A pillar[5]arene-fused cryptand: from orthogonal self-assembly to supramolecular polymer.
A pillar[5]arene-fused cryptand with two different cavities was synthesized successfully. It was found that the novel tricyclic host could associate with two different guest species in an orthogonal manner. And based on this orthogonal self-assembly of two host-guest interactions, a novel type of supramolecular polymer was constructed easily and conveniently.


Exposure to intimate partner violence and internalizing symptoms: The moderating effects of positive relationships with pets and animal cruelty exposure.
It is estimated that more than half of children living in households where intimate partner violence (IPV) occurs are also exposed to animal cruelty (AC). Although prior research links bonds with pets with higher levels of socioemotional competence among school-age children, exposure to AC may negate the protective effects of pet ownership and/or exacerbate the potentially deleterious effect of IPV on children's mental health. The current study evaluates whether and to what extent the associations between exposure to IPV and several indicators of children's mental health vary as a function of children's positive engagement with pets and exposure to AC. Participants included 204 children (aged 7-12 years; 47% female; 57% Latinx) and their maternal caregiver who were recruited from domestic violence agencies in a western U.S. state. Multiple moderation analysis evaluated whether the association between children's exposure to IPV and internalizing and posttraumatic stress symptoms vary as a function of children's positive engagement with pets and exposure to AC. Analyses revealed several moderation effects for positive engagement with pets (e.g., internalizing problems: [b = -.15, t(195) = -2.66, p = .008]; posttraumatic stress symptoms: [b = -.13, t(195) = -2.24, p = .026]), whereas exposure to AC only moderated the association between IPV and anxious/depressed symptoms (b = .32, t(195) = -2.41, p = .017). These findings highlight the potential protective effects of positive engagement with pets and importance of screening for exposure to AC when engaging in trauma-informed work with children exposed to IPV.


Transition of care between paediatric and adult gastroenterology. Chronic viral hepatitis.
Chronic viral hepatitis is a common disease. More than 500 million people have chronic viral hepatitis worldwide. These diseases are due to chronic infection with hepatitis B virus, hepatitis D virus or hepatitis C virus. Chronic viral hepatitis is responsible for severe complications: cirrhosis and hepatocellular carcinoma, which are responsible for major morbidity and mortality worldwide. The prognosis of chronic viral hepatitis depends on the rate of progression of fibrosis, which varies widely from one patient to another. Some factors, such as gender, age, alcohol consumption and immune status, influence the progression of fibrosis. In recent years, treatment of chronic viral hepatitis has markedly improved-especially in chronic hepatitis C, with more than 50% of patients having a sustained response with the combination of pegylated interferon and ribavirin. Also, in chronic hepatitis B, new drugs are available, or being evaluated, and combination therapy could dramatically change future therapeutic strategies.


ChREBP Rather Than SHP Regulates Hepatic VLDL Secretion.
The regulation of hepatic very-low-density lipoprotein (VLDL) secretion plays an important role in the pathogenesis of dyslipidemia and fatty liver diseases. VLDL is controlled by hepatic microsomal triglyceride transfer protein (MTTP). Mttp is regulated by carbohydrate response element binding protein (ChREBP) and small heterodimer partner (SHP). However, it is unclear whether both coordinately regulate Mttp expression and VLDL secretion. Here, adenoviral overexpression of ChREBP and SHP in rat primary hepatocytes induced and suppressed Mttp mRNA, respectively. However, Mttp induction by ChREBP was much more potent than suppression by SHP. Promoter assays of Mttp and the liver type pyruvate kinase gene revealed that SHP and ChREBP did not affect the transcriptional activity of each other. Mttp mRNA and protein levels of Shp-/- mice were similar to those of wild-types; however, those of Chrebp-/-Shp-/- and Chrebp-/- mice were significantly much lower. Consistent with this, the VLDL particle number and VLDL secretion rates in Shp-/- mice were similar to wild-types but were much lower in Chrebp-/- and Chrebp-/-Shp-/- mice. These findings suggest that ChREBP, rather than SHP, regulates VLDL secretion under normal conditions and that ChREBP and SHP do not affect the transcriptional activities of each other.


Molecular basis for the differential subcellular localization of the 38- and 39-kilodalton structural proteins of Borna disease virus.
Borna disease virus (BDV) is a nonsegmented negative-strand (NNS) RNA virus that is unusual because it replicates in the nucleus. The most abundant viral protein in infected cells is a 38/39-kDa doublet that is presumed to represent the nucleocapsid. Infectious particles also contain high levels of this protein, accounting for at least 50% of the viral proteins. The two forms of the protein differ by an additional 13 amino acids that are present at the amino terminus of the 39-kDa form and missing from the 38-kDa form. To examine whether this difference in amino acid content affects the localization of this protein in cells, the 39- and 38-kDa proteins were expressed in transfected cells. The 39-kDa form was concentrated in the nucleus, whereas the 38-kDa form was found in both the nucleus and cytoplasm. Inspection of the extra 13 amino acids present in the 39-kDa form revealed a sequence (Pro-Lys-Arg-Arg) that is very similar to the nuclear localization signals (in both sequence homology and amino-terminal location) of the VP1 proteins of simian virus 40 and polyomavirus. Primer extension analysis of total RNA from infected cells suggests that there are two mRNA species encoding the two forms of the nucleocapsid protein. In infected cells, the 39-kDa form is expressed at about twofold-higher levels than the 38-kDa form at both the RNA and protein levels. The novel nuclear localization of the 39-kDa nucleocapsid-like protein suggests that this form of the protein is targeted to the nucleus, the site for viral RNA replication, and that it may associate with genomic RNA.


Clinical implications of DLL4 expression in gastric cancer.
Delta-like ligand 4 (DLL4)-Notch signaling plays a key role in tumor neovascular development and angiogenesis during tumor growth. The clinical significance of DLL4 expression in gastric cancer has not been clarified. Gastric cancer cell lines and 180 gastric cancer patients were enrolled. DLL4 expression in gastric cancer cells and stroma was identified and evaluated immunohistochemically. The association between DLL4 and clinicopathological factors was also assessed. DLL4 expression was identified in the cellular membrane and cytoplasm of gastric cancer cells by immunoblotting and immunohistochemical staining. DLL4 positivity in cancer cells and stroma was found in 88 (48%) and 41 (22%) of the 180 gastric cancer patients respectively. Both cancer and stromal DLL4 expression significantly correlated with more advanced tumor depth, nodal involvement, and lymphatic and venous invasion. A strongly positive association between cancerous and stromal DLL4 expression was identified (p < 0.01). Both cancerous and stromal DLL4 expression were prognostic markers in gastric cancer as determined by univariate analysis. Cancerous and stromal DLL4 expression was found in 48% and 22% in gastric cancer, and significantly affected postoperative clinical outcomes. Cancerous and stromal DLL4 expression may be an effective target of anti-DLL4 treatment in gastric cancer.


Multinuclear complex formation between Ca(II) and gluconate ions in hyperalkaline solutions.
Alkaline solutions containing polyhydroxy carboxylates and Ca(II) are typical in cementitious radioactive waste repositories. Gluconate (Gluc(-)) is a structural and functional representative of these sugar carboxylates. In the current study, the structure and equilibria of complexes forming in such strongly alkaline solutions containing Ca(2+) and gluconate have been studied. It was found that Gluc(-) significantly increases the solubility of portlandite (Ca(OH)2(s)) under these conditions and Ca(2+) complexes of unexpectedly high stability are formed. The mononuclear (CaGluc(+) and [CaGlucOH](0)) complexes were found to be minor species, and predominant multinuclear complexes were identified. The formation of the neutral [Ca2Gluc(OH)3](0) (log β213 = 8.03) and [Ca3Gluc2(OH)4](0) (log β324 = 12.39) has been proven via H2/Pt-electrode potentiometric measurements and was confirmed via XAS, (1)H NMR, ESI-MS, conductometry, and freezing-point depression experiments. The binding sites of Gluc(-) were identified from multinuclear NMR measurements. Besides the carboxylate group, the O atoms on the second and third carbon atoms were proved to be the most probable sites for Ca(2+) binding. The suggested structure of the trinuclear complex was deduced from ab initio calculations. These observations are of relevance in the thermodynamic modeling of radioactive waste repositories, where the predominance of the binuclear Ca(2+) complex, which is a precursor of various high-stability ternary complexes with actinides, is demonstrated.


[Erythropoietin influence on the blood oxygen transport and prooxidant-antioxidant state during hepatic ischemia-reperfusion].
The parameters of blood oxygen transport, the products of lipid peroxidation and antioxidative factors were determined in rats during the hepatic ischemia/reperfusion (HIR) under preliminary single injections of different doses ofrecombinant human erythropoietin (rhEPO). Hepatic ischemia was induced for 30 min by Pringle maneuver, reperfusion lasted 120 min. The experiments had shown that HIR led to the significant decreases in the hemoglobin oxygen affinity, activation of lipid peroxidation, depletion of the antioxidant system, increases blood transaminases (ALT and AST). rhEPO in dose 100 IU/kg aggravates decreasing hemoglobin oxygen affinity, improves some antioxidant parameters, but didn't correct lipid peroxidation or plasma transaminases during HIR. rhEPO infusion id dose 1000 IU/kg leads to oxyhemoglobin dissociative curve shift left-wards, improves prooxidant-antioxidant balance and plasma ALT, AST activities at the end of re-perfusion period.


Impact of alcohol misuse on family life.
The shame that surrounds problem drinking contributes to delay or failure of remedy; the family tries to hide the drinking of its member from neighbors and even from the doctors. All parties to the illness choose to ignore the alcoholism and its implication for the patient.


Relation between stressful life events, neuropeptides and cytokines: results from the LISA birth cohort study.
Stressful life events evidently have an impact on development of allergic diseases, but the mechanism linking stress to pathological changes of immune system function is still not fully understood. The aim of our study was to investigate the relationship between stressful life events, neuropeptide and cytokine concentrations in children. Within the LISAplus (Life style-Immune system-Allergy) study, blood samples from children of 6 yr of age were analysed for concentration of the neuropeptides vasoactive intestinal peptide (VIP), somatostatin (SOM), substance P (SP) and the Th1/Th2 cytokines interferon-gamma (IFN-gamma) and interleukin (IL)-4. Life events such as severe disease or death of a family member, unemployment or divorce of the parents were assessed with a questionnaire filled in by the parents. For 234 children, blood analysis and questionnaire data regarding life events were available. Children with separated/divorced parents showed high VIP levels and high concentrations of the Th2 cytokine IL-4 in their blood. Severe diseases and death of a family member were neither associated with neuropeptide levels nor with cytokine concentrations. Unemployment of the parents was associated with decreased IFN-gamma concentrations in children's blood but not with neuropeptide levels, whereas children experiencing concomitant severe disease and death of a family member had reduced SP blood levels. The neuropeptide VIP might be a mediator between stressful life events and immune regulation contributing to the Th2 shifted immune response in children with separated/divorced parents. Unemployment of the parents was associated with immune regulation in children on the basis of a still unknown mechanism whereas reduced SP levels seem to have no effect on immune regulation.


Perceived attachments to parents and peers and psychological well-being in adolescence.
This paper reports the findings from a study of 935 adolescents' perceived attachments to their parents and peers, and their psychological health and well-being. Perceived attachment to parents did not significantly differ between males and females. However, females scored significantly higher than males on a measure of attachment to peers. Also, relative to males, they had higher anxiety and depression scores, suggesting poorer psychological well-being. Overall, a lower perceived attachment to parents was significantly associated with lower scores on the measures of well-being. Adolescents who perceived high attachments to both their parents and peers had the highest scores on a measure of self-perceived strengths. In this study, adolescents' perceived attachment to peers did not appear to compensate for a low attachment to parents in regard to their mental ill-health. These findings suggest that high perceived attachment to parents may be a critical variable associated with psychological well-being in adolescence.


Transplacental delivery of genome editing components causes mutations in embryonic cardiomyocytes of mid-gestational murine fetuses.
Genome editing, as exemplified by CRISPR/Cas9, is now recognized as a powerful tool for the engineering of endogenous target genes. It employs only two components, namely, Cas9 in the form of DNA, mRNA, or protein; and guide RNA (gRNA), which is specific to a target gene. When these components are transferred to cells, they create insertion/deletion mutations (indels) within a target gene. Therefore, when fetuses within the uteri of pregnant murine females are exposed to these reagents, fetal cells incorporating them should show mutations in the target gene. To examine a possible genome editing of fetal cells in vivo, we intravenously administered a solution containing plasmid DNA-FuGENE complex to pregnant wild-type female mice [which had been successfully mated with enhanced green fluorescent protein (EGFP)-expressing male transgenic mice] on day 12.5 of gestation. The plasmid DNA induces the expression of gRNA, which was targeted at the EGFP cDNA, and that of the Cas9 gene. All fetuses in the pregnant females should express EGFP systemically, since they are heterozygous (Tg/+) for the transgene. Thus, the delivery of CRISPR system targeted at EGFP in the fetuses will cause a reduced expression of EGFP as a result of the genome editing of EGFP genomic sequence. Of the 24 fetuses isolated from three pregnant females 2 days after gene delivery, 3 were found to have reduced fluorescence in their hearts. Genotyping of the dissected hearts revealed the presence of the transgene construct (Cas9 gene) in all the samples. Furthermore, all the three samples exhibited mutations at the target loci, although normal cells were also present. Thus, transplacental delivery of gene editing components may be a useful tool for developing animal models with heart disorder for heart-related disease research, and gene therapy in congenital heart defects such as hypertrophic cardiomyopathy (HCM). © 2019 IUBMB Life, 9999(9999):1-10, 2019.


An Empirical Comparison of the Profiles of Security Threat Group Offenders with General Offenders.
Datasets of offender attributes, both pre-custody and in-custody, were provided by the Correctional Service of Canada with the goal of exploring whether Security Threat Group (STG) offenders (informally, gang members of various kinds) differ in any systematic way from other offenders. For pre-custody attributes, we show that the entire offender population varies along two almost independent axes, one associated with affinity for violence, and the other with affinity for substance abuse. Within this structure, STG offenders are characteristically less extreme, in either direction, than the general offender population. For approximately two dozen attributes, STG offenders, as a group, tend to have higher values; for a few, they tend to have lower values. For in-custody attributes, the entire offender population forms a triangular structure whose vertices represent: passivity; violence and troublemaking; and involvement in programs leading to partial release. The differences between the STG offender population and the general offender population are small. An offender who is placed at the high end of the propensity for violence axis and/or the high end of the substance abuse axis based on pre-custody attributes is much more likely to be involved in incidents, grievances, and violence while in custody. This may have implications for risk stratification of incoming offenders.


Clustering of protective factors for glucose intolerance and insulin resistance: a cross-sectional study.
A cluster of interrelated factors: a body mass index (BMI) < 25 kg/m(2), moderate exercise and alcohol intake, non-smoking and a favourable dietary pattern has been linked with markedly reduced risk of Type 2 diabetes. The aim of this study was to estimate the prevalence of a similar low-risk group in a sample of middle-aged Irish men and women, and determine whether this cluster is associated with a reduced risk of glucose intolerance (IFG and Type 2 diabetes according to ADA/WHO criteria) and insulin resistance [homeostasis model assessment (HOMA) score in upper quartile of distribution]. A cross-sectional study involving a stratified random sample of 1018 general practice patients, aged 50-69 years. We defined a low-risk group based on the following variables: BMI < 25 kg/m(2); waist-hip ratio < 0.85 for women and 0.90 for men; never smoking status; participation in medium to high level of physical activity; light drinking (3.5-7 units of alcohol per week) and a 'prudent' dietary pattern. Valid data were available for glucose tolerance status and HOMA score and all exposure variables from 684 and 671 participants, respectively. A total of 7.5% of participants had none of the 'protective factors', 24.9% had one, 31.0% two, 23.3% three, 10.0% four, 3.0% five and 0.3% had six protective factors. In multivariate analyses the odds ratios for insulin resistance were 0.59, 0.48, 0.14 and 0.04 in persons with one, two, three and four or more low-risk factors, respectively, relative to those with none. Similar linear inverse trends were observed for glucose intolerance. The findings are consistent with an inverse linear relation between a cluster of core protective, lifestyle-related factors and the prevalence of both glucose intolerance and insulin resistance.


A model of primitive streak initiation in the chick embryo.
Initiation of the primitive streak in avian embryos provides a well-studied example of a pattern-forming event that displays a striking capacity for regulation. The mechanisms underlying the regulative properties are, however, poorly understood and are not easily accounted for by traditional models of pattern formation, such as reaction-diffusion models. In this paper, we propose a new activator-inhibitor model for streak initiation. We show that the model is consistent with experimental observations, both in its pattern-forming properties and in its ability to form these patterns on the correct time-scales for biologically realistic parameter values. A key component of the model is a travelling wave of inhibition. We present a mathematical analysis of the speed of such waves in both diffusive and juxtacrine relay systems. We use the streak initiation model to make testable predictions. By varying parameters of the model, two very different types of patterning can be obtained, suggesting that our model may be applicable to other processes in addition to streak initiation.


Effect of natural polyphenol on the oxidative stability of pecan oil.
We evaluated the antioxidant activity of natural polyphenols which gives high oxidative stability to the pecan oil. The in vitro DPPH radical scavenging, reducing power and total antioxidant activity of tested antioxidants demonstrated that tannic acid displayed the highest DPPH scavenging activity and provided the largest reducing power. During storage of pecan oil, based on oxidative stability tests, we further evaluated the protective effect of polyphenols and synthetic antioxidants on the oxidative stability of pecan oil. The results showed that caffeic acid inhibited oxidation of pecan oil effectively. Sesamol and catechin showed slight improvement in oxidative stability, while ferulic acid, erucic acid and rutin had no effect. Taken together, compared with synthetic antioxidants (TBHQ, BHT, BHA), caffeic acid was observed to be stronger than BHT and BHA and was close to TBHQ.


EMT in breast cancer metastasis: an interplay of microRNAs, signaling pathways and circulating tumor cells.
Epithelial to Mesenchymal Transition (EMT) is a biological process characterized by the transition from immotile epithelial cells to motile mesenchymal cells. Though shown to be implicated in many biological processes, it has also been identified to enhance migration and invasion of cancer cells leading to metastasis. A class of microRNAs called "oncomiRs" plays a significant role in the regulation of malignant transformation and metastasis. In this review, the ability of different signaling pathways in controlling EMT through well-defined regulatory networks, and the role exerted by oncomiRs in regulating the specific signaling pathways like TGF-β, Wnt, Notch and Hedgehog in modulating breast cancer metastasis have been discussed with updated information. Further, this review focuses on the significance of up and down regulated microRNAs in the pathogenesis and progression of breast cancer and how such microRNAs could be treated as potential therapeutic targets to circumvent cancer. As a prospective strategy, we highlight the importance of circulating tumor cells (CTCs) and their derived microRNAs as prognostic indicators and cancer therapy monitoring tools.


[Biomedical aspects of the use of cadaver blood].
The author analyzes historical periods during which Academician S. S. Yudin developed the theory of cadaveric blood and pioneered its practical implementation, storage and the clinical use. Demonstrates the efficacy of the new transfusion medium in the management of patients with emergency conditions. Reviews 3 trends in the investigations carried out in this area: in morbid anatomy and forensic medicine, in experimental and clinical transfusiology, and in biomedical studies. Provides evidence for the fact that blood plasma of sudden death victims and perfusate of the vessels are specific raw materials for obtaining plasmakinase, a fibrinolytic agent, and fibrinogen degradation products as well as another source for obtaining preparations with a directed action. Based on a large factual material, the author shows the possibility, importance, prospects and efficiency of the use of components, preparations and biologically active substances from cadaveric blood plasma.


Do inflammatory markers portend heterotopic ossification and wound failure in combat wounds?
After a decade of war in Iraq and Afghanistan, we have observed an increase in combat-related injury survival and a paradoxical increase in injury severity, mainly because of the effects of blasts. These severe injuries have a devastating effect on each patient's immune system resulting in massive upregulation of the systemic inflammatory response. By examining inflammatory mediators, preliminary data suggest that it may be possible to correlate complications such as wound failure and heterotopic ossification (HO) with distinct systemic and local inflammatory profiles, but this is a relatively new topic. We asked whether systemic or local markers of inflammation could be used as an objective means, independent of demographic and subjective factors, to estimate the likelihood of (1) HO and/or (2) wound failure (defined as wounds requiring surgical débridement after definitive closure, or wounds that were not closed or covered within 21 days of injury) in patients sustaining combat wounds. Two hundred combat wounded active-duty service members who sustained high-energy extremity injuries were prospectively enrolled between 2008 and 2012. Of these 200 patients, 189 had adequate followups to determine the presence or absence of HO, and 191 had adequate followups to determine the presence or absence of wound failure. In addition to injury-specific and demographic data, we quantified 24 cytokines and chemokines during each débridement. Patients were followed clinically for 6 weeks, and radiographs were obtained 3 months after definitive wound closure. Associations were investigated between these markers and wound failure or HO, while controlling for known confounders. The presence of an amputation (p < 0.001; odds ratio [OR], 6.1; 95% CI. 1.63-27.2), Injury Severity Score (p = 0.002; OR, 33.2; 95% CI, 4.2-413), wound surface area (p = 0.001; OR, 1.01; 95% CI, 1.002-1.009), serum interleukin (IL)-3 (p = 0.002; OR, 2.41; 95% CI, 1.5-4.5), serum IL-12p70 (p = 0.01; OR, 0.49; 95% CI, 0.27-0.81), effluent IL-3 (p = 0.02; OR, 1.75; 95% CI, 1.2-2.9), and effluent IL-13 (p = 0.006; OR, 0.67; 95% CI, 0.50-0.87) were independently associated with HO formation. Injury Severity Score (p = 0.05; OR, 18; 95% CI, 5.1-87), wound surface area (p = 0.05; OR, 28.7; 95% CI, 1.5-1250), serum procalcitonin ([ProCT] (p = 0.03; OR, 1596; 95% CI, 5.1-1,758,613) and effluent IL-6 (p = 0.02; OR, 83; 95% CI, 2.5-5820) were independently associated with wound failure. We identified associations between patients' systemic and local inflammatory responses and wound-specific complications such as HO and wound failure. However, future efforts to model these data must account for their complex, time dependent, and nonlinear nature. Level II, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.


The zebrafish cerebellar upper rhombic lip generates tegmental hindbrain nuclei by long-distance migration in an evolutionary conserved manner.
The upper rhombic lip (URL) of the developing mammalian cerebellum produces different neuronal cell types in a temporal sequence. The first neuronal populations arising from this proliferation zone include the progenitors of the parabrachial, parabigeminal, and laterodorsal-pedunculopontine tegmental hindbrain nuclei. By means of expression analysis, histology, and retrograde neuronal tracing, we have identified the zebrafish homologues of these nuclei, namely, the secondary gustatory/viscerosensory nucleus, the nucleus isthmi, and the superior reticular nucleus, respectively, in the embryonic and larval brain of a stable transgenic wnt1:Gal4-VP16-14 x UAS:GFP zebrafish strain. Combining time-lapse confocal imaging with individual cell tracing, we characterize the migratory behavior of these neuronal precursor populations in detail by revealing their migration path, velocity, and directionality. In addition, we identify neuronal progenitors of the secondary gustatory/viscerosensory nucleus and nucleus isthmi/superior reticular nucleus as belonging to the polysialic acid (PSA)-expressing cell population in the cerebellar plate that migrates in a PSA-dependent manner. Finally, we reveal that circuitries involved in the processing of sensory information (visual, gustatory, general viscerosensory) are already established in the zebrafish larva at day 4 of development. Also the wnt1-expressing pretectal neuronal precursors (not originating from the URL) sending mossy fiber-like projections into the cerebellar corpus are established at that time. In sum, our results show that the origin of neurons of some tegmental hindbrain nuclei, namely, nucleus isthmi/superior reticular nucleus and secondary gustatory/viscerosensory nucleus is in the URL, and that the temporal order of cell types produced by the URL and their developmental program are conserved among vertebrate species.


Tissue factor expression in breast cancer tissues: its correlation with prognosis and plasma concentration.
Tissue factor (TF), an initiator of the extrinsic coagulation cascade, is expressed in a wide range of cancer cells and plays important roles in cancer progression and metastasis. Recently, the intracellular function of TF has been revealed to be involved in cancer invasion, independent of the blood coagulation pathway. To evaluate the clinical significance of TF expression, we performed an enzyme-linked immunosorbent assay (ELISA) in the plasma of 67 breast cancer patients and immunohistochemistry in 213 breast cancer tissues. In the ELISA study, we showed an up-regulation of plasma TF concentration in breast cancer patients compared with normal controls. Immunohistochemistry demonstrated that TF was expressed in tumour cells and stromal cells and tumour TF expression closely correlated with stromal TF expression (P = 0.0005). The concentration of plasma TF was associated with tissue TF expression in both tumour and stroma. The multivariate analysis demonstrated that tumour TF expression was an independent prognostic indicator for overall survival (P = 0.0452). Our data show that plasma TF concentration reflects tissue TF expression and tumour TF expression can provide some predictive value for prognosis and distant metastasis, which indicates the importance of TF function in tumour progression.


Characterization of cDNA clones encoding rabbit and human serum paraoxonase: the mature protein retains its signal sequence.
Serum paraoxonase hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. High serum paraoxonase levels appear to protect against the neurotoxic effects of organophosphorus substrates of this enzyme [Costa et al. (1990) Toxicol. Appl. Pharmacol. 103, 66-76]. The amino acid sequence accounting for 42% of rabbit paraoxonase was determined by (1) gas-phase sequencing of the intact protein and (2) peptide fragments from lysine and arginine digests. From these data, two oligonucleotide probes were synthesized and used to screen a rabbit liver cDNA library. A clone was isolated and sequenced, and contained a 1294-bp insert encoding an open reading frame of 359 amino acids. Northern blot hybridization with RNA isolated from various rabbit tissues indicated that paraoxonase mRNA is synthesized predominately, if not exclusively, in the liver. Southern blot experiments suggested that rabbit paraoxonase is coded by a single gene and is not a family member of closely related genes. Human paraoxonase clones were isolated from a liver cDNA library by using the rabbit cDNA as a hybridization probe. Inserts from three of the longest clones were sequenced, and one full-length clone contained an open reading frame encoding 355 amino acids, four less than the rabbit paraoxonase protein. Each of the human clones appeared to be polyadenylated at a different site, consistent with the absence of the canonical polyadenylation signal sequence. Of potential significance with respect to the paraoxonase polymorphism, the derived amino acid sequence from one of the partial human cDNA clones differed at two positions from the full-length clone. Amino-terminal sequences derived from purified rabbit and human paraoxonase proteins suggested that the signal sequence is retained, with the exception of the initiator methionine residue [Furlong et al. (1991) Biochemistry (preceding paper in this issue)]. Characterization of the rabbit and human paraoxonase cDNA clones confirms that the signal sequences are not processed, except for the N-terminal methionine residue. The rabbit and human cDNA clones demonstrate striking nucleotide and deduced amino acid similarities (greater than 85%), suggesting an important metabolic role and constraints on the evolution of this protein.


[Methodological variants in the optimal determination of the activity of natural killers and mononuclear phagocytes by analysis at the single-cell level].
Variants of the method for determination of the natural killer cells (NK-cells), and monocytes-macrophages both in human beings and in mice have been described. Usage of agarose which permits fixing conjugates of the effector cells and a tumour target cell allows determining simultaneously the quantity of effector cells bound with the target and percentage of the cytotoxic effectors. The results in acceptable definition of the effector cells' activity with the use of various kinds of plastic ware, its treatment, diverse types of agarose, temperature and time regimen are adduced. The di-target method of testing is approved using the target cells labelled with fluorescein as well as unlabelled ones. Peculiarities of function disturbances of the NK-cells and monocytes in patients with lung cancer as well as changes in the activity of these effectors in mice CBA depending on the terms of Krebs-2 carcinoma inoculation and on repeated BCG vaccine injection were detected.


B7-H1 costimulation preferentially enhances CD28-independent T-helper cell function.
B7-H1 is a recently described B7-like molecule that costimulates T-cell growth and cytokine secretion without binding to CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4), and inducible costimulator (ICOS). In this report, a mouse homologue of human B7-H1 is identified, and its immunologic functions are studied in vitro and in vivo. Mouse B7-H1 shares 69% amino acid homology to the human counterpart. Similar to human B7-H1, mouse B7-H1 can be induced to express on macrophages, T cells, and B cells and to enhance T-cell proliferation and secretion of interleukin-10 (IL-10), interferon-gamma, and granulocyte-macrophage colony-stimulating factor but not IL-2 and IL-4. Furthermore, B7-H1 preferentially costimulates CD4+ T cells independently of CD28 and enhances mixed lymphocyte responses to allogeneic antigens. In contrast to B7-1, expression of B7-H1 on murine P815 tumor cells by transfection fails to increase allogeneic and syngeneic cytolytic T-cell responses in vitro and in vivo. Administration of B7-H1Ig fusion protein, however, enhances keyhole limpet hemocyanin- specific T-cell proliferation and 2,4,6-trinitrophenyl-specific immunoglobulin G2a antibody production. The study thus identifies a unique costimulatory pathway that preferentially affects T-helper cell functions.


Basement membrane structure in situ: evidence for lateral associations in the type IV collagen network.
To determine molecular architecture of the type IV collagen network in situ, the human amniotic basement membrane has been studied en face in stereo relief by high resolution unidirectional metal shadow casting aided by antibody decoration and morphometry. The appearance of the intact basement membrane is that of a thin sheet in which there are regions of branching strands. Salt extraction further exposes these strands to reveal an extensive irregular polygonal network that can be specifically decorated with gold-conjugated anti-type IV collagen antibody. At high magnification one sees that the network, which contains integral (9-11 nm net diameter) globular domains, is formed in great part by lateral association of monomolecular filaments to form branching strands of variable but narrow diameters. Branch points are variably spaced apart by an average of 45 nm with 4.4 globular domains per micron of strand length. Monomolecular filaments (1.7-nm net diameter) often appear to twist around each other along the strand axis; we propose that super helix formation is an inherent characteristic of lateral assembly. A previous study (Yurchenco, P. D., and H. Furthmayr. 1984. Biochemistry. 23:1839) presented evidence that purified murine type IV collagen dimers polymerize to form polygonal arrays of laterally as well as end-domain-associated molecules. The architecture of this polymer is similar to the network seen in the amnion, with lateral binding a major contributor to each. Thus, to a first approximation, isolated type IV collagen can reconstitute in vitro the polymeric molecular architecture it assumes in vivo.


Cytotoxic and pathogenic properties of Klebsiella oxytoca isolated from laboratory animals.
Klebsiella oxytoca is an opportunistic pathogen implicated in various clinical diseases in animals and humans. Studies suggest that in humans K. oxytoca exerts its pathogenicity in part through a cytotoxin. However, cytotoxin production in animal isolates of K. oxytoca and its pathogenic properties have not been characterized. Furthermore, neither the identity of the toxin nor a complete repertoire of genes involved in K. oxytoca pathogenesis have been fully elucidated. Here, we showed that several animal isolates of K. oxytoca, including the clinical isolates, produced secreted products in bacterial culture supernatant that display cytotoxicity on HEp-2 and HeLa cells, indicating the ability to produce cytotoxin. Cytotoxin production appears to be regulated by the environment, and soy based product was found to have a strong toxin induction property. The toxin was identified, by liquid chromatography-mass spectrometry and NMR spectroscopy, as low molecular weight heat labile benzodiazepine, tilivalline, previously shown to cause cytotoxicity in several cell lines, including mouse L1210 leukemic cells. Genome sequencing and analyses of a cytotoxin positive K. oxytoca strain isolated from an abscess of a mouse, identified genes previously shown to promote pathogenesis in other enteric bacterial pathogens including ecotin, several genes encoding for type IV and type VI secretion systems, and proteins that show sequence similarity to known bacterial toxins including cholera toxin. To our knowledge, these results demonstrate for the first time, that animal isolates of K. oxytoca, produces a cytotoxin, and that cytotoxin production is under strict environmental regulation. We also confirmed tilivalline as the cytotoxin present in animal K. oxytoca strains. These findings, along with the discovery of a repertoire of genes with virulence potential, provide important insights into the pathogenesis of K. oxytoca. As a novel diagnostic tool, tilivalline may serve as a biomarker for K oxytoca-induced cytotoxicity in humans and animals through detection in various samples from food to diseased samples using LC-MS/MS. Induction of K. oxytoca cytotoxin by consumption of soy may be in part involved in the pathogenesis of gastrointestinal disease.


Isotopically Dimethyl Labeling-Based Quantitative Proteomic Analysis of Phosphoproteomes of Soybean Cultivars.
Isotopically dimethyl labeling was applied in a quantitative post-translational modification (PTM) proteomic study of phosphoproteomic changes in the drought responses of two contrasting soybean cultivars. A total of 9457 phosphopeptides were identified subsequently, corresponding to 4571 phosphoprotein groups and 3889 leading phosphoproteins, which contained nine kinase families consisting of 279 kinases. These phosphoproteins contained a total of 8087 phosphosites, 6106 of which were newly identified and constituted 54% of the current soybean phosphosite repository. These phosphosites were converted into the highly conserved kinase docking sites by bioinformatics analysis, which predicted six kinase families that matched with those newly found nine kinase families. The overly post-translationally modified proteins (OPP) occupies 2.1% of these leading phosphoproteins. Most of these OPPs are photoreceptors, mRNA-, histone-, and phospholipid-binding proteins, as well as protein kinase/phosphatases. The subgroup population distribution of phosphoproteins over the number of phosphosites of phosphoproteins follows the exponential decay law, Y = 4.13e-0.098X - 0.04. Out of 218 significantly regulated unique phosphopeptide groups, 188 phosphoproteins were regulated by the drought-tolerant cultivar under the water loss condition. These significantly regulated phosphoproteins (SRP) are mainly enriched in the biological functions of water transport and deprivation, methionine metabolic processes, photosynthesis/light reaction, and response to cadmium ion, osmotic stress, and ABA response. Seventeen and 15 SRPs are protein kinases/phosphatases and transcription factors, respectively. Bioinformatics analysis again revealed that three members of the calcium dependent protein kinase family (CAMK family), GmSRK2I, GmCIPK25, and GmAKINβ1 kinases, constitute a phosphor-relay-mediated signal transduction network, regulating ion channel activities and many nuclear events in this drought-tolerant cultivar, which presumably contributes to the development of the soybean drought tolerance under water deprivation process.


[Smoking and earlier menopause].
To evaluate the impact of smoking on the onset age of menopause. From January of 1998 to January of 2001, 775 postmenopausal women, with ages ranging from 40 to 65 years, were evaluated by means of a questionnaire. They were asked about their birth date; last menstrual bleeding, number of children, smoking habits, use of hormone medication, number of cigarettes per day, and gynecological surgeries. The menopausal status was characterized by blood determinations of FSH (> 30 UI) and estradiol (< 13 pg/mL). Women with surgical menopause, premature menopause and users of hormone replacement therapy were excluded. Of the 775 women included 646 (83%) were not-smokers and 129 (17%) smokers. For the non-smoking group mean age at menopause was 48.6 (+/- 4.1) years and for smokers 47.8 (+/-3.9). Median ages at menopause were 49.2 (+/-3.7) and p=0.464; 47.6 (+/-4.3) and p=0.171); and 46.9 (+/-3.6) and p=0.016 years for women who smoked 1-5, 6-10 and 11 or more cigarettes per day, respectively. Onset of menopause was anticipated by eight months for women who smoke. This finding suggests a greater susceptibility to earlier menopause in accordance with the number of cigarettes smoked per day.


Ewing's sarcoma of the maxilla.
Ewing's sarcoma is an uncommon malignancy that occurs usually in childhood. In most reported cases, the occurrence of this tumor is more in the mandible than the maxilla. A case of Ewing's sarcoma of the maxilla together with its associated structures is presented and discussed with complete clinical, radiographic, and histological evaluation. Although the prognosis remains poor, an increased rate of survival is now associated with early diagnosis and combined therapy.


Concurrent Evolution of Antiaging Gene Duplications and Cellular Phenotypes in Long-Lived Turtles.
There are many costs associated with increased body size and longevity in animals, including the accumulation of genotoxic and cytotoxic damage that comes with having more cells and living longer. Yet, some species have overcome these barriers and have evolved remarkably large body sizes and long lifespans, sometimes within a narrow window of evolutionary time. Here, we demonstrate through phylogenetic comparative analysis that multiple turtle lineages, including Galapagos giant tortoises, concurrently evolved large bodies, long lifespans, and reduced cancer risk. We also show through comparative genomic analysis that Galapagos giant tortoises have gene duplications related to longevity and tumor suppression. To examine the molecular basis underlying increased body size and lifespan in turtles, we treated cell lines from multiple species, including Galapagos giant tortoises, with drugs that induce different types of cytotoxic stress. Our results indicate that turtle cells, in general, are resistant to oxidative stress related to aging, whereas Galapagos giant tortoise cells, specifically, are sensitive to endoplasmic reticulum stress, which may give this species an ability to mitigate the effects of cellular stress associated with increased body size and longevity.


[Acute hematogenic osteomyelitis after impetiginized scabies].
A 15 year old boy with scabies has been treated with local form of therapy for 3 month without effect. He was then admitted to our pediatric clinic with pyrexia and restricted movement of the right knee. The med. history, the consequent laboratory findings, positive bloodcultures, skin swabs and bone scintigraphy lead to diagnosis of acute haem. osteomyelitis. The early antibiotic therapy assured uneventful recovery.


Response of continuous peritoneal dialysis patients to subcutaneous recombinant human erythropoietin differs from that of hemodialysis patients.
The hematologic response of 65 continuous ambulatory peritoneal dialysis (CAPD) patients to subcutaneous recombinant human erythropoietin (rHuEPO) was compared with that of 369 hemodialysis patients (HD). Pretherapy transfusions were more common in HD than CAPD. The response was measured as the change in hematocrit after 70 or more days of therapy (or as the hematocrit change normalized by a weekly dose) in CAPD patients. The weekly rHuEPO dose did not differ, but the dosing frequency was less in CAPD than in HD patients. Hematologic response parameters were greater in CAPD. Multivariate analysis showed that the response in both groups varied inversely with the frequency of dosing and with pretherapy baseline hematocrit. In HD subjects, the response also varied inversely with previous transfusion history. The authors concluded that CAPD patients responded better to rHuEPO than HD patients. This may be a result, in part, of lower ongoing blood losses. Patients with more severe anemias responded less well, whereas more sensitive patients were dosed less frequently.


Utilizing Graph Neural Networks for Breast Cancer Prognosis Prediction with High-dimensional Genomic Data.
An accurate prediction of breast cancer is essential to help physicians make appropriate treatment recommendations to reduce the chance of excessive treatment, avoiding unnecessary anxiety for patients. Cancer prognosis is highly related to patients' genomic features, which are high-dimensional in nature. In this study, we utilize a systems biology feature selector for dimension reduction to select 20 prognostic biomarkers that are considered closely related to breast cancer prognosis from the high dimensional RNA Sequencing (RNA-Seq) data. Furthermore, we establish a graph neural network (GNN) and a multi-layer perception (MLP) graph-level readout method to better extract the underlying gene interactions from the corresponding gene interaction network (GIN). With the help of GINs, the model performs the best among all baseline models, especially in the area under the precision-recall curve (AUPRC) by as large as 23%. The results demonstrate that our approach using GNNs can successfully extract high-dimensional and complicated interactions within genomic data.


Industrial Noise Exposure and Risk Factors for Cardiovascular Disease: Findings from the CORDIS Study.
Previous studies of the association between occupational noise exposure and cardiovascular disease (CVD) or risk factors for CVD are primarily either cross-sectional or retrospective, whereas the design of the CORDIS study was both cross-sectional and longitudinal. It had three phases: Phase I was conducted during 1985-87 among 6,016 employees from 21 factories. Recorded were medical, ergonomic, environmental (including noise levels at the various work stations) and psychological data. Phase II was conducted during 1988-90, at 18 of the 21 original factories and included similar data collected from 3,509 subjects. Phase III was conducted during the years 1995-96 and 4,995 workers who participated in Phases I and II completed questionnaires pertaining to medical, occupational and life style variables. Mortality and cancer morbidity data were obtained over an 8 year follow-up period for all subjects. Results from Phase I, revealed no association between noise exposure and resting blood pressure. Positive association was found for serum lipids in women and in young men. Noise annoyance had an additive effect on this outcome. In addition, recurrent daily noise exposure was found to be associated with elevated acute resting heart rate. Results of Phase II showed that chronic exposure to high noise levels during the 2-4 years of the follow-up resulted in changes of 3.9 mmHg in SBP and 3.3 mmHg in DBP, among workers performing complex jobs. In workers performing simple jobs these changes were 0.3 and 0.4 mmHg. Thus the type of work performed appears to be a significant factor. Results of Phase III revealed that there was a trend for positive association between past noise exposure measured at Phase I and 8 years incidence of cardiovascular morbidity, mortality and total mortality. This trend was statistically significant for total mortality (hazard ratio = 1.97, 95% CI 1.28-4.54) even after controlling for possible confounders. In summary, tests for association between noise exposure and cardiovascular risk factors, or cardiovascular morbidity and mortality, and total mortality have yielded mixed results. Reasons for this are discussed, as well as suggestions for further research.


Lupus low disease activity state is associated with a decrease in damage progression in Caucasian patients with SLE, but overlaps with remission.
To evaluate the prevalence, duration and effect on damage accrual of the 'Lupus Low Disease Activity State' (LLDAS) in a monocentric cohort of patients with systemic lupus erythematosus (SLE). We studied 293 Caucasian patients with SLE during a 7-year follow-up period. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and SELENA-SLEDAI physician global assessment (PGA), and damage by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We considered the following definition of LLDAS: SLEDAI-2K ≤4 without major organ activity, no new disease activity, PGA (0-3)≤1, prednisone ≤7.5 mg/day and well-tolerated immunosuppressant dosages. The effect of LLDAS on SDI was evaluated by multivariate regression analysis. We also evaluated remission defined as clinical SLEDAI-2K=0 and prednisone ≤5 mg/day in patients treated with/without stable immunosuppressants and/or antimalarials. LLDAS lasting 1, 2, 3, 4 or ≥5 consecutive years was achieved by 33 (11.3%), 43 (14.7%), 39 (13.3%), 31 (10.6%) and 109 (37.2%) patients, respectively. Patients who spent at least two consecutive years in LLDAS had significantly less damage accrual compared with patients never in LLDAS (p=0.001), and they were significantly less likely to have an increase in SDI (OR 0.160, 95% CI 0.060 to 0.426, p<0.001). On average, 84% of patients in LLDAS also fulfilled the criteria for remission. LLDAS was associated with a decrease in damage progression in Caucasian patients with SLE. The majority of patients in LLDAS were in remission, which can largely contribute to the protective effect of LLDAS on damage accrual.


Model selection and health effect estimation in environmental epidemiology.
In air pollution epidemiology, improvements in statistical analysis tools can help improve signal-to-noise ratios, and untangle large correlations between exposures and confounders. For this reason, we welcome a novel model-selection approach that helps to identify the time-windows of exposure to pollutants that produces adverse health effects. However, there are concerns about approaches that select a model based on a given data set, and then estimate health effects in the same data. This can create problems when (1) the sample size is small in relation to the magnitude of the health effects; and (2) candidate predictors are highly correlated and likely to have similar effects. Bayesian Model Averaging has been advocated as a way to estimate health effects that accounts for model uncertainty. However, implementations where posterior model probabilities are approximated using BIC, as well as other default choices, may not reflect the ability of each model to provide an estimate of the health effect that is properly adjusted for confounding. Air pollution studies need to focus on estimating health effects while accounting for the uncertainty in the adjustment for confounding factors. This is true especially when model choice and estimation are performed on the same data. The development of appropriate statistical tools remains an open area of investigation.


Associations of behavioural, psychosocial and socioeconomic factors with over- and underweight among German adolescents.
The prevalence of overweight and obesity has dramatically increased in western societies. This paper examines behavioural, psychosocial and socioeconomic factors associated with overweight and underweight among adolescents in Germany. Data from the German part of the 2001/02 Health Behaviour in School-aged Children (HBSC) survey, composed of 5,650 respondents aged 11 to 17 years were analysed. Body mass index (BMI) was calculated based on self-reported weight and height. The overweight category was defined as BMI within or above the 90th percentile of specific BMI values for gender and age in the German national sample. The underweight category was defined as BMI within or below the 10th percentile of this sample. A multinomial logistic regression model was used to investigate the association between behavioural, psychosocial and socioeconomic factors and BMI categories. 9.5% of the boys and 5.4% of the girls were classified as overweight. The prevalence of underweight was 12.6% among boys and 19.1% among girls. Several factors were associated with over- and/or underweight in the bivariate analysis, showing different patterns for gender and BMI categories. In the multivariable model only low family affluence, high sedentary behaviour, and being bullied (for girls only) remained positively associated with being overweight. Being underweight was negatively associated with higher age and low parental occupation; it differed also by region. Despite several variables being associated with overweight and underweight in bivariate models, only three factors remained associated with overweight in multivariable analysis. Other considered variables did not have independent associations with the outcome, but still could be included in respective causal pathways. Our results suggest that preventive strategies focussing on students of low socio-economic status and the avoidance of sedentary behaviours could help to address issues of overweight and obesity.


A qualitative evaluation of weekly reflective practice sessions for the intensive care unit pharmacy team during the COVID-19 pandemic.
Despite well-being initially being high on the agenda for UK health organisations, the COVID-19 pandemic has highlighted significant gaps around provision for well-being of pharmacists in the UK. The COVID-19 intensive care unit (ICU) environment exposed pharmacists to mental, physical and emotional challenges, including high levels of patient mortality. To provide an account of the experience of pharmacists working within an ICU at a large National Health Service hospital who attended reflective practice sessions throughout the first wave of the pandemic. A retrospective, cross-sectional design was used to gather information from eight participants who had attended nine, 30-minute weekly reflective practice sessions. Participants were invited to complete a 10-item online self-report questionnaire. The responses from the questionnaire were analysed using theoretical thematic analysis. Seven participants completed the self-report questionnaire. Thematic analysis of responses identified four themes: (1) permission: both professional and personal 'permission' was necessary for participants to be present for the reflective practice sessions and to attend to their own well-being; (2) containing safe space: reflective practice sessions offered a consistently secure environment from which to explore topics which created challenge, personally and/or professionally; (3) connectedness: the impact of these sessions on participants' relationships with other attendees, as individuals and the group as a whole; and (4) emotional experience: increased awareness of developments around their expression, processing and management of emotion as a result of attending the sessions. This study provides new and important insights into the use of reflective practice for pharmacists working in an ICU during the COVID-19 pandemic. Findings demonstrate heterogeneity in the experience of distress, the need to support the pharmacy profession, and the need to provide opportunities for staff to connect safely with colleagues during such crises. The impact of organisation-led support for the pharmacy profession is discussed as a future direction of research.


Prostate-specific antigen response in black and white patients treated with abiraterone acetate for metastatic castrate-resistant prostate cancer.
Evidence suggests differences in androgen receptor AR signaling between black (B) and white (W) patients with prostate cancer, but pivotal trials of abiraterone acetate (AA) for patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled few black patients, a population with a higher mortality from prostate cancer. Our primary objective was to determine differences in response to AA between B and W patients. We performed a retrospective case-control study of B vs. W patients treated with AA between May 1, 2008 and June 16, 2015 at Duke University Medical Center. Patients were identified (W control patients were matched 2:1 to B patients stratified based on previous docetaxel exposure) through pharmacy records and were eligible if treated with AA for metastatic castration-resistant prostate cancer. Patients with previous enzalutamide use were excluded. The primary objective was to compare the rate of≥90% prostate-specific antigen (PSA) decline from baseline between B vs. W patients. Secondary outcomes included comparing time on therapy, time to PSA progression, and overall survival among groups. Baseline characteristics among patients (n = 45 B, n = 90 W) were identified; these included Karnofsky performance status, PSA, Gleason score, alkaline phosphatase, albumin, hemoglobin, lactate dehydrogenase, opiate use for pain, and metastatic sites. Baseline characteristics among groups were similar except for median hemoglobin (B = 11.4g/dl, W = 12.3g/dl). The proportion of B patients achieving a≥90% PSA level decline was 37.8% vs. 28.9% for W patients (P = 0.296). Statistically significant differences were found in the proportion of patients achieving a≥50% PSA level decline (B = 68.9%, W = 48.9% [P = 0.028]) and≥30% PSA level decline (B = 77.8%, W = 54.4% [P = 0.008]). Rates of primary abiraterone-refractory disease (PSA increase as best response) trended higher in W (31.1%) than in B (15.6%) patients (P = 0.052). Median treatment duration (B = 9.4 mo, W = 8.3 mo) did not differ (Wilcoxon P = 0.444). Median overall survival (B = 27.3 mo [95% CI: 13.9, not estimable], W = 24.8 mo [95% CI: 19, 31.6] [P = 0.669]) and median time to PSA progression (B = 11.0 mo [95% CI: 4.3, 18.0], W = 9.4 mo [95% CI: 6.2, 13.0] [P = 0.917]) did not differ. Black patients may have a higher PSA response to AA than white patients. An ongoing prospective clinical study (NCT01940276) is evaluating outcomes between black and white patients treated with AA.


Pacing-induced heart failure in the dog: evaluation of peripheral vascular alpha-adrenoceptor subtypes.
Postjunctional alpha-adrenoceptor characteristics were evaluated in canine dorsal pedal arterial and saphenous vein rings studied before and after development of severe pacing-induced heart failure (CHF). Before CHF, all agonists produced concentration-dependent increases in tension of both blood vessels. After development of CHF, the responsiveness and sensitivity of the vessels to the alpha 1-agonists and the mixed agonists were significantly increased as compared with control. The maximum responses to BHT 920 and BHT 933 remained unaltered after CHF, but both vessels showed decreased sensitivity to BHT 920. Before CHF, the rank order of potency with respect to norepinephrine (NE) for the dorsal pedal artery was as follows: NE greater than epinephrine greater than methoxamine greater than BHT 933 greater than BHT 920, and for the saphenous vein was epinephrine greater than NE greater than BHT 933 greater than methoxamine greater than BHT 920. At peak CHF, the rank order of potency for the artery was epinephrine greater than NE greater than methoxamine greater than BHT 933 greater than BHT 920, whereas in the vein BHT 920 was approximately 80 times less potent than NE (as compared with being only five times less potent before CHF). Prazosin was a potent, competitive antagonist (pA2 values of 9.2 and 9.0 for the artery and the vein) of methoxamine-induced contractions before development of CHF. Prazosin had a 10-fold lower potency against epinephrine-induced contractions in the dorsal pedal artery, whereas it was not competitive against epinephrine in the saphenous vein. Against the selective alpha 2-agonists, prazosin either showed no antagonism or was not competitive. After CHF, prazosin was non competitive against all agonists tested. Yohimbine was a potent, competitive antagonist against BHT 920 both before and at CHF. Yohimbine had intermediate antagonism against epinephrine and produced no antagonism of methoxamine-induced contractions. We conclude that increased reactivity and sensitivity of the peripheral vasculature to alpha 1-agonists occurs at CHF.


Chronic kidney disease in long duration type 1 diabetes lasting more than 50 years.
There is evidence that microalbuminuria and overt nephropathy may progress more slowly in long duration (> 20 years) type 1 diabetes (T1DM). To explore this further, we examined the characteristics of chronic kidney disease (CKD) in a large cohort of long duration T1DM in the United Kingdom (UK). We studied the UK 'Golden Years' cohort--a group of 400 patients from various parts of the UK with T1DM > 50 years duration. Demographic and clinical information were obtained. HbA(1c), lipids, creatinine and urinary albumin-creatinine ratio (ACR) were measured. Microalbuminuria was defined as 2.5-25.0 mg/mmol for males and 3.5-25.0 mg/mmol for females; macroalbuminuria was defined as an ACR > 25.0 mg/mmol for both sexes. Mean age was 69 years and duration of diabetes 55 years. Nine percent had macroalbuminuria and 27% microalbuminuria. No patient had stage 5 CKD. Microalbuminuria was associated significantly with increased diabetes duration (p = 0.02), male sex (p = 0.02), smoking (p = 0.002), higher HbA(1c) (p < 0.0001), raised triglycerides (p = 0.04), and peripheral vascular disease (PVD) (p < 0.0001). Macroalbuminuria had significant associations with smoking (p = 0.02), raised triglycerides (p = 0.01), raised creatinine (p = 0.02), PVD (p = 0.01) and hypertension (p = 0.01). We conclude that microalbuminuria and CKD are common, even at long duration (> 50 years) of T1DM, and have similar characteristics and associations as they do with shorter disease duration. There is a striking absence, however, of stage 5 CKD, but selection bias may be an important confounder since patients with advanced disease may have not survived.


The distribution of myosin heavy chain isoforms among rat extraocular muscle fiber types.
To determine the distribution of myosin heavy chain isoforms in each extraocular muscle (EOM) fiber type. Serial sections of adult rat EOMs were stained with isoform-specific monoclonal antibodies against an array of myosin heavy chains. Immunofluorescent antibody staining of whole adult rat EOMs, examined by confocal microscopy, demonstrated the longitudinal variations of isoforms along individual fibers. Each global fiber type reacted predominantly with a single isoform-specific antibody and showed no longitudinal variation. Two major orbital fibers were defined, and both contained multiple myosin heavy chains. Both orbital singly and multiply innervated fibers stained proximal and distal to the neuromuscular junction with antibody to embryonic myosin heavy chain, but this isoform was sharply and completely excluded from the domain of the neuromuscular junction. Orbital singly innervated fibers also contained the EOM-specific isoform at the neuromuscular junction. Orbital multiply innervated fibers did not contain the EOM-specific isoform, but additionally contained a slow isoform along their entire length. Adult rat EOMs show unique fiber types with arrangements of myosin heavy chain isoforms not seen in other skeletal muscles. Moreover, unique cellular mechanisms must exist to target each isoform to its proper domain along individual orbital fibers.


Human T-cell lymphotropic virus type 1 open reading frame II-encoded p30II is required for in vivo replication: evidence of in vivo reversion.
Human T-cell lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma and exhibits high genetic stability in vivo. HTLV-1 contains four open reading frames (ORFs) in its pX region. ORF II encodes two proteins, p30(II) and p13(II), both of which are incompletely characterized. p30(II) localizes to the nucleus or nucleolus and has distant homology to the transcription factors Oct-1, Pit-1, and POU-M1. In vitro studies have demonstrated that at low concentrations, p30(II) differentially regulates cellular and viral promoters through an interaction with CREB binding protein/p300. To determine the in vivo significance of p30(II), we inoculated rabbits with cell lines expressing either a wild-type clone of HTLV-1 (ACH.1) or a clone containing a mutation in ORF II, which eliminated wild-type p30(II) expression (ACH.30.1). ACH.1-inoculated rabbits maintained higher HTLV-1-specific antibody titers than ACH.30.1-inoculated rabbits, and all ACH.1-inoculated rabbits were seropositive for HTLV-1, whereas only two of six ACH.30.1-inoculated rabbits were seropositive. Provirus could be consistently PCR amplified from peripheral blood mononuclear cell (PBMC) DNA in all ACH.1-inoculated rabbits but in only three of six ACH.30.1-inoculated rabbits. Quantitative competitive PCR indicated higher PBMC proviral loads in ACH.1-inoculated rabbits. Interestingly, sequencing of ORF II from PBMC of provirus-positive ACH.30.1-inoculated rabbits revealed a reversion to wild-type sequence with evidence of early coexistence of mutant and wild-type sequence. Our data provide evidence that HTLV-1 must maintain its key accessory genes to survive in vivo and that in vivo pressures select for maintenance of wild-type ORF II gene products during the early course of infection.


Sulfonylurea agents exhibit peroxisome proliferator-activated receptor gamma agonistic activity.
Sulfonylurea (SU) agents, including glimepiride and glibenclamide, are the most widely used oral hypoglycemic drugs, which stimulate insulin secretion primarily by binding to the SU receptor on the plasma membrane of pancreatic beta-cells. Thiazolidinediones, such as pioglitazone and rosiglitazone, are other hypoglycemic agents that effectively improve peripheral insulin resistance through activation of peroxisome proliferator-activated receptor gamma (PPARgamma). In the present study, we found that glimepiride specifically induced the transcriptional activity of PPARgamma in luciferase reporter assays. Glimepiride enhanced the recruitment of coactivator DRIP205 and dissociation of corepressors such as nuclear receptor corepressor and silencing mediator for retinoid and thyroid hormone receptors. In addition, glimepride directly bound to PPARgamma in a manner competitive to rosiglitazone, which is a proven ligand for PPARgamma. Furthermore, in 3T3-L1 adipocytes, glimepiride stimulated the transcriptional activity of the gene promoter containing PPAR-responsive element and altered mRNA levels of PPARgamma target genes including aP2, leptin, and adiponectin. Finally, glimepiride induced adipose differentiation in 3T3-F442A cells, which was known to differentiate into adipocytes in a PPARgamma-dependent manner. Most effects observed with glimepiride were also seen with glibenclamide. These data strongly suggest that glimepiride and glibenclamide, both of which belong to SU agents, should have PPARgamma agonist activity, whose potencies were 16-25% of the maximum level achieved by pioglitazone. Our observation that glimepiride and glibenclamide could act not only on SU receptor but also on PPARgamma may give an important clue to the development of novel antidiabetic drugs, which can enhance both insulin secretion from pancreatic beta-cells and peripheral insulin sensitivity.


Bicycle helmet use patterns among children.
To describe and evaluate the helmet use patterns of children younger than 15 years of age in the United States. A national telephone survey of bicycle riders was conducted by means of the Mitofsky-Waksberg method of random-digit dialing, a survey method intended to give all telephone numbers in the continental United States an equal probability of selection. Based on information collected in the survey, a logistic regression model was used to determine and quantify the factors associated with helmet use. Information was collected on the bicycle and helmet use patterns of a national sample of 399 children younger than 15 years of age who rode bicycles during the year preceding the survey. This sample projects to the approximately 26.4 million children who are estimated to have ridden bicycles in 1991. About 26% of all child riders owned or had the use of bicycle helmets, and about 15% were reported to have used their helmets all or more than half of the time when riding. Information is provided on the reasons the children did or did not wear helmets. The logistic regression analysis shows that helmet use by children is systematically related to their personal characteristics (e.g., age and whether they had previously had bicycle-related accidents requiring medical attention), riding patterns (e.g., riding surface), and household demographic characteristics (e.g., geographic location and whether household members had attended college). Helmet use rates among children remain low. Less than one fifth of the children who rode bicycles wore helmets all or more than half of the time in 1991. However, based on comparisons with earlier studies, the results of the analysis suggest that helmet use rates have been rising.


Isolation by distance in a continuous population: reconciliation between spatial autocorrelation analysis and population genetics models.
Analysis of the spatial genetic structure within continuous populations in their natural habitat can reveal acting evolutionary processes. Spatial autocorrelation statistics are often used for this purpose, but their relationships with population genetics models have not been thoroughly established. Moreover, it has been argued that the dependency of these statistics on variation in mutation rates among loci strongly limits their interest for inferential purposes. In the context of an isolation by distance process, we describe relationships between a descriptor of the spatial genetic structure used in empirical studies, Moran's I statistic and population genetics parameters. In particular, we point out that, when Moran's I statistic is used to describe correlation in allele frequencies at the individual level, it provides an estimator of Wright's coefficient of relationship. We also show that the latter parameter, as a descriptor of genetic structure, is not influenced by selfing rate or ploidy level. Under specific finite population models, numerical simulations show that values of Moran's I statistic can be predicted from analytical theory. These simulations are also used to estimate the time taken to approach a structure at equilibrium. Finally, we discuss the conditions under which spatial autocorrelation statistics are little influenced by variation in mutation rates, so that they could be used to estimate gene dispersal parameters.


A Case of Brainstem Anesthesia after Retrobulbar Block for Globe Rupture Repair.
To present a rare case of brainstem anesthesia from retrobulbar block and discuss evidence-based methods for reducing the incidence of this complication. A 72-year-old female, was given a retrobulbar block of 5 mL of bupivacaine 0.5% for postoperative pain management, after a globe rupture repair under general anesthesia. Prior to injection, the patient was breathing spontaneously via the anesthesia machine circuit and had not received any additional narcotics/muscle relaxants for 2.5 hr (with full recovery of neuromuscular blocking agent after anesthetic reversal). Over 7 min, however, there was a steady increase in ETCO2 and the patient became apneic, consistent with brainstem anesthesia. She remained intubated and was transported to the postanesthesia care unit for prolonged monitoring, with eventual extubation. Discussion. Brainstem anesthesia is an important complication to recognize as it can lead to apnea and death. The judicious use of anesthetic volume, shorter needle tips, and mixed formulations can help reduce the chance of brainstem anesthesia. Observation of the contralateral eye 5-10 minutes after injection for pupillary dilation, and prior to surgical draping, can help identify early CNS involvement.


Replication of association between ELAVL4 and Parkinson disease: the GenePD study.
Genetic variants in embryonic lethal, abnormal vision, Drosophila-like 4 (ELAVL4) have been reported to be associated with onset age of Parkinson disease (PD) or risk for PD affection in Caucasian populations. In the current study we genotyped three single nucleotide polymorphisms in ELAVL4 in a Caucasian study sample consisting of 712 PD patients and 312 unrelated controls from the GenePD study. The minor allele of rs967582 was associated with increased risk of PD (odds ratio = 1.46, nominal P value = 0.011) in the GenePD population. The minor allele of rs967582 was also the risk allele for PD affection or earlier onset age in the previously studied populations. This replication of association with rs967582 in a third cohort further implicates ELAVL4 as a PD susceptibility gene.


Evaluation of age and sex differences in locomotion and catalepsy during repeated administration of haloperidol and clozapine in adolescent and adult rats.
Adolescence is associated with characteristic behavioral patterns as well as with substantial neuronal pruning and re-organization of the brain. Recent research has determined that the effects of various centrally active drugs differ in adolescents and adults. This study examined the motor effects of two prototypic antipsychotics in adult [>postnatal day 70 (PN70)] and adolescent (PN30-PN39) rats. Rats were injected daily with saline, 0.3 mg/kg haloperidol, or 10 mg/kg clozapine for 10 days and activity and catalepsy were measured. Adolescents of both sexes were less sensitive to the cataleptic effects of haloperidol than were adults. Male adolescents were also less sensitive to the cataleptic effects of clozapine, although this difference was transitory. In contrast, female adults showed decreased sensitivity to clozapine's effects, differing from all other groups. These results suggest that adolescents of both sexes may be less sensitive to the extrapyramidal motor effects of haloperidol. Translational implications of the clozapine results are less clear; however, results suggest that developmental differences in neurochemical systems affected by clozapine that are also related to motor behavior may play a role. These results also emphasize the importance of age and sex as determinants of the pharmacological effects of these antipsychotics.


Laser Flare Photometry: A Useful Tool for Monitoring Patients with Juvenile Idiopathic Arthritis-associated Uveitis.
We evaluated laser flare photometry (LFP) values in patients with juvenile idiopathic arthritis (JIA)-associated uveitis. Retrospective study. A decrease of the LFP value between baseline visit and 1 month after anti-inflammatory treatment intensification allowed us to define two groups of patients: group 1 (decreased LFP value ≥50%) and group 2 (<50%). We evaluated the prevalence of vision-threatening complications in both groups. Fifty-four patients (87 eyes) were followed for 9.9 ± 5 years. Group 1 eyes (n = 54) had significantly fewer ocular complications than group 2 eyes (n = 33) at both 5 years visit (p = .03) and final visit (p = .047). At the final visit, group 2 eyes had significantly more band keratopathy, trabeculectomy, cataract surgery, glaucoma and papille edema. Group 1 eyes kept a better visual acuity (p < .0001). The decrease of LFP values ≥50% of the initial value 1 month after treatment intensification is a good early prognostic factor.


The effectiveness of self-assessment on the identification of learner needs, learner activity, and impact on clinical practice: BEME Guide no. 10.
Health professionals are increasingly expected to identify their own learning needs through a process of ongoing self-assessment. Self-assessment is integral to many appraisal systems and has been espoused as an important aspect of personal professional behaviour by several regulatory bodies and those developing learning outcomes for clinical students. In this review we considered the evidence base on self-assessment since Gordon's comprehensive review in 1991. The overall aim of the present review was to determine whether specific methods of self-assessment lead to change in learning behaviour or clinical practice. Specific objectives sought evidence for effectiveness of self-assessment interventions to: a. improve perception of learning needs; b. promote change in learning activity; c. improve clinical practice; d. improve patient outcomes. The methods for this review were developed and refined in a series of workshops with input from an expert BEME systematic reviewer, and followed BEME guidance. Databases searched included Medline, CINAHL, BNI, Embase, EBM Collection, Psychlit, HMIC, ERIC, BEI, TIMElit and RDRB. Papers addressing self-assessment in all professions in clinical practice were included, covering under- and post-graduate education, with outcomes classified using an extended version of Kirkpatrick's hierarchy. In addition we included outcome measures of accuracy of self-assessment and factors influencing it. 5,798 papers were retrieved, 194 abstracts were identified as potentially relevant and 103 papers coded independently by pairs using an electronic coding sheet adapted from the standard BEME form. This total included 12 papers identified by hand-searches, grey literature, cited references and updating. The identification of a further 12 papers during the writing-up process resulted in a total of 77 papers for final analysis. Although a large number of papers resulted from our original search only a small proportion of these were of sufficient academic rigour to be included in our review. The majority of these focused on judging the accuracy of self-assessment against some external standard, which raises questions about assumed reliability and validity of this 'gold standard'. No papers were found which satisfied Kirkpatrick's hierarchy above level 2, or which looked at the association between self-assessment and resulting changes in either clinical practice or patient outcomes. Thus our review was largely unable to answer the specific research questions and provide a solid evidence base for effective self-assessment. Despite this, there was some evidence that the accuracy of self-assessment can be enhanced by feedback, particularly video and verbal, and by providing explicit assessment criteria and benchmarking guidance. There was also some evidence that the least competent are also the least able to self-assess accurately. Our review recommends that these areas merit future systematic research to further our understanding of self-assessment. As in other BEME reviews, the methodological issues emerging from this review indicate a need for more rigorous study designs. In addition, it highlights the need to consider the potential for combining qualitative and quantitative data to further our understanding of how self-assessment can improve learning and professional clinical practice.


Antibody response to Haemophilus influenzae type-b conjugate vaccine in children and young adults with congenital asplenia or after undergoing splenectomy.
Absence of the spleen constitutes a risk of infection caused by encapsulated bacteria. The aim of our study was to determine the immune response to Haemophilus influenzae type-b (Hib) conjugate vaccine (HibCV) in asplenic individuals, considering the cause of asplenia, the age when splenectomy was carried out, and previous Hib vaccinations. Twenty asplenic patients, aged five to 25 years, were immunized with a single dose of HibCV. The specific antibody concentrations against HibCV were measured by enzyme-linked immunosorbent assay. Before vaccinations, the geometric mean antibody concentration (GMC) had an average value of 3.21 μg/ml and was comparable for all of the patients, regardless of the causes of asplenia. After vaccinations, the GMC was significantly higher, with an average of 6.78 μg/ml. Further, 4.5 years after vaccinations, the GMC was comparable to that of previously unvaccinated children. Moreover, 17/20 patients had GMC ≥ 1.0 μg/ml, which included all of the children with congenital asplenia, children splenectomized before the age of six years, and only 57% of children splenectomized after that age. HibCV gives asplenic patients long-term protection. Hence, HibCV should be administered regardless of previous vaccinations and time from splenectomy, even if antibody evaluation is not available.


Assessing Readiness to Provide Comprehensive Abortion Care in the Democratic Republic of the Congo After Passage of the Maputo Protocol.
The Democratic Republic of the Congo (DRC) decriminalized abortion under certain circumstances in 2018 through the Maputo Protocol. However, little is known about the readiness of the country's health facilities to provide comprehensive abortion care. Data on 1,380 health facilities from the 2017-2018 DRC Service Provision Assessment (SPA) inventory survey were used to assess readiness to provide abortion care in four domains: termination of pregnancy, basic treatment of postabortion complications, comprehensive treatment of postabortion complications and postabortion contraceptive care. Analyses used a modified application of the emergency obstetric care signal function approach; criteria for readiness were based on World Health Organization guidelines. Thirty-one percent of DRC facilities met the criteria for readiness to provide abortions. The proportion of facilities classified as ready was higher among urban facilities than rural ones (50% vs. 26%), and among hospitals than health centers or reference health centers (72% vs. 25% and 45%, respectively). Few facilities were ready to provide either basic or comprehensive treatment of postabortion complications (4% and 1%); readiness to provide these services was greatest among hospitals (14% and 11%). Only a third of facilities displayed readiness to provide postabortion contraceptive care. Inadequate supplies of medication (e.g., misoprostol, antibiotics, contraceptives) and equipment were the greatest barrier to readiness. Most DRC facilities were not ready to provide comprehensive abortion care. Improving supplies of vital health commodities will improve readiness, and has the potential to reduce the prevalence of unplanned pregnancies and future demand for abortions.


Light-dependent production of dioxygen in photosynthesis.
Oxygen, that supports all aerobic life, is abundant in the atmosphere because of its constant regeneration by photosynthetic water oxidation, which is catalyzed by a Mn₄CaO₅ cluster in photosystem II (PS II), a multi subunit membrane protein complex. X-ray and other spectroscopy studies of the electronic and geometric structure of the Mn₄CaO₅ cluster as it advances through the intermediate states have been important for understanding the mechanism of water oxidation. The results and interpretations, especially from X-ray spectroscopy studies, regarding the geometric and electronic structure and the changes as the system proceeds through the catalytic cycle will be summarized in this review. This review will also include newer methodologies in time-resolved X-ray diffraction and spectroscopy that have become available since the commissioning of the X-ray free electron laser (XFEL) and are being applied to study the oxygen-evolving complex (OEC). The femtosecond X-ray pulses of the XFEL allows us to outrun X-ray damage at room temperature, and the time-evolution of the photo-induced reaction can be probed using a visible laser-pump followed by the X-ray-probe pulse. XFELs can be used to simultaneously determine the light-induced protein dynamics using crystallography and the local chemistry that occurs at the catalytic center using X-ray spectroscopy under functional conditions. Membrane inlet mass spectrometry has been important for providing direct information about the exchange of substrate water molecules, which has a direct bearing on the mechanism of water oxidation. Moreover, it has been indispensable for the time-resolved X-ray diffraction and spectroscopy studies and will be briefly reviewed in this chapter. Given the role of PS II in maintaining life in the biosphere and the future vision of a renewable energy economy, understanding the structure and mechanism of the photosynthetic water oxidation catalyst is an important goal for the future.


Tuning metal oxide defect chemistry by thermochemical quenching.
The low-temperature defect chemistry of monoclinic and tetragonal ZrO2 and hematite Fe2O3 is studied in the non-equilibrium state of thermochemical quenching; that is, rapid cooling starting from a certain high temperature and oxygen chemical potential. This non-equilibrium state is of great interest because many metal oxides are used at low temperatures below their growth temperatures. This paper addresses the importance of considering this non-equilibrium state rather than applying equilibrium thermodynamics as commonly used when studying point defects from first principles. Based on point defect formation energies calculated previously using density functional theory, we compare the type of dominant defects at equilibrium to those at a quenched state originating from a certain initial growth temperature and oxygen partial pressure. The comparison is facilitated by casting the dominant defects in a dominance diagram on the temperature - oxygen partial pressure plane. We consider two scenarios to model the quenched state. In the first, only electronic defects equilibrate whereas all ionic defects are frozen. Whereas, in the second, electronic defects and interstitials are allowed to equilibrate under the assumption of mobile interstitials at low temperatures. We find that new ionic charge compensation modes can appear on the dominance diagram after quenching. Additionally, purely ionic charge compensation modes consisting of vacancies and/or interstitials expand in the dominance diagram at the expense of purely electronic compensation modes. For the ZrO2 phases, we argue that scenario 2 is more realistic and leads to difficulty in achieving n-type doping by thermochemical quenching. For Fe2O3, and regardless of the quenching scenario, iron vacancies occupy a wider zone of domination, which limits the performance of this oxide as a water splitting photoanode. Our study shows that by controlling the growth thermochemical conditions, it is possible to tune the Fermi level of oxides over a considerable range within the band gap by quenching. This provides an extra tool to tune the electric conductivity of metal oxides beyond traditional extrinsic doping. This work indicates that non-equilibrium thermodynamic analysis is necessary to understand and control defect chemistry at low temperatures.


Carbofuran toxicosis in cattle: case history and analytical method.
Thirteen head of crossbred Brahman cattle were exposed to carbofuran which had been mixed with rice to control blackbirds. Three animals died within 20 minutes after eating the contaminated grain, and the other 10 exhibited clinical signs associated with carbamate toxicosis. The 4 most severely affected animals were treated with a subtherapeutic dose of atropine sulfate; they did not respond and subsequently died. The remaining 6 recovered. Samples of rumen contents from the animals that died contained carbofuran concentrations ranging from 2 to 51 mg/kg.


Demographic factors, personal life experiences, and types of intimate partner violence.
This study examines how demographic factors (i.e., age, employment, or income) and personal life experiences (i.e., witnessing intimate partner violence [IPV] in childhood, number of violent partners, violence perpetration, or stressful life events) are related to IPV frequency across types of IPV (i.e., physical assault, psychological aggression, or sexual coercion) in a racially diverse sample. Participants included 126 women recruited from community organizations in the Mid-South, United States who experienced IPV in the past 6 months (Mage = 32.90, SD = 6.82). The majority of the sample self-identified as Black or African American (66%) and reported an annual income below $20,000 (73%). Three linear regressions were run to assess relations between age, employment status, annual income, witnessing IPV in childhood, number of violent partners, violence perpetration, and stressful life events for each type of IPV; all three models also accounted for the other forms of IPV. Psychological aggression was significantly associated with a higher income as well as more frequent physical assault and sexual coercion. Physical assault was linked with younger age, lower income, not witnessing IPV in childhood, IPV perpetration, more psychological aggression, and more sexual coercion. Sexual coercion was associated with more stressful life events, having multiple violent partners, higher psychological aggression, and higher physical assault. Results suggest that interventions should target mutable demographic factors and screen for personal life events to reduce IPV frequency and revictimization across types of IPV. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


North American medical schools' experience with and approaches to the needs of students with physical and sensory disabilities.
To determine the nature and frequency of impairments and related underlying conditions of medical students with physical and sensory disabilities (PSDs), and to assess medical schools' use of relevant publications in setting admission criteria and developing appropriate accommodations. A 25-item survey addressed schools' experiences with students known to have PSDs and their related policies and practices. The survey instrument was directed to student affairs deans at all 163 accredited American and Canadian medical schools. The authors limited the survey to consideration of PSDs, excluding psychiatric, cognitive, and learning disabilities. Eighty-six schools (52.8%) responded, representing an estimated 83,327 students enrolled between 2001 and 2010. Of these students, 0.56% had PSDs at matriculation and 0.42% at graduation. Although 81% of respondents were familiar with published guidelines for technical standards, 71% used locally derived institutional guidelines for the admission of disabled applicants. The most commonly reported accommodations for students with PSDs included extra time to complete tasks/exams (n = 62), ramps, lifts, or accessible entrances (n = 43), and dictated/audio-recorded lectures (n = 40). All responding schools required students' demonstration of physical examination skills; requirements for other technical skills, with or without accommodations, varied considerably. The matriculation and graduation rates of medical students with PSDs remain low. The most frequent accommodations reported were among those required of any academic or clinical setting by the Americans with Disabilities Act. There is a lack of consensus regarding technical standards for admission, suggesting a need to reexamine this critical issue.


PPLN-based OOK and DQPSK optical grooming by amplitude and phase-signal multiplexing through pump depletion.
We propose and characterize a simple, integrable, and wavelength-preserving scheme able to groom a 40 Gbps (D)QPSK signal with a 20 Gbps OOK one into a 20 Gbaud (60 Gbps) 8-APSK signal. The proposed all-optical scheme is based on the second-order nonlinear signal-depletion effect in a single periodically poled lithium niobate (PPLN) waveguide. Performance of the device, characterized by means of BER measurements, attests error-free operation and a power penalty below 4.1 dB.


Predicting Solubility/Miscibility in Amorphous Dispersions: It Is Time to Move Beyond Regular Solution Theories.
The evolving challenges associated with the development of poorly soluble drug molecules have been met with major advances in drug solubilization. In particular, amorphous solid dispersion technology is becoming an increasingly important option to enhance oral bioavailability by creating prolonged drug supersaturation to maximize the driving force for intestinal absorption. A primary concern in the development of amorphous solid dispersions is their physical stability, leading to increasing interest in predictive methodologies to assess the propensity for drug crystallization under various storage conditions. For most drug-excipient combinations of pharmaceutical interest, hydrogen bonding is an important factor in determining miscibility, supersaturation potential, and the influence of water uptake during storage and after administration. The vast majority of publications to date have utilized mathematical models based on regular solution theory such as Flory-Huggins theory to predict drug-polymer miscibility, despite the fact that they were never intended to be applied to hydrogen-bonded systems. In this commentary article, regular solution theory is applied to simple hydrogen-bonded alcohol-alkane solutions to explore trends in the Flory-Huggins χ interaction parameter and possible pitfalls in its interpretation. More recent models that explicitly allow for specific interactions merit greater attention.


The critical early proinflammatory events associated with idiopathic pneumonia syndrome in irradiated murine allogeneic recipients are due to donor T cell infusion and potentiated by cyclophosphamide.
We have hypothesized that lung damage occurring in the peri-bone marrow transplant (BMT) period is critical for the subsequent generation of idiopathic pneumonia syndrome (IPS), a major complication following human BMT. The proinflammatory events induced by a common pre-BMT conditioning regimen, cyclophosphamide (Cytoxan(R)) (Cy) and total body irradiation, were analyzed in a murine BMT model. Electron microscopy indicated that Cy exacerbated irradiation-induced epithelial cell injury as early as day 3 after BMT. Allogenicity was an important contributing factor to lung injury as measured by lung wet and dry weights and decreased specific lung compliance. The most significant pulmonary dysfunction was seen in mice receiving both allogeneic T cells and Cy conditioning. IPS was associated with an influx of T cells, macrophages, and neutrophils early post-BMT. Hydroxyproline levels were not increased, indicating that the injury was not fibrotic early post-BMT. As early as 2 h after chemoradiation, host macrophages increased in number in the lung parenchyma. Continued increases in macrophages occurred if splenic T cells were administered with the donor graft. The expression of costimulatory B7 molecules correlated with macrophage numbers. Frequencies of cells expressing mRNA for the inflammatory proteins TNF-alpha, IL-1beta, and TGFbeta were increased. Cy accelerated the upregulation of TGFbeta and increase in host macrophages. The exacerbation of macrophage activation and severity of IPS was dependent on allogeneic T cells, implicating immune-mediated mechanisms as critical to the outcome of IPS. This demonstration of early injury after BMT indicates the need for very early therapeutic intervention before lung damage becomes profound and irreversible.


[Bilateral habitual fibula head dislocation].
Dislocation of the fibular head is rare. In most of the cases a trauma caused by sports activity, sometimes associated with a tibia fracture, is described. Only a few publications exist about habitual dislocation of the fibular head without history of trauma. This article reports a case of bilateral habitual anterolateral dislocation of the fibular head in a 17-year-old female. There was no information about a neurological or other disease and no sign of generalized ligamentous laxity. Because of marked symptoms with severe pain after each sensation of dislocation which appeared several times a day, the patient was treated by using a part of the biceps tendon for fixation of the reduced fibular head.


Baicalein: A review of its anti-cancer effects and mechanisms in Hepatocellular Carcinoma.
Baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one) is a flavonoid compound derived from the roots of Scutellaria baicalensis. It has historically been used in anti-oxidant, anti-virus, anti-bacteria, anti-inflammatory and anti-allergic therapies. Recently, baicalein has been found to possess anti-cancer activities via its effect on a variety of biological processes involving cell proliferation, metastasis, apoptosis and autophagy and so on. Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and high fatality rate worldwide. Noteworthy, treatment protocols of HCC include conventional resection and chemotherapy, all of which may result in enormous mortality rate. Therefore, there is extreme interest to find a relatively non-toxic medicine which may reduce side effects without compromising therapeutic efficacy. Many studies have showed that baicalein is one such potential candidate. In this review, we summarized the various anti-cancer effects of baicalein on HCC and their underlying molecular mechanisms based on in vitro and in vivo experimental evidences discovered so far. Taken together, baicalein may be developed as a potential, novel anticancer drug for HCC treatment.