acceptor blocks has been studied in solution, in films, and as single chains. While an additional long-wavelength emission apparent in neat films of the copolymer is attributed to interchain exciplex formation, no such long-wavelength emission is apparent in solution or from single molecules. However, in these cases, time-resolved fluorescence measurements indicate the presence of a delayed fluorescence. The kinetics of the delayed emission can be interpreted in terms of an equilibrium between a locally excited and a charge-transfer state at the interface of the copolymer block components. Rate constants and thermodynamic quantities associated with these processes have been evaluated. The single-molecule results allow the assignment of an intramolecular charge-transfer state in an isolated conjugated block copolymer chain.


Factors and methods to modulate DNA hybridization kinetics.
DNA oligonucleotides are widely used in a diverse range of research fields from analytical chemistry, molecular biology, nanotechnology to drug delivery. In these applications, DNA hybridization is often the most important enabling reaction. Achieving control over hybridization kinetics and a high yield of hybridized products is needed to ensure high-quality and reproducible results. Since DNA strands are highly negatively charged and can also fold upon itself to form various intramolecular structures, DNA hybridization needs to overcome these barriers. Nucleation and diffusion are two main kinetic limiting steps although their relative importance differs in different conditions. The effects of length and sequence, temperature, pH, salt concentration, cationic polymers, organic solvents, freezing and crowding agents are summarized in the context of overcoming these barriers. This article will help researchers in the biotechnology-related fields to better understand and control DNA hybridization, as well as provide a landscape for future work in simulation and experiment to optimize DNA hybridization systems.


[Removal of phthalate esters from drinking water using ozone-GAC process].
This study investigated the feasibility of using ozone-GAC process to remove phthalate esters from drinking water through a batch-scale study and adsorption isotherms. Dimethyl phthalate (DMP), diethyl phthalate (DEP) and dibutyl phthalate (DBP) were selected as the representative of phthalate esters. Results indicated that ozonation remove more than 40% DMP, DEP and DBP, GAC absorbed all the DMP, DEP and DBP that had not been oxidized by ozone at the condition of the Empty Bed Contact Time (EBCT) from 4 minutes to 12 minutes. The isotherms for GAC were successful correlated by Freundlich equation, and the date was used to estimate GAC service time. The results indicated that ozone-GAC process is a feasible way to remove DMP, DEP and DBP from drinking water.


Novel graphene oxide/polymer composite membranes for the food industry: structures, mechanisms and recent applications.
The membrane can not only be used as food packaging, but also for the separation, fractionation and recovery of food ingredients. Graphene oxide (GO) sheets are a two-dimensional (2 D) material with a unique structure that exhibit excellent mechanical properties, biocompatibility, and flexibility. The corporation of polymer matrix membrane with GO can significantly improve the permeability, selectivity, and antibacterial activity. In this review, the chemical structures of GO, GO membranes and GO/polymer composite membranes are introduced, the permeation mechanisms of molecules through the membranes are discussed and key factors affecting the permeability are presented in detail. In addition, recent applications in the food industry for filtration, bioreactions and active food packaging are analyzed, and limitations and future trends of GO membranes development are also highlighted. GO/polymer composite membranes exhibit excellent permeability, selectivity and strong barrier properties against bacterial and gas permeation. However, current food material filtration and packaging applications of GO/polymer composite membranes are still in the laboratory stage. Future work can focus on the development of large scale uniformly sized GO production, the homogeneous distribution and tight combination of GO in polymer matrixes, the sensing function of GO in packaging, and the verification method of GO toxicology.


Neuropeptide gastrin-releasing peptide induces PI3K/reactive oxygen species-dependent migration in lung adenocarcinoma cells.
Nerve fibers and neurotransmitters have increasingly been shown to have a role in tumor progression. Gastrin-releasing peptide is a neuropeptide linked to tumor aggressiveness, acting as an autocrine tumor growth factor by binding to its receptor, gastrin-releasing peptide receptor, expressed by many tumors. Although neuropeptides have been previously linked to tumor cell proliferation, more recent studies have uncovered roles for neuropeptides in chemotaxis and metastasis. Understanding the precise roles of such peptides in cancer is crucial to optimizing targeted therapy design. We have previously described that gastrin-releasing peptide acts directly as a chemotactic factor for neutrophils, dependent on PI3K, ERK, and p38. In this study, we investigated roles for gastrin-releasing peptide in lung adenocarcinoma. We asked if gastrin-releasing peptide would act as a proliferative and/or chemotactic stimulus for gastrin-releasing peptide receptor-expressing tumor cells. In A549 cells, a non-small cell lung carcinoma line, the treatment with gastrin-releasing peptide leads to activation of AKT and ERK1/2, and production of reactive oxygen species. Gastrin-releasing peptide induced migration of A549 cells, dependent on gastrin-releasing peptide receptor and PI3K, but not ERK. However, no proliferation was observed in these cells in response to gastrin-releasing peptide, and gastrin-releasing peptide did not promote resistance to treatment with a chemotherapy drug. Our results suggest that, similar to what happens in neutrophils, gastrin-releasing peptide is a migratory, rather than a proliferative, stimulus, for non-small cell lung carcinoma cells, indicating a putative role for gastrin-releasing peptide and gastrin-releasing peptide receptor in metastasis.


Diffuse hyperplastic perilobar nephroblastomatosis.
Nephroblastomatosis is a rare preneoplastic lesion defined as the presence of diffuse or multifocal nephrogenic rests. They are divided into 4 categories: perilobar, intralobar, combined, and universal. The aim of this report is to describe a case of diffuse hyperplastic perilobar nephroblastomatosis. A 1-year-old boy presented with an abdominal mass on the left side. Computed tomography scan showed a homogeneous, isointense enlarged left kidney. A fine needle aspiration cytology was reported as Wilms tumor. After chemotherapy, the left kidney was excised. Nephrectomy specimen presented a thick cortical rim of hyperplastic nephrogenic tissue, well delineated from preserved renal parenchyma without pseudocapsule. Nephroblastomatosis is a rare condition affecting renal parenchyma. Diagnosis is based on imaging studies, such as ultrasound, computed tomography scan, and magnetic resonance imaging. Fine needle aspiration cytology is of limited value. Therapeutic management is controversial. Chemotherapy is used preoperatively, and surgical excision may be an alternative for refractory cases.


A Needs Assessment Among Transgender Patients at an LGBTQ Service Organization in Texas.
Purpose: Transgender adults have difficulty accessing health care due to multiple barriers. This study examined the health care-related needs of transgender patients in Dallas, Texas. Methods: This study examined cross-sectional data from a survey completed by 62 patients who identified as transgender. Results: Many participants reported depression (50%) and anxiety (51%). Over half did not receive preventive screenings (60%) or health care (61%) elsewhere. One-third of patients felt their primary care physician outside the clinic was not transgender-friendly. Conclusion: These findings provide evidence that transgender patients demonstrate increased reported mental health disorders and decreased access to medical care.


Complications During the Recovery Period After Pilonidal Sinus Surgery.
Introduction The current study aims to identify the complications that occur during the postoperative three-week period, which is considered the period of recovery in patients who undergo pilonidal sinus surgery. This identification of complications will help reduce morbidity and treatment costs and improve return to work. Methods This study included a total of 196 patients who underwent pilonidal sinus surgery by a combination of the resection and Limberg flap techniques under spinal anesthesia between the years 2012 and 2016. The postoperative three-week period was examined as the hospital stay period and the post-discharge period. The complications were classified into two groups: surgical and anesthesia. Results were recorded and analyzed using the SPSS statistical software (IBM Corp., Armonk, NY, US). p˂0.05 was considered significant. Results The female-to-male ratio of the patients was 1:4, whereas their average age was 24.15 years, the median age was 22 years, and the average body mass index was 24.79 kg/m². The average lengths of hospital stay in the postoperative period were 1.10, 2.15, and 3.95 days in patients without complications, all of the patients studied, and patients with complications, respectively. The difference between the groups was found statistically significant (p˂0.001). Conclusion Anesthesia-related and surgical complications were prominent in the postoperative hospital stay and post-discharge periods, respectively. The average length of hospital stay in patients with complications during hospital stay was found to be 3.59 times higher than those without complications. The difference between these two categories was statistically significant (p˂0.001).


Synthesis of 2-(2-hydroxyethyl)-1-(2-hydroxyphenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline and pseudosymmetry in its crystal structure.
Natural and synthetic isoquinoline alkaloids display a wide variety of potent biological activities. The title 1-aryl-2-hydroxyethyl-1,2,3,4-tetrahydroisoquinoline, C19H23NO4, crystallizes with two molecules in the asymmetric unit related by pseudo-translation but differing only slightly in conformation. The pseudosymmetry is also reflected in the diffraction pattern. The subset of reflections corresponding to the smaller cell and average structure are on average twice as intense as those subtending the larger cell. Tentative refinement in the subcell leads to a disordered structural model with satisfactory agreement factors and, after appropriate use of restraints, acceptable molecular geometry but significantly larger and more anisotropic displacement parameters. In the correct unit cell, the independent molecules differ with respect to the orientation of the hydroxyethyl group. Intramolecular hydrogen bonding occurs between the hydroxyphenyl group and the N atom.


Stabilizing mechanisms of the loaded and unloaded knee joint.
Knee specimens were placed in an apparatus which imposed cyclic anterior-posterior or rotatory forces, with various compressive loads applied to the joint. Force-displacement graphs or torque-rotation graphs were automatically plotted, giving the laxity under various conditions. The ligaments, capsule, and menisci provided joint stability under no-load conditions. However, under compressive loads, the conformity of the condylar surfaces was an important factor in stabilizing the knee. The mechanism proposed was the uphill movement of the femur as the femur and the tibia were displaced or twisted relative to one another.


In Vitro Drug Susceptibility of Bedaquiline, Delamanid, Linezolid, Clofazimine, Moxifloxacin, and Gatifloxacin against Extensively Drug-Resistant Tuberculosis in Beijing, China.
Extensively drug-resistant tuberculosis (XDR-TB) is a deadly form of TB that can be incurable due to its extreme drug resistance. In this study, we aimed to explore the in vitro susceptibility to bedaquiline (BDQ), delamanid (DMD), linezolid (LZD), clofazimine (CLO), moxifloxacin (MFX), and gatifloxacin (GAT) of 90 XDR-TB strains isolated from patients in China. We also describe the genetic characteristics of XDR-TB isolates with acquired drug resistance. Resistance to MFX, GAT, LZD, CLO, DMD, and BDQ was found in 82 (91.1%), 76 (84.4%), 5 (5.6%), 5 (5.6%), 4 (4.4%), and 3 (3.3%) isolates among the XDR-TB strains, respectively. The most frequent mutations conferring fluoroquinolone resistance occurred in codon 94 of the gyrA gene (57.8%), and the strains with these mutations (69.2%) were associated with high-level MFX resistance compared to strains with mutations in codon 90 (25.0%) (P < 0.01). All 5 CLO-resistant isolates exhibited ≥4-fold upward shifts in the BDQ MIC, which were attributed to mutations of codons 53 (60.0%) and 157 (20.0%) in the Rv0678 gene. Additionally, mutation in codon 318 of the fbiC gene was identified as the sole mutation related to DMD resistance. In conclusion, our data demonstrate that the XDR-TB strains exhibit a strikingly high proportion of resistance to the current anti-TB drugs, whereas BDQ, DMD, LZD, and CLO exhibit excellent in vitro activity against XDR-TB in the National Clinical Center on TB of China. The extensive cross-resistance between OFX and later-generation fluoroquinolones indicates that MFX and GAT may have difficulty in producing the desired effect for XDR-TB patients.


Finding of novel polyhydroxybutyrate producer Loktanella sp. SM43 capable of balanced utilization of glucose and xylose from lignocellulosic biomass.
Polyhydroxybutyrate (PHB) is a potential substitute for plastics derived from fossil fuels, owing to its biodegradable and biocompatible properties. Lignocellulosic biomass could be used to reduce PHB production costs; however, the co-utilization of sugars, such as glucose and xylose, without catabolite repression is a difficult problem to be solved. Here, we selected a novel Loktanella sp. SM43 from a marine environment and optimized the conditions for PHB production. Loktanella sp. SM43 showed high PHB production (66.5% content) from glucose. When glucose and xylose were used together, this strain showed high utilization of both substrates compared to other high PHB-producers such as Halomonas sp. and Cupriavidus necator, which showed glucose preference. Loktanella sp. SM43 showed high growth and PHB production with lignocellulosic hydrolysates. When pine tree hydrolysates were used, PHB production was the highest at 3.66 ± 0.01 g/L, followed by Miscanthus (3.46 ± 0.09 g/L) and barley straw hydrolysate (3.36 ± 0.36 g/L). Overall, these results reveal the potential of Loktanella sp. SM43 to produce PHB using various lignocellulosic hydrolysates as feedstock and the first systematic study for PHB production with Loktanella sp. The approach of screening novel strains is a strategy to overcome co-utilization of sugars without genetic engineering.


Histamine H1 receptors mediate the anorectic action of the pancreatic hormone amylin.
We investigated the role of histamine H1 receptors in mediating the anorectic effect of intraperitoneally injected amylin (5 and 20 microg/kg), the amylin agonist salmon calcitonin (sCT; 10 microg/kg), leptin (1.3 mg/kg), and cholecystokinin (CCK; 20 microg/kg). The experiments were performed with mice lacking functional H1 receptors (H1Rko) and wild-type (WT) controls. The mice were also injected with the H3 antagonist thioperamide (20 mg/kg), which reduces feeding by enhancing the release of endogenous histamine through presynaptic H3 receptors. The feeding-suppressive effect of thioperamide was abolished in H1Rko mice. The anorectic effects of amylin and sCT were significantly reduced in 12-h food-deprived H1Rko mice compared with WT mice [1-h food intake: WT-NaCl 0.51 +/- 0.05 g vs. WT-amylin (5 microg/kg) 0.30 +/- 0.06 g (P < 0.01); H1Rko-NaCl 0.45 +/- 0.05 g vs. H1Rko-amylin 0.40 +/- 0.04 g; WT-NaCl 0.40 +/- 0.09 g vs. WT-sCT (10 microg/kg) 0.14 +/- 0.10 g (P < 0.05); H1Rko-NaCl 0.44 +/- 0.08 g vs. H1Rko-sCT 0.50 +/- 0.06 g]. The anorectic effect of leptin was absent in ad libitum-fed H1Rko mice, whereas CCK equally reduced feeding in WT and H1Rko animals. This suggests that the histaminergic system is involved in mediating the anorectic effects of peripheral amylin and sCT via histamine H1 receptors. The same applies to leptin but not to CCK. H1Rko mice showed significantly increased body weight gain compared with WT mice, supporting the role of endogenous histamine in the regulation of feeding and body weight.


A planet within the debris disk around the pre-main-sequence star AU Microscopii.
AU Microscopii (AU Mic) is the second closest pre-main-sequence star, at a distance of 9.79 parsecs and with an age of 22 million years1. AU Mic possesses a relatively rare2 and spatially resolved3 edge-on debris disk extending from about 35 to 210 astronomical units from the star4, and with clumps exhibiting non-Keplerian motion5-7. Detection of newly formed planets around such a star is challenged by the presence of spots, plage, flares and other manifestations of magnetic 'activity' on the star8,9. Here we report observations of a planet transiting AU Mic. The transiting planet, AU Mic b, has an orbital period of 8.46 days, an orbital distance of 0.07 astronomical units, a radius of 0.4 Jupiter radii, and a mass of less than 0.18 Jupiter masses at 3σ confidence. Our observations of a planet co-existing with a debris disk offer the opportunity to test the predictions of current models of planet formation and evolution.


INVERSION POLYMORPHISM, LONGEVITY, AND BODY SIZE IN A NATURAL POPULATION OF DROSOPHILA BUZZATII.
In this study we present the results of an analysis of differential longevity associated with Drosophila buzzatii second chromosome inversion karyotypes based on the assessment of more than 1000 individuals collected in a natural population. Comparisons of inversion frequencies between emerged and bait-collected flies showed not only that inversion arrangements were associated with differential longevity, but also that selection was sex specific. Because each individual fly was scored for thorax length and karyotype, we were able to show that longevity selection favoring larger flies coupled with the average effect of inversions on thorax length can account for the change of inversion frequencies due to longevity in females. The observed genotypic-by-sex interaction could be an important mechanism involved in the maintenance of the polymorphism. Arrangement 2Jz3 , which was shown to impaired fecundity in two independent previous studies, exhibited a positive effect on longevity. This pattern of negative pleiotropy may be another plausible mechanism accounting for the maintenance of the polymorphism.


Focus on: Hendra virus in Australia.
Cases of Hendra virus infection in horses in Australia have been seen regularly since the virus was first isolated in 1994. Kristopher Hughes, associate professor of equine medicine at Charles Sturt University in Australia, gives an overview of how knowledge of the virus has developed in the past 20 years.


Structure-function requirements of parathyroid hormone for stimulation of 1,25-dihydroxyvitamin D3 production by rat renal proximal tubules.
PTH stimulates synthesis and secretion of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in renal proximal tubule cells through activation of the protein kinase-A (PKA) or the protein kinase-C (PKC) signaling pathway. The relative contribution of the two transducing systems was explored using PTH fragments with selective activation of either PKA or PKC. Rat renal proximal tubules were isolated by Percoll centrifugation, and PKA and PKC activities were measured after treatment with synthetic fragments and analogs of PTH. Rat PTH-(1-34), [Nle8,Nle15,Tyr34]bovine PTH-(3-34), and human PTH-(13-34) increased PKC activity in a dose-dependent manner. All fragments tested stimulated PKC at physiological concentrations (10(-11)-10(-10) M). Rat PTH-(1-34) (10(-7) M) increased PKA activity 4.5-fold, but other fragments failed to stimulate PKA between 10(-12)-10(-6) M. Human PTH-(28-34) stimulation of PKC was variable from experiment to experiment. All four PTH fragments tested increased 1,25-(OH)2D3 secretion by perifused renal proximal tubules at the lowest concentrations that stimulated PKC activity. The adenylate cyclase inhibitor 2',5'-dideoxyadenosine (10(-4) M) reduced PTH-(1-34)-stimulated PKA activity by 60%, but failed to block the rise in 1,25-(OH)2D3 secretion. The results of these studies demonstrate that PTH fragments that contain the PKC translocating domain stimulate 1,25-(OH)2D3 secretion, whereas elimination of the PKA activation domain does not alter the potency of the analogs' 1,25-(OH)2D3-stimulating activity. These results support the concept that PKC translocation may be required for PTH stimulation of 1,25-(OH)2D3 secretion.


Histone H2AX phosphorylation as a predictor of radiosensitivity and target for radiotherapy.
Based on the role of phosphorylation of the histone H2A variant H2AX in recruitment of DNA repair and checkpoint proteins to the sites of DNA damage, we have investigated gammaH2AX as a reporter of tumor radiosensitivity and a potential target to enhance the effectiveness of radiation therapy. Clinically relevant ionizing radiation (IR) doses induced similar patterns of gammaH2AX focus formation or immunoreactivity in radiosensitive and radioresistant human tumor cell lines and xenografted tumors. However, radiosensitive tumor cells and xenografts retained gammaH2AX for a greater duration than radioresistant cells and tumors. These results suggest that persistence of gammaH2AX after IR may predict tumor response to radiotherapy. We synthesized peptide mimics of the H2AX carboxyl-terminal tail to test whether antagonizing H2AX function affects tumor cell survival following IR. The peptides did not alter the viability of unirradiated tumor cells, but both blocked induction of gammaH2AX foci by IR and enhanced cell death in irradiated radioresistant tumor cells. These results suggest that H2AX is a potential molecular target to enhance the effects of radiotherapy.


Quantitative electromyographical changes in cervical dystonia after treatment with botulinum toxin.
Injection of botulinum toxin (BT) into affected neck muscles gives symptomatic relief to patients with cervical dystonia by causing a presynaptic block of acetylcholine release. In a retrospective study of 19 patients, we used the turns-amplitude analysis of the EMG interference pattern for the evaluation of electrophysiological changes as a function of time after BT treatment. EMG was performed immediately before and during injection, and muscles showing abnormally increased activity (> 100 turns/s at rest) were given botulinum toxin A (Oculinum (= Botox)) 40-120 units. A second EMG was done 6-30 weeks later. At attempted rest, the sternocleidomastoid muscle contralateral to the involuntary head rotation showed the most pronounced changes, possibly due to relatively large doses of BT, and the EMG changes were related to the time after BT treatment. Six weeks after treatment the muscle showed decreased turns/s, mean amplitude and ratio (turns/amplitude) at rest. At 30 weeks, turns and mean amplitude reached values as before treatment, while ratio was increased to 175% of the pre-treatment value. This pattern may reflect a reversible and random loss of muscles fibres, due to presynaptic denervation. At maximal voluntary contractions, no correlation was seen between time after BT treatment and quantitative EMG.


The Abelson tyrosine kinase (c-Abl) localization in preimplantation mouse development.
The Abelson family member of non-receptor tyrosine kinase, c-Abl, has an important role in regulation of cellular processes like cell polarity, invasion, proliferation, survival and cell motility. In the present study, we investigated the localization of c-Abl protein during preimplantation mouse embryo development in vitro using immunofluorescence confocal microscopy. We have shown that c-Abl protein is expressed throughout all stages of preimplantation development. We found that c-Abl is asymmetrically localized in egg cortex, which suggests possible roles in positioning of the metaphase II spindle. We also observed strong c-Abl staining in external cells, especially enriched at the apical poles in morula stage and at the E3.5 stage blastocysts, cell membrane enrichment of c-Abl in trophectoderm (TE), the tissue responsible for implantation and placentation. The results indicate that c-Abl may play roles in preimplantation embryo development, especially in TE formation and differentiation.


ALDH1A1 expression is associated with poor differentiation, 'right-sidedness' and poor survival in human colorectal cancer.
Aldehyde dehydrogenase 1A1 (ALDH1A1) encodes an enzyme that oxidizes aldehydes to their corresponding carboxylic acids. In colorectal cancer ALDH1A1 marks cancer stem cells and plays putative roles in tumor progression and drug resistance. However, the potential value of ALDH1A1 as a diagnostic marker or target for therapy remains unclear. Here, we have analyzed ALDH1A1 mRNA and protein levels in relation to clinical, histopathological and molecular tumor features in large series of human colorectal cancer. ALDH1A1 protein levels were determined by immunohistochemistry in a series of primary colorectal tumors and their corresponding liver metastases (n = 158). ALDH1A1 mRNA levels were analyzed in several large patient cohorts of colorectal cancer. ALDH1A1 mRNA and protein levels were then related to overall survival and to clinical, histopathological and molecular tumor features. High levels of ALDH1A1 were associated with a poorly differentiated histology and a right-sided tumor location, but not to a mesenchymal-like molecular subtype. Liver metastases contained significantly higher levels of ALDH1A1 compared to the corresponding primary tumors. Radio- and/or chemotherapy prior to tumor resection was associated with increased ALDH1A1 levels regardless of the molecular subtype. Finally, ALDH1A1 protein expression in primary tumors and metastases correlated with shorter overall survival. ALDH1A1 expression is associated with features of poor prognosis, including a poorly differentiated histology and 'right-sidedness' of the primary tumor, and with shorter overall survival. ALDH1A1 is also highly expressed in therapy-surviving tumors and in liver metastases. These results warrant further research into the potential value of targeting ALDH1A1 in order to improve the efficacy of standard treatment and thereby preventing tumor recurrence.


[Electrophysiological diagnosis of multiple sclerosis].
Evoked potentials (EPs) in a daily practice consist of somatosensory evoked potentials (SEP), visual evoked potentials (VEP), auditory brainstem response (ABR) and motor evoked potentials (MEP). EPs can confirm the presence of lesions in patients with suspected involvement, and document the presence of clinically unsuspected lesions in multiple sclerosis (MS) patients. MEP has the highest sensitivity while VEP is the second sensitive. Furthermore, we are able to obtain an increase in sensitivity by using multimodality evoked potentials (MuEP). By doing so, there is a significant correlation between EP abnormalities and Expanded Disability Status Scale. Thus, EPs are useful for the diagnosis or evaluation of MS and predicting neurological disabilities.


Short- and Long-Term Patient Outcomes From Combined Coronary Endarterectomy and Coronary Artery Bypass Grafting: A Meta-Analysis of 63,730 Patients (PRISMA).
This meta-analysis aimed to compare the short- and long-term outcomes in patients undergoing combined coronary endarterectomy and coronary artery bypass grafting (CE + CABG) versus isolated CABG, and particularly to examine subgroup patients with high-risk profile and patients with diffuse disease in the left anterior descending artery (LAD).Studies published between January 1, 1970 and May 31, 2015 were searched in the literature databases, including Ovid Medline, Embase, PubMed, and ISI Web of Science.A total of 30 eligible studies including 63,730 patients were analyzed.Five authors extracted data from the included studies independently.Meta-analysis on the total patients revealed that CE + CABG was associated with significantly increased 30-day postoperative all-cause mortality compared with isolated CABG (OR = 1.86, 95% CI: 1.66-2.08, z = 10.99, P < 0.0001). Subgroup analysis on patients with high-risk profile and patients with diffuse disease in the LAD showed that 30-day mortality after CE + CABG was 2.6 folds (OR = 2.60, 95% CI: 1.39-4.86, z = 2.99, P = 0.003) and 3.93 folds (OR = 3.93, 95% CI: 1.40-11.0, z = 2.60, P = 0.009) of that after isolated CABG in the respective subgroup. In contrast, the mortality was comparable in CE + off-pump CABG and CE + on-pump CABG groups (OR = 0.53, 95% CI: 0.18-1.55, z = 1.16, P = 0.248). In addition, the incidences of perioperative myocardial infarction (MI) and 30-day postoperative complications, including low output syndrome (LOS), MI, ventricular tachycardia (VT), and renal dysfunction after CE + CABG were significantly higher than those after isolated CABG (all P < 0.05). In high-risk patient subgroup, CE + CABG significantly increased the incidences of postoperative LOS, MI, and renal function compared with isolated CABG (all P < 0.05). The incidence of perioperative myocardial after CE + CABG was 2.86 and 2.92 times of that after isolated CABG in high-risk patients and patients with diffuse disease in LAD, respectively. Analysis on the recent reports (published later than 2000) showed consistent results as the analysis including all the eligible reports. Long-term survival was comparable in CE + CABG and isolated CABG groups (hazardous ratio = 1.16, 95% CI: 0.32-4.22, z = 0.23, P = 0.819).CE + CABG appears to be associated with poor short-term outcomes, particularly in high-risk patients and patients with diffuse disease in the LAD.


Rational design and synthesis of novel diphenyl ether derivatives as antitubercular agents.
A series of triclosan mimic diphenyl ether derivatives have been synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The binding mode of the compounds at the active site of enoyl-acyl carrier protein reductase of M. tuberculosis has been explored. Among them, compound 10b was found to possess antitubercular activity (minimum inhibitory concentration =12.5 µg/mL) comparable to triclosan. All the synthesized compounds exhibited low levels of cytotoxicity against Vero and HepG2 cell lines, and three compounds 10a, 10b, and 10c had a selectivity index more than 10. Compound 10b was also evaluated for log P, pKa, human liver microsomal stability, and % protein binding, in order to probe its druglikeness. Based on the antitubercular activity and druglikeness profile, it may be concluded that compound 10b could be a lead for future development of antitubercular drugs.


CD39/ectonucleoside triphosphate diphosphohydrolase 1 provides myocardial protection during cardiac ischemia/reperfusion injury.
Extracellular adenosine, generated from extracellular nucleotides via ectonucleotidases, binds to specific receptors and provides cardioprotection from ischemia and reperfusion. In the present study, we studied ecto-enzymatic ATP/ADP-phosphohydrolysis by select members of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) family during myocardial ischemia. As a first step, we used a murine model of myocardial ischemia and in situ preconditioning and performed pharmacological studies with polyoxometalate 1, a potent E-NTPDase inhibitor (Na6[H2W12O40]). Polyoxometalate 1 treatment increased infarct sizes and abolished beneficial effects of preconditioning. To define relative contributions of distinct E-NTPDases, we investigated transcriptional responses of E-NTPDases 1 to 3 and 8 to preconditioning. We noted robust and selective induction of E-NTPDase 1 (CD39) transcript and protein. Histological analysis of preconditioned myocardium localized CD39 induction to endothelia and myocytes. Cd39-/- mice exhibited larger infarct sizes with ischemia (cd39+/+ 43.0+/-3.3% versus cd39-/- 52%+/-1.8; P<0.05), and cardioprotection was abrogated by preconditioning (cd39+/+ 13.3%+/-1.5 versus cd39-/- 50.5%+/-2.8; P<0.01). Heightened levels of injury after myocardial ischemia and negligible preconditioning benefits in cd39-/- mice were corrected by infusion of the metabolic product (AMP) or apyrase. Moreover, apyrase treatment of wild-type mice resulted in 43+/-4.2% infarct size reduction (P<0.01). Taken together, these studies reveal E-NTPDase 1 in cardioprotection and suggest apyrase in the treatment of myocardial ischemia.


Inflammation and malnutrition as predictors of mortality in patients on hemodialysis.
Low albumin and high C-reactive protein (CRP) are significant predictors of mortality in hemodialysis (HD) patients. Although, classically, hypoalbuminemia has been attributed to malnutrition, inflammation can also predict the serum albumin concentration in dialysis patients. To establish the influence of nutritional status and inflammation on mortality in HD patients. A cross-sectional study was conducted in 64 patients (35 males; 9 diabetics; mean age 64 +/- 12 years), who had been on HD for 64 +/- 58 months. Nutritional status was assessed from estimated protein caloric intake, dietary recall, anthropometric and biochemical parameters, and serum levels of insulin-like growth factor-1 (IGF-1). CRP was used as a marker of inflammation. Comorbidity was measured using a modified M. Charlson index. The dialysis doses (Kt/V) and protein catabolic rate (PCR) were measured and standardized for actual and ideal body weight. The incidence and causes of death were recorded during the two-year follow-up. During the follow-up period, 18 patients died and 11 were withdrawn from the study after receiving a renal transplant. In multivariante analysis (Cox proportional hazards model), total comorbidity and the levels of CRP and hematocrit (increased) and IGF-1 (decreased) were independent predictors of mortality. Inflammation, as measured by CRP, and malnutrition, as measured by IGF-1 levels, are associated with mid-term mortality in HD patients. High hematocrit was an independent risk factor for mortality. Comorbidity, measured by disease and the degree of functional impairment, was a good predictor of mortality.


Synchronous occurrence of primary neoplasms in the uterus with squamous cell carcinoma of the cervix and adenocarcinoma of the endometrium.
Synchronous primary malignant neoplasms of the uterus are uncommon. Patients with synchronous cervical and endometrial cancers are even rarer. We describe a case of cervical squamous cell carcinoma and endometrial endometrioid adenocarcinoma occurring simultaneously in a 47-year-old woman presenting with massive menstrual bleeding. The concept of synchronous primary malignancies of the genital tract is also reviewed in this report. A 47-year-old overtly obese female presented with menometrorrhagia of over 6 months' duration. Pelvic examination detected a large cervix but apparently normal externals. Magnetic resonance imaging revealed a mass over the cervical region and endometrial lesions in the uterine cavity. Surgical exploration disclosed a cervical tumor and erosion of the endometrium. The pathologic findings were compatible with synchronous occurrence of primary neoplasms in the uterus with squamous cell carcinoma of the cervix and adenocarcinoma of the endometrium. Synchronous genital tract neoplasms are rare but cause more clinical problems than a single neoplasm. It is practical to pay more attention to the differential diagnosis of primary and metastatic tumors. The second primary cancer that occurs in an individual with endometrial cancer may offer an opportunity for early detection. The prognosis for a patient with synchronous gynecologic malignancies does not seem to be worse.


Bcl-2 associated athanogene 5 (Bag5) is overexpressed in prostate cancer and inhibits ER-stress induced apoptosis.
The Bag (Bcl-2 associated athanogene) family of proteins consists of 6 members sharing a common, single-copied Bag domain through which they interact with the molecular chaperone Hsp70. Bag5 represents an exception in the Bag family since it consists of 5 Bag domains covering the whole protein. Bag proteins like Bag1 and Bag3 have been implicated in tumor growth and survival but it is not known whether Bag5 also exhibits this function. Bag5 mRNA and protein expression levels were investigated in prostate cancer patient samples using real-time PCR and immunoblot analyses. In addition immunohistological studies were carried out to determine the expression of Bag5 in tissue arrays. Analysis of Bag5 gene expression was carried out using one-way ANOVA and Bonferroni's Multiple Comparison test. The mean values of the Bag5 stained cells in the tissue array was analyzed by Mann-Whitney test. Functional studies of the role of Bag5 in prostate cancer cell lines was performed using overexpression and RNA interference analyses. Our results show that Bag5 is overexpressed in malignant prostate tissue compared to benign samples. In addition we could show that Bag5 levels are increased following endoplasmic reticulum (ER)-stress induction, and Bag5 relocates from the cytoplasm to the ER during this process. We also demonstrate that Bag5 interacts with the ER-resident chaperone GRP78/BiP and enhances its ATPase activity. Bag5 overexpression in 22Rv.1 prostate cancer cells inhibited ER-stress induced apoptosis in the unfolded protein response by suppressing PERK-eIF2-ATF4 activity while enhancing the IRE1-Xbp1 axis of this pathway. Cells expressing high levels of Bag5 showed reduced sensitivity to apoptosis induced by different agents while Bag5 downregulation resulted in increased stress-induced cell death. We have therefore shown that Bag5 is overexpressed in prostate cancer and plays a role in ER-stress induced apoptosis. Furthermore we have identified GRP78/BiP as a novel interaction partner of Bag5.


Conservative management of triplet ICSI pregnancy on top of synechiae.
A case of complex of obstetrical complications which endangered the life of both the mother and the fetuses was presented. The dilemma the authors faced as a result of spontaneous abortion of one of the triplet was due to rupture of membranes, the remaining twins were at risk of demise. At caesarean section, the patient had severe placenta accreta and torrential haemorrhage that was managed with a Bakri balloon.


The Need for Standardized Assessment of Muscle Quality in Skeletal Muscle Function Deficit and Other Aging-Related Muscle Dysfunctions: A Symposium Report.
A growing body of scientific literature suggests that not only changes in skeletal muscle mass, but also other factors underpinning muscle quality, play a role in the decline in skeletal muscle function and impaired mobility associated with aging. A symposium on muscle quality and the need for standardized assessment was held on April 28, 2016 at the International Conference on Frailty and Sarcopenia Research in Philadelphia, Pennsylvania. The purpose of this symposium was to provide a venue for basic science and clinical researchers and expert clinicians to discuss muscle quality in the context of skeletal muscle function deficit and other aging-related muscle dysfunctions. The present article provides an expanded introduction concerning the emerging definitions of muscle quality and a potential framework for scientific inquiry within the field. Changes in muscle tissue composition, based on excessive levels of inter- and intra-muscular adipose tissue and intramyocellular lipids, have been found to adversely impact metabolism and peak force generation. However, methods to easily and rapidly assess muscle tissue composition in multiple clinical settings and with minimal patient burden are needed. Diagnostic ultrasound and other assessment methods continue to be developed for characterizing muscle pathology, and enhanced sonography using sensors to provide user feedback and improve reliability is currently the subject of ongoing investigation and development. In addition, measures of relative muscle force such as specific force or grip strength adjusted for body size have been proposed as methods to assess changes in muscle quality. Furthermore, performance-based assessments of muscle power via timed tests of function and body size estimates, are associated with lower extremity muscle strength may be responsive to age-related changes in muscle quality. Future aims include reaching consensus on the definition and standardized assessments of muscle quality, and providing recommendations to address critical clinical and technology research gaps within the field.


Sudden cardiac death and sarcoidosis of the heart in a young patient.
Sarcoidosis is a granulomatous disease of unknown etiology affecting any organ, microscopically characterized by noncaseating granulomata. Cardiac involvement in sarcoidosis has been reported. It might be symptomatic or not and even revealed by sudden death. Heart conduction system is rarely investigated at autopsy, even in cases of sudden cardiac death. We present a case of a 32-year-old woman who died suddenly. The examination of the heart conduction system revealed a cardiac sarcoidosis that could explain the sudden death. The review of clinical data of the patient revealed some symptoms consistent/in agreement with this hypothesis. Cardiac sarcoidosis remains a diagnostic challenge and can be easily missed, clinically and pathologically. The retrospective analysis of clinical data and autopsy results of fatal and unusual cases might help to better understand sarcoidosis and its clinical presentations. Examination of the cardiac conduction system is crucial in selected cases of sudden cardiac death.


Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases.
Epithelial barriers of the skin, gastrointestinal tract, and airway serve common critical functions, such as maintaining a physical barrier against environmental insults and allergens and providing a tissue interface balancing the communication between the internal and external environments. We now understand that in patients with allergic disease, regardless of tissue location, the homeostatic balance of the epithelial barrier is skewed toward loss of differentiation, reduced junctional integrity, and impaired innate defense. Importantly, epithelial dysfunction characterized by these traits appears to pre-date atopy and development of allergic disease. Despite our growing appreciation of the centrality of barrier dysfunction in initiation of allergic disease, many important questions remain to be answered regarding mechanisms disrupting normal barrier function. Although our external environment (proteases, allergens, and injury) is classically thought of as a principal contributor to barrier disruption associated with allergic sensitization, there is a need to better understand contributions of the internal environment (hormones, diet, and circadian clock). Systemic drivers of disease, such as alterations of the endocrine system, metabolism, and aberrant control of developmental signaling, are emerging as new players in driving epithelial dysfunction and allergic predisposition at various barrier sites. Identifying such central mediators of epithelial dysfunction using both systems biology tools and causality-driven laboratory experimentation will be essential in building new strategic interventions to prevent or reverse the process of barrier loss in allergic patients.


[Nursing staff education in Brunei].
The only form of medical education in Brunei was nurse staff training until Institute of Medicine of University Brunei Darussalam was established in September 2000. In Brunei, nurse education was organized in 1951 when first group of students in School of Nursing was formed. In 1953 they received certificate of Trained Assistant Nurse. In 1954 more elaborated program of nurse training was introduced. Until 1986, in School of Nursing two levels of educational programs were used--General Nurse Training and Assistant Nurse Training. In 1986, College of Nursing was set up for training higher education nurses. In 1991 first graduates of college of nursing received diplomas of nursing. In 1999 School of Nursing was unified with College of Nursing which became the only educational institution for nurse training. Organizational structure and educational staff of College of Nursing, conditions of entering and diploma issues, curriculum and education courses, post-graduate training and international cooperation are discussed.


Design, Synthesis, Toxicity Estimation and Molecular Docking Studies of N-(furan-2-yl)-1-(5-substituted) phenyl-1,3,4-oxadiazol-2-yl) methanimine as Antitubercular Agents.
A series of novel N-(furan-2-yl)-1-(5-substituted) phenyl-1,3,4-oxadiazol-2-yl) methanimines (Fa-e) were synthesized and evaluated for antitubercular activity against Mycobacterium tuberculosis (H37Rv) strain by using alamar blue assay. The synthesized compounds were characterized based on IR, (1)HMR and mass spectral analysis. The toxicity profile was predicted by organic chemistry portal, a web based application for predicting in silico absorption, distribution, metabolism, excretion and toxicity, and the novel derivatives under study did not show any toxicity issues. The mechanism of action of the titled derivatives was predicted by docking on the Mycobacterium tuberculosis Enoyl-ACP reductase enzyme. The docking study concluded that Fb and Fa possessed good binding energy indicating more prominent interaction towards the active sites NAD and TYR 158. The antitubercular studies showed that the both Fa and Fb possessed significant activity with the MIC as low as 3.125 μg/ml.


[On the development of traditional Mongolian medicine in the 20th century Inner Mongolia].
Being with the changing of world order in the 20th century, the influence of modern science and technology had gradually been expanded into the developing countries. Concerning with the development of traditional Mongolian medicine, the societal changes, cultural transfigurations, and the scientific policies have brought the new era to the medicine in Inner Mongolia. Mongolian medicine had been integrated with Western medicine and Chinese medicine in the end of last century. The transformation of Mongolian medicine in the 20th century has been made by modern medicinal education system, the institutional development and the starting of medical magazines. There has been a medical pluralism phenomenon which has appeared in Inner Mongolia since the last century. This article will demonstrate the development of the 20th century's Mongolian medicine and point out that that will be the important part of its whole history.


Characteristics and predictors of oral cancer knowledge in a predominantly African American community.
To characterize smoking and alcohol use, and to describe predictors of oral cancer knowledge among a predominantly African-American population. A cross-sectional study was conducted between September, 2013 among drag racers and fans in East St. Louis. Oral cancer knowledge was derived from combining questionnaire items to form knowledge score. Covariates examined included age, sex, race, marital status, education status, income level, insurance status, tobacco and alcohol use. Adjusted linear regression analysis measured predictors of oral cancer knowledge. Three hundred and four participants completed questionnaire; 72.7% were African Americans. Smoking rate was 26.7%, alcohol use was 58.3%, and mean knowledge score was 4.60 ± 2.52 out of 17. In final adjusted regression model, oral cancer knowledge was associated with race and education status. Compared with Caucasians, African Americans were 29% less likely to have high oral cancer knowledge (β = -0.71; 95% CI: -1.35, -0.07); and participants with a high school diploma or less were 124% less likely to have high oral cancer knowledge compared with college graduates (β = -1.24; 95% CI: -2.44, -0.41). There was lower oral cancer knowledge among African Americans and those with low education. The prevalence of smoking was also very high. Understanding predictors of oral cancer knowledge is important in future design of educational interventions specifically targeted towards high-risk group for oral cancer.


[The prevention and management of approach-specific complications of abdominal aortic balloon occlusion in pelvic and sacral surgery].
Objective: To investigate the causes,prevention and treatment of femoral artery puncture related complications caused by the application of resuscitative endovascular balloon occlusion of the aorta (REBOA) in the resection of pelvic and sacral tumors. Methods: Clinical data of 23 patients with femoral artery puncture related complications who received REBOA in the resection of pelvic and sacral tumors from August 2010 to August 2018 at the Musculoskeletal Tumor Center,Peking University People's Hospital were retrospectively analyzed.There were 8 males and 15 females,with the an age of (37.0±16.2) years (range:15 to 65 years).Arterial access via the Seldinger technique for REBOA was obtained in the right common femoral artery of 18 cases,and in the left of 6 cases.An arterial sheath with a diameter of 11 to 12 F(1 F≈0.33 mm) was used for the patient.The occurrence and treatment of postoperative complications were analyzed. Results: Acute femoral arterial thrombosis occurred in 18 patients,which was managed by open repair 48 hours postoperatively.Among the 349 patients admitted before 2015 who received hemostasis by compression after femoral artery sheath removal,12 patients (3.4%) developed acute femoral artery thrombosis.While the 476 patients admitted after 2015 who used a vascular stapler to close the femoral artery wound,6 patients (1.3%) developed acute femoral artery thrombosis.One case of retroperitoneal hematoma and 1 case of femoral pseudoaneurysm were found and surgically fixed.Postoperative follow-up was (40±18) months (range:13 to 108 months).Three cases with chronic lower extremity ischemia were confirmed by Doppler ultrasonography during 1 to 5 years follow-up.Two of them had minimal symptoms and denied further treatment,while the other one received femoral-femoral artery bypass surgery to restore distal flow for pain and numbness relief. Conclusions: Acute femoral arterial thrombosis was the most common femoral artery puncture.Technique refinement of REBOA,the use of percutaneous suture device and close follow-up can reduce the approach-specific complications,and help to detect and treat the complications timely,which may popularize the clinical application of REBOA.


Interaction effects of temperature and ozone on lung function and markers of systemic inflammation, coagulation, and fibrinolysis: a crossover study of healthy young volunteers.
Trends in climate suggest that extreme weather events such as heat waves will become more common. High levels of the gaseous pollutant ozone are associated with elevated temperatures. Ozone has been associated with respiratory diseases as well as cardiovascular morbidity and mortality and can reduce lung function and alter systemic markers of fibrinolysis. The interaction between ozone and temperature is unclear. Sixteen healthy volunteers were exposed in a randomized crossover study to 0.3 ppm ozone and clean air for 2 hr at moderate (22°C) temperature and again at an elevated temperature (32.5°C). In each case lung function was performed and blood taken before and immediately after exposure and the next morning. Ozone exposure at 22°C resulted in a decrease in markers of fibrinolysis the next day. There was a 51.8% net decrease in PAI-1 (plasminogen activator inhibitor-1), a 12.1% net decrease in plasminogen, and a 17.8% net increase in D-dimer. These significantly differed from the response at 32.5°C, where there was a 44.9% (p = 0.002) and a 27.9% (p = 0.001) increase in PAI-1 and plasminogen, respectively, and a 12.5% (p = 0.042) decrease in D-dimer. In contrast, decrements in lung function following ozone exposure were comparable at both moderate and elevated temperatures (forced expiratory volume in 1 sec, -12.4% vs. -7.5%, p > 0.05). No changes in systemic markers of inflammation were observed for either temperature. Ozone-induced systemic but not respiratory effects varied according to temperature. Our study suggests that at moderate temperature ozone may activate the fibrinolytic pathway, while at elevated temperature ozone may impair it. These findings provide a biological basis for the interaction between temperature and ozone on mortality observed in some epidemiologic studies.


Socially-induced variation in physiological mediators of parental care in a colonial bird.
Social facilitation of reproduction occurs in humans and animals, and may represent one of the bases of reproduction in groups. However, its underlying physiological mechanisms remain largely unexplored. Here, we found in a colonial bird, the Adélie penguin (Pygoscelis adeliae), that the number of parental interactions (nest relief ceremonies) performed by breeding individuals on the colony was positively related to prolactin levels in other breeding individuals exposed to these interactions (i.e. focal individuals). As prolactin is typically involved in the expression of parental behaviour in birds, this suggests that parental interactions by conspecifics represent social cues that might increase parental motivation in focal individuals. Moreover, parental interactions were not related to corticosterone levels in focal individuals, suggesting that these social cues were not stressful for penguins. However, social stimulation still had a cost for focal individuals, as it was negatively related to their antioxidant defences (a component of self-maintenance). As social stimulation was also positively related to prolactin levels, this highlights the fact that social stimulation acts on the trade-off between reproduction and self-maintenance. For the first time, the results of the current study shed light on the physiological factors potentially underlying social facilitation of parental care. Importantly, they suggest that, even though social facilitation of parental care may increase breeding performance, it can also negatively affect other fitness components.


Understanding the role of PD-L1/PD1 pathway blockade and autophagy in cancer therapy.
Autophagy is a vital, physiological catabolic process for cell survival by which cells clear damaged organelles and recycle nutrients when homeostasis is maintained. Cancer is a complex disease with uncontrolled growth of cancer cells. Recent studies have suggested the role of autophagy in cancer. A complex relationship exists between autophagy and cancer, since autophagy can contribute to the survival or the destruction of malignant cells depending on the stage of tumor development. In this review, we describe in detail the mechanism underlying autophagy in cancer cells and the intricate involvement of the programmed cell death-1 (PD1) receptor with its ligand (PD-L1). The overexpression of PD-L1 receptors on cancer cell membranes has been observed in several types of cancers. The interaction of PD-L1 on cancer cells with PD1 on the surface of T-cells causes cancer cells to escape from the immune system by preventing the activation of new cytotoxic T-cells in the lymph nodes and subsequent recruitment to the tumor. In addition to its immunopathogenicity, PD1 has been related to autophagy. Reduction of this receptor due to treatment increases autophagy, therefore promoting the recycling of nutrients and clearance of toxic species, consequently promoting cell survival. In addition, PD-L1/PD1 engagement can induce autophagy in nearby T-cells due to a decrease in the amino acids tryptophan and arginine and due to the deprivation of nutrients such as glucose followed by a reduction in glucose metabolism. Resistance to cancer therapies is attributed to various pathways in oncogenesis including, inhibition of tumor suppressors, alteration of the tumor metabolic environment, and upregulation of autophagy. Here we explore the interaction between the immunosuppressive PD-L1/PD1 engagement and autophagy mechanisms, and evaluate the impact of inhibition of these pathways in augmenting antitumor efficacy.


Polymer translocation through a nanopore: DPD study.
Translocation of a polymer chain through a narrow pore is explored using 3D explicit solvent dissipative particle dynamics simulation. We study the dependence of the translocation dynamics and translocation time τ on the chain length N, driving force magnitude E, and solvent quality. Two types of driving forces are considered: uniform hydrostatic force, which is applied equally to the chain and solvent particles, and uniform electrostatic force, which is applied selectively to the charged particles in the chain and oppositely charged counterions in the solvent. We concluded that the scaling correlations τ ~ E(-ξ) and τ ~ N(β) are valid only for coil-like chains. For globular chains, the exponents ξ and β could not be identified with a reasonable accuracy. While the found value of ξ agrees with published experimental results and does not depend on the driving force type, the exponent β depends on the driving force and solvent quality. This is explained by nonequilibrium effects, as in the systems considered, the time of translocation is comparable with the time of chain relaxation. These effects, manifested in the changes of chain conformation in the process of translocation, were analyzed on the basis of the variation of the gyration radii of cis and trans segments of the chain in normal and lateral directions. A prominent chain expansion was observed for coils and was insignificant for globules. This work demonstrates the feasibility of the 3D dissipative particle dynamics modeling of translocation phenomena and accounting for the electrostatic interactions with explicit counterions, as well as for the solvent quality, in a computationally efficient manner.


Living donor liver transplantation in 43 children with biliary atresia: a single-center experience from the mainland of China.
There is no large-cohort report on living donor liver transplantation (LDLT) for biliary atresia (BA) patients from the mainland of China. This single-center study describes our initial experience with 43 LDLTs for BA patients aged two years or younger. In this study, the eligibility criteria were BA as the primary diagnosis and two years of age or younger. From October 2006 to December 2010, the clinical data of 43 LDLTs, including pre-operative evaluations, surgical techniques, postoperative complications and outcomes of donors and recipients, were retrospectively analyzed. Donor graft type was the left lateral segment with compatible ABO blood groups. Forty-three recipients were selected in this study. The median patient age at operation was 9 months (range 6-24), and the median body weight was 8 kg (range 5.7-12.5). Fourteen (32.6%) recipients received Kasai operations before liver transplantation. The overall one- and two-year cumulative survival rates for grafts and recipients were 81%, 81% and 76%, 76%, respectively. No donor mortality was encountered, with a minimal morbidity and no long-term sequelae. Nine out of 43 recipients died. Postoperative complications of recipients were biliary leakage and refluxing cholangitis (11/43, 25.6%), hepatic artery thrombosis (4, 9.3%), pulmonary infections (4, 9.3%), portal vein thrombosis (3, 7.0%), wound disruption (3, 7.0%), acute rejection (3, 7.0%), cytomegalovirus infection (2, 4.7%), and intra-abdominal bleeding (1, 2.3%). Despite the relatively low survival rates due to lack of experience initially, LDLT still provides encouraging outcomes for pediatric recipients with BA, even small children under two years old.


Comparison of binding interactions of lomefloxacin to serum albumin and serum transferrin by resonance light scattering and fluorescence quenching methods.
The interaction between lomefloxacin (LMF) and two drug carrier proteins, human serum albumin (HSA) and serum transferrin (TF), were studied and compared by fluorescence quenching, resonance light scattering (RLS), and circular dichroism (CD) spectroscopic along with molecular modeling. Fluorescence data show that LMF has a stronger quenching effect on HSA than on TF. The binding constant and the number of binding sites were calculated as 6.00 x 10(5) M(-1) and 0.77 for HSA, and 4.66 x 10(5) M(-1) and 1.02, for TF, respectively. Also, these binding parameters were calculated by RLS data, as a novel approach and were compared to that obtained from fluorescence. The micro-environment changes of Trp residues were evident in both proteins. The quantitative analysis of the secondary structure in both proteins further confirmed the drug-induced conformational changes. The distance (r) between donors (HSA and TF) and acceptor (LMF) were obtained by fluorescence resonance energy transfer (FRET) theory and found to be 1.83 nm and 1.71 nm for HSA and TF respectively. Moreover, molecular modeling studies suggested the sub-domain IB in HSA and N-lobe in TF as the candidate place for the formation of the binding site of LMF on these proteins.


Retinal and intracranial arteriovenous malformations: Wyburn-Mason syndrome.
A 7-year-old girl who failed a vision screening examination was found to have a retinal arteriovenous malformation (AVM) in her right eye along with a small angioma of her right lower lip. Magnetic resonance imaging and cerebral angiography revealed a large AVM involving the thalamus and basal ganglia as well as a small AVM involving the right ophthalmic artery. The combination of retinal and intracranial AVMs is known as Wyburn-Mason syndrome. The retinal AVMs of this syndrome do not grow or bleed. Visual loss is usually the result of optic neuropathy from associated orbitocranial AVMs. The natural course of the intracranial AVMs of this syndrome is poorly documented. However, they tend to be extensive and inaccessible and therefore difficult to treat.


Changes in microRNA expression during disease progression in patients with chronic viral hepatitis.
MicroRNAs (miRNAs) have been involved in hepatocarcinogenesis, but little is known on their role in the progression of chronic viral hepatitis. Aim of this study was to identify miRNA signatures associated with stages of disease progression in patients with chronic viral hepatitis. MiRNA expression profile was investigated in liver biopsies from patients with chronic viral hepatitis and correlated with clinical, virological and histopathological features. Relevant miRNAs were further investigated. Most of the significant changes in miRNA expression were associated with liver fibrosis stages and included the significant up-regulation of a group of miRNAs that were demonstrated to target the master regulators of epithelial-mesenchymal transition ZEB1 and ZEB2 and involved in the preservation of epithelial cell differentiation, but also in cell proliferation and fibrogenesis. In agreement with miRNA data, immunostaining of liver biopsies showed that expression of the epithelial marker E-cadherin was maintained in severe fibrosis/cirrhosis while expression of ZEBs and other markers of epithelial-mesenchymal transition were low or absent. Severe liver fibrosis was also significantly associated with the down-regulation of miRNAs with antiproliferative and tumour suppressor activity. Similar changes in miRNA and target gene expression were demonstrated along with disease progression in a mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis, suggesting that they might represent a general response to liver injury. Chronic viral hepatitis progression is associated with the activation of miRNA pathways that promote cell proliferation and fibrogenesis, but preserve the differentiated hepatocyte phenotype.


Stent Coating Integrity of Durable and Biodegradable Coated Drug Eluting Stents.
Coatings consisting of a polymer and drug are widely used in drug-eluting stents (DES) and are essential in providing programmable drug release kinetics. Among other factors, stent coating technologies can influence blood compatibility, affect acute and sub-acute healing, and potentially trigger a chronic inflammatory response. The aim of this study was to investigate the short-term (7 and 28 days) and long-term (90 and 180 days) coating integrity of the Xience Prime Everolimus-Eluting Stent (EES), Resolute Zotarolimus-Eluting Stent (ZES), Taxus Paclitaxel-Eluting Stent (PES), and Nobori Biolimus A9-Eluting Stent (BES) in a rabbit ilio-femoral stent model. Stented arteries (n = 48) were harvested and the tissue surrounding the implanted stents digested away with an enzymatic solution. Results demonstrated that the majority of struts of EES were without any coating defects with a few struts showing minor defects. Similarly, for the ZES, most of the struts were without coating defects at all time points except at 180 days. The majority of PES demonstrated mostly webbing and uneven coating. In the BES group, the majority of strut coating showed polymer cracking. Overall, the EES and ZES had fewer coating defects than the PES and BES. Coating defects, however increase over time for the ZES, whereas the percent of coating irregularities remained constant for the EES. These results provide, for the first time, a comparison of the long-term durability of these drug-eluting stent coatings in vivo.


Investigational drugs for the treatment of osteoarthritis.
Osteoarthritis (OA) is a common joint disease with multiple pathophysiological processes, affecting the whole joint. Current therapeutic options such as NSAIDs can provide a palliative effect on symptoms but have limited effect on disease progression. New drugs targeting OA structures may retard disease progression at an earlier stage and delay the need for joint replacement. Some drugs have entered into clinical trials and a few, such as strontium ranelate, do have improvements in both pain and structure changes. However, most of them have failed in clinical trials largely due to increased side effects or the failure to identify the right OA phenotype for the right drug in clinical design. This review describes various investigational drugs developed for the treatment of OA covering those at stages from preclinical experiments to early phase clinical trials. They include drugs for slowing cartilage degradation, regulating cartilage metabolism, targeting subchondral bone, controlling inflammation and relieving pain. Treatment options for OA remain limited. However, with the emergence of sensitive tools to detect early disease progression and identification of different OA phenotypes, disease-modifying anti-OA drugs with increased benefit and reduced risks will become available for OA treatment in the near future.


Production of High-maltose Syrup and High-protein Flour from Rice by an Enzymatic Method.
A novel enzymatic process was developed to simultaneously produce high-maltose syrup and high-protein rice flour from milled rice. This process would greatly increase the commercial value of rice. A slurry of rice flour was first liquefied with α-amylase and then centrifuged, the precipitated fraction being recovered as high-protein rice flour. The supernatant fraction was then saccharified with α-amylase and debranching enzymes (isoamylase and/or pullulanase) together to produce high-maltose syrup under various conditions. The yield of high-maltose syrup was affected by the temperature, pH, DE value of the liquefied starch, the enzyme combination and variety of rice. As an example, 0.64 g of high-maltose syrup (83% maltose and 2.6% glucose) and 0.36 g of high-protein rice flour (29% protein, 39% starch and 14% sugar) could be produced from one gram of dry rice (Taichung Native 1).


Endovascular treatment of swing-segment stenosis in vascular access: current status and future directions.
Swing-segment lesions are a fairly common reason for access failure and predispose to repeated interventions. The pathophysiology, hemodynamic circumstances and the primary intervention might all play a role in early recurrence. Mainly, percutaneous transluminal angioplasty (PTA), bare metal stenting and stent graft implantation have been performed to prolong lesion patency and access circuit patency. The available data on endovascular treatment of swing-segment lesions are scarce, heterogeneous and of poor quality. Moreover, with the continuous evolution of endovascular techniques and introduction of new devices there is a risk of increasing device-specific investigations. In the meantime, PTA is easily discarded in favor of novel stents and stent grafts. However, PTA might still have an important position in the overall treatment strategy to postpone loss of the vascular access site. However, without optimal post-interventional imaging, true PTA results remain obscure and indications for additional stent (graft) implantation unclear. Currently, it seems that different devices are utilized to prolong lesion patency rather than access circuit patency. Obviously, more randomized controlled trials and well-structured multicenter registries may be capable of determining a superior treatment modality for a specific lesion. However, it might be more accurate to identify the optimal sequence of interventions by which the lifespan of the access site is maintained as long as possible.


[Results of percutaneous coronary intervention in a hospital with a low case load].
Since efficacy of small volume centers performing coronary and angioplasty is questioned, we present our data for 2003. In 2003, 669 coronary examinations were performed in our unit (average age 68 years, 67% men) with 215 angioplasties. We take charge essentially Acute Coronary Syndrome (99%), with 37% ACS ST +. The radical approach was taken in 15% of cases. We used anti GP IIb/IIIa in 67% of cases (only abciximab), the rate of stenting was 84% with 43.6% of Direct Stenting. The primary angiographic results were good in 98% of cases. The rate of Restenosis was 6%. The hospital mortality was 2.8%. So we think that coronary and angioplasty in a small volume center can be performed with safety and a level of success in accordance with the data of the literature.


Effect of optical defocus on multifocal ERG responses.
Multifocal electroretinography (mfERG) is a sensitive technique to probe retinal function topographically. Various conditions such as macular degeneration decrease the first-order kernel (K1) response magnitude of mfERG. Previous studies have given inconsistent results on the effect of optical defocus due to poor controls. This study investigated the effect of optical defocus on the K1 response of the central retina using a well-controlled method. Twenty subjects were recruited to undergo mfERG measurement using the VERIS 4.0 system. A four millimetre artificial pupil was fitted before each fully-dilated right eye, optically corrected for the viewing distance. The implicit times and response amplitudes of n1 (first negative trough) and p1 (first positive peak) under three different optical defocus conditions (zero dioptres, +1.00 D and +3.00 D) were measured. The implicit times of n1 and p1 did not demonstrate any significant variation from the central macula to para-macula under different optical defocus conditions. The response amplitude of n1 did not show any changes from the central macula to para-macula but the response amplitude of the central macular p1 showed a significant reduction by 12 per cent under +1.00 D defocus and +3.00 D defocus. Optical defocus causes mild reduction in mfERG at the central macula but there are no significant changes in the periphery. A full optical correction is recommended for mfERG measurement to minimise the reduction of the macular response due to optical defocus.


Readmissions and the quality of care in patients hospitalized with heart failure.
Clinical practice guidelines based on the results of randomized clinical trials recommend that patients with heart failure due to left ventricular systolic dysfunction (LVSD) be treated with angiotensin-converting enzyme inhibitors (ACEI) at doses shown to reduce mortality and readmission. This study examined the relationship between ACEI use at discharge and readmission among patients with heart failure due to LVSD. Data were abstracted from the medical records of 2943 randomly selected patients hospitalized for heart failure in 50 hospitals. The outcome of interest was the number of readmissions occurring up to 21 months after discharge. Six-hundred and eleven patients were eligible for analysis. Compared with patients discharged at a recommended ACEI dose, patients not prescribed an ACEI at discharge had an adjusted rate ratio of readmission (RR) of 1.74 [95% confidence interval (CI) 1.22-2.48], while patients prescribed an ACEI at less than a recommended dose had an RR of 1.24 (95% CI 0.91-1.69) (P = 0.005 for the trend). Our results show that ACEI use at discharge in patients with LVSD is associated with decreased rate of readmission. These findings suggest that compliance with the ACEI prescribing recommendations listed in clinical practice guidelines for patients with heart failure due to LVSD confers benefit.


Crown jewel-structured Au/Pd nanoclusters as novel catalysts for aerobic glucose oxidation.
Low-coordination Au sites have been proved to play a key role in defining the catalytic activity of Au nanoclusters (NCs). At the present time, it is still of great interest and challenge to design and synthesize catalysts containing the desired amount of low-coordinated Au atoms by a simple, easy, and large-scale method. In this study, PVP-protected 'crown jewel'-structured Au/Pd (CJ-Au/Pd) catalyst containing an abundance of top Au atoms were prepared by redox replacement reaction between Pd NCs and Au3+ ions. The catalytic activity of the CJ-Au/Pd NCs for aerobic glucose oxidation is about 3 times higher than that of the Au/Pd alloy NCs prepared by alcohol reduction method, although all of these NCs possess almost the same particle size.


Graft-versus-host disease: a case report of a rare but reversible cause of constrictive pericarditis.
Constrictive pericarditis (CP), although an uncommon cause of heart failure, requires specialist multidisciplinary input and multi-modality imaging to identify the underlying aetiology and treat potentially reversible causes. We report the case of a 74-year-old gentleman referred for assessment of progressive exertional dyspnoea and peripheral oedema, 30 months following treatment of acute myeloid leukaemia with high-dose chemotherapy and allogeneic stem cell transplantation. Clinical examination and cardiac imaging revealed a small pericardial effusion and pericardial thickening with constrictive physiology; however, no aetiology was identified despite diagnostic pericardiocentesis. The patient required recurrent hospital admissions for intravenous diuresis, therefore, following multidisciplinary discussions, surgical partial pericardectomy was performed. Histology suggested graft-vs.-host disease (GvHD) and post-operatively, the patient improved clinically. Following immunomodulatory therapy with ruxolitinib for both pericardial and pulmonary GvHD, his functional status improved further with no subsequent hospital admissions. Although pericardial disease in cancer patients is common, CP is unusual. Determining the underlying aetiology is important for subsequent management, and here, we describe the use of multi-modality imaging to diagnose a rare cause, GvHD, which responded to surgical treatment and immunomodulatory therapy.


Brain perfusion single photon emission computed tomography findings in patients with posttraumatic anosmia and comparison with radiological imaging.
Different techniques in neuroimaging have been proposed for assessment of olfactory dysfunction but they are not without limitations. Recently, some studies showed the usefulness of single photon emission-computed tomography (SPECT) in evaluation of patients with posttraumatic anosmia. This study was designed to assess the possible diagnostic value of SPECT findings in patients with posttraumatic anosmia in comparison with magnetic resonance imaging (MRI)/CT imaging. Sixteen patients who had head trauma and consequently anosmia, which was defined according to Cain's identification test, were included in this study. Two nonanosmic groups, traumatic patients and nontraumatic healthy individuals, were selected as control groups for this study. Qualitative and semiquantitative brain perfusion SPECT was performed by measuring the uptake ratio of the orbital frontal cortex to occipital pole in the sagittal projections (uptake index). All 16 target patients had a previous CT scan and/or MRI. Semiquantitative and qualitative brain perfusion SPECT were compared with radiological imaging. Semiquantitative assessment of brain perfusion SPECT revealed remarkable orbital frontal hypoperfusion as compared with two control groups. 87.5% of anosmic patients showed orbital frontal hypoperfusion (-2 SD below the lowest level in healthy controls). In addition, the semiquantitative SPECT method detected more orbitofrontal abnormality than the qualitative method or radiological imaging (MRI and/or CT). Findings suggest that by using SPECT, posttraumatic anosmia corresponds to the hypoperfusion in the orbital frontal cortex in a great number of patients. Because of its availability, rather low cost, technical ease, and possibility to obtain objective quantitative information, brain perfusion SPECT can be complementary to other diagnostic techniques in the evaluation of olfactory function, although additional neurophysiological and imaging studies are needed.


Factors associated with the health status of internally displaced persons in northern Uganda.
Globally, there are over 24 million internally displaced persons (IDPs) who have fled their homes due to violence and insecurity but who remain within their own country. There have been up to 2 million IDPs in northern Uganda alone. The objective of this study was to investigate factors associated with mental and physical health status of IDPs in northern Uganda. A cross-sectional survey was conducted in November 2006 in IDP camps in the Gulu and Amuru districts of northern Uganda. The study outcome of physical and mental health was measured using the SF-8 instrument, which produces physical (PCS) and mental (MCS) component summary measures. Independent demographic, socio-economic, and trauma exposure (using the Harvard Trauma Questionnaire) variables were also measured. Multivariate regression linear regression analysis was conducted to investigate associations of the independent variables on the PCS and MCS outcomes. 1206 interviews were completed. The respective mean PCS and MCS scores were 42.2 (95% CI 41.32 to 43.10) and 39.3 (95% CI 38.42 to 40.13), well below the instrument norm of 50, indicating poor health. Variables with negative associations with physical or mental health included gender, age, marital status, income, distance of camp from home areas, food security, soap availability, and sense of safety in the camp. A number of individual trauma variables and the frequency of trauma exposure also had negative associations with physical and mental health. This study provides evidence on the impact on health of deprivation of basic goods and services, traumatic events, and fear and uncertainty amongst displaced and crisis affected populations.


A Randomized Controlled Study to Test Front-of-Pack (FOP) Nutrition Labels in the Kingdom of Saudi Arabia.
One common strategy for governments to tackle the non-communicable disease (NCD) epidemic is front-of-package (FOP) nutrition labeling. The Kingdom of Saudi Arabia (KSA) is considering implementing a new FOP label that is based on either France's Nutri-Score (NS), which labels all foods (A = healthiest to E = least healthy) based on overall nutritional quality, or the Chilean warning label (WL) approach, which identifies foods to avoid based on select nutritional characteristics. Using a fully functional online grocery store, this study aimed to test these two promising FOP strategies by randomizing 656 KSA adults into one of the three versions of the store to complete a hypothetical grocery shop: no-label (control), NS, and WL. The NS was modified with a sugar percentage tag given that reducing sugar consumption is one of KSA's public health goals. We found that both modified NS labels and Chilean warning labels positively influenced food and beverage choices among KSA participants, but there were differential effects across the two labels. Relative to the control, NS improved the overall diet quality of the shopping baskets, measured by the weighted (by the number of servings) average NS point (ranging from 0, least healthy, to 55, healthiest), by 2.5 points [95% CI: 1.7, 3.4; p < 0.001], whereas results for WL were not statistically significant (0.6 points [95% CI: -0.2,1.5]). With respect to each nutritional attribute, we found that NS reduced sugar intake per serving, whereas WL was effective at decreasing energy and saturated fat intake per serving from food and beverages purchased. Our results suggest that the NS approach that identifies the healthiness of all foods using a holistic approach appears preferable if the purpose of the label is to improve overall diet quality as opposed to addressing select nutrients to avoid.


Topological sectors, dimer correlations, and monomers from the transfer-matrix solution of the dimer model.
We solve the classical square-lattice dimer model with periodic boundaries and in the presence of a field t that couples to the (vector) flux, by diagonalizing a modified version of Lieb's transfer matrix. After deriving the torus partition function in the thermodynamic limit, we show how the configuration space divides into topological sectors corresponding to distinct values of the flux. Additionally, we demonstrate in general that expectation values are t independent at leading order, and obtain explicit expressions for dimer occupation numbers, dimer-dimer correlation functions, and the monomer distribution function. The last of these is expressed as a Toeplitz determinant, whose asymptotic behavior for large monomer separation is tractable using the Fisher-Hartwig conjecture. Our results reproduce those previously obtained using Pfaffian techniques.


Hepatic glycogen metabolism and insulin receptor status after long-term peripheral insulin delivery in the islet-transplanted diabetic rat.
Severely diabetic (0.15 g/kg streptozocin) rats were transplanted with fetal pancreatic islets under the renal capsule to model peripheral insulin delivery, or into the splenic pulp to model portal delivery. In both groups of transplanted rats, weight gain and blood glucose concentrations were normal. Peripheral insulin delivery abolished the physiologic portal-peripheral insulin concentration gradient but was not associated with peripheral hyperinsulinemia. Incorporation of 3H2O into liver glycogen and the increase in hepatic glycogen concentration after a meal were normal in animals receiving insulin peripherally for 10 wk. Activation of liver glycogen synthase in response to the meal was also normal. Hepatic insulin receptor status in animals with peripheral insulin delivery was identical to that of normal control and splenic pulp islet-transplanted rats. The findings indicate that portal insulin delivery is not a prerequisite for normal hepatic glycogen metabolism in the rat, and that receptor upregulation and increased hepatic extraction of insulin are unlikely to explain the normal hepatic metabolism with peripheral insulin delivery.


Differential response of individual uterine cell types from immature rats treated with estradiol.
The separation of viable epithelial, stromal, and myometrial cells from immature rat uteri is described. The integrity of the separated cells was established by their ability to grow in culture and to exclude trypan blue and by transmission and scanning microscopy. Epithelial preparations contain insignificant contamination by other cells. Stromal fractions are estimated to contain 10% epithelial contamination. Myometrial fractions probably contain significant contamination by stroma, but the amount is difficult to quantify. The three cell types separated from untreated rats or from rats treated with 17 beta-estradiol (E2) differ from each other physiologically. Control epithelial cells incorporated more tritiated cytidine per microgram DNA than stromal or myometrial cells. 17 beta-Estradiol enhanced incorporation of tritiated cytidine into RNA of epithelial cells but not stromal or myometrial cells. RNA to DNA ratios of cells from untreated rats were 1.0 (epithelial), 0.5 (stromal), and 0.6 (myometrial). RNA to DNA ratios rose approximately 30% in all cell types after E2. Estrogen receptor (ER) concentrations, determined by Scatchard analysis under exchange conditions, also differed in the three cell types. Nuclear ER concentrations (as measured in crude nuclear fractions) were significantly higher (P less than 0.01) in epithelial and stromal cell fractions from untreated animals than in the myometrial fraction, i.e. 5.5, 3.8, and 1.2 fmol/microgram DNA, respectively. The chief effect of E2 administration was a significant increase (P less than 0.05) in cytosol ER of all cell types. Epithelial cells had the highest cytosol ER concentration, increasing from 0.5 to 3.1 fmol/microgram DNA 48 h after E2 administration. Although the myometrial cells had the lowest ER concentration, they contained 84-89% of the entire uterine ER by virtue of the proponderance of myometrium in the whole uterus. The differing responses of epithelial and stromal cells, therefore, are diluted or masked by the ER content of the myometrium in assays of whole uterus. Although the total number of ER sites in the cytosol and nucleus (16,900-32,100 sites/cell) in separated stromal cells at various times after E2 stimulation was similar to ER concentrations (20,000-30,000 sites/cell) previously reported for the whole uterus, the partition of ER between cytosol and nucleus (10:90) was different, favoring the nucleus even before E2 administration. ER began to appear in increased amounts in the cytosol only 24 h post E2 administration. When tritiated E2 was given in vivo and its specific binding was assessed in the uterine cells subsequently separated, ER partition between cytosol and nucleus was also heavily in favor of the nucleus. However, when whole uterus was assayed, the partition of ER between cytosol and nucleus (90:10) was exactly the opposite. Possible reasons for this unusual finding are discussed.


One-pot quadruple/triple reaction sequence: a useful tool for the synthesis of natural products.
Multiple reactions in one pot has always been a useful technique for synthetic organic chemists, as it can minimizes solvent usage, time and the number of purification steps when compared to individual multi-step syntheses. In line with this, here in this perspective we discuss a one-pot quadruple/triple reaction sequence comprising an enyne ring-closing metathesis/cross-metathesis/Diels-Alder/aromatization for the synthesis of natural products setting.


Murine hepatic beta-galactoside alpha 2,6-sialyltransferase gene expression involves usage of a novel upstream exon region.
ST6Gal I (beta-galactoside alpha 2,6-sialyltransferase, SiaT-1, ST6N, EC 184.108.40.206) mediates the attachment of the alpha 2,6-sialyl linkage common on N-linked glycans. Previous work suggests substantial inter-species conservation in SIAT1, the gene encoding ST6Gal I. In human and in rat, hepatic-specific SIAT1 transcription is initiated at Exon I. Here we report a surprising departure in the structural organization of the murine ST6Gal I gene. By a combination of primer extension analysis, 5'-RACE analysis, and analysis of genomic sequences, we show that the murine hepatic ST6Gal I mRNA contains a novel region 5' of Exon I. This novel sequence is encoded on a discrete upstream exon, Exon H. In contrast to human and rat hepatic ST6Gal I, the murine mRNA is transcriptionally initiated at the start of Exon H. Differential mRNA blot analysis indicates that transcripts containing Exon H sequences are preferentially expressed in liver.


Improved liquid chromatographic assay for the analysis of pirmenol in plasma and urine.
A sensitive, specific, and rapid high-performance liquid chromatographic procedure was developed for the determination of pirmenol in human biological fluids. Plasma or urine samples were alkalinized and extracted with cyclohexane. The organic extract was evaporated to dryness, reconstituted with the mobile phase, and then chromatographed on a microparticulate spherical trimethylsilane stationary phase with UV detection at 254 nm. The procedure for the assay of pirmenol in plasma was linear from 0.125 to 5.0 micrograms/mL. The reproducibility of the peak area ratios of the standard curves had relative standard deviations between 7.7 and 1.8% and a relative error of 0-4.6% over the linear range. The accuracy for the determination of pirmenol in human plasma containing 0.5, 2.5, and 4.0 micrograms/mL had relative errors of 9.0, 3.8, and 3.6%, respectively. Thirty compounds were tested and found not to interfere in the assay of the drug in plasma, and the method was found to be suitable for clinical samples. The urine procedure was linear between 1.0 and 30.0 micrograms/mL. The reproducibility of the peak areas of the standard curves had relative standard deviations that ranged from 1.9 to 6.2% over the linear range. The accuracy for the determination of pirmenol in human urine containing 5.0, 17.5, and 25.0 micrograms/mL had relative errors of 1.4, 0.5, and 2.8%, respectively.


High-throughput operating room system for joint arthroplasties durably outperforms routine processes.
Recent publications have focused on increased operating room (OR) throughput without increasing total OR time. The authors hypothesized that a system of parallel processing for lower extremity joint arthroplasties sustainably reduces nonoperative time and increases throughput. The high-throughput parallel processing strategy included neuraxial anesthesia performed in an "induction room" adjacent to the OR, patient selection, an additional circulating nurse, and end-of-case transfer of care to a recovery room nurse who transported the patient from the OR to recovery. Instruments and supplies were prepared in a dedicated sterile setup area. Data were extracted from administrative databases. Group comparisons used standard statistical methods; statistical process control was used to evaluate performance over time. There were 688 historic control cases from 299 days over 16 months, and 905 high-throughput cases from 304 days spanning 24 consecutive months starting September 1, 2004. Throughput increased from 2.6 +/- 0.7 (mean +/- SD) to 3.4 +/- 0.8 arthroplasties per day per room. Nonoperative time decreased by 36 min (or 50%) per case. Operative time also decreased by 14 min (12%) per case. The end time for the high-throughput OR day was only 16 min later than control. Nonoperative time, operative time, and throughput remained significantly improved after 2 yr of operation. Contribution margin increased 19.6%. Reorganizing the perioperative work process for total joint replacements sustainably increased OR throughput. Because joint arthroplasties generated a positive margin greater than the incremental cost, the high-throughput system improved financial performance.


Rebound Catatonia Associated With Injectable Paliperidone.
Paliperidone is an atypical antipsychotic medication commonly used to treat schizophrenia, schizoaffective disorder, and bipolar disorder. It is a metabolite of risperidone and has a similar mechanism of action, primarily blocking dopamine 2 receptors (D2 receptors) in the brain. Paliperidone has various adverse effects, including extrapyramidal symptoms, weight gain, and metabolic disturbances. Catatonia is rare but severe side effects can occur in the context of an underlying psychiatric, neurologic, or general medical condition. Paradoxically, antipsychotics for treating schizophrenia or bipolar spectrum disorders can precipitate or worsen catatonic symptoms. The report suggests that 17-19% of all cases diagnosed as catatonia due to other medical conditions are medication-induced. Catatonia is a neuropsychiatric syndrome that presents as a cluster of psychomotor signs and symptoms resulting in movement and behavior aberrations. Various symptoms, including mutism, stupor, rigidity, and abnormal movements, characterize catatonia. Catatonia is a potentially life-threatening condition requiring prompt recognition and management. Here, we present a case of a patient with catatonia associated with long-acting injectable paliperidone intramuscular therapy in a patient with schizophrenia.


Children's fearfulness as a moderator of parenting in early socialization: Two longitudinal studies.
Findings from 2 longitudinal studies replicate and considerably extend past work on child temperament as a moderating link between parenting and successful socialization outcomes. In Study 1 (N = 106 mothers and children), child fearfulness, mother-child positive relationship, and maternal power assertion were assessed at 22 and 33 months; the outcome--children's moral self--was assessed at 56 months. In Study 2 (N = 102 mothers, fathers, and children), child fearfulness and parent-child positive relationship were assessed at 7 and 15 months; parents' power assertion was assessed at 15 months. The outcomes were children's receptive, willing stance toward the parent at 25 months, and rule-compatible conduct without supervision at 38 months. Child fearfulness significantly moderated the impact of parenting: In both studies, for relatively fearless children, mother-child positive relationship predicted future successful socialization outcomes in mother-child dyads. There was no analogous moderation effect in father-child dyads in Study 2. For relatively fearful children, fathers' power assertion in Study 2 predicted poor socialization outcomes. All Temperament x Parenting interactions appeared limited to measures obtained in the 2nd year.


Preparation of polymer nano- and microspheres by vinyl polymerization techniques.
The methodologies and techniques of producing polymer particles (nano- and microspheres) from vinyl monomers are described, with an emphasis on laboratory preparations. Five different techniques are employed in the preparation of polymer micro- and nanoparticles from vinyl monomers. Emulsion polymerization provides particles of about 50-200 nm in diameter, emulsifier free emulsion polymerization produces particles of about 100-1000 nm (0.1-1.0 micron), dispersion polymerization gives particles in the region of 0.3-10 micron, and suspension polymerization leads to the formation of particles of about 20 micron-2 mm. The gap in the 10-20 micron region may be filled by either seeded polymerization or by more elaborately performed suspension polymerization. All of the four techniques mentioned above produce regular, spherical particles. Precipitation polymerization, on the other hand, gives irregularly shaped particles in the range of 0.1-10 micron. An attempt is made to clarify the underlying differences between these techniques and to say how they are practised in the laboratory.