Dietary habits of a school population and implications for oral health.
The study analyzes the consumption of cariogenic foods in a population of children between 6 and 10 years old. Transversal descriptive study on a sample of 369 children who first attended to the Department 9 Dentistry dental office of the Valencia Region Health Agency (Spain). A self-administered food consumption frequency questionnaire was used to evaluate how often the food on the list were consumed by the children. Sticky sugar-rich foods, sugared milk and dairy products, food containing starch and sugar, sugary liquids and food with semihydrolyzed starch were consumed by over 50% of the sample at main meals and between meals. The mean intake of all these food groups, was over five times a week. The older children ate more fruit and foods rich in semihydrolyzed starch at main meals. Sweetened medication significantly reduced with age. Sugar-free sweets were consumed by almost 60% of the sample. The study shows a high intake of food with cariogenic potential, in particular processed food with added sugar and food with semihydrolyzed starch consumed between meals. This situation indicates the need to include health education programs in our population focused to improve the dietary habits of children and teenagers.


[A simple technique for the genotyping of TH01 locus].
It is difficult to differentiate between type 9.3 and 10 at the TH01 locus. Therefore, we designed three primers including allele-specific primer for the type 9.3. Our primer sets gave shorter fragments ranging from 62 to 81 bp than those in other reports, allowing each allelic band to be resolved by 10% non-denaturing polyacrylamide gel electrophoresis and stained with SYBR Green I. TH01 typing was successfully applied to human remains such as sera, whole bloods and blood stains made about 80 years ago without extracting DNA from them. The simple and fast methods for TH01 typing as demonstrated herein will be useful in the field of forensic practice.


Peracetic acid and sodium hypochlorite effectiveness in reducing resistant stages of microorganisms.
A comparative study on the efficacy of peracetic acid and sodium hypochlorite in inactivating resistant stages of microorganisms such as Cryptosporidium, Giardia and Cl. perfingens was carried out. Furthermore the evaluation of the potential reciprocal correlation among the concentrations of the organisms was performed. The results obtained indicate that, at the same experimental conditions, peracetic acid and sodium hypochlorite have nearly similar reduction power against the resistant stages of Giardia and Cl. perfringens. Both the oxidants are instead less efficient in the abatement of Cryptosporidium oocysts. Findings have also confirmed our previous studies on the absence of association between Clostridium and the protozoa.


Transcription initiation at the tet promoter and effect of mutations.
We have identified the startpoint for transcription in vitro of the tetracycline resistance gene (tet) of pBR322 and several deletion and insertion mutations which alter tet promoter structure. Tetracycline resistance in host bacteria correlates qualitatively with the efficiency of DNA fragments from these plasmids to promote tet transcription in vitro. Only in active promoters could we find by computer analysis promoter structures in which the -10 and -35 sequences and the relative spacing of the two regions agree with consensus sequence determinants. These data support the current model of the E. coli promoter sequence. Two promoter mutants gave heterogeneous 5' termini with additional A residues not encoded by the DNA sequence.


Aquifex aeolicus aspartate transcarbamoylase, an enzyme specialized for the efficient utilization of unstable carbamoyl phosphate at elevated temperature.
Aquifex aeolicus, an organism that flourishes at 95 degrees C, is one of the most thermophilic eubacteria thus far described. The A. aeolicus pyrB gene encoding aspartate transcarbamoylase (ATCase) was cloned, overexpressed in Escherichia coli, and purified by affinity chromatography to a homogeneous form that could be crystallized. Chemical cross-linking and size exclusion chromatography showed that the protein was a homotrimer of 34-kDa catalytic chains. The activity of A. aeolicus ATCase increased dramatically with increasing temperature due to an increase in kcat with little change in the Km for the substrates, carbamoyl phosphate and aspartate. The Km for both substrates was 30-40-fold lower than the corresponding values for the homologous E. coli ATCase catalytic subunit. Although rapidly degraded at high temperature, the carbamoyl phosphate generated in situ by A. aeolicus carbamoyl phosphate synthetase (CPSase) was channeled to ATCase. The transient time for carbamoyl aspartate formation was 26 s, compared with the much longer transient times observed when A. aeolicus CPSase was coupled to E. coli ATCase. Several other approaches provided strong evidence for channeling and transient complex formation between A. aeolicus ATCase and CPSase. The high affinity for substrates combined with channeling ensures the efficient transfer of carbamoyl phosphate from the active site of CPSase to that of ATCase, thus preserving it from degradation and preventing the formation of toxic cyanate.


Disturbances of the CD95 (APO-1/Fas) system in disorders of lymphohaematopoietic cells.
Control of tissue homeostasis is maintained through programs that balance proliferation and cell death. Physiologic cell death is primarily mediated through apoptosis. Deregulations of the cellular programs and genes that determine apoptosis have recently been considered to be involved in a variety of human diseases. One of the central regulatory systems for apoptosis is the CD95 (APO-1/Fas) system. Defects in the CD95 cell surface receptor and deregulated expression of CD95 and the CD95 ligand have been shown to be involved in diseases such as lymphoproliferation, AIDS and haematopoietic failure. This review summarizes our current knowledge on the implication of the CD95 system especially in lymphohaematopoietic diseases in humans.


Fragile many-body ergodicity from action diffusion.
Weakly nonintegrable many-body systems can restore ergodicity in distinctive ways depending on the range of the interaction network in action space. Action resonances seed chaotic dynamics into the networks. Long-range networks provide well connected resonances with ergodization controlled by the individual resonance chaos time scales. Short-range networks instead yield a dramatic slowing down of ergodization in action space, and lead to rare resonance diffusion. We use Josephson junction chains as a paradigmatic study case. We exploit finite time average distributions to characterize the thermalizing dynamics of actions. We identify an action resonance diffusion regime responsible for the slowing down. We extract the diffusion coefficient of that slow process and measure its dependence on the proximity to the integrable limit. Independent measures of correlation functions confirm our findings. The observed fragile diffusion is relying on weakly chaotic dynamics in spatially isolated action resonances. It can be suppressed, and ergodization delayed, by adding weak action noise, as a proof of concept.


Effect of adrenalectomy and steroid treatment on rat skin cytosol glucocorticoid receptor.
Using an exchange assay to measure occupied and unoccupied binding sites, the glucocorticoid receptor in rat skin cytosol has been measured after adrenalectomy and parenteral steroid administration. Adrenalectomy increased the number of receptor sites with maximal effect after 5 days, after which numbers decreased to those of intact animals. Injection of adrenalectomized animals with the unlabelled agonist corticosterone resulted in a rapid dose-related decrease in the number of cytosolic receptor sites at 30 min whereas the antagonist progesterone had no effect. It is concluded that changes in glucocorticoid concentration lead to rapid inverse changes in cytosolic receptor.


Pathogenic mechanisms of bradykinin mediated diseases: dysregulation of an innate inflammatory pathway.
Binding of negatively charged macromolecules to factor XII induces a conformational change such that it becomes a substrate for trace amounts of activated factor present in plasma (less than 0.01%). As activated factor XII (factor XIIa or factor XIIf) forms, it converts prekallikrein (PK) to kallikrein and kallikrein cleaves high molecular weight kininogen (HK) to release bradykinin. A far more rapid activation of the remaining unactivated factor XII occurs by enzymatic cleavage by kallikrein (kallikrein-feedback) and sequential cleavage yields two forms of activated factor XII; namely, factor XIIa followed by factor XII fragment (factor XIIf). PK circulates bound to HK and binding induces a conformational change in PK so that it acquires enzymatic activity and can stoichiometrically cleave HK to produce bradykinin. This reaction is prevented from occurring in plasma by the presence of C1 inhibitor (C1 INH). The same active site leads to autoactivation of the PK-HK complex to generate kallikrein if a phosphate containing buffer is used. Theoretically, formation of kallikrein by this factor XII-independent route can activate surface-bound factor XII to generate factor XIIa resulting in a marked increase in the rate of bradykinin formation as stoichiometric reactions are replaced by Michaelis-Menton, enzyme-substrate, kinetics. Zinc-dependent binding of the constituents of the bradykinin-forming cascade to the surface of endothelial cells is mediated by gC1qR and bimolecular complexes of gC1qR-cytokeratin 1 and cytokeratin 1-u-PAR (urokinase plasminogen activator receptor). Factor XII and HK compete for binding to free gC1qR (present in excess) while cytokeratin 1-u-PAR preferentially binds factor XII and gC1qR-cytokeratin 1 preferentially binds HK. Autoactivation of factor XII can be initiated as a result of binding to gC1qR but is prevented by C1 INH. Yet stoichiometric activation of PK-HK to yield kallikrein in the absence of factor XII can be initiated by heat shock protein 90 (HSP-90) which forms a zinc-dependent trimolecular complex by binding to HK. Thus, endothelial cell-dependent activation can be initiated by activation of factor XII or by activation of PK-HK. Hereditary angioedema (HAE), types I and II, are due to autosomal dominant mutations of the C1 INH gene. In type I disease, the level of C1 INH protein and function is proportionately low, while type II disease has a normal protein level but diminished function. There is trans-inhibition of the one normal gene so that functional levels are 30% or less and severe angioedema affecting peripheral structures, the gastrointestinal tract, and the larynx results. Prolonged incubation of plasma of HAE patients (but not normal controls) leads to bradykinin formation and conversion of PK to kallikrein which is reversed by reconstitution with C1 INH. The disorder can be treated by C1 INH replacement, inhibition of plasma kallikrein, or blockade at the bradykinin B-2 receptor. A recently described HAE with normal C1 INH (based on inhibition of activated C1s) presents similarly; the defect is not yet clear, however one-third of patients have a mutant factor XII gene. We have shown that this HAE has a defect in bradykinin overproduction whether the factor XII mutation is present or not, that patients' C1 INH is capable of inhibiting factor XIIa and kallikrein (and not just activated C1) but the functional level is approximately 40-60% of normal, and that α2 macroglobulin protein levels are normal. In vitro abnormalities can be suppressed by raising C1 INH to twice normal levels. Finally, aggregated proteins have been shown to activate the bradykinin-forming pathway by catalyzing factor XII autoactivation. Those include the amyloid β protein of Alzheimer's disease and cryoglobulins. This may represent a new avenue for kinin-dependent research in human disease. In allergy (anaphylaxis; perhaps other mast cell-dependent reactions), the oversulfated proteoglycan of mast cells, liberated along with histamine, also catalyze factor XII autoactivation.


Structure-to-process design framework for developing safer pesticides.
Rational design of pesticides with tunable degradation properties and minimal ecotoxicity is among the grand challenges of green chemistry. While computational approaches have gained traction in predictive toxicology, current methods lack the necessary multifaceted approach and design-vectoring tools needed for system-based chemical development. Here, we report a tiered computational framework, which integrates kinetics and thermodynamics of indirect photodegradation with predictions of ecotoxicity and performance, based on cutoff values in mechanistically derived physicochemical properties and electronic parameters. Extensively validated against experimental data and applied to 700 pesticides on the U.S. Environmental Protection Agency's registry, our simple yet powerful approach can be used to screen existing molecules to identify application-ready candidates with desirable characteristics. By linking structural attributes to process-based outcomes and by quantifying trade-offs in safety, depletion, and performance, our method offers a user-friendly roadmap to rational design of novel pesticides.


Uniformly convergent n-tuple-zeta augmented polarized (nZaP) basis sets for complete basis set extrapolations. I. Self-consistent field energies.
We present a sequence of n-tuple-zeta augmented polarized (nZaP) basis sets designed for extrapolations of both self-consistent field (SCF) and correlation energies to the complete basis set (CBS) limit. These nZaP basis sets (n=2-6) are formulated to give consistent errors throughout the Periodic Table (e.g., a consistent of approximately 1 mhartree/electron error for the 2ZaP SCF energy and a consistent of approximately 1.4 muhartree/electron error for the 6ZaP SCF energy). The SCF energy exhibits systematic convergence to the CBS limit: E(SCF)(nZaP) approximately E(SCF)(CBS)+Ae(-an). A single parameter, a=6.30, describes the 2ZaP through 6ZaP errors of H through Xe within 10%. The SCF rms basis set truncation errors of H through Xe are 33.5mE(h), 4.58mE(h), 0.82mE(h), 0.18mE(h), and 0.047mE(h) for 2ZaP, 3ZaP, 4ZaP, 5ZaP, and 6ZaP, respectively. Linear extrapolations of the (2,3)ZaP, (3,4)ZaP, (4,5)ZaP, and (5,6)ZaP calculations (all with a=6.30) reduce these errors by an order of magnitude to 0.24mE(h), 0.056mE(h), 0.020mE(h), and 0.005mE(h), respectively. A test set of 34 atoms, ions, and molecules gives similar results, and the associated test set of 25 chemical energy differences also gives comparable absolute accuracy. However, the cancellation of errors between reactant and product is lost by extrapolation. As a result, these chemical energy differences show a more modest two-to-fourfold improvement with extrapolation.


The microsurgical assistant.
The increasing indications for microsurgical reconstruction, and the expansion of the field into multiple surgical subspecialities, have led to a need to find ways to conserve operating time, promote increased surgical skill and efficiency, and train and maintain an interest among capable surgeons. The trained microsurgical assistant is a solution to many of these goals and requirements. Since 1979, we have trained 15 nurses, surgeons' assistants, and operating room technicians in this capacity.


Estimating Y chromosome specific microsatellite mutation frequencies using deep rooting pedigrees.
Recently, a set of highly polymorphic chromosome Y specific microsatellites became available for forensic, population genetic and evolutionary studies. However, the lack of a mutation frequency estimate for these loci prevents a reliable application. We therefore used seven chromosome Y tetranucleotide repeat loci to screen 42 males who are descendants from 12 'founding fathers' by a total number of 213 generations. As a result, we were able to estimate an average chromosome Y tetranucleotide mutation frequency of 0.20% (95% CIL 0.05-0.55). This closely matches the often cited Weber and Wong estimate of 0.21% for a set of autosomal tetranucleotide repeats. Expanding the set of microsatellites with two more loci (a tri- and a penta-nucleotide repeat locus) an average chromosome Y microsatellite mutation frequency of 0.21% (95% CIL 0.06-0.49) was found. These estimates suggest that microsatellites on the Y chromosome have mutation frequencies comparable to those on the autosomes. This supports the hypothesis that slippage-generated growth is the driving force behind the microsatellite variability.


Age-related EBV-associated B-cell lymphoproliferative disorders and other EBV + lymphoproliferative diseases: New insights into immune escape and immunodeficiency through staining with anti-PD-L1 antibody clone SP142.
Epstein-Barr virus (EBV) is prevalent among healthy individuals, and is implicated in numerous reactive and neoplastic processes in the immune system. The authors originally identified a series of senile or age-related EBV-associated B-cell lymphoproliferative disorders (LPD) bearing a resemblance to immunodeficiency-associated ones. These LPDs may be associated with immune senescence and are now incorporated into the revised 4th edition of 2017 WHO lymphoma classification as EBV-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS). These EBV+ B-cells often have a Hodgkin/Reed-Sternberg (HRS)-like appearance and are shared beyond the diagnostic categories of mature B-cell neoplasms, mature T-cell neoplasms, classic Hodgkin lymphoma, and immunodeficiency-associated LPD. In addition, peculiar new diseases, such as EBV+ mucocutaneous ulcer and EBV+ DLBCL affecting the young, were recognized. On the other hand, lymphoma classification is now evolving in accord with deeper understanding of the biology of programmed death ligand 1 (PD-L1). Assessing PD-L1 positivity by staining with the anti-PD-L1 monoclonal antibody SP142 provides new insight by discriminating between immune evasion and senescence or immunodeficiency. The aim of the present review is to briefly summarize the diagnostic use of immunostaining with SP142 in malignant lymphomas and/or LPDs that feature tumor and nonmalignant large B-cells harboring EBV.


Coverages and factors associated with influenza vaccination among subjects with chronic respiratory diseases in Spain.
The main influenza complications particularly affect patients over the age of 65 years and those with associated chronic diseases, such as respiratory disorders. This study aims to assess vaccination coverage among Spanish children and adults with chronic respiratory diseases (CRDs), and to describe the factors associated with vaccination in 2003. We analysed 28,113 records of individuals (6869 children and 21,244 adults) included in the Spanish National Health Survey (NHS) for 2003. As a dependent variable, we used the reply ('yes' or 'no') to the question: 'Did you have a 'flu shot in the latest campaign?' We calculated influenza vaccine coverage as the percentage of individuals with a respiratory disorder (asthma and/or chronic bronchitis and/or emphysema) who reported having been vaccinated against influenza in the most recent campaign. We analysed the influence of sociodemographic, health-status, medical visits and lifestyle variables on vaccination. Vaccination coverage was 19.9% in children and 54.7% in adults suffering CRD. In both age groups, coverages were significantly higher than those observed for non-CRD sufferers. Among adults, older age, not smoking and medical visits to their physician in the preceding 2 weeks were the variables independently and significantly associated with a higher likelihood of receiving the vaccine. Among children, financial factors influence vaccination. Vaccination coverage among children with CRDs is very low. Also among adult CRD sufferers, vaccination remains below the desired level, thereby making it necessary for strategies to be implemented aimed at improving the use of influenza vaccine.


[Disorders of humoral regulation of the digestive organ functions in children with malabsorption syndromes].
The authors provide the data obtained during examination of 36 children with celiac disease and 18 children with lactase deficiency. The children's age ranged from 8 months to 15 years. All the children underwent spot biopsy of the gastric and duodenal mucosa followed by immunomorphological PAP-staining of the biopsy specimens and count of the number of gastrin- and somatostatin-producing cells. Gastrin in the blood serum was measured by radioimmunoassay. The children with celiac disease manifested an increase of the number of somatostatin-producing cells in the duodenum and decrease of their number in the pyloric part of the stomach, seen in the acute phase of the disease. The number of gastrin-producing cells remained unchanged. The level of gastrin declined in the acute phase and increased during a remission. The alterations described were found to be related to the atrophic processes in the small intestinal mucosa. In lactase deficiency, no significant alterations were established in the number of pyloric and duodenal endocrine cells or in blood gastrin level.


Preferential depletion of zinc within Costa Rica upwelling dome creates conditions for zinc co-limitation of primary production.
The Costa Rica Dome (CRD) is a wind-driven feature characterized by high primary production and an unusual cyanobacterial bloom in surface waters. It is not clear whether this bloom arises from top-down or bottom-up processes. Several studies have argued that trace metal geochemistry within the CRD contributes to the composition of the phytoplankton assemblages, since cyanobacteria and eukaryotic phytoplankton have different transition metal requirements. Here, we report that total dissolved zinc (Zn) is significantly depleted relative to phosphate (P) and silicate (Si) within the upper water column of the CRD compared with other oceanic systems, and this may create conditions favorable for cyanobacteria, which have lower Zn requirements than their eukaryotic competitors. Shipboard grow-out experiments revealed that while Si was a limiting factor under our experimental conditions, additions of Si and either iron (Fe) or Zn led to higher biomass than Si additions alone. The addition of Fe and Zn alone did not lead to significant enhancements. Our results suggest that the depletion of Zn relative to P in upwelled waters may create conditions in the near-surface waters that favor phytoplankton with low Zn requirements, including cyanobacteria.


Oriented single-crystal-like molecular arrangement of optically nonlinear 2-methyl-4-nitroaniline in electrospun nanofibers.
In-plane aligned nanofibers of organic 2-methyl-4-nitroaniline (MNA) were produced by the electrospinning technique using a 1:1 weight ratio with poly(l-lactic acid). The fibers are capable of enormous efficient optical second harmonic generation as strong as pure MNA crystals in powder form. Structural, spectroscopic, and second harmonic generation polarimetry studies show that the MNA crystallizes within the fibers in an orientation in which the aromatic rings of MNA are predominantly orientated edge-on with respect to the plane of the fiber array and with their dipole moments aligned with the fiber axis. The results show that the electrospinning technique is an effective method to fabricate all-organic molecular functional devices based on polymer nanofibers with guest molecules possessing strong nonlinear optical and/or polar properties.


Significant increased CA199 levels in acute pancreatitis patients predicts the presence of pancreatic cancer.
Carbohydrate antigen 19-9 (CA199) has been identified as a tumor marker for pancreatic cancer but also increases in benign lesions of the digestive system. However, literature associated with the relationship between CA199 and acute pancreatitis (AP) is limited. This study aimed to focus on serum CA199 level measurements in AP patients and the associated clinical significance. From January 2006 to December 2015, 1,609 consecutive patients with AP were admitted to our department and included in the study. The relationships among the etiology of AP, the disease severity, the incidence of pancreatic cancer during hospitalization and CA199 levels were analyzed. Serum CA199 levels were measured for 693 of 1,609 AP patients. Of those patients, 186 (26.8%) had elevated CA199 levels (> 37 U/ml). Patients with high CA199 levels were older and had predominantly biliary causes in comparison with patients with normal CA199 levels. There were no definite specific correlations between CA199 levels and disease severity in AP. In addition, serum levels of CA199 positively correlated with serum alanine aminotransferase, aspartate transaminase, glutamyl transpeptidase, alkaline phosphatase and creatinine levels. After stratification, the incidence of pancreatic cancer increased proportionally to CA199 levels in AP patients. Serum CA199 levels was elevated in patients with AP, especially in patients with biliary pancreatitis. AP patients with significantly increased CA199 levels may have a higher risk for the presence of pancreatic cancer. We recommended routinely monitoring CA199 levels during hospitalization for AP patients.


Neutrophil adhesion molecule expression and serum concentration of soluble adhesion molecules during and after pediatric cardiovascular surgery with or without cardiopulmonary bypass.
Increased neutrophil activation by cardiopulmonary bypass (CPB) during cardiovascular surgery is thought to be responsible for postoperative complications. In children, the contribution of cardiovascular surgery alone to this response is not well-characterized. Children undergoing surgery with CPB (CPB group, n = 35) and without CPB (control, n = 22) were studied (age, 3-17 yr). Blood was drawn 24 h preoperatively before medication, after anesthesia, after connection to CPB, at reperfusion, 4 h to 2 days after surgery, at discharge, and months after surgery. Neutrophil antigen expression and serum concentration of adhesion molecules, interleukin 8, and C5a (fragment of C5 complement) were analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively. With and without CPB, anesthesia and surgery induced decreased LFA-1 (CD11a-CD18), Mac-1 (CD11b-CD18), CD45, and CD54 (intercellular adhesion molecule 1) surface expression and sICAM-1 serum concentrations (all P < 0.001). sL-selectin serum concentration decreased with CPB (P < 0.001) but was not significantly altered in the control. In contrast, CD62L expression increased during CPB (P < 0.001). The time course of all analyzed markers was not significantly different between CPB and control, with the exception of sL-selectin (P = 0.017). One-day preoperative baseline values were reached days to months after surgery. Interleukin 8 and C5a serum concentrations increased after surgery in both the CPB group and the control group. Pediatric cardiovascular surgery leads to reduced adhesiveness and activity of circulating neutrophils. This reduction is more pronounced and sustained with CPB. These data may be useful in the assessment of novel therapeutic strategies.


[Neonatal lupus syndrome: review of the literature].
Neonatal lupus syndrome include skin lesions, hematological and hepatic disorders, and congenital heart block (CHB) in the absence of severe cardiac malformation. This rare disorder is closely linked to transplacental transport of anti-SSA/Ro and anti-SSB/La maternal antibodies. The prevalence of CHB in newborns of anti-Ro/SSA positive women with known connective tissue disease is 2% and the risk of recurrence ranges from 10 to 17%. Skin and systemic lesions are transient, whereas CHB is definitive and is associated with significant morbidity and mortality (estimated at 16-19%). A pacemaker must be implanted in 2/3 of cases. Myocarditis may be associated or may appeared secondarily. Mothers of children with CHB are usually asymptomatic or have Gougerot-Sjögren, or undifferentiated connective tissue disease. Mothers of children with cutaneous manifestations may present with more severe disease and systemic lupus erythematosus. In anti-Ro/SSA positive pregnant women, echocardiograms should be performed at least every 2 weeks from 16 to 24 weeks gestation. Electrocardiogram should be performed for all children. The efficiency of prophylactic treatment of CHB is not established. Therapy for CHB detected in utero is not standardized and involves fluorinated steroids (especially betamethasone).


[Another look at Victor Tausk].
The study of intellectual history necessarily clashes with certain trade union needs among psychoanalysts. And therefore, the story of the struggle between Victor Tausk and Sigmund Freud, when I first wrote about it in 1969, unleashed a storm of polemics which may still not have subsided. Efforts to fill in gaps in history should not be misconstrued as a partisan assault on the creator of psychoanalysis. On the contrary, I believe that an understanding of the tragedies associated with Freud's school adds a human dimension which makes the tale all the more compelling.


Ileal apical sodium-dependent bile acid transporter protein levels are down-regulated through ubiquitin-dependent protein degradation induced by bile acids.
The ileal apical sodium-dependent bile acid transporter (ASBT or SLC10A2) has a crucial role in intestinal bile acid absorption. We previously reported that enterobacteria-mediated bile acid conversion was involved in the alteration of ileal ASBT expression levels. In the present study, to investigate the hypothesis that ileal ASBT protein levels are post-translationally regulated by enterobacteria-associated bile acids, alteration of ileal ASBT protein levels was analysed in mice 12 h and 24 h after anti-bacterial drug ampicillin (ABPC) treatment (100 mg/kg, single shot) that altered bile acid composition in the intestinal lumen. In ABPC-treated mice, enterobacteria-biotransformed bile acid, taurodeoxycholic acid (TDCA) and cholic acid (CA) levels were decreased, whereas taurocholic acid (TCA) and tauro-β-muricholic acid levels were increased in the intestinal lumen. Ileal ASBT protein levels in brush-border membrane vesicles (BBMVs), but not ileal Asbt mRNA levels, were significantly increased in the ABPC-treated mice, and the extent of ubiquitination of the ileal ASBT protein was reduced in the ABPC-treated mice. Treatment of ABPC-pretreated mice with CA or TDCA, but not TCA, significantly decreased ileal ASBT protein levels and increased the extent of ubiquitination of ileal ASBT protein. Treatment of mice with the lysosome inhibitor, chloroquine, or the proteasome inhibitor, MG132, increased ileal ASBT protein levels in BBMVs. CA-mediated reduction of ASBT protein levels in the ABPC-pretreated mice was attenuated by co-treatment with chloroquine or MG132. These results suggest that ileal ASBT protein is degraded by a ubiquitin-dependent pathway in response to enterobacteria-associated bile acids.


Longitudinal Brain Functional Connectivity Changes of the Cortical Motor-Related Network in Subcortical Stroke Patients with Acupuncture Treatment.
In clinical practice, the effectiveness of the rehabilitation therapy such as acupuncture combining conventional Western medicine (AG) on stroke people's motor-related brain network and their behaviors has not been systematically studied. In the present study, seventeen adult ischemic patients were collected and divided into two groups: the conventional Western medicine treatment group (CG) and the AG. The neurological deficit scores (NDS) and resting-state functional MRI data were collected before and after treatment. Compared with the CG patients, AG patients exhibited a significant enhancement of the percent changes of NDS from pre- to posttreatment intervention. All patients showed significant changes of functional connectivity (FC) between the pair of cortical motor-related regions. After treatment, both patient groups showed a recovery of brain connectivity to the nearly normal level compared with the controls in these pairs. Moreover, a significant correlation between the percent changes of NDS and the pretreatment FC values of bilateral primary motor cortex (M1) in all patients was found. In conclusion, our results showed that AG therapy can be an effective means for ischemic stroke patients to recover their motor function ability. The FC strengths between bilateral M1 of stroke patients can predict stroke patients' treatment outcome after rehabilitation therapy.


Bring your own camera to the trap: An inexpensive, versatile, and portable triggering system tested on wild hummingbirds.
The study of animals in the wild offers opportunities to collect relevant information on their natural behavior and abilities to perform ecologically relevant tasks. However, it also poses challenges such as accounting for observer effects, human sensory limitations, and the time intensiveness of this type of research. To meet these challenges, field biologists have deployed camera traps to remotely record animal behavior in the wild. Despite their ubiquity in research, many commercial camera traps have limitations, and the species and behavior of interest may present unique challenges. For example, no camera traps support high-speed video recording. We present a new and inexpensive camera trap system that increases versatility by separating the camera from the triggering mechanism. Our system design can pair with virtually any camera and allows for independent positioning of a variety of sensors, all while being low-cost, lightweight, weatherproof, and energy efficient. By using our specialized trigger and customized sensor configurations, many limitations of commercial camera traps can be overcome. We use this system to study hummingbird feeding behavior using high-speed video cameras to capture fast movements and multiple sensors placed away from the camera to detect small body sizes. While designed for hummingbirds, our application can be extended to any system where specialized camera or sensor features are required, or commercial camera traps are cost-prohibitive, allowing camera trap use in more research avenues and by more researchers.


Advising Consumption of Green Vegetables, Beef, and Full-Fat Dairy Products Has No Adverse Effects on the Lipid Profiles in Children.
In children, little is known about lipid profiles and the influence of dietary habits. In the past, we developed a dietary advice for optimizing the immune system, which comprised green vegetables, beef, whole milk, and full-fat butter. However, there are concerns about a possible negative influence of the full-fat dairy products of the diet on the lipid profile. We investigated the effect of the developed dietary advice on the lipid profile and BMI (body mass index)/BMI-z-score of children. In this retrospective cohort study, we included children aged 1-16 years, of whom a lipid profile was determined in the period between June 2011 and November 2013 in our hospital. Children who adhered to the dietary advice were assigned to the exposed group and the remaining children were assigned to the unexposed group. After following the dietary advice for at least three months, there was a statistically significant reduction in the cholesterol/HDL (high-density lipoproteins) ratio (p < 0.001) and non-HDL-cholesterol (p = 0.044) and a statistically significant increase in the HDL-cholesterol (p = 0.009) in the exposed group, while there was no difference in the BMI and BMI z-scores. The dietary advice has no adverse effect on the lipid profile, BMI, and BMI z-scores in children, but has a significant beneficial effect on the cholesterol/HDL ratio, non-HDL-cholesterol, and the HDL-cholesterol.


Hypertension and renal outcomes in normotensive kidney donors with multiple renal arteries.
Having multiple renal arteries (MRA) has been linked to hypertension development. Whether kidney donors who are left with MRA in the nondonated kidney incur a higher risk of hypertension has not been studied. We compared the development of hypertension, reduced estimated glomerular filtration rate (eGFR), cardiovascular disease, and mortality in 2624 normotensive kidney donors with MRA in the nondonated kidney and to 2624 propensity score matched normotensive donor controls with a single renal artery. In total, 35% of donors had MRA. Donors with MRA were less likely to have undergone a left nephrectomy (51% vs. 83%). Postdonation hypertension was associated with age, male gender, non-White ethnicity, obesity, and family history of hypertension. Having MRA was not associated with risk of hypertension; aHR 0.92 (95% CI 0.82-1.03), P = 0.16. After 17 ± 11 years from donation, a similar proportion of donors with and without MRA developed cardiovascular disease, proteinuria and eGFR <30, <45 and <60 mL/min/1.73 m2 and the multivariable risks of developing these outcomes were similar in the two groups. Our study did not show increased risk for hypertension, reduced eGFR, proteinuria or cardiovascular disease in donors with MRA in the remaining kidney and without hypertension at donation.


[Ultrasonic bone mineral density of calcaneus in 1 816 healthy subjects in Guangxi autonomous region].
To study the relationship between ultrasonic bone mineral density (BMD) of calcaneus and age, height, and body weight, and to establish the normal reference value for stiffness index (SI) of healthy subjects in Guangxi autonomous region and provide scientific foundation for the diagnosis and prevention of osteoporosis. SI of calcaneus in 1 816 healthy adults aged 11-90 years (775 men, 1 041 women) were measured with quantitative ultrasound. According to their ages, all the men and women were divided into 13 groups by 5-year age group. SI reached peak values in 21-25 year group in men (range: 111.45 +/- 21.19) and in 16-20 year group in women (range: 101.26 +/- 17.51). Then the SI value began to decline with aging. The SI featured by a typical dual-peak curve in women and the decrease rate of SI was faster in women than in men over 61 years. Multivariate linear regression analysis showed significantly negative correlation between SI and age (P < 0.001), positive correlation between SI and body weight (P < 0.05 for men; P < 0.01 for women), and positive correlation between SI and height in women (P < 0.01). SI correlates with age, height, and weight. The acquired SI value may provide a reference for the diagnosis of osteoporosis.


Medical Devices; Cardiovascular Devices; Classification of the Steerable Cardiac Ablation Catheter Remote Control System. Final order.
The Food and Drug Administration (FDA) is classifying the steerable cardiac ablation catheter remote control system into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language for the steerable cardiac ablation catheter remote control system's classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device.


Pseudogene HSPA7 is a poor prognostic biomarker in Kidney Renal Clear Cell Carcinoma (KIRC) and correlated with immune infiltrates.
Pseudogenes played important roles in tumorigenesis, while there are nearly no reports about the expression and roles of HSPA7 in the cancer. Firstly, we used Logistic regression, the KS test, the GEPIA database, UALCAN database and qRT-PCR to analyze the expression level of HSPA7 in KIRC, then we used the Cox regression and the Kaplan-Meier curve to analyze the overall survival (OS) of KIRC patients with different Clinico-pathological parameters. Thirdly, we used the multivariate Cox analysis of influencing factors to compare the correlation between the HSPA7 expression level and the clinical parameters. Finally, we used multi-GSEA analysis and the Tumor Immunoassay Resource (TIMER) database to explore the functional role of HSPA7 in KIRC RESULTS: The HSPA7 is highly expressed in KIRC tumor tissues, and its expression is related to clinico-pathological features and survival in KIRC patients. GSEA analysis displayed the high expression of HSPA7 in KIRC were related to several tumor-related and immune-related pathways. With the TIMER database analysis we showed that HSPA7 levels were correlated with the CD4+ T cells, neutrophils and Dendritic Cell. Our study showed that HSPA7 is very important in the tumor progression and may act as a poor prognostic biomarker for KIRC tumor by modulating immune infiltrating cells.


Breast implants and breast cancer screening.
Concern about breast prostheses impairing breast cancer detection has become a priority issue. This article provides a review of the literature on the influence of implants on early detection methods of breast cancer, specifically breast self-examination (BSE), clinical breast examination (CBE), and mammography. Background information on implants is presented, including indications for surgery, types of prostheses, location of placement, and associated complications. Conclusions from the literature suggest that the presence of implants may facilitate BSE and CBE, yet challenge interpretation of mammography. However, there is no evidence that these women will have a later stage diagnosis or a poorer prognosis if diagnosed with breast cancer.


Characterization of drug-specific T cells in phenobarbital-induced eruption.
Phenobarbital has a high potential to elicit adverse reactions including severe skin eruptions and systemic involvements among the worldwide-prescribed drugs. Although phenobarbital hypersensitivity is thought to be mediated by T cells specific to the drug, its precise mechanism remains not fully elucidated. To characterize T cells reactive with phenobarbital, we generated drug-specific T cell clones and lines from PBMCs of patients with phenobarbital hypersensitivity showing various degrees of cutaneous and extracutaneous involvements. Although the TCR Vbeta repertoire and phenotype in the T cell clones/T cell lines were heterogeneous among the patients, Vbeta13.1(+) and Vbeta5.1(+) clones or lines were raised from the individuals examined who possessed different HLA haplotypes. Histopathological examination suggested that Vbeta5.1(+)CD8(+) T cells and Vbeta13.1(+) T cells played a role in cutaneous and extracutaneous involvements, respectively. A Vbeta13.1(+)CD4(+) clone was found to proliferate in response to the Ag with processing-impaired, fixed APCs. Most of the clones and lines belonged to the Th2 phenotype, producing IL-4 and IL-5 but not IFN-gamma upon phenobarbital stimulation. Clones/lines with Th1 or Th0 phenotypes also constituted minor populations. These observations clearly indicate the heterogeneity and a marked individual deviation of reactive T cell subsets among the patients in terms of CD4/8 phenotype, Vbeta repertoire, Ag recognition pattern, and cytokine production; and thus provide evidence whereby each pathogenic T cell subset contributes to special elements of clinical presentation.


Body size and physical exercise, and the risk of multiple sclerosis.
Whether large body size increases multiple sclerosis (MS) risk in men is not well understood. Concurrently, physical exercise could be an independent protective factor. To prospectively investigate the association between body mass index (BMI) and aerobic fitness, indicators of body size and exercise, and MS risk in men. We performed a population-based nested case-control study within the historical cohort of all Norwegian men, born in 1950-1975, undergoing mandatory conscription at the age of 19 years. 1016 cases were identified through linkage to the Norwegian MS registry, while 19,230 controls were randomly selected from the cohort. We estimated the effect of BMI and fitness at conscription on MS risk using Cox regression. Higher BMI (≥25 vs 18.5-<25 kg/m2) was significantly associated with increased MS risk (adjusted relative risk (RRadj) = 1.36, 95% confidence interval (CI): 1.05-1.76). We also found a significant inverse association between aerobic fitness (high vs low) and MS risk independent of BMI (RRadj = 0.69, 95% CI: 0.55-0.88, p-trend = 0.003), remaining similar when men with MS onset within 10 years from conscription were excluded ( p-trend = 0.03). These findings add weight to evidence linking being overweight to an increased MS risk in men. Furthermore, they suggest that exercise may be an additional modifiable protective factor for MS.


Better continuity of care reduces costs for diabetic patients.
To examine the effects of continuity of care on healthcare utilization and expenses for patients with diabetes mellitus. Longitudinal study based on claims data. Data on healthcare utilization and expenses from a 7-year period (2000-2006) were gathered from claims data of the Taiwanese universal health insurance system. The continuity of care index (COCI) was analyzed, and the values were classified into 3 levels. Outcome variables included the likelihood of hospitalization and emergency department visit, pharmaceutical expenses for diabetes-related conditions, and total healthcare expenses for diabetes-related conditions. A generalized estimating equation that considered the effects of repeated measures for the same patients was applied to examine the effects of continuity of care on healthcare utilization and expenses. Compared with patients who had low COCI scores, patients with high or medium COCI scores were less likely to be hospitalized for diabetes related conditions (odds ratio [OR] 0.26, 95% confidence interval [CI] 0.25, 0.27, and OR 0.58, 95% CI 0.56, 0.59, respectively) or to have diabetes-related emergency department visits (OR 0.34, 95% CI 0.33, 0.36, and OR 0.64, 95% CI 0.62, 0.66, respectively). Patients with low COCI scores incurred $126 more in pharmaceutical expenses than patients with high COCI scores. Furthermore, patients with high COCI scores had greater savings ($737) in total healthcare expenses for diabetes-related conditions than patients with low COCI scores. Better continuity of care was associated with less healthcare utilization and lower healthcare expenses for diabetic patients. Improving continuity of care might benefit diabetic patients.


New directions for veterinary technology.
Veterinary technology has generally established itself well in companion-animal and mixed-animal veterinary medical practice, but the career's growth trajectory is uncertain. Michigan State University (MSU) convened a national conference, "Creating the Future of Veterinary Technology-A National Dialogue," in November 2011 to explore ways to elevate the veterinary technician/technologist's role in the veterinary medical profession and to identify new directions in which the career could expand. Veterinary technicians/technologists might advance their place in private practice by not only improving their clinical skills, but by also focusing on areas such as practice management, leadership training, business training, conflict resolution, information technology, and marketing/communications. Some new employment settings for veterinary technicians/technologists include more participation within laboratory animal medicine and research, the rural farm industry, regulatory medicine, and shelter medicine. Achieving these ends would call for new training options beyond the current 2-year and 4-year degree programs. Participants suggested specialty training programs, hybrid programs of various types, online programs, veterinary technician residency programs of 12-18 months, and more integration of veterinary technician/technology students and veterinary medicine students at colleges of veterinary medicine.


Role of RAAS and adipokines in cardiovascular protection: effect of different doses of angiotensin II receptor blocker on adipokines level in hypertensive patients.
The present study was designed to determine the effect of different doses of the angiotensin II receptor blocker (ARB), candesartan, on circulating adiponectin and leptin levels as well as leptin adiponectin ratio (LAR) in hypertensive patients with multiple cardiovascular risk factors.Sixty-nine hypertensive patients were randomized to three groups: group 1 included patients treated with high doses of Candesartan (32 mg); group 2 included patients treated with conventional doses of Candesartan (16 mg); and group 3 included patients that received antihypertensive treatment other than ARBs or angiotensin-converting-enzyme inhibitors. Patients were evaluated for lipid profile, HbA1C, insulin, C-peptide, c-reactive protein, aldosterone, renin, Homeostasis model assessment-insulin resistance, leptin, adiponectin and LAR. Baseline adiponectin, leptin, and LAR levels did not differ significantly between the three groups. After 6 months of treatment, LAR was significantly higher in group 3 than group 1 (P = .007) or group 2 (P = .023). Differences between effects of high (32 mg) and conventional doses (16 mg) of Candesartan on LAR were not observed (P = .678). Marginal across-group differences were detected for posttreatment circulating adiponectin level (P = .064). Univariate general linear model (GLM) analysis of posttreatment LAR detected significant by-group differences even after adjustment for age, gender, baseline values of LAR, and blood pressure. In this model, group was the only significant predictor of LAR after controlling for these variables. Treatment with high doses of the ARB, candesartan, is associated with significantly reduced LAR and marginally increased circulating adiponectin levels in hypertensive patients with multiple cardiovascular risk factors.


Different methods, different results: temporal trends in the study of nested subset patterns in parasite communities.
The search for nested subset patterns has become a powerful tool for understanding the processes shaping parasite communities. Here, we re-examine the results of past studies on nestedness in parasite communities, to assess how sensitive they are to the analytical method used. Using the metric N and the null model RANDOM1, the first method available to study nested patterns, early studies concluded that nestedness was infrequent in parasite communities. In contrast later studies, using instead the metric T and the nestedness temperature calculator (NTC), found that nested subset patterns were very common in parasite communities. Recently, a new algorithm, the binary matrix nestedness temperature calculator (BINMATNEST), has been proposed to quantify nestedness. Using data on 31 helminth communities of fish hosts, we show that applying the NTC yields consistently more significant nested patterns than when N and RANDOM1 are used on the same data. The use of BINMATNEST produced results that depend on the choice of the null model. To provide a benchmark, a straightforward comparison between the observed frequencies of co-occurrences of species with those expected from their prevalence under random assembly was also made for each community. This test indicates that random structure occurs in practically all communities, even those where one of the nestedness analyses found a significant pattern. We demonstrate that the probability of finding a nested pattern in a parasite community depends entirely on the metric and null model chosen for analysis.


Mosaic deletion of 20pter due to rescue by somatic recombination.
We report on a unique case of a mosaic 20pter-p13 deletion due to a somatic repair event identified by allele differentiating single nucleotide polymorphism (SNP) probes on chromosomal microarray. Small terminal deletions of 20p have been reported in a few individuals and appear to result in a variable phenotype. This patient was a 24-month-old female who presented with failure to thrive and speech delay. Chromosomal microarray analysis (CMA) performed on peripheral blood showed a 1.6 Mb deletion involving the terminus of 20p (20pter-20p13). This deletion appeared mosaic by CMA and this suspicion was confirmed by fluorescence in situ hybridization (FISH) analysis. Additionally, the deletion interval at 20p was directly adjacent to 15 Mb of mosaic copy-neutral loss of heterozygosity (LOH). The pattern of SNP probes was highly suggestive of a somatic repair event that resulted in rescue of the deleted region using the non-deleted homologue as a template. Structural mosaicism is rare and most often believed to be due to a postzygotic mechanism. This case demonstrates the additional utility of allele patterns to help distinguish mechanisms and in this case identified the possibility of either a post-zygotic repair of a germline deletion or a post-zygotic deletion with somatic recombination repair in a single step.


Heart Failure Statistics in Korea, 2020: A Report from the Korean Society of Heart Failure.
Heart failure (HF) is a disease with high morbidity and mortality. With ageing society and increasing prevalence of risk factors of HF, the prevalence of HF is expected to increase, as well. In this official report of the Korean Society of Heart Failure the epidemiology of HF in Korea is presented. The data of Korean National Health Insurance big data, the Korean Heart Failure (KorHF) and the Korean Acute Heart Failure (KorAHF) registries have been used. In 2018, the prevalence, incidence, mortality of HF patients, and mortality due to HF were 2,261, 579, 245, and 10.4 per 100.000 persons, respectively. Regarding the temporal trend, there was a continuous increase in HF prevalence (0.77% in 2002, 1.48% in 2013, and 2.24% in 2018) and HF related deaths. The most common etiology for HF was ischemic origin, and the dominant subtype was HF with reduced ejection fraction (EF), defined as EF ≤40%. Of these, 77.6%, 58.0%, and 55.1% received renin-angiotensin-system inhibitors (angiotensin-converting-enzyme inhibitors or angiotensin-receptor-blockers), beta-blockers, and aldosterone-antagonists, respectively. In 2018, 1,542 implantable cardiac defibrillators and 272 cardiac resynchronization therapy devices were implanted, and 176 patients received heart transplantation. With improvement of pharmacologic and non-pharmacological therapy, the survival time of HF has been improving in the last 2 decades; nonetheless, it is associated with enormous increase in medical costs. The prevalence of HF has been increasing in Korea. With improvement of therapy, the prognosis of HF has been improving, too. Nonetheless, appropriate interventions are necessary to prevent HF.


Neutrophil chemotactic factor release and neutrophil alveolitis in asbestos-exposed individuals.
Alveolar neutrophil accumulation occurs in asbestosis. To evaluate a possible role for release of neutrophil chemotactic factor (NCF) in the pathogenesis of asbestosis, spontaneous NCF release from alveolar macrophages obtained by bronchoalveolar lavage (BAL) in eight individuals with asbestosis, 13 asbestos-exposed individuals without asbestosis, and five control subjects has been studied. Alveolar macrophages were incubated in medium (four hours; 37 degrees C), and neutrophil responses to the supernatants were assayed in a microchemotaxis chamber. Alveolar macrophages from subjects with asbestosis released more NCF (97 +/- 19 neutrophils per high-power field [N/HPF]) than controls (3 +/- 1 N/HPF; p less than 0.01). Alveolar macrophages from individuals with asbestos exposure and increased BAL neutrophil proportions (n = 7) released more NCF (93 +/- 24 N/HPF) than individuals with asbestos exposure and normal BAL neutrophil proportions (n = 6; 11 +/- 6 N/HPF; p less than 0.02). The results show that spontaneous NCF release occurs in asbestosis and that NCF release is associated with neutrophil alveolitis in asbestos-exposed individuals without asbestosis, suggesting a pathogenic role for NCF in mediating this neutrophil alveolitis. The results of the study also suggest that the presence of crackles is a better predictor of the presence of neutrophil alveolitis than is an abnormal chest x-ray film.


Satoyoshi Syndrome with Progressive Orofacial Manifestations: A Case History Report.
A young female patient suffering from Satoyoshi syndrome had the first characteristic signs and symptoms of hair loss and progressive spontaneous intermittent painful spasms of limb muscles at age 6.5 years. Thereafter, she developed chronic diarrhea, amenorrhea, and skeletal deformities. In the orofacial region, she suffered from painful spasms of the masseter (jaw closing) muscles, progressive tooth loss, and degeneration of the mandibular condyles. Treatment with steroids and provision of complete dentures improved the signs and symptoms. Early diagnosis and timely provision of multidisciplinary care can minimize complications in these patients and improve their orofacial functions and quality of life.


Virtual reality in urban water management: communicating urban flooding with particle-based CFD simulations.
For communicating urban flood risk to authorities and the public, a realistic three-dimensional visual display is frequently more suitable than detailed flood maps. Virtual reality could also serve to plan short-term flooding interventions. We introduce here an alternative approach for simulating three-dimensional flooding dynamics in large- and small-scale urban scenes by reaching out to computer graphics. This approach, denoted 'particle in cell', is a particle-based CFD method that is used to predict physically plausible results instead of accurate flow dynamics. We exemplify the approach for the real flooding event in July 2016 in Innsbruck.


Association of Infections with the Use of a Temporary Double-Lumen Catheter for Hemodialysis.
The goal of this study was to identify the occurrence of secondary infection due to the use of temporary double-lumen catheters for hemodialysis in 96 patients with acute kidney injury or acute chronic kidney disease. For each patient, we collected a swab from the skin localized in the insertion of catheter before antisepsis; blood cultures from the catheter lumen, peripheral vein, and central venous access in withdrawing catheter; and cultures of catheter tips. Catheters were implanted into a femoral vein in 56.2% of patients. In 67.7% of patients, the catheter remained in place for 1 to 10 days, microbiological colonization was found in 51% of the catheters, 14.3% of patients had a bloodstream infection related to catheter, and 10.4% had an infection at the catheter insertion site. This study pointed out many health concerns related to the use of a catheter.


Pathogenicity of Pasteurella sp. in lumpsuckers (Cyclopterus lumpus L.).
The incidence of disease caused by Pasteurella sp. in farmed lumpsuckers in Norway has been steadily increasing in recent years, causing significant economic losses and fish welfare issues. The disease affects all life stages, both in hatcheries and after release into salmon cages. Therefore, it is important to establish robust challenge models, to be used for vaccine development. Exposure experiments via intramuscular and intraperitoneal injection underlined the high virulence of the bacteria, whereas the cohabitation and bath models allowed the chronic symptoms of the disease to be studied more accurately. Skin lesions and haemorrhage at the base of fins were observed in the more acute cases of the disease. Symptoms including white spots over the skin, especially around the eyes, characterized the chronic cases. The latter were most prominent from the bath challenge model. Histopathology indicated a systemic pattern of disease, whereas qPCR analysis from head kidney showed that bacteria may be present in survivor fish at the end of the challenges. In all the challenge models investigated, Pasteurella sp. was re-isolated from the fish, thus fulfilling Koch's postulates. These findings highlight the importance of screening of lumpsuckers prior to transfer to minimize the risks of carrying over asymptomatic carriers.


Primary malignant melanoma of the gall bladder.
A case of primary malignant melanoma of the gall bladder is reported, in which a 29 year old man presented with acute cholecystitis which led to perforation of the gall bladder and biliary peritonitis. To help in the differentiation between primary and secondary malignant melanoma in the gall bladder and to overcome some of the difficulties posed by the clinical identification of what is often a small or relatively inaccessible primary tumour, it is suggested that certain criteria should be fulfilled before primary melanoma is diagnosed. (i) Tumours must be solitary and arise from the mucosal surface of the gall bladder; (ii) they must either be papillary or polypoid; (iii) they must either display junctional activity or have any other primary sites excluded by history taking, examination, and investigation. If these criteria are applied to the published case reports of primary malignant melanoma, only six cases, including the present one, can be regarded as true primary tumours.


Role of herbivory in shaping the dryland vegetation ecosystem: Linking spiral vegetation patterns and nonlinear, nonlocal grazing.
Self-organized vegetation patterns are an amazing aspect of dryland ecosystems; in addition to being visually appealing, patterns control how these water-deprived systems react to escalating environmental stress. Although there is a wide variety of vegetation patterns, little is known about the mechanisms behind spiral patterns. The well-known models that explain other vegetation patterns such stripes, rings, and fairy circles cannot account for these spirals. Here we have adopted a modeling approach in which the interplay between herbivore grazing and vegetation is found to be the reason why spirals form. To comprehend the nonlinear dependence of grazing on the availability vegetation, we have introduced a grazing term that gets saturated when forage is abundant. To account for the impact of the spatial nonhomogeneity in vegetation layout, it is thought that grazing is dependent on mean vegetation density rather than density at a single site. Results show how the system dynamics is changed fundamentally depending on the different types of grazing response. Incorporation of nonlocality into the herbivore grazing leads to spiral-shaped vegetation patterns only in natural grazing scenarios; however, no patterning is seen in human controlled herbivory. Overall, our research points to the nonlocal, nonlinear grazing behavior of herbivores as one of the major driving forces for the development of spiral patterns.


All-Solid-State Textile Batteries Made from Nano-Emulsion Conducting Polymer Inks for Wearable Electronics.
A rollable and all-solid-state textile lithium battery based on fabric matrix and polymer electrolyte that allows flexibility and fast-charging capability is reported. When immerged into poly(3,4-ethylenedioxythiophene) (PEDOT) nano-emulsion inks, an insulating fabric is converted into a conductive battery electrode for a fully solid state lithium battery with the highest specific energy capacity of 68 mAh/g. This is superior to most of the solid-state conducting polymer primary and/or secondary batteries reported. The bending radius of such a textile battery is less than 1.5 mm while lightening up an LED. This new material combination and inherent flexibility is well suited to provide an energy source for future wearable and woven electronics.


DNA damage caused by ascorbate in the presence of Cu2+ induces mutations.
The DNA damage induced by ascorbate in the presence of Cu2+ was analyzed by sequencing, and the mutagenic consequences of damages to plasmid pUC18 lacZ' were assayed in a forward repairing system in E. coli JM109 in vivo. Ascorbate induced two classes of DNA damage in the presence of Cu2+, one being non-base-specific direct strand cleavage, and the other being sequence-specific base modification labile to alkali treatment. Radicals generated from ascorbate hydroperoxide were involved in DNA damaging reactions. Ascorbate and Cu2+ caused mutations in pUC18 lacZ' gene. The mutation frequency by this method was about 10(-4) at 18% survivors when measured as a loss of alpha-complementation. All the mutations found were single-base substitutions that occurred in the structural part of the lacZ' gene. They were predominantly G:C----A:T transitions.


Diagnostic classification past, present, and future: implications for pharmacotherapy.
Making a diagnosis is a key step in understanding the natural course of a disorder, selecting an appropriate treatment for the disorder, and predicting its response to treatment. Diagnostic proposals can be evaluated in two ways: reliability and validity. The reliability and validity of diagnoses are not one and the same, although establishing reliability is usually a necessary step before being able to evaluate and determine validity. There is little evidence that most psychiatric diagnoses are valid, but the reliability of diagnoses using classification systems developed since 1970 have greatly improved and are important for clinical practice and research. Past and current diagnostic systems have not optimally assisted the search for disorder-specific pathophysiological mechanisms, and they do not provide the specificity that clinicians would like when selecting medication. The Research Domain Criteria project is intended to shift research away from categorical diagnoses to focus on dysregulated neurobiological systems, and this approach ultimately may be more useful for understanding the pathophysiology of mental disorders and improving the development and use of treatment interventions.


Outcomes of stab wounds presenting to Kamuzu Central Hospital in Malawi.
Injuries are a leading cause of morbidity and mortality worldwide, necessitating that we understand the local burden of injury to improve injury-related trauma care and patient outcomes. The characteristics, outcomes, and risk factors for mortality following stab wounds in Malawi are poorly delineated. This is a retrospective, descriptive analysis of patients presenting to Kamuzu Central Hospital in Lilongwe, Malawi, with stab wounds from February 2008 to May 2018. Univariate and bivariate analyses were performed to compare patient and injury characteristics based on mortality. We performed Poisson multivariate regression to predict the factors that increase the relative risk of mortality. During the study, 32,297 patients presented with assault. Of those patients, 2,352 (7.3%) presented with stab wounds resulting in a 3.2% (n=74) overall mortality. The majority of wounds were to the head or cervical spine (n=1,043, 44.6%), while injuries to the chest (n=319, 13.7%) were less frequent. We found an increased relative risk of mortality in patients who presented with an injury to the chest (RR 3.95, 95% CI 1.79-8.72, p=0.001) and who were brought in by the police (RR 33.24, 95% CI 11.23-98.35, p<0.001). In this study, stab wounds accounted for 7.3% of all assault cases, with a 3.2% mortality. Though the commonest site of stab was the head, wounds to the chest conferred the highest relative risk of mortality. A multifaceted approach to reducing mortality is needed. Incorporating training of first responders in basic life support, including the police, may reduce stab-related mortality.


Levels of prostaglandins F2 alpha and E2 and thromboxane B2 in joint fluid in rheumatoid arthritis.
Prostaglandin F2 alpha (PGF2 alpha), prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) levels were determined by radioimmunoassay (RIA) in knee joint fluid in two groups of patients with classical or definite rheumatoid arthritis (RA). One group had no treatment for one week prior to the study. The second group consisted of patients who developed acute exudative arthritis despite the use of various non-steroidal anti-inflammatory drugs (NSAID). The main metabolites of PGF2 alpha in plasma and urine were measured in the untreated group. The conclusion to be drawn from this study are: 1) Treatment with NSAID effectively lowers PGF2 alpha and PGE2 and TXB2 levels in joint fluid. 2) Signs and symptoms of arthritis may persist in spite of lowered levels of PGF2 alpha and PGE2 in the joint fluid. 3) The main metabolites of PGF2 alpha in plasma and urine are above the low-normal limit in untreated patients. 4) The ratio TXB2/PG was low in untreated patients, suggesting that the thromboxane pathway is quantitatively minor in rheumatoid joint inflammation.


Prenatal exposure to perfluorinated chemicals and neurodevelopment in early infancy: The Hokkaido Study.
Perfluorinated chemicals (PFCs) are ubiquitous and persistent pollutants widely detected in blood samples of animals and humans across the globe. Although animal studies have shown the potential neurotoxicity of PFCs, there are few epidemiological studies regarding neurological effects of PFCs in humans, and those studies have had inconclusive results. In this study, we conducted a hospital-based prospective birth cohort study between 2002 and 2005 (n=514) to examine the associations between prenatal perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) exposures and the neurodevelopment of infants at 6 (n=173) and 18 (n=133) months of age. Using the second edition of the Bayley Scales of Infant Development (BSID II), the Mental and Psychomotor Developmental Indices (MDI and PDI, respectively) were assessed. PFOS and PFOA were measured in maternal serum samples by liquid chromatography-tandem mass spectrometry. After controlling for confounders, prenatal PFOA concentrations were associated with the MDI of female (but not male) infants at 6 months of age (β=-0.296; 95% confidence interval (CI): -11.96, -0.682). Furthermore, females born to mothers with prenatal concentrations of PFOA in the fourth quartile had MDI scores -5.05 (95% CI: -10.66 to 0.55) lower than females born to mothers with concentrations of PFOA in the first quartile (p for trend=0.045). However, PFOA concentrations were not significantly associated with neurodevelopmental indices at 18 months of age. In addition, we did not observe any significant association between PFOS concentrations and neurodevelopmental outcomes in early infancy. In conclusion, our results suggest that prenatal PFOA exposure may affect female mental scales of neurodevelopment at 6 months of age. Further studies with larger sample sizes and longer observation periods are required to clarify sex difference of the neurodevelopmental effects.


The cochlear aqueduct: an important landmark in lateral skull base surgery.
The cochlear aqueduct (CA) is used as a landmark in lateral skull base surgery. In this study anatomic relationships between the CA and adjacent neurovascular structures were examined by dissecting 32 temporal bones. Observations of the relationship of the external opening (EO) of the CA with the ninth, tenth, and eleventh cranial nerves, inferior petrosal sinus (IPS), and intrapetrous carotid artery (ICA) were noted. In addition to the distance of the EO of the CA to the vertical portion of the ICA, the entire length of the CA and the width of the EO were also measured. The ninth nerve was the only structure lodged at the EO of the CA in 34.4% of bones. However, in 40.6% of bones only the IPS crossed the EO of the CA, although the ninth nerve was situated just anteroinferiorly in the vicinity of the EO. In 15.6% of bones it was possible to observe both the ninth nerve and the IPS crossing the EO. In 9.4% of bones the EO of the CA was found to be occupied by the tenth and eleventh nerves. It was also observed that the ICA was located anteriorly on the same sagittal plane with the EO in 15.6% of bones. It was concluded that although in 90% of cases the EO of the CA was in close relation with the ninth nerve, other structures such as the IPS, the tenth and eleventh cranial nerves, and the ICA were also at risk during drilling in this area because of their intimate relationships with the EO of the CA.


Effects of major transporter and metabolizing enzyme gene polymorphisms on carbamazepine metabolism in Chinese patients with epilepsy.
The present study aimed to evaluate the effects of SNPs of major transporter and metabolizing enzyme genes on carbamazepine (CBZ) metabolism in Chinese patients with epilepsy. For 210 epileptic patients treated with CBZ as monotherapy, nine SNPs in candidate genes ABCB1, CYP3A4, CYP3A5, POR and EPHX1 were analyzed by PCR-RFLP or direct sequencing. Serum concentrations of CBZ, carbamazepine-10,11-epoxide (CBZE) and carbamazepine-10,11-trans dihydrodiol (CBZD) were determined by HPLC. Dose-adjusted concentrations of CBZ (CDRCBZ), CBZE (CDRCBZE), CBZD (CDRCBZ D) and CBZD:CBZE ratio were used as evaluation parameters for CBZ metabolism. The ABCB1 c.3435C>T was significantly associated with the CDR of CBZ and its major metabolites. CYP3A4*1G and CYP3A5*3 could influence CBZ metabolism, while POR*28 had no effect on it. The EPHX1 c.416A>G and c.128G>C variants were significantly associated with CBZD:CBZE ratio. Our data suggest that certain polymorphisms of major transporter and metabolizing enzyme genes could in part influence interindividual variability of CBZ metabolism in Chinese patients with epilepsy.


Mechanism of cardioventilatory coupling: insights from cardiac pacing, vagotomy, and sinoaortic denervation in the anesthetized rat.
Cardioventilatory coupling (CVC), a temporal alignment between the heartbeat and inspiratory activity, is a major determinant of breath-to-breath variation in observed respiratory rate (f(o)). The cardiac-trigger hypothesis attributes this to adjustments of respiratory timing by baroreceptor afferent impulses to the central respiratory pattern generator. A mathematical model of this hypothesis indicates that apparent CVC in graphical plots of ECG R wave vs. inspiratory time is dependent on the heart rate (HR), the rate of the intrinsic respiratory oscillator (f(i)), and the strength of the hypothetical cardiovascular afferent impulse. Failure to account for HR and f(i) may explain the inconsistent results from previous attempts to identify the neural pathways involved in CVC. Cognizant of these interactions, we factored in the HR-to-f(i) ratio in our examination of the role of the vagus nerve and arterial baroreceptors in CVC by cardiac pacing 29 anesthetized Sprague-Dawley rats and incrementally changing the HR. With the assumption of a relatively constant f(i), CVC could be examined across a range of HR-to-f(o) ratios before and after vagotomy, sinoaortic denervation, and vagotomy + sinoaortic denervation. We confirmed the relation between CVC, HR-to-f(o) ratio, and breath-to-breath respiratory period variability and demonstrated the loss of these relations after baroreceptor elimination. Sham experiments (n = 8) showed that these changes were not due to surgical stress. Our data support the notion that inspiratory timing can be influenced by cardiac afferent activity. We conclude that the putative cardiovascular input arises from the arterial baroreceptors and that the vagus nerve is not critical for CVC.


Transforming Discoveries About Cortical Microcircuits and Gamma Oscillations Into New Treatments for Cognitive Deficits in Schizophrenia.
The major cause of disability in schizophrenia is cognitive impairment, which remains largely refractory to existing treatments. This reflects the fact that antipsychotics and other therapies have not been designed to address specific brain abnormalities that cause cognitive impairment. This overview proposes that understanding how specific cellular and synaptic loci within cortical microcircuits contribute to cortical gamma oscillations may reveal treatments for cognitive impairment. Gamma oscillations are rhythmic patterns of high frequency (∼30-100 Hz) neuronal activity that are synchronized within and across brain regions, generated by a class of inhibitory interneurons that express parvalbumin, and recruited during a variety of cognitive tasks. In schizophrenia, both parvalbumin interneuron function and task-evoked gamma oscillations are deficient. While it has long been controversial whether gamma oscillations are merely a biomarker of circuit function or actually contribute to information processing by neuronal networks, recent neurobiological studies in mice have shown that disrupting or enhancing synchronized gamma oscillations can reproduce or ameliorate cognitive deficits resembling those seen in schizophrenia. In fact, transiently enhancing the synchrony of parvalbumin interneuron-generated gamma oscillations can lead to long-lasting improvements in cognition in mice that model aspects of schizophrenia. Gamma oscillations emerge from specific patterns of connections between a variety of cell types within cortical microcircuits. Thus, a critical next step is to understand how specific cell types and synapses generate gamma oscillations, mediate the effects of gamma oscillations on information processing, and/or undergo plasticity following the induction of gamma oscillations. Modulating these circuit loci, potentially in combination with other approaches such as cognitive training and brain stimulation, may yield potent and selective interventions for enhancing cognition in schizophrenia.


Wogonin potentiates cisplatin-induced cancer cell apoptosis through accumulation of intracellular reactive oxygen species.
Chemoresistance to cisplatin is a major limitation of cisplatin-based chemotherapy in the clinic. The combination of cisplatin with other agents has been recognized as a promising strategy to overcome cisplatin resistance. Previous studies have shown that wogonin (5,7-dihydroxy-8-methoxyflavone), a flavonoid isolated from the root of the medicinal herb Scutellaria baicalensis Georgi, sensitizes cancer cells to chemotheraputics such as etoposide, adriamycin, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TNF. However, the effect of wogonin on cisplatin-induced cytotoxicity has not been previously reported. In this study, the non-small cell lung cancer cell line A549 and the cervical cancer cell line HeLa were treated with wogonin or cisplatin individually or in combination. It was found for the first time that wogonin is able to sensitize cisplatin-induced apoptosis in both A549 cells and HeLa cells as indicated by the potentiation of activation of caspase-3, and cleavage of the caspase-3 substrate PARP in wogonin and cisplatin co-treated cells. Importantly, wogonin robustly induced H2O2 accumulation in these cells, which substantially contributes to the sensitization of cisplatin cytotoxicity by wogonin, as two reactive oxygen species scavengers, butylated hydroxyanisole (BHA) and N-acetyl-L-cysteine (NAC), significantly suppressed the potentiated cytotoxicity caused by wogonin and cisplatin co-treatment. The results from this study provide important new evidence supporting the potential use of wogonin as a cisplatin sensitizer for cancer therapy.


Regulation of mitochondrial structure and function by the F1Fo-ATPase inhibitor protein, IF1.
When mitochondrial respiration is compromised, the F(1)F(o)-ATP synthase reverses and consumes ATP, serving to maintain the mitochondrial membrane potential (Delta psi(m)). This process is mitigated by IF(1). As little is known of the cell biology of IF(1), we have investigated the functional consequences of varying IF(1) expression. We report that, (1) during inhibition of respiration, IF(1) conserves ATP at the expense of Delta psi(m); (2) overexpression of IF(1) is protective against ischemic injury; (3) relative IF(1) expression level varies between tissues and cell types and dictates the response to inhibition of mitochondrial respiration; (4) the density of mitochondrial cristae is increased by IF(1) overexpression and decreased by IF(1) suppression; and (5) IF(1) overexpression increases the formation of dimeric ATP synthase complexes and increases F(1)F(o)-ATP synthase activity. Thus, IF(1) regulates mitochondrial function and structure under both physiological and pathological conditions.


Childhood obesity: a review of increased risk for physical and psychological comorbidities.
Worldwide estimates of childhood overweight and obesity are as high as 43 million, and rates continue to increase each year. Researchers have taken interest in the childhood obesity epidemic and the impact of this condition across health domains. The consequences of childhood and adolescent obesity are extensive, including both medical and psychosocial comorbidities. The purpose of this review was to consolidate and highlight the recent literature on the comorbidities associated with childhood obesity, both nationally and internationally. PubMed and PsychINFO searches were conducted on childhood obesity and comorbidities. The initial search of the terms obesity and comorbidity yielded >5000 published articles. Limits were set to include studies on children and adolescents that were published in peer-reviewed journals from 2002 to 2012. These limits narrowed the search to 938. Review of those articles resulted in 79 that are included in this review. The major medical comorbidities associated with childhood obesity in the current literature are metabolic risk factors, asthma, and dental health issues. Major psychological comorbidities include internalizing and externalizing disorders, attention-deficit hyperactivity disorder, and sleep problems. The high prevalence rates of childhood obesity have resulted in extensive research in this area. Limitations to the current childhood obesity literature include differential definitions of weight status and cut-off levels for metabolic risk factors across studies. Additionally, some results are based on self-report of diagnoses rather than chart reviews or physician diagnosis. Even so, there is substantial support for metabolic risk factors, internalizing disorders, attention-deficit hyperactivity disorder, and decreased health-related quality of life as comorbidities to obesity in childhood. Additional investigations on other diseases and conditions that might be associated with childhood obesity are warranted and intervention research in this area is critical.


Self testing, an emerging component of clinical chemistry.
Self testing as a phase of health delivery has been utilized for approximately 70 years, but within the last two decades there has been an increasing interest in and use of self testing. The practice of self testing has a sound basis, which involves medical relevancy, cost containment, and convenience. It is reasonable to anticipate that self testing will increase in the future as medical needs and available procedures are established. The clinical chemist, the physician, and the industrial producer of test systems all have important roles in self testing. The clinical chemist, whether in a hospital laboratory or in an industrial setting, has the responsibility to create new self-testing procedures that represent expansion and improvement over those currently available. The clinical chemist also has a critical role in the evaluation of new self-testing procedures and in validating their capability of providing high-quality information. The provision of quality-assurance programs and proficiency programs for the user can most effectively be carried out by clinical chemists. The clinical chemist can also play an important role as a consultant, teacher/educator, and trouble shooter in recognizing and helping solve problems that may appear in various areas of self testing. The classic role of the physician has been to diagnose disorders of the patients and provide therapy for effective care. The role of the physician in self testing is quite comparable to his usual role, since the ultimate diagnosis of disease will be carried out by the physician and he will continue to be the source for definition of therapy. A major portion of self testing will be carried out with the recommendation of a physician, and he will maintain a role in the interpretation of results. The physician needs to be familiar with self-testing practices and procedures and be prepared to provide interpretation of self-testing results. Industry supplies an increasing proportion of reagent systems and instruments for the clinical laboratory. The supplying of reagent systems and small instruments for self testing is almost completely a role of industry. The creation and funding of new products for self testing will be provided by industry to a large extent. A critical function of industry is to provide high-quality products and efficient customer service to the self-testing component of health delivery. We have each played a role in self testing over a period of approximately 40 years. During this period self testing has become an important phase of clinical laboratory practice.(ABSTRACT TRUNCATED AT 400 WORDS)


Diagnostic value of thyrotropin concentrations in serum as measured by a sensitive immunoradiometric assay.
A new, highly sensitive immunoradiometric thyrotropin (TSH) assay involving solid-phase-coupled monoclonal antibodies (Boots-Celltech Sucrosep IRMA-TSH) has been evaluated in a wide variety of patients with thyroidal and nonthyroidal illnesses and the results compared with those obtained by conventional diagnostic TSH RIAs. The sensitivity of the present assay ranged from 0.036 to 0.1 milli-int. unit/L (mean 0.056). TSH, measurable in serum of each of 128 euthyroid patients, ranged from 0.1 to 6.3 milli-int. units/L (mean 1.7, SD 1.1). Similar concentrations were found in 15 healthy pregnant women. TSH was undetectable in 27 hyperthyroid patients, of whom six were tested with thyroliberin stimulation and failed to respond. The mean TSH concentration measured in 62 seriously ill hospital patients of 2.7 (SD 2.5) milli-int. units/L was significantly higher (p less than 0.05) than in the euthyroid patients. Basal values and peak TSH responses to thyroliberin testing correlated well (r = 0.63, n = 48), irrespective of clinical diagnosis. We conclude that the present assay readily discriminates between euthyroid and hyperthyroid patients and should replace conventional TSH RIAs in diagnostic laboratories.


The origin, in vitro differentiation, and stemness specificity of progenitor cells.
Since the successful collection of the first progenitor stem cells (SCs), there has been an increased interest in these cells as a model for undiscovered and unlimited potential of differentiation and development. Additionally, it was shown that SC populations display an ability to form pluripotent and/or totipotent cell populations. It was found that human ovarian granulosa cells (GCs) maintain a large capacity for differentiation into several other cell lineages, such as chondrogenic, osteogenic, neurogenic, and adipogenic, particularly during long-term, in vitro culture. In these cases, the specific media supplements that promote various pathways of differentiation, such as leukemia-inhibiting factor (LIF) and/or FSH, are well recognized. However, these are only some examples of the differentiation possibilities of human SCs in vitro and other pathways still require further investigation. Many SC populations, which are directed to differentiate into specific cell types, are also successfully used in several human disease therapies, e.g. leukemia. Moreover, SCs are used for tissue scaffold construction in patients with respiratory and cardiovascular diseases. In this review, the most recent knowledge about the in vitro growth and differentiation capacity of SCs is presented. Furthermore, we discuss the possible worldwide application of SCs in advanced cell and tissue bioengineering. In conclusion, it is suggested that, in the future, SCs will be a basic strategy in human therapy, and their use will open new gates in regenerative and reconstructive medicine in the 21st century.


Investigation of metabolites of tofizopam in man and animals.
The biotransformation of the labelled forms of 1-(3,4-dimethoxy-phenyl)-4-methyl-5-ethyl-7,8-dimethyoxy-5H-2,3-be nzodiazepine (Grandaxin, tofizopam) has been investigated after oral administration in animals and man. The major part of urinary metabolites was found to be conjugated with glucuronic acid. The metabolites were separated using TLC technique and analysed by GLC and GLC-MS. The chief way of the metabolic information of tofizopam is demethylation, however, the position of CH3 elimination as well as the rate of it was different in various species.


Metallo-β-lactamase-producing Enterobacteriaceae isolates at a Taiwanese hospital: lack of distinctive phenotypes for screening.
We investigated the prevalence of metallo-β-lactamases (MBLs) among 1,827 Enterobacteriaceae isolates collected in 2006 and evaluated the VITEK 2 microbiology system, modified Hodge test, and 2 combined disk tests as the screening tools for MBLs by using these isolates and 77 previously characterized IMP-8 producers. The IMP-8 MBL was identified in 18 isolates of 2006, and the IMP-8-positive isolates represented 0.2%, 1.1%, and 5.0% of all Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae isolates, respectively. Only one-third of all MBL producers could be recognized by either VITEK 2 or the Hodge test. MBL production could be identified in 38 (40%) of the 95 IMP-8-producing isolates by the combined disk test using meropenem disks supplemented by phenylboronic acid and EDTA, and only 2 (2.1%) isolates gave positive results in the combined disk test using meropenem disks supplemented with dipicolinic acid. Of all IMP-8 producers, 37.9%, 50.5%, and 32.6% were nonsusceptible to tigecycline, fluoroquinolones, and both, respectively. In conclusion, this study demonstrated the lack of distinct phenotypes that could be easily identified among the IMP-8-producing Enterobacteriaceae isolates at a Taiwanese hospital. Continuous surveillance and monitoring are needed because the widespread of tigecycline- and fluoroquinolone-coresistant MBL producers may become a serious therapeutic problem.


The cost of needlestick injuries associated with insulin administration.
The administration of insulin by a carer or healthcare professional is associated with a risk of needlestick injury. Such injuries create a burden for carers and professionals in terms of anxiety, stress and morbidity as well as the NHS in terms of lost productivity, treatment costs and litigation. This study estimates the economic burden of these injuries to the NHS in the UK based on published estimates of the incidence and cost of needlestick injuries. The findings suggest that such injuries cost the NHS approximately 600,000 pounds sterling per annum. Many of these injuries and their associated costs could be avoided through increased adoption of safety devices. Indeed, evidence suggests that the increased acquisition cost of safety devices could be more than offset by savings resulting from the reduced incidence of needlestick injuries. Trusts are encouraged to implement improved monitoring and surveillance procedures to inform the debate on the appropriate use of safety devices.


Human disease/clinical medical sciences for dentistry in early-years dental graduates: Transition from undergraduate study to clinical practice.
Dental bodies across Europe have published curricula aiming to guide the development of a graduating dentist who is safe and competent, and which also contain direction on what knowledge and understanding of patient's health, drugs and disease a recent graduate should have. A questionnaire to survey Foundation Dentists in Wales regarding their undergraduate teaching and assessment in human disease/clinical medical science for dentistry and how this translates to their knowledge, attitudes and confidence in the dental management of patients who may have chronic disease or disability. A 97% response rate to the questionnaire from Foundation Dentists graduating from schools across the UK showed that the large majority felt their teaching and learning in human disease/clinical medical science for dentistry was appropriately delivered and assessed, and that they were well prepared for independent dental practice and to plan and safely manage treatments for all their patients. This survey of newly qualified dentists representing graduates from different types of dental courses and both newer and long-established schools across the UK reports the foundation dentists felt that they are competent and safe to care for all patients, including those with complex medical histories. The foundation dentists surveyed have completed dental undergraduate courses containing the appropriate education and assessment for human health and disease, such that they are prepared to manage their patient population safely, and are well placed to serve their patients as the population continues to age and the amount of medical morbidity increases.


Risk factors for early childhood caries in disadvantaged populations.
Early childhood caries is a significant international public health problem. The aim of this paper was to review the current evidence of the risk factors for dental caries in disadvantaged children under 6 years of age. Medline, Cochrane, and PubMed database searches were conducted. Systematic reviews were used where available, or meta-analyses; randomized, controlled trials; and cohort, case-control, and cross-sectional studies (in that order). Studies were restricted to those published in English from 1990 to October 2010. Early childhood caries has a complex etiology with biological, behavioral, and sociodemographic influences. Evidence suggests that young children are most likely to develop caries if Streptococcus mutans is acquired at an early age, although this is influenced by other factors, such as oral hygiene, fluoride, diet, dental visit patterns, socioeconomic status, ethnicity, and health literacy. Etiological pathways should be taken into consideration when designing interventions to prevent dental caries in disadvantaged preschool children.


Actuating mechanism and design of a cylindrical traveling wave ultrasonic motor using cantilever type composite transducer.
Ultrasonic motors (USM) are based on the concept of driving the rotor by a mechanical vibration excited on the stator via piezoelectric effect. USM exhibit merits such as simple structure, quick response, quiet operation, self-locking when power off, nonelectromagnetic radiation and higher position accuracy. A cylindrical type traveling wave ultrasonic motor using cantilever type composite transducer was proposed in this paper. There are two cantilevers on the outside surface of cylinder, four longitudinal PZT ceramics are set between the cantilevers, and four bending PZT ceramics are set on each outside surface of cantilevers. Two degenerate flexural vibration modes spatially and temporally orthogonal to each other in the cylinder are excited by the composite transducer. In this new design, a single transducer can excite a flexural traveling wave in the cylinder. Thus, elliptical motions are achieved on the teeth. The actuating mechanism of proposed motor was analyzed. The stator was designed with FEM. The two vibration modes of stator were degenerated. Transient analysis was developed to gain the vibration characteristic of stator, and results indicate the motion trajectories of nodes on the teeth are nearly ellipses. The study results verify the feasibility of the proposed design. The wave excited in the cylinder isn't an ideal traveling wave, and the vibration amplitudes are inconsistent. The distortion of traveling wave is generated by the deformation of bending vibration mode of cylinder, which is caused by the coupling effect between the cylinder and transducer. Analysis results also prove that the objective motions of nodes on the teeth are three-dimensional vibrations. But, the vibration in axial direction is minute compared with the vibrations in circumferential and radial direction. The results of this paper can guide the development of this new type of motor.


Survival advantage of lanthanum carbonate for hemodialysis patients with uncontrolled hyperphosphatemia.
Lanthanum carbonate is a non-calcium phosphate binder that is effective for the treatment of hyperphosphatemia. However, it is unknown whether treatment with lanthanum affects survival. We retrospectively collected data on maintenance hemodialysis patients at 22 facilities (n = 2292) beginning in December 2008, a time point immediately prior to the commercial availability of lanthanum in Japan. We compared 3-year all-cause mortality among patients who initiated lanthanum (n = 560) and those who were not treated with lanthanum during the study period (n = 560) matched by the propensity score of receiving lanthanum. Several sensitivity analyses were performed to test the robustness of the primary analysis. After the market introduction of lanthanum, the percentage of patients receiving the binder increased gradually to 27%. In the propensity score-matched analysis, the mortality rate for the lanthanum group was not significantly lower than the non-lanthanum group [hazard ratio (HR), 0.71; 95% confidence interval (CI), 0.47-1.09). However, stratification by serum phosphorus disclosed significant survival benefit of lanthanum for patients with serum phosphorus >6.0 mg/dL (HR, 0.52; 95% CI, 0.28-0.95), but not in patients with serum phosphorus ≤6.0 mg/dL (HR, 1.00; 95% CI, 0.55-1.84). The survival benefit of lanthanum in patients with serum phosphorus >6.0 mg/dL was consistent across subgroups and robust in different analytical approaches. Treatment with lanthanum was independently associated with a significant survival benefit in hemodialysis patients with inadequately controlled hyperphosphatemia. Further studies are required to confirm these findings.