Rapid divergence of histones in Hydrozoa (Cnidaria) and evolution of a novel histone involved in DNA damage response in hydra.
Histones are fundamental components of chromatin in all eukaryotes. Hydra, an emerging model system belonging to the basal metazoan phylum Cnidaria, provides an ideal platform to understand the evolution of core histone components at the base of eumetazoan phyla. Hydra exhibits peculiar properties such as tremendous regenerative capacity, lack of organismal senescence and rarity of malignancy. In light of the role of histone modifications and histone variants in these processes it is important to understand the nature of histones themselves and their variants in hydra. Here, we report identification of the complete repertoire of histone-coding genes in the Hydra magnipapillata genome. Hydra histones were classified based on their copy numbers, gene structure and other characteristic features. Genomic organization of canonical histone genes revealed the presence of H2A-H2B and H3-H4 paired clusters in high frequency and also a cluster with all core histones along with H1. Phylogenetic analysis of identified members of H2A and H2B histones suggested rapid expansion of these groups in Hydrozoa resulting in the appearance of unique subtypes. Amino acid sequence level comparisons of H2A and H2B forms with bilaterian counterparts suggest the possibility of a highly mobile nature of nucleosomes in hydra. Absolute quantitation of transcripts confirmed the high copy number of histones and supported the canonical nature of H2A. Furthermore, functional characterization of H2A.X.1 and a unique variant H2A.X.2 in the gastric region suggest their role in the maintenance of genome integrity and differentiation processes. These findings provide insights into the evolution of histones and their variants in hydra.


High-level expression of biologically active human alpha 1-antitrypsin in the milk of transgenic mice.
Reduced circulating levels of alpha 1-antitrypsin (alpha 1 AT) are associated with certain alpha 1 AT genotypes and increased susceptibility to emphysema. Unfortunately, the amounts of alpha 1 AT that would be required for replacement therapy are beyond the capacity of plasma fractionation and mammalian cell culture systems. Thus, we have examined the potential of transgenic animals as an alternative means of producing human alpha 1 AT. A hybrid gene constructed by using sequences from the ovine milk protein gene beta-lactoglobulin fused to an alpha 1 AT "minigene" was used to generate transgenic mice. Of 13 independent transgenic mice and mouse lines, 5 expressed the hybrid gene in the mammary gland, 5 in the salivary glands, and 2 in both these tissues. Human alpha 1 AT was secreted into the milk of each of the 7 mice and mouse lines that expressed the hybrid gene in the mammary gland. Four of these mammary-expressing transgenic mice and mouse lines produced concentrations of at least 0.5 mg of alpha 1 AT per ml in their milk; one line (AATB 35) produced 7 mg of this protein per ml. alpha 1 AT from transgenic mouse milk was similar in size to human plasma-derived alpha 1 AT and showed a similar capacity to inhibit trypsin. Expression at equivalent levels in transgenic sheep or cattle would yield sufficient alpha 1 AT for therapeutic purposes.


Quantitative systematic review of randomised controlled trials comparing antibiotic with placebo for acute cough in adults.
To assess whether antibiotic treatment for acute cough is effective and to measure the side effects of such treatment. Quantitative systematic review of randomised placebo controlled trials. Nine trials (8 published, 1 unpublished) retrieved from a systematic search (electronic databases, contact with authors, contact with drug manufacturers, reference lists); no restriction on language. Proportion of subjects with productive cough at follow up (7-11 days after consultation with general practitioner); proportion of subjects who had not improved clinically at follow up; proportion of subjects who reported side effects from taking antibiotic or placebo. Eight trials contributed to the meta-analysis. Resolution of cough was not affected by antibiotic treatment (relative risk 0.85 (95% confidence interval 0.73 to 1.00)), neither was clinical improvement at re-examination (relative risk 0.62 (0.36 to 1.09)). The side effects of antibiotic were more common in the antibiotic group when compared to placebo (relative risk 1.51 (0.86 to 2.64)). Treatment with antibiotic does not affect the resolution of cough or alter the course of illness. The benefits of antibiotic treatment are marginal for most patients with acute cough and may be outweighed by the side effects of treatment.


Intraoperative nerve monitoring reduces recurrent laryngeal nerve injury in geriatric patients undergoing thyroid surgery.
This research was aimed to investigate whether the intraoperative nerve monitoring (IONM) can reduce the incidence of recurrent laryngeal nerve (RLN) injury in geriatric patients undergoing thyroid surgery. This retrospective cohort study included 522 geriatric patients undergoing thyroid surgery between January 2013 and June 2016 in the Sun Yat-sen Memorial Hospital. Patients with IONM during the surgery (n = 340) were compared with patients without IONM (n = 212). RLN injury was verified by direct or indirect laryngoscope and relative factors for injury would be retrospectively analyzed. The use of IONM group showed significant reduction in both total and transient RLN injury incidence, when compared with that in control group (1.76 versus 4.72%, p = .01 and 1.32 versus 3.67%, p = .03, respectively). However, the permanent RLN injury incidence did not show difference between the two groups (p = .3). Our finding showed the use of IONM resulted in significantly reduction in RLN injury incidence. The technology of IONM is safe and convenient to detect, track and monitor the complete function of RLN and to provide the guidance for the surgeons during the thyroid surgery in geriatric patients, who are at high risk of RLN injury.


Similarities of the substrate cleavage catalyzed by proline specific endopeptidase and dipeptidyl peptidase IV.
16 substrates of the types succinyl-alanyl-alanine-pX-anilide, and succinyl-alanyl-proline-pX anilide having different substituents in para-position of the aryl residue were synthesized and characterized. The influence of electronic as well as hydrophobic substituent constants, sigma and pi, on the hydrolysis of the substrates catalyzed by the enzyme Proline Specific Endopeptidase (PSE) has been investigated. In the Hansch approach, the catalytic constants lg kcat and lg (kcat/KM) of succinyl-alanyl-alanine-pX-anilides hydrolyzed by PSE correlate significantly with electronic substituent constants sigma, whereas no correlation in the case of succinyl-alanyl-proline-pX-anilides. The intercorrelation of the constants of the former substrates with corresponding data from Dipeptidyl Peptidase IV (DP IV) catalyzed hydrolysis of alanyl-alanine-pX-anilides suggest that both enzymes act by similar catalytic mechanism.


Environmental factors and uptake of cadmium among brazers using cadmium-containing hard solders.
The influence of different work factors on the uptake of cadmium has been studied in 102 brazers working at least 10% of their work day with cadmium-containing hard solders. The blood concentrations of cadmium varied between less than 1 and 113 micrograms/L (less than 9 and 1010 nmol/L). Blood cadmium concentrations were below 10 micrograms/L (89 nmol/L) in 71 brazers and 31 brazers had levels equal to or above that value. The importance of some environmental factors on the blood-level of cadmium was studied with discrimination analysis. The length of the splice was found to be almost the sole determining factor for the cadmium concentration in blood. All brazers working with splices shorter than 2 cm had blood concentrations below 10 micrograms/L, while 87% of the brazers working with splices longer than 10 cm had blood concentrations equal to or above 10 micrograms/L. Other factors like age, sex, exposure time, smoking habit and brazing method were devoid of any measurable importance.


A Scalable Route to Nanoporous Large-Area Atomically Thin Graphene Membranes by Roll-to-Roll Chemical Vapor Deposition and Polymer Support Casting.
Scalable, cost-effective synthesis and integration of graphene is imperative to realize large-area applications such as nanoporous atomically thin membranes (NATMs). Here, we report a scalable route to the production of NATMs via high-speed, continuous synthesis of large-area graphene by roll-to-roll chemical vapor deposition (CVD), combined with casting of a hierarchically porous polymer support. To begin, we designed and built a two zone roll-to-roll graphene CVD reactor, which sequentially exposes the moving foil substrate to annealing and growth atmospheres, with a sharp, isothermal transition between the zones. The configurational flexibility of the reactor design allows for a detailed evaluation of key parameters affecting graphene quality and trade-offs to be considered for high-rate roll-to-roll graphene manufacturing. With this system, we achieve synthesis of uniform high-quality monolayer graphene ( ID/ IG < 0.065) at speeds ≥5 cm/min. NATMs fabricated from the optimized graphene, via polymer casting and postprocessing, show size-selective molecular transport with performance comparable to that of membranes made from conventionally synthesized graphene. Therefore, this work establishes the feasibility of a scalable manufacturing process of NATMs, for applications including protein desalting and small-molecule separations.


Characterization of drug-drug interactions in patients whose substance intake was objectively identified by detection in urine.
Identification of drug-drug interactions (DDIs) typically relies on patient medication lists which are prone to inaccuracies. This study describes use of a mass spectrometry test to detect recently ingested substances in urine with subsequent identification of DDIs. This was a retrospective analysis of the prevalence of DDIs identified in patients with chronic pain, addiction and/or behavioral health conditions in the U.S. Relationships between patient demographics, polypharmacy and the occurrence of DDIs were also described. Of 15,004 patients, 2964 (20%) had a DDI identified. There was a positive association between the number of substances detected in urine and the number of interactions identified (r = 0.5033, p-value = 0.0001). Of patients with polypharmacy, 15.6% had contraindicated or severe interactions identified compared to only 3.2% of those without polypharmacy. For polypharmacy patients, the youngest population studied had a much higher likelihood of having one or more DDIs identified compared to the other age groups (p-value = 0.0002). By utilizing a mass spectrometry test to objectively detect recently ingested substances followed by identification of DDIs, healthcare providers may be able to better characterize the true incidence of DDIs. Study findings may not be generalizable to healthcare populations outside of pain management, addiction treatment, and behavioral health.


Enhancing the mechanical properties of engineered tissue through matrix remodeling via the signaling phospholipid lysophosphatidic acid.
Knee meniscus fibrocartilage is frequently injured, resulting in approximately 1 million procedures annually in the US and Europe. Its near-avascularity contributes heavily to its inability to heal, and places it as a prime candidate for replacement through regenerative medicine. Here, we describe a novel approach to increase extracellular matrix organization, rather than content, in order to augment the mechanical properties of engineered tissue. To synthesize fibrocartilage, we employ a self-assembling process, which is free of exogenous scaffolds and relies on cell-to-cell interactions to form all-biologic constructs. When treated with the signaling phospholipid lysophosphatidic acid (LPA), tissue constructs displayed increased tensile properties and collagen organization, while total collagen content remained unchanged. LPA-treated constructs exhibited greater DNA content, indicative that the molecule exerted a signaling effect. Furthermore, LPA-treated cells displayed significant cytoskeletal reorganization. We conclude that LPA induced cytoskeletal reorganization and cell-matrix traction, which resulted in matrix reorganization and increased tensile properties. This study emphasizes the potential of non-traditional stimuli, such as signaling phospholipids, for use in tissue development studies. The extension of these results to other collagen-rich tissues represents a promising avenue for future exploration.


A simple laser locking system based on a field-programmable gate array.
Frequency stabilization of laser light is crucial in both scientific and industrial applications. Technological developments now allow analog laser stabilization systems to be replaced with digital electronics such as field-programmable gate arrays, which have recently been utilized to develop such locking systems. We have developed a frequency stabilization system based on a field-programmable gate array, with emphasis on hardware simplicity, which offers a user-friendly alternative to commercial and previous home-built solutions. Frequency modulation, lock-in detection, and a proportional-integral-derivative controller are programmed on the field-programmable gate array and only minimal additional components are required to frequency stabilize a laser. The locking system is administered from a host-computer which provides comprehensive, long-distance control through a versatile interface. Various measurements were performed to characterize the system. The linewidth of the locked laser was measured to be 0.7 ± 0.1 MHz with a settling time of 10 ms. The system can thus fully match laser systems currently in use for atom trapping and cooling applications.


FT-IR microspectroscopic detection of metabolically deuterated compounds in the rat cerebellum: a novel approach for the study of brain metabolism.
Deuteration provides a novel means for studying metabolism in biological organisms and avoids the use of radioisotopes. Ingestion of D2O enriched drinking water causes deuterium to be metabolically incorporated into molecules within tissues. The incorporation of deuterium into various chemical functional groups then can be monitored via infrared spectroscopy. The excellent spatial resolution that can be achieved with Fourier transform infrared (FT-IR) microspectrometers allows collection of infrared spectra from select microscopic regions of tissue specimens. Thus, combining deuteration together with FT-IR microspectroscopy enables analysis of metabolic activities by probing subregions within the microscopic field. In the present study, adult rats were given drinking water containing 30% or 40% D2O for 5 1/2 weeks. Frozen sections were prepared from the cerebellum, and infrared spectra were collected from the molecular layer, granule cell layer and white matter with FT-IR microspectrometers, using both conventional and synchrotron sources. The CD:CH and ND,OD:NH,OH ratios were highest in the molecular layer and lowest in the white matter. The high ratios in the molecular layer are consistent with the active synthesis and recycling at synapses, which are abundant structures in this layer. The low levels in the white matter are consistent with radioactive measures that found slow turnovers of proteins and lipids in myelin, which is the main constituent of white matter. In addition to describing the metabolic incorporation of deuterium, a graphic description of the distribution of chemical functional groups in the various layers of the cerebellum is presented. In summary, this study demonstrates that FT-IR microspectroscopy in conjunction with administration of D2O in drinking water can be used to reveal relative metabolic activities in various layers of the cerebellum. We predict that metabolic activities in other tissues and tissues in different states, e.g., disease states, can be analyzed in a similar manner.


Occurrence of Powdery Mildew Caused by Erysiphe astragali on Astragalus scaberrimus in Inner Mongolia, China.
Astragalus scaberrimus Bunge, a perennial herb, is widely distributed in North and central China, Russia, and Mongolia (POWO, 2023). Due to its tolerance to drought, cold, high salt, low nutrients and alkaline soil, this plant is widely cultivated in China as a forage crop, for water and soil conservation, and for its medicinal properties (Meng, 2015). In 2022, powdery mildew-like signs and symptoms were seen on leaves of A. scaberrimuns cultivated on the campus of Inner Mongolia Agricultural University, Hohhot, Inner Mongolia China. White powder-like masses covered up to 99% of the leaf area with infected plants showing weak growth and senescence. More than 70% of plants (n = 180) exhibited these powdery mildew-infected symptoms. Conidiophores were 70-120 μm long (n = 20) and composed of a basal foot cell, followed by two cells and a conidium. Cylindrical- or ovoid-shaped conidia were 30-45µm long by 9-15 µm wide (n = 20). Brown or light-brown chasmothecia were 100-140 μm in diameter, with flexuous appendages. Based on these morphological characteristics, the fungus was tentatively identified as an Erysiphe sp. (Braun and Cook, 2012; Schmidt and Braun, 2020). Fungal structures were isolated from diseased leaves and genomic DNA of the pathogen was extracted utilizing the method described by Zhu et al. (2022). The internal transcribed spacer (ITS) region was amplified by PCR employing the primers PMITS1/PMITS2 (Cunnington et al., 2003) and the amplicon sequenced by Invitrogen (Shanghai, China). The sequence for the powdery mildew fungus (GenBank accession no.: MW142495) showed 100% identity (645/645 bp) with Erysiphe astragali, which was reported on A. glycyphyllos in Golestan province, Iran (accession no. OP806834). Pathogenicity tests were conducted by brushing the conidia from infected A. scaberrimus leaves onto leaves of four healthy plants, while, the four control plants were brushed in the same manner. All the treated plants were placed in separate growth chambers maintained at 19℃, 65% humidity, with 16 h light/8 h dark photoperiod. Nine days post inoculation, powdery mildew disease signs appeared on inoculated plants, whereas control plants remained asymptomatic. The same results were obtained for two repeated pathogenicity experiments. The powdery mildew fungus was reisolated and identified as E. astragali based on morphological and molecular analysis, thereby fulfilling Koch's postulates. E. astragali causing powdery mildew on A. glycyphyllus were previously reported in Germany with Genbank accesion number of MZ265150 and MZ265151 (Bradshaw et al., 2022). This, to our knowledge, is the first report of powdery mildew caused by E. astragali on A. scaberrimus. The severe occurrence of this destructive powdery mildew disease on A. scaberrimus may adversely affect the utility of the plant for soil conservation or cultivation for medicinal purposes. Identifying the causal agent of powdery mildew will support efforts for the future control and management of diseases on A. scaberrimus.


Long-term effect of dietary fibre intake on glycosylated haemoglobin A1c level and glycaemic control status among Chinese patients with type 2 diabetes mellitus.
Dietary fibre has been linked to lower levels of glycosylated haemoglobin A1c (HbA1c) among diabetes patients. The present study aimed to evaluate the long-term effect of dietary fibre on HbA1c levels among Chinese patients with type 2 diabetes mellitus. Two cross-sectional surveys were conducted in 2006 and 2011, with the second one being a repeat survey on a sub-sample from the initial one. In both surveys, an in-person interview was conducted to collect information on demographic characteristics and lifestyles following a similar protocol. Dietary intake was assessed with a validated FFQ. Anthropometric measures and biochemical assays were performed at the interview. Communities in Pudong New Area of Shanghai, China. Chinese patients (n 934) with type 2 diabetes mellitus. An inverse association was observed between dietary fibre and glycaemic status indicated by HbA1c level in both surveys, although it was significant only in the first survey. Among 497 patients participating in both surveys, dietary fibre intake at the first survey was inversely associated with uncontrolled glycaemic status at the second survey, with adjusted odds ratios across the tertiles of intake being 1·00, 0·72 (95 % CI 0·43, 1·21) and 0·58 (95 % CI 0·34, 0·99; P trend = 0·048). The change in fibre intake was slightly associated with glycaemic status, with each increase in tertile scores of intake linked to a 0·138 % (β = -0·138; 95 % CI -0·002, 0·278) decrease in HbA1c value and a 19 % (OR = 0·81; 95 % CI 0·65, 1·02) reduced risk of uncontrolled glycaemic status at the second survey. Dietary fibre may have a long-term beneficial effect on HbA1c level among Chinese diabetes patients.


Brachial-Ankle Pulse Wave Velocity Could Be a Predictor of Mortality in Patients on Peritoneal Dialysis.
Elevated pulse wave velocity (PWV) has been associated with higher mortality in the general population, chronic kidney disease (CKD) patients, and hemodialysis patients. However, in peritoneal dialysis (PD) patients, this association has received little attention. The aim of this study was to evaluate the association between baseline brachial-ankle PWV (baPWV) levels and total mortality in PD patients. In this single-center retrospective cohort study, 254 incident PD patients with baseline baPWV were followed up from 1 January 2013 to 31 July 2016. Collected baseline data included demographic characteristics and clinical and laboratory measurements. The association of baseline baPWV levels with total mortality was assessed using multivariable-adjusted Cox models. Of 254 patients, mean age was 61.4 (±15.3) years, 61.4% of patients were men, and 22.4% of patients were diabetic. The mean baseline baPWV level was 17.6 (±5.84) m/s. During a mean 31.5 (±20.8) month follow-up period, 45 patients died, of which 13 deaths were caused by cardiovascular disease. After adjusting for sex, age, blood pressure (BP), body mass index (BMI), and hemoglobin, as well as serum albumin, calcium, phosphorus, intact parathyroid hormone (iPTH), uric acid, and medication use, the highest baPWV tertile was significantly associated with a hazard ratio (HR) for total mortality of 2.97 (95% confidence interval [CI], 1.23 - 7.16; p = 0.02). Each 1 m/s higher baseline baPWV level was associated with a 7% (95% CI, 1.03 - 1.12; p = 0.001) higher risk of total mortality. In sensitivity analyses, individuals with baPWV > 21.0 m/s had the highest adjusted risk for total death (HR, 3.22; 95% CI, 1.71 - 6.08; p < 0.001). Higher baseline baPWV levels at the commencement of PD were independently associated with total mortality, which suggests that clinicians could use baPWV as a predictor of higher risk of mortality in PD patients.


Mechanism of cerebral fat embolism in subarachnoid hemorrhage: an experimental study.
Subarachnoid hemorrhage (SAH) may cause neurogenic pulmonary edema (NPE), and chylomicron metabolism may be destroyed in injured lungs. We aimed to investigate the effect of neurogenic pulmonary edema (NPE), if present, on the development of cerebral fat embolism. This study has been conducted on 20 rabbits. Experimental SAH has been applied to half of the animals by injecting homologous blood into the cisterna magna, and the remaining half was applied only isotonic saline solution in the same manner under general anesthesia. After 20 days, all animals were killed. Their lungs and brains were examined histopathologically. Six animals died of SAH between 16 and 20 days, and foamy hemorrhagic parenchymal lesions and intra-alveolar hemorrhage were observed in their lungs. Fat globules were abundantly found in cerebral arteries of six of all the non-surviving animals. But, minimal histopathological changes were found in the lungs and brains of the surviving animals. Cerebral fat embolism was detected in only one animal that was given isotonic solution. SAH may cause NPE and result in lung tissue destruction. Chylomicron metabolism may be disordered in the destructed lungs and leakage of chylomicrons into systemic circulation may be facilitated via destroyed lung barrier. These pathologic processes may lead to cerebral fat embolism.


A novel representation of inter-site tumour heterogeneity from pre-treatment computed tomography textures classifies ovarian cancers by clinical outcome.
To evaluate the associations between clinical outcomes and radiomics-derived inter-site spatial heterogeneity metrics across multiple metastatic lesions on CT in patients with high-grade serous ovarian cancer (HGSOC). IRB-approved retrospective study of 38 HGSOC patients. All sites of suspected HGSOC involvement on preoperative CT were manually segmented. Gray-level correlation matrix-based textures were computed from each tumour site, and grouped into five clusters using a Gaussian Mixture Model. Pairwise inter-site similarities were computed, generating an inter-site similarity matrix (ISM). Inter-site texture heterogeneity metrics were computed from the ISM and compared to clinical outcomes. Of the 12 inter-site texture heterogeneity metrics evaluated, those capturing the differences in texture similarities across sites were associated with shorter overall survival (inter-site similarity entropy, similarity level cluster shade, and inter-site similarity level cluster prominence; p ≤ 0.05) and incomplete surgical resection (similarity level cluster shade, inter-site similarity level cluster prominence and inter-site cluster variance; p ≤ 0.05). Neither the total number of disease sites per patient nor the overall tumour volume per patient was associated with overall survival. Amplification of 19q12 involving cyclin E1 gene (CCNE1) predominantly occurred in patients with more heterogeneous inter-site textures. Quantitative metrics non-invasively capturing spatial inter-site heterogeneity may predict outcomes in patients with HGSOC. • Calculating inter-site texture-based heterogeneity metrics was feasible • Metrics capturing texture similarities across HGSOC sites were associated with overall survival • Heterogeneity metrics were also associated with incomplete surgical resection of HGSOC.


Ten-years follow-up of 20 patients with idiopathic ventricular tachycardia.
The follow-up and characteristics of 20 patients with ventricular tachycardia (VT) and no detectable heart disease is reported. These were 16 men and four women with a mean age of 44 years. Symptoms were present in 18 patients (eight had syncope and ten palpitations or dizziness), VT was sustained in 11 patients and a left bundle branch block morphology with inferior axis was found in 17 patients. In three patients, VT had a right bundle branch block morphology and left-axis deviation. The VT was inducible in 13 patients during the electrophysiological testing (EP) and was sustained in five patients. Medical treatment was introduced in 19 patients. During a mean follow-up of 10 years from the onset of the symptoms and 6 years from the EP testing, one patient died suddenly. He had stopped taking amiodarone 5 months before. In seven patients symptoms recurred and were due to discontinuation of therapy in two cases and inefficacy of previous effective treatment in five patients. After modification of the treatment (three cases), implantation of a pacemaker (one case) and catheter ablation (one case), all patients became asymptomatic. Eleven patients became asymptomatic with the first administered antiarrhythmic therapy. One patient continues to be asymptomatic in spite of discontinuation of his medical therapy. We conclude that patients with VT and no detectable heart disease have a good long-term prognosis and that appropriate therapy can be found in almost all patients.


Epilepsy at the prodromal stages of neurodegenerative diseases.
This review provides a clinically grounded description of the links between epilepsy and early common neurodegenerative diseases (i.e. Alzheimer's disease, Lewy body disease, vascular cognitive impairment, fronto-temporal lobar degeneration). It shows that epilepsy does not only concern demented patients displaying convulsive seizures (whether focal or generalized) and obvious atrophy on brain imaging. On the contrary, unprovoked seizures and epilepsy - commonly involving the temporal lobe - are now reported at the prodromal stages of these diseases, when cognitive complaints are mild or even minimal and brain imaging inconstantly abnormal. Thus epilepsy must be considered as a part of the phenotypic spectrum at any stages of the neurodegenerative diseases. This must be kept in mind in everyday practice, and when defining these diseases with clinic-biological criteria. Such entanglement also explains the growing prevalence of elderly epileptic subjects and the need of a close collaboration between geriatricians, cognitivists and epileptologists.


Unaccounted risk of cardiovascular disease: the role of the microbiome in lipid metabolism.
Not all of the risk of cardiovascular disease can be explained by diet and genetics, and the human microbiome, which lies at the interface of these two factors, may help explain some of the unaccounted risk. This review examines some of the well established links between the microbiome and cardiovascular health, and proposes relatively unexplored associations. Byproducts of microbial metabolism are associated with health and disease: Trimethylamine N oxide is associated with atherosclerosis; whereas short-chain fatty acids are associated with decreased inflammation and increased energy expenditure. More broadly, a large number of association studies have been conducted to explore the connections between bacterial taxa and metabolic syndrome. In contrast, the relationship between the microbiome and triglycerides levels remains poorly understood. We suggest that deeper understanding of the molecular mechanisms that drive linkages between the microbiome and disease can be determined by replacing 16S rRNA gene sequencing with shotgun metagenomic sequencing or other functional approaches. Furthermore, to ensure translatability and reproducibility of research findings, a combination of multiple different complementary '-omic' approaches should be employed.


The role of microbial diversity and composition in minimizing sludge production in the oxic-settling-anoxic process.
The oxic-settling-anoxic (OSA) process, which involves an aerobic tank attached to oxygen- and substrate-deficient external anoxic reactors, minimizes sludge production in biological wastewater treatment. In this study, the microbial community structure of OSA was determined. Principal coordinate analysis showed that among the three operational factors, i.e., (i) redox condition, (ii) external reactor sludge retention time (SRText), and (iii) sludge interchange between aerobic and anoxic reactors, redox condition had the greatest impact on microbial diversity. Generally, reactors with lower oxidation-reduction potential had higher microbial diversity. The main aerobic sequencing batch reactor of OSA (SBROSA) that interchanged sludge with an external anoxic reactor had greater microbial diversity than SBRcontrol which did not have sludge interchange. SBROSA sustained high abundance of the slow-growing nitrifying bacteria (e.g., Nitrospirales and Nitrosomondales) and consequently exhibited reduced sludge yield. Specific groups of bacteria facilitated sludge autolysis in the external reactors. Hydrolyzing (e.g., Bacteroidetes and Chloroflexi) and fermentative (e.g., Firmicutes) bacteria, which can break down cellular matter, proliferated in both the external aerobic/anoxic and anoxic reactors. Sludge autolysis in the anoxic reactor was enhanced with the increase of predatory bacteria (e.g., order Myxobacteriales and genus Bdellovibrio) that can contribute to biomass decay. Furthermore, β- and γ-Proteobacteria were identified as the bacterial phyla that primarily underwent decay in the external reactors.


CD8+ T cells clear influenza virus by perforin or Fas-dependent processes.
Influenza virus infection is controlled in CD4-depleted mice that are also defective for the expression of either Fas (Fas-/-) or perforin (P-/-). Virus-immune P+/+ and P-/- CD8+ T cells can thus function in, respectively, a Fas-/- or Fas+/+ lung environment. The obvious question is whether the P-/- CD8+ set is effective in Fas-/- mice, a conclusion that would tend to favor cytokine secretion as the mode of virus clearance. Short term chimeras were made with P-/- bone marrow, P+/+ or P-/- T cells, and Fas+/+ or Fas-/- irradiated recipients. While the P+/+ CD8+ population cleared the virus from Fas+/+ and Fas-/- respiratory epithelium, the P-/- effectors were operational only if there was the potential for Fas to be expressed on radiation-resistant lung cells. Target cell destruction mediated via the Fas or perforin pathways is clearly the primary mechanism used by CD8+ T cells to terminate this viral pneumonia.


Trends in the prevalence of grandparents living with grandchild(ren) in selected European countries and the United States.
Research from the United States has shown significant increases in the prevalence of three-generation households and in households consisting solely of grandparents and grandchildren. Such shifts in household composition, which are associated with socio-economic disadvantage, may reflect the activation of grandparents as a latent network of support in response to social and demographic changes such as rising partnership disruption. However, to date, little is known in Europe about trends in grandparent households or whether these households are also likely to be disadvantaged. Moreover, we know little about how the familistic and defamilised policy environments in Europe may affect the activation of such latent kin networks. Employing the Integrated Public Use Microdata Series-International and the Office for National Statistics' Longitudinal Study for England and Wales, we used multivariate techniques to investigate changes in prevalence over time in co-residence with a grandchild across Austria, England and Wales, France, Greece, Portugal, Romania, and the United States. We expected increases in grandparent households in Portugal and Greece, familistic societies with few public alternatives to family support. However, only Romania (like the US) showed an increase in the percentage of people aged 40 and over co-residing with their grandchildren in three-generation households between the late 1970s and 2002. Given rises in poverty and limited support for low-income families in Romania, rises in grandparent coresidence may reflect a coping strategy among poorer families to increasing financial hardship. Regardless of the trends, grandparent households in all the countries studied remained associated with socio-economic disadvantage.


Effect of Met-tRNAf deacylase on polypeptide chain initiation in rabbit reticulocyte lysate.
The possible role of Met-tRNAf deacylase in the regulation of protein synthesis in rabbit reticulocyte lysate by the hemin-controlled translational repressor (HCR) or the double-stranded RNA-activated inhibitor (dsI) has been examined. Inhibition of protein synthesis by either HCR or dsI is associated with a marked increase in the steady state level of 48 S initiation complexes, containing a 40 S ribosomal subunit, globin mRNA, and a reduced level of Met-tRNAf, suggesting that the rate of 60 S subunit addition may be inhibited and that subunit-bound Met-tRNAf may become deacylated by Met-tRNAf deacylase. The addition of highly purified Met-tRNAf deacylase to lysate samples incubated with HCR or dsI reduces the [35S]Met-tRNAf labeling of 48 S complexes to even a lower level but has no effect on the high level of [35S]Met-tRNAf associated with 43 S complexes in the plus hemin control. The effect of added deacylase on the labeling of 48 S complexes with [35S]Met-tRNAf can be overcome by adding eIF-5 or a soluble reticulocyte protein that has been termed the reversing factor, but not by the addition of eIF-2. Added deacylase has no effect on the level of mRNA in 48 S complexes or the labeling of these complexes with [35S]fMet-tRNAf. When lysate samples were labeled with Met-tRNAf, purified from wheat germ or yeast, and doubly labeled with 32P at the 5' end and [35S]methionine aminoacylation, HCR reduced the level of 32P and 35S-labeled tRNAMetf in 48 S complexes to a similar degree, suggesting that once it has become deacylated, tRNAMetf dissociates from the 40 S subunit.


Direct detection of regional myocardial ischemia with technetium-99m nitroimidazole in rabbits.
Conventional perfusion scintigraphy assesses disparities in regional myocardial blood flow but does not directly detect hypoxic tissue. Nitroimidazoles labeled with positron-emitting radionuclides have recently shown promise as direct markers of myocardial hypoxia. This study evaluates a new 99mTc-labeled nitroimidazole of potential benefit in standard myocardial scintigraphy. Technetium-99m-labeled nitroimidazole was administered to rabbits during the early reperfusion phase after 10 min (Group 1) or 60 (Group 2) min of coronary occlusion or after 10 min of a fixed coronary occlusion (Group 3). Tracer retention at 1 hr was assessed in relation to microsphere-determined blood flow during coronary occlusion and at tracer injection. The pattern of nitroimidazole retention on autoradiographs was then compared with the pattern of myocardial hypoperfusion defined by fluorescein photography to precisely define tracer localization. The retention of nitroimidazole in Group 1 rabbits (brief occlusion) was independent of both occlusion and reperfusion blood flow and was uniformly distributed on the autoradiographs. In contrast, nitroimidazole retention in Groups 2 and 3 increased with the severity of hypoperfusion during the occlusion phase and precisely delineated the ischemic zone on all autoradiographs. This 99mTc-labeled hypoxia-avid tracer delineates severe ischemia even after blood flow to the compromised myocardium has been restored. This class of compounds can potentially enhance the physiological assessment of patients with ischemic heart disease.


Feasibility and Patient Acceptance of Emergency Department-Based Influenza Vaccination in a Military Medical Center.
Influenza vaccination rates in the United States remain low. Many emergency department (ED) patients may not routinely seek care elsewhere. In a survey of ED visitors, 36.8% of unvaccinated respondents were willing to consider influenza vaccination during their visit. Participants at high risk for influenza complications were more likely to have been previously vaccinated, but unvaccinated participants at high risk were not significantly more likely to consider ED-based vaccination compared with other participants. ED-based influenza vaccination may be an effective method to expand vaccine coverage.


Impaired attribution of emotion to facial expressions in anxiety and major depression.
Recognition of others' emotions is an important aspect of interpersonal communication. In major depression, a significant emotion recognition impairment has been reported. It remains unclear whether the ability to recognize emotion from facial expressions is also impaired in anxiety disorders. There is a need to review and integrate the published literature on emotional expression recognition in anxiety disorders and major depression. A detailed literature search was used to identify studies on explicit emotion recognition in patients with anxiety disorders and major depression compared to healthy participants. Eighteen studies provided sufficient information to be included. The differences on emotion recognition impairment between patients and controls (Cohen's d) with corresponding confidence intervals were computed for each study. Over all studies, adults with anxiety disorders had a significant impairment in emotion recognition (d = -0.35). In children with anxiety disorders no significant impairment of emotion recognition was found (d = -0.03). Major depression was associated with an even larger impairment in recognition of facial expressions of emotion (d = -0.58). Results from the current analysis support the hypothesis that adults with anxiety disorders or major depression both have a deficit in recognizing facial expression of emotions, and that this deficit is more pronounced in major depression than in anxiety.


Gaseous transmitter regulation of hypoxia-evoked catecholamine secretion from murine adrenal chromaffin cells.
Emerging evidence suggests that gaseous molecules, carbon monoxide (CO), and hydrogen sulfide (H2S) generated by heme oxygenase (HO)-2 and cystathionine γ-lyase (CSE), respectively, function as transmitters in the nervous system. Present study examined the roles of CO and H2S in hypoxia-induced catecholamine (CA) release from adrenal medullary chromaffin cells (AMCs). Studies were performed on AMCs from adult (≥6 wk of age) wild-type (WT), HO-2 null, CSE null, and HO-2/CSE double null mice of either gender. CA secretion was determined by carbon fiber amperometry and [Ca2+]i by microflurometry using Fura-2. HO-2- and CSE immunoreactivities were seen in WT AMC, which were absent in HO-2 and CSE null mice. Hypoxia (medium Po2 30-38 mmHg) evoked CA release and elevated [Ca2+]i. The magnitude of hypoxic response was greater in HO-2 null mice and in HO inhibitor-treated WT AMC compared with controls. H2S levels were elevated in HO-2 null AMC. Either pharmacological inhibition or genetic deletion of CSE prevented the augmented hypoxic responses of HO-2 null AMC and H2S donor rescued AMC responses to hypoxia in HO-2/CSE double null mice. CORM3, a CO donor, prevented the augmented hypoxic responses in WT and HO-2 null AMC. CO donor reduced H2S levels in WT AMC. The effects of CO donor were blocked by either ODQ or 8pCT, inhibitors of soluble guanylyl cyclase (SGC) or protein kinase G, respectively. These results suggest that HO-2-derived CO inhibits hypoxia-evoked CA secretion from adult murine AMC involving soluble guanylyl cyclase (SGC)-protein kinase G (PKG)-dependent regulation of CSE-derived H2S.NEW & NOTEWORTHY Catecholamine secretion from adrenal chromaffin cells is an important physiological mechanism for maintaining homeostasis during hypoxia. Here, we delineate carbon monoxide (CO)-sensitive hydrogen sulfide (H2S) signaling as an important mediator of hypoxia-induced catecholamine secretion from murine adrenal chromaffin cells. Heme oxygenase-2 derived CO is a physiological inhibitor of catcholamince secretion by hypoxia and the effects of CO involve inhibition of cystathionine γ-lyase-derived H2S production through soluble guanylyl cyclase-protein kinase G signaling cascade.


Prevalence and prognosis of bone metastases in common solid cancers at initial diagnosis: a population-based study.
Bone is one of the most common target sites for advanced tumours. The objective was to survey the prevalence and prognosis of bone metastases in 12 common solid malignant tumours. A retrospective cohort study. A total of 1 425 332 patients with a primary cancer between 2010 and 2015 were identified using the Surveillance, Epidemiology, and End Results database. We computed the prevalence and prognosis of bone metastases in each cancer and compared their survival in different stages. The Kaplan-Meier method and Cox logistic regression were used to analyse survival and quantify the effect of bone metastases. This study included 89 782 patients with bone metastases at diagnosis. Lung cancer had the highest prevalence (18.05%), followed by liver cancer (6.63%), nasopharyngeal carcinoma (6.33%) and renal cancer (5.45%). Breast cancer (32.1%), prostate cancer (25.9%), thyroid cancer (46.9%) and nasopharyngeal carcinoma (24.8%) with only bone metastases had a 5-year survival rate of over 20%. Compared with patients at the stage previous to metastasis, bone metastases significantly increased the risk of mortality and decreased survival, especially for those with prostate cancer (adjusted HR: 18.24). Other concomitant extraosseous metastases worsened patient survival. Bone was the most common site of metastasis for prostate cancer, while for colorectal cancer, multiorgan metastases were predominant. This study provides the prevalence and prognosis of bone metastases at the initial diagnosis of common solid cancers. In addition, it demonstrates the impact of bone metastases on survival. These results can be used for early screening of metastases, clinical trial design and assessment of prognosis.


Limited survival of adult human testicular tissue as ectopic xenograft.
Grafting of testicular tissue into immunodeficient mice has become an interesting and promising scientific tool for the generation of gametes and the study of testicular function. This technique might potentially be used to generate sperm from patients whose testes need to be removed or are destroyed due to therapeutic intervention or as a consequence of disease. Here we explore whether adult human testicular tissue from patients with different testicular pathologies survives as xenograft. Testis tissue from adult patients with varying degrees of spermatogenesis was grafted into two strains of immunodeficient mice (severe combined immunodeficiency, Nu/Nu). Tissue with active spermatogenesis prior to grafting largely regressed. However, testicular tissue survival was better in cases where spermatogenesis was suppressed prior to grafting and occasionally spermatogonial stem cells survived. Cases with spermatogenic disruption were not corrected by the xenografting. Superior survival of the germinal epithelium and spermatogonia when spermatogenesis was suppressed prior to grafting could provide a novel strategy for germline preservation in pre-pubertal cancer patients. This approach could also be valuable to study the early stages of human spermatogenesis.


Diamond-Based Supercapacitors: Realization and Properties.
In this Spotlight on Applications, we describe our recent progress on the fabrication of surface-enlarged boron-doped polycrystalline diamond electrodes, and evaluate their performance in supercapacitor applications. We begin with a discussion of the fabrication methods of porous diamond materials. The diamond surface enlargement starts with a top-down plasma etching method. Although the extra surface area provided by surface roughening or nanostructuring provides good outcome for sensing applications, a capacitance value <1 mF cm-2 or a surface-enlargement factor <100 fail to meet the requirement of a practical supercapacitor. Driven by the need for large surface areas, we recently focused on the tempated-growth method. We worked on both supported and free-standing porous diamond materials to enhance the areal capacitance to the "mF cm-2" range. With our newly developed free-standing diamond paper, areal capacitance can be multiplied by stacking multilayers of the electrode material. Finally, considering the fact that there is no real diamond-based supercapacitor device up to now, we fabricated the first prototype pouch-cell device based on the free-standing diamond paper to evaluate its performance. The results reveal that the diamond paper is suitable for operation in high potential windows (up to 2.5 V) in aqueous electrolyte with a capacitance of 0.688 mF cm-2 per layer of paper (or 0.645 F g-1). Impedance spectroscopy revealed that the operation frequency of the device exceeds 30 Hz. Because of the large potential window and the ability to work at high frequency, the specific power of the device reached 1 × 105 W kg-1. In the end, we made estimations on the future target performance of diamond supercapacitors based on the existing information.


[Clinical application of artificial blood vessel graft for arteriovenous fistulization].
To investigate the clinical application of artificial blood vessel graft for arteriovenous fistulization. From October 1995 to August 1998, 23 cases with renal failure received PTEF artificial vessels grafting for arteriovenous fistulization in the forearm. The PTFE artificial vessel was 6 mm in diameter, and 40 cm in length. Artificial vessel "U"-shaped loop was formed from elbow incision to wrist incision, and perfused by 20 ml heparin saline. The two ends of artificial vessel were end-to-side anastomosed with superficial cubital vein and cubital artery respectively. All of arteriovenous fistulas were successfully formed, and could be performed hemodialysis periodically. The artificial vessels could be punctured repeatedly, and had sufficient volume of blood flow. It had no rejection, no formation of false aneurysm, and no ischemia in arm or exacerbated reflux to heart. The artificial vessel grafting for arteriovenous fistulization is a safe and convenient technique in clinical practice, especially when there is no autogenous vessels for arteriovenous fistula.


Transhiatal esophagectomy (THE).
In Transhiatal Esophagectomy(THE) two approaches can be used by the surgeon: abdominal and cervical, without thoracotomy. A pioneer of this technique was Orringer, with the largest experience world-wide (1085 patients). THE is associated with a lower morbidity compared with the transthoracic approach, but much controversy exists on whether THE is a suitable operation for cancer, because it is not combined with en-bloc lymphadenectomy. However, overall, there are no statistical differences between the two. Frequently esophageal carcinoma is a systemic disease and thus, the biological behavior and the stage of tumor rather than the technique, play a major role.


Unexpected parasitosis.
Neotrombicula autumnalis is an arthropod living in the soil and parasitizes animals only in its larval stage. Depending on climatic conditions, one to five life cycles can take place in a single year. Human infestation is probably underestimated and can be easily missed due to non-pathognomonic cutaneous manifestations in absence of systemic signs. We describe a case of human trombiculiasis and discuss the diagnostic and therapeutic management of this 'synanthropic' dermatosis.


CIRCINATE PARTITION-LIKE FINDINGS ON CONE MOSAIC IMAGED BY ADAPTIVE OPTICS SCANNING LASER OPHTHALMOSCOPY IN EYES WITH INNER NUCLEAR LAYER MICROCYSTIC CHANGES.
To report cases that showed partition-like, dark areas in the cone mosaic on adaptive optics scanning laser ophthalmoscopy (AO-SLO) images in eyes with inner nuclear layer (INL) microcystic changes. Eyes with INL microcystic changes were imaged by prototype AO-SLO. An eye with Leber hereditary optic neuropathy, an eye with traumatic optic neuropathy, and an eye with retinitis pigmentosa that showed microcystic lesions in the INL were imaged by AO-SLO. The images revealed characteristic, dark, partition-like lesions in the cone mosaic of all the eyes in areas where microcystic changes in the INL were shown by spectral domain optical coherence tomography. The AO-SLO findings in eyes with optic neuropathy were quite similar in shape and size to those seen in eyes with retinitis pigmentosa. We report cases that manifest dark, partition-like areas in the cone mosaic on AO-SLO images. Microcystic lesions in the INL may affect the images of the cone mosaic.


[Prenatal diagnosis of fetal thrombocytopenia].
A case of maternal idiopathic thrombocytopenic purpura complicated by severe fetal thrombocytopenia is reported. Fetal thrombocytopenia was diagnosed by scalp blood-sampling during labour. With discussion of the relevant literature, the authors recommend the use of their method in thrombocytopenic patients in labour. In cases of fetal thrombocytopenia Caesarean section in recommended to prevent trauma and subsequent neonatal haemorrhagic complications.


Macrosomia in well controlled CSII treated Type I diabetic pregnancy.
To survey the effect of tight glycemic control by insulin pumps, of pre-gestational Type 1 diabetic women on pregnancy outcome. Twelve consecutive Type 1, insulin pump treated, diabetic patients followed in the high risk maternal - fetal clinic were ascertained. Data regarding glucose control was assessed and correlated with pregnancy outcome. A total of 14 deliveries (10 singleton) were assessed. There were no miscarriages, one baby that was born with a ventricular septal defect (VSD). Glycemic control was within the acceptable guidelines. HbA1c (%) by trimesters: 6.5 +/- 0.9, 5.9 +/- 0.7, 5.8 +/- 0.6 and average glucose (mg/dL) 121.0 +/- 15.2, 114.8 +/- 13.2, 116.0 +/- 21.1. Average birth weight was 3312.1 +/- 750.2 g with five babies (35%) weighting over 4.0 kg at birth. Birth weight was significantly correlated with HbA1c at the first trimester, mean glucose at trimester 1 and 2, and maternal weight at delivery (r = 0.74, p = 0.045; r = 0.72, p = 0.051; r = 0.74, p = 0.046; r = 0.74, p = 0.04, respectively). Our study of a limited number of patients suggest that women with pre-gestational diabetes obtaining acceptable glycemic goals with insulin pump therapy have increased risk of macrosomia. Current glycemic goals and therapies in treating pre-gestational diabetic patients therefore might not be sufficient to normalise pregnancy outcomes in of women with pre-gestational diabetes.


Dissecting the molecular mechanisms of gene x environment interactions: implications for diagnosis and treatment of stress-related psychiatric disorders.
Epidemiological studies indicate a combined contribution of genetic and environmental factors, mainly exposure to adverse life events, in the risk for psychiatric disease. Understanding how adverse life events interact with genetic predisposition on the molecular level to shape risk and resilience to psychiatric disorders may yield important insight into disease mechanism. Using the example of the molecular mechanisms of interaction of functional genetic variants within the stress-regulating gene FKBP5 and early adversity, it is delineated how this interaction could contribute to transdiagnostic disease risk via a combined genetic and epigenetic disinhibition of FKBP5 transcription. This knowledge may now allow to develop biomarkers for a transdiagnostic subset of psychiatric patients and to personalize treatment.


Method for evaluating material dispersion of dielectric film in the hollow fiber.
A method is proposed to evaluate the material dispersion of dielectric film in dielectric-coated silver hollow fiber. Cauchy's formulas that characterize the dispersion property were obtained for several commonly used dielectric materials by using the measured data of loss spectra of the hollow fibers. The wavelengths of the loss peaks and valleys in the loss spectra can be predicted more accurately when taking into consideration of the material dispersion. The derived Cauchy's formulas play an important role in the design of infrared hollow fiber for multiwavelength delivery.


[Anastomosis dehiscence in anterior resection of the rectum with total excision of the mesorectum].
Anterior rectal resection with total mesorectal excision is currently regarded as the operation of choice in patients with neoplasms of the extraperitoneal rectum. This operation is associated with a significant incidence of anastomotic dehiscence. Some authors, therefore, advise the execution of a protective stoma. From 1987 to 2000, 241 patients with rectal neoplasma were submitted to radical surgery: 183 to anterior rectal resection (extraperitoneal neoplasms in 129 cases and intraperitoneal neoplasms in 54) and 58 to a Miles operation. The total incidence of anastomotic complications was 8.1% (15 patients). In 12 cases (6.5%) a clinical dehiscence was observed, while in 3 patients (1.6%) an asymptomatic fistula was present. In the patients with symptomatic dehiscence a colostomy was performed in 5 cases (42%), while in 7 cases (58%) a conservative approach was adopted (total parenteral nutrition and antibiotic therapy), with complete healing of the fistula. The incidence of anastomotic complications was 9.3% in extraperitoneal neoplasms and 5.6% in intraperitoneal localizations. In relation to the anastomotic technique adopted, the incidence of dehiscences was 25% after 8 Knight-Griffen anastomoses, 16% after 12 manual anastomoses and 7.3% after 163 end-to-end mechanical anastomoses (P = NS). The percentage of anastomotic complications was greater in the period from 1995 to 1997, compared to the period from 1987 to 1994 (12.6% vs 3.8%, P = NS), due to the routine execution of rectal resection in conjunction with total mesorectal excision, particularly at the beginning of the experience, in 1995. In the last 36 cases from 1998 on the incidence of anastomotic complications was reduced to 8.3%, after the learning phase. No related mortality was observed. On the basis of our experience and the evidence reported in the international literature we do not think the execution of a protective stoma is justified after low and ultra-low colorectal anastomosis, except in selected cases.


Dysregulated Sp1/miR-130b-3p/HOXA5 axis contributes to tumor angiogenesis and progression of hepatocellular carcinoma.
Angiogenesis, one of the hallmarks of cancer, is essential for both tumor growth and metastasis. However, its molecular mechanisms in hepatocellular carcinoma (HCC) are largely unknown. Here, we report the role of HOXA5 in tumor angiogenesis of HCC. Methods: The expression of miR-130b-3p and HOXA5 was determined by qRT-PCR and immunohistochemistry, respectively. Capillary tube formation assay, chicken chorioallantoic membrane assay, and subcutaneous xenograft experiments were performed to investigate the role of miR-130-3p and HOXA5. Luciferase reporter assay and chromatin immunoprecipitation assay were performed to evaluate the interaction between Sp1, miR-130b-3p and HOXA5. Results: miR-130b-3p was found up-regulated in HCC and correlated with a poor prognosis. miR-130b-3p promoted HCC angiogenesis both in vitro and in vivo. Mechanistically, HOXA5 was validated as a direct target of miR-130b-3p. Furthermore, we demonstrated that HOXA5 was down-regulated in HCC and its down-regulation was associated with larger tumor size, shorter overall survival, and higher recurrence probability. Moreover, HOXA5 was significantly associated with angiogenesis biomarkers such as CD31 and CD34. Functional studies revealed that the knockdown of HOXA5 also significantly promoted HCC angiogenesis both in vitro and in vivo. Knocking-down HOXA5 significantly provoked HCC cells to induce the capillary tube formation, migration and proliferation of endothelial cells. In xenograft animal models, we found that a decrease of HOXA5 effectively enhanced tumor growth and increased microvessel densities. We further demonstrated that miR-130b-3p could be directly transcriptionally regulated by Sp1. Conclusions: This study showed that a dysregulation in the Sp1/miR-130b-3p/HOXA5 axis contributed to HCC progression and angiogenesis, and that HOXA5 can be considered as a promising therapeutic target for treating HCC.


Primary care detection of chronic kidney disease in adults with type-2 diabetes: the ADD-CKD Study (awareness, detection and drug therapy in type 2 diabetes and chronic kidney disease).
This US, multicenter, observational study assessed the CKD prevalence in adult patients with type-2 diabetes mellitus (T2DM) and characterized the proportion of detected and undiagnosed CKD in the primary care setting using the following: a clinician survey; a patient physical exam and medical history; a single blood draw for estimated glomerular filtration rate (eGFR) and glycosolated hemoglobin (HbA1c); urine dipstick for protein; urine albumin-creatinine ratio (ACR); two patient quality of life questionnaires; and a 15-month medical record review. The study consisted of 9339 adults with T2DM and 466 investigator sites. Of the 9339 enrolled, 9307 had complete data collection for analysis. The 15-month retrospective review showed urine protein, urine ACR, and eGFR testing were not performed in 51.4%, 52.9% and 15.2% of individuals, respectively. Of the 9307 patients, 5036 (54.1%) had Stage 1-5 CKD based on eGFR and albuminuria; however, only 607 (12.1%) of those patients were identified as having CKD by their clinicians. Clinicians were more successful in diagnosing patients with Stage 3-5 CKD than Stages 1 and 2. There were no differences in clinicians' likelihood of identification of CKD based on practice setting, number of years in practice, or self-reported patients seen per week. Awareness or patient self-reported CKD was 81.1% with practitioner detection versus 2.6% in the absence of diagnosis. Primary care of T2DM demonstrates recommended urine CKD testing is underutilized, and CKD is significantly under-diagnosed. This is the first study to show CKD detection is associated with awareness.


Gender as a factor affecting NK cell activity in patients successfully treated for chronic hepatitis C with direct-acting antivirals.
Chronic hepatitis C (CHC) affects the activity of natural killer (NK) cells, but successful interferon- free treatment partially restores it. The goal of this study was to assess whether gender influences NK functionality. We examined 21 post-menopausal women and 24 men with CHC who were treated with direct-acting antivirals (DAA) and 33 healthy volunteers. Using flow cytometry, we analysed KIR2DS4, NKG2D, NKp30, KIR2DL2/DL3, NKG2A and TRAIL on the surface of NK cells. Intracellular granzyme B was also assessed and serum CXCL10 was quantified via ELISA. Overall, patients with CHC had higher expression of KIR2DS4, NKG2A, and NKp30 relative to the control group. Further, CHC patients had a lower percentage of NK cells among lymphocytes relative to the control group. After treatment, KIR2DS4, KIR2DL2/DL, NKG2A, TRAIL and NKp30 on NK cells were decreased whilst the percentage of NK cells and the expression of granzyme B and NKG2D increased. Prior to treatment, serum CXCL10 was elevated, but it was inhibited post-treatment. We observed gender-specific differences in the expression of KIR2DL2/DL3 (higher in women) and NKp30 (elevated in men) compared to CHC/control groups. After treatment, KIR2DL2/DL3, NKp30 and CXCL10 dropped only in the female group while granzyme B increased in the male group. In conclusion, the response of NK cells among men and women of post-menopausal ages with CHC differs. Our research may lead to more studies on the different nature of female and male immune systems in the context of HCV infection and treatment.


Diagnosis of nosocomial pneumonia.
Nosocomial pneumonia occurs in 0.6% of hospitalized patients. The usual causative agents are gram-negative bacilli, Staphylococcus aureus, Streptococcus pneumoniae, and anaerobic bacteria. In immunocompromised hosts, the differential diagnosis also includes fungi, mycobacteria, viruses, Nocardia, and Pneumocystis carinii. Important risk factors for the development of nosocomial pneumonia include prolonged mechanical ventilation, thoracic or upper abdominal surgery, altered mental status, underlying immunosuppression, chronic obstructive pulmonary disease, and the use of antacids or histamine type 2 blockers. Colonization of the oropharynx and tracheal secretions with gram-negative aerobic bacteria is common in hospitalized patients with or without pneumonia. The diagnosis of nosocomial pneumonia is usually based on the clinical features of dyspnea, cough, fever, purulent sputum production, new pulmonary infiltrates, hypoxemia, and leukocytosis. However, the clinician must recognize that the presence of these features is neither sensitive nor specific in the diagnosis of nosocomial pneumonia. Microbiologic diagnosis is also difficult because blood cultures are usually negative, and cultures of tracheal secretions, although usually sensitive, are not specific. Invasive procedures may prove useful, but most have yet to be studied in large groups of patients with nosocomial pneumonia.


Stress and Anxiety Levels Are Associated with Erythrocyte Fatty Acids Content in Young Women.
Objective: Recent studies have revealed that fatty acid profile can be associated with psychological disorders. However, evidence on stress and anxiety is scarce. The aim of this study was to investigate the relationship between stress and anxiety, defined as mood states, and erythrocyte fatty acid (FA) profile. Method : This case-control study was conducted on 45 female students with degrees of stress and anxiety without depression disorder and 45 matched controls with no depression, stress, or anxiety. Self-administered questionnaires included a 28-item Food Frequency questionnaire and Depression Anxiety Stress Scales (DASS-21), which were used to measure dietary patterns and psychological disorders, respectively. Erythrocyte membrane fatty acids were analyzed using gas-liquid chromatography. Results: Docosahexaenoic acid (DHA) was significantly lower in the case group (p = 0.008). Hydrogenated fats were associated with degrees of stress and anxiety (OR = 1.53, p = 0.019), while linoleate and DHA were inversely associated with stress and anxiety scores (OR = 0.37, p = 0.05; OR = 0.31, p = 0.014, respectively). Monounsaturated FAs (MUFAs) and total RBC trans FA were associated with increased risk of stress and anxiety (OR = 1.81, p < 0.001; OR = 3.38, p = 0.003, respectively). Conclusion: Trans-fatty acids may be related to stress and anxiety scales but linoleate and DHA could decrease the risk. The effect of MUFAs may be regarded as a result of compensatory biological mechanisms.


Sandostatin and carcinoid tumours in France: experience in the Lyon area.
Twenty-two patients with moderate to severe carcinoid syndrome received Sandostatin in doses ranging from 50 to 500 micrograms b.i.d. subcutaneously in addition to their usual drug therapies. Symptoms were reported improved in 60% of patients following a test period of Sandostatin. Lack of effect was observed in 5 patients and a lethal complication (obstructing intestinal tumour) occurred in 1. Of 13 patients who received Sandostatin for 3-36 months, 9 remain under control; 3 patients died - 1 from carcinoid spread and the other 2 from unrelated causes. Side effects have been few and mild. In summary, Sandostatin is a valuable agent in the management of carcinoid syndrome.


Regulation of inducible nitric oxide synthase by cAMP-elevating phospho-diesterase inhibitors.
Among the numerous genes controlled by cyclic adenosine monophosphate (cAMP)/protein kinase A signalling machinery is the gene encoding the inducible nitric oxide synthase (iNOS), an enzyme catalyzing the synthesis of a highly reactive free radical nitric oxide (NO). While being a major microbicidal and tumoricidal molecule, iNOS-derived NO has also been implicated in tissue destruction, as well as in regulation of inflammatory/immune cell function in various disorders associated with excessive inflammation. A feasible way for cAMP-dependent therapeutic control of inflammation, including iNOS-mediated NO synthesis, could involve the administration of drugs that block the enzymatic activity of cAMP-degrading phosphodiesterases (PDE). Indeed, cAMP-elevating PDE inhibitors can influence iNOS activation in different cell types in vitro, and their potent anti-inflammatory effects in experimental disease models and clinical studies were frequently accompanied with profound modulation of NO production. A set of conflicting data has been generated over the years, ranging from strong suppression to marked enhancement of NO release by cAMP-increasing PDE inhibitors, depending on cell-type, iNOS stimuli, and/or the agents used. The present review summarizes the data on iNOS modulation by cAMP-elevating PDE inhibitors and possible mechanisms behind it, speculating on its contribution to the therapeutic effects of these drugs.


Risk, autonomy, and responsibility: informed consent for prenatal testing.
Why is informed consent required for prenatal testing? Consent is routinely sought, but examination of the theory behind and the implementation of informed consent for prenatal testing suggests that we need to reconceptualize both the risks and the responsibilities involved in offering and accepting such prenatal tests.


Atypical femoral neck fracture after prolonged bisphosphonate therapy.
Of the drugs developed to prevent and treat osteoporosis, bisphosphonate has played a very important role in preventing osteoporotic fractures. However, case reports describing atypical femoral fractures in patients using long-term bisphosphonates have emerged. The majority of atypical femur fractures occurs in the lateral aspect of the subtrochanteric or femur diaphysis, which is explained by accumulation of tensile stress in these areas. Although the superior cortex of the femur neck withstands maximum tensile stress, to our knowledge, there have been only two reports (three cases) of atypical femoral neck fracture. In addition, none of those case reports revealed detailed pathology related to suppressed bone turnover rate. We encountered an incomplete femoral neck fracture and diagnosed it as "atypical" on the basis of the patient's lack of trauma and medication history and pathological findings. For patients with groin pain, minimal or no trauma, and a history of long-term bisphosphonate use, an atypical femoral neck fracture should be considered.


Factors Affecting Activity Limitation in the Elderly: Data Processed from the Korea National Health and Nutrition Examination Survey, 2016.
The aim of this study was to compare the sociodemographic characteristics, depression, and the health-related quality of life outcome, among the Korean elderly population, with and without activity limitation. The data used was drawn from the raw data of the seventh Korea National Health and Nutrition Examination Survey (N = 8,150). There were 1,632 records for individuals aged 65 or older extracted from the seventh Korea National Health and Nutrition Examination Survey database, 199 of those had missing responses (n = 1,433). Differences within the sociodemographic characteristic, the Patient Health Questionnaire-9, and the EuroQol-5 Dimension were analyzed using logistic regression analysis according to the presence or absence of activity limitation. The prevalence of activity limitation among the elderly individuals surveyed was 19.9%. In the unadjusted regression analysis, the odds ratios of all independent variables (age, gender, education level, type of region, family income, the Patient Health Questionnaire-9, all 5 domains of the EuroQol-5 Dimension) between the elderly individuals with and without activity limitation, were significant. Although, in the adjusted logistic regression analysis, it was observed that the only factors that were significantly associated with activity limitation were the Patient Health Questionnaire-9, EuroQol-5 Dimension, type of region, and family income. These findings demonstrated that activity limitation in elderly individuals is associated with the sociodemographic characteristics of family income and type of region of residence, as well as depression and the health-related quality of life outcome.


Simple febrile convulsions in children: explain and reassure the parents.
(1) Simple febrile convulsions (brief and generalised) in children carry a high risk of recurrence during new febrile episodes (30-50%), especially while the child is under the age of 3 years. These relapses are rarely severe and only occur during a minority of febrile episodes. Later onset of epilepsy is rare. (2) Long term treatment with phenobarbital and valproic acid reduce the risk of relapse but carry a risk of bothersome or severe adverse effects. These treatments are rarely warranted in this setting. (3) Oral diazepam administration to a febrile child has moderate preventive efficacy, which is further limited by the difficulty of timing the treatment correctly. Oral diazepam has frequent but generally mild adverse effects. (4) Antipyretics are not very effective at preventing febrile convulsions but can make the child more comfortable. (5) Parents are often upset when they first see their child have a febrile convulsion. It is important to take the time to reassure them.


Quantitative Analysis of the Association Between Follow-Up Duration and Severity of Limbal Stem Cell Deficiency or Visual Acuity in Aniridia.
This study aimed to quantitatively analyze the association between follow-up duration and the severity of limbal stem cell deficiency (LSCD) or visual acuity in patients with aniridia. A total of 52 eyes of 27 patients with aniridia were enrolled at Osaka University Hospital. Medical records were retrospectively reviewed to obtain information on the severity of LSCD and corrected distance visual acuity (CDVA). LSCD severity was based on a modified severity grading scale. We used an ordered logistic regression model to examine the association between follow-up duration and LSCD severity, and a linear regression model with a generalized linear mixed model for the association between follow-up duration and visual acuity. The mean follow-up duration was 5.2 ± 6.3 years. The mean age at the last follow-up visit was 40.5 ± 18.9 years. The mean CDVA was 1.52 ± 1.09 logMAR. At the last follow-up, 1 examined eye (1.9%) was categorized as stage 0, 7 (13.5%) as Ia, 9 (17.3%) as Ib, 5 (9.6%) as Ic, 2 (3.8%) as IIb, 12 (23.1%) as IIc, and 11 (21.2%) as III. Five eyes (9.6%) were unclassifiable. There was a significant association between follow-up duration and LSCD severity (odds ratio per +1 year, 1.41; P < 0.001). CDVA significantly decreased as follow-up duration increased. Each increase of 1 year in the follow-up duration was associated with a mean difference of +0.021 logMAR (95% confidence interval [CI] 0.01-0.03; P < 0.001). We quantitatively demonstrate that LSCD severity and visual impairment significantly progress as follow-up duration increases.


Regio- and Enantioselective Catalytic δ-C-H Amidation of Dioxazolones Enabled by Open-Shell Copper-Nitrenoid Transfer.
Controlling regio- and enantioselectivity in C-H functionalization reactions is of paramount importance due to their versatile synthetic utilities. Herein, we describe a new approach for the asymmetric δ-C(sp3)-H amidation catalysis of dioxazolones using a Cu(I) precursor with a chiral bisoxazoline ligand to access six-membered lactams with high to excellent regio- and enantioselectivity (up to >19:1 rr and >99:1 er). Combined experimental and computational mechanistic studies unveiled that the open-shell character of the postulated Cu-nitrenoids enables the regioselective hydrogen atom abstraction and subsequent enantio-determining radical rebound of the resulting carbon radical intermediates. The synthetic utility of this asymmetric cyclization was demonstrated in the diastereoselective introduction of additional functional groups into the chiral δ-lactam skeleton as well as in the rapid access to biorelevant azacyclic compounds.


Acinar cell carcinoma of gastric ectopic pancreas origin: a case report and literature review.
Primary pancreatic-type acinar cell carcinoma of the stomach is extremely rare, often misdiagnosed, and of unclear origin. We report the case of a primary pure pancreatic-type acinar cell carcinoma of the stomach in a 58-year-old woman. This is the first reported case to exhibit residual ectopic pancreatic tissue adjacent to the tumor serving as evidence for the origin of the carcinoma. Furthermore, we summarized the clinicopathological features of pancreatic-type acinar cell carcinoma of the stomach in order to further understand this solid tumor. Primary pancreatic-type acinar cell carcinoma of the stomach is rare. Data on tumors of this histological type are still relatively scarce, and more in-depth research is needed to elucidate their molecular biological characteristics and prognosis.


Functional Characterization of PhapLEAFY, a FLORICAULA/LEAFY Ortholog in Phalaenopsis aphrodite.
The plant-specific transcription factor LEAFY (LFY) is considered to be a master regulator of flower development in the model plant, Arabidopsis. This protein plays a dual role in plant growth, integrating signals from the floral inductive pathways and acting as a floral meristem identity gene by activating genes for floral organ development. Although LFY occupies an important position in flower development, the functional divergence of LFY homologs has been demonstrated in several plants including monocots and gymnosperms. In particular, the functional roles of LFY genes from orchid species such as Phalaenopsis that contain unique floral morphologies with distinct expression patterns of floral organ identity genes remain elusive. Here, PhapLFY, an ortholog of Arabidopsis LFY from Phalaenopsis aphrodite subsp. formosana, a Taiwanese native monopodial orchid, was isolated and characterized through analyses of expression and protein activity. PhapLFY transcripts accumulated in the floral primordia of developing inflorescences, and the PhapLFY protein had transcriptional autoactivation activity forming as a homodimer. Furthermore, PhapLFY rescues the aberrant floral phenotypes of Arabidopsis lfy mutants. Overexpression of PhapLFY alone or together with PhapFT1, a P. aphrodite subsp. formosana homolog of Arabidopsis FLOWERING LOCUS T (FT) in rice, caused precocious heading. Consistently, a higher Chl content in the sepals and morphological changes in epidermal cells were observed in the floral organs of PhapLFY knock-down orchids generated by virus-induced gene silencing. Taken together, these results suggest that PhapLFY is functionally distinct from RICE FLORICAULA/LEAFY (RFL) but similar to Arabidopsis LFY based on phenotypes of our transgenic Arabidopsis and rice plants.


Are human made disasters different?
The author distinguishes natural from human made disasters, and identifies their traumatic effects. He stresses the impact on both individuals and communities. Lessons learned from the NYC World Trade Center bombings are offered. He concludes with a universal prescription for responding to disasters.


Synchronous and metachronous gastric gist with pancreatic adenocarcinoma: report of 2 cases and a review of literature.
We report two cases of a Gastrointestinal Stromal Tumor (GIST) synchronous and metachronous, respectively, with pancreatic adenocarcinoma. To our knowledge, this is the first report of a GIST involved 3 years after a ductal pancreatic adenocarcinoma. Data from the literature and our cases seem to suggest that incidental GIST may occur synchronously and metachronously with other cancers more frequently than expected. Thus, the patients with a diagnosis of pancreatic adenocarcinoma may have undergone a strict follow up for GIST.


Rehabilitation services for the Pacific.
The Pacific Basin Rehabilitation Research and Training Center was created to help meet the challenges of rehabilitating people in rural remote communities in the United States-associated Pacific. We describe the center, the special region it serves, some of its many programs, and some of the ways it is helping communities in this region provide services that are appropriate and sensitive to the culture, the environment, and the disability.


A new class of noninactivating K+ channels from aplysia capable of contributing to the resting potential and firing patterns of neurons.
From the nervous system of Aplysia, we have cloned a new class of noninactivating K+ channels (aKv5.1) that are activated at low voltage and are capable of contributing to the resting potential and firing patterns of neurons. Expression of aKv5.1 in Aplysia neuron R15 revealed that aKv5.1 exerts an unusual control over cell excitability; it increased the resting potential by more than 20 mV and abolished the spontaneous bursting activity of the cell. In its ability to suppress the endogenous rhythm of R15, aKv5.1 differs in its actions from transient, inactivating K+ channels such as aKv1.1a, an Aplysia homolog of Shaker. aKv1.1a shortens the duration of the spike and increases the afterpotential, but does not suppress bursting. Thus, by expressing different classes of K+ channels, it is possible to redesign, in specific ways, the signaling capabilities of specific, identified neurons.


Auxetic metamaterials from disordered networks.
Recent theoretical work suggests that systematic pruning of disordered networks consisting of nodes connected by springs can lead to materials that exhibit a host of unusual mechanical properties. In particular, global properties such as Poisson's ratio or local responses related to deformation can be precisely altered. Tunable mechanical responses would be useful in areas ranging from impact mitigation to robotics and, more generally, for creation of metamaterials with engineered properties. However, experimental attempts to create auxetic materials based on pruning-based theoretical ideas have not been successful. Here we introduce a more realistic model of the networks, which incorporates angle-bending forces and the appropriate experimental boundary conditions. A sequential pruning strategy of select bonds in this model is then devised and implemented that enables engineering of specific mechanical behaviors upon deformation, both in the linear and in the nonlinear regimes. In particular, it is shown that Poisson's ratio can be tuned to arbitrary values. The model and concepts discussed here are validated by preparing physical realizations of the networks designed in this manner, which are produced by laser cutting 2D sheets and are found to behave as predicted. Furthermore, by relying on optimization algorithms, we exploit the networks' susceptibility to tuning to design networks that possess a distribution of stiffer and more compliant bonds and whose auxetic behavior is even greater than that of homogeneous networks. Taken together, the findings reported here serve to establish that pruned networks represent a promising platform for the creation of unique mechanical metamaterials.


The role of transrectal fine needle aspiration cytology in the diagnosis of prostatic nodules suspicious of malignancy--a study of 126 cases.
Transrectal fine needle aspiration cytology by Franzen technique was carried out in 126 patients having enlarged prostate which were suspicious of malignancy by clinical per rectal examination. Analysis showed benign adenoleiomyomatous hyperplasia in 40 cases, chronic prostatitis in 4 cases, tuberculosis of prostate in 4 cases, malignancy in 76 cases and 2 cases were reported as suspicious of malignancy. Comparison of aspiration cytology with histopathology, serial serum acid phosphatase estimation, repeat a spiration cytology after hormone therapy with or without orchiectomy and clinical follow up showed accuracy of cytologic diagnosis of 98.4 per cent. False negative was 1.6 per cent. There was no false positive diagnosis. No complication was encountered in this procedure.


[Comparative clinical study of pharmacokinetics and bioequivalence of Relonova and Maxalt].
Evaluation of the bioequivalence of the tested Relonova, tablets, 10 mg and Maxalt, tablets, 10 mg drugs on an empty stomach in healthy volunteers. The pharmacokinetic analysis population included 40 volunteers, the safety analysis population included 40 volunteers. The average age of randomized volunteers (men - 20, women - 20) was 29.3±8.9 years, height 1.71±0.09 m, body weight 70.86±11.66 kg, mean BMI 24.18±2.81 kg/m2. The method used high performance liquid chromatography with tandem mass spectrometric detection. Statistical analysis of the obtained data was performed based on the assumption of a log-normal distribution of the parameters AUC0-72 and Cmax. The ratio of geometric means for the key pharmacokinetic parameters (AUC0-t, AUC0-inf and Cmax) of rizatriptan is close to 90%, CI is within the acceptable range for bioequivalent drugs (80-125%). The intrasubject variability (CVintra) for rizatriptan was 23.74% (Cmax), 10.94% (AUC0-t). The average profiles of the pharmacokinetic curves of rizatriptan when taking the test and reference drugs have similar shapes. Relonova and reference Maxalt are bioequivalent. The results of the study make it possible to recommend Relonova for further clinical study and wide practical application.


Comparison of the effects of gamma radiation and low temperature hydrogen peroxide gas plasma sterilization on the molecular structure, fatigue resistance, and wear behavior of UHMWPE.
The effects of gamma radiation and low temperature hydrogen peroxide gas plasma (HPGP) sterilization on structure and cyclic mechanical properties were examined for orthopedic grade ultra-high-molecular-weight polyethylene (UHMWPE) and compared to each other as well as to no sterilization (control). Density was monitored with a density gradient column and was found to be directly influenced by the sterilization method employed: Gamma radiation led to an increase, while plasma did not. Oxidation of the polymer was studied by observing changes in the carbonyl peak with Fourier transform infrared spectrometry and was found to be strongly affected by both gamma radiation and subsequent aging, while plasma sterilization had little effect. Gamma radiation resulted in embrittlement of the polymer and a decreased resistance to fatigue crack propagation. This mechanical degradation was a direct consequence of postradiation oxidation and molecular evolution of the polymer and was not observed in the plasma-sterilized polymer. Both gamma radiation and plasma sterilization led to improved wear performance of the UHMWPE compared to the nonsterile control material.


[Methods for detection of myocardial viability in patients with heart failure].
Myocardial ischaemia may lead to impaired function of the myocardium. Chronic severe myocardial ischaemia may lead to hibernation, a vegetative state with long-lasting dysfunction of the heart. Hibernation is a potentially reversible condition, which may respond to successful revascularization. If myocardial viability is proven, revascularization of the myocardial territory in question might translate into improved subject prognosis. We present an overview of the existing literature on methods for detection of myocardial viability, and the clinical effects of revascularization.


Development of UHPLC-MS/MS method for simultaneous determination of tacrolimus and sirolimus in human whole blood and comparisons with two immunoassays.
Tacrolimus (TAC) and sirolimus (SIR) antirejection medications are widely used in organ transplantation. We aimed to develop an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) assay for quantifying TAC and SIR simultaneously and evaluating agreement with chemiluminescence microparticle immunoassay (CMIA) and electrochemiluminescence immunoassay (ECLIA). Whole blood samples collected from 209 TAC and 208 SIR patients were assessed by UHPLC-MS/MS, CMIA and ECLIA. The agreement of the three techniques was assessed using the Bland-Altman plot. The UHPLC-MS/MS assay had a calibration range of 1-100 ng/ml for TAC and SIR. The accuracy and precision were -2.73-4.32% and <4.71% for TAC, respectively, and 0.07-4.84% and <6.5% for SIR, respectively. The three methods had good correlation. In comparison with UHPLC-MS/MS, two immunoassays showed a slight deviation in proportion. An UHPLC-MS/MS method for simultaneously detecting TAC and SIR in human whole blood was developed, validated and comparatively analyzed with CMIA and ECLIA. For determining TAC and SIR, immunoassays displayed acceptable analytical performances in terms of precision and correlation compared with UHPLC-MS/MS. However, further investigation is warranted to examine the novel method.


Engineering Morphology and Electron Redistribution of a Ni/WO3 Mott-Schottky Bifunctional Electrocatalyst for Efficient Alkaline Urea Splitting.
Construction of the desired morphology and nanointerface to expose the active sites and modulate the electronic structure offers an effective approach to boosting urea splitting for energy-saving hydrogen generation. Herein, we fabricate a Ni/WO3 Mott-Schottky heterojunction electrocatalyst with a hedgehog-like structure supported on Ni foam toward alkaline urea splitting. Different Ni/WO3 morphologies, such as microspheres, hedgehog-like structures, octahedrons, and cubes, were obtained when various ratios of Ni/W feeds were used. The Mott-Schottky nanointerfaces between Ni and WO3 domains are visually confirmed by high-resolution transmission electron microscopy images, which also accelerated the charge transfer rate. Benefiting from the high electrochemically active surface area and enhanced charge transferability, the optimal Ni/WO3 electrode exhibits outstanding catalytic activity toward hydrogen generation with a low overpotential of 163 mV at 100 mA cm-2 in alkaline solution and reduced cell voltage of 1.67 V when coupled with urea oxidation reaction. Theoretical calculations reveal that the Ni sites in Ni/WO3 optimize the H adsorption energy (ΔGH*) with the |ΔGH*| value of 0.097 eV, much lower than that of Ni (0.35 eV) and WO3 (0.235 eV). This work demonstrates important guidance in designing an efficient electrocatalyst for urea splitting.


Randomised clinical trial: a comparative dose-finding study of three arms of dual release mesalazine for maintaining remission in ulcerative colitis.
Comparative data regarding different regimens of oral mesalazine (mesalamine) for maintaining remission in ulcerative colitis are limited. To evaluate whether 3.0 g mesalazine once-daily (OD) is superior to the standard treatment of 0.5 g mesalazine three times daily (t.d.s.) and to prove the therapeutic equivalence of OD vs. t.d.s. dosing of total 1.5 g mesalazine for remission maintenance in patients with ulcerative colitis. A 1-year, multicentre, double-blind, double-dummy study was undertaken in patients with endoscopically and histologically confirmed ulcerative colitis in remission. Patients were randomised to oral mesalazine 3.0 g OD, 1.5 g OD or 0.5 g t.d.s. The primary efficacy endpoint was the proportion of patients still in clinical remission at the final visit, with clinical relapse being defined as CAI score >4 and an increase of ≥3 from baseline. The primary efficacy endpoint occurred in 162/217 3.0 g OD patients (75%), 129/212 1.5 g OD patients (61%) and 150/218 0.5 g t.d.s. patients (69%) in the intention-to-treat population, and in 152/177 (86%), 121/182 (67%) and 144/185 (78%) in the per protocol population respectively; 3.0 g OD was superior to both low-dose regimens for the primary endpoint (i.e. P < 0.001, 3.0 g OD vs. 1.5 g OD; P = 0.024, 3.0 g OD vs. 0.5 g t.d.s.; superiority test, per protocol population). Safety analysis, including comprehensive renal monitoring, revealed no concern in any treatment group. Mesalazine 3.0 g once daily was the most effective dose for maintenance of remission in ulcerative colitis of the three regimens assessed, with no penalty in terms of safety.


A Dual Route Model for Regulating Emotions: Comparing Models, Techniques and Biological Mechanisms.
The aim of this article is to present recent applications of emotion regulation theory and methods to the field of psychotherapy. The term Emotion Regulation refers to the neurocognitive mechanisms by which we regulate the onset, strength, and the eventual expression of our emotions. Deficits in the regulation of emotions have been linked to most, if not all, psychiatric disorders, with patients presenting either dysregulated emotions, or dysfunctional regulatory strategies. We discuss the implications of regulating emotions from two different theoretical perspectives: the Cognitive Emotion Regulation (CER), and the Experiential-Dynamic Emotion Regulation (EDER) model. Each proposes different views on how emotions are generated, dysregulated and regulated. These perspectives directly influence the way clinicians treat such problems. The CER model views emotional dysregulation as due to a deficit in regulation mechanisms that prioritizes modifying or developing cognitive skills, whilst the EDER model posits emotional dysregulation as due to the presence of dysregulatory mechanisms that prioritizes restoring natural regulatory processes. Examples of relevant techniques for each model are presented including a range of cognitive-behavioral, and experiential (including both dynamic and cognitive) techniques. The aim of the paper is to provide a toolbox from which clinician may gain different techniques to enhance and maintain their patient's capacity for emotional regulation. Finally, the biological mechanisms behind the two models of emotion regulation are discussed as well as a proposal of a dual route model of emotion regulation.


Low therapeutic value of D-penicillamine in a short-term prospective trial in primary biliary cirrhosis.
A small double-blind controlled trial to evaluate the short-term effects of D-penicillamine therapy was carried out in 24 patients with primary biliary cirrhosis (PBC). The daily dose of D-penicillamine was increased monthly by 250 mg until a total of 1 g daily was reached. Two out of 11 patients (18%) were withdrawn because of side-effects, as also were 4 out of 13 (31%) patients receiving the placebo. Transient improvement in symptoms was observed in 4 of 11 patients on D-penicillamine, but also in 5 of 13 patients from the placebo group. The proportion of patients showing a fall in serum IgM, IgG and hepatic copper was significantly larger for the D-penicillamine group than for the placebo group. No improvement in liver tests was observed, but the progression of inflammatory periportal liver cell destruction (piecemeal necrosis) was retarded in patients on D-penicillamine (p = 0.02). Data analysis within the D-penicillamine group showed that lowering the dose of D-penicillamine to 500 mg daily abolished the effect on the serum immunoglobulins and hepatic copper. The beneficial effect of D-penicillamine therapy appears to be small and dose-related; side effects should not prevent its use, provided the drug is introduced slowly.


Category 3 and 4 Controlled Drugs Users' Perceptions of Participating in Drug-Abuse-Health Prevention Lectures in Taiwan.
This study was designed to explore Category 3 and 4 controlled drug users' perceptions of participating in health-prevention lectures. A phenomenological approach was used. Twelve participants were interviewed after completing the lectures. Findings revealed five themes (1) mixed emotions; (2) self-development; (3) finding the lectures lacked practicality and relevance; (4) highlighting three stages for discontinuing drug-usage; and, (5) suggesting tips for the advancement of lectures. These findings could be used as a map to help health professionals understand drug users' perceptions of attending health prevention lectures and provide insight into how young people might stop using drugs.


Effects of neurofeedback on the dysregulation profile in children with ADHD: SCP NF meets SDQ-DP - a retrospective analysis.
As children with attention-deficit/hyperactivity disorder (ADHD) usually show psychopathological signs beyond their core symptoms (e.g. elevated scores of the dysregulation profile (DP) in 30-40%), treatments with a broader approach to self-regulation skills may be supportive. Neurofeedback (NF) may reflect such an option. Aim of the present analysis was to compare the effects of slow cortical potential (SCP) NF and θ/β NF on the DP using data from a previous trial. Thirty children with ADHD (aged 8-12 years) and a DP score in the Strengths and Difficulties Questionnaire (SDQ-DP) ⩾ 3 were included. NF treatment consisted of one block of SCP NF and one block of θ/β NF (18 units per block) allowing an intraindividual comparison. Effects of the NF protocols were also contrasted to a control group (n = 18) that completed an attention skills training (between-group analysis). Regarding the SDQ-DP, SCP NF was superior to θ/β NF and the control condition. Effects of SCP NF and θ/β NF on ADHD symptom severity were not significantly different. The SDQ-DP score did not correlate with EEG-related measures previously found to be predictors for SCP NF on ADHD symptoms. SCP NF may reflect a more general approach to improve cognitive, emotional and behavioral self-regulation skills. If confirmed in a larger sample, the SDQ-DP score could be used as an indication criterion and contribute to the individualization of NF in ADHD. Overall, the differential effect provides further evidence for the specificity of NF effects.


Differential effect of anti-B7-1 and anti-M150 antibodies in restricting the delivery of costimulatory signals from B cells and macrophages.
B7-1 and M150 are potent costimulatory molecules expressed on B cells and macrophages. We have examined the capacity of Abs against B7-1 and M150 in differentially inhibiting the costimulatory signals delivered by macrophages and B cells to OVA-specific CD4+ T cells. The anti-B7-1 Ab significantly blocked the proliferation of Th cells, MLR, T cell help to B cells, and secretion of IFN-gamma when B cells were used to provide costimulation, but not when macrophages were used. In contrast, anti-M150 Ab significantly decreased the proliferation of Th cells, MLR, and production of IFN-gamma, when macrophages were utilized to provide costimulatory signals, but not when B cells were used as APC. However, when macrophages activated with IFN-gamma were used as a source of costimulation, like anti-M150 Ab, Ab to B7-1 also down-regulated the activation of Th cells. The significance of this finding is that M150 is a potent first costimulatory signal for initiating proliferation and secretion of IFN-gamma and providing cognate help for B cells by Th cells when the macrophage is used as an accessory cell. M150-induced IFN-gamma production induces the expression of B7-1 on the surface of macrophages, which then delivers a second cosignal for Th cells. B7-1 works efficiently when B cell provides cosignal. Both of the molecules promote Th1 activity, as evidenced by the inhibition of the secretion of IFN-gamma but not IL-4 by Th cells with anti-M150 and B7-1 Abs.