Aortic valve replacement with the Starr-Edwards prosthesis: a comparison of the first and second decades of follow-up.
There are few prostheses in current use that allow 20-year follow-up. This report compares the rates of valve-related complications during the first and second decades following aortic valve replacement with the Silastic ball prosthesis. (table; see text) Valve-related complication rates with this prosthesis have been low overall. Performance characteristics of this valve have remained stable through the second decade of follow-up. These results should be used as the standard in the evaluation of long-term results with other more recently introduced mechanical and tissue valves.


Vulvar embryonal rhabdomyosarcoma: a case report.
Embryonal rhabdomyosarcoma (ERMS) is a rare malignant neoplasm found in both male and female children. It typically presents as a protruding vaginal mass with vaginal bleeding in girls less than 8 years of age. It is often seen as the sarcoma botryoides histologic sub type. This report represents the first case study of ERMS presenting as a vulvar mass. The article further explores the etiologies of pediatric vulvar masses, including ERMS, and the suggested diagnostic and treatment modalities.


Focal nodular hyperplasia of the liver: a sequela of tumor therapy.
Focal nodular hyperplasia (FNH) of the liver occurs with increased frequency in oncology patients after completion of tumor therapy. Its development may be related to the vascular damage induced by such therapy. We present three children who developed FNH after undergoing antineoplastic therapy for non-hepatic primary tumors. Recognition of this association in the appropriate patient population might obviate the need for biopsy.


Identification of Pneumocystis carinii DNA by polymerase chain reaction in necropsy lung samples from children dying of respiratory tract illnesses.
Polymerase chain reaction for Pneumocystis carinii DNA was performed on necropsy lung samples from children by means of P carinii -specific primers.P carinii DNA was identified in 22 of 22 (100%) samples with histologically proven P carinii pneumonia and 13 of 75 (17%) with non-P carinii pneumonia respiratory illness (sensitivity, 100%; specificity, 83%). The low specificity precludes the use of polymerase chain reaction as an alternative to histopathologic diagnosis.


Chronic papaverine treatment: the effect of repeated injections on the simian erectile response and penile tissue.
To investigate the effect of chronic papaverine treatment, seven monkeys underwent repeated intracavernous injections for one year. One monkey died after 56 injections; the others received a total of 100 each. The strength and duration of erection were recorded after each injection, and the erectile tissue was examined histologically at the end of the study. Over the long term, papaverine maintains its erection-inducing capability, but it does cause pathologic changes in the erectile tissue: minimal to marked fibrosis at the injection site and hypertrophy of smooth muscle in the non-injected area of the corpus.


Molecular and phenotypic traits of in-vitro-selected mutants of Bifidobacterium resistant to rifaximin.
Nucleotide mutations inside a core region of the rpoB gene, encoding the beta subunit of RNA polymerase, were found in rifaximin-resistant mutants of Bifidobacterium. Five different missense mutations of codons 513, 516, 522 and 529 were identified. Further aspects of rifaximin resistance were investigated, using Bifidobacterium infantis BI07 as a model strain. Partial resistance of RNA polymerase of a BI07 mutant at a rifaximin concentration >10 microg/mL was observed by cell-free transcription assay. Mass spectrometry detection of rifaximin in the cellular pellet of the BI07 resistant mutant, as well as changes in biosynthesis of saturated and cyclopropane fatty acids during growth, suggested a reduction in membrane permeability for the antibiotic moiety.


Surgical choice of proximal gastric cancer in China: a retrospective study of a 30-year experience from a single center in China.
Background: Total gastrectomy with D2 lymphadenectomy is indicated for proximal advanced gastric cancer located in the upper one-third of the stomach; however, due to preserved function and clinical benefits of a proximal gastrectomy, the choice of a surgical method for patients with proximal early-stage gastric cancer remains controversial.Methods: We conducted a retrospective study involving 649 patients with proximal gastric cancer. The clinical-pathological features, characteristics, lymph node metastatic patterns, prognosis, postoperative complications, and recurrence were compared between the patients who underwent proximal and total gastrectomies with different T and N stages.Results: The lymph node metastatic rates among T stages were significantly different. There was no difference in overall survival rates for stage Ia, Ib, and IIa patients but significant difference in T3 and T4 stages who underwent proximal and total gastrectomy. Complications were more frequently detected in patients who underwent total gastrectomy than proximal gastrectomy.Conclusion: Considering the survival benefits and preserved function, proximal gastrectomy can be performed safely in stage Ia and Ib gastric cancer (T1N0, T1N1, and T2N0) with an excellent remission rate. Proximal gastrectomy is not recommended for advanced gastric cancer.


Advances in the therapy of bacterial bloodstream infections.
Advances in the diagnostic and therapeutic management of patients with bloodstream infections (BSIs) have been achieved in the last years, improving clinical outcome. However, mortality associated with some pathogens, such as Staphylococcus aureus and Enterococcus spp., is still high. In addition, the spread of antibiotic resistance, mainly among Gram-negative bacteria, reduces treatment options in some circumstances. Therefore, interest in new drugs, combination regimens and optimal dosing schedules is rising. Our aim is to summarize the current evidence on available antibiotic regimens for patients with bacterial BSI, focusing on drug choice, combination regimens and optimal dosing schedules. We selected bacteria that are difficult to manage because of virulence factors (i.e. methicillin-susceptible S. aureus), tolerance to antibiotic activity (i.e. Enterococcus faecalis), and/or susceptibility patterns (i.e. methicillin-resistant S. aureus, vancomycin-resistant enterococci, carbapenem-resistant Enterobacteriaceae, multidrug-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii). MEDLINE search with English language and publication in the last 5 years as limits. The literature gaps on the use of new drugs, the uncertainties regarding the use of combination regimens, and the need to optimize dosing schedules in some circumstances (e.g. augmented renal clearance, renal replacement therapy, high inoculum BSI sources, and isolation of bacteria showing high MICs) have been revised.


Herpes zoster.
Herpes zoster is a disorder frequently encountered in adults. The natural history is often poorly appreciated and management is frustrating. Recent studies have critically evaluated newer therapeutic modalities. The epidemiology, clinical manifestations, complications and therapeutic alternatives of herpes zoster deserve review.


Correction: The contribution of the basal ganglia and cerebellum to motor learning: A neuro-computational approach.
[This corrects the article DOI: 10.1371/journal.pcbi.1011024.].


School sport policy and school-based physical activity environments and their association with observed physical activity in middle school children.
Empirical research on the effects of school sport policies on children's physical activity is limited. This study examined sport policies (intramural vs. varsity), physical settings within schools, and supervision in relation to physical activity using the System for Observing Play and Leisure in Youth (SOPLAY). Data were collected on physical activity levels of children in four middle schools. Regression analyses assessed the main effects of sport policy, type of physical activity setting, and supervision as well as interactions. Regression models were stratified by gender. Children in intramural schools were more likely to use indoor spaces and be boys. Regression models indicated that varsity sport programs were associated with lower physical activity levels among boys but not girls. Significant associations between type of physical activity settings and physical activity levels were observed only for boys. Adult supervision was not associated with children's physical activity levels. Finally, descriptive results showed athletic facilities were under-utilized in all schools.


Improving suction technology for nerve activity recording.
Extracellular recording of nerve activities using suction electrodes is an easy yet powerful tool in characterizing neural activities in physiology and pathological conditions. The key factors that determine the quality of suction electrode recordings have not been fully investigated. New Methods: Here, we proposed a biophysical model to study the mechanisms underlying suction technology for axon recording. The model focuses on the interpretation of the recorded single neuron activity based on the location of the electrode, the integrity of the recorded tissue, and the tightness of the suction. To directly test these model predictions, we applied two channel recordings from the nerves in Aplysia californica, and analyzed the shape of the extracellularly recorded single neuron activity under various conditions. We found that both the recording site and the integrity of the neural tissue impact the shape of the action potentials traveling along the axon. In practice, the tightness of the suction is the key parameter for high-quality recordings using a suction electrode. Comparison with Existing Methods: Experimental protocols that can improve precise positioning of the electrode tip to the target nerve, avoid tissue damage, enhance suction force, and maintain tightness are essential for high-quality suction recording from axons. Current methods have not emphasized on achieving and maintaining of the suction pressure during experimentation, and have sometimes ignored the impact of suction electrode position or tissue damage to the quality of the recorded neural signal. A combined theoretical analysis and experimental approach is essential in improving neural recording technology. The work provides theoretical and practical guidelines to improve suction technology. This work also provides valuable insights to the improvement of several other extracellular recording technology in laboratory research or clinical settings.


Exploring the redox balance inside gram-negative bacteria with redox-sensitive GFP.
Aerobic bacteria are continuously fighting potential oxidative stress due to endogenous and exogenous reactive oxygen species (ROS). To achieve this goal, bacteria possess a wide array of defenses and stress responses including detoxifying enzymes like catalases and peroxidases; however until now, the dynamics of the intra-bacterial redox balance remained poorly understood. Herein, we used redox-sensitive GFP (roGFP2) inside a variety of gram-negative bacteria to study real-time redox dynamics immediately after a challenge with hydrogen peroxide. Using this biosensor, we determined the individual contributions of catalases and peroxidases and found that each enzyme contributes more to rapid detoxification or to prolonged catalytic activity. We also found that the total catalytic power is affected by environmental conditions. Additionally, using a Salmonella strain that is devoid of detoxifying enzymes, we examined endogenous ROS production. By measuring endogenous ROS production, we assessed the role of oxidative stress in toxicity of heavy metals and antibiotics. We found that exposure to nickel induced significant oxidative stress whereas cobalt (which was previously implicated to induce oxidative stress) did not induce ROS formation. Since a turbulent debate evolves around oxidative stress as a general killing mechanism by antibiotics (aminoglycosides, fluoroquinolones and β-lactams), we measured oxidative stress in bacteria that were challenged with these antibiotics. Our results revealed that antibiotics do not induce ROS formation in bacteria thereby disputing a role for oxidative stress as a general killing mechanism. Together, our results expose how the intra-bacterial redox balance in individual microorganisms is affected by environmental conditions and encounters with stress-inducing compounds. These findings demonstrate the significant potential of roGFP2 as a redox biosensor in gram-negative bacteria to investigate redox dynamics under a variety of circumstances.


Harmonized molecular classification; assessment of a single-test ProMisE NGS tool.
Despite recommendations for integrating molecular classification of endometrial cancers (EC) into pathology reporting and clinical management, uptake is inconsistent. To assign ProMisE subtype, all molecular components must be available (POLE mutation status, mismatch repair (MMR) and p53 immunohistochemistry (IHC)) and often these are assessed at different stages of care and/or at different centres resulting in delays in treatment. We assessed a single-test DNA-based targeted next generation sequencing (NGS) molecular classifier (ProMisE NGS), comparing concordance and prognostic value to the original ProMisE classifier. DNA was extracted from formalin-fixed paraffin embedded (FFPE) ECs that had previously undergone ProMisE molecular classification (POLE sequencing, IHC for p53 and MMR). DNA was sequenced using the clinically validated Imagia Canexia Health Find It™ amplicon-based NGS gene panel assay to assess for pathogenic POLE mutations (unchanged from original ProMisE), TP53 mutations (in lieu of p53 IHC), and microsatellite instability (MSI) (in lieu of MMR IHC),with the same order of segregation as original ProMisE used for subtype assignment. Molecular subtype assignment of both classifiers was compared by concordance metrics and Kaplan-Meier survival statistics. The new DNA-based NGS molecular classifier (ProMisE NGS) was used to determine the molecular subtype in 164 ECs previously classified with ProMisE. 159/164 cases were concordant with a kappa statistic of 0.96 and an overall accuracy of 0.97. Prognostic differences in progression-free, disease-specific and overall survival between the four molecular subtypes were observed for the new NGS classifier, recapitulating the survival curves of the original ProMisE classifier. ProMisE NGS was 100% concordant between matched biopsy and hysterectomy samples. ProMisE NGS is feasible on standard FFPE material, demonstrates high concordance with the original ProMisE classifier and maintains prognostic value in EC. This test has the potential to facilitate implementation of molecular classification of EC at the time of first diagnosis.


Removal enhancement of 1-naphthol and 1-naphthylamine in single and binary aqueous phase by acid-basic interactions with polymer adsorbents.
In the present study removal performance of 1-naphthol and 1-naphthylamine from wastewater by single and binary adsorption was compared. Synergistic effects were investigated in single-solute, binary-solute, and the preloading adsorption systems at 293 K. Two commercial polystyrene adsorbents Amberlite XAD-4, a macroporous adsorbent, and NDA-100, a hyper-cross-linked adsorbent, were employed here for their frequent use in organic pollutants removal from contaminated waters. All the adsorption isotherms of 1-naphthol and 1-naphthylamine on both adsorbents were found to be well represented by the Langmuir equation. Adsorption capacity of the primary solute was enhanced in the presence of the co-solute, arising presumably from the synergistic effect caused by the laterally acid-base interaction between the adsorbed 1-naphthol and 1-naphthylamine molecules. Due to the stronger adsorption affinity of 1-naphthylamine to nonpolar adsorbents, adsorption enhancement of 1-naphthylamine in the presence of 1-naphthol is greater than that of 1-naphthol in the presence of 1-naphthylamine. The greater synergistic effect of 1-naphthol/1-naphthylamine equimolar mixtures on XAD-4 than that on NDA-100 partly results from the larger average pore size of the former adsorbent. A modified extended Langmuir model is proved to well describe the synergistic adsorption of 1-naphthol/1-naphthylamine equimolar mixtures in the binary-solute system. The synergistic coefficient of one adsorbate is linearly correlated with the amount of the other adsorbed on the adsorbent.


Design and analysis of arm-in-cage experiments: inference for three-state progressive disease models with common periodic observation times.
We develop statistical methods for designing and analyzing arm-in-cage experiments used to test the efficacy of insect repellents and other topical treatments. In these experiments, a controlled amount of the treatment is applied to a volunteer's forearm, which then is exposed to the insects by being placed into a special cage. Arms are not kept in the cages continuously, but rather placed there periodically for a brief period of time, during which it is noted whether an insect lands (but does not bite) or (lands and) bites. Efficacy of a repellent can be described using a progressive three-state model in which the first two states represent varying degrees of protection (no landing and landing without biting) and the third state occurs once protection is completely lost (biting). Because subjects within a treatment group follow the same cage visit schedule, transition times between states are interval censored into one of several fixed intervals. We develop an approach that uses a mixture of nonparametric and parametric techniques for estimating the parameters of interest when sojourn times are dependent. Design considerations for arm-in-cage experiments are addressed and the proposed methods are illustrated on data from a recent arm-in-cage experiment as well as simulated data.


Radiological evaluation of the ascending aorta following repair of type A dissection.
A patient with persistent chronic dissection proximal to an aortic interposition graft for repair of a type A dissection prompted us to review the computed tomographic (CT) findings in 14 other such patients 5-47 months after surgery. No other case of proximal aortic dissection was identified although dilatation of the aortic root proximal to the graft was present in 8 patients (57%). Persistent dissection distal to the graft in 11 patients (79%) was in keeping with that reported by other workers. Chronic dissection proximal to the surgical repair of a dissection seems a rare although important complication.


Azathioprine-induced EBV-positive mucocutaneous ulcer.
Epstein-Barr virus (EBV)-positive mucocutaneous ulcer was recently described as a clinicopathologic entity occurring secondary to iatrogenic or age-related immune suppression. The histopathology of EBV-positive mucocutaneous ulcer reveals a polymorphous infiltrate including atypical large B-cells and Reed-Sternberg-like cells which are CD20-positive, CD30-positive and EBV-positive. The disorder follows an indolent and self-limited course. We report a case of EBV-positive mucocutaneous ulcer secondary to prolonged use of azathioprine for the treatment of pemphigoid and highlight the need for recognition of this disorder by dermatopathologists and dermatologists.


Prescribing for children.
Many children receive urgent care within emergency departments. Children are at increased risk from the use of medicines for a number of reasons, including the need to calculate a weight or age-based dose or administration of a fraction or proportion of an adult formulation of medicine. Aspects of good practice from the English National Service Framework (NSF) for Children, Young People and Maternity Services are highlighted. The importance of good medicines reconciliation is discussed. Websites that support emergency care practitioners to address medicines adherence and counselling of parents and children on use of medicines are presented. The drug related needs of children and young people must be assessed on an individual basis. Guidelines are outlined to support safe prescribing and medicines administration.


Jasmonic Acid Induces Endoplasmic Reticulum Stress with Different Outcome in Cultured Normal and Tumor Epidermal Cells.
Plant hormones produce cytotoxic effect on human cells and can trigger the processes unrelated to cell death, e.g., biosynthetic system stress. The goal of this study was to investigate activation of the endoplasmic reticulum (ER) stress by jasmonic acid (JA) and to distinguish between the responses of cultured immortalized non-tumorigenic HaCaT cells and epidermoid carcinoma A431 cells to this plant hormone. JA was used in the concentration of 2 mM, as it suppressed cell proliferation in both cell lines. We analyzed expression of genes associated with the activation of ER stress (GRP78, ATF4, CHOP), the structure of the ER and Golgi complex, and synthetic processes in the HaCaT and A431 cell lines. JA induced expression of genes responsible for the activation of ER stress and caused hypertrophic changes in the Golgi complex in both cell lines. However, the patterns of gene expression in the HaCaT and A431 cells were different, and higher levels of involucrin synthesis were observed in A431 but not in HaCaT cells, suggesting that JA activated differentiation of the tumor A431 cells only. Therefore, JA induced ER stress in both cell lines, but the consequences of ER stress were different for the epidermal immortalized non-tumorigenic and tumor cells.


Exploration of novel clusters and prognostic value of immune‑related signatures and identify HAMP as hub gene in colorectal cancer.
Immune checkpoint inhibitors currently serve an important role in prolonging patients' overall survival. However, the prognostic signatures of immune checkpoint inhibitors in colorectal cancer (CRC) remain uncertain and more knowledge on the genetic characteristics of colorectal cancer is needed. Patients with CRC from The Cancer Genome Atlas were classified into high-immunity group and low-immunity group based on median scores from single-sample gene set enrichment analysis using the GSVA package. We explored immune status by immune scores, stromal scores and tumor purity scores in ESTIMATE package and surveyed the difference of immune cells distribution with CIBERSORT package. Eighteen genes were selected using the LASSO Cox regression method and a prognostic risk model was constructed. Compared with patients in the low-risk group, those in the high-risk group had a significantly shorter survival time. For assessment of the prognostic validity of the risk model, receiver operating characteristic curves with areas under the curve of 0.769, 0.774 and 0.771 for 1, 3 and 5 years respectively. Differences in molecular mechanisms between high- and low-risk groups were analyzed using the clusterProfiler package. Tumor Immune Dysfunction and Exclusion data were downloaded and analyzed. The top 5 enriched pathways in the high-risk group involved 'calcium signaling', 'dilated cardiomyopathy', 'extracellular matrix receptor interaction', 'hypertrophic cardiomyopathy' and 'neuroactive ligand receptor interaction'. HAMP was identified as a hub gene, which was highly expressed in tumor samples. The results of the present study indicate that the prognostic model based on both immune-related genes and HAMP has the potential to support personalized treatment.


Improved method for the immobilization of heparin.
The optimal conditions for immobilizing heparin through its terminal formyl group were investigated. When Amino Sepharose (1 g) was suspended in 1 ml of phosphate buffer (pH 7) containing 30 mg of heparin and 3 mg of sodium cyanoborohydride, with shaking at room temperature, the maximum immobilization of heparin (10 mg of heparin per gram of wet gel) was reached within 2 days. The Heparin Sepharose thus obtained was stable: no significant loss of the heparin content was observed after storage for 4 months at 4 degrees C. Heparin was also immobilized by the same method with Amino TSK gel G5000PW instead of Amino Sepharose 4B and was successfully applied to the high-performance liquid affinity chromatography of fibronectin and thrombin.


A review of public policy issues in promoting the development and commercialization of pharmacogenomic applications: challenges and implications.
This article reviews the regulatory, social, policy, and other issues that will shape the development of pharmacogenomics applications. We identify and analyze 19 key public policy issues, ranging from the economic incentives for linked diagnostic-drug development, to the regulation of tests and drugs, and to privacy and informed consent. Challenging technical, business, and policy-related issues might either hinder progress in the field of pharmacogenomics or potentially accelerate it, depending on how they are addressed and resolved. How well the numerous important stakeholders - both private and public - address these issues will be critical for pharmacogenomics to deliver on its promise.


Aggregation and amyloid fibril formation of the prion protein is accelerated in the presence of glycogen.
Prion diseases like Creutzfeldt-Jakob disease in humans or scrapie in sheep and goats are infectious neurodegenerative diseases. Their infectious agent, called prion, is composed mainly of aggregated and misfolded prion protein and non-proteinaceous components. An example of such a common non-proteinaceous secondary component of natural prions is the polysaccharide scaffold. We studied the influence of such a polysaccharide on the conformational transition of PrP applying an in vitro conversion system. Here we report that glycogen supports and accelerates PrP amorphous aggregation similar to seeded aggregation and leads to co-aggregates. Furthermore, PrP fibril formation was highly accelerated in the presence of glycogen.


A novel synthetic oleanolic acid derivative with amino acid conjugate suppresses tumour growth by inducing cell cycle arrest.
Oleanolic acid (3beta-hydroxy-olean-12-en-28-oic acid; OA) has a wide variety of bioactivities and is used for medicinal purposes in many Asian countries. Various derivatives of OA have been synthesized in attempts to improve the potency. Here we describe the anti-tumour activity of a novel OA derivative, N-[(3beta)-3-(acetyloxy)-28-oxoolean-12-en-28-yl]-glycine methyl ester (AOA-GMe). AOAGMe was a more potent inhibitor of the growth of B16 melanoma cells than its parent compound OA, both in-vitro and in-vivo. AOA-GMe also exhibited dose-dependent inhibition of human K562 leukaemia cells, but had almost no toxicity in normal human peripheral blood mononuclear cells. AOA-GMe induced cell cycle arrest in G0/G1 and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D, cyclin-dependent kinase CDK4 and phosphorylated retinoblastoma protein, and increases in the cyclin-dependent kinase inhibitor p15. OA did not show such activities. These results suggest that AOA-GMe may induce growth arrest in tumour cells through regulation of proteins involved in the cell cycle.


A neuropathological study of dementia in nursing homes over a 17-year period, in Shimane Prefecture, Japan.
In Japan, vascular dementia (VD) has been responsible for the majority of all dementia cases in both epidemiological and neuropathological studies. Recently, however, several epidemiological investigations have shown that the rate of VD has decreased and senile dementia of the Alzheimer type (SDAT) is now the major cause of dementia, though few neuropathological investigations show that the majority of dementia is SDAT. The purpose of the study was to clarify the rates of dementia types in Japanese nursing home residents and to compare the ratio of SDAT to VD in the first and second halves of the study. One hundred and twenty-two demented nursing home residents (48 men and 74 women) were evaluated neuropathologically over a period of 17 years in Shimane prefecture, Japan. All subjects died between 1976 and 1992. The average age at death was 81.4 +/- 9.4 years for men, 85.0 +/- 7.2 for women and 83.6 +/- 8.3 for total samples. In classifying dementia type, SDAT accounted for 34% (41 cases); VD 35% (42); mixed dementia 11% (14); and 'other' dementia 20% (25) of all samples. Comparison of the first 9-year period with the second 8-year period revealed the ratio of SDAT to VD tended to increase (from 0.83 to 1.15). This increasing tendency was found both in men (from 0.53 to 0.7) and in women (from 1.13 to 1.44). These tendencies, however, were not statistically significant. There was no change statistically in the ratio of SDAT to VD between the first half of the study and the second half. However, there was an increasing tendency of the ratio in our study.


[Effect of recombinant gamma interferon on allergic skin reaction and bronchoconstriction].
Gamma-interferon (IFN-gamma) has immunosuppressive and immunostimulatory effects. Net results in clinical disease are difficult to predict. We studied possible anti-allergic effects of IFN-gamma in a double blind study in 30 patients with bronchial asthma. We performed quantitative skin prick and bronchial allergen provocation tests using each patient's main allergen prior to and after 20 injections of either recombinant IFN-gamma (100 micrograms each) or placebo, measuring skin wheal area, specific airway resistance (SRaw) and the maximal expiratory flow at 50% of vital capacity (MEF50). IFN-gamma reduced skin wheal area significantly but had no effect on allergic bronchoconstriction.


Effect of radiant heat induced by a diode laser (445 nm) on setting process of glass-ionomer cements monitored by Fourier transform infrared spectroscopy.
The aim of this study was to investigate the effect of thermal energy induced by a diode laser (445 nm) on the setting reactions of conventional glass ionomer cements (GICs) by using Fourier transform infrared spectroscopy (FTIR) and to compare it with that induced by a LED device. Four GICs were investigated in this study (GlassIonomer FX Ultra, Ketac Universal Aplicap, Equia Fill, and Riva Self Cure). The experimental groups of the study were as follows (n = 5): Group 1 (control) - the specimens after mixing were left to set without any treatment; Group 2 - the specimens were irradiated for 60 s using a LED (Valo™) at 1400 mW/cm2 (fluence ∼ 1.4 J/cm2); Group 3 - the specimens were also irradiated for 60 s using a diode laser (SIROLaser Blue), which emits at 445 ± 5 nm with average output power of 0.7 W (fluence ∼ 1.4 J/cm2). FTIR analysis of the GIC specimens was followed to assess the changes in the COO-/CO ratios of the setting reaction and its progress in time. Both laser and LED treatments improved the setting reactions of the GICs compared to the control group (p < 0.05). However, this phenomenon was not observed in all materials implying that it may be material dependent. Radiant heat treatments using diode laser or LED may be beneficial for the rate and progress of setting reaction of the conventional GICs. The composition and handling of the materials may be crucial for their final properties and the overall clinical behavior.


Glue embolization of a ruptured celiac trunk pseudoaneurysm via the gastroduodenal artery.
Percutaneous transcatheter embolization of splanchnic artery aneurysms is a minimally invasive and alternative therapy to conventional surgical intervention. Due to a high-grade stenosis at the origin of the celiac trunk, a retrograde approach to the celiac trunk pseudoaneurysm via the gastroduodenal artery was necessary. To prevent undesirable embolization into the peripheral left gastric artery initial occlusion of the central portion of the left gastric artery was performed with microcoils using a Tracker catheter. Complete occlusion of the celiac trunk itself and the short adjacent segments of the celiac artery was achieved by using a mixture of N-butyl-2-cyanoacrylate and ethiodized oil as the embolizing agent.


Apparent life-threatening events and sudden infant death on a monitor.
This review summarises recent data on mechanisms for apparent life-threatening events (ALTE) and sudden infant death (SID) which show that (i). recordings obtained during ALTE allow the detection of previously unrecognised but preventable mechanisms in a significant proportion of infants and should thus be performed routinely in infants with such a history, (ii). in recordings obtained during SID and idiopathic ALTE, prolonged apnoea was found in only a minority, while severe hypoxaemia appeared to the common mechanism, (iii). it remains yet unclear by which mechanism this hypoxaemia develops, with upper and/or lower airway obstruction, rebreathing of expired air and intrapulmonary shunting being potential candidates, (iv). there is evidence that arousal fails during SID, which could be related to known risk factors such as tobacco smoke exposure, whereas (v). gasping occurred during the majority of SID cases where respiratory patterns have been analysed, but it remains unclear why gasping remains ineffective in resuscitating the infant from hypoxaemia.


Mediastinal Staging in Non-Small Cell Lung Cancer.
In the absence of distant metastases, lung cancer treatment is determined by the results of mediastinal lymph node staging. Occult mediastinal lymph node metastases can be missed by radiologic and needle-based staging methods. Aggressive staging of mediastinal lymph nodes improves staging accuracy. Improved accuracy of mediastinal lymph node staging results in more appropriate lung cancer treatment. Improved accuracy of mediastinal lymph node staging can improve stage-specific survival from lung cancer.


Meta-Analysis Comparing Apixaban Versus Rivaroxaban for Management of Patients With Nonvalvular Atrial Fibrillation.
To compare the efficacy and safety of apixaban and rivaroxaban for the prevention of stroke in patients with nonvalvular atrial fibrillation (NVAF) by way of a meta-analysis informed by real-world evidence. Systematic review and meta-analysis of observational studies including patients with NVAF on apixaban and rivaroxaban, which reported stroke/systemic embolism and/or major bleeding. Prospero registration number: CRD42021251719. Estimates of relative treatment effect (based on hazard ratios[HRs]) were pooled using the inverse variance method. Fixed-effects and random effect analyses were conducted. Exploratory meta-regression analyses that included study-level covariates were conducted using the metareg (meta-regression) command of Stata Statistical Software: Release 15.1 (College Station, Texas. StataCorp LLC.). Study level covariates explored in the meta-regression analyses were CHA2DS2-VASc and HAS-BLED scores. A total of 10 unique retrospective real-world evidence studies reported comparative estimates for apixaban versus rivaroxaban in patients with NVAF and were included in the meta-analysis. Adjusted HR was 0.88 (95% [confidence interval] CI 0.81 to 0.95), indicating a significantly lower hazard of stroke/systemic embolism associated with apixaban versus rivaroxaban. Pairwise meta-analysis for a major bleeding episode was significantly lower with apixaban compared with rivaroxaban (HR 0.62; 95% CI 0.56 to 0.69), whereas apixaban was associated with a lower risk of gastrointestinal bleeding compared with rivaroxaban (HR 0.57; 95% CI 0.50 to 0.64). In conclusion, this study suggests that patient CHA2DS2-VASc and HAS-BLED scores might be an important factor when selecting which direct oral anticoagulants to use, given the relation these scores have on treatment outcomes. Apixaban is associated with lower rates of both major and gastrointestinal bleeding than rivaroxaban, with no loss of efficacy.


Computational design and molecular modeling of the interaction of nicotinic acid hydrazide nickel-based complexes with H2S gas.
The application of nickel complexes of nicotinic acid hydrazide ligand as a potential gas-sensor and adsorbent material for H2S gas was examined using appropriate density functional theory (DFT) calculations with the ωB97XD/Gen/6-311++G(d,p)/LanL2DZ method. The FT-IR spectrum of the synthesized ligand exhibited a medium band at 3178 cm-1 attributed to ν(NH) stretching vibrations and strong bands at 1657 and 1600 cm-1 corresponding to the presence of ν(C[double bond, length as m-dash]O) and ν(C[double bond, length as m-dash]N) vibration modes. In the spectrum of the nickel(ii) complex, the ν(C[double bond, length as m-dash]O) and ν(C[double bond, length as m-dash]N) vibration bands experience negative shifts to 1605 cm-1 and 1580 cm-1, respectively, compared to the ligand. This indicates the coordination of the carbonyl oxygen and the azomethine nitrogen atoms to the Ni2+ ion. Thus, the sensing mechanism of the complexes indicated a short recovery time and that the work function value increases for all complexes, necessitating an excellent H2S gas sensor material. Thus, a profound assertion was given that the complex sensor surfaces exhibited very dense stability with regards to their relevant binding energies corresponding to various existing studies.


Large cooperativity and microkelvin cooling with a three-dimensional optomechanical cavity.
In cavity optomechanics, light is used to control mechanical motion. A central goal of the field is achieving single-photon strong coupling, which would enable the creation of quantum superposition states of motion. Reaching this limit requires significant improvements in optomechanical coupling and cavity coherence. Here we introduce an optomechanical architecture consisting of a silicon nitride membrane coupled to a three-dimensional superconducting microwave cavity. Exploiting their large quality factors, we achieve an optomechanical cooperativity of 146,000 and perform sideband cooling of the kilohertz-frequency membrane motion to 34±5 μK, the lowest mechanical mode temperature reported to date. The achieved cooling is limited only by classical noise of the signal generator, and should extend deep into the ground state with superconducting filters. Our results suggest that this realization of optomechanics has the potential to reach the regimes of ultra-large cooperativity and single-photon strong coupling, opening up a new generation of experiments.


Follow, filter, filler? Social media usage and cosmetic procedure intention, acceptance, and normalization among young adults.
Today, young people spend much of their lives online where they encounter abundant appearance-focused content. In light of the important role that social media platforms like Instagram play in young people's attitudes towards the cosmetic surgery industry, this study investigates passive and active social media usage in relation to young adults' perceptions of cosmetic procedures. In a cross-sectional survey study among 470 Instagram users aged 18-25 years (Mage = 21.00, SDage = 2.26), young adults indicated a low cosmetic procedure intention themselves, but overestimated the prevalence of cosmetic procedures undertaken by others. Considering passive social media use, young adults who follow influencers who had undergone cosmetic procedures reported higher intentions to have cosmetic procedures themselves, and following influencers who had not undergone procedures was related to lower intentions. In terms of active social media usage, frequency of Instagram posting was generally insignificant in relation to acceptance of and intention to undergo cosmetic procedures. Yet, those who used filters to edit pictures more frequently reported increased cosmetic procedure acceptance and intention. Overall, this paper offers a nuanced perspective on the relation between young adults' perceptions of cosmetic procedures and their social media behaviors, highlighting the importance of specific appearance-oriented social media usage.


Reamed Versus Unreamed Intertrochanteric Femur Fractures, Is It Time?
This study compares the intraoperative and postoperative outcomes of the traditional technique of femoral canal reaming to placement of an unreamed 10-mm nail. Retrospective cohort study. Academic Level I Trauma Center, Southeastern US. Intertrochanteric femur fractures treated with a CMN (January 2016-December 2018) were retrospectively identified. Inclusion criteria were as follows: low-energy mechanism, at least 60 years of age, and long CMN. Exclusion criteria were as follows: short CMN, polytrauma, and subtrochanteric fractures. Records were reviewed for demographics, hematologic markers, transfusion rates, operative times, and postoperative complications. Variables were assessed with a χ or Student T-test. Significance was set at 0.05. Sixty-five patients were included (37 reamed and 28 unreamed), with a mean age of 76.2 years and mean body mass index of 25.1. Between the reamed and unreamed groups, respectively, mean nail size was 11.0 (SD 1.1) and 10.0 (SD 0.0), P < 0.001; mean blood loss was 209.1 mL (SD 177.5) and 195.7 mL (SD 151.5), P = 0.220; 55% (21/38), and 43% (12/28) were transfused, P = 0.319; operative time was 98.2 (SD 47.3) and 81.5 minutes (SD 40.7); P = 0.035. Changes in hemoglobin/hematocrit were not significant between the study groups. Two patients from the reamed group experienced implant failure due to femoral head screw cut out and returned to the operating room. Two patients from the unreamed group returned to operating room for proximal incision infection, without implant removal. One reamed patient and 2 unreamed patients died before 6-month follow-up. Unreamed CMNs for geriatric intertrochanteric femur fractures provide shorter operative times with no difference in perioperative complications. Both reamed and unreamed techniques are safe and effective measures for fixation of these fractures. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Comparative tolerability of 2- and 15-minute intravenous infusions of pantoprazole.
The safety and tolerability of 80 mg i.v. pantoprazole administered as a 2-minute versus a 15-minute infusion were studied. In a single-blind, randomized, multiple-dose, parallel-group study, 48 healthy participants (ages 18-45 years) were randomly assigned for treatment with 80 mg i.v. pantoprazole infused for 2 or 15 minutes once daily for seven days. A blinded evaluator assessed the injection site for phlebitis and infiltration on a 5-point scale at specified intervals. Participants completed the visual analogue scale (VAS) for pain and burning at baseline and at 5 minutes postinjection. More than 99% of the preinfusion and postinfusion infiltration scores and >95% of the phlebitis scores were rated as zero in 48 healthy participants. A total of 7 infiltration scores (1%) and 72 postinfusion phlebitis scores (5%) of greater than 0 were recorded, all of which were mild in nature. Forty-one phlebitis scores of 1 and 1 score of 2 were from 12 participants in the 2-minute group, and 20 scores of 1 and 10 scores of 2 were from 8 participants in the 15-minute group. VAS assessments showed that the perception of pain and burning was not greater in the 2-minute group. There were no significant differences in adverse events between the two groups. The safety and tolerability profiles of i.v. pantoprazole administered as a 2-minute infusion were similar to those of the 15-minute infusion. This protocol may result in the savings of staff time with no additional discomfort to the patient.


Nitric oxide deficiency in the internal anal sphincter of patients with chronic anal fissure.
Anal fissure is a common condition affecting young to middle-aged adults. It causes severe pain on defecation and rectal bleeding. The aetiology remains uncertain. Spasm of the internal anal sphincter is a constant feature. Nitric oxide (NO) is the major inhibitory neurotransmitter of the internal anal sphincter (IAS). In other spasmodic conditions of the GI tract a lack of normal nitric oxide synthase (NOS) activity has been reported. The aim of this preliminary study was to compare the presence of NOS in the internal sphincters of patients with and without chronic anal fissure. Internal anal sphincter biopsies were taken under general anaesthesia from patients having lateral internal sphincterotomy for chronic anal fissure and from sphincter of patients having abdominoperineal resections as controls. Sections of IAS were stained to show the presence of NADPH diaphorase (and hence presence of NOS). Internal anal sphincter was taken from 6 patients with chronic anal fissure and 6 controls. IAS taken from patients with chronic anal fissure showed little NOS presence compared with controls. It may be that there is an abnormal failure of relaxation of internal sphincter in those patients who develop chronic anal fissure caused by an intrinsic lack of neural NOS in the internal anal sphincter.


Objective cognitive functioning in patients with stress-related disorders: a cross-sectional study using remote digital cognitive testing.
Patients with stress-related mental disorders often report cognitive impairment, but studies investigating objective cognitive impairment in patients with stress-related disorders have produced inconsistent findings. The primary aim of this study was to investigate objective cognitive functioning in patients diagnosed with the stress-related disorders adjustment disorder or exhaustion disorder, compared to a healthy normative group. Secondary aims were to conduct subgroup analyses of cognitive functioning between the diagnostic groups and explore associations between self-reported symptoms and cognitive functioning. Cognitive test results on a digitally self-administered cognitive test battery from 266 patients (adjustment disorder, n = 131; exhaustion disorder, n = 135) were cross-sectionally compared with results from a healthy normative group (N = 184 to 692) using one-tailed t-tests. ANOVAs were conducted for subgroup analyses, and regression analyses for associations between self-reported symptoms and cognitive functioning. Effect sizes were calculated. Patients performed significantly worse than the normative group on all measures with small to moderate effect sizes ranging from d = -.13 to -.57. Those diagnosed with exhaustion disorder performed worse than norms on more measures than did patients with adjustment disorder, but no significant differences between diagnostic groups were found on any measure. Self-reported memory impairment was weakly associated with one of two memory measures. No clear associations between self-reported burnout symptoms and objective cognitive functioning were found. This study adds to the literature indicative of small to moderate objective cognitive impairments in patients diagnosed with stress-related mental disorders. Further exploration into mechanisms of cognitive functioning in different populations is needed for development of theoretical models that may explain the weak correlation between self-reported symptoms and objective measures. ClinicalTrial.gov: NCT04797273. Trial registration date 15 March 2021. This study was also pre-registered on Open Science Framework (osf.io) with https://doi.org/10.17605/OSF.IO/TQXZV .


Systematic Review of Racial, Socioeconomic, and Insurance Status Disparities in the Treatment of Pediatric Neurosurgical Diseases in the United States.
Increasing light is being shed on how race, insurance, and socioeconomic status (SES) may be related to outcomes from disease in the United States. To better understand the impact of these health care disparities in pediatric neurosurgery, we performed a systematic review of the literature. We conducted a systematic review using PRISMA guidelines and MeSH terms involving neurosurgical conditions and racial, ethnic, and SES disparities. Three independent reviewers screened articles and analyzed texts selected for full analysis. Thirty-eight studies were included in the final analysis, of which all but 2 were retrospective database reviews. Thirty-four studies analyzed race, 22 analyzed insurance status, and 13 analyzed SES/income. Overall, nonwhite patients, patients with public insurance, and patients from lower SES were shown to have reduced access to treatment and greater rates of adverse outcomes. Nonwhite patients were more likely to present at an older age with more severe disease, less likely to undergo surgery at a high-volume surgical center, and more likely to experience postoperative morbidity and mortality. Underinsured and publicly insured patients were more likely to experience delay in surgical referral, less likely to undergo surgical treatment, and more likely to experience inpatient mortality. Health care disparities are present within multiple populations of patients receiving pediatric neurosurgical care. This review highlights the need for continued investigation into identifying and addressing health care disparities in pediatric neurosurgery patients.


Mediterranean diet and infertility: a systematic review with meta-analysis of cohort studies.
The Mediterranean diet (MD) is a dietary pattern with evidence of positive health impact, and some nutrients in this diet have already been researched for their effectiveness in fertility. However, there are still questions about whether high adherence to the MD could be a factor that contributes to positive fertility outcomes in infertile men and women. A systematic review and meta-analysis were conducted to determine whether a greater adherence to the MD can improve fertility markers and outcomes in infertile men and women. The MEDLINE, BVS, SciELO, CENTRAL, and Embase databases and gray literature were searched from their inception to May 2022. Data were included from cohort studies that addressed MD and outcomes. Data searches, article selection, data extraction, and risk-of-bias assessments were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 11 studies met the inclusion criteria (n = 13 157 women and 1338 men). Greater adherence to the MD was associated with live births (I2 = 83.16%; odds ratio [OR], 0.652; 95%CI, 0.408-3.194), pregnancy rate (I2 = 93.83%; OR, 1.192; 95%CI, 0.349-4.325), sperm concentration >15 × 106/mL (I2 = 32.97%; OR 2.862; 95%CI, 1.583-5.174), and sperm count > 39 × 106/mL (I2 = 48.1%; OR, 2.543; 95%CI, 1.319-4.904); however, in an inconsistent scenario regarding the meta-analysis. Current evidence of high adherence to MD and fertility markers is insufficient to support their clinical application, even though it indicates sperm improvement and a possibility of better pregnancy outcomes. PROSPERO registration no. 169396.


(1E,4E)-1-(3-Nitro-phen-yl)-5-phenyl-penta-1,4-dien-3-one.
In the title compound, C(17)H(13)NO(3), the dihedral angle between the benzene rings is 31.21 (5)°. In the crystal, inversion dimers linked by pairs of C-H⋯O hydrogen bonds occur. A C-H⋯π inter-action is also indicated.


Engagement of the National Institute of Parasitic Diseases in control of soil-transmitted helminthiasis in China.
Soil-transmitted helminthiases (STHs) have been widely transmitted in China and the control of STHs was initiated by NIPD-CTDR since its foundation. Three national surveys on STHs have been carried out in China, and the infection rate has dropped from 53.58% in the first national survey (1988-92) to 4.49% in the third national survey (2014-16) due to strong interventions including mass drug administration, health education and environment improvement. National surveillance of STHs started in 2006 and has been implemented successively until now, which allows to understand the endemic status and trends of STHs prevalence in China. Surveillance has been expanded to 30 provinces of China since 2016. Integrated pilot programmes have been implemented between 2006 and 2009, in which an integrated strategy, with health education and control of infection sources as key components, was adopted. Since 2019, new control pilots have been started, which will be continued for five successive years to further explore appropriate control strategies in the current "new era". With the decline of infection rate of STHs, China is approaching the elimination stage for STHs. In order to achieve this final target, poverty alleviation programmes should be integrated with precise control measures, according to real situations.


Sevoflurane and isoflurane monoanesthesia abolished the phrenic long-term facilitation in rats.
Phrenic long-term facilitation (pLTF) is a form of respiratory plasticity, manifested by prolonged increase in peak amplitude of phrenic nerve activity (PNA) after episodes of acute intermittent hypoxia (AIH). The aim was to investigate the effects of sevoflurane and isoflurane monoanesthesia at equipotent anesthetic doses on the expression of amplitude pLTF. Experiments were performed on Sprague-Dawley anesthetized, vagotomized, and mechanically ventilated rats. Two experimental groups, sevoflurane and isoflurane, and a control group (urethane-anesthetized) were formed. Peak amplitude of phrenic nerve activity, respiratory frequency and breathing rhythm parameters (Ti, inspiratory duration; Te, expiratory duration; and Ttot, total respiratory time duration) were analyzed during hypoxic episodes, and at 15, 30, and 60min after the last hypoxic episode. In the control group average PNA increased by 173.03±70.16% (p<0.001), at 60min after the last hypoxic episode compared to baseline values. Therefore amplitude pLTF was induced. In the sevoflurane and isoflurane groups PNA failed to increase, and in fact decreased by 15.79±15.18% and 31.00±11.00%, respectively (p>0.05). Amplitude pLTF was abolished during sevoflurane and isoflurane monoanesthesia.


MultiWaver 2.0: modeling discrete and continuous gene flow to reconstruct complex population admixtures.
Our goal in developing the MultiWaver software series was to be able to infer population admixture history under various complex scenarios. The earlier version of MultiWaver considered only discrete admixture models. Here, we report a newly developed version, MultiWaver 2.0, that implements a more flexible framework and is capable of inferring multiple-wave admixture histories under both discrete and continuous admixture models. MultiWaver 2.0 can automatically select an optimal admixture model based on the length distribution of ancestral tracks of chromosomes, and the program can estimate the corresponding parameters under the selected model. Specifically, for discrete admixture models, we used a likelihood ratio test (LRT) to determine the optimal discrete model and an expectation-maximization algorithm to estimate the parameters. In addition, according to the principles of the Bayesian Information Criterion (BIC), we compared the optimal discrete model with several continuous admixture models. In MultiWaver 2.0, we also applied a bootstrapping technique to provide levels of support for the chosen model and the confidence interval (CI) of the estimations of admixture time. Simulation studies validated the reliability and effectiveness of our method. Finally, the program performed well when applied to real datasets of typical admixed populations, such as African Americans, Uyghurs, and Hazaras.


Coffee consumption and stomach cancer risk in a cohort of Swedish women.
Few prospective studies have examined the relationship between coffee consumption and risk of stomach cancer, and the findings have been inconsistent. We prospectively investigated the association of long-term coffee consumption with risk of stomach cancer in a population-based cohort study of 61,433 Swedish women. Information on coffee consumption was collected with a food-frequency questionnaire at baseline (1987-1990) and updated in 1997. During a mean follow-up of 15.7 years from 1987 through June 2005, 160 incident cases of stomach cancer were diagnosed. Coffee consumption was positively associated with the risk of stomach cancer. Compared to women who consumed 1 or fewer cups of coffee per day, the multivariate hazard ratios were 1.49 (95% = 0.97-2.27) for women who drank 2-3 cups per day and 1.86 (95% CI = 1.07-3.25) for those who drank 4 or more cups per day (p for trend = 0.01). An increase of 1 cup of coffee per day was associated with a statistically significant 22% increased risk of stomach cancer (hazard ratio = 1.22; 95% CI = 1.05-1.42). These prospective data suggest that coffee consumption may increase the risk of stomach cancer in a dose-response manner. This finding needs to be confirmed in other prospective studies.


Chronic long-term electrostimulation creates a unique metabolic enzyme profile in rabbit fast-twitch muscle.
Long-term low-frequency stimulation (up to 120 days) of rabbit fast-twitch tibialis anterior muscle led, in a first-order-like time course, to changes in enzyme activities of energy metabolism which became stable with ongoing stimulation after 50 days. The glycolytic enzymes decreased to 30-40% of their normal values, but remained 2-3-fold higher than in heart or soleus muscle. The LDH isozyme pattern ultimately resembled that of the slow-twitch soleus muscle. Citrate synthase activity increased 3.7-fold which brought this enzyme to a value 45% above that of heart. These results indicate that chronic stimulation does not simply convert the fast-twitch muscle into a soleus-like slow-twitch muscle, but creates a tissue of unique metabolic properties.


Direct measurement of peptidoglycan cross-linking in bacteria by 15N nuclear magnetic resonance.
Cross-polarization magic angle spinning 9.12-MHz 15N nuclear magnetic resonance was used to measure the extent of peptidoglycan cross-linking within intact bacterial cells and isolated cell walls of Aerococcus viridans ATCC 10400 grown in the presence of L-[epsilon-15N]lysine. A value of 49% for the cross-linking index was found for normal cells, while for those grown in the presence of low levels of penicillin G (0.1 micrograms/ml), the cross-linking index was reduced to 35%.


Knowledge of hereditary prostate cancer among high-risk African American men.
To measure knowledge of hereditary prostate cancer in a group of high-risk African American men. Cross-sectional, correlational pilot study. Four geographic sites: Detroit, MI; Houston, TX; Chicago, IL; and Columbia, SC. 79 men enrolled in the African American Hereditary Prostate Cancer Study. Telephone interviews. Knowledge of hereditary prostate cancer. Knowledge of hereditary prostate cancer was low. The high percentage of incorrect responses on questions that measure genetic testing, prevention, and risk based on a positive family history highlights educational needs. A critical need exists for nurses to educate high-risk African American men about hereditary prostate cancer.


Measurement of time-dependent CP asymmetries in B0-->D(*)+/-D+/- decays.
We present a first measurement of CP asymmetries in neutral B decays to D+D-, and updated CP asymmetry measurements in decays to D(*+)D- and D(*-)D+. We use fully reconstructed decays collected in a data sample of (232+/-3) x 10(6) gamma(4S)-->BB events in the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. We determine the time-dependent asymmetry parameters to be SD(*+)(D-)=-0.54+/-0.35+/-0.07, CD(*+)(D-)=0.09+/-0.25+/-0.06, SD(*-)(D+)=-0.29+/-0.33+/-0.07, CD(*-)(D+)=0.17+/-0.24+/-0.04, SD+(D-)=-0.29+/-0.63+/-0.06, and CD+(D-)=0.11+/-0.35+/-0.06, where in each case the first error is statistical and the second error is systematic.


Massive Device-Related Thrombus After LAA Occlusion: Intraoperative Insights Into Mechanism.
In patients with a contraindication to oral anticoagulation, the left atrial appendage occlusion devices are an approved alternative. Device-related thrombus is a recognized complication, but underlying mechanisms are incompletely understood. In this case series, the authors describe potentially the same mechanism of thrombosis with intraoperative images of incomplete endothelialization. (Level of Difficulty: Intermediate.).


Effective range of non-cell autonomous activator and inhibitor peptides specifying plant stomatal patterning.
Stomata are epidermal valves that facilitate gas exchange between plants and their environment. Stomatal patterning is regulated by the EPIDERMAL PATTERING FACTOR (EPF) family of secreted peptides: EPF1 enforces stomatal spacing, whereas EPIDERMAL PATTERNING FACTOR-LIKE9 (EPFL9), also known as Stomagen, promotes stomatal development. It remains unknown, however, how far these signaling peptides act. Utilizing Cre-lox recombination-based mosaic sectors that overexpress either EPF1 or Stomagen in Arabidopsis cotyledons, we reveal a range within the epidermis and across the cell layers in which these peptides influence patterns. To determine their effective ranges quantitatively, we developed a computational pipeline, SPACE (stomata patterning autocorrelation on epidermis), that describes probabilistic two-dimensional stomatal distributions based upon spatial autocorrelation statistics used in astrophysics. The SPACE analysis shows that, whereas both peptides act locally, the inhibitor EPF1 exerts longer range effects than the activator Stomagen. Furthermore, local perturbation of stomatal development has little influence on global two-dimensional stomatal patterning. Our findings conclusively demonstrate the nature and extent of EPF peptides as non-cell autonomous local signals and provide a means for quantitative characterization of complex spatial patterns in development.This article has an associated 'The people behind the papers' interview.


A Cadaver-Based Biomechanical Evaluation of a Novel Posterior Approach to Sacroiliac Joint Fusion: Analysis of the Fixation and Center of the Instantaneous Axis of Rotation.
The purpose of this study was to assess the stabilizing effect of a posterior joint fixation technique using a novel cortical allograft implant in unilateral and bilateral fixation constructs. We hypothesize that fixation would reduce the joint's range of motion during flexion-extension, axial rotation, and lateral bending loads. We also hypothesize that fixation would shift the center of the instantaneous axis of rotation during the predominant flexion-extension motions towards the implant's location, and that this shift would be correlated with the reduction in flexion-extension range of motion. Six cadaveric sacroiliac joint specimens were tested under intact, unilateral fixation, and bilateral fixation conditions. The total range of motion (ROM) of the sacroiliac joint in flexion-extension, lateral bending, and axial rotation were evaluated by an optical tracking system, in a multidirectional flexibility pure moment model, between ± 7.5 Nm applied moment loads. The centers of the instantaneous axis of rotation (cIAR) of the sacroiliac joint were evaluated during flexion-extension loading. A correlation analysis was performed between the ROM reduction in flexion-extension upon implantation and shift of the cIAR to the graft implantation site. Unilateral and bilateral fixations generated sacroiliac joint ROM reductions in flexion-extension, lateral bending, and axial rotation motions. Fixation shifted the cIAR to the graft implantation site. Reduction in the total range of motion had a moderate correlation with the shift of the cIAR. Our novel posterior approach presents a multifaceted mechanism for stabilizing the joint: first, by the reduction of the total range of motion in all planes of motion; second, by shifting the centers of the instantaneous axis of rotation towards the implant's location in the predominant plane of motion, ensuring little to no motion at the implantation site, thus promoting fusion in this region.


Sexuality, embodiment and attachment style in anorexia nervosa.
Recent studies hypothesized that sexual dysfunctions represent not just complications of eating disorders (EDs), rather they should be attributed to the core psychopathology of these disorders. Therefore, disorders of the embodiment and insecure attachment may play a role in maintaining an abnormal sexual functioning, given their known relations with core ED features. The aim of the study was to investigate the relationship between sexual dysfunctions and both disorders of the embodiment and attachment style in people with anorexia nervosa (AN). 111 adult women with AN and 120 healthy subjects completed the Symptom Checklist-90, Eating Disorder Examination Questionnaire, Identity and Eating Disorders, Attachment Style Questionnaire and the Childhood Trauma Questionnaire-Short Form. Patients reported worse scores than controls in all areas assessed. In patients, low sexual desire was found to be associated with general and ED-specific psychopathology, and with disorders of embodiment and attachment style. Sexual dysfunctions had no associations with traumatic experiences. Dietary restriction showed an association with low sexual desire through embodiment disorder and Discomfort with Closeness, as confirmed by the serial mediation model. The present study suggests that disorders of embodiment maintained by pathological eating behaviours have a key role in the development of sexual dysfunctions in EDs, through the compromise of intimacy. Level III, cross-sectional study with comparisons between cases and controls.


Distinct structural and dynamic components of portal hypertension in different animal models and human liver disease etiologies.
Liver fibrosis is the static and main (70%-80%) component of portal hypertension (PH). We investigated dynamic components of PH by a three-dimensional analysis based on correlation of hepatic collagen proportionate area (CPA) with portal pressure (PP) in animals or HVPG in patients. Different animal models (bile duct ligation: n = 31, carbon tetrachloride: n = 12, thioacetamide: n = 12, choline-deficient high-fat diet: n = 12) and patients with a confirmed single etiology of cholestatic (primary biliary cholangitis/primary sclerosing cholangitis: n = 16), alcohol-associated (n = 22), and metabolic (NASH: n = 19) liver disease underwent CPA quantification on liver specimens/biopsies. Based on CPA-to-PP/HVPG correlation, potential dynamic components were identified in subgroups of animals/patients with lower-than-expected and higher-than-expected PP/HVPG. Dynamic PH components were validated in a patient cohort (n = 245) using liver stiffness measurement (LSM) instead of CPA. CPA significantly correlated with PP in animal models (Rho = 0.531; p < 0.001) and HVPG in patients (Rho = 0.439; p < 0.001). Correlation of CPA with PP/HVPG varied across different animal models and etiologies in patients. In models, severity of hyperdynamic circulation and specific fibrosis pattern (portal fibrosis: p = 0.02; septa width: p = 0.03) were associated with PH severity. In patients, hyperdynamic circulation (p = 0.04), vascular dysfunction/angiogenesis (VWF-Ag: p = 0.03; soluble vascular endothelial growth factor receptor 1: p = 0.03), and bile acids (p = 0.04) were dynamic modulators of PH. The LSM-HVPG validation cohort confirmed these and also indicated IL-6 (p = 0.008) and hyaluronic acid (HA: p < 0.001) as dynamic PH components. The relative contribution of "static" fibrosis on PH severity varies by type of liver injury. Next to hyperdynamic circulation, increased bile acids, VWF-Ag, IL-6, and HA seem to indicate a pronounced dynamic component of PH in patients.


Antiplatelet therapy in the era of late stent thrombosis.
Drug-eluting stents (DES) are the treatment of choice for obstructive coronary artery disease when percutaneous intervention is feasible. Although there are concerns regarding increased incidence of stent thrombosis, subsequent myocardial infarction, and death in patients receiving DES, careful analysis of large randomized trials has shown that risk of stent thrombosis with both bare metal stents (BMS) and DES is small. However, late stent thrombosis seems to occur more frequently with DES and seems to be closely associated with the discontinuation of dual antiplatelet therapy with aspirin and a thienopyridine derivative (usually clopidogrel). Before placing a DES in a patient, the interventional cardiologist must ensure that there are no conditions under which a patient or physician may have to discontinue dual antiplatelet therapy within a year after stent placement. If the cardiologist anticipates premature discontinuation of thienopyridine and aspirin therapy, his or her alternative is to place a BMS or recommend bypass surgery. If a situation arises in which dual antiplatelet therapy may have to be interrupted (eg, emergency or semi-elective surgery), it is strongly recommended that the treating physician consult a cardiologist and follow published guidelines.


Antidepressant-like effect of Ganoderma lucidum spore polysaccharide-peptide mediated by upregulation of prefrontal cortex brain-derived neurotrophic factor.
A 28-kDa polysaccharide-peptide (PGL) with antidepressant-like activities was isolated from spores of the mushroom Ganoderma lucidum. It was unadsorbed on DEAE-cellulose. Its internal amino acid sequences manifested pronounced similarity with proteins from the mushrooms Lentinula edodes and Agaricus bisporus. The monosaccharides present in 28-kDa PGL comprised predominantly of glucose (over 90%) and much fewer galactose, mannose residues, and other residues. PGL manifested antidepressant-like activities as follows. It enhanced viability and DNA content in corticosterone-injured PC12 cells(a cell line derived from a pheochromocytoma of the rat adrenal medulla with an embryonic origin from the neural crest containing a mixture of neuroblastic cells and eosinophilic cells) and reduced LDH release. A single acute PGL treatment shortened the duration of immobility of mice in both tail suspension and forced swimming tests. PGL treatment enhanced sucrose preference and shortened the duration of immobility in mice exposed to chronic unpredictable mild stress (CUMS). Chronic PGL treatment reversed the decline in mouse brain serotonin and norepinephrine levels but did not affect dopamine levels. PGL decreased serum corticosterone levels and increased BDNF mRNA and protein levels and increased synapsin I and PSD95 levels in the prefrontal cortex. This effect was completely blocked by pretreatment with the BDNF antagonist K252a, indicating that PGL increased synaptic proteins in a BDNF-dependent manner.Key points• An antidepressive polysaccharide-peptide PGL was isolated from G. lucidum spores.• PGL protected PC12 nerve cells from the toxicity of corticosterone.• PGL upregulated BDNF expression and influenced key factors in the prefrontal cortex.


Eplingiella fruticosa (Lamiaceae) essential oil complexed with β-cyclodextrin improves its anti-hyperalgesic effect in a chronic widespread non-inflammatory muscle pain animal model.
Eplingiella fruticosa (Lamiaceae), formally known as Hyptis fruticosa, is an important aromatic medicinal herb used in folk medicine in northeastern Brazil. We aimed to evaluate the anti-hyperalgesic effect of essential oil obtained from E. fruticosa (HypEO) complexed with βCD (HypEO-βCD) in a chronic widespread non-inflammatory muscle pain animal model (a mice fibromyalgia-like model, FM). The HypEO was extracted by hydro distillation and its chemical composition was determined by GC-MS/FID. Moreover, Fos protein expression in the spinal cord was assessed by immunofluorescence. (E)-caryophyllene, bicyclogermacrene, 1,8-cineole, α-pinene, β-pinene and 21 other compounds were identified in the HypEO. The treatment with HypEO-βCD produced a longer-lasting anti-hyperalgesic effect compared to HypEO, without alterations in motor coordination or myorelaxant effects. Moreover, HypEO and HypEO-βCD produced a significant anti-hyperalgesic effect over 7 consecutive treatment days. Immunofluorescence assay demonstrated a decrease in Fos protein expression in the spinal cord (p < 0.001). We demonstrated that the anti-hyperalgesic effect produced by HypEO was improved after complexation with β-CD and this seems to be related to the central pain-inhibitory pathway, suggesting the possible use of E. fruticosa for chronic pain management.


Temperature enhanced effects of chlorine exposure on the health status of the sentinel organism Mytilus galloprovincialis.
It now is widely recognised that the global temperature is rising, a phenomenon which could alter the effects of pollution on wildlife. In order to assess the role of temperature and exposure to chlorine due to cooling water discharges, a battery of metabolic, oxidative stress and histological parameters were evaluated in Mytilus galloprovincialis after 15 and 30 days at 15 °C and at two increased temperatures (+5 and +10 °C). Diverse gill pathologies such as haemolymphatic sinus dilatation, an increased number of mucocytes and granulocytes as well as a lower number of cilia were observed after 30 days exposure at higher temperatures. Protein, amino acid, triglyceride and fatty acid levels decreased when the temperature increased, as a consequence of higher energetic demand. Similarly, acetylcholinesterase, catalase and glutathione S-transferase activities showed an inhibition at higher temperatures, although gill lipid peroxidation levels remained unaffected. Our results suggest that increased temperatures induce deterioration in the health status of the mussels and in their defensive capacity against a polluted environment.


Part of the 23S RNA located in the 11S RNA fragment is a constituent of the ribosomal peptidyltransferase centre.
Upon irradiation, 3-[4-benzoylphenyl]propionyl-PhetRNA bound to the P-site of poly(U)-primed ribosomes is exclusively cross-linked to 23S RNA. It is shown that the photoreaction only occurs with pyrimidine nucleotides. The site of the cross-link is located within an 11S RNA fragment, which comprises the 1100 nucleotides at the 3'-end of 23S RNA. The cross-linked Phe tRNA derivative is still functionally active in peptide bond formation. The site labelled on the 11S fragment is therefore an integral part of the peptidyltransferase centre.


Robotic Surgery for Stone Disease.
To evaluate recent literature regarding the role of robotic technology in the treatment of nephrolithiasis with particular attention to complex technical procedures. Robotic platforms including single-port robotics have been widely adopted in urological practice for the treatment of both malignant and benign conditions and has led to an expansion of the utilization of robot-assisted surgery to tackle challenging clinical scenarios such as bladder neck reconstruction, upper urinary tract reconstruction, and more recently complex stone disease. Presently, the American Urological Association guidelines on the surgical management of stones advise against using robotic, open, or laparoscopic techniques as a first-line approach for most patients with stone disease with the exception for patients with anatomical abnormalities, large or complex stones, or patients requiring a concomitant reconstructive operation. Clinicians have demonstrated the safety and feasibility of surgical robotics in the treatment of stone disease for a variety of operations including robotic pyeloplasty, pyelolithotomy, ureterolithotomy, and surgical interventions in urinary diversions as well as novel technologies for robotic ureteroscopy and percutaneous access. Numerous clinicians have demonstrated the safety and feasibility of using robot-assisted surgery to treat nephrolithiasis, mainly in complex renal anatomy. Further research is necessary to identify the best candidates for utilization of robotics in complex stone disease, and further technological developments will continue to further advance the use of these platforms in the treatment of nephrolithiasis.


Assessment of nutritional status: functional indicators of pediatric nutriture.
The author speaks to the need to update our conceptual approach and our technical capacities for nutritional status assessment and to devise innovative ways to apply them to pediatric practice. The article discusses and evaluates conventional, static indices of nutriture and the importance of history and the physical examination. Focus is then placed on the concept of the functional assessment of nutritional status and its potential for clinical use.


Subjects' hypnotizability level affects somatosensory evoked potentials to non-painful and painful stimuli.
We evaluated the working hypothesis that the EEG activity associated to non-painful and painful stimuli in condition of waking state (no hypnotic procedure) was related to the hypnotizability level. Hypnotizability level was measured in 16 healthy subjects through the Italian version of the Stanford Hypnotic Susceptibility Scale (SHSS, score: 0-12). EEG data (56 electrodes) were recorded during non-painful and painful electrical stimuli applied to the left index finger. Cortical activity (vertex N1-P2 complex) was compared in subjects with low hypnotizability level (N=8, SHSS:0-6) vs. subjects with high hypnotizability level (N=8, SHSS:7-12). The amplitude of the N1-P2 complex was lower in the High-hypnotizability compared to the Low-hypnotizability group over primary sensorimotor cortex (C3 and C4 electrodes) and centro-parietal midline areas (Cz and Pz electrodes) for non-painful and painful stimuli. The SHSS showed a statistically significant negative correlation with the vertex N1-P2 complex at C3 and Cz (r=-0.5, p<0.05) electrodes for non-painful stimuli. Compared to the Low-hypnotizability subjects, High-hypnotizability subjects showed a reduced cortical activity related to non-painful and painful stimuli. The results suggest a relationship between hypnotizability and cortical activity related to non-painful and painful stimuli in the condition of waking state (no hypnotic effect).


Primary structure and tissue-specific expression of human beta-hydroxyisobutyryl-coenzyme A hydrolase.
beta-Hydroxyisobutyryl-CoA (HIBYL-CoA) hydrolase is responsible for the specific hydrolysis of HIBYL-CoA, a saline catabolite, as well as the hydrolysis of beta-hydroxypropionyl-CoA, an intermediate in a minor pathway of propionate metabolism. We have obtained the amino acid sequences of several tryptic peptides derived from purified rat liver HIBYL-CoA hydrolase, and the NH2-terminal peptize sequence was matched to the translated sequence of a human expressed sequence tag present in the data base of the IMAGE Consortium (Lawrence Livermore National Laboratory, Livermore, CA). The complete nucleotide sequence and the deduced amino acid sequence showed no similarity to the sequences of well known thioesterases but showed significant homology to the enoyl-CoA hydratase/isomerase enzyme family. The cDNA fragment corresponding to the mature (processed) protein was expressed in Escherichia coli. The purified recombinant enzyme displayed substrate specificity very similar to that of the rat enzyme and was specifically bound by polyclonal antibodies raised against purified rat liver HIBYL-CoA hydrolase. Northern and Western blot analyses with various human tissues indicated predominant expression in liver, heart, and kidney, with discrepancies occurring in the amounts of HIBYL-CoA hydrolase mRNA compared to stably expressed protein in several tissues.


Behavior disturbance in 8-year-old children with early treated phenylketonuria. Report from the MRC/DHSS Phenylketonuria Register.
Using the Rutter Behavior Questionnaire, schoolteachers assessed the frequency of common abnormal behavior in 544 8-year-old children with phenylketonuria who were born in the United Kingdom and in whom the diagnosis was made by routine testing in infancy, either during the early years of screening (cohort 1, births 1964 to 1971) or after a national reorganization of the program (cohort 2, births 1972 to 1977). All children received treatment before 4 months of age. Two matched control subjects were assessed for each patient. Compared with the controls, patients in cohorts 1 and 2 receiving a strict low-phenylalanine (phe) diet (average phe concentration less than 600 mumol/L) were 1.5 and 1.7 times, respectively, more likely to have deviant behavior; those receiving a less well controlled diet were 2.5 and 1.9 times, respectively, more likely to show such behavior. Patients more often had mannerisms, hyperactivity, and signs of anxiety and were less responsive and more solitary than were controls. On the other hand, they were not more aggressive, untruthful, or disobedient, nor absent from school more frequently. The increased frequency of deviant behavior may be the result of both psychologic stress and neurologic impairment.


Anatomical and functional brain imaging evidence of lenticulo-insular anomalies in Smith Magenis syndrome.
Smith Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome ascribed to an interstitial deletion of chromosome 17p11.2. The neurobehavioral phenotype of SMS includes mental retardation, speech delay, hyperactivity, attention deficit, decreased sensitivity to pain, self-injury, aggressive behavior and sleep disturbance. Therefore, we performed anatomical and functional brain imaging studies in five SMS boys. Anatomical magnetic resonance imaging (MRI) was analyzed using optimized voxel-based morphometry (VBM). This method can detect structural anomalies not apparent on visual inspection of the scans. Two comparison groups with similar mean age were studied: Group A with 12 healthy control children and Group B with 5 children with idiopathic mental retardation. In addition, positron emission tomography (PET) and water-labeled method were used to investigate a putative localized brain dysfunction in SMS. The control group was composed of mentally retarded children (Group B). A significant bilateral decrease of grey matter concentration was detected in the insula and lenticular nucleus in SMS children. In addition, a significant hypoperfusion was found in the same regions in SMS. These anatomo-functional evidences of bilateral insulo-lenticular anomalies in SMS are consistent with neurobehavioral symptoms of the disease. The identification of localized brain anomalies in SMS may help in understanding how this well-defined genetic entity can lead to a relatively specific severe neurobehavioral syndrome.


The guggulsterone derivative GG-52 inhibits NF-κB signaling in bone marrow-derived dendritic cells and attenuates colitis in IL-10 knockout mice.
We previously demonstrated that the novel guggulsterone derivative guggulsterone-52 (GG-52) inhibited the activation of nuclear factor (NF)-κB signaling in intestinal epithelial cells and had preventive and therapeutic effects on dextran sulfate sodium-induced acute colitis. This study investigates the anti-inflammatory effects of GG-52 on bone marrow-derived dendritic cells (BMDCs) and chronic colitis in IL-10(-/-) mice. BMDCs were generated from the femurs of C57BL/6 wild-type and IL-10(-/-) mice. BMDCs were stimulated with lipopolysaccharide (LPS) in the presence or absence of GG-52. The effect of GG-52 on NF-κB signaling in BMDCs was examined by real-time RT-PCR for IL-12p40 and TNF-α gene expression, western blotting for IκBα degradation, and electrophoretic mobility shift assay. For in vivo studies, wild-type or IL-10(-/-) mice were treated with or without GG-52. Colitis was quantified by the evaluation of histopathological findings. Double immunofluorescence staining for CD11c and phosphorylated IκB kinase (IKK)-α was performed to detect IKK activation in DCs in colonic tissue. GG-52 significantly inhibited LPS-induced IL-12p40 and TNF-α gene expression, IκBα degradation, and NF-κB DNA binding activity in BMDCs. In the IL-10(-/-) mouse model chronic colitis, administration of GG-52 significantly reduced the severity of colitis as assessed by histopathology, and suppressed IKK activation in DCs in colonic tissue. These results indicate that the novel guggulsterone derivative GG-52 blocks NF-κB activation in BMDCs and ameliorates chronic colitis in IL-10(-/-) mice, which suggest that GG-52 is a potential therapeutic agent for inflammatory bowel diseases.


Relative bioavailability of an extemporaneously prepared aprepitant oral suspension in healthy adults.
Use of aprepitant for chemotherapy-induced nausea and vomiting prophylaxis in patients unable to swallow capsules is hindered by the lack of a commercially available oral liquid formulation in many jurisdictions. A stable oral suspension can be extemporaneously prepared using commercially available capsules. We aimed to determine the bioavailability of this aprepitant suspension relative to the capsule. This two-period crossover study enrolled 17 healthy adult volunteers. Volunteers received a single 125 mg aprepitant dose during each study period. Order of formulation presentation (capsule vs suspension first) was randomized. Thirteen blood samples were collected over a 48-h period. Aprepitant plasma concentrations were determined using liquid chromatography-mass spectroscopy. Relative bioavailability was defined as the geometric least squares mean ratio for area under the concentration versus time curve (AUC) from time zero to infinity of the aprepitant suspension versus the capsule. Bioequivalence, defined as per Health Canada guidelines, was assessed as a secondary aim. Relative bioavailability of the aprepitant suspension was 82.3% (90% CI: 69.09-98.00%). Bioequivalence was not established: geometric least squares mean ratios (suspension/capsule) for AUC time zero to 48 h and maximum concentration were 87.8% (90% CI: 75.48-102.16%) and 86.1% (90% CI: 75.59-98.16%), respectively. No serious adverse events were observed. With a relative bioavailability of 82.3%, the extemporaneous aprepitant oral suspension was well-absorbed relative to the capsule. Though not bioequivalent to the oral capsule, the clinical use of this aprepitant oral suspension in adult and pediatric patients unable to swallow capsules is likely to be effective and safe.


Investigation of the chemical profile and anti-inflammatory mechanisms of flavonoids from Artemisia vestita Wall. ex Besser via targeted metabolomics, zebrafish model, and network pharmacology.
Artemisia vestita Wall. ex Besser is wildly distributed in the western high-altitude area of China and has been used as a Tibetan medicine to treat inflammatory diseases. We previously demonstrated the total flavonoids of Artemisia vestita Wall. ex Besser (TFA) showed obvious anti-inflammatory effects and its content was 276.62 mg/g. However, the chemical profile, active ingredients, and anti-inflammatory mechanisms of TFA are not clear. This study aimed to study the components of TFA, evaluate the anti-inflammatory effects of TFA, and preliminarily predict the anti-inflammatory mechanism of TFA. TFA was prepared by the semi-biomimetic extraction method and purified by macroporous resin. The components of TFA were analyzed based on LC-MS combined with the targeted metabolomics method. The anti-inflammatory activity of TFA was evaluated using CuSO4-induced and tail cutting-induced zebrafish inflammation models. Based on the network pharmacology method, the anti-inflammatory mechanism of the main components of TFA was preliminarily predicted. A total of 185 components were identified in TFA. TFA showed significant anti-inflammatory effects on CuSO4-induced and tail cutting-induced zebrafish inflammation models. According to network pharmacology prediction and experimental verification, 10 compounds were identified as the main active ingredients, including 3,7-di-O-methylquercetin, Hesperetin 5-O-glucoside, Myricitrin, et al. Twenty key targets were recognized, such as TNF, AKT1, VEGFA, MMP9, EGFR, PTGS2 et al. Moreover, the TNF signaling pathway and NOD-like receptor signaling pathway were identified to play vital roles in the anti-inflammatory effects of TFA. This study revealed the chemical profile of TFA and identified the main active ingredients, key targets, and pathways of TFA in anti-inflammatory effects, which is helpful to elucidate the pharmacodynamic substances and action mechanisms of Artemisia vestita Wall. ex Besser, to promote its clinical rational application.


Reversing "Flip-Flop" Phenomenon of 131 I and Glucose Avidity in RET-Fusion Positive Radioiodine-Refractory Thyroid Cancer Lesions After Treatment of Pralsetinib.
A 61-year-old man presented with papillary thyroid cancer in radioiodine-refractory status after high-activity 131 I treatments following thyroidectomy. FDG-avid neck and pulmonary metastases but without 131 I-uptake were detected. CCDC6-RET fusion was identified from the tumor lesion. He was treated with pralsetinib, a RET inhibitor, followed by another high-activity 131 I therapy. Posttherapeutic scan displayed restoration of 131 I avidity at those lesions only shown on previous FDG PET/CT. Reduced FDG avidity of those lesions and decreased serum antithyroglobulin antibody titer were also noticed. This case illustrated successfully reinduced 131 I avidity in papillary thyroid cancer through redifferentiation with target therapy to suppress tumor RET overexpression.


The Evolution of mHealth Solutions for Heart Failure Management.
In the last decade, the uptake of information and communication technologies and the advent of mobile internet resulted in improved connectivity and penetrated different fields of application. In particular, the adoption of the mobile devices is expected to reform the provision and delivery of healthcare, overcoming geographical, temporal, and other organizational limitations. mHealth solutions are able to provide meaningful clinical information allowing effective and efficient management of chronic diseases, such as heart failure. A variety of data can be collected, such as lifestyle, sensor/biosensor, and health-related information. The analysis of these data empowers patients and the involved ecosystem actors, improves the healthcare delivery, and facilitates the transformation of existing health services. The aim of this study is to provide an overview of (i) the current practice in the management of heart failure, (ii) the available mHealth solutions, either in the form of the commercial applications, research projects, or related studies, and (iii) the several challenges related to the patient and healthcare professionals' acceptance, the payer and provider perspective, and the regulatory constraints.


ABA may promote or delay peach fruit ripening through modulation of ripening- and hormone-related gene expression depending on the developmental stage.
Peach (Prunus persica laevis L. Batsch) was chosen as a model to further clarify the physiological role of ABA during fruit ripening. To this aim, branches bearing one fruit at mid-S3, S3/S4 and S4 stages of fruit development and characterized by a different ripening index (I(AD)), as revealed by a non-destructive device called a DA-meter, were treated with ABA (0.02 mM) for 1 and 5 days. Exogenously applied ABA interfered with the progression of ripening leading to less ripe or riper fruit depending on the physiological stage. To better understand the molecular basis of ABA interference with ripening, the time-course changes in the expression of ethylene-, cell wall-, and auxin-related genes as well as other genes (NCED, PIP, LOX, AOS and SOT) was evaluated in the fruit mesocarp. Real-time PCR analyses revealed that in mid-S3 fruit transcript levels of ethylene biosynthesis and signaling (ACS1, ACO1, ETR2, ERF2), cell wall softening-related (PG, PMEI, EXP1, EXP2) and auxin biosynthesis, conjugation, transport and perception (TRPB, IGPS, Aux/IAA, GH3, PIN1 and TIR1) genes were substantially down-regulated on day 5 indicating a ripening delay. On the contrary, in more advanced stages (S3/S4 and S4) the same genes were early (day 1) up-regulated suggesting an acceleration of ripening. Transcript profiling of other ripening-related genes revealed changes that were in accord with a ripening delay (mid-S3) or acceleration (S3/S4 and S4). Thus, in peach fruit, ABA appears to modulate ripening through interference not only with ethylene and cell wall but also with auxin-related genes.


Percutaneous intentional extraluminal (subintimal) recanalization of crural arteries.
Patients with critical limb ischaemia (CLI) often have occlusive disease of the crural arteries. Therefore attempts at treating CLI by minimally invasive means has to be directed towards recanalization of occluded crural arteries. Subintimal angioplasty of long occlusions of the crural arteries is safe and effective and is therefore an excellent alternative to reconstructive surgery in patients who are frequently elderly and frail. It is also relatively cheap when compared to bypass surgery.


A novel nanosonosensitizer for sonodynamic therapy: in vivo study on a colon tumor model.
The particles in a liquid decrease the ultrasonic intensity threshold needed for cavitation onset. In this study, a new nanoconjugate composed of protoporphyrin IX and gold nanoparticles was used as a nucleation site for cavitation. The nonradiative relaxation time of protoporphyrin IX in the presence of gold nanoparticles is longer than the similar time without gold nanoparticles. This study was conducted on colon carcinoma tumors in BALB/c mice. The tumor-bearing mice were randomly divided into 6 groups (each containing 15 mice): (1) control, (2) protoporphyrin IX, (3) gold nanoparticle-protoporphyrin IX conjugate, (4) ultrasound alone, (5) ultrasound + protoporphyrin IX, and (6) ultrasound + gold nanoparticle-protoporphyrin IX conjugate. In the respective groups as indicated above, protoporphyrin IX or the gold nanoparticle-protoporphyrin IX conjugate was injected into the tumors. Ultrasound irradiation was performed on the tumors 24 hours after injection. Antitumor effects were estimated by evaluation of the relative tumor volume, doubling time, and 5-folding time for the tumors after treatment. The cumulative survival fraction of the mice and percentage of the lost tissue volume (treated) were also assessed in the different groups. A significant difference in the average relative volumes of the tumors 13 days after treatment was found between the ultrasound + gold nanoparticle-protoporphyrin IX group and the other groups (P < .05). The longest doubling and 5-folding times were observed in the ultrasound + gold nanoparticle-protoporphyrin IX and ultrasound + protoporphyrin IX groups. Protoporphyrin IX conjugated to gold nanoparticles has been introduced as a promising compound and a new sonosensitizer for improving the tumor response to sonodynamic therapy by reducing the relative tumor volume and increasing the cumulative survival fraction.


The synaptic vesicle membrane: origin, axonal distribution, protein components, exocytosis and recycling.
The paper discusses functional and molecular aspects of the synaptic vesicle membrane during its life cycle. The distribution of the synaptic vesicle membrane compartment in an entire cholinergic neuron is monitored using colloidal gold labelling and a monoclonal antibody against the synaptic vesicle membrane protein SV2. This provides new insights concerning vesicle origin and fate in the various compartments of the neuron. A new synaptic vesicle membrane protein (svp25) of Mr 25,000 with properties similar to synaptophysin as well as a synaptic vesicle binding phosphoprotein of the presynaptic membrane (Mr 92,000) likely to be involved in vesicle exocytosis are described. The membrane compartment recycled on induced transmitter release contains synaptic vesicle but not plasma membrane markers and encloses both newly synthesized transmitter and a sample of extracellular medium.


Dasatinib-Induced CMV Hepatitis in an Immunocompetent Patient: A Rare Complication of a Common Drug.
Dasatinib is a common anticancer drug used in the treatment of leukemia. Several side effects have been reported, the most common being myelosuppression, diarrhea, edema, and nausea. Three papers have been published reporting hepatic side effects of dasatinib treatment. A rare side effect of dasatinib treatment is reactivation of latent cytomegalovirus (CMV) infection. Never before has dasatinib therapy shown to be the cause of CMV hepatitis in an immunocompetent patient. We present a case of an immunocompetent patient who was treated with the standard dose of dasatinib therapy and subsequently developed CMV hepatitis. Well-known side effects of dasatinib therapy are understood and documented; unknown adverse drug reactions can occur and should be monitored for. This is a significant finding given the high rate of CMV seropositivity in the general population.


Peripapillary choroidal thickness after intravitreal ranibizumab injections in eyes with neovascular age-related macular degeneration.
The purpose of this study was to investigate peripapillary choroidal thickness (CT) in eyes with neovascular age-related macular degeneration (AMD) and to assess whether peripapillary CT is affected by intravitreal injection of ranibizumab (IVR) in eyes with neovascular AMD. Peripapillary and subfoveal CT were measured in spectral domain optical coherence tomography images from 39 eyes of neovascular AMD patients and 39 eyes of age-matched controls retrospectively. The patients were treated with 0.5 mg IVR monthly for 3 months and retreated as needed. Peripapillary CT at baseline, 3 months and 6 months was measured at four locations (superior, nasal, inferior and temporal areas). The mean peripapillary and subfoveal baseline CTs of the eyes with neovascular AMD (153.3 ± 45.3 μm and 228.6 ± 78.6 μm) were not different from those of the controls (149.0 ± 42.3 μm and 221.4 ± 54.1 μm; P = 0.665 and P = 0.639, respectively). Subfoveal CT decreased at 3 months (213.8 ± 75.8 μm, P < 0.001) and 6 months (215.1 ± 72.8 μm, P = 0.002) following IVR treatment. Mean peripapillary CT did not show significant changes at 3 months (149.6 ± 43.8 μm, P = 0.156) or 6 months (150.0 ± 43.4 μm, P = 0.187). Subanalysis revealed that only temporal peripapillary CT decreased from baseline (167.1 ± 54.5 μm) to 3 months (159.4 ± 50.8 μm, P = 0.010) and was sustained at 6 months (160.6 ± 49.6, P = 0.026). However, superior, nasal and inferior peripapillary CT did not show significant changes after IVR. Changes in peripapillary CT after IVR were limited to the macular area. This result may suggest that IVR does not affect CT outside of the macula in the eyes of patients with neovascular AMD.