An optimized low-pressure tourniquet murine hind limb ischemia reperfusion model: Inducing acute ischemia reperfusion injury in C57BL/6 wild type mice.
Acute ischemia reperfusion injury in skeletal muscle remains an important issue in several fields of regenerative medicine. Thus, a valid model is essential to gain deeper insights into pathophysiological relations and evaluate possible treatment options. While the vascular anatomy of mice regularly prevents sufficient vessel occlusion by invasive methods, there is a multitude of existing models to induce ischemia reperfusion injury without surgical procedures. Since there is no consensus on which model to prefer, this study aims to develop and evaluate a novel, optimized low-pressure tourniquet model. C57BL/6 mice underwent an ischemic procedure by either tourniquet or invasive artery clamping. A sham group served as control. With exception of the sham group, mice underwent 2 hours of ischemia followed by 4 hours of reperfusion. Groups were compared using microcirculatory and spectroscopic measurements, distinctions in tissue edema, histological and immunohistochemical analyses. Both procedures led to a significant decrease in tissue blood flow (- 97% vs. - 86%) and oxygenation (- 87% vs. - 75%) with a superiority of the low-pressure tourniquet. Tissue edema in the tourniquet cohort was significantly increased (+ 59%), while the increase in the clamping cohort was non-significant (+ 7%). Haematoxylin Eosin staining showed significantly more impaired muscle fibers in the tourniquet group (+ 77 p.p. vs. + 11 p.p.) and increased neutrophil infiltration/ROI (+ 51 vs. + 8). Immunofluorescence demonstrated an equal increase of p38 in both groups (7-fold vs. 8-fold), while the increase in apoptotic markers (Caspase-3, 3-Nitrotyrosine, 4-Hydroxynonenal) was significantly higher in the tourniquet group. The low-pressure tourniquet has been proven to produce reproducible and thus reliable ischemia reperfusion injury. In addition, significantly less force was needed than previously stated. It is therefore an important instrument for studying the pathophysiology of ischemia reperfusion injury and for the development of prophylactic as well as therapeutic interventions.


Genetic differences in the endocrine responses to the thyrotrophin-releasing hormone stimulation test in patients with a major depressive episode.
The thyrotrophin-releasing hormone (TRH) stimulation test is becoming useful in the diagnosis of depression, but the optimum concentration of TRH required remains uncertain. The test was performed on a carefully selected group of patients with primary unipolar major depressive episodes with melancholia, who were severely depressed, using TRH 200 micrograms and 500 micrograms (groups 1 and 2). The thyroid-stimulating hormone (TSH), growth hormone (GH) and prolactin (PRL) levels were measured in response to TRH. Responses obtained were compared with respect to hormonal and genetic subgroups. Comparing groups 1 and 2 revealed significant differences in the GH responses (P = 0,0059). A similar significant difference was found in the GH response (P = 0,0102) elicited by the women in each group. Comparison of the genetic subgroups of groups 1 and 2 revealed a significant difference in the PRL response of both the genetic spectrum (P = 0,0258) and the group without a genetic history (P = 0,0259) of alcoholism or depression. The TSH response in the genetic spectrum group was also significantly higher (P = 0,0008) in group 2. Further investigations of the responses elicited in the different genetic subgroups may reveal important variables for the investigation of the pathogenesis of depression.


A molecular characterization of marsupial filarioid nematodes of the genus Breinlia.
Here we present the genetic relationships of 26 specimens of the genus Breinlia (Nematoda: Filarioidea) from a range of Australian marsupials using markers in the small subunit of nuclear ribosomal RNA and mitochondrial cytochrome c oxidase subunit 1 (cox1) genes and compare them with morphological determinations. The molecular data support the validity of most of the morpho-species included in the study and provide provisional insights into the phylogeny of the genus in Australian mammals, with dasyuroid marsupials appearing to be the original hosts. The recent discovery of Breinlia annulipapillata in the eye of a human brings this genus of parasites into the group of emerging infectious parasitic diseases.


Broad Coping Repertoire Mediates the Effect of the Combined Behavioral Intervention on Alcohol Outcomes in the COMBINE Study: An Application of Latent Class Mediation.
Few studies have found support for coping as a mechanism of behavior change (MOBC) following coping skills training interventions for alcohol use disorder (AUD). One potential reason for null findings is heterogeneity in the patterns of coping skills acquired during treatment. This study sought to identify latent classes of coping and to test the latent class variable as a mediator of the effect of a combined behavioral intervention for AUD. Secondary analyses of data from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) Study (N = 1,124; mean age = 44.4 years; 69.1% male; 23.2% non-White), a multisite study of medication and behavioral treatments for individuals with AUD. Latent class mediation models were estimated to test whether patterns of alcohol-specific coping mediated the effect of combined behavioral intervention with medication management, as compared with medication management only, on drinking outcomes 12 months following treatment. Three classes were identified, which differed in repertoire broadness, or the degree in which a wide range of different skills were used. Coping repertoire class was a significant mediator of the effect of the combined behavioral intervention on drinking outcomes. Receiving the combined behavioral intervention, in addition to medication management, predicted a greater likelihood of expected classification in the broad coping repertoire class, which in turn was associated with significant improvements in drinking outcomes. Using the novel methodological approach of latent class mediation, this study identified coping repertoire as a significant mediator of behavioral intervention efficacy for AUD. Future work examining heterogeneity in mediators and outcomes may help refine AUD treatment to be maximally effective.


Lactational Exposure to Di (2-ethylhexyl) Phthalate Impairs the Ovarian and Uterine Function of Adult Offspring Rat.
Phthalates, a class of chemicals used as plasticizers, are economically important due to several industrial applications. Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used phthalate plasticizer, and it has been described as a potent antiandrogen in males. In this study, lactating dams were exposed via oral gavage to corn oil (vehicle) and DEHP (1, 10, and 100 mg/kg body weight) from postnatal day 1 to 21, and the effects were evaluated in the ovary and uterus of F(1) progeny. DEHP exposure significantly decreased the body weight and organ weight in a dose-dependent manner. Serum levels of estradiol, testosterone, and progesterone were decreased but anogenital distance was unaffected. The mRNA expressions of luteinizing hormone receptor, follicle-stimulating hormone receptor, androgen receptor, estrogen receptor (ERα and ERβ), progesterone receptor, peroxisome proliferator-activated receptor γ, 3β hydroxysteroid dehydrogenase, aromatase, and steroidogenic acute regulatory protein were altered in the ovary of F1 progeny rats. Our finding suggest that lactational exposure to DEHP has transgenerational effect on female reproductive system.


T-peak to T-end Interval Predicts Appropriate Shocks in Patients with Heart Failure Undergoing Implantable Cardioverter Defibrillator Implantation for Primary Prophylaxis.
T-wave peak to T-wave end interval (Tp-e) correlates with dispersion of ventricular repolarization. The purpose of this study was to assess the ability of Tp-e to predict appropriate implantable cardioverter defibrillator (ICD) shocks and all-cause mortality in patients who underwent ICD implantation for primary prophylaxis. Two hundred twenty-eight patients with left ventricular ejection fraction ≤35% and an ICD implanted were followed-up prospectively. Patients divided into two subgroups according to presence of appropriate ICD shocks (Group 1: 112 patients with ICD shocks, Group 2: 116 patients without shocks). End points were appropriate ICD therapy due to ventricular tachycardia (VT)/ventricular fibrillation (VF), death, and a combined end point of VT/VF or death. During a mean follow-up of 22.3 ± 7.7 months, appropriate ICD shocks were observed in 112 of 228 patients (49.1%). The mean duration of the Tp-e Group 1 was significantly longer than Group 2 (115.3 ± 22.2 vs 104.7 ± 20.2 ms, P < 0.001). Ischemic etiology and Tp-e duration were found to be independent predictors of ICD therapy. When the patients were divided into two groups based on Tp-e interval, there was no significant difference regarding the mortality between groups (21.2% vs 21.8%, P: 0.186). However, appropriate ICD shocks due to VT/VF (37.5% vs 58.8%, P < 0.001) and combined end point (39.4% vs 64.5%, P: 0.002) were significantly higher in patients with longer Tp-e group. Tp-e interval independently predicts appropriate ICD shocks in patients with systolic dysfunction and ICDs implanted for primary prevention.


Characterisation of the Whole Blood mRNA Transcriptome in Holstein-Friesian and Jersey Calves in Response to Gradual Weaning.
Weaning of dairy calves is an early life husbandry management practice which involves the changeover from a liquid to a solid feed based diet. The objectives of the study were to use RNA-seq technology to examine the effect of (i) breed and (ii) gradual weaning, on the whole blood mRNA transcriptome of artificially reared Holstein-Friesian and Jersey calves. The calves were gradually weaned over 14 days (day (d) -13 to d 0) and mRNA transcription was examined one day before gradual weaning was initiated (d -14), one day after weaning (d 1), and 8 days after weaning (d 8). On d -14, 550 genes were differentially expressed between Holstein-Friesian and Jersey calves, while there were 490 differentially expressed genes (DEG) identified on d 1, and 411 DEG detected eight days after weaning (P < 0.05; FDR < 0.1). No genes were differentially expressed within breed, in response to gradual weaning (P > 0.05). The pathways, gene ontology terms, and biological functions consistently over-represented among the DEG between Holstein-Friesian and Jersey were associated with the immune response and immune cell signalling, specifically chemotaxis. Decreased transcription of several cytokines, chemokines, immunoglobulin-like genes, phagocytosis-promoting receptors and g-protein coupled receptors suggests decreased monocyte, natural killer cell, and T lymphocyte, chemotaxis and activation in Jersey compared to Holstein-Friesian calves. Knowledge of breed-specific immune responses could facilitate health management practices better tailored towards specific disease sensitivities of Holstein-Friesian and Jersey calves. Gradual weaning did not compromise the welfare of artificially-reared dairy calves, evidenced by the lack of alterations in the expression of any genes in response to gradual weaning.


Should surgical patients be screened for human immunodeficiency virus infection?
There are increasingly strong arguments for the introduction of wider screening of all kinds of patients, including surgical patients, to diagnose otherwise undetected human immunodeficiency virus (HIV) infection in order to facilitate earlier treatment of HIV infection with zidovudine. Wider screening may also help to limit the spread of HIV in the community as infected patients may be counselled and more effective public health measures planned. In areas of high prevalence voluntary universal screening test programmes should be encouraged whereas in areas of low to medium prevalence more selective screening tests would be appropriate on people belonging to risk groups. Screening of patients undergoing elective surgery for infection control purposes is most appropriate in areas of low to medium prevalence so that extra precautions in the operating theatre can be selected for those patients who are screened and deemed to be at high risk. Screening methods include taking a comprehensive clinical history to include specific questions about risk group behaviour, questionnaire methods, serological screening tests and a combination of these three types of approach. Screening HIV antibody tests are recommended, with informed consent, of those patients who belong to risk groups. A further benefit of screening for infection control purposes occurs in the event of a sharps injury when prior testing of the source patient helps to facilitate decision making about the giving of immediate zidovudine prophylaxis.


Elderly patients with adult-onset growth hormone deficiency are not osteopenic.
The age-related decline in GH secretion has been implicated in the development of osteoporosis. GH-deficient adults show a significant reduction in bone mineral density (BMD), which is greater in those with childhood-onset GH deficiency than in those with GH deficiency occurring in adult life. To determine whether GH deficiency in late adult life causes a reduction in BMD beyond the decline observed with increasing age, we studied 21 patients over the age of 60 yr with GH deficiency caused by organic pituitary disease and 23 controls of similar age and sex distribution and BMI. Dual energy x-ray absorptiometry was used to determine total bone mass and BMD at the hip and in the lumbar spine. Serum osteocalcin was determined in all subjects and urinary deoxypyridinoline/creatinine ratio in 19 patients and 21 controls. The median (range) known duration of GH deficiency in the patients was 8 yr (range, 4-41 yr). The median (range) total bone mass was 2774 g (range, 1534-3734) in the patients and 2717 g (range, 1235-3549) in the controls (P = 0.42). Specific measurements of BMD made at L2-L4, the right femoral neck, the right femoral trochanter, and Ward's triangle were 1.234 (range, 0.778-1.507) vs. 1.144 g/cm2 (range, 0.809-1.466; P = 0.48), 0.921 (range, 0.605-1.372) vs. 0.96 g/cm2 (range, 0.534-1.315; P = 0.62), 0.92 (range, 0.523-1.229) vs. 0.915 g/cm2 (range, 0.353-1.313; P = 0.68), and 0.773 (range, 0.408-1.289) vs. 0.806 g/cm2 (range, 0.353-1.154; P = 0.81) in the patients and controls, respectively. The median (range) serum osteocalcin was 11.5 (range, 3.6-23.0) vs. 15.1 ng/mL (range, 0.7-40.5; P = 0.019) in the patients and controls, respectively. The median (range) deoxypyridinoline cross-links/creatinine ratio was 3.5 micromol/mol (range, 0.8-8.3) in the patients and 4.9 micromol/mol (range, 3.0-9.7) in the controls (P 0.038). There was a significant correlation between serum insulin-like growth factor I and total bone mass in the controls, but not in the patients. These data demonstrate that BMD is not significantly altered in GH-deficient adults over the age of 60 yr. Markers of bone formation and resorption are decreased, however, suggesting that bone turnover is reduced. Further studies are required to determine whether the reduction in bone turnover in these patients is of benefit.


Evaluating Antibody-Dependent Cell-Mediated Cytotoxicity by Chromium Release Assay.
Antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism in which immune cell activation is induced by the cross-linking of CD16 with the Fc region of antibodies that at the same time bind specifically to cell surface antigens. ADCC stimulates the secretion of perforin, granzymes, and cytokines leading to lysis of the malignant cells. Natural killer (NK) cells express the CD16 receptor and can therefore be activated by ADCC to kill tumor cells. To study the cytotoxicity of NK cells against cancer cells, an ADCC-based assay is described: the chromium release assay. In this method, the antibody trastuzumab, which binds specifically to HER2-positive malignant cells, is used to trigger ADCC.


Occurrence of a large molecular size form of polyphosphate-glucose phosphotransferase in extracts of Mycobacterium tuberculosis H37Ra.
Extracts prepared by sonicating Mycobacterium tuberculosis H37Ra cells with subsequent centrifugation at 18,000 X g proved to contain a very large molecular size form of polyphosphate-glucose phosphotransferase. The enzyme was separable by polyacrylamide gel electrophoresis, DEAE-cellulose chromatography or ultracentrifugation. When rechromatographed at alkaline pH values, it gave rise to one of the soluble forms of lower molecular weight. The conversion also took place as a result of n-butanol extraction or salting out with ammonium sulfate and heating of dissolved pellet. Under certain conditions the lower-molecular weight enzyme converted to the higher-molecular weight form by association with a hitherto undefined cell constituent. It is assumed that both ionic and hydrophobic forces play a role in this interconversion phenomenon.


Treatment of digitalis intoxication by charcoal hemoperfusion (CHP).
In the present communication, we demonstrate the removal of digoxin both in vitro and in vivo from digoxin intoxicated dogs by use of hemoperfusion over activated charcoal. In vitro drug removal was 33 ml/min at mean blood flow rates of 160 ml/min. By 30 mins of in vitro perfusion 51% of drug was removed from the reservoir and by 2 1/2 hrs 83%. In vivo clearance in dogs was 55 ml/min at blood flow rates of 150 ml/min. In view of the poor success that has been encountered in the treatment of digoxin intoxication with other modalities, charcoal hemoperfusion may represent an effective method of rapid digoxin removal from blood.


Cl- channels in apoptosis.
A remarkable feature of apoptosis is the initial massive cell shrinkage, which requires opening of ion channels to allow release of K+, Cl-, and organic osmolytes to drive osmotic water movement and cell shrinkage. This article focuses on the role of the Cl- channels LRRC8, TMEM16/anoctamin, and cystic fibrosis transmembrane conductance regulator (CFTR) in cellular apoptosis. LRRC8A-E has been identified as a volume-regulated anion channel expressed in many cell types. It was shown to be required for regulatory and apoptotic volume decrease (RVD, AVD) in cultured cell lines. Its presence also determines sensitivity towards cytostatic drugs such as cisplatin. Recent data point to a molecular and functional relationship of LRRC8A and anoctamins (ANOs). ANO6, 9, and 10 (TMEM16F, J, and K) augment apoptotic Cl- currents and AVD, but it remains unclear whether these anoctamins operate as Cl- channels or as regulators of other apoptotic Cl- channels, such as LRRC8. CFTR has been known for its proapoptotic effects for some time, and this effect may be based on glutathione release from the cell and increase in cytosolic reactive oxygen species (ROS). Although we find that CFTR is activated by cell swelling, it is possible that CFTR serves RVD/AVD through accumulation of ROS and activation of independent membrane channels such as ANO6. Thus activation of ANO6 will support cell shrinkage and induce additional apoptotic events, such as membrane phospholipid scrambling.


New directions for dental education in Japan.
To meet recent changes in the oral health sciences, general science, and social needs, the guidelines for the dental curriculum were revised by the Japanese Deans Meeting in 1994. This new program addresses the need to modify both undergraduate and postgraduate dental education in Japan. Lifelong education for dentists has been also modified recently. Reforming of dental education is pushed forward with the concept of continuity and flexibility. In this report, an overview of dental education and the most recent dental curriculum in Japan is briefly discussed.


Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes.
Activation of the hepatocyte growth factor/Met receptor is involved in muscle regeneration, through promotion of proliferation and inhibition of differentiation in myogenic stem cells (MSCs). We previously described that the specific expression of an oncogenic version of the Met receptor (Tpr-Met) in terminally-differentiated skeletal muscle causes muscle wasting in vivo. Here, we induced Tpr-Met in differentiated myotube cultures derived from the transgenic mouse. These cultures showed a reduced protein level of myosin heavy chain (MyHC), increased phosphorylation of Erk1,2 MAPK, the formation of giant sacs of myonuclei and the collapse of elongated myotubes. Treatment of the cultures with an inhibitor of the MAPK kinase pathway or with an inhibitor of the proteasome increased the expression levels of MyHC. In addition, the inhibition of the MAPK kinase pathway prevented the formation of myosacs and myotube collapse. Finally, we showed that induction of Tpr-Met in primary myotubes was unable to produce endoreplication in their nuclei. In conclusion, our data indicate that multinucleated, fused myotubes may be forced to disassemble their contractile apparatus by the Tpr-Met oncogenic factor, but they resist the stimulus toward the reactivation of the cell cycle.


Slew-rate dependence of tracer magnetization response in magnetic particle imaging.
Magnetic Particle Imaging (MPI) is a new biomedical imaging technique that produces real-time, high-resolution tomographic images of superparamagnetic iron oxide nanoparticle tracers. Currently, 25 kHz and 20 mT/μ0 excitation fields are common in MPI, but lower field amplitudes may be necessary for patient safety in future designs. Here, we address fundamental questions about MPI tracer magnetization dynamics and predict tracer performance in future scanners that employ new combinations of excitation field amplitude (Ho ) and frequency (ω). Using an optimized, monodisperse MPI tracer, we studied how several combinations of drive field frequencies and amplitudes affect the tracer's response, using Magnetic Particle Spectrometry and AC hysteresis, for drive field conditions at 15.5, 26, and 40.2 kHz, with field amplitudes ranging from 7 to 52 mT/μ0. For both fluid and immobilized nanoparticle samples, we determined that magnetic response was dominated by Néel reversal. Furthermore, we observed that the peak slew-rate (ωHo) determined the tracer magnetic response. Smaller amplitudes provided correspondingly smaller field of view, sometimes resulting in excitation of minor hysteresis loops. Changing the drive field conditions but keeping the peak slew-rate constant kept the tracer response almost the same. Higher peak slew-rates led to reduced maximum signal intensity and greater coercivity in the tracer response. Our experimental results were in reasonable agreement with Stoner-Wohlfarth model based theories.


Small-molecule immunostimulants. Synthesis and activity of 7,8-disubstituted guanosines and structurally related compounds.
A series of 7,8-disubstituted guanosine derivatives was designed and prepared as potential B-cell-selective activators of the humoral immune response. These compounds were evaluated for their ability to act as B-cell mitogens and to augment the antibody response of B cells to sheep red blood cell (SRBC) challenge (adjuvanticity). In addition, they were tested for their ability to stimulate the natural killer (NK) cell response in murine in vitro cell assays. Certain of the compounds demonstrated in vivo activity when administered either intravenously, subcutaneously, or orally. Analogues with a medium-length alkyl chain (2-4 carbons, 5-7) on the 7-position of 7-alkyl-8-oxoguanosines were found to be particularly potent. Compounds bearing hydroxyalkyl, aminoalkyl, or substituted aminoalkyl substituents on this 7-position were weakly active. However, benzyl groups, including those substituted with heteroatoms (e.g., p-nitrobenzyl, 14), were active. Oxo, thioxo, and seleno groups on C-8 of the guanosine ring all imparted strong activity, whereas other larger substituents did not (e.g., N = CN). Stereochemical inversion of the 2'-hydroxyl on the ribose ring in this series, giving arabinose analogue 70, lessened activity. However, removal of the 2'-hydroxyl, either with (64) or without (73) removal of the 3'-hydroxyl, resulted in excellent activity and improved solubility; 64 also displayed good oral in vivo activity as well. A series of ketals involving the 2',3'-hydroxyls were prepared; certain of the nonpolar ketals (e.g., 48) were remarkably active, pointing to an ancillary hydrophobic binding region that can augment activity. 5'-Phosphate derivative 57 was fairly active, and acyclovir analogue 90 displayed good NK-selective activity: other N-9 sugar mimetics were also active (97-104), although this activity did not carry over into the human B-cell assay. A total of 80 compounds were prepared and evaluated for their immunostimulating activity. Within this group, compounds could be divided into those that were active in all three assays, those that displayed some measure of selectivity for the adjuvanticity assay, and those that preferentially activated NK responses. Because of its overall biological profile and ease of synthesis, 7-allyl-8-oxoguanosine (6; loxoribine, RWJ-21757) was chosen for further development. It is among the most potent compounds evaluated in the three biological assays.


Lidocaine sensitizes the cytotoxicity of cisplatin in breast cancer cells via up-regulation of RARβ2 and RASSF1A demethylation.
It has been reported that lidocaine is toxic to various types of cells. And a recent study has confirmed that lidocaine exerts a demethylation effect and regulates the proliferation of human breast cancer cell lines. To recognize a potential anti-tumor effect of lidocaine, we evaluated the DNA demethylation by lidocaine in human breast cancer lines, MCF-7 and MDA-MB-231 cells, and determined the influence of demethylation on the toxicity to these cells of cisplatin, which is a commonly utilized anti-tumor agent for breast cancer. Results demonstrated that lidocaine promoted a significant global genomic demethylation, and particularly in the promoters of tumor suppressive genes (TSGs), RARβ2 and RASSF1A. Further, the lidocaine treatment increased cisplatin-induced apoptosis and enhanced cisplatin-induced cytotoxicity. The combined treatment with both lidocaine and cisplatin promoted a significantly higher level of MCF-7 cell apoptosis than singular lidocaine or cisplatin treatment. Moreover, the abrogation of RARβ2 or RASSF1A expression inhibited such apoptosis. In conclusion, the present study confirms the demethylation effect of lidocaine in breast cancer cells, and found that the demethylation of RARβ2 and RASSF1A sensitized the cytotoxicity of cisplatin in breast cancer cells.


Matrix analysis for fast learning of neural networks with application to the classification of acoustic spectra.
Neural networks are increasingly being applied to problems in acoustics and audio signal processing. Large audio datasets are being generated for use in training machine learning algorithms, and the reduction of training times is of increasing relevance. The work presented here begins by reformulating the analysis of the classical multilayer perceptron to show the explicit dependence of network parameters on the properties of the weight matrices in the network. This analysis then allows the application of the singular value decomposition (SVD) to the weight matrices. An algorithm is presented that makes use of regular applications of the SVD to progressively reduce the dimensionality of the network. This results in significant reductions in network training times of up to 50% with very little or no loss in accuracy. The use of the algorithm is demonstrated by applying it to a number of acoustical classification problems that help quantify the extent to which closely related spectra can be distinguished by machine learning.


Assessment of a collaborative treatment model for trimodal management of esophageal cancer.
Patients with esophageal cancer often receive care in a collaborative (multi-institutional) treatment model as opposed to a single institutional model. The effect of a collaborative model on the quality of trimodality therapy and survival is unknown. The National Cancer Database (NCDB) was used to identify patients receiving neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy for esophageal cancer between 2012-2017. Patients who received neoadjuvant therapy and surgery at a single institution were compared to those that received collaborative treatment across multiple institutions. Outcomes included adherence to guideline recommended multiagent chemotherapy, receipt of 41.4-50.4 Gy of radiation, R0 resection, pathologic complete response (pCR), and 5-year survival. Sociodemographics, comorbidities, and tumor characteristics were assessed in bivariate and multivariable analysis. Among 8,396 patients identified, 39% received treatment at a single institution, while 61% received collaborative treatment. Median travel distance to the site of esophagectomy was two times greater for patients receiving collaborative treatment (30 vs. 15 miles; P<0.001). Patients in the collaborative cohort were less likely to receive guideline-recommended multiagent chemotherapy (85% vs. 96%; P<0.001) and 41.4-50.4 Gy of radiation (89% vs. 91%; P=0.01). R0 resection rates were similar (94.4% vs. 93.7%; P=0.17). Patients who received collaborative treatment had an increased rate of pCR (24% vs. 22%; P=0.02). Overall, 90-day and 5-year survival were 92.9% and 42.6% respectively and did not differ significantly between the two groups. Collaborative trimodality treatment of esophageal cancer is a common and reasonable practice model, which may alleviate patient travel burden with only a modest impact on the quality of CRT, pCR, 90-day survival, and 5-year survival.


Infection of duck plague carriers with Pasteurella multocida and P. anatipestifer.
Mallards (Anas platyrhynchos platyrhynchos) and white pekin ducks (Anas platyrhynchos domesticus) were infected with duck plague virus and challenged with LD20's of Pasteurella multocida and P. anatipestifer. There was no difference between mortality rates of duck plague-infected ducks and controls, suggesting that these organisms do not act synergistically under the conditions of our experiments. There was a difference of about 500-fold between the LD20 of P. multocida for mallards and that for white pekin ducks, indicating that mallards are much more susceptible to avian cholera than white pekin ducks.


Multi-agency practice for developing a blended diet for children fed via gastrostomy.
The administration of a blended diet via a gastrostomy tube to children with complex needs is an evolving area of practice. Healthcare professionals must provide guidance, promote best practice and optimise patient safety where patients and families choose a blended diet in preference to the prescribed commercial feed. The Aneurin Bevan Health University Health Board in Newport, Wales, took a collaborative approach, by working with parents as equal partners, to enable a child with complex needs to receive a blended diet at school. The development of a protocol and risk-assessed approach enabled the delivery of bespoke flexible care that met the holistic needs of the child and family and improved the child's quality of life. The initiative also led to positive outcomes for the school and wider community.


Early experience of coronary artery bypass grafting with a new self-closing clip device.
We are in the midst of development of several new anastomotic devices for use in coronary artery bypass grafting surgery. This study was designed to examine one of these devices (a new self-closing clip) for left internal thoracic artery-left anterior descending coronary artery anastomosis. Its feasibility and the quality of anastomosis were evaluated. Fourteen patients who underwent first-time elective coronary artery bypass surgery were enrolled between July and December 2000. The left internal thoracic artery was anastomosed to the left anterior descending coronary artery in an interrupted manner with Coalescent U-clips (Coalescent Surgical, Inc, Sunnyvale, Calif). Immediate patency was checked with a transit-time flowmeter. Selective angiography was performed 6 months after surgical intervention. Five patients underwent on-pump coronary bypass grafting, 9 on the beating heart. One patient was excluded from the study intraoperatively because of a poor target site necessitating a 2-cm-long anastomosis. Left internal thoracic artery-left anterior descending artery anastomoses were created with an average of 11.8 clips in 15.9 minutes. Mean graft flow was 45.6 mL/min. Neither conversion to standard suture technique nor revision of anastomosis was necessary. There tended to be a learning curve in the anastomosis on the beating heart. Postoperative lengths of stay in the intensive care unit and the hospital were 20.7 hours and 3.9 days, respectively. Neither death nor major complication was seen, except for temporary atrial fibrillation in 2 patients. Graft patency at 6 months was 100% (FitzGibbon grade A). Left internal thoracic artery-left anterior descending artery anastomoses can be created safely and effectively with new self-closing clips on the beating, as well as the arrested, heart. Midterm patency was shown to be perfect by means of angiography.


[Population biology of cestode genus Triaenophorus in natural and man-made water bodies].
A comparative study of the frequencies of occurrence and distribution of the abundances of pike parasites, tapeworms of the genus Triaenophorus, was carried out in natural lakes and water bodies contaminated by the Kostomuksha mining and concentration mill (Northern Karelia). We demonstrate that the wide presence of T. crassus and T. nodulosus in natural northern lakes is due to the diversity of aquatic organisms and the structure of trophic relations. The abundance of both species is modeled by the negative binomial distribution. Relations in the host-parasite system are stable. Estimates of the parameter k of the negative binomial distribution reflect the changes in the interactions in the host-parasite system. T. nodulosus has survived in the man-made water body storing the highly mineralized recirculated water from the mill. Disturbance-related distinctions were detected in the parameters of the T. nodulosus abundance distribution in the host population. In the Okunevoye Lake, where the water discharged from the tailings dump is more diluted, the infection rates in pike did not differ from those in undisturbed water bodies.


A Biomechanical Assessment of Biceps Femoris Repair Techniques.
Knee injuries encountered in clinical practice can involve avulsions of the biceps femoris from the fibula and proximal tibia. Advances in tendon repair methods now allow for repairs with increased surface areas using modern suture anchor techniques. Despite descriptions of repair techniques, there are no biomechanical studies on the biceps femoris for comparison. The objective of this controlled laboratory study was to determine the failure load of the native biceps femoris distal insertion and to evaluate modern repair techniques. Our hypothesis was 2-fold: (1) Suture repairs to the tibia and fibula would perform better on tensile testing than repairs to the fibula alone, and (2) complex bridge repairs, similar to those frequently used in rotator cuff surgery, would perform better on tensile testing than simple repairs. Controlled laboratory study. A total of 40 paired, fresh-frozen cadaveric specimens were dissected, identifying the biceps femoris and its insertion on the proximal tibia and fibula. The native biceps femoris footprint was left intact in 8 specimens and tested to failure on a uniaxial materials testing machine evaluating tensile properties, while in the other 32 specimens, the biceps femoris insertion was dissected using a No. 15 scalpel blade, underwent repair, and was then tested to failure on a uniaxial materials testing machine evaluating tensile properties. Four repair constructs were evaluated, with 8 specimens allocated for each: construct 1 involved a simple repair (ie, passing suture through tissue in a running Krackow fashion and tying at the anchor site) to the fibula with 2 suture anchors, construct 2 involved a simple repair to the fibula and tibia with 3 suture anchors, construct 3 was a fibular repair with a tibial suture bridge involving the fibula and tibia and 3 suture anchors, construct 4 involved a transosseous repair through the fibula and 1 suture anchor on the tibia. Analysis of variance was used to evaluate for significance of the mean failure load and stiffness between groups. The mean (±95% CI) failure loads were the following: native biceps femoris, 1280 ± 247.0 N; simple fibular repair, 173 ± 84.6 N; simple fibular and tibial repair, 176 ± 48.1 N; fibular repair with tibial suture bridge, 191 ± 78.5 N; and transosseous repair, 327 ± 66.3 N. The mean stiffness values were the following: native, 46 ± 13.0 N/mm; simple fibular repair, 16 ± 5.1 N/mm; simple fibular and tibial repair, 14 ± 5.4 N/mm; fibular repair with tibial suture bridge, 13 ± 2.8 N/mm; and transosseous repair, 15 ± 2.5 N/mm. Interconstruct comparison of failure loads revealed no statistical difference between constructs utilizing anchors alone. The transosseous repair showed a significant difference for the failure load when compared with each anchor repair construct (P = .02, .02, and .04 for constructs 1, 2, and 3, respectively). Interconstruct comparison of stiffness revealed no statistical difference between all constructs (P > .86). None of the repair techniques re-created the failure load or stiffness of the native biceps femoris tendon (P = .02). In this biomechanical study, no difference was found between the mean failure loads of different biceps femoris repair constructs involving suture anchors alone and No. 2 braided polyester and ultra-high-molecular-weight polyethylene suture. A technique involving transosseous fibular tunnels and 2-mm suture tape illustrated a greater mean failure load than repairs relying on suture anchors for fixation. Understanding the tensile performance of biceps femoris repair constructs aids clinicians with preoperative and intraoperative decisions. Current biceps femoris repair techniques do not approximate the native strength of the tendon. A transosseous style of repair offers the highest failure load.


Microbial redox cycling enhances ecosystem thermodynamic efficiency and productivity.
Microbial life in low-energy ecosystems relies on individual energy conservation, optimizing energy use in response to interspecific competition and mutualistic interspecific syntrophy. Our study proposes a novel community-level strategy for increasing energy use efficiency. By utilizing an oxidation-reduction (redox) reaction network model that represents microbial redox metabolic interactions, we investigated multiple species-level competition and cooperation within the network. Our results suggest that microbial functional diversity allows for metabolic handoffs, which in turn leads to increased energy use efficiency. Furthermore, the mutualistic division of labour and the resulting complexity of redox pathways actively drive material cycling, further promoting energy exploitation. Our findings reveal the potential of self-organized ecological interactions to develop efficient energy utilization strategies, with important implications for microbial ecosystem functioning and the co-evolution of life and Earth.


In silico identification of miRNAs and their target genes and analysis of gene co-expression network in saffron (Crocus sativus L.) stigma.
As an aromatic and colorful plant of substantive taste, saffron (Crocus sativus L.) owes such properties of matter to growing class of the secondary metabolites derived from the carotenoids, apocarotenoids. Regarding the critical role of microRNAs in secondary metabolic synthesis and the limited number of identified miRNAs in C. sativus, on the other hand, one may see the point how the characterization of miRNAs along with the corresponding target genes in C. sativus might expand our perspectives on the roles of miRNAs in carotenoid/apocarotenoid biosynthetic pathway. A computational analysis was used to identify miRNAs and their targets using EST (Expressed Sequence Tag) library from mature saffron stigmas. Then, a gene co- expression network was constructed to identify genes which are potentially involved in carotenoid/apocarotenoid biosynthetic pathways. EST analysis led to the identification of two putative miRNAs (miR414 and miR837-5p) along with the corresponding stem- looped precursors. To our knowledge, this is the first report on miR414 and miR837-5p in C. sativus. Co-expression network analysis indicated that miR414 and miR837-5p may play roles in C. sativus metabolic pathways and led to identification of candidate genes including six transcription factors and one protein kinase probably involved in carotenoid/apocarotenoid biosynthetic pathway. Presence of transcription factors, miRNAs and protein kinase in the network indicated multiple layers of regulation in saffron stigma. The candidate genes from this study may help unraveling regulatory networks underlying the carotenoid/apocarotenoid biosynthesis in saffron and designing metabolic engineering for enhanced secondary metabolites.


Flexible ligand docking using conformational ensembles.
Molecular docking algorithms suggest possible structures for molecular complexes. They are used to model biological function and to discover potential ligands. A present challenge for docking algorithms is the treatment of molecular flexibility. Here, the rigid body program, DOCK, is modified to allow it to rapidly fit multiple conformations of ligands. Conformations of a given molecule are pre-calculated in the same frame of reference, so that each conformer shares a common rigid fragment with all other conformations. The ligand conformers are then docked together, as an ensemble, into a receptor binding site. This takes advantage of the redundancy present in differing conformers of the same molecule. The algorithm was tested using three organic ligand protein systems and two protein-protein systems. Both the bound and unbound conformations of the receptors were used. The ligand ensemble method found conformations that resembled those determined in X-ray crystal structures (RMS values typically less than 1.5 A). To test the method's usefulness for inhibitor discovery, multi-compound and multi-conformer databases were screened for compounds known to bind to dihydrofolate reductase and compounds known to bind to thymidylate synthase. In both cases, known inhibitors and substrates were identified in conformations resembling those observed experimentally. The ligand ensemble method was 100-fold faster than docking a single conformation at a time and was able to screen a database of over 34 million conformations from 117,000 molecules in one to four CPU days on a workstation.


Amphotericin-B-loaded polymersomes formulation (PAMBO) based on (PEG)₃-PLA copolymers: an in vivo evaluation in a murine model.
This paper deals with in vivo evaluation of a new amphotericin-B-loaded polymersomes (PAMBO) formulation in terms of pharmacokinetics, toxicity, tissue distribution profile, and its efficacy in a murine model of disseminated candidiasis. Pharmacokinetic and tissue distribution studies of the PAMBO showed sustained levels of the drug in plasma as well as in target organs which harbor fungal and leishmanial infection. PAMBO was found to be much less toxic than Fungizone. It was observed that 700% increment in the dose is tolerated without observable toxicity which is supported by survival, biochemical, and histopathological results. PAMBO showed a significant improvement in the survival rate of immunosuppressed mice infected with Candida albicans as compared to control. It also showed better dose to dose (1 mg/kg) efficacy as compared to Fungizone and a significant improvement in the life expectancy at 3 and 5 mg/kg dose levels in the animals. Colony forming unit (CFU) counts in the target organs revealed significant reduction in Candida burden with PAMBO treatment. Kidney, spleen, and lung were cleared of infection, although liver was carrying a very low level of infection. Overall, PAMBO formulation is found to be more efficacious and less toxic in a fungal mice model.


"Ow!": spontaneous verbal pain expression among young children during immunization.
Although self-reports are a commonly used means of assessing pain in clinical settings, little is understood about the nature of children's spontaneous verbal expressions of pain. The purpose of this study was to describe verbalizations of pain among children receiving a preschool immunization and to examine how pain verbalizations correspond to children's facial expressions and self-reports of pain intensity. Fifty-eight children between the ages of 4 years 8 months and 6 years 3 months (67% female) were videotaped while receiving their routine preschool immunization. Global ratings of facial expression and detailed transcription and coding of pain verbalizations were undertaken. Children provided self-reports of pain using a 7-point faces pain scale. Fifty-three percent of children used verbalizations spontaneously to express their pain. The modal verbalization was the interjection "Ow!," which expressed negative affect and was specific to the experience of pain. Older children were less likely to use verbalizations to express their pain. Children who used verbalizations to express pain displayed greater facial reactions to pain and rated their pain experience as being more intense than children who did not use words to express their pain. Results indicate that many young children do not spontaneously use verbalizations to express pain from immunization. When 5-year-olds use verbalizations to express pain, the verbalizations are most often brief statements that express negative affect and directly pertain to pain. Knowledge of how children verbalize pain may lead to an improved ability to assess and manage pediatric pain.


RPE transplantation and its role in retinal disease.
Retinal pigment epithelial (RPE) transplantation aims to restore the subretinal anatomy and re-establish the critical interaction between the RPE and the photoreceptor, which is fundamental to sight. The field has developed over the past 20 years with advances coming from a large body of animal work and more recently a considerable number of human trials. Enormous progress has been made with the potential for at least partial restoration of visual function in both animal and human clinical work. Diseases that have been treated with RPE transplantation demonstrating partial reversal of vision loss include primary RPE dystrophies such as the merTK dystrophy in the Royal College of Surgeons (RCS) rat and in humans, photoreceptor dystrophies as well as complex retinal diseases such as atrophic and neovascular age-related macular degeneration (AMD). Unfortunately, in the human trials the visual recovery has been limited at best and full visual recovery has not been demonstrated. Autologous full-thickness transplants have been used most commonly and effectively in human disease but the search for a cell source to replace autologous RPE such as embryonic stem cells, marrow-derived stem cells, umbilical cord-derived cells as well as immortalised cell lines continues. The combination of cell transplantation with other modalities of treatment such as gene transfer remains an exciting future prospect. RPE transplantation has already been shown to be capable of restoring the subretinal anatomy and improving photoreceptor function in a variety of retinal diseases. In the near future, refinements of current techniques are likely to allow RPE transplantation to enter the mainstream of retinal therapy at a time when the treatment of previously blinding retinal diseases is finally becoming a reality.


Safety and Antiviral Activity of EGFR Inhibition by Erlotinib in Chronic Hepatitis C Patients: A Phase Ib Randomized Controlled Trial.
Significant hepatocellular carcinoma (HCC) risk persists after chronic hepatitis C (CHC) cure. Preclinical studies have shown that erlotinib, an oral epidermal growth factor receptor (EGFR) inhibitor, has an antiviral activity and HCC chemopreventive effect. Erlotinib is metabolized in the liver, and its safety in patients with CHC is unknown. This study aimed to assess the safety and antiviral activity of erlotinib in patients with CHC. In this investigator-initiated dose-escalation phase Ib prospective randomized double-blind placebo-controlled study, noncirrhotic hepatitis C virus (HCV) patients received placebo or erlotinib (50 or 100 mg/d) for 14 days with a placebo-erlotinib ratio of 1:3. Primary end points were safety and viral load reduction at the end of treatment (EOT). The secondary end point was viral load reduction 14 days after EOT. This study analyzed data of 3 patients receiving placebo, 3 patients receiving erlotinib 50 mg/d, and 3 patients receiving erlotinib 100 mg/d. One grade 3 adverse event was reported in the placebo group (liver enzymes elevation), leading to treatment discontinuation and patient replacement, and 1 in the erlotinib 100 mg/d group (pericarditis), which was not considered to be treatment-related. Grade 2 skin rash was observed in 1 erlotinib 100 mg/d patient. No significant HCV-RNA level reduction was noted during treatment, but 2 of the 3 patients in the erlotinib 100 mg/d group showed a decrease of >0.5 log HCV-RNA 14 days after EOT. Erlotinib demonstrated to be safe in noncirrhotic CHC patients. An antiviral activity at 100 mg/d confirms a functional role of EGFR as an HCV host factor in patients. These results provide perspectives to further study erlotinib as an HCC chemopreventive agent in patients with CHC.


Cathepsin expression in oral squamous cell carcinoma: relationship with clinicopathologic factors.
Proteases are involved in the invasion and metastasis of carcinoma cells. In vivo, oral carcinoma cells easily invade the bone tissue and metastasize to the submandibular and neck lymph nodes. Cathepsin expression has been shown in some neoplastic tissues and serves as a prognostic indicator. The purpose of this study was to investigate the relationship between clinicopathohistologic grades and cathepsin expressions in oral squamous cell carcinoma and to investigate which cathepsin provides prognostic information for patients with oral carcinoma. Immunohistochemical studies were performed on 78 carcinoma samples with monoclonal antibodies against cathepsins B, H, and L, and a polyclonal antibody against cathepsin D. Serial sections were stained by hematoxylin-eosin staining and classified by Anneroth's classification. Cathepsin B, H, L and D activities of blood serum were determined. Positive results indicative of the presence of cathepsin were investigated to determine any correlation between a particular cathepsin and histologic malignancy grades, tumor cell growth, serum cathepsin activities, and clinical factors. Cathepsins B, H, L, and D were positive in every case. Although the labeling indices for cathepsins B (CB-LI), H (CH-LI), and D (CD-LI) for the cancer cases showed significant differences from those of controls, cathepsin L (CL-LI) of cancer cases showed no difference from that of controls (P <.05). A close correlation was found between CD-LI and T categories of TNM classification (P <.05), and between CD-LI and PCNA-LI (P <.05). Furthermore, a close correlation was found between CD-LI and N categories in TNM classification (P <.05). Pathologically, a close correlation was found between CB-LI or CD-LI and the pattern and/or stage of invasion (P <.05). Cathepsin D and B expression were closely correlated with carcinoma invasion and progression. These proteases may be useful in determining the prognoses of patients with oral carcinoma.


Calreticulin silencing inhibits extracellular matrix synthesis of human gingival fibroblasts cultured on three-dimensional poly(lactic-co-glycolic acid) scaffolds by inhibiting the calcineurin/nuclear factor of activated T cells 3 signalling pathway.
The retraction and compression of gingival tissue have a significant impact on the efficiency and stability of orthodontic treatment, but the underlying molecular mechanism has not been fully elucidated. The aim of the current study was to investigate the effects of mechanical forces on the expression level of calreticulin (CRT), the activity of the calcineurin (CaN)/nuclear factor of activated T cells (NFAT) 3 signalling pathway, and extracellular matrix (ECM) synthesis in human gingival fibroblasts (HGFs) cultured on three-dimensional (3D) poly(lactic-co-glycolic acid) (PLGA) scaffolds and to further explore the mechanical transduction pathways that may be involved. A mechanical force of 25 g/cm2 was applied to HGFs for 0, 6, 24, 48, or 72 h. The expression of CRT, CaN, NFAT3, phosphorylated NFAT3 (p-NFAT3) and type I collagen (COL-I) were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Subsequently, small interfering RNA (siRNA) was used to knock down the expression of CRT in HGFs, and the impacts of the applied force on the expression levels of CaN, NFAT3, p-NFAT3, and COL-I were also evaluated by RT-qPCR and western blotting. The application of mechanical force on HGFs cultured on 3D PLGA scaffolds led to a significant increases in CRT, CaN, and COL-I expression as well as a decrease in p-NFAT3 expression. However, the effects of mechanical force on CaN, p-NFAT3, and COL-I expression were reversed following downregulation of CRT and displayed a significant decrease in CaN/NFAT3 activity and COL-I synthesis. This study showed that the CaN/NFAT3 signalling pathway and CRT appear to be involved in the mechanotransduction of HGFs, and downregulation of CRT inhibits COL-I synthesis potentially via the CaN/NFAT3 signalling pathway. Taken together, these findings ultimately provide novel insight into the mechanisms underlying mechanical force-induced ECM synthesis, which may be conducive to the development of targeted therapeutics to treat fibrotic diseases, including gingival fibrosis caused by orthodontic treatment.


Stimuli-responsive Drug Delivery Nanocarriers in the Treatment of Breast Cancer.
Stimuli-responsive drug-delivery nanocarriers (DDNs) have been increasingly reported in the literature as an alternative for breast cancer therapy. Stimuli-responsive DDNs are developed with materials that present a drastic change in response to intrinsic/chemical stimuli (pH, redox and enzyme) and extrinsic/physical stimuli (ultrasound, Near-infrared (NIR) light, magnetic field and electric current). In addition, they can be developed using different strategies, such as functionalization with signaling molecules, leading to several advantages, such as (a) improved pharmaceutical properties of liposoluble drugs, (b) selectivity with the tumor tissue decreasing systemic toxic effects, (c) controlled release upon different stimuli, which are all fundamental to improving the therapeutic effectiveness of breast cancer treatment. Therefore, this review summarizes the use of stimuli-responsive DDNs in the treatment of breast cancer. We have divided the discussions into intrinsic and extrinsic stimuli and have separately detailed them regarding their definitions and applications. Finally, we aim to address the ability of these stimuli-responsive DDNs to control the drug release in vitro and the influence on breast cancer therapy, evaluated in vivo in breast cancer models.


Next-Hop Relay Selection for Ad Hoc Network-Assisted Train-to-Train Communications in the CBTC System.
In the communication-based train control (CBTC) system, traditional modes such as LTE or WLAN in train-to-train (T2T) communication face the problem of a complex and costly deployment of base stations and ground core networks. Therefore, the multi-hop ad hoc network, which has the characteristics of being relatively flexible and cheap, is considered for CBTC. However, because of the high mobility of the train, it is likely to move out of the communication range of wayside nodes. Moreover, some wayside nodes are heavily congested, resulting in long packet queuing delays that cannot meet the transmission requirements. To solve these problems, in this paper, we investigate the next-hop relay selection problem in multi-hop ad hoc networks to minimize transmission time, enhance the network throughput, and ensure the channel quality. In addition, we propose a multiagent dueling deep Q learning (DQN) algorithm to optimize the delay and throughput of the entire link by selecting the next-hop relay node. The simulation results show that, compared with the existing routing algorithms, it has obvious improvement in the aspects of delay, throughput, and packet loss rate.


A relevant universal coverage proposal.
Karen Davis and Cathy Schoen offer a strategic vision for universal coverage that attempts to move beyond ideological battles that have stifled progress. However, I believe that there are a few specific shortcomings with the proposal's logic that could thwart political consensus. I review some of these shortcomings and make suggestions for incremental technical improvements. In particular, I suggest that future versions of the proposal consider administering the tax credits as a "passthrough" from the government through employers to individuals. I also believe that reform proposals should address more directly the issues of provider accountability and patient information needs.


Ineffectiveness of single-dose human antiserum to core glycolipid (E. coli J5) for prophylaxis of bacteremic, gram-negative infections in patients with prolonged neutropenia.
It has been recently established that serum from human volunteers immunized with E. coli J5 vaccine prevents death of patients with gram-negative shock. The present study addressed the question whether the prophylactic administration of a similar amount of J5 antiserum could protect neutropenic patients from acquiring gram-negative infections. One hundred patients, the majority of which had acute non-lymphoblastic (63%) and lymphoblastic (29%) leukemia, presented 109 episodes of neutropenia. Sixty of the 100 patients underwent bone marrow transplantation. All patients were given one unit of either pre-immune (control) or J5 antiserum serum from volunteers at the onset of neutropenia. When compared to control serum, J5 antiserum given prophylactically did not reduce the number of febrile days, the number of gram-negative bacteremic episodes, or death from these infections. This inability to demonstrate a beneficial effect of prophylaxis with a single unit of J5 antiserum in prolonged neutropenia may have several explanations that are discussed.


Solution blow spinning-polyacrylonitrile-assisted cellulose acetate nanofiber membrane.
Cellulose-based nanofiber membrane fabrication remains a global challenge, especially the use of alternative and sustainable sources of cellulosic materials. Herein, an easy and highly scalable cellulose-based nanofiber membrane was successfully fabricated using a solution blow spinning (SBS) method. Such membrane fabrication was carried out with the assistance of an easy-to-spin precursor polymer (i.e. polyacrylonitrile (PAN)). Through this strategy, cellulose acetate (CA) was successfully spun into a ready-to-use membrane. The formation of CA with the PAN nanofiber is concentration-dependent and requires high air pressure to effectively overcome the composite precursor's surface tension and eventually produce nanofibers. Favourable CA concentration in PAN (i.e. 50%-65% v/v CAN/PAN) is important to the formation of sufficient molecular entanglement with PAN in solution. Upon fulfilling the optimized CA concentration, high air pressure (i.e. ≥3 bars) is used to produce jet-like polymeric fibers of PAN dragging off CA, forming numerous nanofibers which are then collected into a substrate forming a membrane. Characterizations of the CA/PAN composite nanofiber were carried out using scanning electron microscopy, Fourier transform infrared, thermogravimetric analysis and differential scanning calorimetry (DSC). Such unique composite nanofiber membranes have potential as filters and adsorbent membranes for air and water/wastewater applications, as well as for biorefinery applications.


'I can't leave everything in the hands of my husband': Economic constraints and gender roles in care-seeking in post-Ebola Guinea.
The 2014-2016 Ebola epidemic in West Africa had enduring effects on health systems and healthcare utilisation. This study explores the intersection of economic constraints and gender roles in Guinea to understand delays in care-seeking post-Ebola. In-depth interviews (n = 45) and focus group discussions (n = 24) were conducted with mothers, male heads of household, grandmothers, and health workers in rural and urban areas in Basse-Guinée and Guinée Forestière. A thematic analysis identified salient themes related to gender and economic constraints on health care-seeking. Participants, particularly men, emphasised the high cost of seeking care, which led to delays as women secured funds. Men's engagement in care-seeking included providing funds and permission, picking up medication, and giving appointment reminders. As principal actors when 'navigating' the healthcare system, women were intimately involved in economic decisions and responsible for securing funds for services - even when lacking direct financial control. Essentialist descriptions of men as 'providers' and women as 'navigators', therefore, masked nuances in care-seeking and economic responsibilities. Programmes must acknowledge men's engagement in care-seeking and address both the economic barriers women face when seeking care and their economic roles. Greater attention to the complex intersection of economic constraints and gender roles could address care-seeking delays.


Association between promoter methylation of DAPK gene and HNSCC: A meta-analysis.
The death-associated protein kinase (DAPK) is a tumor suppressor gene, which is a mediator of cell death of INF-γ-induced apoptosis. Aberrant methylation of DAPK promoter has been reported in patients with head and neck squamous cell carcinoma (HNSCC). However, the results of these studies are inconsistent. Hence, the present study aimed to evaluate the association between the promoter methylation of DAPK gene and HNSCC. Relevant studies were systematically searched in PubMed, Web of Science, Ovid, and Embase. The association between DAPK promoter methylation and HNSCC was assessed by odds ratio (ORs) and 95% confidence intervals (CI). To evaluate the potential sources of heterogeneity, we conducted the meta-regression analysis and subgroup analysis. Eighteen studies were finally included in the meta-analysis. The frequency of DAPK promoter methylation in patients with HNSCC was 4.09-fold higher than the non-cancerous controls (OR = 3.96, 95%CI = 2.26-6.95). A significant association between DAPK promoter methylation and HNSCC was found among the Asian region and the Non-Asia region (Asian region, OR = 4.43, 95% CI = 2.29-8.58; Non-Asia region, OR = 3.39, 95% CI = 1.18-9.78). In the control source, the significant association between DAPK promoter methylation and HNSCC was seen among the autologous group and the heterogeneous group (autologous group, OR = 2.71, 95% CI = 1.49-4.93; heterogeneous group, OR = 9.50, 95% CI = 2.98-30.27). DAPK promoter methylation was significantly correlated with alcohol status (OR = 1.85, 95% CI = 1.07-3.21). The results of this meta-analysis suggested that aberrant methylation of DAPK promoter was associated with HNSCC.


[Spatiotempaoral distribution patterns of photosynthetic photon flux density, air temperature, and relative air humidity in forest gap of Pinus koraiensis-dominated broadleaved mixed forest in Xi-ao Xing' an Mountains].
A continuous measurement of photosynthetic photon flux density (PPFD), air temperature, and relative air humidity was made in the forest gap in primary Pinus koraiensis-dominated broadleaved mixed forest in Xiao Xing' an Mountains to compare the spatiotemporal distribution patterns of the parameters. The diurnal maximum PPFD in the forest gap appeared between 11:00 and 13:00 on sunny and overcast days. On sunny days, the maximum PPFD during various time periods did not locate in fixed locations, the diurnal maximum PPFD occurred in the canopy edge of northern part of the gap; while on overcast days, it always occurred in the center of the gap. The mean monthly PPFD in the gap was the highest in June and the lowest in September, with the largest range observed in July. The maximum air temperature happened between 9:00 and 15:00 on sunny days, between 15:00 and 19:00 on overcast days, the locations were 8 m in the southern part of gap center both on sunny and overcast days. From 5:00 to 9:00, the air temperature at measured positions in the gap was higher on overcast days than on sunny days; but from 9:00 to 19:00, it was opposite. The mean monthly air temperature was the highest in June, and the lowest in September. The maximum relative humidity appeared between 5:00 and 9:00 on sunny and overcast days, and occurred in the canopy border of western part of the gap, with the relative air humidity on overcast days being always higher than that on sunny days. The mean monthly relative humidity was the highest in July, and the lowest in June. The heterogeneity of PPFD was higher on sunny days than on overcast days, but the heterogeneities of air temperature and relative humidity were not obvious. The maximum PPFD, air temperature, and relative humidity were not located in the same positions among different months during growing season. For mean monthly PPFD and air temperature, their variation gradient was higher in and around the center of gap; while for mean monthly relative humidity, it was higher in the edge of forest gap.


[Effect of induction delivery on maternal-neonatal outcomes in 41 gestational weeks primiparae].
To estimate the maternal-neonatal morbidity associated with induction deliveries compared with spontaneous deliveries in 41 gestational weeks uncomplicated primiparae. Three hundred and seventy-four uncomplicated primiparous deliveries at 41 gestational weeks at Peking Union Medical College Hospital from Sept 2002 to Apr 2007 were reviewed, including 225 women undergoing induced labor and 149 women undergoing spontaneous labor. The induction methods included drug induction (173), rupture of membrane induction (5) and combined drug with rupture of membrane induction (47). The maternal morbidity, delivery method, maternal cost on hospital stay and neonatal asphyxia associated with induction deliveries or spontaneous deliveries were retrospectively analyzed. (1) There was no maternal death. The caesarean section rate in the induction group (44.0%, 99/225) was significantly higher than that of spontaneous group (18.1%, 27/149; P<0.05). (2) No statistically significant difference (P>0.05) was observed between induction group and spontaneous group in the following puerperal complications: postpartum hemorrhage (2.7%, 6/225 and 1.3%, 2/149 respectively), puerperal morbidity (0.9%, 2/225 and 0.7%, 1/149 respectively), severe amniotic fluid contamination (11.6%, 26/225 and 13.4%, 20/149 respectively), wound infection (0.9%, 2/225 and 0.7%, 1/149 respectively) ,urinary retention(4.4%, 10/225 and 3.4%, 5/149 respectively), traumata (0.4%, 1/225 and 0 respectively) and neonatal asphyxia (1.3%, 3/225 and 2.0%, 3/149 respectively). (3) The average duration of first stage of labor in the induction group (413 min) was not significantly different from that of spontaneous group (461 min; P>0.05). In the induction group, more women had precipitate labors (P<0.05) and the average duration of the second stage of labor was shorter than that of spontaneous group (40 min and 48 min, P<0.05). (4) Spontaneous group had shorter maternal hospital stay [(5.7 +/- 1.9) days vs (6.9 +/- 2.7) days, P<0.05] and caesarean section after induction had the highest hospital expense (P<0.05). Induction delivery at 41 weeks of gestation increases the rates of caesarean section, precipitate labor, clinical workload and hospital costs. Induction delivery as a prevention method of over due labor needs to be further discussed. Uncomplicated pregnancies of 41 weeks should be intentionally monitored if continued surveillance is possible. They should wait for spontanous delivery, and decision of induction should be made based on its benefit to the case.


Comparison of laparoscopic vs. open surgery for rectal cancer.
This study was conducted to evaluate the safety of laparoscopic radical resection for rectal cancer. A total of 64 cases of rectal cancer patients undergoing radical surgery between January, 1998 and March, 2010 were collected. The patients were divided into the laparoscopic rectal surgery group (LS group, n=31) and the open surgery group (OS group, n=33). Operation time, postoperative recovery, complications and tumor-free survival rate were compared between the two groups. The inclusion criteria were as follows: Standard Karnofsky score >70 prior to surgery, definitive pathological diagnosis and complete clinical data. The exclusion criteria were concomitant tumors affecting survival. With the Dixon operation, the LS group had a longer operation time compared with the OS group (271.2±56.2 vs. 216.0±62.7 min, respectively; P=0.036), and an earlier time of oral intake (3.0±0.9 vs. 4.7±1.0 days, respectively; P=0.000). There were no significant differences between the LS and OS groups in terms of intraoperative blood loss, number of lymph nodes retrieved, duration of postoperative hyperthermia and hospitalization time (P>0.05). With the Miles operation, there were no obvious differences between the LS and OS groups regarding operation time, intraoperative blood loss, number of lymph nodes retrieved, time of oral intake, duration of postoperative hyperthermia and hospitalization time (P>0.05). Furthermore, there were no significant differences between the LS and OS groups with the Dixon or Miles operation in terms of 3-year tumor-free survival rate (P>0.05). Thus, laparoscopic surgery appears to be a safe and feasible option for the treatment of rectal cancer.


Receptors for immunoglobulin isotype on T and B lymphocytes from untreated patients with chronic lymphocytic leukaemia.
Peripheral blood lymphocytes from eighteen untreated patients with chronic lymphocytic leukaemia (CLL) were analysed for the proportions of T and B lymphocytes with receptors for IgM, IgG or IgA. T lymphocytes with Fc receptors for IgM (T mu cells) or IgA (T alpha) cells were found in proportions comparable to those found in the controls. However, the proportion of T lymphocytes with receptors for IgG (T gamma cells) was significantly increased (P < 0.001) resulting in an abnormally low ratio of T mu/T gamma (P < 0.001), when compared with normal controls. The proportion of B cells bearing Fc receptors for IgM, IgG or IgA was determined simultaneously. No significant differences were found between the normal controls and the patients with CLL. In vitro treatment of the purified T and B lymphocyte preparations with human leucocyte interferon, did not alter the proportions of the lymphocytes expressing Fc receptors for various immunoglobulin isotypes. The significance of these findings is discussed.


Thylacine 1 is expressed segmentally within the paraxial mesoderm of the Xenopus embryo and interacts with the Notch pathway.
The presomitic mesoderm of vertebrates undergoes a process of segmentation in which cell-cell interactions mediated by the Notch family of receptors and their associated ligands are involved. The vertebrate homologues of Drosophila &Dgr ; are expressed in a dynamic, segmental pattern within the presomitic mesoderm, and alterations in the function of these genes leads to a perturbed pattern of somite segmentation. In this study we have characterised Thylacine 1 which encodes a basic helix-loop-helix class transcription activator. Expression of Thylacine is restricted to the presomitic mesoderm, localising to the anterior half of several somitomeres in register with domains of X-Delta-2 expression. Ectopic expression of Thylacine in embryos causes segmentation defects similar to those seen in embryos in which Notch signalling is altered, and these embryos also show severe disruption in the expression patterns of the marker genes X-Delta-2 and X-ESR5 within the presomitic mesoderm. Finally, the expression of Thylacine is altered in embryos when Notch signalling is perturbed. These observations suggest strongly that Thylacine 1 has a role in the segmentation pathway of the Xenopus embryo, by interacting with the Notch signalling pathway.


A modern concept of cerebrospinal fluid diagnosis in oto- and rhinorrhea.
Three successive CSF investigations make it possible to identify even the smallest amount of cerebrospinal fluid (CSF) in cases of otorrhea and rhinorrhea: 1. Immunological identification of beta 2-transferrin. 2. Laboratory fluorescein identification. 3. Endoscopic fluorescein detection. As a screening procedure the beta 2-transferrin identification method is always used as the first step towards clarifying a suspect liquorrhea. In addition both fluorescein tests are used for the diagnosis depending on the result of the beta 2-transferrin identification and further measures. As a result of recent practical experience special attention is paid to the test analyses; the various possibilities of taking samples as well as mailing them. A newly developed diagnostic plan of procedure should (by using practical examples) underline the clinical significance. This study describes the most up-to-date level in CSF diagnosis and demonstrates that, when combined with a corresponding X-ray investigation, a much more exact range of indication for the surgical treatment of fractures of the base of the skull and CSF leaks is possible.


Childhood environmental harshness and unpredictability negatively predict eHealth literacy through fast life-history strategy.
eHealth literacy-the ability to obtain, understand, evaluate, and use health information from the Internet-is important to maintaining and improving personal health. Prior research found that people differ notably in the levels of eHealth literacy, and this study tests a theoretical account of some of those individual differences. Drawing on life history theory, we propose that low eHealth literacy is partly the outcome of people adopting a resource-allocation strategy emphasizing early and fast reproduction, namely, a fast life-history strategy. We conducted a cross-sectional survey study (N = 1,036) that measured Chinese adult respondents' eHealth literacy, childhood environmental harshness and unpredictability, and fast life-history strategy. Covariates included health-information seeking online, self-rated health, sex, age, education level, and monthly income. Supporting a life-history explanation of eHealth literacy, childhood environmental harshness and unpredictability negatively predicted eHealth literacy through fast life-history strategy and mainly the insight-planning-control dimension of it. Harshness, not unpredictability, also directly and negatively predicted eHealth literacy after fast life-history strategy was controlled for. Our findings suggest that the psychological mechanisms associated with human life-history strategies produce at least some of the individual differences in levels of eHealth literacy, including those related to neuroticism, socioeconomic status, self-rated health and social capital. Thus, a possible way to increase future generation's eHealth literacy and thereby their health is to reduce the harshness and unpredictability of the environment in which they grow up, thereby making them more likely to adopt a relatively slow life-history in their adulthood.


Mechanical approach to the neutrons spectra collimation and detection.
Neutrons spectra from most of known sources require being collimated for numerous applications; among them one is the Neutron Activation Analysis. High energy neutrons are collimated through a mechanical procedure as one of the most promising methods. The output energy of the neutron beam depends on the velocity of the rotating Polyethylene disks. The collimated neutrons are then measured by an innovative detection technique with high accuracy.


Optimization and deconvolution of lithium fluoride TLD-100 in diagnostic radiology.
Lithium fluoride (LiF) TLD-100 is one of the most commonly used thermoluminescent (TL) materials for the measurement of entrance surface dose (ESD) in diagnostic radiology. However, the minimum detectable dose (MDD) achieved, as derived from measurements of the random uncertainty present in the background signal, is usually quoted as being 50-100 microGy. A more appropriate definition of MDD for use in the clinical setting is the dose at which measurements exhibit a specified level of random uncertainty. This definition will give rise to a higher value for the MDD. An MDD of 50-100 microGy precludes accurate measurement of ESD in high tube potential (kVp) chest or neonatal radiography. Techniques described in the specialist literature for the reduction of the MDD of LiF were assessed both in the laboratory, and during a patient dose survey of high kVp chest radiography. Optimization of the pre-irradiation annealing and post-irradiation TL read heating cycles in terms of sensitivity and precision resulted in an MDD of 5/80 microGy (derived from background signal variation and 20% random uncertainty at 95% confidence limits, respectively). Deconvolution of the glowcurve was found to result in an MDD of approximately 10 microGy. Clinical measurements were contrasted with calculated values derived from ionization chamber measurements of tube output. The results support the hypothesis that glowcurve deconvolution permits the measurement of ESDs from low dose examinations using basic TL dosimetry equipment available to virtually all medical physics departments.


Eelectrocardiographic findings during bronchoscopy. Use of the Sanders' ventilating attachment.
The incidence of cardiac dysrhytmias was investigated in 50 patients during bronchoscopy performed under general anaesthesia using the bronchoscope with Sanders ventilating attachment. The results were compared with similar investigations utilising alternative methods of anesthesia. Sinus tachycardia occurred frequently, but was less severe than during previous investigation. The incidence of dysrhytmias 16% overall, was less than with earlier methods. Only 2 patients (4%) exhibited a dysrhythmia of any significance. It is concluded that use of the Sanders ventilating attachment represents a genuine advance during anaesthesia for bronchoscopy.


Delayed valproic acid toxicity: a retrospective case series.
We estimate how often an initially undetectable or nontoxic valproic acid (VPA) concentration misrepresents the potential toxicity of an acute VPA overdose. All patients followed up by the San Diego and San Francisco Divisions of the California Poison Control System between January 1997 and June 1999 with a documented serum VPA concentration of 120 microg/mL or greater at any time were identified through a search of poison center databases. Cases involving patients who had serial VPA concentrations and an initial VPA concentration that was unmeasurable or less than 100 microg/mL were also identified. The methods of decontamination, clinical outcomes, highest measured concentration, and times after ingestion of the initial and highest measured concentration of VPA were determined by means of chart review for these cases. Of the 173 patients identified with VPA concentrations of 120 microg/mL or greater, 21 (12.1%) had a detectable initial concentration not in the toxic range, and 5 (2.9%) had initial concentrations of less than the limit of detection. These 26 cases involved acute ingestion of VPA preparations. Four of these 26 patients were discharged to home or to a psychiatric facility after the initial results were obtained. Delayed toxicity might occur in patients after an acute overdose of enteric-coated VPA. Initial serum VPA concentrations might be misleading. Serial measurements documenting declining VPA concentrations or prolonged observation are recommended to determine whether a patient is medically safe for discharge or psychiatric placement.


Clinical utility of evolocumab in the management of hyperlipidemia: patient selection and follow-up.
Inhibition of PCSK9 is a novel therapeutic strategy aimed at reducing low-density-lipoprotein cholesterol (LDL-C) and cardiovascular risk. Evolocumab is a fully humanized monoclonal antibody that inhibits PCSK9, an enzyme that binds to LDL receptors and prevents them from recycling to the hepatocyte surface. Clinical trials have demonstrated 50%-70% reductions in LDL-C with evolocumab when used in combination with statin therapy. The recent FOURIER trial demonstrated that evolocumab further reduces cardiovascular events, but not mortality, in high-risk patients already receiving statin therapy. Furthermore, evolocumab did not affect neurocognitive function and was not associated with antidrug-antibody production in over 60,000 patient-years of drug exposure. Appropriate candidates for evolocumab primarily are individuals at high cardiovascular risk, including those with familial hypercholesterolemia and/or established cardiovascular disease, who are already on statin therapy. At this time, the use of evolocumab monotherapy seems appropriate only for individuals deemed statin-intolerant despite attempting several statins. Consideration must be given toward patient willingness to self-inject evolocumab and issues concerning third-party coverage, given the current costs of evolocumab.


Analysis of health care professionals' incident reports on medical devices in Croatia.
To assess the quantity and quality of incident reports on medical devices by health care professionals from 2012 to 2021 and evaluate the effect of reporting on manufacturers' post-market surveillance. Eighty-five incident reports were scored according to a self-developed evaluation system, and categorized as excellent, good, medium, qualified, and unqualified. The completeness of data in critical fields was assessed. For each report, the type and city of the reporter, and medical device risk class were extracted to calculate the frequency of report occurrence per risk class and outcomes for reportable reports. The number of reports received from health care professionals was low; the highest number of reports in a year was 17. The majority of reports were deemed as unqualified (61.18%) and only 4.71% as excellent. Still, 67.65% of incident reports importantly affected the manufacturer's post-market surveillance, either as added information that contributes to risk monitoring or directly triggering a field safety corrective action. The number of total reports and reports per year shows extensive underreporting in Croatia, and the quality of the provided reports is insufficient.


Controlling adsorption of semiflexible polymers on planar and curved substrates.
We study the adsorption of semiflexible polymers such as polyelectrolytes or DNA on planar and curved substrates, e.g., spheres or washboard substrates via short-range potentials using extensive Monte Carlo simulations, scaling arguments, and analytical transfer matrix techniques. We show that the adsorption threshold of stiff or semiflexible polymers on a planar substrate can be controlled by polymer stiffness: adsorption requires the highest potential strength if the persistence length of the polymer matches the range of the adsorption potential. On curved substrates, i.e., an adsorbing sphere or an adsorbing washboard surface, the adsorption can be additionally controlled by the curvature of the surface structure. The additional bending energy in the adsorbed state leads to an increase of the critical adsorption strength, which depends on the curvature radii of the substrate structure. For an adsorbing sphere, this gives rise to an optimal polymer stiffness for adsorption, i.e., a local minimum in the critical potential strength for adsorption, which can be controlled by curvature. For two- and three-dimensional washboard substrates, we identify the range of persistence lengths and the mechanisms for an effective control of the adsorption threshold by the substrate curvature.


Promising perspectives for ruminal protection of polyunsaturated fatty acids through polyphenol-oxidase-mediated crosslinking of interfacial protein in emulsions.
Previously, polyunsaturated fatty acids (PUFA) from linseed oil were effectively protected (>80%) against biohydrogenation through polyphenol-oxidase-mediated protein crosslinking of an emulsion, prepared with polyphenol oxidase (PPO) extract from potato tuber peelings. However, until now, emulsions of only 2 wt% oil have been successfully protected, which implies serious limitations both from a research perspective (e.g. in vivo trials) as well as for further upscaling toward practical applications. Therefore, the aim of this study was to increase the oil/PPO ratio. In the original protocol, the PPO extract served both an emulsifying function as well as a crosslinking function. Here, it was first evaluated whether alternative protein sources could replace the emulsifying function of the PPO extract, with addition of PPO extract and 4-methylcatechol (4MC) to induce crosslinking after emulsion preparation. This approach was then further used to evaluate protection of emulsions with higher oil content. Five candidate emulsifiers (soy glycinin, gelatin, whey protein isolate (WPI), bovine serum albumin and sodium caseinate) were used to prepare 10 wt% oil emulsions, which were diluted five times (w/w) with PPO extract (experiment 1). As a positive control, 2 wt% oil emulsions were prepared directly with PPO extract according to the original protocol. Further, emulsions of 2, 4, 6, 8 and 10 wt% oil were prepared, with 80 wt% PPO extract (experiment 2), or with 90, 80, 70, 60 and 50 wt% PPO extract, respectively (experiment 3) starting from WPI-stabilized emulsions. Enzymatic crosslinking was induced by 24-h incubation with 4MC. Ruminal protection efficiency was evaluated by 24-h in vitro batch simulation of the rumen metabolism. In experiment 1, protection efficiencies were equal or higher than the control (85.5% to 92.5% v. 81.3%). In both experiments 2 and 3, high protection efficiencies (>80%) were achieved, except for emulsions containing 10 wt% oil emulsions (<50% protection), which showed oiling-off after enzymatic crosslinking. This study demonstrated that alternative emulsifier proteins can be used in combination with PPO extract to protect emulsified PUFA-rich oils against ruminal biohydrogenation. By applying the new protocol, 6.5 times less PPO extract was required.


Direct identification and decongestion of Fermi resonances by control of pulse time ordering in two-dimensional IR spectroscopy.
We show that it is possible to both directly measure and directly calculate Fermi resonance couplings in benzene. The measurement method used was a particular form of two-dimensional infrared spectroscopy (2D-IR) known as doubly vibrationally enhanced four wave mixing. By using different pulse orderings, vibrational cross peaks could be measured either purely at the frequencies of the base vibrational states or split by the coupling energy. This capability is a feature currently unique to this particular form of 2D-IR and can be helpful in the decongestion of complex spectra. Five cross peaks of the ring breathing mode nu13 with a range of combination bands were observed spanning a region of 1500-4550 cm(-1). The coupling energy was measured for two dominant states of the nu13+nu16 Fermi resonance tetrad. Dephasing rates were measured in the time domain for nu13 and the two (nu13+nu16) Fermi resonance states. The electronic and mechanical vibrational anharmonic coefficients were calculated to second and third orders, respectively, giving information on relative intensities of the cross peaks and enabling the Fermi resonance states of the combination band nu13+nu16 at 3050-3100 cm(-1) to be calculated. The excellent agreement between calculated and measured spectral intensities and line shapes suggests that assignment of spectral features from ab initio calculations is both viable and practicable for this form of spectroscopy.


Potential Resilience to Post-traumatic Stress Disorder and Common Mental Disorders among Lay Health Workers Working on the Friendship Bench Programme in Zimbabwe.
The Friendship Bench is a successful task-shifting intervention for addressing common mental disorders in Zimbabwe. The intervention takes a cognitive behavioural therapy and problem-solving approach provided by lay health workers (LHWs). The LHWs live in the same environment as their clients and are thus exposed to the same traumas and stressors as are their clients. Little is known about the long-term psychological effects on LHWs involved in this type of work. A random sample of LHWs (n=182) was assessed using the Posttraumatic Stress Disorder Checklist (PCL-5) and the Shona Symptom Questionnaire (SSQ-14), both locally validated. The prevalence of PTSD and CMD was low among all surveyed LHWs. Eleven (6%) and 17 (11%) presented with probable PTSD and CMD, respectively. Despite living and working in the same settings as their clients, the Friendship Bench LHWs show good mental health outcomes.


Rapid Pressureless Sintering of Glasses.
Silica glasses have wide applications in industrial fields due to their extraordinary properties, such as high transparency, low thermal expansion coefficient, and high hardness. However, current methods of fabricating silica glass generally require long thermal treatment time (up to hours) and complex setups, leading to high cost and slow manufacturing speed. Herein, to obtain high-quality glasses using a facile and rapid method, an ultrafast high-temperature sintering (UHS) technique is reported that requires no additional pressure. Using UHS, silica precursors can be densified in seconds due to the large heating rate (up to 102 K s-1 ) of closely placed carbon heaters. The typical sintering time is as short as ≈10 s, ≈1-3 orders of magnitude faster than other methods. The sintered glasses exhibit relative densities of > 98% and high visible transmittances of ≈90%. The powder-based sintering process also allows rapid doping of metal ions to fabricate colored glasses. The UHS is further extended to sinter other functional glasses such as indium tin oxide (ITO)-doped silica glass, and other transparent ceramics such as Gd-doped yttrium aluminum garnet. This study demonstrates an UHS proof-of-concept for the rapid fabrication of high-quality glass and opens an avenue toward rapid discovery of transparent materials.


Feline Niemann-Pick Disease With a Novel Mutation of SMPD1 Gene.
A 4-month-old female mixed-breed cat showed gait disturbance and eventual dysstasia with intention tremor and died at 14 months of age. Postmortem histological analysis revealed degeneration of neuronal cells, alveolar epithelial cells, hepatocytes, and renal tubular epithelial cells. Infiltration of macrophages was observed in the nervous system and visceral organs. The cytoplasm of neuronal cells was filled with Luxol fast blue (LFB)-negative and periodic acid-Schiff (PAS)-negative granules, and the cytoplasm of macrophages was LFB-positive and PAS-negative. Ultrastructurally, concentric deposits were observed in the brain and visceral organs. Genetic and biochemical analysis revealed a nonsense mutation (c.1017G>A) in the SMPD1 gene, a decrease of SMPD1 mRNA expression, and reduced acid sphingomyelinase immunoreactivity. Therefore, this cat was diagnosed as having Niemann-Pick disease with a mutation in the SMPD1 gene, a syndrome analogous to human Niemann-Pick disease type A.


Alcohol-induced tolerance and physical dependence in mice with ethanol insensitive alpha1 GABA A receptors.
Although many people consume alcohol (ethanol), it remains unknown why some become addicted. Elucidating the molecular mechanisms of tolerance and physical dependence (withdrawal) may provide insight into alcohol addiction. While the exact molecular mechanisms of ethanol action are unclear, gamma-aminobutyric acid type A receptors (GABA(A)-Rs) have been extensively implicated in ethanol action. The alpha1 GABA(A)-R subunit is associated with tolerance and physical dependence, but its exact role remains unknown. In this report, we tested the hypothesis that alpha1-GABA(A)-Rs mediate in part these effects of ethanol. Ethanol-induced behavioral responses related to tolerance and physical dependence were investigated in knockin (KI) mice that have ethanol-insensitive alpha1 GABA(A)-Rs and wildtype (WT) controls. Acute functional tolerance (AFT) was assessed using the stationary dowel and loss of righting reflex (LORR) assays. Chronic tolerance was assessed on the LORR, fixed speed rotarod, hypothermia, and radiant tail-flick assays following 10 consecutive days of ethanol exposure. Withdrawal-related hyperexcitability was assessed by handling-induced convulsions following 3 cycles of ethanol vapor exposure/withdrawal. Immunoblots were used to assess alpha1 protein levels. Compared with controls, KI mice displayed decreased AFT and chronic tolerance to ethanol-induced motor ataxia, and also displayed heightened ethanol-withdrawal hyperexcitability. No differences between WT and KI mice were seen in other ethanol-induced behavioral measures. Following chronic exposure to ethanol, control mice displayed reductions in alpha1 protein levels, but KIs did not. We conclude that alpha1-GABA(A)-Rs play a role in tolerance to ethanol-induced motor ataxia and withdrawal-related hyperexcitability. However, other aspects of behavioral tolerance and physical dependence do not rely on alpha1-containing GABA(A)-Rs.


Unilateral lymphadenopathy due to the use of granulocyte colony stimulating factor.
A 36-year-old woman was admitted to our hospital after modified radical mastectomy operation. Adjuvant chemotherapy was administered using TAC regimen. Severe neutropenia occurred after chemotherapy. Granulocyte colony stimulating factor (G-CSF) was given to treat neutropenia. On the second day of G-CSF use, the patient complained of swelling of her neck on the left side, which subsided spontaneously after discontinuation of G-CSF medication. However, the same symptom recurred following G-CSF use on the second cycle of chemotherapy. B-mode ultrasound showed swollen lymph nodes and biopsy revealed no evidence of metastasis. Therefore, the unilateral lymphadenopathy is considered to be the side effect of G-CSF, which is very rare.


Diffusion MR: A New Diagnostic Tool for Elastofibroma Dorsi.
Elastofibroma dorsi is a benign lesion commonly presents as a palpable enlarging mass at the inferior pole of the scapula. Clinical presentation and radiological characteristics are often enough to suggest an accurate diagnosis. Increased awareness of the characteristic appearance and location of these benign lesions will increase radiologic diagnosis and decrease the need for biopsy. Ten patients were admitted with a complaint of asymptomatic or painful subcutaneous masses localized at subscapulary region. Thorax computed tomography, magnetic resonance imaging (MRI) and a new feasible technique in differential diagnosis with malignancy and probable diagnosis of elastofibroma dorsi and diffusion-weighted MRI were used for diagnosis. Surgery was applied to all patients, frozen-section biopsies of the lesions at the preoperative period, and final pathologies were all benign. Totally resection of whole lesions as en-bloc excision without any rest was performed at all patients. Postoperative and follow-up periods were uneventful. Diffusion MRI can play an important role in the future and save the patients, especially medically poor ones, from the potential risks of surgery. Necessary further examinations for probable bilaterally lesions will save the patient from the risk of a second operation.


Nest relocation and excavation in the Florida harvester ant, Pogonomyrmex badius.
The Florida harvester ant (Pogonomyrmex badius) excavates deep nests in the sandy soils of the Gulf and Atlantic coastal plains. Nest relocations of over 400 colonies in a north Florida coastal plains pine forest were tracked and mapped from 2010 to 2013. Individual colonies varied from one move in two years to four times a year, averaging about one per year. Almost all moves occurred between May and November peaking in July when more than 1% of the colonies moved per day. Move directions were random, and averaged 4 m, with few moves exceeding 10 m. Distance moved was not related to colony size. Over multiple moves, paths were random walks around the original nest location. Relocation is probably intrinsic to the life history of this species, and the causes of relocation remain obscure--the architecture of old and new nests was very similar, and neither the forest canopy nor the density or size of neighbors was correlated with relocation. Monitoring entire relocations (n = 20) showed that they were usually completed in 4 to 6 days. Moves were diurnal, peaking in the mornings and afternoons dipping during mid-day, and ceasing before sundown. Workers excavated the new nest continuously during the daytime throughout the move and beyond. A minority of workers carried seeds, charcoal and brood, with seeds being by far the most common burden. The proportion of burdened workers increased throughout the move. Measured from year to year, small colonies gained size and large ones lost it. Colonies moving more than once in two years lost more size than those moving less often, suggesting that moving may bear a fitness cost. Colony relocation is a dramatic and consistent feature of the life history of the Florida harvester ant, inviting inquiry into its proximal and ultimate causes.


Vocalizations and behavior of two commercial stocks of chickens.
Vocalization and behavior comparisons were made between two commercial egg-laying stocks maintained under high intensity, battery-cage housing. Data obtained at approximately 35 weeks of age from both stocks in the same house showed significantly more pushes and steps in Stock B than in Stock A flocks. Also, the frequency range of vocalizations emitted was greater for Stock B than for Stock A pullets. This difference was attributed to an increased number of disturbance calls and shriek -like sounds called " baaks ".