A comparison of external fixation and locked intramedullary nailing in the treatment of femoral diaphysis fractures from gunshot injuries.
We studied the safety and incidence of complications from the treatment of gunshot-induced femur diaphysis fractures with locked intramedullary nailing in comparison to external fixation. Patients who had femoral diaphysis fracture operations due to gunshot injuries (107 femurs of 99 patients) between 2003 and 2014 were retrospectively reviewed, and 66 femurs of 60 patients were place into two groups (Group A: intramedullary nailing-38 femurs of the 36 patients; Group B: external fixator-28 femurs of 24 patients). The mean follow-up was 76.3 months (22-131). The study outcomes were patient complications, infection rate, union time, need for secondary surgery, functional assessment with lower extremity functional scale, and radiological evaluation with orthoroentgenograms. The mean age of the patients was 37.3 ± 7.4 years in Group A and 39 ± 6.1 years in Group B. There was no significant difference between the two groups in age, gender or follow-up. There were two deep infections (5.2%) in Group A and one deep infection (3.5%) in Group B. Delayed union was observed in four patients (10.5%) in Group A and in two patients (7.1%) in Group B. There was one non-union (2.6%) and one non-union (3.5%) in Group A and Group B, respectively. There was no significant difference between the two groups in incidence of union, delayed union or deep infection. The mean union time was 3.1 ± 2.5 months in Group A and 5.8 ± 1.4 months in Group B. The union time was significantly lower in the intramedullary nailing group (p = 0.023). There were no significant differences between the two groups in regards to radiological and functional evaluation. This study showed similar complication rates and functional results both for external fixator and intramedullary nailing for the treatment of femoral diaphysis fractures due to gunshot injuries. Level 3 retrospective comparative clinical study.


Discontinuation symptoms: comparison of brief interruption in fluoxetine and paroxetine treatment.
Abrupt interruption or cessation of selective serotonin reuptake inhibitor (SSRI) treatment may result in discontinuation or treatment interruption symptoms. Recent reports suggested these symptoms occur more frequently with shorter half-life SSRIs. Previous studies indicated a 5-8-day treatment interruption resulted in fewer discontinuation-emergent adverse events in fluoxetine-treated patients than in paroxetine-treated patients. This study examines the effects of shorter treatment interruption (3-5 days), as would occur if patients miss just a few doses of medication. Patients successfully treated for depression with fluoxetine or paroxetine underwent treatment interruption in a double-blind fashion. Treatment interruption-emergent symptoms were assessed using the Discontinuation-Emergent Signs and Symptoms checklist. Other assessments included the Montgomery-Asberg Depression Rating Scale, Clinical Global Impressions-Severity scale and a social functioning questionnaire. Of 150 patients enrolled, 141 completed the study. Following treatment interruption, fluoxetine-treated patients experienced fewer treatment interruption-emergent events than did paroxetine-treated patients. The paroxetine treatment group also experienced significant increases in depressive symptoms, clinical global severity scores and difficulty in social functioning; the fluoxetine treatment group did not. These results are consistent with reports suggesting abrupt interruption of treatment with paroxetine is more often associated with somatic and psychological symptoms than is abrupt interruption of fluoxetine. Patients treated with fluoxetine appeared to be protected by its longer half-life.


Genome engineering using CRISPR-Cas9 system.
The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 system is an adaptive immune system that exists in a variety of microbes. It could be engineered to function in eukaryotic cells as a fast, low-cost, efficient, and scalable tool for manipulating genomic sequences. In this chapter, detailed protocols are described for harnessing the CRISPR-Cas9 system from Streptococcus pyogenes to enable RNA-guided genome engineering applications in mammalian cells. We present all relevant methods including the initial site selection, molecular cloning, delivery of guide RNAs (gRNAs) and Cas9 into mammalian cells, verification of target cleavage, and assays for detecting genomic modification including indels and homologous recombination. These tools provide researchers with new instruments that accelerate both forward and reverse genetics efforts.


A critical review about methodologies for the analysis of mucoadhesive properties of drug delivery systems.
Mucoadhesion is a useful strategy for drug delivery systems, such as tablets, patches, gels, liposomes, micro/nanoparticles, nanosuspensions, microemulsions and colloidal dispersions. Moreover, it has contributed to many benefits like increased residence time at application sites, drug protection, increased drug permeation and improved drug availability. In this context, investigation into the mucoadhesive properties of pharmaceutical dosage forms is fundamental, in order to characterize, understand and simulate the in vivo interaction between the formulation and the biological substrate, contributing to the development of new mucoadhesive systems with effectiveness, safety and quality. There are a lot of in vivo, in vitro and ex vivo methods for the evaluation of the mucoadhesive properties of drug delivery systems. However, there also is a lack of standardization of these techniques, which makes comparison between the results difficult. Therefore, this work aims to show an overview of the most commonly employed methods for mucoadhesion evaluation, relating them to different proposed systems and using artificial or natural mucosa from humans and animals.


Role of the mTOR signaling pathway in the rapid antidepressant action of ketamine.
Some patients with major depressive disorder remain resistant to antidepressant medication. A randomized, placebo-controlled, double-blind trial demonstrated that a single subanesthetic dose (0.5 mg/kg) of the N-methyl-D-aspartate receptor antagonist ketamine caused a rapid antidepressant effect within hours in treatment-resistant patients with major depressive disorder. However, the precise cellular mechanisms underlying ketamine's rapid antidepressant actions were unclear, although it is proposed that the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor might be involved in these mechanisms. Recently, Li et al. reported the role of the mammalian target of rapamycin (mTOR) signaling pathway, a ubiquitous protein kinase involved in protein synthesis and synaptic plasticity, in ketamine's rapid antidepressant effects. Here, these findings are put into context and their significance is discussed.


NADPH oxidases of the brain: distribution, regulation, and function.
The NADPH oxidase is a multi-subunit enzyme that catalyzes the reduction of molecular oxygen to form superoxide (O(2)(-)). While classically linked to the respiratory burst in neutrophils, recent evidence now shows that O(2)(-) (and associated reactive oxygen species, ROS) generated by NADPH oxidase in nonphagocytic cells serves myriad functions in health and disease. An entire new family of NADPH Oxidase (Nox) homologues has emerged, which vary widely in cell and tissue distribution, as well as in function and regulation. A major concept in redox signaling is that while NADPH oxidase-derived ROS are necessary for normal cellular function, excessive oxidative stress can contribute to pathological disease. This certainly is true in the central nervous system (CNS), where normal NADPH oxidase function appears to be required for processes such as neuronal signaling, memory, and central cardiovascular homeostasis, but overproduction of ROS contributes to neurotoxicity, neurodegeneration, and cardiovascular diseases. Despite implications of NADPH oxidase in normal and pathological CNS processes, still relatively little is known about the mechanisms involved. This paper summarizes the evidence for NADPH oxidase distribution, regulation, and function in the CNS, emphasizing the diversity of Nox isoforms and their new and emerging role in neuro-cardiovascular function. In addition, perspectives for future research and novel therapeutic targets are offered.


Haemodynamic responses during head-up tilt and tilt reversal in two groups with chronic autonomic failure: pure autonomic failure and multiple system atrophy.
Continuous haemodynamic responses to head-up tilt (HUT) and its reversal were studied in 21 subjects with sympathetic denervation due to primary chronic autonomic failure; 10 had pure autonomic failure (PAF; peripheral failure) and 11 had multiple system atrophy (MSA; central failure); 8 healthy subjects (controls) also were studied. Supine systolic, diastolic and mean arterial pressure (MAP) and total peripheral resistance (TPR) were highest in PAF. The MAP response to HUT and tilt reversal were different between groups. After HUT, MAP increased in controls (12+/-4 mmHg), but decreased in PAF and MSA (41+/-4 & 19+/-4 mmHg respectively); the fall in PAF was greater than in MSA. With tilt reversal, MAP returned promptly, but not entirely to pretilt levels in controls, with small (insignificant) overshoots in MSA and PAF. The TPR response to HUT and tilt reversal was different between groups. After HUT, TPR increased in controls (0.31+/-0.04 PRU), decreased in PAF (0.23+/-0.1 PRU) and was unchanged in MSA. With tilt reversal, TPR remained elevated (15 %) above baseline in the controls and rose in PAF (13 %) with no change in MSA. There were no differences in supine heart rate (HR), stroke volume (SV) or cardiac output (CO) between the three groups; HR, SV or CO responses to HUT or tilt reversal also did not differ between the groups. Thus, after HUT, MAP decreased, with greater hypotension induced in PAF than MSA. Since CO did not differ between groups, the decrease in TPR appears to account for the greater fall in BP in PAF than in MSA. The elevated TPR at rest pre-tilt and after tilt reversal probably contributed to supine hypertension in PAF. These haemodynamic observations may aid therapeutic strategies to reduce orthostatic hypotension and prevent supine hypertension.


Focused assessment with sonography for trauma (FAST) identifies liver injury following cardiopulmonary resuscitation.
Liver trauma is a recognised rare complication of cardiopulmonary resuscitation (CPR) and may be difficult to detect. We report a case of intraperitoneal haemorrhage due to liver injury following CPR in a 50-year-old man admitted to the intensive care unit. The haemorrhage was diagnosed with focused assessment with sonography for trauma (FAST). FAST can rapidly and easily diagnose liver injury. FAST is recommended for excluding haemoperitoneum in patients who are haemodynamically unstable after resuscitation.


Diffusion, fragmentation, and coagulation processes: analytical and numerical results.
We formulate dynamical rate equations for physical processes driven by a combination of diffusive growth, size fragmentation, and fragment coagulation. Initially, we consider processes where coagulation is absent. In this case we solve the rate equation exactly leading to size distributions of Bessel type which fall off as exp(-x(3/2)) for large x values. Moreover, we provide explicit formulas for the expansion coefficients in terms of Airy functions. Introducing the coagulation term, the full nonlinear model is mapped exactly onto a Riccati equation that enables us to derive various asymptotic solutions for the distribution function. In particular, we find a standard exponential decay exp(-x) for large x and observe a crossover from the Bessel function for intermediate values of x . These findings are checked by numerical simulations, and we find perfect agreement between the theoretical predictions and numerical results.


Feasibility and Efficacy of Microwave Ablation Combined with Iodine-125 Seed Implantation in Local Control of Recurrent Retroperitoneal Liposarcomas: Initial Clinical Experience.
The objective of the present study was to evaluate the feasibility, safety, and short-term efficacy of microwave ablation (MWA) combined with iodine-125 (125I) seed implantation in recurrent retroperitoneal liposarcomas (rRPLs). From September 2012 to March 2015, 11 patients were enrolled in this prospective study. Eleven tumors (median, 9 cm; range, 5.5-12.5 cm) were treated with computerized tomography-guided MWA for 11 sessions and 125I seed implantation for 18 sessions. 125I seed implantation was performed 4 weeks after MWA. There were no procedure-related deaths. Post-MWA pain (grade ≥2) was the most common complication (6 of 11 patients, 54.5%), and fever (grade ≥2) was observed in two patients. Reversible nerve injury, defined as transient limb paresthesia or leg weakness, was observed in one patient. There were fewer complications associated with the 125I seed implantation procedure compared with the MWA procedure. All 11 patients who underwent the MWA procedure achieved a partial response (PR), according to the modified Response Evaluation Criteria in Solid Tumors, 1 month post-ablation; after 125I seed implantation was performed, a complete response was observed in three, five, and six target tumors in 3, 6, and 12 months, respectively. In selected patients with rRPLs, MWA combined with 125I seed implantation is feasible and safe with favorable local control efficacy. This study evaluated the feasibility, safety, and short-term efficacy of microwave ablation (MWA) combined with iodine-125 (125I) seed implantation in recurrent retroperitoneal liposarcomas (rRPLs). Results suggest that a single session of MWA may be not sufficient in large-volume rRPLs and that as a supplement treatment, 125I seed implantation is safe and easy accessible. MWA combined with 125I seed has excellent local control effectiveness, and long-term efficacy and survival benefit still need to be more comprehensively evaluated.


5-Episinuleptolide Decreases the Expression of the Extracellular Matrix in Early Biofilm Formation of Multi-Drug Resistant Acinetobacter baumannii.
Nosocomial infections and increasing multi-drug resistance caused by Acinetobacter baumannii have been recognized as emerging problems worldwide. Moreover, A. baumannii is able to colonize various abiotic materials and medical devices, making it difficult to eradicate and leading to ventilator-associated pneumonia, and bacteremia. Development of novel molecules that inhibit bacterial biofilm formation may be an alternative prophylactic option for the treatment of biofilm-associated A. baumannii infections. Marine environments, which are unlike their terrestrial counterparts, harbor an abundant biodiversity of marine organisms that produce novel bioactive natural products with pharmaceutical potential. In this study, we identified 5-episinuleptolide, which was isolated from Sinularia leptoclados, as an inhibitor of biofilm formation in ATCC 19606 and three multi-drug resistant A. baumannii strains. In addition, the anti-biofilm activities of 5-episinuleptolide were observed for Gram-negative bacteria but not for Gram-positive bacteria, indicating that the inhibition mechanism of 5-episinuleptolide is effective against only Gram-negative bacteria. The mechanism of biofilm inhibition was demonstrated to correlate to decreased gene expression from the pgaABCD locus, which encodes the extracellular polysaccharide poly-β-(1,6)-N-acetylglucosamine (PNAG). Scanning electron microscopy (SEM) indicated that extracellular matrix of the biofilm was dramatically decreased by treatment with 5-episinuleptolide. Our study showed potentially synergistic activity of combination therapy with 5-episinuleptolide and levofloxacin against biofilm formation and biofilm cells. These data indicate that inhibition of biofilm formation via 5-episinuleptolide may represent another prophylactic option for solving the persistent problem of biofilm-associated A. baumannii infections.


Analysis of inhibitory action of modified U1 snRNAs on target gene expression: discrimination of two RNA targets differing by a 1 bp mismatch.
The modified U1 snRNA gene can suppress expression of a target transgene. In the present study, its potential utility to inhibit a dominant negative/gain of function mutation is explored. Using a green fluorescent protein (GFP) target gene, inhibition was achieved in all cells transduced with U1antiGFP directed at multiple sites within GFP. Using a chloramphenicol acetyltransferase (CAT) target gene, inhibition was not increased by increasing the hybridization domain from 10 to 16 bp or when a site in an upstream exon or intron was targeted. To determine if a U1 anti-target design could discriminate between two transcripts that differ by a 1-2 bp mismatch, GFPtpz and GFPsaph were chosen as targets because they share sequence homology except for three regions where a 1, 2 or 3 bp mismatch exists. The results demonstrated that U1antiGFP correctly reduced its cognate GFP expression by >90% and therefore U1 anti-target constructs are able to discriminate a 1 or 2 bp mismatch in their target mRNA. Thus, these U1 anti-target constructs may be effective in a strategy of somatic gene therapy for a dominant negative/gain of function mutation due to the discreteness of its discrimination. It may complement other anti-target strategies to reduce the cellular load of a mutant transcript.


Recent advances in the synthesis of luminescent tetra-coordinated boron compounds.
Tetra-coordinated boron compounds offer a plethora of luminescent materials. Different chelation around the boron center (O,O-, N,C-, N,O-, and N,N-) has been explored to tune the electronic and photophysical properties of tetra-coordinated boron compounds. A number of fascinating molecules with interesting properties such as aggregation induced emission, mechanochromism and tunable emission by changing the solvent polarity were realised. Owing to their rich and unique properties, some of the molecules have shown applications in making optoelectronic devices, probes and so on. This perspective provides an overview of the recent developments of tetra-coordinated boron compounds and their potential applications.


Immunoreactive endothelins in human follicular fluid.
Endothelin levels were measured by means of [125I]endothelin-1,2,3 radioimmunoassay in the follicular fluids of 22 mature ovarian follicles of 11 patients, obtained during ovum pickup. In all but 1 of the follicles, endothelin levels were detectable and ranged between 0.2 and 3.6 pg/ml (mean 1.47 +/- 0.99). In this preliminary study, no correlation was found between follicular endothelin levels and oocyte fertilization or the hormonal ovarian response during the follicular phase.


Syntheses, structures, and luminescent properties of dipyridylamine-functionalized anthracene and its complexes.
A novel multidentate ligand with 2,2'-dipyridylamine functionalities, 1,8-bis[4-(2,2'-dipyridylamino)phenylacetylenyl]anthracene (1), has been synthesized through a double Sonogashira coupling reaction and characterized by NMR spectroscopic, elemental, and X-ray diffraction analyses. Compound 1 can bind to either one metal center as a tetradentate ligand or two metal centers as a double-bidentate ligand. In the double-bidentate mode, the distance between the two metal centers may vary significantly. Compound 1 displays bright blue luminescence in the solid state and in solution with a quantum efficiency of 64% relative to 9,10-diphenylanthracene. While the dirhodium complex of 1 shows no luminescence, the two zinc complexes of 1 display blue luminescence with quantum efficiencies slightly lower than that of 1. Organic light-emitting devices (OLEDs) using 1 as the emitter show a maximum current efficiency of 7 cd/A.


Systemic capillary leak syndrome associated with compartment syndrome.
Systemic capillary leak syndrome is characterized by recurrent hypovolemic shock attributable to increased systemic capillary leakage. A 26-year-old woman was admitted because of recurrent episodes of hypovolemic shock. Hemoconcentration, hypoalbuminemia, and monoclonal gammopathy were observed. We diagnosed systemic capillary leak syndrome. Three years later, she again had an attack of systemic capillary leak syndrome complicated with pretibial compartment syndrome. This case emphasizes the importance of muscle compartment pressure monitoring during volume resuscitation in patients with systemic capillary leak syndrome.


Delaying effect of humidity on leaf unfolding in Europe.
Understanding the drivers of plant phenology is critical to predict the impact of future warming on terrestrial ecosystem carbon cycling and feedbacks to climate. Using indoor growth chambers, air humidity is reported to influence spring phenology in temperate trees. However, previous studies have not investigated the effect of air humidity on the spring phenology using long-term and large-scale ground observations. Therefore, the role of humidity in spring phenology in temperate trees still remains poorly understood. Here, we synthesized 229,588 records of leaf unfolding dates in eight temperate tree species, including four early-successional and four late-successional species, at 1716 observation sites during 1951-2015 in Europe, and comprehensively analyzed the effect of humidity on the spring phenology. We found that rising humidity significantly delayed spring leaf unfolding for all eight temperate tree species. Leaf unfolding was more sensitive to humidity in early-successional species compared to late-successional species. In addition, the delaying effect of humidity on leaf unfolding increased as temperature warmed over the past 65 years. Our results provide evidence that spring leaf unfolding of temperate trees was significantly delayed by rising humidity. The delaying effect of humidity may restrict earlier spring phenology induced by warming, especially for early-successional species, under future climate warming scenarios in temperate forests.


Dynamics and Sorption Kinetics of Methanol Monomers and Clusters on Nopinone Surfaces.
Organic-organic interactions play important roles in secondary organic aerosol formation, but the interactions are complex and poorly understood. Here, we use environmental molecular beam experiments combined with molecular dynamics simulations to investigate the interactions between methanol and nopinone, as atmospheric organic proxies. In the experiments, methanol monomers and clusters are sent to collide with three types of surfaces, i.e., graphite, thin nopinone coating on graphite, and nopinone multilayer surfaces, at temperatures between 140 and 230 K. Methanol monomers are efficiently scattered from the graphite surface, whereas the scattering is substantially suppressed from nopinone surfaces. The thermal desorption from the three surfaces is similar, suggesting that all the surfaces have weak or similar influences on methanol desorption. All trapped methanol molecules completely desorb within a short experimental time scale at temperatures of 180 K and above. At lower temperatures, the desorption rate decreases, and a long experimental time scale is used to resolve the desorption, where three desorption components are identified. The fast component is beyond the experimental detection limit. The intermediate component exhibits multistep desorption character and has an activation energy of Ea = 0.18 ± 0.03 eV, in good agreement with simulation results. The slow desorption component is related to diffusion processes due to the weak temperature dependence. The molecular dynamics results show that upon collisions the methanol clusters shatter, and the shattered fragments quickly diffuse and recombine to clusters. Desorption involves a series of processes, including detaching from clusters and desorbing as monomers. At lower temperatures, methanol forms compact cluster structures while at higher temperatures, the methanol molecules form layered structures on the nopinone surface, which are visible in the simulation. Also, the simulation is used to study the liquid-liquid interaction, where the methanol clusters completely dissolve in liquid nopinone, showing ideal organic-organic mixing.


Evaluation of an education program for elementary school children with asthma.
To evaluate the effectiveness of a comprehensive asthma management education program for 7- to 12-year-old children with asthma, entitled Roaring Adventures of Puff (RAP), 18 elementary schools in Edmonton were randomized to intervention and control groups. Participating in the program were 76 students with asthma in the intervention schools and 86 in the control schools. Children in the intervention schools had statistically significant improvements in unscheduled doctor visits, missed school days, moderate-to-severe parent rating of severity, severity of shortness of breath, limitations in the kind of play, and correct use of medications. Unscheduled doctor visits and missed school days were the only significant improvements in the control group; however, improvements were about half that of the intervention group. The results showed that a comprehensive, school-based asthma education program is feasible and improves outcomes.


A possible mechanism for PTSD symptoms in patients with traumatic brain injury: central autonomic network disruption.
Patients with traumatic brain injuries (TBI) often develop post traumatic stress disorder (PTSD). This syndrome, defined and diagnosed by psychological and behavioral features, is associated with symptoms such as anxiety and anger with an increase of arousal and vigilance, as well as flashbacks and nightmares. Many of these features and symptoms observed in PTSD may be in part the result of altered autonomic nervous system (ANS) activity in response to psychological and physical challenges. Brain imaging has documented that TBI often induces white matter damage to pathways associated with the anterior limb of the internal capsule and uncinate fasciculus. Since these white matter structures link neocortical networks with subcortical and limbic structures that regulate autonomic control centers, injury to these pathways may induce a loss of inhibitory control of the ANS. In this review, the autonomic features associated with PTSD are discussed in the context of traumatic brain injury. We posit that TBI induced damage to networks that regulate the ANS increase vulnerability to PTSD. The means by which the vulnerability can be measured and tested are also discussed.


Ribozymes in the age of molecular therapeutics.
Ribozymes are RNA molecules capable of sequence-specific cleavage of other RNA molecules. Since the discovery of the first group I intron ribozyme in 1982, new classes of ribozymes, each with their own unique reaction, target site specifications, and potential applications, have been identified. These include hammerhead, hairpin, hepatitis delta, varkud satellite, groups I and II intron, and RNase P ribozymes, as well as the ribosome and spliceosome. Meanwhile, ribozyme engineering has enabled the in vitro selection of synthetic ribozymes with unique properties. This, along with advances in ribozyme delivery methods and expression systems, has led to an explosion in the potential therapeutic applications of ribozymes, whether for anti-cancer or anti-viral therapy, or for gene repair.


[Thyroid function in organic lesions of the hypothalamo-pituitary area].
The aim of our work was the retrospective evaluation of thyroid function in patients with organic lesions of hypothalamo-pituitary system. In the group of 57 examined patients (31 females and 26 males), 43 were affected by pituitary adenomas, in the other patients organic lesions were caused by other tumors of central nervous system (2), tuberculosis (3) developmental or vascular disorders (5), nonspecific inflammation (1). Pituitary tumors (predominantly macroadenomas) were the cause of acromegaly in 14 cases, Cushing's disease in 9 and hyperprolactinaemia in 5. Next 14 subjects, were affected by nonsecreting pituitary tumors with a visual-field defects or different level of hypopituitarism and diabetes insipidus hypothalamo-hypophyseal. In 6 persons clinical manifestations of hypothyroidism with a low level of free thyroxin and normal TSH were observed. Surgical cure with transsphenoidal or transcranial operation was performed in 54 patients. Next 23 of the patients had lowered thyroxine level as a consequence of surgery. Considering the whole 57 person group with organic lesions of the hypothalamo-pituitary system, 29 patients (50.8%) were affected by secondary or tertiary hypothyroidism as a result of sellar and parasellar area illness or their surgical treatment. We didn't observe any correlation between TSH and FT4 in the patients with normal or low plasma FT4 levels. (1) secondary or tertiary hypothyroidism is a common consequence of organic lesions of the sellar and parasellar area or is due by their surgical treatment; (2) laboratory examination of thyroid function in these patients can not be evaluated only by TSH assessment, but also by thyroid hormone plasma level estimation because of the disturbances in thyroid an hypothalamo-pituitary system feedback.


Fe2+ -catalyzed oxidative cleavages of Ca2+ -ATPase reveal novel features of its pumping mechanism.
We have analyzed the Fe2+ -catalyzed oxidative cleavages of Ca2+ -ATPase in the presence of Ca2+, with or without the ATP analog 5'-adenylyl-beta,gamma-imidodiphosphate (AMP-PNP) or in the presence of the inhibitor thapsigargin. To identify the positions of cleavages as precisely as possible, we have used previously identified proteinase K and tryptic fragments as a standard, advanced mass spectrometry techniques, as well as specific antibodies. A number of cleavages are similar to those described for Na+,K+ -ATPase or other P-type pumps and are expected on the basis of the putative Mg2+ binding residues near the phosphorylated Asp351 in E1 or E2P conformations. However, intriguing new features have also been observed. These include a Fe2+ site near M3, which cannot be due to the presence of histidine residues as it was postulated in the case of Na+,K+ -ATPase and H+,K+ -ATPase. This site could represent a Ca2+ binding zone between M1 and M3, preceding Ca2+ occlusion within M4, 5, 6, and 8. In addition, we present evidence that, in the non-crystalline state, the N- and P-domain may approach each other, at least temporarily, in the presence of Ca2+ (E1Ca2 conformation), whereas the presence of Mg.ATP stabilizes the N to P interaction (E1.Mg.ATP conformation).


The effect of tubular perfusion with PGE2, PGF2 alpha, and PGI2 on the tubuloglomerular feedback control in the rat.
The prostaglandins (PG) of the renal medulla might affect the nephron and the cortical arteriolar function via the tubular route. To investigate this question PGE2 (1 microgram/mL), PGF2 alpha (10 micrograms/mL), or PGI2 (1 ng/mL) was added to the tubular perfusion solution when the characteristics of the tubuloglomerular feedback (TGF) control were measured. The experiments were performed on Sprague-Dawley rats. The proximal tubular stop-flow pressure (PSF) was measured upstream to a wax block, while at the same time the distal nephron was perfused with prostaglandin-containing or prostaglandin-free solutions at different flow rates varying from 0 to 50 nL/min. The maximal drop in PSF (delta PSF) and the tubular flow rate at which 50% of the delta PSF response was obtained, the turning point (TP), were determined. When PGE2 or PGF2 alpha was added to the tubular perfusion solution in the control animals a significant increase in feedback sensitivity was found. After 10 min of tubular PGI2 perfusion the feedback sensitivity was almost completely abolished, with a delta PSF of 0.8 mmHg (1 mmHg = 133.322 Pa) (control 8.4 mmHg) and a TP of greater than 40 nL/min (control 22 nL/min). After nephrectomy the feedback sensitivity was reduced, with a delta PSF of 2.0 mmHg and a TP of greater than 40 nL/min. When PGE2 was added to the tubular perfusion solution in the uninephrectomized animals, the feedback sensitivity was increased to the control level, with a delta PSF of 8.2 mmHg and a TP of 20.0 nL/min.(ABSTRACT TRUNCATED AT 250 WORDS)


Ocean Data Assimilation in Support of Climate Applications: Status and Perspectives.
Ocean data assimilation brings together observations with known dynamics encapsulated in a circulation model to describe the time-varying ocean circulation. Its applications are manifold, ranging from marine and ecosystem forecasting to climate prediction and studies of the carbon cycle. Here, we address only climate applications, which range from improving our understanding of ocean circulation to estimating initial or boundary conditions and model parameters for ocean and climate forecasts. Because of differences in underlying methodologies, data assimilation products must be used judiciously and selected according to the specific purpose, as not all related inferences would be equally reliable. Further advances are expected from improved models and methods for estimating and representing error information in data assimilation systems. Ultimately, data assimilation into coupled climate system components is needed to support ocean and climate services. However, maintaining the infrastructure and expertise for sustained data assimilation remains challenging.


Reactions of tertiary phosphines with alcohols in aqueous media.
The phosphines R(2)R'P [R = R' = Me, Et, (n)Pr, (i)Pr, (CH(2))(3)OH; Me(2)PhP and MePh(2)P] react with 2- or 4-hydroxybenzyl alcohols, including "lignin-type" vanillyl, syringyl, and alpha-methylvanillyl alcohols, in a 1:1 ratio in aqueous media, to give zwitterionic phosphobetaine products; these on treatment with aq HCl form the corresponding phosphonium chlorides in good to excellent yields. The syringyl derivative [3,5-(OMe)(2)-4-OH-C(6)H(2)CH(2)PEt(3)]Cl was structurally characterized by X-ray analysis. Kinetically, the reactivity of the benzyl alcohols, studied with the water-soluble [HO(CH(2))(3)](3)P, decreases with substituents in the order 2-hydroxy > 4-hydroxy > vanillyl > syringyl > alpha-methylvanillyl, while 3-hydroxybenzyl alcohol is unreactive; the trend is consistent with reactivity requiring the presence of an ortho- or para-OH substituent in the aromatic ring of the alcohol, and that the reactions proceed via a carbocation species stabilized as a quinone methide. Triethylphosphine reacts with coniferyl alcohol at the C=C moiety to give a zwitterionic intermediate that is again converted by aq HCl to a phosphonium chloride; no reaction was observed with cinnamyl alcohol. The effect on a phenolic pK(a) by incorporation of a phosphonium substituent is also measured.


Prevention of glomerular crescent formation in glomerulonephritis by mycophenolate mofetil in rats.
Glomerular crescent formation is a prominent feature of aggressive forms of glomerulonephritis (GN) and is associated with a poor prognosis. We investigated whether the potent immunosuppressive agent mycophenolate mofetil (MMF) could prevent crescent formation in a model of anti-glomerular basement membrane (GBM) GN in the rat. GN with glomerular crescents was induced by the injection of anti-GBM antibody to female Wistar-Kyoto (WKY/NCrj) rats. The experimental rats were divided into two groups: rats received vehicle (0.5% carboxymethylcerlose) or MMF (20 mg/kg/day) orally. Body weight was measured and the urine and blood samples were evaluated. The rats were sacrificed at day 14, and histological analysis was performed. The mRNA expression of cytokines and adhesion molecules in the kidney was analysed by reverse transcription-polymerase chain reaction (RT-PCR). Marked proteinuria, glomerular crescent formation and glomerulosclerosis were observed in this model, and these were significantly reduced by MMF treatment. Marked glomerular macrophage and T-cell infiltration was also observed, and MMF treatment significantly inhibited macrophage but not T-cell infiltration. RT-PCR and immunohistochemical analysis revealed that mRNA and protein expression of osteopontin was decreased by the treatment with MMF. In addition, MMF treatment in the early stages of GN could inhibit proteinuria, glomerular crescent formation and glomerulosclerosis. These findings suggest therapeutic potential for MMF in the inhibition of glomerular crescent formation in GN and provide new insights into the mechanism underlying the amelioration of crescentic GN by MMF treatment.


Report on the incidence of squamous cell carcinomas affecting the eyelids in England over a 15-year period (2000-2014).
The authors report on trends in the incidence of squamous cell carcinoma (SCC) affecting the eyelids in England over a 15-year period and identify associations between demographic factors and SCC risk. The National Cancer Registration and Analysis Service identified all cases of eyelid SCC in England between 2000 and 2014. The crude and age-standardised rates of eyelid SCCs in England were calculated. The association of SCC with several known demographic risk factors was then examined to assess their importance in periocular cases. Over the 15 years studied, there were 4022 patients in England diagnosed with a first episode of SCC affecting the eyelids. The age-standardised number of reported cases rose between 2000 and 2014 by a mean of 0.0137 cases per 100 000 population per year (equivalent to a rise in SCC incidence of approximately 2% per year). The mean age-standardised incidence rate of SCC during the study period was 0.63 cases per 100 000 population per year.Age was exponentially correlated with incidence, with an approximate doubling of the risk for every decade over the age of 60. The relative risk of eyelid SCC in men compared with women was 1.9. Social deprivation quintile by income was not found to be associated with risk of SCC. The incidence of eyelid SCC in England is rising. In addition, the age-standardised and population-standardised rate of SCC is also rising. A higher risk of SCC is strongly correlated with age and male sex but not with deprivation.


Co-occurrence patterns of litter decomposing communities in mangroves indicate a robust community resistant to disturbances.
Mangroves are important coastal ecosystems known for high photosynthetic productivity and the ability to support marine food chains through supply of dissolved carbon or particular organic matter. Most of the carbon found in mangroves is produced by its vegetation and is decomposed in root associated sediment. This process involves a tight interaction between microbial populations, litter chemical composition, and environmental parameters. Here, we study the complex interactions found during litter decomposition in mangroves by applying network analysis to metagenomic data. Leaves of three species of mangrove trees typically found in the southeast of Brazil (Rhizophora mangle, Laguncularia racemosa, and Avicennia schaueriana) were collected in separate litter bags and left on three different mangroves for 60 days. These leaves were subsequently used for metagenome sequencing using Ion Torrent technology. Sequences were annotated in MG-RAST and used for network construction using MENAp. The most common phyla were Proteobacteria (classes Gamma and Alphaproteobacteria) followed by Firmicutes (Clostridia and Bacilli). The most abundant protein clusters were associated with the metabolism of carbohydrates, amino acids, and proteins. Non-metric multidimensional scaling of the metagenomic data indicated that substrate (i.e., tree species) did not significantly select for a specific community. Both networks exhibited scale-free characteristics and small world structure due to the low mean shortest path length and high average clustering coefficient. These networks also had a low number of hub nodes most of which were module hubs. This study demonstrates that under different environmental pressures (i.e., plant species or mangrove location) the microbial community associated with the decaying material forms a robust and stable network.


Spontaneous sieving of water from ethanol using angstrom-sized nanopores.
Ethanol is widely used as a precursor in products ranging from drugs to cosmetics. However, distillation of ethanol from aqueous solution is energy intensive and expensive. Here, we show that angstrom-sized nanopores with precisely controlled pore sizes can spontaneously remove water from ethanol-water mixtures through molecular sieving at room temperature and pressure. For small-diameter nanotubes, water-filling is observed, but ethanol is completely excluded, as evidenced by time-dependent density functional theory (TD-DFT) calculations and spectroscopy measurements. Potential of mean force calculations were performed to determine how the free energy barriers for water and ethanol-filling of the nanotubes change with increasing pore size. Water/ethanol selectivity ratio reaching as high as 6700 is observed with a (6,4) nanotube, which has a pore size of 0.204 nm. This selectivity vanishes as the pore size increases beyond 0.306 nm. These findings provide insights that may help realize energy efficient molecular sieving of ethanol and water.


Flavanone and flavonol glycosides from the leaves of Thevetia peruviana and their HIV-1 reverse transcriptase and HIV-1 integrase inhibitory activities.
Two new flavanone glucosides, (2R)- and (2S)-5-O-beta-D-glucopyranosyl-7,4'-dihydroxy-3',5'-dimethoxyflavanone[pervianoside I (3), peruvianoside II(4)] and a new flavonol glycoside, quercetin 3-O-[beta-D-glucopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->6)]-beta-D-galactopyranoside] (peruvianoside III, 13) were isolated from the leaves of Thevetia peruviana Schum., together with nine known flavonol glycosides and two known iridoid glucosides. The structures of all compounds were determined on the basis of chemical and spectroscopic methods. Their inhibitory effects against HIV-1 reverse transcriptase and HIV-1 integrase were also investigated.


Synthesis and cytotoxicity of 2alpha-amido docetaxel analogues.
Various 2-amido docetaxel analogues were prepared and evaluated for their cytotoxicities. Among them, m-methoxy and m-chlorobenzoylamido analogues were most active but not superior to docetaxel and paclitaxel, and D-seco analogues inactive. Change of 2-benzoate to 2-benzamide may not improve their activities to drug-resistant cell lines.


New directions in inflammation and immunity: the multi-functional role of the extracellular RNA/RNase system.
In the mid-eighties of the last century, extracellular-proteolipid complexes have been identified in tumor patients and circulating RNA was suggested to represent a specific secretory product of cancer cells. The presence of specific types of RNA in a variety of cancer types proved to be useful in cancer diagnosis. It has been suggested that extracellular RNA and DNA are not inert molecules, but contain biological activities. Recent data have demonstrated that extracellular RNA is likely to present the up to now undefined "natural foreign surface", serving as an initiating factor in blood coagulation in vivo. Yet, extracellular RNA seems to have even more functions. Investigations on blood-brain-barrier have shown that extracellular RNA mediates endothelial permeability. Ample success has been achieved in administrating RNase in different animal models of vascular diseases, thereby significantly delaying thrombus formation and reducing cerebral edema formation with neuroprotection in acute stroke models. Furthermore, extracellular mammalian RNA was found to decrease tumor yield in a murine model system, suggesting that extracellular RNA might trigger immune response. Finally, extracellular nucleic acids were identified as danger signals involved in innate immunity related to neutrophil-mediated bacterial killing and haemocyte activation and coagulation in the insects. Thus, a new area of research on extracellular RNA functions with promising future perspectives just started in the field of inflammation and immunity.


Active control of anapole states by structuring the phase-change alloy Ge2Sb2Te5.
High-index dielectric nanoparticles supporting a distinct series of Mie resonances have enabled a new class of optical antennas with unprecedented functionalities. The great wealth of multipolar responses has not only brought in new physical insight but also spurred practical applications. However, how to make such a colorful resonance palette actively tunable is still elusive. Here, we demonstrate that the structured phase-change alloy Ge2Sb2Te5 (GST) can support a diverse set of multipolar Mie resonances with active tunability. By harnessing the dramatic optical contrast of GST, we realize broadband (Δλ/λ ~ 15%) mode shifting between an electric dipole resonance and an anapole state. Active control of higher-order anapoles and multimodal tuning are also investigated, which make the structured GST serve as a multispectral optical switch with high extinction contrasts (>6 dB). With all these findings, our study provides a new direction for realizing active nanophotonic devices.


Synthesis of β-Galactooligosaccharide Using Bifidobacterial β-Galactosidase Purified from Recombinant Escherichia coli.
Galactooligosaccharides (GOSs) are known to be selectively utilized by Bifidobacterium, which can bring about healthy changes of the composition of intestinal microflora. In this study, β-GOS were synthesized using bifidobacterial β-galactosidase (G1) purified from recombinant E. coli with a high GOS yield and with high productivity and enhanced bifidogenic activity. The purified recombinant G1 showed maximum production of β-GOSs at pH 8.5 and 45°C. A matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis of the major peaks of the produced β-GOSs showed MW of 527 and 689, indicating the synthesis of β-GOSs at degrees of polymerization (DP) of 3 and DP4, respectively. The trisaccharides were identified as β-D-galactopyranosyl-(1→4)-O-β-D-galactopyranosyl-(1→4)-O-β-D-glucopyranose, and the tetrasaccharides were identified as β-D-galactopyranosyl-(1→4)-O-β-D-galactopyranosyl- (1→4)-O-β-D-galactopyranosyl-(1→4)-O-β-D-glucopyranose. The maximal production yield of GOSs was as high as 25.3% (w/v) using purified recombinant β-galactosidase and 36% (w/v) of lactose as a substrate at pH 8.5 and 45°C. After 140 min of the reaction under this condition, 268.3 g/l of GOSs was obtained. With regard to the prebiotic effect, all of the tested Bifidobacterium except for B. breve grew well in BHI medium containing β-GOS as a sole carbon source, whereas lactobacilli and Streptococcus thermophilus scarcely grew in the same medium. Only Bacteroides fragilis, Clostridium ramosum, and Enterobacter cloacae among the 17 pathogens tested grew in BHI medium containing β-GOS as a sole carbon source; the remaining pathogens did not grow in the same medium. Consequently, the β-GOS are expected to contribute to the beneficial change of intestinal microbial flora.


Income barriers faced by individuals in receipt of Temporary Assistance for Needy Families (TANF).
Research surrounding welfare to work programs suggests a number of potential factors that mediate welfare dependency ranging from a person's degree of employment barriers to their psychological well-being. This study explores how employment barriers, health barriers, background barriers, human capital barriers, and psychological well-being of individuals in receipt of TANF are related to earned income. Findings indicate that employment barriers, background barriers, human capital, and perceived locus of control are significant factors in determining welfare recipients' future earned income. Other barriers including physical health and psychological well-being such as depression, happiness, life satisfaction and optimism were not strong predictors of earned income.


Overcommitment as a predictor of effort-reward imbalance: evidence from an 8-year follow-up study.
The effort-reward imbalance (ERI) model includes the personal characteristic of overcommitment (OC) and the job-related characteristics of effort, reward, and ERI, all of which are assumed to play a role in an employee's health and well-being at work. The aim of the present longitudinal study was to shed more light on the dynamics of the ERI model by investigating the basic hypotheses related to the role of OC in the model, ie, to establish whether an employee's OC could be a risk factor for an increased experience of high effort, low reward, and high ERI at work. The study was based on 5-wave, 8-year follow-up data collected among Finnish professionals in 2006 (T1, N=747), 2008 (T2, N=422), 2010 (T3, N=368), 2012 (T4, N=325), and 2014 (T5, N=273). The participants were mostly male (85% at T1) and the majority of them worked in technical fields. OC, effort, reward, and ERI were measured at each time point with the 23-item ERI scale. Three cross-lagged structural equation models (SEM) were estimated and compared by using full information maximum likelihood method: (i) OC predicted later experiences of effort, reward, and ERI (normal causation model), (ii) effort, reward, and ERI predicted later OC (reversed causation model), and (iii) associations in normal causal and reversed causal models were simultaneously valid (reciprocal causation model). The results supported the normal causation model: strong OC predicted later experiences of high effort, low reward and high ERI. High OC is a risk factor for an increased experience of job strain factors; that is, high effort, low reward, and high ERI. Thus, OC is a risk factor not only for an employee's well-being and health but also for an increasing risk for perceiving adverse job strain factors in the working environment.


The histochemical demonstration of protein-bound sulfhydryl groups and disulfide bonds in human hair by a new staining method (DACM staining).
A new fluorogenic maleimide DACM, i.e., N(7-dimethyl amino-4-methyl coumarinyl) maleimide, does not fluoresce by itself. It is specifically combined with --SH groups and becomes fluorescent (lambda ex: 400 nm, lambda em: 485 nm). At this range of excitation the frozen skin section has no native fluorescence because the emission maximum of DACM does not overlap with any of aromatic residues of proteins such as tryptophane. S--S groups can be demonstrated with DACM by inhibiting native --SH and then reducing SS to --SH. --Sh was generally abundant at the bulb region. --SH of hair cortex was more concentrated at keratogenous zone. Further up in the follicle, --SH of hair cortex was gradually decreased, although at the region of isthmus, --SH reaction of the hair cortex was still moderately strong. Outer root sheath had --SH from the upper bulb to the surface of the epidermis. One the other hand, no S--S was demonstrable at the bulb region. At the level of keratogenous zone, however, S--S linkages of hair cortex and inner root sheath began to appear and further up in the follicle S--S linkages were increased gradually. Outer root sheath had no S--S linkages by DACM staining up until it is keratinized along the hair canal in the upper follicle. The concentration of --SH and S--S thus seemed to be reciprocal; --SH is found in non-keratinized tissues, whereas S--S is abundant in keratinized areas. These findings are at some variance with conventional data, which suggest, for example, that --SH groups disappear suddenly above the keratogenous zone.


Factors affecting terrestrial movement in the amphibious mangrove rivulus (Kryptolebias marmoratus).
We hypothesised that the exploration tendency of the amphibious mangrove rivulus Kryptolebias marmoratus would be inhibited in the terrestrial environment because of constraints on terrestrial locomotion or orientation. Using a novel object test, we showed that the fish explored objects in the aquatic but not the terrestrial environment, supporting the existence of constraints on terrestrial exploration. In further tests of the effects of extrinsic factors on terrestrial movement between aquatic refuges, shallow water depth simulating desiccation risk and the presence of a conspecific simulating intraspecific competition increased emersion outside of refuges, while high water salinity had no effect. These extrinsic factors had little effect on terrestrial movement between different aquatic refuges, except possibly for the lowest water depth tested. A significant association observed between emersion activity and movement between aquatic refuges suggested that terrestrial movement in K. marmoratus might depend on the tendency of individuals to emerse.


Support for the use of thermoplastic bite impressions to aid in the identification of missing and unknown children.
This paper presents a response to the editorial opinion expressed in the position paper "Promotion of the Use of a Thermoplastic Material to Aid in the Identification of Unidentified Human Remains," published on page 14 of this issue of the JOURNAL OF THE MASSACHUSETTS DENTAL SOCIETY. No references were cited in that paper: Because the mission of the American Board of Forensic Odontology (ABFO) is to "promote and enhance the science of forensic odontology" and realizing that the ABFO Guidelines on bite mark evidence has failed law enforcement in several high-profile cases in the past, it is necessary to publish a referenced response addressing some of the statements that were made in the ABFO article.


Cardioprotection of Electroacupuncture for Enhanced Recovery after Surgery on Patients Undergoing Heart Valve Replacement with Cardiopulmonary Bypass: A Randomized Control Clinical Trial.
We attempted to investigate cardioprotection of electroacupuncture (EA) for enhanced recovery after surgery on patients undergoing heart valve replacement with cardiopulmonary bypass. Forty-four patients with acquired heart valve replacement were randomly allocated to the EA group or the control group. Patients in the EA group received EA stimulus at bilateral Neiguan (PC6), Ximen (PC4), Shenting (GV24), and Baihui (GV20) acupoints twenty minutes before anesthesia induction to the end of surgery. The primary end point was cardioprotection effect of electroacupuncture postoperatively and the secondary endpoints were quality of recovery and cognitive functioning postoperatively. The present study demonstrated that electroacupuncture reduced the occurrence of complications and played a role of cardioprotective effect on patients after heart valve replacement surgery with cardiopulmonary bypass, and it benefits patients more comfortable and contributes to recovery after surgery. This trial is registered with ChiCTR-IOC-16009123.


The relative abuse liability of oral oxycodone, hydrocodone and hydromorphone assessed in prescription opioid abusers.
Abuse of prescription opioids has risen precipitously in the United States. Few controlled comparisons of the abuse liability of the most commonly abused opioids have been conducted. This outpatient study employed a double-blind, randomized, within-subject, placebo-controlled design to examine the relative abuse potential and potency of oral oxycodone (10, 20 and 40 mg), hydrocodone (15, 30 and 45 mg), hydromorphone (10, 17.5 and 25mg) and placebo. Healthy adult volunteers (n=9) with sporadic prescription opioid abuse participated in 11 experimental sessions (6.5h in duration) conducted in a hospital setting. All three opioids produced a typical mu opioid agonist profile of subjective (increased ratings of liking, good effects, high and opiate symptoms), observer-rated, and physiological effects (miosis, modest respiratory depression, exophoria and decrements in visual threshold discrimination) that were generally dose-related. Valid relative potency assays revealed that oxycodone was roughly equipotent to or slightly more potent than hydrocodone. Hydromorphone was only modestly more potent (less than two-fold) than either hydrocodone or oxycodone, which is inconsistent with prior estimates arising from analgesic studies. These data suggest that the abuse liability profile and relative potency of these three commonly used opioids do not differ substantially from one another and suggest that analgesic potencies may not accurately reflect relative differences in abuse liability of prescription opioids.


Effect of a postoperative exercise program on arteriovenous fistula maturation: A randomized controlled trial.
Exercises after arteriovenous fistula (AVF) creation may help to improve maturation; however, their usefulness has only been examined in indirect, non-comparative studies or small trials. Between June 2013 and November 2014, we included all ambulatory patients with stages 5-5D chronic kidney disease who were candidates for the creation of a native AVF in our center. After surgery, all patients were randomized to an exercise group or a control group with single-blind control. At 1 month postoperatively, clinical maturation (expert nurse inspection) and ultrasonographic maturation (flow >500 mL/min, venous diameter >5 mm and depth <6 mm) were assessed in all patients. A total of 72 patients were randomized, 3 were lost to follow-up, and 69 were finally analyzed. The mean age was 66.8 years (standard deviation 13.8), 70.0% were men, and 65.2% were in pre-dialysis. After surgery (42.0% had distal AVF), the patients were randomized (31 controls, 38 exercise group). At 1 month after surgery, global clinical and ultrasonographic maturation was assessed in 88.4% and 78.3% of AVF, respectively (kappa = 0.539). Non-significant differences in clinical or ultrasonographic maturation were seen between exercise and control group (94.7% vs. 80.6%, P = 0.069; 81.6% vs. 74.2%, P = 0.459). A stepwise logistic regression was performed to control previously analyzed asymmetrically distributed confounding factors (AVF localization), revealing that the exercise group showed greater clinical, but not ultrasonographic, maturation (odds ratio [OR] 5.861, 95% confidence interval: 1.006-34.146 and OR 2.403, 0.66-8.754). A postoperative controlled exercise program after AVF creation seems to increase 1-month clinical AVF maturation in distal accesses. Furthermore, exercise programs should be taken into account, especially in distal accesses.


The effect of antimicrobial activity of Teucrium Polium on Oral Streptococcus Mutans: a randomized cross-over clinical trial study.
The purpose of this study is to determine the effect of a mouthwash containing Teucriumpolium herb on Streptococcus mutans in mouth. This study was a randomized, crossover, double-blind clinical trial, where we selected 22 volunteers (dental students) randomly and we divided them into two groups. The study had two phases. In each phase, one group acted as the intervention group, while the other one was the control group. Both the intervention and control groups were given the mouthwash with and without Teucriumpolium, respectively. S. mutans of saliva were measured before and after each phase to compare the effects of the mouthwashes. A three-week washout period was considered between the two phases. An independent two-sample t-test was utilized to compare the mean of S. mutans colonies. Additionally, we used a standard AB/BA crossover model to find the results of the treatment and the impact of carryover on the residual's biological effects. The significance level was considered 0.05 in this experiment. There is no significant difference observed between the two groups in the number of S. mutans before using the mouthwashes. When the mouthwash containing Teucriumpolium was used, there was a significant decrease in the number of S. mutans colonies in both phases' extract (P = 0.002). The results of this study indicate the mouthwash containing aqueous extract of Teucrium polium can majorly reduce the colonization of S. mutans in human saliva. Ethical issues approved by the Ethics Committee of the Rafsanjan University of Medical Sciences with the approval number of 937/9/31, IRCT code Number of IRCT2013121815842N1 and it was approved on 06/16/2014. The study was conducted in the period of September to November 2014.


Facial and perioral primary impetigo: a clinical study.
Impetigo is the most common skin infection in children. The face, especially the perioral region, is one of the most frequently involved areas. Impetigo is a disease that interests the pediatric dentist, as it poses significant problems in its differential diagnosis from other conditions. Sixteen otherwise healthy children were examined suffering from facial and perioral impetigo. The typical clinical appearance was scattered, painless, slightly pruritic erosions covered by "honey-colored" crusts. In 4 children impetigo was localized in the facial and perioral area, whereas in all other cases lesions were diffused in perioral area and several regions throughout the body. Four children exhibited neck lymphadenopathy and one had mild fever. The treatment of impetigo included the application of topical measures with the systemic antibiotic chemotherapy.


Course of Chronic Trypanosoma cruzi Infection after Treatment Based on Parasitological and Serological Tests: A Systematic Review of Follow-Up Studies.
Chagas disease is caused by the flagellate protozoan Trypanosoma cruzi (T. cruzi). It is endemic in Latin American countries outside the Caribbean. The current criterion for cure in the chronic phase of the disease is the negativization of at least two serological tests such as enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IIF) and indirect hemagglutination assay (IHA). The serological evolution of treated subjects with chronic T. cruzi infection is variable. Treatment failure is indicated by a positive parasitological and/or molecular test (persistence of parasitemia). To summarize the pattern of response to treatment of parasitological, molecular and serological tests performed during the follow-up of subjects with chronic T. cruzi infection. Electronic searches in relevant databases and screening of citations of potentially eligible articles were accomplished. Organizations focusing on neglected infectious diseases were asked for help in identifying relevant studies. Included studies were randomized controlled trials (RCTs), quasi-RCTs, and cohort studies involving adults and children with chronic infection who received trypanocidal treatment (benznidazole or nifurtimox) and were followed over time. The assessment of risk of bias was performed separately for each study design. The Cochrane Collaboration's tool and the guidelines developed by Hayden et al. were used. Two reviewers extracted all data independently. A third review author was consulted in case of discordant opinion. Additional analyses were defined in ad-hoc basis. Scatter plots for percentage of positive parasitological and molecular tests and for negative serological tests were developed by using the lowess curve technique. Heterogeneity was measured by I2. The protocol was registered in PROSPERO, an international prospective register of systematic review protocols (Registration Number CRD42012002162). Out of 2,136 citations screened, 54 studies (six RCTs and 48 cohort studies) were included. The smoothed curves for positive xenodiagnosis and positive polymerase chain reaction (PCR) were characterized by a sharp decrease at twelve month posttreatment. Afterwards, they reached 10-20% and 40% for xenodiagnosis and PCR, respectively. The smoothed curves for negative conventional serological tests increased up to 10% after 48 months of treatment. In the long-term, the rate of negativization was between 20% and 45%. The main sources of bias identified across cohort studies were the lack of control for confounding and attrition bias. In general, RCTs were judged as low risk of bias in all domains. The level of heterogeneity across included studies was moderate to high. Additional analysis were incomplete because of the limited availability of data. In this regard, the country of origin of study participants might affect the results of parasitological and molecular tests, while the level of risk of bias might affect serological outcomes. Subgroup analysis suggested that seronegativization occurs earlier in children compared to adults. We acknowledge that there is a dynamic pattern of response based on parasitological, molecular and serological tests in subjects chronically infected with T. cruzi after treatment. Our findings suggest a trypanocidal effect in the long-term follow-up. Further research is needed to explore potential sources of heterogeneity and to conduct reliable subgroup analysis.


Active change detection by pigeons and humans.
Detecting change is vital to both human and nonhuman animals' interactions with the environment. Using the go/no-go dynamic change detection task, we examined the capacity of four pigeons to detect changes in brightness of an area on a computer display. In contrast to our prior research, we reversed the response contingencies so that the animals had to actively inhibit pecking upon detecting change in brightness rather than its constancy. Testing eight rates of change revealed that this direct report change detection contingency produced results equivalent to the earlier indirect procedure. Corresponding tests with humans suggested that the temporal dynamics of detecting change were similar for both species. The results indicate the mechanisms of change detection in both pigeons and humans are organized in similar ways, although limitations in the operations of working memory may prevent pigeons from integrating information over the same time scale as humans.


Dorsal raphe serotonin neurotransmission is required for the expression of nursing behavior and for pup survival.
Proper maternal care is an essential factor of reproductive success in mammals, involving a repertoire of behaviors oriented toward the feeding and care of the offspring. Among the neurotransmitters involved in the initiation of these behaviors, serotonin (5-HT) seems to play an important role. Here we compared pup-oriented maternal behaviors in mice with constitutive 5-HT depletion, the tryptophan hydroxylase 2-knock-out (Tph2-KO) and the Pet1-KO mice. We report that the only common pup-oriented defect in these 2 hyposerotoninergic models is a defective nursing in parturient mice and altered nursing-like (crouching) behavior in virgin mice, while pup retrieval defects are only present in Tph2-KO. Despite a normal mammary gland development and milk production, the defect in appropriate nursing is responsible for severe growth retardation and early lethality of pups born to hyposerotonergic dams. This nursing defect is due to acute rather constitutive 5-HT depletion, as it is reproduced by adult knockdown of Tph2 in the dorsal raphe nucleus in mothers with a prior normal maternal experience. We conclude that 5-HT innervation from the dorsal raphe is required for both the initiation and maintenance of a normal nursing behavior. Our findings may be related to observations of reduced maternal/infant interactions in human depression.


Surface tonsillar microflora versus deep tonsillar microflora in recurrent acute tonsillitis.
One hundred patients suffering from recurrent acute tonsillitis were studied. One hundred tonsils were cultured. Surface bacteria were compared to deep bacteria. In 48 per cent of the cases a different pathogen was cultured from the interior of the tonsil as compared to the surface culture. This fact may explain recurrence of tonsillitis and makes the reliability of the conventional tonsillar culture questionable. Surgical extirpation of the tonsils seems to be the only treatment since deep bacteria remain unidentified and resist the antibiotic therapy that may affect only the surface microflora.


Cognition in Schizophrenia: A Systematic Review of Wechsler Adult Intelligence Scale Studies.
Objective: To critically analyze the evidence regarding changes in verbal and performance intelligence quotient (IQ) in patients with schizophrenia. Data Sources: An English-language-only search was conducted in the PubMed, Cochrane Library, and LILACS databases for articles with study objectives that included Wechsler Adult Intelligence Scale (WAIS) assessment of cognitive functions in patients with schizophrenia. Descriptors were defined based on Medical Subject Headings, where associations of psychotic disorders related to the schizophrenia spectrum were suggested, as well as the "Wechsler Scales" descriptor. The search was conducted in November 2022 with no restriction on the date of publication to select studies that used any of the WAIS editions. Study Selection: Articles that met the inclusion criteria were selected after title and summary identification and full-text review. Results: A total of 28 articles were identified. All studies presented total IQ scores, but only 20 showed results for verbal IQ (n = 20) or performance IQ (n = 19). Analyzed data indicated patients had average performance on verbal comprehension features but low average performance on perceptual reasoning, working memory, and processing speed indices. Conclusions: Executive function deficits were found in the analyzed studies, which reflect difficulties in planning and impulse control-characteristics present in the diagnosis of schizophrenia. The identification of this neuropsychological functioning contributes to the understanding of the cognitive dynamics found in schizophrenia and may help in early diagnosis, reinforcing the hypothesis that cognitive performance may be one of the indicators of psychopathologic expression. Prim Care Companion CNS Disord 2023;25(5):22r03456. Author affiliations are listed at the end of this article.


Trends in fluid consumption and beverage choices among adults reveal preferences for ayran and black tea in central Turkey.
Beverages are globally significant sources of water in the diet. There is a lack of knowledge about fluid intake from beverage and water consumption in Turkey. Thus, the aim of this study was to examine the type of drinks preferred at meals and snacks as well as the daily fluid, beverage and water intakes based on age and gender. A cross-sectional survey was administered to 3411 randomly chosen adult participants (n = 1522 male, n = 1919 female) representing the general profile of central Turkey. The survey consisted of a demographic/personal information questionnaire, 24-hour dietary recalls and mealtime-based beverage frequency questionnaires. Body weights and heights were measured. Daily average total fluid consumption was 2270 mL/day, of which water was 1470 mL/day, and other beverages were 800 mL/day. More than 90% of the participants drank black tea at breakfast and snacks. For lunch and dinner, young participants' major choices were carbonated soft drinks followed by ayran (diluted salty plain yoghurt); middle aged and older participants' choices were ayran followed by black tea. Carbonated soft drinks were preferred over ayran in subjects aged 19-39 years. Older participants prefer healthy, traditional choices such as ayran and black tea, but younger participants prefer high energy-containing drinks with low nutritional value. Thus, this unique information contributes to the data on beverage consumption patterns in different countries and might be useful for increasing consumption of nutritious fluids and decreasing sugar usage in Turkey.


Measuring the Microphase Separation Scale of Polyurethanes with a Vibration-Induced Emission-Based Ratiometric "Fluorescent Ruler".
Polyurethanes (PUs) are a very attractive type of segmented polymer with unique mechanical properties derived from thermodynamic incompatibility between flexible soft segments and hard segments. The performance of PUs is closely related to their microphase separation structures, in which the hard domains serve as physical cross-linking points in the soft matrix. Studying the microphase separation of PUs in a facile manner is thus of great significance but challenging due to the complexity of the internal structures of PUs. N,N'-disubstituted-dihydrophenazine (DPAC) derivatives, the typical molecules featured with vibration-induced emission (VIE) attribute, can emit fluorescence varying with surrounding environment. In this proof-of-concept work, a series of DPAC derivatives were employed as built-in ratiometric "fluorescent rulers" to measure the degree of microphase separation in PUs modulated by temperature variation. The fluorescence of selected DPAC-doped PU films is dependent on the temperature, providing a theoretical basis for this concept. The feasibility of these fluorescent rulers was further validated by the small-angle X-ray scattering (SAXS) analysis. The SAXS curves show significant change in q range of 0.02 to 0.15 Å-1 with the variation in temperature, showing the changes in the internal microstructure. The polydisperse hard sphere model analysis of the scattering data revealed that the volume fraction of hard spheres has a defined relationship with the fluorescence intensity ratio of orange-red light and blue light, thereby demonstrating a novel fluorimetry method for measuring and monitoring the microphase separation of polyurethanes.


Conceptualising social media addiction: a longitudinal network analysis of social media addiction symptoms and their relationships with psychological distress in a community sample of adults.
Problematic social media use has been identified as negatively impacting psychological and everyday functioning and has been identified as a possible behavioural addiction (social media addiction; SMA). Whether SMA can be classified as a distinct behavioural addiction has been debated within the literature, with some regarding SMA as a premature pathologisation of ordinary social media use behaviour and suggesting there is little evidence for its use as a category of clinical concern. This study aimed to understand the relationship between proposed symptoms of SMA and psychological distress and examine these over time in a longitudinal network analysis, in order better understand whether SMA warrants classification as a unique pathology unique from general distress. N = 462 adults (Mage = 30.8, SDage = 9.23, 69.3% males, 29% females, 1.9% other sex or gender) completed measures of social media addiction (Bergen Social Media Addiction Scale), and psychological distress (DASS-21) at two time points, twelve months apart. Data were analysed using network analysis (NA) to explore SMA symptoms and psychological distress. Specifically, NA allows to assess the 'influence' and pathways of influence of each symptom in the network both cross-sectionally at each time point, as well as over time. SMA symptoms were found to be stable cross-sectionally over time, and were associated with, yet distinct, from, depression, anxiety and stress. The most central symptoms within the network were tolerance and mood-modification in terms of expected influence and closeness respectively. Depression symptoms appeared to have less of a formative effect on SMA symptoms than anxiety and stress. Our findings support the conceptualisation of SMA as a distinct construct occurring based on an underpinning network cluster of behaviours and a distinct association between SMA symptoms and distress. Further replications of these findings, however, are needed to strengthen the evidence for SMA as a unique behavioural addiction.


Cytomegalovirus colitis in a pediatric heart transplant patient.
Cytomegalovirus colitis is one of the sequelae of cytomegalovirus infection in transplant patients and can be associated with severe consequences. This case details the clinical, radiographic, and laboratory features of this infection in a child after heart transplantation where early recognition and treatment resulted in complete resolution of the disease.


Structure-function relationships in heme-proteins.
Biological systems rely on heme-proteins to carry out a number of basic functions essential for their survival. Hemes, or iron-porphyrin complexes, are the versatile and ubiquitous active centers of these proteins. In the past decade, discovery of new heme-proteins, together with functional and structural research, provided a wealth of information on these diverse and biologically important molecules. Structure determination work has shown that nature has used a variety of different scaffolds and architectures to bind heme and modulate functions such as redox properties. Structural data have also provided insights into the heme-linked protein conformational changes required in many regulatory heme-proteins. Remarkable efforts have been made towards the understanding of factors governing redox potentials. Site-directed mutagenesis studies and theoretical calculations on heme environments investigated the roles of hydrophobic and electrostatic residues, and analyzed the effect of heme solvent accessibility. This review focuses on the structure-function relationships underlying the association of heme in signaling and iron metabolism proteins. In addition, an account is given about molecular features affecting heme's redox properties; this briefly revisits previous conclusions in the light of some more recent reports.


Selective induction, purification and characterization of a laccase isozyme from the basidiomycete Trametes sp. AH28-2.
The white-rot fungus Trametes sp. AH28-2 can synthesize extracellular laccase by induction in cellobiose-based liquid culture medium. Both yields and composition of laccase isozymes, produced by Trametes sp. AH28-2, would be quite different with induction by different small-molecule aromatic compounds, o-toluidine, guaiacol and 3,5-dihydroxytoluene, which affected microbial growth and the synthesis of laccase isozymes differentially. Higher concentrations of the three inducers could considerably increase laccase isozymes yields but not change the laccase composition. Coculturing of Trametes sp. AH28-2 with either Aspergillus oryzae or Gloeophyllum trabeum showed a few effects on laccase production. Laccase isozyme, laccase B, was selectively induced by 3,5-dihydroxytoluene and purified to homogeneity by two-step chromatography. Purified laccase B appeared as blue, with a broad peak at about 600 nm and a shoulder peak at about 330 nm. The ratio of absorbance at 280 nm to that at 600 nm was 21. Every molecule of laccase B had approximately four copper atoms. Molecular mass of laccase B was estimated to be 74 kDa on SDS-PAGE, 72 kDa by FPLC and was determined to be 71 454 Da by mass spectrum. After being treated with N-glycosidase F, laccase B lost 25% of its molecular mass. The isoelectric point of laccase B was 4.0. Its optimal pH and temperature for oxidizing guaiacol were respectively 4.7 and 45 C. The half-life of the enzyme at 60 C was 14.0 min. The enzyme showed a good stability in a range of pH value of 3.5-7.5. The K(m) values of the enzyme toward substrates syringaldazine, guaiacol, ABTS, and DMOP were respectively 28.0, 1249.0, 177.0 and 109.8 μM. The corresponding V(max) are 504.0, 1910.0, 117.4 and 159.0 μM min(-1) mg(-1). In addition, activity of laccase B was inhibited strongly by sodium azide and cyanide, mildly by SDS and trifluoroacetic acid, but only weakly by dimethyl sulfoxide.


The Convex Mixture Distribution: Granger Causality for Categorical Time Series.
We present a framework for learning Granger causality networks for multivariate categorical time series based on the mixture transition distribution (MTD) model. Traditionally, MTD is plagued by a nonconvex objective, non-identifiability, and presence of local optima. To circumvent these problems, we recast inference in the MTD as a convex problem. The new formulation facilitates the application of MTD to high-dimensional multivariate time series. As a baseline, we also formulate a multi-output logistic autoregressive model (mLTD), which while a straightforward extension of autoregressive Bernoulli generalized linear models, has not been previously applied to the analysis of multivariate categorial time series. We establish identifiability conditions of the MTD model and compare them to those for mLTD. We further devise novel and efficient optimization algorithms for MTD based on our proposed convex formulation, and compare the MTD and mLTD in both simulated and real data experiments. Finally, we establish consistency of the convex MTD in high dimensions. Our approach simultaneously provides a comparison of methods for network inference in categorical time series and opens the door to modern, regularized inference with the MTD model.


Motion Correction in Optical Resolution Photoacoustic Microscopy.
In this paper, we are proposing a novel motion correction algorithm for high-resolution OR-PAM imaging. Our algorithm combines a modified demons-based tracking approach with a newly developed multi-scale vascular feature matching method to track motion between adjacent B-scan images without needing any reference object. We first applied this algorithm to correct motion artifacts within one three-dimensional (3D) data segment of rat iris obtained with OR-PAM imaging. We then extended the application of this algorithm to correct motions to obtain vasculature imaging in the whole mouse back. In here, we stitched five adjacent 3D data segments (large field-of-view) obtained while changing the focus of OR-PAM differently for each subarea. The results showed that the motion artifacts of both large blood vessels and microvessels could be accurately corrected in both cases. Compared to the manually stitching method and the traditional SIFT algorithm, the algorithm proposed in this paper has better performance in stitching adjacent data segments. The high accuracy of the motion correction algorithm makes it valuable in OR-PAM for high-resolution imaging of large animals and for quantitative functional imaging.


[Clinical characteristics and prognosis of mediastinal fibrosis].
Objective: To investigate the clinical characteristics and prognosis of mediastinal fibrosis. Methods: Twelve patients with mediastinal fibrosis diagnosed between 2008 and 2015 in our hospital were studied retrospectively. Clinical manifestations, radiological characteristics, endoscopic features, treatment and prognosis were analyzed. Results: There were 3 males and 9 females, with a mean age of 68.8 years.Six patients had previous tuberculosis infection. The most common clinical symptoms were dyspnea on exertion (11 cases), cough (7 cases), and wheezing (6 cases). Chest CT scans revealed an infiltrative mediastinal process, with a discrete mass, enlargement of mediastinal lymph nodes, mediastinal lymph node calcification (9 case). Twelve patients had bronchial and pulmonary artery compression at lobar or segmental levels, 7 cases had localized pulmonary edema, and 6 cases had pulmonary atelectasis. The principal findings of bronchoscopy were distortion of bronchus with stenosis, multiple pigmentation of bronchial mucosa, and bronchial mucosal edema. Pulmonary hypertension (PH) was the main severe complication. One patients suffered from sudden death after bronchoscopy. Eleven patients were followed for 3 month to 7 years, and 5 patients got progression. Anti-tuberculosis therapy with or without corticosteroid was not beneficial. Conclusion: Tuberculosis was the leading cause of mediastinal fibrosis in our study, which was characterized with diffuse bronchial and pulmonary artery compression at lobar or segmental levels, and multiple pigmentation of bronchial mucosa.Anti-tuberculosis therapy with or without corticosteroids was not beneficial.


A 3D Composited Flexible Sensor Based on Percolative Nanoparticle Arrays to Discriminate Coupled Pressure and Strain.
Flexible mechanical sensors based on nanomaterials operate on a deformation-response mechanism, making it challenging to discern different types of mechanical stimuli such as pressure and strain. Therefore, these sensors are susceptible to significant mechanical interference. Here, we introduce a multifunctional flexible sensor capable of discriminating coupled pressure and strain without cross-interference. Our design involves an elastic cantilever fixed on the pillar of the flexible main substrate, creating a three-dimensional (3D) substrate, and two percolative nanoparticle (NP) arrays are deposited on the cantilever and main substrate, respectively, as the sensing materials. The 3D flexible substrate could confine pressure/strain loading exclusively on the cantilever or main substrate, resulting in independent responses of the two nanoparticle arrays with no cross-interference. Benefitting from the quantum transport in nanoparticle arrays, our sensors demonstrate an exceptional sensitivity, enabling discrimination of subtle strains down to 1.34 × 10-4. Furthermore, the suspended cantilever with one movable end can enhance the pressure perception of the NP array, exhibiting a high sensitivity of -0.223 kPa-1 and an ultrahigh resolution of 4.24 Pa. This flexible sensor with multifunctional design will provide inspiration for the development of flexible mechanical sensors and the advancement of decoupling strategies.


[HIV infection and acquired immunodeficiency syndrome. I].
This is the first of three articles on AIDS, in which the story of HIV infection, its etiology and pathogenesis, its pathology and clinical features, and finally its hygienic-prophylactic measures will be reviewed in the light of our present knowledge. Although the subject has been amply illustrated by many writers, it has been deemed useful to review it in this journal in order to present readers with an account of what is known so far and what must be the subject of further rapidly evolving research.


Sound velocities of Fe and Fe-Si alloy in the Earth's core.
Compressional wave velocity-density (V(P)--ρ) relations of candidate Fe alloys at relevant pressure-temperature conditions of the Earth's core are critically needed to evaluate the composition, seismic signatures, and geodynamics of the planet's remotest region. Specifically, comparison between seismic V(P)--ρ profiles of the core and candidate Fe alloys provides first-order information on the amount and type of potential light elements--including H, C, O, Si, and/or S-needed to compensate the density deficit of the core. To address this issue, here we have surveyed and analyzed the literature results in conjunction with newly measured V(P)--ρ results of hexagonal closest-packed (hcp) Fe and hcp-Fe(0.85)Si(0.15) alloy using in situ high-energy resolution inelastic X-ray scattering and X-ray diffraction. The nature of the Fe-Si alloy where Si is readily soluble in Fe represents an ideal solid-solution case to better understand the light-element alloying effects. Our results show that high temperature significantly decreases the V(P) of hcp-Fe at high pressures, and the Fe-Si alloy exhibits similar high-pressure V(P)--ρ behavior to hcp-Fe via a constant density offset. These V(P)--ρ data at a given temperature can be better described by an empirical power-law function with a concave behavior at higher densities than with a linear approximation. Our new datasets, together with literature results, allow us to build new V(P)--ρ models of Fe alloys in order to determine the chemical composition of the core. Our models show that the V(P)--ρ profile of Fe with 8 wt % Si at 6,000 K matches well with the Preliminary Reference Earth Model of the inner core.


Atherosclerosis imaging.
Atherosclerosis imaging has become increasingly important in the understanding of the natural history of coronary artery disease and the processes leading to luminal narrowing, as well as in the assessment of disease burden and therapy efficacy. Intravascular ultrasound (IVUS) has emerged as the new gold standard for atherosclerosis imaging because it provides cross-sectional images of both the arterial wall and lumen with excellent resolution, reveals the diffuse nature of atherosclerosis and the involvement of reference segments, and takes into account vessel wall remodelling. In addition to its clinical indications, IVUS is now widely used as the primary efficacy assessment measure of several antiatherosclerotic approaches in randomized clinical trials. The advantages of using IVUS include its ability to reveal antiatherosclerotic effects within a relatively short period of time and with a reasonable sample size, in contrast to trials assessing angiographic changes or clinical events. IVUS can also help to determine dose-response relationships in the development of novel pharmacological agents. IVUS is currently the ideal imaging modality for clinical trials examining the progression or regression of atherosclerosis.


Significant Associations of Neurological Complications of Herpes Zoster With Stroke in Rheumatoid Arthritis Patients.
Accumulating evidence suggests an increased risk of stroke after herpes zoster (HZ). This risk is elevated in immunocompromised patients. The incidence of HZ in Asia is higher than in Western countries. However, the epidemiology of HZ and HZ-related stroke among rheumatoid arthritis (RA) patients in Asia remains unclear. We conducted a retrospective cohort study using a population-based database to investigate the epidemiology of HZ in RA patients in Taiwan during the period of 2000-2011. A total of 27 609 newly diagnosed and eligible RA cases were identified, and 110 436 non-RA cases were matched for age and sex at a ratio of 4:1. HZ risk increased by 2.53-fold (P<0.0001) in RA patients compared with the general population. Exposure to corticosteroids (adjusted odds ratio=1.73, P<0.0001), adalimumab (adjusted odds ratio=1.61, P=0.002), and rituximab (adjusted odds ratio=2.06, P=0.008) was associated with an increased risk of HZ in RA patients. A significant association between the use of methotrexate or corticosteroids and HZ risk was dose-dependent (Ptrend<0.0001). Elevated risk of stroke was observed in RA patients with HZ (adjusted hazard ratio=1.27, P=0.047), particularly in those with neurological complications (adjusted hazard ratio=1.54, P=0.015). A 2.30-fold significantly increased risk of stroke within 90 days after HZ occurrence was observed in RA patients compared with those without HZ (P=0.02). Furthermore, death risk increased in RA patients with HZ (adjusted hazard ratio=1.18, P=0.026). The risk of HZ and HZ-related stroke has increased in RA patients. Monitoring the occurrence of HZ in RA patients and preventing HZ-related stroke or mortality during a specific immunosuppressive therapy are important.


Optical biopsy approach to basal cell carcinoma and melanoma based on all-optically integrated photoacoustic and optical coherence tomography.
Basal cell carcinoma (BCC) and melanoma (MM), with the highest morbidity and mortality, respectively, are considered as two skin cancers of concern in dermatology. Histological studies have demonstrated that vascular patterns and collagenous stroma serve as key parameters for BCC and MM classification. In this Letter, we sought to identify BCC and MM based on the dual parameters of vascular patterns and scattering structures provided by all-optically integrated photoacoustic and optical coherence tomography (AOPA/OCT). The imaging capability of the AOPA/OCT was verified by the mimic phantoms. Furthermore, in vivo characterization of vasculatures and tissue structures from BCC and MM mice were successfully achieved with high resolution. Results prove the feasibility of AOPA/OCT as a novel method to dedicate to the in vivo biopsy of skin cancers which shows new insights into the study of skin diseases in early stages.


A comparison of the phenolic profile and antioxidant activity of different Cichorium spinosum L. ecotypes.
Wild greens are considered a rich source of phenolic compounds and antioxidants and an essential part of the so-called Mediterranean diet. In the present study, Cichorium spinosum L. ecotypes, cultivated or collected in situ from wild plants from the eastern Mediterranean, were evaluated regarding their phenolic composition and antioxidant activity. Significant differences were observed among the various studied ecotypes regarding their phenolic compound content and profile, especially between wild and cultivated ecotypes, as well as the phenolic acid content between commercial products and cultivated plants. The antioxidant activity also varied among the various studied ecotypes and growing conditions, with commercial products having the highest antioxidant activity, whereas wild ecotypes showed lower antioxidant activity. Cichorium spinosum leaves are a rich source of chicoric and 5-O-caffeoylquinic acid, while significant differences in total phenolic acids, flavonoids and phenolic compound content and in antioxidant activity were observed among the studied ecotypes, as well as between the tested growing conditions. According to the results of the present study, further valorization of C. spinosum species has great potential, since it could be used as a new alternative species in the food industry. © 2017 Society of Chemical Industry.


Signet ring cell carcinoma of the extrahepatic bile duct diagnosed by preoperative biopsy: a case report.
A 73-year-old woman was admitted because of obstructive jaundice. Computed tomography revealed a stricture in the lower bile duct with enhanced bile duct wall. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a tapering stenosis at the lower bile duct. Transpapillary histological biopsy using biopsy forceps through ERCP was performed; the diagnosis of signet ring cell carcinoma (SRCC) of the bile duct was established. Regional lymph node enlargement and distant metastases were not detected on diagnostic imaging. Pancreaticoduodenectomy with pylorus preservation was performed. Histological examination of the resected specimen confirmed SRCC of the extrahepatic bile duct coexisting with adenocarcinoma (ADC) of the extrahepatic bile duct with negative resection margins. However, tumor cells directly invaded the pancreatic parenchyma and the muscle layer of the duodenum, prompting us to administer adjuvant chemotherapy to the patient, with no sign of tumor recurrence at 1-year follow-up. Almost all tumors originating from the extrahepatic bile duct are ADC and other histological variants are rare. Of these, SRCC is extremely rare and only four cases have been reported. Furthermore, to the best of our knowledge, this is the first case report regarding the preoperative diagnosis of SRCC of the bile duct. Current reports indicate that younger age and Asian ethnicity are the clinical features of SRCC of the extrahepatic bile duct. Immunohistochemical staining of CK7, CK20 and MUC2 may be useful for predicting prognosis. Chemotherapy has not resulted in increased survival rates and only surgical resection currently serves as a curative treatment.


Expression of HER2 and C-KIT in nasopharyngeal carcinoma: implications for a new therapeutic approach.
We sought to determine the expression and prognostic significance of HER2 and c-KIT proteins in nasopharyngeal carcinoma (NPC). In this retrospective study, immunohistochemical stains for HER2 and c-KIT were performed on formalin-fixed paraffin-embedded sections from 49 patients with NPC who were treated at our hospital from 1971 to 2000. The clinical and immunohistochemical data were correlated, including gender, ethnic origin, age, histological type, EBV status (EBER in situ hybridization), stage, and overall survival. HER2 expression was not found in the tested samples. C-KIT overexpression was found in 33% (16/49) of the patients. Nine of the 16 samples (56%) were strongly positive for c-KIT protein (staining of >50% of the tumor cells). C-KIT expression was associated with younger age. C-KIT was not found in patients with squamous carcinoma or in those with negative EBV status, although these two groups consisted of only five patients each. Although c-KIT-positive cases tended to be associated with slightly better survival, this was not statistically significant. C-KIT protein was expressed in one third of the NPC patients in this study, only in EBV-positive, undifferentiated, or nonkeratinizing carcinoma patients. Further study is needed to check whether c-KIT expression is correlated with c-KIT DNA mutations and to test the possibility of treatment with imatinib mesylate (Gleevec). HER2 protein was negative in the same tested specimens.


A comparison of synthetic data generation and federated analysis for enabling international evaluations of cardiovascular health.
Sharing health data for research purposes across international jurisdictions has been a challenge due to privacy concerns. Two privacy enhancing technologies that can enable such sharing are synthetic data generation (SDG) and federated analysis, but their relative strengths and weaknesses have not been evaluated thus far. In this study we compared SDG with federated analysis to enable such international comparative studies. The objective of the analysis was to assess country-level differences in the role of sex on cardiovascular health (CVH) using a pooled dataset of Canadian and Austrian individuals. The Canadian data was synthesized and sent to the Austrian team for analysis. The utility of the pooled (synthetic Canadian + real Austrian) dataset was evaluated by comparing the regression results from the two approaches. The privacy of the Canadian synthetic data was assessed using a membership disclosure test which showed an F1 score of 0.001, indicating low privacy risk. The outcome variable of interest was CVH, calculated through a modified CANHEART index. The main and interaction effect parameter estimates of the federated and pooled analyses were consistent and directionally the same. It took approximately one month to set up the synthetic data generation platform and generate the synthetic data, whereas it took over 1.5 years to set up the federated analysis system. Synthetic data generation can be an efficient and effective tool for enabling multi-jurisdictional studies while addressing privacy concerns.