[Analysis of TGFBI gene mutation in a Chinese family affected with Reis-Bucklers corneal dystrophy].
To analyze the clinical features and TGFBI gene mutation in a Chinese family affected with Reis-Bucklers corneal dystrophy. Genomic DNA was extracted from 53 members including 9 patients from the family. The 17 exons and splice region of introns of the TGFBI gene were amplified by PCR and directly sequenced. All family members were subjected to ophthalmologic examination. A heterozygous mutation (R124L) was found in exon 4 of the TGFBI gene among all patients from the family. The same mutation was not found among unaffected family members. The inheritance pattern of the family was identified as autosomal dominant, and the Reis-Bucklers corneal dystrophy in the family was diagnosed as the geographic type. The R124L mutation of the TGFBI gene probably underlies the pathogenesis of Reis-Bucklers corneal dystrophy in this Chinese family. Molecular genetic approach is useful for the proper diagnosis of this type of corneal dystrophy.


Reactive oxygen species activate focal adhesion kinase, paxillin and p130cas tyrosine phosphorylation in endothelial cells.
Reactive oxygen species (ROS), particularly hydroxyl radical (HO*), increase neutrophil adherence to hypoxanthine-xanthine oxidase (HX-XO)-treated human umbilical vein endothelial cells (HUVEC) in culture. This adherence is inhibited by the tyrosine kinase inhibitors genistein (30 microM) and herbimycin A (0.9 microM), suggesting the involvement of tyrosine kinase. Phosphorylation of several HUVEC proteins in the range of 120-130 and 70 kDa was found to depend on the XO concentration and stimulation time. This phosphorylation was inhibited by the antioxidants dimethylthiourea (DMTU, 0.75 to 7.5 mM) and pentoxifylline (Ptx, 0.1 mM), and by the iron chelators desferrioxamine (DF, 1 mM) and hydroxybenzyl ethylene diamine (HBED, 0.5 mM), suggesting the involvement of HO*. Three tyrosine-phosphorylated proteins, focal adhesion kinase (p125FAK), paxillin (PAX) and p130cas were isolated and characterized by immunoprecipitation and western blotting. Antioxidants and iron chelators reduced their phosphorylation. HUVEC treated with ROS for 15 min showed actin stress fiber formation. Cytochalasin D (5 microM) inhibited tyrosine phosphorylation and PMN-HUVEC adherence, showing the importance of cytoskeleton integrity in these two functions. In conclusion, HO*, which is involved in increased PMN-HUVEC adhesion, also increases tyrosine phosphorylation on three major cytoskeleton proteins which seem to play a role in this adhesion.


Validity and Reliability of 11-face Faces Pain Scale in the Iranian Elderly Community with Chronic Pain.
Accurate pain assessment in elderly population is essential for pain management and nurses have a pivotal role. The 11-face Faces Pain Scale (FPS-11) is a well-established pain assessment measure that has not been validated in the Iranian elderly. The aim was to study the property assessment of the Iranian version of FPS-11 (FPS-11-IR) among elderly outpatients with chronic pain. This is a cross-sectional validation study that conducted in three outpatient clinics in Tehran, Iran, in 2017. Older people aged ≥60 years (n = 217) with chronic knee pain due to degenerative joint disease were participated. The construct validity was examined by applying contrast constructs, and the face validity was determined by rank-ordering test. To assess concurrent validity, the Spearman's correlation coefficient was calculated between the scores of 11-point Numeric Rating Scale (NRS) and FPS-11-IR. Test-retest reliability was determined in 1-week interval. Most of elderly participants (72%) agreed that pain construct displays in faces of the FPS-11-IR and participants" agreement on face rank ordering were vary for each face, ranging from 80% to 100%. Spearman's correlation coefficient between FPS-11-IR and NRS scores was very strong (r = 0.91, P < 0.01). Intraclass correlation coefficient between test-retest scores was 0.96 that indicates excellent reliability. The FPS-11-IR is a reliable and valid pain assessment scale to use in geriatric patients chronic pain.


KTaO3 -The New Kid on the Spintronics Block.
Long after the heady days of high-temperature superconductivity, the oxides came back into the limelight in 2004 with the discovery of the 2D electron gas (2DEG) in SrTiO3 (STO) and several heterostructures based on it. Not only do these materials exhibit interesting physics, but they have also opened up new vistas in oxide electronics and spintronics. However, much of the attention has recently shifted to KTaO3 (KTO), a material with all the "good" properties of STO (simple cubic structure, high mobility, etc.) but with the additional advantage of a much larger spin-orbit coupling. In this state-of-the-art review of the fascinating world of KTO, it is attempted to cover the remarkable progress made, particularly in the last five years. Certain unsolved issues are also indicated, while suggesting future research directions as well as potential applications. The range of physical phenomena associated with the 2DEG trapped at the interfaces of KTO-based heterostructures include spin polarization, superconductivity, quantum oscillations in the magnetoresistance, spin-polarized electron transport, persistent photocurrent, Rashba effect, topological Hall effect, and inverse Edelstein Effect. It is aimed to discuss, on a single platform, the various fabrication techniques, the exciting physical properties and future application possibilities of this family of materials.


A novel analgesic dipeptide from bovine brain is a possible Met-enkephalin releaser.
It is generally accepted that morphine exerts its analgesic effect by binding to specific opiate receptors in the brain and spinal cord. Since Hughes et al. isolated and identified two endogenous pentapeptides, Met- and Leu-enkephalin, from the brain and found that they acted as agonists at opiate receptors, alpha-, beta- and gamma-endorphins, larger peptides than enkephalins and having morphine-like activity, have been identified in either the brain or pituitary of various species. Several studies have demonstrated that enkephalins possess analgesic properties and that they are distributed in the pain-mediated pathways in the central nervous system. These findings suggest that enkephalins are important neurotransmitters or neuromodulators regulating pain transmission. We now report the isolation of a novel substance which has a Met-enkephalin releasing action. Our findings suggest the possibility of a regulating mechanism for the release of endogenous opioid peptides, especially Met-enkephalin.


Spin-orbit interaction in bent carbon nanotubes: resonant spin transitions.
We develop an effective tight-binding Hamiltonian for spin-orbit (SO) interaction in bent carbon nanotubes (CNT) for the electrons forming the π bonds between the nearest neighbor atoms. We account for the bend of the CNT and the intrinsic spin-orbit interaction which introduce mixing of π and σ bonds between the p(z) orbitals along the CNT. The effect contributes to the main origin of the SO coupling-the folding of the graphene plane into the nanotube. We discuss the bend-related contribution of the SO coupling for resonant single-electron spin and charge transitions in a double quantum dot. We report that although the effect of the bend-related SO coupling is weak for the energy spectra, it produces a pronounced increase of the spin transition rates driven by an external electric field. We find that spin-flipping transitions driven by alternate electric fields have usually larger rates when accompanied by charge shift from one dot to the other. Spin-flipping transition rates are non-monotonic functions of the driving amplitude since they are masked by stronger spin-conserving charge transitions. We demonstrate that the fractional resonances-counterparts of multiphoton transitions for atoms in strong laser fields-occurring in electrically controlled nanodevices already at moderate ac amplitudes-can be used to maintain the spin-flip transitions.


Mediating effect of self-control in the relationship between psychological distress and food addiction among college students.
Psychological distress is a possible trigger contributing to food addiction, which is characterized by a loss of behavioral control and compulsive food intake. However, little is known about its underlying mechanisms. Self-control, an important self-regulation skill, may mediate the effect of psychological distress on food addiction. A cross-sectional survey was used to explore the direct relationship between psychological distress and food addiction, and the mediating role of self-control in this relationship. Food addiction, psychological distress, and self-control were evaluated using the Chinese versions of the Yale Food Addiction Scale 2.0, Depression-Anxiety-Stress Scale, and Self-control Scale, respectively. Correlation analyses showed that food addiction was positively correlated with psychological distress, but negatively related to self-control. Structural equation modeling revealed the mediating role of self-control in the relationship between food addiction and psychological distress. As a significant predictor of food addiction, psychological distress may induce food addiction directly or indirectly through the effect of self-control. These findings provide a deeper understanding of the relationship between psychological distress and food addiction, and the underlying mechanism. As such, psychological distress and self-control should be included in prevention and intervention strategies to address food addiction among college students.


Breast cancer dissemination promoted by a neuregulin-collagenase 3 signalling node.
Advances in the treatment of breast cancer have resulted in increased survival. However, in the metastatic setting, the disease remains incurable. Therefore, understanding of the mechanisms that promote dissemination of breast cancer cells may favor the development of novel therapeutic strategies to fight those tumors. Here, we show that the ErbB ligands, Neuregulins (NRGs), promote metastatic dissemination of breast cancer cells by switching on a kinase-metalloproteinase network. Clinicopathological analyses demonstrated that NRG expression in breast tumors associated to lymph node invasion and poor patient outcome. Preclinical in vivo analyses showed that NRG expression favored in situ tumor growth, local spreading and metastatic dissemination. Genomic, biochemical and functional studies identified matrix metalloproteinases, particularly stromelysin 2 and collagenase 3, as key mediators of the NRG-induced dissemination properties of breast cancer cells. Mechanistic analyses demonstrated that NRG augmented metalloproteinase expression through a route controlled by ERK1/2 kinases. ERK1/2 increased collagenase 3 expression by controlling the activity of an SBF1-related transcription factor. In conclusion, we describe a pathway linked to breast cancer dissemination. The clinical availability of agents that target some of the components of this signalling pathway suggests that patients with tumors fed by NRGs or other factors able to activate the ERK-Collagenase 3 route may benefit from agents that act on that signalling axis.


Estimating potential illegal land development in conservation areas based on a presence-only model.
Conservation areas are facing increasing threats from anthropogenic land use activities. It is important to reasonably recognize and predict suspected illegal land development in advance. However, traditional methods easily suffer from selection bias due to the lack of accurate and reliable absence data. To tackle this problem, we have presented a novel method for estimating potential illegal land development based on the presence-only maximum entropy (MAXENT) model. The principle of MAXENT can guarantee that no additional unknown information (e.g., inaccurate pseudo-absence samples) will be introduced into the estimation procedure. This method was applied to the conservation areas in a fast-growing city, and the robustness of the MAXENT models was confirmed by the high AUC scores (over 0.80). The results indicated that the proposed method performs more effectively than the presence-absence random forest model. In addition, topographic conditions and proximity to transportation networks played dominant roles in the emergence of suspected illegal land development. Moreover, the probability map generated by MAXENT suggests that a considerable amount of forest, farmland, grassland, and water bodies will face a high degree of danger. Therefore, both superior and local governments should pay much more attention to regions with a higher potential for illegal land development. In summary, our findings are expected to support decision-making in the management and assessment of conservation areas in fast-growing regions. More importantly, the proposed method can be further applied to illegal land development estimation in many other regions.


A computational account of how individuals resolve the dilemma of dirty money.
Money can be tainted when it is associated with direct or indirect harm to others. Deciding whether to accept "dirty money" poses a dilemma because money can be used to help others, but accepting dirty money has moral costs. How people resolve the dilemma of dirty money remains unknown. One theory casts the dilemma as a valuation conflict that can be resolved by integrating the costs and benefits of accepting dirty money. Here, we use behavioral experiments and computational modeling to test the valuation conflict account and unveil the cognitive computations employed when deciding whether to accept or reject morally tainted cash. In Study 1, British participants decided whether to accept "dirty" money obtained by inflicting electric shocks on another person (versus "clean" money obtained by shocking oneself). Computational models showed that the source of the money (dirty versus clean) impacted decisions by shifting the relative valuation of the money's positive and negative attributes, rather than imposing a uniform bias on decision-making. Studies 2 and 3 replicate this finding and show that participants were more willing to accept dirty money when the money was directed towards a good cause, and observers judged such decisions to be more praiseworthy than accepting dirty money for one's own profit. Our findings suggest that dirty money can be psychologically "laundered" through charitable activities and have implications for understanding and preventing the social norms that can justify corrupt behavior.


Higher order aberrations and visual function in a young Asian population of high myopes.
To examine the associations between higher order aberrations (HOAs), visual performance, demographics, and ocular characteristics in a young Asian population with high myopia. This was a retrospective review of military pre-enlistees conducted between March 2014 to September 2018. Visual acuity and contrast sensitivity were tested under photopic, mesopic and simulated night conditions. Ocular, corneal and internal HOAs were measured with a Hartmann-Shack wavefront aberrometer (KR-1W, Topcon Co., Tokyo, Japan). 522 eyes of 263 consecutive subjects with severe high myopia (defined as spherical equivalent refraction [SER] ≤ -10.00D) in at least one eye, and high myopia (SER ≤ -6.00D) in the fellow eye, [mean (SD) SER -11.85 (2.03D)] were analysed. The mean (SD) age of subjects was 18.5 (1.6) years. Chinese eyes had significantly greater internal total HOA root-mean-square (RMS) compared to Malay eyes [mean difference (SD) 0.0246 (0.007) μm, p < 0.001). More negative SER was associated with greater ocular total HOA (p = 0.038), primary coma (p = 0.003) and tetrafoil (p = 0.025) RMS, as well as more positive ocular (p = 0.003) and internal primary spherical aberration (p = 0.009). Greater ocular total HOAs was associated with reduced visual acuity in simulated night conditions and low contrast, decreased contrast sensitivity under mesopic and simulated night conditions (all p < 0.05). Greater HOAs were associated with Chinese ethnicity and more negative SER in a young Asian population with high myopia. Greater HOAs were associated with poorer visual performance in low luminance and reduced contrast conditions.


Interaction of prostaglandins with adrenal microsomal cytochrome P-450 in the guinea pig.
Studies were carried out to investigate the effects of prostaglandins (PG) in vitro on adrenal microsomal steroid and drug metabolism in the guinea pig. The addition of PGE1, PGE2, PGA1, PGF1 alpha or PGF2 alpha to isolated adrenal microsomes produced typical type I difference spectra. The sizes of the spectra (delta A385-420) produced by prostaglandins were smaller than those produced by various steroids including progesterone, 17-hydroxyprogesterone and 11 beta-hydroxyprogesterone. However, the affinities of prostaglandins and steroids for adrenal microsomal cytochrome P-450, as estimated by the spectral dissociation constants, were similar. Prior addition of prostaglandins to isolated adrenal microsomes did not affect steroid binding to cytochrome P-450 or the rate of steroid 21-hydroxylation. In contrast, prostaglandins inhibited adrenal metabolism of ethylmorphine and diminished the magnitude of the ethylmorphine-induced spectral change in adrenal microsomes. The results indicate that prostaglandins inhibit adrenal drug metabolism by interfering with substrate binding to cytochrome P-450. Since 21-hydroxylation was unaffected by PG, different cytochrome P-450 moieties are probably involved in adrenal drug and steroid metabolism.


Down-regulation of Fas-ligand mRNA in Sjögren's syndrome patients with enlarged exocrine glands.
We have reported that Sjögren's syndrome (SS) patients with enlarged exocrine glands (EEG) formerly referred to as Mikulicz's disease were defective with Fas-ligand (FasL) expression in PBL and lacrimal glands (LGs). To investigate the mechanisms of reduced FasL expression in SS patients with EEG, FasL mRNA expression level was determined using real-time PCR. The FasL gene promoter region (from - 1197 to - 3) was also amplified using PCR and specific primers. Expression of the FasL mRNA in the LGs and PBLs of three SS patients with EEG was significantly decreased. Direct sequencing revealed a heterozygous point mutation ( - 259T/C) in the FasL gene promoter region in one SS patient with EEG. A luminescent beta-galactosidase (beta-gal) reporter assay using a pbetagal Enhancer Vector demonstrated that beta-gal activity from the vector including the mutant ( - 259C) FasL (pbetagal/mFasL) gene promoter region (735 +/- 42) was similar (p = 0.13) to that from a pbetagal Enhancer Vector without the gene promoter region (603 +/- 66). On the other hand, the beta-gal activity was significantly lower (p < 0.0001) than that from a vector including the wild-type ( - 259T) FasL (pbetagal/wFasL) (3226 +/- 148). In conclusion, the down-regulation of FasL in SS patients with EEG may be due to transcriptional regulation, and the point mutation at - 259T/C in the FasL gene promoter region may lead to the down-regulation of FasL mRNA expression and the lymphoproliferative process observed in SS patients with EEG.


MW polyomavirus and STL polyomavirus present in tonsillar tissues from children with chronic tonsillar disease.
We aimed to explore the frequency of all 13 human polyomaviruses (HPyVs), especially MW polyomavirus (MWPyV) and STL polyomavirus (STLPyV), in tonsillar tissues from Chinese children with chronic tonsillar disease. We examined 99 swabs from mucosal surfaces of palatine tonsils, in which six HPyVs were detected. MWPyV and STLPyV were each detected in two samples. This provides new evidence for the hypothesis that the lymphoid system may play a role in HPyV infection and persistence. We need to define their role in tonsillar disease in the future.


Mapping intracellular pH in tumors using amide and guanidyl CEST-MRI at 9.4 T.
In principle, non-invasive mapping of the intracellular pH (pHi ) in vivo is possible using endogenous chemical exchange saturation transfer (CEST)-MRI of the amide and guanidyl signals. However, the application for cancer imaging is still impeded, as current state-of-the-art approaches do not allow for simultaneous compensation of concomitant effects that vary within tumors. In this study, we present a novel method for absolute pHi mapping using endogenous CEST-MRI, which simultaneously compensates for concentration changes, superimposing CEST signals, magnetization transfer contrast, and spillover dilution. Compensation of the concomitant effects was achieved by a ratiometric approach (i.e. the ratio of one CEST signal at different B1 ) in combination with the relaxation-compensated inverse magnetization transfer ratio MTRRex and a separate first-order polynomial-Lorentzian fit of the amide and guanidyl signals at 9.4 T. Calibration of pH values was accomplished using in vivo-like model suspensions from porcine brain lysates. Applicability of the presented method in vivo was demonstrated in n = 19 tumor-bearing mice. In porcine brain lysates, measurement of pH was feasible over a broad range of physiologically relevant pH values of 6.2 to 8.0, while being independent of changes in concentration. A median pHi of approximately 7.2 was found in the lesions of 19 tumor-bearing mice. The presented method enables non-invasive mapping of absolute pHi values in tumors using CEST-MRI, which was so far prevented by concomitant effects. Consequently, pre-clinical studies on pHi changes in tumors are possible allowing the assessment of pHi in vivo as a biomarker for cancer diagnosis or treatment monitoring.


The post-stroke depression and its impact on functioning in young and adult stroke patients of a rehabilitation unit.
Stroke is a leading cause of disability and a major public health problem. To determine frequency and degree of post-stroke depression (PSD) and its impact on functioning in young and adult stroke patients in a rehabilitation unit. The study included 72 stroke patients (aged 29-59 years) who were attending rehabilitation. The patients were assessed for depressive symptoms by Beck Depression Inventory (BDI), and their functioning by using the Stroke Impact Scale (SIS) and the Barthel Index of Activities of Daily Living (ADL). Forty-eight patients had different degrees of depression: borderline clinical depression (13.8%), moderate depression (34.7%), severe depression (15.2%) or extreme depression (2.9%). There were no significant differences of BDI scores in 30-39, 40-49 and 50-59 years groups. Statistically significant correlations were between BDI score and SIS score, between BDI score and ADL index, and between SIS score and ADL index in men, women and total study patients. More than half of the PSD patients had a moderate degree of depression. Significant correlations were noticed between depressive symptoms and functional status evaluated both by an instrument of assessing stroke impact upon general health and an instrument for assessing the everyday activities.


A high visceral adipose tissue-to-skeletal muscle ratio as a determinant of major complications after pancreatoduodenectomy for cancer.
Complication rates after pancreatic resections remain high despite improvement in perioperative management. The effects of body composition and the relationship among different body compartments on surgical morbidity are not comprehensively investigated. The aim of this study was to assess whether the evaluation of different body compartments and their relationship was associated with the development of major postoperative complications after pancreatoduodenectomy (PD) for cancer. We retrospectively analyzed 124 patients who underwent PD and had a staging computed tomography (CT) scan at our center. CT scan was used to measure abdominal skeletal muscle area and volume, as well as visceral fat area (VFA) and volume. The total abdominal muscle area (TAMA) was then normalized for height. The severity of complications was assessed. Univariate and multivariate analyses were performed to investigate correlations between the above variables and postoperative complications. The receiver operating characteristic curve methodology was used to investigate the predictive ability of each parameter. Major complications occurred in 42 patients (33.9%). The prevalence of sarcopenia was 24.2%. Regression analyses revealed no correlation between abdominal muscular and adipose tissue areas. Univariate analysis showed that the depletion of muscle area normalized for height was not per se predictive of complications (P = 0.318). Multivariate logistic regression showed that the VFA/TAMA was the only determinant of major complications (odds ratio, 3.20; 95% confidence interval, 1.35-7.60; P = 0.008). The model predictive performance was 0.735 (area under the curve) with a sensitivity of 64.3% and a specificity of 74.4%. Sarcopenic obesity is a strong predictor of major complications after PD for cancer.


Effects of NMDA receptor antagonists and antipsychotics on high frequency oscillations recorded in the nucleus accumbens of freely moving mice.
Abnormal oscillatory activity associated with N-methyl-D-aspartate (NMDA) receptor hypofunction is widely considered to contribute to the symptoms of schizophrenia. This study aims to characterise the changes produced by NMDA receptor antagonists and antipsychotics on accumbal high-frequency oscillations (HFO; 130-180 Hz) in mice. Local field potentials were recorded from the nucleus accumbens of freely moving mice. Systemic injection of ketamine and MK801 both dose-dependently increased the power of HFO and produced small increases in HFO frequency. The atypical antipsychotic drug, clozapine, produced a robust dose-dependent reduction in the frequency of MK801-enhanced HFO, whilst haloperidol, a typical antipsychotic drug, had little effect. Stimulation of NMDA receptors (directly or through the glycine site) as well as activation of 5-HT1A receptors, reduced the frequency of MK801-enhanced HFO, but other receptors known to be targets for clozapine, namely 5-HT2A, 5-HT7 and histamine H3 receptors had no effect. NMDA receptor antagonists and antipsychotics produce broadly similar fundamental effects on HFO, as reported previously for rats, but we did observe several notable differences. In mice, HFO at baseline were weak or not detectable unlike rats. Post-injection of NMDA receptor antagonists HFO was also weaker but significantly faster. Additionally, we found that atypical antipsychotic drugs may reduce the frequency of HFO by interacting with NMDA and/or 5-HT1A receptors.


Conversations Change People and People Change the World.
Nursing salons are casual gatherings where nurses from all walks of life and areas of practice engage in thoughtful conversations about the nursing profession.


A Review of Brain and Pituitary Gland MRI Findings in Patients with Ataxia and Hypogonadism.
The association of cerebellar ataxia and hypogonadism occurs in a heterogeneous group of disorders, caused by different genetic mutations often associated with a recessive inheritance. In these patients, magnetic resonance imaging (MRI) plays a pivotal role in the diagnostic workflow, with a variable involvement of the cerebellar cortex, alone or in combination with other brain structures. Neuroimaging involvement of the pituitary gland is also variable. Here, we provide an overview of the main clinical and conventional brain and pituitary gland MRI imaging findings of the most common genetic mutations associated with the clinical phenotype of ataxia and hypogonadism, with the aim of helping neuroradiologists in the identification of these disorders.


Molecular mechanism of the carboxyl terminus of Hsc70-interacting protein in TAU hyperphosphorylation induced by AlCl3 in N2a cells.
Aluminum (Al) is recognized as a neurotoxin. Studies have confirmed that the neurotoxicity induced by Al may be related to tau hyperphosphorylation. Phosphorylated tau is degraded through the ubiquitin-proteasome pathway (UPP), in which the carboxyl terminus of Hsc70-interacting protein (CHIP) plays an important role. However, whether the CHIP plays a role in regulating tau hyperphosphorylation induced by Al is yet to be determined. The purpose of this study was to explore the molecular mechanism of the CHIP in tau hyperphosphorylation induced by AlCl3 in N2a cells. Mouse neuroblastoma cells (N2a) were exposed to different concentrations of AlCl3 (0, 0.5, 1, and 2 mM) and treated with CHIP/CHIP shRNA/CHIP (ΔU-box)/CHIP (ΔTPR) plasmid transfection. The cell viability was determined by the CCK-8 kit. Protein expression was detected by Western blot. The interaction between CHIP and AlCl3 exposure on the proteins was analyzed by factorial design ANOVA. The results showed that Al can cause tau hyperphosphorylation, mainly affecting the pThr231, pSer262, and pSer396 sites of tau in N2a cells. UPP is involved in the degradation of tau hyperphosphorylation induced by Al in N2a cells, of which CHIP may be the main regulatory target. Both the U-box and TPR domains of CHIP are indispensable and play an important role in the regulation of tau hyperphosphorylation induced by AlCl3 in N2a cells.


Prevalence of family violence amongst women attending an abortion clinic in New Zealand.
To measure the prevalence of family violence reported by women seeking a termination of pregnancy (TOP). A cross sectional survey involving consecutive women at one Health Waikato abortion clinic. Participants completed a self-administered questionnaire in private counselling rooms. Sixty-two of the 125 women invited to participate did so (response rate: 49.6%). The reported lifetime prevalence of physical or sexual abuse was 50.8%. The reported lifetime prevalence of physical abuse was 43.3% and that of sexual abuse was 32.2%. The reported prevalence of physical abuse within the last year was 13.3%, and of sexual abuse within the last year was 8.5%. Of women reporting a lifetime history of physical abuse, 69% reported that her partner was the perpetrator/one of the perpetrators of abuse. The study demonstrated a high prevalence of family violence amongst women attending an abortion clinic. Consideration should be given to screening for family violence in abortion clinics in New Zealand. Screening should be accompanied by the provision of appropriate information and support for women with family violence issues.


Stimulated-Raman-scattering amplification of attosecond XUV pulses with pulse-train pumps and application to local in-depth plasma-density measurement.
We present a scheme for amplifying an extreme-ultraviolet (XUV) seed isolated attosecond pulse via stimulated Raman scattering of a pulse-train pump. At sufficient seed and pump intensity, the amplification is nonlinear, and the amplitude of the seed pulse can reach that of the pump, one order of magnitude higher than the initial seed amplitude. In the linear amplification regime, we find that the spectral signature of the pump pulse train is imprinted on the spectrum of the amplified seed pulse. Since the spectral signature is imprinted with its frequency downshifted by the plasma frequency, it is possible to deduce the electron density in the region of interaction. This region can be of micrometer length scale longitudinally. By varying the delay between the seed and the pump, this scheme provides a local electron-density measurement inside solid-density plasmas that cannot be probed with optical frequencies, with micrometer resolution.


Isolation and evaluation of dextral-specific and dextral-enriched cDNA clones as candidates for the handedness-determining gene in a freshwater gastropod, Lymnaea stagnalis.
The handedness of gastropods is genetically determined. The freshwater gastropod Lymnaea stagnalis is a normally dextral species, but contains minor sinistral populations. The gene responsible for handedness determination in this species is predicted to function maternally and specifically in the dextral-ovipositing snail. In this study, we used differential screening and cDNA subtraction to isolate eight "dextral genes" that are specific to, or enriched in, the dextral-ovipositing strains of L. stagnalis. These genes were promising candidates for the handedness-determining gene. In order to determine whether the true handedness-determining gene was among them, we tested for genetic correlations between the level of expression of each dextral gene and the handedness phenotype, i.e., the chirality of the next generation offspring, by using a collection of backcross F2 progeny of F1 offspring from crosses between dextral and sinistral strains. Although the present study could not identify the handedness-determining molecules, this approach appears to be promising for the isolation of such developmentally important genes.


The effect of 6-hydroxydopamine on habituation of activity in the developing rat pup.
The role of brain catecholaminergic mechanisms in habituation of activity was investigated in rat pups treated with 6-hydroxydopamine (6-OHDA). Intracisternal administration of this agent in the neonatal period resulted in a permanent and significant depletion of brain dopamine to 35.5% of controls while brain norepinephrine remained unchanged. Activity levels in normal developing rat pups increased rapidly between 15-22 days, then declined at maturity (26 days), while activity in 6-OHDA treated animals during this peak period of behavioral arousal increased to a significantly greater degree than that of their littermate controls. Habituation of activity, defined as the decrement of spontaneous activity, was calculated by regression over the first 30 min of observation. At both 5 and 8 days of age 6-OHDA and control rat pups exhibited low levels of activity whose decrease with time did not differ significantly and this pattern continued through 12 days of age. However, by 15 days of age activity in control animals declined by 19% each 10 min period compared to only a 10% decline found in 6-OHDA animals. At 19 days normal rat pups declined by 10% compared to a significantly reduced decrement of 3% found in treated animals, but these differences were no longer apparent by 22, 26, or 29 days of age. Our results are consistent with the notion that habituation of activity is a complex phenomenon mediated in part by catecholaminergic systems.


Comparison of circulating lipid profiles between fasting humans and three animal species used in preclinical studies: mice, rats and rabbits.
Circulating lipid metabolites are associated with many physiological and biological processes in the body, and therefore could be used as biomarkers for evaluating drug efficacy and safety in preclinical studies. However, differences in circulating lipid profiles among humans and animals often used in preclinical studies have not been fully investigated. We performed lipidomic analysis to obtain circulating lipid profiles of fasted humans (Caucasian, n = 15) and three animal species used in preclinical studies (mice [BALB/c, n = 5], rats [Sprague-Dawley, n = 5], and rabbits [New Zealand White, n = 5]) by using liquid chromatography-mass spectrometry. Our data showed marked differences in lipid profiles among humans and these animal species. Furthermore, we observed that the levels of many lipid metabolites, such as poly-unsaturated fatty acid-containing cholesteryl esters, ether-type phosphoglycerolipids, and sulfatides, were significantly different (p < 0.05) by more than 10-fold in these animals (depending on the animal species) from humans. Our data could be useful while extrapolating the data on the biomarker candidates identified in preclinical studies into clinical studies.


Protonation of two adjacent tyrosine residues influences the reduction of cytochrome c by diphenylacetaldehyde: a possible mechanism to select the reducer agent of heme iron.
We have shown that diphenlacetaldehyde (DPAA) is able to promote mitochondrial DeltaPsi disruption accompanied by damage in mitochondrial DNA, lipids, and proteins [Almeida, A. M.; Bechara, E. J. H.; Vercesi, A. E.; Nantes, I. L. Free Radic. Biol. Med. 27:744-747; 1999]. In this work, DPAA was used as a model of carbonyl reagent for cytochrome c. The results suggest that DPAA is a redox cytochrome c modifier. Conversion of Fe(III) to Fe(II) cytochrome c promoted by DPAA is pH dependent. The second-order rate determined for heme iron reduction (k2) is 698 M(-1) s(-1) and this process occurs with an activation energy of 8.5 +/- 0.8 kcal/mol. Analysis of the pH profile suggests the presence of two ionizable cytochrome c groups (pKa1 = 8.9 and pKa2 = 11.4) related to the electron transfer from DPAA to heme iron. The heats of ionization of the two prototropic groups, pKa1 (DeltaH(ion) = 6.5 kcal/mol, DeltaS(ion) = -29.0 cal/mol.K), and pKa2 (DeltaH(ion) = 5.0 kcal/mol, DeltaS(ion) = -24.0 cal/mol.K), suggest involvement of two tyrosine residues, probably Y67 and Y74, related to DPAA-promoted heme iron reduction. The cytochrome c chemical modification by iodination of tyrosine groups significantly decreased the reduction rate promoted by DPAA, and shifted the pH(opt) value from 10.0 to 9.25. The cytochrome c-promoted DPAA electron abstraction quickly produces the expected enol-derived radical, as indicated by 3,5-dibromo-4-nitrosobenzenesulfonate (DBNBS) spin trapping EPR measurements. This radical reacts with molecular oxygen, producing a peroxyl intermediate radical that, via a putative dioxetane intermediate, promotes formation of benzophenone as the main final product of this reaction, detected by high-performance liquid chromatography coupled with tandem mass spectrometry.


Acute anoxia stimulates proliferation in adult neural stem cells from the rat brain.
Hypoxic-ischemic damage is a major challenge for neuronal tissue. In the present study, we investigated the effects of anoxia and glucose deprivation on adult neural stem cells (NSCs) in vitro. We assessed glucose deprivation, anoxia and the combination of the latter separately. After 24 h of anoxia, cell numbers increased up to 60% compared to normoxic controls. Whereas nearly all normoxic cells incorporated the mitotic marker BrdU (99%), only 85% of the anoxic cells were BrdU-positive. Counting of interphase chromosomes showed 8-fold higher cell division activity after anoxia. The number of necrotic cells doubled after anoxia (14% compared to 7% after normoxia). Apoptosis was measured by two distinct caspases assays. Whereas the total caspase activity was reduced after anoxia, caspase 3/7 showed no alterations. Glucose deprivation and oxygen glucose deprivation both reduced cell viability by 56 and 53%, respectively. Under these conditions, total caspases activity doubled, but caspase 3/7 activity remained unchanged. Erythropoietin, which was reported as neuroprotective, did not increase cell viability in normoxia, but moderately under oxygen glucose deprivation by up to 6%. Erythropoietin reduced total caspase activity by nearly 30% under all the conditions, whereas caspase 3/7 activity was not affected. Our results show that anoxia increases proliferation and viability of adult NSCs, although a fraction of NSCs does not divide during anoxia. In conclusion, anoxia increased cell viability, cell number and proliferation in NSCs from the rat brain. Anoxia turned out to be a highly stimulating environmental for NSCs and NSCs died only when deprived of glucose. We conclude that the availability of glucose but not of oxygen is a crucial factor for NSC survival, regulating apoptotic pathways via caspases activity other than the caspases 3/7 pathway. Therefore, we conclude that NSCs are dying from glucose deprivation, not from hypoxic-ischemic damage.


Influence of echocardiography in pre-operative cardiac catheterization in congenital heart disease.
The influence of echocardiography on pre-operative cardiac catheterization was assessed in a retrospective analysis comparing two 12-month periods. Of 245 operations in 1983, 200 (82%) had pre-operative cardiac catheterization when two-dimensional echocardiography only was used in the pre-operative assessment compared to 162 of 238 (68%) operations in July 1985-June 1986 when pulsed Doppler echocardiography also was used (P less than 0.001). Significant reductions in pre-operative cardiac catheterization were present in both open (87/87 vs 89/102, P less than 0.001) and closed (113/158 vs 73/136, P less than 0.005) heart procedures. The group with the most significant reduction in pre-operative cardiac catheterization before open heart surgery were children with atrial septal defects; of the closed heart surgical groups, the greatest reductions were in patent ductus arteriosus, coarctation of the aorta and tetralogy of Fallot. Echocardiogram diagnostic errors occurred in 22/245 (9%) in 1983 compared to 9/238 (4%) in 1985/86 (P less than 0.05). Echocardiography has resulted in a significant reduction in pre-operative cardiac catheterization and has become more accurate in diagnosis.


Superiority of dutasteride 0.5 mg and tamsulosin 0.2 mg for the treatment of moderate-to-severe benign prostatic hyperplasia in Asian men.
To assess the effectiveness and safety of dutasteride 0.5 mg + tamsulosin 0.2 mg combination compared with tamsulosin 0.2 mg in Asian men with moderate-to-severe benign prostatic hyperplasia. A 4-week, single-blind, placebo, run-in was followed by a 2-year double-blind randomized controlled trial in men age ≥50 years with symptomatic benign prostatic hyperplasia, International Prostate Symptom Score ≥12, prostate volume ≥30 cc, prostate-specific antigen ≥1.5 and ≤10 ng/mL, peak urinary flow >5 and ≤15 mL/s, and voided volume of ≥125 mL. Participants were randomized to oral daily dutasteride 0.5 mg + tamsulosin 0.2 mg combination or tamsulosin 0.2 mg. The primary efficacy end-point was change in International Prostate Symptom Score at year 2. Data from 607 participants showed a significant reduction in International Prostate Symptom Score (P < 0.05) at month 24, along with greater improvements (P ≤ 0.006) in peak urinary flow at every assessment and significant prostate volume reduction at months 12 and 24 (P < 0.001) in the combination group. Combination therapy was associated with a significant reduction in the risk of acute urinary retention or benign prostatic hyperplasia-related surgery (P = 0.012), primarily due to a significant reduction in the risk of acute urinary retention (P = 0.005). The safety and tolerability profile of combination therapy was consistent with the known profiles for the individual monotherapies. Dutasteride 0.5 mg + tamsulosin 0.2 mg combination therapy showed better clinical outcomes than tamsulosin 0.2 mg monotherapy, making it an effective and safe treatment option for Asian men with moderate-to-severe benign prostatic hyperplasia.


Mechanistic insights into nucleosomal H2B monoubiquitylation mediated by yeast Bre1-Rad6 and its human homolog RNF20/RNF40-hRAD6A.
Histone H2B monoubiquitylation plays essential roles in chromatin-based transcriptional processes. A RING-type E3 ligase (yeast Bre1 or human RNF20/RNF40) and an E2 ubiquitin-conjugating enzyme (yeast Rad6 or human hRAD6A), together, precisely deposit ubiquitin on H2B K123 in yeast or K120 in humans. Here, we developed a chemical trapping strategy and successfully captured the transient structures of Bre1- or RNF20/RNF40-mediated ubiquitin transfer from Rad6 or hRAD6A to nucleosomal H2B. Our structures show that Bre1 and RNF40 directly bind nucleosomal DNA, exhibiting a conserved E3/E2/nucleosome interaction pattern from yeast to humans for H2B monoubiquitylation. We also find an uncanonical non-hydrophobic contact in the Bre1 RING-Rad6 interface, which positions Rad6 directly above the target H2B lysine residue. Our study provides mechanistic insights into the site-specific monoubiquitylation of H2B, reveals a critical role of nucleosomal DNA in mediating E3 ligase recognition, and provides a framework for understanding the cancer-driving mutations of RNF20/RNF40.


Metformin Decreases Risk of Tuberculosis Infection in Type 2 Diabetes Patients.
Metformin may show an antibiotic effect, but whether its use can reduce the risk of tuberculosis infection has rarely been investigated in population-based studies. This is a retrospective cohort analysis of the Taiwan's National Health Insurance database. New-onset type 2 diabetes patients, 148,468 ever users and 15,799 never users of metformin, identified during 1999⁻2005 were followed up until 31 December 2011 for the incidence of tuberculosis infection. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. A total of 360 never users and 1976 ever users developed a tuberculosis infection with respective incidence of 510.91 and 282.94 per 100,000 person⁻years. The overall hazard ratio of presenting a tuberculosis infection among metformin ever users in respect to never users was 0.552 (95% confidence interval: 0.493⁻0.617). The hazard ratios for the first (<27.10 months), second (27.10⁻58.27 months), and third (>58.27 months) tertile of cumulative duration of metformin therapy were 1.116 (0.989⁻1.261), 0.543 (0.478⁻0.618), and 0.200 (0.171⁻0.233), respectively; and were 1.037 (0.918⁻1.173), 0.533 (0.469⁻0.606), and 0.249 (0.215⁻0.288), respectively, for the first (<817,000 mg), second (817,000⁻2,047,180 mg), and third (>2,047,180 mg) tertile of cumulative doses of metformin. The findings were consistent when analyses were restricted to pulmonary tuberculosis. Additionally, regular users of metformin tended to have greater benefit than irregular users. Metformin use is associated with a reduced risk of tuberculosis infection in a dose⁻response pattern in type 2 diabetes patients.


ran1+ controls the transition from mitotic division to meiosis in fission yeast.
We have investigated the genetic and physiological control of meiosis in fission yeast. Nutritionally depleted h+/h- diploid cells become irreversibly commited to meiosis immediately prior to the initiation of premeiotic S phase. Premeiotic DNA synthesis requires matP+, matM+, mei2+ and mei3+ but not the mitotic cell cycle control gene, cdc2+. ran1+ is an essential gene, loss of which provokes sexual conjugation, premeiotic DNA synthesis, pseudo-meiosis and the sporulation of haploid cells. Our experiments suggest that sexual differentiation is achieved physiologically by the inhibition of ran1+ activity in a two-step process. In the first step, partial inhibition of ran1+ in starved haploid cells, leads to cell cycle arrest in G1 followed by sexual conjugation. In the second step, a pathway requiring the matP+, matM+ and mei3+ genes of the newly-formed zygote, further inhibits ran1+ and thereby commits the cell to meiosis. mei2+ is required for meiotic commitment after full inhibition of ran1+. ran1+ is normally essential for vegetative cell reproduction but is inessential in cells which have abnormally high levels of cAMP-dependent protein kinase. We propose that the ran1+ gene encodes a highly controlled protein kinase which shares key substrates with cAMP-dependent protein kinase.


Orbital hematoma secondary to frontal sinusitis.
A 30-year-old woman had an orbital hematoma with frontal sinusitis. This complication of infection in the paranasal sinuses has not been previously described, but is explainable in anatomic terms. On computed tomographic scanning, the degree of enhancement with contrast infusion was striking and may aid in future diagnosis of this condition.


Organometallic Platinum(II) Photosensitisers that Demonstrate Ligand-Modulated Triplet-Triplet Annihilation Energy Upconversion Efficiencies.
A series of 2-phenylquinoxaline ligands have been synthesised that introduce either CF3 or OCF3 electron-withdrawing groups at different positions of the phenyl ring. These ligands were investigated as cyclometalating reagents for platinum(II) to give neutral complexes of the form [Pt(C^N)(acac)] (in which C^N=cyclometalating ligand; acac=acetyl acetonate). X-ray crystallographic studies on three examples showed that the complexes adopt an approximate square planar geometry. All examples revealed strong Pt-Pt linear contacts of 3.2041(6), 3.2199(3) and 3.2586(2) Å. The highly coloured complexes display efficient visible absorption at 400-500 nm (ϵ ≈5000 M-1 cm-1 ) and orange red photoluminescent characteristics (λem =603-620 nm; Φem ≤37 %), which were subtly tuned by the ligand. Triplet emitting character was confirmed by microsecond luminescence lifetimes and the photogeneration of singlet oxygen with quantum efficiencies up to 57 %. Each complex was investigated as a photosensitiser for triplet-triplet annihilation energy upconversion using 9,10-diphenylanthracene as the annihilator species: a range of good upconversion efficiencies (ΦUC 5.9-14.1 %) were observed and shown to be strongly influenced by the ligand structure in each case.


Regulation of platelet Rac1 and Cdc42 activation through interaction with calmodulin.
Rac1 and Cdc42 are members of the Rho family of small GTPases and have been shown to induce lamellipodia and filopodia formation, respectively. This leads to changes in cytoskeleton organization and as a consequence affects cell migration. In the present work we demonstrate that endogenous Rac1 and Cdc42 interact with calmodulin (CaM) in a Ca(2+)-dependent fashion. The interaction of Rac1 and Cdc42 with CaM was shown to be direct. This novel interaction was further confirmed in platelets using co-immunoprecipitation studies. Using CaM database analysis and in vitro peptide competition assays we have identified a 14 amino acid region in Rac1 that is essential for CaM binding. The scrambled form of the peptide did not bind CaM demonstrating specificity of the predicted CaM binding region in Rac1. A similar region capable of binding CaM exists in Cdc42. Furthermore, using the optimal activation time-point for each GTPase, the role of CaM in the function of Rac1 and Cdc42 was examined. Results demonstrate that in human platelets, thrombin caused maximal activation of Rac1 and Cdc42 at ~60 s and ~25 s respectively. The potent CaM antagonist W7 abolished thrombin-mediated activation of Rac1. However, addition of W7 resulted in the activation of Cdc42 over basal and W7 did not inhibit thrombin-mediated activation of Cdc42. The less potent CaM inhibitor, W5, did not have any effect on Rac1 and Cdc42 activation. The results demonstrate that in platelets, binding of CaM to Rac1 increases its activation while its binding to Cdc42 reduces the activation of this GTPase. This suggests an important role for CaM in coordinating Rac1 and Cdc42 activation and in the regulation of cytoskeleton remodeling.


Vascular Risk Reduction in Obesity through Reduced Granulocyte Burden and Improved Angiogenic Monocyte Content following Bariatric Surgery.
Bariatric surgery, in addition to the benefit of sustained weight loss, can also reduce cardiometabolic risk and mortality. Lifelong vessel maintenance is integral to the prevention of cardiovascular disease. Using aldehyde dehydrogenase activity, an intracellular detoxifying enzyme present at high levels within pro-vascular progenitor cells, we observed an association between chronic obesity and "regenerative cell exhaustion" (RCE), a pathology whereby chronic assault on circulating regenerative cell types can result in adverse inflammation and diminished vessel repair. We also describe that, at 3 months following bariatric surgery, systemic inflammatory burden was reduced and pro-angiogenic macrophage precursor content was improved in subjects with severe obesity, suggesting the restoration of a microenvironment to support vessel homeostasis. These data suggest that bariatric surgery may reverse deleterious events that predispose patients with morbid obesity to cardiovascular risk.


Pretreatment systemic inflammation response index (SIRI) is an independent predictor of survival in unresectable stage III non-small cell lung cancer treated with chemoradiotherapy: a two-center retrospective study.
Circulating immune cells influence the efficacy of cancer therapy. This study aimed to investigate the prognostic values of different peripheral blood leukocyte (PBL) biomarkers in non-small lung cancer (NSCLC) patients treated with chemoradiotherapy. An independent cohort of 176 stage III NSCLC patients who were diagnosed at Shanghai Pulmonary Hospital and Zhejiang Cancer Hospital between April, 2010, and September, 2018, and had available pretreatment peripheral blood tests was enrolled. The patients were all treated with concurrent or sequential chemoradiotherapy according to international clinical guidelines, with conventional fractionated radical radiotherapy. The receiver operating characteristic curve and the Youden index were used to determine the optional cutoff values of PBL biomarkers for distinguishing prognosis. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify the factors significantly correlated with overall survival. The cohort had a median follow-up time of 21.7 (3.1-121) months. The 3- and 5-year OS rates of all patients were 34.7% and 27.5%, respectively. Univariate analysis showed that gender (P=0.011), smoking (P=0.011), tumor-node-metastasis (TNM) stage (P=0.002), pretreatment peripheral blood neutrophil-to-leukocyte ratio (P=0.013), and systemic inflammation response index (SIRI, P<0.001) were all correlated with OS in NSCLC patients. Moreover, multivariate analysis revealed that TNM stage (HR =1.541, 95% CI: 1.166-2.036, P=0.010) and SIRI (HR =1.868, 95% CI: 1.016-3.436, P=0.018) were significantly and independently associated with OS. However, the median OS of stage IIIB NSCLC patients with low SIRI (≤2.0) was longer than that of stage IIIA NSCLC patients with high SIRI (>2.0) (33.9±4.1 vs. 19.6±2.5 months). Pretreatment peripheral blood SIRI was found to be a simple independent predictor of OS in stage III NSCLC patients who underwent chemoradiotherapy. As a novel prognostic marker, the prognostic value of the SIRI is superior to that of the NLR. Low SIRI could be a better prognostic stratification factor for NSCLC patients with different TNM stages.


Numerical simulation of assay of the calcium pump of intact red blood cells.
An assay of the Ca pump ATPase of intact human RBCs is described in a companion paper (Wu, L., Hinds, T. R. and Vincenzi, F. F. (1992) Biochim. Biophys. Acta 1106, 56-62). The assay is based on the rapid loss of ATP in RBCs that occurs when the cells are exposed to the ionophore, A23187, in the presence of Ca. An unexpected finding was that the initial loss of ATP follows pseudo-first-order kinetics. This was unexpected because the ATP content of RBCs is somewhat higher than the Km of the Ca pump for ATP. Thus, the initial loss of ATP would be expected to follow zero-order kinetics; at least if the Ca pump ATPase operated with Michaelis kinetics. We performed a series of computer simulations of the Ca pump ATPase to investigate the possible cause of the unexpected pseudo-first-order behavior. The results confirmed that the data can not be accounted for by Michaelis kinetics of the Ca pump ATPase. Possible effects of adenylate kinase were tested and were also not found to account for the pseudo-first-order behavior of an ATPase operating with Michaelis kinetics. The enzymatic properties of the Ca pump ATPase were re-examined. It was found that the Ca pump ATPase exhibits positive cooperativity toward ATP. The apparent cooperativity was 1.91. In simulations it was found that positive cooperativity of the Ca pump ATPase in the range of 1.5 to 2.0 could account for the pseudo-first-order behavior. Excellent fit of the simulation data to first-order behavior was true with or without any contribution from adenylate kinase. Rate constants of ATP loss were thus examined using cooperativity of 2.0. Over a wide range the rate constant of the loss of ATP was directly proportional to the assumed Vmax of the Ca pump ATPase, but only if the data were limited to loss of less than 67% of the initial ATP. It is suggested, therefore, that the rate constant for the initial loss of ATP in intact RBCs, as stimulated by the ionophore A23187, can be taken as a measure of the capacity of the Ca pump ATPase.


Prebiotics, faecal transplants and microbial network units to stimulate biodiversity of the human gut microbiome.
Accumulating evidence demonstrates the intimate association between human hosts and the gut microbiome. Starting at birth, the sterile gut of the newborn acquires a diverse spectrum of microbes, needed for immunological priming. However, current practices (caesarean sections, use of formula milk) deprive newborns from being exposed to this broad spectrum of microbes. Unnecessary use of antibiotics and excessive hygienic precautions (e.g. natural versus chlorinated drinking water) together with the Western diet further contribute to a decreased microbial diversity in the adult gut. This has been correlated with recurrent Clostridium difficile infection, inflammatory bowel diseases and obesity, among others. A healthy gut microbiome is thus characterized by a diverse network of metabolically interacting microbial members. In this context, we review several existing and novel approaches to manage the gut microbiome. First, prebiotic compounds should be re-defined in the sense that they should enhance the ecological biodiversity rather than stimulating single species. Recent studies highlight that structurally different polysaccharides require specific primary degraders but also enhance a similar network of secondary degraders that benefit from cross-feeding. A faecal transplantation is a second approach to restore biodiversity when the microbiota is severely dysbiosed, with promising results regarding C. difficile-associated disease and obesity-related metabolic syndromes. A final strategy is the introduction of key microbial network units, i.e. pre-organized microbial associations, which strengthen the overall microbial network of the gut microbiome that supports human health.


Lovastatin and phospholipase Cgamma regulate constitutive and protein kinase C dependent integrin mediated interactions of human T-cells with collagen.
We previously reported that human interleukin (IL)-2 dependent T cell lines derived from very late antigen (VLA)-1(+) CD45RO(+) peripheral blood (PB) T-cells adhere constitutively to collagen type IV, whereas lines from VLA-1(-) PB lymphocytes (L) adhere weakly. Here we report that the latter are induced to adhere by phorbol 12-myristate 13-acetate (PMA). Both PMA dependent and constitutive adhesion, including that of a Herpes Virus Saimiri (HVS) infected CD4(+)VLA-1(+) clone (HVST) were inhibited by anti-VLA-1 monoclonal antibodies (mAb), by inhibitors of phospholipase C (PLC)gamma and by lovastatin but not by a MEK1 inhibitor, whereas only PMA induced adhesion was blocked by inhibition of protein-kinase (PK) C. Furthermore, lovastatin enhanced PLCgamma and anti VLA-1 mAb blockade, and its effect was not reversed by mevalonic acid (MVA). Lovastatin also inhibited interferon (IFN)gamma secretion by T cells triggered with anti-CD3 and in cells detaching from collagen IV. These results suggest new ways for functional modulation of activated T-cells interacting with collagen.


A nationwide family study of pulmonary embolism: identification of high risk families with increased risk of hospitalized and fatal pulmonary embolism.
Family history is an important risk factor for deep venous thrombosis. However, few studies have determined the importance of family history of pulmonary embolism (PE). This nationwide study aimed to determine the familial risks of fatal and hospitalized PE. The Swedish Multi-Generation Register for subjects aged 0 to 76 years old born since 1932 were linked to the Hospital Discharge Register and Cause of Death Register for the period 1964-2008. Standardized incidence ratios (SIRs) for first hospitalization or death (without previous hospitalization for PE) with a main diagnosis of PE were calculated for individuals whose parent or siblings were hospitalized with or died from PE, compared to those whose parent or siblings were not affected by PE. A total of 20,860 individuals were hospitalized for PE and 862 died due to primary fatal PE (without previous hospitalization for PE). The familial SIR for individuals with one sibling with hospitalized PE was 2.49 (95% CI 1.62-3.83). The familial SIR for siblings with two affected probands was 114.29 (95% CI 56.57-223.95). The familial SIRs for individuals with a parent or sibling hospitalized for PE were significantly increased for fatal PE (1.76; 95% CI 1.38-2.21) and hospitalized PE (2.13; 95% CI 2.04-2.23). Spouses had low overall familial risk for PE (1.09; 95% CI, 1.03-1.14). The high familial risk in multiplex sibling families suggests the existence of strong genetic risk factors for PE. Familial factors and possibly genetic factors are important risk factors for primary fatal pulmonary embolism.


Transferrin receptors during rabbit reticulocyte maturation.
Experiments were performed to examine the fate of transferrin receptors in reticulocytes as these cells mature in vivo to erythrocytes. Reticulocytosis, synchronized by administration of actinomycin D, was induced in adult rabbits. Simultaneous measurements were made of haematological parameters and the interaction between transferrin and reticulocytes while the cells matured in vivo to erythrocytes. As the reticulocytes matured there was a parallel decline in their ability to take up transferrin and transferrin iron. At the same time, there was a proportionate decrease in the density of receptors for transferrin on the reticulocyte surface. The affinity of the receptors for transferrin remained unaltered during the maturation process. It was concluded that the inability of erythrocytes to take up transferrin or its iron is due primarily to the loss of transferrin receptors from the maturing reticulocyte surface.


Increased sulfiredoxin-1 levels as compensatory mechanism against reactive oxygen species in women with gestational diabetes mellitus
This study aimed to investigate the correlation between serum Sulfiredoxin-1 (Srx-1) levels and gestational diabetes mellitus (GDM). A total of 40 patients diagnosed with GDM according to the American Diabetes Association Criteria and 40 age matched and gestational age-matched healthy pregnant women as a control group were included in this cross-sectional study. Serum Srx-1 levels and other demographic and laboratory variables were analyzed. Fasting plasma glucose, first and second-hour plasma glucose levels, fasting insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR), and Srx-1 levels were significantly different in patients with GDM than control (p<0.05). Plasma Srx-1 levels significantly correlated with fasting plasma glucose, first and second-hour plasma glucose levels, fasting insulin levels, and HOMA-IR of patients with GDM (p<0.05), whereas no correlation in the control group. This is the first study demonstrating an association between serum Srx-1 levels and GDM. Our results suggest increased serum Srx-1 levels may be a novel predictive marker for GDM. More randomized-controlled trials are needed to evaluate Srx-1 as a marker for adverse fetal results; closer monitoring is warranted with high Srx-1 levels.


Role of membrane transport in the regulation of skeletal muscle glutamine turnover.
This paper reviews present understanding of the role played by the sarcolemmal glutamine transporter, system N(m), in control of intramuscular glutamine concentration. Glutamine transport in skeletal muscle is a saturable, stereospecific, Na dependent and insulin sensitive process. The activity of system N(m) is subject to modification during muscle denervation, diabetes and exposure to bacterial products in a manner consistent with the observed negative glutamine balance exhibited by muscle during such circumstances. The modification in transporter activity appears to be dependent on factors influencing the distribution of Na across the sarcolemma, the resting membrane potential and the active carrier population in the sarcolemma (possibly through up or down regulation of the number of transporter molecules). Derangements in net membrane glutamine transport during pathophysiological conditions may help, partly, to account for the loss in muscle glutamine which in turn may influence control of protein and carbohydrate metabolism in muscle. The free intramuscular glutamine concentration appears to act as a positive signal in the control of muscle protein turnover and glycogen synthesis, a finding that may have important therapeutic implications for limiting muscle wasting. The kinetic properties of the glutamine transporter and the dipeptidase activity in the muscle vascular bed allow the intramuscular glutamine pool to be repleted following administration of glutamine dipeptides (such as Ala-Gln) with the result that a net anabolic shift in protein balance and an amelioration in muscle glutamine efflux takes place.


Natural uORF variation in plants.
Taking advantage of natural variation promotes our understanding of phenotypic diversity and trait evolution, ultimately accelerating plant breeding, in which the identification of causal variations is critical. To date, sequence variations in the coding region and transcription level polymorphisms caused by variations in the promoter have been prioritized. An upstream open reading frame (uORF) in the 5' untranslated region (5' UTR) regulates gene expression at the post-transcription or translation level. In recent years, studies have demonstrated that natural uORF variations shape phenotypic diversity. This opinion article highlights recent researches and speculates on future directions for natural uORF variation in plants.


Coverage of soft tissue defects in acute surgery for deep burns of the limbs.
Burns of the limbs affect 48.6% of burn patients. Injury mechanisms condition their depth and degree of extension. Injury of the hands and/or the joint areas entails considerable risk of retraction. Coverage is consequently doubly challenging, it is a matter not only of compensating for a soft tissue defects, but also of striving to prevent early (infectious) and late (amplitude limitation, pain, loss of function…) complications. Thoroughgoing assessment of the initial injury and associated lesions is conducive to rapid determination of a therapeutic strategy tailored to the relevant functional issues and subsequent rehabilitation. Following a summary of the epidemiological elements and the medical context of management, a review of existing treatments has been drawn up based on the data in the literature and current professional recommendations. Emergency procedures, the different types of excision and the possibilities of autologous covering and skin substitutes are reported. Last but not least, routinely validated indications are synthesized.


Coagulation disorders and liver disease.
A definite association exists between hepatic disease and abnormalities of the coagulation system. These abnormalities can be detected by both routine and specialized coagulation tests. Extrahepatic causes of coagulation defects must first be ruled out by anamnesis, physical findings, and clinical laboratory tests before attributing the coagulopathies to hepatic disease. The routine use of coagulation tests to diagnose hepatic disease is not practical in veterinary medicine at the present time, but it can be a valuable adjunct to existing tests for hepatic disease and as a prognostic indicator during the course of treatment for established chronic disease.


Phospholipase A2 activity-dependent and -independent fusogenic activity of Naja nigricollis CMS-9 on zwitterionic and anionic phospholipid vesicles.
CMS-9, a phospholipase A(2) (PLA(2)) from Naja nigricollis venom, induced the death of human breast cancer MCF-7 cells accompanied with the formation of cell clumps without clear boundaries between cells. Annexin V-FITC staining indicated that abundant phosphatidylserine appeared on the outer membrane of MCF-7 cell clumps, implying the possibility that CMS-9 may promote membrane fusion via anionic phospholipids. To validate this proposition, fusogenic activity of CMS-9 on vesicles composed of zwitterionic phospholipid alone or a combination of zwitterionic and anionic phospholipids was examined. Although CMS-9-induced fusion of zwitterionic phospholipid vesicles depended on PLA(2) activity, CMS-9-induced fusion of vesicles containing anionic phospholipids could occur without the involvement of PLA(2) activity. Membrane-damaging activity of CMS-9 was associated with its fusogenicity. Moreover, CMS-9 induced differently membrane leakage and membrane fusion of vesicles with different compositions. Membrane fluidity and binding capability with phospholipid vesicles were not related to the fusogenicity of CMS-9. However, membrane-bound conformation and mode of CMS-9 depended on phospholipid compositions. Collectively, our data suggest that PLA(2) activity-dependent and -independent fusogenicity of CMS-9 are closely related to its membrane-bound modes and targeted membrane compositions.


Atherogenic risk in men suffering from occupational stress.
Blue-collar workers suffering from chronic occupational stress exhibit significantly higher values of an atherogenic index (ratio between low density and high density lipoprotein cholesterol assessed by quantitative lipoprotein electrophoresis) as compared to men exposed to less stress at work. Chronic occupational stress is defined by interactions of objective (job instability, shift work) and subjective (perceived job insecurity, perceived increase of work load) indicators as assessed by structured interviews. Findings from a prospective epidemiologic study on 416 middle-aged men at entry covering a 2-year period of observation hold true after controlling for several confounding factors such as body weight, age, cigarette smoking and chronic alcohol consumption. Results are in line with experimental animal studies on the influence of chronic social stress on the development of atherosclerosis.


Population dynamics of two snail species, Planaxis sulcatus and Cerithium moniliferum, and their trematode species at Heron Island, Great Barrier Reef.
The population dynamics of the prosobranch snail Planaxis sulcatus and its trematode parasites on 600 m of beachrock on the southern side of Heron Island, Great Barrier Reef, were studied. Populations of Planaxis show little mixing, due to lack of long-distance movements. From March 1973 to June 1975, an increase in the numbers of small and medium-sized snails occurred, but the biomass (dry tissue weight) of the snail population did not change. Snails were infected with one species of Aspidogastrea and six species of cerariae. Infections with cercariae did not significantly affect the relative weight of the snails. Multiple infections were random, i.e. neither negative nor positive interactions between trematode species could be demonstrated. Proportions of uninfected snails and snails infected with various trematode species remained more or less constant from July 1973 to February 1975.The population dynamics of the prosobranch snail Cerithium moniliferum and its 11 species of cercariae and one species of Aspidogastrea in a small area at Heron Island were studied. Numbers of large snails decreased and numbers of small snails increased from August 1973 to June 1975. The biomass of the Cerithium population increased only slightly. Prevalence of infection changed significantly only in large snails.Infections of Cerithium moniliferum and Peristernia australiensis with an aspidogastrid species decreased strongly from January 1971 to March/April 1972 and had not recovered by mid 1975.Seasonal fluctuations could not be demonstrated for any of the snails or parasites.The data for Planaxis suggest equilibrium conditions and saturation of the habitat.


Presurgical evaluation of retroauricular subcutaneous tissue thickness in BAHA surgery.
A growing population of implanted patients benefit from the Bone-Anchored Hearing Aid (BAHA). An important step in the surgery is subcutaneous tissue reduction. The proper preparation of the implant site depends on relevant tissue removal, which is combined with incision, surgical technique, and preliminary retroauricular tissue thickness. Prospective analysis. Authors attempt to measure the retroauricular subcutaneous tissue thickness and try to trace the correlation between retroauricular subcutaneous tissue thickness with objective parameters such as sex, height, weight, and age. Group of hundred randomly selected patients were enrolled in the study. Standard ultrasound with liner transducer probe was applied to measure the tissue thickness. Sex, weight, height, and age were correlated with retroauricular tissue thickness; results also were calculated for body mass index. The retroauricular subcutaneous tissue thickness ranged between 2.0 and 11.0 mm with the mean value of 5.25 mm. Statistical validation revealed strong correlation with weight and body mass index. Statistical difference was found between retroauricular subcutaneous tissue thickness and sex, confirming women to have thinner subcutaneous tissue than men. The age of the patient also was predictive but without the linear correlation. Conducted measurements revealed no association between retroauricular subcutaneous tissue thickness and height of the patients enrolled in the study. Our results provide a predictive value during preoperative counseling of patients and planning the surgery. Basic information obtained during the examination can help choose the optimal implantation technique. The ultrasound examination applied in the study turned to be an easy and reliable method to assess the retroauricular tissue thickness before the surgery.


Semisynthetic UbH2A reveals different activities of deubiquitinases and inhibitory effects of H2A K119 ubiquitination on H3K36 methylation in mononucleosomes.
Using a genetically incorporated azidonorleucine for ubiquitin installation, we prepared multi-milligram quantities of H2AK119ub (ubH2A). With a native isopeptide linkage, the synthetic ubH2A was used to study the activity of deubiquitinases and crosstalk between H2A ubiquitination and H3K36 methylation in the context of chemically defined mononucleosomes.


New mutations in the APC gene in familial adenomatous polyposis: detection, characterization, and analysis.
The spectrum of mutations in the APC gene in familial adenomatous polyposis was detected in a sampling from the Russian population. Fifteen new mutations were found. Deletions associated with the loss of only 1 or 2 nucleotides (89% cases) prevailed among new (unique) mutations, while all known deletions were caused by the loss of 4 or 5 nucleotides. The detected differences in the deletion characteristics between unique and repeated mutations in the APC gene were typical of samples of patients from a number of populations. Samplings from different populations were heterogeneous by this sign. The incidence of 1-2-nucleotide deletions among unique and repeated deletions in the APC gene in patient samplings from different countries were in negative correlation.


High affinity estrogen binding by rabbit liver.
Macromolecular binding components for [3H]estradiol-17beta are present to cytosol prepared from rabbit liver. When cytosol from sexually mature male liver was incubated with [3H]estradiol and analyzed for binding on low ionic strength sucrose gradients, two peaks of binding activity were detected. One peak had a sedimentation coefficient of 4--5 S and the other had a sedimentation coefficient of 8--9 S. The two components differed from each other regarding steroid specificity and various physiocochemical parameters. [3H]estradiol binding to the 4--5 S component was not inhibited by estrogens, 5alpha-dihydrotestosterone, progesterone or cortisol. Binding to this component did not appear to be saturable and label was rapidly stripped from it by charcoal. Estradiol binding to the 8--9 S component was estrogen specific, saturable and of high affinity. The specific binder dissociates on high ionic strength sucrose gradients and sediments as a 4--5 S moiety. The specific binding protein has a Kd of 3.05 . 10(-10) M and a dissociation half-time of 33 h and there are 35.2 fmol of binding sites/mg cytosol protein. Estrogen binders are also present in liver cytosol from sexually mature female and sexually immature male rabbits. During prolonged incubation of [3H]estradiol with mature male liver cytosol at 0--5 degrees C polar metabolites of estradiol are produced.


Potential neurotoxic activity of diverse molecules released by astrocytes.
Astrocytes are the main support cells of the central nervous system. They also participate in neuroimmune reactions. In response to pathological and immune stimuli, astrocytes transform to reactive states characterized by increased release of inflammatory mediators. Some of these molecules are neuroprotective and inflammation resolving while others, including reactive oxygen species (ROS), nitric oxide (NO), matrix metalloproteinase (MMP)- 9, L-glutamate, and tumor necrosis factor α (TNF), are well-established toxins known to cause damage to surrounding cells and tissues. We hypothesized that similar to microglia, the brain immune cells, reactive astrocytes can release a broader set of diverse molecules that are potentially neurotoxic. A literature search was conducted to identify such molecules using the following two criteria: 1) evidence of their expression and secretion by astrocytes and 2) direct neurotoxic action. This review describes 14 structurally diverse molecules as less-established astrocyte neurotoxins, including C-X-C motif chemokine ligand (CXCL)10, CXCL12/CXCL12(5-67), FS-7-associated surface antigen ligand (FasL), macrophage inflammatory protein (MIP)- 2α, TNF-related apoptosis inducing ligand (TRAIL), pro-nerve growth factor (proNGF), pro-brain-derived neurotrophic factor (proBDNF), chondroitin sulfate proteoglycans (CSPGs), cathepsin (Cat)B, group IIA secretory phospholipase A2 (sPLA2-IIA), amyloid beta peptides (Aβ), high mobility group box (HMGB)1, ceramides, and lipocalin (LCN)2. For some of these molecules, further studies are required to establish either their direct neurotoxic effects or the full spectrum of stimuli that induce their release by astrocytes. Only limited studies with human-derived astrocytes and neurons are available for most of these potential neurotoxins, which is a knowledge gap that should be addressed in the future. We also summarize available evidence of the role these molecules play in select neuropathologies where reactive astrocytes are a key feature. A comprehensive understanding of the full spectrum of neurotoxins released by reactive astrocytes is key to understanding neuroinflammatory diseases characterized by the adverse activation of these cells and may guide the development of novel treatment strategies.


Blockade of cardiac nerves by intrapericardial local anaesthetics in the conscious rabbit.
Local anaesthetic drugs were instilled into the pericardial sac of conscious rabbits through a chronically implanted catheter. Twenty mg of procaine HCl always caused complete blockade of cardiac vagal and sympathetic efferent nerves, tested by eliciting the baroreceptor-heart rate reflex, and abolished the reflex depression of renal sympathetic nerve activity elicited by impeding left ventricular outflow. It also slowed heart rate by a direct effect on the sinoatrial pacemaker. When the same dose of procaine was given intravenously there were only transient changes in blood pressure, heart rate and the baroreceptor-heart rate reflex. Lignocaine HCl and bupivacaine HCl were relatively less effective in blocking cardiac sympathetic efferent nerves. Intrapericardial procaine can be used in conscious animals to elucidate the part played by the cardiac receptor reflexes in control of the circulation.


The diagnostic performance of CESM and CE-MRI in evaluating the pathological response to neoadjuvant therapy in breast cancer: a systematic review and meta-analysis.
Neoadjuvant chemotherapy (NAC) is an important method for breast cancer treatment. By monitoring its pathological response, the selection of clinical treatment strategies can be guided. In this study, the meta-analysis was used to compare the accuracy of contrast-enhanced MRI (CE-MRI) and contrast-enhanced spectral mammography (CESM) in detecting the pathological response of NAC. Literatures associated to CE-MRI and CESM in the evaluation of pathological response of NAC were searched from PubMed, Cochrane Library, web of science, and EMBASE databases. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was used to assess the quality of studies. Pooled sensitivity, specificity, and the area under the SROC curve were calculated to evaluate the diagnostic accuracy of CE-MRI and CESM in monitoring the pathological response of NAC. There were 24 studies involved, 18 of which only underwent CE-MRI examination, three of which only underwent CESM examination, and three of which underwent both CE-MRI and CESM examination. The pooled sensitivity and specificity of CE-MRI were 0.77 (95%CI, 0.67-0.84) and 0.82 (95%CI, 0.73-0.89), respectively. The pooled sensitivity and specificity of CESM were 0.83 (95%CI, 0.66-0.93) and 0.82 (95%CI, 0.68-0.91), respectively. The AUCs of SROC curve for CE-MRI and CESM were 0.86 and 0.89, respectively. Compared to CE-MRI, CESM has equal specificity, greater sensitivity and excellent performance, which may have a brighter prospect in evaluating the pathological response of breast cancer to NAC. CESM showed equal specificity, greater sensitivity, and excellent performance than CE-MRI.


A multiphysics model to predict periventricular white matter hyperintensity growth during healthy brain aging.
Periventricular white matter hyperintensities (WMH) are a common finding in medical images of the aging brain and are associated with white matter damage resulting from cerebral small vessel disease, white matter inflammation, and a degeneration of the lateral ventricular wall. Despite extensive work, the etiology of periventricular WMHs remains unclear. We pose that there is a strong coupling between age-related ventricular expansion and the degeneration of the ventricular wall which leads to a dysregulated fluid exchange across this brain-fluid barrier. Here, we present a multiphysics model that couples cerebral atrophy-driven ventricular wall loading with periventricular WMH formation and progression. We use patient data to create eight 2D finite element models and demonstrate the predictive capabilities of our damage model. Our simulations show that we accurately capture the spatiotemporal features of periventricular WMH growth. For one, we observe that damage appears first in both the anterior and posterior horns and then spreads into deeper white matter tissue. For the other, we note that it takes up to 12 years before periventricular WMHs first appear and derive an average annualized periventricular WMH damage growth rate of 15.2 ± 12.7 mm2/year across our models. A sensitivity analysis demonstrated that our model parameters provide sufficient sensitivity to rationalize subject-specific differences with respect to onset time and damage growth. Moreover, we show that the septum pellucidum, a membrane that separates the left and right lateral ventricles, delays the onset of periventricular WMHs at first, but leads to a higher WMH load in the long-term.


Increases in BMI contribute to worsening inflammatory biomarkers related to breast cancer risk in women: a longitudinal study.
Inflammatory adipokines and cytokines play a pivotal role in linking obesity and breast cancer (BC) risk in women. We investigated the longitudinal associations between BMI change and trajectories of inflammatory biomarkers related to BC risk. A longitudinal study was conducted among 442 Chinese women with 3-year repeated measures from 2019 to 2021. Plasma circulating inflammatory biomarkers related to BC risk, including adiponectin (ADP), resistin (RETN), soluble leptin receptor (sOB-R), insulin-like growth factor-binding protein-3 (IGFBP-3), and C-reactive protein (CRP), were examined annually. Linear mixed-effect models (LMM) were applied to investigate associations of time-varying BMI with trajectories of biomarkers. We additionally examined the modification effect of baseline BMI groups, menopausal status, and metabolic syndrome. BMI was associated with increased levels of RETN, CRP, sOB-R, and decreased levels of ADP at baseline. An increasing BMI rate was significantly associated with an average 3-year increase in RETN (β = 0.019, 95% CI 0.004 to 0.034) and sOB-R (β = 0.022, 95% CI 0.009 to 0.035), as well as a decrease in ADP (β = - 0.006, 95% CI - 0.012 to 0.001). These associations persisted across different baseline BMI groups. An increasing BMI rate was significantly associated with an average 3-year increase in CRP levels among normal weight (β = 0.045, 95% CI 0.001 to 0.088) and overweight (β = 0.060, 95% CI 0.014 to 0.107) women. As BMI increased over time, a more remarkable decrease in ADP was observed among women with metabolic syndrome (β = - 0.016, 95% CI - 0.029 to - 0.004) than those without metabolic syndrome at baseline. A higher increase rate of BMI was associated with poorer trajectories of inflammatory biomarkers related to BC risk. Recommendations for BMI reduction may benefit BC prevention in women, particularly for those with metabolic syndrome.


Predictors of intracranial hemorrhage in patients treated with catheter-directed thrombolysis for deep vein thrombosis.
Although acute intracranial hemorrhage (ICH) is a rare complication of catheter-directed thrombolysis (CDT), it remains a major concern associated with the use of CDT. The incidence and clinical predictors of developing ICH in the setting of CDT are not known. The National Inpatient Sample database was used to identify all patients with proximal lower extremity or caval deep vein thrombosis (DVT) from January 2005 to December 2013 in the United States. Multivariate logistic regression was performed to identify the clinical predictors of ICH between patients with DVT who had received anticoagulation therapy alone and those who had been treated with CDT plus anticoagulation therapy. Of 138,049 patients with proximal lower extremity or caval DVT, 7119 (5.2%) had received anticoagulation therapy and CDT. Of the patients treated with anticoagulation alone, ICH had occurred in 0.2% compared with 0.7% for those treated with CDT (P < .01). The independent predictors of ICH in the CDT cohort were a history of stroke (odds ratio [OR], 19.4; 95% confidence interval [CI], 8.8-42.8; P < .01), chronic kidney disease (OR, 2.2; 95% CI, 1.1-4.7; P = .03), age >74 years (OR, 2.2; 95% CI, 1.2-4.3; P = .02), male sex (OR, 1.8; 95% CI, 1.01-3.3; P = .048). Of those patients treated with anticoagulation alone, the risk factors for the development of ICH were a history of stroke, hospital teaching status, and age >74 years. The results from the present nationwide observational study showed that of patients with DVT treated with CDT, the independent predictors for developing ICH were a history of stroke, chronic kidney disease, male sex, and age >74 years.


Predictors of nursing students' intentions to participate in an internationalization-at-home program: The roles of expectancies for success and subjective task value.
Internationalization-at-home programs are a unique opportunity for those who had been planning to study abroad to learn global clinical practices and cultures at home. However, the factors influencing the motivation of students to join such programs remain unexplored. To investigate the relationship among expectancies for success, subjective task value, and the intention to participate in an internationalization-at-home program, and to identify key factors predicting such an intention among undergraduate nursing students. A descriptive correlational design with a predictive approach was adopted. A total of 522 undergraduate and postgraduate nursing students in a Hong Kong university participated in the study. Intention to participate in the program was assessed using the Comprehensive Relative Autonomy Index. Expectancies for success and subjective task value were assessed as potential predictors. A multiple linear regression analysis was adopted to examine the predictive effects. The participants were aged 17-31 years (mean = 20.95, SD = 2.39). Those who reported having previously participated in the program (β = 0.10, p-value = .014), greater intercultural communication competence (β = 0.14, p-value = .003), greater perceived social competence (β = 0.11, p-value = .031), and a higher subjective value of the program (β = 0.28, p-value<.001) expressed a greater intention to join the program. Collectively, the three variables accounted for 14.7 % of the variances in intention to participate in the program. Cultural self-efficacy, intercultural communication competence, perceived social competence, individual interest, foreign language learning motivation, and subjective value of the program were found to be key factors predicting the intention of nursing students to participate in internationalization-at-home. Future studies can provide interventions to address these factors and enhance the benefits of internationalization-at-home programs.


Variation of antibody responses to Plasmodium falciparum MSP1-19 antigen with parasitaemia and IL4vntr polymorphism in Khartoum state, Sudan.
A hospital-based cross-sectional study was conducted at Khartoum state to investigate the variation of antibody responses to Plasmodium falciparum 19-kDa C-terminal region of merozoite surface protein 1 antigen and the variation of human IL4 polymorphism with parasitaemia. Measurements of natural acquisition of anti-Plasmodium falciparum MSP1-19 IgG, IgG1 and IgG3 antibodies were performed using ELISA. Molecular characterization of IL4vntr polymorphism was achieved. We were able to detect a statistically significant negative correlation between parasitaemia and different age groups (r = - 0.262 and p value = 0.043) and with anti-P.fMSP1-19 IgG1 (r = - 0.418, p value = 0.047). Anti-P.fMSP1-19 IgG showed a significant difference among age groups (p < 0.001). Only anti-P.fMSP1-19 IgG showed a significant association with general appearance (p value < 0.001). The mean for total anti-P.fMSP1-19 IgG3 was statistically significantly higher in females compared to males (p value < 0.001). There was no significant difference in the distribution of human IL4 vntr genotypic and allelic frequencies between cases and control group as well as among different clinical manifestation.We concluded that IgG1 levels to MSP1-19 were found to be negatively correlated with parasitaemia and anti-PfMSP1-19 IgG was significantly increased in ill and severely ill with age considered as a cofactor. Further studies are needed to ascertain the role of IgG and IgG1 in protection and to investigate the IgG and subclasses' response against other antigenic markers. These findings are valuable for advancing vaccine development by providing evidence supporting merozoite antigens as targets of protective immunity in humans.


Flow-through Omental Flap for Vascularized Lymph Node Transfer: A Novel Surgical Approach for Delayed Lymphatic Reconstruction.
The vascularized omental free flap has been described as a reliable option for the treatment of peripheral lymphedema. However, the flap has been associated with venous hypertension which may require venous supercharging or intra-flap arteriovenous fistula creation to offload the arterial inflow. The aim of this study is to introduce and present our experience using a flow-through omental flap as a novel approach to optimize flap hemodynamics. A retrospective review of a prospectively maintained quality improvement database was performed. Seven consecutive patients with unilateral breast cancer-related lymphedema (BCRL) who underwent delayed lymphatic reconstruction using a flow-through omental free flap were identified. In all patients, the right gastroepiploic artery and vein were anastomosed to the proximal end of the radial artery and to one venae comitante, respectively. An anastomosis of the distal end of the radial artery to the left gastroepiploic artery was performed. The flap was then supercharged by anastomosing the left gastroepiploic vein to the cephalic or basilic vein. There were no flap losses or other surgical complications. A distinct advantage of this inset includes the ability to moderate the arterial in-flow to the omental flap to avoid an inflow-outflow mismatch and alleviate venous hypertension. Further study is needed to validate this technique in a larger study sample with longer follow-up.


Rotational atherectomy does not reduce recurrent in-stent restenosis: results of the angioplasty versus rotational atherectomy for treatment of diffuse in-stent restenosis trial (ARTIST).
Aim of this trial was to compare rotational atherectomy followed by balloon angioplasty (rotablation [ROTA] group) with balloon angioplasty (percutaneous transluminal coronary angioplasty [PTCA] group) alone in patients with diffuse in-stent restenosis. The ARTIST study is a multicenter, randomized, prospective European trial with 298 patients with in-stent restenosis>70% (mean lesion length, 14 +/- 8 mm) in stents, implanted in coronary arteries for >/= 3 months. In the PTCA group, angioplasty was performed at the discretion of the local investigator, and rotablation was performed by using a stepped-burr approach followed by adjunctive PTCA with low (</= 6 atm) inflation pressure. Intravascular ultrasound during the intervention and at follow-up was used in a substudy in 86 patients (45 PTCA, 41 ROTA). Angiography demonstrated no difference regarding the short-term outcome, with equivalent procedural success rates defined as remaining stenosis <30% (89% PTCA, 88% ROTA). However, the results showed that, in the long term, PTCA was a significantly better strategy than ROTA. Mean net gain in minimal lumen diameter was 0.67 mm and 0.45 mm for PTCA and ROTA, respectively (P=0.0019). Mean gain in diameter stenosis was 25% and 17% (P=0.002), resulting in restenosis (>/= 50%) rates of 51% (PTCA) and 65% (ROTA) (P=0.039). By intravascular ultrasound, the major difference was the missing stent over-expansion during PTCA after ROTA. Six-month event-free survival was significantly higher after PTCA (91.3%) compared with ROTA (79.6%, P=0.0052). In terms of the primary objective of the study, PTCA produced a significantly better long-term outcome than ROTA followed by adjunctive low-pressure PTCA.


F- and M-wave conduction velocity in amyotrophic lateral sclerosis.
The F-wave was used to estimate motor nerve conduction velocity (MNCV) along the proximal segment of the fastest axons of the deep peroneal nerve (anterior-horn cells to knee) in 13 patients with amyotrophic lateral sclerosis (ALS) and in 21 age- and sex-matched control subjects. Measurements were based on the shortest latency of 100 F-waves obtained after supramaximal stimulation at the ankle and knee. The MNCV was estimated with the F-wave and conventional M-response methods in the distal segment (knee to ankle) of the nerve. Our results showed that proximal-nerve conduction is faster than distal conduction both in control subjects and in ALS patients. In ALS, there was a moderate reduction of MNCV, which was of equal degree in both the proximal and distal segments of the deep peroneal nerve. In control subjects and in ALS patients, no statistically significant difference was found between the MNCV estimated for the knee-to-ankle segment by conventional means and that obtained by the F-wave method. This indicates that the F-wave of shortest latency is conducted by the fastest surviving motor fibers, as in the initial components of the M-response--demonstrating that it is legitimate to make direct comparison of F- and M-latencies in estimating the proximal MNCV.


Transanal extirpation for early rectal cancer.
Transanal extirpation was performed in 38 patients with adenocarcinoma of the rectum. In 17 patients (group I) the tumor extended into the submucosa only, and in 14 patients (group II) tumors extended into, but not through, the muscularis propria. There was a significant difference in local recurrence between groups I and II. None of the patients in group I and six of the patients (42.6 percent) in group II developed local recurrences (P = 0.02). The 5-year actuarial survival probability was 100 and 82.6 percent, respectively. Transanal extirpation is an alternative to transsphincteric and abdominoperineal resection in the treatment of early well or moderately well-differentiated cancer of the rectum. The surgical procedure is simple and has few complications; however, only tumors extending no deeper than the submucosa are suitable for this treatment. The operation should be followed by frequent sigmoidoscopies and rectal palpation. The procedure should be defined as an excisional biopsy until results from the histologic examination are presented.