Regulation of N-cadherin-based cell-cell interaction by JSAP1 scaffold in PC12h cells.
We previously reported that the level of c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1), a scaffold protein for JNK signaling, increases dramatically during nerve growth factor (NGF)-induced differentiation of PC12h cells. In the present study, we investigated the function of JSAP1 during PC12h cell differentiation by knocking down the level of JSAP1. The depletion of JSAP1 caused NGF-treated PC12h cells to form aggregates and impaired their differentiation. The aggregation was not observed in JSAP1-depleted cells that were untreated or treated with epidermal growth factor. Immunocytochemical studies indicated that N-cadherin, but not E-cadherin, was localized to sites of cell-cell contact in the aggregated cells. Furthermore, an inhibitory anti-N-cadherin antibody completely blocked the aggregation. Taken together, these results suggest that JSAP1 regulates cell-cell interactions in PC12h cells specifically in the NGF-induced signaling pathway, and does so by modulating N-cadherin.


Decellularized cartilage matrix as a novel biomatrix for cartilage tissue-engineering applications.
Damage of cartilage structures in the head and neck region as well as in orthopedic sites are frequently caused by trauma, tumor resection, or congenital defects. Despite a high demand in many clinical fields, until today, no adequate cartilage replacement matrix is available for these fields of application. Materials that are clinically applied for joint cartilage repair still need optimization due to difficult intraoperative handling and risk of early mechanical damage. We have developed and applied a novel chemical process to completely decellularize and sterilize human and porcine cartilage tissues (meniscus cartilage and nasal septum) to generate a new type of bioimplant matrix. To characterize this matrix and to determine the effect of the decellularization process, the content of denatured collagen (w(D)) and the content of glycosaminoglycans (GAGs) (w(G)) were determined. Possible cytotoxic effects and cellular compatibility of the matrix in vitro have been examined by seeding processed cartilage biomatrices with human primary chondrocytes as well as murine fibroblasts (L929). Vitality and state of metabolism of cells were measured using MTS assays. Both cell types adhered to scaffold surfaces and proliferated. No areas of growth inhibition or cytotoxic effects were detected. New synthesis of cartilage-specific extracellular matrix was observed. By histological staining, electron microscopy, and μCT analysis, an increase of matrix porosity, complete cell elimination, and high GAG removal were demonstrated. Being from natural-origin, processed xenogenic and allogeneic cartilage biomatrices are highly versatile with regard to shape, size, and biomechanics, making them promising candidates for various biomedical applications.


Hyperoxia in the intensive care unit: why more is not always better.
Hyperoxic inspired gas is essential for patients with hypoxic respiratory failure; it is also suspected, however, as a contributor to the pathogenesis of acute lung injury. Several recent studies in humans, animals, and cell culture have identified mechanisms by which hyperoxia may exert deleterious effects on critically ill patients. This review identifies relevant new findings regarding hyperoxic lung injury in the context of providing guidance for future clinical studies. Recent studies have clarified the roles of both receptor-mediated and mitochondrial cell death pathways in experimental hyperoxic lung injury. Studies in animals demonstrate that hyperoxia interacts with mechanical stretch to augment ventilator-induced lung injury. Finally, studies in humans implicate hyperoxia in impairment of host defense responses to infections. Although hyperoxia has not been conclusively identified as a clinically important cause of lung injury in humans, animal data strongly implicate it. Reports of interaction effects between hyperoxia and both mechanical ventilation and host defense suggest that clinical studies of hyperoxia must take these variables into account. Accumulating data about how hyperoxia initiates cell death provide guidance for development of both biomarkers to identify hyperoxia-induced injury and pharmacological interventions to limit hyperoxia's adverse effects.


Derivation of clinical predictors of failed rescue shock during out-of-hospital ventricular fibrillation.
Failed rescue shocks have been shown to decrease the likelihood of survival in the treatment of out-of-hospital ventricular fibrillation (VF). Avoidance of failed shocks may improve survival. We sought to derive clinical predictors that could be used by emergency medical services (EMS) personnel to identify a subset of VF patients whose first rescue shock is likely to fail, making them candidates for a cardiopulmonary resuscitation (CPR)-first strategy. After gaining institutional review board approval from all three institutions, we merged data from Los Angeles, Pittsburgh, and Royal Oak into a new cardiac arrest database. We used classification and regression tree (CART) analyses to build the model. We defined a failed first rescue shock as one in which there was no return of spontaneous circulation (ROSC); the postshock electrocardiographic (ECG) rhythm was VF, pulseless electrical activity (PEA), or asystole; or subsequent shocks were delivered (indicating that the first shock had failed). The database contains 5,046 cases, of which 1,777 (35%) had VF as the initial ECG rhythm. Sufficient data were present for 748 cases. Using unwitnessed collapse, a response time of >6 minutes, and absence of bystander CPR (BCPR) on EMS arrival as predictors, 35 of 35 (100%, 95% confidence interval [CI] 100-91.4%) cases had failed first rescue shocks. Second shock failure was predicted in 162 of 164 (99%) cases. Unwitnessed collapse, response time>6 minutes, and absence of BCPR may be useful in predicting which VF patients are likely to have failed first shocks and would thereby benefit from a CPR-first strategy. Stacked rescue shocks most often fail, and this outcome can also be predicted.


Expression of periostin and its clinicopathological relevance in gastric cancer.
To investigate the expression and localization of periostin in gastric cancer and its clinical relevance. Reverse transcriptase polymerase chain reaction was used to measure periostin mRNA expression. Western blotting was carried out to detect periostin protein expression. Immunohistochemistry was performed to localize and quantify the expression of periostin in benign gastric diseases and gastric cancer, and immunostaining results were correlated with gastric cancer pathological stages. Periostin expression was low at both mRNA and protein levels in normal gastric tissues, but was overexpressed in gastric cancer tissues. Immunohistochemical staining revealed that periostin was overexpressed in primary gastric cancer, as well as in metastatic lymph nodes, but only faint staining was found in benign gastric ulcers. By quantitative analysis of the immunostaining results, periostin expression was increased 2.5-4-fold in gastric cancer, compared to that in benign gastric disease, and there was a trend toward increasing periostin expression with tumor stage. This observation demonstrated that periostin was overexpressed in gastric cancer and lymph node metastasis, which suggests that periostin plays an important role in the progression and metastasis of gastric cancer.


Effectiveness of stop smoking interventions among adults: protocol for an overview of systematic reviews and an updated systematic review.
Tobacco smoking is the leading cause of cancer, preventable death, and disability. Smoking cessation can increase life expectancy by nearly a decade if achieved in the third or fourth decades of life. Various stop smoking interventions are available including pharmacotherapies, electronic cigarettes, behavioural support, and alternative therapies. This protocol outlines an evidence review which will evaluate the benefits and harms of stop smoking interventions in adults. The evidence review will consist of two stages. First, an overview of systematic reviews evaluating the benefits and harms of various stop smoking interventions delivered in or referred from the primary care setting will be conducted. The second stage will involve updating a systematic review on electronic cigarettes identified in the overview; randomized controlled trials will be considered for outcomes relating to benefits while randomized controlled trials, non-randomized controlled trials, and comparative observational studies will be considered for evaluating harms. Search strategies will be developed and peer-reviewed by medical information specialists. The search strategy for the updated review on e-cigarettes will be developed using that of the candidate systematic review. The MEDLINE®, PsycINFO, Embase, and the Cochrane Library electronic databases will be searched as of 2008 for the overview of reviews and from the last search date of the selected review for the updated review. Organizational websites and trial registries will be searched for unpublished or ongoing reviews/studies. Two reviewers will independently screen the title and abstracts of citations using the liberal accelerated method. Full-text screening will be performed independently by two reviewers. Extracted data will be verified by a second reviewer. Disagreements regarding full-text screening and data extraction will be resolved by consensus or third-party adjudication. The methodological quality of systematic reviews, risk of bias of randomized and non-randomized trials, and methodological quality of cohort studies will be evaluated using AMSTAR 2, the Cochrane risk of bias tool, and a modified version of the Scottish Intercollegiate Guidelines Network critical appraisal tool, respectively. The GRADE framework will be used to assess the quality of the evidence for outcomes. The evidence review will evaluate the benefits and harms of various stop smoking interventions for adults. Findings will be used to inform a national tobacco cessation guideline by the Canadian Task Force on Preventive Health Care. PROSPERO (CRD42018099691, CRD42018099692).


Evaluation of liver tissue damage and grasp stability using finite element analysis.
Minimizing tissue damage and maintaining grasp stability are essential considerations in surgical grasper design. Most past and current research analyzing graspers used for tissue manipulation in minimally invasive surgery is based on in vitro experiments. Most previous work assessed tissue injury and grasp security by visual inspection; only a few studies have quantified it. The goal of the present work is to develop a methodology with which to compute tissue damage magnitude and grasp quality that is appropriate for a wide range of grasper-tissue interaction. Using finite element analysis (FEA), four graspers with varying radii of curvature and four graspers with different tooth sizes were analyzed while squeezing and pulling liver tissue. All graspers were treated as surgical steel with linear elastic material properties. Nonlinear material properties of tissue used in the FEA as well as damage evaluation were derived from previously reported in vivo experiments. Computed peak stress, integrated stress, and tissue damage were compared. Applied displacement is vertical and then horizontal to the tissue surface to represent grasp and retraction. A close examination of the contact status of each node within the grasper-tissue interaction surface was carried out to investigate grasp stability. The results indicate less tissue damage with increasing radius of curvature. A smooth wave pattern reduced tissue damage at the cost of inducing higher percentage of slipping area. This methodology may be useful for researchers to develop and test various designs of graspers. Also it could improve surgical simulator performance by reflecting more realistic tissue material properties and predicting tissue damage for the student.


Bioactive Glasses: From Parent 45S5 Composition to Scaffold-Assisted Tissue-Healing Therapies.
Nowadays, bioactive glasses (BGs) are mainly used to improve and support the healing process of osseous defects deriving from traumatic events, tumor removal, congenital pathologies, implant revisions, or infections. In the past, several approaches have been proposed in the replacement of extensive bone defects, each one with its own advantages and drawbacks. As a result, the need for synthetic bone grafts is still a remarkable clinical challenge since more than 1 million bone-graft surgical operations are annually performed worldwide. Moreover, recent studies show the effectiveness of BGs in the regeneration of soft tissues, too. Often, surgical criteria do not match the engineering ones and, thus, a compromise is required for getting closer to an ideal outcome in terms of good regeneration, mechanical support, and biocompatibility in contact with living tissues. The aim of the present review is providing a general overview of BGs, with particular reference to their use in clinics over the last decades and the latest synthesis/processing methods. Recent advances in the use of BGs in tissue engineering are outlined, where the use of porous scaffolds is gaining growing importance thanks to the new possibilities given by technological progress extended to both manufacturing processes and functionalization techniques.


Necrotizing infections of the perineum.
During a 6-year period, 10 patients were treated for severe necrotizing infections of the perineum (Fournier's gangrene) at the Edward Hines Veterans Administration Hospital (Hines, Ill). All were male, and their average age was 60 years. When known, duration of symptoms was 2 to 5 days. Prodromal signs such as edema, erythema, and pain frequently developed into rapidly spreading, full-thickness cutaneous gangrene in less than 24 hours. All patients had significant concomitant disease; 60% were diabetic. All patients had expedient and aggressive initial debridement, usually within 24 hours of presentation to the surgical service. Each patient had a "second-look" debridement within 1 or 2 days. Debridement was done an average of 2.6 times per patient. The cause of the infection was noted in seven patients--five with perirectal abscess and two with urethral trauma. Suprapubic catheters were placed in both patients with urethral trauma. Diverting colostomy was done on two patients who had perirectal abscess as a nidus; eight patients were treated without colostomy. Polymicrobial bacteriologic flora were found in all patients, with a predominance of Escherichia coli, Bacteroides sp, and staphylococci. Broad spectrum antibiotics and early nutritional supplementation were given. Hospital stay averaged 4 weeks (range, 3 to 12 weeks). One patient died (mortality of 10%). Successful management of these patients requires expedient diagnosis, aggressive nutritional supplementation, and early and repeated debridement as clinically indicated. We have not found diverting colostomy to be a necessary part of the management of these patients even when the nidus is perirectal.


Thrombosis: new culprits in an old disorder.
Venous thrombosis is a cause of considerable morbidity and mortality. Over the past several years, several new causes of thrombophilia have been identified and have dramatically altered the approach to patients presenting with thrombosis. Newly described abnormalities associated with thrombophilia include the syndrome of activated Protein C resistance (APCR), the prothrombin 20210A mutation, hyperhomocysteinemia, and elevated levels of coagulation factors VIII and XI. Clinicians can now frequently determine causes of thromboses that have previously been deemed idiopathic. Though the risk factors for VTE are becoming better defined, the cost-effective approach to diagnosis and therapeutic implications are not entirely clear at this point.


Pyrrolidine dithiocarbamate inhibits induction of immunoproteasome and decreases survival in a rat model of amyotrophic lateral sclerosis.
Pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear transcription factor kappa-B (NF-kappaB) and an antioxidant, has beneficial effects in animal models of various diseases, including arthritis, brain ischemia, spinal cord injury, Alzheimer's disease, and Duchenne muscular dystrophy. Because inflammation and oxidative damage are also hallmarks of amyotrophic lateral sclerosis (ALS), we studied the effect of oral PDTC treatment on G93A-superoxide dismutase 1 (SOD1) transgenic (TG) rat model of human ALS and observed that PDTC treatment significantly decreases the survival. PDTC treatment evoked the end stage of the disease at 121 +/- 21 days, whereas untreated TG animals reached the end stage at 141 +/- 13 days (p < 0.01). The DNA binding activity of NF-kappaB was not altered in G93A-SOD1 TG rats by PDTC treatment. The copper concentration in the spinal cord was increased after PDTC treatment both in G93A-SOD1 TG and wild-type rats, suggesting that increased copper may enhance the neurotoxicity of mutant SOD1. The amount of ubiquitinated proteins were significantly higher and proteasomal activity was decreased in the spinal cords of PDTC-treated TG rats compared with other groups, suggesting that PDTC treatment decreases proteasome function. Immunoblotting and immunocytochemistry showed that the level of immunoproteasome but not constitutive proteasome was increased in glia of G93A-SOD1 TG rats along with disease development. PDTC treatment completely blocked the induction of immunoproteasome expression without affecting constitutive proteasome. These results suggest that PDTC acts as an immunoproteasome inhibitor in mutant SOD1 rats and that immunoproteasome may help the nervous system to cope with deleterious effects of SOD1-G93A mutation.


Factors that influence prescribers in their selection and use of COX-2 selective inhibitors as opposed to non-selective NSAIDs.
To identify factors that influence prescribers in their selection and use of cyclo-oxygenase-2 (COX-2) selective inhibitors as opposed to non-selective non-steroidal anti-inflammatory drugs (NSAIDs) and report the tendency to co-prescribe gastro-protection with these agents. All 579 general practitioners (GPs) in one geographical area, Lothian, Scotland, UK. Postal questionnaires; simple and factorial designed case series questionnaire. Categorisation of responses to clinical and non-clinical factors into highly, partially or not influential. The quantitative influence of the most prominent clinical factors on prescribing choice and the tendency of co-prescription of gastro-protection with these agents. Responses from 229 (40%) GPs suggested the following as most influential: Drug Evaluation Panel recommendations, Lothian Joint Formulary, local practice formulary, history of peptic ulcer disease (PUD), history of gastro-intestinal (GI) adverse effects with NSAIDs and advanced age. Advice from other physicians, patient demand, history of alcohol gastritis, history of gastro-oesophageal reflux disease, history of functional dyspepsia, concomitant use of low dose aspirin and concomitant use of gastro-protective agents were regarded to have moderate influence. Information directly from pharmaceutical industry and regular smoking were regarded as having weak influence. An 18% response to the factorial designed questionnaire using the most prominent clinical factors suggested that history of either GI adverse effects associated with non-selective NSAIDs or PUD resulted in more pronounced increase in the frequency (15%) of decision to prescribe COX-2 selective inhibitors than advanced age (10%). Concomitant use of low dose aspirin had little effect on GPs' decisions. The mean percentage of GPs choosing to co-prescribe gastro-protection was higher with non-selective NSAIDs (64%) than with COX-2 selective inhibitors (22%). Local authoritative guidance and history of GI complications highly influenced the GPs in their use and choice of either COX-2 selective inhibitors or non-selective NSAIDs. As expected the use of gastro-protection was more frequently chosen with non-selective NSAIDs than COX-2 selective inhibitors.


Enhancing dream pleasure with Senoi strategy.
A strategy to increase pleasure and reduce displeasure in dreaming and dream-related behaviors involved three skill sessions in which participants (N = 63) practiced (a) positive expectations for content and outcome of dreams; (b) thought stopping for unpleasant dreams; and (c) self-suggestion that dreams would be recalled and would be pleasant. Findings from pre- and post-survey schedules (pleasure and displeasure ) and from a daily dream behavior check list showed that dreaming and behaviors associated with dreaming were significantly more pleasurable 12 weeks after the dream interventions and maintenance of a daily dream record. A 6-month follow-up showed the changes to be still in effect.


[Transesophageal atrial pacing in bradyarrhythmia disorders of heart rhythm (preliminary report)].
The aim of the paper was to assess the contribution of transesophageal atrial stimulation in bradyarrhythmic derangements of the heart rhythm. The main purpose was to make the diagnostic simpler and safer. Since the series of patients involved is small, our results are to be considered as a preliminary report. (1) When only dysfunction of the sinoatrial node is involved, the method yields results comparable to those obtained by invasive electrophysiological examination. Compared to the latter, invasive approach, the great advantage of the presented method is its repeatability and simplicity. (2) Greater caution is required on evaluating the conductivity, as it can not be reliably determined in the His-Purkinje system. (Tab. 2, Fig. 5, Ref. 12.)


[C(6)H(5)NH(CH(3))(2)](2)Te(2)I(10): secondary I...I bonds build up a 3D network.
The crystal structure of [C(6)H(5)NH(CH(3))(2)](2)Te(2)I(10) consists of the N,N-dimethylanilinium cation and a hitherto unreported tellurium iodide anion Te(2)I(10)(2)(-) [crystal data: C(8)H(12)NTeI(5), monoclinic, P2(1)/c, a = 9.4787(2) A, b = 14.2874(3) A, c = 13.6869(3) A, beta = 95.1918(8) degrees, V = 1845.96(7) A(3), Z = 4]. The Te(2)I(10)(2)(-) dianion is based on two edge-sharing TeI(6)(2)(-) octahedra, and interestingly, it builds up a three-dimensional Te(IV)-I open framework through extensive interconnecting I.I contacts. These I.I contacts (3.66-3.80 A) are significantly shorter than the corresponding sum of van der Waals radii (4.0 A) and may potentially promote charge carrier migration throughout the Te-I network. This material can also be drop-cast into thin films from a heated DMF solution.


An adaptive state estimator for detecting contaminants in bioreactors.
An algorithm is presented for detecting the appearance of contaminants during batch or fed-batch fermentations, using only presently available on-line measurements. Its adaptive nature enables it to rely on almost no prior knowledge of the real process. The necessary on-line measurements are total biomass and its production rate; it is also shown how a physical variable such as oxygen uptake can be used alone instead. The algorithm's properties are studied theoretically and through simulations. These were confirmed by on-line experimental results, obtained with a Yeast culture, both pure and contaminated by a Bacteria. The algorithm does not detect contaminants when none are there, and it also provides a convergent estimate of a pure culture's specific growth rate. Contaminated cultures are recognized by the algorithm, and this detection can be made more or less conservative. After detection, the various estimates may diverge, due to general observability difficulties, though this divergence can itself be monitored. Moreover, the algorithm is easy to tune and its qualitative behavior is quite insensitive to its adjustable parameters. A practical criterion and scheme for implementation are proposed. The generality of the approach, which far exceeds the experimental system used, is finally discussed.


Paritaprevir/ritonavir-ombitasvir and dasabuvir, the 3D regimen for the treatment of chronic hepatitis C virus infection: a concise review.
The treatment for chronic hepatitis C has been revolutionized with the development of direct-acting antiviral agents. Several regimens have been approved and are currently used in clinical practice, treating a wide range of patient populations infected with hepatitis C. The interferon-free combination of paritaprevir/ritonavir-ombitasvir and dasabuvir (PrOD or the three-drug [3D] regimen) with or without ribavirin is indicated for the treatment of chronic hepatitis C in both treatment-naïve and experienced patients infected with genotype 1, including those coinfected with HIV and patients post-liver transplantation. More recently, paritaprevir/ritonavir-ombitasvir (PrO, or 2D regimen) has been approved in hepatitis C virus patients infected with genotype 4. This review will summarize pharmacokinetic and clinical efficacy data for the 3D regimen in an attempt to help the clinicians delineate its place in the ever-increasing direct-acting antiviral armamentarium for the treatment of chronic hepatitis C.


Electrochemical Synthesis of New Isoxazoles and Triazoles Tethered with Thiouracil Base as Inhibitors of Histone Deacetylases in Human Breast Cancer Cells.
Histone deacetylases (HDACs) are an attractive drug target for the treatment of human breast cancer (BC), and therefore, HDAC inhibitors (HDACis) are being used in preclinical and clinical studies. The need to understand the scope of the mode of action of HDACis, as well as the report of the co-crystal structure of HDAC6/SS-208 at the catalytic site, provoked us to develop an isoxazole-based lead structure called 4-(2-(((1-(3,4-dichlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)thio) pyrimidin-4-yl) morpholine (5h) and 1-(2-(((3-(p-tolyl) isoxazol-5-yl)methyl)thio) pyrimidin-4-yl) piperidin-4-one (6l) that targets HDACs in human BC cells. We found that the compound 5h or 6l could inhibit the proliferation of BC cells with an IC50 value of 8.754 and 11.71 µM, respectively. Our detailed in silico analysis showed that 5h or 6l compounds could target HDAC in MCF-7 cells. In conclusion, we identified a new structure bearing triazole, isoxazole, and thiouracil moiety, which could target HDAC in MCF-7 cells and serve as a base to make new drugs against cancer.


Dynamically evoked, discrete-threshold electromyography in the extreme lateral interbody fusion approach.
because the psoas muscle, which contains nerves of the lumbar plexus, is traversed during the extreme lateral interbody fusion (XLIF) approach, appropriate nerve monitoring is needed to avoid nerve injury during surgery and prevent approach-related neural deficit. This study was performed to assess the effectiveness of dynamically evoked electromyography (EMG) to detect and prevent neural injury during the XLIF approach. one hundred two patients undergoing XLIF at L3-4 and/or L4-5 were enrolled in a prospective, multicenter, nonrandomized clinical study. The EMG threshold values for each of the 3 successive dilators were recorded at the surface of the psoas muscle, mid-psoas, and on the spine. At each location, the dilators were rotated 360°, taking recordings immediately posterior, superior, anterior, and inferior. For each dilator, the authors noted the rotational position (the angle in degrees) at which the lowest threshold was found. Findings of pre- and postoperative neurological examinations were also recorded. nerves were identified within proximity of the dilators (alert-level EMG feedback) in 55.7% of all cases during the XLIF approach. Although nerves were more commonly identified in the posterior margin (63%), there was significant variability in the location of nerves identified. Despite the fact that the posterior half of the disc space was targeted in 90% of cases, no significant long-lasting neural deficits were identified in any case; 27.5% experienced new iliopsoas/hip flexion weakness and 17.6% experienced new postoperative upper medial thigh sensory loss. Transient motor deficits were identified in 3 patients (2.9%), and all had resolved by the 6-month follow-up visit. the ability to identify and report a discrete, real-time EMG threshold during the transpsoas approach helps to avoid nerve injury and is required for the safe performance of the XLIF procedure. Additionally, nerve location is variable, thus reinforcing the need for real-time directional and proximity information.


Influence of poultry carcass skin sample site on the effectiveness of trisodium phosphate against Listeria monocytogenes.
The aim of this study was to determine the influence of skin sample site on the efficacy of trisodium phosphate (TSP) solutions in reducing Listeria monocytogenes populations on chicken carcasses during refrigerated storage. Chicken skin samples from the legs, the breasts, and the dorsal area inoculated with L. monocytogenes (10(8) CFU/ml) were dipped for 15 min in sterile tap water (control) or in 8, 10, or 12% TSP. L. monocytogenes counts and surface pH values were determined after 0, 1, 3, and 5 days of storage at 2 degrees C. For all sampling times and TSP concentrations, the reductions in L. monocytogenes numbers in breast skin were significantly larger (P < 0.05) than those in leg skin or dorsal skin. No significant differences were found in pH values as an effect of skin site. Our results suggest that skin sampling site is an important factor that needs to be considered when decontamination protocols are developed for poultry carcasses with the TSP treatment.


Electronic excitation spectra of radical anions of cyanoethylenes and cyanobenzenes: symmetry adapted cluster-configuration interaction study.
Electronic excitation spectra of the radical anions of cyanoethylenes (trans-dicyanoethylene and tetracyanoethylene) and cyanobenzenes (1,2-dicyanobenzene: o-DCNB, 1,3-dicyanobenzene: m-DCNB, and 1,4-dicyanobenzene: p-DCNB) were studied by the symmetry adapted cluster-configuration interaction (SAC-CI) method. Theoretical calculations predicted positive electron affinities for all the molecules in good agreement with the experimental observations. Electronic excitation spectra of open-shell radicals is a topic that has not been studied as much as such spectra of closed-shell molecules, but this can be easily addressed using SAC-CI theory. The present paper systematically describes the calculation procedures for radical anions by investigating several basis sets, including anion diffuse and Rydberg functions. The calculated excitation energies were in good agreement with the experimental UV∕NIR (near infrared region) spectra, which had been observed by one of the present authors in 2-methyltetrahydrofuran matrix frozen to transparent glassy solids at 77 K. For p-DCNB, the SAC-CI theoretical spectrum agreed particularly well with the experimental spectrum. An extremely weak π*(SOMO) - π* excitation at 1.41 eV predicted in the present work, but had been overlooked in the previous experimental spectrum published in 1988, was confirmed to be real by a careful re-examination of the old spectrum.


Expression of Hsp70 in kidney cells exposed to ochratoxin A.
Ochratoxin A (OTA) is a possible etiological agent of endemic nephropathy, a chronic renal disease with high prevalence in limited geographic areas. Ochratoxicosis has many characteristics of different pathological states in which heat shock proteins (Hsps) are usually induced. The most inducible heat shock proteins belong to the Hsp70 family. We determined the level of expression of Hsp70 by the Western blot analysis in kidneys of rats treated with low doses of OTA and in LLC-PK1 and MDCK cells exposed to OTA. Estimation of cell viability and release of lactate dehydrogenase (LDH) confirmed the toxic effects of OTA on cultured cells. OTA affects the relative distribution of two Hsp70 isoforms (68-kDa and 74-kDa isoforms), but does not change total amount of Hsp70 in rat kidney. No changes in the Hsp70 level were detected in LLC-PK1 and MDCK cells treated with OTA, although the cells were seriously injured, as was seen from the reduced cell viability and increased release of LDH. Both cell lines were capable of having Hsp70 induced following a heat shock. However, exposure of the cells to OTA before the heat shock challenge prevented Hsp70 induction. Results of the study show that OTA does not induce Hsp70 in rat kidney or in cultured kidney cells. The absence of Hsp70 protective effects in the cells and tissues might be a possible explanation for the cumulative destructive effects of OTA and a silent onset of endemic nephropathy in humans and of OTA-induced experimental nephrotoxicity in animals.


Action potential duration determines sarcoplasmic reticulum Ca2+ reloading in mammalian ventricular myocytes.
After sarcoplasmic reticulum (SR) Ca2+ depletion in intact ventricular myocytes, electrical activity promotes SR Ca2+ reloading and recovery of twitch amplitude. In ferret, recovery of twitch and caffeine-induced contracture required fewer twitches than in rabbit or rat. In rat, there was no difference in action potential duration at 90% repolarization (APD90) at steady state (SS) versus at the first post-depletion (PD) twitch. The SS APD90 was similar in ferret and rabbit (but longer than in rat). However, compared to SS, the PD APD90 was lengthened in ferret, but shortened in rabbit. When rabbit myocytes were subjected to AP-clamp patterns during SR Ca2+ reloading (ferret- or rabbit-type APs), reloading was much faster using the ferret AP templates. We conclude that the faster SR Ca2+ refilling in ferret is due to the increased Ca2+ influx during the longer PD AP. The PD versus SS APD90 difference was suppressed by thapsigargin in ferret (indicating Ca2+ dependence). In rabbit, the PD AP shortening depended on the preceding diastolic interval (rather than Ca2+), because rest produced the same AP shortening, and SS APD90 increased as a function of frequency (in contrast to ferret). Transient outward current (Ito) was larger and recovered from inactivation much faster in ferret than in rabbit. Moreover, slow Ito recovery (tau approximately 3 s) in rabbit was a much larger fraction of Ito. Our data and a computational model (including two Ito components) suggest that in rabbit the slowly recovering Ito is responsible for short post-rest and PD APs, for the unusual frequency dependence of APD90, and ultimately for the slower post-depletion SR Ca2+ reloading.


Effects of ketanserin on epicardial coronary arteries after coronary angioplasty in patients with stable angina.
Previous studies have demonstrated the development of vasoconstriction immediately after percutaneous coronary angioplasty (PTCA), distal to the dilated stenosis, presumably resulting from endothelial injury. We have investigated the role of 5-HT2 receptors in mediating vasomotor changes in proximal and distal coronary segments and coronary stenoses, immediately after successful PTCA in patients with chronic stable angina. We compared the effects of the intracoronary infusion of 1 mg ketanserin (5-HT2 receptor antagonist) on proximal and distal coronary arterial segments immediately after PTCA in both vessels subjected to PTCA and control vessels. Coronary diameters, before and after angioplasty and after ketanserin administration, of proximal and distal segments and coronary stenoses were measured by computerized quantitative coronary angiography (CAAS system) in 12 patients (10 male, two female; mean age 54 +/- 6 years) with stable angina subjected to PTCA. After coronary angioplasty, vasoconstriction was observed in the segment distal to the dilated stenosis but not in the distal segments of control vessels (-0.12 +/- 0.04 and -0.02 +/- 0.02 mm respectively; P < 0.05). After ketanserin infusion significant dilatation was found in the distal segments of both PTCA vessels and control vessels, but the dilatation was greater in the PTCA vessels (P < 0.05). No significant changes were found in the proximal segments of either PTCA or control vessels, or at the PTCA site. In conclusion, the vasoconstriction distal to the site of PTCA is mediated, at least in part, via 5-HT2 receptors.


Coordinated functions of Akt/PKB and ETS1 in tubule formation.
We investigated the inter-relationship between two downstream effectors of vascular endothelial growth factor (VEGF), the serine threonine kinase Akt (also known as protein kinase B) and the transcription factor ETS1, during tubulogenesis. Human endothelial cell culture and the in vivo Drosophila tracheal systems are employed in comparative analysis. We show that VEGF stimulates the expression of ETS1 through a phosphatidylinositol-3-kinase (PI3K)/Akt-dependent pathway in primary endothelial cells. Activation of Akt results in vessel formation in vitro, a process that is blocked by expression of antisense ETS1. The functional relationship between ETS and Akt was then tested in the homologous tubular system in Drosophila. Contrary to expectation, ETS1 and Akt did not form a linear positive regulatory pathway in vivo. Instead, genetic analyses suggest that the Drosophila ETS1 homologue Pointed is required for cell motility per se while Drosophila Akt (Dakt1) is responsible for organized and restricted cell movement that is essential for tubule formation. Taken together, our results show that ETS1 and Akt control different aspects of cell motility that are integrated in the precise regulation of vascular tubule formation.


One- and Two-Particle Correlation Functions in the Cluster Perturbation Theory for Cuprates.
The physics of high-Tc superconducting cuprates is obscured by the effect of strong electronic correlations. One way to overcome this problem is to seek an exact solution at least within a small cluster and expand it to the whole crystal. Such an approach is at the heart of cluster perturbation theory (CPT). Here, we developed CPT for the dynamic spin and charge susceptibilities (spin-CPT and charge-CPT), with the correlation effects explicitly taken into account by the exact diagonalization. We applied spin-CPT and charge-CPT to the effective two-band Hubbard model for the cuprates obtained from the three-band Emery model and calculated one- and two-particle correlation functions, namely, a spectral function and spin and charge susceptibilities. The doping dependence of the spin susceptibility was studied within spin-CPT and CPT-RPA, that is, the CPT generalization of the random phase approximation (RPA). In the underdoped region, both our methods resulted in the signatures of the upper branch of the spin excitation dispersion with the lowest excitation energy at the (π,π) wave vector and no presence of low-energy incommensurate excitations. In the high doping region, both methods produced a low energy response at four incommensurate wave vectors in qualitative agreement with the results of the inelastic neutron scattering experiments on overdoped cuprates.


Right atrial thrombus removal with use of the ŌNŌ retrieval device.
Intracardiac masses and specifically right atrial thrombi can be difficult to manage and carry a high mortality rate. Typically, surgical removal or mechanical thrombectomy can be performed though may not be suitable for all patients. We present a unique case of a sickle cell patient with a large pedunculated right atrial thrombus that was successfully extracted using the novel ŌNŌ Retrieval Device.


[Nutrigenomics--about genetics and nutrition].
Nutrigenomics is a promising multidisciplinary field that focus on studying the interactions between nutritional factors, genetic factors and health outcomes. Its goal is to achieve more efficient individual dietary intervention strategies aimed at preventing disease, improving quality of life and achieving healthy aging. Somehow, nutrigenomics has been used for decades in certain rare monogenic diseases such as phenylketonuria. It has the potential to provide a basis for personalized dietary recommendations based on the individual's genetic makeup in order to prevent common multifactorial disorders (such as metabolic syndrome) decades before their clinical manifestation. Preliminary results regarding gene-diet interactions in many diseases are for the most part inconclusive because of the limitations of current designs. Success in this area will require the integration of various disciplines (e.g. biotechnology, medicine, biology, economics) and will require investigators to work on ethnic groups. This knowledge should lead to successful dietary recommendations partly based on genetic factors that may help to reduce disease risk more efficiently than the current universal recommendations based mainly on epidemiological studies. We discuss nutrigenomic issues and show examples for this new, with a wide research area, field of science.


Enhancing Anticancer Potency of a 13-Substituted Berberine Derivative with Cationic Liposomes.
Cationic liposomal formulations of the telomeric G-quadruplex stabilizing ligand, 13-(2-naphthylmethoxy)berberine bromide (1), have been developed with the purpose of delivering 1 into the nucleus of cancer cells for potential telomere targeting. Berberine derivative 1 was encapsulated in various cationic lipids 2-4 by the thin film evaporation method; these lipids are cationic after amine protonation. The most appropriate liposomal berberine formulation was that of 1 and the cholesterol derived cationic lipid 4 in a weight ratio of 1 : 20 with 76.5% encapsulation efficiency of 1. Cellular uptake studies in the HeLa and HT-29 cancer cells lines showed that the liposomal berberine derivative uptake in the cells was higher and more stable than for berberine derivative 1 alone while free 1 was completely decomposed in the cells within 60 min exposure to the cells. Anticancer activity of the liposomal berberine derivative 1 based on 4 was greater than that for the free berberine derivative 1 in the MCF-7, HeLa and HT-29 cell line by 2.3-, 4.9- and 5.3-fold, respectively, and also, interestingly, superior to the anticancer drug doxorubicin against the HT29 cancer cell line.


Suture versus tack fixation of mesh in laparoscopic umbilical hernia repair.
Mesh fixation in laparoscopic umbilical hernia repair is poorly studied. We compared postoperative outcomes of laparoscopic umbilical hernia repair in suture versus tack mesh fixation. Patients who underwent laparoscopic umbilical hernia repair were separated by method of mesh fixation: sutures versus primarily tacks. Medical history and follow-up data were collected through medical records. The primary outcome of this study was the recurrence rates of hernias. Postoperative major and minor complications, such as surgical site infection, small-bowel obstruction, and seroma formation, were regarded as secondary outcomes. Additionally, a telephone interview was conducted to assess postoperative pain, recovery time, and overall patient satisfaction. Eighty-six patients were identified: 33 in the suture group and 53 in the tacks group. The number of emergent cases was increased in the tacks group (6 vs 0; P = .022). Mean follow-up time was 2.7 years for both groups. Documented postoperative follow-up was obtained in 29 (90%) suture group and 31 (58%) tacks group patients. Hernia recurrence occurred in 3 and 2 patients in the sutures and tacks groups, respectively (P was not significant). No differences were found in secondary outcomes, including subjective outcomes from telephone interviews, between groups. There are no differences in postoperative complication rates in suture versus tack mesh fixation in laparoscopic umbilical hernia repair.


Usefulness of urinalysis in following patients with distal ureterolithiasis.
The determine the usefulness of urinalysis in monitoring patients with distal ureterolithiasis. Patients with microhematuria who were found to have a distal ureteral stone and who were candidates for conservative management were enrolled in the study. Patients were typically seen in clinic at 1 to 2 weeks after initial diagnosis and reassessed. A urinalysis, including office dipstick and automated laboratory analysis using the IQ 200 IRIS analyzer, were performed. The absence or presence of microhematuria was determined and compared with results of repeated unenhanced helical CT of the abdomen and pelvis to determine the sensitivity, specificity, and positive and negative predictive values of urinalysis. Twenty-nine patients were enrolled in this prospective study. The mean age of the patients was 43.5 years. The sex distribution was predominantly male, with 72% men and 28% women. Ultimately, 18 patients are included in our analysis with the remainder either lost to follow-up or excluded because of protocol violation. Average distal stone size was 4.1 mm (range 2.0-6.5 mm). Stones were evenly distributed between the right and the left ureters, with 50% on either side. Mean time to follow-up was 18 days with a range of 2 to 63 days. The sensitivity of urinalysis was determined to be 40% (8%-72%) while the specificity was 63% (28%-98%). The predictive value of a positive test was 57% (19%-95%) and the predictive value of a negative test was 55 % (25%-85%). The confidence interval for each of these parameters is inclusive of the value of 50%, indicating that urinalysis is no better than randomness in predicting presence or absence of a stone by CT. The absence or presence of microhematuria does not accurately predict whether a distal ureteral stone has passed or is still present. In those patients who need or want to know whether a stone is still present, unless a stone is strained, we suggest repeated CT imaging.


[Quality indicators for the assessment of ST-segment elevation acute myocardial infarction (STEMI) networks. How hospital discharge records could be integrated with Emergency medical services data: the Emilia-Romagna STEMI network experience].
The assessment of the regional network for ST-segment elevation acute myocardial infarction (STEMI) is fundamental for quality assurance. Since 2011 all Italian Health Authorities, in addition to hospital discharge records (HDR), must provide a standardized information flow (ERD) about emergency department (ED) and emergency medical system (EMS) activities. The aim of this study was to evaluate whether data integration of ERD with HDR may allow the development of appropriate quality indicators. Patients admitted to coronary care units (CCU) for STEMI between January 1 to December 31, 2013, were identified from the regional HDR database. All data were linked to those of the regional ERD database. Four quality indicators were defined: 1) rates of EMS activation, 2) rates of EMS direct transfer to the catheterization laboratory (Cath-lab), 3) transfer rates from a Spoke to a Hub hospital with angioplasty facilities, and 4) median time spent in ED. In 2013, 2793 patients with STEMI were admitted to the CCU. Of these, 1684 patients (60%) activated EMS and were transported to Spoke or Hub hospitals; 955 (57%) entered directly in CCU/Cath-lab; 677 were transferred directly to a Hub hospital ED without being admitted to a Spoke hospital. The median ED time in Hub hospital was 47 min (IQR 24-136) and in Spoke hospital 53 min (IQR 30-131). The integration among administrative data banks (i.e., HDR with ERD) allowed the assessment of the regional STEMI network and the identification of potentially useful quality indicators. Their easy availability should enable comparisons with local, national and international standards, and may favor quality improvement.


[History of the treatment of scoliosis].
Scoliosis remains a challenge to treatment, in spite of continuous efforts since the earliest times. The author describes the technical innovations with added efficiency, but even today one cannot avoid treatment without instrumentation and fusion, an always difficult indication on account of the variety of cases. Research is very active worldwide and accounts for great expectations (the role of the melatonin complex, the genetics of evolution factors, or the imagery of the EOS system). For the more deformed however treatment still remains unchanged in its principle: correction and fusion.


Diversity of Cultivable Protease-Producing Bacteria in Laizhou Bay Sediments, Bohai Sea, China.
Protease-producing bacteria are widespread in ocean sediments and play important roles in degrading sedimentary nitrogenous organic materials. However, the diversity of the bacteria and the proteases involved in such processes remain largely unknown especially for communities in enclosed sea bays. Here, we investigated the diversity of the extracellular protease-producing bacteria and their protease types in Laizhou Bay. A total of 121 bacterial isolates were obtained from sediment samples in 7 sites and their protease types were characterized. The abundance of cultivable protease-producing bacteria was about 104 CFU g-1 of sediment. Phylogenetic analysis based on 16S rRNA gene sequences suggest that the isolates belonged to 17 genera from 4 phyla including Firmicutes, Actinobacteria, Proteobacteria and Bacteroidetes, and mainly dominated by the genera Pseudoalteromonas (40.5%), Bacillus (36.3%), and Photobacterium (5.8%). The diversity and community structure varied among different sampling sites but no significant correlation was observed with soil sediment's characteristics. Enzyme activity and inhibition tests further revealed that all isolates secreted proteases that were inhibited by serine and/or metalloprotease inhibitors, and a smaller proportion was inhibited by inhibitors of cysteine and/or aspartic proteases. Furthermore, all isolates effectively degraded casein and/or gelatin with only a few that could hydrolyze elastin, suggesting that the bacteria were producing different kinds of serine proteases or metalloproteases. This study provided novel insights on the community structure of cultivable protease-producing bacteria near the Yellow River estuary of an enclosed sea bay.


DNA binding of L1 is required for human papillomavirus morphogenesis in vivo.
The role of putative DNA-binding domains of human papillomavirus (HPV) capsid proteins for DNA encapsidation in vivo is still unknown. We have now analyzed mutants of the major capsid protein L1 of HPV type 33, which are defective for DNA binding, for their ability to encapsidate DNA using an in vivo packaging approach. Since the DNA-binding domain and the nuclear localization signal (NLS) of L1 overlap, both a carboxy-terminal deletion mutant (L1-1/470) and a substitution mutant (L1-1/477M9) were analyzed. L1-1/477M9 has the classical NLS replaced by a noncanonical NLS taken from the human hnRNP protein A1. The mutant proteins were defective for DNA binding in contrast to wild-type (wt) L1 proteins of several HPV types. L1-1/470 localized to the cytoplasm when expressed in human cell lines, whereas L1-1/477M9 was found mainly in the nucleus. When coexpressed with wt L2, mutant L1 proteins colocalized with L2 in nuclear domains 10 (ND10) similar to wt L1 and assembled into virus-like particles incorporating L2. Wt L1 and L2 but not mutant L1 proteins and wt L2 efficiently encapsidated DNA and transferred it into cells, suggesting that physical interaction of L1 with DNA is essential for DNA inclusion into VLPs. We also compared the infectivity of histone-free DNA-containing pseudovirions generated in vitro with the infectivity of pseudovirions generated in vivo, which most likely harbor DNA in the form of chromatin. Pseudovirions generated in vivo were, on a per genome basis, four to five times more infectious than pseudovirions generated in vitro, even though no structural or biochemical difference was obvious. This indicates that chromatin may enhance the infectivity of pseudovirions.


[Nrp-1 expression in healing process of traumatic brain injury combined with tibial fracture].
To examine the expression of neuropilin-1 (Nrp-1), semaphorin 3A (Sema3A) and vascular endothelial growth factor (VEGF) in the healing process of tibial fracture after traumatic brain injury and to explore the mechanism of Nrp-1 in the formation of pathological callus after nerve injury. Methods: A total of 192 Wister female rats, 8-10 weeks old and weighing 220-250 g, were randomly divided into a control group (Group C), a tibia fracture group (Group F), a traumatic brain injury group (Group TBI), a traumatic brain injury combined with the tibia fracture group (Group TBI+F) (n=48 in each group). Tissue samples were collected at 3, 5, 7, 14, 21 and 28 days, respectively (n=8 for each time point). The expression of Nrp-1 in callus tissues were examined by immunohistochemistry and Western blot, while the expression of Sema3A and VEGF were detected by Western blot. Results: Compared with the Group F , the expression of Nrp-1 in chondrocytes of bone formation area and cartilage area was higher in the Group TBI+F, particularly at the 7th , 14th and 21st day (P<0.05), while the expression of Nrp-1 in osteoblast cells of fresh bone trabecula region was lower in the Group TBI+F, particularly at the 14th and 21st day (both P<0.05). Western blot showed that the expression of Nrp-1, Sema 3A and VEGF had the same trends in the Group TBI+F and the Group F. However, at each time point, the expression of Nrp-1 in the Group TBI+F was significantly higher and slowly decreased, particularly at the 14th, 21st and 28th day (all P<0.05). Meanwhile, the ratio of Sema 3A/VEGF in the Group TBI+F was significantly higher than that in the Group F, with statistical difference (P<0.05). Conclusion: The Nrp-1 is expressed abnormally in the process of fracture healing after nerve injury. It may play a role in the formation of pathological callus after nerve injury by promoting the preliminary and proliferation of chondrocytes, and inhibiting the growth of nerve fibers in the soft callus as well as the differentiation of osteoblast cell.


Multidisciplinary intervention of early, lethal metastatic prostate cancer: Report from the 2015 Coffey-Holden Prostate Cancer Academy Meeting.
The 2015 Coffey-Holden Prostate Cancer Academy Meeting, themed: "Multidisciplinary Intervention of Early, Lethal Metastatic Prostate Cancer," was held in La Jolla, California from June 25 to 28, 2015. The Prostate Cancer Foundation (PCF) sponsors an annual, invitation-only, action-tank-structured meeting on a critical topic concerning lethal prostate cancer. The 2015 meeting was attended by 71 basic, translational, and clinical investigators who discussed the current state of the field, major unmet needs, and ideas for addressing earlier diagnosis and treatment of men with lethal prostate cancer for the purpose of extending lives and making progress toward a cure. The questions addressed at the meeting included: cellular and molecular mechanisms of tumorigenesis, evaluating, and targeting the microenvironment in the primary tumor, advancing biomarkers for clinical integration, new molecular imaging technologies, clinical trials, and clinical trial design in localized high-risk and oligometastatic settings, targeting the primary tumor in advanced disease, and instituting multi-modal care of high risk and oligometastatic patients. This article highlights the current status, greatest unmet needs, and anticipated field changes that were discussed at the meeting toward the goal of optimizing earlier interventions to potentiate cures in high-risk and oligometastatic prostate cancer patients.


Zopiclone: Is there cause for concern in addiction services and general practice?
To examine the research on the dependence and abuse potential of zopiclone and the concerns that may be raised for addiction treatment services and General Practice. The focus is on four main areas: Problems that may arise from recommended use; Driving; Issues relating to dependence, and Abuse or recreational misuse. Internet-based searches were carried out using the key descriptors of zopiclone and driving, road traffic accidents, dependence, withdrawal, abuse, misuse and overdose. Problems arising from recommended use are rare and almost always confined to common side-effects. Driving-related studies indicate the potential for driving impairment for up to 12 hours following use and this has clear implications for both addiction services and general practice. The likelihood of dependence increases once recommended doses and time-frames are exceeded and vulnerable populations such as psychiatric patients and those with addiction problems are at risk. Somewhat contrary to impressions that Zopiclone has little or no abuse potential, there is evidence that this medication is prescribed at higher than recommended doses and for longer than recommended. It can also be obtained readily other than by prescription. The potential for deliberate abuse may now be regarded as established, albeit at low levels compared to the benzodiazepines and this requires a degree of vigilance by prescribers and care managers.


Liquid-crystal-enabled electrophoresis of spheres in a nematic medium with negative dielectric anisotropy.
We describe electrophoresis of spherical dielectric particles in a uniformly aligned nematic medium with a negative dielectric anisotropy. A spherical particle that orients the liquid crystal (LC) perpendicularly to its surface moves under the application of a uniform direct current or alternating current electric field. The electric field causes no distortions of the LC director far away from the sphere. Electrophoresis in the nematic LC shows two types of nonlinearity in the velocity versus field dependence. The velocity component parallel to the applied electric field grows linearly with the field, but when the field is high enough, it also shows a cubic dependence. The most interesting is the second type of nonlinear electrophoresis that causes the sphere to move perpendicularly to the applied field. This perpendicular component of velocity is proportional to the square of the field. The effect exists only in an LC and disappears when the material is melted into an isotropic fluid. The quadratic effect is caused by the dipolar symmetry of director distortions around the sphere and is classified as an LC-enabled electrophoresis (LCEEP). The nonlinear electrophoretic mobility of particles in LCEEP offers a rich variety of control parameters to design three-dimensional trajectories of particles for microfluidic and optofluidic applications.


Test-retest variability of retinal nerve fiber layer thickness and macular ganglion cell-inner plexiform layer thickness measurements using spectral-domain optical coherence tomography.
To evaluate the test-retest variability of spectral-domain optical coherence tomography (OCT) in measurement of retinal nerve fiber layer (RNFL) thickness and macular ganglion cell-inner plexiform layer (GCIPL) thickness. A total of 65 eyes of healthy subjects were enrolled in this observational cross-sectional study. RNFL thickness and GCIPL thickness were measured using the repeat scan optic cube and macular cube protocol using Cirrus HD-OCT (software version 6.0). A single operator obtained 3 measurements during 1 session to determine test-retest variability. Intrasession repeatability was defined by intraclass correlation, limits of agreement, and coefficient of variation. The mean age of patients was 37.89±15.11 years (range, 10 to 70 y). The mean RNFL thickness readings as measured during 3 sessions were 93.89±9.73, 93.63±10.00, and 93.55±9.64 μm and average GCIPL thickness measurements were 82.90±4.61, 82.98±4.24, and 83.06±4.36 μm, respectively. Coefficient of variation was 1.2 for average RNFL thickness and 0.82 for average GCIPL thickness. The intraclass correlation coefficient showed a good correlation between repeat measurements for both average RNFL and GCC thicknesses (0.994 and 0.990, respectively). The limits of agreement (95% confidence interval) for the 3 sessions ranged from -3.61 to 4.13 μm for the average RNFL thickness and -2.55 to 2.40 μm for GCIPL thickness measurements. In healthy eyes, Cirrus HD-OCT shows excellent intrasession repeatability for RNFL and GCIPL thickness measurements.


[A Masonic invalid feeding cup].
Description and reproduction of an extremely rare faience Creil-et-Montereau invalid feeding cup, made between 1849 and 1867, with a yellow ground and decorated with subjects symbolic of freemasonry.


Thylakoid membrane protein topography: transmembrane orientation of the chloroplast cytochrome b-559 psbE gene product.
Protease accessibility and antibody to a COOH-terminal peptide were used as probes for the in situ topography of the Mr 10,000 psbE gene product (alpha subunit) of the chloroplast cytochrome b-559. Exposure of thylakoid membranes to trypsin or Staphylococcus aureus V8 protease cleaved the alpha subunit to a slightly smaller polypeptide (delta Mr approximately -1000) as detected on Western blots, without loss of reactivity to COOH-terminal antibody. The disappearance of the parent Mr 10,000 polypeptide from thylakoids in the presence of trypsin correlated with the appearance of the smaller polypeptide with delta Mr = -750, the conversion having a half-time of approximately 15 min. Exposure of inside-out vesicles to trypsin resulted in almost complete loss of reactivity to the antibody, showing that the COOH terminus is exposed on the lumenal side of the membrane. Removal of the extrinsic polypeptides of the oxygen-evolving complex resulted in an increase of the accessibility of the alpha subunit to trypsin. These data establish that the alpha subunit of cytochrome b-559 crosses the membrane once, as predicted from its single, 26-residue, hydrophobic domain. The NH2 terminus of the alpha polypeptide is on the stromal side of the membrane, where it is accessible, most likely at Arg-7 or Glu-6/Asp-11, to trypsin or V8 protease, respectively. As a consequence of this orientation, the single histidine residue in the alpha subunit is located on the stromal side of the hydrophobic domain.(ABSTRACT TRUNCATED AT 250 WORDS)


Diagnostic value of transvaginal four-dimensional hysterosalpingo-contrast sonography combined with recanalization in patients with tubal infertility.
A retrospective study was designed to evaluate the diagnostic value of transvaginal four-dimensional hysterosalpingo-contrast sonography (TVS 4D-HyCoSy) combined with recanalization versus laparoscopy for patients with tubal infertility. A total of 195 patients undergoing TVS 4D-HyCoSy were analyzed retrospectively. Of these, 72 patients underwent laparoscopy, which was the gold standard. The endpoints were coincidence rate (defined as a parameter consistent with results arising from TVS 4D-HyCoSy and laparoscopic examination using dye), sensitivity, specificity, positive predictive value, negative predictive value, and Youden index for TVS 4D-HyCoSy. A total of 385 fallopian tubes were assessed by TVS 4D-HyCoSy, of which 147 (38.2%) were tubal patency, 178 (46.2%) as partial tubal obstruction, and 60 (15.6%) as complete tubal obstruction. Of 195 patients, 72 patients with 144 fallopian tubes underwent laparoscopy and a total coincidence rate of 90.97% compared with TVS 4D-HyCoSy. The sensitivity, specificity, positive predictive value, negative predictive value, and Youden index for 4D-HyCoSy versus laparoscopy were 97.7%, 86.7%, 98.4%, 81.3%, and 0.84, respectively. TVS 4D-HyCoSy represents a highly useful method for diagnosing tubal patency. However, further large-scale studies are warranted to investigate our findings in patients with tubal infertility.


Denitrification gene pools, transcription and kinetics of NO, N2O and N2 production as affected by soil pH.
The N(2)O : N(2) product ratio of denitrification is negatively correlated with soil pH, but the mechanisms involved are not clear. We compared soils from field experiments where the pH had been maintained at different levels (pH 4.0-8.0) by liming (> or = 20 years), and quantified functional gene pools (nirS, nirK and nosZ), their transcription and gas kinetics (NO, N(2)O and N(2)) of denitrification as induced by anoxic incubation with and without a carbon substrate (glutamate). Denitrification in unamended soil appeared to be based largely on the activation of a pre-existing denitrification proteome, because constant rates of N(2) and N(2)O production were observed, and the transcription of functional genes was below the detection level. In contrast, glutamate-amended soils showed sharp peaks in the transcripts of nirS and nosZ, increasing the rates of denitrification and pH-dependent transient accumulation of N(2)O. The results indicate that the high N(2)O : N(2) product ratio at low pH is a post-transcriptional phenomenon, because the transcription rate of nosZ relative to that of nirS was higher at pH 6.1 than at pH 8.0. The most plausible explanation is that the translation/assembly of N(2)O reductase is more sensitive to low pH than that of the other reductases involved in denitrification.


From the Editors.
The features of Canadian healthcare vary from jurisdiction to jurisdiction but all health systems face the same pan-Canadian obligations and share similar challenges that reflect regional and national realities as well as global trends and tensions (Forest and Martin, 2018). How the country's health stewards approach those challenges - whether they eschew or pursue solutions to complex, seemingly intractable problems - is critical. It can either strengthen or still the ability to adapt and address the shifting needs of current and future populations.


Tumor rejection antigen gp96/grp94 is an ATPase: implications for protein folding and antigen presentation.
Immunization of mice with gp96/grp94 heat shock proteins (HSPs) elicits tumor-specific cellular immunity to the tumors from which gp96 is isolated. However, the cDNA sequence of gp96 is identical among tumors and normal tissues. This raises the question regarding the structural basis of the specific immunogenicity of gp96. As HSPs bind a wide array of molecules including peptides, we have proposed that gp96 may not be immunogenic per se, but may chaperone antigenic peptides. Furthermore, gp96 is localized predominantly in the lumen of the endoplasmic reticulum (ER) suggesting that it may act as a peptide acceptor and as accessory to peptide loading of MHC class I molecules. We demonstrate here that gp96 molecules contain ATP-binding cassettes, bind ATP and possess an Mg(2+)-dependent ATPase activity. Gp96 preparations are also observed to contain tightly bound peptides, which can be eluted by acid extraction. These properties of gp96 are consistent with its proposed roles in chaperoning antigenic peptides and in facilitating MHC class I--peptide assembly in the ER lumen. We present a model to explain how interaction of gp96 with MHC class I may result in transfer of peptides to the latter.


Effect of oxygen radicals and differential expression of catalase and superoxide dismutase in adult Heligmosomoides polygyrus during primary infections in mice with differing response phenotypes.
The ability of oxygen radicals to kill Heligmosomoides polygyrus adult worms was examined by assessing parasite survival following incubation with hydrogen peroxide and acetaldehyde/xanthine oxidase, generators of H2O2 and H2O2/O2(-), respectively. H. polygyrus worms could tolerate levels of < 0.25 mM hydrogen peroxide and < 0.5 mM/20 mU acetaldehyde/xanthine oxidase for 20 h, but, at higher concentrations, marked sex-dependent susceptibility was observed, with males being more sensitive to H2O2 and O2(-) than female worms. The ability to evade free radical-mediated damage was also evaluated by measuring superoxide dismutase (SOD) and catalase levels in worms isolated at different time points from four strains of mice with differing resistance phenotypes. Levels of both catalase and SOD in female worms isolated from 'rapid'[(SWRxSJL)F1], 'fast' (SWR) or 'intermediate' (BALB/c), but not 'slow' (C57BL/10), responder mice showed a strain-dependent increase with time. Moreover, male worms were rejected faster than female worms in the 'rapid', 'fast' and 'intermediate' responder strains of mice. The results suggest that host-derived free radicals can damage adult worms and that female worms can increase production of their scavenging enzymes in response to the immune onslaught that eventually leads to worm expulsion in mice with 'fast', 'rapid' or 'intermediate' response phenotypes.


Effects of dopamine antagonists on retinal B-wave recovery after retinal ischemia.
Retinal ischemia was developed by occlusion of the central retinal artery for 30 minutes. The artery was reperfused thereafter, and the recovery of the b-wave amplitude was determined as an indication of the recovery of retinal function after ischemia. Following ischemia, it was found that dopamine antagonists, including chlofluperol, metoclopramide, trifluperol and droperidol, increased in b-wave amplitude recovery significantly over the control b-wave recovery. Similar effects were observed with haloperidol and loxapine, but to a lesser extent. The results correlated well with the improvement of retinal blood flow by these dopamine antagonists (4,5). Neither floropipamide, a dopamine antagonist, nor bromocriptine, a dopamine agonist, affected the b-wave recovery after ischemia. These results also correlate well with the inability of these agents to increase the retinal blood flow measured by the microsphere technique (4,5). These findings suggest that most of the dopamine antagonists, with the exception of floropipamide, could be used for the treatment and/or prevention of ischemic retinopathy.


Molecular mechanisms of isoniazid resistance in Mycobacterium tuberculosis and Mycobacterium bovis.
Genetic and biochemical studies have suggested a link between reduced catalase activity and resistance to isoniazid in Mycobacterium tuberculosis. In this study, we examined the molecular mechanisms of resistance to isoniazid with six in vitro mutants of the M. tuberculosis complex (Mycobacterium bovis and M. tuberculosis). Five of six mutants resistant to isoniazid were negative by catalase assays. Immunoblot analyses using a polyclonal antibody against the katG gene product (catalase-peroxidase) demonstrated that the enzyme is not produced in four of these isoniazid-resistant strains. A complete deletion of the katG gene was detected in only one of these isoniazid-resistant M. tuberculosis complex strains by Southern blot analyses. In two other resistant strains, partial deletions of the katG gene were identified. A point mutation which resulted in the insertion of a termination codon in the katG coding sequence caused a catalase-negative phenotype in a fourth strain. Of the two resistant strains which produce the enzyme, one was shown to be negative by a catalase assay. Single-stranded conformational polymorphism and DNA sequence analyses identified a mutation in the katG gene of this strain which may contribute to reduced enzymatic activity and subsequent isoniazid resistance. These data demonstrate that genetic alterations to the katG gene other than complete deletions are prevalent and may contribute significantly to the number of cases of isoniazid-resistant tuberculosis.


Polymeric immunoglobulin receptor and galectin-3-binding protein are raised in biliary atresia: Reveals a proteomic-based study.
To identify and evaluate differentially expressed plasma proteins in biliary atresia (BA), we performed plasma proteome profiling using liquid chromatography with tandem mass spectrometry (LC-MS/MS) in 20 patients with BA and 10 control children. Serological assays validated the most significant and highly upregulated proteins in a cohort of 45 patients and 15 controls. Bioinformatics tools were used for functional classification and protein-protein interactions of differentially expressed proteins (DEPs). Of 405 proteins detected in patients and 360 in controls, 242 proteins, each with ≥2 unique peptides (total of 3230 peptides), were common in both groups. Compared to controls, 90 proteins in patients were differentially expressed and were dysregulated. Twenty-five were significantly upregulated with polymeric immunoglobulin receptor (PIgR), galectin-3-binding protein (Gal-3BP), complement C2, the most prominent, and 15 had low expression. The bioinformatic analysis revealed functional interaction between DEPs and their role in an inflammatory immune response. Enzyme immunoassay for PIgR and Gal-3BP in patients' plasma showed their levels raised significantly (p = 0.0021 and p = 0.0369, respectively). The PIgR and Gal-3BP are novel proteins upregulated in BA and may be tested further for their utility as potential circulating disease biomarker(s). SIGNIFICANCE: The study shows that plasma PIgR and GAL-3BP levels are significantly raised in infants with BA within the first 3 months of life. If tested in a larger cohort, these proteins may be found to have their diagnostic potential and utility as disease biomarkers. The study also provides valuable information on the involvement of several DEPs in innate immune response, chronic inflammation, and fibrosis. This strengthens the hypothesis that the immune-mediated inflammatory processes are responsible for the progressive nature of BA.


Plasmonic Supercrystals.
For decades, plasmonic nanoparticles have been extensively studied due to their extraordinary properties, related to localized surface plasmon resonances. A milestone in the field has been the development of the so-called seed-mediated growth method, a synthetic route that provided access to an extraordinary diversity of metal nanoparticles with tailored size, geometry and composition. Such a morphological control came along with an exquisite definition of the optical response of plasmonic nanoparticles, thereby increasing their prospects for implementation in various fields. The susceptibility of surface plasmons to respond to small changes in the surrounding medium or to perturb (enhance/quench) optical processes in nearby molecules, has been exploited for a wide range of applications, from biomedicine to energy harvesting. However, the possibilities offered by plasmonic nanoparticles can be expanded even further by their careful assembly into either disordered or ordered structures, in 2D and 3D. The assembly of plasmonic nanoparticles gives rise to coupling/hybridization effects, which are strongly dependent on interparticle spacing and orientation, generating extremely high electric fields (hot spots), confined at interparticle gaps. Thus, the use of plasmonic nanoparticle assemblies as optical sensors have led to improving the limits of detection for a wide variety of (bio)molecules and ions. Importantly, in the case of highly ordered plasmonic arrays, other novel and unique optical effects can be generated. Indeed, new functional materials have been developed via the assembly of nanoparticles into highly ordered architectures, ranging from thin films (2D) to colloidal crystals or supercrystals (3D). The progress in the design and fabrication of 3D supercrystals could pave the way toward next generation plasmonic sensors, photocatalysts, optomagnetic components, metamaterials, etc. In this Account, we summarize selected recent advancements in the field of highly ordered 3D plasmonic superlattices. We first analyze their fascinating optical properties for various systems with increasing degrees of complexity, from an individual metal nanoparticle through particle clusters with low coordination numbers to disordered self-assembled structures and finally to supercrystals. We then describe recent progress in the fabrication of 3D plasmonic supercrystals, focusing on specific strategies but without delving into the forces governing the self-assembly process. In the last section, we provide an overview of the potential applications of plasmonic supercrystals, with a particular emphasis on those related to surface-enhanced Raman scattering (SERS) sensing, followed by a brief highlight of the main conclusions and remaining challenges.


Development of a 3D CT-scanner using a cone beam and video-fluoroscopic system.
We describe the design and implementation of a system that acquires three-dimensional (3D) data of high-contrast objects such as bone, lung, and blood vessels (enhanced by contrast agent). This 3D computed tomography (CT) system is based on a cone beam and video-fluoroscopic system and yields data that is amenable to 3D image processing. An X-ray tube and a large area two-dimensional detector were mounted on a single frame and rotated around objects in 12 seconds. The large area detector consisted of a fluorescent plate and a charge coupled device (CCD) video camera. While the X-ray tube was rotated around the object, a pulsed X-ray was generated (30 pulses per second) and 360 projected images were collected in a 12-second scan. A 256 x 256 x 256 matrix image was reconstructed using a high-speed parallel processor. Reconstruction required approximately 6 minutes. Two volunteers underwent scans of the head or chest. High-contrast objects such as bronchial, vascular, and mediastinal structures in the thorax, or bones and air cavities in the head were delineated in a "real" 3D format. Our 3D CT-scanner appears to produce data useful for clinical imaging and 3D image processing.


Genotoxicity of acrylamide and glycidamide.
Acrylamide, a known rodent carcinogen, is found in the human diet. However, the mechanism by which acrylamide exerts its carcinogenic effects remains unclear. Normal human bronchial epithelial cells and Big Blue mouse embryonic fibroblasts that carry a lambda phage cII transgene were treated in vitro with acrylamide, its primary epoxide metabolite glycidamide, or water (control) and then subjected to terminal transferase-dependent polymerase chain reaction to map the formation of DNA adducts within the human gene encoding p53 (TP53) and the cII transgene. The frequency and spectrum of glycidamide-induced mutations in cII were examined by using a lambda phage-based mutation detection system and DNA sequence analysis, respectively. All statistical tests were two-sided. Acrylamide and glycidamide formed DNA adducts at similar specific locations within TP53 and cII, and DNA adduct formation was more pronounced after glycidamide treatment than after acrylamide treatment at all doses tested. Acrylamide-DNA adduct formation was saturable, whereas the formation of most glycidamide-DNA adducts was dose-dependent. Glycidamide treatment dose-dependently increased the frequency of cII mutations relative to control treatment (P<.001). Glycidamide was more mutagenic than acrylamide at any given dose. The spectrum of glycidamide-induced cII mutations was statistically significantly different from the spectrum of spontaneously occurring mutations in the control-treated cells (P=.038). Compared with spontaneous mutations in control cells, cells treated with glycidamide or acrylamide had more A-->G transitions and G-->C transversions and glycidamide-treated cells had more G-->T transversions (P<.001). The mutagenicity of acrylamide in human and mouse cells is based on the capacity of its epoxide metabolite glycidamide to form DNA adducts.


Adding bit of esthetics with science modification of batwing mastopexy for breast conservation in a young patient with giant fibroadenoma breast.
A 19-year-old girl presented with a lump in her right breast and with a history of surgery for the similar complaint 3 years back. Ultrasound was suggestive of benign solitary lesion of size 16 cm × 10 cm. Core biopsy was suggestive of phyllodes tumor, and the histopathology report of previous surgery was also suggestive of phyllodes tumor. Wide excision of the tumor and reconstruction was done with batwing mastopexy and with a slight modification of the described technique so that to avoid contralateral reduction mammoplasty in a young unmarried girl. Postoperative histopathology was suggestive of fibroadenoma measuring 15 cm × 8 cm with all margins free of tumor, and it is probably one of the biggest fibroadenomas reported so far. On follow-up, no significant disparity noted between the appearances of both breasts.


[Liver transplantation 1994].
Transplantation of the liver has progressed in recent years and has become universally accepted for numerous indications in end-stage liver diseases, predominantly primary biliary cirrhosis, sclerosing cholangitis, biliary atresia and liver-related metabolic disorders. In fulminant and subfulminant hepatitis, prognosis has been improved considerably by liver transplantation. The debate still persists whether liver transplantation might be indicated in diseases recurring after transplantation, such as HBV cirrhosis. Alcoholic cirrhosis as an indication for transplantation remains still controversial. The risk of tumor recurrence after transplantation for small hepatocellular carcinoma in cirrhosis can be calculated; adjuvant chemotherapy might increase prognosis. Transplantation for other malignant liver tumors seems to be obsolete.


A study on microbial and chemical characterization of mechanically deboned chicken in Tehran, Iran.
This study aimed to investigate microbial, chemical, and heavy metal contamination of mechanically deboned chicken (MDC) in Iran. A total of 24 samples of MDC were obtained from meat plants. TBC of the three samples were acceptable. E. coli and S. aureus were detected in 21 and 6 samples, respectively. Three of the samples were contaminated with Salmonella spp. Campylobacter was not detected in any of the samples. The moisture content of MDC was in the range of 41% to 75%. Ash had a range of 0.74% to 1.4%. The maximum protein content of the MDC was 21.98% and fat content was in the range of 2.1% to 20%. The highest PV was 15.18 mEq/kg. All of the samples were polluted with Pb, Cd, and As. In conclusion, MDC had microbial and chemical contamination. It is necessary to develop more strict criteria for control of the chicken paste processing method.


Demographic and obstetric factors influencing pregnancy outcome in twin gestations.
Our purpose was to identify the influence of parity and previous preterm delivery on pregnancy outcome in twin gestations. A retrospective comparative analysis of women with twin gestations completing an outpatient preterm labor surveillance program between April 1995 and February 2000 was performed. Included were those enrolled at <24 weeks' gestation. Parity, maternal age, prepregnancy body mass index (BMI), cerclage, tocolytic use, and pregnancy outcome were identified. Data were divided into nulliparas, multiparas without previous preterm delivery, and those with previous preterm delivery. Analysis of variance and the Pearson chi2 test were used for statistical analysis. Data were analyzed for 1268 twin pregnancies. The mean gestational age at delivery for the multiparous women without a history of previous preterm delivery (35.3 +/- 2.7 weeks) was significantly greater than the mean gestational age at delivery for nulliparous (34.4 +/- 3.2 weeks) and multiparous women with a previous preterm delivery (34.0 +/- 3.1 weeks), P <.001. The greater gestational age at delivery in the multiparous women without a previous preterm delivery was associated with a significantly shorter newborn hospital stay and a lower need for mechanical ventilation use compared with the other groups (all P values < or =.001). In twin gestations, multiparous women without history of previous preterm delivery have a significantly greater gestational age at delivery, a lower incidence of cerclage, and a reduced neonatal hospital stay than do nulliparous women or those with a history of a previous preterm delivery.


Chromium supplementation enhances antibody response to vaccination with tetanus toxoid in cattle.
Nineteen multiparous late-pregnant dairy cows were divided into an experimental group (n = 10) and a control group (n = 9). Animals in the experimental group were fed a diet supplemented with chromium chelate admixed into wheat meal at 5 mg per animal per day. The supplementation was started 4 weeks before calving and stopped by the end of week 3 after calving. All the cows were vaccinated with tetanus toxoid in the fifth and sixth week of lactation. Monitoring of the characteristics of non-specific immunity did not show any significant between-group differences in total and differential leucocyte counts, percentages of lymphocyte subpopulations, activities of lectin-stimulated lymphocytes, phagocytic activities, and the contents of total immunoglobulins and lysozyme in blood sera. Tetanus toxoid-specific antibody titres, those of the IgG2 isotype in particular, were higher in the experimental group than in the control animals. These results indicate that chromium supplementation at the level used in this experiment modulated the regulation of functions of the immune system.


How computer science can help in understanding the 3D genome architecture.
Chromosome conformation capture techniques are producing a huge amount of data about the architecture of our genome. These data can provide us with a better understanding of the events that induce critical regulations of the cellular function from small changes in the three-dimensional genome architecture. Generating a unified view of spatial, temporal, genetic and epigenetic properties poses various challenges of data analysis, visualization, integration and mining, as well as of high performance computing and big data management. Here, we describe the critical issues of this new branch of bioinformatics, oriented at the comprehension of the three-dimensional genome architecture, which we call 'Nucleome Bioinformatics', looking beyond the currently available tools and methods, and highlight yet unaddressed challenges and the potential approaches that could be applied for tackling them. Our review provides a map for researchers interested in using computer science for studying 'Nucleome Bioinformatics', to achieve a better understanding of the biological processes that occur inside the nucleus.


Inactivation of the GR in the nervous system affects energy accumulation.
The homeostatic regulation of body weight protects the organism from the negative consequences of starvation and obesity. Glucocorticoids (GCs) modulate this regulation, although the underlying mechanisms remain unclear. To address the role of central GRs in the regulation of energy balance, we studied mice in which GRs have selectively been inactivated in the nervous system. Mutant mice display marked growth retardation. During suckling age this is associated with normal fat deposition causing a 60% temporary increase of percent body fat, compared with control littermates. After weaning, fat and protein depositions are reduced so that adults are both smaller and leaner than their controls. Decreased food intake and, after weaning, reduced metabolic efficiency account for these developmental disturbances. Plasma levels of leptin and insulin, two important energy balance regulators, are elevated in young mutants but normal in adults. Leptin/body fat ratio is higher at all ages, suggesting disturbed control of circulating leptin as a consequence of chronically elevated GC levels in mutant animals. Adult mutants display increased hypothalamic CRH and NPY levels, but peptide levels of melanin concentrating hormone and Orexin A and B are unchanged. The increased levels of plasma GCs and hypothalamic CRH may act as catabolic signals most likely leading to persistently reduced energy accumulation.


Efficacy of depot leuprolide in premenstrual syndrome: effect of symptom severity and type in a controlled trial.
To determine whether depot leuprolide is effective in premenstrual syndrome (PMS) and whether symptom type or severity affects therapeutic or hormonal responses and the incidence of adverse events. Twenty-five women who met strict diagnostic criteria for PMS completed a double-blind, placebo-controlled, 6-month crossover trial at a university medical center. Depot leuprolide (3.75 mg/month) or saline was administered intramuscularly for three consecutive treatment cycles. Efficacy, adverse events, and hormone concentrations were assessed at each visit. Repeated-measures analysis of variance was used to analyze continuous data, and ordinal and binary data were analyzed using nonparametric techniques. Depot leuprolide treatment was significantly more effective than placebo on all rating scales. Irritability, neurologic symptoms, breast tenderness, and fatigue were most responsive to treatment. Symptoms were reduced to follicular phase levels only in women without premenstrual depression. Those with moderate premenstrual depression improved but remained clinically symptomatic, whereas the group with severe premenstrual depression showed no improvement on any efficacy measure. Adverse events were lowest in those without premenstrual depression and highest in those with severe depression. Leuprolide suppressed estradiol and progesterone in most premenstrual depression groups but had varying effects on gonadotropins. Leuprolide treatment reduced both behavioral and physical symptoms and was well tolerated in the absence of severe premenstrual depression. Women should be evaluated for depression severity before receiving a GnRH agonist. The differential response to leuprolide suggests that it may possess diagnostic value in determining distinct subtypes of PMS.


Functional and metabolic effects of cardioplegia induced by a young's solution (YNG solution) as assessed in isolated atrial preparations and in isolated perfused heart preparations of the guinea pig.
p6e protective effects of Young's solution (YNG solution), a cardioplegic solution, on the myocardial function and metabolism were assessed in isolated atrial preparations and isolated perfused heart preparations of the guinea pig. In atrial preparations, the time to arrest of the contraction became shorter as the concentrations of the K+, Mg++, and K+-Mg++ solutions increased, while the time to resumption of the contraction was lengthened. There was no difference in the time to arrest between K+ and K+-Mg++ solutions, but the time to resumption was reduced with K+-Mg++ solution to about half the value with K+ solution. YNG solution represented an optimum solution for obtaining a quick cardiac arrest and quick resumption of contraction. In the isolated perfused heart, the time to arrest was similar for all the cardioplegic solutions used and the heart stopped in diastole. However, the time to arrest was longer with cold Krebs-Henseleit's solution (cold cardioplegia). The time to resumption of the contraction was the shortest with YNG solution, which yielded the highest mitochondrial respiratory control ratio (RCR) and ADP/O ratio. There was a negative correlation between the time to resumption of contraction and mitochondrial RCR or ADP/O ratio (r = -0.50 and -0.58, respectively).


Construction of durable superhydrophobic and anti-icing coatings via incorporating boroxine cross-linked silicone elastomers with good self-healability.
The fragility of the micro-nano structure makes superhydrophobic coatings highly susceptible to stress, resulting in a decrease in their superhydrophobic and anti-icing performance. In this work, we proposed a new insight to improve durability by incorporating a thin layer of self-healable elastomer with a dynamic network on the micro-nano structure. We constructed superhydrophobic coatings (EP/SiO2/BFVSE) with a three-layered structure of the epoxy resin/silica nanoparticle/silicon elastomer. The silicon elastomer (BFVES) with a B-O dynamic cross-linked network and fluorinated moieties was synthesized by graft polymerization on vinyl silicon oil. The preparation route is facile and convenient for mass production. BFVES has rapid self-healing properties for scratches at room-temperature, underwater and at -18 °C. EP/SiO2/BFVSE preserved apparently higher CAs after being immersed in pH = 1, pH = 13, and NaCl solutions for 96 h as compared with the EP/SiO2 coating. In a water striking environment, the CA of EP/SiO2/BFVSE was slightly decreased to 153°. SEM images further reveal that the recovery of superhydrophobicity and icephobicity is attributed to the self-healing behavior of the boroxine-containing silicon elastomer. The EP/SiO2/BFVSE coating also possesses additional self-healing ability under chemical oxidation. The high durability of the self-healable superhydrophobic coating enables great application potential in aircraft, marine vessels, and outdoor facilities in harsh environments.


A single administration of peritoneal dialysis fluid in the rat induces an acute inflammatory exudate.
Peritoneal macrophages from uninfected continuous ambulatory peritoneal dialysis (CAPD) patients in general show two different, endogenous peroxidatic activity (PA) patterns: exudate and negative. This suggests, in accordance with the animal model, that a chronic inflammatory state is present in CAPD patients, which may be caused by mechanical stimulation or the dialysis fluid. Therefore we studied in the rat model the intraperitoneal (i.p.) administration of peritoneal dialysis fluid and physiological saline. Our results on the number of neutrophilic granulocytes, the number of macrophages and the PA pattern indicate that a single i.p. administration of commercial dialysis fluid induced an acute exudate, especially when compared with the minor saline effect. These results are confirmed by the lower percentage of macrophages positive for the differentiation antigen ED2 and in addition the higher number of Fc-receptor positive peritoneal cells, when compared with the saline effect. These findings strongly suggest that the continuous administration of the dialysis fluid, as used in CAPD patients, is the inducer of the chronic inflammatory exudate in these patients.


Efficacy of transsphenoidal hypophysectomy in treatment of dogs with pituitary-dependent hyperadrenocorticism.
The long-term survival, disease-free fractions, and the complications of hypophysectomy in 150 dogs with pituitary-dependent hyperadrenocorticism (PDH) were examined in a prospective study. Long-term survival and disease-free fractions in relation to pituitary size were analyzed by the Kaplan-Meijer estimate procedure. The 1-, 2-, 3-, and 4-year estimated survival rates were 84% (95% confidence interval [CI], 76-89%), 76% (67-83%), 72% (62-79%), and 68% (55-77%), respectively. Treatment failures included procedure-related mortalities (12 dogs) and incomplete hypophysectomies (9 dogs). The 1-, 2-, 3-, and 4-year estimated relapse-free fractions were 88% (CI: 80-93%), 75% (64-83%), 66% (54-76%), and 58% (45-70%), respectively. Postoperative reduction of tear production (58 eyes in 47 dogs) was often reversible but remained low until death in 11 eyes of 10 dogs. Central diabetes insipidus (CDI) occurred more frequently (62%) in dogs with enlarged pituitaries than in dogs with nonenlarged pituitaries (44%). Survival and disease-free fractions after hypophysectomy were markedly higher in dogs with nonenlarged pituitaries than in dogs with enlarged pituitaries. Transsphenoidal hypophysectomy is an effective treatment for PDH in dogs. The survival and disease-free fractions after hypophysectomy decrease and the incidence of CDI increases with increasing pituitary size. Therefore, early diagnosis of PDH is important and transsphenoidal hypophysectomy is expected to have the best outcome when used as primary treatment for dogs with nonenlarged or moderately enlarged pituitaries.


Controlling the structure of manganese(II) phosphates by the choice and ratio of organophosphate and auxiliary ligands.
Tetranuclear manganese(II) phosphates [Mn(dipp)(bpy)](4)4 H(2)O (1) and [Mn(4)(dmpp)(2)(dmppH)(4)(bpy)(4)(H(2)O)(2)]H(2)O (2) have been prepared from Mn(OAc)(2)4 H(2)O and 2,6-diisopropylphenyl phosphate (dippH(2)) or 2,6-dimethylphenyl phosphate (dmppH(2)) in the presence of 2,2'-bipyridine (bpy). In contrast, the reaction between [Mn(bpy)(2)(OAc)(ClO(4))]H(2)O and dippH(2) affords [Mn(bpy)(2)(dippH)](2)2 ClO(4)2 CH(3)OH (3). The reactions of Mn(OAc)(2)4 H(2)O, dippH(2), and pyridine (py) or 3,5-dimethylpyrazole (dmpz) in CH(3)CN under reflux afford hexanuclear complexes [Mn(6)(dipp)(6)(py)(8)]2CH(3)CN (4) and [Mn(6)(dipp)(6)(dmpz)(6)(AcOH)(2)]2 H(2)O (5), respectively. Although compounds 1 and 2 are tetrameric, the former is a closed cubane-like structure resembling the D4R secondary building unit of zeolites, whereas the latter exists in a staircase structure with fused Mn(2)O(4)P(2) rings. The core structure of 3 contains a Mn(2)O(4)P(2) eight-membered ring that resembles the S4R building block of zeolites. Single-crystal X-ray diffraction studies reveal that compounds 4 and 5 have a similar core structure and differ from each other by the neutral ligands coordinated to manganese ions. All six phosphate ligands exist in a doubly deprotonated [(RO)PO(3) (2-)] form and exhibit two types of binding modes [5.222] and [3.111]. An interesting feature of compounds 1-5 is that although they are oligonuclear complexes, there is an absence of oxido bridges. The magnetic properties of compounds 1-5 have been investigated in the temperature range 5-298 K, and it was found that all the compounds obey the Curie law.


The bitter truth about morality: virtue, not vice, makes a bland beverage taste nice.
To demonstrate that sensory and emotional states play an important role in moral processing, previous research has induced physical disgust in various sensory modalities (visual, tactile, gustatory, and olfactory modalities, among others) and measured its effects on moral judgment. To further assess the strength of the connection between embodied states and morality, we investigated whether the directionality of the effect could be reversed by exposing participants to different types of moral events prior to rating the same neutral tasting beverage. As expected, reading about moral transgressions, moral virtues, or control events resulted in inducing gustatory disgust, delight, or neutral taste experiences, respectively. Results are discussed in terms of the relation between embodied cognition and processing abstract conceptual representations.