Point mutations within the streptococcal regulator of virulence (Srv) alter protein-DNA interactions and Srv function.
Group A Streptococcus (GAS) possesses a complex regulatory system enabling the organism to colonize a range of physiologically distinct host sites. Within this network of regulators is the streptococcal regulator of virulence (Srv). Srv is a member of the CRP/FNR family of transcriptional regulators and is most similar to pleiotropic regulatory factor A (PrfA), a positive regulator of virulence in Listeria monocytogenes. Members of this family possess a characteristic C-terminal helix-turn-helix motif (HTH) that facilitates binding to DNA targets. Genome scanning identified four targets in GAS that were similar to the consensus DNA target recognized by PrfA. Furthermore, previous amino acid sequence alignments identified conserved residues within the Srv HTH which are necessary for function in PrfA and CRP. Here we investigated the ability of Srv to interact with DNA and evaluated the role of the HTH in this interaction. Purified recombinant Srv (rSrv) was found to co-purify with an untagged form of Srv. Glutaraldehyde cross-linking and gel-filtration chromatography indicated that this co-purification is likely due to the ability of Srv to oligomerize. Electrophoretic mobility shift assays (EMSAs) demonstrated that rSrv retarded the mobility of DNA targets and a supershift analysis confirmed the observation was rSrv-dependent. Competition EMSA indicated that rSrv had a higher relative affinity for the DNA targets studied than non-specific DNA. Site-directed mutagenesis of residues predicted to be in or near the HTH resulted in a decrease or abrogation of DNA binding. Complementation of MGAS5005Deltasrv with one of these site-directed mutants failed to restore wild-type SpeB activity. Taken together, these data suggest that the Srv HTH is necessary for DNA binding and Srv function.


Draft genome sequences of three emerging beta-lactamase-producing Escherichia coli in the camel production system in Northern Kenya.
We report the draft genome sequences and annotation of three beta-lactamase-producing Escherichia coli ( E.coli) strains isolated from fecal samples of healthy camels in Laikipia county, Kenya. This data adds to the online genome resources to support the ongoing antimicrobial resistance surveillance in the livestock-wildlife interface.


Selective inhibition of RNA tumor virus replication in vitro and evaluation of candidate antiviral agents in vivo.
A limited number of biologically active materials were examined for their relative ability to selectively inhibit the replication of Gross or Rauscher murine leukemia virus (MLV) in Swiss mouse embryo cells by means of the UV-XC plaque-reduction assay. Among the compounds demonstrating significant antiviral activity against Gross MLV in vitro were 1-(4-fluorobenzyloxy) adenosine (FBAR), polyadenylic acid [poly(A)], the carbocyclic analogue of 6-methylthiopurine ribonucleoside (C-MeMPR), 3-(2,4-dinitrophenylhydrazonemethyl)rifamycin SV (AF/DNFI), and phosphonoacetic acid (PAA). Five compounds that exhibited significant antiviral activity against MLV in vitro were tested for similar activity against Rauscher MLV in vivo. Three of these selected compounds, pyrazofurin (pyrazomycin), ribavirin (Virazole), and 9-beta-D-arabinofuranosyladenine (ara-A), produced a significant (50%-100%) inhibition of virus-induced splenomegaly development in mice, whereas the other two candidate inhibitors, 3-deazauridine (deazaUR) and rifamycin SV, the other two candidate inhibitors, 3-deazauridine (deazaUR) and rifamycin SV, failed to demonstrate any in vivo activity in this 21-day leukemogenesis assay. The administration of an inhibitor of adenosine deaminase (Co-vidarabine) in combination with ara-A resulted in an enhanced antiviral response in both infected cell cultures and animals. Co-vidarabine also increased the potency of ara-AMP against Gross MLV in vitro, indicating the probable dephosphorylation of the compound to ara-A and its subsequent deamination to ara-H in this system.


Understanding the evolutionary structural variability and target specificity of tick salivary Kunitz peptides using next generation transcriptome data.
Ticks are blood-sucking arthropods and a primary function of tick salivary proteins is to counteract the host's immune response. Tick salivary Kunitz-domain proteins perform multiple functions within the feeding lesion and have been classified as venoms; thereby, constituting them as one of the important elements in the arms race with the host. The two main mechanisms advocated to explain the functional heterogeneity of tick salivary Kunitz-domain proteins are gene sharing and gene duplication. Both do not, however, elucidate the evolution of the Kunitz family in ticks from a structural dynamic point of view. The Red Queen hypothesis offers a fruitful theoretical framework to give a dynamic explanation for host-parasite interactions. Using the recent salivary gland Ixodes ricinus transcriptome we analyze, for the first time, single Kunitz-domain encoding transcripts by means of computational, structural bioinformatics and phylogenetic approaches to improve our understanding of the structural evolution of this important multigenic protein family. Organizing the I. ricinus single Kunitz-domain peptides based on their cysteine motif allowed us to specify a putative target and to relate this target specificity to Illumina transcript reads during tick feeding. We observe that several of these Kunitz peptide groups vary in their translated amino acid sequence, secondary structure, antigenicity, and intrinsic disorder, and that the majority of these groups are subject to a purifying (negative) selection. We finalize by describing the evolution and emergence of these Kunitz peptides. The overall interpretation of our analyses discloses a rapidly emerging Kunitz group with a distinct disulfide bond pattern from the I. ricinus salivary gland transcriptome. We propose a model to explain the structural and functional evolution of tick salivary Kunitz peptides that we call target-oriented evolution. Our study reveals that combining analytical approaches (transcriptomes, computational, bioinformatics and phylogenetics) improves our understanding of the biological functions of important salivary gland mediators during tick feeding.


Does Forest Loss Increase Human Disease? Evidence from Nigeria.
It is estimated that about one quarter of the global disease burden in terms of healthy life years lost and about one quarter of all premature deaths can be attributed to modifiable environmental factors (Pruss-Ustun and Corvalan 2006). Three infectious diseases--diarrhea, respiratory infections, and malaria--account for the largest absolute burden in developing countries with children facing the greatest impacts. There is a growing body of evidence demonstrating the health burden of air and water pollution, as well as important productivity and income effects (see, for example, reviews of the literature in Pattanayak and Pfaff 2009 and Greenstone and Jack 2016). Studies that focus on the impacts of natural resource degradation are fewer. Notably, Garg (2016) provides the first causal estimates of the impact of sustained forest cover on reduced malarial incidence in Indonesia, demonstrating a large and previously understudied cost of forest cover loss. In this paper, we extend this new literature on the health impacts of environmental degradation by estimating the causal impact of forest loss on infectious disease incidence in young children using temporal and spatial variation in the last decade in Nigeria. Our estimation strategy involves geolinking a new high-resolution dataset of global forest change to child-level health data from the Nigeria Demographic and Health Surveys from 2008 and 2013. We find that forest loss significantly increases the incidence of malaria, though it does not affect the incidence of diarrhea and respiratory diseases. The impact of forest loss on malaria is large (one standard deviation of forest loss increases malaria incidence by around 4.5 percent in children under five) and the dynamic pattern of the impact suggests a temporary ecological disturbance consistent with findings in Garg (2016) and the tropical medicine literature.


[Postoperative treatment of patients after pancreatectomy. Closely meshed monitoring of blood sugar (author's transl)].
A report is presented on the postoperative treatment of 4 patients who had undergone duodeno-pancreatectomy because of chronic pancreatitis. When the patients co-operate well satisfactory metabolic compensation can be achieved with small doses of insulin. Replacement of the pancreatic enzymes with the appropriate preparations can be particularly well monitored by means of the fat content of the faeces. The substitution of vitamins A, D, K, and B12 parenterally at intervals of several weeks is also advisable as a safety measure. A method is described for the closely meshed monitoring of the blood sugar. This method is suitable in co-operative patients who are capable of collecting capillary blood for achieving a particularly good control of the metabolic state.


Intensive monitoring of adverse drug reactions in hospitalized patients of two medical units at a tertiary care teaching hospital.
To detect incidence of adverse drug reactions (ADRs) in hospitalized patients and to assess their causality, seriousness, preventability, and the possible economic impact. This was a prospective study carried out in two medical units at a tertiary care, teaching hospital, for about 18 months. All the admitted patients who developed an ADR after admission (group A) or who were admitted primarily for the treatment of an ADR (group B) were included. Descriptive statistics with 95% CI, χ(2), χ(2) for the trend and kappa test were used. Out of 6601 patients, 140 patients developed 154 ADRs with an incidence of 2.12%. Causality of the majority of the ADRs in group A was 'possible' while those in group B was 'probable'. Among 109 ADRs (34 serious) in group A, 38 were preventable. On the other hand, out of 45 serious ADRs in group B, 19 were preventable. The total cost of 154 ADRs in 140 patients was Rs. 1,49,803 with an average of Rs. 1070 per patient. The preventable cost for 57/154 ADR was Rs. 96,310. Around 2% of the hospital patients develop ADRs. A large number of these ADRs were preventable. A substantial saving can be made if adequate caution is exerted.


[Disorders of neurotrophic control during reflex action on the axoplasmic transport].
Experimental studies on 66 pubertal rats were carried out to explore the neurotrophic control under the conditions of reflex actions on the axoplasmic transport. Causing blockade of the axoplasmic transport, both experimental reflex actions on the nerve and the cytostatic colchicine result in the removal of the trophic control.


Expression of obestatin and ghrelin in papillary thyroid carcinoma.
Ghrelin and obestatin are two peptide hormones with opposing roles in the control of appetite: orexigenic and anorexigenic, respectively. Loss of appetite is a common, serious complication of many forms of malignancy. The goals of this study were to investigate: (i) whether there are differences in ghrelin and obestatin peptide expression in thyroid tissues from a series of papillary carcinoma cases and normal controls, and (ii) whether there are correlations between tissue ghrelin and obestatin levels in series of papillary carcinoma cases and normal controls. Immunohistochemical analysis showed that in sections of benign human thyroid tissue, anti-ghrelin antibody reacted with intense staining in colloid-filled follicles. In benign thyroid tissues, colloids displayed plentiful dispersion in comparison with papillary microcarcinomas, whereas colloids in malignant thyroid tissues were uncommon. We found markedly lower tissue ghrelin levels in thyroid tissue of patients with papillary carcinomas, compared with normal thyroid tissues (P = 0.001). Immunohistochemical analysis also showed that obestatin in papillary carcinoma stained positively to various degrees. Obestatin tissue levels in papillary carcinomas tended to be slightly higher than those in normal thyroid tissue, but this was not statistically significant (P = 0.29). We also report that thyroid tissue of patients with Hashimoto's thyroiditis produced ghrelin and obestatin at similar levels as in normal thyroid tissue, even though colloid in Hashimoto's disease is scarce. We conclude that depressed expression of ghrelin, but not obestatin, is specific to papillary carcinoma, and this difference might constitute a diagnostic tool to differentiate papillary carcinoma from normal thyroid tissue. We currently do not know how these peptides are regulated and what factors are involved in papillary carcinoma, which inhibit the expression of ghrelin but not obestatin. This issue warrants further studies.


Deficiency of Adipose Aryl Hydrocarbon Receptor Protects against Diet-Induced Metabolic Dysfunction through Sexually Dimorphic Mechanisms.
The molecular mechanisms underlying diet-induced obesity are complex and remain unclear. The activation of the aryl hydrocarbon receptor (AhR), a xenobiotic sensor, by obesogens may contribute to diet-induced obesity through influences on lipid metabolism and insulin resistance acting at various sites, including adipose tissue. Thus, our hypothesis was that conditional AhR depletion, specifically from mature adipose tissue (CadKO), would improve high-fat diet (HFD)-induced metabolic dysfunction. CadKO protects mice from HFD-induced weight gain. CadKO females eat fewer calories, leading to increased energy expenditure (EE) and improved glucose tolerance on HFD. Our exploration of adipose tissue biology suggests that the depletion of AhR from adipocytes provides female mice with an increased capacity for adipogenesis and lipolysis, allowing for the maintenance of a healthy adipocyte phenotype. The HFD-induced leptin rise was reduced in CadKO females, but the hypothalamic leptin receptor (LepR) was increased in the energy regulatory regions of the hypothalamus, suggesting an increased sensitivity to leptin. The estrogen receptor α (ERα) was higher in CadKO female adipose tissue and the hypothalamus. CadKO males displayed a delayed progression of obesity and insulin resistance. In males, CadKO ameliorated proinflammatory adipocytokine secretion (such as TNFα, IL1β, IL6) and displayed reduced inflammatory macrophage infiltration into adipose depots. Overall, CadKO improves weight control and systemic glucose homeostasis under HFD challenge but to a more profound extent in females. CadKO facilitates a lean phenotype in females and mediates healthy adipose-hypothalamic crosstalk. In males, adipose-specific AhR depletion delays the development of obesity and insulin resistance through the maintenance of healthy crosstalk between adipocytes and immune cells.


Regulation of airway inflammation and remodeling in asthmatic mice by TLR3/TRIF signal pathway.
This paper aims to investigate the effect of Toll-like receptors 3 (TLR3)/TIR-domain-containing adapter-inducing interferon-β (TRIF) signal pathway on the airway inflammation and remodeling in asthmatic mice. C57BL/6 and TLR3-/- mice were randomly divided into three groups (10 mice per group), including Control group (mice inhaled phosphate buffer saline (PBS)), Asthma group (mice inhaled ovalbumin (OVA)) and polyriboinosinic-ribocytidylic acid (poly (I: C)) group (asthmatic mice were injected intraperitoneally with TLR3 agonist poly (I: C)). Hematoxylin-eosin (HE) staining, Wright-Giemsa staining, Enzyme-linked immunosorbent assay (ELISA), Immunohistochemistry, Hydroxyproline assay, quantitative real time polymerase chain reaction (qRT-PCR) and Western blot were used to assess for the indices of airway inflammation and remodeling. In terms of WT mice, all asthma groups with or without the addition of poly (I: C) showed exaggerated inflammation and remodeling in the airways as compared to Control group, which were more seriously in poly (I: C) group than Asthma group. Furthermore, we observed the significant inhibition of airway inflammation and remodeling in the TLR3-/- mice in both Asthma no matter with or without addition of poly (I: C) than the WT mice. TLR3 knockout could obviously relieve the airway inflammation and remodeling in asthma through inhibiting TLR3/TRIF signaling pathway.


Disconnect between inflammation and joint destruction after treatment with etanercept plus methotrexate: results from the trial of etanercept and methotrexate with radiographic and patient outcomes.
To determine the relationship between disease activity and radiographic progression of joint destruction in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX), those treated with etanercept, and those treated with the combination of MTX plus etanercept. Baseline, 12-month, and 24-month data from the Trial of Etanercept and Methotrexate with Radiographic and Patient Outcomes database were analyzed. The dependent variable was the 1-year change in the modified Sharp/van der Heijde score (Sharp score); therefore, 2 interval changes per patient were available. Interval change in the Sharp score was modeled by time (years), treatment, disease activity, and the interaction (disease activity x treatment). Disease activity was reflected by the time-averaged Disease Activity Score (taDAS) and the time-averaged C-reactive protein (taCRP) level, which were calculated per 1-year interval. Generalized mixed linear modeling (GMLM) was used to adjust for within-patient correlation. GMLM confirmed a significant interaction between treatment and the taCRP level and taDAS with respect to the change in Sharp score (P = 0.012 and P = 0.03, respectively). In patients treated with MTX alone, radiographic progression increased with an increasing taCRP level or taDAS, although progression rates were low in patients whose disease was in remission and in those with low-to-moderate disease activity. This relationship was less clear in patients treated with etanercept and was absent in those who received combination therapy. Combination therapy with MTX plus etanercept uncouples the classic relationship between disease activity and radiographic progression in patients with RA.


Dream contents and failing memories.
Mentation during sleep states is thought to originate in an activation of brain circuits that encode inherited and experiential memories. Spontaneous degradation of the strengths of synapses occurs in all brain circuits because of "turnover" of molecules essential for synaptic function. In circuits employed frequently during waking, synaptic strengths are refreshed and maintained in their dedicated or functional ranges largely through use, by virtue of activity-dependent synaptic plasticity. In circuits employed infrequently during waking, synaptic strengths are refreshed largely during sleep, by circuit activations induced by spontaneous, self-generated, largely low-frequency brain waves, also by virtue of activity-dependent synaptic plasticity. The outputs of circuits activated during sleep do not necessarily rise to the level of 'unconscious' awareness. Such an absence of awareness of the outputs of individual circuits, that is, an absence of dreaming, is proposed to be the primitive condition in animals that sleep. On the other hand, temporal binding of these outputs is accompanied by the thoughts and perceptions of dreams, which is proposed to be the advanced condition. Linking or serial ordering of otherwise 'static' thoughts and perceptions gives rise to continuous, often narrative and veridical, dreams. In all cases, dream contents are derived from the memories--not necessarily veridical--encoded in the reinforced circuitry. In the absence of synaptic strength refreshments during sleep, synaptic strengths in infrequently used circuits would weaken and the circuits would become incompetent, with their encoded memories degraded or lost. Maintenance of synaptic strengths in infrequently used circuitry during sleep apparently does not always achieve perfection. Weakened synapses begin to occur in circuits in appreciable numbers in children after the age of about 5 years. When these 'incompetent' circuits (with weakened synapses) are activated during sleep, there are minimal influences on dream contents, namely, distortions that make some objects, such as animals, faces, and scenes, unrecognizable. As weakened synapses increase in numbers with age, the numbers of distorted objects in dreams also increase. In adults, people in as many as 80% of dreams may be unrecognizable. Besides the normal weakening of synaptic strengths, some synapses become defective, in consequence of deleterious, adventitious, exogenous influences, for example, radiation. As these faulty synapses accumulate in old memories, activation of circuits incorporating them during sleep leads to dreams with incoherent, bizarre, or impossible contents. The infrequent activation of such old, incompetent circuits in some waking conditions leads to false memories, delusions, or hallucinations.


[An Analysis of Perforated Gastric Cancer with Acute Peritonitis in Our Hospital].
Perforated gastric cancer is relatively rare and the incidence is reported about 1% of all the cases of gastric cancer. We retrospectively analyzed the clinical data of the consecutive 12 patients with perforated gastric cancer who underwent operation in our hospital between January 2005 and December 2016. There were 5 men and 7 women, with an average age of 65.8 years old(34-87). Perforated gastric cancer occurred in the region U(1 cases), M(6 cases), L(5 cases). There were 11 cases with distant metastasis. We could successfully diagnosed as perforated gastric cancer in 8 cases before emergency operation. Gastrectomy was performed in 5 cases. However, the curative resection was performed only 1 case. Prognosis of perforated gastric cancer is poor. We considered as an appropriate two-step surgical strategy that the first step of surgery is an acute peritonitis treatment followed by radical gastrectomy with lymphadenectomy.


Estimation of carcass fat and protein in northern pintails (Anas acuta) during spring migration.
Foraging in stopover areas influences nutritional condition of birds during spring migration. Our purpose was to determine if body mass, percent carcass water, and serum biochemistry would predict energy reserves (carcass fat and protein) in northern pintails (Anas acuta) at a spring staging area, Lake St. Pierre in Québec, Canada (46 degrees 11 'N, 73 degrees 08 'W). Northern pintails were collected during spring 1997 (14 April-9 May). In this staging area, body mass and percent body water successfully estimated carcass protein and fat in male northern pintails, but only carcass protein in females. None of the seven blood parameters we used accurately estimated nutritional reserves in staging northern pintails. These findings suggest that investigators must use direct estimates of carcass reserves to examine nutrient reserve requirements for egg production, migration, or body maintenance during spring migration.


Photoswitchable nonlinear optical properties of azobenzene-based supramolecular complexes: insights from density functional theory.
Density functional theory (DFT) calculations were performed for a series of supramolecular assemblies containing azobenzene (Azo-X where X = I, Br and H) and alkoxystilbazole subunits to evaluate their electronic, linear and nonlinear optical properties. These assemblies are derivatives of azobenzene, obtained by the substitution of electron-withdrawing and electron-donating groups onto the molecular skeleton. The interaction energies (Eint) of all the designed supramolecular complexes (IA-IF, IIA-IIF and IIIA-IIIF) range from -1.0 kcal mol-1 to -7.7 kcal mol-1. The electronic properties of these hydrogen/halogen bond driven supramolecular assemblies such as vertical ionization energies (VIE), HOMO-LUMO energy gap (GH-L), excitation energies, density of states (DOS) and natural population (NPA) analyses were also computed. The non-covalent interaction index (NCI) and quantum theory of atoms in molecules (QTAIM) analyses were also performed to validate the nature of inter- and intra-molecular interactions in these complexes. A substantial enhancement in the first hyperpolarizability (β0) values of the designed supramolecular complexes was observed, which is driven by the charge transfer from the pyridyl moiety of alkoxystilbazole to Azo-X. The highest β0 value of 1.3 × 104 au was observed for the supramolecular complex of p-nitro substituted azobenzene with alkoxystilbazole (ID complex). Moreover, the results show that the substitution of electron-withdrawing groups on Azo-X can also bring larger β0 values for such complexes. It was confirmed on a purely theoretical basis that both the types of noncovalent interactions present and the substituent group incorporated influence the nonlinear optical (NLO) response of the systems. Furthermore, the β0 values of the E (trans) and Z (cis) forms were compared to demonstrate the two-way photoinduced switching mechanism.


Beta1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis.
Beta1 integrins are highly expressed on chondrocytes, where they mediate adhesion to cartilage matrix proteins. To assess the functions of beta1 integrin during skeletogenesis, we inactivated the beta1 integrin gene in chondrocytes. We show here that these mutant mice develop a chondrodysplasia of various severity. beta1-deficient chondrocytes had an abnormal shape and failed to arrange into columns in the growth plate. This is caused by a lack of motility, which is in turn caused by a loss of adhesion to collagen type II, reduced binding to and impaired spreading on fibronectin, and an abnormal F-actin organization. In addition, mutant chondrocytes show decreased proliferation caused by a defect in G1/S transition and cytokinesis. The G1/S defect is, at least partially, caused by overexpression of Fgfr3, nuclear translocation of Stat1/Stat5a, and up-regulation of the cell cycle inhibitors p16 and p21. Altogether these findings establish that beta1-integrin-dependent motility and proliferation of chondrocytes are mandatory events for endochondral bone formation to occur.


Clinical evaluation of single-stage advanced versus rotated flaps in the treatment of gingival recessions.
Several procedures have been reported for the surgical correction of gingival recession (GR), including the laterally positioned flap (LPF) and the coronally advanced flap (CAF), performed as single- or two-stage procedures without or with, respectively, the preceding placement and healing of a free gingival graft. The objective of the present report was to compare the efficacy of single-stage LPF and CAF techniques in the treatment of localized maxillary GR defects. Thirty-six patients, 10 men and 26 women, with average age of 34 + or - 9 years with Miller Class I GR defects were randomly assigned to be treated by either a CAF (n = 18) or LPF (n = 18). Clinical parameters, including recession height, the width of keratinized tissue (WKT), probing depth, and vertical clinical attachment level were assessed at the mid-buccal site. Visual plaque score and bleeding on probing were also assessed dichotomously. Clinical recordings were performed at baseline and 6 months later. Intermeasurements differences were analyzed with a chi-square or a Wilcoxon test, with significance set at alpha<0.05. Both flap designs were effective in treating recession defects resulting in similar improvements for percentage of root coverage, frequency of complete root coverage, and gain in clinical attachment level. The LPF resulted in significantly more gains in WKT than the CAF. The results obtained by CAF in the treatment of Miller Class I maxillary GR are clinically similar to the LPF albeit with more limited gains in WKT.


XIENCE V everolimus-eluting coronary stent system: a novel second generation drug-eluting stent.
Drug-eluting stents (DES) have been shown to be safe and significantly reduce clinical events and angiographic restenosis in the percutaneous treatment of coronary artery disease. Currently, three DES have been approved in Europe and Northern America: the sirolimus-eluting stent (SES), the paclitaxel-eluting stent (PES) and the zotarolimus-eluting stent (ZES). Everolimus, an analog of sirolimus, is an immunosuppressive and antiproliferative agent. In three studies, the SPIRIT I, FUTURE I and II, the everolimus-eluting stent has proven to be safe, well-tolerated and has shown very favorable clinical and angiographic results. Compared with earlier-generation DES, the XIENCE V everolimus-eluting coronary stent system (Advanced Cardiovascular Systems Inc., an Abbott Vascular Company, CA, USA) may provide enhanced deliverability, radiopacity with thinner strut filaments and, owing to a durable polymer, sustained drug elution and vascular compatibility.


[Pathophysiology of heart failure today].
In chronic heart failure mechanisms which regulate myocardial contractility are defective (Frank-Starling mechanism, force-frequency-relationship, beta-adrenergic responsiveness). Neuroendocrine mechanisms induce the progression of left ventricular dysfunction to chronic heart failure (renin-angiontensin-aldosterone system, endothelin system, sympathetic nervous system). Angiotensin II and norepinephrine induce programmed cell death (apoptosis) in myocardial cells, thereby contributing to the progression of left ventricular function to heart failure. Established principles for treatment are based on the antagonism of these neuroendocrine mechanisms. New concepts like augmentation of myocardial regeneration by stem cells are an attractive perspective for innovative treatments of heart failure. The characterization of the underlying mechanisms can offer potential new strategies of the treatment of these malignant condition.


[Evaluation of a fast test for direct research on streptococcal group A from pharyngeal samples].
Importance of streptococcal pharyngitis rapid diagnosis is increasing. 645 patients with pharyngoamygdalitis were tested. The correlation between bacteriologic culture and rapid test is 86%, the sensibility of the test is 68%, its specificity is 92%, while the predictive positive and negative values are 75% and 90%. These results show the interest of the rapid test for the diagnosis of streptococcal pharyngitis.


[Studies on the fine stereostructure of taxoids].
The anticancer drug taxol is a new type antimicrotubular drug. The structure-activity relationship study on taxol and its analogs has indicated the importance of the C13 side chain and the C4-C5-C20 epoxypropane group. The crystal structures of 4 taxoids having the basic skeleton with 5/7/6 membered ring and three types of 10 taxoids having the basic skeleton with 6/8/6 membered ring have been analyzed. The effects of the induction by different substructures at C4 on the stereostructures of taxoids were studied, and the relationship between the 6/8/6/4 skeleton and the anticancer activity was discussed from the crystallographic point.


Qualitative visual environment retrieval.
A system for retrieval of an unstructured environment under static and dynamic scenarios is proposed. The use of cylindrical mosaics or omnidirectional images is exploited for providing a rich description about the surrounding environment spanning 360 degrees. The environment description is based on defining the attributes of the nodes of a graph derived from the angular partitions of the captured images. Content-based image retrieval for each of these partitions is performed on an exemplar image database to annotate the nodes of the graph. The complete environment description is recovered by collating the retrieval results over all the partitions based on a simple voting scheme. This offers a qualitative description of the location in a totally natural and unstructured surrounding. The experiments yield quite promising results.


Interleukin 1 beta and the stimulation of Langerhans cell migration: comparisons with tumour necrosis factor alpha.
Epidermal Langerhans cells (LC) and the cells into which they mature are believed to play a pivotal role in cutaneous immune function. The induction phase of contact sensitization is associated with the migration of LC from the skin and their accumulation as dendritic cells (DC) in lymph nodes draining the site of exposure. We have demonstrated previously that tumour necrosis factor alpha (TNF-alpha), an epidermal cytokine produced by keratinocytes, provides one signal for LC migration. We describe here experiments designed to evaluate the influence of interleukin 1 beta (IL-1 beta), a product exclusively of LC in murine epidermis, on LC migration, LC morphology and DC accumulation, and to compare the effects of this cytokine with those of TNF-alpha. Both cytokines induced a significant reduction in the frequency of epidermal LC and the arrival of DC in draining lymph nodes. Changes in both parameters were induced more rapidly following intradermal administration of TNF-alpha than were observed after treatment with IL-1 beta. However, the reduction in LC frequency was more persistent with IL-1 beta. Both cytokines caused the activation of LC, characterized by the acquisition of a more dendritic morphology and the increased expression of Ia molecules. These results demonstrate that IL-1 beta and TNF-alpha can each stimulate the migration of epidermal LC, but that the changes induced by these cytokines are not identical.


Re(VII) complex of N-fused tetraphenylporphyrin.
By treatment of N-fused tetraphenylporphyrin rhenium(I) tricarbonyl complex with trimethylamine N-oxide, oxidation of the metal center proceeded to afford N-fused tetraphenylporphyrin rhenium(VII) trioxo complex, which was quite stable against air, light and heat.


Outcomes of Patients with Monoclonal Gammopathy of Undetermined Significance with and without Atrial Fibrillation: A Retrospective Cohort Analysis of the Nationwide Inpatient Sample Database.
Monoclonal gammopathy of undetermined significance (MGUS) is a non-malignant precursor of multiple myeloma (MM). MGUS has been suggested to be associated with a higher risk of cardiovascular diseases, including AFIB, but it is still unclear whether this association is real. Studies are lacking on the impact of atrial fibrillation on health outcomes in this population. The association of AFIB in this population is lagging and merits further investigation. The study conducted a retrospective analysis of the Nationwide Inpatient Sample (NIS) for 2018, including adult patients with primary diagnoses of MGUS and AFIB. Patients were divided into two groups based on AFIB presence. Outcomes assessed included complications, length of stay, mortality, hospital charges, and discharge disposition. The study included 9007 patients with MGUS of whom 2404 had AFIB. Patients with both MGUS and AFIB had higher rates of acute kidney injury [AKI] (31.5% vs. 27.5%; p = 0.002) and pericarditis (2% vs. 1.2%; p = 0.029). They also had longer hospital stays (5 vs. 4 days; p < 0.001) and higher hospitalization costs ($43,729 vs. $41,169; p < 0.001). The study showed that the prevalence of AFIB in MGUS patients is high. Patients with AFIB had increased rates of complications (AKI and pericarditis) and higher mortality compared to patients without AFIB. Further studies screening for AFIB in this patient population are warranted.


Chilling-responsive DEMETER-LIKE DNA demethylase mediates in poplar bud break.
Annual dormancy-growth cycle is a developmental and physiological process essential for the survival of deciduous trees in temperate and boreal forests. Seasonal control of shoot growth in woody perennials requires specific genetic programmes responding to environmental signals. The environmental-controlled mechanisms that regulate the shift between winter dormancy and the growth-promoting genetic programmes are still unknown. Here, we show that dynamics in genomic DNA methylation levels are involved in the regulation of dormancy-growth cycle in poplar. The reactivation of growth in the apical shoot during bud break process in spring is preceded by a progressive reduction of genomic DNA methylation in apex tissue. The induction in apex tissue of a chilling-dependent poplar DEMETER-LIKE 10 (PtaDML10) DNA demethylase precedes shoot growth reactivation. Transgenic poplars showing downregulation of PtaDML8/10 caused delayed bud break. Genome-wide transcriptome and methylome analysis and data mining revealed that the gene targets of DEMETER-LIKE-dependent DNA demethylation are genetically associated with bud break. These data point to a chilling-dependent DEMETER-like DNA demethylase mechanisms being involved in the shift from winter dormancy to a condition that precedes shoot apical vegetative growth in poplar.


Advancement in Coronary Angiography or Percutaneous Coronary Intervention Using the Distal Transradial Artery Access in Acute Coronary Syndrome and Complex Coronary Artery Disease.
As the incidence of coronary heart disease increases annually, coronary angiography and percutaneous coronary intervention procedures are also increasing. The femoral artery and radial artery paths are commonly used for percutaneous coronary intervention, but their clinical application is limited to a certain extent due to many postoperative complications. The distal transradial access path is a new surgical path for coronary angiography and percutaneous coronary intervention. In this study, we reviewed the most relevant and recent articles related to distal transradial access and found that coronary angiography or interventional therapy using the distal transradial access path is safe and effective in patients with acute coronary syndrome and complex coronary artery disease. The distal transradial access path is expected to be the first choice for coronary angiography or percutaneous coronary intervention in patients with acute coronary syndrome and complex coronary artery disease.


Adhesion of Staphylococcus aureus to bovine mammary epithelial cells induced by growth in milk whey.
Staphylococcus aureus strains isolated from bovine intramammary infection (mastitis) were tested for adhesion to bovine mammary epithelial cells after growth in milk whey or TSB. Bacteria grown in milk whey adhered more efficiently to mammary gland epithelial cells in vitro than the corresponding homologous bacteria grown in TSB. Trypsin treatment of milk whey-grown S. aureus had no effect on their adherence. Whereas, pretreatment with periodate significantly decreased bacterial adherence capacity. Periodate treatment of TSB-grown bacteria had no effect on adhesion to the mammary gland epithelial cells.


Combination of bone marrow mesenchymal stem cells and cartilage fragments contribute to enhanced repair of osteochondral defects.
Cartilage tissue engineering using stem cells and biomaterials is considered a promising approach despite poor outcomes. We hypothesise that articular cartilage fragments provides native environmental cues to enhance stem cell differentiation. As such we evaluated the chondrogenic differentiation and repair of critical size defect in a human explant osteochondral model (OD) using bone marrow derived mesenchymal stem cells (BM-MSCs) and homogenised cartilage. BM-MSCs were established from the bone-marrow plugs of patients undergoing total knee arthroplasty and characterized. Osteochondral tissue was trimmed and a central drill defect (∼2mm) was made. Chondrogenic repair was evaluated by filling the OD defect area with either BM-MSCs (Group II), homogenized cartilage (Group III) or a combination of both BM-MSCs and homogenized cartilage (Group IV). OD with no added cell or tissue served as control (Group I). Samples were maintained in chondrogenic differentiation medium for 28 days. Microscopic images showed maximal OD closure in Group IV. Partial OD closure was observed in Group II and to a lesser extent in Group III. Haematoxylin-eosin staining revealed immature cartilaginous matrix in Group II and more mature matrix in Group IV. Sircol™ Assay showed increased collagen deposition in both Group II and Group IV. Immunostaining for both groups revealed positive staining for type II collagen. Combining BM-MSCs and homogenised cartilage demonstrated enhanced cartilage formation and defect filling in a human ex-vivo osteochondral model.


Effects of transforming growth factor beta 1 and L-ascorbate on synthesis and distribution of proteoglycans in murine osteoblast-like cells.
Proteoglycans synthesized by osteoblasts are incorporated into bone matrix and thought to play a role in bone metabolism. Transforming growth factor (TGF) beta affects the synthesis of matrix proteins, including proteoglycans, in various stromal cells, and proteoglycans, especially decorin, are associated with matrix collagen. In the present study, the effects of TGF-beta 1 and L-ascorbate, a factor essential for collagen synthesis, on the synthesis and distribution of proteoglycans were examined using murine osteoblast-like MC3T3-E1 cells. TGF-beta 1 stimulated the synthesis of proteoglycans in MC3T3-E1 cells. Among various proteoglycans, the synthesis of decorin was preferentially enhanced by TGF-beta 1, and the effect was more pronounced on secreted decorin compared to that associated with the cell/matrix layer. TGF-beta 1 also stimulated the initiation and elongation of the dermatan sulfate glycosaminoglycan chain, resulting in a larger molecular size of decorin. TGF-beta 1 influenced the synthesis of a heparan sulfate proteoglycan only slightly. L-ascorbate had no effect on the synthesis of proteoglycans, but increased those associated with the cell/matrix layer. Furthermore, when L-ascorbate was added to the culture along with TGF-beta 1, the percentage of proteoglycans associated with the cell/matrix layer increased from 25.8 +/- 1.0 to 41.0 +/- 0.5%. These data demonstrate that TGF-beta 1 markedly stimulates the synthesis of proteoglycans, especially decorin, mainly as a secreting form, that the accumulation of decorin into matrix is enhanced by L-ascorbate, and that the effects of TGF-beta 1 and L-ascorbate are additive.(ABSTRACT TRUNCATED AT 250 WORDS)


Hyperbaric oxygen therapy reduces visual field defect after macular hole surgery.
One of the serious complications that may arise after macular hole (MH) surgery is a temporal visual fields (TVF) defect. We hypothesized that hyperbaric oxygen (HBO) therapy improves the visual field (VF) in these patients. Vitrectomy for MH was performed on 73 eyes from 1994 to 1997. TVF defect was detected in 19 eyes and, of that 19, 12 patients were followed. Seven patients were treated with HBO therapy and 5 were controls. HBO was performed for approximately 110 minutes a day with 100% oxygen inhalation and a maximum of 2.8 atmospheric pressure. This continued for 20 days. The preoperative VF determined by kinetic perimetry was considered to be 100%, and the VF following HBO therapy was compared with that standard. We detected VF defect (postoperative VF area average 71.9+/-12.8% of the preoperative VF). In all 5 patients who had no HBO therapy, TVF defects remained, while the TVF recovered remarkably in all patients treated with HBO therapy. The VF recovered to 81.7+/-16.7% of the preoperative VF after 3 days of HBO, and to 91.6+/-15.8% months after HBO therapy. We speculated that the cause of TVF defect is likely to be chorioretinal circulation disturbance during surgery, and that HBO activates the retinal cells and improves VF. We conclude that HBO is useful in the treatment of TVF defect after macular hole surgery.


Citizen participation in health decision-making: past experience and future prospects.
Every couple of decades governments decide that they need to involve citizens more in public decision-making processes. The significant changes that have occurred over the past decade, including a growing loss of faith in the traditional institutions of government, have once again prompted political decision-makers to explore options for enhanced citizen participation. In the health care sector, reforms occurring during the 1990s were couched in terms such as "enhanced responsiveness," "improved accountability," and "increased citizen participation." In the new millennium, governments and regional health authorities have been relatively silent on this issue. As has been the case in the past, a wide range of opinions exist about what citizen participation is and how governments should proceed. Without either conceptual clarity or practical direction, governments have been slow to articulate what they hope to achieve or how they intend to get there. The purpose of this paper is to examine the concept of citizen participation within the context of a series of basic questions from which decision-makers might draw some policy relevance. Rather than taking a particular disciplinary perspective (i.e. health promotion), the authors have chosen to review a broad spectrum of existing literature to provide a better understanding of what is known about citizen participation, both good and bad. As such, the paper is meant to be a point of departure for an informed discussion of the possibilities for improved citizen participation in health (care) decision-making.


Risk factors for endemic Acinetobacter Baumannii colonization: A case-case study.
Acinetobacter baumannii causes increasingly resistant nosocomial infections worldwide. Although some patients are already colonized with A baumannii on hospital admission, others become colonized with endemic strains that are more likely to be antibiotic-resistant. Colonization increases risk of infection and transmission to others. This study aimed to identify risk factors for colonization with endemic compared to sporadic A baumannii among hospitalized patients. The study population were patients colonized with A baumannii at a single medical center during a 17-month period of active surveillance. Endemic A baumannii (cases) had a repetitive extragenic palindromic (REP) type that occurred 10 or more times during the surveillance period. Cases carrying 1 of the 5 endemic REP types were matched to comparison cases (controls) carrying sporadic strains by facility and time. There were 69 cases with REP-1, and 64 with REP-2-5. After adjustment, each unit increase in Schmid score was associated with a 70% increase in REP-1 carriage (P = .04) and a 50% increase in REP-2-5 (P = .07). Days in the intensive care unit prior to colonization, longer length of stay, immunosuppression, and the Charlson comorbidity index were not significantly associated with carriage of endemic strains. Following best practices for antibiotic stewardship and hygiene will help minimize the emergence and persistence of A baumannii strains adapted to the health care environment.


Job dynamics of veterinary professionals in an academic research institution. I. Retention and turnover of veterinary technicians.
The turnover of veterinary technicians within an animal resources program averaged 33% annually over 18 y, peaking at 67% in 1998 to 1999. Insufficient retention of veterinary technicians led to diversion of veterinarian effort to technical tasks and to increased allocation of administrative resources for supervising and managing an expanding team of veterinary technicians. To identify factors and trends related to poor retention, address any causes, and reduce turnover, a retrospective analysis of employment records was done. The retention of veterinary technicians was significantly greater for the 9 technicians hired from veterinary private practice rather than for any of 3 other general sources: promotions from the animal care staff, transfers from other research institutions, and miscellaneous sources. Veterinary technician turnover was reduced from a mean of 60% over 1995 to 1999 to an average of 26% during 2000 to 2004. Higher retention was associated with management practices that included renewed concentration on recruiting and interviewing strategies and emphasis on training and career development including merit raises for technician certification through the American Association for Laboratory Animal Science. Higher retention yielded correspondingly greater experience on the job as the mean tenure increased from 1.1 y in 2000 to 2.8 y in 2004. The most valued attributes related to employment by veterinary technicians as determined by survey were to do meaningful work, earn a good living, and have a committed team of coworkers.


Radiographic visualisation of seropositive rheumatoid arthritis in carriers of HLA-B27.
A group of 11 B27-positive, seropositive patients with rheumatoid arthritis was compared with 11 matched B27-negative seropositive patients. The radiographs of all limb joints, the sacroiliac joints, and the cervical spine were read blindly. Ten patients in each group were radiographed 2-6 times during observation periods of 3-13 years; one patient in each group was only examined once. The prevailing picture of both groups was that of progressive erosive rheumatoid arthritis, although two small differences were found: Erosions of the apophyseal joints of the cervical spine and slight periosteal new bone formation of the shoulder, hip, and knee regions occurred more often in the B27-positive than in the B27-negative group.


Abrogation of the fibrotic effect of transforming growth factor-beta in dermal wound healing.
The growth factor, transforming growth factor-beta1, which under normal circumstances promotes wound healing by stimulating local fibroblasts to produce collagen and other extracellular matrix proteins, has also been implicated as the primary causative agent of fibrosis. Because transforming growth factor-beta1 is capable of stimulating its own production by fibroblasts, its normally beneficial effects may become amplified to the point where excess extracellular matrix accumulation occurs, thereby causing abnormal scarring. Therefore, strategies that block or counter the effects of transforming growth factor-beta1 may be useful in preventing or decreasing fibrosis. One such strategy is the use of glucocorticoid steroids such as dexamethasone, which normally have the opposite effect of transforming growth factor-beta1, namely the impairment of wound healing. When used in conjunction with transforming growth factor-beta1, glucocorticoid steroids may normalize the effect of transforming growth factor-beta1 on collagen synthesis, thereby reducing excessive collagen deposition and fibrosis.


Metabolomic LC-MS/MS analyses and meta 16S rRNA gene analyses on cecal feces of Japanese rock ptarmigans reveal fundamental differences between semi-wild and captive raised individuals.
Ex situ conservation of Japanese rock ptarmigans began in 2015 with the aim of reintroducing artificially raised birds into their original habitat. However, the current raising method in captivity seems insufficient in terms of the survivability of artificially raised birds in natural conditions. Feeding management is one potential reason for such insufficiency. In this study, we performed a comprehensive analysis of the hydrophilic metabolites by LC-MS/MS for the cecal feces of Japanese rock ptarmigans under in situ and ex situ conservation to reveal their gut chemical environment. We also analyzed the developmental processes of cecal microbiomes both in situ semi-wild and ex situ captive individuals. Metabolites of nucleic acid were rich in the in situ individuals, and free amino acids were rich in the ex situ individuals. The differences in the microbiome composition between in situ and ex situ individuals were also pronounced; major genera of in situ individuals were not detected or few in ex situ individuals. The alpha diversity of the cecal microbiome of semi-wild chicks at 1 week of age was almost the same as that of their hens, while it was very low in captive individuals. Sub-therapeutic use of oxytetracycline, a diet rich in protein and energy, and isolation from adult birds are considered to be causes for these great differences in gut chemical and microbiological environment between in situ and ex situ individuals.


Cognitive and non-cognitive factors associated with posttraumatic stress symptoms in mothers of children with type 1 diabetes.
The experience of having a child diagnosed with type 1 diabetes mellitus (T1DM) can negatively impact on the mother's well-being and trigger posttraumatic stress symptoms. To date, only one study has examined the role of non-cognitive factors in predicting the occurrence of PTSD in parents of children diagnosed with diabetes. However, in the broader PTSD literature is has been shown that both non-cognitive variables and cognitive variables predict PTSD in traumatized populations. The current study aimed to investigate the relationship of both non-cognitive (trauma severity, psychiatric history and social support) and cognitive variables (negative cognitive appraisals and dysfunctional cognitive appraisals) with PTSD in mothers of children recently diagnosed with diabetes. A single group survey design and self-report questionnaires were used to investigate the relationship between both non-cognitive (trauma severity, psychiatric history and history of trauma, and social support) and cognitive factors (negative cognitive appraisals and dysfunctional strategies) and PTSD symptoms in mothers of children who had been diagnosed with type 1 diabetes in the last 5 years. All cognitive variables were positively associated with PTSD symptoms. In contrast, of the non-cognitive variables, only social support was significantly (negatively) associated with PTSD symptoms. Moreover, regression analysis found that cognitive variables explained variance in PTSD symptoms over and above that contributed by the non-cognitive variables. This supports the cognitive model of PTSD. The implications of the study with regards to early detection of and therapies for PTSD in this population are discussed.


Photoluminescence and spectroelectrochemistry of single ag nanowires.
We present strong photoluminescence from single Ag nanowires (NWs), their disordered blinking behavior, and their dependence on substrate potential. The stochastic bursts (<10 ms) in the photoluminescence trajectories of single Ag NWs in air are observed and attributed to the photoactivated fluorescence silver clusters. The dynamic changes in the photoluminescence are analyzed using autocorrelation function, statistical analysis of the stochastic durations, and probability density function to reveal the disordered nature of the spontaneous photochemical reaction at each individual Ag NWs under laser irradiation. Stable PL is observed for single Ag NWs in alkaline electrolyte and is found to be highly dependent on the electrochemical potential. The PL from single Ag NWs is found to be weakly dependent on polarization direction of the incident light and strongly dependent on the interactions with adjacent NWs.


A case of primary progressive aphasia. A 14-year follow-up study with neuropathological findings.
Primary progressive aphasia has been clinically defined as a progressive language deficit leading to the dissolution of almost all language functions with relative preservation of other cognitive functions until late in the course of the disease. Two types of language impairment have been described for primary progressive aphasia, which differ with respect to the degree of fluency of spontaneous speech. Whereas some authors have emphasized non-fluency as a defining characteristic of primary progressive aphasia, others have proposed that phonemic rather than semantic paraphasias in naming, both in the fluent and the non-fluent subtype, should be used as a criterion to distinguish primary progressive aphasia from slowly progressive aphasia in other forms of degenerative brain disease. Patients with fluent speech and semantic dementia, as typically seen in Alzheimer's disease, produce semantic paraphasias and circumlocutions rather than phonemic errors in naming. This paper reports the long-term follow-up of a patient with fluent aphasic speech, whose language profile over a decade was similar to that of patients with semantic dementia. Neuropathological examination revealed no evidence of Alzheimer's disease. Pick's disease or Pick variant, but showed spongiform changes of cortical layers (II and III) in temporal and, less severely, in frontal gyri. The present case indicates that semantic dementia is not a reliable indicator of probable Alzheimer's disease and supports the notion that there are different subtypes of primary progressive aphasia which cannot be defined by fluency or by the presence of phonemic paraphasia. Progress in identifying the neuropathological correlates of these subtypes in cases with lobar atrophy and spongiform changes should be expected from hereditary variants of progressive disorder.


Incidence and Causes of Intentional Fetal or Neonatal Demise in Twin-Twin Transfusion Syndrome.
The aim of this study is to evaluate the incidence and causes of intentional fetal and neonatal demise in twin-twin transfusion syndrome (TTTS). All TTTS pregnancies managed at our centre between 2000 and 2014 were included. We evaluated incidence and causes of intentional fetal/neonatal demise, defined as termination of pregnancy, selective fetal reduction, or withdrawal of neonatal intensive care. Intentional fetal/neonatal demise occurred in 9.8% (110/1,122) of fetuses and was due to termination of pregnancy (2.2%), selective fetal reduction (4.2%), or withdrawal of neonatal intensive care (3.4%). Reasons for termination of pregnancy included complications of laser treatment (72.0%), severe fetal anomaly (20.0%), and unwanted pregnancy (8.0%). Reasons for selective fetal reduction were technical difficulties to perform laser surgery (51.1%), fetal complications (38.3%), and parental preference for fetal reduction rather than laser treatment (10.6%). Reasons for withdrawal of neonatal intensive care treatment were severe cerebral injury (47.4%), severe pulmonary complications (15.8%), birth asphyxia (5.3%), multiple complications of TTTS and/or prematurity combined (21.1%), or other (10.5%). Intentional fetal or neonatal demise in TTTS occurs frequently and is often due to complications after laser surgery and/or severe (cerebral) injury in affected fetuses or neonates.


Ultrastructure of spindle cell squamous carcinoma.
A 63-year-old white male presented with a nine-month history of a nontender ulcerated lesion on his ear. Light microscopy demonstrated a moderately well circumscribed lesion in the dermis which abutted upon epidermis. There was no evidence of continuity between the tumor and overlying epithelium. The tumor was very cellular with an admixture of cells - spindle, polyhedral and bizarre giant cells. Mitotoc figures were abundant and frequently abnormal. We interpreted this lesion to have the clinical and pathologic features of an atypical fibroxanthoma (AFX). Ultrastructure, however, showed abundant tonofilaments and desmosomes indicative of an epithelial origin and therefore most consistent with a spindle cell squamous carcinoma (SCSC). It is urged that, when possible, electron microscopy be performed on problematic cases diagnosed either as an AFX or spindle cell squamous carcinoma since it is the most valid basis on which a correct diagnosis can be made.


Engineering a sandwiched Si/I/LNOI structure for 180-GHz-bandwidth electro-optic modulator with fabrication tolerances.
Electro-optical modulators are essential for scalable photonic integrated circuits and are promising for many applications. The convergence of silicon (Si) and lithium niobate (LN) allows for a compact device footprint and large-scale integration of modulators. We propose a sandwiched Si/I/LNOI modulator for broad modulation with CMOS-compatible fabrication tolerances. There is a thin film SiO2 spacer sandwiched between Si and LN, which is engineered to tailor optical and electrical properties and enhance index matching. Moreover, the SiO2 spacer is also exploited to inhibit the radiation loss induced by mode coupling. The modulator shows a bandwidth of ∼180 GHz with a halfwave voltage of 3 V. Such a device is considerably robust to the fabrication deviations, making it promising for massive and stable manufacturing.


Synthesis and biological activity of beta-ionone-derived alcohols for cancer chemoprevention.
Secondary products of plant mevalonate metabolism suppress the synthesis of mevalonate, the rate-limiting intermediate in the biosynthesis of isoprenoid derived compounds that stimulate cell proliferation. They exert their inhibitory action by the suppression of the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR). They exhibit low toxicity and have proven their efficacy in animal cancer chemoprevention studies but their growth inhibitory activities leave room for improvement. We have chosen beta-ionone (1) as a lead compound for the development of more potent inhibitors of mevalonate pathways. A series of ionone-derived alcohols have been synthesized and tested on an in-vitro model system (B16F10 mouse melanoma). We have found several derivatives which show higher growth inhibitory properties and are promising candidates for further improvement of activity.


Atypical Presentation of Lip Nodules in Clinically Diagnosed Juvenile Hyaline Fibromatosis.
Juvenile hyaline fibromatosis (JHF) is a rare, hereditary disease characterized by abnormal hyaline deposits within the skin, soft tissues, joints, and bones. The condition itself is often debilitating, with no curative treatment available. A definitive diagnosis is established by genetic testing. However, the hallmarks of gingival hypertrophy, subcutaneous scalp nodules, and joint contractures can be used as a clinical guide when genetic testing is unavailable. Here, we report an unusual case of a five-year-old child clinically diagnosed with juvenile hyaline fibromatosis with atypical nodules exclusively confined to the perioral region.


Haemophilus influenzae cellulitis of the extremities.
A brief case report is described of a 10-month-old male with Haemophilus influenzae cellulitis of the upper extremity. A review of the literature concerning this pathogen in extremity cellulitis follows, with discussion of epidemiology, site of infection, response to therapy, and possible pathogenesis.


ORL nursing: where we have been and where we are going.
In 1873, formal training for nurses in the United States began on the east coast with the formation of hospital-based schools (Schoor & Kennedy, 1999). Upon completion of the two to three year program, graduate nurses took positions in private homes as private duty nurses. Hospitals needed only a few supervisory nurses since student nurses provided most of the patient care. The popularity of private duty nursing continued for many years and was slowly replaced by hospital staff nursing in the 1930s. This article provides an overview of ORL nursing and the advent of certification in ORL specialty nursing.


Social Determinants of Cardiovascular Risk, Subclinical Cardiovascular Disease, and Cardiovascular Events.
Background Although there is research on the impact of social determinants of health (SDOHs) on cardiovascular health, most existing evidence is based on individual SDOH components. We evaluated the impact of cumulative SDOH burden on cardiovascular risk factors, subclinical atherosclerosis, and incident cardiovascular disease events. Methods and Results We included 6479 participants from the MESA (Multi-Ethnic Study of Atherosclerosis). A weighted aggregate SDOH score representing the cumulative number of unfavorable SDOHs, identified from 14 components across 5 domains (economic stability, neighborhood and physical environment, community and social context, education, and health care system access) was calculated and divided into quartiles (quartile 4 being the least favorable). The impact of cumulative SDOH burden on cardiovascular risk factors (hypertension, diabetes, dyslipidemia, smoking, and obesity), systemic inflammation, subclinical atherosclerosis, and incident cardiovascular disease was evaluated. Increasing social disadvantage was associated with increased odds of all cardiovascular risk factors except dyslipidemia. Smoking was the risk factor most strongly associated with worse SDOH (odds ratio [OR], 2.67 for quartile 4 versus quartile 1 [95% CI, 2.13-3.34]). Participants within SDOH quartile 4 had 33% higher odds of increased high-sensitivity C-reactive protein (OR, 1.33 [95% CI, 1.11-1.60]) and 31% higher risk of all cardiovascular disease (hazard ratio, 1.31 [95% CI, 1.03-1.67]), yet no greater burden of subclinical atherosclerosis (OR, 1.01 [95% CI, 0.79-1.29]), when compared with those in quartile 1. Conclusions Increasing social disadvantage was associated with more prevalent cardiovascular risk factors, inflammation, and incident cardiovascular disease. These findings call for better identification of SDOHs in clinical practice and stronger measures to mitigate the higher SDOH burden among the socially disadvantaged to improve cardiovascular outcomes.


Hearing Screening Alternative Using a Website-Based Application.
Indonesians encounter several barriers to regular functional hearing assessment. Hearing loss screening is only provided by tertiary-care hospitals that are not reachable by people in remote regions. This study aimed to develop a website-based hearing screening application that is accessible and inexpensive. Subjects and. This comparative study was conducted between July and August 2022 in the Otolaryngology Clinic of Muhammadiyah Bandung Hospital with noise levels below 50 dB. The hearing screening was conducted using a website-based application (www.Screenout.id) and audiogram as the gold standard method. On ScreenOut, patients heard sounds with frequencies at 500, 1,000, 2,000, 4,000, and 8,000 Hz and sound intensity of each frequency at 35, 55, and 75 dB using earphones. A total of 133 participants were enrolled in our study. ScreenOut showed high sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (90.9%, 98.9%, 93.6%, 99.4%, and 84.8%, respectively). Regarding hearing threshold, a very strong correlation was found between ScreenOut and audiogram, ranging between r=0.843 and r=0.899. Aside from that, there was no significant difference in hearing threshold values between ScreenOut and audiogram. Many advantages of the ScreenOut were found, including low-cost, accessibility, and easy-to-use interface, making it favorably used in low-middle-income countries such as Indonesia.


Teaching fidelity.
Working therapeutically with individuals or couples either following an affair or prior to its occurrence requires teaching them about risks to monogamy and the challenges of recovering from infidelity. Risks to monogamy include cultural myths about both infidelity and marriage that may be shared not only by lay persons, but also by their ill-informed therapists. Exacerbating risks to fidelity are physiological components of emotional and physical attraction that contribute to cognitive and affective disorientation. Therapists can promote fidelity and recovery from infidelity by attending to the fundamental tasks of modeling compassion, debunking myths regarding infidelity, confronting individuals with their own choices, promoting emotional closeness, and helping individuals to understand both their own and their partner's learned attitudes that distract them from maintaining a faithful marriage. Several cases illustrate these fundamental therapeutic tasks.


Histopathologic analysis of transjugular intrahepatic portosystemic shunts.
This prospective study was undertaken in 17 patients treated with 22 transjugular intrahepatic portosystemic shunt (TIPS) procedures and aimed to evaluate the nature and causes of short- and long-term shunt abnormalities. Specimens were collected after autopsy in 6 patients and after liver transplantation in 11 patients; the time from shunting ranging from 4 to 385 days. During the first 2 weeks the shunt surface was covered by poorly organized fibrin platelet clots that were mixed with inflammatory and red blood cells. Thereafter, a pseudointima developed, initially made of loose granulation tissue that was formed by edema, myofibroblasts, neo-capillaries, collagen fibers, and inflammatory cells. This pseudo-intima extended with time as the myofibroblasts increased in number, as the collagen fibers thickened, and as the inflammatory cells grew more scarce. Its thickness ranged from 50 to 3,500 microm, the maximal values being observed in the middle of the shunt. The shunt was obstructed by a clot in 4 patients (18%). In 7 shunts (31.8%) the pseudo-intima was thicker than 1,000 microm and was referred to as hyperplastic pseudo-intima. It showed more dense inflammatory infiltrate and anarchic deposition of more scarce collagen fibers. Pseudo-intima hyperplasia was associated with previously diagnosed thrombosis, which had been treated by dilatation in 2 cases and by biliary deposits in 3 cases, while it remained unexplained in 2 cases. Accordingly, this study confirms the following: 1) that early TIPS obstruction results from thrombosis; 2) that 2 weeks after insertion, the stent is covered by a smooth pseudo-intima; 3) that thereafter, pseudo-intimal hyperplasia is the main cause of TIPS stenosis or occlusion; and 4) that biliary secretions and previous thrombosis could be important triggering mechanisms for this pseudo-intima overgrowth.


Comparison of symptoms of younger and older patients undergoing coronary artery bypass surgery.
Little is known about the symptom experience throughout the trajectory of recovery for patients after coronary artery bypass surgery (CABS). This study investigates the preoperative and postoperative symptoms experienced by younger (< 65 years) and older (> or = 65 years) patients (N= 102) who had undergone CABS. Reported preoperative symptoms were angina, shortness of breath, dizziness, and sweating. At 1 week post-CABS, symptoms were incisional pain, wound drainage, chest congestion, shortness of breath, dizziness, sweating, swollen feet, and loss of appetite; incisional pain and swollen feet were reported by a few patients at 6 weeks after CABS. The incidence and frequency of postoperative symptoms declined over time. There were several age-related differences in symptom reports prior to and at 1 and 6 weeks after the procedure. Such information can be used to plan the care of patients undergoing CABS, to prepare them for normal recovery, and to determine the need for symptom management by health care providers.


Memory Effects of Ion-Selective Electrodes: Theory and Computer Simulation of the Time-Dependent Potential Response to Multiple Sample Changes.
A straightforward theoretical description of the time-dependent response of ion-selective membrane electrodes to multiple sample changes is presented. The derivation makes use of an approximation for the ion fluxes in the membrane, and of the superposition of partial fluxes induced by the step-changes. The general theory allows for any number of samples and ions. It is applied for the analysis of memory effects that reflect the influence of preceding samples on subsequent measurements. Various phenomena are discussed, including super-, near-, or sub-nernstian responses, shifts of apparent reference potentials, and potential dips with domains of reversed slopes. The theoretical results agree well with virtual experiments based on computer simulation.


[What Enhances Teachers' Health at Inclusive Primary Schools? A Mixed-Methods Approach].
Teachers' suggestions to enhance their health at inclusive primary schools ("Schwerpunktgrundschulen") were analyzed by quantitative content analysis taking personal or job-related parameters of effort and strain into consideration. The paper and pencil cross-sectional study was conducted by Institut für Lehrergesundheit (IFL) between August 2013 and April 2015 at 14 schools in Rhineland-Palatinate. Overall response rate was 46.3% (143/309 teachers). The answers to the open-ended question "Which concrete job-related measures would enhance your wellbeing or health situation at your work place?" was categorized and quantified. An analysis of the item-non-response was undertaken. The aim was to identify by logistic regression, personal or job-related parameters of effort or strain associated with a specific category. Data from 143 teachers were analyzed. 79 teachers made 362 suggestions to enhance the health situation at their work place. Making a suggestion was not related to socio-demographic parameters. 33.6% of the teachers addressed physical environmental conditions of work, e. g., climatic or acoustic conditions or the availability of space for recreation. 29.4% of the teachers made suggestions concerning human resource strategy (e. g., "double teaching"). 9.1% of the teachers referred to aspects of relationships with colleagues. After regression analysis, there were relationships between suggestions of single categories and specific job-related parameters of effort. Furthermore, teachers under (high) strain - here: teachers who (very) strongly experienced their work as hazardous to health - showed significantly higher odds to make suggestions of the categories "Colleagues" (aOR 3.71; 95%CI 1.00-13.76) or "External Support" (e. g., "supervision") (aOR 3.92; 95%CI 1.15-13.41) than teachers experiencing less stress. Teachers of inclusive primary schools are ready to take active part in health-related organizational development. The development of problem- and group-specific measures of intervention will be facilitated by the combined analysis of qualitative and quantitative data.


[SSR markers linked with early stability in rice].
One hundred and thirty hybrids derived from the crosses between nine rice strains stabilized in early generation and seven cultivars (Oryza sativa L.). In their F2 populations, 32 uniform strains of different agronomic traits were observed. In the same combination of these uniform strains,there were strains segregating in the Mendelian manner. SSR markers analysis showed that F2 and F3 populations of the uniform strains and their F1 plants displayed the same markers indicating all the uniform strains were homozygous. All the marker bands of parents were simultaneously present on their progeny chromosomes, indicating that the uniform strains must true hybrid origin. The SSR markers of F2 population of segregating strains and their F1 plants showed that the segregating strains were heterzygosity. SSR marker band sites of RM276, RM258, RM248 and RM1 loci in most uniform strains presented at high frequencies bands site different from their parent's. We suggested that during the gamete formation,the genes that linked to ga-1, Rf and ga-8 mutated at certain frequency,and followed by a somatic meiosis of the fecundated zygote. Thus a haploid cell may develop into a homozygous embryo,and the F1 plant was homozygous and the progeny stabilized in early generation.


Suppression of the macrophage proteasome by ethanol impairs MHC class I antigen processing and presentation.
Alcohol binge-drinking (acute ethanol consumption) is immunosuppressive and alters both the innate and adaptive arms of the immune system. Antigen presentation by macrophages (and other antigen presenting cells) represents an important function of the innate immune system that, in part, determines the outcome of the host immune response. Ethanol has been shown to suppress antigen presentation in antigen presenting cells though mechanisms of this impairment are not well understood. The constitutive and immunoproteasomes are important components of the cellular proteolytic machinery responsible for the initial steps critical to the generation of MHC Class I peptides for antigen presentation. In this study, we used an in-vitro cell culture model of acute alcohol exposure to study the effect of ethanol on the proteasome function in RAW 264.7 cells. Additionally, primary murine peritoneal macrophages obtained by peritoneal lavage from C57BL/6 mice were used to confirm our cell culture findings. We demonstrate that ethanol impairs proteasome function in peritoneal macrophages through suppression of chymotrypsin-like (Cht-L) proteasome activity as well as composition of the immunoproteasome subunit LMP7. Using primary murine peritoneal macrophages, we have further demonstrated that, ethanol-induced impairment of the proteasome function suppresses processing of antigenic proteins and peptides by the macrophage and in turn suppresses the presentation of these antigens to cells of adaptive immunity. The results of this study provide an important mechanism to explain the immunosuppressive effects of acute ethanol exposure.


Applications of the universal DNA microarray in molecular medicine.
Integration of molecular medicine into standard clinical practice will require the availability of diagnostics that are sensitive, rapid, and robust. The backbone technology underlying the diagnostic will likely serve double duty during clinical trials in order to first validate the biomarkers that contribute to both drug response and disease stratification. PCR/LDR/Universal DNA microarray is a promising technology to help drive the transition from the current paradigms of clinical decision making to the new era of personalized medicine. By uncoupling the mutation detection step from array hybridization, this technology becomes fully programmable. It exploits full use of the sensitivity that the ligase detection reaction can provide, while maintaining a rapid read out on a universal microarray. Thus, PCR/LDR/Universal DNA microarray is 50-fold more sensitive and 10-fold more rapid than conventional hybridization-only arrays. The intent of this article is to provide investigators with a perspective on current uses of this approach, as well as to serve as a practical guide to implementation.


Benzotriazole and tolyltriazole as aquatic contaminants. 1. Input and occurrence in rivers and lakes.
The complexing agents benzotriazole (BT) and tolyltriazole (TT) are not only widely applied as anticorrosives, e.g., in aircraft deicer and anti-icer fluid (ADAF), but they are also used for so-called silver protection in dishwasher detergents. Due to their low biodegradability and limited sorption tendency, BT and TT are only partly removed in wastewater treatment. Residual concentrations of BT and TT were determined in ambient surface waters in Switzerland including 7 rivers which have distinct water flows and receive treated wastewater effluents at various dilution ratios. A maximum BT concentration of 6.3 microg/L was found in the Glatt River, and a maximum mass flow of 277 kg BT per week was observed in the Rhine River. In most cases, TT was about a factor 5-10 less abundant. During winter 2003/4, BT mass flows at 2 locations in the lower stretch of the Glatt River clearly indicated the input from nearby Zurich airport, where BT was applied as an anticorrosive ADAF component. BT concentrations measured in the three lakes Greifensee, Lake Zurich, and Lake Geneva were approximately 1.2, 0.1-0.4, and 0.2 microg/L, respectively. The observed environmental occurrences indicate that BT and TT are ubiquitous contaminants in the aquatic environment and that they belong to the most abundant individual water pollutants.


Differential scanning calorimetric study of the thermal stability of xylanase from Streptomyces halstedii JM8.
The thermal stability of two xylanases with molecular masses of 45 (Xys1L) and 35 (Xys1S) kDa has been characterized thermodynamically by high-sensitivity scanning microcalorimetry in the pH range 3.0-9.0. Thermal denaturation of Xys1L reveals three thermodynamically independent domains, and that of Xys1S, which is a proteolytic fragment of Xys1L (without a C-terminal part), reveals two thermodynamically independent domains, each of which follows a two-state thermal unfolding process under our experimental conditions. Nevertheless, the thermodynamic parameters of unfolding for each domain do not fit some of the correlations obtained for most compact globular proteins. It is known that if delta Hres(T) and delta Sres(T) are plotted against temperature for a number of water-soluble compact globular proteins, they all have a common value at approximately 110 degrees C (383 K). Calculation of the variations in the enthalpy and entropy of unfolding per residue for each domain of xylanase with temperature gave us delta Hres(383) and delta Sres(383) values of approximately 3 kcal/(mol of residue) and 9 cal/(K.mol of residue), respectively. This is practically 2-fold larger than those apparent for most medium-sized globular protein values. These discrepancies might be related to features of the folded and/or unfolded states of the protein.


The interaction between alcohol and the residual effects of thiopental anesthesia.
During ambulatory surgery, barbiturates, such as thiopental, may impair psychomotor performance several hours after administration. It was hypothesized that if patients drink alcohol 4 h after thiopental injection, the increase in psychomotor impairment would be greater than that seen after alcohol ingestion alone. Twelve healthy men volunteered to participate in a double-blind, placebo-controlled, crossover study with a Latin square design. On each testing day, the subjects received intravenous injections of either 5 mg/kg of 2.5% thiopental or an equal volume of saline for 30 s. Four hours after injection, the subjects consumed a beverage with or without 0.7 g/kg alcohol. Psychomotor performance and mood were assessed at five times: prior to injection, at 1 h and 3 h after injection, and at 1 h and 3 h after consumption of beverage. Both thiopental and alcohol had strong independent effects on the dependent measures in this study. In addition, body sway, one of the nine psychomotor tests used to assess impairment, was greater after thiopental and alcohol than after alcohol alone. Of eleven adjectives used to assess mood, lightheadedness was cited most frequently after a combination of thiopental and alcohol than after each alone. Based on our tests of performance and mood, an interaction between thiopental and alcohol is evident; in addition, the interaction between both drugs may exert deleterious effects on higher levels of central nervous system integration.


[The value of diuretics in monotherapy of hypertension].
To represent the usefulness of thiazide diuretics as monotherapy of primary hypertension. Moderate doses of thiazide diuretics can produce a reduction in blood pressure equal to that of beta blockers, calcium antagonists and ACE inhibitors, and achieve an equally high response rate. The advantages and disadvantages of the specific action profile of these diuretics are described. Discussions about the reduction in cardiovascular mortality is represented and practical conclusions drawn. The specific indications for monotherapy with thiazide diuretics include systolic, diastolic and isolated systolic hypertension in the elderly hypertensive, and hypertension in NYHA III and IV cardiac insufficiency. Suggestions for their use in practice are given.


Unusual spin dynamics in topological insulators.
The dynamic spin susceptibility (DSS) has a ubiquitous Lorentzian form around the Zeeman energy in conventional materials with weak spin orbit coupling, whose spectral width characterizes the spin relaxation rate. We show that DSS has an unusual non-Lorentzian form in topological insulators, which are characterized by strong SOC, and the anisotropy of the DSS reveals the orientation of the underlying spin texture of topological states. At zero temperature, the high frequency part of DSS is universal and increases in certain directions as ω(d-1) with d = 2 and 3 for surface states and Weyl semimetals, respectively, while for helical edge states, the interactions renormalize the exponent as d = 2K - 1 with K the Luttinger-liquid parameter. As a result, spin relaxation rate cannot be deduced from the DSS in contrast to the case of usual metals, which follows from the strongly entangled spin and charge degrees of freedom in these systems.


Elevation of circulating proadrenomedullin-N terminal 20-peptide in thyrotoxicosis.
Adrenomedullin (AM) is a recently discovered peptide which has potent vasodilatory activity. We have found that the plasma adrenomedullin level is elevated in hyperthyroidism, suggesting a potential role of AM in the decrease of vascular resistance in thyrotoxicosis. Proadrenomedullin, a precursor of adrenomedullin, yields another peptide termed proadrenomedullin-N terminal 20-peptide (PAMP). PAMP also has potent vasodilatory activity. Although the regulation of secretion of AM and PAMP is not fully understood and the mechanism by which the plasma AM level is elevated in hyperthyroidism remains unknown, it is of interest to determine the plasma concentration of PAMP in thyrotoxicosis. We measured the plasma concentration of immunoreactive AM and PAMP in newly recruited untreated thyrotoxic Graves' patients using specific antibodies to each peptide. Not only AM, but also the plasma concentration of PAMP in thyrotoxic patients was significantly (P < 0.01) elevated (4.7 +/- 0.9 pmol/l), compared to that in control subjects (2.6 +/- 0.8 pmol/l). The correlation was marginally significant between the plasma AM concentration and serum free thyroid hormone levels. The plasma PAMP level tended to be more elevated when thyrotoxicosis was severe but the correlation was not statistically significant. Correlation was not demonstrated between the AM and PAMP levels in thyrotoxic patients. Elevation of the plasma adrenomedullin and proadrenomedullin-N terminal 20-peptide levels raises the possibility of involvement of these vasodilatory peptides in the haemodynamic changes in thyrotoxicosis.


[Spinal epidural cavernous angioma. Apropos of 2 cases. Review of the literature].
We report 2 cases of spinal epidural cavernous angiomas revealed by paraplegia, and present the main cases reported in the literature since 1895. The diagnosis of this uncommon affection seems to be difficult to establish only upon clinical and radiological features. In spite of recent advances in neuroradiological imaging, these kinds of angiomas still remain an operative and histopathological discovery. A laminectomy was performed revealing a vascular lesion which was totally extirpated. Functional recovery was achieved in both cases.


Phage-like packing structures with mean field sequence dependence.
Packing of double-stranded DNA in phages must overcome both electrostatic repulsions and the problem of persistence length. We consider coarse-grained models with the ability to kink and with randomly generated disorder. We show that the introduction of kinking into configurations of the DNA polymer packaged within spherical confinement results in significant reductions of the overall energies and pressures. We use a kink model which has the ability to deform every 24 bp, close to the average length predicted from phage sequence. The introduction of such persistence length defects even with highly random packing models increases the local nematic ordering of the packed DNA polymer segments. Such local ordering allowed by kinking not only reduces the total bending energy of confined DNA due to nonlinear elasticity but also reduces the electrostatic component of the energy and pressure. We show that a broad ensemble of polymer configurations is consistent with the structural data. © 2016 Wiley Periodicals, Inc.


Age, male gender, and atrial fibrillation predict lower extremity amputation or revascularization in patients with peripheral artery diseases: a population-based investigation.
By using the National Health Insurance (NHI) claim data of Taiwan, we sought to determine the predictors for nontraumatic lower extremity amputation (LEA) or peripheral revascularization procedures (PRP) in patients with peripheral artery disease (PAD). From the NHI claim data, we identified 12,206 patients with newly diagnosed PAD between 1998 and 2008, and followed them up to 2008. We explored the age, gender, and whether the patients had concomitant comorbid conditions, such as diabetes mellitus (DM), hypertension (HTN), atrial fibrillation (AF), stroke, hospitalization for coronary artery disease (CAD), myocardial infarction (MI), or heart failure (HF), and whether they were taking cilostazol at the time of recruitment. We searched for clinical parameters that might be important determinants for LEA or PRP in the study population. Of the 12,206 patients, 150 (1.2%) were found to undergo either LEA or PRP or both (LEA 81, PRP 53, both PRP and LEA 16). Old age, male gender, and history of hospitalization for CAD or MI and AF were found to be risk predictors for both procedures. Patients with DM were at lower risk for PRP (odds ratio 0.418, p = 0.001). Patients who were taking cilostazol had higher risk for LEA or PRP. HTN was not a risk predictor for LEA or PRP. From this nationwide study, we found that among PAD patients in Taiwan, age, male gender, AF, and hospitalization for CAD or MI are risk predictors for future LEA or PRP. DM is a negative predictor for PRP while both DM and HTN are not risk predictors for LEA.


On predator-prey systems and small-gain theorems.
This paper deals with an almost global convergence result for Lotka-Volterra systems with predator-prey interactions. These systems can be written as (negative) feedback systems. The subsystems of the feedback loop are monotone control systems, possessing particular input-output properties. We use a small-gain theorem, adapted to a context of systems with multiple equilibrium points to obtain the desired almost global convergence result, which provides sufficient conditions to rule out oscillatory or more complicated behavior that is often observed in predator-prey systems.


[Study of the effect of JNK signal transduction pathway in intense noise-induced apoptosis in cochlea of guinea pig].
To investigate the mechanism of intense noise-induced cochlea cells death in guinea pig, and the effect of JNK signal transduction pathway in the procedure of cochlea cells apoptosis by intense noise-induced. Thirty-two guinea pigs were randomly divided into 4 groups. The guinea pigs in the experiment groups were exposed to 4 kHz narrow band noise at 120 dB SPL for 4 h. After the noise expose for 1, 4, 14 days of the experiment guinea pigs, ABR of the guinea pigs on experiment and control groups were tested before put them to death. Four guinea pig's cochleas of every group were taken to paraffin section, and the rest was extracted the total cochlear's protein. Apoptosis was tested by terminal deoxynucleotidyl Transferase (TdT)-mediated deoxyuridine triphosphate (d-UTP) nick and labeling method (TUNEL). The phosphorylation of JNK and c-Jun were tested by immunohistochemistry and western blot methods. Tunel-Positive cells in the Corti's, SGC and SV of experiment groups, and there have significant differences compared with the control group (P<0.01) and Tunel-Positive cells are most in 1 d experiment group. The positive cells of P-JNK and P-c-Jun could be detected in guinea pig's cochleas after noise exposed, but no positive cells were found in the control. Protein levels of P-JNK and P-c-Jun were risen up and activated quickly after noise exposed, and achieved peak in 1 d, 4 d and then fallen-offs, but still maintained higher levels within 14 d. Intense noise causes cochlea cell lesion by inducing apoptosis to result in and JNK signal transduction pathway plays an important role in the procedure of apoptosis.


Comparative analysis of the in vivo kinetic properties of various bone substitutes filled into a peri-implant canine defect model.
Deproteinized bovine bone or synthetic hydroxyapatite are 2 prevalent bone grafting materials used in the clinical treatment of peri-implant bone defects. However, the differences in bone formation among these materials remain unclear. This study evaluated osteogenesis kinetics in peri-implant defects using 2 types of deproteinized bovine bone (Bio-Oss® and Bio-Oss/Collagen®) and 2 types of synthetic hydroxyapatite (Apaceram-AX® and Refit®). We considered factors including newly generated bone volume; bone, osteoid, and material occupancy; and bone-to-implant contact. A beagle model with a mandibular defect was created by extracting the bilateral mandibular third and fourth premolars. Simultaneously, an implant was inserted into the defect, and the space between the implant and the surrounding bone walls was filled with Bio-Oss, Bio-Oss/Collagen, Apaceram-AX, Refit, or autologous bone. Micro-computed tomography and histological analyses were conducted at 3 and 6 months postoperatively (Refit and autologous bone were not included at the 6-month time point due to their rapid absorption). All materials demonstrated excellent biocompatibility and osteoconductivity. At 3 months, Bio-Oss and Apaceram-AX exhibited significantly greater volumes of formation than the other materials, with Bio-Oss having a marginally higher amount. However, this outcome was reversed at 6 months, with no significant difference between the 2 materials at either time point. Apaceram-AX displayed notably slower bioresorption and the largest quantity of residual material at both time points. In contrast, Refit had significantly greater bioresorption, with complete resorption and rapid maturation involving cortical bone formation at the crest at 3 months, Refit demonstrated the highest mineralized tissue and osteoid occupancy after 3 months, albeit without statistical significance. Overall, the materials demonstrated varying post-implantation behaviors in vivo. Thus, in a clinical setting, both the properties of these materials and the specific conditions of the defects needing reinforcement should be considered to identify the most suitable material.


Elucidating the molecular basis of MSH2-deficient tumors by combined germline and somatic analysis.
In a proportion of patients presenting mismatch repair (MMR)-deficient tumors, no germline MMR mutations are identified, the so-called Lynch-like syndrome (LLS). Recently, MMR-deficient tumors have been associated with germline mutations in POLE and MUTYH or double somatic MMR events. Our aim was to elucidate the molecular basis of MSH2-deficient LS-suspected cases using a comprehensive analysis of colorectal cancer (CRC)-associated genes at germline and somatic level. Fifty-eight probands harboring MSH2-deficient tumors were included. Germline mutational analysis of MSH2 (including EPCAM deletions) and MSH6 was performed. Pathogenicity of MSH2 variants was assessed by RNA analysis and multifactorial likelihood calculations. MSH2 cDNA and methylation of MSH2 and MSH6 promoters were studied. Matched blood and tumor DNA were analyzed using a customized next generation sequencing panel. Thirty-five individuals were carriers of pathogenic or probably pathogenic variants in MSH2 and EPCAM. Five patients harbored 4 different MSH2 variants of unknown significance (VUS) and one had 2 novel MSH6 promoter VUS. Pathogenicity assessment allowed the reclassification of the 4 MSH2 VUS and 6 probably pathogenic variants as pathogenic mutations, enabling a total of 40 LS diagnostics. Predicted pathogenic germline variants in BUB1, SETD2, FAN1 and MUTYH were identified in 5 cases. Three patients had double somatic hits in MSH2 or MSH6, and another 2 had somatic alterations in other MMR genes and/or proofreading polymerases. In conclusion, our comprehensive strategy combining germline and somatic mutational status of CRC-associated genes by means of a subexome panel allows the elucidation of up to 86% of MSH2-deficient suspected LS tumors.


Tracking an invasion front with environmental DNA.
Data from environmental DNA (eDNA) may revolutionize environmental monitoring and management, providing increased detection sensitivity at reduced cost and survey effort. However, eDNA data are rarely used in decision-making contexts, mainly due to uncertainty around (1) data interpretation and (2) whether and how molecular tools dovetail with existing management efforts. We address these challenges by jointly modeling eDNA detection via qPCR and traditional trap data to estimate the density of invasive European green crab (Carcinus maenas), a species for which, historically, baited traps have been used for both detection and control. Our analytical framework simultaneously quantifies uncertainty in both detection methods and provides a robust way of integrating different data streams into management processes. Moreover, the joint model makes clear the marginal information benefit of adding eDNA (or any other) additional data type to an existing monitoring program, offering a path to optimizing sampling efforts for species of management interest. Here, we document green crab eDNA beyond the previously known invasion front and find that the value of eDNA data dramatically increases with low population densities and low traditional sampling effort, as is often the case at leading-edge locations. We also highlight the detection limits of the molecular assay used in this study, as well as scenarios under which eDNA sampling is unlikely to improve existing management efforts.


Thermo-/pH-Dual-Sensitive PEG/PAMAM Nanogel: Reaction Dynamics and Plugging Application of CO2 Channeling.
Smart hydrogels, owing to their exceptional viscoelastic and deformable capacity in response to environmental stimulation involving temperature and pH, have been successfully applied in oilfields for purposes such as water and/or gas shutoff treatments. However, the CO2 breakthrough problem in low permeability reservoirs has not been well solved. In this work, a rheological method-based Avrami dynamics model and Dickinson dynamics model were employed to investigate the dynamic gelation process of thermo-/pH-dual-sensitive PEG/PAMAM nanogels to further our understanding of the microstructure of their gelation and pertinence plugging application. Plugging experiments were performed by alternating injections of CO2 and hydrogel solution in a slug type on three fractured low permeability cores with a backpressure of 13 MPa. The nanogels presented a secondary growth pattern from three to one dimension from micrometer to nanometer size with a morphological transformation from a sphere to an irregular ellipsoid or disk shape. The phase transition temperature was 50 °C, and the phase transition pH was 10. If both or either were below these values, the hydrogel swelled; otherwise, it shrank. Plugging results show that the plugging efficiency was higher than 99%. The maximum breakthrough pressure was 19.93 MPa, and the corresponding residual pressure remained 17.64 MPa for a 10 mD core, exhibiting great plugging performance and high residual resistance after being broken through by CO2.