Predictors of Sustained Prescription Opioid Use After Admission for Trauma in Adolescents.
The study objectives are to describe the longitudinal trajectory of prescription opioid use among adolescents requiring a trauma admission and then identify predictors of sustained opioid use. Randomly sampled adolescents (12-18 years) admitted to a Level I trauma center were surveyed. Follow-up assessments were obtained at 2, 5, and 12 months. Self-reported prescription opioid use, defined as "taking an opioid prescribed by a physician," was obtained at baseline and every follow-up time point. At the baseline interview, validated mental health measures and pain scales were obtained as well as preinjury substance use. A fixed-effects mixed Poisson regression analysis was performed to predict prescription opioid use over time. A total of 120 adolescents (mean age 15.5 years [1.9 standard deviation], 75% male) completed the baseline interview with 98% follow-up at 12 months. At baseline, 7% of adolescents reported prescription opioid use before their trauma, with rates of prescription opioid use of 52% at 2 months, 13.3% at 5 months, and 12.5% at 12 months after discharge. After adjusting for demographic characteristics and injury severity score, those with sustained prescription opioid use were more likely to report preinjury marijuana use and higher baseline pain scores. Approximately one in eight adolescents (12.5%) was using prescription opioids 12 months after injury hospitalization. Readily identifiable risk factors predicted sustained prescription opioid use, including preinjury marijuana use and baseline pain score. Screening for substance use including marijuana at the time of injury could help identify patients at risk for both substance use problems and sustained prescription opioid use.


Recent Advances in Computer-aided Antiviral Drug Design Targeting HIV-1 Integrase and Reverse Transcriptase Associated Ribonuclease H.
Acquired immunodeficiency syndrome (AIDS) has been a chronic, life-threatening disease for a long time. Though, a broad range of antiretroviral drug regimens is applicable for the successful suppression of virus replication in human immunodeficiency virus type 1 (HIV-1) infected people. The mutation-induced drug resistance problems during the treatment of AIDS forced people to continuously look for new antiviral agents. HIV-1 integrase (IN) and reverse transcriptase associated ribonuclease (RT-RNase H), two pivotal enzymes in HIV-1 replication progress, have gained popularity as druggable targets for designing novel HIV-1 antiviral drugs. During the development of HIV-1 IN and/or RT-RNase H inhibitors, computer-aided drug design (CADD), including homology modeling, pharmacophore, docking, molecular dynamics (MD) simulation and binding free energy calculation, represent a significant tool to accelerate the discovery of new drug candidates and reduce costs in antiviral drug development. In this review, we summarized the recent advances in the design of single- and dual-target inhibitors against HIV-1 IN or/and RT-RNase H as well as the prediction of mutation-induced drug resistance based on computational methods. We highlighted the results of the reported literatures and proposed some perspectives on the design of novel and more effective antiviral drugs in the future.


[Brain metabolism alterations in patients with anorexia nervosa observed in 1H-MRS].
The causes of metabolic brain changes in patients with anorexia nervosa are still not fully explained. The purpose of this study was to use the 1H-MRS method in investigating metabolic changes in the brain of patients with anorexia nervosa. We studied 10 patients for visible alternations in brain metabolism and compared the results to healthy controls. 1H-MRS was acquired by the method of single voxels in white and grey matter. Proton MRS was performed after image guided localization using stimulated echo acquisition mode (STEAM) sequence with a short echo time of 20 ms. For data evaluation we used standard Siemens software and the additional PC. Choosing of the MRS sequences was related with particular interest in metabolites of short time echo: myoinositol and lipids. Besides this we evaluated peaks of: N-acetylaspartate (NAN), creatine (Cr) and choline (Cho). The results show significant differences in the levels of metabolites connected with fatty metabolism. In white matter we observed the reduction of lip-peak. The data was evaluated approximately and presented as lip:Cr. We did not observe any differences in other metabolites. As far as we know similar results had been reported and our study confirmed significant disorders in metabolism of these chemicals in patients with anorexia nervosa.


Brain activity during driving with distraction: an immersive fMRI study.
Non-invasive measurements of brain activity have an important role to play in understanding driving ability. The current study aimed to identify the neural underpinnings of human driving behavior by visualizing the areas of the brain involved in driving under different levels of demand, such as driving while distracted or making left turns at busy intersections. To capture brain activity during driving, we placed a driving simulator with a fully functional steering wheel and pedals in a 3.0 Tesla functional magnetic resonance imaging (fMRI) system. To identify the brain areas involved while performing different real-world driving maneuvers, participants completed tasks ranging from simple (right turns) to more complex (left turns at busy intersections). To assess the effects of driving while distracted, participants were asked to perform an auditory task while driving analogous to speaking on a hands-free device and driving. A widely distributed brain network was identified, especially when making left turns at busy intersections compared to more simple driving tasks. During distracted driving, brain activation shifted dramatically from the posterior, visual and spatial areas to the prefrontal cortex. Our findings suggest that the distracted brain sacrificed areas in the posterior brain important for visual attention and alertness to recruit enough brain resources to perform a secondary, cognitive task. The present findings offer important new insights into the scientific understanding of the neuro-cognitive mechanisms of driving behavior and lay down an important foundation for future clinical research.


Is Nicotine Replacement a Safe Alternative to Smoking in Plastic Surgery Patients?
E-cigarettes, nicotine transdermal patches, and nicotine chewing gum are occasionally used as cigarette replacements by patients, but it is unknown if their use is a safe alternative to smoking in the perioperative period. All patients undergoing major surgery at a single outpatient ambulatory surgery center for a 5-year period were tested for urine cotinine, a nicotine metabolite, the day of surgery. Patients were divided into 4 groups: never smoked (group A), quit smoking with negative urine test (group B), continued to smoke (group C), and quit smoking with positive urine test (group D). Statistical significance of complications among groups was tested using right tailed chi-square test and point biserial correlation coefficient calculations. To control for confounding factors, age and BMI of each group were compared using unequal sample size and variance t tests. Four hundred seventy patients were included in the study. Patient count in each group was group A n = 380, group B n = 48, group C n = 32, and group D n = 10. Complication frequency was as follows D > C > A > B. Statistically significant differences were observed between D + C (cotinine positive) and A + B (cotinine negative) P = 0.0001 and between D (nicotine replacement) and B (nicotine abstinence) P = 0.00026. There was neither statistical difference between groups A and B, nor C and D. Nicotine replacement carries similar risks as continued smoking and is not as safe as abstinence in the perioperative period in plastic surgery patients. Importantly, patients who stopped smoking for the surgery had equivalent risk for postoperative complications as patients who had never smoked.


Cyclosporin and plasma exchange in thrombotic thrombocytopenic purpura: long-term follow-up with serial analysis of ADAMTS13 activity.
We hypothesized that cyclosporin (CSA) as adjunct to plasma exchange (PE) improves the efficacy of PE in idiopathic thrombotic thrombocytopenic purpura (TTP) via suppression of the antibody inhibitor of ADAMTS13. Our preliminary findings with CSA and PE as the upfront treatment of TTP suggested that the addition of CSA to PE significantly decreased the exacerbation (disease recurrence within 30 d of the last PE) rates compared to a cohort that received corticosteroids and PE as their upfront therapy of TTP. We present an updated analysis with long-term follow-up of 18 patients with idiopathic TTP treated with concurrent CSA and PE with analysis of serial measurements of ADAMTS13 activity, antigen and inhibitor concentration in the context of clinical outcome data. Overall, 16/18 (89%) patients achieved remission, similar to historical remission rates in idiopathic TTP with PE with only one patient suffering an exacerbation. Clinical responses correlated with improvements in ADAMTS13 activity and suppression of the antibody inhibitor of ADAMTS13. These data suggest that the efficacy of CSA is at least in part related to its suppression of the antibody inhibitor of ADAMTS13 and a subsequent improvement in ADAMTS13 activity and antigen.


Exercise to Lower Postprandial Lipemia: Why, When, What and How.
We review recent findings on the ability of exercise to lower postprandial lipemia (PPL). Specifically, we answer why exercise is important in lowering PPL, when it is most effective to exercise to achieve this, what the preferred exercise is and how exercise reduces PPL. Most findings confirm the power of exercise to lower PPL, which is an independent risk factor for cardiovascular disease. Exercise is most effective when performed on the day preceding a high- or moderate-fat meal. This effect lasts up to approximately two days; therefore, one should exercise frequently to maintain this benefit. However, the time of exercise relative to a meal is not that important in real-life conditions, since one consumes several meals during the day; thus, an exercise bout will inevitably exert its lowering effect on PPL in one or more of the subsequent meals. Although moderate-intensity continuous exercise, high-intensity intermittent exercise, resistance exercise and accumulation of short bouts of exercise throughout the day are all effective in lowering PPL, submaximal, high-volume interval exercise seems to be superior, provided it is tolerable. Finally, exercise reduces PPL by both lowering the rate of appearance and increasing the clearance of triacylglycerol-rich lipoproteins from the circulation.


[Practical aspects of using silufol sheets to analyze fat-soluble vitamins].
The authors studied the mobility of the fat-soluble vitamins, A, D, K1 and beta-carotene in organic solvents and their mixtures on silufol plates, the influence of the chromatography conditions and the chamber saturation with the solvent vapors on the Rf values of fat-soluble vitamins, as well as the rate of beta-carotene tocopherol (vitamin E) and phylloquinone (vitamin K1) destruction under the effect of the day and ultra-violet light. The data obtained are presented. Phylloquinone and carotene proved to be most destroyed, while tocopherol was more resistant under the same conditions. Silufol plates can be used for the control of the production of vitamins, their analysis in varying biological objects, as well as in biochemistry, medicine and pharmaceutics.


Use of IC tags in short-term carcinogenicity study on CB6F1 TGrasH2 mice.
We studied the effect of IC tags, subcutaneously implanted animal identification tools, on rasH2 mice. A 26-week short-term carcinogenicity study was performed on a total of 299 mice including 75 male and female rasH2 mice each, and 74 male and 75 female non-Tg mice from the same litter as the rasH2 mice divided into a non-IC tag group, the IC-tag group, acetone group, TPA group and MNU group (all of the animals except for those in the non-IC tag group) had IC tags implanted subcutaneously in their backs. The administration methods of the positive control drugs TPA (2.5 micro g/kg, 3 times/week, percutaneously) and MNU (75 mg/kg, single intraperitoneal injection) were based on the protocol of the ILSI/HESI international collaborative study. The results showed no differences in the tumorigenic incidence and organs developing tumors between the IC tag and non-IC tag groups in both rasH2 and non-Tg mice. In the positive control MNU group, the tumorigenic incidence and organs developing tumors were the same as the background data and no promotion of carcinogenesis was observed. In all IC tag groups including the TPA group and MNU group, a fibrous capsule was formed around the IC tags subcutaneously, but no inflammatory changes or neoplastic changes were observed. From these findings, it was concluded that the IC tag has no effect on a 26-week carcinogenicity test of rasH2 mice under the conditions of the present study.


Accurate Classical Polarization Solution with No Self-Consistent Field Iterations.
We present a new solution for classical polarization that does not require any self-consistent field iterations, the aspect of classical polarization that makes it computationally expensive. The new method builds upon our iEL/SCF Lagrangian scheme that defines a set of auxiliary induced dipoles whose original purpose was to serve as a time-reversible initial guess to the SCF solution of the set of real induced dipoles. In the new iEL/0-SCF approach the auxiliary dipoles now drive the time evolution of the real induced dipoles such that they stay close to the Born-Oppenheimer surface in order to achieve a truly SCF-less method. We show that the iEL/0-SCF exhibits no loss of simulation accuracy when analyzed across bulk water, low to high concentration salt solutions, and small solutes to large proteins in water. In addition, iEL/0-SCF offers significant computational savings over more expensive SCF calculations based on traditional 1 fs time step integration using symplectic integrators and is as fast as reversible reference system propagator algorithms with an outer 2 fs time step.


The rise and fall of dietetics and of nutrition science, 4000 BCE-2000 CE.
To outline the history of dietetics since its beginnings in recorded history, and of nutrition science in its first phase beginning in the mid-nineteenth century and then its second phase in the second half of the twentieth century. Three narrative overviews: of dietetics from its beginnings until after the end of the medieval and then Renaissance periods in Europe; of nutrition science in its first phase from its beginnings in the mid-nineteenth century until the middle of the twentieth century, with reasons for its rise; and of nutrition science in its second phase in the second half of the twentieth century, with reasons for its decline. In its third phase in the twenty-first century, the new nutrition science should regain much of the vision and scope of its preceding disciplines.


Copper(I) cyanide networks: synthesis, structure, and luminescence behavior. Part 2. Piperazine ligands and hexamethylenetetramine.
A variety of photoluminescent, and in some cases thermochromic, metal-organic networks of CuCN were self-assembled in aqueous reactions with amine ligands: (CuCN) 2(Pip) ( 1a), (CuCN) 20(Pip) 7 ( 1b), (CuCN) 7(MePip) 2 ( 2), (CuCN) 2(Me 2Pip) ( 3a), (CuCN) 4(Me 2Pip) ( 3b), (CuCN) 7(EtPip) 2 ( 4), (CuCN) 4(Et 2Pip) ( 5), (CuCN) 3(BzPip) 2 ( 6a), (CuCN) 5(BzPip) 2 ( 6b), (CuCN) 7(BzPip) 2 ( 6c), (CuCN) 4(BzPip) ( 6d), (CuCN) 2(Bz 2Pip) ( 7), (CuCN)(Ph 2CHPip) ( 8a), (CuCN) 2(Ph 2CHPip) ( 8b), (CuCN) 3(HMTA) 2 ( 9a), (CuCN) 5(HMTA) 2 ( 9b), and (CuCN) 5(HMTA) ( 9c) (Pip = piperazine, MePip = N-methylpiperazine, Me 2Pip = N, N'-dimethylpiperazine, EtPip = N-ethylpiperazine, Et 2Pip = N, N'-diethylpiperazine, BzPip = N-benzylpiperazine, Bz 2Pip = N, N'-dibenzylpiperazine, Ph 2CHPip = N-(diphenylmethyl)piperazine, and HMTA = hexamethylenetetramine). New X-ray structures are reported for 1b, 2, 3b, 4, 5, 6a, 6d, 7, 8b, 9b, and 9c. An important structural theme is the formation of (6,3) (CuCN) 2(piperazine) sheets with or without threading of independent CuCN chains. Strong luminescence at ambient temperature is observed for all but complexes 6 and 7. All luminescent compounds show a broad emission band in the blue region at about 450 nm attributable to metal-to-ligand charge transfer behavior based on the large Stokes shift between excitation and emission maxima. 3, 8, and 9 are thermochromic due to an additional lower energy emission band, which is absent at 77 K.


An Innovative, Comprehensive Faculty Recruitment and Development Program at One U.S. Dental School: Early Results.
Dental faculty recruitment and development are critical to replenish and cultivate sufficient and adequately prepared educators to educate future generations of dentists. At Rutgers School of Dental Medicine, the From Practice to Preceptor (FP2P) program, now in the last of its five years of funding from the U.S. Health Resources and Services Administration (HRSA), has an overall aim of recruiting, training, and retaining a diverse and well-prepared dental faculty workforce. The FP2P program introduced novel methods for recruiting and preparing new faculty members since its goal is to help participants transition from being practicing dentists to becoming part- or full-time faculty members. The recruitment and selection process has emphasized reaching community practitioners in general or pediatric dentistry, individuals from underrepresented groups, and those with a passion for teaching. The two-year program with weekly meetings was designed to develop participants' skills to meet the teaching, clinical, and administrative roles of dental faculty. The aims of this study were to determine if the program recruitment methods used would result in participants who were more ethnically and racially diverse than the school's current faculty and to determine if, after training, participants perceived they had increased knowledge, skills, and abilities in specified areas as compared to before training. Participants completed pre- and post-program surveys assessing their perceived level of preparedness in critical competencies for dental faculty. Surveys were completed by 94% of participants in cohorts one through four; 75% (n=15) of cohorts two and three completed both the pre- and post-program surveys, which were used for this analysis. Over 30% of the 35 participants to date were from an underrepresented group. Survey results suggest the participants increased their perceived preparedness in administrative, clinical, and educational competencies. Follow-up is needed to ascertain how many go on to become dental educators and whether they are better prepared to succeed as new faculty compared to nonparticipants.


Synchronization of coverage, benefits, and payment to drive innovation.
More than 35% of Medicare beneficiaries receive care from providers operating under some form of shared savings/risk type of pay-for-performance incentive. Implementation of payment reform without a corresponding change to coverage, benefit, and other payment requirements, however, creates conflicting incentives that may nullify the intended aim of payment reform: to improve health outcomes, while saving costs. If related policies do not evolve to align with payment reform, those entities contracted to receive new bundled payments, such as hospitals or physician groups, will only be able to redesign care to the extent that care meets the myriad of related payment policy requirements. Shifting greater medical management authority from payers to entities managing the payment bundles is a gradual process, as the experience of commercial payers proves. Transitioning the responsibility for modifying coverage, benefit, and payment requirements from CMS to principal accountable bundlers (PABs) will depend on the PAB's degree of financial risk sharing as well as scope of the episode.


Biochemical and ultrastructural studies of proteoheparan sulfates synthesized by PYS-2, a basement membrane-producing cell line.
The mouse teratocarcinoma-derived cell line, PYS-2, has been shown to produce laminin, a basement membrane-specific glycoprotein. In these studies we demonstrate that PYS-2 cells synthesize and secrete into the culture medium a proteoglycan which contains only heparan sulfate as its sulfated polysaccharide side chains, as well as type IV procollagen and laminin. The apparent molecular weights of the proteoglycan and its heparan sulfate side chain were estimated to be 400,000 and 25,000, respectively, by gel chromatography. A proteoheparan sulfate with properties closely similar, if not identical, to those of the proteoglycan in the medium, together with two heparan sulfate single chains of different molecular size, were extracted from the cell layer with 2% SDS in the presence of protease inhibitors. Ultrastructurally, a fine fibrillar intercellular matrix was recognized which contained discrete 100-200 A diameter ruthenium red-positive granules interspersed throughout the filamentous meshwork. The PYS-2 cultures were shown by immunofluorescence to react with antibodies against the heparan sulfate-containing proteoglycan isolated from the mouse EHS sarcoma (Hassell, J. R., P. G. Robey, H. J. Barrach, J. Wilczek, S. I. Rennard, and G. R. Martin. 1980. Proc. Natl. Acad. Sci. U. S. A. 77:4494-4498). Immunoelectron microscopic examination, using the same antibodies, revealed that the proteoheparan sulfate was located not only at the edges but also within the interstices of the matrix. These findings indicate that PYS-2 cells synthesize and secrete a proteoglycan with properties similar to those of basement membrane proteoglycan. These cells may therefore serve as a useful model system for the study of the biosynthesis and structure of basement membranes.


Le interferon mRNA from human fibroblasts.
Human F and Le interferon can be clearly distinguished on the basis of different antigenic properties and host range. After inoculation with Newcastle disease virus (NDV), GM-258 fibroblasts produced Le as well as F interferon; in contrast, only F interferon was detectable after stimulation with poly(I) . poly(C). Polyadenylylated mRNA isolated from fibroblasts induced with poly(I) . poly(C) or NDV was injected into Xenopus laevis oocytes and the interferon activities thus produced were analyzed. Only F interferon production was demonstrable in oocytes injected with mRNA from cells induced with poly(I) . poly(C), whereas both F and Le interferons were made in oocytes injected with mRNA from NDV-induced cultures. The time course of accumulation of F and Le interferon mRNAs in NDV-induced cells corresponded to the kinetics of F and Le interferon synthesis in intact cells. The ratio of F and Le interferons made in oocytes was similar to that observed in intact GM-258 cells. F and Le interferon mRNA activities isolated from GM-258 cells could not be separated by sucrose density gradient centrifugation. However, the profile of F mRNA activity was more heterogeneous and its peak sedimented somewhat more slowly than that of Le interferon mRNA. These results suggest that the varying ratios of F and Le interferon synthesis in different cells after different modes of stimulation are determined at the level of mRNA. The induction mechanisms of F and Le interferon mRNA synthesis appear to be closely related but not identical.


Evidence for model-based computations in the human amygdala during Pavlovian conditioning.
Contemporary computational accounts of instrumental conditioning have emphasized a role for a model-based system in which values are computed with reference to a rich model of the structure of the world, and a model-free system in which values are updated without encoding such structure. Much less studied is the possibility of a similar distinction operating at the level of Pavlovian conditioning. In the present study, we scanned human participants while they participated in a Pavlovian conditioning task with a simple structure while measuring activity in the human amygdala using a high-resolution fMRI protocol. After fitting a model-based algorithm and a variety of model-free algorithms to the fMRI data, we found evidence for the superiority of a model-based algorithm in accounting for activity in the amygdala compared to the model-free counterparts. These findings support an important role for model-based algorithms in describing the processes underpinning Pavlovian conditioning, as well as providing evidence of a role for the human amygdala in model-based inference.


Respiratory activity of the soil from several habitats in the Botanical Garden in Poznań.
The paper presents studies on the respiratory activity of the soil from two habitats of the Botanical Garden: the steppe and the dune. The abundance of bacteria and fungi in the soils was also estimated. Respiration in the rhizosphere soil was found to be more intense than in the non-rhizosphere soil. Our observations have shown that soil respiration depends largely on the abundance of microorganisms. Under various habitat conditions, however, the microorganisms populations are characterized by some peculiarities of their metabolic activities. These manifest themselves in differences in respiratory activity of various soils independent of additional easily available energetic material introduced into the soil.


Correction of backscatter-induced systematic errors in ring laser gyroscopes.
In ring laser gyroscopes, backscatter coupling between the counterpropagating beams leads to systematic errors in measured rotation rates. We show the errors can be derived from the nearly independent optical frequency perturbations of the separate beams. In a process of double backscatter each beam is scattered first into the other beam direction, then rescattered back into itself, giving phase and amplitude perturbations. The analysis proceeds from a purely passive ring cavity, through inclusion of a gain medium and gain saturation. The rotation rate errors may be estimated and corrected from the modulations of the counterpropagating beams. The method is demonstrated with real data.


Chemically functionalized carbon nanotubes.
Since their discovery, carbon nanotubes have attracted the attention of many a scientist around the world. This extraordinary interest stems from their outstanding structural, mechanical, and electronic properties. In fact, apart from being the best and most easily available one-dimensional (1D) model system, carbon nanotubes show strong application potential in electronics, scanning probe microscopy, chemical and biological sensing, reinforced composite materials, and in many more areas. While some of the proposed applications remain still a far-off dream, others are close to technical realization. Recent advances in the development of reliable methods for the chemical functionalization of the nanotubes provide an additional impetus towards extending the scope of their application spectrum. In particular, covalent modification schemes allow persistent alteration of the electronic properties of the tubes, as well as to chemically tailor their surface properties, whereby new functions can be implemented that cannot otherwise be acquired by pristine nanotubes.


DST results in nonpsychotic depressed outpatients.
In two studies using the dexamethasone suppression test (DST) to evaluate the efficacy of newer antidepressants in depressed outpatients, the authors found a DST nonsuppression rate of 13% (11 of 86 patients). Thirty-three of the DST suppressors received an antidepressant and 42 received placebo; the drug-treated group showed a significant therapeutic response. The low rate of DST nonsuppression in these depressed outpatients, a finding consistent with that of other investigators, does not confirm or refute reports that these patients are relatively resistant to placebo in comparison with active medication. The authors recommend that DST results not be used as selection criteria in studies assessing newer therapies for depressed outpatients.


Cooccurrence of Metastatic Papillary Thyroid Carcinoma and Salmonella Induced Neck Abscess in a Cervical Lymph Node.
Cervical lymph node metastasis is common in patients with papillary thyroid carcinoma (PTC). Salmonella species are rarely reported as causative agents in focal infections of the head and neck. The cooccurrence of lymph node metastasis from PTC and a bacterial infection is rare. This report describes a 76-year-old woman with a cervical lymph node metastasis from PTC and Salmonella infection of the same lymph node. The patient presented with painful swelling in her left lateral neck region for 15 days, and neck ultrasonography and computed tomography showed a cystic mass along left levels II-IV. The cystic mass was suspected of being a metastatic lymph node; modified radical neck dissection was performed. Histopathological examination confirmed the presence of PTC in the resected node and laboratory examination of the combined abscess cavity confirmed the presence of Salmonella Typhi. Following antibiotic sensitivity testing of the cultured Salmonella Typhi, she was treated with proper antibiotics. Cystic lesions in lymph nodes with metastatic cancer may indicate the presence of cooccurring bacterial infection. Thus, culturing of specimen can be option to make accurate diagnosis and to provide proper postoperative management.


Inheritance of Polycomb-dependent chromosomal interactions in Drosophila.
Maintenance of cell identity is a complex task that involves multiple layers of regulation, acting at all levels of chromatin packaging, from nucleosomes to folding of chromosomal domains in the cell nucleus. Polycomb-group (PcG) and trithorax-group (trxG) proteins maintain memory of chromatin states through binding at cis-regulatory elements named PcG response elements or cellular memory modules. Fab-7 is a well-defined cellular memory module involved in regulation of the homeotic gene Abdominal-B (Abd-B). In addition to its action in cis, we show here by three-dimensional FISH that the Fab-7 element leads to association of transgenes with each other or with the endogenous Fab-7, even when inserted in different chromosomes. These long-distance interactions enhance PcG-mediated silencing. They depend on PcG proteins, on DNA sequence homology, and on developmental progression. Once long-distance pairing is abolished by removal of the endogenous Fab-7, the derepressed chromatin state induced at the transgene locus can be transmitted through meiosis into a large fraction of the progeny, even after reintroduction of the endogenous Fab-7. Strikingly, meiotic inheritance of the derepressed state involves loss of pairing between endogenous and transgenic Fab-7. This suggests that transmission of nuclear architecture through cell division might contribute to inheritance of chromatin states in eukaryotes.


Integrating environmental health into an undergraduate community health nursing course.
Nurses are often the first members of the healthcare system to whom the public turns when environmental health hazards cause concern. Yet most nursing programs include scant formal environmental health content. This article describes a project that integrated significant environmental health content into an undergraduate community health nursing course. The revised course included additional environmental health classroom content and field experiences. Details are provided regarding changes to classroom content, revision of written assignments to include environmental health issues, planning and implementation of nursing student field experiences with environmental health professionals, and evaluations of the revised course. The article concludes with three recommendations to guide other schools of nursing, wishing to integrate environmental health into their curricula.


Hypoxic gene activation by lipopolysaccharide in macrophages: implication of hypoxia-inducible factor 1alpha.
Hypoxia-inducible factor 1 (HIF-1) regulates many genes induced by low oxygen conditions. The expression of important hypoxic genes such as glucose transporter 1 and vascular endothelial growth factor are increased in macrophages during wound healing and in the presence of the endotoxin, lipopolysaccharide (LPS). Recent studies have demonstrated that nonhypoxic stimuli can also activate HIF-1 in a cell-specific manner. Here, we demonstrate that in macrophages, LPS can control the activation of hypoxia-regulated genes through the HIF-1 pathway. We show that in these cells, protein expression levels of HIF-1alpha are strongly increased to levels comparable to hypoxic induction. HIF-1alpha mRNA levels are markedly increased following LPS stimulation, suggesting a transcriptional induction. In functional studies, the LPS-induced HIF-1 complex could specifically bind to the HIF-1 DNA-binding motif. Additionally, when cells were transfected with an HIF-1-specific reporter construct, LPS could strongly activate the expression of the reporter to levels that surpassed those observed after hypoxic induction. This induction was blocked by the cotransfection of a dominant-negative form of HIF-1alpha. These results indicate that the HIF-1 complex is involved in macrophage gene activation following LPS exposure and identify a novel pathway that could play a determinant role during inflammation and wound healing.


Potentiometric batch and flow injection analysis of betaine hydrochloride.
Novel PVC membrane electrodes for the determination of betaine ion based on the formation of betaine-tetraphenylborate (Be-TPB) and betaine-phosphotungstate (Be-PT) ion-exchangers as electroactive materials are described. The sensors show a fast, stable, near Nernstian response for 6.92 x 10(-6) to 7.94 x 10(-3) M and 1.0 x 10(-4) to 1.0 x 10(-2) M betaine hydrochloride (Be.Cl) in case of Be-TPB electrode applying batch and flow injection analysis (FIA), respectively, and 2.95 x 10(-5) to 2.26 x 10(-3) M and 3.16 x 10(-5) to 1.0 x 10(-2) M in case of Be-PT electrode for batch and FIA electrodes, respectively, at 25 degrees C over the pH range of 3.5-10 with a cationic slope of 60.2 and 59.1 mV decade(-1) and a fast potential response of < or =15 s. The lower detection limits are 7.94 x 10(-6) and 3.18 x 10(-5) M Be.Cl for Be-TPB and Be-PT electrodes, respectively. Selectivity coefficient data for some common inorganic cations, sugars, amino acids and the components other than betaine, of the mixed drug investigated show negligible interference. The electrodes have been applied to the direct potentiometric determination of betaine hydrochloride in water and in a pharmaceutical preparation under batch and FIA conditions. Potentiometric titrations of Be.Cl with NaTPB and PTA as titrants were monitored with the developed betaine electrodes as an end point indicator electrode. The determination of Be.Cl shows an average recovery of 100.8% with mean relative standard deviation of 0.61%. The effect of temperature on the electrodes was also studied.


Lipase catalyzed modification of milkfat.
Decreasing consumption of high fat milk and dairy products is driving the dairy industry to seek other uses for increasing surplus of milkfat. Enzyme catalyzed modification of milkfat using lipases is receiving particular attention. This review examines lipase-mediated modification of milkfat. Especial attention is given to industrial applications of lipases for producing structured and modified milkfat for improved physical properties and digestibility, reduced caloric value, and flavor enhancement. Features associated with reactions such as hydrolysis, transesterification, alcoholysis and acidolysis are presented with emphasis on industrial feasibility, marketability and environmental concerns. Future prospects for enzyme catalyzed modification of milk fat are discussed.


Thermodynamics and kinetics of a Brownian motor.
Nonequilibrium fluctuations, whether generated externally or by a chemical reaction far from equilibrium, can bias the Brownian motion of a particle in an anisotropic medium without thermal gradients, a net force such as gravity, or a macroscopic electric field. Fluctuation-driven transport is one mechanism by which chemical energy can directly drive the motion of particles and macromolecules and may find application in a wide variety of fields, including particle separation and the design of molecular motors and pumps.


[A case of liver metastasis from bile duct cancer effectively treated with hepatic artery infusion chemotherapy].
We performed hepatic artery infusion chemotherapy (HAI) combined with 5-FU-MMC-EPIR for bile duct cancer metastasized to the liver. We report a case for which we obtained PR. The case was a 59-year-old woman, who was diagnosed to have multiple liver metastases with an increase of CEA and LDH after 6 months from absolute curative resection for middle bile duct cancer. The patient was catheterized into the proper hepatic artery through the right femoral artery, and 5-FU 500 mg qw, MMC 4 mg q2w, and EPIR 30 mg q4w were infused via a reservoir. Two months after the treatment was begun, CEA and LDH values became normal. At the same time, PR was obtained and was shown upon CT, which continued for 5 months. After an 8-month period during which the patient was an outpatient at PS-0, multiple bone metastases appeared, and the radiotherapy was combinedly utilized for each lesion. The side effect of this method was decrease of leukocytes and blood platelets, but it disappeared by discontinuing medication. The patient died two years after the first operation, a year and four months from the time HAI was begun. It was possible to continue this treatment with PS 1-2 on an outpatient basis until one month before the patient's death. We concluded that hepatic artery infusion chemotherapy is an effective therapeutic method.


Benzyloxycarbonylprolylprolinal, a transition-state analogue for prolyl oligopeptidase, forms a tetrahedral adduct with catalytic serine, not a reactive cysteine.
N-Benzyloxycarbonyl-l-prolyl-l-[1-13C]prolinal was synthesized starting with reduction of l-[1-13C]Pro to l-[1-13C]prolinol, followed by coupling with N-benzyloxycarbonyl-l-Pro to N-benzyloxycarbonyl-l-Pro-l-[1-13C]prolinol (Z-Pro-[1-13C]prolinol), and finally oxidation of the alcohol to the aldehyde with dimethyl sulphoxide. While the 13C NMR chemical shift of the aldehyde carbon is 202 p.p.m., that of the aldehyde hydrate is between 91.6 and 91.8 p.p.m., that of the dithiothreitol adduct is between 74.8 and 75.0 p. p.m., and that in the presence of the serine protease prolyl oligopeptidase is at 92.3 p.p.m.. The linewidth of the latter is 114 Hz, roughly consistent with the molecular mass of 80 kDa reported for the enzyme. Inverse detection experiments gave a 1H resonance at 5.29 p.p.m. with a linewidth of 80 Hz, also consistent with the expected chemical shift and linewidth for a hemiacetal bound to such a large enzyme, while the free hydrate gave resonances at 5.18 and 5. 25 p.p.m., with very much narrower linewidths. It is concluded that Z-Pro-prolinal, a putative transition-state analogue for prolyl oligopeptidase, forms a tetrahedral complex with the enzyme at its catalytic serine, rather than at a neighbouring cysteine that was found to be highly reactive according to chemical modification studies.


Safety, efficacy, and cost analysis of thymoglobulin induction therapy with intermittent dosing based on CD3+ lymphocyte counts in kidney and kidney-pancreas transplant recipients.
In view of the superior T-cell depletion and prolonged half-life of thymoglobulin, we initiated a protocol to administer thymoglobulin intermittently based on peripheral blood CD3+ lymphocyte counts. In this prospective study, 41 consecutive high-risk cadaver transplant recipients (panel reactive antibody level >30%, repeat transplant recipients, simultaneous pancreas and kidney or pancreas after kidney recipients, prolonged cold-ischemia time, prolonged donor hypotension, non-heart-beating donors) who received thymoglobulin induction therapy were included. The first dose (1.5 mg/kg) of thymoglobulin was administered intraoperatively. CD3+ lymphocyte count in the peripheral blood was determined daily and repeat doses were administered when the CD3+ count was >20 cells/mm3. Calcineurin inhibitors (CI) in low doses were introduced when the allograft function recovered and the serum creatinine level dropped by at least 25% from the pretransplant level. Thymoglobulin treatment was discontinued once therapeutic CI drug levels were achieved. Concomitant immunosuppression consisted of mycophenolate mofetil and prednisone. The mean individual thymoglobulin dose was 104 mg (1.4 mg/kg), and the total cumulative dose per patient was 318 mg (4.2 mg/kg). Patients received an average of three doses and a mean of six CD3 counts were obtained per patient. Introduction of CI was delayed for an average of 6 days posttransplantation. At a mean follow-up of 340 days, two (4.9%) patients died; three (7.3%) renal allografts and two (18.2%) pancreas allografts were lost. Five (12.2%) patients developed a total of six acute rejection episodes. The mean serum creatinine in the 38 patients with a functioning kidney was 1.47 mg/dl, and the mean blood glucose in the 9 pancreas allograft recipients was 89 mg/dl. Cytomegalovirus (CMV) infection occurred in one (2.4%) patient. No posttransplant lymphoproliferative disorders were seen in this patient cohort. The hospital pharmacy charge for a 100-mg dose of thymoglobulin at this center was $2,165, and the laboratory charge for a single CD3 determination was $70. In this study, the average charges per patient for the total dose of thymoglobulin and six CD3 determinations were $7305. In comparison, the charge for daily administration of 104 mg of thymoglobulin (which was the mean dose) for 6 days (mean time to CI therapy initiation) would be $13,510 and for 10 days (mean time to therapeutic CI levels) would be $22,516. This represents a savings of 46% and 68%, respectively. Intermittent thymoglobulin therapy, based on peripheral blood CD3+ lymphocyte counts, is safe and associated with low acute rejection rate in high-risk kidney and kidney-pancreas transplant recipients. A mean of three doses resulted in adequate suppression of CD3+ lymphocytes permitting delayed introduction of CI in low doses until recovery of renal function occurred. When compared to traditional daily administration, intermittent therapy results in significant cost savings and reduces the total cumulative dose of this potent immunosuppressive agent.


Octogenarian liver grafts: Is their use for transplant currently justified?
To analyse the impact of octogenarian donors in liver transplantation. We present a retrospective single-center study, performed between November 1996 and March 2015, that comprises a sample of 153 liver transplants. Recipients were divided into two groups according to liver donor age: recipients of donors ≤ 65 years (group A; n = 102), and recipients of donors ≥ 80 years (group B; n = 51). A comparative analysis between the groups was performed. Quantitative variables were expressed as mean values and SD, and qualitative variables as percentages. Differences in properties between qualitative variables were assessed by χ2 test. Comparison of quantitative variables was made by t-test. Graft and patient survivals were estimated using the Kaplan-Meier method. One, 3 and 5-year overall patient survival was 87.3%, 84% and 75.2%, respectively, in recipients of younger grafts vs 88.2%, 84.1% and 66.4%, respectively, in recipients of octogenarian grafts (P = 0.748). One, 3 and 5-year overall graft survival was 84.3%, 83.1% and 74.2%, respectively, in recipients of younger grafts vs 84.3%, 79.4% and 64.2%, respectively, in recipients of octogenarian grafts (P = 0.524). After excluding the patients with hepatitis C virus cirrhosis (16 in group A and 10 in group B), the 1, 3 and 5-year patient (P = 0.657) and graft (P = 0.419) survivals were practically the same in both groups. Multivariate Cox regression analysis demonstrated that overall patient survival was adversely affected by cerebrovascular donor death, hepatocarcinoma, and recipient preoperative bilirubin, and overall graft survival was adversely influenced by cerebrovascular donor death, and recipient preoperative bilirubin. The standard criteria for utilization of octogenarian liver grafts are: normal gross appearance and consistency, normal or almost normal liver tests, hemodynamic stability with use of < 10 μg/kg per minute of vasopressors before procurement, intensive care unit stay < 3 d, CIT < 9 h, absence of atherosclerosis in the hepatic and gastroduodenal arteries, and no relevant histological alterations in the pre-transplant biopsy, such as fibrosis, hepatitis, cholestasis or macrosteatosis > 30%.


Methodologies for Operando ATR-IR Spectroscopy of Magnesium Battery Electrolytes.
We explore the suitability of operando attenuated total reflection infrared (ATR-IR) spectroscopy methodologies for the study of organoaluminate electrolytes for Mg battery applications. The "all-phenyl complex" in tetrahydrofuran (THF), with the molecular structure [Mg2Cl3·6THF]+[AlPh4]-, is used as an exemplar electrolyte to compare two different spectroelectrochemical cell configurations. In one case, a Pt gauze is used as a working electrode, while in the second case, a thin (∼10 nm) Pt film working electrode is deposited directly on the surface of the ATR crystal. Spectroscopic measurements indicate substantial differences in the ATR-IR response for the two configurations, reflecting the different spatial arrangements of the working electrode with respect to the ATR sampling volume. The relative merits and potential pitfalls associated with the two approaches are discussed.


Midtrimester diagnosis and anomalies in the dup(22q) syndrome: correlation of aneuploidy with low maternal serum alpha-fetoprotein and oligohydramnios.
We present the first reported case of prenatally diagnosed dup(22q) syndrome in a 20-year-old woman referred for genetic counseling because of a low maternal serum alpha-fetoprotein value. An ultrasound study at 22 weeks demonstrated oligohydramnios, intrauterine growth retardation, multiple facial malformations, and a cardiac defect. Fetal karyotype was 46, XYdup(22)(pter----q13:: q12----qter) by amniocentesis. Necropsy following pregnancy termination confirmed all prenatally delineated anomalies. Comparison is made with the complete and partial proximal dup(22q) syndromes. We emphasize the correlation between aneuploidy and the presence of low maternal serum alpha-fetoprotein, oligohydramnios, and midgestational intrauterine growth retardation.


Determination of thiabendazole in fruits and vegetables by competitive-inhibition enzyme immunoassay.
An enzyme immunoassay (EIA) was developed for analysis of thiabendazole (TBZ) in fruits and vegetables. A commercial kit using a polyclonal antibody for benomyl-carbendazim was used. Total analysis time, including sample preparation, was 35 min. As many as 8 samples can be analyzed simultaneously, with a limit of quantitation of 9 ppb. The assay's dynamic range ran from 9 to 304 ppb TBZ. Intra-assay coefficients of variation (CVs) ranged from 5.0 to 9.6% for standards and 11 to 30% for samples. Interassay CVs varied from 4.4 to 15% for standards and from 10 to 24% for samples. Average recovery from 29 samples spiked at 50-50,000 ppb was 116%. A total of 107 food products comprising 12 different fruits and vegetables and their processed products were analyzed for their TBZ content by EIA and liquid chromatography (LC). Of these samples, 84 were positive for TBZ by both methods, with a correlation coefficient (r) of 0.989. Eight samples had none detected by either technique, and 15 were positive for carbendazim. Concentrations of TBZ ranged from 11 to 94,000 ppb. The immunoassay with methanol sonication shows promise as a rapid screening method for TBZ in foods.


Liquid-based and conventional cytology for bronchial washings/bronchoalveolar lavages in the diagnosis of malignancy - An institutional experience.
Liquid-based cytology (LBC) has been developed as an alternative for conventional cytology (CC) in cervical smears. It is now increasingly being used all over the world for cervical cancer screening. However, its role and diagnostic accuracy in bronchial wash (BW)/bronchoalveolar lavage (BAL) specimens remains undetermined. To assess and compare the diagnostic performance and accuracy of LBC with CC for detecting malignancy in bronchial specimens. This was a retrospective analytical hospital-based study. Bronchial specimens (BW/BAL) received over a period of 4.5 years were reviewed. The samples were processed by CC from June 2010 to September 2012 (2.25 years) and by LBC from October 2012 to December 2014 (2.25 years). Data were retrieved from the records of cytology laboratory and compared among both the groups. Detection rate for histologically or cytologically verified samples was calculated. A total of 559 cases verified by histological and cytological follow-up were evaluated. These included 247 CC cases and 312 LBC cases. The positive diagnostic rate for malignancy in CC was 28.6% whereas that for LBC was 32.9%. The negative diagnostic rates were 66.5% and 66.3% for CC and LBC, respectively. However, unsatisfactory rates had shown a good reduction from 4.4% in CC to 0.6% after LBC introduction. The smears showed more homogeneous distribution of cells with elimination of obscuring factors such as blood, inflammation, and mucus. The diagnostic accuracy of LBC was slightly better than CC. The unsatisfactory rates showed reduction in LBC preparation. Thus, LBC is a viable alternative to CC and has the advantages of standardization of preparation with decrease in unsatisfactory rates.


[Biochemical changes in the peripheral blood in cows 45 days after parturition].
Blood samples were collected from v. jugularis in five-day intervals from parturition to postpartum day 45 in the rearing conditions of a dairy cow production herd, consisting of 10 groups with 10 pluriparous cows each (crossbreds of Bohemian Pied cattle with Holstein-Friesian cattle). In blood serum the following activities were determined photometrically: aspartate aminotransferase--AST (0.36-0.47 mukat.l-1), gamma-glutamyl transferase--GMT (0.50-0.83 mukat.l-1) and lactate dehydrogenase--LD (7.22-9.10 mukat.l-1); their average values were at an almost constant level. Only did AST and GMT values decrease slightly from day 25 after parturition. The glucose average content on the day of parturition (4.07 mmol.l-1) steeply decreased to postpartum day 5 (2.79 mmol.l-1), and later on, it increased irregularly. The average values of total protein (66.7-73.2 g per 1) slightly increased from postpartum day 20. The values of urea (2.33-2.37 mmol.l-1) and bilirubin (3.49-5.15 mmol.l-1) did not show any larger changes in dependence on the time elapsing from parturition. The average content of creatinine (124-162 mmol.l-1) increased irregularly from postpartum day 15 and then it decreased. Cholesterol concentrations were gradually increasing from 2.58 mmol.l-1 on the day of parturition to 4.99 mmol.l-1 on day 45 after parturition. The average contents of calcium (2.20-2.66 mmol.l-1) and phosphorus (1.75-2.27 mmol.l-1) were irregularly increasing until day 20 after parturition. Also the average content of magnesium (0.86-1.15 mmol.l-1) rose from day 25 after parturition.


Organic thin film transistor with poly(4-vinylbiphenyl) blended 6,13-bis(triisopropylsilylethynyl)pentacene on propyleneglycolmonomethyletheracetate dielectric surface.
This paper presents the latest results in the use of soluble materials, such as organic semiconductors (OSCs) and gate-dielectrics, for simplified processing of organic thin film transistors (OTFTs). In this work, the fabrication of a solution-processed OTFT, with 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS-pentacene) and TIPS-pentacene mixed with poly(4-vinylbiphenyl) (PVBP) as the OSC, and propyleneglycolmonomethyletheracetate (PGMEA) as the gate-dielectric, is described. From electrical measurements, we observed exemplary I-V characteristics for these TFTs. Device performance characteristics have been obtained, including the charge carrier mobility (micro) of 1.47 x 10(-2) cm2Ns, threshold voltage (V(T)) of -11.36 V, current on/off ratio (I(ON/OFF)) of 1.08 x 10(4), sub-threshold swing (SS) of 2.13 V/decade for an OTFT with PVBP blended TIPS-pentacene and micro of 1.39 x 10(-4) cm2/Vs, V(T) of 0.7 V, I(ON/OFF) of 1.64 x 10(3), SS of 4.21 V/decade for an OTFT without polymer binder, individually.


Implementation of HIV Self-Testing to Reach Men in Rural uMkhanyakude, KwaZulu-Natal, South Africa. a DO-ART Trial Sub Study.
Background: KwaZulu-Natal, South Africa has one of the highest HIV prevalence rates globally. Persons <35 years and men have lower rates of HIV testing. HIV self-testing (HIVST) may overcome many barriers of facility-based HIV testing in order to identify HIV positive young persons and men and link them to care. We investigated whether HIVST distribution was a feasible approach to reach men and assessed the proportion of participants who reported their HIVST results, tested positive and linked to care. Methods: Teams comprised of a nurse, clinic research assistant, and recruiters distributed HIVST kits in rural uMkhanyakude, KwaZulu-Natal from August-November 2018 with a focus on testing men. Workplaces (farms), social venues, taxi ranks, and homesteads were used as HIVST kit distribution points following community sensitisation through community advisory boards and community leaders. HIVST kits, demonstration of use, and small incentives to report testing outcomes were provided. The Department of Health provided confirmatory testing and HIV care at clinics. Results: Over 11 weeks in late 2018, we distributed 2,634 HIVST kits of which 2,113 (80%) were distributed to persons aged <35 years, 2,591 (98%) to men and 356 (14%) to first time testers. Of the HIVST distributed, 2,107 (80%) reported their results to the study team, and 157 (7%) tested positive. Of persons who tested positive, 107/130 (82%) reported having a confirmatory test of which 102/107 (95%) were positive and initiated on ART. No emergencies or social harms were reported. Conclusion: Large scale distribution of HIVST kits targeting men in rural KwaZulu-Natal is feasible and highly effective in reaching men, including those who had not previously tested for HIV. While two-thirds of persons who tested HIV positive initiated ART, additional linkage strategies are needed for those who do not link after HIVST. HIVST should be used as a tool to reach men in order to achieve 95% coverage in the UNAIDS testing and care cascade in KwaZulu-Natal.


DNA-based visual majority logic gate with one-vote veto function.
A molecular logic gate is a basic element and plays a key role in molecular computing. Herein, we have developed a label-free and enzyme-free three-input visual majority logic gate which is realized for the first time according to DNA hybridization only, without DNA replacement and enzyme catalysis. Furthermore, a one-vote veto function was integrated into the DNA-based majority logic gate, in which one input has priority over other inputs. The developed system can also implement multiple basic and cascade logic gates.


Evaluation of transmural distribution of viable muscle by myocardial strain profile and dobutamine stress echocardiography.
Transmural distribution of viable myocardium in the ischemic myocardium has not been quantified and fully elucidated. To address this issue, we evaluated transmural myocardial strain profile (TMSP) in dogs with myocardial infarction using a newly developed tissue strain imaging. TMSP was obtained from the posterior wall at the epicardial left ventricular short-axis view in 13 anesthetized open-chest dogs. After control measurements, the left circumflex coronary artery was occluded for 90 min to induce subendocardial infarction (SMI). Subsequently, latex microbeads (90 microm) were injected in the same artery to create transmural infarction (TMI). In each stage, measurements were done before and after dobutamine challenge (10 microg.kg(-1).min(-1) for 10 min) to estimate transmural myocardial viability. Strain in the subendocardium in the control stage increased by dobutamine (from 53.6 +/- 17.1 to 73.3 +/- 21.8%, P < 0.001), whereas that in SMI and TMI stages was almost zero at baseline and did not increase significantly by dobutamine [from 0.8 +/- 8.8 to 1.3 +/- 7.0%, P = not significant (NS) for SMI, from -3.9 +/- 5.6 to -1.9 +/- 6.0%, P = NS for TMI]. Strain in the subepicardium increased by dobutamine in the control stage (from 23.9 +/- 6.1 to 26.3 +/- 6.4%, P < 0.05) and in the SMI stage (from 12.4 +/- 7.3 to 27.1 +/- 8.8%, P < 0.005), whereas that in the TMI stage did not change (from -1.0 +/- 7.8 to -0.7 +/- 8.3%, P = NS). In SMI, the subendocardial contraction was lost, but the subepicardium showed a significant increase in contraction with dobutamine. However, in TMI, even the subepicardial increase was not seen. Assessment of transmural strain profile using tissue strain imaging was a new and useful method to estimate transmural distribution of the viable myocardium in myocardial infarction.


Potentials for infant mental health: Congress themes and moral development.
Themes of the Congress carried forward the pioneering contributions of Rene Spitz and Takeo Doi. Contributions to infant mental health included those dealing with: (a) relatedness, (b) positive rewards of infancy, (c) disruptions of relatedness and rewards, (d) assessments, and (e) interventions. Contributions from infant mental health and bridging to the future included those regarding: (a) prevention, (b) policy, and (c) advances for science and practice. Knowledge from infant mental health is seen to fill a gap in our current moral discourse. Biologically based, universal moral processes of reciprocity and empathy develop in infancy, with regulation from parenting. Parenting, suffering under conditions of deprivation and adversity, can benefit from interventions designed to promote positive outcomes for conduct. Implications stem from a wider awareness of global needs. An expressed resolve of many is to provide consultation for regions needing our help and to formulate a declaration of infant rights for guiding actions.


19-Hydroxylase inhibition of adrenal mitochondrial P450 11 beta/18/19-hydroxylase by a suicide inhibitor.
19-Nor-deoxycorticosterone (19-nor-DOC) is a mineralocorticoid that is increased in some forms of experimental and human hypertension. The pivotal step in 19-nor-DOC biosynthesis is adrenal P450 19-hydroxylase, but this enzyme has not been clearly distinguished from P450 11 beta/18-hydroxylase. This study attempted to specifically inhibit adrenal 19-hydroxylation of deoxycorticosterone (DOC) using a suicide aromatase inhibitor, 19-acetylenic androstenedione (19-AA). Purified bovine P450 11 beta/18/19-hydroxylase was incubated with excess substrate DOC, adrenodoxin, and adrenodoxin reductase in the presence of increasing doses of the inhibitor, 19AA. 11 beta-, 18-, and 19-hydroxylation were measured by quantification of corticosterone, 18-OH-DOC, and 19-OH-DOC respectively. Measurements of these products demonstrated that 11 beta- and 18-hydroxylation was not inhibited whereas 19-hydroxylation was inhibited as manifested by decreased 19-OH-DOC formation (p less than .05). The IC50 of 19-AA was approximately 10(-12) M. The specific inhibition of 19-hydroxylation suggests that the 19-hydroxylase may be an enzyme distinct from the P450 11 beta/18-hydroxylase. This further suggests that 19-nor-DOC biosynthesis may be under independent regulation and may be amendable to specific in vivo inhibition.


The effect of the increasing prevalence of maternal obesity on perinatal morbidity.
In this study, we assessed the temporal trends and relative and attributable perinatal risks of maternal obesity over a 20-year period. We conducted a retrospective cohort study between 1980 and 1999 by using a computerized perinatal database of all women who received prenatal care and delivered their infants within a regional health care system. The main outcome measures were as follows: (1) annual mean body weight and the percentage of women classified as obese at the first prenatal visit (primary definition > or = 200 lb; secondary definitions > or = 250 lb, > or = 300 lb, body mass index > 29 kg/m(2)); and (2) relative and attributable risks of obesity for selected maternal and perinatal morbidities in successive 5-year periods. From 1980 to 1999, the mean maternal weight of women at the first prenatal visit increased 20% (144-172 lb), as did the percentage of women > or = 200 lb (7.3-24.4), the percentage > or = 250 lb (1.9-10.7), the percentage > or = 300 lb (0.5-4.9), and the percentage with a body mass index > 29 kg/m(2) (16.3-36.4), P < .01 for all. Controlling for maternal age, race, and smoking status, obese women were at increased risk at each period for cesarean delivery (range of adjusted relative risk, 1.5-1.8), gestational diabetes (range, 1.8-2.9), and large (> 90th percentile) for gestational age infants (range, 1.8-2.2). From the earliest 5-year period (1980-1984) to the most recent (1995-1999), the percentage of obesity-attributable cesarean deliveries more than tripled from 3.9 to 11.6. Similar percentage increases were observed for the obesity-attributable risks for gestational diabetes (12.8-29.6) and large for gestational age infants (6.5-19.1). Trends for secondary obesity definitions were similar, although the magnitude of the increased attributable risks was smaller. Efforts to reduce the frequency of certain perinatal morbidities will be constrained unless effective measures to prevent, or limit the risks of, maternal obesity are developed and implemented.


[Immediate recurrent laryngeal nerve reconstruction in the treatment of thyroid cancer invading the recurrent laryngeal nerve].
To explore the application of immediate recurrent laryngeal nerve reconstruction in the treatment of thyroid cancer invading the recurrent laryngeal nerve. Ten patients with thyroid cancer invading unilateral recurrent laryngeal nerve underwent radical surgery and immediate recurrent laryngeal nerve reconstruction. The reconstructive surgical approach included recurrent laryngeal nerve decompression surgery, end-to-end anastomosis of the recurrent laryngeal nerve, anastomosis of ansa cervicalis nerve to the recurrent laryngeal nerve, and nerve-muscle pedicle (NMP) technique. Among the ten patients, one underwent nerve decompression, one underwent end-to-end anastomosis of the recurrent laryngeal nerve, seven had anastomosis of ansa cervicalis to recurrent laryngeal nerve, and one case had anastomosis of ansa cervicalis to recurrent laryngeal nerve combined with nerve-muscle pedicle (NMP) technique. The effect of surgery was evaluated by videolaryngoscopy, maximum phonation time (MPT), phonation efficiency index (PEI) and voice assessment. T-test was used in the statistical analysis. All of the 10 patients had no complications including tumor recurrence and hypoparathyroidism after the surgery. Their hoarseness symptoms were improved, and the patients returned to normal or near-normal voice. Postoperative videolaryngoscopy showed that paralyzed vocal cord returned to normal muscle tone and volume, and the vocal cord vibration and mucosal wave were symmetric and the patients got good glottal closure. The pre- and post-operative maximum phone times of the patients were (4.52 ± 0.89) s and (11.91 ± 1.87) s, respectively (P < 0.01). The pre- and post-operative phonation efficiency indices were (1.37 ± 0.43) s/L and (4.02 ± 1.33) s/L, respectively (P < 0.05). In patients with thyroid cancer invading unilateral recurrent laryngeal nerve, immediate recurrent laryngeal nerve reconstruction following radical surgery of thyroid cancer can effectively achieve recovery in phonation function and improve the quality of life of the patients.


[Treatment strategies of complex lesions in patients with acute Stanford type A dissection of important branches involvement].
Acute Stanford type A aortic dissection with important branches involved is more complex, could lead to organ malperfusion syndrome even organ failure. The understanding of pathological anatomy, classification, staging, and the pathophysiological change has increasingly mature, but not complete. In addition, the treatment strategy for complex lesions is diversified, some questions may not reach consensus. Fully understanding of the anatomical and pathophysiology is very important for surgeons to choose reasonable treatment strategy. As the rapid development of the basic research, imaging techniques and the concept of surgery procedures, the manage technique of Stanfrod type A dissection and branch vessels at the same time is getting seriously, the related issues also need further discussions.


[Surgical resection of multiple liver metastases of rectal neuroendocrine tumors].
We report a case of surgically resected multiple liver metastases of rectal neuroendocrine tumors (NET), which could not be controlled by medical treatment. A 66-year-old man was diagnosed as having multiple liver metastases of rectal NET 5 years after the initial diagnosis. Although we performed 5 rounds of transcatheter arterial infusion (TAI) and administered 4 cycles of 5-fluorouracil, Leucovorin, and oxaliplatin( mFOLFOX6), the metastasis gradually spread. The patient was admitted to our hospital to undergo hepatectomy. Extended right hepatectomy and partial resection of the lateral segment were performed. The pathological diagnosis was metastasis of rectal NET and it was classified as grade 2 NET according to the 2010 World Health Organization (WHO) classification. The patient received intramuscular injections of sustained-release octreotide( 30 mg every 4 weeks) after surgery. One year and 2 months after surgery, he shows no signs of recurrence.


Assessing the Link Between Statins and Insulin Intolerance: A Systematic Review.
There has been mixed and inconclusive evidence regarding the relationship between statin usage and insulin intolerance. This systematic review aims to comprehensively explore the link between the use of statins and insulin intolerance. We systematically searched MEDLINE, PubMed, PubMed Central (PMC), and Google Scholar databases for online English articles with full text. We excluded conference proceedings, editorials, commentaries, preclinical studies, abstracts, and preprints. The search across databases initially identified 667 articles. After eliminating duplicates and analyzing the remaining articles based on the inclusion and exclusion criteria, 11 articles were selected. The included studies had a total of 46,728,889 participants. The findings suggest that the use of statins is associated with a decrease in insulin sensitivity and insulin resistance. This systematic review provides evidence that the use of statins may have an adverse effect on insulin sensitivity and increase insulin resistance. These findings may have important clinical implications for individuals on statin therapy, especially those at risk of developing diabetes.


Transfection of an Fc gamma receptor cDNA induces T cells to become phagocytic.
The human receptor Fc gamma RIIA for the Fc portion of IgG (Fc gamma) was expressed in a human T-cell line and conferred on these cells the ability to perform IgG antibody-stimulated phagocytosis. Crosslinking Fc gamma RIIA with anti-Fc gamma RII monoclonal antibody also induced tyrosine phosphorylation of multiple proteins including Fc gamma RIIA, ZAP-70, p72SYK, and phospholipase C gamma 1 subunit and an increase in intracellular Ca2+ concentration. The T cell receptor-associated zeta-chain was not tyrosine-phosphorylated after crosslinking of Fc gamma RIIA, suggesting that the Fc gamma RIIA-mediated signals were independent of CD3. Fc gamma RIIA-mediated signal transduction was defective in a transfected mutant T-cell line exhibiting reduced expression of the tyrosine kinases LCK and FYN. These studies indicate that certain T cells can assume phagocytic properties after transfection of cDNA encoding an Fc gamma receptor with the capability of inducing a phagocytic signal.


A Novel R848-Conjugated Inactivated Influenza Virus Vaccine Is Efficacious and Safe in a Neonate Nonhuman Primate Model.
Influenza virus infection of neonates poses a major health concern, often resulting in severe disease and hospitalization. At present, vaccines for this at-risk population are lacking. Thus, development of an effective vaccine is an urgent need. In this study, we have used an innovative nonhuman primate neonate challenge model to test the efficacy of a novel TLR 7/8 agonist R848-conjugated influenza virus vaccine. The use of the intact virus represents a step forward in conjugate vaccine design because it provides multiple antigenic targets allowing for elicitation of a broad immune response. Our results show that this vaccine induces high-level virus-specific Ab- and cell-mediated responses in neonates that result in increased virus clearance and reduced lung pathology postchallenge compared with the nonadjuvanted virus vaccine. Surprisingly, the addition of a second TLR agonist (flagellin) did not enhance vaccine protection, suggesting that combinations of TLR that provide increased efficacy must be determined empirically. These data support further exploration of this new conjugate influenza vaccine approach as a platform for use in the at-risk neonate population.


Ethnic differences in the predictors of drug and alcohol abuse in hospitalized adolescents.
This study examined psychosocial correlates of drug and alcohol abuse in hospitalized adolescents and the extent to which these associations may be affected by ethnicity. Four hundred fifty-eight psychiatric inpatients, ages 12-19, completed measures of psychological functioning, environmental stress, drug abuse, and alcohol abuse. Multiple regression analyses examined the joint and independent predictors of drug and alcohol abuse for European Americans, Latino Americans, and African Americans separately. Seven variables--age, depression, impulsivity, low self-esteem, delinquent predisposition, low peer insecurity, and history of child abuse--jointly predicted drug abuse for all groups, and predicted alcohol abuse for European Americans and Latino Americans. However, several differences were noted with respect to which variables made independent contributions to the model. Such differences may reflect distinct risk factors for drug and alcohol abuse in these three ethnic groups and may also have implications for prevention and treatment programs.


Modulation of oxidative DNA damage by repair enzymes XRCC1 and hOGG1.
The influence of DNA repair gene polymorphisms (XRCC1: Arg194Trp, Arg280His, Arg399Gln; APE1: Asp148Glu; hOGG1: Ser326Cys) on oxidative DNA damage is controversial and was investigated in 214 German workers with occupational exposure to vapors and aerosols of bitumen,compared to 87 German construction workers without exposure, who were part of the Human Bitumen Study. Genotypes were determined by real-time polymerase chain reaction (PCR), and actual smoking habits by a questionnaire and cotinine analysis. Oxidative DNA damage in white blood cells (WBC) collected pre- and postshift was measured as 8-oxodGuo adducts/10(6) dGuo by a hjigh-performance liquid chromatography electron capture detection (HPLC-ECD) method, followed by calculation of the difference between post- and preshift values (Δ8-oxodGuo/10(6) dGuo). The 214 bitumen exposed workers showed higher median Δ8-oxodGuo values than the 87 references. In the whole study group (n=301) there was a trend for increasing adduct values for XRCC1 Arg(GG)399Gln(AA) during a shift, especially in nonsmokers (n=108. Referents (n=87) displayed a similar trend for hOGG1 Ser(CC)326Cys(GG). In contrast, XRCC1 Arg(GG)280His(AA) showed a decrease of median Δ8-oxodGuo/10(6) dGuo values in workers with exposure to vapors and aerosols of bitumen (n=214), especially in smokers (n=145). XRCC1 Arg194Trp and APE1 Asp148Glu displayed no marked association with Δ8-oxodGuo levels. Data indicate that the combination of different variants in DNA damage repair enzymes may modulate the production of 8-oxoguanine adducts in WBC produced by xenobiotics during a shift.


Use of a Regression Model to Study Host-Genomic Determinants of Phage Susceptibility in MRSA.
Staphylococcus aureus is a major agent of nosocomial infections. Especially in methicillin-resistant strains, conventional treatment options are limited and expensive, which has fueled a growing interest in phage therapy approaches. We have tested the susceptibility of 207 clinical S. aureus strains to 12 (nine monovalent) different therapeutic phage preparations and subsequently employed linear regression models to estimate the influence of individual host gene families on resistance to phages. Specifically, we used a two-step regression model setup with a preselection step based on gene family enrichment. We show that our models are robust and capture the data's underlying signal by comparing their performance to that of models build on randomized data. In doing so, we have identified 167 gene families that govern phage resistance in our strain set and performed functional analysis on them. This revealed genes of possible prophage or mobile genetic element origin, along with genes involved in restriction-modification and transcription regulators, though the majority were genes of unknown function. This study is a step in the direction of understanding the intricate host-phage relationship in this important pathogen with the outlook to targeted phage therapy applications.


A morphological and histological study of the postnatal development of intervertebral discs in the lumbar spine of the rabbit.
Some basic features in the development of the structure of the annulus fibrosus and nucleus pulposus in the rabbit, as described by previous workers, have been confirmed in the present study. However, the greater thickness of the anterior part of the disc, as compared with the posterior region, and the distinctive arrangement of lamellae in the posterior part of the disc, cannot be attributed, as conventionally claimed from studies of the human spine, to a secondary curvature in the lumbar spine associated with an upright posture: for these features are present in the lumbar spine of the quadrupedal rabbit with its primary curvature. Secondary ossification produces a plate-like epiphysis separating the growth cartilage from the intervertebral disc. A distinct cartilaginous plate, limiting the nucleus pulposus in the rabbit intervertebral disc, only becomes apparent when collagen fibres cease to traverse the area above and below the nucleus pulposus.


Toward a standardized system for hepatocellular carcinoma diagnosis using computed tomography and MRI.
Contrast-enhanced computed tomography and MRI are frequently used for the noninvasive diagnosis of hepatocellular carcinoma (HCC). Despite their important role in diagnosis and management of HCC, until recently, there has been no standardized system for their interpretation, reporting and data collection. In 2008, the American College of Radiology convened a committee to develop such a standardized system. This article reviews the role of computed tomography and MRI in the diagnosis and management of HCC; the need for a standardized imaging interpretation system; current HCC imaging criteria included in management guidelines endorsed by the European Association for the Study of Liver, American Association for Study of Liver Diseases, United Network for Organ Sharing and Asian Pacific Association for the Study of the Liver; and the limitations of these criteria. The article then provides an overview of the Liver Imaging Reporting and Data System and discusses future directions.


Scaling up cervical cancer prevention in Western Kenya: Treatment access following a community-based HPV testing approach.
To evaluate access to treatment after community-based HPV testing as testing within screen-and-treat programs has the potential to lower mortality from cervical cancer in low-resource settings. A prospective cohort study was conducted in western Kenya in 2018. Women aged 25-65 years underwent HPV self-testing. HPV-positive women were referred for cryotherapy. Participant data were obtained from questionnaires during screening and treatment. The proportion successfully accessing treatment and variables associated with successful treatment was determined. Of the 750 women included, 140 (18.6%) tested positive for HPV. Of them, 135 were notified of their results, of whom 77 (59.2%) sought treatment and 73 (52.1%) received cryotherapy. Women who received treatment had a shorter time from screening to result notification (median 92 days, interquartile range [IQR] 84-104) compared to those who did not (97 days, IQR 89-106; P=0.061). In adjusted analyses, women with a history of cervical cancer screening (odds ratio [OR] 11, 95% confidence interval [CI] 1.42-85.20) and those electing result notification through a home visit (OR 4, 95% CI 1.23-14.17) were significantly more likely to acquire treatment at follow-up. Linkage to treatment after community-based HPV screening in this population was low, highlighting the need for strategies aimed at strengthening treatment linkage in similar settings.


Claims data analyses unable to properly characterize the value of neurologists in epilepsy care.
To determine the association of a neurologist visit with health care use and cost outcomes for patients with incident epilepsy. Using health care claims data for individuals insured by United Healthcare from 2001 to 2016, we identified patients with incident epilepsy. The population was defined by an epilepsy/convulsion diagnosis code (ICD codes 345.xx/780.3x, G40.xx/R56.xx), an antiepileptic prescription filled within the succeeding 2 years, and neither criterion met in the 2 preceding years. Cases were defined as patients who had a neurologist encounter for epilepsy within 1 year after an incident diagnosis; a control cohort was constructed with propensity score matching. Primary outcomes were emergency room (ER) visits and hospitalizations for epilepsy. Secondary outcomes included measures of cost (epilepsy related, not epilepsy related, and antiepileptic drugs) and care escalation (including EEG evaluation and epilepsy surgery). After participant identification and propensity score matching, there were 3,400 cases and 3,400 controls. Epilepsy-related ER visits were more likely for cases than controls (year 1: 5.9% vs 2.3%, p < 0.001), as were hospitalizations (year 1: 2.1% vs 0.7%, p < 0.001). Total medical costs for epilepsy care, nonepilepsy care, and antiepileptic drugs were greater for cases (p ≤ 0.001). EEG evaluation and epilepsy surgery occurred more commonly for cases (p ≤ 0.001). Patients with epilepsy who visited a neurologist had greater subsequent health care use, medical costs, and care escalation than controls. This comparison using administrative claims is plausibly confounded by case disease severity, as suggested by higher nonepilepsy care costs. Linking patient-centered outcomes to claims data may provide the clinical resolution to assess care value within a heterogeneous population.


Closure of a femoral pseudoaneurysm by transcutaneous short guidewire embolization.
Femoral pseudoaneurysm (PSA) is a well-recognized complication following catheter-based diagnostic or interventional procedures. We report a patient who developed a pseudoaneurysm following the insertion of a Steinman pin for a fractured shaft of the right femur following a road traffic accident. The treatment of choice for a femoral pseudoaneurysm is ultrasound-guided compression repair. As this modality of treatment was not applicable to our patient, the pseudoaneurysm was closed by transcutaneous short guidewire embolization technique.


A three-dimensional description of heating patterns in vascularised tissues during hyperthermic treatment.
A three-dimensional finite difference computer model has been developed to calculate temperature distributions in vascularised tissues in hyperthermia. Besides offering the possibility of calculating temperature distributions according to the conventional ' bioheat transfer' method, this model allows the introduction of several discrete blood vessels and can describe their influence on the temperature distribution. The model can be used to evaluate all types of heating techniques. First calculations on discrete large vessels show inhomogeneities caused by these vessels in the temperature distribution in tissue in hyperthermia. The theory and model presented can form the basis of a new bioheat transfer theory, with a vessel-temperature related bioheat transfer heat-sink term able to describe the small-scale temperature variation problems in local hyperthermia.


Cycle affects imidacloprid efficiency by mediating cytochrome P450 expression in the brown planthopper Nilaparvata lugens.
Circadian clocks influence most behaviours and physiological activities in animals, including daily fluctuations in metabolism. However, how the clock gene cycle influences insects' responses to pesticides has rarely been reported. Here, we provide evidence that cycle affects imidacloprid efficacy by mediating the expression of cytochrome P450 genes in the brown planthopper (BPH) Nilaparvata lugens, a serious insect pest of rice. Survival bioassays showed that the susceptibility of BPH adults to imidacloprid differed significantly between the two time points tested [Zeitgeber Time 8 (ZT8) and ZT4]. After cloning the cycle gene in the BPH (Nlcycle), we found that Nlcycle was expressed at higher levels in the fat body and midgut, and its expression was rhythmic with two peaks. Knockdown of Nlcycle affected the expression levels and rhythms of cytochrome P450 genes as well as susceptibility to imidacloprid. The survival rates of BPH adults after treatment with imidacloprid did not significantly differ between ZT4 and ZT8 after double-stranded Nlcycle treatment. These findings can be used to improve pesticide use and increase pesticide efficiency in the field.


Oestrogens and puberty.
Oestrogens induce the development of female reproductive tissues. Endogenous human oestrogens include oestradiol, oestrone and oestriol. Oestrogen signalling in target tissues is dependent on the tissue concentration of oestrogen and the interaction of oestrogen receptors with an array of cell-specific co-regulator proteins. The diverse mechanisms of oestrogen signalling are complex and incompletely understood. In puberty, oestrogen is derived from both gonadal and peripheral sources. Originally, oestrogen was only thought to drive feminization in females; now, oestrogen is known to be important for pubertal development of males as well. Oestrogen is required for normal maturation of the neuroendocrine-gonadal axis and bone in both sexes, and a variety of other tissues are also responsive to oestrogen. Abnormal puberty can be associated with either excessive or inadequate oestrogen production. Girls deficient in oestrogen should receive replacement in physiological doses. Aromatase inhibitors and anti-oestrogens may prove to be useful therapeutic tools in some types of abnormal puberty.


Density-dependent effects on Anguillicola crassus (Nematoda) within its European eel definitive host.
Density-dependent effects on adult and larval stages of the introduced nematode parasite Anguillicola crassus in the European eel definitive host were examined in the laboratory in naturally infected fish, and in field samples. The effect of adult nematode subpopulations on larval development over time and the effect of increasing adult intensity on the gravid female subpopulations were investigated. At high adult subpopulations the movement of larvae from the swimbladder wall into the swimbladder lumen appears to be inhibited, and A. crassus larvae to be arrested in development in a density-dependent manner. The number of gravid females per host reaches a constant level, and so the proportion of gravid female nematodes per adult subpopulation decreases relative to further increasing total adult nematode numbers. Both these mechanisms have the potential to regulate infrapopulations of A. crassus within the eel definitive host and thus the parasite suprapopulation.


Opportunities to improve the care of patients with kidney transplant failure.
Patients initiating dialysis after a failed kidney transplant are a subgroup of chronic kidney disease (CKD) patients who have not been characterized. Exposure to immunosuppressive medications differentiates these patients from the general incident end-stage renal disease (ESRD) population. Data from the Health Care Financing Administration 2728 form were used to determine the hematocrit, erythropoietin use, serum albumin and glomerular filtration rate (GFR) among 4643 patients with failed kidney transplants who initiated dialysis between April 1995 and December 1998. At dialysis initiation, the mean hematocrit, serum albumin and GFR were 27.5%, 3.3 g/dL, and 8.4 mL/min/1.73 m2, respectively, and only 35% of patients had received erythropoietin. In a multivariate analysis, patients <45 years, females, patients of non-White race, non-diabetic patients, hemodialysis patients and patients with a lower serum albumin had a higher odds for hematocrit <30%. Erythropoietin use was associated with female gender, White race, increased time since transplantation, being employed, peritoneal dialysis, and higher serum albumin. Patients >/=45 years and patients with diabetes or congestive heart failure had higher odds for hypoalbuminemia, while employed patients, peritoneal dialysis patients, patients with higher hematocrit and patients who had received erythropoietin had lower odds of hypoalbuminemia. Despite being known to specialty physicians, patients with failed kidney transplants initiate dialysis at levels of hematocrit, serum albumin, and GFR that may be suboptimal and similar to those in the general incident ESRD population. Socioeconomic factors remain important barriers to the provision of CKD care even among these patients with established specialty physician contact. Improved CKD care could improve the outcomes of this unique subgroup of CKD patients.


Case report: Multiple epstein-barr virus-associated smooth muscle tumours in a child with IL-2-inducible T-cell kinase mutation of undetermined clinical significance.
EBV-associated smooth muscle tumours (EBV-SMTs) are uncommon neoplasms associated with immunodeficiency. The pathogenesis of EBV-SMTs is poorly understood. IL-2-inducible T-cell kinase (ITK), a member of the Tec family of tyrosine kinases, is the predominant Tec kinase in T cells. Researchers have shown that ITK is involved in the pathogenesis of autoimmune diseases and carcinogenesis, and the loss of ITK function due to mutation in patients can lead to EBV-associated lymphoproliferation. Multiple Epstein-Barr virus-associated smooth muscle tumours with ITK mutation have rarely been reported. A 6-year-old female child was admitted to the hospital due to recurrent bilateral hip pain for more than one year. Tumours were found in the lung, near the intracranial cavernous sinus and in the lumbar spine and paraspinal soft tissues by CT and MRI. The patient underwent vertebral tumour biopsy, which suggested low-grade myogenic or inflammatory myofibroblastic tumours, so the patient was given three courses of chemotherapy without symptom relief or mass reduction. The patient underwent lumbar mass resection, the pathological results indicated EBV-SMT, and a novel germline homozygous deletion mutation in the ITK gene was detected. The deletion mutation in this gene has not yet been reported and the clinical significance of the pathogenicity of the variant is unknown. Intrabronchial mass resection was performed under fibre bronchoscopy, and the pathological results indicated EBV-SMT. No significant recurrence or progression was observed after more than 2 years of follow-up. We present a rare case of multiple EBV-SMTs combined with ITK gene mutation. Some of the tumours were removed, and some were treated conservatively. There was no significant recurrence or progression after more than two years of follow-up. The optimal treatment regimen still needs to be further explored, and the relationship between ITK gene mutation at this locus and immunodeficiency and EBV-SMT warrants further investigation.


Selective pathway choice of a single central axonal fascicle by a subset of peripheral neurons during leech development.
In the CNS of leech, the central projections of peripheral sensory neurons segregate into three distinct axonal tracts during early development. We have previously shown that a subset of these neurons, recognized by the monoclonal antibody lan 4-2, projects axons into only one of these fascicles (Johansen et al., 1992, Neuron 8, 599). Here we report on a developmental and biochemical characterization of another fascicle-specific antigen labeled by the monoclonal antibody lan 3-6. By immunocytochemistry and double labelings we demonstrate that the lan 3-6 epitope is expressed only by a small subgroup of the peripheral neurons in Macrobdella embryos. The axons of these neurons selectively fasciculate in the CNS, but to only one of the three lan 3-2-positive tracts, which is different from the previously described lan 4-2-positive tract. These observations support the existence of a hierarchy of guidance cues mediating specific tract formation in this system. A biochemical analysis of the antigen suggests that it is likely to be a glycosylated protein with a molecular weight of approximately 200 kDa. Thus, the restricted expression of the lan 3-6 antigen and its biochemical properties are consistent with the hypothesis that this antigen may be playing a role in axonal guidance.


Comparison and validation of scoring systems in a cohort of patients treated for biliary acute pancreatitis.
There are a few prospective studies assessing the severity of acute pancreatitis with exclusive criteria for biliary etiology. The aim of this study was to assess the reliability of prediction of the severity and mortality of acute biliary pancreatitis by using the Ranson, Acute Physiology And Chronic Health Evaluation II and III, Simplified Acute Physiology Score II, and Mortality Probability Model (MPM) II systems. Fifty-eight patients with acute biliary pancreatitis were studied prospectively. Disease severity scores and mortality predictions were calculated using the collected data in the first 24 hours of admission and for Ranson score in the first 48 hours. Discrimination and calibration characteristics of each system were determined by using area under receiver operating characteristics curve and Hosmer-Lemeshow goodness-of-fit test, respectively. Among 58 patients included, there were 4 mortalities (6.8%). Fifteen patients (25.8%) had severe disease, and 5 patients (8.6%) had systemic and local complications. All systems had reliable power of discrimination and calibration. Among systems tested MPM II was the best performing as far as discrimination, and calibration characteristics are considered. The items of MPM II that were positive in patients with severe pancreatitis were those related to systemic perfusion. Mortality Probability Model II predicted mortality at admission is better than the other systems in predicting the severity of pancreatitis. Results also indicate the important role of systemic perfusion at the early phases of acute pancreatitis in the progression of disease.


What type of cell death occurs in chronic cerebral hypoperfusion? A review focusing on pyroptosis and its potential therapeutic implications.
Chronic cerebral hypoperfusion (CCH) is a major global disease with chronic cerebral blood flow reduction. It is also the main cause of cognitive impairment and neurodegenerative diseases. Pyroptosis, a novel form of cell death, is characterized by the rupture of the cell membrane and the release of pro-inflammatory mediators. In recent years, an increasing number of studies have identified the involvement of pyroptosis and its mediated inflammatory response in the pathological process of CCH. Therefore, preventing the activation of pyroptosis following CCH is beneficial to inhibit the inflammatory cascade and reduce brain injury. In this review, we discuss the research progress on the relationship between pyroptosis and CCH, in order to provide a reference for research in related fields.


Aberrant intermolecular disulfide bonding in a mutant HLA-DM molecule: implications for assembly, maturation, and function.
HLA-DM (abbreviated DM) is an MHC-encoded glycoprotein that catalyzes the selective release of peptides, including class II-associated invariant chain peptides, from MHC class II molecules. To perform its function, DM must assemble in the endoplasmic reticulum (ER), travel to endosomes, and interact productively with class II molecules. We have described previously an EBV-transformed B cell line, 7.12.6, which displays a partial Ag presentation defect and expresses a mutated DM beta-chain with Cys79 replaced by Tyr. In this study, we show that HLA-DR molecules in 7.12.6 have a defect in peptide loading and accumulate class II-associated invariant chain peptides (CLIP). Peptide loading is restored by transfection of wild-type DMB. The mutant DM molecules exit the ER slowly and are degraded rapidly, resulting in greatly reduced levels of mutant DM in post-Golgi compartments. Whereas wild-type DM forms noncovalent alphabeta dimers, such dimers form inefficiently in 7.12.6; many mutant DM beta-chains instead form a disulfide-bonded dimer with DM alpha. Homodimers of DM beta are also detected in 7.12.6 and in the alpha-chain defective mutant, 2.2.93. We conclude that during folding of wild-type DM, the native conformation is stabilized by a conserved disulfide bond involving Cys79beta and by noncovalent contacts with DM alpha. Without these interactions, DM beta can form malfolded structures containing interchain disulfide bonds; malfolding is correlated with ER retention and accelerated degradation.


Structures and Spectroscopic Properties of F-(H2O) n with n = 1-10 Clusters from a Global Search Based On Density Functional Theory.
Using a genetic algorithm incorporated in density functional theory, we explore the ground state structures of fluoride anion-water clusters F-(H2O) n with n = 1-10. The F-(H2O) n clusters prefer structures in which the F- anion remains at the surface of the structure and coordinates with four water molecules, as the F-(H2O) n clusters have strong F--H2O interactions as well as strong hydrogen bonds between H2O molecules. The strong interaction between the F- anion and adjacent H2O molecule leads to a longer O-H distance in the adjacent molecule than in an individual water molecule. The simulated infrared (IR) spectra of the F-(H2O)1-5 clusters obtained via second-order vibrational perturbation theory (VPT2) and including anharmonic effects reproduce the experimental results quite well. The strong interaction between the F- anion and water molecules results in a large redshift (600-2300 cm-1) of the adjacent O-H stretching mode. Natural bond orbital (NBO) analysis of the lowest-energy structures of the F-(H2O)1-10 clusters illustrates that charge transfer from the lone pair electron orbital of F- to the antibonding orbital of the adjacent O-H is mainly responsible for the strong interaction between the F- anion and water molecules, which leads to distinctly different geometric and vibrational properties compared with neutral water clusters.


Simulated shift work disrupts maternal circadian rhythms and metabolism, and increases gestation length in sheep.
Shift work impairs metabolic health, although its effects during pregnancy are not well understood We evaluated the effects of a simulated shift work protocol for one-third, two-thirds or all of pregnancy on maternal and pregnancy outcomes in sheep. Simulated shift work changed the timing of activity, disrupted hormonal and cellular rhythms, and impaired maternal glucose tolerance during early pregnancy. Gestation length was increased in twin pregnancies, whereas singleton lambs were lighter at a given gestational age if mothers were subjected to shift work conditions in the first one-third of pregnancy. Exposure to rotating night and day shifts, even if only in early pregnancy, may adversely affect maternal metabolic and pregnancy outcomes. Shift workers are at increased risk of developing type 2 diabetes and obesity; however, the impact during pregnancy on maternal metabolism is unknown. Using a large animal model, we assessed the impact of simulated shift work (SSW) exposure during pregnancy on maternal circadian rhythms, glucose tolerance and pregnancy outcomes. Following mating, ewes were randomly allocated to a control photoperiod (CON 12 h light, 12 h dark) or to SSW, where the timing of light exposure and food presentation was reversed twice each week for one-third, two-thirds or all of pregnancy. Maternal behaviour followed SSW cycles with increased activity during light exposure and feeding. Melatonin rhythms resynchronized within 2 days of the photoperiod shift, whereas peripheral circadian rhythms were arrhythmic. SSW impaired glucose tolerance (+29%, P = 0.019) and increased glucose-stimulated insulin secretion (+32%, P = 0.018) in ewes with a singleton fetus in early but not late gestation. SSW exposure did not alter rates of miscarriage or stillbirth, although it extended gestation length in twin pregnancies (+2.4 days, P = 0.032). Relative to gestational age, birth weight was lower in singleton progeny of SSW than CON ewes (-476 g, P = 0.016). These results have implications for the large number of women currently engaged in shift work, and further studies are required to determine progeny health impacts.