YOCAS©® Yoga Reduces Self-reported Memory Difficulty in Cancer Survivors in a Nationwide Randomized Clinical Trial: Investigating Relationships Between Memory and Sleep.
Background Interventions are needed to alleviate memory difficulty in cancer survivors. We previously showed in a phase III randomized clinical trial that YOCAS©® yoga-a program that consists of breathing exercises, postures, and meditation-significantly improved sleep quality in cancer survivors. This study assessed the effects of YOCAS©® on memory and identified relationships between memory and sleep. Survivors were randomized to standard care (SC) or SC with YOCAS©® . 328 participants who provided data on the memory difficulty item of the MD Anderson Symptom Inventory are included. Sleep quality was measured using the Pittsburgh Sleep Quality Index. General linear modeling (GLM) determined the group effect of YOCAS©® on memory difficulty compared with SC. GLM also determined moderation of baseline memory difficulty on postintervention sleep and vice versa. Path modeling assessed the mediating effects of changes in memory difficulty on YOCAS©® changes in sleep and vice versa. YOCAS©® significantly reduced memory difficulty at postintervention compared with SC (mean change: yoga=-0.60; SC=-0.16; P<.05). Baseline memory difficulty did not moderate the effects of postintervention sleep quality in YOCAS©® compared with SC. Baseline sleep quality did moderate the effects of postintervention memory difficulty in YOCAS©® compared with SC (P<.05). Changes in sleep quality was a significant mediator of reduced memory difficulty in YOCAS©® compared with SC (P<.05); however, changes in memory difficulty did not significantly mediate improved sleep quality in YOCAS©® compared with SC. In this large nationwide trial, YOCAS©® yoga significantly reduced patient-reported memory difficulty in cancer survivors.


Superior adsorption performance of citrate modified graphene oxide as nano material for removal organic and inorganic pollutants from aqueous solution.
This work addressed one step preparation method to form a novel nano material composite of graphene oxide nanosheet (GO) functionalized with low-cost tri-sodium citrate (C), using, teteraethylorthosilicate (TEOS) as a cross-linker. The prepared composite (GO-C) was characterized using various advanced techniques. Among these techniques, the TGA provided interesting information concerning the functionalization process. Within this process, the (-OH) groups that located at the GO-surface were consumed in the modification process which leads to increase the thermal stability of the resulted composite. Cationic organic methylene blue (MB) and crystal violet (CV), and inorganic copper (Cu2+) and cobalt (Co2+) pollutants were displayed as a model to assess their removal performance by the developed composite (GO-C) from aqueous solution, through batch technique. According to Langmuir isotherm the GO-C present an excellent adsorption capacity for MB (222.22 mg g-1), CV (270.27 mg g-1), Cu2+ (163.4 mg g-1) and Co2+ (145.35 mg g-1) which were more than the adsorption capacities found in literature. Additionally, the regenerated composite presents higher removal ability than the original composite.


PRMT1-mediated arginine methylation promotes postnatal calvaria bone formation through BMP-Smad signaling.
PRMT1 deficiency leads to severely compromised craniofacial development in neural crest cells and profound abnormalities of the craniofacial tissues. Here, we show PRMT1 controls several key processes in calvarial development, including frontal and parietal bone growth rate and the boundary between sutural and osteogenic cells. Pharmacologic PRMT1 inhibition suppresses MC3T3-E1 cell viability and proliferation and impairs osteogenic differentiation. In this text, we investigate the cellular events behind the morphological changes and uncover an essential role of PRMT1 in simulating postnatal bone formation. Inhibition of PRMT1 alleviated BMP signaling through Smads phosphorylation and reduced the deposition of the H4R3me2a mark. Our study demonstrates a regulatory mechanism whereby PRMT1 regulates BMP signaling and the overall properties of the calvaria bone through Smads methylation, which may facilitate the development of an effective therapeutic strategy for craniosynostosis.


Evaluation of hypoxia inducible factor expression in inflammatory and neurodegenerative brain models.
The neuroinflammatory process is thought to contribute to the progression of neurological disorders and brain pathologies. The release of pro-inflammatory cytokines and chemokines by activated glial cells, astrocytes and microglia plays an important role in this process. However, the role of hypoxia-inducible factor-1α (HIF-1α), the key transcription factor regulating the expression of hypoxia-inducible genes, during glial activation is less known. Thus, we examined the significance of HIF-1α in three experimental models: first in an acute model of inflammation induced by pro-inflammatory cytokines TNF-α, IL-1β and IFN-γ; secondly, in a chronic model of inflammation using an APPswe/PS1dE9 (APP/PS1) transgenic mouse model of Alzheimer's disease and thirdly via the inhibition of the PI3K/AKT pathway in a model of neuronal apoptosis. During acute glial inflammation induced by in vitro administration of TNF-α, IL-1β and IFN-γ, mRNA expression levels of HIF-1α were significantly upregulated; however, this effect was blocked by SP600126, a pharmacological inhibitor of mitogen-activated protein kinases (MAPKs). These data suggest that MAPKs could be involved in HIF-1α regulation. In addition, we observed that HIF-1α is not involved in the neuronal apoptotic process mediated by PI3-kinase inhibition, which is regulated by c-Jun. Finally, we did not detect significant differences in the expression of HIF-1α mRNA in APP/PS1 mice during the course of the study (3-12 months of age). Thus, we demonstrated that HIF-1α has a prominent role in acute but not in chronic inflammatory processes, such as the one which occurs in the APP/PS1 experimental model of AD. Moreover, HIF-1α is not involved in neuronal apoptosis after PI3K/AKT inhibition.


Monitoring stepwise proteolytic degradation of peptides by supramolecular domino tandem assays and mass spectrometry for trypsin and leucine aminopeptidase.
A label-free optical detection method has been designed that allows direct monitoring of enzymatic peptide digestion in vitro. The method is based on the addition of a reporter pair, composed of the macrocyclic host cucurbit[7]uril (CB7) and the fluorescent dye acridine orange (AO), to detect the proteolytic degradation of peptides. The enzymatic activity of trypsin and leucine aminopeptidase (LAP) was investigated using H-LSRFSWGA-OH as a substrate. The substrate as well as the intermediary and final products (i.e., H-FSWGA-OH and phenylalanine) formed during its enzymatic hydrolysis differ in their binding affinity to the receptor CB7, which results in varying degrees of dye displacement and, therefore, different fluorescence intensities. CB7 showed a relatively weak binding constant of K approximately 10(4) M(-1) with the substrate, a relatively strong binding constant of K > or = 10(6) M(-1) with H-FSWGA-OH (which is a final product formed by trypsin digestion and the intermediary product formed during the enzymatic activity of LAP), and a moderate binding constant of K < or = 10(5) M(-1) with phenylalanine. Owing to this differential binding affinity of CB7 with the substrate and the corresponding products, the digestion of a peptide by trypsin was followed as a decrease in fluorescence signal, while the complete degradation of the peptide by LAP was monitored as a decrease and a subsequent increase in fluorescence signal. The k(cat)/K(M) value for trypsin (2.0 x 10(7) min(-1) M(-1)) was derived from the change in fluorescence signal with time. Additionally, the complete degradation of the peptide by LAP was also followed by mass spectrometry. The use of a supramolecular sensing ensemble (macrocyclic host and dye) as a fluorescent reporter pair gives this method the flexibility to adapt for monitoring the stepwise degradation of different biologically relevant peptides by other proteases.


Age-related decline in the matrix contents and functional properties of human periodontal ligament stem cell sheets.
In this study, periodontal ligament (PDL) stem cells (PDLSCs) derived from different-aged donors were used to evaluate the effect of aging on cell sheet formation. The activity of PDLSCs was first determined based on their colony-forming ability, surface markers, proliferative/differentiative potentials, senescence-associated β-galactosidase (SA-βG) staining, and expression of pluripotency-associated transcription factors. The ability of these cells to form sheets, based on their extracellular matrix (ECM) contents and their functional properties necessary for osteogenic differentiation, was evaluated to predict the age-related changes in the regenerative capacity of the cell sheets in their further application. It was found that human PDLSCs could be isolated from the PDL tissue of different-aged subjects. However, the ability of the PDLSCs to proliferate and to undergo osteogenic differentiation and their expression of pluripotency-associated transcription factors displayed age-related decreases. In addition, these cells exhibited an age-related increase in SA-βG expression. Aged cells showed an impaired ability to form functional cell sheets, as determined by morphological observations and Ki-67 immunohistochemistry staining. Based on the production of ECM proteins, such as fibronectin, integrin β1, and collagen type I; alkaline phosphatase (ALP) activity; and the expression of osteogenic genes, such as ALP, Runt-related transcription factor 2, and osteocalcin, cell sheets formed by PDLSCs derived from older donors demonstrated a less potent osteogenic capacity compared to those formed by PDLSCs from younger donors. Our data suggest that the age-associated decline in the matrix contents and osteogenic properties of PDLSC sheets should be taken into account in cell sheet engineering research and clinical periodontal regenerative therapy.


Reversed halo sign in invasive fungal infections: criteria for differentiation from organizing pneumonia.
The purpose of this study was to identify CT scan findings that differentiate the reversed halo sign (RHS) caused by invasive fungal infection (IFI) from the RHS caused by organizing pneumonia (OP). We retrospectively reviewed CT scans of patients with RHS caused by IFI or OP. The study included 15 patients with proven or probable IFI (eight men and seven women) and 25 patients with biopsy-proven OP (13 women and 12 men). The CT images were reviewed individually by two chest radiologists who were blinded to the final diagnosis. Reticulation inside the RHS was observed in 14 of the 15 patients with IFI (93%) and in no patient with OP. The maximal thickness of the consolidation rim was 2.04 ± 0.85 cm for IFI and 0.50 ± 0.22 cm for OP. Pleural effusion was noted in 11 of the 15 patients with IFI (73%) and in no patient with OP. Other parenchymal abnormalities, such as consolidation and ground-glass and linear opacities, were observed in both groups. The number of lesions showing the RHS did not differentiate IFI and OP. The presence of reticulation inside the RHS, outer rim thickness > 1 cm, and associated pleural effusion strongly suggest the diagnosis of IFI rather than OP.


Role of stretch-activated channels on the stretch-induced changes of rat atrial myocytes.
The role of stretch-activated channels (SACs) on the stretch-induced changes of rat atrial myocytes was studied using a computer model that incorporated various ion channels and transporters including SACs. A relationship between the extent of the stretch and the activation of SACs was formulated in the model based on experimental findings to reproduce changes in electrical activity and Ca(2+) transients by stretch. Action potentials (APs) were significantly changed by the activation of SACs in the model simulation. The duration of the APs decreased at the initial fast phase and increased at the late slow phase of repolarisation. The resting membrane potential was depolarised from -82 to -70 mV. The Ca(2+) transients were also affected. A prolonged activation of SACs in the model gradually increased the amplitude of the Ca(2+) transients. The removal of Ca((2+)) permeability through SACs, however, had little effect on the stretch-induced changes in electrical activity and Ca(2+) transients in the control condition. In contrast, the removal of the Na(+) permeability nearly abolished these stretch-induced changes. Plotting the peaks of the Ca((2+)) transients during the activation of the SACs along a time axis revealed that they follow the time course of the Na(i)(+) concentration. The Ca((2+)) transients were not changed when the Na(i)(+) concentration was fixed to a control value (5.4mM). These results predicted by the model suggest that the influx of Na(+) rather than Ca(2+) through SACs is more crucial to the generation of stretch-induced changes in the electrical activity and associated Ca(2+) transients of rat atrial myocytes.


Critical micellar concentrations of keto derivatives of selected bile acids: thermodynamic functions of micelle formation.
The knowledge of the process of formation of molecular aggregates of bile acids in aqueous media and of the corresponding critical micellar concentrations (CMCs) is of great significance because of the biological importance of these compounds and their pharmacological applications. In view of this, the present study is concerned with the determination of CMCs of cholic and chenodeoxycholic acids and their keto derivatives at different temperatures with the aim to calculate the standard thermodynamic functions of micelle formation. Based on the molecular descriptors for tested compounds and entropy of micelle formation, the method of principal component analysis (PCA) allowed grouping of the behavior of tested molecules at 30, 50 and 70 degrees C. To one group belong cholic acid and its keto derivatives, the other group consisting of chenodeoxycholic and deoxycholic acids and their keto derivatives. For each group, the derived multiple linear regression equations of the entropy dependence on temperature contains different independent variables. A main difference between the two groups of tested bile acids is in the energy of dipole-dipole interaction, which appears to be temperature dependent, and in the case of the latter group comes into play as an independent variable already in the regression equation derived for 30 degrees C. The most remarkable changes of the descriptors with temperature were observed in the group of cholic acid and its derivatives.


Developing neuronal populations of the cat retinal ganglion cell layer.
An improved flat-mount procedure demonstrates that the developing ganglion cell layer of the cat retina contains two morphologically distinct populations of presumed neurons at all ages between embryonic day 36 (E36) and adulthood. One population resembles the adult "classical neurons" composing the ganglion cells and bar-cells of Hughes, while the remaining cells, which are smaller and possess much less Nissl substance, presumably correspond to precursors of the adult microneurons. Although the total neuron population of the retinal ganglion cell layer remains quite constant at all studied ages, its component subpopulations alter significantly during prenatal development; some 50% of classical neurons disappear before birth and the microneuron population doubles during the same period. An obvious centroperipheral gradient exists for classical neurons by stage E47, but the microneuron density gradient only becomes apparent at birth. A 2:1 centroperipheral ratio for the total neuron population is also apparent at E47. Centroperipheral neuronal density gradients continue to increase during postnatal growth. Loss of classical neurons during prenatal life as a result of cell death or transformation into microneurons, has been postulated as a mechanism for determining neuron density gradients. Cell death does occur in the ganglion cell population but it is not yet established whether microneurons of the ganglion cell layer originate from ganglion cell transformation or migrate as a differentiated class from the ventricular layer. However, it can be concluded that not all microneurons originate from ganglion cell transformation, because the total loss of classical neurons is less than the increase in microneuron numbers during development. The population magnitudes of both neuronal classes in the ganglion cell layer stabilise after birth. However, it is during the postnatal period that the adult cruciate density topography is achieved by both populations. It is concluded that differential areal growth is the prime mechanism for postnatal cell redistribution.


Differential induction of p53 in immature and adult rat brain following lithium-pilocarpine status epilepticus.
Activation of the tumor suppressor gene, p53, has been strongly implicated in selective neuronal cell death. This study investigated p53 expression in the immature and adult rat brain following status epilepticus induced by the administration of lithium-pilocarpine (LPSE). Both p53 mRNA and protein were examined in relation to neuronal degeneration using in situ hybridization and immunohistochemistry, respectively. Injured cells with eosinophilic cytoplasm with increased p53 mRNA were observed in hippocampal subfields, piriform cortex, amygdala and thalamus. p53 mRNA levels reached a peak by 8 h and returned to baseline by 24 h after the onset of LPSE. The magnitude of p53 mRNA induction was greatest in 21-day-old rats. In contrast to the cellular expression pattern of p53 mRNA, immunohistochemistry demonstrated that p53 protein was increased in all of the eosinophilic cells. Further, double-labeling studies revealed that p53 protein was elevated in neurons that were degenerating. This was supported by colocalization of activated caspase 3 in some cells with damaged DNA. These results provide additional evidence for a critical role for the p53 pathway in excitotoxic neuronal cell death due to status epilepticus.


EasySpin, a comprehensive software package for spectral simulation and analysis in EPR.
EasySpin, a computational package for spectral simulation and analysis in EPR, is described. It is based on Matlab, a commercial technical computation software. EasySpin provides extensive EPR-related functionality, ranging from elementary spin physics to data analysis. In addition, it provides routines for the simulation of liquid- and solid-state EPR and ENDOR spectra. These simulation functions are built on a series of novel algorithms that enhance scope, speed and accuracy of spectral simulations. Spin systems with an arbitrary number of electron and nuclear spins are supported. The structure of the toolbox as well as the theoretical background underlying its simulation functionality are presented, and some illustrative examples are given.


Complete genome sequence of the 2,3-butanediol-producing Klebsiella pneumoniae strain KCTC 2242.
Here we report the full genome sequence of Klebsiella pneumoniae KCTC 2242,consisting of a 5.26-Mb chromosome (57.6% GC%; 5,035 genes [4,923 encoding known proteins, 112 RNA genes]) and a 202-kb plasmid (50.2% GC%; 229 genes [229 encoding known proteins]).


Nail Mineral Composition Changes Do Not Reflect Bone Mineral Changes Caused by Boron Supplementation.
Nails have been found to be a non-invasive and readily available tissue whose mineral content can change because of a change in dietary mineral intake. Thus, this study was undertaken to determine whether boron (B) supplementation would change the concentrations of some mineral elements in nails and whether these changes correlated with changes induced in bone. Female New Zealand White rabbits (aged 8 months, 2-2.5 kg weight) were fed a grain-based, high-energy diet containing 3.88 mg B/kg. The rabbits were divided into four treatment groups: controls receiving no supplemental B (N: 7; C) and three groups supplemented with 30 mg B/L in drinking water as borax decahydrate (Na2B4O7∙10H2O, N: 10; BD), borax anhydrous (Na2B4O7, N: 7; Bah), and boric acid (H3BO3, N: 7; BA). Boron, calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), phosphorus (P), potassium (K), sodium (Na), sulfur (S), and zinc (Zn) concentrations in nails were determined by inductively coupled plasma atomic emission spectroscopy. Parametric and non-parametric multiple group comparisons and post hoc tests were performed and whether a correlation between nail and tibia and femur mineral elements concentrations were determined. A p-value of < 0.05 was considered statistically significant. Boron was not detectable in control nails but was found in the nails of the three B supplemented groups. Boron supplementation markedly increased the Ca concentration in nails with the effect greatest in the BA and BD groups. The P and Mg concentrations also were increased by B supplementation with the effect most marked in the BA group. In contrast, B supplementation decreased the Na concentration with the effect most noticeable in the BD and Bah groups. The Zn concentration in nails was not affected by BA and BD supplementation but was decreased by Bah supplementation. Boron supplementation did not significantly affect the concentrations of Cu, Fe, Mo, K, and S in nails. No meaningful significant correlations were found between nail mineral elements and tibia and femur mineral elements found previously. Nails can be an indicator of the response to boron supplementation but are not useful to indicate changes in mineral elements in bone in response to B supplementation.


Tuberous sclerosis. Comparison of computed tomography and conventional neuroradiology.
Sixty-two patients with tuberous sclerosis were studied by skull radiography. In addition, 16 had CT scanning, 26 had air studies, and 5 had cerebral angiography. Both subependymal and parenchymal tubers were shown on CT; all had a higher density than the brain and none were enhanced by contrast material. CT showed tubers in 13 of 16 patients, including 4 of 6 patients with glioma and hydrocephalus. Air studies showed subependymal tubers in 12 of 26 patients. Four other patients had intraventricular gliomas but no tubers. Skull radiographs showed spotty calcification, compatible with tuberous sclerosis, in 30 cases. Four patients had calcification compatible with tumor. Angiograms were nonspecific, showing intraventricular masses but no tubers.


The radiologic investigation of bovine lameness associated with infection.
Infections, primarily of the limbs, are a significant part of our bovine lameness practice here at the Western College of Veterinary Medicine. The majority of these infections relate to the foot. More proximal lesions do occur, however, as detailed in the preceding section. It is interesting to note that such lesions are not assessed radiographically in practice until such time as antibiotics are judged to be ineffective. This period of medical treatment is often lengthy and expensive. The efficacy of potential, as well as ongoing, treatment often is better determined after a clinical and radiologic assessment of the animal. Indeed, radiology can be a paying proposition for both the producer and the practitioner, to say nothing of its obvious benefits to the animal.


RNA sequencing analysis reveals increased expression of interferon signaling genes and dysregulation of bone metabolism affecting pathways in the whole blood of patients with osteogenesis imperfecta.
Osteogenesis imperfecta (OI) is a rare genetic disorder in which the patients suffer from numerous fractures, skeletal deformities and bluish sclera. The disorder ranges from a mild form to severe and lethal cases. The main objective of this pilot study was to compare the blood transcriptional landscape of OI patients with COL1A1 pathogenic variants and their healthy relatives, in order to find out different gene expression and dysregulated molecular pathways in OI. We performed RNA sequencing analysis of whole blood in seven individuals affected with different OI severity and their five unaffected relatives from the three families. The data was analyzed using edgeR package of R Bioconductor. Functional profiling and pathway analysis of the identified differently expressed genes was performed with g:GOSt and MinePath web-based tools. We identified 114 differently expressed genes. The expression of 79 genes was up-regulated, while 35 genes were down-regulated. The functional analysis identified a presence of dysregulated interferon signaling pathways (IFI27, IFITM3, RSAD12, GBP7). Additionally, the expressions of the genes related to extracellular matrix organization, Wnt signaling, vitamin D metabolism and MAPK-ERK 1/2 pathways were also altered. The current pilot study successfully captured the differential expression of inflammation and bone metabolism pathways in OI patients. This work can contribute to future research of transcriptional bloodomics in OI. Transcriptional bloodomics has a strong potential to become a major contributor to the understanding of OI pathological mechanisms, the discovery of phenotype modifying factors, and the identification of new therapeutic targets. However, further studies in bigger cohorts of OI patients are needed to confirm the findings of the current work.


In vivo and in vitro activity of oil extract of garlic (Allium sativum Linnaeus) against Schistosoma japonicum cercariae.
The activity of garlic oil extract against Schistosoma japonicum cercariae was evaluated. The in vitro and in vivo cercaricidal activities against S. japonicum larvae were determined. Exposure to ≥ 10-6 (v/v) garlic emulsions for 30 min led to 100% cercariae mortality; pre-exposure treatment with ≥ 10-4 (v/v) garlic emulsions showed 100% preventive efficacy against S. japonicum infection, while pre-treatment with 10-5 and 10-6 (v/v) emulsions achieved 20%-40% preventive efficacy and 35.2%-63.6% worm burden reduction. Garlic oil extract has activity against S. japonicum larvae and a promising preventive efficacy against S. japonicum infection.


Mitral valve remodeling in the development of obstructive hypertrophic cardiomyopathy.
Approximately 2/3 of patients with hypertrophic cardiomyopathy (HCM) have significant left ventricular outflow tract obstruction (LVOTO), which is caused by the interaction mitral valve apparatus and the hypertrophied septum. The contribution of mitral valve remodeling to the development of obstruction over time has never been described. We analyzed retrospectively 40 patients with HCM and no baseline obstruction followed up for a median of 2179 days. At follow up, 13 patients developed significant LVOTO. Patients who developed LVOTO had longer posterior leaflets and longer anterior leaflet residual length.


Norcocaine and cocaethylene distribution patterns in hair samples from light, moderate, and heavy cocaine users.
Even though hair analysis often seems to be the best choice for retrospective monitoring of cocaine intake, differentiating between incorporated cocaine and external contamination is widely debated. In this study we report results obtained in 90 hair samples from addicts. All samples were analyzed for cocaine, benzoylecgonine, norcocaine, cocaethylene, and tropococaine by gas chromatography-mass spectrometry (GC-MS) techniques coupled with direct immersion solid-phase micro-extraction. Cocaine concentrations were stratified into three classes of usage: light (0.5-3 ng/mg), moderate (3.1-10 ng/mg) and heavy (10.1-40 ng/mg). The Substance Abuse and Mental Health Services Administration cut-off criteria for establishing active cocaine use were applied to the results. For all samples criteria were cocaine levels above 0.5 ng/mg (ranging from 1.63 to 39.29 ng/mg, mean 9.49 ng/mg), benzoylecgonine concentrations ≥ 0.05 ng/mg (ranging from 0.19 to 5.77 ng/mg, mean 1.40), and benzoylecgonine to cocaine % ratio ≥5% (from 6.43 to 26.09%). Norcocaine was present in 58.9% of samples (concentration range: 0.22-3.14 ng/mg) and was strongly predictive only of heavy cocaine use (sensitivity 100% for cocaine concentrations above 9.58 ng/mg). Twenty hair samples from moderate and heavy users tested positive for cocaethylene (concentration range: 0.22-1.98 ng/mg, mean 0.73 ng/mg). This study on hair samples with no chance of false positive cases highlights the very limited applications of testing minor cocaine metabolites for definitive proof of active cocaine consumption. © 2015 The Authors. Drug Testing and Analysis Published by John Wiley & Sons, Ltd.


Antigen load and viral sequence diversification determine the functional profile of HIV-1-specific CD8+ T cells.
Virus-specific CD8(+) T lymphocytes play a key role in the initial reduction of peak viremia during acute viral infections, but display signs of increasing dysfunction and exhaustion under conditions of chronic antigen persistence. It has been suggested that virus-specific CD8(+) T cells with a "polyfunctional" profile, defined by the capacity to secrete multiple cytokines or chemokines, are most competent in controlling viral replication in chronic HIV-1 infection. We used HIV-1 infection as a model of chronic persistent viral infection to investigate the process of exhaustion and dysfunction of virus-specific CD8(+) T cell responses on the single-epitope level over time, starting in primary HIV-1 infection. We longitudinally analyzed the polyfunctional epitope-specific CD8(+) T cell responses of 18 patients during primary HIV-1 infection before and after therapy initiation or sequence variation in the targeted epitope. Epitope-specific CD8(+) T cells responded with multiple effector functions to antigenic stimulation during primary HIV-1 infection, but lost their polyfunctional capacity in response to antigen and up-regulated programmed death 1 (PD-1) expression with persistent viremic infection. This exhausted phenotype significantly decreased upon removal of stimulation by antigen, either in response to antiretroviral therapy or by reduction of epitope-specific antigen load in the presence of ongoing viral replication, as a consequence of in vivo selection of cytotoxic T lymphocyte escape mutations in the respective epitopes. Monofunctionality increased in CD8(+) T cell responses directed against conserved epitopes from 49% (95% confidence interval 27%-72%) to 76% (56%-95%) (standard deviation [SD] of the effect size 0.71), while monofunctionality remained stable or slightly decreased for responses directed against escaped epitopes from 61% (47%-75%) to 56% (42%-70%) (SD of the effect size 0.18) (p < 0.05). These data suggest that persistence of antigen can be the cause, rather than the consequence, of the functional impairment of virus-specific T cell responses observed during chronic HIV-1 infection, and underscore the importance of evaluating autologous viral sequences in studies aimed at investigating the relationship between virus-specific immunity and associated pathogenesis.


Recording Methods and the Capabilities of Modern Respiratory Rate Monitoring Devices (literature review).
Determination of respiratory rate is a necessary task in assessing the state of health in humans. This review provides a description of modern devices used for recording and monitoring respiratory rate. The advantages and disadvantages of the principles of operation of these devices are discussed.


The occurrence, progression and development of four types of gastric mucosal atrophic lesions and their histopathological characteristics.
To investigate the occurrence and development of gastric mucosal atrophic lesions and their histopathological characteristics. Histopathological diagnosis and immunohistochemical staining using the EnVision two-step method were conducted on 1969 gastric mucosal atrophic lesions obtained from gastroscopic biopsy specimens. A total of 48-month three-stage endoscopic biopsy follow-ups were performed. When the gastric mucosal epithelium was affected by infection, chemical irritation, or immune or genetic factors, the gastric mucosal epithelium glands atrophied, the mucosa became thinner, the number of glands decreased, the intestinal epithelium progressed to metaplasia and smooth muscle fibre became hyperplasia. Such changes may lead to the proliferation and dysplasia of epithelial cells of the gastric mucosa and neoplastic hyperplasia in nature; this is referred to as gastric mucosal atrophic lesions in this study. According to this definition, the present study divided gastric mucosal atrophy into four types: (1) glandular atrophy of the lamina propria; (2) compensatory proliferative atrophy; (3) intestinal metaplasia atrophy; and (4) smooth muscle proliferative atrophy. The incidence rates of the above were 40.1% (789/1969), 14.3% (281/1969), 27.8% (547/1969) and 17.9% (352/1969), respectively. One- to 4-year follow-ups found that the changes were not significant and that the percentages of patients with disease exacerbation were 85.7% (1688/1969) and 9.8% (192/1969). The percentages of patients who developed low-grade intraepithelial neoplasia and high-grade intraepithelial neoplasia were 2.8% (55/1969) and 1.1% (21/1969), respectively; 0.7% (13/1969) of patients developed intramucosal cancer. Gastric mucosal atrophic lesions and histopathological staging are based on the morphological characteristics of gastric mucosal atrophy and the hypothesis of malignant transformation of cells during the occurrence and development of mucosal atrophy. Mastering pathological staging is beneficial to clinicians for enacting precise treatment and is important for reducing the incidence of gastric cancer.


Temporary atrial standstill.
Temporary atrial standstill is a relatively rare event requiring intraatrial electrogram recordings for its documentation. Previous reports have emphasized its relationship to drug intoxication, infarction, the immediate post open-heart surgery period, or the premorbid state; significant impairment of atrial excitability is usual. The occurrence of atrial standstill in the presence of intact atrial excitability suggests "electrical isolation" of the atria. The three patients we describe manifested temporary atrial standstill while maintaining atrial excitability. Diffuse conduction system disease and drug effects played a contributory role.


Development of a Frailty Index from Routine Hospital Data in Perioperative and Critical Care.
Frailty is common in surgical and intensive care unit (ICU) populations, yet it is not routinely measured. Frailty indices are able to quantify this condition across a range of health deficits. We aimed to develop a frailty index (FI) from routinely collected hospital data in a surgical and ICU population. Prospective observational single-center cohort study. Tertiary referral metropolitan Australian hospital. A total of 336 individuals aged 65 and older undergoing surgery or aged 50 and older admitted to the ICU. Routine admission health data were used to derive an FI comprising 36 health deficits. We examined the FI correlation with existing frailty tools (Clinical Frailty Scale [CFS] and Edmonton Frail Scale [EFS]) and assessed its predictive ability for negative outcomes including 30-day mortality. Median FI was .17 (interquartile range [IQR]) = .10-.24) for ICU patients and .17 (IQR = .11-.25) for surgical patients; maximum FI was .58, and 25% (95% confidence interval [CI] = 10.4-29.6) of patients overall were diagnosed with frailty (FI score ≥.25). Correlation was strong between the FI and the EFS: ρ = .76 (95% CI = .70-.83) for ICU patients and .71 (95% CI = .64-.78) for surgical patients, and the CFS was .77 (95% CI = .70-.84) for ICU patients and .72 (95% CI = .65-.79) for surgical patients. The FI had good discriminative ability for prediction of 30-day mortality in ICU patients (multivariate odds ratio for each increase in FI of .1 = 2.04 [95% CI = 1.19-3.48]), comparable with the performance of the Acute Physiology and Chronic Health Evaluation III score (ICU patients) and the Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity score (surgical patients). It is feasible to construct an FI from hospital admission data in a cohort of critically ill and surgical patients.


First record of Aleiodes (Hemigyroneuron) (Hymenoptera: Braconidae: Rogadinae) from the Arabian Peninsula: description of new species with remarkable wing venation convergence to Gyroneuron and Gyroneuronella.
A new species of Aleiodes (Hemigyroneuron) from Saudi Arabia is described and illustrated. It represents the first species known from outside of sub-Saharan Africa, Madagascar, South East Asia and the East Palaearctic. It belongs to a species group comprising A. (H.) plurivena, glandularis and sharkeyi, but displays even more derived wing venation which is remarkably convergent with that of two distantly related rogadine genera, Gyroneuron and Gyroneuronella.


Journal Club: Shoulder MRI utilization: relationship of physician MRI equipment ownership to negative study frequency.
The purpose of this article is to determine whether ownership of MRI equipment by ordering physicians influences the frequency of negative shoulder MRI scans. A retrospective review was performed of 1140 consecutive shoulder MRI scans ordered by two separate referring physician groups serving the same geographic community. The first group (financially incentivized) owned the scanners used and received technical fees for their use. The second group (non-financially incentivized) did not own the scanners used and had no direct financial interest. All examinations were performed with identical protocols and were interpreted by a single radiologist group without financial interest in the imaging equipment used. The frequency of negative examinations and the number of abnormalities in each positive study was tabulated for each group. A total of 1140 shoulder MRI scans met inclusion criteria; 255 were negative (142 for the financially incentivized group and 113 for the non-financially incentivized group). There were 25.6% more negative scans in the financially incentivized group (p=0.047). There was no statistically significant difference in the average number of lesions per positive scan (1.67 for the financially incentivized group and 1.71 for the non-financially incentivized group; p=0.34). No statistically significant difference was found in the frequency of 19 of 20 examined lesions. Shoulder MRI examinations referred by physicians with a financial interest in the imaging equipment used were significantly more likely to be negative. Positive examinations exhibited no statistically significant difference in the number of lesions per scan or in the frequency of 19 of 20 lesion subtypes. This finding suggests a highly similar distribution and severity of disease among the two patient groups.


Development of a percutaneous cerebrospinal fluid collection technique in F-344 rats and evaluation of cell counts and total protein concentrations.
A simple technique for cerebrospinal fluid (CSF) collection was developed in F-344 rats. Cell counts and total protein concentrations were evaluated to assess sample quality. While the 50 to 70 mu L samples of CSF collected on three different days showed a progressive decrease in the total erythrocyte and nucleated cell counts, no significant changes were observed in the total protein concentrations. Progressive decreases in the total erythrocyte count correlated positively with the decreases in volume of CSF collected. Our data suggest that collection of less than 50 mu L of CSF will give a better quality of CSF in F-344 rats. This is the first report of cellular and protein parameters in the CSF of F-344 rats.


Evolution of Ate-Organoiron(II) Species towards Lower Oxidation States: Role of the Steric and Electronic Factors.
Ate-iron(II) species such as [Ar3 FeII ]- (Ar=aryl) are key intermediates in Fe-catalyzed couplings between aryl nucleophiles and organic electrophiles. They can be active species in the catalytic cycle, or lead to Fe0 and FeI oxidation states, which can themselves be catalytically active or lead to unwished organic byproducts. Analysis of the reactivity of the intermediates obtained by step-by-step displacement of the mesityl groups in high-spin [Mes3 FeII ]- by less hindered phenyl ligands was performed, and uncovered the crucial role of both steric and electronic parameters in the formation of the Fe0 and FeI oxidation states. The formation of quaternized [Ar4 FeII MgBr(THF)]- intermediates allows the bielectronic reductive elimination energy required for the formation of Fe0 to be reduced. Similarly, the small steric pressure of the aryl groups in [Ar3 FeII ]- enables the formation of aryl-bridged [{FeII (Ar)2 }2 (μ-Ar)2 ]2- species, which afford the FeI oxidation state by bimetallic reductive elimination. These results are supported by 1 H NMR, EPR, and 57 Fe Mössbauer spectroscopies, as well as by DFT calculations.


In Vivo Tracking of Streptococcal Infections of Subcutaneous Origin in a Murine Model.
Generation of plasmin in vivo by Streptococcus pyogenes is thought to localize the active protease complexes to the pathogen surface to aid in tissue dissemination. Here, we chose to follow cutaneous streptococcal infections by the use of non-invasive bioluminescence imaging to determine if this pathogen can be followed by this approach and the extent of bacterial spread in the absence of canonical plasminogen activation by streptokinase. Mice were injected subcutaneously with either bioluminescent strains of streptococci, namely Xen20 and Xen10 or S. pyogenes ALAB49. Bioluminescence imaging was performed daily and results were correlated with microbiological and histological analyses. Comparative analysis of chronologic non-invasive datasets indicated that Xen20 did not disseminate from the initial infection site. Contrary to this, microbiological and histological analyses of Xen20 mice for total bacterial burden indicated sepsis and widespread pathogen involvement. The use of bioluminescence in microbe-based studies requires genomic and pathologic characterization to correlate imaging results with underlying pathology.


Work as a street vendor, associated traffic-related air pollution exposures and risk of adverse pregnancy outcomes in Accra, Ghana.
Street vending, a dominant occupation in urban areas of developing countries exposes the vendors to several environmental pollutants. We investigated whether work as street vendor impairs foetal growth and shortens gestational duration, and evaluated to what extent exposure to traffic-related air pollution is responsible for these adverse effects. A cross-sectional study was conducted among mothers and their newborns accessing postnatal services at the Korle Bu Teaching Hospital in Accra, Ghana in 2010, focusing on 105 street vendors and a reference group of 281 mothers. We categorized exposure to traffic-related air pollution on the basis of street vending activity patterns and traffic density in the working area. Multivariate linear regression analysis adjusting for age, social class, marital status and gravidity of mothers, sex of neonate, and indoor air pollution, indicated a 177 g (95% CI: 324, 31) reduction in birth weight among street vendors. Sensitivity analysis performed by restricting the analysis to term births showed further reductions in birth weight. Generalized linear models adjusting for confounders indicated a 35% (risk ratio (RR)=1.35; 95% CI: 0.87, 2.12) increased risk of LBW, albeit statistically not significant. LBW risk increased in the sensitivity analysis but was also not statistically significant. The risk of PTB was not associated with street vending (RR=1.03; 95% CI: 0.67, 1.58). The exposure-response relations observed were not consistent. Moderate activity patterns and high traffic density jointly was associated with a statistically significant 84% (RR=1.84; 95% CI: 1.05, 3.24) increased risk of LBW. Street vending during pregnancy is a determinant of average foetal growth and risk of LBW. More research is required to further quantify their effects on pregnancy outcomes and safeguard maternal and perinatal health in developing countries.


Beyond DNA Repair: DNA-PKcs in Tumor Metastasis, Metabolism and Immunity.
The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a key component of the DNA-PK complex that has a well-characterized function in the non-homologous end-joining repair of DNA double-strand breaks. Since its identification, a large body of evidence has demonstrated that DNA-PKcs is frequently overexpressed in cancer, plays a critical role in tumor development and progression, and is associated with poor prognosis of cancer patients. Intriguingly, recent studies have suggested novel functions beyond the canonical role of DNA-PKcs, which has transformed the paradigm of DNA-PKcs in tumorigenesis and has reinvigorated the interest to target DNA-PKcs for cancer treatment. In this review, we update recent advances in DNA-PKcs, in particular the emerging roles in tumor metastasis, metabolic dysregulation, and immune escape. We further discuss the possible molecular basis that underpins the pleiotropism of DNA-PKcs in cancer. Finally, we outline the biomarkers that may predict the therapeutic response to DNA-PKcs inhibitor therapy. Understanding the functional repertoire of DNA-PKcs will provide mechanistic insights of DNA-PKcs in malignancy and, more importantly, may revolutionize the design and utility of DNA-PKcs-based precision cancer therapy.


A hidden infection: Racemose neurocysticercosis causing hydrocephalus; a case report.
Neurocysticercosis (NCC) is the most common helminthic central nervous system infection (CNS) in the Western hemisphere and the most common cause of acquired epilepsy worldwide. Due to its relatively prolonged latent period and clinical similarity to other infectious diseases - including bacterial or viral meningitis and other helminthic infections - NCC may be difficult to diagnose, especially for clinicians who rarely encounter it. This case report discusses a patient with obstructive hydrocephalus and eosinophilic meningitis secondary to racemose NCC. The diagnosis process was initially complicated by the patient's history of pork allergy and absence of radiographic evidence of helminthic CNS infection. Further investigation showed a 4th ventricle multi-cystic lesion causing hydrocephalus which prompted a surgical intervention with a ventriculoperitoneal shunt (VPS) in conjunction with anti-helminthic medical treatment. At 1-year follow-up, the patient has reported recurrence of VPS related complications. Larval cysts typically deposit within the brain parenchyma, making them easily detected on head computed tomography (CT) scans and leading to neurologic sequelae such as epilepsy. In this case, the absence of CT evidence of NCC and the patient's lifelong history of pork allergy slowed the diagnosis process. Racemose NCC is a rare subset of the disease in which cyst clusters occupy the extra parenchymal space, thereby changing the symptomatic profile and making the cysts more difficult to visualize in imaging studies. In this case, magnetic resonance imaging (MRI) was the best imaging modality to diagnosis extra parenchymal NCC and guide its surgical management.


Machine Learning Methods for Exploring Sequence Determinants of 3D Genome Organization.
In higher eukaryotic cells, chromosomes are folded inside the nucleus. Recent advances in whole-genome mapping technologies have revealed the multiscale features of 3D genome organization that are intertwined with fundamental genome functions. However, DNA sequence determinants that modulate the formation of 3D genome organization remain poorly characterized. In the past few years, predicting 3D genome organization based on DNA sequence features has become an active area of research. Here, we review the recent progress in computational approaches to unraveling important sequence elements for 3D genome organization. In particular, we discuss the rapid development of machine learning-based methods that facilitate the connections between DNA sequence features and 3D genome architectures at different scales. While much progress has been made in developing predictive models for revealing important sequence features for 3D genome organization, new research is urgently needed to incorporate multi-omic data and enhance model interpretability, further advancing our understanding of gene regulation mechanisms through the lens of 3D genome organization.


A Computational Examination of the Uncatalyzed Meinwald Rearrangement of Monoterpene Epoxides.
Epoxides are relatively reactive compounds and may undergo decomposition or rearrangement reactions at elevated temperatures, and gas chromatographic analysis of essential oils may cause thermal decomposition or rearrangement of epoxide components at gas chromatographic temperatures. Density functional theory (DFT) calculations were carried out using the B3LYP functional at the 6-31 1++G**//6-3 IG* level of theory on the Meinwald rearrangements of α- pinene oxide (two different mechanisms leading to transpinocamphone and a-campholenal), cis-limonene oxide (leading to trans-dihydrocarvone), tran s- limonene oxide (leading to cisdihydrocarvone), 6,7-epoxymyrcene (leading to 2-methyl-6-methylene-7-octen-3-one), and 1,2-epoxy-2,5-dimethyl-3-viny4- hexene (two mechanisms leading to 5-methyl-3-vinyl-4-hexenal and 8-methyl-5,7-nonadien-2-one). Free energies of activation for the uncatalyzed Meinwald rearrangement of common monoterpene epoxides are relatively large, being of the order of 70 kcal/mol, and are, therefore, not predicted to be important reactions at gas chromatographic temperatures.


Bayesian dynamic network actor models with application to South Korean COVID-19 patient movement data.
Motivated by the ongoing COVID-19 pandemic, this article introduces Bayesian dynamic network actor models for the analysis of infected individuals' movements in South Korea during the first three months of 2020. The relational event data modelling framework makes use of network statistics capturing the structure of movement events from and to several country's municipalities. The fully probabilistic Bayesian approach allows to quantify the uncertainty associated to the relational tendencies explaining where and when movement events are established and where they are directed. The observed patient movements' patterns at an early stage of the pandemic can provide interesting insights about the spread of the disease in the Asian country.


Super-selective angiographic embolisation of a branch of the anterior pudendal artery for the treatment of intractable post-operative bleeding.
We describe a case of post-operative bleeding after a posterior fascial defect repair. This was refractive to exploration and vaginal packing so laparotomy would have been necessary. Superselective cannulation demonstrated bleeding from a branch of the anterior pudendal artery which had crossed the midline making identification difficult during vaginal exploration. The bleeding vessel was embolised using a mixture of PVA300 and Spongistan gel foam and the bleeding ceased. The use of embolisation in the peri-operative phase is discussed.


Retrograde left atrial catheterization in children with congenital heart disease.
Entry into the left atrium during cardiac catheterization may be essential for full assessment of the hemodynamic situation, particularly for the accurate calculation of pulmonary blood flow and pulmonary arteriolar resistance. The retrograde transaortic transmitral technique of left atrial catheterization has been described in adults but no detailed reports are available for the pediatric age group. Experience of this technique in 43 children with congenital heart disease is now presented, with a success rate of 67 per cent and a low incidence of complications. This method compares favorably with other methods of left atrial catheterization when the interatrial septum is intact.


Evidence in vitro that hepatic lipase reduces the concentration of apolipoprotein A-I in rabbit high-density lipoproteins.
Incubation of rabbit plasma in vitro with hepatic lipase resulted in the hydrolysis of triacylglycerol in high-density lipoproteins (HDL) and a reduction in HDL particle size. These changes were accompanied by a decrease in the concentration of apolipoprotein A-I (apo A-I) in the HDL. The loss of apo A-I was demonstrated independently by ultracentrifugation, size exclusion chromatography and gradient gel-immunoblot analysis. It was unrelated to hydrolysis of HDL phospholipids but did correlate with the reduction in HDL particle size. These studies suggest that the concentration of apo A-I in HDL may be influenced by factors which regulate the metabolism of HDL core lipid constituents.


Age as a prognostic factor for breast and regional nodal recurrence following breast conserving surgery and irradiation in stage I and II breast cancer.
To evaluate the association between age and breast/regional nodal relapse following breast conserving surgery and irradiation. The results of treatment in 511 patients with 519 Stage I and II breast cancers treated at Mallinkrodt Institute of Radiology and affiliated hospitals between 1958 and 1988 were reviewed. Seventy women, of whom 96% had axillary dissections, were 39 years of age or younger. These young patients were more likely to have chemotherapy (p < 0.0001), and tumor bed reexcision (p < 0.01), and less likely to have an undissected axilla (p < 0.01), or estrogen receptor positive tumor (p = 0.02) than the older women (> 40 years). Although breast recurrence tended to appear earlier in the younger patients (12% at 5 years for those < 40 years vs. 6% at 5 years for those older), by 7 years the breast failure rate for the two groups was the same (12%), p = 0.13. In the 37 women 35 years of age or younger, the actuarial rate of breast recurrence was 9% at 7 years. Compared to other series in the literature, in which cancers were grossly excised without regard to the microscopic margins of resection, and reexcision was not routinely performed, young women treated with breast conserving surgery and irradiation at our institution frequently underwent reexcision of the tumor bed (57%), and had negative pathologic margins of resection (75%). Regional nodal relapse was in general uncommon, and not seen with increased frequency in the youngest cohort. Our experience suggests that young age is not a contraindication to breast conserving surgery and irradiation. Although breast cancers in this cohort may have certain features rendering them prone to local failure, we believe this risk can be mitigated by appropriate patient selection and optimal surgical resection.


Blockade of the brachial plexus abolishes activation of specific brain regions by electroacupuncture at LI4: a functional MRI study.
Our aim was to test the hypothesis that electroacupuncture (EA) at acupuncture point LI4 activates specific brain regions by nerve stimulation that is mediatied through a pathway involving the brachial plexus. Twelve acupuncture naive right-handed volunteers were allocated to receive three sessions of EA at LI4 in a random different order (crossover): (1) EA alone (EA); EA after injection of local anaesthetics into the deltoid muscle (EA+LA); and (3) EA after blockade of the brachial plexus (EA+NB). During each session, participants were imaged in a 3 T MRI scanner. Brain regions showing change in blood oxygen level-dependent (BOLD) signal (activation) were identified. Subjective acupuncture sensation was quantified after functional MRI scanning was completed. Results were compared between the three sessions for each individual, and averaged. Blockade of the brachial plexus inhibited acupuncture sensation during EA. EA and EA+LA activated the bilateral thalamus, basal ganglia, cerebellum and left putamen, whilst no significant activation was observed during EA+NB. The BOLD signal of the thalamus correlated significantly with acupuncture sensation score during EA. Blockade of the brachial plexus completely abolishes patterns of brain activation induced by EA at LI4. The results suggest that EA activates specific brain regions through stimulation of the local nerves supplying the tissues at LI4, which transmit sensory information via the brachial plexus. ChiCTR-OO-13003389.


Ductal involvement by cells of atypical lobular hyperplasia in the breast: a long-term follow-up study of cancer risk.
A cohort study of women with ductal involvement by cells of atypical lobular hyperplasia (DIALH) revealed an incidence of 1.4% in benign biopsy specimens. When combined with diagnostic lobular unit alterations of atypical lobular hyperplasia (ALH), a consequent risk of invasive carcinoma of 6.8 times that in the general population was found. This relative risk for women with ALH and DIALH approaches the risk for lobular carcinoma in situ, whereas the risk for ALH with or without DIALH is 4.3 and the risk for ALH without DIALH is reduced to 2.7. Only definitive changes of DIALH with an insinuated characteristic population of cells between attenuated luminal cells and basement membrane should be so diagnosed. DIALH in association with lobular alterations that are borderline with regard to a diagnosis of lobular carcinoma in situ will increase the certainty that a medically meaningful increased risk for subsequent invasive cancer is indicated.


Carbon and hydrogen isotope fractionation of benzene and toluene during hydrophobic sorption in multistep batch experiments.
The application of compound-specific stable isotope analysis (CSIA) for evaluating degradation of organic pollutants in the field implies that other processes affecting pollutant concentration are minor with respect to isotope fractionation. Sorption is associated with minor isotope fractionation and pollutants may undergo successive sorption-desorption steps during their migration in aquifers. However, little is known about isotope fractionation of BTEX compounds after consecutive sorption steps. Here, we show that partitioning of benzene and toluene between water and organic sorbents (i.e. 1-octanol, dichloromethane, cyclohexane, hexanoic acid and Amberlite XAD-2) generally exhibits very small carbon and hydrogen isotope effects in multistep batch experiments. However, carbon and hydrogen isotope fractionation was observed for the benzene-octanol pair after several sorption steps (Δδ(13)C=1.6 ± 0.3‰ and Δδ(2)H=88 ± 3‰), yielding isotope fractionation factors of αC=1.0030 ± 0.0005 and αH=1.195 ± 0.026. Our results indicate that the cumulative effect of successive hydrophobic partitioning steps in an aquifer generally results in insignificant isotope fractionation for benzene and toluene. However, significant carbon and hydrogen isotope fractionation cannot be excluded for specific sorbate-sorbent pairs, such as sorbates with π-electrons and sorbents with OH-groups. Consequently, functional groups of sedimentary organic matter (SOM) may specifically interact with BTEX compounds migrating in an aquifer, thereby resulting in potentially relevant isotope fractionation.


Do phytotoxic allelochemicals remain in ashes after burning Chrysanthemoides monilifera subsp. monilifera (boneseed)?
Australia is facing challenges in controlling Chrysanthemoides monilifera subsp. monilifera (boneseed). However, burning has achieved some success in this regard. We aimed to investigate the comparative phytotoxicity of boneseed dried powder and ashes (burnt at 450°C and 250°C). Phenolic compounds in powder and ashes were measured using Folin-Ciocalteu assay and HPLC. The phytotoxicity of boneseed powder and ash extracts was assessed through germination bioassay on Lactuca sativa and the phytotoxicity of litter and ashes was evaluated using field soil, both in growth chamber. Burning of boneseed reduced total phenolics in ashes of boneseed organs by 99% and 100% both at high and low temperatures. The four phenolic compounds that were detected in boneseed were either absent or at negligible levels in the ashes, with inversely related to temperature. Both boneseed ash extracts and litter ash-mediated soil significantly reduced phytotoxicity displaying increased germination, biometric and biochemical parameters of test species compared with unburnt powder extracts and litter powder-mediated soil respectively, with greater reduction of phytotoxicity found for ashes produced at the lower temperature. Interestingly, the ash extracts and litter ash-mediated soil were found to stimulate some of those parameters of the test species compared to control. There was no excessive reactive oxygen species (ROS) produced in test species exposed to ash extracts compared with unburnt powder extracts. These findings suggest that burning of boneseed is an appropriate method of weed control and that this approach will reduce phytotoxicity of this species on native plants.


Polydactyly of the hands and feet.
Polydactyly of the hand, of the foot, and of the hand combined with the foot were studied. As noted in previous reports of polydactyly, inherited cases represent about 10% of polydactyly of the hand or foot, and unilateral involvement is more common than bilateral. In 495 cases of polydactyly 27 patients had polydactyly of the hands and feet. The extra digits in 21 of those 27 were in the same digital rays of the hand and foot. There were 14 inherited cases (51.9%) and most were an autosomal dominant, but some were an autosomal recessive. Both hand and/or feet were involved in 22 cases. Most cases of preaxial polydactyly of the hand combined with central polydactyly of the foot were sporadic and unilateral. All cases of both preaxial and postaxial (polyaxial) polydactyly were inherited and bilateral. Two pairs of sisters had the same clinical features. The parent (mother or father) also had the same deformities in the inherited cases.


Cerebral blood flow tomography with xenon-133.
Cerebral blood flow (CBF) can be measured tomographically by inhalation of Xenon-133. The calculation is based on taking a sequence of tomograms during the wash-in and wash-out phase of the tracer. Due to the dynamic nature of the process, a highly sensitive and fast moving single photon emission computed tomograph (SPECT) is required. Two brain-dedicated SPECT systems designed for this purpose are mentioned, and the method is described with special reference to the limitations inherent in the soft energy of the 133Xe primary photons. CBF tomography can be used for a multitude of clinical and investigative purposes. This article discusses in particular its use for the selection of patients with carotid occlusion for extracranial/intracranial bypass surgery, for detection of severe arterial spasm after aneurysm bleeding, and for detection of low flow areas during severe migraine attacks. The use of other tracers for CBF tomography using SPECT is summarized with emphasis on the 99mTc chelates that freely pass the intact blood-brain barrier. The highly sensitive brain-dedicated SPECT systems described are a prerequisite for achieving high resolution tomograms with such tracers.


A survey of persisting leg and/or foot pain in vascular surgery patients.
Two surveys were performed on more than 100 postoperative peripheral vascular procedure patients in order to ascertain the incidence and extent of prolonged lower limb pain. There was a significant number of patients who continued to experience moderate or greater degrees of disability associated with their pain at more than 7 months postoperatively. A multidisciplinary approach to the management of peripheral vascular patients is discussed.


Peripheral nerve injuries in the pediatric population: a review of the literature. Part I: traumatic nerve injuries.
This article reviews the clinical results that can be obtained after repair of a traumatic peripheral nerve injury in the pediatric population. A systematic review of the published literature has been made. Functional outcome after major nerve injuries is sometimes disappointing in adults. However, children have been reported to experience much better functional results after nerve repair than adults. Moreover, recovery generally is faster in children. The superior capacity of children's central nervous system to adapt to external or internal environmental changes (neural plasticity) and the shorter recovery distance from the axon repair site to the target muscle are claimed to be crucial determinants of their favorable outcomes. Moreover, even in the pediatric population, it has been demonstrated that functional results are better the younger the patient is, including better clinical results in those injured in early childhood (< 6 years old) than in those injured in adolescence. Other favorable prognostic factors include the type of nerve injury (with complete transections doing less well than crush injuries) and the timing of surgery (with better outcomes after early repairs). All efforts should be done to repair in a timely and adequate fashion traumatic peripheral nerve injuries in children, as the results are good.


Purification of immunologically active HLA-A and -B antigens by a series of monoclonal antibody columns.
Serologically and biochemically pure preparations of detergent and papain-solubilized HLA-A2 and HLA-B7 antigens were isolated by high pH elution from a series of immunoaffinity columns constructed from monoclonal antibodies with specificity for HLA-A2 and HLA-B7 antigens. These preparations retained the immunological activity and quaternary structure of the native molecule and should provide suitable reagents for insertion into liposomes and probing the role of major histocompatibility antigens in lymphocyte interactions.


Heated environment offsets the cardiovascular responses to prolonged rowing exercise in competitive athletes.
Prolonged rowing exercise sessions are often prescribed considering competitive training schedules, and under hostile environments (e.g., heated ambient). The study aimed to investigate the effect of heat stress (HS) on physical performance, Lactate concentration ([Lac]), and cardiorespiratory responses during prolonged exercise sessions in competitive rowers. Twelve rowers performed preliminary exercise tests (2-km test and five-step incremental lactate test) to assess the target workload intensity corresponding to a 2.5 mmol.L-1 of [Lac]. On two separate days, participants were enrolled in two exercise sessions of 12 km in a rowing machine under HS (∼30 °C) and thermal comfort (TC 22 °C) conditions. Heart rate (HR), stroke volume (SV), cardiac output (CO), oxygen uptake (VO2), [Lac], and the rating of perceptual exertion (RPE) were obtained. From baseline, HS increased the maximum temperature of the face compared to TC. Workload and VO2 reduced while RPE increased at 9- and 12-km of rowing exercise under HS compared to TC. From baseline to the last stage of exercise, HS shifted SV downwards and HR upwards compared to TC. Consequently, CO did not change between thermal conditions (TC vs. HS). Therefore, HS provokes a cardiovascular drift during prolonged rowing in comparison to TC. The last stages of prolonged rowing sessions under HS seem to be critical to physical performance and relative perceptual of effort in rowers.


Experimental and theoretical investigation into the response to shock wave for booster explosives JO9C, JH14, JH6, and insensitive RDX.
In order to reduce the vulnerability, the responses to shock waves for booster explosives JO9C, JH14, JH6, and insensitive RDX were evaluated using shock wave partition loading test. To explain the experimental results, molecular dynamics simulation, intermolecular interaction and bond dissociation energy (BDE), and shock initiation pressures were evaluated using the B3LYP, MP2 (full), and M06-2X methods with the 6-311 + + G(2df,2p) basis set. The order of the responsivity is JO9C > JH14 > JH6 > insensitive RDX. The binding energies follow the order of JH14* ≈ JO9C* < insensitive RDX* < JH6*. The interaction energies and BDEs are in RDX∙∙∙(CH3COOCa)+ > RDX∙∙∙CH3COOH > RDX∙∙∙CH2FCH2F. Thus, it can be inferred that for the RDX-based explosives, the stronger the binding energy, intermolecular interaction, and BDE are, the more insensitive the booster is, and thus, the larger energy has to be consumed to overcome the above three kinds of energies during the initiation process, leading to the smaller energy output and weaker response. However, it should be noted that it is mainly the density and the type of explosive that influence the depth of the dent produced on the steel witness block. The essence of the responses to shock waves is revealed by the reduced density gradient, atoms in molecules, and surface electrostatic potentials. HIGHLIGHTS: • Response of booster to shock wave was evaluated by shock wave partition loading test. • Responsivity to shock wave is explained by binding energy, intermolecular interaction, and BDE. • Shock initiation pressures were evaluated. • Essence of responses to shock wave is revealed by RDG, AIM and ESP.


Lexical effects on spoken word recognition performance among Mandarin-speaking children with normal hearing and cochlear implants.
This investigation aimed to examine the effects of word frequency and lexical neighborhood density on spoken word recognition of monosyllables and disyllables in Mandarin by normal hearing children and children with cochlear implants. The lexical characteristics were incorporated from the Neighborhood Activation Model (NAM), which suggests that words in the mental lexicon are organized into similarity neighborhoods. The difficulty of a listener's task is affected by the frequency of the target word and the density of the lexical neighbors from which that word must be identified. The Monosyllabic Lexical Neighborhood Test and the Disyllabic Lexical Neighborhood Test in Mandarin Chinese (Mandarin LNT and MLNT) were developed to take into account the effects of these linguistic and cognitive demands on speech perception performance. Three stages were conducted in this investigation. In the first stage, Mandarin words of monosyllables and disyllables were selected and their lexical properties were calculated from the CHILDES database. Four lexically "easy" and four lexically "hard" word lists in Mandarin LNT as well as two word lists across lexical properties among disyllables were determined based on their relative word frequencies and neighborhood densities. In the second stage, word stimuli were verified by 30 children of the NH group and 36 children from the CI group. In the third stage, the inter-list equivalency and test-retest reliability of word lists across lexical properties were determined, and the correlations of Mandarin LNT and MLNT with other measures and inter-rater reliability were also investigated. Word recognition scores were higher among disyllables than among monosyllables. Lexically "easy" disyllabic words were better recognized than their "hard" counterparts and the monosyllables among two groups of children. However, no lexical effects on word recognition of Mandarin monosyllables were observed for either group. No significant differences were found among word lists in each combination of syllable structure and lexical property. Inter-rater reliability, inter-list equivalency, and test-retest reliability were revealed. The Mandarin LNT and MLNT were found to be highly reliable measures of spoken word recognition (r = 0.84; p < 0.01) with acceptable equivalency between lists (r = 0.638-0.876). Lexical effects on Mandarin word recognition were only demonstrated among disyllabic words by NH and the CI children, while Mandarin homophones appearing in monosyllabic words were suggested. Lexical effects on spoken word recognition in Mandarin are not substantially demonstrated as in English, but the Mandarin LNT and MLNT provided reliable information on the spoken word recognition of pediatric CI users in the initial stage after implantation as well as in the rehabilitation progress.


Blocking IL-25 signalling protects against gut inflammation in a type-2 model of colitis by suppressing nuocyte and NKT derived IL-13.
Interleukin-25 (IL-25) is a potent activator of type-2 immune responses. Mucosal inflammation in ulcerative colitis is driven by type-2 cytokines. We have previously shown that a neutralizing anti-IL-25 antibody abrogated airways hyperreactivity in an experimental model of lung allergy. Therefore, we asked whether blocking IL-25 via neutralizing antibodies against the ligand or its receptor IL-17BR could protect against inflammation in an oxazolone-induced mouse model of colitis. Neutralizing antibodies to IL-25 or IL-17BR were administered to mice with oxazolone-induced colitis, a model of ulcerative colitis. The disease onset was evaluated by weight loss and degree of colon ulceration. Also, lamina propria and mesenteric lymph node (MLN) infiltrates were assessed for mucosal inflammation and cultured in vitro to determine cytokine production. We found that in oxazolone colitis IL-25 production derives from intestinal epithelial cells and that IL-17BR(+) IL-13-producing natural killer T (NKT) cells and nuocytes drive the intestinal inflammation. Blocking IL-25 signalling considerably improved the clinical aspects of the disease, including weight loss and colon ulceration, and resulted in fewer nuocytes and NKT cells infiltrating the mucosa. The improved pathology correlated with a decrease in IL-13 production by lamina propria cells, a decrease in the production of other type-2 cytokines by MLN cells, and a decrease in blood eosinophilia and IgE. IL-25 plays a pro-inflammatory role in the oxazolone colitis model, and neutralizing antibodies to IL-25 or IL-17BR can slow the ongoing inflammation in this disease. Because this model mimics aspects of human ulcerative colitis, these antibodies may represent potential therapeutics for reducing gut inflammation in patients.


Short- and long-term major adverse cardiac events in patients undergoing percutaneous coronary intervention with stenting for acute myocardial infarction complicated by cardiogenic shock.
To determine the risk of short- and long-term mortality and major adverse cardiac events (MACE) in acute myocardial infarction (AMI) patients complicated by cardiogenic shock (CS) in the contemporary practice of primary percutaneous coronary intervention with stenting. Of the 1,755 consecutive AMI patients undergoing percutaneous coronary intervention with stenting enrolled, 103 had CS at admission. Primary endpoints were early mortality (within 30 days after the index event) and late mortality (from day 31 up to 4 years). Secondary endpoints included MACE [all-cause death, myocardial infarction or target vessel revascularization (TVR)], myocardial infarction, TVR and stent thrombosis. Thirty-day mortality was higher among CS patients, and CS was a strong independent predictor of a higher risk of early death (adjusted HR 3.64, 95% CI 2.44-5.44). The late mortality rate was significantly higher in CS patients, and CS was also a predictor of higher risk of death at a 4-year follow-up (adjusted HR 1.95, 95% CI 1.11-3.45). Recurrent AMI, TVR and stent thrombosis rates were similar among patients with and without CS. CS complicating AMI is still a severe clinical event, mainly with regard to a significant higher risk of early mortality, but also associated with a worse prognosis in 30-day survivors.


The Senior Fitness Test as a functional measure in Parkinson's disease: a pilot study.
This pilot study aimed to determine if the Senior Fitness Test (SFT) battery can be applied to subjects with Parkinson's disease (PD) and whether its results can be reliable indicators of disease severity. Thirty people with mild to moderate PD performed the SFT and completed the Parkinson's Disease Questionnaire (PDQ-39) and the Unified Parkinson's Disease Rating Scale (UPDRS). To compare the metric properties of the SFT battery with the UPDRS and the PDQ-39, a SFT sum-score was created. The tests that compose the SFT were successfully completed by the patients, except for the "Two-Minute Step Test" (2MST), which had to be shortened. We observed a strong correlation among the SFT's sum-score and the total scores of the PDQ-39 and the UPDRS. Some correlation was also found among the SFT's sum-score and the analyzed subscales, except for those assessing mental and cognitive levels. The SFT appears to be a useful tool to assess functional fitness in people with PD: it can be carried out in the clinical setting albeit with some minor modifications. However, its validity as an indicator of disease severity remains to be confirmed.


A nonlinear association between body roundness index and all-cause mortality and cardiovascular mortality in general population.
The aim of the study was to investigate the association between body roundness index (BRI) and all-cause mortality and cardiovascular mortality in general population. A retrospective cohort study. The status of cardiovascular mortality and all-cause mortality of participants were followed through 31 December 2015. Multivariate adjusted Cox restricted cubic spline regression models and Kaplan-Meier survival curves were used to evaluate the relationship between BRI and cardiovascular mortality and all-cause mortality. A sample of 47 356 participants from the National Health and Nutrition Examination Surveys 1999-2014 with aged ≥18 years. Mean age was 47 years and female were 49·9 %. During a median follow-up of 92 months, 4715 participants died from any cause, with 985 died of CVD. In multivariate adjusted Cox regression, compared with the lowest quartile of Body roundness index (BRI), the hazard ratios (HR) for all-cause mortality from other quartiles were 0·83, 95 % CI (0·75, 0·92), 0·73, 95 % CI (0·65, 0·81) and 0·80, 95 % CI (0·72, 0·89), respectively (Pfor trend < 0·05) and the HR for cardiovascular mortality from other quartiles were 0·79, 95 % CI (0·62, 1·00), 0·78, 95 % CI (0·62, 0·99) and 0·79, 95 % CI (0·62, 1·01), respectively (P for trend > 0·05). In the restricted cubic spline regression models, the relationship was showed U-shaped between BRI and all-cause mortality and cardiovascular mortality. In Kaplan-Meier survival curves, the lowest cumulative survival rate of cardiovascular mortality and all-cause mortality was recorded in the highest BRI quartile. The U-shaped association between BRI and all-cause mortality and cardiovascular mortality in a large population-based cohort was observed.


Effect of cooking procedures of kiymali pide, a traditional Turkish fast-food, on destruction of Escherichia coli O157:H7.
The objective of the present study was to obtain data about cooking time and temperature of kiymali pide in the restaurants and to investigate thermal inactivation of E. coli O157:H7 during experimental kiymali pide making. A field study was conducted in randomly selected 23 of 87 pide restaurants. Processing parameters including oven temperature, cooking period and post-cooking temperature were determined. Kiymali pide samples were prepared using ground beef filling experimentally inoculated with E. coli O157:H7 (7.6 log10 CFU/g). Pide samples were cooked at a conventional oven at 180 °C for 180, 240, 270, 300 and 330 s. Results of the current study suggest that cooking kiymali pide at 180 °C for at least 330 s (5.5 min) may provide sufficient food safety assurance (≥6 log10 CFU/g) for E. coli O157:H7.


Interaction of phenolic acids with trypsin: Experimental and molecular modeling studies.
Trypsin is a kind of protease for digestion and food processing, whose activity can be inhibited by phenolic acids in plant foods. However, most reports explained the inhibitory difference of phenolic acids based on the number and position of substituent groups, which failed to reveal the comprehensive inhibitory mechanism. In this work, the inhibitory effects of 11 common phenolic acids on trypsin were investigated. Amongst the tested cinnamic and benzoic acid derivatives, caffeic acid and gallic acid showed the strongest anti-trypsin activity with a noncompetitive inhibition pattern, respectively. The fluorescence analysis displayed that both the quenching rate constant (Kq) and binding constant (KA) of caffeic acid were higher than those of gallic acid. Molecular docking illustrated their different binding modes with trypsin. The ONIOM calculations revealed that the binding capacity of caffeic acid was higher than that of gallic acid, which could explain their difference in their inhibitory behaviors.


Childhood thyroid cancer. Characteristics and long-term outcome in children irradiated for benign conditions of the head and neck.
To determine the characteristics and long-term outcome of radiation-induced thyroid cancer in children. Retrospective review of a cohort of 4296 irradiated patients who received childhood radiation treatment to the head and neck area at the same hospital. Forty-one children who were younger than 20 years when thyroid cancer developed in them and 77 adults in whom thyroid cancer developed. All 118 cases were diagnosed before 1974 and were followed up for a median of 19.4 years. Children presented with clinically palpable lymph nodes more often than adults (30.7% vs 15.1%, P = .05) and had more recurrences (39% vs 16%, P = .05). Despite these frequent recurrences, only one patient (an adult) died of thyroid cancer. Seventy percent of the recurrences occurred during the first 10 years of follow-up, but recurrences continued after 20 years. The adults had previously identified factors that predicted the risk of recurrences, but none could be identified in the children. The presentation and relatively good outcome of radiation-induced thyroid cancer in children is similar to that in nonirradiated children. Frequent and late recurrences call for lifelong follow-up.


Engineered autologous cartilage tissue for nasal reconstruction after tumour resection: an observational first-in-human trial.
Autologous native cartilage from the nasal septum, ear, or rib is the standard material for surgical reconstruction of the nasal alar lobule after two-layer excision of non-melanoma skin cancer. We assessed whether engineered autologous cartilage grafts allow safe and functional alar lobule restoration. In a first-in-human trial, we recruited five patients at the University Hospital Basel (Basel, Switzerland). To be eligible, patients had to be aged at least 18 years and have a two-layer defect (≥50% size of alar subunit) after excision of non-melanoma skin cancer on the alar lobule. Chondrocytes (isolated from a 6 mm cartilage biopsy sample from the nasal septum harvested under local anaesthesia during collection of tumour biopsy sample) were expanded, seeded, and cultured with autologous serum onto collagen type I and type III membranes in the course of 4 weeks. The resulting engineered cartilage grafts (25 mm × 25 mm × 2 mm) were shaped intra-operatively and implanted after tumour excision under paramedian forehead or nasolabial flaps, as in standard reconstruction with native cartilage. During flap refinement after 6 months, we took biopsy samples of repair tissues and histologically analysed them. The primary outcomes were safety and feasibility of the procedure, assessed 12 months after reconstruction. At least 1 year after implantation, when reconstruction is typically stabilised, we assessed patient satisfaction and functional outcomes (alar cutaneous sensibility, structural stability, and respiratory flow rate). Between Dec 13, 2010, and Feb 6, 2012, we enrolled two women and three men aged 76-88 years. All engineered grafts contained a mixed hyaline and fibrous cartilage matrix. 6 months after implantation, reconstructed tissues displayed fibromuscular fatty structures typical of the alar lobule. After 1 year, all patients were satisfied with the aesthetic and functional outcomes and no adverse events had been recorded. Cutaneous sensibility and structural stability of the reconstructed area were clinically satisfactory, with adequate respiratory function. Autologous nasal cartilage tissues can be engineered and clinically used for functional restoration of alar lobules. Engineered cartilage should now be assessed for other challenging facial reconstructions. Foundation of the Department of Surgery, University Hospital Basel; and Krebsliga beider Basel.


Isolation of a five-polypeptide cytochrome b-f complex from spinach chloroplasts.
A simple rapid purification of a cytochrome b-f complex from spinach chloroplasts is described. Novel features of the method include: 1) EDTA treatment of thylakoids prior to detergent extraction; 2) affinity chromatography over equine cytochrome c linked to Sepharose 4B; and 3) inclusion of the protease inhibitor phenylmethylsulfonyl fluoride. Cytochrome b-f complex is obtained in good yield, free of exogenous lipid, and with high plastoquinol:plastocyanin oxidoreductase activity. The complex contains 2 eq of cytochrome b-563 per eq of cytochrome f and a Rieske iron-sulfur center. Polyacrylamide gel electrophoresis in the presence of dodecyl sulfate indicates that the complex is composed of five distinct polypeptides of Mr = 37,000, 33,500, 22,000, 19,000, and 16,500. Only the Mr = 33,500 and 22,000 polypeptides stain for heme. The Mr = 37,000 component in this preparation is absent from cytochrome b-f complex isolated by another procedure (Hurt, E., and Hauska, G. (1981) Eur. J. Biochem. 117, 591-599). The complex described here also differs in its spectrum at 77 K, its stability, and its buoyant density.


Association of inflammatory cytokine gene polymorphisms with inflammatory bowel disease in a Moroccan cohort.
The purpose of this study was to investigate whether common variants in inflammatory and immune response genes influence inflammatory bowel disease (IBD) risk among Moroccan patients. Using a candidate gene approach, 10 single-nucleotide polymorphisms mapping on six genes (MIF_rs755622, TNFA_rs1800629, IL6_rs2069840, IL6R_rs2228145, IL6ST_rs2228044, IL17A (rs2275913, rs4711998, rs7747909, rs8193036, rs3819024)) were assessed in 510 subjects grouped in 199 IBD and 311 healthy controls. Genotyping was performed with the TaqMan allelic discrimination technology. The results were analyzed using PLINK software. The frequency of allele A for TNFA rs1800629 was significantly higher in ulcerative colitis (UC) patients compared with controls (30.16 vs 16.72%; P=0.0005; odds ratio (OR)=2.15; 95% confidence interval (CI)=1.39-3.32). Statistically significant association to UC was also found under dominant AA+AG vs GG (OR=1.85, 95% CI=1.07-3.21; P=0.02) and recessive models (OR=8.38; 95% CI=2.86-24.53; P=0.0001). In the same way, an association of TNFA rs1800629 variant was observed with IBD under recessive model AA vs AG+GG (OR=4.10; 95% CI=1.56-10.76; P=0.004). No evidence of significant associations was found for the remaining investigated polymorphisms. Our data suggest that TNFA gene promoter polymorphism participates in determining IBD susceptibility in Moroccan patients.


The "replication crisis" in the public eye: Germans' awareness and perceptions of the (ir)reproducibility of scientific research.
Several meta-analytical attempts to reproduce results of empirical research have failed in recent years, prompting scholars and news media to diagnose a "replication crisis" and voice concerns about science losing public credibility. Others, in contrast, hoped replication efforts could improve public confidence in science. Yet nationally representative evidence backing these concerns or hopes is scarce. We provide such evidence, conducting a secondary analysis of the German "Science Barometer" ("Wissenschaftsbarometer") survey. We find that most Germans are not aware of the "replication crisis." In addition, most interpret replication efforts as indicative of scientific quality control and science's self-correcting nature. However, supporters of the populist right-wing party AfD tend to believe that the "crisis" shows one cannot trust science, perhaps using it as an argument to discredit science. But for the majority of Germans, hopes about reputational benefits of the "replication crisis" for science seem more justified than concerns about detrimental effects.


Risk factors for mortality in patients with anti-MDA5 antibody-positive dermatomyositis: A meta-analysis and systematic review.
To determine the prognostic factors of dermatomyositis with anti-melanoma differentiation-associated gene 5 (MDA5) antibody, a rare disease and often complicated by life-threatening, rapidly progressive interstitial lung disease. Herein, we searched the Medline, Embase, and Cochrane Library databases and extracted studies published before August 23, 2022. Pooled analysis of hazard ratios (HRs) or odds ratios was used to identify prognostic factors for mortality among patients with anti-MDA5 antibody-positive dermatomyositis (MDA5+ DM). Twenty-nine cohorts with 2,645 patients were included in this meta-analysis. Factors related to poor prognosis included old age (HR 1.54, 95% confidence interval (CI) 1.41-1.69, p < 0.01), male sex (HR 2.07, 95% CI 1.34-3.18, p < 0.01), rapidly progressive interstitial lung disease (RP-ILD) (HR 9.34, 95% CI 6.39-13.6, p < 0.01), high levels of ferritin (HR 1.05, 95% CI 1.01-1.08, p < 0.01), C-reactive protein (CRP) (HR 1.12, 95% CI 1.06-1.19, p < 0.01), creatine kinase (HR 1.05, 95% CI 1.03-1.07, p < 0.01), and lactate dehydrogenase (LDH) (HR 1.27, 95% CI 1.12-1.45, p < 0.01), whereas oxygen index (HR 0.990, 95% CI 0.988-0.992, p < 0.01), partial pressure of oxygen (HR 0.933, 95% CI 0.906-0.961, p < 0.01), forced vital capacity (HR 0.962, 95% CI 0.928-0.998, p = 0.038), and lymphocyte count (HR 0.421, 95% CI 0.282-0.629, p < 0.01) were associated with better outcomes. Old age, male sex, hypoxemia, low forced vital capacity, lymphocytopenia, and high levels of ferritin, CRP, creatine kinase, and LDH are risk factors for mortality in patients with MDA5+ DM. However, a cautious interpretation of these results and further quality investigation are warranted.


Molecular characterization of penaeidins from two Atlantic Brazilian shrimp species, Farfantepenaeus paulensis and Litopenaeus schmitti.
We report here the molecular cloning of new members of the penaeidin family from two Atlantic penaeids from Brazil, Litopenaeus schmitti and Farfantepenaeus paulensis. The presence of penaeidins in the granular hemocytes of both shrimps was first evidenced by immunofluorescence, using polyclonal antibodies raised against L. vannamei penaeidin Litvan PEN3-1. cDNAs from the hemocytes of both Brazilian species were obtained by reverse transcription and the sequences encoding penaeidins were amplified by PCR, using primers based on penaeidin consensus sequences. Five penaeidin clones were obtained. According to the international penaeidin classification (PenBase, http://www.penbase.immunaqua.com), the deduced amino acid sequences of two clones from L. schmitti and two from F. paulensis belong to the PEN2 subgroup and one clone from L. schmitti to the PEN4 subgroup of penaeidins. Surprisingly, no penaeidin from the PEN3 subgroup was obtained in both shrimp species, even though this subgroup appears to be the most commonly expressed in the hemocytes of penaeids.


Pilot Outcome Results of Culturally Adapted Evidence-Based Substance Use Disorder Treatment with a Southwest Tribe.
Although American Indians/Alaska Natives (AI/ANs) have exhibited high rates of alcohol and drug use disorders, there is a paucity of substance use disorder treatment outcome research. In addition, there exists controversy about whether evidence-based treatments (EBTs) are culturally appropriate given they were derived mainly by and for non-Hispanic White populations and do not explicitly include aspects of AI/AN culture and worldview. In this pilot study, we collaboratively culturally adapted two EBTs, Motivational Interviewing and Community Reinforcement Approach (MICRA), and evaluated substance use and psychological outcomes at 4- and 8-months post baseline assessment. In preparation for a larger randomized clinical trial (RCT), eight tribal members (75% male) participated in this pilot treatment study. Measures included substance use, urine screens, self-efficacy, psychological distress, and hopelessness. All participants completed follow-up assessments at 4- and 8-months. Due to small sample size, effect sizes were calculated to evaluate outcomes pre- and post-treatment. Despite high rates of abstinence at baseline, percent days abstinent (PDA) increased at the 8-month time point for the most commonly used substances (alcohol, Hedges's g = 0.59, and marijuana, g = 0.60) and for all substances combined (excluding tobacco, g = 0.56). Improvements in psychological distress (g = -0.66) and 5 of the 7 Addiction Severity Index domains (range of g = -0.42 to -0.98) also emerged. Results suggest that culturally adapted EBTs yield significant improvements in alcohol use, psychological distress, and legal problems among AI/ANs. Future research using RCT methodology is needed to examine efficacy and effectiveness.


A TetR family transcriptional regulator, SP_2854 can affect the butenyl-spinosyn biosynthesis by regulating glucose metabolism in Saccharopolyspora pogona.
Butenyl-spinosyn produced by Saccharopolyspora pogona exhibits strong insecticidal activity and a broad pesticidal spectrum. Currently, important functional genes involve in butenyl-spinosyn biosynthesis remain unknown, which leads to difficulty in efficiently understanding its regulatory mechanism, and improving its production by metabolic engineering. Here, we identified a TetR family transcriptional regulator, SP_2854, that can positively regulate butenyl-spinosyn biosynthesis and affect strain growth, glucose consumption, and mycelial morphology in S. pogona. Using targeted metabolomic analyses, we found that SP_2854 overexpression enhanced glucose metabolism, while SP_2854 deletion had the opposite effect. To decipher the overproduction mechanism in detail, comparative proteomic analysis was carried out in the SP-2854 overexpressing mutant and the original strain, and we found that SP_2854 overexpression promoted the expression of proteins involved in glucose metabolism. Our findings suggest that SP_2854 can affect strain growth and development and butenyl-spinosyn biosynthesis in S. pogona by controlling glucose metabolism. The strategy reported here will be valuable in paving the way for genetic engineering of regulatory elements in actinomycetes to improve important natural products production.


Effect of cooling on intracellular transport and secretion of thyroglobulin.
The effect of cooling to 20 degrees C on the intracellular transport and secretion of thyroglobulin was studied by incubating open thyroid follicles isolated from porcine thyroid tissue. Follicles were labeled with 3H-leucine or 3H-galactose and the secretion of labeled thyroglobulin into the incubation medium was followed by chase incubations under various experimental conditions. The observations indicate that the transport of thyroglobulin is inhibited at three sites of the intracellular pathway by cooling to 20 degrees C, i.e., between the RER cisternae and the Golgi cisternae, between the latter and the exocytic vesicles, and between these vesicles and the extracellular space (corresponding to the follicle lumen). The secretion of 3H-leucine-labeled thyroglobulin decreased linearly between 37 degrees and 20 degrees C; within this temperature range the activation energy for secretion, calculated from Arrhenius plots, was found to be 37 kcal/mol. Below 20 degrees C the secretion was scarcely measurable. It is suggested that the three transport blocks at 20 degrees C result mainly from inhibition of membrane fission and fusion due to phase transition in membrane lipids.


Review of Low-Level Bioacoustic Behavior in Wild Cetaceans: Conservation Implications of Possible Sleeping Behavior.
Shallow, low-activity, low-biosonar parabolic-shaped dives were observed in biologging data from tagged harbor porpoises in Danish waters and identified as potential sleeping behavior. This behavioral state merits consideration in assessing the context for noise exposure and passive acoustic monitoring studies. Similar dives have also been reported for other cetacean species. The existence of low-level bioacoustic dives that may represent that sleeping has implications for the mitigation of not only noise exposure but also of bycatch as well as legal repercussions given the protected status of sleeping, as a part of resting, under many legislative regimes.


[Study of tooth movement under different loading force system by FEM].
To investigate different type of tooth movement under different force systems by simulating clinical loading force systems. Develop a three-dimensional finite element model of upper central incisor, which consists of 945 isoparametric elements, 1245 nodes. Analyse the types of tooth movement under different force system with a horizontal force of 1 N being applied at the upper central incisor. Different force systems(M/F) lead to different types of tooth movement. This study showed the relation between them. When M/F =-9.15:1,it bringed the result of the controlled tipping movement, When M/F=-10.30 -10.50:1, it bringed the bodily movement; While M/F=-10.90:1, it lead to the root movement. This study suggested that it is necessary to adopt different loading force systems in order ot obtain determined tooth movement.


Beta-glucans and cancer: The influence of inflammation and gut peptide.
Dietary β-glucans are soluble fibers with potentially health-promoting effects. Gut peptides are important signals in the regulation of energy and glucose homeostasis. This article reviews the effects of different enriched β-glucan food consumption on immune responses, inflammation, gut hormone and cancer. Gut hormones are influenced by enriched β-glucan food consumption and levels of such peptide as YY, ghrelin, glucagon-like peptide 1 and 2 in humans influence serum glucose concentration as well as innate and adaptive immunity. Cancer cell development is also regulated by obesity and glucose dishomeostasy that are influenced by β-glucan food consumption that in turn regulated gut hormones.