Computational experiments support a competitive function in the CA3 region of the hippocampus.
The comprehension of activities and functions of complex brain structures requires, among other things, information on simultaneous activities in several regions. Results reported in the literature using multi(micro/macro)electrode recordings or imaging techniques provide incomplete information due either to the small size and/or small number of investigated regions or to the poor spatiotemporal resolution, respectively. This is particularly true for the hippocampus and its subfields, and mathematical modeling and computer simulation have been used with the aim of obtaining information when this is lacking. Global activities in the CA3 field of the hippocampus, and in particular the genesis of theta rhythm and sharp waves, have been investigated here by a mathematical model formulated within the frame of a kinetic theory of neural systems. The model has taken into account data of experimental results both on different PSPs recorded in hippocampal neurons and on recurrent pyramidal collateral geometries. The computational 'experiments' to which the model was subjected suggest that the sharp waves arise through a selective and short block of the fast inhibitory neurons of CA3, produced by a medial septum inhibitory input, whereas the theta activity is produced by a durable, continuous inhibition of the slow inhibitory neurons. Information obtained also suggests that the recurrent pyramidal collaterals subserve a competitive, rather than a cooperative, organization. Based on these results a hypothesis on the possible functional organization of the CA3 field and of the entire hippocampus has been formulated. According to this hypothesis, the CA3 imposes a serial order on the flow of activity arriving at the hippocampus from the entorhinal cortex and from its connected polymodal cortical regions. This ordering permits cortical activities, arriving at CA3 on appropriate time intervals, to produce effects in regions of brain to which the CA3 projects. The competing cortical activities are lost.


Distribution and levels of cellular retinol- and cellular retinoic acid-binding protein in various types of rat testis cells.
The distribution and levels of cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding protein (CRABP) were measured in rat testicular peritubular and Sertoli cells and in isolated rat pachytene spermatocytes and spermatids. Two Sertoli cell preparations, one containing some germ cells and another that had been osmotically shocked to destroy germ cells, were examined. CRBP and CRABP levels were measured by specific and sensitive radioimmunoassays. Testicular peritubular cell cytosol preparations were found to contain high levels of CRBP (1.48 +/- 0.87 microgram CRBP/mg protein) but CRABP could not be detected. The mean CRBP level in Sertoli cell preparations that contained some germ cells was 0.93 +/- 0.24 microgram CRBP/mg protein; this value was similar to the level of 1.11 +/- 0.20 microgram CRBP/mg protein measured for Sertoli cells free of germ cells. The level of CRABP found in Sertoli cell preparations containing germ cells (0.81 +/- 0.32 microgram CRABP/mg protein) was approximately five times greater than was observed in Sertoli cells free of germ cells (0.16 +/- 0.03 microgram CRABP/mg protein). CRBP and CRABP levels in cultured Sertoli cells were not affected by time in culture for up to five days of culture. Pachytene spermatocytes and spermatids were very enriched in CRABP (0.72 +/- 0.26 microgram CRABP/mg protein for spermatocytes and 0.65 +/- 0.21 microgram CRABP/ml protein for spermatids). A search for a high molecular weight retinol-binding protein did not demonstrate the existence of such a protein in Sertoli cell-conditioned medium. In summary, these studies provide quantitative information about the distribution of the cellular retinoid-binding proteins in the cell types that compose the rat testis.(ABSTRACT TRUNCATED AT 250 WORDS)


Factors associated with body weight status of Iranian postgraduate students in university of putra malaysia.
Good nutrition, a balanced diet and regular physical activity are foundations of good health. Research has found that dietary patterns change dramatically following the arrival of students in a foreign country. However, nutritional status of Iranian students studying oversea has never been investigated. The objective of this study was to determine factors associated with body weight status of Iranian postgraduate students in Universiti of Putra Malaysia (UPM). A cross-sectional study was conducted to determine the body weight status of 210 Iranian postgraduate students aged between 22 and 55 years in University of Putra Malaysia. The associations between body weight status and socio demographics factors and also lifestyle factors (smoking and physical activity) were assessed. Anthropometric factors (height, weight, BMI and waist and hip circumferences) were measured. Chi-square, Spearman Rho and Pearson tests were used for data analysis. From a total of 210 postgraduate students 110 were females, and 100 males. No significant correlation was observed between smoking and BMI (P = 0.4). However, statistically significant correlations were observed between gender (P = 0.007), physical activity (P = 0.02), using protein (P = 0.005), carbohydrate (P = 0.002), fat (P = 0.001), fiber (P = 0.003), vitamin C (P = 0.04), calcium (P = 0.005), waist circumference (P = 0.02), hip circumference (P = 0.001), Waist to Hip Ratio (P = 0.002), and BMI. The nutritional behavior of university students was poor. Therefore, it is essential to encourage young people, including university students to enrich their diets with milk, beans, fruit, and vegetables to decrease the risks of nutrition related disorders.


Nonrandom packaging of host RNAs in moloney murine leukemia virus.
Moloney murine leukemia virus (MLV) particles contain both viral genomic RNA and an assortment of host cell RNAs. Packaging of virus-encoded RNA is selective, with virions virtually devoid of spliced env mRNA and highly enriched for unspliced genome. Except for primer tRNA, it is unclear whether packaged host RNAs are randomly sampled from the cell or specifically encapsidated. To address possible biases in host RNA sampling, the relative abundances of several host RNAs in MLV particles and in producer cells were compared. Using 7SL RNA as a standard, some cellular RNAs, such as those of the Ro RNP, were found to be enriched in MLV particles in that their ratios relative to 7SL differed little, if at all, from their ratios in cells. Some RNAs were underrepresented, with ratios relative to 7SL several orders of magnitude lower in virions than in cells, while others displayed intermediate values. At least some enriched RNAs were encapsidated by genome-defective nucleocapsid mutants. Virion RNAs were not a random sample of the cytosol as a whole, since some cytoplasmic RNAs like tRNA(Met) were vastly underrepresented, while U6 spliceosomal RNA, which functions in the nucleus, was enriched. Real-time PCR demonstrated that env mRNA, although several orders of magnitude less abundant than unspliced viral RNA, was slightly enriched relative to actin mRNA in virions. These data demonstrate that certain host RNAs are nearly as enriched in virions as genomic RNA and suggest that Psi- mRNAs and some other host RNAs may be specifically excluded from assembly sites.


Secular and age distribution of scrotal cancer in Connecticut and a review of United States literature.
In contrast with the expectations of the authors and with reports suggesting a decline in risk for scrotal cancer, Connecticut Tumor Registry data neither showed detectable decrease in risk over the 45-year-period for all 95 scrotal malignancies nor for the 71 epithelial cancers. The age distribution of scrotal cancer in Connecticut was similar to that of the more common tumors thought to be caused by exogenous agents. The risk increased up to age 75 in a geometric fashion, followed by a plateau and decline in risk among the very elderly. United States literature on scrotal cancer points to a change in occupational risks; this literature and recent occupational data from Connecticut suggest that metalworking may have been associated with a high proportion of cases in recent decades. Evidence is lacking that scrotal cancer and its most recent marker of carcinogenic risk have been fully eliminated.


Bis-dinuclear (Cu-Gd)2 complexes with a probable helicate structure.
Two ligands have been designed to simultaneously favour complexation of 3d and 4f metal ions and the formation of helical structures. This synthetic strategy has allowed the isolation of two bis-dinuclear (Cu-Gd)(2) complexes [L(i)(2)Cu(2)Gd(2)(NO(3))(6)] derived from 3-alkoxysalicylaldehyde and 4,4'-diaminodiphenylmethane. The magnetic data shows that both bis-dinuclear complexes behave as two practically independent (Cu-Gd) pairs, each presenting a ferromagnetic interaction (J= 4.6 cm(-1)). Very weak additional antiferromagnetic interactions, probably originating from intra- and/or intermolecular [small pi] stackings, are suggested by the decrease in chiMT below 8 K.


The role of ABC transporters' gene polymorphism in the etiology of intrahepatic cholestasis of pregnancy.
The etiology of intrahepatic cholestasis of pregnancy (ICP) involves environmental, hormonal and genetic factors. It is thought that ICP may be related to the polymorphic variants of several genes involved in the metabolism and transport of bile acids (BA). The goal of our study was to evaluate the possible role of genetic polymorphic variants of ABC transporters in patients with ICP. 96 women with ICP (mean age of 30.42 years, mean gestational age of 36.83 gestation weeks) and 211 healthy pregnant women (mean age of 30.68 years, mean gestational age of 39.05 gestation weeks) were enrolled in the study. Genetic analysis was performed using a polymerase chain reaction / restriction fragment length polymorphism (PCR/RFLP) method. The following polymorphisms were analysed: 1331T > C (V444A) ABCB11 and 1954A > G (R652G) ABCB4. Our analysis of frequency of genotypes and alleles of the 1954A > G ABCB4 polymorphism revealed no significant differences between the ICP and control groups. For the 1331T > C polymorphism of the ABCB11 gene the results revealed a higher frequency of 1331CC genotypes in the ICP group (39.58% vs. 29.38%. OR = 1.57, p = 0.05). Also, the frequency of the 1331C allele was higher in the ICP group compared to the control group (64.06% vs. 55.69%, OR = 1.42, p = 0.03). The overrepresentation of mutated variants of the 1331T > C ABCB11 polymorphism in the ICP group suggests its contribution to the etiology of the intrahepatic cholestasis of pregnancy. Analysis of genotypes' co-existence pointed to the possibility of the mutated variants of polymorphism 1954A > G ABCB4 and 1331T > C ABCB11 having a summation effect on the development of ICP.


Microparticle surface protein are associated with experimental venous thrombosis: a preliminary study.
Microparticles are small membrane vesicles released from activated cells and are associated with thrombosis and inflammation. Microparticle contain a unique subset of surface protein derived form the parent cell and may be responsible for their diverse biological functions. To identify these proteins, juvenile baboons (Papio anubis, n = 4) underwent iliac vein thrombosis with 6-hour balloon occlusion. Plasma samples were taken at baselines and at 2 days postthrombosis for microparticle analysis. Microparticles were extracted from platelet-poor plasma, digest separately with trypsin and tagged using isobaric tagging for relative and absolute quantitation reagents. The digests were subjected to 2-dimensional liquid chromatographic separation followed by matrix-assisted laser desorption/ionization tandem mass spectrometry. Peak lists were generated and searched against all primate sequences. For protein identity, a minimum of 2 peptides at 95% confidence interval was required. Later, isobaric tagging for relative and absolute quantitation ratios were generated comparing relative protein level of day 2 to baseline. The proteomic analysis was performed twice for each blood sample, totaling 8 experiments. Proteins were considered elevated of depressed if the isobaris tagging for relative and absolute quantitation ratio deviated by 20% changes from normal and a P value less than .05. Significantly, 7 proteins were differentially expressed on day 2 compared to baseline, and appeared in at least 3 animals and regulated in at least 4 experiment. Among these 7 proteins, upregulated proteins include various forms of fibrinogen and alpha-1-antichymotrypsin and downregulated proteins include immunoglobulins. These proteins influence thrombosis and inflammation through hemostatic plug formation (fibrinogen), inhibiting neutrophil adhesion (alpha-1-antichymoptrypsin), and immunoregulation (immunoglobulins). Further studies are needed to confirm the mechanistic role of these proteins in the pathogenesis of venous thrombosis.


Role of matrix metalloproteinases in radicular cysts and periapical granulomas.
The aim of the present study was to evaluate the expression and distribution of different classes of matrix metalloproteinases (MMPs) in radicular cysts and periapical granulomas. Twenty consecutive specimens of radicular cysts and 20 of periapical granulomas were selected. Expression of MMP-2, -9, -8, -13, -3 was immunohistochemically evaluated. The intensity of expression of the MMPs was evaluated using a semi-quantitative analysis: low = +; intermediate = ++; high = +++. Positive expression of MMPs was present with different distribution. MMP-9 expressed differently in the lesions. Indeed, in periapical granulomas low expression was found in endothelial cells and fibroblasts, whilst high intensities were only detected in inflammatory cells. On the contrary, in radicular cysts the high intensities were mainly present in keratinocytes and fibroblasts. MMP-8 was mainly expressed in inflammatory cells of periapical granulomas. MMP-2 and -3 presented a low intensity of expression in both groups. MMP-13 showed a variable pattern of distribution in the different cell types of the two different lesions. The present investigation supports the role of MMPs in the inflammatory process leading to the development of radicular cysts and periapical granulomas. The results of the present study suggested that the increased enlargement of radicular cysts, compared to periapical granulomas, might be related to a higher expression of MMP-9. On the other hands, the higher intensity of expression of MMP-8 in periapical granulomas could be related to an active inflammatory process. MMP-8 could play an important role in the inflammation processes during the development of periapical lesions.


Bleeding during pregnancy as a reason for interventions by emergency medical services teams in Poland.
Vaginal bleeding during pregnancy is associated with risks to the health and life of the woman and/or the foetus. Moreover, it is usually unanticipated, which requires on-site care to be provided to the woman. Such care is handled by emergency medical services (EMS) teams until specialist obstetric care can be provided. The purpose of study was to analyze the characteristics of EMS team responses to calls regarding pregnant women with vaginal bleeding, considering the location of call: urban vs. rural area. The study was based on a retrospective analysis of 5,487 EMS team interventions due to vaginal bleeding in pregnant women in Poland. The data analyzed included the period January 2018-December 2019, obtained from the National Monitoring Centre of Emergency Medical Services. The teams were more commonly dispatched to pregnant women in rural areas, who were more likely to be older and in the course of a second (27.52% vs. 26.88%) or subsequent pregnancy (34.00% vs. 27.49%), to have had one (28.22% vs. 26.75%) or more previous births (28.87% vs. 22.87%), and to have antepartum bleeding (23.91% vs. 20.36%) than those from urban areas. The mean time between receipt of the call and patient hand-over at the hospital by the EMS team was longer in rural areas (50.00 vs. 37.23 minutes). EMS teams responding to calls from rural areas regarding pregnant women with vaginal bleeding were most commonly dispatched in the summer, and the mean time between the receipt of the call and patient hand-over at the hospital was longer than in the calls from urban areas. Compared to patients calling from urban areas, those from rural areas were also more likely to be pregnant for the second or subsequent time, to have antepartum bleeding, and to have given birth before.


Spindle assembly checkpoint satisfaction occurs via end-on but not lateral attachments under tension.
To ensure accurate chromosome segregation, the spindle assembly checkpoint (SAC) prevents anaphase until all kinetochores attach to the spindle. What signals the SAC monitors remains unclear. We do not know the contributions of different microtubule attachment features or tension from biorientation to SAC satisfaction nor how these possible cues change during attachment. In this study, we quantify concurrent Mad1 intensity and report on SAC silencing, real-time attachment geometry, occupancy, and tension at individual mammalian kinetochores. We show that Mad1 loss from the kinetochore is switch-like with robust kinetics and that tension across sister kinetochores is established just before Mad1 loss events at the first sister. We demonstrate that CenpE-mediated lateral attachment of the second sister can persistently generate this metaphase-like tension before biorientation, likely stabilizing sister end-on attachment, yet cannot induce Mad1 loss from that kinetochore. Instead, Mad1 loss begins after several end-on microtubules attach. Thus, end-on attachment provides geometry-specific molecular cues or force on specific kinetochore linkages that other attachment geometries cannot provide.


The comparative safety of abciximab versus eptifibatide in patients on dialysis undergoing percutaneous coronary intervention: Insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2).
We sought to evaluate the patterns of use and outcomes associated with eptifibatide and abciximab administration among dialysis patients who underwent percutaneous coronary intervention (PCI). Contraindicated medications are frequently administered to dialysis patients undergoing PCI often resulting in adverse outcomes. Eptifibatide is a glycoprotein IIb/IIIa inhibitor that is often used during PCI and is contraindicated in dialysis. We included dialysis patients who underwent PCI from January 2010 to September 2015 at 47 hospitals in Michigan. We compared outcomes between patients who received eptifibatide compared with abciximab. Both groups required concurrent treatment with unfractionated heparin only. In-hospital outcomes included repeat PCI, bleeding, major bleeding, need for transfusion, and death. Optimal full matching was used to adjust for non-random drug administration. Of 177 963 patients who underwent PCI, 4303 (2.4%) were on dialysis. Among those, 384 (8.9%) received eptifibatide and 100 (2.3%) received abciximab. Prior to matching, patients who received eptifibatide had higher pre-procedural hemoglobin levels (11.3 g/dL vs. 10.7 g/dL; P < 0.001) and less frequently had a history of myocardial infarction (36.5% vs. 52.0%; P = 0.005). After matching, there were no significant differences in in-hospital outcomes between eptifibatide and abciximab including transfusion (aOR: 1.15; 95%CI: 0.55-2.40; P = 0.70), bleeding (1.47; 0.64-3.40; P = 0.36), major bleeding (4.68; 0.42-52.3; P = 0.21), repeat PCI (0.38; 0.03-4.23; P = 0.43), and death (1.53; 0.2-9.05; P = 0.64). Despite being contraindicated in dialysis, eptifibatide was used approximately 3.5 times more frequently than abciximab among dialysis patients undergoing PCI but was associated with similar in-hospital outcomes.


The role of the complement system in innate immunity.
Complement is a major component of innate immune system involved in defending against all the foreign pathogens through complement fragments that participate in opsonization, chemotaxis, and activation of leukocytes and through cytolysis by C5b-9 membrane attack complex. Bacterias and viruses have adapted in various ways to escape the complement activation, and they take advantage of the complement system by using the host complement receptors to infect various cells. Complement activation also participates in clearance of apoptotic cells and immune complexes. Moreover, at sublytic dose, C5b-9 was shown to promote cell survival. Recently it was also recognized that complement plays a key role in adaptive immunity by modulating and modifying the T cell responses. All these data suggest that complement activation constitutes a critical link between the innate and acquired immune responses.


Cell Surface Transporters and Novel Drug Developments.
Despite the numerous scientific and technological advances made within the last decade the attrition rates for new drug discovery remain as high as 95% for anticancer drugs. Recent drug development has been in part guided by Lipinski's Rule of 5 (Ro5) even though many approved drugs do not comply to these rules. With Covid-19 vaccine development strategy dramatically accelerating drug development perhaps it is timely to question the generic drug development process itself to find a more efficient, cost effective, and successful approach. It is widely believed that drugs permeate cells via two methods: phospholipid bilayer diffusion and carrier mediated transporters. However, emerging evidence suggests that carrier mediated transport may be the primary mechanism of drug uptake and not diffusion as long believed. Computational biology increasingly assists drug design to achieve desirable absorption, distribution, metabolism, elimination and toxicity (ADMET) properties. Perfecting drug entry into target cells as a prerequisite to intracellular drug action is a logical and compelling route and is expected to reduce drug attrition rates, particularly gaining favour amongst chronic lifelong therapeutics. Novel drug development is rapidly expanding from the utilisation of beyond the rule of five (bRo5) to pulsatile drug delivery systems and fragment based drug design. Utilising transporters as drug targets and advocating bRo5 molecules may be the solution to increasing drug specificity, reducing dosage and toxicity and thus revolutionising drug development. This review explores the development of cell surface transporter exploitation in drug development and the relationship with improved therapeutic index.


Compelling reasons for recommending IUDs to any woman of reproductive age.
The intrauterine device (IUD) is a highly effective method of contraception that, as opposed to other countries around the world, is underutilized in the United States by women of all ages. Lingering concerns about the safety of IUDs are in large part responsible for their lack of adoption, but a systematic review published recently nullified some of the major safety concerns about IUD use. The author summarized the methodologically sound evidence regarding the risk of upper-genital-tract infection and infertility associated with IUD use and reported that a slightly increased risk of pelvic inflammatory disease (PID) exists only in the first month following IUD insertion; that the risk of PID in women with symptomless sexually transmitted diseases (STDs) having an IUD inserted is similar to the risk in women not having an IUD inserted; and that there appears to be no negative effect on fertility following IUD removal. In addition, Mirena provides noncontraceptive benefits, such as treatment for menorrhagia, dysmenorrhea, and anemia, and ParaGard may help protect against endometrial cancer. An IUD is also a safer alternative to sterilization for perimenopausal women seeking a long-term and also reversible method of contraception. While both IUDs are suitable for many women of all ages, there are differences in their mechanisms of action, physical characteristics, and clinical effects that make each more or less appropriate for certain women.


Expression, oncological and immunological characterizations of BZW1/2 in pancreatic adenocarcinoma.
Background: Despite the progress in early diagnosis and treatment, prognosis of pancreatic adenocarcinoma (PAAD) is still poor. Basic leucine zipper and W2 domain-containing protein 1 (BZW1) and protein 2 (BZW2) are attached to the basic leucine zipper (bZIP) superfamily. Recently, BZW1 was identified as an important role in glycolysis of PAAD. However, the comprehensive reports about BZW1/2 in PAAD are not sufficient. Methods: RNA-seq data in the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were retrospectively analyzed. We explored the expression of BZW1/2 in PAAD tissues and the associations between BZW1/2 and prognosis. In addition, the potential roles of BZW1/2 in tumor microenvironment (TME) of PAAD were analyzed. Finally, clinicopathological data of 49 patients with PAAD in our institution were collected. Immunohistochemistry was used to determine the expression of BZW1/2 in PAAD samples. Results: BZW1 and BZW2 were upregulated in PAAD tissues compared to normal tissues (p < 0.05). The expression of BZW1/2 were not significantly correlated with gender, grade and stage of PAAD (p > 0.05). High expression of BZW2 was an independent predictor for poor prognosis of PAAD (HR 1.834, 95%CI 1.303-2.581, p = 0.001). And a nomogram to predict overall survival (OS) of PAAD was established with a C-index of 0.685. BZW1 and BZW2 expression were positively associated with T cell mediated immune response to tumor cell and Th2 cells in xCell database. Tumor Immune Single-Cell Hub (TISCH) analyses indicated that BZW1 and BZW2 were mainly expressed in B cells and malignant cells. External cohort furtherly validated that high expression of BZW1 and BZW2 were predictors for poor prognosis of PAAD. Conclusion: We found that BZW1 and BZW2 are highly expressed in malignant cells and B cells in the TME of PAAD. BZW2 is an independent predictor for OS of PAAD. BZW1 and BZW2 expression are positively associated with T cell mediated immune response to tumor cell and Th2 cells in PAAD.


Heterogeneity and Factorial Structure in Alzheimer's Disease: A Cognitive Perspective.
Alzheimer's disease (AD) patients show heterogeneous cognitive profiles which suggest the existence of cognitive subgroups. A deeper comprehension of this heterogeneity could contribute to move toward a precision medicine perspective. In this study, we aimed 1) to investigate AD cognitive heterogeneity as a product of the combination of within- (factors) and between-patients (sub-phenotypes) components, and 2) to promote its assessment in clinical practice by defining a small set of critical tests for this purpose. We performed factor mixture analysis (FMA) on neurocognitive assessment results of N = 230 patients with a clinical diagnosis of AD. This technique allowed to investigate the structure of cognitive heterogeneity in this sample and to characterize the core features of cognitive sub-phenotypes. Subsequently, we performed a tests selection based on logistic regression to highlight the best tests to detect AD patients in our sample. Finally, the accuracy of the same tests in the discrimination of sub-phenotypes was evaluated. FMA revealed a structure characterized by five latent factors and four groups, which were identifiable by means of a few cognitive tests and were mainly characterized by memory deficits with visuospatial difficulties ("Visuospatial AD"), typical AD cognitive pattern ("Typical AD"), less impaired memory ("Mild AD"), and language/praxis deficits with relatively spared memory ("Nonamnestic AD"). The structure of cognitive heterogeneity in our sample of AD patients, as studied by FMA, could be summarized by four sub-phenotypes with distinct cognitive characteristics easily identifiable in clinical practice. Clinical implications under the precision medicine framework are discussed.


A transcriptome analysis of isoamyl alcohol-induced filamentation in yeast reveals a novel role for Gre2p as isovaleraldehyde reductase.
A transcriptome analysis was performed of Saccharomyces cerevisiae undergoing isoamyl alcohol-induced filament formation. In the crucial first 5 h of this process, only four mRNA species displayed strong and statistically significant increases in their levels of more than 10-fold. Two of these (YEL071w/DLD3 and YOL151w/GRE2) appear to play important roles in filamentation. The biochemical activities ascribed to these two genes (d-lactate dehydrogenase and methylglyoxal reductase, respectively) displayed similarly timed increases to those of their respective mRNAs. Mutants carrying dld3 mutations displayed reduced filamentation in 0.5% isoamyl alcohol and needed a higher concentration of isoamyl alcohol to effect more complete filament formation. Hence, DLD3 seems to be required for a full response to isoamyl alcohol, but is not absolutely essential for it. Mutants carrying gre2 mutations were derepressed for filament formation and formed large, invasive filaments even in the absence of isoamyl alcohol. These results indicate a previously unsuspected and novel role for the GRE2 gene product as a suppressor of filamentation by virtue of encoding isovaleraldehyde reductase activity.


Laterality and otorhinolaryngology: a review.
Laterality of paired organs involves the function of the eyes, ears, hands and feet. Whilst most people have a right-handed preference, about 10 per cent are left-handed. Similarly, the right eye is usually preferred to the left. Medicine is both taught and practised for those with right hand and eye preference, and left-handed medical students and doctors must negotiate the right-handed world. This brief review looks at society's attitudes, medical training and the practice of otolaryngology in the UK towards laterality and handedness. Literature review. Studies suggest that left-handers are more versatile and so are more ambidextrous. Conversely, this may result in problems when a right-hander tries to undertake a procedure with the non-dominant hand. Cultures and attitudes are changing towards those who are left-handed. Left-handed surgeons may encounter difficulties in the clinical environment throughout their training.


Effect of Vitamin B6 on Osteoporosis Fracture.
Osteoporosis is a medical condition that causes bones to become weak and brittle, making them more likely to break or fracture. This condition occurs when the body loses too much bone, makes too little bone, or both. Bones are living tissues that are constantly being broken down and rebuilt. However, as we age, this process slows down, and our bodies may be unable to replace bone as quickly as it is broken down. This can lead to a loss of bone density, making bones weaker and more prone to fracture. Unfortunately, osteoporosis often has no symptoms until a bone is broken, so taking steps to prevent this condition is essential. This may include getting enough calcium and vitamin D, engaging in weight-bearing exercise, quitting smoking, limiting alcohol intake, and taking medication if prescribed by a doctor. Vitamin B6, also known as pyridoxine, is a water-soluble vitamin that plays a vital role in various bodily functions. It is part of the B-vitamin complex and is essential for metabolizing proteins, carbohydrates, and fats. Vitamin B6 produces neurotransmitters such as serotonin, which helps regulate mood, and dopamine, which is involved in motivation and reward. Several previous studies have found that women with higher intakes of vitamin B6 have higher bone mineral density (BMD) of the hips and spine than women with lower intakes. Another study found that men and women with higher blood levels of vitamin B6 had higher BMD in the hips and spine.


Novel Strategy to Improve the Performance of Localization in WSN.
A novel strategy of discrete energy consumption model for WSN based on quasi Monte Carlo and crude Monte Carlo method is developed. In our model the discrete hidden Markov process plays a major role in analyzing the node location in heterogeneous media. In this energy consumption model we use both static and dynamic sensor nodes to monitor the optimized energy of all sensor nodes in which every sensor state can be considered as the dynamic Bayesian network. By using this method the power is assigned in terms of dynamic manner to each sensor over discrete time steps to control the graphical structure of our network. The simulation and experiment result shows that our proposed methods are better in terms of localization accuracy and possess minimum computational time over existing localization method.


Surface-enhanced Raman spectroscopy and density functional theory study on 4,4'-bipyridine molecule.
The molecular geometry and vibrational frequencies of 4,4'-bipyridine (BPE) in the ground state were calculated using density functional theory (DFT) methods (B3LYP) with 6-31++G(d,p) basis set. The optimized geometric bond lengths and bond angles are obtained by DFT employing the hybrid of Beckes non-local three parameter exchange and correlation functional and Lee-Yang-Parr correlation functional. Fourier transform infrared (FT-IR), Fourier transform Raman (FT-Raman) and near-infrared surface-enhanced Raman scattering (NIR-SERS) spectra of BPE on the silver foil substrate have been recorded. All FT-IR, FT-Raman and NIR-SERS band were assigned on the basis of the B3LYP/6-31++G(d,p) method. The vibrational frequencies obtained by DFT(3LYP) are in good agreement with observed results. The NIR-SERS of BPE excited by 1064nm laser line is little difference with that excited by visible laser line. This phenomenon is result to the increase of the contribution of CHEM enhancement effect. Surface selection rules derived from the electromagnetic enhancement model were employed to infer the orientations of BPE on the silver foil substrate surface. Some vibrational frequency which are sensitive to the planar or non-planar structure of BPE, and to the dihedral angle were concluded.


GENOTYPE-ENVIRONMENT INTERACTION FOR JUVENILE GROWTH IN THE HARD CLAM MERCENARIA MERCENARIA (L.).
Offspring from half-sib and full-sib families of the hard clam, Mercenaria mercenaria were reared in five locations along the Atlantic Coast to test for the presence of genotype-environment interaction for juvenile growth rate. Location effects upon growth rate variation were prevalent; of the genetic effects, the additive genetic by location variance was predominant with the nonadditive genetic by location component contributing to a lesser degree to the interaction variance. The additive and nonadditive variation over all environments was negligible. Genotype-environment interaction was found to be at least partially due to a change in the amount of genetic variation expressed at each location; with significant additive variation detected at Charleston and Georgetown, SC sites and significant nonadditive variation at Millsboro, DE. Genetic covariance/correlation analysis indicated that reversals in relative family performance across locations were prevalent, implying the possibility of habitat specialization among genotypes. In addition, graphical analysis produced no evidence of a ubiquitously superior genotype. These analyses suggest that genotype-environment interaction should act to constrain the evolution of juvenile growth rate in Mercenaria, preserve any heritable variation associated with this trait and may lead to the development of phenotypic plasticity for growth.


Sexual behavior and sexually transmitted diseases in street-based female sex workers in Rajshahi City, Bangladesh.
We analyzed the sexual behavior and sexually transmitted diseases (STDs) of street-based female sex workers (SFSWs) of Rajshahi city and examined their socio-demographic profiles. Among the SFSWs attending three drop-in centers (DIC) named PIACT, PROVA, and Suraksha Madhumita in Rajshahi, 150 self-motivated and willing individuals were interviewed through a structured questionnaire to obtain obstetric histories and socio-demographic information. Among these SFSWs, 56.7% were infected with two or more pathogens of STDs, with gonorrhea, chlamydia, herpes, syphilis, and trichomoniasis observed in 23.3, 27.3, 24.0, 17.3, and 20.0%, respectively. We found a strong association between the prevalence of STDs among SFSWs and their socio-demographic profiles. Illiterate and comparatively older SFSWs who spent very little money for health purposes, had larger numbers of children, and used condoms inconsistently were observed to be at higher risk of STDs. These results observed with bivariate analysis were also confirmed by logistic regression analysis.


Molecular epidemiology of hepatitis delta virus (HDV) in Iran: a preliminary report.
To identify hepatitis delta virus (HDV) genetic variability and its circulating genotypes amongst infected Iranian patients, 25 patients with positive anti-HDV status from different parts of Iran were enrolled in this cross-sectional study. A portion of the HDV delta antigen was amplified, sequenced, and subjected to molecular and phylogenetic analysis. Clinical features and virological markers were evaluated. HDV RNA could be detected in 88% of anti-HDV positive cases (22 patients) with chronic hepatitis B virus (HBV) infection and liver cirrhosis. Phylogenetic analysis revealed that all Iranian patients were infected by genotype I (clade 1) of HDV, supported by a high bootstrap value (100%, 1,000 replicates). All HDV-positive patients were coinfected with genotype D1 of HBV. No significant association was determined between demographic, clinical, and virological variables in the population studied. In conclusion, the present molecular epidemiology survey reveals that clade 1 of HDV is predominant among coinfected HBV patients in Iran.


Effect of different surface penetrating sealants on the roughness of a nanofiller composite resin.
This study evaluated the effectiveness of different sealants applied to a nanofiller composite resin. Forty specimens of Filtek Z-350 were obtained after inserting the material in a 6x3 mm stainless steel mold followed by light activation for 20 s. The groups were divided (n=10) according to the surface treatment applied: Control group (no surface treatment), Fortify, Fortify Plus and Biscover LV. The specimens were subjected to simulated toothbrushing using a 200 g load and 250 strokes/min to simulate 1 week, 1, 3 and 6 months and 1 and 3 years in the mouth, considering 10,000 cycles equivalent to 1 year of toothbrushing. Oral-B soft-bristle-tip toothbrush heads and Colgate Total dentifrice at a 1:2 water-dilution were used. After each simulated time, surface roughness was assessed in random triplicate readings. The data were submitted to two-way ANOVA and Tukey's test at a 95% confidence level. The specimens were observed under scanning electron microscopy (SEM) after each toothbrushing cycle. The control group was not significantly different (p>0.05) from the other groups, except for Fortify Plus (p<0.05), which was rougher. No significant differences (p>0.05) were observed at the 1-month assessment between the experimental and control groups. Fortify and Fortify Plus presented a rougher surface over time, differing from the baseline (p<0.05). Biscover LV did not differ (p>0.05) from the baseline at any time. None of the experimental groups showed a significantly better performance (p>0.05) than the control group at any time. SEM confirmed the differences found during the roughness testing. Surface penetrating sealants did not improve the roughness of nanofiller composite resin.


Surface pH and bond strength of a self-etching primer/adhesive system to intracoronal dentin after application of hydrogen peroxide bleach with sodium perborate.
This study compared the dentin bond strength of a self-etching primer/adhesive system with dentin surface pH with or without bleaching and observed the morphological changes in bleached dentin treated with a self-etching primer. Dentin disks were prepared from the coronal-labial region of 32 human anterior teeth. The pulpal surfaces of the dentin disks were polished with 600-grit SiC paper under running water. The dentin surfaces on all specimens were bleached with a mixture of 30% hydrogen peroxide and sodium perborate in 100% humidity at 37 degrees C for one week. The bleaching agent was then rinsed off with water for 5, 15 or 30 seconds. All specimens were stored in water at 37 degrees C. Half of the five-second rinsing specimens were stored in water for an additional week. Dentin surface pH with or without bleaching was examined using a pH-imaging microscope (SCHEM-100). A self-etching primer/adhesive system (Clearfil SE Bond) was applied to bleached or unbleached dentin according to the manufacturer's instructions. After 24-hour water storage, the bonded specimens were prepared for microtensile testing. Microtensile bond strength (microTBS) to dentin was measured using a universal-testing machine (EZ test, Shimadzu, Japan) at a crosshead speed of 1.0 mm/minute. Data were analyzed by one-way ANOVA and Scheffe's test (alpha=0.05). The pH values of the dentin surfaces of the 5 and 15 second rinsing groups were significantly higher than the control group (p<0.05), while the 30-second rinsing and one-week water storage groups had similar surface pH values to the control group (p<0.05). The microTBS of 5, 15 and 30 second rinsing specimens after bleaching were significantly lower than the control specimens (p<0.05). However, after one-week of water storage, the microTBS returned to the control group. The application of a bleaching agent increased the pH value of the dentin surface and decreased the bond strength of the self-etching primer/adhesive system. One-week water storage after bleaching recovered the surface pH and the microTBS to dentin.


[Central giant cell granuloma of the mandible. Definition and differential diagnosis].
The synopsis of radiographic examination (uni- or multilocular radiolucency), histologic findings (giant cells throughout a benign fibroblastic matrix), blood chemistry analysis (normal serum parathyroid hormone) and clinical features provides the definitive diagnosis of giant cell granuloma, allowing the clearly defined surgical management of this lesion. The case history of a 48-year-old female patient who presented with a giant cell granuloma in the right mandible is used to illustrate this controversially discussed intra-osseous lesion. The potential therapeutic change from radical operative treatment, including functional maintenance, to conservative procedures is emphasized.


Virtual Reality and Augmented Reality in Plastic Surgery: A Review.
Recently, virtual reality (VR) and augmented reality (AR) have received increasing attention, with the development of VR/AR devices such as head-mounted displays, haptic devices, and AR glasses. Medicine is considered to be one of the most effective applications of VR/AR. In this article, we describe a systematic literature review conducted to investigate the state-of-the-art VR/AR technology relevant to plastic surgery. The 35 studies that were ultimately selected were categorized into 3 representative topics: VR/AR-based preoperative planning, navigation, and training. In addition, future trends of VR/AR technology associated with plastic surgery and related fields are discussed.


Lipid Carriers in Cancer: Context Matters.
Investigating immune suppression mechanisms in cancer may inform on strategies to overcome resistance to current immunotherapies, common across solid tumor types but near ubiquitous in pancreatic ductal adenocarcinoma (PDAC). A recent study by Kemp and colleagues in Cancer Research identified an immuno-modulatory axis originating in tumor-associated macrophages whereby macrophage-derived apolipoprotein E (APOE) activates NF-κB in tumor cells in a paracrine manner, inducing expression of immunosuppressive chemokines. In contrast, APOE promotes antitumor immunity in other cancer types including melanoma, highlighting the context dependency of APOE signaling and its impact on the tumor microenvironment. As new immunotherapy approaches increasingly aim to modulate both the myeloid and lymphoid compartments of the PDAC immune milieu, identification of specific mechanisms that foster macrophage-mediated immune suppression may facilitate the development of effective strategies that enable the immune system to tackle these tumors.See related article by Kemp et al., p. 4305.


Ornithine δ-aminotransferase OsOAT is critical for male fertility and cold tolerance during rice plant development.
Cold stress is a major factor limiting the production and geographical distribution of rice (Oryza sativa) varieties. However, the molecular mechanisms underlying cold tolerance remain to be elucidated. Here, we report that ornithine δ-aminotransferase (OsOAT) contributes to cold tolerance during the vegetative and reproductive development of rice. osoat mutant was identified as a temperature-sensitive male sterile mutant with deformed floral organs and seedlings sensitive to cold stress. Comparative transcriptome analysis showed that OsOAT mutation and cold treatment of the wild-type plant led to similar changes in the global gene expression profiles in anthers. OsOAT genes in indica rice Huanghuazhan (HHZ) and japonica rice Wuyungeng (WYG) are different in gene structure and response to cold. OsOAT is cold-inducible in WYG but cold-irresponsive in HHZ. Further studies showed that indica varieties carry both WYG-type and HHZ-type OsOAT, whereas japonica varieties mostly carry WYG-type OsOAT. Cultivars carrying HHZ-type OsOAT are mainly distributed in low-latitude regions, whereas varieties carrying WYG-type OsOAT are distributed in both low- and high-latitude regions. Moreover, indica varieties carrying WYG-type OsOAT generally have higher seed-setting rates than those carrying HHZ-type OsOAT under cold stress at reproductive stage, highlighting the favorable selection for WYG-type OsOAT during domestication and breeding to cope with low temperatures.


Gamma-glutamyl transpeptidase activity mediates NF-kappaB activation through lipid peroxidation in human leukemia U937 cells.
Gamma-glutamyl transpeptidase (GGT) is a key enzyme in the catabolism of glutathione (GSH). Recently, it has been reported that the extracellular cleavage of GSH by GGT induced the production of reactive oxygen species (ROS), suggesting that GGT plays a pro-oxidant role. In the present study, we investigated the nature of the oxidative stress generate by glutathione and GGT and the possibility that this stress affects the activity of NF-kappaB a prototypical oxidant-stress-responsive transcription factor. We found that, in the presence of iron, a natural substrate of GGT, glutathione induces lipid peroxidation in U937 cells. This induction depends on GGT activity as it is prevented by the Serine/Borate complex, a GGT inhibitor. We found that y-glutamyl transpeptidase activity induces NF-kappaB DNA binding activity, an effect which is significantly reduced by the addition of GGT inhibitors (Serine/Borate complex and Acivicin). Moreover, we show that lipid peroxidation is involved in GGT-dependent NF-kappaB activation since vitamin E, which completely inhibits GGT-induced generation of lipid peroxides, prevents the GGT-dependent NF-kappaB activation. Finally, inhibition of GGT by either the Serine/Borate complex or by Acivicin resulted in cell apoptosis. This finding suggests that GGT-mediated NF-kappaB activation plays a role in the control of apoptosis in U937 cells.


Transantral-ethmoidal decompression of optic canal fracture.
A case of indirect trauma to the optic nerve was successfully treated with transethmoidal decompression. The literature was reviewed, and reports of poor results from neurosurgical procedures are cited. Improved results from transethmoidal decompression of the optic nerve have been reported by Japanese authors but, in our opinion, without proper selection of cases. Early diagnosis of traumatic compression of the intracanalicular optic nerve as evidenced by delayed and/or progressive vision loss following injury, coupled with prompt transantral-ethmoidal surgical decompression, should yield gratifying results in the treatment of this uncommon condition.


Interaction of infectious viral particles with a quaternary ammonium chlorid (QAC) surface.
The antiviral activity of a surface-bonded quaternary ammonium chloride (QAC) was examined in this study. The mechanism of inactivation was elucidated by a combination of infectivity assay, radioactive labeling assay, and sedimentation analysis. Although the virions are still infectious when attached onto the chemically modified surface, we found these viruses are inactivated if they are eluted from the surface. The inactivation is caused by the disruption of the viral envelope with subsequent release of the nucleocapsid. No evidence indicates the released nucleocapsid is further disrupted. An enveloped virus shows a much higher affinity for the QAC-treated surface than a nonenveloped one due to hydrophobic interaction. The QAC-treated beads can effectively remove the enveloped viruses at low protein concentrations. The titer of herpes simplex virus was reduced by a factor of nearly 5 logarithm units in a 0.5 wt % bovine serum albumin solution with less that 10% protein loss. However, the presence of proteins in the solution reduced both the rate and capacity of this nonspecific adsorption-inactivation process. As a consequence, the removal efficiency is relatively poor in solutions with high protein content.


A randomized, double-blind, placebo-controlled study of oral antioxidant supplement therapy in patients with dry eye syndrome.
To evaluate the efficacy of oral antioxidant supplementation in the treatment of patients with dry eye syndrome (DES). A prospective, randomized, double-blinded study compared the effects of an antioxidant supplement (containing anthocyanosides, astaxanthin, vitamins A, C, and E, and several herbal extracts, including Cassiae semen and Ophiopogonis japonicus) with placebo on patients with DES. We assessed dry eye symptoms, visual acuity, Schirmer's test, tear film breakup time, cornea and conjunctiva fluorescein staining, serum anti-SSA/anti-SSB antibodies, and the level of reactive oxygen species (ROS) in tears. The supplementation period was 8 weeks and patients were followed up every 4 weeks for 16 weeks. A linear mixed model was used to compare the groups, while within-group differences were tested by repeated-measures analysis of variance. Forty-three patients, 20 and 23 in treatment and placebo groups, respectively, completed the study. Liver and renal functions were normal. Diastolic blood pressure decreased in the treatment group. There were no significant differences in systolic blood pressure, dry eye symptoms, serum anti-SSA and anti-SSB, visual acuity, intraocular pressure, or fluorescein corneal staining between the groups. Tear film breakup time scores and Schirmer's test without topical anesthesia significantly improved in the treatment group. Tear ROS level differed between the groups and decreased after treatment. Overall subjective impression revealed a significant improvement with treatment compared with placebo. Oral antioxidant supplementations may increase tear production and improve tear film stability by reducing tear ROS. The vegetable-based antioxidant supplement used in this study is safe and can be utilized as an adjuvant therapy to conventional artificial tear therapy for patients with DES.


miR-146a-5p targets interleukin-1 receptor-associated kinase 1 to inhibit the growth, migration, and invasion of breast cancer cells.
MicroRNAs (miRNAs) are associated with the formation and progression of many types of cancers. In the present study, the aim was to elucidate the involvement of miR-146a-5p in the regulation of human breast cancer (BC) cell growth and invasion, as well as the mechanisms underlying its effects. Reverse transcription-quantitative polymerase chain reaction results revealed that miR-146a-5p was markedly downregulated in BC tissues relative to those of adjacent normal tissues. miR-146a-5p expression was also markedly downregulated in BC cells. Overexpression of miR-146a-5p significantly suppressed the proliferation, invasion and migration of BC MDA-MB-453 and MCF7 cells. Furthermore, the results indicated that miR-146a-5p downregulated the expression of interleukin-1 receptor-associated kinase 1 (IRAK1) by directly binding to its 3'-untranslated region in BC cells. Furthermore, IRAK1 expression was observed to be markedly upregulated and inversely correlated with miR-146a-5p expression in BC tissues. Mechanical studies indicated that restoring IRAK1 expression reversed the miR-146a-5p-induced inhibitory effects on proliferation and invasion of BC cells. In conclusion, miR-146a-5p may act as a tumor suppressor in BC by directly targeting IRAK1. These results highlighted the potential of miR-146a-5p as a novel therapeutic target for the treatment of BC.


Effect of a dihydropyridine-type calcium channel blocker on vascular remodeling after experimental balloon angioplasty.
Aim of the study was to evaluate the influence of the dihydropyridine derivative BW 9798 on intimal hyperplasia in a carotid artery injury model of New Zealand White rabbits on a high cholesterol diet. In carotid arteries of 50 New Zealand White rabbits atherosclerotic lesions were induced by cholesterol diet and electrostimulation of the artery. In 40 animals the resulting primary lesion was subjected to balloon angioplasty (BA). Three days prior to BA animals received BW 9798 or placebo per os until sacrifice three days or 28 days after BA. BW 9798 lead to increased cross sectional area by 128.3% and an increased luminal area by 157% after 28 days after BA compared with placebo. However the degree of stenosis did not significantly decrease. The cell count of the different layers of the arteries decreased by 64.5% in the intima and by 62.6% compared with placebo treated animals after BA. Additionally the number of smooth muscle cell (SMC) layers in the neointima was significantly lower in BW 9798 treated animals than in placebo animals (8±3 vs 14±9, p<0.05) although the proliferation was not changed by BW 9798 treatment 3 days after BA. BW 9798 leads to significant changes in vessel wall geometry although the influence on vascular remodeling of this compound is unclear. It can be speculated that the compound affects the homeostasis of extracellular matrix, invasion of inflammatory cells into the vessel wall and the expression of cytokines. However, further investigation needs to clarify the role of BW 9798 on remodelling after BA.


Analytical expressions of the front shape of non-quasi-neutral plasma expansions with anisotropic electron pressures.
An analytical expression is proposed to describe the front shape of a non-quasi-neutral plasma expansion with anisotropic electron pressures. It is of significance in the study of ultrashort plasma expansions generated from laser-foil interactions and anisotropic astroplasma expansions in space science. It is found that the plasma front shape depends on the relationship between the ratio of the longitudinal and the transverse temperature of hot electrons kappa;(2) and the electron-ion mass ratio mu . For kappa;(2)(micro,1] , the ion front is a part of an ellipse and the major axis is in the lower-temperature axis. For kappa;(2)< or =micro , the ion front is composed by a part of a hyperbolic and a small pointed projection at the center. In the strongly anisotropic region, there is an ultrashort anomalous plasma emission of tens of femtoseconds at the angle of near 90 degrees . The ion-velocity distribution and angular-energy distribution at the ion front have also been given. Particularly, anomalous positron emissions exist in the electron-positron plasma anisotropic expansion.


Portents from Orwell's 1984: Bureaucracies, Ministries of Truth and Plenty - challenges facing the administration of mental healthcare in Australia.
We reflect upon the processes of mental health administration in Australia with reference to George Orwell's novel, 1984. Mental healthcare in Australia is distorted by politicisation, spin and a refusal to acknowledge the reality of the current situation. These challenges for mental healthcare demonstrate some similarities with the Ministries of Truth and Plenty, which conversely performed as their opposites in Orwell's novel. Psychiatrists and their professional bodies should play a greater role in advocacy for clinician-led, evidence-based services in partnership with our communities.


Thymic NF-κB-inducing kinase regulates CD4+ T cell-elicited liver injury and fibrosis in mice.
The liver is an immunologically-privileged organ. Breakdown of liver immune privilege has been reported in chronic liver disease; however, the role of adaptive immunity in liver injury is poorly defined. Nuclear factor-κB-inducing kinase (NIK) is known to regulate immune tissue development, but its role in maintaining liver homeostasis remains unknown. This study aimed to assess the role of NIK, particularly thymic NIK, in regulating liver adaptive immunity. NIK was deleted systemically or conditionally using the Cre/loxp system. Cluster of differentiation [CD]4+ or CD8+ T cells were depleted using anti-CD4 or anti-CD8 antibody. Donor bone marrows or thymi were transferred into recipient mice. Immune cells were assessed by immunohistochemistry and flow cytometry. Global, but not liver-specific or hematopoietic lineage cell-specific, deletion of NIK induced fatal liver injury, inflammation, and fibrosis. Likewise, adoptive transfer of NIK-null, but not wild-type, thymi into immune-deficient mice induced liver inflammation, injury, and fibrosis in recipients. Liver inflammation was characterized by a massive expansion of T cells, particularly the CD4+ T cell subpopulation. Depletion of CD4+, but not CD8+, T cells fully protected against liver injury, inflammation, and fibrosis in NIK-null mice. NIK deficiency also resulted in inflammation in the lung, kidney, and pancreas, but to a lesser degree relative to the liver. Thymic NIK suppresses development of autoreactive T cells against liver antigens, and NIK deficiency in the thymus results in CD4+ T cell-orchestrated autoimmune hepatitis and liver fibrosis. Thus, thymic NIK is essential for the maintenance of liver immune privilege and liver homeostasis. We found that global or thymus-specific ablation of the NIK gene results in fatal autoimmune liver disease in mice. NIK-deficient mice develop liver inflammation, injury, and fibrosis. Our findings indicate that thymic NIK is essential for the maintenance of liver integrity and homeostasis.


Short- and long-term response of the adult dog ovary after 1200 R whole-body X-irradiation and transfusion of mononuclear leukocytes.
The effect of 1200 R whole-body X-irradiation after transfusion of mononuclear blood cells was investigated in 34 dog ovaries (beagle) for 6-1460 days after irradiation. Morphological observations suggest that gonadal and extragonadal function regenerated after irradiation. Follicular growth started 60 days after irradiation. The time required for follicular maturation was inferred to be about 110 days and the time of first ovulation about 170 days. Graafian follicles and corpora lutea were found 2, 3 and 4 years later. A pregnancy occurred 2 years after irradiation. Larger, growing and vesicular follicles were primarily affected by irradiation-induced atresia with damage of the granulosa. Oocytes appeared to be normal, even without the supporting granulosa cells ('naked oocytes'). The interstitial cortical tissue of the ovaries reacted in two ways. Either, it remained inactive (radiation effect I) or it showed the endocrine structure of mature interstitial gland cells (radiation effect II). Microadenomata were observed 195 days after irradiation.


Commentary: Contested Wills and Will Contests.
When disinherited heirs challenge a will drafted by a person suspected of having dementia, a legal battle may ensue. The "lucid interval," a brief return to competence from a state of dementia, has been invoked in years past to establish the validity of contested wills. Shulman et al., having reviewed the medical and legal literature, make a convincing argument that no such period of competence occurs in the course of dementia. A neuropsychiatric autopsy is outlined in this commentary to provide a method of determining the validity of a last will and testament, by applying the clinical method described when witness statements do not provide accurate guidance.


Phagocytosis: A Fundamental Process in Immunity.
One hundred years have passed since the death of Élie Metchnikoff (1845-1916). He was the first to observe the uptake of particles by cells and realized the importance of this process for the host response to injury and infection. He also was a strong advocate of the role of phagocytosis in cellular immunity, and with this he gave us the basis for our modern understanding of inflammation and the innate and acquired immune responses. Phagocytosis is an elegant but complex process for the ingestion and elimination of pathogens, but it is also important for the elimination of apoptotic cells and hence fundamental for tissue homeostasis. Phagocytosis can be divided into four main steps: (i) recognition of the target particle, (ii) signaling to activate the internalization machinery, (iii) phagosome formation, and (iv) phagolysosome maturation. In recent years, the use of new tools of molecular biology and microscopy has provided new insights into the cellular mechanisms of phagocytosis. In this review, we present a general view of our current knowledge on phagocytosis. We emphasize novel molecular findings, particularly on phagosome formation and maturation, and discuss aspects that remain incompletely understood.


Dual Gold-Catalyzed Formal Tetradehydro-Diels-Alder Reactions for the Synthesis of Carbazoles and Indolines.
This work reports a dual gold-catalyzed tetradehydro-Diels-Alder reaction for the synthesis of nitrogen-containing aromatic heterocycles. Under the catalytic system (IPrAuNTf2 /DIPEA), indolines and carbazoles as well as other N-containing aromatic heterocycles were prepared in high yields with good functional group tolerance. Unlike the traditional thermal tetradehydro-Diels-Alder reactions, diluted reaction concentration and radical prohibitors are not required for this protocol. Experimental data support a mechanism involving gold vinylidene species, which undergoes a 6 π electrocyclization, followed with 1,2-hydrogen shift.


Annexin A3 is a potential angiogenic mediator.
Angiogenesis is a complex process that is regulated by a variety of angiogenic activators and inhibitors. Disruption of the balanced angiogenesis leads to the progress of diseases such as tumor growth, rheumatoid arthritis, and various blood vessel-related disorders. Even though a number of proteins involved in angiogenesis have been identified so far, more protein factors remain to be identified due to complexity of the process. Here we report that annexin A3 (ANXA3) induces migration and tube formation of human umbilical vein endothelial cells. High level of vascular endothelial growth factor (VEGF), a prominent angiogenic factor, is also detected in conditioned medium obtained from cells transfected with ANXA3 expression plasmid. Reporter assays show that ANXA3 enhances hypoxia-inducible factor-1 (HIF-1) transactivation activity. Taken together, our results suggest that ANXA3 is a novel angiogenic factor that induces VEGF production through the HIF-1 pathway.


Equating rehabilitation outcome scales: developing common metrics.
Transparency with regard to measuring devices is one of the fundamental requirements for progress in science. The ability to derive comparable measures from different measuring devices is the cornerstone of transparency. To this end, progress in measuring and understanding rehabilitation outcomes requires that there is a method of measuring outcomes that is independent of the particular collection of items that is used to assess the outcomes. The purpose of this study is to develop a equivalence between the PECS Motor Skills and Cognition and Communication LifeScales with the FIM Motor Skills and Cognitive items. However, only the results of the Motor Skills Scale are reported here in the interest of brevity. This equating is based on approximately 500 simultaneous evaluations using bout the PECS and FIM scales on admission and discharge. The patients in this study were consecutive admissions to a free-standing rehabilitation hospital in early 1998. Patients from five diagnostic groups were included in this study, Brain Injury, Spinal Cord Injury, Stroke, Neuromuscular, and Musculoskeletal. The results indicate that it is possible to construct a common equal interval translation between the PECS and FIM for the two scales. Measures on the common metric can be based to either scale and are independent of the number of items completed. This use of these anchored scales will allow institutions using either the PECS and FIM to make direct comparisons of clinical outcomes with other institutions, independent of the particular outcome tool used to evaluate patients.


Perceived value of trauma autopsy among trauma medical directors and coroners.
Although autopsy is acknowledged as essential for improving quality of medical care of trauma patients and accuracy of injury surveillance systems, the autopsy rate has remained well below 100% for certain categories of trauma. We obtained recent documentation of the frequency of autopsy among trauma-related deaths in Ohio, and surveyed coroners and trauma program medical directors (TMDs) about the perceived benefits and challenges of performing autopsy. Copies of death certificates were obtained for the years 1996-2001. Death and autopsy rates were calculated and examined for trends over time. Surveys covering the topics of mechanisms of injury prompting autopsy, uses and users of autopsy data, and barriers to performing autopsy were sent to Ohio's coroners, coroners from nearby states, and Ohio TMDs. The chi(2)-test for trend analysed autopsy rates over time, while responses among groups were compared using the chi(2)-test. The autopsy rate for injury related deaths increased from 50% in 1996 to 66.5% in 2001 (p=.0018). During the study period the volume of autopsies rose by 18%, from 2990 to 3546. There was no review by the coroner in almost 10% of trauma deaths. TMDs more often indicated that autopsies advance medical knowledge than did Ohio and non-Ohio coroners (62.9% versus 33.4% and 47.6%, respectively, p=.016). TMDs more frequently reported themselves as users of autopsy information than did Ohio and non-Ohio coroners (91.4% versus 14.6% and 20%, respectively, p<.0001). All groups reported inadequate funds and personnel as the two most common barriers to performing autopsies, although TMDs were more likely to identify these as barriers than coroners (p<.0001). Almost 27% of Ohio coroners agreed with the statement, "I do not feel that trauma-related autopsies are necessary". Significant barriers exist to improving autopsy rates among trauma patients who die. These include not only more well-recognised impediments such as inadequate funds and personnel, but less commonly reported issues concerning differing points of view on the role of trauma-related autopsy among coroners and TMDs. To improve trauma-related autopsy rates, each of these issues requires attention and cooperation among all parties.


Fatal haemorrhage from the innominate artery complicating tracheostomy.
A fatal haemorrhage of the innominate artery complicating tracheostomy for obstructive carcinoma of the larynx is reported. The possible mechanism of the rupture is discussed and methods of management are suggested.


Pittsburgh Pneumonia Agent in a cadaveric renal transplant recipient.
Pittsburgh Pneumonia Agent, Legionella micdadei, is a recently recognized source of pulmonary infection in immunocompromised hosts. A literature review suggests a typical pattern of clinical and radiologic presentation, of which the following case is representative. Eighteen of twenty-one infections have occurred in recipients of cadaveric renal transplants, defining a population at risk. The onset often occurred within days to weeks of bolus doses of corticosteroids. Fever, often accompanied by mild pulmonary symptoms usually developed, coupled with nodular or segmental chest infiltrates which were often well defined or rapidly expansile. Recognition of this pattern followed by prompt open lung biopsy may lead to increased survival.


Crossed and uncrossed segmental synaptic effects on rectus abdominis motoneurons from cutaneous and cutaneous-muscle nerve in spinal cats and alpha-chloralose-anesthetized cats.
Segmental synaptic responses evoked by stimulation of the dorsal cutaneous and cutaneous-muscle (CD) nerve or the ventral cutaneous and cutaneous-muscle (CV) nerve were investigated with intracellular recording from rectus abdominis (RA) motoneurons in 49 spinal cats and 28 alpha-chloralose-anesthetized cats. No monosynaptic and few disynaptic connections existed in the circuit from the ipsilateral or contralateral CD or CV nerves to RA motoneurons in spinal cats. Polysynaptic EPSP responses equal to or over trisynaptic connections were dominant. In alpha-chloralose-anesthetized cats, RA motoneurons exhibited significantly more polysynaptic EPSP responses at lower stimulus intensities (1.5T and 2T) of ipsilateral CV nerve stimulation than at those of contralateral CV nerve stimulation. The result that there was no monosynaptic or disynaptic PSP in RA motoneurons produced by low-intensity stimulation of the ipsilateral CD or CV nerve containing the cutaneous-muscle nerves indicated that Ia afferents from the cutaneous-muscle did not connect mono- or di-synaptically to the RA motoneuron. RA motoneurons exhibited more polysynaptic IPSP responses in alpha-chloralose-anesthetized cats than in spinal cats. Segmental pathways from the CD or CV nerves to RA motoneurons might receive inhibitory descending inputs from the upper spinal cord or the brain, in contrast to those from the same nerves to obliquus externus abdominis motoneurons previously reported.


Effects of lipid emulsion and multivitamins on the growth of microorganisms in peripheral parenteral nutrition solutions.
Blood stream infections caused by Bacillus cereus or Serratia marcescens in patients receiving peripheral parenteral nutrition (PPN) have occasionally been reported in Japan, but these microorganisms are not major causes of blood stream infections in patients receiving total parenteral nutrition via a central venous catheter. In Japan, commercially available PPN solutions contain amino acids, glucose, and electrolytes, but not contain lipid emulsion (LE) and multivitamins (MV). In this study, the effects of LE and MV on the growth of microorganisms such as Bacillus cereus, Serratia marcescens, Staphylococcus aureus, and Candida albicans in PPN solutions were investigated. A commercial 3% amino acid and 7.5% glucose solution with electrolytes (AF) was used as the base solution to prepare test solutions (LAF, AFV, and LAFV) containing LE, MV, or both. Specifically, 20% LE was added to AF in a ratio of 1:9 to prepare LAF. MV was added to AF and LAF to prepare AFV and LAFV, respectively. A specified number of each microorganism was added to each 100 mL of AF, LAF, AFV, and LAFV in sterile plastic flasks, and all flasks were allowed to stand at room temperature. The number of colony forming units per mL of each microorganism was counted at 0, 24, and 48 hours after the addition of each microorganism. Both Bacillus cereus and Serratia marcescens increased rapidly in AF as well as in LAF, AFV, and LAFV. Staphylococcus aureus did not increased in AF, but increased slightly in LAF and increased rapidly in AFV and LAFV. Candida albicans increased slightly in AF and increased rapidly in LAF, AFV, and LAFV. The results suggest the followings: if microbial contamination occurs, 1) Bacillus cereus and Serratia marcescens can grow rapidly in PPN solutions consisting of amino acids, glucose and electrolytes; 2) Staphylococcus aureus cannot grow without LE and MV, but can grow rapidly with MV; 3) Candida albicans can grow slowly without LE and MV, and the addition of LE or MV accelerates its growth.


[The terminal cancer patient. Problems of medical care and need for improvement].
On the basis of personal experience of many patients affected by neoplastic lesions, the conviction that the assistance provided to a terminal cancer patient in the hospital ward is deficient and takes no account of the medical, emotional, social and spiritual needs of the patient and his family, is expressed. It would be advisable for assistance to terminale patients to be supplied in adequate centres operating on multidepartmental bases, with the participation of experts in antalgic treatment and psychological problems.


Live fast, die soon: cell cycle progression and lifespan in yeast cells.
Our understanding of lifespan has benefited enormously from the study of a simple model, the yeast Saccharomyces cerevisiae. Although a unicellular organism, yeasts undergo many of the processes directly related with aging that to some extent are conserved in mammalian cells. Nutrient-limiting conditions have been involved in lifespan extension, especially in the case of caloric restriction, which also has a direct impact on cell cycle progression. In fact, other environmental stresses (osmotic, oxidative) that interfere with normal cell cycle progression also influence the lifespan of cells, indicating a relationship between lifespan and cell cycle control. In the present review we compile and discuss new findings related to how cell cycle progression is regulated by other nutrients. We centred this review on the analysis of phosphate, also give some attention to nitrogen, and the impact of these nutrients on lifespan.


Fascinating Magnetic Energy Storage Nanomaterials: A Brief Review.
In this brief review, the importance of nanotechnology in developing novel magnetic energy storage materials is discussed. The discussion covers recent patents on permanent magnetic materials and especially covers processing of permanent magnets (rare-earth and rare-earth free magnets), importance of rare-earth permanent magnets and necessity of rare-earth free permanent magnets. Magnetic energy storage materials are those magnetic materials which exhibit very high energy product (BH)max (where B is the magnetic induction in Gauss (G) whereas H is the applied magnetic field in Oersted (Oe)). (BH)max is the direct measure of the ability of a magnetic material to store energy. In this context, processing of magnetic energy storage composite materials constituted by soft and hard magnetic materials played a predominant role in achieving high (BH)max values due to the exchange coupling phenomenon between the soft and hard magnetic phases within the composite. Magnetic energy storage composites are normally composed of rare-earth magnetic materials as well as rare-earth free magnetic materials. Nanotechnology's influence on the enhancement of energy product due to the exchange coupling phenomenon is of great prominence and therefore discussed in this review.


Sandwich-Structured Upconversion Nanoprobes Coated with a Thin Silica Layer for Mitochondria-Targeted Cooperative Photodynamic Therapy for Solid Malignant Tumors.
Upconversion nanoparticles-based photodynamic nanotheranostic agents (UCNPs-PDT) have received great interest due to improved tissue penetration, weak autofluorescence, and low biotoxicity. However, conventional UCNPs-PDT are often limited by low energy transfer efficiency from UCNPs to photosensitizer (PS) molecules and insufficient generation and limited diffusion distance of reactive oxygen species (ROSs). Herein, an "all in one" nanotheranostic agent has been developed which has multicolor sandwich-structured UCNPs (SWUCNPs) as the core, a thin silica layer with a mitochondria-targeted group for loading dual PS as the medium layer, and polyethylene glycol-folic acid (PEG-FA) chains as the outer layer. Multicolor SWUCNPs simultaneously achieve two-photon fluorescence imaging and serve as energy donor for dual PS molecules. The thin luminescence layer and silica layer control most UCNPs activators and PS molecules in the effective energy transfer distance to guarantee a high energy transfer efficiency. Via FA-mediated endocytosis, the nanotheranostic agent is selectively endocytosed by cancer cells, is released from the endosome/lysosome, targets the mitochondria, and in situ produces ROSs under excitation from NIR, leading to significant mitochondria-mediated cell apoptosis. Furthermore, the established nanotheranostic agent shows tumor targetability, increased generation of ROSs, high PDT efficacy, significant cell apoptosis, minimal systemic cytotoxicity, and efficacious in vivo tumor inhibition.


Should vitamin B12 status be considered in assessing risk of neural tube defects?
There is a strong biological premise for including vitamin B12 with folic acid in strategies to prevent neural tube defects (NTDs), due to the closely interlinked metabolism of these two vitamins. For example, reduction of B12 deficiency among women of reproductive age could enhance the capacity of folic acid to prevent NTDs by optimizing the cellular uptake and utilization of natural folate cofactors. Vitamin B12 might also have an independent role in NTD prevention, such that adding it in fortification programs might be more effective than fortifying with folic acid alone. Globally, there is ample evidence of widespread vitamin B12 deficiency in low- and middle-income countries, but there is also considerable divergence of vitamin B12 status across regions, likely due to genetic as well as nutritional factors. Here, I consider the evidence that low vitamin B12 status may be an independent factor associated with risk of NTDs, and whether a fortification strategy to improve B12 status would help reduce the prevalence of NTDs. I seek to identify knowledge gaps in this respect and specify research goals that would address these gaps.


Dampening of positive affect prospectively predicts depressive symptoms in non-clinical samples.
Past research has convincingly shown that a ruminative response style to negative affect (NA) predicts concurrent and prospective levels of depressive symptoms. Recent findings suggest that how people respond to positive affect (PA) might also be involved in the development of depressive symptoms, although this has heretofore not been tested prospectively. Participants from two non-clinical samples (total N=487) completed measures of depressive symptoms, response styles to NA (negative rumination) and response styles to PA (positive rumination and mood dampening) at two assessments separated by a 3-month (Sample 1) and 5-month period (Sample 2). Results in both samples showed that increased dampening responses to PA predict depressive symptoms at follow-up, even when taking into account baseline depressive symptoms and ruminative responses to NA. The results suggest that (dampening) responses to PA add useful information above and beyond (ruminative) responses to NA in predicting depression symptoms prospectively.


Protein kinase CK2 holoenzyme promotes start-specific transcription in Saccharomyces cerevisiae.
In Saccharomyces cerevisiae, the entrance into S phase requires the activation of a specific burst of transcription, which depends on SBF (SCB binding factor, Swi4/Swi6) and MBF (MCB binding factor, Mbp1/Swi6) complexes. CK2 is a pleiotropic kinase involved in several cellular processes, including the regulation of the cell cycle. CK2 is composed of two catalytic subunits (α and α') and two regulatory subunits (β and β'), both of which are required to form the active holoenzyme. Here we investigate the function of the CK2 holoenzyme in Start-specific transcription. The ckb1Δ ckb2Δ mutant strain, bearing deletions of both genes encoding CK2 regulatory subunits, shows a delay of S-phase entrance due to a severe reduction of the expression of SBF- and MBF-dependent genes. This transcriptional defect is caused by an impaired recruitment of Swi6 and Swi4 to G1 gene promoters. Moreover, CK2 α and β' subunits interact with RNA polymerase II, whose binding to G1 promoters is positively regulated by the CK2 holoenzyme. Collectively, these findings suggest a novel role for the CK2 holoenzyme in the activation of G1 transcription.


Low-field magnetic resonance imaging: increased safety for pacemaker patients?
The number of low-field (<0.5 T) magnetic resonance (MR) scanners installed worldwide is increasing due to a favourable cost and safety profile and improved patient comfort using an open-scanner design. Therefore, the aim of our study was to evaluate a strategy for the safe performance of magnetic resonance imaging (MRI) at a field strength of 0.2 T, in pacemaker (PM) patients without limitations on scan region, PM dependency, or the presence of abandoned leads. One hundred and fourteen PM patients, including PM-dependent patients and patients with abandoned leads, examined at a 0.2 T MR scanner due to an urgent clinical need for an MRI examination, were evaluated. All PMs were reprogrammed before MRI: if heart rate was <60 bpm, the asynchronous mode (with a rate of 80 bpm) was programmed to avoid MR-induced inhibition; if heart rate was >60 bpm, sense-only mode (ODO/OVO/OAO) was used to avoid MR-induced competitive pacing and potential proarrhythmia. Patients were monitored with electrocardiogram (ECG) and pulse oximetry. All PMs were interrogated before and after MRI, including measurement of lead impedance, pacing capture threshold (PCT), and battery voltage. All MRI scans were completed safely. No induction of arrhythmias or inhibition of PM output occurred. There were no statistically significant changes in lead impedance, PCT, or battery voltage (P>0.05). Low-field MRI of PM patients, including high-risk PM patients and MRI scan regions, can be performed with an acceptable risk-benefit ratio under controlled conditions.


Targeting Integrins for Cancer Therapy - Disappointments and Opportunities.
Integrins mediate adhesive interactions between cells and their environment, including neighboring cells and extracellular matrix (ECM). These heterodimeric transmembrane receptors bind extracellular ligands with their globular head domains and connect to the cytoskeleton through multi-protein interactions at their cytoplasmic tails. Integrin containing cell-matrix adhesions are dynamic force-responsive protein complexes that allow bidirectional mechanical coupling of cells with their environment. This allows cells to sense and modulate tissue mechanics and regulates intracellular signaling impacting on cell faith, survival, proliferation, and differentiation programs. Dysregulation of these functions has been extensively reported in cancer and associated with tumor growth, invasion, angiogenesis, metastasis, and therapy resistance. This central role in multiple hallmarks of cancer and their localization on the cell surface makes integrins attractive targets for cancer therapy. However, despite a wealth of highly encouraging preclinical data, targeting integrin adhesion complexes in clinical trials has thus far failed to meet expectations. Contributing factors to therapeutic failure are 1) variable integrin expression, 2) redundancy in integrin function, 3) distinct roles of integrins at various disease stages, and 4) sequestering of therapeutics by integrin-containing tumor-derived extracellular vesicles. Despite disappointing clinical results, new promising approaches are being investigated that highlight the potential of integrins as targets or prognostic biomarkers. Improvement of therapeutic delivery at the tumor site via integrin binding ligands is emerging as another successful approach that may enhance both efficacy and safety of conventional therapeutics. In this review we provide an overview of recent encouraging preclinical findings, we discuss the apparent disagreement between preclinical and clinical results, and we consider new opportunities to exploit the potential of integrin adhesion complexes as targets for cancer therapy.


Life-space and cognitive decline in a community-based sample of African American and Caucasian older adults.
Life-space, a measure of movement through one's environment, may be viewed as one aspect of environmental complexity for older adults. We examined the relationship between life-space and subsequent change in cognitive function. Participants were 624 community-dwelling Medicare beneficiaries (49% African American) who completed in-home assessments at baseline and follow-up 4 years later. The Life-Space Assessment was used at baseline to measure extent, frequency, and independence of participants' movement within and outside the home. Cognitive decline was measured with the Mini-Mental State Examination (MMSE). In a regression model adjusted for baseline MMSE, age, gender, race, residence (rural/urban), and education, greater life-space at baseline predicted reduced cognitive decline (beta = -.177, p <.001). This association remained statistically significant in subsequent models that examined what proportion of the observed association was explained by baseline physical activity, physical function, vascular risk factors, comorbidity, and psychosocial factors. Physical function accounted for the largest proportion (37.3%) of the association between life-space and cognitive decline. There was no significant interaction between life-space and race, gender, or age in predicting cognitive decline. In a logistic regression analysis, participants in the highest quartile of life-space had 53% reduced odds of substantial cognitive decline (> or =4 points on MMSE) compared to those in the lowest quartile. These preliminary findings suggest that life-space may be a useful identifier of older adults at risk for cognitive decline. Future research should investigate the potential reciprocal relationship between life-space and cognitive function as well as the interrelationship between these factors and physical function.


Crossed pectoralis major myocutaneous flap for recurrent oral cavity cancers.
Oral cavity cancers are fairly common and have propensity to recur locally. Since Pectoralis Major Myocutaneous (PMMC) flap is the most widely used first flap for reconstruction, it is exhausted at the earliest and recurrence poses a formidable challenge for reconstructive surgeon. Present study evaluated the feasibility of contralateral Pectoralis Major Myocutaneous Flap for reconstruction after resection of recurrent tumour. This was a study of the patients presenting with recurrent oral cavity cancer after exhausted ipsilateral Pectoralis Major Myocutaneous Flap (PMMC) in whom we used contralateral Pectoralis Major Myocutaneous Flap (Crossed PMMC Flap) for reconstruction between October 2013 to June 2016. Five patients with recurrence underwent reconstruction with contralateral Pectoralis Major Myocutaneous Flap. In all the flap was successfully used to reconstruct defects involving the entire buccal mucosa and in one patient the flap could be used to reconstruct full thickness resection defect(crossed bipedal PMMC Flap) with ease. Crossed Pectoralis Major Myocutaneous Flap can be used safely and reliably for reconstruction of the buccal mucosal defect and in selected patients even for full thickness cheek defect as folded bipaddle Pectoralis Major Myocutaneous Flap.


Determination of the recombination correction factor kS for some specific plane-parallel and cylindrical ionization chambers in pulsed photon and electron beams.
It has been shown from an evaluation of the inverse reading of the dosemeter (1/M) against the inverse of the polarizing voltage (1/V), obtained with a number of commercially available ionization chambers, using dose per pulse values between 0.16 and 5 mGy, that a linear relationship between the recombination correction factor kS and dose per pulse (DPP) can be found. At dose per pulse values above 1 mGy the method of a general equation with coefficients dependent on the chamber type gives more accurate results than the Boag method. This method was already proposed by Burns and McEwen (1998, Phys. Med. Biol. 43 2033) and avoids comprehensive and time-consuming measurements of Jaffé plots which are a prerequisite for the application of the multi-voltage analysis (MVA) or the two-voltage analysis (TVA). We evaluated and verified the response of ionization chambers on the recombination effect in pulsed accelerator beams for both photons and electrons. Our main conclusions are: (1) The correction factor k(S) depends only on the DPP and the chamber type. There is no influence of radiation type and energy. (2) For all the chambers investigated there is a linear relationship between kS and DPP up to 5 mGy/pulse, and for two chambers we could show linearity up to 40 mGy/pulse. (3) A general formalism, such as that of Boag, characterizes chambers exclusively by the distance of the electrodes and gives a trend for the correction factor, and therefore (4) a general formalism has to reflect the influence of the chamber construction on the recombination by the introduction of chamber-type dependent coefficients.


Perinatal antibiotics alter preterm infant EEG and neurobehavior in the Family Nurture Intervention trial.
Early exposure to antibiotics has been shown to increase risk for poor neurobehavioral development, particularly with regard to attention deficit disorders. Clinically, electroencephalography (EEG) is increasingly used as a biomarker of these deficits. Less is known about the effects of antibiotics on neurobehavioral and neurophysiological outcomes in preterm infants, a population at particularly high risk for attention deficits and perinatal antibiotic exposure. This study examines the effects of perinatal antibiotic exposure on neonatal EEG and attention deficits as measured by the Child Behavior Checklist in 4- to 5-year-old children who were enrolled in an NICU-based randomized controlled trial comparing Family Nurture Intervention (FNI) to standard care. Antibiotic-exposed infants had increased attention problems and there was a main effect of antibiotic exposure such that exposed infants had higher EEG power. This effect was fourfold greater in infants who received standard NICU care compared to those who received the intervention, suggesting a buffering effect of the intervention. We hypothesize that the relationship between antibiotic exposure and altered neurodevelopment may be due to effects of antibiotics on the microbiome, and that FNI may buffer these adverse consequences.


Antifouling and Antibacterial Properties Constructed by Quaternary Ammonium and Benzyl Ester Derived from Lysine Methacrylamide.
Hemocompatibility and antibacterial property are essential for blood contact devices and medical intervention materials. In this study, positively charged quaternary ammonium (QAC) and hydrophobic benzyl group (OBzl) were introduced onto hydrophilic lysine methacrylamide (LysAAm) to obtain two monomers LysAAm-QAC and LysAAm-OBzl, respectively. The structure characterizations of LysAAm-QAC and LysAAm-OBzl were determined by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and time-of-flight secondary ion mass spectrometry. LysAAm-QAC and LysAAm-OBzl were cografted onto a silicon wafer with different feeding ratios to construct antifouling and antibacterial properties. The results of fibrinogen adsorption and platelet adhesion proved that the modified sample with the feeding ratio of 3:7 had superior antifouling property. Furthermore, an antimicrobial test with both 2 and 24 h indicated that the modified sample with the feeding ratio of 3:7 had antibacterial ability. The antifouling property was provided by the high surface coverage of LysAAm-QAC and LysAAm-OBzl (91.49%) and the hydrophilic main structure LysAAm on LysAAm-QAC and LysAAm-OBzl (water contact angle was 43.6°). The antibacterial property was improved with the proportion of LysAAm-OBzl (43.6-58.5%) because the increasing hydrophobic OBzl enhanced the ability to insert into the membrane of bacteria and raise the bactericidal efficiency. In application, LysAAm-QAC and LysAAm-OBzl with the feeding ratio of 3:7 were grafted onto the surface of poly(styrene-b-(ethylene-co-butylene)-b-styrene), and a bifunctional surface with antifouling and antibacterial properties was fabricated, which had promising applications in blood contact devices and medical intervention materials.


Typing of killer-cell immunoglobulin-like receptors and their cognate human leukocyte antigen class I ligands predicts survival of Chinese Han patients with metastatic non-small-cell lung cancer.
Non-small-cell lung cancer (NSCLC) may establish an immunosuppressive tumor microenvironment that is conducive to tumor growth. Natural killer (NK) cells play a pivotal role in immunological surveillance. Activation of NK cells partially depends on the interactions between killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands. We herein investigated the association of KIRs and HLA ligands with survival in metastatic NSCLC (mNSCLC) patients treated with chemotherapy in a Chinese Han population. Polymerase chain reaction with sequence-specific primers was used to type 15 KIRs at the DNA and mRNA level and 6 HLA ligands in 70 mNSCLC patients. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard regression model was applied for multivariate survival analysis, with the stepwise selection, to determine independent predictors of survival. It was observed that patients with KIR2DS4del gene expression at the mRNA level or HLA-Bw4T80 exhibited poor overall survival (OS). The multivariate analysis revealed that HLA-Bw4T80 and KIR2DS4del expression were independent predictors of OS. This observation indicated that the KIR/HLA ligand is a promising predictor of survival in mNSCLC and may also provide a strategy for treatment stratification and patient management.


Neurofibromatosis and Schwannomatosis.
Neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis are a group of related classically inherited but often times sporadic tumor suppressor syndromes. Neuro-oncologists should recognize these syndromes, initiate necessary tests in patients with a clinical suspicion, and support genetic counseling of patients and families. In this review, clinical presentation, diagnostic criteria, day-to-day management including supportive care as well as updates on genetics, and experimental treatment strategies are discussed.


Is It Love or Is It Control? Assessing Warning Signs of Dating Violence.
The purpose of this study was to develop and evaluate the Relationship Red Flags Scale, a measure of ability to recognize warning signs of dating violence. The factor structure and psychometric properties of this measure were tested with independent samples of college women and men, and test-retest reliability was assessed with college women. Specifically, our first study examined the factor structure, validity, and reliability of the Relationship Red Flags measure with a sample of 433 undergraduate women. Confirmatory factor analyses provided support for a 25-item five-factor structure (i.e., Monitoring Behaviors, Controlling Behaviors, Demeaning Behaviors, Threatening and Aggressive Behaviors, and Jealous and Possessive Behaviors). Internal consistency reliability was adequate and the validity of the measure was supported for use with college women (negative correlations were found among measures of warning signs and acceptance of dating violence). Our second study replicated these findings with an independent sample of 330 college men. Finally, a third investigation found that the measure demonstrated adequate test-retest reliability with an independent sample of 47 college women.


Quantitative steps in symbiogenesis and the evolution of homeostasis.
The merging of two independent populations of heterotrophs and autotrophs into a single population of mixotrophs has occurred frequently in evolutionary history. It is an example of a wide class of related phenomena, known as symbiogenesis. The physiological basis is almost always (reciprocal) syntrophy, where each species uses the products of the other species. Symbiogenesis can repeat itself after specialization on particular assimilatory substrates. We discuss quantitative aspects and delineate eight steps from two free-living interacting populations to a single fully integrated endosymbiotic one. The whole process of gradual interlocking of the two populations could be mimicked by incremental changes of particular parameter values. The role of products gradually changes from an ecological to a physiological one. We found conditions where the free-living, epibiotic and endobiotic populations of symbionts can co-exist, as well as conditions where the endobiotic symbionts outcompete other symbionts. Our population dynamical analyses give new insights into the evolution of cellular homeostasis. We show how structural biomass with a constant chemical composition can evolve in a chemically varying environment if the parameters for the formation of products satisfy simple constraints. No additional regulation mechanisms are required for homeostasis within the context of the dynamic energy budget (DEB) theory for the uptake and use of substrates by organisms. The DEB model appears to be dosed under endosymbiosis. This means that when each free-living partner follows DEB rules for substrate uptake and use, and they become engaged in an endosymbiotic relationship, a gradual transition to a single fully integrated system is possible that again follows DEB rules for substrate uptake and use.


[The prognostic importance of the stage in patients operated for carcinoma of the endometrium (author's transl)].
The operative specimens of 216 patients who underwent operation for adenocarcinoma of the endometrium stage I and stage II were thoroughly examined. It was found that measuring the maximal depth of infiltration of the carcinoma in relation to the thickness of the uterine wall and other morphological criteria of the tumours such as tumour grading, and carcinomatous lymphangiosis have greater prognostic value than clinical staging and the length of the uterine cavity to the sound. In contradistinction to other observations we found that patients with a short length of the uterus had more often recurrences and distant metastases than patients with a long uterine length to the sound.