Pseudomonas aeruginosa nfuA: Gene regulation and its physiological roles in sustaining growth under stress and anaerobic conditions and maintaining bacterial virulence.
The role of the nfuA gene encoding an iron-sulfur ([Fe-S]) cluster-delivery protein in the pathogenic bacterium Pseudomonas aeruginosa was investigated. The analysis of nfuA expression under various stress conditions showed that superoxide generators, a thiol-depleting agent and CuCl2 highly induced nfuA expression. The expression of nfuA was regulated by a global [2Fe-2S] cluster containing the transcription regulator IscR. Increased expression of nfuA in the ΔiscR mutant under uninduced conditions suggests that IscR acts as a transcriptional repressor. In vitro experiments revealed that IscR directly bound to a sequence homologous to the Escherichia coli Type-I IscR-binding motifs on a putative nfuA promoter that overlapped the -35 element. Binding of IscR prevented RNA polymerase from binding to the nfuA promoter, leading to repression of the nfuA transcription. Physiologically, deletion of nfuA reduced the bacterial ability to cope with oxidative stress, iron deprivation conditions and attenuated virulence in the Caenorhabditis elegans infection model. Site-directed mutagenesis analysis revealed that the conserved CXXC motif of the Nfu-type scaffold protein domain at the N-terminus was required for the NfuA functions in conferring the stress resistance phenotype. Furthermore, anaerobic growth of the ΔnfuA mutant in the presence of nitrate was drastically retarded. This phenotype was associated with a reduction in the [Fe-S] cluster containing nitrate reductase enzyme activity. However, NfuA was not required for the maturation of [Fe-S]-containing proteins such as aconitase, succinate dehydrogenase, SoxR and IscR. Taken together, our results indicate that NfuA functions in [Fe-S] cluster delivery to selected target proteins that link to many physiological processes such as anaerobic growth, bacterial virulence and stress responses in P. aeruginosa.


[Determination of uranium in human tissues by the fission track method].
Several Japanese human soft tissues were analyzed for uranium by the fission track method. The tissues which were examined included lung, liver, kidney, spleen and muscle. The average concentration of uranium in the lung was estimated to be 1.86 ppb-wet and was the highest of all the tissues analysed. The results of the present work are consistent with the reported values for U.K. and U.S.A. human tissues.


Accuracy of Total Hip Arthroplasty Templating Using Set Calibration Magnifications.
Background Templating for total hip arthroplasty has been adopted over recent decades as a reliable and accurate method for pre-operative planning. The use of calibration markers for this process provides a recognised benefit at the expense of cost, availability and error. Many surgeons use a set magnification of 118% to account for calibration errors when templating total hip arthroplasty. This study aims to assess the accuracy of templating with standardised magnifications and assess the effect of BMI on templating accuracy. Materials and methods A retrospective analysis was performed using a single-surgeon series of 119 consecutive total hip arthroplasties. Anteroposterior radiographs were taken pre- or post-operatively without calibration hardware. Pre-operatively, the total hip arthroplasty was templated on TraumaCad (BrainLab Inc, Westchester, IL) using either 118% or 119% calibration magnification. Post-operative magnification was calibrated using the known femoral head diameter. Templated and implanted prostheses were compared for size. Results At 118%, 61.1% of cups matched those templated with 96.3% of cups within two sizes. At 119%, 52.5% of cups used matched their templates with 100% within two sizes. There was no significant difference between 118% and 119% cup size prediction (p=0.49). A trend was noticed in increasing magnification error with increasing BMI. However, BMI had no significant effect on the accuracy of templating cup size within two cup sizes (p=0.58). Conclusion. Templating acetabular cups using a set magnification of 118% or 119% yields accurate results and provides a reliable method to template without calibration equipment. Whilst BMI can affect magnification error, this has no significant effect on the accuracy of implanted cups and stems within two sizes.


The Gerbode defect or left ventricular to right atrial shunt assessed by transthoracic 3D echocardiography.
We report the case a 14-year-old male presented with a perimembranous ventricular septal defect. 2D echocardiography showed both left ventricular to right ventricular and atrial shunt. Left and right ventricular 3D "en face" views of the defect were obtained. 3D echocardiography delineated the morphologic nature of the ventricular septal defect, its shape, and the direction in which the defect extends into the ventricular septum. Other anatomic structures such as the tricuspid valve leaflet, the right ventricular outflow tract, and the aortic valve can be displayed in their realistic spatial distribution. These findings have clinical implications when surgical repair is planned.


[A man's role in recurrent miscarriage in a spouse].
In a review article based on the published literature and their own research, the authors examine the role of a man in recurrent miscarriage and reproductive losses in a spouse. Detailed description is presented of the negative impact of elevated levels of sperm DNA fragmentation on the course of pregnancy, especially during the first trimester, on the occurrence of recurrent miscarriage or missed abortion, on the effectiveness of assisted reproductive technology (ART) programs. The etiology and pathogenesis of damage to sperm DNA are described. Outlined are positive effects of correcting adverse lifestyle factors, the role of varicocelectomy and antioxidant therapy, and advances in ART. The review specifies the role of different male karyotype abnormalities (translocations) in the pathogenesis of pregnancy loss. The implications of urologic surgery, preimplantation genetic diagnosis in solving this problem are discussed. New treatment strategies using correction of male disorders for couples with recurrent miscarriage are offered.


Tumors of the liver.
This update on childhood liver tumors has been devoted to recent developments in the biology and treatment of the more frequent and clinically important varieties. The controversial aspects of clinicopathologic correlations and treatment of hepatoblastomas have been addressed.


Investigating the cytotoxic and apoptotic effects of sunitinib upon K-562 chronic myelogenous leukemia cell line and assessment of gene profiling.
Tyrosine kinase inhibitors (TKIs) which efficiently inhibit BCR-ABL are highly effective for clinical treatment of chronic myeloid leukemia (CML), but development of resistance to TKIs is a big challenge to treatment. Sunitinib is a multitargeted TKI targeting vascular endothelial growth factor receptor and is defined a safe and effective candidate target, but its effect on other signaling pathways is unknown. To investigate the cytotoxic and apoptotic effect of sunitinib in CML cell model K-562 on JAK-STAT signaling pathway components, suppressor genes and oncogenes, hematopoiesis-related genes, cell cycle and VEGF pathway components, and mRNA level expression changes was aimed. Sunitinib's effective dose cytotoxic IC50 was determined by trypan blue and WST-1 cell proliferation assay tests. Expression levels of target genes were determined by quantitative reverse transcriptase polymerase chain reaction simultaneously after sunitinib application. Protein expression analysis was determined by "WesternBreeze Chromogenic Kit-Anti-Rabbit" based on the principles of the application kit by Western blot analysis. Assessing the cytotoxicity of K-562 cells following sunitinib treatment revealed that sunitinib decreased cell proliferation in a time- and dose-dependent manner. According to the sunitinib inhibition curve, IC50 dose was calculated as 3.5 μM at 48th h for K-562 cells and apoptosis assays pointed that sunitinib induces apoptotic cell death of leukemic cells at moderate levels. Our study supports that sunitinib might be used as a novel therapeutic target to trigger apoptosis in CML cells which in turn might accelerate therapeutic response in regard to inhibiting oncogenes and enhancing tumor suppressors in cooperation with cell cycle regulatory genes.


RNA sequencing analyses in infants patients with coarctation of the aorta.
Coarctation of the aorta (CoA) is a serious innate heart disease. Although surgery results are generally good, some complications such as recoarctation and aortic aneurysm or persistent hypertension were serious threats to patient's health. To better understand the pathology of CoA and its underlying molecular mechanism is particularly important for early diagnosis and preventing the occurrence of its complications. However, the mechanisms of CoA remain unclear, especially for infants. RNA sequencing (RNA-seq) was used to identify the differentially expressed genes (DEGs) in vascular tissues of 12 patients with CoA and 10 normal participants form 3- to 34-month-old infants. The characteristic of DEGs were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunochemical staining (IHC) in vessels of patients with CoA and normal infants. A total of 2491 DEGs with the false discovery rate less than 0.05(> 1.5-fold, P < 0.05 change) were identified, including 443 upregulated genes and 2048 downregulated genes. The Gene Ontology enrichment analysis showed that 26 out of the 2491 DEGs identified were associated with cardiovascular diseases. These 26 genes were mainly associated with extracellular matrix (ECM) and smooth muscle cells (SMCs) differentiation. Three DEGs, that is, CNN1 (calponin), α-actinin1 and myosin heavy chain 11 MYH11, were validated using qRT-PCR and Western blot analysis. In addition, immunochemical staining showed that calponin and MYH11 were highly expressed on the surface and in the deep layers of the thickened intima respectively. This study comprehensively characterized the CoA transcriptome. Migration of extracellular matrix (ECM) and smooth muscle cells (SMCs) to the subendothelial space may be the major characteristic of CoA in infants.


Kinetics of the reaction of renin with nine synthetic peptide substrates.
A number of peptides have been synthesized which represent portions of the tetradecapeptide renin substrate molecule, and which contain the hydrolyzable leu-leu bond. An automatic chemical method for determination of the velocity of the reaction of renin with these compounds was developed. Application of the method at several levels of substrate concentration permitted construction of Lineweaver-Burk plots, and calculation of Michaelis constants (K(m)) and maximal velocities (V(max)). The results show that the maximum affinity of the enzyme (lowest K(m)) for substrate is achieved only with the full tetradecapeptide molecule (asp(1)-arg(2)-val(3)-tyr(4)-ileu(5)-his(6)-pro(7)-phe(8)-his(9)-leu(10)-leu(11)-val(12)-tyr(13)-ser(14)). Removal of asp(1) and arg(2) from the N-terminal increases the K(m) eight-fold. Further, moderate increase in K(m) occurs when the next amino acids, val(3), tyr(4) and ileu(5), are removed. The further removal of his(6) results in a marked reduction in the V(max). Removal of ser(14) from the C-terminal of the nonapeptide his(6)-pro(7)-phe(8)-his(9)-leu(10)-leu(11)-val(12)-tyr(13)-ser(14) does not greatly affect the K(m) nor the V(max). Further removal of tyr(13) from this compound results in complete loss of substrate activity. It is suggested that the compounds his(6)-pro(7)-phe(8)-his(9)-leu(10)-leu(11)-val(12)-tyr(13)-ser(14) or his(6)-pro(7)-phe(8)-his(9)-leu(10)-leu(11)-val(12)-tyr(13) might be used as substrates for the chemical assay and standardization of renin.


Psychological Symptoms in Obesity and Related Factors.
This study aimed to investigate the relationship between levels of depression and anxiety symptoms and quality of life, self-esteem in obesity. Fifty-two subjects whose Body Mass Index (BMI) is 30 kg/m2 and over and 43 control whose BMI is normal were recruited for this study. The socio demographic data form, Hamilton Depression Rating Scale (HAM-D17), Hamilton Anxiety Rating Scale (HAM-A), Quality of Life Scale Short Form (WHOQOL-Brief-TR), Coopersmith Self Esteem Scale (CSES), The Eating Attitudes (EAT), were applied to the participants. In this study most of the patients are women, married, postgraduated and live in urban areas. It was determined to scores of HAM-D17, HAM-A and EAT are higher in obese group than control group; WHOQOL-Brief-TR physical field scores was lower in obese group than control group. CSES scores wasn't difference between obese and control group. In obese group, there was HAM-D17 and HAM-A scores a negative correlation between quality of life physical field score, negative correlation between CSES score, positive correlation between EAT scale score. There is no correlation between scores of HAM-D17 and HAM-A and BMI. Our results suggest that depressive and anxiety levels are high in induvidual with obesity. They have problems in eating attitudes and their quality of life especially physical field is poor. The psychological symptoms have negative effects on the quality of life, self-esteem, and eating attitudes. Our results suggest that psychiatric support to improving positive effects quality of life and self-esteem in individual with obesity.


Cytokine and Chemokine Profile in Patients with Multiple Myeloma Treated with Bortezomib.
The aim of the study was to determine the levels of selected cytokines and chemokines in the serum of multiple myeloma (MM) patients treated with bortezomib-based regimens. A total of 71 MM patients were examined: 41 with primary refractory disease (17) or early relapse (28), and 30 who were bortezomib sensitive with no progression for at least six months. Patients who demonstrated CR or PR after bortezomib-based therapies longer than six months after treatment discontinuation were designated bortezomib sensitive. Serum cytokine levels were assayed with Bio-Rad Bio-Plex Pro Human Cytokine 27-Plex Assay on the MAGPIX Multiplex Reader and the Bio-Plex® 200 System (Bio-Rad). Higher levels of MIP-1α and lower levels of MIP-1β and IL-9 were associated with better responses to bortezomib-based treatment, and higher levels of IL-1ra and IL-8 were associated with bone involvement. MCP-1 was elevated in patients with hemoglobin < 10 g/dl compared to those without anemia. The levels of IL-8, MIP-1α, and TNF-α were significantly higher in patients with renal insufficiency. Only MIP-1α was elevated in patients with hypercalcemia compared to patients with normal calcium levels. In conclusion, distinct cytokines are involved in the pathogenesis of MM and may play a prominent role in the prediction of treatment response. However, a single measurement of serum cytokines should be interpreted with caution and further studies are needed.


Induction of chromosome breaks and sister chromatid exchanges in patients with Hodgkin's disease by two combination chemotherapy regimens of different leukemogenic potential.
The success of various combination chemotherapies in the treatment of cancer is compromised by their potential to cause secondary leukemia. Previous studies have suggested that the alkylating agents used in some regimens are the major etiological factor in these leukemias. In this study, we compared the abilities of two standard regimens used in the treatment of Hodgkin's disease to cause chromosome breaks and sister chromatid exchanges, the two most common types of chromosomal damage induced by alkylating agents. These regimens are MOPP [mechlorethamine-vincristine (Oncovin)-procarbazine-prednisone] and CVPP-ABDIC [cyclophosphamide-vinblastine-procarbazine-prednisone-doxorubicin (Adriamycin)-bleomycin-dacarbazine-1-(2-chloroethyl)-3-cyclohexyl-1- nitrosourea]. Our study demonstrated that (a) levels of spontaneous chromosome breaks and sister chromatid exchanges were low in untreated Hodgkin's disease patients; (b) significantly higher levels of these damages were induced in patients receiving eight cycles of CVPP-ABDIC, as compared with their pretreatment levels; (c) significantly elevated levels of sister chromatid exchanges, but not chromosome breaks, were induced in patients receiving two cycles of MOPP; and (d) no differences in the effect of these two regimens on cell cycle kinetics were observed. Although MOPP therapy has been reported to have higher rates of secondary leukemia than CVPP-ABDIC, our studies show that eight cycles of CVPP-ABDIC are more potent than two cycles of MOPP in inducing chromosome damage in patients during treatments.


Effect of beta-blockade on the interpretation of the exercise ECG: ST level versus delta ST/HR index.
The diagnostic value of exercise-induced ST segment depression is considered to be decreased in patients receiving beta-blockers. One approach to improving predictive accuracy has been to use the ratio of maximal change in exercise-induced ST segment depression to the corresponding maximal change in heart rate (delta ST/HR index). The present study compared these two ECG methods. The records of exercise tests performed on 3047 male veterans were screened to exclude patients with prior revascularization procedures or myocardial infarction, those receiving digoxin, and those with certain resting ECG abnormalities; the use of beta-blocker drugs at the time of testing was also noted. All exercise tests were sign/symptom limited. Significant angiographic coronary disease was defined as greater than or equal to 75% reduction in luminal diameter of at least one coronary artery. Disease severity was evaluated in an expanded study group that included patients with prior myocardial infarction. Mean maximal heart rate was 21 beats.min-1 lower for those receiving beta-blockers (p less than 0.05), but there was no difference in mean metabolic equivalent (MET) level achieved. The diagnostic accuracy of an abnormal test result for determination of the presence or absence of coronary artery disease was not significantly different in the subgroup taking beta-blockers versus the subgroup not taking beta-blockers (N = 200), and use of the delta ST/HR index did not improve test performance. For discrimination of severe disease, test accuracy was also unaffected by beta-blockers and was not improved by the delta ST/HR index (N = 454).(ABSTRACT TRUNCATED AT 250 WORDS)


The Burden of Cystoscopic Bladder Cancer Surveillance: Anxiety, Discomfort, and Patient Preferences for Decision Making.
To examine discomfort, anxiety, and preferences for decision making in patients undergoing surveillance cystoscopy for non-muscle-invasive bladder cancer (NMIBC). Veterans with a prior diagnosis of NMIBC completed validated survey instruments assessing procedural discomfort, worry, and satisfaction, and were invited to participate in semistructured focus groups about their experience and desire to be involved in surveillance decision making. Focus group transcripts were analyzed qualitatively, using (1) systematic iterative coding, (2) triangulation involving multiple perspectives from urologists and an implementation scientist, and (3) searching and accounting for disconfirming evidence. Twelve patients participated in 3 focus groups. Median number of lifetime cystoscopy procedures was 6.5 (interquartile range 4-10). Based on survey responses, two-thirds of participants (64%) experienced some degree of procedural discomfort or worry, and all participants reported improvement in at least 2 dimensions of overall well-being following cystoscopy. Qualitative analysis of the focus groups indicated that participants experience preprocedural anxiety and worry about their disease. Although many participants did not perceive themselves as having a defined role in decision making surrounding their surveillance care, their preferences to be involved in decision making varied widely, ranging from acceptance of the physician's recommendation, to uncertainty, to dissatisfaction with not being involved more in determining the intensity of surveillance care. Many patients with NMIBC experience discomfort, anxiety, and worry related to disease progression and not only cystoscopy. Although some patients are content to defer surveillance decisions to their physicians, others prefer to be more involved. Future work should focus on defining patient-centered approaches to surveillance decision making.


Differential Proteomics for Distinguishing Ischemic Stroke from Controls: a Pilot Study of the SpecTRA Project.
A diagnostic blood test for stroke is desirable but will likely require multiple proteins rather than a single "troponin." Validating large protein panels requires large patient numbers. Mass spectrometry (MS) is a cost-effective tool for this task. We compared differences in the abundance of 147 protein markers to distinguish 20 acute cerebrovascular syndrome (ACVS) patients who presented to the Emergency Department of one urban hospital within < 24 h from onset) and from 20 control patients who were enrolled via an outpatient neurology clinic. We targeted proteins from the stroke literature plus cardiovascular markers previously studied in our lab. One hundred forty-one proteins were quantified using MS, 8 were quantified using antibody protein enrichment with MS, and 32 were measured using ELISA, with some proteins measured by multiple techniques. Thirty proteins (4 by ELISA and 26 by the MS techniques) were differentially abundant between mimic and stroke after adjusting for age in robust regression analyses (FDR < 0.20). A logistic regression model using the first two principal components of the proteins significantly improved discrimination between strokes and controls compared to a model based on age alone (p < 0.001, cross-validated AUC 0.93 vs. 0.78). Significant proteins included markers of inflammation (47%), coagulation (40%), atrial fibrillation (7%), neurovascular unit injury (3%), and other (3%). These results suggest the potential value of plasma proteins as biomarkers for ACVS diagnosis and the role of plasma-based MS in this area.


Ramadan Perspective Epidemiology and Education in Diabetes (RAPEED) Study.
Ramadan fasting is one of the five pillars of Islam and is obligatory for all healthy adult and adolescent Muslims. A significant number of patients with diabetes observe fasting during Ramadan. The objectives of this Ramadan Perspective Epidemiology and Education in Diabetes (RAPEED) study were to find out the current knowledge, attitude, and practices about Ramadan fasting among people with diabetes in Bangladesh. This retrospective cross-sectional study recruited 648 subjects with diabetes mellitus attending the Endocrinology outpatient department of a tertiary level hospital of Bangladesh within two months of the end of Ramadan in 2016. Socio-demographic data, data related to diabetes treatment, complications and co-morbidities; changes in lifestyle and diabetes treatment during Ramadan and frequency of hypoglycemia were collected from all. The mean age of the study population was 50.32±12.1 years and the majority (98.6%) had type 2 diabetes and 63.9% were overweight or obese. The majority (89.35%) of the patients fasted in Ramadan and among them, more than half of the fasters received physicians' advice for Ramadan fasting (60.6%) and changed diabetes medication (69.90%) during Ramadan. Although the amount of total food consumption was unchanged in more than one half (60.6%) of the fasters, majority of them reduced sugar-sweet intake (75.5%), increased fluid drinking (75.8%) and decreased physical activity (75.8%) during the month. A large portion (37.48%) of them did not check blood glucose and more than half (54.06%) of fasters failed to visit their physicians during Ramadan. Among them 14.85% experienced mild to moderate episodes of hypoglycemia and none had severe hypoglycemia and the most (61.6%) episodes of hypoglycemia occurred in the late evening. Hypoglycemic episodes were more frequent among insulin users, patients who had received fasting advice from physicians and in those who had adjusted diabetes drugs before Ramadan fasting. Safe Ramadan fasting is a great challenge not only for the patients but also the consulting physicians. Current study reflects the necessity of both physicians' expertise and patients' awareness for safe fasting.


State-space modeling of the dynamics of temporal plant cover using visually determined class data.
A lot of vegetation-related data have been collected as an ordered plant cover class that can be determined visually. However, they are difficult to analyze numerically as they are in an ordinal scale and have uncertainty in their classification. Here, I constructed a state-space model to estimate unobserved plant cover proportions (ranging from zero to one) from such cover class data. The model assumed that the data were measured longitudinally, so that the autocorrelations in the time-series could be utilized to estimate the unobserved cover proportion. The model also assumed that the quadrats where the data were collected were arranged sequentially, so that the spatial autocorrelations also could be utilized to estimate the proportion. Assuming a beta distribution as the probability distribution of the cover proportion, the model was implemented with a regularized incomplete beta function, which is the cumulative density function of the beta distribution. A simulated dataset and real datasets, with one-dimensional spatial structure and longitudinal survey, were fit to the model, and the parameters were estimated using the Markov chain Monte Carlo method. Then, the validity was examined using posterior predictive checks. As a result of the fitting, the Markov chain successfully converged to the stationary distribution, and the posterior predictive checks did not show large discrepancies. For the simulated dataset, the estimated values were close to the values used for the data generation. The estimated values for the real datasets also seemed to be reasonable. These results suggest that the proposed state-space model was able to successfully estimate the unobserved cover proportion. The present model is applicable to similar types of plant cover class data, and has the possibility to be expanded, for example, to incorporate a two-dimensional spatial structure and/or zero-inflation.


Shaping behavior in voice therapy.
This study demonstrates the process of learning and shaping of behavior which occurs during a program of therapy for individuals with hyperfunctional hoarse voice quality. First a therapy program delineating the techniques and criteria to be used was written. The program was presented during 16 individual half-hour sessions over an eight-week period to three clients known to have vocal nodules. The clients' responses were charted at various points from audiotape recordings of each therapy session using a modification of the Boone-Prescott analysis system, to obtain data to demonstrate the learning processes. It was concluded that: (1) the client's behaviors in this vocal rehabilitation program reflected a learning process; (2) facilitating techniques were used to modify or shape behavior through successive approximations to the terminal goal; (3) self-evaluation is an important factor needed to bring about successful changes in behavior; (4) analysis of client's behaviors in relation to the learning process can aid in evaluating the effectiveness of the facilitating techniques; and (5) from such evaluation intraclient and interclient program changes are derived hopefully resulting in a greater success rate and maximum benefits from time spent in therapy.


The effect of CXCL1 on human fetal oligodendrocyte progenitor cells.
Chemokine CXCL1 is abundantly present in proliferative zones during brain development and in regions of remyelination, suggesting that it influences development of oligodendrocyte progenitors (OPC) in these regions. We studied in vitro the effects and possible mechanisms by which CXCL1 acts on human fetal OPC. In organotypic slice cultures of human fetal cortical ventricular/subventricular (VZ/SVZ) zones, blocking of CXCL1 signaling reduced significantly the proliferation of OPC. Moreover, exogenously added CXCL1 induced increase of OPC proliferation. Treatments of purified OPC cultures and cell depletion experiments demonstrated that this effect of CXCL1 was mainly indirect, mediated through astrocytes. We identified that CXCL1 acted through the extracellular signal regulated kinase (ERK1/2) pathway, activated primarily in astrocytes. In vitro, astrocytes stimulated with CXCL1 released several cytokines, but only the release of interleukin-6 (IL-6) was completely blocked by inhibition of ERK1/2 pathway. When released IL-6 was neutralized in slices, a decrease in OPC proliferation was demonstrated, while addition of IL-6 was able to return OPC proliferation in astrocyte-depleted slices to the control level. These results suggest that in the human fetal brain CXCL1 promotes proliferation of early OPC, acting in part through an ERK1/2-dependent pathway and release of IL-6 from astrocytes.


Electroencephalographic and autonomic predictors of relapse in alcohol-dependent patients.
Measures of electroencephalographic and autonomic activity were recorded from 17 alcohol-dependent patients (after 7-10 and 14-17 days of abstinence) and 14 age-matched non-drug-dependent controls (after comparable intervals). The alcohol-dependent group was divided into subgroups of abstinence-prone or relapse-prone patients, based on their 3-month posttreatment outcome. Data analyses revealed that relapse-prone patients evidenced more electroencephalographic beta-activity at the vertex lead, and a larger amplitude carotid pulse than abstinence-prone patients and controls. The implications of these preliminary findings for relapse prediction and typological development are discussed.


Women's experience of using the Mooncup.
The Mooncup is a menstrual cup that is an alternative to conventional sanitary protection. We aimed to determine whether the Mooncup is tolerated by asking 53 healthy female volunteers to record the frequency of changing sanitary protection and leakage over three menstrual cycles with regular sanitary protection and three cycles with the Mooncup. We measured the frequency of leakage and changing the Mooncup along with acceptability of the Mooncup. A total of 126 baseline cycles and 71 cycles with the Mooncup were recorded. The Mooncup leaked 0.5 times less frequently and required to be changed 2.8 times less frequently, on average, during one menstrual period than regular sanitary protection. Of the participants, 55% will carry on using the Mooncup for sanitary protection. Thus, we have concluded that, the Mooncup is acceptable for most women but could not be used for the objective measurement of menstrual blood loss because of the leakage that did occur.


Indium(III) chloride catalyzed highly diastereoselective domino synthesis of indenodithiepines and indenodithiocines.
An atom-economical diastereoselective synthesis of indenodithiepines and indenodithiocines has been developed via a domino reaction of propargylic alcohols and dithioacetals in the presence of InCl3 as a catalyst. A range of functionalized dithiepines and dithiocines, fused to the indene ring, were obtained in good to excellent yields under mild conditions.


Cytokine production and surface marker expression in acute and stable multiple sclerosis: altered IL-12 production and augmented signaling lymphocytic activation molecule (SLAM)-expressing lymphocytes in acute multiple sclerosis.
Ag-stimulated IL-2 production and mitogen-stimulated type 1 and type 2 cytokine production by PBMC, as well as expression of Th1- and Th2-associated phenotypical markers, of B7-1, B7-2, and CD95 (Fas) on the surface of immune cells, and the serum concentration of soluble Apo-1/Fas were evaluated in multiple sclerosis (MS) patients with either acute (AMS) or stable (SMS) disease and in healthy controls (HC). Results showed that 1) Ag-stimulated IL-2 production is reduced in MS patients compared with that in HC; 2) mitogen-stimulated type 1 cytokine production is increased, and IL-10 production is reduced in MS patients compared with those in HC, and in AMS patients compared with those in SMS; 3) whereas production of the metabolically active p70 heterodimers is comparable in SMS, AMS, and HC, production of the p70 heterodimer and the p40 chains (total IL-12) is increased in SMS compared with that in AMS and HC; 4) CD4+, CD4+ SLAM+, and CD4+ CD7+ lymphocytes (preferentially type 1 cytokine-producing lymphocytes) are increased in MS compared with levels in HC; 5) B7-2- as well as Fas+-expressing monocytes are augmented in MS compared with those in HC, and serum soluble Apo-1/Fas is augmented in AMS compared with SMS and HC. These results confirm that a complex imbalance in both cytokine production and the Fas system is present in MS and indicate that different cytokine profiles may be observed in patients with acute or stable disease. The data also suggest that peculiar phenotypic populations are over-represented in MS patients, and for the first time show that SLAM expression is correlated with dysregulation of type 1 and type 2 cytokine production in human pathology.


ALDH2-deficiency as genetic epidemiologic and biochemical model for the carcinogenicity of acetaldehyde.
Humans are cumulatively exposed to acetaldehyde from various sources including alcoholic beverages, tobacco smoke, foods and beverages. The genetic-epidemiologic and biochemical evidence in ALDH2-deficient humans provides strong evidence for the causal relationship between acetaldehyde-exposure due to alcohol consumption and cancer of the upper digestive tract. The risk assessment has so far relied on thresholds based on animal toxicology with lower one-sided confidence limit of the benchmark dose values (BMDL) typically ranging between 11 and 63 mg/kg bodyweight (bw)/day dependent on species and endpoint. The animal data is problematic for regulatory toxicology for various reasons (lack in study quality, problems in animal models and appropriateness of endpoints - especially cancer - for transfer to humans). In this study, data from genetic epidemiologic and biochemical studies are reviewed. The increase in the daily exposure dose to acetaldehyde in alcohol-consuming ALDH2-deficients vs. ALDH2-actives was about twofold. The acetaldehyde increase due to ALDH2 inactivity was calculated to be 6.7 μg/kg bw/day for heavy drinkers, which is associated with odds ratios of up to 7 for head and neck as well as oesophageal cancer. Previous animal toxicology based risk assessments may have underestimated the risk of acetaldehyde. Risk assessments of acetaldehyde need to be revised using this updated evidence.


Chronic School Absenteeism Among Children With Selected Developmental Disabilities: National Health Interview Survey, 2014-2016.
In the United States, 14% of all public school students are chronically absent from school, missing 15 or more days per year (1). Chronic school absenteeism has been associated with poor academic performance, poor school engagement, and greater school dropout (2,3). Previous research has also found that children with chronic health conditions are more likely to have suboptimal school achievement, such as an inability to complete high school or obtain a GED, when compared with youth who did not have a chronic health condition (4). Past research has explored associations between school attendance and health conditions; however, studies have been limited in size and were not nationally representative (5,6). Further, many studies focused on chronic physical health conditions and few explored relationships for individual developmental disabilities (DDs) (7). This report examines the association between selected DDs and chronic school absenteeism among children aged 5-17 years using the National Health Interview Survey (NHIS).


Two pathways for the formation of ethylene in CO reduction on single-crystal copper electrodes.
Carbon monoxide is a key intermediate in the electrochemical reduction of carbon dioxide to methane and ethylene on copper electrodes. We investigated the electrochemical reduction of CO on two single-crystal copper electrodes and observed two different reaction mechanisms for ethylene formation: one pathway has a common intermediate with the formation of methane and takes place preferentially at (111) facets or steps, and the other pathway involves selective reduction of CO to ethylene at relatively low overpotentials at (100) facets. The (100) facets seem to be the dominant crystal facets in polycrystalline copper, opening up new routes to affordable (photo)electrochemical production of hydrocarbons from CO(2).


A mutation in the 530 loop of Escherichia coli 16S ribosomal RNA causes resistance to streptomycin.
Oligonucleotide-directed mutagenesis was used to introduce an A to C transversion at position 523 in the 16S ribosomal RNA gene of Escherichia coli rrnB operon cloned in plasmid pKK3535. E. coli cells transformed with the mutated plasmid were resistant to streptomycin. The mutated ribosomes isolated from these cells were not stimulated by streptomycin to misread the message in a poly(U)-directed assay. They were also restrictive to the stimulation of misreading by other error-promoting related aminoglycoside antibiotics such as neomycin, kanamycin or gentamicin, which do not compete for the streptomycin binding site. The 530 loop where the mutation in the 16S rRNA is located has been mapped at the external surface of the 30S subunit, and is therefore distal from the streptomycin binding site at the subunit interface. Our results support the conclusion that the mutation at position 523 in the 16S rRNA does not interfere with the binding of streptomycin, but prevents the drug from inducing conformational changes in the 530 loop which account for its miscoding effect. Since this effect primarily results from a perturbation of the translational proofreading control, our results also provide evidence that the 530 loop of the 16S rRNA is involved in this accuracy control.


Primary tumors of the esophagus other than squamous cell carcinoma--histologic classification and statistics in the surgical and autopsied materials in Japan.
Clinicopathological features of 405 patients with esophageal tumors other than squamous cell carcinoma, which were resected surgically at 68 institutions in Japan, were analyzed and compared with those of 4,995 cases of esophageal malignant neoplasms autopsied during 19 years (1958-1976) in Japan. Of 405 surgical cases, 149 were benign tumors, most of which (89%) were leiomyomas. The incidence of malignant tumors other than squamous cell carcinoma was 2.1% in the surgical, and 7.2% in the autopsied cases of esophageal cancer. Malignancies were classified into 15 histologic types. Most of them did not differ in sex and age incidence or location of the primary site from squamous cell carcinoma, except for adenocarcinomas, in which there was a greater incidence of occurrence in the lower portion of the esophagus. Carcinosarcomas and pseudosarcomas showed peculiar clinical and pathological characteristics. Overall prognosis was poor except in cases of pseudosarcoma and leiomyosarcoma.


A Biopsychosocial Model of Mealtime Management in Persons with Dementia, an Asset-Based Approach to Patient-Centered Care.
Considering the rapid increase in the population over the age of 65, there is increasing need to consider models of care for persons with dementia (PWD). One common deficit associated with dementia progression is difficulty with successful participation in mealtimes. Difficulty participating in mealtimes in PWD is not the result of one factor, but rather a confluence of biological, psychological, and social characteristics common in dementia. Factors leading to mealtime difficulties for PWD may include changes in cognitive status, altered sensorimotor functioning, and increased reliance on caregiver support. The complex nature of biological, psychological, and social factors leading to mealtime difficulty highlights the need for a pragmatic model that caregivers can utilize to successfully support PWD during mealtimes. Existing models of dementia and mealtime management were reviewed and collated to create a model of mealtime management that considers this complex interplay. The Biopsychosocial Model of Mealtime Management builds on past research around patient-centered care and introduces an asset-based approach to capitalize on a PWD's retained capabilities as opposed to compensating for disabilities associated with dementia. We hope this model will provide a framework for caregivers to understand what factors impact mealtime participation in PWD and provide appropriate means on intervention.


A systems level analysis of epileptogenesis-associated proteome alterations.
Despite intense research efforts, the knowledge about the mechanisms of epileptogenesis and epilepsy is still considered incomplete and limited. However, an in-depth understanding of molecular pathophysiological processes is crucial for the rational selection of innovative biomarkers and target candidates. Here, we subjected proteomic data from different phases of a chronic rat epileptogenesis model to a comprehensive systems level analysis. Weighted Gene Co-expression Network analysis identified several modules of interconnected protein groups reflecting distinct molecular aspects of epileptogenesis in the hippocampus and the parahippocampal cortex. Characterization of these modules did not only further validate the data but also revealed regulation of molecular processes not described previously in the context of epilepsy development. The data sets also provide valuable information about temporal patterns, which should be taken into account for development of preventive strategies in particular when it comes to multi-targeting network pharmacology approaches. In addition, principal component analysis suggests candidate biomarkers, which might inform the design of novel molecular imaging approaches aiming to predict epileptogenesis during different phases or confirm epilepsy manifestation. Further studies are necessary to distinguish between molecular alterations, which correlate with epileptogenesis versus those reflecting a mere consequence of the status epilepticus.


Incidence and Seasonal Variation of Distal Radius Fractures in Korea: a Population-based Study.
The present study aimed to investigate the incidence and seasonal variation of distal radius fractures (DRFs) in Korea. We analyzed a nationwide database acquired from the Korean Health Insurance Review and Assessment Service from 2011 to 2015. We used International Classification of Diseases, 10th revision codes and procedure codes to identify patients of all ages with newly diagnosed DRFs. An average of about 130,000 DRFs occurred annually in Korea. The incidence of DRF, by age group, was highest in the 10 to 14-year-old age group for males and the highest in the 70s age group for females, with a rapid increase of incidence after 50 years. The peak incidence of DRF occurred during winter; however, the incidence greatly varied annually when compared with that of other seasons. The incidence of DRFs during the winter season was correlated with the average temperature. The annual incidence of DRF was 130,000 in Korea. The incidence increased under an intense cold surge during winter. Active preventive measures are recommended especially in women exceeding 50 years considering the higher incidence in this age group.


Diazaborolyl-boryl push-pull systems with ethynylene-arylene bridges as 'turn-on' fluoride sensors.
Two linear π-conjugated systems with 1,3-diethyl-1,3,2-benzodiazaborolyl [C(6)H(4)(NEt)(2)B-] as a donor group and dimesitylboryl (-BMes(2)) as acceptor were synthesised with -ethynylene-phenylene- (-C≡C-1,4-C(6)H(4)-, 3) and -ethynylene-thiophene- (-C≡C-2,5-C(4)H(2)S-12) bridges between the boron atoms. An assembly (20) consisting of two diazaborolyl-ethynylene-phenylene-boryl units, [C(6)H(4)(NCy)(N')B-C≡C-1,4-C(6)H(4)-BMes(2)] joined via a 1,4-phenylene unit at the nitrogen atoms (N') of the diazaborolyl units was also synthesised. The three push-pull systems, 3, 12 and 20, form salts on fluoride addition with the BMes(2) groups converted into (BMes(2)F)(-) anions. The molecular structures of 3, 12 and (NBu(4))(12·F) were elucidated by X-ray diffraction analyses. The borylated systems 3, 12 and 20 show intense blue luminescence in cyclohexane with quantum yields (Φ(fl)) of 0.99, 0.44 and 0.94, respectively, but weak blue-green luminescence in tetrahydrofuran (Φ(fl) = 0.02-0.05). The charge transfer nature of these transitions is supported by TD-DFT computations with the CAM-B3LYP functional. Addition of tetrabutylammonium fluoride to tetrahydrofuran solutions of 3 and 20 resulted in strong violet-blue luminescence with emission intensities up to 46 times more than the emission intensities observed prior to fluoride addition. Compounds 3 and 20 are demonstrated here as remarkable 'turn-on' fluoride sensors in tetrahydrofuran solutions.


Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration.
The selenoenzyme glutathione peroxidase 4 (Gpx4) is an essential mammalian glutathione peroxidase, which protects cells against detrimental lipid peroxidation and governs a novel form of regulated necrotic cell death, called ferroptosis. To study the relevance of Gpx4 and of another vitally important selenoprotein, cytosolic thioredoxin reductase (Txnrd1), for liver function, mice with conditional deletion of Gpx4 in hepatocytes were studied, along with those lacking Txnrd1 and selenocysteine (Sec) tRNA (Trsp) in hepatocytes. Unlike Txnrd1- and Trsp-deficient mice, Gpx4-/- mice died shortly after birth and presented extensive hepatocyte degeneration. Similar to Txnrd1-deficient livers, Gpx4-/- livers manifested upregulation of nuclear factor (erythroid-derived)-like 2 (Nrf2) response genes. Remarkably, Gpx4-/- pups born from mothers fed a vitamin E-enriched diet survived, yet this protection was reversible as subsequent vitamin E deprivation caused death of Gpx4-deficient mice ~4 weeks thereafter. Abrogation of selenoprotein expression in Gpx4-/- mice did not result in viable mice, indicating that the combined deficiency aggravated the loss of Gpx4 in liver. By contrast, combined Trsp/Txnrd1-deficient mice were born, but had significantly shorter lifespans than either single knockout, suggesting that Txnrd1 plays an important role in supporting liver function of mice lacking Trsp. In sum our study demonstrates that the ferroptosis regulator Gpx4 is critical for hepatocyte survival and proper liver function, and that vitamin E can compensate for its loss by protecting cells against deleterious lipid peroxidation.


Exact relations between homoclinic and periodic orbit actions in chaotic systems.
Homoclinic and unstable periodic orbits in chaotic systems play central roles in various semiclassical sum rules. The interferences between terms are governed by the action functions and Maslov indices. In this article, we identify geometric relations between homoclinic and unstable periodic orbits, and derive exact formulas expressing the periodic orbit classical actions in terms of corresponding homoclinic orbit actions plus certain phase space areas. The exact relations provide a basis for approximations of the periodic orbit actions as action differences between homoclinic orbits with well-estimated errors. This enables an explicit study of relations between periodic orbits, which results in an analytic expression for the action differences between long periodic orbits and their shadowing decomposed orbits in the cycle expansion.


The Children, Caregivers, and Community (C3) study of together growing strong: A protocol for an observational, place-based initiative in Sunset Park, Brooklyn.
Reaching population-level impact for families in poverty requires moving beyond a sole focus on individuals, to a wider focus on interactions between individuals and their broader environmental contexts. Place-based initiatives have emerged as a policy response to promote community-level change around these broader interactions between individuals and their local communities through addressing long-standing disparities in housing, employment, education, and health. Together Growing Strong (TGS) is one such place-based initiative focused on transforming the health, wellbeing, and development of young children and their families in Sunset Park, Brooklyn. The Children, Caregivers, and Community (C3) Study is an outcomes-based study designed to assess the trajectories of children and families in Sunset Park along indicators such as family health and wellbeing and child development in relation to TGS program participation. The aims, scope, and protocol of the C3 Study are the subjects of this paper.


Decellularization of canine kidney for three-dimensional organ regeneration.
Kidney regeneration is required for dogs with end-stage renal failure. Decellularization is one of the bioengineering techniques, which involves the removal of all tissue cells and cellular components and conservation of the extracellular matrix (ECM). Studies in rats have shown that decellularized kidney has regenerative potential; however, there are no reports on renal decellularization in dogs. Here, we showed the decellularization of the canine kidney. The renal artery of the cadaveric canine kidney was cannulated and the whole kidney was frozen at -80°C. After completely thawing, it was perfused with physiological saline and sodium dodecyl sulfate (0.5%, 6 h) through the cannulated renal artery to achieve decellularization. To assess the efficiency of the decellularization protocol, histological and immunohistochemical analysis of decellularized kidney was performed. The results of hematoxylin and eosin (H and E) staining revealed that the decellularized canine kidney had no apparent cellular components. In addition, 4',6-diamidino-2-phenylindole (DAPI) staining showed no visible nuclear components within the whole decellularized kidney. Therefore, both H and E and DAPI staining showed decellularization of the canine kidney. Our decellularization protocol also preserved the basement membrane of glomerulus, shown by periodic acid methenamine silver, periodic acid-Schiff, fibronectin, and collagen type IV stain. Our decellularization protocol could eliminate cellular components and remaining native ECM structures of canine kidney. These results could promote further research into canine kidney regeneration, which may be the first small step to regenerate the canine kidney waiting for renal transplantation.


Efficacy of adalimumab in the treatment of axial spondylarthritis without radiographically defined sacroiliitis: results of a twelve-week randomized, double-blind, placebo-controlled trial followed by an open-label extension up to week fifty-two.
To evaluate the efficacy and safety of the tumor necrosis factor (TNF) antagonist adalimumab in patients with axial spondylarthritis (SpA) without radiographically defined sacroiliitis refractory to conventional treatment. Patients with active axial SpA (n = 46) were randomized to receive placebo or adalimumab at a dosage of 40 mg subcutaneously every other week for 12 weeks, followed by an open-label extension that continued up to week 52. The diagnosis of axial SpA required the presence of 3 of 6 diagnostic criteria, including 2 of the following 3 criteria: inflammatory back pain, HLA-B27 positivity, or acute inflammation of the spine or sacroiliac joints on magnetic resonance imaging, in the absence of radiographic evidence of sacroiliitis. The primary end point was a 40% response according to the improvement criteria of the Assessment of SpondyloArthritis international Society (ASAS40). All 46 patients (22 receiving adalimumab and 24 receiving placebo) completed the 12-week trial; 38 patients completed the extension period to week 52. At week 12, an ASAS40 response was achieved by 54.5% of the adalimumab-treated patients, as compared with 12.5% of the placebo-treated patients (P = 0.004). After switching to adalimumab, a similar degree of efficacy was also achieved by the patients who were initially treated with placebo. Efficacy was maintained in all patients until week 52. Young age at study entry and an elevated C-reactive protein concentration were the best predictors of achieving an ASAS40 response. Serious adverse events occurred in 5 patients, none of which was related to the study drug. Adalimumab is the first TNF antagonist to demonstrate good clinical efficacy and safety in patients with axial SpA without radiographically defined sacroiliitis.


Comprehensive analytical strategy for biomonitoring of pesticides in urine by liquid chromatography–orbitrap high resolution masss pectrometry.
In this study we propose an analytical strategy that combines a target approach for the quantitative analysis of contemporary pesticide metabolites with a comprehensive post-target screening for the identification of biomarkers of exposure to environmental contaminants in urine using liquid chromatography coupled to high-resolution mass spectrometry (LC–HRMS). The quantitative method for the target analysis of 29 urinary metabolites of organophosphate (OP) insecticides, synthetic pyrethroids, herbicides and fungicides was validated after a previous statistical optimization of the main factors governing the ion source ionization and a fragmentation study using the high energy collision dissociation (HCD) cell. The full scan accurate mass data were acquired with a resolving power of 50,000 FWHM (scan speed, 2 Hz), in both ESI+ and ESI− modes, and with and without HCD-fragmentation. The method – LOQ was lower than 3.2 μg L−1 for the majority of the analytes. For post-target screening a customized theoretical database was built, for the identification of 60 metabolites including pesticides, PAHs, phenols, and other metabolites of environmental pollutants. For identification purposes, accurate exact mass with less than 5 ppm, and diagnostic ions including isotopes and/or fragments were used. The analytical strategy was applied to 20 urine sample collected from children living in Valencia Region. Eleven target metabolites were detected with concentrations ranging from 1.18 to 131 μg L−1. Likewise, several compounds were tentatively identified in the post-target analysis belonging to the families of phthalates, phenols and parabenes. The proposed strategy is suitable for the determination of target pesticide biomarkers in urine in the framework of biomonitoring studies, and appropriate for the identification of other non-target metabolites.


[Krakow Program for Secondary Prevention of Ischaemic Heart Disease. Part III. Secondary prevention of ischaemic heart disease after discharge].
Even though the majority of actions undertaken within the secondary prevention of ischaemic heart disease should be initiated while the patient is still hospitalized, the maximum benefit (measured as decreased cardiovascular risk) achieved depends mostly on the continuation and modification of these actions in the postdischarge period. There is not much known about the quality of medical care provided for patients after hospitalization due to ischaemic heart disease. The aim of the study was to assess the quality of postdischarge care in the field of secondary prevention of ischaemic heart disease. Consecutive patients (age > or = 70 years; residing in the Cracow province) were identified according to the following clinical diagnoses or procedures: acute myocardial infarction, unstable angina, CABG and PCI. Out of 536 patients 418 took part in the control visit 6-18 months after discharge. Risk factors and medication used were assessed. High total cholesterol (> or = 5.2 mmol/l) was found in 65.8% of patients, high blood pressure (> or = 140/90 mmHg) in 46.2%, obesity (BMI > or = 30 kg/m2) in 24.6%, fasting glucose over 6.0 mmol/l in 17.7% and smoking in 16.3%. The frequency of antiplatelet drugs and beta-blockers use decreased whereas that of lipid-lowering drugs increased in the postdischarge period. The highest frequency of use of antiplatelets and lipid-lowering drugs, as well as the best control of hypercholesterolemia was found in the PCI group, whereas the lowest frequency of smoking was found in the CABG group. Insufficient control of risk factors and the frequency of secondary prevention using drugs was found. There is a need to intensify secondary prevention in patients with ischaemic heart disease in the postdischarge period.


Outcomes of a quality improvement project integrating mental health into primary care.
Depression is commonly seen, but infrequently adequately treated, in primary care clinics. Improving access to depression care in primary care clinics has improved outcomes in clinical trials; however, these interventions are largely unstudied in clinical settings. This study examined the effectiveness of a quality improvement project improving access to mental healthcare in a large primary care clinic. A before-after study evaluating the efficacy of the integration of a primary mental healthcare (PMHC) clinic into a large primary care clinic at the White River Junction, Vermont Veterans Affairs Medical Center (VAMC). In the before period (2003), a traditional referral and schedule model was used to access mental healthcare services. Patients who had screened positive for depression using a depression screen for 6 months after entry into either model were retrospectively followed. VA clinics without a PMHC were used as a control. The proportion of patients who received any depression treatment and guideline-adhering depression treatment in each model was compared, as well as the volume of patients seen in mental health clinics and the wait time to be seen by mental health personnel. 383 and 287 patients screened positive for depression at VAMC and the community-based outreach clinic, respectively. Demographics of the before and after cohorts did not differ. The PMHC model was associated with a greater proportion of patients who had screened positive for depression obtaining some depression treatment (52.3% vs 37.8%; p<0.001), an increase in guideline-adherent depression treatment for depression (11% vs 1%; p<0.001). Implementation of the PMHC model was associated with more rapid and improved treatment for depression in the population of patients who screened positive for depression. More widespread implementation of this model should be investigated.


Sideline management of acute dislocation of the glenohumeral joint- a unique approach to athlete self-reduction.
The acute anterior dislocation of the glenohumeral joint (GHJ) poses a challenge to sports medicine providers at all levels and in all settings. This macrotraumatic injury occurs in athletes who participate in a wide variety of sports, most typically as a result of contact or collision mechanisms. Quick and effective relocation of the GHJ is an important skill for on the sideline or on the field management of this type of dislocation when appropriate and allowable by facility protocol. This clinical suggestion describes one possible technique for athlete self-reduction that may be appropriate in some circumstances. This is in contrast to forcible reduction by the health professional, which is outside of the scope of this clinical commentary. 5.


Aperture effect correction in spectroscopic full-field optical coherence tomography.
Spatially resolved spectroscopic optical coherence tomography (OCT) has been demonstrated to be a convenient tool for spectral analysis in turbid media. For a full-field OCT configuration using a Mirau objective in the visible range, we found that the effective numerical aperture varies over the field of view, leading to field-dependent spectral shifts in the reconstructed spectra. Interferograms recorded with quasi-monochromatic lights are theoretically fitted with a general Mirau interference formula, and we propose a numerical correction method for white-light spectroscopy. The method is then tested successfully for the measure of the reflectivity of a plane gold sample.


The mouse "tool box" for meiotic studies.
Besides availability, there are numerous advantages to using mice for meiotic studies: (1) techniques exist for enriching the population of spermatocytes at particular meiotic stages; (2) spermatogenesis in mice is highly synchronized and testis sections afford a highly accurate method of staging meiotic events; (3) knock-out mice provide a rich source of meiotic mutants. Coupled with antibody localization techniques these tools, singularly and in combination, provide multiple means of temporally and physically dissecting meiosis.


The History of Cardiothoracic Surgery at Emory University.
Over the past 50 years, the Emory Cardiothoracic Surgical Program has become one of the premier training programs in the United States. During this time, the Emory program has been sequentially led by Drs Osler Abbott, Charles Hatcher, and Robert Guyton. The program has grown from single faculty member to 25, and the culture of team collaboration, clinical excellence, research, and teaching established by Dr Hatcher has continued under the leadership of Dr Guyton for the past 26 years.


Diversification rates indicate an early role of adaptive radiations at the origin of modern echinoid fauna.
Evolutionary radiations are fascinating phenomena corresponding to a dramatic diversification of taxa and a burst of cladogenesis over short periods of time. Most evolutionary radiations have long been regarded as adaptive but this has seldom been demonstrated with large-scale comparative datasets including fossil data. Originating in the Early Jurassic, irregular echinoids are emblematic of the spectacular diversification of mobile marine faunas during the Mesozoic Marine Revolution. They diversified as they colonized various habitats, and now constitute the main component of echinoid fauna in modern seas. The evolutionary radiation of irregular echinoids has long been considered as adaptive but this hypothesis has never been tested. In the present work we analyze the evolution of echinoid species richness and morphological disparity over 37 million years based on an extensive fossil dataset. Our results demonstrate that morphological and functional diversifications in certain clades of irregular echinoids were exceptionally high compared to other clades and that they were associated with the evolution of new modes of life and so can be defined as adaptive radiations. The role played by ecological opportunities in the diversification of these clades was critical, with the evolution of the infaunal mode of life promoting the adaptive radiation of irregular echinoids.


Mycotic aortic aneurysm following treatment of pyogenic vertebral osteomyelitis.
Mycotic aortic aneurysm is a surgical emergency. However, its bizarre presentations could delay the golden hour of surgical reconstruction which is the mainstay of treatment. We report a case of mycotic aneurysm of the aortic arch which developed in the postoperative period after surgical treatment of pyogenic vertebral osteomyelitis at the lower thoracic level.


Intravascular coagulation and fibrinolysis syndrome (ICF) in acute non-promyelocytic leukemia.
Three cases of acute non-promyelocytic leukemia complicated with intravascular coagulation and fibrinolysis syndrome were described. The blood clotting system and fibrinolysis studies in all 3 cases revealed a significant increase of FDP level and shortening of fibrinolysis time as well as a decrease of fibrinogen content in 2 cases. In one patient the recovery from ICF syndrome and complete acute leukemia remission of 8 months duration was obtained. The further 2 cases failed to improve: in one of them the ICF syndrome appeared in relapse of acute myelocytic leukemia after 2 years of its duration and in the remaining one acute undifferentiated cell leukemia of fulminating course developed in the patient suffering from bone marrow aplasia.


Characterization of Molecular Identity and Pathogenicity of Rice Blast Fungus in Hunan Province of China.
The blast (Magnaporthe oryzae) resistance (R) gene is the most economical and environmental method to control rice blast disease. Characterization of molecular identity and pathogenicity of M. oryzae benefits the deployment of effective blast R genes. In order to identify blast R genes that would be effective in Hunan Province,182 M. oryzae strains were analyzed with a Chinese differential system (CDS), repetitive element-based polymerase chain reaction (rep-PCR), and the presence and absence of avirulence (AVR) genes by PCR amplification with gene-specific primers. Identified blast R genes were validated with 24 monogenic lines (ML) carrying 24 major R genes. In total, 28 races (isolates) of M. oryzae was identified with CDS, and classified into 20 distinct groups with rep-PCR. Interestingly, AVR-Pia, AVR-Pik, AVR-Pizt, AVR-Pib, and AVR-Pi9 were detected in more than 86.8% of the isolates; AVR-Pita1 was in 51.3% and AVR-Pii was in only 2.5%. In contrast, pathogenicity assays on 24 ML demonstrated that Pi9, Piz5, Pikh, and Pikm were more effective, with resistant frequencies of 91.6, 91, 87.9, and 87.3%, respectively; Pia, Piks, Pit, Pi12, and Pib were less than 15%. These findings revealed the complexity of a genetic basis of rice blast resistance, and shed light on useful blast R genes in Hunan Province.


Vulnerable populations and morally tainted experiments.
This article addresses the dilemma facing an editor when he or she has to decide whether or not to publish a manuscript that describes unethical research. I will explore three options the editor may follow: a) publish the unethical research; b) publish it with an explicit condemnation of the methods used; c) reject the article on moral grounds. I will consider the importance of deterring unethical research, why the deterrence argument has been overlooked and the relevance it has in developing countries which seem to be more exposed to morally tainted experiments. I will suggest a combined policy. For cases in which the ethical problems are serious -- where basic human rights are not respected, where consent has been given without complete or proper information or voluntary participation by subjects, or where deceit has been practised -- I would support the strong policy of rejecting the article on moral grounds. For dubious cases, where the risk assessment can be doubted or where there are suspicions of ethical problems, I argue for a policy under which the article is published along with a serious discussion of the ethical problems suspected, allowing a rebuttal by the authors. In this way, while maintaining a strong deterrent policy, we recognize that sometimes it is not so clear if a research project was unethical, and only in such cases (where the ethical problems are dubious), the article may be published with an editorial.


[THE ATOMIC-FORCE MICROSCOPY STUDY OF STRUCTURAL FUNCTIONAL CHARACTERISTICS OF NEUTROPHILS IN PATIENTS WITH CHRONIC OBSTRUCTIVE LUNG DISEASES IN PHASE OF EXACERBATION].
The technique of atomic-force microscopy was applied to analyze the structural functional characteristics (morphology, force of adhesion, rigidity of membrane) of neutrophils in patients with chronic obstructive disease of lungs in phase of exacerbation. The regimen of force spectroscopy was applied to implement quantitative evaluation of module of elasticity (Young module) of cell membrane and force of adhesion of neutrophils. The study established decreasing of size of neutrophils, increasing of granularity of cytoplasm, increasing of Young module and force of adhesion in patients with chronic obstructive disease of lungs in phase of exacerbation.


Use of 2-[125I]iodomelatonin to characterize melatonin binding sites in chicken retina.
2-[125I]Iodomelatonin binds with high affinity to a site possessing the pharmacological characteristics of a melatonin receptor in chicken retinal membranes. The specific binding of 2-[125I]iodomelatonin is stable, saturable, and reversible. Saturation experiments indicated that 2-[125I]iodomelatonin labeled a single class of sites with an affinity constant (Kd) of 434 +/- 56 pM and a total number of binding sites (Bmax) of 74.0 +/- 13.6 fmol/mg of protein. The affinity constant obtained from kinetic analysis was in close agreement with that obtained in saturation experiments. Competition experiments showed a monophasic reduction of 2-[125I]iodomelatonin binding with a pharmacological order of indole amine affinities characteristic of a melatonin receptor: 2-iodomelatonin greater than 6-chloromelatonin greater than or equal to melatonin greater than or equal to 6,7-dichloro-2-methylmelatonin greater than 6-hydroxymelatonin greater than or equal to 6-methoxymelatonin much greater than N-acetyltryptamine greater than N-acetyl-5-hydroxytryptamine greater than 5-methoxytryptamine greater than 5-hydroxytryptamine (inactive). The affinities of these melatonin analogs in competing for 2-[125I]iodomelatonin binding sites were correlated closely with their potencies for inhibition of the calcium-dependent release of [3H]dopamine from chicken and rabbit retinas, indicating association of the binding site with a functional response regulated by melatonin. The results indicate that 2-[125I]iodomelatonin is a selective, high-affinity radioligand for the identification and characterization of melatonin receptor sites.


Regulation of enamel hardness by its crystallographic dimensions.
Enamel is a composite biomaterial comprising a minor organic matrix (~2%) and a hierarchically organized inorganic ultrastructure (~96-98%). Surprisingly, to date there is no available information in the literature regarding the possible role of the enamel ultrastructure on the nanoscale level in tooth macroscopic properties. Understanding this relationship is of special interest for restorative purposes in dentistry. Accordingly, this study was designed to investigate how enamel nanocrystals regulate its hardness. We performed microindentation analysis on 100 extracted human teeth. The tooth enamel hardness was quantified and correlated with changes in enamel chemical composition and crystallographic dimensions obtained from Fourier transform infrared spectroscopy and X-ray diffraction, respectively. Enamel hardness was not related to the variability in organic content, but was associated with the size of apatite crystals along the c-axis. This association followed the Hall-Petch model for polycrystalline materials, indicating that the optimal size of apatite nanocrystals (larger than the critical size) provides enamel with the greatest hardness, which enables teeth to survive the heavy wear over a human lifetime.


The empirical correlation between size and two-photon absorption cross section of CdSe and CdTe quantum dots.
The tuning of CdSe quantum dot (QDs) sizes, and consequently their corresponding two-photon absorption (TPA) cross section, has been systematically investigated. As the size (diameter) of the quantum dots increases, the TPA cross section is found to be empirically related via a power-law proportionality of 3.5+/-0.5 and 5.6+/-0.7 to the diameters of CdSe and CdTe QDs, respectively. The results are tentatively rationalized via a theoretical model of two-photon excitation properties in a system incorporating excitons and defects.


Improving tumor uptake and excretion kinetics of 99mTc-labeled cyclic arginine-glycine-aspartic (RGD) dimers with triglycine linkers.
This report describes the synthesis of two new cyclic RGD (Arg-Gly-Asp) dimers, 3 (E[G(3)-c(RGDfK)](2)) and 4 (G(3)-E[G(3)-c(RGDfK)](2)), and their corresponding conjugates 5 (HYNIC-E[G(3)-c(RGDfK)](2): HYNIC = 6-(2-(2-sulfonatobenzaldehyde)hydrazono)nicotinyl) and 6 (HYNIC-G(3)-E[G(3)-c(RGDfK)](2)). Integrin alpha(v)beta(3) binding affinities of 5 and 6 were determined by displacement of (125)I-echistatin bound to U87MG glioma cells. (99)(m)Tc complexes 7 ([(99m)Tc(5)(tricine)(TPPTS)]: TPPTS = trisodium triphenylphosphine-3,3',3''-trisulfonate) and 8 ([(99m)Tc(6)(tricine)(TPPTS)]) were prepared in high yield and high specific activity. Biodistribution and imaging studies were performed in athymic nude mice bearing U87MG glioma and MDA-MB-435 breast cancer xenografts. It was found that G(3) linkers are particularly useful for increasing integrin alpha(v)beta(3) binding affinity of cyclic RGD dimers and improving the tumor uptake and clearance kinetic of their (99)(m)Tc radiotracers. Complex 8 is a very promising radiotracer for the early detection of integrin alpha(v)beta(3)-positive tumors and may have the potential for noninvasive monitoring of tumor growth or shrinkage during antiangiogenic treatment.


Leiomyoma Originated From Inferior Vena Cava Mimicking an Adrenal Malignant Tumor on 18F-FDG PET/CT.
PET/CT was performed on an asymptomatic 62-year-old woman with a suspected adrenal mass and revealed the lesion with high F-FDG avidity and inferior vena cava involvement. A malignant nonfunctioning adrenal tumor was suspected. However, histopathology of the resected lesion revealed a leiomyoma arising from the inferior vena cava.


[The value of serologic inflammatory parameters in the diagnosis of alopecia areata].
Even recently, focal processes or inflammatory diseases have repeatedly been discussed as the possible causes of alopecia areata (AA) and corresponding diagnostic measures are still recommended. Therefore, we initially attempted to find definite indications of processes like these in AA patients by means of serologic parameters of inflammation and ESR as well as supplementary clinical focal diagnostics. The data obtained revealed increased titers of antistreptolysin in 2.9% and antistreptococcal DNase B in 25.7%, positive C-reactive protein in 8.6%, positive rheumatoid factor in 4.3%, and elevated ESR in 11.7% of the cases. After these data had carefully been compared to those in healthy persons, only the titer of antistreptococcal DNase B and the ESR were found to be increased. In the majority of the cases, these elevations correlated with concomitant bacterial infections detected by clinical focal diagnostics. Antistreptococcal DNase B titer and ESR seem to be the most appropriate of all our test parameters to provide some indications of a focal process or concomitant inflammatory diseases. The remaining parameters are not indicated in AA.


[Study on chemical constituents in rhigome of Ervatamia hainanensis].
To investigate the chemical constituents of the rhizome of Ervatamia hainanensis. The solvent extraction and silica column chromatography were used to separate the chemical constituents, and their structures were identified by physico chemical properties and spectra analysis. Twelve compounds were isolated and their structures were identified as voacangine (1), ibogaine (2), ibogamine (3), coronaridine (4), 19-heyneanine (5), 19-epi-heyneanine (6), 3-hydroxyl coronaridine (7), coronaridine hydroxyindolenine (8), 3-(2-oxopropyl) coronaridine (9), vobasine (10), alpha-amyrin (11), alpha-amyrin acetate (12). Compounds 1, 2, 6, 11 and 12 were first found from this plant.


There's no place like home: first-year use of the "I Know" home testing program for chlamydia and gonorrhea.
In response to high chlamydia and gonorrhea morbidity, particularly among young African American and Latina women, the Los Angeles County Department of Public Health launched a free home testing program for Chlamydia trachomatis and Neisseria gonorrhoeae. The primary objectives were to increase chlamydia and gonorrhea testing by removing key barriers and to motivate young women to screen routinely for these sexually transmitted diseases (STDs). The program was promoted with a social marketing campaign urging women to order home collection kits online or by telephone. In the program's first year, 2927 kits were ordered and 1543 testable specimens returned; 131 women (8.5%) had a positive test result. The strong response, high morbidity, and program scalability indicated strong potential as a new tool for STD control.


Congestive heart failure in patients with normal left ventricular systolic function: a manifestation of diastolic dysfunction.
Diastolic dysfunction is a relatively common problem that may be mild and asymptomatic or may present with congestive heart failure and severe disabling symptoms. It is frequently due to coronary artery disease or left ventricular hypertrophy and it is especially common in the older population. The pathophysiology is related to increased left ventricular passive stiffness and impaired or slowed myocardial relaxation. Patients with diastolic dysfunction are best treated with calcium channel blocking agents or beta-blocking agents (drugs that are generally avoided in patients with significant systolic dysfunction). Most treatment is based on symptomatic relief, and therefore periods of cautious trial and error are the rule. Congestive symptoms are treated with agents that reduce pulmonary venous pressure; in general positive inotropic agents and arterial vasodilators are not useful in heart failure that is due to diastolic dysfunction.


Localization of a calcium sensitive binding site for gelsolin on actin subdomain I: implication for severing process.
The binding of the N-terminal domain (S1) of gelsolin to monomeric actin has been extensively documented. In contrast, the location of the C-terminal calcium dependent domains (S4-6) interacting with the actin filament during the severing process remains uncertain. In this study, we have identified a new interface that supports calcium dependent gelsolin binding to actin. This site is located in a critical position towards actin-actin contact in the filament and in the vicinity of the phalloidin site. Using specific antibody and synthetic peptides derived from actin sequence within 105-132 residues, this interface was finally ascribed to the segment 112-120 on the actin subdomain-1.


Bioassay for the determination of the intra- and extracellular activity of aminopeptidases in immobilized tomato cells.
Permeabilized tomato cells were cross-linked with glutaraldehyde in the absence of a carrier. The immobilized cells demonstrated significantly lower aminopeptidase (AP) activities than untreated control cells. However, when immobilized with pectate and alginate gels, the tomato cells retained their AP activities. A new method for the determination of the activity of both extra- and intracellular AP was developed, based on enzyme-catalyzed hydrolysis of a series of synthetic beta-naphthylamides (betaNA) of the L-amino acids Ala, Arg, Leu, Pro, Tyr, or of the synthetic beta-methoxynaphthylamides (betaMNA) of Ala and Arg. Extracellular AP--produced by calli, cell-suspension culture, or seedlings of tomato cells grown on agar--hydrolyzed these peptidic substrates to the free naphthalene amines and amino acids. Staining with Fast Garnet GBC salt under formation of bright reddish azo dyes readily allowed the determination of AP activities. For the tomato-cell suspension, the intracellular activity accounted for 91.3-93.9% of the total activity, and the extracellular one for 6.1-8.7%, respectively. Our method permits the rapid, simple, and specific determination of plant aminopeptidases.


Role of the endocannabinoid system in the regulation of the skeletal muscle response to exercise.
Exercise is a valuable tool in the prevention and treatment of cardiometabolic diseases like obesity and type 2 diabetes. Interestingly, endocannabinoids (eCBs), involved in a large range of physiological processes, are elevated with both obesity and acute exercise. In this review we outline this paradox overlap in the context of metabolic health and delineate the transcriptomic response of skeletal muscle to acute and chronic aerobic and resistance exercise in relation to the endocannabinoid system by utilizing a meta-analyses tool. We show that exercise modulates the expression of receptors and enzymes involved in the synthesis and breakdown of eCBs and discuss that eCBs possibly interfere with the anti-inflammatory effect of exercise. The endocannabinoid system (ECS), consisting of certain endogenous lipids (i.e. endocannabinoids), their receptors and associated metabolic enzymes, is involved in the modulation of a plethora of cognitive and physiological processes. Besides its role in the control of, for example, mood formation and immune responses, the ECS takes part in the regulation of appetite and energy metabolism [1,2]. In this current opinion review we will focus on the increased activity of the ECS that is associated with cardiometabolic diseases like obesity and type 2 diabetes (T2D), which paradoxically overlaps with the acute physiological response to exercise. After 1) outlining the role of the ECS in metabolic health, we will 2) discuss the link between endocannabinoid (eCB) action in skeletal muscle and cardiometabolic disease, 3) investigate how exercise modulates the gene expression of ECS components in skeletal muscle and 4) delineate the impact of the ECS on the immune response by skeletal muscle.


Electrically evoked otoacoustic emissions from the apical turns of the gerbil cochlea.
Electrically evoked otoacoustic emissions were measured with current delivered to the second and third turns of the gerbil cochlea. The emission magnitude and phase are dependent on the characteristic frequency (CF) of the stimulating microelectrode location. The death of the animal resulted in an initial increase in emission below the CF of the electrode location and a decrease in emission near the CF of the electrode location. The group delay of the electrically evoked emission phase data is twice as large as the acoustically evoked cochlear microphonic (CM) data obtained by Schmiedt and Zwislocki [J. Acoust. Soc. Am. 61, 133-149 (1977)]. This suggests the possibility of two separate propagation modes for the forward and reverse traveling waves.


Macrophage colony-stimulating factor-, granulocyte-macrophage colony-stimulating factor-, or IL-3-dependent survival of macrophages, but not proliferation, requires the expression of p21(Waf1) through the phosphatidylinositol 3-kinase/Akt pathway.
Mouse bone marrow-derived macrophages proliferate in the presence of macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor, or IL-3, but undergo apoptosis in their absence. Inhibition of extracellular signal-regulated kinases (ERK)-1/2 blocks growth factor-dependent proliferation but not survival, indicating that the two processes require independent signaling pathways. Although M-CSF induces the activation of other kinase pathways, such as c-Jun N-terminal kinase, p38, and phosphatidylinositol 3-kinase (PI-3K), these pathways are not required for proliferation. However, PI-3K is the only one necessary for the induction of survival, as demonstrated using the inhibitors LY294002 and Wortmannin. Growth factors also activate Akt kinase and a transient expression of the cdk inhibitor p21(Waf1), which inhibits apoptosis but is not required for proliferation. PI-3K inhibitors also block growth factor-dependent expression of p21(Waf1) and the activation of Akt. Moreover, the survival induced by cyclosporin A or decorin is also dependent on the PI-3K/Akt kinases and p21(Waf1). These findings demonstrate that the induction of p21(Waf1) through the PI-3K/Akt pathway is a general survival response of macrophages. Our results show that growth factors in macrophages use two pathways: one for proliferation, mediated by ERK, and the other for survival, which requires the PI-3K/Akt kinases and p21(Waf1).


[STENTING VERSUS PALLIATIVE SURGERY IN PATIENTS WITH MALIGNANT GASTROINTESTINAL STENOSIS].
Retrospective analysis of the results of stenting versus surgical palliation in patients with malignant gastrointestinal stenosis. 85 patients underwent endoscopic stenting (41) or surgical intervention (44). Level of stenosis: gastric outlet (23/38), multi-level gastric obstruction (2/3), duodenum or jejunum (12/3), gastrojejunoanastomosis (3/0) and gastroduodenoanastomosis (1/0). 49 self-expanding metal stents were implanted in 41 patients. 41 gastroenteroanastomoses and 3 jejunostomas were performed in surgical group. Stents were successfully inserted in all patients. Early complications were observed in 3 (7.3%) patients after stenting and in 9 (20.5%) after surgical palliation, p = 0.0755. Postoperative lethality was 2,4% (1 patient) after stenting and 31.8% (14 patients) after surgery, p = 0.0003. Mean hospital stay was 15 days in stenting group and 23 days in surgical group, p < 0.001. There was no statistically significant difference in long-term results, neither in late complications (p = 0.3691), nor in survival (p =0.3697). Endoscopic placement of self-expanding stents is an effective method of restoration of oral intake in patients with malignant gastrointestinal obstruction. Stenting is associated with equal rates of early and late complications, lower mortality and decreased in-hospital stay as compared with surgery, and therefore may be recommended as a final palliation in inoperable patients.


Relationship between the Interannual Variations of Summer Convective Afternoon Rainfall Activity in Taiwan and SSTA(Niño3.4) during 1961-2012: Characteristics and Mechanisms.
This study examines the interannual variation of the Convective Afternoon Rainfall (CAR) activity (including frequency and intensity) in Taiwan during the summers (JJA) of 1961-2012 with a focus on identifying its relationship with the changes in sea surface temperature anomalies over the Niño3.4 region [SSTA(Niño3.4)] and the underlying physical mechanisms. Our analyses show that during the colder (warmer) phase of SSTA(Niño3.4), the subtropical high system over the region east of Taiwan is enhanced (weakened), the local surface wind convergence is enhanced (weakened), and the local thermal instability is enhanced (weakened), which facilitates (suppresses) the formation of CAR in Taiwan. This consistent negative relationship between the interannual variation of CAR frequency in Taiwan and SSTA(Niño3.4) occurs throughout 1961-2012. In contrast, the relationship between the interannual variation of CAR intensity in Taiwan and SSTA(Niño3.4) changed from positively correlated to negatively correlated in the late 1980s. This change is attributed to the change in the moisture supply for maintaining the CAR intensity in Taiwan from an increase (decrease) in the warmer (colder) phase of SSTA(Niño3.4) before the mid-1980s to the opposite after the late 1980s. These findings highlight how the rainfall characteristics in East Asia may change in response to changes in SSTA(Niño3.4).


Molecular Simulations of Laser Spike Annealing of Block Copolymer Lamellar Thin-Films.
We use molecular dynamics simulations to study the phase behavior of a coarse-grained lamella-forming A-b-B diblock copolymer under thin-film soft confinement for different heating cycle lengths, film thicknesses, and substrate-polymer affinities. This model describes the effect on thin-film morphology with a free surface (air-polymer interface) and a solid substrate. Our simulation results were first validated by showing that they capture changes for the order-disorder transition temperature with annealing conditions consistent with those found in laser spike annealing experiments, when the vertical lamella phase formed on neutral substrates. In addition, simulations with a substrate selective for a particular block revealed the formation of other phases, including a mixed vertical-horizontal lamella and a metastable island phase having horizontal but incomplete lamella layers. The nanoscale roughness features of this island phase, and hence its surface wettability, can be tuned with suitable choices of chemistry and annealing conditions.


Patient specific simulation of body surface ECG using the finite element method.
Recent studies, supported by advances in computer science, have successfully simulated the excitation and repolarization processes of the heart, based on detailed cell models of electrophysiology and implemented with realistic morphology. In this study, we extend these approaches to simulate the body surface electrocardiogram (ECG) of specific individuals. Patient-specific finite element models of the heart and torso are created for four patients with various heart diseases, based on clinical data including computer tomography, while the parallel multi-grid method is used to solve the dynamic bi-domain problem. Personalization procedures include demarcation of nonexcitable tissue, allocation of the failing myocyte model of electrophysiology, and modification of the excitation sequence. In particular, the adjustment of QRS morphology requires iterative computations, facilitated by the simultaneous visualization of the propagation of excitation in the heart, average QRS vector in the torso, and 12-lead ECG. In all four cases we obtained reasonable agreement between the simulated and actual ECGs. Furthermore, we also simulated the ECGs of three of the patients under bi-ventricular pacing, and once again successfully reproduced the actual ECG morphologies. Since no further adjustments were made to the heart models in the pacing simulations, the good agreement provides strong support for the validity of the models. These results not only help us understand the cellular basis of the body surface ECG, but also open the possibility of heart simulation for clinical applications.


The Tripod School Climate Index: An Invariant Measure of School Safety and Relationships.
Recently revised standards for social work practice in schools encourage data-informed school climate interventions that implicitly require invariant measures of school climate. Invariant measures have the same meaning, scale, and origin across different groups of respondents. Although noninvariant measures bias statistical analyses and can lead users to erroneous conclusions, most school climate measures have not been tested for invariance. This study examines the invariance of the Tripod School Climate Index. Exploratory, confirmatory, and multiple-group confirmatory factor analyses were conducted on data collected from 66,531 students across 222 schools. Results indicate that the index is an excellent fit for the data and invariant by student grade level, demographic background, prior achievement, and dropout risk. Results imply that student responses can be validly aggregated to create school-level scores. The index will not bias studies of school climate interventions or bivariate analyses comparing perceptions of school climate across subgroups of students attending the same school. Given the centrality of school climate interventions to social work practice in schools and the consequences of noninvariance, the development of an index with these properties is an important contribution to the field.


Allergic diseases in children with attention deficit hyperactivity disorder: a systematic review and meta-analysis.
Reports of frequent manifestation of allergic diseases in children with attention deficit hyperactivity disorder (ADHD) have been the subject of mounting clinical interest. However, evidence supporting the association between ADHD and allergies is inconsistent and has yet to be systematically reviewed. The objective of this study was to compile and assess available studies on the association between ADHD and allergic diseases in children. A comprehensive search using MEDLINE, EMBASE, the Cochrane library, and CINAHL databases was completed in 23 November 2015. The inclusion criteria for studies were that the research assessed allergic diseases in children, 18 years of age and younger, with a diagnosis of ADHD and that a distinct comparison group was incorporated. Any comparative studies, encompassing both randomized controlled trials and observational studies, were considered for inclusion. Two review authors independently assessed the quality of the selected studies by the use of validated assessment tools, performed data extraction and conducted meta-analysis according to Cochrane Collaboration guidelines. Five eligible studies were included in this systematic review. Of these studies, three were case-control and two were cross sectional studies. A majority of information from the five studies was classified as having low or unclear risk of bias. The meta-analysis showed an association between children with ADHD and asthma compared with the control groups (OR: 1.80, 95% CI: 1.57 - 2.07; five studies, low quality of evidence), but did not indicate an association between food allergy and ADHD (OR: 1.13, 95% CI: 0.88 - 1.47; three studies very low quality of evidence). The odds of experiencing allergic rhinitis, atopic dermatitis, and allergic conjunctivitis were slightly higher in children with ADHD compared with control groups, though a substantial statistical heterogeneity was notable in the overall effect estimates. The findings from this review and meta-analysis show that children with ADHD are more likely to have asthma, allergic rhinitis, atopic dermatitis, and allergic conjunctivitis than their counterparts. Interventions including strategies for managing allergies in children with ADHD would be beneficial.


Ring-closing metathesis in the synthesis of BC ring-systems of taxol.
BC ring-systems of taxol with different or no protecting group for the C1,C2-diol moiety have been efficiently synthesized. The eight-membered B ring is formed by a ring-closing metathesis reaction (RCM) between the C10 and C11 carbon atoms. The influence of the 1,2-diol protecting group on the RCM reaction has been studied in detail.


Identifying Stress-Exacerbated Thermal-Injury Induced MicroRNAs.
Using a model of combat and operational stress reaction (COSR), our lab recently showed that exposure to an unpredictable combat stress (UPCS) procedure prior to a thermal injury increases pain sensitivity in male rats. Additionally, our lab has recently shown that circulating extracellular vesicle-microRNAs (EV-miRNAs), which normally function to suppress inflammation, were downregulated in a male rat model of neuropathic pain. In this current study, male and female rats exposed to UPCS, followed by thermal injury, were evaluated for changes in circulating EV-miRNAs. Adult female and male Sprague Dawley rats were exposed to a UPCS procedure for either 2 or 4 weeks. Groups consisted of the following: nonstress (NS), stress (S), NS + thermal injury (TI), and S + TI. Mechanical sensitivity was measured, and plasma was collected at baseline, throughout the UPCS exposure, and post-thermal injury. EV-miRNA isolation was performed, followed by small RNA sequencing and subsequent data analysis. UPCS exposure alone resulted in mechanical allodynia in both male and female rats at specific time points. Thermal-injury induction occurring at peak UPCS resulted in increased mechanical allodynia in the injured hind paw compared to thermal injury alone. Differential expression of the EV-miRNAs was observed between the NS and S groups as well as between NS + TI and S + TI groups. Consistent differences in EV-miRNAs are detectable in both COSR as well as during the development of mechanical sensitivity and potentially serve as key regulators, biomarkers, and targets in the treatment of COSR and thermal-injury induced mechanical sensitivity. PERSPECTIVE: This article presents the effects of unpredictable combat stress and thermal injury on EV-contained microRNAs in an animal model. These same mechanisms may exist in clinical patients and could be future prognostic and diagnostic biomarkers.


Intracellular Delivery Using Nanosecond-Laser Excitation of Large-Area Plasmonic Substrates.
Efficiently delivering functional cargo to millions of cells on the time scale of minutes will revolutionize gene therapy, drug discovery, and high-throughput screening. Recent studies of intracellular delivery with thermoplasmonic structured surfaces show promising results but in most cases require time- or cost-intensive fabrication or lead to unreproducible surfaces. We designed and fabricated large-area (14 × 14 mm), photolithography-based, template-stripped plasmonic substrates that are nanosecond laser-activated to form transient pores in cells for cargo entry. We optimized fabrication to produce plasmonic structures that are ultrasmooth and precisely patterned over large areas. We used flow cytometry to characterize the delivery efficiency of cargos ranging in size from 0.6 to 2000 kDa to cells (up to 95% for the smallest molecule) and viability of cells (up to 98%). This technique offers a throughput of 50000 cells/min, which can be scaled up as necessary. This technique is also cost-effective as each large-area photolithography substrate can be used to deliver cargo to millions of cells, and switching to a nanosecond laser makes the setup cheaper and easier to use. The approach we present offers additional desirable features: spatial selectivity, reproducibility, minimal residual fragments, and cost-effective fabrication. This research supports the development of safer genetic and viral disease therapies as well as research tools for fundamental biological research that rely on effectively delivering molecules to millions of living cells.


Endothelial cell apoptosis in sepsis.
To discuss a potential role for endothelial cell apoptosis in the pathogenesis of sepsis. Studies published in biomedical journals and studies from the authors' laboratory. In vitro and in vivo studies of endothelial cell apoptosis in endotoxin and sepsis models. Relevant studies that investigate the role of apoptosis in endotoxemia and sepsis are presented. The divergent results of the different studies and the potential reasons for the discrepant findings are presented. The importance of apoptosis in sepsis and the potential impact on endothelial cells and organ function are highlighted. Apoptosis is an important mechanism of lymphocyte and gastrointestinal epithelial cell death in sepsis. Although abundant in vitro studies indicate that endothelial cell apoptosis can occur in response to certain pathogenic organisms (e.g., Rickettsia rickettsii), data documenting endothelial cell apoptosis in in vivo models of sepsis are lacking. Because endothelial cells that undergo apoptosis detach from the vessel basement membrane, enter the circulation, and are rapidly cleared, it may be difficult to detect endothelial cell apoptosis in in vivo models of sepsis. The impact of endothelial cell apoptosis in sepsis may either be detrimental or beneficial to host survival, depending on the particular pathogen.