The male perineal sling: comparison of sling materials.
Urinary incontinence continues to be a significant problem for patients after radical prostatectomy. The male perineal sling is emerging as a safe and effective treatment option for postprostatectomy stress urinary incontinence. We compare the efficacy of porcine dermal collagen and silicone mesh as the sling material. Of 36 patients with postprostatectomy stress urinary incontinence a porcine dermal collagen sling was placed in 20 and a silicone mesh sling was placed in 16. The sling was placed at the bulbar urethra and secured to 3 titanium bone screws anchored into the medial aspect of bilateral inferior pubic rami. Results at 12 months were compared. In the dermis group 9 (56%) patients were cured of incontinence (no pads daily), 5 (31%) had significant improvement (decrease of 50% or more in pads daily) and 2 (13%) had no change in symptoms. In the silicone mesh group 14 (87%) patients were cured of incontinence and 2 (13%) were significantly improved. Results showed that a previously placed artificial urinary sphincter led to poorer outcomes but a history of radiation therapy did not affect results. The most common complication was temporary urinary retention observed in 1 (5%) patient in the dermis group and 2 (12%) in the silicone mesh group. Early results demonstrate that the male sling is a safe and efficacious treatment option for postprostatectomy urinary incontinence. This study demonstrates superior outcomes with the synthetic silicone mesh sling compared to the porcine dermal collagen.


Biotechnological and Biochemical Utilization of Lignin.
This chapter provides an overview of the biosynthesis and structure of lignin. Moreover, examples of the commercial use of lignin and its promising future implementation are briefly described. Many applications are still hampered by the properties of technical lignins. Thus, the major challenge is the conversion of lignins into suitable building blocks or aromatics in order to open up new avenues for the usage of this renewable raw material. This chapter focuses on details about natural lignin degradation by fungi and bacteria, which harbor potential tools for lignin degradation and modification, which might help to develop eco-efficient processes for lignin utilization.


Polymorphisms of DNA repair genes XPD (Lys751Gln) and XRCC1 (Arg399Gln), and the risk of age-related cataract: a meta-analysis.
A meta-analysis of available studies was used to test the association between two DNA repair genes and age-related cataract. A systematic search of the Chinese National Knowledge Infrastructure, EMBASE and PubMed databases identified six studies that were analyzed. Meta-analysis was used to evaluate single nucleotide polymorphisms (SNP) of the DNA repair gene xeroderma pigmentosum complementation group D (XPD) (Lys751Gln) and the X-ray repair cross-complementing gene 1 (XRCC1) (Arg399Gln). Only articles published before June 6, 2014, were included. The quality of the studies was determined using Newcastle-Ottawa Scale tools. The summary odds ratio (OR) and corresponding confidence interval (CI) for XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms and risk of age-related cataract were estimated by random and fixed-effects models. Sensitivity analysis was employed to determine the robustness of the conclusions. Six studies, with a total of 1518 patients with cataractous lenses and 1437 subjects with clear lenses, were included in the meta-analysis. XRCC1 Arg399Gln polymorphisms were associated with cataract risk (recessive model: ORfixed = 0.79, 95% CI: 0.67-0.93; dominant model: ORfixed = 0.84, 95% CI: 0.64-1.11; additive model: ORfixed = 0.82, 95% CI: 0.72-0.92). Analysis of Chinese, but not non-Chinese subgroups, confirmed this association. The OR of XPD Lys751Gln polymorphisms for cataract was not significant. The associations remained significant after sensitivity analysis. This meta-analysis indicates that XRCC1 Arg399Gln polymorphisms, but not XPD Lys751Gln polymorphisms, are associated with risk of age-related cataract.


A novel yeast secretion signal isolated from 28K killer precursor protein encoded on the linear DNA plasmid pGKL1.
Saccharomyces cerevisiae harboring linear dsDNA plasmids, pGKL1 and pGKL2, secretes a killer toxin consisting of 97, 31 and 28 kilodalton subunits (Nucleic Acids Res., 15, 1031-1046, 1987). We isolated the DNA encoding the N-terminal pre-sequence of the 28K precursor protein and constructed a new secretion vector in S. cerevisiae. Mouse alpha-amylase fused to the 28K signal sequence was secreted into the culture medium with a high efficiency similar to those fused to the mating factor alpha and 97K-31K killer signal sequences. This data clearly indicates that 28K presequence functions as a secretion signal. Glycosylated and nonglycosylated alpha-amylase molecules were detected in the culture medium. The secretion of alpha-amylase was blocked by sec18-1 mutation. The secreted alpha-amylase recovered from the medium was found to migrate faster in SDS-polyacrylamide gel than the precursor form of alpha-amylase synthesized in vitro. These lines of evidence suggest that mouse alpha-amylase fused to 28K killer signal sequence was processed, glycosylated and secreted through the normal secretion pathway of the yeast.


Coexistence of Philadelphia-positive chronic granulocytic leukemia and diffuse large B-cell lymphoma at initial diagnosis.
We describe the rare coexistence at the time of diagnosis of Philadelphia positive chronic myelogenous leukemia (Ph+ CML) and non-Hodgkin's lymphoma (NHL). At the time of diagnosis, cytogenetic analysis of peripheral blood and bone marrow cells revealed the Ph chromosome translocation in all examined metaphases. The lymph node biopsy showed features of diffuse large B-cell lymphoma (DLBCL). This case may be of interest due to: (1) the rare coexistence of Ph+ CML and NHL at diagnosis, (2) the fact, that in contrary with previously reported cases in patients with antecedent or concurrent diagnosis of CML, where precursor lymphoblastic lymphomas are prevalent, in our patient clinical and laboratory findings revealed a diffuse large B-cell lymphoma, and (3) that the present case is an additional one confirming the poor outcome of patients with simultaneous occurrence of these two clinical entities.


Bayesian species identification under the multispecies coalescent provides significant improvements to DNA barcoding analyses.
DNA barcoding methods use a single locus (usually the mitochondrial COI gene) to assign unidentified specimens to known species in a library based on a genetic distance threshold that distinguishes between-species divergence from within-species diversity. Recently developed species delimitation methods based on the multispecies coalescent (MSC) model offer an alternative approach to individual assignment using either single-locus or multiloci sequence data. Here, we use simulations to demonstrate three features of an MSC method implemented in the program bpp. First, we show that with one locus, MSC can accurately assign individuals to species without the need for arbitrarily determined distance thresholds (as required for barcoding methods). We provide an example in which no single threshold or barcoding gap exists that can be used to assign all specimens without incurring high error rates. Second, we show that bpp can identify cryptic species that may be misidentified as a single species within the library, potentially improving the accuracy of barcoding libraries. Third, we show that taxon rarity does not present any particular problems for species assignments using bpp and that accurate assignments can be achieved even when only one or a few loci are available. Thus, concerns that have been raised that MSC methods may have problems analysing rare taxa (singletons) are unfounded. Currently, barcoding methods enjoy a huge computational advantage over MSC methods and may be the only approach feasible for massively large data sets, but MSC methods may offer a more stringent test for species that are tentatively assigned by barcoding.


iPS Cells-The Triumphs and Tribulations.
The year 2006 will be remembered monumentally in science, particularly in the stem cell biology field, for the first instance of generation of induced pluripotent stem cells (iPSCs) from mouse embryonic/adult fibroblasts being reported by Takahashi and Yamanaka. A year later, human iPSCs (hiPSCs) were generated from adult human skin fibroblasts by using quartet of genes, Oct4, Sox2, Klf4, and c-Myc. This revolutionary technology won Yamanaka Nobel Prize in Physiology and Medicine in 2012. Like human embryonic stem cells (hESCs), iPSCs are pluripotent and have the capability for self-renewal. Moreover, complications of immune rejection for therapeutic applications would be greatly eliminated by generating iPSCs from individual patients. This has enabled their use for drug screening/discovery and disease modelling in vitro; and for immunotherapy and regenerative cellular therapies in vivo, paving paths for new therapeutics. Although this breakthrough technology has a huge potential, generation of these unusual cells is still slow, ineffectual, fraught with pitfalls, and unsafe for human use. In this review, I describe how iPSCs are being triumphantly used to lay foundation for a fully functional discipline of regenerative dentistry and medicine, alongside discussing the challenges of translating therapies into clinics. I also discuss their future implications in regenerative dentistry field.


Cappariloside A shows antiviral and better anti-inflammatory effects against influenza virus via regulating host IFN signaling, in vitro and vivo.
This study aimed to evaluate the efficacy and mechanisms of Cappariloside A, a chemically synthesized compound, against virus and inflammation induced by influenza virus. The inhibitory activity of Cappariloside A against influenza virus was determined by plaque assay and cytopathic effect inhibition assay. Quantitative real-time PCR, enzyme-linked immunosorbent assay and Bio-Plex methods were used to quantify cytokine and chemokine expression profiles. Effects of Cappariloside A were also evaluated in a mouse model of influenza virus infection. We successfully synthesized Cappariloside A, which could inhibit replication of a variety of viruses, including influenza viruses H1N1 and H3N2, PIV3 and ADV in vitro. Cappariloside A could also inhibit progeny virus replication at concentrations of 2 and 1 mg/mL. Simultaneously, it significantly reduced the expressions of IL-6, IP-10, MIG and RANTES/CCL-5 stimulated by A/PR/8/34 (H1N1) at a range of doses, even 0.5 mg/mL. Similar anti-inflammatory activity was detected in cells induced by avian influenza virus H9N2 or lipopolysaccharide. In addition, Cappariloside A clearly inhibited inflammatory response induced by mouse lung-adapted influenza strain PR8/H1N1. Furthermore, Cappariloside A strongly inhibited phosphorylated STAT1 levels and IFN-β and IL-29 expressions induced by PR8/H1N1. Cappariloside A also inhibited IP-10 and CCL-5/RANTES expressions induced by exogenous human recombinant IFN-β. Cappariloside A not only shows broad-spectrum antiviral efficacy, but more effectively impairs the upregulations of pro-inflammatory factors in host cells induced by influenza virus. The potential antiviral mechanism of Cappariloside A is through inhibiting the activation of the host IFN signaling pathway.


A microNewton thrust stand for average thrust measurement of pulsed microthruster.
A torsional thrust stand has been developed for the study of the average thrust for microNewton pulsed thrusters. The main body of the thrust stand mainly consists of a torsional balance, a pair of flexural pivots, a capacitive displacement sensor, a calibration assembly, and an eddy current damper. The behavior of the stand was thoroughly studied. The principle of thrust measurement was analyzed. The average thrust is determined as a function of the average equilibrium angle displacement of the balance and the spring stiffness. The thrust stand has a load capacity up to 10 kg, and it can theoretically measure the force up to 609.6 μN with a resolution of 24.4 nN. The static calibrations were performed based on the calibration assembly composed of the multiturn coil and the permanent magnet. The calibration results demonstrated good repeatability (less than 0.68% FSO) and good linearity (less than 0.88% FSO). The assembly of the multiturn coil and the permanent magnet was also used as an exciter to simulate the microthruster to further research the performance of the thrust stand. Three sets of force pulses at 17, 33.5, and 55 Hz with the same amplitude and pulse width were tested. The repeatability error at each frequency was 7.04%, 1.78%, and 5.08%, respectively.


Higher pain level and lower functional capacity are associated with the number of altered kinematics in women with patellofemoral pain.
This study investigated whether women with patellofemoral pain (PFP) present kinematic alterations in proximal, local, and distal factors simultaneously, and determined the association between the number of kinematic alterations, pain level, and functional status. A three-dimensional motion analysis system was used to analyze the peak hip adduction, peak knee flexion, and peak rearfoot eversion, addressing the proximal, local, and distal factors, respectively, in fifty women. Functional status and pain level were assessed using the anterior knee pain scale (AKPS) and a visual analogic scale. Receiver operating characteristic curves were calculated to identify participants with and without kinematic alterations and the number of them was obtained for each participant. Associations between the number of kinematic alterations, pain level, and AKPS score were determined by the Pearson correlation. Results showed that 52% of women with PFP presented at least two kinematic alterations of which 24% were local/proximal, 16% local/distal, and 12% proximal/distal. Three kinematic alterations were found in 48% of the women with PFP. A strong positive correlation was found between the number of kinematic alterations and pain (r=0.78; p<0.001). A strong negative correlation was found between the number of altered kinematics and functional status (r=-0.79; p<0.001). Findings revealed that women with PFP presented at least two kinematic alterations and a higher number of kinematic alterations was associated with higher pain levels and lower functional status. Clinicians should carefully assess movement pattern of women with PFP as it could indicate a more severe condition, which is associated with a poor prognosis.


Improving professional competence--the way ahead?
Globally, there has been considerable interest from the public, medical profession, and governments in ensuring that doctors are fit for practice. Appropriate accountability for the profession has become an important contemporary issue. With doubts emerging on the effectiveness of professionally led regulation, a variety of different mechanisms have been devised to ensure that patients receive appropriate and good quality care. This paper reviews regulation of the medical profession and indicates the way in which doctors in the UK are held accountable for their practice.


[Trans-sternal organ-sparing interventions in the surgical treatment of bilateral bullous diseases of the lungs].
Generalization of an experience with using the transsternal access for the simultaneous treatment of the bilateral bullous disease of the lungs in 14 patients is presented. Under analysis were the nearest and long-term results (up to 18 months). Technical aspects of the surgery of bullous disease and its bilateral form in particular were considered. Postoperative complications were hemorrhage and paresis of the right diaphragm cupola. There were no lethal outcomes. An experience of other surgeons in this field is analyzed.


Starvation and nutrient resuscitation of Klebsiella pneumoniae isolated from oil well waters.
Klebsiella pneumoniae isolated from oil well waters reduced in size in response to nutrient starvation. The cells remained viable during starvation and later were able to grow rapidly when stimulated by nutrients. The heterotrophic potential, culture absorbance and extracellular polysaccharide production decreased during cell starvation whereas an initial increase in colony-forming units was observed on agar plates. Transmission electron microscopy (TEM) after 24 d revealed that the cells had changed to small rods or cocci between 0.5 by 0.25 micron and 0.87 by 0.55 micron. When transferred to half-strength brain heart infusion medium, TEM showed cell division and rod-shaped cells after 45 min and full resuscitation within 4 h. Cell response was much slower in sodium citrate medium and resuscitation took 8 h.


Molecular Mechanism of Dopamine Transport by Human Dopamine Transporter.
Dopamine transporters (DATs) control neurotransmitter dopamine (DA) homeostasis by reuptake of excess DA, assisted by sodium and chloride ions. The recent resolution of DAT structure (dDAT) from Drosophila permits us for the first time to directly view the sequence of events involved in DA reuptake in human DAT (hDAT) using homology modeling and full-atomic microseconds accelerated simulations. Major observations are spontaneous closure of extracellular gates prompted by DA binding; stabilization of a holo-occluded intermediate; disruption of N82-N353 hydrogen bond and exposure to intracellular (IC) water triggered by Na2 dislocation; redistribution of a network of salt bridges at the IC surface in the inward-facing state; concerted tilting of IC-exposed helices to enable the release of Na(+) and Cl(-) ions; and DA release after protonation of D79. The observed time-resolved interactions confirm the conserved dynamics of LeuT-fold family, while providing insights into the mechanistic role of specific residues in hDAT.


Passive auditory stimulation improves vision in hemianopia.
Techniques employed in rehabilitation of visual field disorders such as hemianopia are usually based on either visual or audio-visual stimulation and patients have to perform a training task. Here we present results from a completely different, novel approach that was based on passive unimodal auditory stimulation. Ten patients with either left or right-sided pure hemianopia (without neglect) received one hour of unilateral passive auditory stimulation on either their anopic or their intact side by application of repetitive trains of sound pulses emitted simultaneously via two loudspeakers. Immediately before and after passive auditory stimulation as well as after a period of recovery, patients completed a simple visual task requiring detection of light flashes presented along the horizontal plane in total darkness. The results showed that one-time passive auditory stimulation on the side of the blind, but not of the intact, hemifield of patients with hemianopia induced an improvement in visual detections by almost 100% within 30 min after passive auditory stimulation. This enhancement in performance was reversible and was reduced to baseline 1.5 h later. A non-significant trend of a shift of the visual field border toward the blind hemifield was obtained after passive auditory stimulation. These results are compatible with the view that passive auditory stimulation elicited some activation of the residual visual pathways, which are known to be multisensory and may also be sensitive to unimodal auditory stimuli as were used here. DRKS00003577.


Is luteinizing hormone needed for optimal ovulation induction?
The role of luteinizing hormone in the natural menstrual cycle is not disputed. There are, however, a variety of opinions regarding the potential role of exogenous luteinizing hormone in ovulation induction and whether it is actually needed. The recent introduction into clinical practice of recombinant gonadotropins has been paralleled by recent advances in the knowledge of the endocrine and paracrine mechanisms that regulate human folliculogenesis. On this basis, this review analyses whether or not all patients need luteinizing hormone for follicular growth stimulation. In addition, new opportunities for improved treatment are considered as a result of the availability of recombinant human luteinizing hormone both in patients with ovulatory disorders and those undergoing multiple follicular development for assisted reproduction.


Human interleukin 6 is a direct promoter of maturation of megakaryocytes in vitro.
The response of cells of the murine megakaryocytic lineage to human interleukin 6 (IL-6) was assessed in serum-depleted cultures using a variety of biological assays. IL-6 alone had no influence on megakaryocytic colony formation but augmented the numbers of these colonies induced by the multipotent colony-stimulating factor interleukin 3. However, in liquid marrow cultures, IL-6 alone promoted marked increments in megakaryocytic size and the activity of acetyl-cholinesterase, a marker enzyme of the lineage. Moreover, IL-6 induced a significant shift toward higher ploidy classes when megakaryocytic DNA was quantitated by flow cytometry. To determine whether the influence of IL-6 on megakaryocytic maturation was direct, the factor was added to cultures of single megakaryocytes isolated from megakaryocytic colonies. Fifty-four percent of these cells increased in size compared with 19% of those grown without IL-6. The data show that human IL-6 is a potent direct-acting growth factor for murine megakaryocytes with activity promoting maturation of that lineage.


Video calls for dispatcher-assisted cardiopulmonary resuscitation can improve the confidence of lay rescuers--surveys after simulated cardiac arrest.
Many mobile phones allow two-way video communication, which permits callers to hear and see each other. If used during medical emergencies, bystanders can receive supervision and guidance from medical staff based on visual information. We investigated whether video calls from mobile phones could improve the confidence of lay rescuers. High school students (n = 180) were randomly assigned in groups of three to communicate via video calls or via ordinary mobile phone calls. They received realtime guidance from experienced nurse dispatchers at an emergency medical dispatch centre during 10-min scenarios of simulated cardiac arrest. Each student answered a questionnaire to assess understanding, confidence and usefulness of the technology. The mean age was 17.3 years in the video group and 17.9 years in the audio group. There were 27% male participants in the video group and 34% male participants in the audio group. Seventy-three percent of the students in the video group and 71% in the audio group reported previous cardiopulmonary resuscitation training. Rescuers who had not used video phones had a greater tendency to comment on immature video call technology, while some who had used video phones complained about poor sound quality during video calls. The majority of rescuers in both groups believed that video calls were superior to audio calls during medical emergencies, and this proportion was significantly higher in the video group (P = 0.0002). We found that visual contact and supervision through video calls improved rescuers' confidence in stressful emergencies.


Untargeted proteomics reveals upregulation of stress response pathways during CHO-based monoclonal antibody manufacturing process leading to disulfide bond reduction.
Monoclonal antibody (mAb) interchain disulfide bond reduction can cause a loss of function and negatively impact the therapeutic's efficacy and safety. Disulfide bond reduction has been observed at various stages during the manufacturing process, including processing of the harvested material. The factors and mechanisms driving this phenomenon are not fully understood. In this study, we examined the host cell proteome as a potential factor affecting the susceptibility of a mAb to disulfide bond reduction in the harvested cell culture fluid (HCCF). We used untargeted liquid-chromatography-mass spectrometry-based proteomics experiments in conjunction with a semi-automated protein identification workflow to systematically compare Chinese hamster ovary (CHO) cell protein abundances between bioreactor conditions that result in reduction-susceptible and reduction-free HCCF. Although the growth profiles and antibody titers of these two bioreactor conditions were indistinguishable, we observed broad differences in host cell protein (HCP) expression. We found significant differences in the abundance of glycolytic enzymes, key protein reductases, and antioxidant defense enzymes. Multivariate analysis of the proteomics data determined that upregulation of stress-inducible endoplasmic reticulum (ER) and other chaperone proteins is a discriminatory characteristic of reduction-susceptible HCP profiles. Overall, these results suggest that stress response pathways activated during bioreactor culture increase the reduction-susceptibility of HCCF. Consequently, these pathways could be valuable targets for optimizing culture conditions to improve protein quality.


A case of primordial odontogenic tumor: A new entity in the latest WHO classification (2017).
Primordial odontogenic tumor (POT) is a rare lesion in the jaw which has been included as a new entity of benign mixed epithelial and mesenchymal odontogenic tumour in the latest World Health Organization (WHO) classification (2017). Only seven cases have been reported. It typically occurs in the posterior mandible. We report an additional case of POT in the maxilla of an 8-year-old girl presenting with an asymptomatic buccal enlargement. A well-defined, unilocular, radiolucent lesion was observed radiographically. Histologically, the tumor was mostly composed of loose fibrous connective tissue resembling dental papilla and a single layer of columnar epithelium covering the periphery of the tumor. In part, cords or nests of epithelium were present in the mesenchyme close to the periphery. Nestin, a marker of odontogenic ectomesenchyme, was positive in the mesenchymal tumor cells. We finally diagnosed the lesion as POT considering the possibility of other odontogenic tumors like ameloblastic fibroma or developing odontoma as a differential diagnosis. The patient shows no recurrence after 16 months. This case is the first report from Japan using this novel diagnosis POT after it was recognized and defined in the latest WHO classification.


Correlation study of two routine bacteriology systems with previously characterised strains.
The objective of this study was to evaluate the performance of the VITEK 2 and Advanced Expert System (bioMérieux) for antimicrobial testing of previously characterised Gram-positive and Gram-negative bacterial strains. These strains obtained from bioMérieux, Mrcy Le Toille, France, were well characterized with regard to the existing resistance mechanisms and the Minimal Inhibitory Concentration (MIC) values were determined by agar dilution. VITEK 2 was also compared with the Sceptor system (Becton Dickinson) routinely used in our laboratory. The results obtained were equally good for VITEK 2 and Sceptor with a rate of agreement between the two systems of 91.4% and 88.2% respectively. When the results were evaluated in relation to the different antibiotic concentrations, the agreement was 94% for VITEK 2 and 62% for Sceptor. The resistance mechanisms associated with each resistance pattern were determined by the Advanced Expert System (AES) in 79.6% of strains. The VITEK 2 provided, in 3-4 hours, an acceptable level of accuracy in testing antimicrobial sensitivity in Gram-positive and Gram-negative strains with diverse mechanisms of resistance found in clinical situations.


Electromagnetic instability in plasmas heated by a laser field.
Electromagnetic instability is investigated in homogeneous plasmas heated by a laser wave in the range α=v_{0}^{2}/v_{t}^{2}≤2, where v_{0} is the electron quiver velocity and v_{t} is the thermal velocity. The anisotropic electron distribution function that drives unstable quasistatic electromagnetic modes is calculated numerically with the Vlasov-Landau equation in the high ion charge number approximation. A dispersion relation of electromagnetic waves which accounts for further nonlinear terms on v_{0}^{2} from previous results is derived. In typical simulation with ion charge number Z=13, a temperature T=5keV, a density n=9.8×10^{20}cm^{-3}, and a laser wavelength λ_{laser}=1.06μm, growth rates larger than 10^{12}s^{-1} in the quasicollisionless wave-number range were found for α≥1. In the same physical conditions and in the mildly collisional range a growth rate about 10^{11}s^{-1} was also obtained. The extent of the growth wave-number region increases significantly with increasing α.


Community outreach for patients who have difficulties in maintaining contact with mental health services: longitudinal retrospective study of the Japanese outreach model project.
Japan still has the highest ratio of beds devoted to psychiatric patients in the world. In 2011, in order to reduce re-hospitalization of patients who became disconnected from regular contact with outpatient medical services, the Japanese Ministry established the Japanese Outreach Model Project (JOMP). In this study, we will explicate the JOMP project protocol and investigate the rate and length of hospital admission, impairments of social function and problematic behavior at the follow-up period (6- and 12-month) and time of services provided by JOMP. This longitudinal retrospective study used survey data collected from 32 outreach teams of 21 prefectures in Japan during September 2011 to July 2013. The outcome variables were assessed at baseline, 6-month and 12-month as to whether or not participants had been admitted to the hospital. Data from 162 participants with mental illness who had difficulties in maintaining contact with mental health services were analyzed. Repeated measures analysis of variance provided a significant effect of the intervention over time. The rate of hospital admission of JOMP participants was 24.1% at 6-months and 27.2% at the 12-month follow-up. The average length of hospital-stay at baseline and 12-months was 38.7 days (SD 84.7). Compared with the baseline, the average score of the Global Assessment Functioning and the Social Behavioral Schedule were significantly improved after the 6-month and 12-month follow-up. The activity log showed that among the most often delivered JOMP services were to "prevent exacerbation of somatic symptoms" and "care for families". These results suggest that JOMP has a strong potential to both reduce readmission rates and the length of hospital stay compared with the Japanese regular outpatient care by public insurance, and improve social function and problematic behavior. The JOMP teams provided long-term support for families. As of April 2014 JOMP was included in the National Health Insurance program in a limited way therefore an evaluation of JOMP team fidelity on readmissions must be examined.


Characterisation of atypical Aeromonas salmonicida infection in Arctic charr Salvelinus alpinus and European grayling Thymallus thymallus.
Cultured stocks of Arctic charr Salvelinus alpinus and European grayling Thymallus thymallus are vulnerable to infection by achromogenic atypical Aeromonas salmonicida (AAS). In Finland, natural stocks of both fish species have to be supported by restocking, and AAS infection poses a threat to successful restocking because no preventive means are available. In this study, we analysed AAS isolates from Arctic charr and European grayling and from other sources genetically, and characterised the signs and pathology of AAS infection in Arctic charr and European grayling both under farming conditions and after experimental challenge. AAS outbreaks were recorded in 1 fish farm over an 8 yr period. Among various salmonid fishes under farming conditions, only Arctic charr and European grayling were susceptible to AAS infection. The disease caused by AAS could be reproduced in both species using the same AAS strain in an experimental challenge. The course of the disease and pathology of natural and experimental AAS infection differed between the 2 species, even though only 1 strain was used for challenge. Isolates of AAS from Arctic charr and European grayling were genetically identical within a single river water basin. However, genetic heterogeneity was observed among the isolates from different water basins. In both species, AAS caused systemic infection. The results suggest that the same AAS strain could be used to develop a vaccine to protect both Arctic charr and European grayling from AAS infection.


Sediment: curse or blessing for Tonle Sap Lake?
It has been claimed that Tonle Sap Lake is rapidly filling with sediment as a result of increasing sediment yields from the catchment. Infilling of the lake basin would have serious implications for the magnitude of flooding in central Cambodia and the Mekong Delta region and threaten the lake's unique ecosystem. In this article, we synthesize the results of radiocarbon dating of sediment cores and hydrodynamic modeling results to provide an empirically based assessment of this issue. We find that current sedimentation rates within the lake basin proper are low and have been for several millennia. However, sedimentation at the lake margin and in its floodplain is relatively high, which presents a range of issues for riparian communities.


Distal promoter regions are responsible for differential regulation of human orosomucoid-1 and -2 gene expression and acute phase responses.
Human orosomucoid (ORM) is a major acute-phase plasma protein, encoded by 2 highly homologous genes, ORM1 and ORM2. Human ORM induction is assumed to be regulated by each proximal promoter region, where putative glucocorticoid responsive elements and CCAAT/enhancer binding protein (C/EBP)β binding sites are located. However, the details of the differential regulation of these genes remain unknown. To explore this, we assessed the role of the distal promoter region of each ORM in HeLa cells. Luciferase-reporter activities of full constructs, containing approximately 1.1 kbp (FULL), and those of deletion constructs, containing up to 188 bp region (DEL) upstream of the transcription start sites of ORM1 and ORM2 were compared under both basal and inducer-treated conditions. For ORM1 and ORM2 DEL constructs, significantly increased activities after dexamethasone (DEX) treatments (alone and combined with interleukin (IL)-1β) were observed. Significantly higher FULL construct activities than DEL construct activities were observed for ORM1 after IL-1β treatment, while those for ORM2 were significantly lower at basal level and after DEX treatments. Upon C/EBPβ overexpression, FULL construct activities were significantly higher than those of DEL constructs at basal level and after IL-1β treatment for ORM1, and at basal level and after inducer-treatments for ORM2. Higher transcription-induction activity in the distal promoter region was evident for ORM1 in the absence of C/EBPβ overexpression, and for ORM2 under C/EBPβ overexpression conditions. These findings suggest that the ORM distal promoter region differentially regulates expression of ORM genes at basal level and in acute phase responses.


One-month repeatability of emotional responses to alcohol.
Thirty-four subjects in the Colorado Alcohol Research on Twins and Adoptees (CARTA) were brought back between 30 to 60 days after their initial testing to be retested on all the CARTA procedures. As before, subjects were given a dose of ethanol (0.8 g/kg) calculated to bring their blood alcohol concentration (BAC) to near 0.10 g/dl. Additional doses were given at the end of each of the next 2 hr to maintain their BAC near peak for approximately 3 hr. During both testings, subjects' self-reports of their emotional responses and perceived intoxication following alcohol dosing were only minimally correlated with their alcohol metabolism parameters and reported average level of alcohol use. Repeatabilities (test-retest correlations) for subjects' self-reports of positive affect and of intoxication following alcohol dosing were consistently high, in contrast to earlier reports of minimal repeatabilities for alcohol metabolism and responses to alcohol on physiological, motor coordination, reaction time, and perceptual speed measures. Tester ratings of the subjects' levels of intoxication were also moderately stable between the two testings.


Bioevaluation of Ranatuerin-2Pb from the Frog Skin Secretion of Rana pipiens and its Truncated Analogues.
Antimicrobial peptides (AMPs) are considered as a promising agent to overcome the drug-resistance of bacteria. Large numbers of AMPs have been identified from the skin secretion of Rana pipiens, including brevinins, ranatuerins, temporins and esculentins. In this study, the cDNA precursor of a broad-spectrum antimicrobial peptide, ranatuerin-2Pb, was cloned and identified. Additionally, two truncated analogues, RPa and RPb, were synthesised to investigate the structure-activity relationship of ranatuerin-2Pb. RPa lost antimicrobial activity against Candida albicans, MRSA, Enterococcus faecalis and Pseudomonas aeruginosa, while RPb retained its broad-spectrum antimicrobial activity. Additionally, ranatuerin-2Pb, RPa and RPb demonstrated inhibition and eradication effects against Staphylococcusaureus biofilm. RPb showed a rapid bacterial killing manner via membrane permeabilization without damaging the cell membrane of erythrocytes. Moreover, RPb decreased the mortality of S. aureus infected Galleria mellonella larvae. Collectively, our results suggested that RPb may pave a novel way for natural antimicrobial drug design.


Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary Cancer Screening.
For the determination of creatine kinase (CK)-MB, the immunoinhibition method is utilized most commonly. However, the estimated CK-MB activity may be influenced by the presence of CK isoenzymes in some conditions like cancer. Thus, a CK-MB-to-total-CK ratio more than 1.0 could be found in such a situation. The study aimed to explore the relationship of cancer to high CK-MB-to-total-CK ratio. From January 2011 to December 2014, laboratory data on all CK-MB and total CK test requests were extracted at Far Eastern Memorial Hospital (88,415 requests). Patients with a CK-MB-to-total-CK ratio more than 1.0 were registered in this study. Clinical data including tumor location, tumor TNM stage and metastatic status were also collected. A total of 846 patients were identified with a CK-MB-to-total-CK ratio more than 1.0. Of these, 339 (40.1%) were diagnosed with malignancies. The mean CK-MB-to-total-CK ratio was significantly higher in malignancy than in non-malignancy (1.35±0.28 vs 1.25±0.23, p<0.001) groups. The most frequent malignancy with a CK-MB-to-total-CK ratio more than 1.0 was colorectal cancer (1.42±0.28, 16.5%, n=56), followed by lung cancer (1.38±0.24, 15.9%, n=54) and hepatocellular carcinoma (14.5%, n=49). Higher CK-MB-to-total-CK ratios in hematological malignancies (1.44±0.41)were also noted. Additionally, the CK-MB-to-total-CK ratio was markedly higher in advanced stage malignancy than in early stage (1.37±0.26 vs. 1.29±0.31, p=0.014) and significantly higher in liver metastasis than in non-liver metastasis (1.48±0.30 vs. 1.30±0.21, p<0.001). The CK-MB-to-total-CK ratio is an easily available indicator and could be clinically utilized as a primary screening tool for cancer. Higher ratio of CK-MB-to-total-CK was specifically associated with certain malignancies, like colorectal cancer, lung cancer and hepatocellular carcinoma, as well as some cancer-associated status factors such as advanced stage and liver metastasis.


Antifogging and antireflection coatings fabricated by integrating solid and mesoporous silica nanoparticles without any post-treatments.
Antifogging and -reflection coatings were fabricated on glass and poly(methyl methacrylate) (PMMA) substrates by integrating solid silica nanoparticles of 25 nm (S-25) and mesoporous silica nanoparticles (MSNs) of 45 nm via layer-by-layer assembly without any post-treatments. Superhydrophilicity and a maximum transmittance of 98.5% in the visible spectral range was achieved for the (PDDA/S-25)4/(PDDA/MSNs) coating deposited on slide glass. The maximum transmittance even reached as high as 99.3% in the visible spectral range by applying a coating of (PDDA/S-25)8/(PDDA/MSNs) on PMMA substrate. Scanning and transmission electron microscopy were used to observe the morphology and structure of nanoparticles and coating surfaces. Optical properties were characterized by UV-visible spectrophotometer. Surface wettability was studied by a contact angle/interface system. The influence of mesopores was also discussed on the transmission and wetting properties of coatings. The high porosity of mesoporous nanoparticles and loose stacking of solid and mesoporous nanoparticles are considered to significantly contribute to the enhancements of both light transmission and hydrophilicity.


The role of single and mixed biofilms in Clostridioides difficile infection and strategies for prevention and inhibition.
Clostridioides difficile infection (CDI) is a serious disease with a high recurrence rate. The single and mixed biofilms formed by C. difficile in the gut contribute to the formation of recurrent CDI (rCDI). In parallel, other gut microbes influence the formation and development of C. difficile biofilms, also known as symbiotic biofilms. Interactions between members within the symbiotic biofilm are associated with the worsening or alleviation of CDI. These interactions include effects on C. difficile adhesion and chemotaxis, modulation of LuxS/AI-2 quorum sensing (QS) system activity, promotion of cross-feeding by microbial metabolites, and regulation of intestinal bile acid and pyruvate levels. In the process of C. difficile biofilms control, inhibition of C. difficile initial biofilm formation and killing of C. difficile vegetative cells and spores are the main targets of action. The role of symbiotic biofilms in CDI suggested that targeting interventions of C. difficile-promoting gut microbes could indirectly inhibit the formation of C. difficile mixed biofilms and improved the ultimate therapeutic effect. In summary, this review outlines the mechanisms of C. difficile biofilm formation and summarises the treatment strategies for such single and mixed biofilms, aiming to provide new ideas for the prevention and treatment of CDI.


Atypical haemolytic uraemic syndrome: a case report of a rare cause of reversible cardiomyopathy.
Atypical haemolytic uraemic syndrome (aHUS) is a life-threatening, genetic disease of complement-mediated thrombotic microangiopathy that typically presents as anaemia, thrombocytopenia, and renal failure. Cardiomyopathy is seen in up to 10% of aHUS cases, but the aetiology is not well-understood. A 63-year-old man recently was diagnosed with a thrombotic microangiopathy most consistent with aHUS by renal biopsy after presentation with acute renal failure requiring haemodialysis. He was started on therapy with complement inhibitor, eculizumab. Six weeks after diagnosis, he presented with progressive dyspnoea on exertion and chest pain. An echocardiogram demonstrated an acute drop in left ventricular ejection fraction to 20-25% with global hypokinesis. Left heart catheterization showed moderate, non-obstructive coronary artery disease. Cardiac magnetic resonance imaging demonstrated diffuse myocardial oedema. Endomyocardial biopsy revealed an arteriole with obliterative changes and a few possible fragmented red blood cells suggestive of thrombotic microangiopathy. There was no biopsy evidence of immune complex deposition or myocarditis. He was treated for heart failure and was maintained on eculizumab. On repeat echocardiogram 3 months later, the patient had complete recovery of his ejection fraction (60-65%). In this report, we describe complete recovery of aHUS-associated heart failure with eculizumab therapy and demonstrate for the first time that the aetiology of aHUS-associated heart failure is likely an acute thrombotic microangiopathy involving small intramyocardial arterioles, as demonstrated by cardiac biopsy.


Metritis, valvular endocarditis, and septicemia by Actinobacillus equuli in a gilt in the United States.
A 1-year-old pregnant Yorkshire gilt was found dead with no previous clinical signs. Gross findings included metritis, splenomegaly, and valvular endocarditis. Bacterial endocarditis (in the mitral and tricuspid valves) and metritis with dissemination to multiple organs was diagnosed by using histologic examination. Gram-negative coccobacillary organisms present in the valvular lesions were characterized as Actinobacillus equuli by using polymerase chain reaction examination on formalin-fixed, paraffin-embedded tissues (FFPE). A. equuli is rarely reported as a cause of septicemia in pigs in Europe. A. equuli in pigs in the United States has been reported only twice and not, to our knowledge, in the last 30 years. This is the first time that molecular techniques have been used to characterize this organism in FFPE porcine tissues.


Multi-color fluorescent reporter dengue viruses with improved stability for analysis of a multi-virus infection.
Reporter virus is a versatile tool to visualize and to analyze virus infections. However, for flaviviruses, it is difficult to maintain the inserted reporter genes on the viral genome, limiting its use in several studies that require homogeneous virus particles and several rounds of virus replication. Here, we showed that flanking inserted GFP genes on both sides with ribosome-skipping 2A sequences improved the stability and the consistency of their fluorescent signals for dengue-virus-serotype 2 (DENV2) reporter viruses. The reporter viruses can infect known susceptible mammalian cell lines and primary CD14+ human monocytes. This design can accommodate several fluorescent protein genes, enabling the generation of multi-color DENV2-16681 reporter viruses with comparable replication capabilities, as demonstrated by their abilities to maintain their fluorescent intensities during co-infections and to exclude superinfections regardless of the fluorescent tags. The reported design of multi-color DENV2 should be useful for high-throughput analyses, single-cell analysis, and characterizations of interference and superinfection in animal models.


A Phase II Randomized Trial to Explore the Potential for Pharmacokinetic Drug-Drug Interactions with Stiripentol or Valproate when Combined with Cannabidiol in Patients with Epilepsy.
In recent randomized, placebo-controlled, phase III trials, highly purified cannabidiol demonstrated efficacy with an acceptable safety profile in patients with Lennox-Gastaut syndrome or Dravet syndrome. It is anticipated that antiepileptic drugs such as stiripentol and valproate will be administered concomitantly with cannabidiol. This trial evaluated the effect of cannabidiol on steady-state pharmacokinetics of stiripentol or valproate in patients with epilepsy, and the safety and tolerability of cannabidiol. This phase II, two-arm, parallel-group, double-blind, randomized, placebo-controlled trial recruited male and female patients with epilepsy aged 16-55 years. Patients receiving a stable dose of stiripentol or valproate were randomized 4:1 to receive concomitant double-blind cannabidiol or placebo. Patients received plant-derived, highly purified cannabidiol medicine (Epidiolex® in the USA; Epidyolex® in the EU; 100 mg/mL oral solution) at a dose of 20 mg/kg/day from day 12 to 26, following a 10-day dose-escalation period. Blood samples for pharmacokinetic evaluations were collected on days 1 and 26 before stiripentol/valproate dosing and up to 12 h postdose. Treatment-emergent adverse events (AEs) were recorded. In total, 35 patients were recruited to the stiripentol arm (n = 14) or the valproate arm (n = 21). Both the safety and the pharmacokinetic populations of the stiripentol arm comprised 14 patients (2 placebo; 12 cannabidiol). The safety population of the valproate arm comprised 20 patients (4 placebo; 16 cannabidiol; one withdrew before receiving treatment); the pharmacokinetic population comprised 15 patients (3 placebo; 12 cannabidiol). Concomitant cannabidiol led to a small increase in stiripentol exposure (17% increase in maximum observed plasma concentration [Cmax]; 30% increase in area under the concentration-time curve over the dosing interval [AUCtau]). Concomitant cannabidiol also had little effect on valproate exposure (13% decrease in Cmax; 17% decrease in AUCtau) or its metabolite, 2-propyl-4-pentenoic acid (4-ene-VPA) (23% decrease in Cmax; 30% decrease in AUCtau). All changes in exposure are expressed as the dose-normalized geometric mean (CV%) day 26 to day 1 ratio. The most common AE was diarrhea; most AEs were mild. Two patients discontinued cannabidiol because of serious AEs (rash [n = 1] in the stiripentol arm; hypertransaminasemia [n = 1] in the valproate arm). A separate in vitro study investigated the bidirectional effect of cannabidiol, or its metabolite 7-carboxy-cannabidiol, on valproate plasma protein binding; no change in plasma protein binding was observed for either compound. The clinical relevance of the increase in stiripentol exposure is unknown; patients receiving cannabidiol and stiripentol concomitantly should be monitored for adverse reactions as individual patient responses may vary. Coadministration of cannabidiol did not affect the pharmacokinetics of valproate or its metabolite, 4-ene-VPA, in adult patients with epilepsy. Safety results were consistent with the known safety profile of cannabidiol at a dose of 20 mg/kg/day. Clinicaltrials.gov: NCT02607891.


Novel multi-layer APPPA microcapsules for oral delivery: preparation condition, stability and permeability.
Oral therapy utilizing cell microencapsulation has shown promise in the treatment of many diseases. Current obtainable microcapsule membranes, however, show inadequate stability in the gastrointestinal (GI) environment, thus restricting the general application of live cells for oral therapy. To overcome this limitation, we have previously developed a novel multilayer alginate/poly-L-lysine/pectin/poly-L-lysine/alginate microcapsule (APPPA) with demonstrated improvement on membrane stability over the frequently reported alginate/poly-L-lysine/alginate (APA) microcapsules. In this study, we further examined the effects of preparation conditions on microcapsule formation, and assessed the membrane strength and GI stability. Results showed that increased membrane strength of the APPPA microcapsules was attained by using pectin with low degree of esterification as the mid-layer material, saline as the solvent for the preparation solutions and washing medium, and 0.1 M CaCl2 as the gelling solution for alginate cores. Resistance of this membrane to the simulated GI fluids was also investigated. Permeability of and release profiles from the APPPA microcapsules were found comparable to the APA microcapsules. These findings suggested that the multi-layer APPPA microcapsule formulation may have potential in oral delivery of proteins, live bacterial cells and other biomedical applications.


Acute effects of capacitive and resistive electric transfer (CRet) on the Achilles tendon.
This study aimed to investigate the acute effects of capacitive and resistive electric transfer (CRet) on Achilles tendon elongation during muscle contraction, as well as the circulation in the peritendinous region. Sixteen healthy men participated in this study. All 16 participants underwent 2 interventions: (1) CRet trial and (2) CRet without power (sham trial). Tendon elongation was measured four times. Using near-infrared spectroscopy, the blood circulation (volume of total-hemoglobin (Hb), oxygenated hemoglobin (oxy-Hb), and deoxygenated hemoglobin (deoxy-Hb)) was measured for 5 min before the intervention and for 30 min after the intervention. The differences between the measurements obtained before and after intervention were compared between the two interventions. The changes in tendon elongation and deoxy-Hb were not significantly different between the interventions. Total- and oxy-Hb were significantly increased in the CRet trial compared with the sham trial. In addition, the increases in total-Hb and oxy-Hb lasted for 30 min after the CRet intervention (CRet vs. sham: oxy-Hb: F = 8.063, p = 0.001, total-Hb: F = 4.564, p = 0.011). In conclusion, CRet significantly improved blood circulation in the peritendinous region.


Highly Efficient Real-Time TRPV1 Screening Methodology for Effective Drug Candidates.
Transient receptor potential vanilloid 1 (TRPV1) agonists that bind to the vanilloid pocket are being actively studied in the pharmaceutical industry to develop novel treatments for chronic pain and cancer. To discover synthetic vanilloids without the side effect of capsaicin, a time-consuming process of drug candidate selection is essential to a myriad of chemical compounds. Herein, we propose a novel approach to field-effect transistors for the fast and facile screening of lead vanilloid compounds for the development of TRPV1-targeting medications. The graphene field-effect transistor was fabricated with human TRPV1 receptor protein as the bioprobe, and various analyses (SEM, Raman, and FT-IR) were utilized to verify successful manufacture. Simulations of TRPV1 with capsaicin, olvanil, and arvanil were conducted using AutoDock Vina/PyMOL to confirm the binding affinity. The interaction of the ligands with TRPV1 was detected via the fabricated platform, and the collected responses corresponded to the simulation analysis.


Improving estimation of entropy production rate for run-and-tumble particle systems by high-order thermodynamic uncertainty relation.
Entropy production plays an important role in the regulation and stability of active matter systems, and its rate quantifies the nonequilibrium nature of these systems. However, entropy production is hard to experimentally estimate even in some simple active systems like molecular motors or bacteria, which may be modeled by the run-and-tumble particle (RTP), a representative model in the study of active matters. Here we resolve this problem for an asymmetric RTP in one dimension, first constructing a finite-time thermodynamic uncertainty relation (TUR) for a RTP, which works well in the short observation time regime for entropy production estimation. Nevertheless, when the activity dominates, i.e., the RTP is far from equilibrium, the lower bound for entropy production from TUR turns out to be trivial. We address this issue by introducing a recently proposed high-order thermodynamic uncertainty relation (HTUR), in which the cumulant generating function of current serves as a key ingredient. To exploit the HTUR, we adopt a method to analytically obtain the cumulant generating function of the current we study, with no need to explicitly know the time-dependent probability distribution. The HTUR is demonstrated to be able to estimate the steady state energy dissipation rate accurately because the cumulant generating function covers higher-order statistics of the current, including rare and large fluctuations besides its variance. Compared to the conventional TUR, the HTUR could give significantly improved estimation of energy dissipation, which can work well even in the far from equilibrium regime. We also provide a strategy based on the improved bound to estimate the entropy production from a moderate amount of trajectory data for experimental feasibility.


[Olanzapine long-acting post-injection syndrome: a case report and brief review].
The introduction of long-acting injectable atypical antipsychotics has ensured adherence to treatment in patients with low awareness of the disorder, with an acceptable rate of side effects. In the case of long acting olanzapine injection in particular, has particular relevance the existence of a special side-effect called post-injection syndrome. This rare side effect consisting in the presence of symptoms of olanzapine overdose after intramuscular administration of medication has led to restrictions on the use of the drug and the need for patient observation for three hours after each injection. We report a case of postinjection syndrome, to our knowledge, the first in Spain since the commercialization of Zypadhera. As in most cases described in the literature have symptoms of overdosage of olanzapine (dysarthria, sedation, fatigue, etc.) that are selflimiting without any therapeutic measure and are accompanied by supratherapeutic plasma levels of olanzapine.


Binding and degradation of [125I]human growth hormone in rat adipocytes.
Iodinated human GH [( 125I]hGH) binds to both specific and nonspecific sites on the surface of adipocytes isolated from the epididymal fat of normal rats. When adipocytes were incubated at 37 C with 1 nM [125I]hGH, specific binding increased for 30-60 min and thereafter remained approximately constant as long as the hormone was present in the medium. When cells that had bound [125I]hGH were removed from the incubation medium and reincubated in hormone-free medium at 37 C, half of the specifically bound 125I was released into the medium about every 30 min, and about half of the nonspecifically bound 125I was released in about 60 min. These rates were seen regardless of whether the time allowed for hormone binding was 15, 30, or 60 min. About 90% of the 125I released was soluble in 5% trichloroacetic acid and was in the form of iodotyrosine. The rate of 125I release from specific binding sites decreased by a factor of 4 when the temperature was lowered from 37 to 17 C. Replacement of some of the sodium chloride in the buffer with 25 mM ammonium chloride had little or no effect on the amount on 125I that bound to cells when [125I]hGH was present in the medium, but virtually completely blocked the release of 125I from cells transferred to hormone-free medium. Ammonium chloride also significantly reduced both the release of 125I from nonspecific binding sites and the amount of 125I recovered in trichloroacetic acid-soluble form. Cloroquine, leupeptin, or colchicine nearly doubled the specific binding of [125I]hGH after 180 min and markedly slowed the release of 125I when cells were transferred to hormone-free medium. All of these agents also significantly reduced the rate of release of 125I from nonspecific binding sites. Incubation of adipose tissue from hypophysectomized rats with ammonium chloride, leupeptin, or colchicine failed to alter the ability of GH to increase glucose oxidation, induce refractoriness, or promote lipolysis in the presence of theophylline. We conclude that GH binds virtually irreversibly to both specific and nonspecific sites on the adipocyte surface and is then internalized and degraded in the lysosomones. These events appear to be independent of the cellular processes that lead to expression to GH responses.


[Treatment of fronto-orbital malformations associated with craniostenosis].
From 1977 to 1982, 13 children affected by craniostenosis involving the supraorbital ridge were treated by surgery and subsequently followed up. Six cases of plagiocephaly, one of brachycephaly, three of Apert's syndrome, and three cases of Crouzon's disease were operated on, employing in seven cases classical lineal craniectomies, an in six other, craniotomies with advancement and remodelling. The results obtained are discussed in terms of functional and cosmetic improvement, the therapeutic criterion being in terms corresponding with the gravity of the malformation and the age at which the surgical operation was carried out.


DEVELOPMENT OF COORDINATION ABILITIES IN 6-10 YEARS OLD BOYS WITH POSTURAL DISORDERS.
The aim: To develop, substantiate and experimentally test the methodology for the development of coordination abilities in 6-10 years old boys with postural disorders during their physical education training sessions. Materials and methods: The experimental (EG) and the control groups (CG) were formed to organize the pedagogical experiment. The EG included 17 boys and the CG consisted of 19 boys. The EG was engaged in sports activities according the developed methodology and the CG followed the current school curricula on physical education. Results: The methodology for the development of coordination abilities in 6-10 years old boys with postural disorders in the process of their physical education has been developed. Its peculiarity lies in the accentuated influence on the vestibular, motor and visual analyzers with the help of a system of exercises aimed at controlling movements in space in static positions and during movement. Conclusions: The obtained results testify to the effectiveness of the developed methodology. The EG boys had significantly higher indicators of static balance and coordination abilities at body position change, as well as general coordination of movements (p ≤ 0.05) at the end of the academic year than those of the CG. In addition, the number of 6-10 years old boys with various postural disorders decreased by 7.4 % (from 26.8 % to 19.4 %).


Automatic interstitial photodynamic therapy planning via convex optimization.
Finding a high-quality treatment plan is an essential, yet difficult, stage of Photodynamic therapy (PDT) as it will determine the therapeutic efficacy in eradicating malignant tumors. A high-quality plan is patient-specific, and provides clinicians with the number of fiber-based spherical diffusers, their powers, and their interstitial locations to deliver the required light dose to destroy the tumor while minimizing the damage to surrounding healthy tissues. In this work, we propose a general convex light source power allocation algorithm that, given light source locations, guarantees optimality of the resulting solution in minimizing the over/under-dosage of volumes of interest. Furthermore, we provide an efficient framework for source selection with concomitant power reallocation to achieve treatment plans with a clinically feasible number of sources and comparable quality. We demonstrate our algorithms on virtual test cases that model glioblastoma multiforme tumors, and evaluate the performance of four different photosensitizers with different activation wavelengths and specific tissue uptake ratios. Results show an average reduction of the damage to organs-at-risk (OAR) by 29% to 31% with comparable runtime to existing power allocation techniques.


Genetic Alterations in Pendrin (SLC26A4) Gene in Adult Hypothyroid Patients.
Current study was aimed to screen the SLC26A4 gene in 127 nonautoimmune and noncongenital hypothyroid patients, who were under optimal iodine nutrition and devoid of any characteristics of Pendred syndrome from eastern part of Indian population. 8 single nucleotide variants/mutations were identified in heterozygous state in 20% patient population, which include 1 novel nonsynonymous (p.C18S), 1 novel intronic (g.942C>A), 3 known nonsynonymous (p.S23X, p.V239D, and p.I455F), and 3 known intronic (g.23034G>T, g.29641C>G, and g.33893T>C) variants. Only g.23034G>T was noted also in homozygous state in 2% patient population. However, Controls exhibited only the variations g.23034G>T and p.I455F. Therefore, present study reports for the first time that the observed novel variants in pendrin gene might be linked with autoimmune negative hypothyroidism, without any characteristics of Pendred syndrome and/or congenital hypothyroidism. While, all observed known variants/mutations were reported with either Pendred syndrome and/or congenital hypothyroidism earlier, but never with nonautoimmune adult hypothyroidism solely. Thereby, the absence of any features of Pendred syndrome and/or congenital hypothyroidism in patients with observed known nonsynonymous variants/mutations may be due to either heterozygous state of each variant or differential domain specific activity of ions trafficking in the respective organ. The analysis of amino acid change at least for p.C18S, p.S23X, and p.V239D in correlation with phenotypic characteristics of respective patients might assume a possible effect on protein structure and function. Altogether, we report for the first time that genetical variations in SLC26A4 gene could play an important role in development of nonautoimmune adult hypothyroidism.


Pregnant mothers' knowledge, attitude, practice and its predictors towards nutrition in public hospitals of Southern Ethiopia: A multicenter cross-sectional study.
Insufficient nutrition can predisposes women to infection, pregnancy losses, preeclampsia and anaemia as well birth of underweight baby whose survival is threatened. Therefore, this study was aimed to assess pregnant mothers' nutrition knowledge, attitude, practice and associated factors. A multicenter cross-sectional study was conducted among 378 participants who were selected using a systematic random sampling technique. Quantitative data were collected using a structured and interviewer-administered questionnaire, which consisted of questions on sociodemographic features, obstetrics characteristics and pregnant women's nutrition knowledge, attitude and practice. Data entry and analysis were done using Statistical Package for the Social Sciences statistical version 23. Binary logistic regression analysis was done to identify associated factors. All variables with p-value of < 0.23 in bivariate analysis were included in multivariate analysis, and finally, statistical significance was declared at p-value < 0.05 with 95% confidence interval. From 378 women participated, a total of 231 (61.1%) respondents were in age range of 25-34 years. About 148 (39.1%) of women were not knowledgeable, 153 (40.5%) had an unfavourable attitude, and 47.7% had poor dietary practice. Knowledge (adjusted odds ratio = 4.5; 95% confidence interval: 2.88, 10.06, p = 0.03), attitude (adjusted odds ratio = 3.6; 95% confidence interval: 2.43, 6.66, p = 0.04) and practice (adjusted odds ratio = 3.6; 95% confidence interval: 2.43, 6.66, p = 0.036) were all significantly associated with maternal education. Regarding their occupation, merchant women were seven times (adjusted odds ratio = 7.02; 95% confidence interval: 2.88, 17.09, p = 0.01) more likely to have knowledge and government employees were six times (adjusted odds ratio = 6.05; 95% confidence interval: 3.58, 13.05, p = 0.04) more likely to be knowable than housewives. Moreover, multiparous women were 4.77 times (adjusted odds ratio = 4.77; 95% confidence interval: 1.15, 8.66, p = 0.002) more likely to be knowledgeable compared to primigravida women. Monthly income was also associated to attitude (adjusted odds ratio = 0.45, 95% confidence interval: 0.10, 1.66, p = 0.03). Women who had a favourable attitude were five times (adjusted odds ratio = 5.25; 95% confidence interval: 2.36, 9.62, p = 0.04) more likely to have good nutritional practices during pregnancy. Pregnant women's knowledge, attitude and practice towards nutrition in this area were low. The educational status of women was associated with knowledge; attitude and practice. Likewise, occupation and parity were associated with knowledge; and attitude was also found to be a determinant factor of nutritional practice. Therefore, community nutritional education and antenatal nutritional counselling need to be strengthened in the area.


Identification of Whole Mitochondrial Genomes from Venezuela and Implications on Regional Phylogenies in South America.
Recent studies have expanded and refined the founding haplogroups of the Americas using whole mitochondrial (mtDNA) genome analysis. In addition to pan-American lineages, specific variants have been identified in a number of studies that show higher frequencies in restricted geographical areas. To further characterize Native American maternal lineages and specifically examine local patterns within South America, we analyzed 12 maternally unrelated Yekuana whole mtDNA genomes from one village (Sharamaña) that include the four major Native American haplogroups A2, B2, C1, and D1. Based on our results, we propose a reconfiguration of one subhaplogroup A2 (A2aa) that is specific to South America and identify other singleton branches across the four haplogroups. Furthermore, we show nucleotide diversity values that increase from north to south for haplogroups C1 and D1. The results from our work add to the growing mitogenomic data that highlight local phylogenies and support the rapid genetic differentiation of South American populations, which has been correlated with the linguistic diversity in the region by previous studies.


Recombinant pronapin precursor produced in Pichia pastoris displays structural and immunologic equivalent properties to its mature product isolated from rapeseed.
2S albumin storage proteins from rapeseed (Brassica napus), called napins, consist of two different polypeptide chains linked by disulphide bridges, which are derived by proteolytic cleavage from a single precursor. The precursor form of the napin BnIb (proBnIb) has been cloned using a PCR strategy and sequenced. The amino-acid sequence deduced from the clone includes 31 residues of the small chain and 75 of the large chain, which are connected by the peptide Ser-Glu-Asn. Expression of the cDNA encoding proBnIb has been carried out in the methylotrophic yeast Pichia pastoris. The induced protein was secreted to the extracellular medium at a yield of 80 mg.L(-1) of culture and was purified by means of size-exclusion chromatography and reverse phase-HPLC. Recombinant proBnIb appeared properly folded as its molecular and spectroscopic properties were equivalent to those of the mature heterodimeric protein. As 2S albumin storage proteins from Brassicaceae have been shown to be type I allergy inducers, the immunological activity of the recombinant proBnIb was analysed as a measure of its structural integrity. The immunological properties of the recombinant precursor and the natural napin were indistinguishable by immunoblotting and ELISA inhibition using polyclonal antisera and sera of patients allergic to mustard and rapeseed. In conclusion, the recombinant expression of napin precursors in P. pastoris has been shown to be a successful method for high yield production of homogeneous and properly folded proteins whose polymorphism and complex maturation process limited hitherto their availability.


The effect of positive parenting on adolescent life satisfaction: the mediating role of parent-adolescent attachment.
This study explores the impact of positive parenting on adolescents' life satisfaction and the mediating role of parent-adolescent attachment, based on the family systems theory and attachment theory. The sample included 5,047 adolescents (2,353 males, 2,694 females) with a mean age of 16.65 (SD = 1.21) from Henan Province, China. This study used the Positive Parenting Scale, the Inventory of Parent and Peer Attachment and the Satisfaction with Life Scale to survey 5,047 adolescents. The results showed that: (1) father's positive parenting positively predicted adolescent life satisfaction, while mother's positive parenting did not significantly predict adolescent life satisfaction; (2) Father-adolescent attachment and mother-adolescent attachment play a mediating role in the relationship between fathers' positive parenting, mothers' positive parenting, and adolescent life satisfaction, respectively; (3) Differences in the mechanisms of father's positive parenting and mother's positive parenting on adolescent life satisfaction. Among them, mothers' positive parenting positively predicts mother-adolescent attachment, which in turn affects adolescent life satisfaction. On the other hand, fathers' positive parenting can influence adolescent life satisfaction through two pathways: by positively predicting father-adolescent attachment and by positively predicting mother-adolescent attachment. The research findings indicate that father's and mother's positive parenting have different direct effects on adolescent's life satisfaction, and both can indirectly influence adolescent life satisfaction through the mediating variables of father-adolescent and mother-adolescent attachment. These findings have important theoretical and practical implications for promoting family education and adolescent psychological well-being.


Thyroid hormone regulates oligodendrocyte accumulation in developing rat brain white matter tracts.
Thyroid hormone (TH) is necessary for normal axonal myelination. Myelin basic protein (MBP) is a structural protein essential for myelin function. In this study, we demonstrate that perinatal hypothyroidism regulates MBP mRNA levels via indirect mechanisms. We observed decreased MBP mRNA accumulation in the hypothyroid rat brain at postnatal (PN) d 10 and 50. Acute TH replacement did not rescue hypothyroid MBP mRNA levels at PN5, 10, or 50. TH is necessary for normal intrahemispheric commissure development including the anterior commissure (AC) and the corpus callosum (CC). We determined that perinatal hypothyroidism decreases AC area and cellularity in the developing rat brain by PN10 and 50. In the developing CC, hypothyroidism initially increases area and cellularity by PN5, but then ultimately decreases area and cellularity by PN50. MBP-expressing oligodendrocytes are a recognized target of TH and are responsible for myelination within intrahemispheric commissures. We found that hypothyroidism reduces the number of mature oligodendrocytes within both the AC and CC. This reduction is noted at PN5, 10, and 50 in the AC and by PN10 and 50 in the CC. Together, these data suggest that TH regulates MBP mRNA levels through indirect mechanisms. These data demonstrate the complex mechanisms whereby TH regulates myelination in the developing brain.


Technical analysis, contestation and politics in policy agenda setting and implementation: the rise and fall of primary care maternal services from Ghana's capitation policy.
Why issues get on the policy agenda, move into policy formulation and implementation while others drop off in the process is an important field of enquiry to inform public social policy development and implementation. This paper seeks to advance our understanding of health policy agenda setting, formulation and implementation processes in Ghana, a lower middle income country by exploring how and why less than three months into the implementation of a pilot prior to national scale up; primary care maternal services that were part of the basket of services in a primary care per capita national health insurance scheme provider payment system dropped off the agenda. We used a case study design to systematically reconstruct the decisions and actions surrounding the rise and fall of primary care maternal health services from the capitation policy. Data was collected from July 2012 and August 2014 through in-depth interviews, observations and document review. The data was analysed drawing on concepts of policy resistance, power and arenas of conflict. During the agenda setting and policy formulation stages; predominantly technical policy actors within the bureaucratic arena used their expertise and authority for consensus building to get antenatal, normal delivery and postnatal services included in the primary care per capita payment system. Once policy implementation started, policy makers were faced with unanticipated resistance. Service providers, especially the private self-financing used their professional knowledge and skills, access to political and social power and street level bureaucrat power to contest and resist various aspects of the policy and its implementation arrangements - including the inclusion of primary care maternal health services. The context of intense public arena conflicts and controversy in an election year added to the high level political anxiety generated by the contestation. The President and Minister of Health responded and removed antenatal, normal delivery and postnatal care from the per capita package. The tensions and complicated relationships between technical considerations and politics and bureaucratic versus public arenas of conflict are important influences that can cause items to rise and fall on policy agendas.


Preoperative AFU Is a Useful Serological Prognostic Predictor for Colorectal Liver Oligometastasis Patients Undergoing Hepatic Resection.
Background: Preoperative alpha-l-fucosidase (AFU) has been used as a diagnostic biomarker for several cancers, but its role as a prognostic predictor in colorectal cancer liver oligometastasis (CLOM) patients after radical surgery has not been well defined. This study aimed to investigate the prognostic significance of preoperative serum AFU for CLOM patients after hepatic resection. Methods: A retrospective data set was collected to evaluate the prognostic value of preoperative AFU in CLOM patients after radical hepatic resection. A total of 269 patients with histopathologically confirmed CLOM were enrolled. The optimal cut-off value of preoperative AFU was determined using X-tile software. Univariate and multivariate analyses were used to identify the prognostic significance of preoperative serum AFU. Results: The X-tile software showed that the optimal cut-off value of preoperative AFU was set at 30.8 U/L. Patients with preoperative AFU≤30.8 and >30.8 were classified into high and low AFU groups, respectively. Female patients and those with a single liver metastasis had a higher tendency to have a preoperative AFU≤30.8 U/L; patients with lower clinical risk score (CRS) were more likely to have AFU >30.8 U/L than patients with higher CRS. The results showed that preoperative AFU was an independent prognostic factor for overall survival (OS) (P=0.041). Patients with a preoperative AFU≤30.8 U/L had a lower OS rate than those with AFU>30.8 U/L. Furthermore, for patients with lower CRS scores (0-2), the tendency clearly showed that patients with higher preoperative AFU had a better prognosis (P=0.029). Conclusions: Higher preoperative serum AFU can predict better survival in CLOM patients after hepatic resection, especially for CLOM patients with lower CRS scores.


[Effect of intraduodenal oligopeptide on rat pancreatic exocrine secretion and release of secretin and CCK].
We investigated whether intraduodenal (id) oligopeptide with three or four amino acids residues (pH 7.0) stimulates pancreatic exocrine secretion and release of endogenous plasma secretin and CCK in anesthetized rats. Id administration of oligopeptides in three doses (25, 100, 400 mg/hr) at a speed of 4 ml/hr resulted in dose-related increases in pancreatic secretion of pancreatic juice volume, bicarbonate, and amylase outputs (r = 0.598, 0.673, and 0.426, P less than 0.05 -- 0.001), and plasma concentrations of secretin and CCK (r = 0.743, 0.425, P less than 0.001 and 0.05). Intravenous administration of CCK-antagonist, CR1505 (5 mg/kg.hr) markedly inhibited oligopeptide-stimulated amylase output, but did not affect pancreatic juice volume and bicarbonate output. These results suggest that id oligopeptide increases pancreatic exocrine secretion and releases endogenous secretin and CCK.


Size distribution of metastatic lymph nodes with extranodal extension in patients with papillary thyroid cancer: a pilot study.
Extranodal extension (ENE) is a documented negative prognostic factor in patients with papillary thyroid cancer (PTC). ENE is presumed to manifest in larger lymph nodes. Yet, to date, no study has proven this. This is a pilot study that specifically examines the size distribution of positive lymph nodes manifesting ENE in patients with PTC. An Institutional Review Board approved review examined the size of all lymph nodes demonstrating ENE in postoperative PTC patients that underwent surgery for PTC under the care of a single surgeon between 2004 and 2014. All patients in the study had regional metastatic lymph nodes with ENE. Analysis of the size distribution for all lymph nodes with ENE was performed. A total of 47% of lymph nodes with ENE were ≤10 mm. RESULTS indicate that clinically nonevident, small lymph nodes are at risk of harboring aggressive disease biology reflected in ENE. A total of 47% of all nodes fell within Randolph et al.'s classification of "small" lymph nodes, while 59% of the nodes with ENE were <1.5 cm-the threshold size that was deemed to be prognostically significant by Ito et al. It is apparent that clinically nonevident regional lymph nodes can have adverse histologic features and that the previous presumption that nodes with ENE only appear in clinically evident, macroscopic nodes is flawed.


[A patient with long-term, unrecognized leishmaniasis].
A man from Surinam presented at the Department of Internal Medicine with a perforated septum and progressive collapse of the nose. This condition had existed for 22 years, though earlier analysis had not revealed the cause. Microscopic analysis showed a granulomatous inflammatory reaction, with cultures revealing of Leishmania. The diagnosis was mucocutaneous leishmaniasis and PCR indicated Leishmania braziliensis complex. The patient was treated for mucocutaneous leishmaniasis by a 28-day course of intravenous sodium-stibogluconate therapy. Initially, treatment was stopped briefly due to neurotoxicity, but was recommenced and successfully completed. After treatment the infection parameters returned to normal and the patient was referred for reconstructive nasal surgery. Due to a low parasitic load mucocutaneous leishmaniasis can be difficult to detect, especially in chronic cases. However, the use of molecular techniques has improved both the sensitivity and specificity of detection. The ability to distinguish between different species and sub-species is of prognostic and therapeutic relevance.


Evidence that TASK1 channels contribute to the background current in AH/type II neurons of the guinea-pig intestine.
Neurons that have AH (designation of neurons with a prominent and prolonged after hyperpolarizing potential that follows the action potential) electrophysiological characteristics and type II morphology (AH/type II neurons) are the first neurons in reflex circuits in the small intestine. Thus, the state of excitation of these neurons strongly influences the properties of enteric reflexes. The resting outward current in the type II neurons is reduced, causing depolarization and increased excitability, when protein kinase C (PKC) or synaptic inputs are activated, suggesting that regulation of background channels is an important determinant of the state of excitability of these neurons. However, the channels that carry the background current are not yet identified. We used intracellular microelectrodes to record from myenteric AH/type II neurons of the guinea-pig ileum, immunohistochemistry to localize channels and reverse transcriptase-polymerase chain reaction (RT-PCR) to characterize channel transcripts. The blockers of TASK1 channels, bupivacaine (1 mM) and methanandamide (10 muM), depolarized AH/type II neurons by 11.6 mV and 7.9 mV, respectively, and increased resting input resistance by about 30%. The reversal potential determined for the effect of bupivacaine was -92 mV, indicating that bupivacaine acts at K(+) channels, without significant action on other channel types that are open at rest. The membrane potential of type II neurons was depolarized by acidification to pH 6.4, but this depolarization was associated with decreased input resistance and was not reduced by bupivacaine. Thus an unidentified current that is activated by reduced pH masks effects on TASK channels. Slow excitatory post-synaptic potentials in the neurons were reduced in amplitude by methanandamide, suggesting that they are generated in part by closure of TASK1 channels. TASK1 immunoreactivity occurred in all type II neurons (determined by double labeling for IB4 and NeuN), but no type II neurons were immunoreactive for TASK2 or TASK3. These latter channels were localized to non-type II neurons. Transcripts for TASK1, TASK2, TASK3 and other two-pore-domain potassium channels were found in ganglion extracts. It is concluded that TASK1 channels contribute to the resting outward current in AH/type II neurons, and that neurotransmitters that evoke slow depolarizations in these neurons do so through the closure of resting K(+) channels that include TASK1 channels.


Evolution by recombination and transspecies polymorphism in the MHC class I gene of Xenopus laevis.
The patterns of major histocompatibility complex (MHC) evolution involve duplications, deletions, and independent divergence of loci during episodes punctuated by natural selection. Major differences in MHC evolution among taxa have previously been attributed to variation in linkage patterns of class I and class II MHC genes. Here we characterize patterns of evolution in the MHC class Ia gene of Xenopus laevis in terms of polymorphism, recombination, and extent of transspecies polymorphism. We also compare these patterns to see if a correlation exists with linkage or separation of the MHC class I and class II regions as seen in amphibians and teleost fishes. In X. laevis, we find high levels of polymorphism. Also, genetic exchange is relatively frequent and occurs in intron II, reshuffling allelic forms of exons 2 and 3. Evolutionary relationships among class I alleles show an intermingling of alleles from divergent Xenopus species rather than a species-specific clustering. Results indicate that the patterns of evolution are similar to those found in salmonid fishes and are different from the mode of evolution seen in primates. Similar patterns of class Ia evolution in salmonid fishes and X. laevis suggest that nonlinkage of class I and class II regions alone is insufficient to explain some patterns of MHC evolution in salmonids.


The Association Between STAT4 rs7574865 Polymorphism and the Susceptibility of Autoimmune Thyroid Disease: A Meta-Analysis.
Objectives: The signal transducer and activator of transcription 4 (STAT4) gene encodes an important transcription factor that transmits signals induced by several cytokines associated with autoimmune diseases and has been identified as a susceptibility gene for numerous autoimmune disorders. The association between STAT4 rs7574865 polymorphism and the susceptibility of autoimmune thyroid disease (AITD) has been investigated in previous case-control studies. However, the investigation results were inconsistent. Hence, a meta-analysis was performed to draw a more reliable conclusion about it. Methods: All relevant studies were searched in Embase, PubMed, Web of Science, and China National Knowledge Infrastructure, till August 20, 2018. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the association. Results: A total of five independent case-control studies with 1707 AITD patients and 2316 controls were included in the present meta-analysis. The overall pooled analysis indicated that STAT4 rs7574865 polymorphism was significantly associated with AITD susceptibility [TT vs. GG: OR = 1.63, 95%CI = 1.24-2.15, P Z = 0.0005; TT vs. (TG+GG): OR = 1.55, 95%CI = 1.26-1.91, P Z < 0.0001]. However, the subgroup analysis showed a significant association of STAT4 rs7574865 polymorphism with AITD susceptibility in Asian population, but not in African population. STAT4 rs7574865 polymorphism was significantly associated both with Graves' disease (GD) and Hashimoto's thyroiditis (HT) susceptibility. Conclusion: This meta-analysis showed a significant association between STAT4 rs7574865 polymorphism and AITD susceptibility. However, further studies with larger sample sizes and other ethnicities are still required to confirm the findings.


Emergency Department Frequent Users for Acute Alcohol Intoxication.
A subset of frequent users of emergency services are those who use the emergency department (ED) for acute alcohol intoxication. This population and their ED encounters have not been previously described. This was a retrospective, observational, cohort study of patients presenting to the ED for acute alcohol intoxication between 2012 and 2016. We collected all data from the electronic medical record. Frequent users for alcohol intoxication were defined as those with greater than 20 visits for acute intoxication without additional medical chief complaints in the previous 12 months. We used descriptive statistics to evaluate characteristics of frequent users for alcohol intoxication, as well as their ED encounters. We identified 32,121 patient encounters. Of those, 325 patients were defined as frequent users for alcohol intoxication, comprising 11,370 of the encounters during the study period. The median maximum number of encounters per person for alcohol intoxication in a one-year period was 47 encounters (range 20 to 169). Frequent users were older (47 years vs. 39 years), and more commonly male (86% vs. 71%). Frequent users for alcohol intoxication had higher rates of medical and psychiatric comorbidities including liver disease, chronic kidney disease, ischemic vascular disease, dementia, chronic obstructive pulmonary disease, history of traumatic brain injury, schizophrenia, and bipolar disorder. In this study, we identified a group of ED frequent users who use the ED for acute alcohol intoxication. This population had higher rates of medical and psychiatric comorbidities compared to non-frequent users.


[News and perspectives in insulin treatment].
Insulin therapy is a therapeutic cornerstone in patients with type 1 diabetes and also in numerous patients with type 2 diabetes especially with longer history of diabetes. The initiation of insulin therapy in type 2 diabetes patients is often delayed which is at least partially due to suboptimal pharmacokinetic characteristics of available insulins. The development of novel insulins with more favorable characteristics than those of current insulins is therefore still ongoing. The aim of this paper is to review current knowledge of novel insulins that have been recently introduced to the market or are getting close to routine clinical use. We will also focus on the perspectives of insulin therapy in the long-term run including the alternative routes of insulin administration beyond its classical subcutaneous injection treatment.Key words: alternative routes of insulin administration - diabetes mellitus - hypoglycemia - insulin - insulin analogues.


Jandu Yani U 'For All Families' Triple P-positive parenting program in remote Australian Aboriginal communities: a study protocol for a community intervention trial.
The population-based (Lililwan) study of fetal alcohol spectrum disorder (FASD) revealed a high prevalence of FASD in the remote communities of the Fitzroy Valley, Western Australia (WA) and confirmed anecdotal reports from families and teachers that challenging child behaviours were a significant concern. In response, Marninwarntikura Women's Resource Centre initiated a partnership with researchers from The University of Sydney to bring the positive parenting program (Triple P) to the Valley. Triple P has been effective in increasing parenting skills and confidence, and improving child behaviour in various Indigenous communities. Extensive consultation with community leaders, service providers, Aboriginal health networks and academic institutions was undertaken and is ongoing. Based on community consultations, the intervention was adapted to acknowledge local cultural, social and language complexities. Carers of children born after 1 January 2002 and living in the Fitzroy Valley are invited to participate in Group Triple P, including additional Stepping Stones strategies for children with complex needs. Programme are delivered by local community service workers, trained and accredited as Triple P providers or 'parent coaches'. Assessments for parent coach pretraining and post-training includes their perceived ability to deliver the intervention and the cultural appropriateness of the programme. Carers complete preintervention and postintervention and 6-month follow-up assessments of parenting practices, self-efficacy and child behaviour. Approval was granted by the University of Sydney Human Ethics Committee, WA Aboriginal Health Ethics Committee, WA Country Health Services Ethics Committee and Kimberley Aboriginal Health Planning Forum. Consultation with community is imperative for efficacy, engagement, community ownership and sustainability of the programme, and will be ongoing until findings are disseminated. Anonymous findings will be disseminated through peer-reviewed journals, community feedback sessions and scientific forums.


Diagnosis of Helicobacter pylori infection in adults and children by using the Malakit Helicobacter pylori, a commercially available enzyme-linked immunosorbent assay.
Malakit Helicobacter pylori (Biolab, Limal, Belgium) is a second-generation enzyme-linked immunosorbent assay (ELISA) for the detection of Helicobacter pylori infection. We evaluated its ability to diagnose H. pylori infection in 489 asymptomatic pregnant women, 427 asymptomatic children, and 95 symptomatic children. 87 asymptomatic adults (17.8%), 31 asymptomatic children (7.3%), and 27 symptomatic children (28.4%) were seropositive. We observed an increase in H. pylori infection with age. 13C-urea breath tests were performed for all seropositive and 100 randomly selected seronegative asymptomatic adults. They were also performed for all seropositive and 65 randomly chosen seronegative asymptomatic children. Breath tests were positive for 86 of 87 (98.9%) seropositive adults, 30 of 31 seropositive children (96.8%), and no seronegative individual. Compared with those of culture, the sensitivity and specificity of the Malakit Helicobacter pylori were both 96%. We conclude that the Malakit Helicobacter pylori is equally suitable for adults and children. Therefore, this ELISA can be proposed as an important alternative to other more time-consuming and/or more expensive diagnostic tests for the detection of H. pylori.


Node Location Privacy Protection Based on Differentially Private Grids in Industrial Wireless Sensor Networks.
Wireless sensor networks (WSNs) are widely applied in industrial application with the rapid development of Industry 4.0. Combining with centralized cloud platform, the enormous computational power is provided for data analysis, such as strategy control and policy making. However, the data analysis and mining will bring the issue of privacy leakage since sensors will collect varieties of data including sensitive location information of monitored objects. Differential privacy is a novel technique that can prevent compromising single record benefits. Geospatial data can be indexed by a tree structure; however, existing differentially private release methods pay no attention to the concrete analysis about the partition granularity of data domains. Based on the overall analysis of noise error and non-uniformity error, this paper proposes a data domain partitioning model, which is more accurate to choose the grid size. A uniform grid release method is put forward based on this model. In order to further reduce the errors, similar cells are merged, and then noise is added into the merged cells. Results show that our method significantly improves the query accuracy compared with other existing methods.


The thermoelectric power of Al-0.99 wt.% Fe alloys in the AC magnetic field.
The melt structure of Al-0.99 wt.% Fe alloys in the AC magnetic field have been studied with thermoelectric power by the four-point probe technique and microstructure with the liquid quenching method. The melt temperature is in the range of 913 K-1013 K. The thermoelectric power increases due to the AC magnetic field and decreases after the AC magnetic field stops, then keeps stable. Some characteristic parameters of thermoelectric power in the recovery process are used to represent the variation of melt structure. The α-Al phase refinement in the AC magnetic field is attributed to the persistent variation of melt structure. The persistent variation of thermoelectric power can be used to characterize the variation of the α-Al phase size. The hardness increases and the diffraction peaks of some planes reduce, which can reflect the uniform and disorder melt structure in the AC magnetic field.


Using alternative teaching and learning approaches to deliver clinical microbiology during the COVID-19 pandemic.
The COVID-19 (coronavirus disease 2019) pandemic has had significant impacts upon higher education teaching. Clinical microbiology teaching is primarily focused on a combination of practical skill development and didactic delivery of content. In the pandemic, the absence of in-person teaching has led to educators adapting in-person content for online platforms and delivery. This commentary covers alternative innovative and engaging teaching approaches to deliver clinical microbiology content during the COVID-19 pandemic.


Insulin, not C-peptide (proinsulin), is present in crinophagic bodies of the pancreatic B-cell.
We have obtained evidence by autoradiography and immunocytochemistry that mature secretory granules of the pancreatic B-cell gain access to a lysosomal compartment (multigranular or crinophagic bodies) where the secretory granule content is degraded. Whereas the mature secretory granule content shows both insulin and C-peptide (proinsulin) immunoreactivities, in crinophagic bodies only insulin, but not C-peptide, immunoreactivity was detectable. The absence of C-peptide (proinsulin) immunoreactivity in multigranular bodies, i.e., in early morphological stages of lysosomal digestion, was compatible with the ready access and breakdown of C-peptide and/or proinsulin by lysosomal degrading enzymes, while the insulin crystallized in secretory granule cores remained relatively protected. However, in the final stage of lysosomal digestion, i.e., in residual bodies where the secretory granule core material is no longer present, insulin immunoreactivity became undetectable. Lysosomal digestion thus appears to be a normal pathway for insulin degradation in the pancreatic B-cell.