[A questionnaire survey on the theory of postoperative infection prophylaxis in orthopedics].
A questionnaire survey on the theory of postoperative infection prophylaxis was conducted to obtain the consensus on perioperative antimicrobial use among orthopedists in Japan in the period from April to September 2000. Fifty of the 91 orthopedists replied, and the following consensus was obtained. An antimicrobial prophylaxis (AMP) agent should be chosen based on their efficacy against the pathogens expected to be contaminants, such as Staphylococcus spp., and Streptococcus spp., Use an AMP agent that achieves a bactericidal concentration in both the serum and operating site. Use an AMP agent that has little unfavourable side effects. Use an AMP agent that affects minimally the normal bacterial flora. The most commonly used agents are the penicillins and first and second generation cephalosporins. The optimal strategy for most commonly used agents entails infusion of the first dose between approximately 30 minutes pre and post-skin incision and the therapeutic levels should be maintained throughout the operation. The AMP agents having no cross-resistance to the prophylactic agents should be used, if postoperative infection is suspected or developed. The most commonly used agent for both clean operations with or without foreign implants and dirty operations is cefazolin (CEZ), followed by cefotiam (CTM) and flomoxef (FMOX).


Whole-brain radiotherapy and stereotactic radiosurgery in brain metastases: what is the evidence?
The overall local treatment paradigm of brain metastases, which includes whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS), continues to evolve. Local therapies play an important role in the management of brain metastases. The choice of local therapy depends on factors that involve the patient (performance status, expected survival, and age), the prior treatment history, and the tumor (type and subtype, number, size, location of metastases, and extracranial disease status). Multidisciplinary collaboration is required to facilitate an individualized plan to improve the outcome of disease in patients with this life-limiting complication. There has been concern about the neurocognitive effects of WBRT. A number of approaches that mitigate cognitive dysfunction, such as pharmacologic intervention (memantine) or a hippocampal-sparing strategy, have been studied in a prospective manner with WBRT. Although there has been an increase in the use of SRS in the management of brain metastases in recent years, WBRT retains an important therapeutic role.


In vitro effect of plasma during phenylhydrazine-induced erythrocyte oxidative damage.
Erythrocytes were incubated for 60 min either in plasma or phosphate-buffered saline containing 10 mM phenylhydrazine hydrochloride. Plasma prevented the decrease in membrane fluidity observed in saline-phenylhydrazine incubated erythrocytes but these cells showed decreases in both filterability and active extrusion of Na+ that were nearly 100% lower than those found in erythrocytes incubated in plasma-phenyl-hydrazine. Also erythrocyte lipid peroxidation, as measured as thiobarbituric acid reactive products, was 100% higher in the presence of plasma. These results suggest that plasma could play "in vivo" an active role during oxidant-induced erythrocyte damage, contributing significantly to the hemolytic effects of oxidation.


Enhancement by cyclic AMP of antibody-induced suppression of the fourth component of complement.
Our laboratory has shown that short-term treatment in vivo or in vitro with monospecific antibody to individual complement components can have long-term effects on the production of those components. In vitro studies have focused on the fourth component of complement (C4) in a guinea pig model. Uniform splenic fragments have been used to mimic the in vivo microenvironment of the C4-producing macrophages. A 4-day exposure to anti-C4 antibody led to a reduction of secreted C4 for 1 to 2 wk and a reduction of intracellular C4 that persisted even longer. In an attempt to understand how short-term exposure to antibody can specifically and permanently disrupt the C4-producing cell, we have determined whether C4 suppression could be enhanced by components that modulate cellular functions through their role as secondary intracellular messengers. We found that compounds which elevated cellular levels of cAMP by any of three mechanisms all enhanced antibody-induced suppression of C4.


Management of Type 2 Diabetes Mellitus through Telemedicine.
Type 2 diabetes mellitus T2DM has a huge and growing burden on public health, whereas new care models are not implemented into clinical practice; in fact the purpose of this study was to test the effectiveness of a program of integrated care for T2DM, compared with ordinary diligence. "Progetto Diabete Calabria" is a new organizational model for the management of patients with diabetes mellitus, based on General Practitioners (GPs) empowerment and the use of a web-based electronic health record, shared in remote consultations among GPs and Hospital Consultants. One-year change in glucose and main cardiovascular risk factors control in 104 patients (Cases) following this integrated care program has been evaluated and compared with that of 208 control patients (Controls) matched for age, gender, and cardiometabolic profile, and followed in an ordinary outpatient medical management by the Consultants only. Both patient groups had Day Hospitals before and after the study period. The mean number of accesses to the Consultants during the study was 0.6 ± 0.9 for Cases, and 1.3 ± 1.5 for Controls (p<0.0001). At follow-up, glycated hemoglobin (HbA1c) significantly decreased from 58 ± 6 to 54 ± 8 mmol/mol in Cases only (p=0.01); LDL cholesterol decreased in both groups; body mass index decreased in Cases only, from 31.0 ± 4.8 to 30.5 ± 4.6 kg/m(2) (p=0.03). The present study demonstrates that a health care program based on GPs empowerment and taking care plus remote consultation with Consultants is at least as effective as standard outpatient management, in order to improve the control of T2DM.


The Rorschach: projective technique or psychometric test?
Various approaches to the Rorschach Technique are described in terms of the idiographic-nomothetic axis and the perceptual-content axis. It is suggested that it is most productive to view the Rorschach as a projective tool, with perceptual scoring a secondary factor. Current efforts at objectification of the Rorschach are not seen as useful as efforts to enhance its projective qualities. Some possible ways are discussed in which the projective value of the instrument can be maximized.


Changes in hepatitis A and B vaccination rates in adult patients with chronic liver diseases and diabetes in the U.S. population.
Professional societies recommend hepatitis A and hepatitis B immunization for individuals with chronic liver disease (CLD), but the degree of implementation is unknown. Data were obtained from the National Health and Nutrition Examination Surveys (NHANES) conducted in 1999-2008. For the entire study population and for those with CLD and diabetes, we determined the rates and independent predictors of history of hepatitis A and hepatitis B (HepA and HepB) vaccinations, of their effectiveness, and of seroprevalence of hepatitis A antibody and anti-HB surface antibody. In total, 24,871 participants from NHANES were included: 14,886 (1999-2004) and 9,985 (2005-2008). Of these individuals, 14.0% had CLD and 8.6% had diabetes. During the study period, HepA vaccination in CLD increased from 13.3% ± 1.0% to 20.0% ± 1.5%, HepB vaccination increased from 23.4% ± 1.2% to 32.1% ± 1.5%. Of subtypes of CLD, HepA vaccination rates increased only in nonalcoholic fatty liver disease (NAFLD), whereas HepB vaccination increased for patients with hepatitis C and nonalcoholic fatty liver disease. In the diabetic cohort, HepA vaccination rates increased from 9.3% ± 1.1% to 15.4% ± 1.7% and HepB rates increased from 15.2% ± 1.5% to 22.4% ± 1.7%. All changes were similar to those observed in the general population. The quality measure (QM) for HepA in the general population decreased from 44.4% ± 1.2% in 1999-2004 to 41.7% ± 1.9% in 2005-2008, and similar changes were noted for all subcohorts. On the other hand, QM for HepB increased from 31.7% ± 0.9% to 40.7% ± 1.0% in the population, whereas no changes in QM were noted in any diagnostic cohort except for NAFLD. Although vaccination rates in CLD and diabetic cohorts are increasing, they remain low. Given the public health implications of acute hepatitis A and hepatitis B in patients with CLD, better implementation of the vaccination recommendations for these populations is warranted.


Blue Light Imaging and Linked Color Imaging for the Characterization of Mucosal Changes in Chronic Gastritis: A Clinicians View and Brief Technical Report.
Blue light imaging (BLI) and linked color imaging (LCI) are new imaging modalities for the endoscopic evaluation of mucosal changes within the digestive tract. There is little experience with these modalities in the characterization of chronic gastritis (CG) intestinal metaplasia (IM) and atrophy in the stomach. In a single-center observational pilot study, we correlated endoscopic findings with histology in selected patients. Findings from 29 patients were included in the analysis. Six patients had macroscopically normal gastric mucosa at endoscopy, and this was confirmed histologically in 5 of them. At endoscopy, 15 patients had the presence of IM in the antrum predicted, and this was confirmed histologically in 11 (73%). In the corpus, we predicted the presence of IM in 14 patients, and this was confirmed in 11 (78%) at histology. Eleven patients had the endoscopic suspicion of atrophy in antrum, which was confirmed in 9 patients (82%). In total, 14 patients had endoscopic suspicion of atrophy in corpus mucosa at endoscopy, but only 10 were confirmed in histology (71%). The concordance of endoscopic classification and histology was 93% for antrum and 88% for corpus. The positive predictive value and negative predictive value for IM were 0.74 and 0.83 and for atrophy 0.63 and 0.97, respectively. LCI and BLI are helpful in characterization of mucosal changes in CG. The ability to rule out premalignant conditions by endoscopy only reflects the clinical use and harbors significant clinical implications.


Cytotoxic Effects of Artemisia annua L. and Pure Artemisinin on the D-17 Canine Osteosarcoma Cell Line.
Artemisia annua has been used for centuries in Traditional Chinese Medicine. Although used as an antimalarial drug, its active compound artemisinin and the semisynthetic derivatives have also been investigated for their anticancer properties, with interesting and promising results. The aims of this research were to evaluate (i) the cytotoxicity and the antiproliferative effect of pure artemisinin and a hydroalcoholic extract obtained from A. annua on the D-17 canine osteosarcoma cell line and (ii) the intracellular iron concentration and its correlation with the cytotoxic effects. Both artemisinin and hydroalcoholic extract induced a cytotoxic effect in a dose-dependent manner. Pure artemisinin caused an increase of cells in the S phase, whereas the hydroalcoholic extract induced an evident increase in the G2/M phase. A significant decrease of iron concentration was measured in D-17 cells treated with pure artemisinin and hydroalcoholic extract compared to untreated cells. In conclusion, although preliminary, the data obtained in this study are indicative of a more potent cytotoxic activity of the hydroalcoholic extract than pure artemisinin, indicating a possible synergistic effect of the phytocomplex and a mechanism of action involving iron and possibly ferroptosis. Considering the similarities between human and canine osteosarcomas, progress in deepening knowledge and improving therapeutic protocols will probably be relevant for both species, in a model of reciprocal translational medicine.


Adult sinonasal soft tissue sarcoma: analysis of 48 cases from the French Sarcoma Group database.
The aim of this study was to determine the frequency of primary sinonasal adult sarcoma, identify histological subtypes, and analyze prognostic factors. Retrospective review. Forty-eight adult sinonasal sarcomas included in the French Sarcoma Group database (Conticabase) were reviewed. The most frequent tumor types were alveolar rhabdomyosarcoma (33.3%), embryonal rhabdomyosarcoma (14,6%), unclassified sarcoma (14.6%), and leiomyosarcoma (12.5%). All round cell tumors were rhabdomyosarcomas. The 5-year overall survival (OS), metastasis-free survival (MFS), and local recurrence-free survival (LRFS) rates were 62.3%, 73%, and 88.8%, respectively. Histotype was a prognostic factor for OS, MFS, and LRFS, with the worst prognosis associated with rhabdomyosarcomas, regardless of the subtype. The tumor grade influenced the OS and MFS. Surgery was a predictive factor for a complete response. These results suggest that sinonasal tract should be considered as an unfavorable site for rhabdomyosarcoma. Moreover, surgery should always be considered in treatment.


Funding and infrastructure among large-scale clinical trials examining cardiovascular diseases in Japan: evidence from a questionnaire survey.
Large-scale clinical trials with thousands of participants are often needed to evaluate the risk reductions of cardiac events and/or death. Many recent clinical trials have evaluated the incidences of cardiac events using hard endpoints, especially in cardiovascular and metabolic medicine. A high investigation cost is involved in conducting a large-scale clinical trial, and obtaining sufficient funding is essential. The infrastructural environment of clinical trials is currently inadequate in Japan. We conducted a questionnaire-based survey to address this issue. The present study sought to clarify the current situation surrounding large-scale clinical trials in terms of funding and infrastructure, and to inform discussion about improving the financial and infrastructural situation for clinical trials. We sent questionnaires to 119 sponsors of large-scale clinical trials between August 2007 and December 2007, and between July 2009 and August 2009. Answers to each question were summarized and data were statistically analyzed. We received responses from the sponsors of 63 (52.9%) out of 119 trials to which questionnaires were sent. The results revealed that 25 trials (39.7%) were funded by foundations, and 21 trials (33.3%) were funded by public agencies. All of the foundations involved in conducting clinical trials, where funding sources were specified, were funded by private organizations such as pharmaceutical companies. All of the clinical trials with a cost of JPY 300 million (USD 3.27 million) or more were funded by private organizations, and none were funded solely by public agencies. The sponsors of 23 trials (36.5%) responded that the trial was 'not registered' to clinical trial registry. The questionnaire responses revealed that there were still many trials whose funding sources were unclear and many sponsors were unaware of their responsibilities in managing and/or financing the costs of clinical trials. These findings indicate that further discussion is required to establish appropriate frameworks and/or rules regarding funding, while considering conflicts of interest. This discussion should take place as soon as possible to facilitate appropriate clinical trials.


Bilateral sudden hearing loss and metastatic pancreatic adenocarcinoma.
We report a rare case of bilateral sudden and profound hearing loss caused by bilateral temporal bone metastasis from a primary adenocarcinoma of the tail of the pancreas. The hearing loss was the patient's only reason to seek medical care. Seventh nerve involvement was very minimal, when compared with that of the eighth nerve.


When to institutionalize the elderly.
Comprehensive evaluation and follow-up of the chronically ill aged patient may show that he can stay at home with support from family and community services. Guidelines are given for choosing a nursing home when necessary.


Quinones as the redox signal for the arc two-component system of bacteria.
The Arc two-component signal transduction system mediates adaptive responses of Escherichia coli to changing respiratory conditions of growth. Under anaerobic conditions, the ArcB sensor kinase autophosphorylates and then transphosphorylates ArcA, a global transcriptional regulator that controls the expression of numerous operons involved in respiratory or fermentative metabolism. We show that oxidized forms of quinone electron carriers act as direct negative signals that inhibit autophosphorylation of ArcB during aerobiosis. Thus, the Arc signal transduction system provides a link between the electron transport chain and gene expression.


Immobilized thrombin receptor agonist peptide accelerates wound healing in mice.
To accelerate the healing processes in wound repair, attempts have been repeatedly made to use growth factors including thrombin and its peptide fragments. Unfortunately, the employment of thrombin is limited because of its high liability and pro-inflammatory actions at high concentrations. Some cellular effects of thrombin in wound healing are mediated by the activation of protease activated receptor-1 (PAR-1). The thrombin receptor agonist peptide (TRAP:SFLLRN) activates this receptor and mimics the effects of thrombin, but TRAP is a relatively weak agonist. We speculated that the encapsulated peptide may be more effective for PAR-1 activation than nonimmobilized peptide and developed a novel method for TRAP encapsulation in hydrogel films based on natural and synthetic polymers. The effects of an encapsulated TRAP in composite poly(N-vinyl caprolactam)-calcium alginate (PVCL) hydrogel films were investigated in a mouse model of wound healing. On day 7 the wound sizes decreased by about 60% under TRAP-chitosan-containing PVCL films, as compared with control films without TRAP. In the case of TRAP-polylysine-containing films no significant decrease in wound sizes was found. The fibroblast/macrophage ratio increased under TRAP-containing films on day 3 and on day 7. The number of proliferating fibroblasts increased to 150% under TRAP-chitosan films on day 7 as compared with control films. The number of [3H]-thymidine labeled endothelial and epithelial cells in granulation tissues was also enhanced. Thus, the immobilized TRAP to PVCL-chitosan hydrogel films were found to promote wound healing following the stimulation of fibroblast and epithelial cell proliferation and neovascularization. Furthermore, TRAP was shown to inhibit the secretion of the inflammatory mediator PAF from stimulated rat peritoneal mast cells due to augmentation of NO release from the mast cells. The encapsulated TRAP is suggested to accelerate wound healing due to the anti-inflammatory effects and earlier development of the proliferative phase of wound healing.


An Analysis of Irregular Discharges From Residential Treatment Programs in the Department of Veterans Affairs Health Care System.
Veteran populations are frequently diagnosed with mental health conditions such as substance use disorder and PTSD. These conditions are associated with adverse outcomes including a higher risk of suicide. The Veterans Health Administration (VHA) has designed a robust mental health system to address these concerns. Veterans can access mental health treatment in acute inpatient, residential, and outpatient settings. Residential programs play an important role in meeting the needs of veterans who need more structure and support. Residential specialty types in the VHA include general mental health, substance use disorder, PTSD, and homeless/work programs. These programs are affiliated with a DVA facility (i.e., medical center). Although residential care can improve outcomes, there is evidence that some patients are discharged from these settings before achieving the program endpoint. These unplanned discharges are referred to using language such as against medical advice, self-discharge, or irregular discharge. Concerningly, unplanned discharges are associated with patient harm including death by suicide. Although there is some initial evidence to locate factors that predict irregular discharge in VHA residential programs, no work has been done to examine features associated with irregular discharge in each residential specialty. We conducted a retrospective cohort study of patients who were discharged from VHA residential treatment programs between January 2018 and September 2022. We included the following covariates: Principal diagnosis, gender, age, race/ethnicity, number of physical health conditions, number of mental health diagnostic categories, marital status, risk of homelessness, urbanicity, and service connection. We considered two discharge types: Regular and irregular. We used logistic regression to determine the odds of irregular discharge using models stratified by bed specialty as well as combined odds ratios and 95% CIs across program specialties. The primary purposes are to identify factors that predict irregular discharge and to determine if the factors are consistent across bed specialties. In a secondary analysis, we calculated facility-level adjusted rates of irregular discharge, limiting to facilities with at least 50 discharges. We identified the amount of residual variation that exists between facilities after adjusting for patient factors. A total of 279 residential programs (78,588 patients representing 124,632 discharges) were included in the analysis. Substance use disorder and homeless/work programs were the most common specialty types. Both in the overall and stratified analyses, the number of mental health diagnostic categories and younger age were predictors of irregular discharge. In the facility analysis, there was substantial variation in irregular discharge rates across residential specialties even after adjusting for all patient factors. For example, PTSD programs had a mean adjusted irregular discharge rate of 15.3% (SD: 7.4; range: 2.1-31.2; coefficient of variation: 48.4%). Irregular discharge is a key concern in VHA residential care. Patient characteristics do not account for all of the observed variation in rates across residential specialty types. There is a need to develop specialty-specific measures of irregular discharge to learn about system-level factors that contribute to irregular discharge. These data can inform strategies to avoid harms associated with irregular discharge.


Systemic amyloidosis: a rare presentation of mesenteric angina.
A 64-year-old man presented with an eight-month history of increasing postprandial epigastric pain and a 15 kg weight loss. Computed tomography of the abdomen, panendoscopy and mesenteric angiography failed to explain the cause of the patient's mesenteric angina. Systemic amyloidosis involving intestinal small vasculature without larger arterial involvement was diagnosed at autopsy after the patient died of an asystolic cardiac arrest. Mesenteric angina without evidence of ischemic enteritis or pseudo-obstruction is a rare manifestation of amyloidosis.


Atomic-scale structural evolution and stability of supercooled liquid of a Zr-based bulk metallic glass.
In this Letter, direct experimental evidence is provided for understanding the thermal stability with respect to crystallization in the Zr(41.2)Ti(13.8)Cu(12.5)Ni(10)Be(22.5) glass-forming liquid. Through high-resolution transmission electron microscopy, the atomic-structure evolution in the glass-forming liquid during the isothermal annealing process is clearly revealed. In contrast with the existing theoretical models, our results reveal that, prior to nanocrystallization, there exists a metastable state prone to forming icosahedralike atomic clusters, which impede the subsequent crystallization and hence stabilize the supercooled liquid. The outcome of the current research underpins the topological origin for the excellent thermal stability displayed by the Zr-based bulk metallic glass.


Long-Lasting Efficacy of Coatings for Bronze Artwork Conservation: The Key Role of Layered Double Hydroxide Nanocarriers in Protecting Corrosion Inhibitors from Photodegradation.
The photodegradation kinetics of 2-mercaptobenzothiazole (MBT), a corrosion inhibitor for copper-based alloys, is studied in high amorphous polyvinyl alcohol coatings subjected to either UV irradiation or indoor light exposure. The photodegradation process proceeds rapidly, thus compromising the anticorrosion ability of the coating. The encapsulation of MBT into layered double hydroxide (LDH) nanocarriers slows down its decomposition kinetics by a factor of three. Besides preserving the corrosion inhibitor, such a strategy allows a controlled release of MBT triggered by corrosion-related stimuli, for example, presence of chloride species and acid pH. The developed coating guarantees long-lasting corrosion protection even at low amounts of inhibitor-loaded LDH nanocarriers (ca. 5 wt %). This also reflects in a high transparency, which makes the protective coating suitable for demanding applications, such as the conservation of high-value metal works of art.


CT Utilization in a Level One Trauma Center in South Africa.
Introduction Computed tomography (CT) imaging forms an important component in the evaluation and management of patients with traumatic injuries. Many South African emergency departments (EDs) have a significant trauma-related workload, especially in the public sector, where there are limitations in resources relating to CT scanners. It is important to gauge the impact of traumatic injuries on CT utilization. The primary objectives were to quantify the number and type of CT imaging studies trauma patients received, as well as to determine the frequency of radiologically significant findings in a level one trauma center. The secondary objectives were to determine the CT utilization rate and describe the demographics of patients who received imaging. Methods This was a retrospective, quantitative, descriptive, cross-sectional study undertaken over two months at the level one trauma center of a tertiary, academic, public sector teaching hospital in Johannesburg, South Africa. The radiology department's picture archiving and communication system (PACS) was used to evaluate the reports of trauma patients who were referred for a CT scan. The trauma center register was used to calculate the CT utilization rate. Results There were 5,058 trauma patients seen in the two months. A total of 1,277 CT scans were performed on 843 patients. CT brain accounted for 52% of all scans performed. Radiologically significant findings were demonstrated in 407 scans (354 patients), i.e. 31.9% of scans and 42% of patients. CT chest and peripheral angiogram demonstrated radiologically significant findings in 60.5% and 50.9% of scans respectively. Assault accounted for 55.8% of the injuries sustained and road traffic accidents accounted for 33.2%. The overall CT utilization rate was 16.7% i.e. 843 out of the 5,058 trauma patients underwent a CT scan. Conclusions South Africa has a substantial trauma burden which commonly necessitates CT utilization. It is concerning that blunt and penetrating assault continues to dominate these traumatic presentations. Worldwide, there is a broad range of described CT utilization rates and the findings at this level one trauma center fall within that range. ED clinicians are encouraged to continue carefully using this scarce resource in the trauma setting.


Analyzing gene coexpression data by an evolutionary model.
Coexpressed genes are tentatively translated into proteins that are involved in similar biological functions. Here, we constructed gene coexpression networks from collected microarray data of the organisms Arabidopsis thaliana, Saccharomyces cerevisiae, and Escherichia coli. Their degree distributions show the common property of an overrepresentation of highly connected nodes followed by a sudden truncation. In order to analyze this behavior, we present an evolutionary model simulating the genetic evolution. This model assumes that new genes emerge by duplication from a small initial set of primordial genes. Our model does not include the removal of unused genes but selective pressure is indirectly taken into account by preferentially duplicating the old genes. Thus, gene duplication represents the emergence of a new gene and its successful establishment. After a duplication event, all genes are slightly but iteratively mutated, thus altering their expression patterns. Our model is capable of reproducing global properties of the investigated coexpression networks. We show that our model reflects the mean inter-node distances and especially the characteristic humps in the degree distribution that, in the biological examples, result from functionally related genes.


Transfer of motor learning across arm configurations.
It has been suggested that the learning of new dynamics occurs in intrinsic coordinates. However, it has also been suggested that elements that encode hand velocity, and hence act in an extrinsic frame of reference, play a role in the acquisition of dynamics. To reconcile claims regarding the coordinate system involved in the representation of dynamics, we have used a procedure involving the transfer of force-field learning between two workspace locations. Subjects made point-to-point movements while holding a two-link manipulandum. Subjects were first trained to make movements in a single direction at the left of the workspace. They were then tested for transfer of learning at the right of the workspace. Two groups of subjects were defined. For the subjects in group j, movements at the left and right workspace locations were matched in terms of joint displacements. For the subjects in group h, movements in the two locations had the same hand displacements. Workspace locations were chosen such that for group j, the paths (for training and testing) that were identical in joint space were orthogonal in hand space. The subjects in group j showed good transfer between workspace locations, whereas the subjects in group h showed poor transfer. These results are in agreement with the idea that new dynamics are encoded in intrinsic coordinates and that this learning has a limited range of generalization across joint velocities.


Synthetic bromated furanone inhibits autoinducer-2-mediated communication and biofilm formation in oral streptococci.
Autoinducer-2 (AI-2) is a widespread communication-signal molecule that allows bacteria to sense and react to environmental factors. In some streptococci AI-2 is reported to be involved in virulence expression and biofilm formation. It has earlier been shown that the alga Delisea pulchra produces bromated furanones, which prevent bacterial colonization of the algae. We have previously published a novel and simple synthesis of (Z)-5-bromomethylene-2(5H)-furanone. In this study we showed that our synthesized furanone inhibited biofilm formation and bioluminescence induction by Streptococcus anginosus, Streptococcus intermedius, and Streptococcus mutans, as well as bioluminescence induction by Vibrio harveyi BB152. We suggest that the effect is linked to interference with the AI-2 signaling pathway because adding furanone to the medium had no effect on the ability of the AI-2-defective S. anginosus luxS and S. intermedius luxS mutants to form biofilms.


Energetics of side chain packing in staphylococcal nuclease assessed by exchange of valines, isoleucines, and leucines.
To examine the importance of side chain packing to protein stability, each of the 11 leucines in staphylococcal nuclease was substituted with isoleucine and valine. The nine valines were substituted with leucine and isoleucine, while the five isoleucines, previously substituted with valine, were substituted with leucine and methionine. These substitutions conserve the hydrophobic character of these side chains but alter side chain geometry and, in some cases, size. In addition, eight threonine residues, previously substituted with valine, were substituted with isoleucine to test the importance of packing at sites normally not occupied by a hydrophobic residue. The stabilities of these 58 mutant proteins were measured by guanidine hydrochloride denaturation. To the best of our knowledge, this is the largest library of single packing mutants yet characterized. As expected, repacking stability effects are tied to the degree of side chain burial. The average energetic cost of moving a single buried methyl group was 0.9 kcal/mol, albeit with a standard deviation of 0.8 kcal/mol. This average is actually slightly greater than the value of 0.7-0.8 kcal/mol estimated for the hydrophobic transfer energy of a methylene from octanol to water. These results appear to indicate that van der Waals interactions gained from optimal packing are at least as important in stabilizing the native state of proteins as hydrophobic transfer effects.


Expression of genes associated with immunoproteasome processing of major histocompatibility complex peptides is indicative of protection with adjuvanted RTS,S malaria vaccine.
Patterns of expressed genes in the peripheral blood mononuclear cells of persons who were receiving RTS,S/AS01 or RTS,S/AS02 malaria vaccine and were undergoing experimental challenge with mosquito-borne falciparum malaria were examined to identify markers associated with protection. Thirty-nine vaccine recipients were assessed at study entry; on the day of the third vaccination; at 24 h, 72 h, and 2 weeks after vaccination; and on day 5 after challenge. Of 39 vaccine recipients, 13 were protected and 26 were not. Eleven vaccine recipients exhibited delayed onset of parasitemia. All infectivity control subjects developed parasitemia. Prediction analysis of microarrays identified genes corresponding with protection. Gene set enrichment analysis identified sets of genes associated with protection after the third vaccination and before challenge. After the third vaccination and before challenge, differential expression of genes in the immunoproteasome pathway distinguished protected and nonprotected persons. At 5 days after challenge, differential expression of genes associated with programmed cell death distinguished between subjects protected and not protected from malaria blood-stage infection. The up-regulation of genes associated with the efficient processing of major histocompatibility complex peptides suggests a potential role of the vaccine in conferring major histocompatibility complex class 1-mediated protection and may represent a useful surrogate marker of vaccine efficacy without the need for challenge.


Veterinary autoimmunity: autoimmune diseases in domestic animals.
The first spontaneous animal model of autoimmunity was the New Zealand black mouse, discovered in 1959. Interestingly, although several models of induced autoimmunity were demonstrated in a variety of rodents, the recognition of autoimmune disease in dogs came somewhat later. Dog breeding and selection of traits within certain dog breeds have become an important enterprise with intensive husbandry and selection criteria being applied to each breed standard. This has resulted in breeding for specific phenotypic characteristics. This selection has inadvertently led to the propagation of a number of autoimmune diseases in dogs. For example, systemic lupus erythematosus (SLE), autoimmune hemolytic anemia and thrombocytopenia, autoimmune myasthenia gravis, and diabetes mellitus are now fairly common. In the final analysis, the appearance of autoimmunity in dogs reflects their breeding selection and illustrates the importance of genetics in the development of autoimmune disease.


Structure-function analysis of the EGF-CFC family member Cripto identifies residues essential for nodal signalling.
Cripto is the founding member of the family of EGF-CFC genes, a class of extracellular factors essential for early vertebrate development. In this study we show that injection of Cripto recombinant protein in mid to late zebrafish Maternal-Zygotic one-eyed pinhead (MZoep) blastulae was able to fully rescue the mutant phenotype, thus providing the first direct evidence that Cripto activity can be added extracellularly to recover oep-encoded function in zebrafish early embryos. Moreover, 15 point mutations and two deletion mutants were generated to assess in vivo their functional relevance by comparing the ability of cripto wild-type and mutant RNAs to rescue the zebrafish MZoep mutant. From this study we concluded that the EGF-CFC domain is sufficient for Cripto biological activity and identified ten point mutations with a functional defective phenotype, two of which, located in the EGF-like domain, correspond to loss-of-function mutations. Finally, we have developed a three-dimensional structural model of Cripto protein and used it as a guide to predict amino acid residues potentially implicated in protein-protein interaction.


Design and Fabrication of α-MnO2-Nanorods-Modified Glassy-Carbon-Electrode-Based Serotonin Sensor.
Serotonin is a very important monoamine neurotransmitter, which takes part in biological and psychological processes. In the present scenario, design and fabrication of a serotonin electrochemical sensor is of great significance. In this study, we have synthesized α-MnO2 via a hydrothermal synthesis method using potassium permanganate as a precursor. The physiochemical properties, such as structural and phase-purity of the prepared α-MnO2, were investigated by various characterization techniques and methods (powder X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy). Furthermore, the serotonin sensor was fabricated using α-MnO2 as an electrode modifier or electro-catalyst. The bare glassy carbon electrode (GCE) was adopted as a working substrate, and its active carbon surface was modified with the synthesized α-MnO2. This modified GCE (α-MnO2/GCE = MGCE) was explored as a serotonin sensor. The electrochemical investigations showed that the MGCE has excellent electro-catalytic properties towards determination of serotonin. The MGCE exhibits an excellent detection limit (DL) of 0.14 µM, along with good sensitivity of 2.41 µAµM-1 cm-2. The MGCE also demonstrated excellent selectivity for determination of serotonin in the presence of various electro-active/interfering molecules. The MGCE also exhibits good cyclic repeatability, stability, and storage stability.


Acute pulmonary response of mice to multi-wall carbon nanotubes.
Widespread use of carbon nanotubes is predicted for future and concerns have been raised about their potential health effects. The present study determined the pulmonary response of mice to multi-wall carbon nanotubes (MWCNTs). The MWCNT suspension in sterile phosphate-buffered saline (PBS) was introduced into mice lungs by oropharyngeal aspiration. Female C57Bl mice were treated with either 20 or 40 microg of MWCNTs in 40 microl PBS and control groups received equal volume of PBS. From each group, half of the mice were euthanized at day 1 and the remaining half at day 7 post treatment. Bronchoalveolar lavage (BAL) fluids, serum, and lung tissue samples were analyzed for inflammatory and oxidative stress markers. The results showed significant cellular influx by a single exposure to MWCNTs. Yields of total cells and the number of polymorphonuclear leukocytes in BAL cells were significantly elevated in MWCNT-treated mice post-treatment days 1 and 7. Analysis of cell-free BAL fluids showed significantly increased levels of total proteins, lactate dehydrogenase, tumor necrosis factor-alpha, interleukin-1beta, mucin, and surfactant protein-D (SP-D) in MWCNT-treated mice at day 1 post treatment. However, these biomarkers returned to basal levels by day 7 post exposure except mucin and SP-D. An increase in the urinary level of 8-hydroxy-2'-deoxyguanosine in mice treated with MWCNT suggested systemic oxidative stress. Western analysis of lung tissue showed decreased levels of extracellular superoxide dismutase (SOD) protein in MWCNT-treated mice but copper/zinc and manganese SOD remained unchanged. It is concluded that a single treatment of MWCNT is capable of inducing cytotoxic and inflammatory response in the lungs of mice.


Nafion-Modified PEDOT:PSS as a Transparent Hole-Transporting Layer for High-Performance Crystalline-Si/Organic Heterojunction Solar Cells with Improved Light Soaking Stability.
We demonstrate the chemistry of amphiphilic perfluorosulfonic copolymer Nafion-coated conductive poly(3,4-ethyelenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and its effect on the photovoltaic performance of PEDOT:PSS/crystalline Si (c-Si) heterojunction solar cells. The highly hydrophilic sulfonate group of insulating, chemically stable Nafion interacts with PSS in PEDOT:PSS, which reduce the Coulombic interaction between PEDOT and PSS. The highly hydrophobic fluorocarbon backbone of Nafion favorably interacts with hydrophobic PEDOT of PEDOT:PSS. These factors give rise to the extension of π-conjugation of PEDOT chains. Silver paste used as a top grid electrode diffused into the Nafion layer and contacted with underneath Nafion-modified PEDOT:PSS layer. As a consequent, solution-processed Nafion-coated PEDOT:PSS/c-Si heterojunction solar cells exhibited a higher power conversion efficiency of 14.0% with better stability for light soaking rather than that of the pristine PEDOT:PSS/c-Si device by adjusting the layer thickness of Nafion. These findings originate from the chemical stability of hydrophobic fluorocarbon backbone of Nafion, diffusivity of silver paste into Nafion and contact with PEDOT:PSS, and Nafion as an antireflection layer.


IBBOMSA: An Improved Biogeography-based Approach for Multiple Sequence Alignment.
In bioinformatics, multiple sequence alignment (MSA) is an NP-hard problem. Hence, nature-inspired techniques can better approximate the solution. In the current study, a novel biogeography-based optimization (NBBO) is proposed to solve an MSA problem. The biogeography-based optimization (BBO) is a new paradigm for optimization. But, there exists some deficiencies in solving complicated problems such as low population diversity and slow convergence rate. NBBO is an enhanced version of BBO, in which, a new migration operation is proposed to overcome the limitations of BBO. The new migration adopts more information from other habitats, maintains population diversity, and preserves exploitation ability. In the performance analysis, the proposed and existing techniques such as VDGA, MOMSA, and GAPAM are tested on publicly available benchmark datasets (ie, Bali base). It has been observed that the proposed method shows the superiority/competitiveness with the existing techniques.


Simvastatin as add-on therapy to interferon β-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial.
Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective. We aimed to establish whether add-on of simvastatin, a statin with anti-inflammatory properties, improves this efficacy. We enrolled treatment-naive patients with relapsing-remitting multiple sclerosis in a multicentre, placebo-controlled, double-blind, randomised, parallel-group trial of simvastatin (80 mg daily) as add-on treatment to intramuscular interferon beta-1a (30 μg weekly). After starting treatment with interferon beta, patients were randomly assigned (in computer-generated blocks of four patients) to simvastatin 80 mg per day or placebo for 1-3 years. Patients and treating and evaluating physicians were masked to treatment allocation. The primary outcome measure was annual rate of documented relapses; analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00492765. We randomly assigned 307 patients to interferon beta plus simvastatin (n=151) or plus placebo (n=156). Annual rate of documented relapses was 0·19 (95% CI 0·13 to 0·28) in the simvastatin group and 0·14 (95% CI 0·09 to 0·23) in the placebo group (absolute difference 0·059, 95% CI -0·21 to 0·09; p=0·35). Time to first documented relapse (20th percentile) was 18·1 months in patients on simvastatin and 21·5 months in those on placebo (hazard ratio 1·21, 95% CI 0·74 to 1·99; p=0·51). Mean number of new or enlarging T2 lesions was 2·96 in the simvastatin group and 2·52 in the placebo group (ratio of new lesions, 1·17, 95% CI 8·89 to 1·55; p=0·25). Eight (6%) patients on simvastatin and 17 (13%) on placebo had no disease activity (odds ratio 0·42, 95% CI 0·17 to 1·00; p=0·05). No unexpected adverse events were seen. Generally, adverse events were mild and there were no group differences in infections or musculoskeletal disorders, including myalgia (five [3%] patients on simvastatin and nine [6%] on placebo). Rhabdomyolysis and myoglobinuria were not reported and there were no differences in serum creatine phosphokinase. We found no beneficial effect of simvastatin as add-on therapy to interferon beta-1a. Although unlikely, we can not exclude that combination of other statins with other disease-modifying drugs still could be beneficial. Biogen Idec.


Reconstruction of metabolic networks from high-throughput metabolite profiling data: in silico analysis of red blood cell metabolism.
We investigate the ability of algorithms developed for reverse engineering of transcriptional regulatory networks to reconstruct metabolic networks from high-throughput metabolite profiling data. For benchmarking purposes, we generate synthetic metabolic profiles based on a well-established model for red blood cell metabolism. A variety of data sets are generated, accounting for different properties of real metabolic networks, such as experimental noise, metabolite correlations, and temporal dynamics. These data sets are made available online. We use ARACNE, a mainstream algorithm for reverse engineering of transcriptional regulatory networks from gene expression data, to predict metabolic interactions from these data sets. We find that the performance of ARACNE on metabolic data is comparable to that on gene expression data.


[Postoperative pain management in clinics of otolaryngology].
To investigate pain relieving efficacy of six agents which are used in postoperative pain management after otolaryngologic operations. 120 adult patients (63 females, 57 males; mean age 36; range 18 to 76 years) were included in the study. The same intraoperative anesthesia was applied to all the patients. The following medications were randomly given to the patients who declared pain in the sixth hour after the operation: naproxen sodium, meloxicam, rofecoxib, paracetamol, dipyrone, and etodolac in proper dosage to form groups of 20 for each medication. Before and after the application of pain reliever tablets, visual analog scale (VAS) and numerical rating scale (NRS) were used to inquire whether the agents were effective in relieving pain. ANOVA (one way), paired t-test, Kruskal-Wallis, and Student's t-test were used as statistical methods. p values <0.05 were considered to indicate statistical significance. All the groups had similar VAS values before medication (p>0.05). When VAS values of each group were assessed after medication, it was recorded that naproxen sodium (p=0.020) and meloxicam (p=0.001) were effective. When the difference of NRS values between "before medication" and "after medication" was compared among the groups, all the agents significantly changed NRS values, but no inter-group differences were found (p>0.05). In terms of NRS scores, the effectiveness of six different analgesic agents which had been used to reduce postoperative pain was confirmed. Moreover, naproxen sodium and meloxicam were found to be more effective than the other agents when taken in the postoperative period for the adult patients according to VAS values.


Imaging the halogen bond in self-assembled halogenbenzenes on silver.
Halogens are among the most electronegative elements, and the variations in size and polarizability of halogens require different descriptions of the intermolecular bonds they form. Here we use the inelastic tunneling probe (itProbe) to acquire real-space imaging of intermolecular-bonding structures in the two-dimensional self-assembly of halogenbenzene molecules on a metal surface. Direct visualization is obtained for the intermolecular attraction and the "windmill" pattern of bonding among the fully halogenated molecules. Our results provide a hitherto missing understanding of the nature of the halogen bond.


Frigatebird behaviour at the ocean-atmosphere interface: integrating animal behaviour with multi-satellite data.
Marine top predators such as seabirds are useful indicators of the integrated response of the marine ecosystem to environmental variability at different scales. Large-scale physical gradients constrain seabird habitat. Birds however respond behaviourally to physical heterogeneity at much smaller scales. Here, we use, for the first time, three-dimensional GPS tracking of a seabird, the great frigatebird (Fregata minor), in the Mozambique Channel. These data, which provide at the same time high-resolution vertical and horizontal positions, allow us to relate the behaviour of frigatebirds to the physical environment at the (sub-)mesoscale (10-100 km, days-weeks). Behavioural patterns are classified based on the birds' vertical displacement (e.g. fast/slow ascents and descents), and are overlaid on maps of physical properties of the ocean-atmosphere interface, obtained by a nonlinear analysis of multi-satellite data. We find that frigatebirds modify their behaviours concurrently to transport and thermal fronts. Our results suggest that the birds' co-occurrence with these structures is a consequence of their search not only for food (preferentially searched over thermal fronts) but also for upward vertical wind. This is also supported by their relationship with mesoscale patterns of wind divergence. Our multi-disciplinary method can be applied to forthcoming high-resolution animal tracking data, and aims to provide a mechanistic understanding of animals' habitat choice and of marine ecosystem responses to environmental change.


How does the perceived green human resource management impact employee's green innovative behavior? -From the perspective of theory of planned behavior.
Employees' green innovative behavior encouraged by enterprises plays an important role in the enterprise sustainable development. The study explores the impact of perceived green human resource management on employees' innovative behavior. Drawing upon the planned behavior theory, this study examines how perceived green human resource management impact employees' green innovation behavior. Through three-stage questionnaire survey, 207 samples are obtained and hierarchical regression is employed to test the hypothesis., Data analysis results show that perceived green human resource management has a directly positive effect on employees' green innovative behavior. Green behavior intention, self-efficacy of environmental protection behavior, and identity with the company's green environmental protection system are the mediators between perceived green human resource management and employees' green innovative behavior. Meanwhile, the results demonstrate that there is a chain mediating relationship among these variables. In addition, green supply chain management moderates the relationship between the identity of a green environmental protection system and employees' green innovative behavior. These conclusions transcend the macro perspective and open the black box between green human resource management and enterprise performance. Enterprise should take a holistic view to play the role of green human resource management and supply chain management in the implementation of environmental strategy.


Permanent renal failure induced by pentastarch.
Background. Controversy exists with volume resuscitation using crystalloids or colloids. Renal dysfunction has been reported with some colloids and osmotic agents, but remains poorly defined. Patient. We report the case of a 67-year-old male who had normal kidney function at baseline and who developed anuric ARF in relation to the administration of >10 litres of 10% pentastarch. A renal biopsy confirmed hydropic changes in tubular cells compatible with colloid-induced damage. Conclusion. This case demonstrates that hydroxyethyl starch preparations may be associated with acute kidney injury, and one should carefully consider their use, especially in patients with pre-existing renal dysfunction. Osmotic tubular cell lesions may be long lasting and irreversible.


Effects of latency on the quality and quantity of bone produced by dentoalveolar distraction osteogenesis.
Infrabony defects in the alveolus pose a substantial treatment complication for restorative dentists. The properties of regenerate bone produced by dentoalveolar distraction, with and without a latency period, remain largely unknown. Six male foxhound dogs between 1 and 2 years of age underwent osteotomies around the mandibular second premolar to create a dentoalveolar segment that was distracted (1 mm/day for 10 days) through a large periodontal defect created in the third premolar area. A split-mouth design was used, with 1 randomly selected side starting distraction immediately, and the other side starting distraction after a 5-day latency period. The nonlatency and latency sides had 7 and 6 weeks of consolidation, respectively. Microcomputed tomography scans (taken at 15 and 60 μm) were used to evaluate bone quality and quantity of the regenerate bone, as well as the maturational differences in the regenerate. The transport segments were distracted 7 to 8 mm over 10 days. The majority (>75%) of the specimens showed complete or almost complete vertical and buccolingual bone fill. Except for trabecular separation, there were no significant differences between the latency and nonlatency sides in the quantity or quality of bone produced. Although relative bone volume tended to increase between the mesial and distal aspects of the regenerate, there were no significant differences in material properties in the regenerate. The control bone was denser and greater in quantity than the regenerate bone. Except for slight differences in maturation, latency had little or no effect on the regenerate bone produced. Dentoalveolar distraction immediately after alveolar bone surgery appears to produce bone of adequate quantity and quality for dental implant restorations.


Potential Therapeutic Strategies and Substances for Facial Nerve Regeneration Based on Preclinical Studies.
Despite advances in microsurgical technology and an improved understanding of nerve regeneration, obtaining satisfactory results after facial nerve injury remains a difficult clinical problem. Among existing peripheral nerve regeneration studies, relatively few have focused on the facial nerve, particularly how experimental studies of the facial nerve using animal models play an essential role in understanding functional outcomes and how such studies can lead to improved axon regeneration after nerve injury. The purpose of this article is to review current perspectives on strategies for applying potential therapeutic methods for facial nerve regeneration. To this end, we searched Embase, PubMed, and the Cochrane library using keywords, and after applying exclusion criteria, obtained a total of 31 qualifying experimental studies. We then summarize the fundamental experimental studies on facial nerve regeneration, highlighting recent bioengineering studies employing various strategies for supporting facial nerve regeneration, including nerve conduits with stem cells, neurotrophic factors, and/or other therapeutics. Our summary of the methods and results of these previous reports reveal a common feature among studies, showing that various neurotrophic factors arising from injured nerves contribute to a microenvironment that plays an important role in functional recovery. In most cases, histological examinations showed that this microenvironmental influence increased axonal diameter as well as myelination thickness. Such an analysis of available research on facial nerve injury and regeneration represents the first step toward future therapeutic strategies.


Time-Resolved Small RNA Sequencing Unravels the Molecular Principles of MicroRNA Homeostasis.
Argonaute-bound microRNAs silence mRNA expression in a dynamic and regulated manner to control organismal development, physiology, and disease. We employed metabolic small RNA sequencing for a comprehensive view on intracellular microRNA kinetics in Drosophila. Based on absolute rate of biogenesis and decay, microRNAs rank among the fastest produced and longest-lived cellular transcripts, disposing up to 105 copies per cell at steady-state. Mature microRNAs are produced within minutes, revealing tight intracellular coupling of biogenesis that is selectively disrupted by pre-miRNA-uridylation. Control over Argonaute protein homeostasis generates a kinetic bottleneck that cooperates with non-coding RNA surveillance to ensure faithful microRNA loading. Finally, regulated small RNA decay enables the selective rapid turnover of Ago1-bound microRNAs, but not of Ago2-bound small interfering RNAs (siRNAs), reflecting key differences in the robustness of small RNA silencing pathways. Time-resolved small RNA sequencing opens new experimental avenues to deconvolute the timescales, molecular features, and regulation of small RNA silencing pathways in living cells.


Conversion of Apricot Cyanogenic Glycosides to Thiocyanate by Liver and Colon Enzymes.
Some of the edible plants like apricot kernel, flaxseed, and cassava generate hydrogen cyanide (HCN) when cyanogenic glycosides are hydrolyzed. Rhodanese (thiosulfate: cyanide sulfurtransferases of TSTs; EC: 18.104.22.168) is a sulfide-detoxifying enzymes that converts cyanides into thiocyanate and sulfite. This enzyme exists in a liver and kidneys in abundance. The present study is to evaluate the conversion of apricot cyanogenic glycosides into thiocyanate by human hepatic (HepG2) and colonal (HT-29) cells, and the induction of the enzymes in the rat. The effects of short term exposure of amygdalin to rats have also been investigated. Cytosolic, mitochondrial, and microsomal fractions from HepG2 and HT-29 cells and normal male Spraque-Dawley rats were used. When apricot kernel extract was used as substrate, the rhodanese activity in liver cells was higher than the activity in colon cells, both from established human cell line or animal tissue. The cytosolic fractions showed the highest rhodanese activity in all of the cells, exhibiting two to three times that of microsomal fractions. Moreover, the cell homogenates could metabolize apricot extract to thiocyanate suggesting cellular hydrolysis of cyanogenic glycoside to cyanide ion, followed by a sulfur transfer to thiocyanate. After the consumption of amygdalin for 14 days, growth of rats began to decrease relative to that of the control group though a significant change in thyroid has not been observed. The resulting data support the conversion to thiocyanate, which relate to the thyroid dysfunction caused by the chronic dietary intake of cyanide. Because Korean eats a lot of Brassicaceae vegetables such as Chinese cabbage and radish, the results of this study might indicate the involvement of rhodanese in prolonged exposure of cyanogenic glycosides.


Safety studies on epigallocatechin gallate (EGCG) preparations. Part 1: genotoxicity.
Public interest in green tea has grown recently due to the potential health benefits from its consumption. Epigallocatechin gallate (EGCG), a principal polyphenolic component of green tea, is considered key to these healthful qualities. Although numerous studies have evaluated the anti-cancer effects of green tea and EGCG, few have examined the safety of EGCG consumption. The genotoxic potential of a concentrated EGCG preparation was tested in Salmonella and L5178Y tk+/- mouse lymphoma cell assays to further define the safety of Teavigo, a high-concentration EGCG extract of Camellia sinensis leaves produced by the same novel method. No mutagenic activity was detected in the bacterial system; however, a clastogenic 'trend' from the formation of hydrogen peroxide was noted in the murine cells. The oral administration of 500, 1000, or 2000 mg EGCG/kg to mice did not induce micronuclei formation in bone marrow cells. Similarly, administering 400, 800, or 1200 mg EGCG/kg/day in their diet for 10 days did not induce bone marrow cell micronuclei and produced plasma EGCG concentrations comparable to those reported in human studies. The intravenous injection of 10, 25 and 50 mg EGCG/kg/day to rats resulted in much higher plasma concentrations and demonstrated an absence of genotoxic effects. From these studies, it is concluded that Teavigo (EGCG) is not genotoxic.


Classic hypoglossal-facial nerve anastomosis after acoustic neuroma resection. A review of 46 cases.
To clarify the factors contributing to patient satisfaction with facial movement after the classic hypoglossal-facial nerve anastomosis, we examined 46 such patients who consented to an interview and video-recording. No correlation was seen between the physician's evaluation of returned function (according to Yanagihara's 40-point scale and the grading system of House-Brackmann) and the scores (full marks: 100 points) the patients assigned to their own facial movements. Instead the scores that the patients assigned were closely related to subjective oral dysfunction, such as difficulty in masticating, articulating, and swallowing. Those scores did not correlate with eye-related functional deficits. These findings indicate that modified techniques to minimize the hypoglossal nerve deficit may enhance patient satisfaction without sacrificing recovery of facial movements.


Effect of Candidatus Liberibacter asiaticus infection on susceptibility of Asian citrus psyllid, Diaphorina citri, to selected insecticides.
In the present investigation, the effect of Candidatus Liberibacter asiaticus (Las), a bacterium considered to be responsible for causing huanglongbing (HLB) disease in citrus, on the physiology of its vector, the Asian citrus psyllid (ACP) Diaphorina citri Kuwayama, was determined. Specifically, the effects of Las infection on the susceptibility of ACP to selected insecticides were determined. Furthermore, total protein content and general esterase activity were quantified in Las-infected and uninfected ACP to gain insight into the possible mechanism(s) responsible for altered susceptibility to insecticides owing to Las infection. LC(50) values were significantly lower in Las-infected than in uninfected ACP adults for chlorpyrifos and spinetoram. Furthermore, there was a general trend towards lower LC(50) values for three other insecticides for Las-infected ACP; however, the differences were not statistically significant. Total protein content (µg mL(-1)) was significantly lower in Las-infected (23.5 ± 1.3 in head + thorax; 27.7 ± 1.9 in abdomen) than in uninfected (29.7 ± 2.1 in head + thorax; 35.0 ± 2.3 in abdomen) ACP. Likewise, general esterase enzyme activity (nmol min(-1) mg(-1) protein) was significantly lower in Las-infected (111.6 ± 4.5 in head + thorax; 109.5 ± 3.7 in abdomen) than in uninfected (135.9 ± 7.5 in head + thorax; 206.1 ± 23.7 in abdomen) ACP. Susceptibility of ACP to selected insecticides from five major chemistries was greater in Las-infected than in uninfected ACP. The lower total protein content and reduced general esterase activity in Las-infected than in uninfected ACP may partly explain the observed higher insecticide susceptibility of Las-infected ACP.


[Interprofessional cohabitation within a psychiatric hospital.].
The results of a survey on interprofessional collaboration in a psychiatrie hospital indicated difficulties in staff coordination as well as differences between professions in job satisfaction and belief in the institution's effectiveness. Reasons for these differences and suggestions for improvement of the present system are cited.


Fracture of the talus as a complication of subtalar arthroereisis.
Subtalar joint arthroereisis remains a popular procedure for a flexible flatfoot deformity. Potential complications of the procedure have been discussed in published reports and are often believed to have resulted from shortcomings related to the mechanical properties of the biomaterial, implant size, and/or implant placement. In the present report, we describe the case of a talar neck fracture with migration of the implant after subtalar joint arthroereisis performed 10 years earlier. The 19-year-old patient was treated with implant removal and open reduction internal fixation and bone void filler and recovered unremarkably thereafter.


Ocular dirofilariasis.
Dirofilaria is a parasite of domestic and wild animals that can infect humans accidentally. It is being reported in increasing numbers from Mediterranean countries like Italy. In India this infection is occasionally being reported. We report three cases of ocular dirofilariasis from the state of Assam presenting as periorbital and subconjunctival cysts. The parasites were identified as Dirofilaria repens. The purpose of this article is to take note of this emerging zoonosis in Assam; also to review literature in the cases reported.


[Bladder calculus after augmentation ileocystoplasty in children].
Of 12 children who had undergone augmentation ileocystoplasty for treatment of neurogenic bladder, 3 developed bladder calculi 9 to 19 months after the operation. All these 3 children had simultaneously undergone procedure to ensure urinary continence together with ileocystoplasty, and postoperative persistent bacteriuria was found in these 3 children. Component of bladder calculi was magnesium-ammonium phosphate in 2 and calcium phosphate in the other child, and all were successfully removed by endoscopic lithotripsy. These data suggest that postoperative persistent bacteriuria as well as procedures to ensure urinary continence might play a role in the formation of bladder calculus after augmentation cystoplasty.


Effect of Roux-en-Y gastric bypass on the pharmacokinetic-pharmacodynamic relationships of liquid and controlled-release formulations of oxycodone.
The physiological changes following Roux-en-Y gastric bypass (RYGB) surgery may impact drug release from mechanistically different controlled-release tablets, making generic substitution inappropriate. This study aimed to characterise the pharmacokinetic-pharmacodynamic relationships of oxycodone from a lipid-based and water-swellable controlled-release tablet in RYGB patients. Twenty RYGB patients received 10-mg oral solution oxycodone or 20-mg controlled-release (water-swellable or lipid-based) oxycodone in a three-way, randomised, semiblinded and cross-over study. Blood sampling and pupillary recordings were conducted over a 24-h period. A previously established pharmacokinetic-pharmacodynamic model of these three formulations in healthy volunteers was used in the analysis as a reference model. No differences in absorption kinetics were seen between controlled-release formulations in patients. However, the absorption lag time was 11.5 min in patients vs 14 min in healthy volunteers for controlled-release tablets (P < 0.001). Furthermore, oral bioavailability was 14.4% higher in patients compared to healthy volunteers regardless of formulation type (P < 0.001). Oxycodone pharmacodynamics were not significantly affected by formulation or patient status. However, baseline pupil diameter was inversely correlated with age (P < 0.001) and plasma concentrations of oxycodone at half-maximum effect were 31% lower in males compared to females (P < 0.05). Generic substitution of monophasic lipid-based and water-swellable controlled-release oxycodone tablets may be considered safe in RYGB patients.


Alkyl hydrogen atom abstraction reactions of the CN radical with ethanol.
We present a study of the abstraction of alkyl hydrogen atoms from the β and α positions of ethanol by the CN radical in solution using the Empirical Valence Bond (EVB) method. We have built separate 2 × 2 EVB models for the Hβ and Hα reactions, where the atom transfer is parameterized using ab initio calculations. The intra- and intermolecular potentials of the reactant and product molecules were modelled with the General AMBER Force Field, with some modifications. We have carried out the dynamics in water and chloroform, which are solvents of contrasting polarity. We have computed the potential of mean force for both abstractions in each of the solvents. They are found to have a small and early barrier along the reaction coordinate with a large energy release. Analyzing the solvent structure around the reaction system, we have found two solvents to have little effect on either reaction. Simulating the dynamics from the transition state, we also study the fate of the energies in the HCN vibrational modes. The HCN molecule is born vibrationally hot in the CH stretch in both reactions and additionally in the HCN bends for the Hα abstraction reaction. In the early stage of the dynamics, we find that the CN stretch mode gains energy at the expense of the energy in CH stretch mode.


Solid-State NMR characterization of autofluorescent fibrils formed by the elastin-derived peptide GVGVAGVG.
The characterization of the molecular structure and physical properties of self-assembling peptides is an important aspect of optimizing their utility as scaffolds for biomaterials and other applications. Here we report the formation of autofluorescent fibrils by an octapeptide (GVGVAGVG) derived via a single amino acid substitution in one of the hydrophobic repeat elements of human elastin. This is the shortest and most well-defined peptide so far reported to exhibit intrinsic fluorescence in the absence of a discrete fluorophore. Structural characterization by FTIR and solid-state NMR reveals a predominantly β-sheet conformation for the peptide in the fibrils, which are likely assembled in an amyloid-like cross-β structure. Investigation of dynamics and the effects of hydration on the peptide are consistent with a rigid, water excluded structure, which has implications for the likely mechanism of intrinsic fibril fluorescence.


[Nuclear factor-kappa B and intercellular adhesion molecule-1 expression in airway epithelial cells from smoking rats].
To investigate the changes and of nuclear factor-kappa B (NF-kappaB) and intercellular adhesion molecule (ICAM)-1 expression in airway epithelial cells from smoking rats. Wistar rats (n = 39) were randomly divided into a nonsmoking control group and 2 smoking groups-smoking for 1 month and 3 months, with 13 rats in each group. Immunohistochemistry and in situ hybridization staining were used to semiquantitatively analyse the changes of NF-kappaB and ICAM-1 expression in airway epithelial cells. (1) The percentages of positive cells for NF-kappaB nuclear staining in bronchiolar epithelial cells in 1 month smoking group (63 +/- 4)% and 3 month smoking group [(51 +/- 5)%] were significantly higher than that in the control group [(27 +/- 5)%] (P < 0.01 respectively). (2) ICAM-1 mRNA expression in bronchial and bronchiolar epithelial cells in the 1 month smoking group (0.645 +/- 0.038, 0.747 +/- 0.041) and the 3 month smoking group (0.688 +/- 0.062, 0.809 +/- 0.023) was significantly higher than those in the control group (0.526 +/- 0.023, 0.635 +/- 0.044), (P < 0.01 respectively), and the expression of ICAM-1 mRNA in the 3 month smoking group was higher than that in the 1 month smoking group (P < 0.05 and P < 0.01 respectively). (3) ICAM-1 protein expression in the main bronchial and bronchiolarepithelial cells in the 1 month smoking group (0.73 +/- 0.04, 0.94 +/- 0.05) and the 3 month smoking group (0.77 +/- 0.04, 0.99 +/- 0.03) was significantly higher than those in the control group (0.57 +/- 0.04, 0.83 +/- 0.04) (P < 0.01 respectively), and the expression of ICAM-1 protein in the 3 month smoking group was higher than those in the 1 month smoking group (P < 0.05 respectively). (4) ICAM-1 mRNA and protein expression in bronchioles were significantly higher than those in the bronchi (P < 0.01 respectively) in all groups. (5) The percentage of cells staining positive for nuclear NF-kappaB correlated with ICAM-1 protein expression in bronchioles from the 1 month smoking group (r = 0.462, P < 0.05). NF-kappaB and ICAM-1 may play an important role in smoking-induced airway inflammation.


[Digestive localizations of scleroderma].
Systemic scleroderma involves the gastro-intestinal tract in over 50 p. 100 of cases, the commonest target organs being the oesophagus, the small intestine, the colon and the stomach in that order. The G-I symptoms of this collagenosis are all related to disorder of motility secondary to disturbances of innervation and then to atrophy of the smooth muscle and fibrous infiltration. Oesophageal involvement results in gastro-oesophageal reflux and/or dysphagia due to the lack of tonicity of the lower oesophageal sphincter and a reduction of peristalsis. Disease of the small intestine may cause pseudo-intestinal obstruction or a secondary malabsorption syndrome due to abnormal intraluminal bacterial flora. Colonic involvement causes severe constipation with formation of faecoliths. Finally, scleroderma may be complicated by an acute abdominal syndrome: occlusion due to diffuse reduction in small intestinal motility, peritonitis due to perforation of the small intestine, ileo-colonic infarction, gastro-intestinal haemorrhage complicating telangiectasia. Treatment is purely symptomatic: classical remedies for gastro-oesophageal reflux and its complications, and antibiotics for malabsorption syndromes.


The segregation of the Escherichia coli origin and terminus of replication.
Escherichia coli chromosome replication forks are tethered to the cell centre. Two opposing models describe how the chromosomes segregate. In the extrusion-capture model, newly replicated DNA is fed bi-directionally from the forks toward the cell poles, forming new chromosomes in each cell half. Starting with the origins, chromosomal regions segregate away from their sisters progressively as they are replicated. The termini segregate last. In the sister chromosome cohesion model, replication produces sister chromosomes that are paired along much of their length. The origins and most other chromosomal regions remain paired until late in the replication cycle, and all segregate together. We use a combination of microscopy and flow cytometry to determine the relationship of origin and terminus segregation to the cell cycle. Origin segregation frequently follows closely after initiation, in strong support of the extrusion-capture model. The spatial disposition of the origin and terminus sequences also fits this model. Terminus segregation occurs extremely late in the cell cycle as the daughter cells separate. As the septum begins to invaginate, the termini of the completed sister chromosomes are transiently held apart at the cell centre, on opposite sides of the cell. This may facilitate the resolution of topological linkages between the chromosomes.


SSA with CWT and k-Means for Eye-Blink Artifact Removal from Single-Channel EEG Signals.
Recently, the use of portable electroencephalogram (EEG) devices to record brain signals in both health care monitoring and in other applications, such as fatigue detection in drivers, has been increased due to its low cost and ease of use. However, the measured EEG signals always mix with the electrooculogram (EOG), which are results due to eyelid blinking or eye movements. The eye-blinking/movement is an uncontrollable activity that results in a high-amplitude slow-time varying component that is mixed in the measured EEG signal. The presence of these artifacts misled our understanding of the underlying brain state. As the portable EEG devices comprise few EEG channels or sometimes a single EEG channel, classical artifact removal techniques such as blind source separation methods cannot be used to remove these artifacts from a single-channel EEG signal. Hence, there is a demand for the development of new single-channel-based artifact removal techniques. Singular spectrum analysis (SSA) has been widely used as a single-channel-based eye-blink artifact removal technique. However, while removing the artifact, the low-frequency components from the non-artifact region of the EEG signal are also removed by SSA. To preserve these low-frequency components, in this paper, we have proposed a new methodology by integrating the SSA with continuous wavelet transform (CWT) and the k-means clustering algorithm that removes the eye-blink artifact from the single-channel EEG signals without altering the low frequencies of the EEG signal. The proposed method is evaluated on both synthetic and real EEG signals. The results also show the superiority of the proposed method over the existing methods.


Stability of IGF-I concentration despite divergent results of repeated GH stimulating tests indicates poor reproducibility of test results.
Growth hormone (GH) secretion is routinely assessed in provocative tests. However, some limitations of these tests have been reported, including a weak correlation between spontaneous GH secretion and GH peak in stimulating tests, poor reproducibility of test results and normalisation of previously decreased GH response to stimulation in the repeated provocative tests. The observed discrepancies between the results of consecutive GH stimulating tests in the same patient may be explained either by real changes in GH secretion or by the poor reproducibility of GH response to stimulation. Normalisation of previously decreased GH secretion should entail the increase of insulin-like growth factor-I (IGF-I) concentration, while stability of IGF-I secretion despite divergent GH response to stimulation in repeated tests might indicate the poor reproducibility of GH stimulating tests. continue with The aim of the study was a comparison of GH peak in repeated stimulating tests and of corresponding, simultaneously measured IGF-I concentration. The investigation comprised 84 children with short stature who underwent repeated GH tests and IGF-I evaluation. In 60 patients each of two different tests (with clonidine and with glucagon, in standard doses) was performed twice, together with IGF-I measurement during both evaluations. In 20 patients (remaining in the same pubertal stage during the time period between the procedures in question) at least one test, together with IGF-I measurement, was repeated within one year. The correlation between the results of GH tests, repeated during the two evaluations, was weak (r=0.22, p<0.05 for all patients and r=0.25, p<0.05 for the patients examined 2 times within 1 year), with the high within-subject variability (43.4 % and 59.5 %, respectively). Conversely, the correlation between two values of IGF-I SDS was good both for all patients (r=0.65, p<0.05) and especially for the patients examined twice within 1 year (r=0.96, p<0.05), with low within-subject variability for the latter subgroup of patients (11.2 %). The same GH stimulating tests, performed twice in the same patient, led to different conclusions (either the confirmation of GHD diagnosis or its exclusion) in most of examined patients. Poor reproducibility of GH stimulating tests, rather than the possibility of short-term changes in GH secretion, was confirmed.


The digital heart-lung unit: applications of exponential technology.
Exponential technologies such as virtual reality (VR), computational modelling, and additive manufacturing have emerged in the field of cardiology and cardiothoracic surgery. An increasing number of publications that evaluate the clinical role of these technologies are becoming available. Moreover, there is an increase in the number of hospitals and departments that have implemented digital and exponential solutions in clinical workflow. In our centre, we have adopted various exponential technologies in order to improve clinical pre-procedural workflow, patient care, and training and education. In order to provide our view and approach on the implementation of these technologies, in this article, we provide an overview of the currently applied modalities including immersive VR, three-dimensional (3D) computational modelling, VR-based simulations, and additive manufacturing (3D printing). Moreover, we present the potential of these applications in cardiovascular and cardiothoracic medicine, and additionally, we will provide key facilitators, challenges, and recommendations to adopting these technologies in clinical practice.


18F-FDG PET/CT and 68Ga-DOTATOC PET/CT in Diffuse Pancreatic Neuroendocrine Tumor.
We present 2 cases of pancreatic neuroendocrine tumor with diffuse involvement of the entire pancreas. One case with G2 pancreatic neuroendocrine tumor showed nearly normal pancreatic shape and signal intensity on MRI, normal pancreatic FDG uptake, and diffuse pancreatic Ga-DOTATOC uptake. The other case with G3 pancreatic neuroendocrine tumor showed diffusely enlarged pancreas with abnormal MR signal intensity and increased FDG uptake. These 2 cases indicate that neuroendocrine tumor should be included in the differential diagnosis of diffuse pancreatic diseases. Somatostatin receptor imaging may be helpful for the diagnosis of diffuse pancreatic neuroendocrine tumor in equivocal cases.


Risk factors for adverse outcome in infancy in meconium ileus cystic fibrosis infants: A multicentre Italian study.
Meconium ileus (MI) is a risk factor for poor outcomes in cystic fibrosis (CF) patients. The aim of this study was to identify the risk factors for poor 12-month clinical outcomes in MI-CF newborns. This retrospective, multicentre, observational study of MI-CF infants born 2009-2015 recorded their pre- and neonatal histories, intestinal occlusion treatments, post-surgical history, nutrition, CF diagnosis, and compared the patients with 12-month faltering growth or chronic Pseudomonas aeruginosa respiratory infection (cases) with the others (controls). About 25% of the 85 patients enrolled by 13 Italian CF centres (24% premature, 18% of low birth weight) had prenatally diagnosed bowel obstruction, and 39% had complex MI. Seventy-one required surgery (the 33 with complex MI and 38 with simple MI), of whom 58 (82%) required post-surgical intensive care, including 25 (35%) needing ventilatory support. Forty-six (54%) were breastfed; exclusively parenteral nutrition was started in 52 (61%). Cholestasis was diagnosed in 21%. Thirty-one (37%) experienced negative outcomes: the only risk factors were prenatally diagnosed intestinal obstruction and a need for intensive care and oxygen therapy. The cases had significantly higher first blood immunoreactive trypsinogen (b-IRT) levels (P = .008). Logistic regression showed that the probability of having negative outcome is decreased in the absence of cholestasis (Odds Ratio = 0.125) and a need for intensive therapy (OR = 0.141), and increased by not having been breastfed (OR = 2.921). High b-IRT levels, prenatally diagnosed intestinal obstruction, a severe post-surgical clinical picture and early liver disease are risk factors for negative outcomes. Breastfeeding may be protective.


Life style-related diseases of the digestive system: colorectal cancer as a life style-related disease: from carcinogenesis to medical treatment.
Life style-related diseases are associated with an increased risk of colorectal cancer (CRC). Recently, an association has been demonstrated between obesity and CRC. CRC has been associated with markers of insulin or glucose control, and insulin resistance might be the unifying mechanism by which several risk factors affect colorectal carcinogenesis. We evaluated the association between the number of aberrant crypt foci (ACF) and obesity, insulin resistance, hyperlipidemia, and other factors of life style-related disease. As a result, age, body mass index (BMI), waist circumference, and visceral fat obesity were significantly associated with the number of ACF. These results suggest that visceral fat obesity is an important target for CRC prevention. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily and is highly expressed in CRC. PPARgamma ligand administration for 1 to 8 months significantly reduced the number of ACF in human subjects. PPARgamma ligand is a promising candidate as a chemopreventive agent. Further investigation is needed to elucidate these mechanisms.


decompTumor2Sig: identification of mutational signatures active in individual tumors.
The somatic mutations found in a tumor have in most cases been caused by multiple mutational processes such as those related to extrinsic carcinogens like cigarette smoke, and those related to intrinsic processes like age-related spontaneous deamination of 5-methylcytosine. The effect of such mutational processes can be modeled by mutational signatures, of which two different conceptualizations exist: the model introduced by Alexandrov et al., Nature 500:415-421, 2013, and the model introduced by Shiraishi et al., PLoS Genetics 11(12):e1005657, 2015. The initial identification and definition of mutational signatures requires large sets of tumor samples. Here, we present decompTumor2Sig, an easy to use R package that can decompose an individual tumor genome into a given set of Alexandrov-type or Shiraishi-type signatures, thus quantifying the contribution of the corresponding mutational processes to the somatic mutations identified in the tumor. Until now, such tools were available only for Alexandrov signatures. We demonstrate the correctness and usefulness of our approach with three test cases, using somatic mutations from 21 breast cancer genomes, from 435 tumor genomes of ten different tumor entities, and from simulated tumor genomes, respectively. The decompTumor2Sig package is freely available and has been accepted for inclusion in Bioconductor.


Mechanical and electronic properties of Janus monolayer transition metal dichalcogenides.
The mechanical and electronic properties of Janus monolayer transition metal dichalcogenides MXY (M = Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W; X/Y = S, Se, Te) were investigated using density functional theory. Results show that breaking the out-of-plane structural symmetry can be used to tune the electronic and mechanical behavior of monolayer transition metal dichalcogenides. The band gaps of monolayer WXY and MoXY are in the ranges of 0.16-1.91 and 0.94-1.69 eV, respectively. A semiconductor to metallic phase transition occurred in Janus monolayer MXY (M = Ti, Zr and Hf). The monolayers MXY (M = V, Nb, Ta and Cr) show metallic characteristics, which show no dependence on the structural symmetry breaking. The mechanical properties of MXY depended on the composition. Monolayer MXY (M = Mo, Ti, Zr, Hf and W) showed brittle characteristic, whereas monolayer CrXY and VXY are with ductile characteristic. The in-plane stiffness of pristine and Janus monolayer MXY are in the range between 22 and 158 N m-1. The tunable electronic and mechanical properties of these 2D materials would advance the development of ultra-sensitive detectors, nanogenerators, low-power electronics, and energy harvesting and electromechanical systems.


Two new N-oxide Lycopodium alkaloids from Huperzia serrata.
Two new Lycopodium alkaloids, N-oxidehuperzine E (1) and N-oxidehuperzine F (2), along with two known alkaloids, huperzines E (3) and F (4), were isolated from Huperzia serrata (Thunb.) Trev. Their structures were elucidated by spectroscopic and chemical transformations.


Nontuberculous mycobacteria in soils of La Pampa province (Argentina).
The presence of nontuberculous mycobacteria (NTM) was investigated in forty soil samples belonging to the four physiographic regions (Eastern, Central, Southern and Western) that constitute La Pampa province. The presence of NTM in 67.5% of these soil samples was determined. The density of mycobacteria ranged 25-4,500 mycobacteria g-1 dry soil (mean = 516 CFU g-1). Significant differences were found in relation to both the investigated regions (p < 0.01) and the soil pH (r = 0.44*) (P = 0.02). The mycobacteria represented less than 0.00001% of the total aerobic bacteria found in the soils. Twenty-seven isolated mycobacteria were classified according to the culture, biochemical, enzymatic characteristics and antibiotic sensitivity. Mycobacterium fortitium was the dominant mycobacterium and was detected in 63% of the positive soils. This species showed ability for living in sandy to sandy loam soils, within a wide pH range (6.5-9.7) and organic matter (4.15-83.63 g kg-1). Two other species were M. phlei (range = 50-4,500 CFU g-1) and M. kansasii (range = 50-500 CFU g-1).


Teaching acoustic phonetics to undergraduates in communication sciences and disorders: Course structure and sample projects.
Virtually all undergraduate communication sciences and disorders programs require a course that covers acoustic phonetics. Students typically have a separate phonetics (transcription) course prior to taking the acoustic phonetics course. This paper describes a way to structure an acoustic phonetics course into two halves: a first half that focuses on the source, including basic acoustics (simple harmonic motion, harmonics), vocal fold vibration, modes of phonation, and intonation, and a second half that focuses on the filter, including resonance and tube models, vowel formants, and consonant acoustics. Thus, basic acoustic properties are interwoven with specific examples of speech-related acoustics. In addition, two projects that illustrate concepts from the two halves of the course (one on fundamental frequency and the other on vowel formants) are presented.


A rare case of osteoma in the frontal sinus: anatomical and histological description.
The purpose of this paper is to present a rare case of osteoma localized in the left frontal sinus. A 22-year-old woman who arrived at the Department of Neurosurgery of the University Emergency Hospital, Bucharest, Romania, presented a vertical asymmetry of the eyeballs but displayed no clinical signs like pain or diplopia. The computer tomography exam was used for preoperatory diagnostic. Histopathology was performed after surgery using Hematoxylin and Eosin staining. The Nikon Eclipse microscope was used to examine the slides. The histopathology exam shows a compact osteoma with dense and non-Haversian bone tissue and parallel bony trabeculae. A few spaces for the marrow were also found. The osteocytes were small and no fibrous cells were discovered. The computer tomography and histopathology exam were the investigations that lead us to a true diagnostic of dense osteoma. This tumor was the first case of frontal sinus osteoma histologically described in the Romanian population.


Optimized mouse model for the imaging of tumor metastasis upon experimental therapy.
Development of new cancer treatments focuses increasingly on the relation of cancer tissue with its microenvironment. A major obstacle for the development of new anti-cancer therapies has been the lack of relevant animal models that would reproduce all the events involved in disease progression from the early-stage primary tumor until the development of mature metastatic tissue. To this end, we have developed a readily imageable mouse model of colorectal cancer featuring highly reproducible formation of spontaneous liver metastases derived from intrasplenic primary tumors. We optimized several experimental variables, and found that the correct choice of cell line and the genetic background, as well as the age of the recipient mice, were critical for establishing a useful model system. Among a panel of colorectal cancer cell lines tested, the epithelial carcinoma HT29 line was found to be the most suitable in terms of producing homogeneous tumor growth and metastases. In our hands, SCID mice at the age of 125 days or older were the most suitable in supporting consistent HT29 tumor growth after splenic implantation followed by reproducible metastasis to the liver. A magnetic resonance imaging (MRI) protocol was optimized for use with this mouse model, and demonstrated to be a powerful method for analyzing the antitumor effects of an experimental therapy. Specifically, we used this system to with success to verify by MRI monitoring the efficacy of an intrasplenically administered oncolytic adenovirus therapy in reducing visceral tumor load and development of liver metastases. In summary, we have developed a highly optimized mouse model for liver metastasis of colorectal cancer, which allows detection of the tumor load at the whole body level and enables an accurate timing of therapeutic interventions to target different stages of cancer progression and metastatic development.


Economic crisis and mental health.
Literature from the past year was examined to learn whether economic recessions have an effect on mental disorders including depression and suicides. Economic recessions and crises have a context-dependent negative impact on mental health disorders. These appear in low-income and middle-income countries whereas some affluent countries are offering provisions that help unemployed persons to escape the detrimental consequences. The Asian economic crisis led to a sharp unemployment-related increase in suicide mortality in east Asian countries. In European Union countries rising unemployment was associated with significant short-term increases in premature deaths from intentional violence including suicides. It seems that active labour market programmes existing in some Organization for Economic Cooperation and Development countries can prevent some adverse health effects of economic downturns. As mental health consequences of economic crises are context dependent, the current situation needs monitoring. Enough services for those in need should be provided and advocacy for societal support measures is of great importance.


Silencing of the XAF1 gene by promoter hypermethylation in cancer cells and reactivation to TRAIL-sensitization by IFN-beta.
XIAP-associated factor 1 (XAF1) is a putative tumor suppressor that exerts its proapoptotic effects through both caspase-dependent and -independent means. Loss of XAF1 expression through promoter methylation has been implicated in the process of tumorigenesis in a variety of cancers. In this report, we investigated the role of basal xaf1 promoter methylation in xaf1 expression and assessed the responsiveness of cancer cell lines to XAF1 induction by IFN-beta. We used the conventional bisulfite DNA modification and sequencing method to determine the methylation status in the CpG sites of xaf1 promoter in glioblastoma (SF539, SF295), neuroblastoma (SK-N-AS) and cervical carcinoma (HeLa) cells. We analysed the status and incidence of basal xaf1 promoter methylation in xaf1 expression in non-treated cells as well as under a short or long exposure to IFN-beta. Stable XAF1 glioblastoma knock-down cell lines were established to characterize the direct implication of XAF1 in IFN-beta-mediated sensitization to TRAIL-induced cell death. We found a strong variability in xaf1 promoter methylation profile and responsiveness to IFN-beta across the four cancer cell lines studied. At the basal level, aberrant promoter methylation was linked to xaf1 gene silencing. After a short exposure, the IFN-beta-mediated reactivation of xaf1 gene expression was related to the degree of basal promoter methylation. However, in spite of continued promoter hypermethylation, we find that IFN-beta induced a transient xaf1 expression, that in turn, was followed by promoter demethylation upon a prolonged exposure. Importantly, we demonstrated for the first time that IFN-beta-mediated reactivation of endogenous XAF1 plays a critical role in TRAIL-induced cell death since XAF1 knock-down cell lines completely lost their IFN-beta-mediated TRAIL sensitivity. Together, these results suggest that promoter demethylation is not the sole factor determining xaf1 gene induction under IFN-beta treatment. Furthermore, our study provides evidence that XAF1 is a crucial interferon-stimulated gene (ISG) mediator of IFN-induced sensitization to TRAIL in cancer.


The severity of growth hormone deficiency correlates with the severity of cardiac impairment in 100 adult patients with hypopituitarism: an observational, case-control study.
In 100 patients with hypopituitarism and 80 sex- and age-matched healthy subjects, we correlated the severity of cardiac impairment to the severity of GH deficiency (GHD). By the GH peak after arginine plus GHRH test (normal > 16.5 microg/liter), the patients were classified as severe GHD (n = 56), partial GHD (n = 27), and non-GHD (n = 17). Compared with controls, decreased left ventricular ejection fraction at rest was found only in severe GHD patients (55.0 +/- 8.8 vs. 63.4 +/- 4.5%, P < 0.001); decreased left ventricular ejection fraction response on effort in severe (-4.6 +/- 17.4 vs. 15.2 +/- 9.1%, P < 0.001) and partial GHD patients (3.6 +/- 6.6 vs. 14.6 +/- 8.3%, P < 0.001); decreased diastolic filling at rest in severe (2.53 +/- 0.68 vs. 3.01 +/- 0.48 end-diastolic volume per second, P < 0.001) and partial GHD (2.61 +/- 0.45 vs. 2.89 +/- 0.54 end-diastolic volume per second, P = 0.004) patients; and decreased exercise duration and capacity in all the patient groups. A normal systolic performance on effort was found in 21.4% of severe GHD, 55.6% of partial GHD, all non-GHD, and 93.7% of controls. A normal diastolic filling at rest was found in 57.1% of severe GHD, 74.1% of partial GHD, 76.5% of non-GHD, and 90% of controls. In conclusion, cardiac performance is correlated with the GH status because significant impairment was found in patients with severe and partial GHD but not in non-GHD hypopituitary patients.