Hanging radiograph in idiopathic scoliosis patients: significance as a preoperative stress X-ray.
Before corrective surgery for idiopathic scoliosis, the stress X-rays are indispensable to collect information regarding the reducibility of deformity, deciding fusion levels, and categorizing curve types and so on. The hanging radiograph has not been conducted preoperatively so far as known. The objective of this study was to investigate retrospectively the significance of the hanging radiograph for prediction of the curve correction with surgical procedure by comparing with the side-bending and the traction radiographs. The subjects enrolled in current study were 22 cases of idiopathic scoliosis who performed posterior instrumentation and fusion by ISOLA method between 2008 and 2014. They included 2 males and 20 females, with a mean age of 16 years and 8 months. The type of curves by Lenke classification were type 1 in 20 cases, type 2 in 1 case, and type 3 in 1 case. We investigated the correction rates of main thoracic curves in side-bending, traction, and hanging positions and compared them with that after surgery. In addition, correction indices were also calculated and compared among these stress X-rays. The correction rate after surgery was 65.9% that was statistically higher than those in side-bending (44.2%), traction (46.6%), and hanging (22.1%) positions. There were statistical correlations between the correction rates after surgery and in side-bending position (R=0.73) and those after surgery and in traction position (R=0.57). However, there was no statistical correlation between the correction rates after surgery and in hanging position (R=-0.01). With regard to the correction indices, that in hanging position (3.67) was statistically higher than those in side-bending (1.51) and traction (1.45) positions. The correction rates in side-bending and traction positions seem to be useful to estimate the amount of curve correction before surgery. Whereas, that in hanging position did not have any significance as preoperative evaluation.


Standing posture at work and overweight exacerbate varicose veins: Shimane CoHRE Study.
Varicose veins (VV) in legs are commonly observed in the general global population. However, the prevalence of and risk factors for VV in Japan are not clear. This study aimed at clarifying the risk factors for VV in traditional rural areas of Shimane prefecture. Subjects (113 men and 205 women aged ≥45 years) were recruited from health examinations in those areas in 2012. VV were defined as a reflux of blood in the great and/or small saphenous vein and incompetent perforating veins detected by ultrasonography. Risk factors for VV were analyzed using logistic regression models that included various parameters. We also investigated the possible interaction between standing at work and overweight and calculated the synergistic index. VV were found in 20.1% of the subjects (12.4% of men and 24.4% of women). The previously known risk factors of prolonged upright standing posture during work, higher body mass index (BMI), female sex, and age were also significant factors for VV. There was a significant combined effect of overweight (BMI ≥25) and prolonged upright standing posture at work [adjusted odds ratio = 3.42; 95% confidence interval (CI), 1.07-10.89], although the synergistic effect was not significant [synergistic index = 1.3; 95% CI, 0.2-8.7]. The prevalence of VV in the traditional rural area of Shimane prefecture was comparable to that reported previously in European countries. Our results confirm that exposure to both prolonged standing at work and overweight exacerbate VV development. This finding is useful to develop strategies for VV prevention.


Structural Information from Single-molecule FRET Experiments Using the Fast Nano-positioning System.
Single-molecule Förster Resonance Energy Transfer (smFRET) can be used to obtain structural information on biomolecular complexes in real-time. Thereby, multiple smFRET measurements are used to localize an unknown dye position inside a protein complex by means of trilateration. In order to obtain quantitative information, the Nano-Positioning System (NPS) uses probabilistic data analysis to combine structural information from X-ray crystallography with single-molecule fluorescence data to calculate not only the most probable position but the complete three-dimensional probability distribution, termed posterior, which indicates the experimental uncertainty. The concept was generalized for the analysis of smFRET networks containing numerous dye molecules. The latest version of NPS, Fast-NPS, features a new algorithm using Bayesian parameter estimation based on Markov Chain Monte Carlo sampling and parallel tempering that allows for the analysis of large smFRET networks in a comparably short time. Moreover, Fast-NPS allows the calculation of the posterior by choosing one of five different models for each dye, that account for the different spatial and orientational behavior exhibited by the dye molecules due to their local environment. Here we present a detailed protocol for obtaining smFRET data and applying the Fast-NPS. We provide detailed instructions for the acquisition of the three input parameters of Fast-NPS: the smFRET values, as well as the quantum yield and anisotropy of the dye molecules. Recently, the NPS has been used to elucidate the architecture of an archaeal open promotor complex. This data is used to demonstrate the influence of the five different dye models on the posterior distribution.


Simple adjustment of the sequence weight algorithm remarkably enhances PSI-BLAST performance.
PSI-BLAST, an extremely popular tool for sequence similarity search, features the utilization of Position-Specific Scoring Matrix (PSSM) constructed from a multiple sequence alignment (MSA). PSSM allows the detection of more distant homologs than a general amino acid substitution matrix does. An accurate estimation of the weights for sequences in an MSA is crucially important for PSSM construction. PSI-BLAST divides a given MSA into multiple blocks, for which sequence weights are calculated. When the block width becomes very narrow, the sequence weight calculation can be odd. We demonstrate that PSI-BLAST indeed generates a significant fraction of blocks having width less than 5, thereby degrading the PSI-BLAST performance. We revised the code of PSI-BLAST to prevent the blocks from being narrower than a given minimum block width (MBW). We designate the modified application of PSI-BLAST as PSI-BLASTexB. When MBW is 25, PSI-BLASTexB notably outperforms PSI-BLAST consistently for three independent benchmark sets. The performance boost is even more drastic when an MSA, instead of a sequence, is used as a query. Our results demonstrate that the generation of narrow-width blocks during the sequence weight calculation is a critically important factor that restricts the PSI-BLAST search performance. By preventing narrow blocks, PSI-BLASTexB upgrades the PSI-BLAST performance remarkably. Binaries and source codes of PSI-BLASTexB (MBW = 25) are available at https://github.com/kyungtaekLIM/PSI-BLASTexB .


Kinetics of 5-aza-2'-deoxycytidine phosphorylation in mouse spleen and L1210 leukemic cell extracts.
Out of different nucleosides and deoxynucleosides testes for their ability to block the phosphorylation of labeled 5-aza-2'-deoxycytidine in the presence of ATP and the cell-free extract from mouse spleen only deoxycytidine and cytosine arabinoside depressed the reaction significantly. With the same system the phosphate donor specificity for 5-aza-2'-deoxycytidine and deoxycytidine was determined. All of the 5'-triphosphates used were less efficient donors with respect to the analogue than to the natural substrate. The apparent Michaelis constants for the phosphorylation of 5-aza-2'-deoxycytidine and deoxycytidine were 2.9 and 2.5 x 10(-5) M, respectively. Using the extract from L1210 leukemic cells the Km constant for 5-aza-2'-deoxycytidine was 6.4 x 10(-5) M and that for deoxycytidine 2.7 x 10(-5) M. The Ki constants with the spleen extract were 1.2 x 10(-3) M for 5-aza-2'-deoxycytidine and 5.8 x 10(-6) M for deoxycytidine. Both compounds acted as competitive inhibitors of one another.


Interactions between head blight pathogens: consequences for disease development and toxin production in wheat spikes.
Head blight (HB) is one of the most damaging diseases on wheat, inducing significant yield losses and toxin accumulation in grains. Fungal pathogens responsible for HB include the genus Microdochium, with two species, and the toxin producer genus Fusarium, with several species. Field studies and surveys show that two or more species can coexist within a same field and coinfect the same plant or the same spike. In the current study, we investigated how the concomitant presence of F. graminearum and another of the HB complex species influences the spike colonization and the toxin production by the fungi. To study these interactions, 17 well-characterized isolates representing five species were inoculated alone or in pairs on wheat spikes in greenhouse and field experiments. The fungal DNA in the grains was estimated by quantitative PCR and toxin contents (deoxynivalenol and nivalenol) by ultraperformance liquid chromatography-UV detection-tandem mass spectrometry. The responses of the different isolates to the presence of a competitor were variable and isolate specific more than species specific. The development of the most aggressive isolates was either unchanged or a slightly increased, while the development of the less aggressive isolates was reduced. The main outcome of the study was that no trend of increased toxin production was observed in coinoculations compared to single inoculations. On the contrary, the amount of toxin produced was often lower than expected in coinoculations. We thus conclude against the hypothesis that the co-occurrence of several HB-causing species in the same field might aggravate the risk linked to fusarium toxins in wheat production.


DNA supercoiling and aerobic regulation of transcription from the Klebsiella pneumoniae nifLA promoter.
Expression from the K. pneumoniae nifLA promoter is oxygen sensitive and is also inhibited by the DNA gyrase inhibitor coumermycin A1 under anaerobic growth conditions. The activity of this promoter was found to be highly sensitive to changes in DNA topology in vitro. Transcription was completely dependent on negative supercoiling at physiological salt concentrations although transcription from linear or fully relaxed closed circular templates was detectable at KCl concentrations lower than 50 mM. These observations suggest that aerobic regulation of nif transcription may be mediated through the level of DNA supercoiling.


Developmental and neurobehavioural toxicity study of arsenic on rats following gestational exposure.
To characterize developmental and behavioral alterations induced by arsenic exposure, Albino rats were exposed to arsenic (0, 1.5, 3.0 and 4.5 mg/kg/day/po) from gestation day 8 to till parturition and the offspring were observed over the first 3 postnatal weeks, until they were weaned on post-natal day (PND) 21. Once the pups were delivered (PND0), the treatment was discontinued. All pups were assessed for physical development, reflex development, strength and motor coordination from standard neurobehavioural developmental test batteries beginning on PND1. Gestational administration of arsenic at tested dose levels, showed no significant changes in the day of appearance of eye opening, startle reflex, negative geotaxis and spontaneous alteration performance in comparison to the control group. The number of live fetuses, mean fetal body weight and percentages of resorptions or malformations per litter were not affected by arsenic exposure. No treatment-related malformations or developmental variations were noted at any exposure level, suggesting that arsenic exposure at this dose level did not adversely affect behavioural endpoints of developmental toxicity.


Effects of Clostridium difficile toxin A on K562/A02 cell proliferation, apoptosis and multi-drug resistance.
The aim of the present study was to investigate the cytotoxic effect and multi-drug resistance (MDR) of Clostridium difficile toxin A (TcdA) on K562/A02 cells, and understand its underlying molecular pathways. K562/A02 cells were treated with TcdA at different concentrations for 24, 48 and 72 h, and the inhibition effect and drug resistance of TcdA on K562/A02 cell proliferation was assessed by methyl thiazolyl tetrazolium colorimetric assay. Furthermore, cell cycle-apoptosis was analyzed by flow cytometry, P-glycoprotein (P-gp) expression was determined by western blot analysis and caspase-3 activity was measured using a caspase-3 activity kit. TcdA inhibited K562/A02 cell proliferation in a time- and dose-dependent manner. The inhibition rate of K562/A02 cells reached 8.76±0.76, 28.55±0.43, 47.89±0.27, 58.08±0.06 and 57.70±0.79% following treatment with 50, 100, 200, 400 and 800 ng/ml TcdA, respectively, for 24 h. K562/A02 cells in the G0/G1 phase increased and cells in the S phase decreased following treatment with TcdA (P<0.05), and the apoptotic rates in the 200 and 400 ng/ml concentration groups were 14.05 and 22.89%, respectively. In addition, TcdA (50 ng/ml) significantly inhibited the proliferation of K562/A02 cells and reduced the half maximal inhibitory concentration of these drugs in combination with chemotherapy drugs. The reversal folds were 3.09, 2.89 and 2.79, respectively. Furthermore, TcdA treatment was associated with the upregulation of P-gp in K562/A02 cells, and caspase-3 activity was observed to increase in K562/A02 cells following TcdA treatment, when compared with untreated controls (P<0.05). These findings suggested that TcdA may be able to inhibit K562/A02 cell growth, induce cell apoptosis by decreasing P-gp levels and caspase-3 activation, and partially reverse MDR. Further studies are required to evaluate the potential of TcdA as a candidate for the chemotherapy of hematologic malignancies.


Nanostructure, effective properties, and deformation pattern of the cochlear outer hair cell cytoskeleton.
We consider the mechanical properties of the outer hair cell cytoskeleton. The cytoskeleton is represented as a set of microdomains of different sizes and orientations composed of actin filaments and spectrin crosslinks. An intermediate material between domains is also introduced. The domain characteristics are randomly generated and the histograms of the cytoskeleton stiffness moduli are obtained. We solve an inverse problem and estimate the stiffness of the crosslink and connective molecule in the intermediate material. We discovered a pattern of highly inhomogeneous deformation of the cytoskeleton where the circumferential strain is primarily determined by the deformation of the intermediate material.


Immunogold-EM analysis reveal brefeldin a-sensitive clusters of auxin in Arabidopsis root apex cells.
Immunogold electron microscopy (EM) study of Arabidopsis root apices analyzed using specific IAA antibody and high-pressure freeze fixation technique allowed, for the first time, vizualization of subcellular localization of IAA in cells assembled intactly within plant tissues. Our quantitative analysis reveals that there is considerable portion of IAA gold particles that clusters within vesicles and membraneous compartments in all root apex cells. There are clear tissue-specific and developmental differences of clustered IAA in root apices. These findings have significant consequences for our understanding of this small molecule which is controlling plant growth, development and behavior.


Effects of sleep deprivation on cardiac autonomic and pituitary-adrenocortical stress reactivity in rats.
A demanding life style, often associated with restricted time for sleep, is a growing problem in our society and may become a major health issue in the near future. Since the physiological stress system plays a critical role in coping with a challenge, it is important to know whether this system is affected by sleep loss. Although some information is available concerning the effect of sleep loss on the basal activity of the two main limbs of the stress system, the sympathetic-adrenomedullary (SAM) and the hypothalamic-pituitary-adrenocortical (HPA) axes, little is known about the effect of sleep loss on the subsequent response to a stressor. This study investigated the effects of sleep deprivation on cardiac autonomic and HPA axis (re)activity, under baseline conditions and in response to an acute emotional stressor (15-min of restraint). Rats were subjected to 48 h of sleep deprivation by placing them in slowly rotating wheels. Electrocardiographic recordings were performed via radiotelemetry and autonomic balance was quantified via time-domain indexes of heart rate variability. HPA axis activity was examined by collecting blood samples which were analyzed for plasma ACTH and corticosterone concentrations. The results show that sleep deprivation produced a tonic increase of heart rate and HPA axis activity. When the animals in a state of sleep debt were exposed to an acute restraint stress, a blunted parasympathetic antagonism was observed following sympathetic activation, together with an increased susceptibility to cardiac arrhythmias. The HPA axis response to restraint stress was also altered, but while pituitary ACTH response was attenuated, adrenal corticosterone release was unchanged, indicating an increased adrenocortical sensitivity to ACTH. The data show that sleep deprivation not only affects the baseline activity of the stress system, but it also alters its response to a subsequent stressor.


Zebrafish tenascin-W, a new member of the tenascin family.
A cDNA clone encoding tenascin-W, a novel member of the tenascin family, was isolated from a 20- to 28-h postfertilization (hpf) zebrafish cDNA library on the basis of the conserved epidermal growth factor-like domains represented in all tenascin molecules. An open reading frame of 2796 base pairs encodes a mature protein consisting of heptad repeats, a cysteine-rich amino terminal region, 3.5 epidermal growth factor-like repeats, five fibronectin type III homologous repeats, and a domain homologous to fibrinogen. These domains are the typical modular elements of molecules of the tenascin family. Sequence comparison demonstrated that TN-W shares homologies with the members of the tenascin family but is not a species homolog of any identified tenascin. The expression pattern of tn-w was analyzed by in situ hybridization in 1-day-old embryos, in 3-day-old larvae, and in juvenile zebrafish. At 24-25 hpf, tn-w mRNA was expressed in the lateral plate mesoderm, most conspicuously in the presumptive sclerotome. Migrating cells of sclerotomal and neural crest origins also showed high levels of expression. At 3 days, expression by sclerotomal and neural crest cells continued to be observed while expression in the somitic mesoderm was decreased. In juvenile fish, tn-w was expressed weakly by cells in the myosepta and, more strongly, by presumably nonneuronal cells in the dorsal root ganglia. In these tissues and at the same developmental stages, the expression of tn-w partially overlapped with the distribution of tn-c mRNA. In addition, tn-c was expressed in the central nervous system (CNS) and in the axial mesoderm, neither of which expressed tn-w at any of the age stages examined. The expression pattern of tn-w suggests an involvement in neural crest and sclerotome cell migration and in the formation of the skeleton. Similar and possibly overlapping functions could also be performed by tn-c, which appears to have additional functions during the development of the CNS.


Depressive symptoms and immune response to meningococcal conjugate vaccine in early adolescence.
Research findings in psychoneuroimmunology document reliable, bidirectional linkages among psychological processes, the nervous system, and the immune system. However, available data are based almost entirely on animal and adult human studies; the application to children and adolescents is uncertain. We capitalized on the experimental leverage provided by a routine vaccination to examine the link between mood symptoms and the immune response to a vaccine challenge in early adolescence. One hundred twenty-six 11-year-olds for whom vaccine response data were available were assessed at prevaccination and 4 weeks, 3 months, and 6 months following vaccination; self-report ratings of depression and anxiety as well as measures of psychosocial and somatic risk were assessed prior to vaccine response. Analyses indicated that children's internalizing mood symptoms were associated with elevated and persistently higher antibody responses, with evidence extending to two of the four serogroups. The associations remained after controlling for multiple possible confounders (social class, body mass index, sleep, psychosocial risk, and pubertal status). The observed enhanced vaccine response associated with depressive and anxious symptoms in early adolescence may reflect an important developmental difference in immune system-brain interplay between adults and children, and it underscores the need for further developmental studies of psychoneuroimmunology.


Identification of neuronal structures and pathways corresponding to clinical functioning in galactosemia.
Classic galactosemia (OMIM# 230400) is an autosomal recessive disorder due to galactose-1-phosphate uridyltransferase deficiency. Newborn screening and prompt treatment with a galactose-free diet prevent the severe consequences of galactosemia, but clinical outcomes remain suboptimal. Five men and five women with classic galactosemia (mean age = 27.2 ± 5.47 years) received comprehensive neurological and neuropsychological evaluations, electroencephalogram (EEG) and magnetic resonance imaging (MRI). MRI data from nine healthy controls (mean age = 30.22 ± 3.52 years) were used for comparison measures. Galactosemia subjects experienced impaired memory, language processing, visual-motor skills, and increased anxiety. Neurological examinations revealed tremor and dysarthria in six subjects. In addition, there was ataxia in three subjects and six subjects had abnormal gait. Mean full scale IQ was 80.4 ± 17.3. EEG evaluations revealed right-sided abnormalities in five subjects and bilateral abnormalities in one subject. Compared to age- and gender-matched controls, subjects with galactosemia had reduced volume in left cerebellum white matter, bilateral putamen, and left superior temporal sulcus. Galactosemia patients also had lower fractional anisotropy and higher radial diffusivity values in the dorsal and ventral language networks compared to the controls. Furthermore, there were significant correlations between neuropsychological test results and the T1 volume and diffusivity scalars. Our findings help to identify anatomic correlates to motor control, learning and memory, and language in subjects with galactosemia. The results from this preliminary assessment may provide insights into the pathophysiology of this inborn error of metabolism.


LyGDI is a promising biomarker for ovarian cancer.
LyGDI is an inhibitor of Rho protein activation by blocking its transformation between guanosine 5'-diphosphate- and guanosine 5'-triphosphate-bound states. The aim of this study was to investigate the usefulness of LyGDI as a biomarker for the detection of ovarian cancer, and its specificity and sensitivity were compared with those of cancer antigen 125 (CA125). The serum levels of LyGDI were determined by enzyme-linked immunosorbent assay in 42 patients with ovarian disease, including 30 ovarian cancers and 12 benign ovarian lesions, and 76 healthy controls. The expression of LyGDI was also evaluated by immunohistochemical staining in resected ovarian tissues of these patients. The serum LyGDI level of cancers was significantly greater than those of the benign and healthy groups (P = 0.002 and P < 0.0001, respectively), whereas no difference was observed between the benign and control groups (P = 0.889). Based upon receiver operating characteristic curve analysis, LyGDI levels were able to distinguish ovarian cancer from benign ovarian disease (P = 0.0001) and healthy control (P < 0.0001; areas under the receiver operating characteristic curves, 0.876 and 0.833, respectively). For ovarian cancers, 83.3% (25/30) or 80.0% (24/30) was identified by serum LyGDI (> or = 1.5 ng/mL) alone or by CA125 (>35 U/mL) alone. It is of particular importance to note that all cancer patients were identified by use of both markers, and the specificity was 83.3% for the benign group. Moreover, in early-stage cancers, 88.9% (8/9) had elevated serum LyGDI levels as compared with 44.4% (4/9) elevation of CA125 levels (P = 0.125). Immunohistochemical staining confirmed the expression of LyGDI on cancerous epithelial cells other than benign ovarian epithelium. These results suggest that LyGDI has significant potential as a marker for detection of ovarian cancer in the patients with ovarian enlargement, including detection of early-stage cancers.


Brain activity associated with Dual-task performance of Ankle motor control during cognitive challenge.
Skilled Ankle motor control is frequently required while performing secondary cognitively demanding tasks such as socializing and avoiding obstacles while walking, termed "Dual tasking." It is likely that Dual-task performance increases demand on the brain, as both motor and cognitive systems require neural resources. The purpose of this study was to use functional MRI to understand which brain regions are involved in resolving Dual-task interference created by requiring high levels of Ankle motor control during a cognitive task. Using functional MRI, brain activity was measured in sixteen young adults during performance of visually cued Ankle plantar flexion to a target (Ankle task), a cognitive task (Flanker task), and both tasks simultaneously (Dual task). Dual-task performance did not impact the Ankle task (p = 0.78), but did affect behavior on the Flanker task. Response times for both the congruent and incongruent conditions during the Flanker task were significantly longer (p < 0.001, p = 0.050, respectively), and accuracy for the congruent condition decreased during Dual tasking (p < 0.001). Activity in 3 brain regions was associated with Dual-task Flanker performance. Percent signal change from baseline in Brodmann area (BA) 5, BA6, and the left caudate correlated with performance on the Flanker task during the Dual-task condition (R2 = 0.261, p = 0.04; R2 = -0.258, p = 0.04; R2 = 0.303, p = 0.03, respectively). Performance of Ankle motor control may be prioritized over a cognitive task during Dual-task performance. Our work advances Dual-task research by elucidating patterns of whole brain activity for Dual tasks that require Ankle motor control during a cognitive task.


Direct demonstration of specific suppressor T cells in the mice tolerant to type III pneumococcal polysaccharide: two-step requirement for development of detectable suppressor cells.
Spleen cells from CAF1 mice made tolerant to type III pneumococcal polysaccharide (S3) with S3 coupled to syngeneic spleen cells (S3-SC) develop S3-specific suppressor T cells (Ts). These Ts could be demonstrated consistently only when spleen cells from tolerant mice were cultured in vitro with the specific antigen and the specific tolerogen. Spleen cells from normal mice cultured under the same conditions did not suppress the antibody response to S3. When different numbers of Ts were transferred to normal CAF1 mice, an unusual dose-effect pattern was observed. Maximal suppression of the S3 response occurred when relatively low numbers of Ts, 3 to 30 x 10(5) per recipient, were transferred, whereas larger numbers of cells, 150 x 10(5) per recipient, were not suppressive. These results indicate that a presumably T-independent antigen, S3, can activate antigen-specific Ts. These Ts exhibit unusual dose effects upon transfer and require both an in vivo induction period and in vitro activation for development of maximal activity. These latter observations suggest that S3 may activate a different population of T cells with suppressor function than do conventional T-dependent antigens. The loss of suppression observed when greater than optimal numbers of cells were transferred suggests that a second type of T cell, which has the ability to 'neutralize' the activity of S3-specific Ts, is also induced in the same spleen cell population.


Highly Enhanced Thermochromic Performance of VO2 Film Using "Movable" Antireflective Coatings.
The VO2 film with "movable" antireflective (AR) coating was initially designed and successfully prepared to deal with the challenges that VO2 faced. The "movable" AR layer, including water and other organic solvents, not only endowed VO2 with active-passive regulation mode but also dramatically enhanced the thermochromic performance. Furthermore, we combined solid and movable antireflection layer for further structural optimization, and the result turned out to be superior to any multilayer structure reported previously. We believe that this revolutionary concept of AR coating will open up a new avenue for low-cost smart window applications.


Improved Digit Span in Children after a 6-Week Intervention of Playing a Musical Instrument: An Exploratory Randomized Controlled Trial.
Previous studies have reported that music training not only improves children's musical skills, but also enhances their cognitive functions. However, there is a disagreement about what domain(s) might be affected. Moreover, effects of short-term (<several months) instrumental training have not been examined, although more basic studies have suggested neuroplasticity within several weeks. Consequently, the present exploratory pilot study investigated the effect of a six-week instrumental practice program (i.e., playing the keyboard harmonica) on children's cognitive functions using a randomized controlled trial. Forty children (aged 6-8 years) were randomly assigned to either the experimental group (n = 20), which received a 6-week (12-session) keyboard harmonica curriculum, or an untrained control group (n = 20). Different from traditional instrumental training, the curriculum did not use musical scores to emphasize creating association between sound (auditory modality) and finger movement (somato-motor system). Cognitive measurements included verbal ability, processing speed, working memory, and inhibitory control, which were administered before and after the curriculum in both groups. After the 6-week training, only the experimental group showed a significant improvement in the Digit Span test (especially in the Digit Span Backward) that measures working memory. However, no significant influences were found on the other cognitive tests. The result suggests that several weeks of instrumental music training may be beneficial to improving children's working memory. In addition, we used an inexpensive and portable keyboard harmonica; therefore, our instructional method is easy to apply in classrooms or other circumstances. If the method is applied to music lessons in schools or in the community, it may help improve children's working memory.


Sedentary lifestyle associated with mortality in rural patients with heart failure.
The incidence of mortality five years after the onset of symptomatic heart failure is about 50%. Lifestyle behaviors differ substantially and likely lead to prognostic differences. We sought to determine the factors associated with all-cause mortality in patients with heart failure, particularly the impact of a sedentary lifestyle on mortality. This is a secondary analysis of a randomized controlled trial (REMOTE-HF) to improve self-care through education and counseling ( N=602). We conducted an unadjusted Cox proportional hazards regression analysis with sedentary lifestyle as a predictor of mortality, then added depressive symptoms as a confounder. A Kaplan-Meier survival analysis assessed time to event comparing sedentary lifestyle. Cox models included variables of clinical relevance as well as all significant variables from baseline characteristics associated with all-cause mortality. The mean ± SD age was 66 ± 12.4 years, 41% were women, and 90% were of white race. There were 125 all-cause deaths over 24 months. Sedentary lifestyle was associated with a 75% increase in the expected hazard of all-cause mortality (hazards ratio 1.75; p = 0.003; 95% CI 1.21-2.54) after adjusting for moderate to severe depressive symptoms. Two Cox models showed an 89 and 95% increase, respectively, in all-cause mortality in sedentary participants holding all other variables constant. Sedentary lifestyle is strongly associated with all-cause mortality, independent of having moderate to severe depressive symptoms. Clinicians and researchers have an important role in promoting sustained and safe physical activity to improve survival. Other important modifiable targets to improve survival include depressive symptoms, low literacy, and low body mass index. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique Identifier: NCT00415545.


Approaches to intervention among children and adolescents.
An analysis of current dietary intakes of preschool and school children and adolescents belonging to poor income groups in India indicate that they suffer from deficiencies of several nutrients with associated clinical and functional consequences. The observed deficiencies include energy, calcium, iron, zinc, vitamin A, riboflavin, ascorbic acid, and folate. Some degree of protein deficiency is also present. The best strategy to correct the deficiencies of these nutrients is the food-based approach where nutrient-rich food supplements are formulated with nutrient-rich familiar foods and given to children at the household level. Another strategy for helping mothers and preschool children to achieve the recommended daily intakes is to fortify with micronutrients the supplementary foods currently targeted to them for improving their energy and protein intake. This can be achieved by expanding the current supplementary feeding program to school children and adolescents.


Large vessel vasculitis with myelodysplastic syndrome.
A 71-year-old woman presented with a high-grade fever, neck pain, anemia and thrombocytopenia. After performing further examinations, we concluded that she had simultaneously developed large vessel vasculitis and myelodysplastic syndrome (MDS). Although glucocorticoid administration improved her clinical symptoms, the MDS transformed into acute myeloid leukemia and she died one year after receiving the diagnosis. The occurrence of immune-mediated disorders in patients with MDS is a well-known phenomenon; however, large vessel vasculitis is a rare complication of MDS. Our case suggests that the association between systemic vasculitis and MDS may result in poor outcomes.


Active control of radiation from a piston set in a rigid sphere.
Active control of the sound radiated from a piston set in a rigid sphere with a set of control point sources around is considered in this paper, where the scattering sound field of the control sound from the rigid sphere has been taken into account to minimize the total radiated sound power. Analytic results of the sound power are obtained and numerical simulations show that it is possible to reduce the radiation from a small piston set in a rigid sphere similar to the size of a human head up to a certain frequency. It is found that the introduction of the scattering object makes significant differences from the active control without scattering objects. This being the case, the scattering object makes the active noise control easier. To increase the global reduction of sound-power output, the optimal number and locations of the control sources and the optimal number and locations of error sensors are discussed. Finally, experiments with one control source and one error sensor around a head simulator have been carried out to verify the simulation results.


Vital signs monitoring in hospitals at night.
Vital signs are important indicators of patients' clinical condition and inform required interventions. This article reports on a review of the literature on current practice, which showed that nurses' compliance with monitoring protocols is poor, particularly at night. This has important implications for patient safety and outcomes.


Intestinal cell apoptosis and Bcl-2 expression.
Programmed cell death (apoptosis) is a normal characteristic of cells with a limited life span like the enterocyte and the usual mode of death for proliferative crypt cells subjected to radiation or chemotherapy. The Bcl-2 proto-oncogene is considered a major regulator of apoptosis. We investigated the relationship of enterocyte apoptosis and Bcl-2 expression in rat intestine and tissue culture cells. Fragmentation of DNA and levels of Bcl-2 transcripts were evaluated in rat enterocyte fractions of the crypt-to-villus axis of differentiation and in IEC tissue culture cells. A low percentage of isolated nuclei from each enterocyte fraction showed features of DNA fragmentation, including crypt cells. Detectable DNA fragmentation was seen in IEC cells only when cells were subjected to long-term confluent culture conditions. Bcl-2 mRNA was not detected in isolated rat intestinal cells but was detected in IEC cells where its level increased with serum deprivation and long-term culture. We conclude that increased Bcl-2 expression may be important in rescue of proliferative enterocytes subjected to stress.


Reproductive outsourcing: an empirical ethics account of cross-border reproductive care in Canada.
Cross-border reproductive care (CBRC) can be defined as the movement from one jurisdiction to another for medically assisted reproduction (MAR). CBRC raises many ethical concerns that have been addressed extensively. However, the conclusions are still based on scarce evidence even considering the global scale of CBRC. Empirical ethics appears as a way to foster this ethical reflection on CBRC while attuning it with the experiences of its main actors. To better understand the 'in and out' situation of CBRC in Canada, we conducted an ethnographic study taking a 'critically applied ethics' approach. This article presents a part of the findings of this research, obtained by data triangulation from qualitative analysis of pertinent literature, participant observation in two Canadian fertility clinics and 40 semidirected interviews. Based on participants' perceptions, four themes emerged: (1) inconsistencies of the Canadian legal framework; (2) autonomy and the necessity to resort to CBRC; (3) safety and the management of CBRC individual risks; and (4) justice and solidarity. The interaction between these four themes highlights the problematic of 'reproductive outsourcing' that characterised the Canadian situation, a system where the controversial aspects of MAR are knowingly pushed outside the borders.


Molecular cloning and biochemical characterization of a myotoxin inhibitor from Bothrops alternatus snake plasma.
Phospholipases A(2) (PLA(2)s) are important components of Bothrops snake venoms, that can induce several effects on envenomations such as myotoxicity, inhibition or induction of platelet aggregation and edema. It is known that venomous and non-venomous snakes present PLA(2) inhibitory proteins (PLIs) in their blood plasma. An inhibitory protein that neutralizes the enzymatic and toxic activities of several PLA(2)s from Bothrops venoms was isolated from Bothrops alternatus snake plasma by affinity chromatography using the immobilized myotoxin BthTX-I on CNBr-activated Sepharose. Biochemical characterization of this inhibitory protein, denominated αBaltMIP, showed it to be a glycoprotein with Mr of ~24,000 for the monomeric subunit. CD spectra of the PLA(2)/inhibitor complexes are considerably different from those corresponding to the individual proteins and data deconvolution suggests that the complexes had a relative gain of helical structure elements in comparison to the individual protomers, which may indicate a more compact structure upon complexation. Theoretical and experimental structural studies performed in order to obtain insights into the structural features of αBaltMIP indicated that this molecule may potentially trimerize in solution, thus strengthening the hypothesis previously raised by other authors about snake PLIs oligomerization.


Hiccup and apparent myoclonus after hydrocodone: review of the opiate-related hiccup and myoclonus literature.
The author recently encountered a patient with hiccups, intermittently accompanied by apparent focal rhythmic diaphragmatic myoclonus after hydrocodone administration. Review of the literature disclosed a paucity of previous reports of hiccup, but many reports of myoclonus after opiate administration. A wide variety of opiates and routes of administration have been implicated, but high doses and the presence of other agents (antipsychotics, antiemetics, nonsteroidal antiinflammatory agents, antidepressants) may pose special risks. Review of the literature suggests three types of opiate-related myoclonus. Opiate-induced myoclonus (OIM) is often generalized and is either periodic or associated with rigidity. Opiate-induced myoclonus frequently occurs in the context of underlying medical conditions, D2 antagonist coadministration, or other drugs (nonsteroidal anti-inflammatory agents, antidepressants), and usually responds to either naloxone or benzodiazepines. Intrathecal OIM has not been linked to D2 antagonist coadministration or benzodiazepine responsiveness but may be associated with non-steroidal antiinflammatory agents. Opiate withdrawal myoclonus may be stimulus-sensitive, associated with D2 antagonist coadministration, and responsive to benzodiazepines and unresponsive to naloxone. There are several problems in interpreting the literature, and more study is needed. Opiatergic, serotonergic, dopaminergic, and other mechanisms are considered.


Inhibitory effect of androgen on the synthesis of proteinase F in the male mouse submandibular gland.
Androgenic regulation of one of the esteroproteinases (proteinase F) in the mouse submandibular gland was studied using specific antiserum. In contrast to esteroproteinases such as proteinases A, D or P-esterase, proteinase F content in male but not in female mice was increased by gonadectomy and decreased by the injection of various androgens. In-vivo incorporation of [3H]leucine into proteinase F in males was increased after castration and decreased by the injection of testosterone propionate; androgens inhibited the de-novo synthesis of proteinase F in male mice. The dose-response curves for testosterone propionate and time-courses following castration or after the injection of testosterone propionate were reciprocal between proteinase F and total esteroproteinase activity. Proteinase F, like other esteroproteinases in the submandibular gland of the mouse, was localized in granular convoluted tubular cells. These data indicate that granular convoluted tubular cells of the male mouse submandibular gland synthesize both androgen-inducible proteinases and androgen-inhibitory proteinase (proteinase F).


A rapid and efficient method for site-directed mutagenesis using one-step overlap extension PCR.
A rapid method is described to efficiently perform site-directed mutagenesis based on overlap extension polymerase chain reaction (OE-PCR). Two template DNA molecules in different orientations relative to only one universal primer were amplified in parallel. By choosing a high dilution of mutagenic primers it was possible to run an overlap extension PCR in only one reaction without purification of intermediate products. This method which we have named one-step overlap extension PCR (OOE-PCR) can in principle be applied to every DNA fragment which can be cloned into a multiple cloning site of any common cloning vector.


Targeting the Vessel Underdogs: Therapeutic Approaches for Microvessel Dysfunction in the Heart.
From an obscure and overlooked beginning, the function of the microvessels in the heart has received increasing attention after the Women's Ischemia Syndrome Evaluation study concluded roughly a decade ago. This review defines the contribution of the coronary microcirculation in the development of heart disease and focuses on the therapeutic methods to reverse coronary microvascular dysfunction. Tissue engineering approaches in the past have largely neglected vascular cells in the attempts to design augmented myocardial tissue, but groups are now making advances that incorporate a functional microcirculation with cardiomyocytes that may advance this line of research. This review covers the definition and classification of coronary microvascular disease, as well as the successful (and unsuccessful) therapeutic approaches in the literature.


CO oxidation catalyzed by oxide-supported Au25(SR)18 nanoclusters and identification of perimeter sites as active centers.
In this work, we explore the catalytic application of atomically monodisperse, thiolate-protected Au(25)(SR)(18) (where R = CH(2)CH(2)Ph) nanoclusters supported on oxides for CO oxidation. The solution phase nanoclusters were directly deposited onto various oxide supports (including TiO(2), CeO(2), and Fe(2)O(3)), and the as-prepared catalysts were evaluated for the CO oxidation reaction in a fixed bed reactor. The supports exhibited a strong effect, and the Au(25)(SR)(18)/CeO(2) catalyst was found to be much more active than the others. Interestingly, O(2) pretreatment of the catalyst at 150 °C for 1.5 h significantly enhanced the catalytic activity. Since this pretreatment temperature is well below the thiolate desorption temperature (~200 °C), the thiolate ligands should remain on the Au(25) cluster surface, indicating that the CO oxidation reaction is catalyzed by intact Au(25)(SR)(18)/CeO(2). We further found that increasing the O(2) pretreatment temperature to 250 °C (above the thiolate desorption temperature) did not lead to any further increase in activity at all reaction temperatures from room temperature to 100 °C. These results are in striking contrast with the common thought that surface thiolates must be removed-as is often done in the literature work-before the catalyst can exert high catalytic activity. The 150 °C O(2)-pretreated Au(25)(SR)(18)/CeO(2) catalyst offers ~94% CO conversion at 80 °C and ~100% conversion at 100 °C. The effect of water vapor on the catalytic performance is also investigated. Our results imply that the perimeter sites of the interface of Au(25)(SR)(18)/CeO(2) should be the active centers. The intact structure of the Au(25)(SR)(18) catalyst in the CO oxidation process allows one to gain mechanistic insight into the catalytic reaction.


Evaluation of non-invasive multispectral imaging as a tool for measuring the effect of systemic therapy in Kaposi sarcoma.
Diffuse multi-spectral imaging has been evaluated as a potential non-invasive marker of tumor response. Multi-spectral images of Kaposi sarcoma skin lesions were taken over the course of treatment, and blood volume and oxygenation concentration maps were obtained through principal component analysis (PCA) of the data. These images were compared with clinical and pathological responses determined by conventional means. We demonstrate that cutaneous lesions have increased blood volume concentration and that changes in this parameter are a reliable indicator of treatment efficacy, differentiating responders and non-responders. Blood volume decreased by at least 20% in all lesions that responded by clinical criteria and increased in the two lesions that did not respond clinically. Responses as assessed by multi-spectral imaging also generally correlated with overall patient clinical response assessment, were often detectable earlier in the course of therapy, and are less subject to observer variability than conventional clinical assessment. Tissue oxygenation was more variable, with lesions often showing decreased oxygenation in the center surrounded by a zone of increased oxygenation. This technique could potentially be a clinically useful supplement to existing response assessment in KS, providing an early, quantitative, and non-invasive marker of treatment effect.


Severe lung involvement in systemic scleromyxoedema: a highly unusual finding.
Scleromyxoedema is a rare systemic disorder characterized by a lichenoid papular rash. Although scleromyxoedema can involve any organ, very few cases of pulmonary involvement have been reported. Moreover, there are no reports in the literature on treatment of this condition, especially with lung transplantation. The authors report a case of scleromyxoedema in a young man with neurological, skin and respiratory involvement, the latter being mainly characterized by pulmonary emphysema. Due to the serious respiratory compromise, and to the stability of the systemic lesions, a bilateral lung transplantation was performed with successful results at 4.5 yrs. In conclusion, lung transplantation may be required in patients with severe respiratory failure caused by scleromyxoedema.


Lung and diaphragm protective ventilation: a synthesis of recent data.
: To adhere to the Hippocratic Oath, to 'first, do no harm', we need to make every effort to minimize the adverse effects of mechanical ventilation. Our understanding of the mechanisms of ventilator-induced lung injury (VILI) and ventilator-induced diaphragm dysfunction (VIDD) has increased in recent years. Research focuses now on methods to monitor lung stress and inhomogeneity and targets we should aim for when setting the ventilator. In parallel, efforts to promote early assisted ventilation to prevent VIDD have revealed new challenges, such as titrating inspiratory effort and synchronizing the mechanical with the patients' spontaneous breaths, while at the same time adhering to lung-protective targets. This is a narrative review of the key mechanisms contributing to VILI and VIDD and the methods currently available to evaluate and mitigate the risk of lung and diaphragm injury. Implementing lung and diaphragm protective ventilation requires individualizing the ventilator settings, and this can only be accomplished by exploiting in everyday clinical practice the tools available to monitor lung stress and inhomogeneity, inspiratory effort, and patient-ventilator interaction.


RETICULOENDOTHELIAL FUNCTION AND THE IMMUNE RESPONSE.
Hyperphagocytic activity of the reticuloendothelial system induced in mice by the injection of glucan is associated with a significant increase in the primary and secondary immune responsiveness of these animals to sheep erythrocytes. Conversely, the administration of an agent which reduces endothelial phagocytosis is associated with significant depression of both primary and secnation of both factors.


Pediatric Post-Traumatic Headache and Implications for Return to Sport: A Narrative Review.
Headache attributed to mild traumatic injury of the head (aka: mild traumatic brain injury, mTBI), frequently abbreviated to Post-Traumatic Headache (PTH), is one of the most common and disabling symptoms after a head injury. PTH often phenotypes to migraine. Evidence for treating PTH in the pediatric population is limited. Widely accepted guidelines do not exist to aid the clinician and there are currently no placebo-controlled trials for the pharmacologic management of PTH in this age group. Recommendations for when to return a child or adolescent to sport if they develop and/or are being treated for persistent PTH (PPTH) are lacking. The objective of this narrative review is to review the implications of returning an adolescent with PPTH to sport. Pediatric neurologists with special qualification in headache collaborated on this narrative review. Literature was searched up until Oct 2019 for articles pertaining to PTH, concussion, mTBI, and the return of a pediatric athlete to sport after mTBI. Article inclusion was at the discretion of the authors. There was author consensus regarding all recommendations made. The authors recommend that strict adherence to the guidelines that return to sport cannot occur until a child is symptom free at rest, off any medication, may be unreasonable in certain situations. Symptom stability is the proposed new concept for return to sport.


Rapid enumeration of respiratory viruses.
Virus detection and enumeration has become increasingly important in fields ranging from medicine and biotechnology to environmental science. Although there are a wide variety of techniques that can be used to count viruses, there is demand for a rapid and more accurate means for virus enumeration. In this work, the performance of a flow cytometer that was designed and custom-built specifically for rapid detection of single viruses was evaluated. The instrument, designated a single nanometric particle enumerator (SNaPE), was characterized and calibrated using fluorescent polystyrene nanospheres. The reliability of the instrument with respect to virus enumeration was demonstrated for three medically relevant viruses, adenovirus-5, respiratory syncytial virus, and influenza A, treated with a fluorescent nucleotide stain. In each case, the SNaPE yielded a virus particle concentration consistent with, but slightly lower than, transmission electron microscopy (TEM) results, as expected. In addition, on the basis of calibration of signal intensity, the average peak height for a given virus was correlated with genome size, as expected. In contrast to time-consuming analyses such as TEM and plaque titers, SNaPE analysis of pure virus samples (including sample handling, data collection, and data processing) can be completed within 1 h.


Dithiazolylthienothiophene Bisimide: A Novel Electron-Deficient Building Unit for N-Type Semiconducting Polymers.
N-type (electron-transporting) semiconducting polymers are essential materials for the development of truly plastic electronic devices. Here, we synthesized for the first time dithiazolylthienothiophene bisimide (TzBI), as a new family for imide-based electron-deficient π-conjugated systems, and semiconducting polymers by incorporating TzBI into the π-conjugated backbone as the building unit. The TzBI-based polymers are found to have deep frontier molecular orbital energy levels and wide optical bandgaps compared to the dithienylthienothiophene bisimide (TBI) counterpart. It is also found that TzBI can promote the π-π intermolecular interactions of the polymer backbones relative to TBI most probably because the thiazole ring, which replaced the thiophene ring, at the end of the framework gives a more coplanar backbone. In fact, TzBI-based polymers function as the n-type semiconducting material in both organic field-effect transistor (OFET) and organic photovoltaic (OPV) devices. Notably, one of the TzBI-based polymers provides a power conversion efficiency of 3.3% in the all-polymer OPV device, which could be high for a low-molecular-weight polymer (<10 kDa). Interestingly, while many of the n-type semiconducting polymers utilized in OPVs have narrow bandgaps, the TzBI-based polymers have wide bandgaps. This is highly beneficial for complementing the visible to near-IR light absorption range when blended with p-type narrow bandgap polymers that have been widely developed in the last decade. The results demonstrate great promise and possibility of TzBI as the building unit for n-type semiconducting polymers.


Influence of prior intravenous thrombolysis on outcome after failed mechanical thrombectomy: ETIS registry analysis.
Despite constant improvements in recent years, sufficient reperfusion after mechanical thrombectomy (MT) is not reached in up to 15% of patients with large vessel occlusion stroke (LVOS). The outcome of patients with unsuccessful reperfusion after MT especially after intravenous thrombolysis (IVT) use is not known. We investigated the influence of initial IVT in this particular group of patients with failed intracranial recanalization. We conducted a retrospective analysis of the Endovascular Treatment in Ischemic Stroke (ETIS) registry from January 2015 to December 2019. Patients presenting with LVOS of the anterior circulation and final modified Thrombolysis in Cerebral Infarction score (mTICI) of 0, 1 or 2a were included. Posterior circulation, isolated cervical carotid occlusions and successful reperfusions (mTICI 2b, 2c or 3) were excluded. The primary endpoint was favorable outcome (modified Rankin Scale score of 0-2) after 3 months. Secondary endpoints were safety outcomes including mortality, any intracranial hemorrhage (ICH), parenchymal hematoma (PH) and symptomatic intracranial hemorrhage (sICH) rates. Among 5076 patients with LVOS treated with MT, 524 patients with insufficient recanalization met inclusion criteria, of which 242 received IVT and 282 did not. Functional outcome was improved in the MT+IVT group compared with the MT alone group, although the difference did not reach statistical significance (23.0% vs 12.9%; adjusted OR=1.82; 95% CI 0.98 to 3.38; p=0.058). However, 3 month mRS shift analysis showed a significant benefit of IVT (adjusted OR=1.68; 95% CI 1.56 to 6.54). ICH and sICH rates were similar in both groups, although PH rate was higher in the MT+IVT group (adjusted OR=3.20; 95% CI 1.56 to 6.54). Among patients with LVOS in the anterior circulation and unsuccessful MT, IVT was associated with improved functional outcome even after unsuccessful MT. Despite recent trials questioning the place of IVT in the LVOS reperfusion strategy, these findings emphasize a subgroup of patients still benefiting from IVT.


Enzymatic barriers to peptide and protein absorption.
Continuing advances in biotechnology promise to provide a large number of peptides and proteins that would significantly expand the range of pharmaceuticals to treat diseases now poorly controlled. Even at this early stage, it is clear that the success of these entities as drugs of the future would depend, at least in part, on the success in overcoming the obstacles in their delivery. Chief among these are the ubiquitous enzymatic barriers. These include the site of administration, where the peptide is placed, the vascular endothelium that peptides must cross to enter the circulation, the blood that distributes the peptide to its target site, and the liver and kidneys where the peptide is metabolized and eliminated, respectively. The review examines: (1) the nature and efficiency of the enzymatic barriers in degrading peptides and proteins at various absorption sites, and (2) the strategies that can be used to perturb these barriers. These sites include the subcutaneous and intramuscular spaces and the intestinal, nasal, buccal, rectal, vaginal, and ocular surfaces.


Protective Effect of Chokeberry (Aronia melanocarpa L.) Extract against Cadmium Impact on the Biomechanical Properties of the Femur: A Study in a Rat Model of Low and Moderate Lifetime Women Exposure to This Heavy Metal.
The hypothesis that the consumption of Aronia melanocarpa berries (chokeberries) extract, recently reported by us to improve bone metabolism in female rats at low-level and moderate chronic exposure to cadmium (1 and 5 mg Cd/kg diet for up to 24 months), may increase the bone resistance to fracture was investigated. Biomechanical properties of the neck (bending test with vertical head loading) and diaphysis (three-point bending test) of the femur of rats administered 0.1% aqueous chokeberry extract (65.74% of polyphenols) or/and Cd in the diet (1 and 5 mg Cd/kg) for 3, 10, 17, and 24 months were evaluated. Moreover, procollagen I was assayed in the bone tissue. The low-level and moderate exposure to Cd decreased the procollagen I concentration in the bone tissue and weakened the biomechanical properties of the femoral neck and diaphysis. Chokeberry extract administration under the exposure to Cd improved the bone collagen biosynthesis and femur biomechanical properties. The results allow for the conclusion that the consumption of chokeberry products under exposure to Cd may improve the bone biomechanical properties and protect from fracture. This study provides support for Aronia melanocarpa berries being a promising natural agent for skeletal protection under low-level and moderate chronic exposure to Cd.


Femtosecond x-ray streak camera based on photoelectron filter technology for laser fusion.
A femtosecond x-ray streak camera based on photoelectron filter technology is reported in this paper. Photoelectrons are collimated through the slit and channel of the photoelectron filter, so that transit time spread and space charge effect of electrons are reduced. A planar-focusing high-voltage electron-optical system is designed to match the filter. The channel length of the filter is 300 μm, and the slit width is 20 μm. The streak tube using the photoelectron filter is 273 mm in length, and the extraction field value between the Au photocathode and the filter is 10 kV/mm. An experimental platform is set up to calibrate the streak camera, which is excited by a 266 nm, 130 fs UV laser. The experimental results show that temporal resolution is 357 fs and dynamic range is 182:1 of this developed camera.


Resistin reinforces interferon λ-3 to eliminate hepatitis C virus with fine-tuning from RETN single-nucleotide polymorphisms.
The effect of resistin (RETN) on the response to anti-HCV therapy remains unclear. A prospective cohort study was performed using 655 consecutive HCV patients, of whom 513 had completed a course of interferon-based therapy. Multivariate and GEE analyses revealed four RETN single-nucleotide polymorphisms (SNPs), rs34861192, rs3219175, rs3745367 and rs1423096, to be synergistically associated with resistin levels. After adjusting for co-factors such as interferon λ-3 (IFNL3)-rs12979860, the resistin level and the hyper-resistinemic genotype at the 4 RETN SNPs were positively and negatively associated with a sustained virological response (SVR), respectively. RETN-rs3745367 was in linkage disequilibrium with IFNL3-rs12979860. Compared to non-SVR patients, SVR patients had higher levels of pre-therapy resistin, primarily originating from intrahepatic lymphocytes, stellate cells, Kupffer cells, hepatic progenitor cells and hepatocytes. This difference diminished over the course of therapy, as only SVR patients exhibited a 24-week post-therapy decrease in resistin. Both resistin and IFNL3 mRNAs were upregulated, but only resistin mRNA was upregulated by recombinant resistin in peripheral blood mononuclear cells with and without hyper-resistinemic genotypes of the 4 RETN SNPs, respectively. Fine-tuned by RETN SNPs, intrahepatic, multi-cellular resistin reinforced IFNL3 in eliminating HCV via immunomodulation to counteract pro-inflammation. These results encourage the development of novel resistin-targeted anti-viral agents.


An interesting case of peripheral vascular disease, vascular reperfusion, and subsequent development of pain due to Paget's disease of bone.
To present a case of Paget's disease of bone that was unmasked after vascular reperfusion. In this case study, we review the presentation, evaluation, diagnosis, and management of a patient with Paget's disease and peripheral vascular disease. A 79-year-old-woman with a history of coronary artery heart disease and recent finding of a T5 compression fracture was hospitalized for evaluation of right lower extremity claudication. Angiography demonstrated a focal complete occlusion of the distal right femoral and popliteal arteries. A self-expanding stent was placed in the distal femoral and popliteal arteries. Approximately 48 hours after the procedure, the patient developed severe, right lower leg pain. On endocrine evaluation, the patient was found to have clinical signs suggesting Paget's disease of bone, which was subsequently confirmed by imaging. This patient's development of severe pain following reperfusion of distal femoral and popliteal arteries is in keeping with the known and aforementioned hypervascularity of pagetic bone. The finding of increased warmth over an area of skeletal deformation should always raise the possibility of Paget's disease of bone.


Comparison of primary and delayed wound closure of dog-bite wounds.
Primary bite wound suturing in the emergency department remains controversial in some cases. We conducted a study to investigate the infection rate and cosmetic appearance between primary wound closure and delayed wound closure in dog bite wounds in humans. All patients with bite wounds were treated with oral antibiotic medications. We adopted a randomized cohort study, dividing the patients who needed wound closure into two groups: 60 patients for primary closure, and 60 patients for delayed closure, and compared the infection rate and wound cosmetic appearance scores. In the primary closure group, four people (6.7%) developed a wound infection without systemic infection. In the delayed closure group, three people (5%) developed a wound infection (p = 0.093), but there were not any patients that developed a systemic infection. Thirty-three patients (55%) in the primary closure group had optimal cosmetic scores, whereas 20 patients (33.3%) in the delayed closure group had optimal cosmetic scores (p = 0.012). Although primary wound closure for dog bites may be associated with a higher infection rate, the cosmetic appearance after primary closure was still acceptable.


The effectiveness of acupuncture for chronic pain with depression: A systematic review protocol.
Chronic pain is a major public health problem and 30% to 45% of sufferers experience severe depression. Acupuncture is often used to treat both depression and a range of pain disorders. We aim to conduct a systematic review of randomized controlled trials (RCTs) to evaluate the efficacy of acupuncture for patients experiencing chronic pain with depression. To identify relevant RCTs, the following databases will be searched electronically from their inception to July 1, 2017: PubMed, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, the Allied and Complementary Medicine Database, the Cumulative Index to Nursing and Allied Health Literature, Chinese medical databases, and others. Manual retrieval will also be conducted. RCTs that evaluated acupuncture as the sole or adjunct treatment for patients with chronic pain and depression will be included. The primary outcomes will be based on a visual analog pain measurement scale and the Hamilton Depression Scale. The secondary outcomes will include scores on a numerical rating scale, verbal rating scale, and the Hospital Anxiety and Depression Scale. The study selection, data extraction, and study quality evaluation will be performed independently by 2 researchers. If the data permit, meta-analysis will be performed using RevMan V5.3 statistical software. If the data are not appropriate for meta-analysis, descriptive analysis or subgroup analysis will be conducted. The methodological quality of the included trials will be assessed using the Cochrane risk-of-bias criteria and the Standards for Reporting Interventions in Controlled Trials of Acupuncture checklist. This study will provide a high-quality synthesis of current evidence of acupuncture for chronic pain with depression from several scales including visual analog pain measurement scale, the Hamilton Depression Scale, a numerical rating scale, verbal rating scale and the Hospital Anxiety and Depression Scale. The conclusion of our study will provide updated evidence to judge whether acupuncture is an effective intervention for patients suffered from chronic pain with depression.


Protective effect of medicinal fungus Xylaria nigripes mycelia extracts against hydrogen peroxide-induced apoptosis in PC12 cells.
Xylaria nigripes ( XN) is a medicinal fungus that was used traditionally as a diuretic, nerve tonic, and for treating insomnia and trauma. In this study, we elucidated possible mechanisms of neuroprotective effects of XN mycelia extracts. XN mycelia were produced by fermentation. Hot water extract and 70% ethanol extract of XN mycelia were evaluated on hydrogen peroxide (H2O2)-induced apoptosis in PC12, a rat pheochromocytoma cell line. Both XN extracts effectively protected PC12 cells against H2O2-induced cell damage by inhibiting release of lactate dehydrogenase, decreasing DNA damage, restoring mitochondrial membrane potential, and arresting abnormal apoptosis through upregulation of Bcl-2 and downregulation of Bax and caspase 3. Compared to water extract, ethanol extract showed not only greater neuroprotective effects but also a higher antioxidant activity by scavenging DPPH radicals, inhibiting lipid peroxidation, and reducing power. High phenolic content and antioxidant activity may provide the neuroprotective properties of XN ethanol extract.


Surgical treatment of lumbar stenosis in achondroplasia.
The authors conducted a study to evaluate the results of a unique surgical procedure for treating primary lumbar stenosis in patients with achondroplasia, based on its distorted anatomical dimensions. A consecutive single-center series of 36 achondroplastic dwarfs with symptomatic lumbar stenosis underwent dynamic lumbar myelography to determine the most stenotic lumbar segment. This level was surgically decompressed by selective widening of the lumbar interapophyseolaminar diameter; laminectomy was not performed. The L2-3 level was decompressed in 97% of the cases and the L1-2 and L3-4 levels in 58 and 61%, respectively. Lower lumbar levels were rarely affected by stenosis. Stenosis typically did not occur at the level of the lamina, where the pseudoscalloping of the vertebral body compensates for the spinal narrowing, obviating the need for laminectomy. Complete relief of symptoms was demonstrated in 25 (71.4%) of 35 patients. Tolerable disease remained in eight patients (22.9%) postoperatively. In two cases (5.7%) surgery resulted in no benefit. One case was lost to follow up. The presence of a lumbar epidural hematoma complicated one procedure. In this series the interapophyseolaminar decompression was demonstrated to be an effective and safe procedure for the treatment of symptomatic stenosis in achondroplasia. The upper lumbar segments, particularly the L2-3 level, were most frequently involved. Dynamic lumbar myelography proved mandatory in demonstrating the symptomatic level.


Erratum to: Upstream signalling of mTORC1 and its hyperactivation in type 2 diabetes (T2D).
The original version of this article unfortunately contained typographical errors in the text and figures. This article has been updated to correct these errors as red highlighting in this pages.


Generalized cable equation model for myelinated nerve fiber.
Herein, the well-known cable equation for nonmyelinated axon model is extended analytically for myelinated axon formulation. The myelinated membrane conductivity is represented via the Fourier series expansion. The classical cable equation is thereby modified into a linear second order ordinary differential equation with periodic coefficients, known as Hill's equation. The general internal source response, expressed via repeated convolutions, uniformly converges provided that the entire periodic membrane is passive. The solution can be interpreted as an extended source response in an equivalent nonmyelinated axon (i.e., the response is governed by the classical cable equation). The extended source consists of the original source and a novel activation function, replacing the periodic membrane in the myelinated axon model. Hill's equation is explicitly integrated for the specific choice of piecewise constant membrane conductivity profile, thereby resulting in an explicit closed form expression for the transmembrane potential in terms of trigonometric functions. The Floquet's modes are recognized as the nerve fiber activation modes, which are conventionally associated with the nonlinear Hodgkin-Huxley formulation. They can also be incorporated in our linear model, provided that the periodic membrane point-wise passivity constraint is properly modified. Indeed, the modified condition, enforcing the periodic membrane passivity constraint on the average conductivity only leads, for the first time, to the inclusion of the nerve fiber activation modes in our novel model. The validity of the generalized transmission-line and cable equation models for a myelinated nerve fiber, is verified herein through a rigorous Green's function formulation and numerical simulations for transmembrane potential induced in three-dimensional myelinated cylindrical cell. It is shown that the dominant pole contribution of the exact modal expansion is the transmembrane potential solution of our generalized model.


Functions of the ATP hydrolysis subunits (RecB and RecD) in the nuclease reactions catalyzed by the RecBCD enzyme from Escherichia coli.
The RecBCD enzyme from Escherichia coli is an ATP-dependent nuclease and helicase. Two of its subunits, the RecB and RecD proteins, are DNA-dependent ATPases. We have purified RecB and RecD proteins with mutations in their consensus ATP binding sites to study the functions of these subunits in the ATP-dependent nuclease activities of RecBCD. Reconstituted heterotrimeric enzymes were prepared by mixing wild-type RecB or RecB-K29Q mutant protein (RecB*) with purified RecC protein, and with a histidine-tagged wild-type RecD (hD) or mutant hRecD-K177Q (hD*) protein. RecBCD and all four reconstituted enzymes (wild-type, two single mutants, and the double mutant) cleave a single-stranded DNA oligomer substrate (25-mer) in the absence of ATP at rates of 0.03 to 0.06 min-1. The nuclease reaction catalyzed by RecB*ChD* is not stimulated significantly by ATP, while the reactions catalyzed by RecBCD, RecBChD, RecBChD*, and RecB*ChD are 300 to 3000 fold faster in the presence of 0.5 mM ATP. RecB*ChD* also has very low ATP hydrolysis activity (approximately 10(3)-fold less than RecBCD), as do the individual mutant RecB* and hRecD* proteins (approximately 100-fold less than RecB or hRecD). The products from the ATP-stimulated nuclease reaction with the oligomer substrate suggest a mechanism where two DNA molecules bind to the enzyme in opposite orientations and are cleaved by the nuclease active site. Cleavage towards the 3'-end of one oligomer (observed with RecBChD*) depends on the wild-type RecB subunit, while RecD-dependent cleavage (observed with RecB*ChD) occurs towards the 5'-end of the second bound oligomer.


Dementia associated with psychiatric disorders.
Functional psychiatric disorders are associated with a variety of cognitive deficits and, in some instances, severe cognitive impairment. This paper reviews the cognitive profile of patients with schizophrenia, depression, bipolar and anxiety disorders, as well as the longitudinal course and clinical outcome of the cognitive impairment associated with these conditions. The paper also discusses some of the mechanisms that may contribute to the expression of the cognitive deficits in these disorders and their potential relationship with common causes of dementia.


Quantitative Magnetic Resonance Imaging to Assess Progression and Rupture Risk of Aortic Aneurysms: A Scoping Review.
In current practice, the diameter of an aortic aneurysm is utilized to estimate the rupture risk and decide upon timing of elective repair, although it is known to be imprecise and not patient-specific. Quantitative magnetic resonance imaging (MRI) enables the visualization of several biomarkers that provide information about processes within the aneurysm and may therefore facilitate patient-specific risk stratification. We performed a scoping review of the literature on quantitative MRI techniques to assess aortic aneurysm progression and rupture risk, summarized these findings, and identified knowledge gaps. Literature concerning primary research was of interest and the medical databases PubMed, Scopus, Embase, and Cochrane were systematically searched. This study used the PRISMA protocol extension for scoping reviews. Articles published between January 2010 and February 2023 involving animals and/or humans were included. Data were extracted by 2 authors using a predefined charting method. A total of 1641 articles were identified, of which 21 were included in the scoping review. Quantitative MRI-derived biomarkers were categorized into hemodynamic (8 studies), wall (5 studies) and molecular biomarkers (8 studies). Fifteen studies included patients and/or healthy human subjects. Animal models were investigated in the other 6 studies. A cross-sectional study design was the most common, whereas 5 animal studies had a longitudinal component and 2 studies including patients had a prospective design. A promising hemodynamic biomarker is wall shear stress (WSS), which is estimated based on 4D-flow MRI. Molecular biomarkers enable the assessment of inflammatory and wall deterioration processes. The ADAMTS4-specific molecular magnetic resonance (MR) probe showed potential to predict abdominal aortic aneurysm (AAA) formation and rupture in a murine model. Wall biomarkers assessed using dynamic contrast-enhanced (DCE) MRI showed great potential for assessing AAA progression independent of the maximum diameter. This scoping review provides an overview of quantitative MRI techniques studied and the biomarkers derived from them to assess aortic aneurysm progression and rupture risk. Longitudinal studies are needed to validate the causal relationships between the identified biomarkers and aneurysm growth, rupture, or repair. In the future, quantitative MRI could play an important role in the personalized risk assessment of aortic aneurysm rupture. The currently used maximum aneurysm diameter fails to accurately assess the multifactorial pathology of an aortic aneurysm and precisely predicts rupture in a patient-specific manner. Quantitative magnetic resonance imaging (MRI) enables the detection of various quantitative parameters involved in aneurysm progression and subsequent rupture. This scoping review provides an overview of the studied quantitative MRI techniques, the biomarkers derived from them, and recommendations for future research needed for the implementation of these biomarkers. Ultimately, quantitative MRI could facilitate personalized risk assessment for patients with aortic aneurysms, thereby reducing untimely repairs and improving rupture prevention.


Review of the novelties presented at the 27th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (II).
The new insights presented at the 5th Joint Triennial Congress of the European and Americas Committees on Treatment and Research in Multiple Sclerosis (ECTRIMS and ACTRIMS) held in Amsterdam, the Netherlands, 19-22 October 2011, have been summarized at the fourth edition of Post-ECTRIMS meeting held in Madrid in November 2011. Regional grey-matter atrophy is more sensitive to cognitive impairment than global grey-matter atrophy measures. In patients with clinically isolated syndrome cognitive impairment does not predict conversion to multiple sclerosis (MS) after 5-years of follow-up. Focusing on central nervous system plasticity and functional reorganization in MS, an early intervention can improve clinical aspects and enhances brain plasticity. Preservation of a potential for plasticity provides a rationale for rehabilitation interventions even in later stages of disease. Therapeutical strategies have focused on stem cell-mediated remyelination and immunomodulation functions, on cellular infiltration into the brain, and on new ways for immuno-modulation for the development of future therapies in MS. Encouraging findings from clinical trials with current and emerging disease-modifying therapy being developed was also a key theme at this edition. Positive results have been reported for rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab, teriflunomide, BG-12, and laquinimod, including a favorable safety profile. Since armamentarium for the treatment of MS is fast increasing, concerns exist about the risk of severe adverse events with their use. This aspect reinforces the importance of disease registries as a proactive tool for monitoring drug safety in the post-approval setting.


Effects of Kamishoyosan, a Traditional Japanese Kampo Medicine, on Pain Conditions in Patients with Intractable Persistent Dentoalveolar Pain Disorder.
There are patients who suffer from persistent dentoalveolar pain disorder (PDAP) which is a pain of the teeth, either dentoalveolar pain or nonodontogenic toothache, and its cause has not yet been identified. An effective intervention for PDAP has not yet been established. Interventions for patients with PDAP are generally pharmacological treatments such as antidepressants, anticonvulsants, and pregabalin. However, these medicines are not always effective for patients. The pain disorder in the orofacial region including temporomandibular disorder (TMD) and PDAP was effectively treated with our original exercise therapy. However, we did observe some intractable cases of PDAP even when our original exercise therapy was used. This paper presents our findings in which Kamishoyosan improved the pain intensity in 14 out of 15 PDAP patients refractory to our original exercise therapy.


Dual-Domain Calibration Transfer Using Orthogonal Projection.
We report the use of dual-domain regression models, which were built utilizing a wavelet prism decomposition and paired with transfer by orthogonal projection, for the calibration transfer of near-infrared (NIR) spectra. The new method is based on obtaining specific frequency components for a spectrum via wavelet analysis, projecting the frequency components of the primary instrument onto the subspace orthogonal to the mean instrumental difference between spectra from the primary and the secondary instrument, and weighting each frequency component model according to the cross-validation error of the frequency components of the projected primary instrument's spectra to generate a stacked ensemble model robust to contributions to the spectra from instrumental variations. The method, which does not require property values from the secondary data set, is tested on three NIR data sets, and is compared with orthogonal projection in the wavelength domain, orthogonal signal correction, and with model updating approaches. For the data sets we examined, we show that the prediction performance of the new method is competitive with orthogonal projections in the wavelength domain, as well as orthogonal signal correction and model updating approaches, both of which require property values for spectra from the secondary instrument. Examination of the spectral data reconstructed from the projected frequency components indicates that aspects of the data that may be attributable to instrumental or physical phenomena (i.e., instrumental baseline shifts or discretized intensity changes which may be attributed to scatter) are suppressed, but those associated with the chemical phenomena are retained. The benefits of orthogonal projection on each individual frequency component are further corroborated by the fact that the models based on frequency component projection generalize better to unseen instruments compared with the other methods.


Hydrogen Peroxide Triggers a Dual Signaling Axis To Selectively Suppress Activated Human T Lymphocyte Migration.
H2O2 is an early danger cue required for innate immune cell recruitment to wounds. To date, little is known about whether H2O2 is required for the migration of human adaptive immune cells to sites of inflammation. However, oxidative stress is known to impair T cell activity, induce actin stiffness, and inhibit cell polarization. In this study, we show that low oxidative concentrations of H2O2 also impede chemokinesis and chemotaxis of previously activated human T cells to CXCL11, but not CXCL10 or CXCL12. We show that this deficiency in migration is due to a reduction in inflammatory chemokine receptor CXCR3 surface expression and cellular activation of lipid phosphatase SHIP-1. We demonstrate that H2O2 acts through an Src kinase to activate a negative regulator of PI3K signaling, SHIP-1 via phosphorylation, providing a molecular mechanism for H2O2-induced chemotaxis deficiency. We hypothesize that although H2O2 serves as an early recruitment trigger for innate immune cells, it appears to operate as an inhibitor of T lymphocyte immune adaptive responses that are not required until later in the repair process.


Interactions between intracellular Ca2+ stores: Ca2+ released from the NAADP pool potentiates cADPR-induced Ca2+ release.
Cells possess multiple intracellular Ca2+-releasing systems. Sea urchin egg homogenates are a well-established model to study intracellular Ca2+ release. In the present study the mechanism of interaction between three intracellular Ca2+ pools, namely the nicotinic acid adenine dinucleotide phosphate (NAADP), the cyclic ADP-ribose (cADPR) and the inositol 1',4',5'-trisphosphate (IP3)-regulated Ca2+ stores, is explored. The data indicate that the NAADP Ca2+ pool could be used to sensitize the cADPR system. In contrast, the IP3 pool was not affected by the Ca2+ released by NAADP. The mechanism of potentiation of the cADPR-induced Ca2+ release, promoted by Ca2+ released from the NAADP pool, is mediated by the mechanism of Ca2+-induced Ca2+ release. These data raise the possibility that the NAADP Ca2+ store may have a role as a regulator of the cellular sensitivity to cADPR.


Identification and suppression of decomposition during carbodiimide-mediated reactions of Boc-amino acids with phenols, hydroxylamines and amino acid ester hydrochlorides.
N-tert-Butoxycarbonylamino acids (Boc-Xaa-OH) were coupled with p-nitrophenol (HONp) in dichloromethane using N,N'-dicyclohexylcarbodiimide (DCC) and N-ethyl-N'(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), and the products were identified and quantitated by high-performance liquid chromatography. Boc-Xaa-OH with Xaa = Val was coupled also with pentafluorophenol (HOPf) and hydroxy-containing additives (HOR), and the products were similarly determined as the methylamides. EDC-mediated reactions of Boc-Xaa-OH gave 8-25% of Boc-Xaa-Xaa-OR as well as Boc-Xaa-OR for R = Ph, Np, Pf, benzotriazole (Bt) and 5-norbornene-endo-2,3-dicarboxamide; DCC-mediated couplings, 5-7% for R = Np and Bt. No dimer was formed in couplings with N-hydroxysuccinimide or 3-hydroxy-4-oxo-3,4-dihydro-1,2,3-benzotriazine. Dimerization was eliminated from DCC-mediated reactions by the addition of 1 equiv. of N-methylmorpholine, from the EDC-mediated reactions by carrying them out in pyridine. Dimerization is attributed to formation of the intermediate 2-alkoxy-5(4H)-oxazolone that undergoes fragmentation to the N-carboxyanhydride, which reacts with the alcohol giving amino acid ester. Ester produces dimer by aminolysis of the O-acylisourea. Decomposition (1.4%) was also detected by analysis for H-Val-Phe-OMe in DCC-mediated reactions of Boc-valine with H-Phe-OMe, and was demonstrated to be caused by the hydrochloride of the ester salt that had been neutralized with N-methylmorpholine. Decomposition was eliminated by the addition of 5% of pyridine, which also had the beneficial effect of suppressing N-acylurea formation.


Effect of Health Care on Quality of Life among Human Immunodeficiency Virus Infected Adults With and Without Visceral Leishmaniasis in northwest Ethiopia: A Longitudinal Follow-Up Study.
There has been a scarcity of data on the effect of health care on the quality of life (QoL) of human immunodeficiency virus (HIV)- and visceral leishmaniasis (VL)- coinfected patients over time. We sought to assess the change that health care brings about in the QoL of HIV patients with and without VL and its predictors in 6 months. A total of 465 HIV patients without VL and 125 HIV-VL-coinfected patients were enrolled in the longitudinal follow-up study from October 2015 to September 2016. Data on QoL at baseline and in 6 months were collected by trained nurses through face-to-face interviews using a short Amharic version of World Health Organization QoL instrument for HIV clients. Multiple linear regressions were used to assess the predictors of health-related QoL. There was an improvement in all of the domains of QoL at the sixth month follow-up compared with the baseline for both groups of patients (P < 0.001). Lack of social support and income were associated with the low improvement in QoL in most of the domains in both groups. Compared with patients having severe acute malnutrition, patients having moderate acute malnutrition and normal nutritional status were better in most of the QoL domains in both groups of patients. Both antiretroviral and anti-VL treatments showed improvement in all dimensions of QoL. Income, social support, and nutritional status were the predictors for most of the QoL domains.


Identification of Risk Factors for Multidrug-Resistant Organisms in Community-Acquired Bacterial Pneumonia at a Community Hospital.
Background: The 2019 Infectious Disease Society of America (IDSA) guidelines for the management of community-acquired bacterial pneumonia encourage the identification of locally validated risk factors for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa to guide empiric therapy decisions for patients with community-acquired pneumonia (CAP). The guidelines urge clinicians to perform local validation to determine prevalence and risk factors pertinent to their institution. Objective: To determine the percentage of community-acquired pneumonia caused by multidrug-resistant organisms (MDROs) and assess risk factors potentially associated with multidrug-resistant organisms CAP at our hospital. Methods: This was a retrospective case control study analyzing patients admitted to the 344-bed community hospital with bacterial community-acquired pneumonia between January 1, 2019 and December 31, 2019. Univariate analysis and multivariate regression were performed to assess potential risk factors for MDRO pathogens. Results: MDROs were isolated in 41.3% of patients with culture-positive CAP (n=19/46), and 3.6% of patients with microbiological culture data within 48 hours of admission (19/527). Among patients with culture-positive CAP, hospitalization in the previous 90 days and receipt of antibiotics in the previous 90 days occurred more frequently in MDRO patients than non-MDRO patients (37% vs 11%, P=.032). No risk factors reached statistical significance in the multivariate regression. There were no differences in clinical outcomes between MDRO and non-MDRO patients. Conclusions: This study demonstrated a low overall prevalence of MDRO pathogens in patients with CAP. Potential risk factors for MDRO included hospitalization within the past 90 days and antibiotic use within the past 90 days.


Enhanced magnetocrystalline anisotropy of Fe30Co70 nanowires by Cu additives and annealing.
The use of 3d transition metal-based magnetic nanowires (NWs) for permanent magnet applications requires large magnetocrystalline anisotropy energy (MAE), which in combination with the NWs' magnetic shape anisotropy yields magnetic hardening and an enhancement of the magnetic energy product. Here, we report on the significant increase in MAE by 125 kJ m(-3) in Fe30Co70 NWs with diameters of 20-150 nm embedded in anodic aluminum oxide templates by adding 5 at.% Cu and subsequent annealing at 900 K. Ferromagnetic resonance (FMR) reveals that this enhancement of MAE is twice as large as the enhancement of MAE in annealed, but undoped NWs. X-ray diffraction (XRD) analysis suggests that upon annealing the immiscible Cu in FeCo NWs causes a crystal reorientation with respect to the NW axis with a considerable distortion of the bcc FeCo lattice. This strain is most likely the origin of the strongly enhanced MAE.


Aggressive Metastatic Inflammatory Myofibroblastic Tumor After Allogeneic Stem Cell Transplant With Fatal Pulmonary Toxicity From Crizotinib.
Inflammatory myofibroblastic tumors (IMTs) are rare tumors with an intermediate spectrum of biological behavior. IMTs are uncommon secondary malignancies after hematopoietic stem cell transplant. The presence of anaplastic lymphoma kinase rearrangements in 50% of IMTs has led to therapeutic trials with crizotinib, although limited experience remains with crizotinib use in children. We describe the first reported case of a highly aggressive and metastatic IMT (secondary malignancy) in an 8-year-old girl following umbilical cord blood transplant. Although tumor response was demonstrated with anaplastic lymphoma kinase inhibition, she later developed fatal pulmonary toxicity from diffuse alveolar damage, a feature felt most likely to be due to crizotinib.


Optimal enteral feeding in children with gastric dysfunction: surgical jejunostomy vs image-guided gastrojejunal tube placement.
Long-term feeding access in children who fail initial gastrostomy is a management quandary. Although image-guided gastrojejunal feeding tube placement (IGJ) is becoming the access of choice in many centers, few studies have compared long-term results with surgical jejunostomy (SJ). The authors compare outcomes with these 2 techniques. A retrospective review of 20 children requiring jejunal feeding access after failing initial gastrostomy was done. Procedures were performed at a tertiary referral center by interventional radiologists (IGJ) or board-certified pediatric surgeons (SJ). Initially, patients underwent IGJ (n = 14) or SJ (n = 6). Image-guided gastrojejunal feeding tube placement patients required gastrostomy at an average age of 23.8 months, with conversion to IGJ an average of 17.2 months later. SJ patients required gastrostomy at average age of 16.2 months, with conversion to SJ 30.7 months later. Of 14 patients undergoing IGJ, 7 (50%) eventually required SJ because of recurring tube management issues. Thus, 13 patients ultimately had SJ, with 11 (85%) Roux-en-Y jejunostomies. Mean operating time for SJ was 158 minutes, with an average of 5.1 days to initiation of feeds, 11 days to full feeds, and 19.9 days to discharge (range, 3-66 days). Image-guided gastrojejunal feeding tube placement patients averaged 4.6 tube adjustments per year requiring fluoroscopic guidance. Surgical jejunostomy averaged 1.5 tube adjustments per year requiring outpatient hospital visits. Image-guided gastrojejunal feeding tube placement patients averaged 3.9 hospital d/y secondary to feeding tube management issues, whereas SJ patients averaged 1.4 hospital days per year. In this group of children with long-term jejunal feeding access, half of those with IGJ eventually required SJ. Surgical jejunostomy required fewer adjustments and hospitalizations per year. Although initially more invasive than IGJ, SJ may provide more stable feeding access with fewer complications. This represents the first published report comparing long-term outcomes between IGJ and SJ.


EGFR induces expression of IRF-1 via STAT1 and STAT3 activation leading to growth arrest of human cancer cells.
Recently, we reported that epidermal growth factor receptor (EGFR) induce expression of a module of genes known to be inducible by interferons and particularly interferon-gamma. Here we show that the module is tightly regulated by EGFR in the 2 human cancer cell lines that overexpress EGFR, A431 and HN5. The module of genes included the tumor suppressor IRF-1, which was used as a prototypical member to further investigate the regulation and function of the module. Ligand-activated EGFR induce expression of IRF-1 via phosphorylation of STAT1 and STAT3. In contrast, cells expressing the constitutively active cancer specific receptor EGFRvIII are unable to mediate phosphorylation of these STATs and thereby incapable of inducing IRF-1. We also demonstrate that IRF-1 is expressed in an EGF dose-dependent manner, which correlates with inhibition of cell proliferation, and that the regulation of IRF-1 is partially dependent on intracellular Src family kinase activity. Treatment with the dual specific Abl/c-Src kinase inhibitor AZD0530 significantly reduces the growth inhibitory effect of high EGF concentrations, signifying that EGFR induced IRF-1 is responsible for the observed growth inhibition. In addition, we show that media from these EGF treated cancer cells upregulate the activation marker CD69 on both B-cells and T-cells in peripheral blood. Taken together, these results suggest that cells acquiring sustained high activity of oncogenes such as EGFR are able to activate genes, whose products mediate growth arrest and activate immune effector cells, and which potentially could be involved in alerting the immune system in vivo leading to elimination of the transformed cells.


Development of an Injection Mold with High Energy Efficiency of Vulcanization for Liquid Silicone Rubber Injection Molding of the Fisheye Optical Lens.
Liquid silicone rubber (LSR) techniques are experiencing exponential growth, particularly in the field of high technology due to the low-temperature flexibility, superior heat stability, chemical resistance, and aging resistance of LSR components. Enhancing the curing rate of LSR parts in liquid silicone rubber injection molding is an important research topic. In this study, an injection mold with high energy efficiency of vulcanization for the liquid silicone rubber injection molding of a fisheye lens was developed and implemented. The LSR injection mold has a conformal heating channel (CHC) and conformal cooling channel (CCC) simultaneously. The function of CHC is to enhance the curing rate of a fisheye lens in the LSR injection molding to meet the requirements of sustainable manufacturing. The curing rates of a fisheye lens were numerically examined using the Moldex3D molding simulation software. It was found that the curing rate of the fisheye optical lens cured by injection mold with CHC was better than that of the injection mold with a conventional heating channel. The curing efficiency could be increased by about 19.12% when the heating oil temperature of 180 °C was used to cure the fisheye optical lens. The simulation results showed that the equation y = -0.0026x3 + 1.3483x2 - 232.11x + 13,770 was the most suitable equation for predicting the curing time (y) through the heating oil temperature (x). It was found that the trend of the experimental results was consistent with the simulation results. In addition, the equation y = -0.0656x2 + 1.5827x - 0.894 with the correlation coefficient of 0.9974 was the most suitable equation for predicting the volumetric shrinkage of the fisheye optical lens (y) through the heating oil temperature (x). The volume shrinkage of the fisheye optical lens cured by injection mold with CHC was very similar to that of the injection mold with a conventional heating channel. The maximum volume shrinkage of the fisheye optical lens cured at 180 °C was about 8.5%.