Prevention of mother-to-child transmission of hepatitis B virus (HBV) during pregnancy and the puerperium: current standards of care.
Mother-to-child transmission (MTCT) of hepatitis B virus continues to occur despite the interventions of hepatitis B vaccination and immunoglobulin. The most significant risk factor in transmission is high maternal viral load. Being aware of viral replicative activity permits risk stratification and allows the opportunity for additional preventative measures such as antiviral therapy. Retrospective audit of investigations and clinical management among hepatitis B surface antigen-positive pregnant women from three maternity services across Victoria over a five-year period from 2006 to 2011. Over the study period at the three institutions, there were 46,855 births, and 398 hepatitis B-positive pregnant women. 87% of the women were non-Australian-born. Viral load testing was performed in <20% of all pregnancies, and hepatitis B e antigen status assessed in 33%. Only 18% of the women with hepatitis B were referred for specialist care, but if referred, they were more likely to have an assessment of viral replicative status performed. Compliance with administration of neonatal hepatitis B immunoglobulin and birth-dose vaccination was high (>90%). There is scope for considerable improvement in referral and assessment of pregnant women with hepatitis B infection. Guidelines addressing the issue of maternal viral replicative status and the need for antiviral therapy may assist in guiding clinical management.


From Local Hydration Motifs in Aqueous Acetic Acid Solutions to Macroscopic Mixing Thermodynamics: A Quantitative Connection from THz-Calorimetry.
We report the results of THz measurements (30-440 cm-1) of aqueous acetic acid solutions over the full mixing range (XAcAc = 0-1). We recorded spectroscopic observables as a function of the acetic acid concentration in the frequency range of the intermolecular stretch at 150 cm-1 and of the librational modes at 350-440 cm-1. This allowed us to unravel changes in hydrophobic and hydrophilic hydration motifs, respectively. By means of a novel THz-calorimetry approach, we quantitatively correlated these changes in local hydration motifs to excess mixing entropy and enthalpy. We find that ΔHmix is determined by both hydrophobic and hydrophilic solvation contributions. In contrast, ΔSmix is governed by hydrophobic cavity formation. Our results further suggest that acetic acid-water mixtures are systems at the edge of phase separation due to endothermic contributions from both hydrophilic and hydrophobic solvation in a large portion of the miscibility range. Our work establishes a quantitative relationship between the balance of local hydrophobic and hydrophilic solvation motifs and the macroscopic mixing thermodynamic properties.


Ab initio chemical kinetics of methyl formate decomposition: the simplest model biodiesel.
The energetics and kinetics of methyl formate decomposition have been investigated by high-level ab initio calculations with rate constant predictions. The paucity of reliable experimental data for methyl formate has been circumvented by studying a very similar system, namely, the decarboxylation of acetic acid, in order to help validate the theoretical calculations. Our study shows that methyl formate decomposes to methanol and carbon monoxide, almost exclusively, with a high pressure limit rate constant of k(1)(infinity) = 2.128 x 10(12)T(0.735) exp(-34,535/T) s(-1), and the decomposition of acetic acid to methane and carbon dioxide proceeds with a rate constant, k(4)(infinity), of 1.668 x 10(10)T(1.079) exp -35,541/T s(-1). Experimental values for the formation enthalpy of methyl formate are discussed, and it is shown that these can be reconciled with our computed value for DeltaH(f) (298.15 K) of -360.1 +/- 2.2 kJ mol(-1). In turn, bond dissociation energies for all single bonds in the molecule are presented.


The relation between seborrheic keratoses and malignant solid tumours. A case-control study.
In order to establish whether or not here is an association between cancer and intense growth of seborrheic keratosis, the so-called Leser-Trelat sign, we conducted a case control study in which the number and features of seborrheic keratosis in 82 patients with recent solid tumours, were compared with 82 age- and sex-matched controls. Neither numbers nor features of seborrheic keratosis differed significantly in patients and controls. Eruptive seborrheic keratosis was noted in only one patient and one control. This study showed that solid malignancies are not generally associated with an increase in the number or size of seborrheic keratosis lesions, thus suggesting that they are not controlled by a hypothetical secretion of growth factors by tumours. Our results suggest that Leser-Trelat is either a coincidence, or at most a very rare sign of unusual types of cancer. We also showed that multiple cherry angiomas, previously reported to be a paraneoplastic sign, are not regularly associated with solid tumours.


Disruption of I kappa B alpha regulation by antisense RNA expression leads to malignant transformation.
NF-kappa B transcription factors regulate the expression of a variety of genes involved in immune regulation and cell growth. In most cell types NF-kappa B proteins are localized in an inactive form in the cytoplasm coupled to the inhibitory I kappa B proteins. Viruses, cytokines, lipopolysaccharides and other stimulating agents promote the dissociation of the cytosolic NF-kappa B/I kappa B complexes, via phosphorylation and degradation of I kappa B, resulting in the translocation of DNA binding, NF-kappa B complexes to the nucleus. To further understand the association of I kappa B with cell growth regulation, the effect of ectopic expression of sense and antisense I kappa B genes was examined in NIH3T3 cells. Overexpression of I kappa B alpha antisense RNA but not I kappa B gamma antisense RNA decreased the steady state levels of I kappa B alpha protein, altered NF-kappa B DNA binding and gene activity and, most importantly, induced malignant transformation as measured by saturation density, growth in soft agar and tumorigenicity in nude mice. In contrast, overexpression of I kappa B alpha resulted in decreased saturation density, a flattened cellular morphology and decreased NF-kappa B dependent reporter gene activity. These results indicate that overexpression of an I kappa B alpha antisense RNA may disrupt the NF-kappa B/I kappa B autoregulatory loop, leading to cellular transformation. Our results raise the interesting possibility that I kappa B alpha represents a potential tumor suppressor activity.


Mitochondrial abnormalities are more frequent in muscles undergoing sarcopenia.
The hypothesis that the accumulation of electron transport system (ETS) abnormalities and sarcopenia are linked was investigated. Vastus lateralis, soleus, and adductor longus muscles were studied in 5-, 18-, and 36-mo-old male Fischer 344 x Brown Norway F(1) hybrid rats. A significant decrease in soleus and vastus lateralis muscle mass was observed with age. Adductor longus was resistant to muscle mass loss. Multiple serial sections were analyzed for the activities of cytochrome-c oxidase (COX) and succinate dehydrogenase (SDH). The number of fibers exhibiting a COX(-)/SDH(++) phenotype increased with age in both vastus lateralis and soleus muscles. No ETS-abnormal fibers were identified in adductor longus at any age. Cross-sectional area of ETS-abnormal fibers decreased in the abnormal region (region displaying COX(-)/SDH(++) phenotype), whereas control fibers did not. The vastus lateralis muscle, which undergoes a high degree of sarcopenia, exhibited more ETS abnormalities and associated fiber loss than the soleus and adductor longus muscles, which are more resistant to sarcopenia, suggesting a direct association between ETS abnormalities and fiber loss.


Analysis of the chromosomal region 19q13.4 in two Chinese families with recurrent hydatidiform mole.
Familial recurrent hydatidiform mole is an extremely rare autosomal recessive condition in which affected individuals have a predisposition to molar pregnancies that are diploid but biparental, rather than androgenetic, in origin. A gene for this condition has been previously mapped to a 1.1 Mb region of chromosome 19q13.4. However, investigation of further families is needed to refine the location of the specific gene(s) involved. We have recently identified two novel Chinese families in which four affected women had recurrent pregnancy loss including 14 complete hydatidiform moles (CHM). Fluorescent microsatellite genotyping was used to determine the origin of CHM in both families. Using a panel of polymorphic microsatellite markers, genotyping and haplotype analysis of the 19q13.4 chromosomal region was performed in both families. Genotyping of CHM from affected individuals confirmed their biparental origin and diagnosis of familial recurrent hydatidiform mole in both families. However, no significant homozygosity for the 19q13.4 candidate region was found in affected members of either family. Genotyping and haplotype analysis has shown that a mutation in 19q13.4 is unlikely to be responsible for recurrent CHM in the two Chinese families investigated and provides further evidence to support the hypothesis that, although extremely rare, this condition shows genetic heterogeneity.


Diagnosing erectile dysfunction: flow-chart.
Erectile dysfunction (ED) has been defined by the National Institute of Health (NIH) as the inability to achieve and/or maintain an erection for a satisfactory sexual intercourse. Discordant data have been reported on ED epidemiology with prevalence ranging from 12% to 52%. A recent study reported an ED prevalence of 12.8% in Italy. ED is a symptom, sometimes the first, of different internal diseases. ED can mark the point where evaluation and prevention of important diseases (such as diabetes, arterial hypertension, atherosclerosis) hitherto unknown by the patients, can begin. The andrologist's cultural baggage must include the ability to identify the pathology that can determine ED and the capacity to programme a specific diagnostic workup.


A review of the mechanism of DDIT4 serve as a mitochondrial related protein in tumor regulation.
DDIT4 is a mitochondrial and tumor-related protein involved in anti-tumor therapy resistance, proliferation, and invasion, etc. Its expression level increases under the stress such as chemotherapy, hypoxia, and DNA damage. A number of clinical studies have confirmed that DDIT4 can change the behavior of tumor cells and the prognosis of patients with cancer. However, the role of DDIT4 in promoting or suppressing cancer is still inconclusive. This article summarized the four characteristics of DDIT4 including a mitochondria-related protein, interactions with various protein molecules, immune and metabolic cell related proteins and participator in the oxygen sensing pathway, which may be related to the progress of cancer.


Intra-frame motion deterioration effects and deep-learning-based compensation in MR-guided radiotherapy.
Current commercially available hybrid magnetic resonance linear accelerators (MR-Linac) use 2D+t cine MR imaging to provide intra-fractional motion monitoring. However, given the limited temporal resolution of cine MR imaging, target intra-frame motion deterioration effects, resulting in effective time latency and motion artifacts in the image domain, can be appreciable, especially in the case of fast breathing. The aim of this work is to investigate intra-frame motion deterioration effects in MR-guided radiotherapy (MRgRT) by simulating the motion-corrupted image acquisition, and to explore the feasibility of deep-learning-based compensation approaches, relying on the intra-frame motion information which is spatially and temporally encoded in the raw data (k-space). An intra-frame motion model was defined to simulate motion-corrupted MR images, with 4D anthropomorphic digital phantoms being exploited to provide ground truth 2D+t cine MR sequences. A total number of 10 digital phantoms were generated for lung cancer patients, with randomly selected eight patients for training or validation and the remaining two for testing. The simulation code served as the data generator, and a dedicated motion pattern perturbation scheme was proposed to build the intra-frame motion database, where three degrees of freedom were designed to guarantee the diversity of intra-frame motion trajectories, enabling a thorough exploration in the domain of the potential anatomical structure positions. U-Nets with three types of loss functions: L1 or L2 loss defined in image or Fourier domain, referred to as NNImgLoss-L1 , NNFloss-L1 and NNL2-Loss were trained to extract information from the motion-corrupted image and used to estimate the ground truth final-position image, corresponding to the end of the acquisition. Images before and after compensation were evaluated in terms of (i) image mean-squared error (MSE) and mean absolute error (MAE), and (ii) accuracy of gross tumor volume (GTV) contouring, based on optical-flow image registration. Image degradation caused by intra-frame motion was observed: for a linearly and fully acquired Cartesian readout k-space trajectory, intra-frame motion resulted in an imaging latency of approximately 50% of the acquisition time; in comparison, the motion artifacts exhibited only a negligible contribution to the overall geometric errors. All three compensation models led to a decrease in image MSE/MAE and GTV position offset compared to the motion-corrupted image. In the investigated testing dataset for GTV contouring, the average dice similarity coefficients (DSC) improved from 88% to 96%, and the 95th percentile Hausdorff distance (HD95 ) dropped from 4.8 mm to 2.1 mm. Different models showed slight performance variations across different intra-frame motion amplitude categories: NNImgLoss-L1 excelled for small/medium amplitudes, whereas NNFloss-L1 demonstrated higher DSC median values at larger amplitudes. The saliency maps of the motion-corrupted image highlighted the major contribution of the later acquired k-space data, as well as the edges of the moving anatomical structures at their final positions, during the model inference stage. Our results demonstrate the deep-learning-based approaches have the potential to compensate for intra-frame motion by utilizing the later acquired data to drive the convergence of the earlier acquired k-space components.


Squeezing fluoride out of water with a neutral bidentate antimony(V) Lewis acid.
Because of hydration, fluoride ions in water typically elude complexation by neutral Lewis acids. Here, we show how this limitation can be overcome with a bidentate Lewis acid containing two antimony(V) centers. This derivative (2) is obtained by the simple reaction of 4,5-bis(diphenylstibino)-9,9-dimethylxanthene (1) with two equivalents of 3,4,5,6-tetrachlorobenzoquinone (o-chloranil). It features two square-pyramidal stiborane units oriented in a face-to-face fashion. Titration experiments show that this new bidentate Lewis acid binds fluoride in aqueous solutions containing 95% water with a binding constant (K) of 700±30 M(-1). The structure of the fluoride adduct confirms fluoride anion chelation between the two antimony centers.


Vaccine-induced gag-specific T cells are associated with reduced viremia after HIV-1 infection.
The contribution of host T-cell immunity and HLA class I alleles to the control of human immunodeficiency virus (HIV-1) replication in natural infection is widely recognized. We assessed whether vaccine-induced T-cell immunity, or expression of certain HLA alleles, impacted HIV-1 control after infection in the Step MRKAd5/HIV-1 gag/pol/nef study. Vaccine-induced T cells were associated with reduced plasma viremia, with subjects targeting ≥3 gag peptides presenting with half-log lower mean viral loads than subjects without Gag responses. This effect was stronger in participants infected proximal to vaccination and was independent of our observed association of HLA-B*27, -B*57 and -B*58:01 alleles with lower HIV-1 viremia. These findings support the ability of vaccine-induced T-cell responses to influence postinfection outcome and provide a rationale for the generation of T-cell responses by vaccination to reduce viremia if protection from acquisition is not achieved. Clinical trials identifier: NCT00095576.


Unusual applications of ureteroscopy.
Six cases of combined percutaneous and ureteroscopic opening or reanastomosis of completely occluded ureters are described. All patients had previously had nephrostomy tubes inserted to salvage their kidneys.


Changes in response to metrazole during fever in juvenile rats; a new model for febrile convulsions?
Previous models for febrile convulsions have used environmentally induced hyperthermia as the stimulus to induce convulsions. Changes in response to metrazole during yeast-induced fever in juvenile rats are reported here. Animals were more susceptible to metrazole during the rising phase of fever but showed some resistance to its convulsant effects once the fever was established and following defervescence. It is suggested that this may form the basis of a physiologically more appropriate model for the study of the pathogenesis of febrile convulsions.


Expression of furA is modulated by NtcA and strongly enhanced in heterocysts of Anabaena sp. PCC 7120.
Fur (ferric uptake regulator) proteins are principally responsible for maintaining iron homeostasis in prokaryotes. Iron is usually a scarce resource. Its limitation reduces photosynthetic rates and cell growth in cyanobacteria in general and especially in cyanobacteria that are fixing dinitrogen, a process that requires the synthesis of numerous proteins with a high content of iron. This paper shows that in the diazotrophic cyanobacterium Anabaena sp. strain PCC 7120, levels of furA mRNA and FurA protein increase significantly in response to nitrogen deprivation, and that furA up-regulation takes place specifically in proheterocysts and mature heterocysts. Great differences in a Northern blot, probed with furA, of RNA from an ntcA mutant relative to wild-type Anabaena sp. were attributable to binding of NtcA, a global regulator of nitrogen metabolism, to the promoter of furA and to the promoter of the furA antisense transcript alr1690-alpha-furA.


Treatment of a giant coronary aneurysm with a novel technique: scaffolding (tunnel) stenting to support PTFE-covered stents: insights from intravascular ultrasound.
This report describes a patient with progressive angina and a giant coronary aneurysm in the right coronary artery. Percutaneous treatment was performed using a novel technique consisting of implantation of a long stent that provided scaffolding or bridge for the subsequent implantation of two polytetrafluoroethylene-covered stents. Complete closure of the aneurysm was successfully achieved. In the angiogram performed 3 months later for recurrent angina, a localized narrowing at the distal stent edge (corresponding to severe underexpansion of the stent struts on intravascular ultrasound) was observed. This was successfully treated with balloon angioplasty. The technical details of this new technique are described.


Vitamin D levels and their impact on mineral metabolism in HIV infected patients: an exploratory study.
Vitamin D has immunomodulating properties. The nuclear receptor for vitamin D is expressed in several immune cells, which convert 25-hydroxyvitamin D (25OHD) to the active form 1,25 hydroxyvitamin D [1,25(OH)2 D]. Under conditions of infection, 1,25(OH)2 D promotes production of cathelicidin (an antimicrobial peptide) in monocytes and activated macrophages. In vitro studies have shown the ability of cathelicidin to inhibit replication of human immunodeficiency virus (HIV-1) in T CD4 lymphocytes and macrophages. To evaluate vitamin D levels and their impact on mineral metabolism in HIV infected patients. Seventy-four clinical records of HIV/AIDS patients seen at the outpatients clinic were reviewed. The following data were collected: age, sex, time since diagnosis of HIV, HIV-1 viral load, CD4 counts (absolute value and percentage), and mineral metabolism determinations: 25OHD, intact parathormone (iPTH); serum calcium (sCa); serum phosphorus (sP) and serum crosslaps (sCTX). Vitamin D levels were stratified as follows: optimal: ≥30ng/ml; insufficient: 21-29ng/ml; moderately deficient: 20≥ -25OHD- >10 ng/ml and severely deficient ≤10 ng/ml. Fifty-five clinical records were included; 82% of patients had 25OHD levels below 30ng/ml (insufficient: 23.6%, moderately deficient: 36.4%; and severely deficient: 21.8%). A significantly higher serum PTH levels in the moderately and severely deficient groups than in the optimal and insufficient groups was observed (p<0.05 and p<0.03 respectively). A weak negative correlation was observed between serum 25OHD and PTH levels (r=-0.268; p<0.004). Sub-optimal vitamin D levels are frequently observed in HIV/AIDS patients on antiretroviral therapy (ART). Systematic assessment of mineral metabolism is considered necessary in HIV/AIDS positive patients.


Protein Tagging, Destruction and Infection.
Cells possess protein quality control mechanisms to maintain proper cellular homeostasis. In eukaryotes, the roles of the ubiquitination and proteasome-mediated degradation of cellular proteins is well established. Recent studies have elucidated protein tagging mechanisms in prokaryotes, involving transfer messenger RNA (tmRNA) and pupylation. In this review, newer insights and bioinformatics analysis of two distinct bacterial protein tagging machineries are discussed. The machinery for tmRNAmediated tagging is present in several eubacterial representatives, e.g. Escherichia coli, Mycobacterium tuberculosis, Bacillus subtilis etc., but not in two archaeal representatives, such as Thermoplasma acidophilum and Sulfolobus solfataricus. On the other hand, the machinery involving tagging with the prokaryotic ubiquitin-like protein (Pup) is absent in most bacteria but is encoded in some eubacterial representatives, e.g. Mycobacterium tuberculosis and Mycobacterium leprae. Furthermore, molecular details on the relationship between protein tagging and enzymes involved in protein degradation in bacteria during infection are emerging. Several pathogenic bacteria that do not express the major ATP-dependent proteases, Lon and Caseinolytic protease (ClpP), are avirulent. Also, some ATP-independent peptidases, such as PepA and PepN, modulate the infection process. The roles of bacterial proteins involved in tagging and degradation during infection are discussed. These aspects add a new dimension to better understanding of the peculiarities of host-pathogen interactions.


Metamemory in multiple sclerosis.
MS patients and age- and education-matched normal controls were administered several laboratory tests of metamemory and a questionnaire designed to measure subjects' capability to appraise their ability to remember events that might occur in everyday life. On laboratory tasks involving newly acquired information, MS patients with poor recognition memory abilities or poor performance on the Wisconsin Card Sorting Test (WCST) exhibited impairments on one test of metamemory; patients with deficits in both recognition and on the WCST showed more extensive impairments in metamemory. In contrast to their performance on tests involving newly acquired information, all groups of MS patients predicted their ability to recognize answers to general information questions that they could not recall as accurately as controls, and, like controls, they also searched their memories longer for answers to items that they believed they would recognize. In general, the results support the hypothesis that both trace-access and inferential mechanisms, which are thought to involve the prefrontal cortex, contribute to metamemory, but the nature of the memory task importantly influences the accuracy of metamemory, as well. Results from the questionnaire indicated that many MS patients with demonstrable memory deficits do not acknowledge their memory difficulties. Hence, patient self-reports about memory are likely to be unreliable sources of information for clinical purposes.


Goal attainment scaling: current methodological challenges.
To validate the underlying mathematical process of Goal Attainment Scaling (GAS), as an illustration of the problems encountered by patient-generated indexes in the quest of patient-centred outcomes. Data are simulated to represent the type of input to GAS. Rasch analysis is used to linearize the response categories for each variable associated with each goal, thus making it possible to compare the ordinal non-linear outcome of the GAS process with its linear equivalent, under the assumption of strict unidimensionality. Using a minimum clinically important difference (MCID), the level of difference between the two estimates is assessed. Over 14% of the simulated cases showed a magnitude of difference in change scores between the ordinal and linear-based GAS scores greater than the MCID. These differences were most likely to occur when patients start or finish their GAS scores at the margins of the score range, where non-linearity is greatest. The results show that the GAS process does not support mathematical operations such as multiplication. Apparent clinically meaningful changes scores can be generated solely from the non-linear nature of ordinal scores. Using patient-centred approaches to measurements such as GAS presents formidable scientific challenges. Suggestions are made which, in the context of GAS applications, may overcome some of these limitations. This involves the establishment of 'item banks' of goals which can be pre-calibrated onto a unidimensional metric such that linearized versions of the various scores (e.g., difficulty) could be imported into the process.


Tris(pentafluoroethyl)germane: Deprotonation and Hydrogermylation Reactions.
Owing to the highly electron-withdrawing C2 F5 groups, the tris(pentafluoroethyl)germane (C2 F5 )3 GeH represents an interesting Brønsted acidic compound. The germane is accessible by the treatment of the corresponding halogenogermanes (C2 F5 )3 GeX (X=Cl, Br) with Bu3 SnH. After clarifying its molecular structure in the solid state by X-ray diffraction, the acidity of (C2 F5 )3 GeH was examined by treatment with different bases, for example, 1,8-bis(dimethylamino)naphthalene. The resulting germanate(II) ion [Ge(C2 F5 )3 ]- serves as a germyl group transfer reagent. The reaction with main-group and transition-metal complexes or organohalides opens access to a variety of different compounds, the structures of which were mostly determined by X-ray diffraction. The corresponding tricarbonylnickelate(0) complex [(CO)3 NiGe(C2 F5 )3 ]- also gives information about the π-acceptor properties of the [Ge(C2 F5 )3 ]- ligand. Furthermore, hydrogermylation reactions of (C2 F5 )3 GeH with alkynes afforded different stereoisomers (α,β-cis, β-trans) depending on the respective reaction conditions and substrates.


Repeated sampling of individual bivalve mollusks I: intraindividual variability and consequences for haemolymph constituents of the Manila clam, Ruditapes philippinarum.
Components of the haemolymph are understood to constitute the internal defense system of bivalve mollusks and their levels are often considered to be indicators of "health"; however, relatively little proof exists of the role that these elements play in the success or failure of defense against a pathogen. A change associated with infection may be the consequence of disease rather than a measure of the capacity to respond effectively to a pathogen. One way to assess whether haemocyte or serum-component concentrations are related to resistance to microbial infection is to sample individuals over time, both before and after they are experimentally or naturally infected. But sampling itself may alter the parameter being assessed. In addition, interindividual variation is large and the degree of intraindividual variation over time is largely unknown. To evaluate intra- vs interindividual variability measured over time and to assess the effects of repeated sampling, we subjected Manila clams, Ruditapes philippinarum, to multiple haemolymph samplings during both field and laboratory experiments, and measured four parameters: haemocyte density, protein concentration, and the activities of leucine amino peptidase and DOPA-oxidase. A repeated-measures ANOVA indicated that individuals with high or low levels at one sampling, tended to have high or low levels, respectively, at the other sampling times. Furthermore, the index of individuality, which is the ratio of intra- to interindividual variability, for these four parameters was comparable to that for human serum components. Repeated sampling had no measured effect on field-deployed clams, which were sampled at intervals of 1-3 months, but significantly depressed values in laboratory-held clams sampled at 1-month intervals. Results demonstrated relative intraindividual constancy in the measured variables and suggested that minimizing sample frequency and volume, and maintaining animals in a comparatively natural environment should all facilitate repeated sampling with minimum injury to experimental mollusks.


Presence of vascular loops entering internal acoustic channel may increase risk of Sudden sensorineural hearing loss and reduce recovery of these patients.
To analyze whether there is correlation between branching patterns of anterior inferior cerebellar artery/posterior inferior cerebellar artery (AICA/PICA) in cerebellopontine angle (CPA) area, as demonstrated by three-dimensional fast imaging employing steady-state acquisition (3D FIESTA) magnetic resonance imaging (MRI) and 1) idiopathic sudden sensorineural hearing loss (ISSNHL) outcomes and 2) recovery of ISSNHL. We evaluated patients with idiopathic SSNHL for branching patterns of AICA/PICA in CPA area, as demonstrated by 3D FIESTA MRI. Sixty-eight patients with SSNHL (32 [47.1%] women; mean age 45.3 ± 14.6 [minimum-maximum: 18-77]) and 38 healthy volunteers [17 (44.7%) women; mean age 48.6 ± 14.0 (minimum-maximum: 26-81)] were included in this study. We evaluated patients for branching patterns and classified as type IA, IB, IIA, and IIB. Branching patterns were evaluated at the diseased side of the patients and both sides of the control group. Pretreatment and posttreatment audiological values were also studied. AICA/PICA branching patterns in control group versus study group in the affected side were: 26 (34.2%) versus 12 (17.6%) subjects had type IA; seven (9.2%) versus nine (13.2%) subjects had type IB; 31 (40.8%) versus 23 (33.8%) subjects had type IIA; and 12 (15.8) versus 24 (35.3%) subjects had type IIB branching patterns, respectively. Presence of vascular loops entering internal acoustic channel (type IIB branching pattern) was more prominent in the study group (P = 0.017). In addition, type IIB branching pattern was significantly associated with unresponsiveness to treatment (18 [75%] of 24 patients with type IIB were unresponsive and 14 [47.0%] of 30 patients with nontype IIB were unresponsive, P < 0.001). Type IIB branching pattern has been shown to be more common in patients with ISSNHL, and these patients come across with unresponsiveness to standard therapy more than the other branching types. 3b. Laryngoscope, 127:210-215, 2017.


Glymphatic System in the Central Nervous System, a Novel Therapeutic Direction Against Brain Edema After Stroke.
Stroke is the destruction of brain function and structure, and is caused by either cerebrovascular obstruction or rupture. It is a disease associated with high mortality and disability worldwide. Brain edema after stroke is an important factor affecting neurologic function recovery. The glymphatic system is a recently discovered cerebrospinal fluid (CSF) transport system. Through the perivascular space and aquaporin 4 (AQP4) on astrocytes, it promotes the exchange of CSF and interstitial fluid (ISF), clears brain metabolic waste, and maintains the stability of the internal environment within the brain. Excessive accumulation of fluid in the brain tissue causes cerebral edema, but the glymphatic system plays an important role in the process of both intake and removal of fluid within the brain. The changes in the glymphatic system after stroke may be an important contributor to brain edema. Understanding and targeting the molecular mechanisms and the role of the glymphatic system in the formation and regression of brain edema after stroke could promote the exclusion of fluids in the brain tissue and promote the recovery of neurological function in stroke patients. In this review, we will discuss the physiology of the glymphatic system, as well as the related mechanisms and therapeutic targets involved in the formation of brain edema after stroke, which could provide a new direction for research against brain edema after stroke.


Quality of life measurement after stroke: uses and abuses of the SF-36.
The Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) is widely used to measure health status after stroke. However, a fundamental assumption for its valid use after stroke has not been comprehensively tested: is it legitimate to generate scores for 8 scales and 2 summary measures using the standard algorithms? We tested this assumption. SF-36 data from 177 people after stroke were examined (71% male; mean age, 62). We tested 6 scaling criteria to determine the legitimacy of generating the 8 SF-36 scale scores using Likert's method of summed ratings, and we tested 2 scaling criteria to determine the appropriateness of the standard SF-36 algorithms for weighting and combining scale scores to generate 2 summary measures (physical and mental). Scaling assumptions were fully satisfied for 6 of the 8 scales, but 3 of these 6 scales had notable floor and/or ceiling effects. Assumptions for generating 2 SF-36 summary measures were not satisfied. In this sample, 5 of the 8 SF-36 scales had limited validity as outcome measures after stroke, and the reporting of physical and mental summary scores was not supported. Results raise questions about the use of the SF-36 in stroke, and the SF-12 that is developed from it, and highlight the importance of testing scaling assumptions when applying existing scales to new populations.


Central and Peripheral Inflammation in Mild Cognitive Impairment in the Context of Alzheimer's Disease.
Mild cognitive impairment (MCI) is characterized by an abnormal decline in mental and cognitive function compared with normal cognitive aging. It is an underlying condition of Alzheimer's disease (AD), an irreversible neurodegenerative disease. In recent years, neuroinflammation has been investigated as a new leading target that contributes to MCI progression into AD. Understanding the mechanism underlying inflammatory processes involved in the early onset of the disease could help find a safe and effective way to diagnose and treat patients. In this article, we assessed over twenty different blood and cerebrospinal fluid (CSF) inflammatory biomarker concentrations with immunoassay methods in patients with MCI (mild cognitive impairment), non-impaired control (NIC), and serum healthy control (HC). We performed group comparisons and analyzed in-group correlations between the biomarkers. We included 107 participants (mean age: 64.7 ± 7.8, women: 58.9%). CSF osteopontin and YKL-40 were significantly increased in the MCI group, whereas serum C-reactive protein and interleukin-6 were significantly higher (p < 0.001) in the NIC group compared with the MCI and HC groups. Stronger correlations between interleukin-1β and inflammasome markers were observed in the serum of the MCI group. We confirmed specific inflammatory activation in the central nervous system and interleukin-1β pathway upregulation in the serum of the MCI cohort.


First report of bacterial kidney disease in coho salmon Oncorhynchus kisutch in Russia.
This paper describes the first case of bacterial kidney disease (BKD) to be identified in coho salmon Oncorhynchus kisutch in Russia. The fish in question was caught in Lake Bolshoi Vilyui on the Kamchatka Peninsula. The diseased fish had foci of granulomatous inflammation in the kidneys. The diagnosis was confirmed by isolating the bacterium Renibacterium salmoninarum from kidney tissue in pure culture, and by determining the partial 16S RNA gene sequence of the isolate. This is the first detection of this pathogen in the genus Oncorhynchus in Russia, and detection of BKD in coho salmon indicates that the pathogen is present in the natural fish populations of Kamchatka. Therefore, it will be necessary to conduct screening studies of mature salmon selected for artificial reproduction, for the presence of BKD signs and asymptomatic infection with R. salmoninarum, which will allow us to estimate the prevalence of the pathogen.


Glucose metabolism in completed suicide: a forensic-pathological pilot study.
To determine whether antemortem blood levels of glycated hemoglobin (HbA1c) and glucose predict completed suicide and, by extension, whether markers of glucose metabolism might be associated with a prosuicidal trait or state. From consecutively performed autopsies, samples of blood and vitreous humor from 17 suicide victims and 27 non-suicide controls were compared with regard to levels of glucose, lactate, and HbA1c. Mean HbA1c was higher, and mean estimated blood glucose lower, among suicide victims, although tests revealed no significant differences (P=0.171 and P=0.395, respectively). HbA1c levels exceeding 48.0 mmol/mol, which were indicative of persistent hyperglycemia, were twice as common in suicide victims (59% vs 30%; P=0.068). The finding of this pilot study suggest that deranged glucose metabolism may reflect biological events antecedent to, or concomitant with, completed suicide, with the following clinical implications: recurring hyperglycemia due to defective glucose transport, which may give rise to depression and suicidal ideation, and elevated HbA1c levels, which may represent an assayable correlate to neurobiological conditions predisposing to suicide.


Decrease of anterior ciliary arterial pressure with increased ocular pressure.
The relationship of the ocular pressure to the anterior ciliary arterial pressure was studied by measuring the pressure of the anterior ciliary artery using a modified pressure chamber. Of the 40 subjects, 9 were normal, 16 were ocular hypertensive patients, and 15 were primary, open-angle, glaucoma patients. A significant negative correlation was found between the anterior ciliary arterial pressure and the ocular pressure such that the former decreases as the latter increases. These results support the concept that the blood flow in the anterior ciliary artery is from the inside of the eye to the outside.


Induction and turnover of fructose 1,6-bisphosphatase in HL-60 leukemia cells by calcitriol.
Fructose 1,6-bisphosphatase mRNA and enzyme activity in HL-60 cells were rapidly and markedly induced by calcitriol (formerly known as 1 alpha,25-dihydroxyvitamin D3). The activity reached 70-80 times the basal level after 96 h. The enzyme activity in the cells incubated for 96 h with calcitriol decreased immediately after its withdrawal but after a 24-h incubation the activity in the cells continued to increase slightly and then decreased slowly. Calcitriol increased the enzyme activity dose-dependently with maximal stimulation at 10 nM and half-maximal at 2.1 nM. The rate of synthesis of fructose 1,6-bisphosphatase almost paralleled the increase in mRNA level during treatment with calcitriol. When calcitriol was removed from media after incubation for either 24 h or 96 h, fructose-1,6-bisphosphatase mRNA and fructose-1,6-bisphosphatase synthesis decreased rapidly to the basal level. The enzyme was only slightly degraded in the cells incubated with calcitriol for 24 h followed by the subsequent culture without calcitriol but it was degraded with a half-life estimated to be approximately 64 h in the same cells followed by culturing with calcitriol. In the cells incubated for 96 h, the same degradation rate (i.e. half-life approximately 64 h) was observed irrespective of the following culture with or without calcitriol. Calcitriol did not affect the degradation rate of total soluble proteins.


A new rhodamine-based colorimetric cyanide chemosensor: convenient detecting procedure and high sensitivity and selectivity.
By applying an indirect strategy, a new rhodamine-based dye (I) was successfully developed as a colorimetric chemosensor for the sensitive detection of cyanide. In the presence of copper ions, the colorless solution of compound I changed to magenta; however, upon the addition of trace cyanide, the magenta color faded to colorless immediately, with a detection limit as low as 0.013 ppm (DeltaA = 0.054), much lower than the Maximum Contaminant Level for cyanide in drinking water (0.20 ppm) set by the US Environmental Protection Agency. Other anions, including Cl(-), I(-), IO(3)(-), SO(4)(2-), NO(2)(-), Br(-), H(2)PO(4)(-), F(-), SCN(-), HSO(4)(-), and ClO(4)(-), had nearly no influence on the probing behavior of dye I toward cyanide.


Altered gene expression related to glomerulogenesis and podocyte structure in early diabetic nephropathy of db/db mice and its restoration by pioglitazone.
Glomerular injury plays a pivotal role in the development of diabetic nephropathy. To elucidate molecular mechanisms underlying diabetic glomerulopathy, we compared glomerular gene expression profiles of db/db mice with those of db/m control mice at a normoalbuminuric stage characterized by hyperglycemia and at an early stage of diabetic nephropathy with elevated albuminuria, using cDNA microarray. In db/db mice at the normoalbuminuric stage, hypoxia-inducible factor-1alpha (HIF-1alpha), ephrin B2, glomerular epithelial protein 1, and Pod-1, which play key roles in glomerulogenesis, were already upregulated in parallel with an alteration of genes related to glucose metabolism, lipid metabolism, and oxidative stress. Podocyte structure-related genes, actinin 4alpha and dystroglycan 1 (DG1), were also significantly upregulated at an early stage. The alteration in the expression of these genes was confirmed by quantitative RT-PCR. Through pioglitazone treatment, gene expression of ephrin B2, Pod-1, actinin 4alpha, and DG1, as well as that of oxidative stress and lipid metabolism, was restored concomitant with attenuation of albuminuria. In addition, HIF-1alpha protein expression was partially attenuated by pioglitazone. These results suggest that not only metabolic alteration and oxidative stress, but also the alteration of gene expression related to glomerulogenesis and podocyte structure, may be involved in the pathogenesis of early diabetic glomerulopathy in type 2 diabetes.


Current methods of sedation in dental patients - a systematic review of the literature.
The main objective of this systematic literature review is to identify the safest and most effective sedative drugs so as to ensure successful sedation with as few complications as possible. A systematic literature review of the PubMed MEDLINE database was carried out using the key words "conscious sedation," "drugs," and "dentistry." A total of 1,827 scientific articles were found, and these were narrowed down to 473 articles after applying inclusion and exclusion criteria. These 473 studies were then individually assessed for their suitability for inclusion in this literature review. A total of 21 studies were selected due to their rigorous study design and conduciveness to further, more exhaustive analysis. The selected studies included a total of 1,0003 patients classified as ASA I or II. Midazolam was the drug most frequently used for successful sedation in dental surgical procedures. Ketamine also proved very useful when administered intranasally, although some side effects were observed when delivered via other routes of administration. Both propofol and nitrous oxide (N2O) are also effective sedative drugs. Midazolam is the drug most commonly used to induce moderate sedation in dental surgical procedures, and it is also very safe. Other sedative drugs like ketamine, dexmedetomidine and propofol have also been proven safe and effective; however, further comparative clinical studies are needed to better demonstrate which of these are the safest and most effective.


Prostaglandin D2 inhibits fibroblast migration.
Fibroblasts play an important role in the repair and remodelling processes following injury. Prostaglandin D2 (PGD2) is a potent mediator in inflammatory processes. In this study, the effect of the PGD2 on human foetal lung fibroblasts (HFL-1) chemotaxis induced by human plasma fibronectin (HFn) was investigated using the blindwell chamber technique. PGD2 inhibited HFL-1 chemotaxis to HFn (20 microg x mL(-1)) by 20.8 +/- 3.8% (p<0.05). Checkerboard analysis of HFn-directed migration confirmed that PGD2 inhibited both chemotaxis and chemokinesis. The effect of PGD2 was concentration-dependent and the inhibitory effect diminished with time. The PGD2 receptor (DP) agonist BW245C (500 nM) had a similar effect, inhibiting chemotaxis to 39.4 +/- 6.3%. The inhibitory effects of both PGD2 and BW245C on HFL-1 chemotaxis were blocked by the DP receptor antagonist AH6809 (2 microM). The inhibitory effect of PGD2 on fibroblast chemotaxis was also blocked by the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) inhibitor, KT5720, suggesting a DP receptor-initiated, cAMP-dependent effect mediated by PKA. Prostaglandin D2 appears to inhibit fibroblast chemotaxis, perhaps by modulating the rate of fibroblast migration. Such an effect may contribute to regulation of the wound healing response following injury in asthma patients.


Paclitaxel, 5-fluorouracil, hydroxyurea, and concomitant radiation therapy for poor-prognosis head and neck cancer.
A series of phase I and phase II studies investigating multiagent concomitant chemoradiotherapy in patients with poor-prognosis head and neck cancer have been conducted at the University of Chicago. Drug combinations initially included 5-fluorouracil (5-FU) and hydroxyurea, with the more recent addition of cisplatin; in the most recent trial, paclitaxel was substituted for cisplatin. The primary end point of these trials was definition of maximum tolerated doses in combination with radiation therapy. All radiation therapy was given concomitantly with chemotherapy on an every-other-week schedule (total dose, </=75 Gy). Maximum tolerated doses of the two-drug combination of hydroxyurea and 5-FU were defined at 1 g given orally twice daily for a total of 11 doses and 800 mg/m2/d for 5 days (by continuous intravenous infusion), respectively. When cisplatin was added to this regimen, the observed myelosuppression necessitated the addition of granulocyte colony-stimulating factor. The recommended phase II doses for the three-drug combination were cisplatin 100 mg/m2 every 28 days, 5-FU 800 mg/m2/d for 5 days, and hydroxyurea 1 g orally twice daily for 11 doses. The feasibility of administering radiation at 1.5 Gy twice daily with chemotherapy was also established, which allowed the administration of 75 Gy over 5 cycles (10 weeks). The initial review of this trial suggested substantial toxicity, particularly mucositis and myelosuppression; however, local and regional control rates also were high. Most recently, paclitaxel has replaced cisplatin in this regimen. Recommended phase II doses were hydroxyurea 0.5 g orally twice daily for 11 doses, 5-FU 600 mg/m2/d for 5 days, and paclitaxel 20 mg/m2/d for 5 days, with radiation therapy administered twice daily in 1. 5-Gy fractions. A formal phase II study of this regimen in previously untreated patients with stage IV disease has recently completed accrual and is awaiting analysis. Evaluation of a simplified paclitaxel administration schedule (1-hour infusion on day 1 of chemoradiotherapy between the two radiation fractions) is under way. In addition, the feasibility of substituting gemcitabine for hydroxyurea is undergoing evaluation. Future trials in this disease should focus on developing new combinations that are less toxic and have similar efficacy.


Gastric xanthelasma may be a warning sign of intestinal metaplasia: A cross‑sectional study.
Certain conflicting conclusions have been drawn that gastric xanthelasma is related to H. pylori, atrophic gastritis, intestinal metaplasia, and early gastric cancer. The aim of this study was to examine the relationship between gastric xanthelasma and upper gastrointestinal (GI) endoscopic or pathological features. A cross‑sectional study was completed. A total of 8,634 patients who underwent stomach biopsy and who had no gastrectomy history were enrolled in the study. The patients were divided into two groups according to the presence or absence of gastric xanthelasma. The relationship between gastric xanthelasma and demographic characteristics (including age and sex), endoscopic features (including peptic ulcer, bile reflux, and gastric poly), or pathological features (including atrophy, intestinal metaplasia, H. pylori, dysplasia, and gastric cancer) was analyzed. Age/sex matched analysis was also performed to exclude the influence of age and sex. The results revealed that out of the 8,634 patients, 3.54% patients had xanthelasma. Gastric xanthelasma was significantly associated with age (55.76 vs. 49.17 years, P<0.0001), duodenal ulcer (OR 0.860, 95% CI 0.369‑0.923), atrophy (OR 1.839, 95% CI 1.432‑2.362), and intestinal metaplasia (OR 3.296, 95% CI 2.612‑4.159). Binary logistic analysis revealed that age (OR 1.027, 95% CI 1.017‑1.037) and intestinal metaplasia (OR 2.700, 95% CI 2.090‑3.487) were independently related to gastric xanthelasma. Age/sex matched control binary logistic analysis revealed that gastric xanthelasma was significantly associated with presence of intestinal metaplasia (OR 2.338, 95% CI 1.659‑3.297). There was no difference in the number (P=0.427) and location (P>0.05) of gastric xanthelasma for intestinal metaplasia. In conclusion, gastric xanthelasma may be an independent endoscopic warning sign of intestinal metaplasia.


Characteristics associated with behavioral symptoms related to dementia in long-term care residents.
This article describes care for behavioral symptoms related to dementia (BSRD) and identifies their potential correlates among 347 residents with dementia living in 45 assisted living facilities and nursing homes from four states. The prevalence of BSRD was associated with staff training and resident cognition, mood, mobility, and psychotropic use. Attention to staff training and depression management might improve BSRD.


Replantation of permanent incisors in children using Emdogain.
The aim of this study was to determine whether application of an enamel matrix protein derivative, Emdogain (Biora AB Malmo, Sweden) to the root surface of avulsed permanent incisors would improve postreplantation outcomes in a pediatric population. Between June 1999 and May 2002, 25 avulsed permanent maxillary incisors (22 centrals and three laterals) were treated with Emdogain and followed for up to 32 months, mean duration 20.6 months (range: 6.9-32.5 months). Mean patient age at the time of treatment was 12.0 years (range: 7.7-17.6 years) and mean extra-alveolar duration was 185 min (range: 100-300 min). At the end of their follow-up each of the replanted incisors demonstrated radiographic evidence of replacement root resorption and clinical evidence of ankylosis. None of the replanted teeth were affected by inflammatory root resorption and there was no evidence of infection. When compared with the control samples from Barrett and Kenny (Endod Dent Traumatol 1997;15:269-72.) and Andersson et al. (Endod Dent Traumatol 1989;5:38-47.) this sample treated with the Emdogain protocol demonstrated significantly less root resorption than either of the control samples (anova, P < 0.0001). Although the Emdogain protocol did not produce periodontal regeneration, it did eliminate inflammatory resorption and infection and led to significantly less root resorption compared with the two historical controls.


Safety of Intravenous Methamphetamine Administration During Ibudilast Treatment.
Methamphetamine dependence is a significant public health concern without any approved medications for treatment. We evaluated ibudilast, a nonselective phosphodiesterase inhibitor, to assess the safety and tolerability during intravenous methamphetamine administration. We conducted a randomized, double-blind, placebo-controlled, within-subjects crossover clinical trial. Participants received ibudilast (20 mg twice daily followed by 50 mg twice daily) and placebo, with order determined by randomization, and then underwent intravenous methamphetamine challenges (15 and 30 mg). We monitored cardiovascular effects, methamphetamine pharmacokinetics, and reported adverse events. Ibudilast treatment had similar rates of adverse events compared with placebo, and there was no significant augmentation of cardiovascular effects of methamphetamine. Pharmacokinetic analysis revealed no clinically significant change in maximum concentration or half-life of methamphetamine with ibudilast. Methamphetamine administration during ibudilast treatment was well tolerated without additive cardiovascular effects or serious adverse events, providing initial safety data to pursue ibudilast's effectiveness for the treatment of methamphetamine dependence.


Comparison of readmission and early revision rates as a quality metric in total knee arthroplasty using the Nationwide Readmission Database.
After release of the Comprehensive Care for Joint Replacement bundle, there has been increased emphasis on reducing readmission rates for total knee arthroplasty (TKA). The potential for a separate, clinically-relevant metric, TKA revision rates within a year following surgery, has not been fully explored. Based on this, we compared rates and payments for TKA readmission and revision procedures as metrics for improving quality and cost. We utilized the 2013 Nationwide Readmission Database (NRD) to examine national readmission and revision rates, the reasons for revision procedures, and associated costs for elective TKA procedures. As data are not linked across years, we examined revision rates for TKA completed in the month of January by capturing revision procedures in the subsequent following 11-month period to approximate a 1-year revision rate. Diagnosis and procedure codes for revision procedures were collected. Average readmission and revision procedure costs were then calculated, and the cost distributed across the entire TKA population. We identified 20,851 patients having TKA surgery. The mean unadjusted 30- and 90-day TKA readmission rates were 3.4% and 5.8%, respectively. In contrast, the mean unadjusted 3-month and approximate 1-year reoperation rates were 1.0% and 1.6%, respectively. The most common cause for revision was periprosthetic joint infection, which accounting for 62% of all reported revision procedures. The mean payment for 90-day readmission was roughly half ($10,589±$11,084) of the mean inpatient payment for single reoperation procedure at 90 days ($20,222±$17,799). Importantly, nearly half (46%) of all 90-day readmissions were associated with a reoperation event within the first year. Readmission following TKA is associated with a 1-year reoperation in approximately half of patients. These reoperations represent a significant patient burden and have a higher per episode cost. Early reoperation may represent a more clinically relevant target for quality improvement and cost containment.


Molecular genetic analysis of 400-year-old human remains found in two Yakut burial sites.
The excavation of five frozen graves at the Sytygane Syhe and Istekh-Myrane burial sites (dated at 400 years old) in central Yakutia revealed five human skeletons belonging to the Yakut population. To investigate the origin and evolution of the Yakut population as well as the kinship system between individuals buried in these two sites, DNA was extracted from bone samples and analyzed by autosomal short tandem repeats (STRs) and by sequencing hypervariable region I (HV1) of the mitochondrial DNA (mtDNA) control region. The results showed a diversity of sepulchral organizations linked probably to the social or genetic background of the subjects. Comparison of STR profiles, mitochondrial haplotypes, and haplogroups with data from Eurasian populations indicated affinities with Asian populations and suggested a relative specificity and continuity of part of the Yakut mitochondrial gene pool during the last five centuries. Moreover, our results did not support a Central Asian (with the exception of maternal lineage of West Eurasian origin) or Siberian origin of the maternal lineages of these ancient Yakut subjects, implying an ethnogenesis of the Yakut population probably more complex than previously proposed.


Chicken Microchromosomes in the Lampbrush Phase: A Cytogenetic Description.
Lampbrush chromosomes are giant, transcriptionally active, meiotic chromosomes found in oocytes of all vertebrates with the exception of mammals. Lampbrush chromosomes offer a convenient tool for cytogenetic mapping and, in particular, have been instrumental in mapping genes and linkage groups on chicken (GGA) chromosomes. Whereas cytogenetic maps of macrochromosome GGA1-10 and microchromosome GGA11-16 lampbrush bivalents have been established, identification and description of smaller microchromosome bivalents are still missing. In this work, we used specific FISH probes for the identification of 12 chicken lampbrush chromosomes formed by GGA17-28. Our observations on chromomere and lateral loop arrangement and chiasma position allowed us to construct the respective cytogenetic maps for these microchromosomes. For the 10 smallest chicken microchromosomes, GGA29-38, no individual molecular tags are available, yet they can be collectively marked using the PO41 repeat. The reported results contribute to building of working cytogenetic maps of the chicken karyotype.


An NF1 motif plays a central role in hepatitis B virus enhancer.
The hepatitis B virus enhancer plays an important role in transcription regulation of the viral genes in a liver-specific manner. In animal models a homologous element seems to be involved in activation of cellular oncogenes and tumorigenesis. Previously, the enhancer was divided into several functional domains, whereby each one seemed to be required for optimal transcription activity. To gain more information on the mode of action of these elements and their role in viral genome, we mutagenized the individual enhancer elements and analyzed their functions in three different experimental systems. All show that the NF1b motif of the enhancer plays a central role, with the most dramatic results obtained from the cell-free in vitro transcription assay. Furthermore, an intact viral genome mutated at the NF1b site is a poor template for the synthesis of the 3.5-kb pregenomic RNA. These data are rather unexpected, given the ubiquitous appearance of this factor. On the other hand, our findings are in agreement with a large number of recently reported cases in which NF1 seems to determine tissue-specific expression of a wide range of cellular and viral promoters.


Prevention of experimental allergic encephalomyelitis by bacterial lipopolysaccharides: inhibition of cell-mediated immunity.
The immunization of Lewis rats with bacterial lipopolysaccharides (LPS) precomplexed to guinea pig myelin basic protein (BP) in complete Freund's adjuvant inhibits the development of experimental allergic encephalomyelitis (EAE) in these animals. These protected animals fail to manifest significant in vivo delayed-type hypersensitivity skin tests and in vitro lymphocyte proliferative responses to BP. Our results indicated that LPS induces a nonspecific reduction in immune reactivity of BP in Lewis rats.


Visceral mast cell tumour with eosinophilia and eosinophilic peritoneal and pleural effusions in a cat.
A cat with weight loss, pyrexia and recurrent lethargy and depression was found to have pleural and peritoneal eosinophilic effusions, peripheral eosinophilia, eosinophilic lymphadenitis and a massively enlarged mesenteric lymph node. Visceral mast cell neoplasia was diagnosed after histopathological examination of a biopsy of the mass. Palliative chemotherapy was attempted unsuccessfully and the cat was euthanased.


A novel microduplication of ARID1B: Clinical, genetic, and proteomic findings.
Genetic alterations of ARID1B have been recently recognized as one of the most common mendelian causes of intellectual disability and are associated with both syndromic and non-syndromic phenotypes. The ARID1B protein, a subunit of the chromatin remodeling complex SWI/SNF-A, is involved in the regulation of transcription and multiple downstream cellular processes. We report here the clinical, genetic, and proteomic phenotypes of an individual with a unique apparent de novo mutation of ARID1B due to an intragenic duplication. His neurodevelopmental phenotype includes a severe speech/language disorder with full scale IQ scores 78-98 and scattered academic skill levels, expanding the phenotypic spectrum of ARID1B mutations. Haploinsufficiency of ARID1B was determined both by RNA sequencing and quantitative RT-PCR. Fluorescence in situ hybridization analysis supported an intragenic localization of the ARID1B copy number gain. Principal component analysis revealed marked differentiation of the subject's lymphoblast proteome from that of controls. Of 3426 proteins quantified, 1014 were significantly up- or down-regulated compared to controls (q < 0.01). Pathway analysis revealed highly significant enrichment for canonical pathways of EIF2 and EIF4 signaling, protein ubiquitination, tRNA charging and chromosomal replication, among others. Network analyses revealed down-regulation of: (1) intracellular components involved in organization of membranes, organelles, and vesicles; (2) aspects of cell cycle control, signal transduction, and nuclear protein export; (3) ubiquitination and proteosomal function; and (4) aspects of mRNA synthesis/splicing. Further studies are needed to determine the detailed molecular and cellular mechanisms by which constitutional haploinsufficiency of ARID1B causes syndromic and non-syndromic developmental disabilities.


Ritanserin, a 5-HT2 receptor blocker, as add-on treatment in narcolepsy.
In a double-blind placebo-controlled trial, ritanserin (a 5-HT2 receptor blocker) 5 mg/day or placebo was added to the usual medication in 28 patients with narcolepsy during 4 wk. The effect was assessed by means of polysomnography, daily and weekly subjective evaluations, and Multiple sleep latency tests (MSLT). During the night ritanserin increased the amount of nonrapid eye movement slow wave sleep and reduced wakefulness after sleep onset. It improved the feeling of being refreshed in the morning after awakening and reduced subjective daytime sleepiness. The drug did not significantly influence sleep latency in the MSLT.


The characteristics of embryonal carcinoma cells in teratocarcinomas.
The orchiectomy specimens and the respective lymphadenectomies of 33 teratocarcinomas (teratoma and embryonal carcinoma) and 30 embryonal carcinomas were identified in a series of 457 consecutive germ cell tumors of the testis. Although teratocarcinomas were larger tumors the retroperitoneal lymphadenectomies revealed metastases in only 10 of 33 (30%) teratocarcinomas as compared to 19 of 30 (63%) embryonal carcinomas. Even after subtracting the teratoma component and stratifying for size of the embryonal carcinoma component, the teratocarcinomas were still less likely to metastasize than comparably sized pure embryonal carcinomas. Statistical significance was found between the differences in size and the differences in the rates of metastases, before and after stratifying for size of the embryonal carcinoma component of the teratocarcinomas. Further, all embryonal carcinomas metastasized as embryonal carcinoma while only 5 teratocarcinomas metastasized as embryonal carcinoma. This study supports experimental evidence that the embryonal carcinoma cells in teratocarcinomas are not necessarily identical to embryonal carcinoma cells in embryonal carcinomas.


An in vivo stathmokinetic study of cell proliferation in human gastric carcinoma and gastric mucosa.
Cell production rates were studied in a group of eleven patients with carcinoma of the stomach using an in vivo technique with vincristine. In normal pyloric mucosa estimates ranged from 8 to 15 cells/1000 cells/hr, and in the carcinomas from 3 to 24 cells/1000 cells/hr. Because of the very large variation in the data, comparison between individual tumours and normal mucosa is not regarded as being worth-while at this stage. The implications of these results for previous human in vivo stathmokinetic experiments are also discussed.


Radiological and radionuclide investigation of malignant otitis externa.
This study looks at case series of malignant otitis externa, outlines detailed structural (radiological) and functional (radionuclide) investigations, and discusses their utility in the initial diagnosis, patient management and follow up of this condition. Patients were investigated by computerized tomography (CT), magnetic resonance imaging (MRI), two-phase planar and single-photon emission tomography (SPECT), technetium-99m methylenediphosphonate bone scans, gallium-67 planar and SPECT scans, and indium-111 or technetium-99m labelled WBC planar and SPECT scintigraphy. We discuss example case reports with the various radiological and scintigraphic findings and outline a protocol for rational investigation. It is concluded that CT and/or MRI should be supported by routine SPECT bone imaging for initial diagnosis of malignant otitis externa. Routine SPECT bone imaging further supplemented by gallium scintigraphy should be the investigation of choice in the follow up of these cases for assessing response to treatment and disease recurrence.


Homosexuality via canalized sexual development: a testing protocol for a new epigenetic model.
We recently synthesized and reinterpreted published studies to advance an epigenetic model for the development of homosexuality (HS). The model is based on epigenetic marks laid down in response to the XX vs. XY karyotype in embryonic stem cells. These marks boost sensitivity to testosterone in XY fetuses and lower it in XX fetuses, thereby canalizing sexual development. Our model predicts that a subset of these canalizing epigenetic marks stochastically carry over across generations and lead to mosaicism for sexual development in opposite-sex offspring--the homosexual phenotype being one such outcome. Here, we begin by outlining why HS has been under-appreciated as a commonplace phenomenon in nature, and how this trend is currently being reversed in the field of neurobiology. We next briefly describe our epigenetic model of HS, develop a set of predictions, and describe how epigenetic profiles of human stem cells can provide for a strong test of the model.


Surface complexation modeling of carbonate effects on the adsorption of Cr(VI), Pb(II), and U(VI) on goethite.
Dissolved carbonate species are known to affect the sorption behavior of trace species. The macroscopic description of these interactions with a thermodynamic approach has been limited by the lack of data on the binary interaction between carbonate and relevant mineral surfaces. This work follows from two detailed studies of carbonate adsorption on goethite (4, 13). It shows that independent triple-layer surface complexation modeling (TLM) of carbonate adsorption allows successful descriptions of carbonate-trace element ternary sorption on this oxide, using relatively simple and optimal stoichiometries. Carbonate adsorption was considerably enhanced in the presence of Pb(II), despite an invariant total Pb(II) sorption to equilibration with up to 1% C02(g). Both the Pb(II)-carbonate system behavior and the anion-like pH adsorption behavior of U(VI) in the presence of C02 were successfully modeled using binary and ternary metal-bound surface complexes. The significant reduction of Cr(VI) adsorption edges to lower pH values in the presence of C02 was accurately simulated and explained via site competition and surface electrostatic repulsion effects on the predicted inner- and outer-sphere Cr(VI) surface complexes formed. The results of this research are highly relevant to modeling of metal transport field data and of potential soil remediation schemes using carbonate.


[Fetal and maternal amniocentesis complications].
The aim of this study was to estimate the incidence of complications due to the prenatal invasive diagnosis performed by amniocentesis at the Department of Prenatal Diagnosis of the Second University of Naples. A total of 1.580 patients who underwent amniocentesis from January 2001 to December 2003, were submitted to a telephone interview concerning the complications that occurred after the invasive diagnosis. Only 1.416 patients out of the total patients interviewed answered correctly to the questionnaire. The complications that occurred in the first 24 h from amniocentesis (early complications) included light contractions and lipothymia respectively in 8.3% and 6.7% of cases; losses of amniotic fluid took place in 1.06% while bleedings were observed in 0.85% of cases. The incidence of abortions occurred in the week following amniocentesis was 0.78%. Preterm labor occurred in only 6% of the patients submitted to amniocentesis, spontaneous labor at term in 43% and cesarean section in 51%. The Apgar index at birth was normal in 95.7% of cases. In the remaining 4.3% pathologies like hypoglycemia or respiratory distress, which promptly regressed, were observed. Early complications and the incidence of abortions were significantly and independently associated with the double needle puncture but not with maternal age or the placenta specimen obtained during amniocentesis. A careful observation of the technique and the protocol, as well as a careful selection of patients are necessary presuppositions in order to further decrease the occurrence of complications due to amniocentesis.


The incidence of pressure sores within a National Health Service Trust hospital during 1991.
The prevalence of pressure sores has been frequently reported. However, such measures fail to identify how many patients develop sores, while longitudinal changes in prevalence rates are difficult to interpret. This paper provides the first report of the incidence of pressure sores across the population of a single NHS Trust hospital. During 1991, 360 patients developed sores, an incidence of 4.03 patients per 100 admissions. Within orthopaedic wards, the incidence was higher, with 10.3 patients per 100 admissions developing sores.


Thermal Casimir effect in the plane-sphere geometry.
The thermal Casimir force between two metallic plates is known to depend on the description of material properties. For large separations the dissipative Drude model leads to a force a factor of 2 smaller than the lossless plasma model. Here we show that the plane-sphere geometry, in which current experiments are performed, decreases this ratio to a factor of 3/2, as revealed by exact numerical and large-distance analytical calculations. For perfect reflectors, we find a repulsive contribution of thermal photons to the force and negative entropy values at intermediate distances.


Toll-like receptor 9 gene mutations and polymorphisms in Japanese ulcerative colitis patients.
To investigated gene mutations and polymorphisms of TLR9 in Japanese ulcerative colitis (UC) patients. Three single nucleotide polymorphisms (SNPs) in TLR9 were identified in healthy controls, and were assessed in 48 UC patients and 47 healthy controls. Control subjects were matched for age, sex and date of blood sampling from among a subgroup of participants. TLR9 -1486CC, 1174GG and 2848AA increase the risk of UC [odds ratio (OR) 2.64, 95% confidence interval (95% CI): 1.73-6.53, P = 0.042], and TLR9 -1486TT, 1174AA and 2848GG decrease the risk of UC (OR 0.30, 95% CI: 0.10-0.94, P = 0.039), although there were no correlations between SNPs and disease phenotype or TLR9 mRNA expression. TLR9 polymorphisms are associated with increased susceptibility to UC.


Focal stimulation of the mossy fibers releases endogenous dynorphins that bind kappa 1-opioid receptors in guinea pig hippocampus.
Physiological release of endogenous opioids in guinea pig hippocampal slices was detected in an in vitro competition binding assay using [3H]U69,593, a kappa 1-selective radioligand. Veratridine-induced opioid release caused a decrease in [3H]U69,593 binding that was blocked by either tetrodotoxin addition or the removal of calcium from the incubation buffer. Focal electrical stimulation of opioid peptide-containing afferent pathways resulted in a decrease in [3H]U69,593 binding, whereas stimulation of a major afferent lacking endogenous opioid immunoreactivity had no effect. The addition of 6-cyano-7-nitroquinoxaline-2,3-dione blocked the reduction in [3H]U69,593 binding caused by perforant path stimulation, but not the reduction caused by mossy fiber stimulation, suggesting that the primary source of endogenous kappa ligands was likely to be the dentate granule cells. Antisera against dynorphin A(1-8) or dynorphin B peptides inhibited the effects of mossy fiber stimulation in the [3H]U69,593 displacement assay. Antisera against other prodynorphin- and proenkephalin-derived opioid peptides had no effect. As shown by receptor autoradiography, the distribution of kappa 1 binding sites was limited to the molecular layer of the dentate gyrus and the presubiculum region of temporal hippocampal slices. These results indicate that prodynorphin-derived opioids released under physiological conditions from the mossy fibers act at kappa 1 receptors in the guinea pig dentate gyrus.


Synergism of epidermal growth factor receptor-targeted immunotherapy with photodynamic treatment of ovarian cancer in vivo.
Epithelial ovarian cancer often develops resistance to standard treatments, which is a major reason for the high mortality associated with the disease. We examined the efficacy of a treatment regimen that combines immunotherapy to block the activity of epidermal growth factor receptor (EGFR), overexpression of which is associated with the development of resistant ovarian cancer, and photodynamic therapy (PDT), a mechanistically distinct photochemistry-based modality that is effective against chemo- and radioresistant ovarian tumors. We tested a combination regimen consisting of C225, a monoclonal antibody that inhibits the receptor tyrosine kinase activity of EGFR, and benzoporphyrin derivative monoacid A (BPD)-based PDT in a mouse model of human ovarian cancer. Therapeutic efficacy was evaluated in acute treatment response and survival studies that used 9-19 mice per group. Analysis of variance and Wilcoxon statistics were used to analyze the data. All statistical tests were two-sided. Mice treated with PDT + C225 had the lowest mean tumor burden compared with that in the no-treatment control mice (mean percent tumor burden = 9.8%, 95% confidence interval [CI] = 2.3% to 17.3%, P < .001). Mean percent tumor burden for mice treated with C225 only or PDT only was 66.6% (95% CI = 58.7% to 74.4%, P < .001) and 38.2% (95% CI = 29.3% to 47.0%, P < .001), respectively. When compared with PDT only or C225 only, PDT + C225 produced synergistic reductions in mean tumor burden (P < .001, analysis of variance) and improvements in survival (P = .0269, Wilcoxon test). Median survival was approximately threefold greater for mice in the PDT + C225 group than for mice in the no-treatment control group (80 days versus 28 days), and more mice in the PDT + C225 group were alive at 180 days (3/9; 33% [95% CI = 7% to 70%]) than mice in the C225-only (0/12; 0% [95% CI = 0% to 22%]) or PDT-only (1/10; 10% [95% CI = 0.2% to 44%]) groups. A mechanistically nonoverlapping combination modality consisting of receptor tyrosine kinase inhibition with C225 and BPD-PDT is well tolerated, effective, and synergistic in mice.


[Criteria for diagnosing DIC].
The differences between reagents of prothrombin time (PT), fibrinogen and fibrin and fibrinogen degradation products(FDP) were examined in patients with disseminated intravascular coagulation (DIC) and without DIC. The sensitivity of the PT ratio for DIC is lowered by the PT reagent with a high international sensitivity index, and the difference between PT reagents was marked. The sensitivity of PT-international normalized ratio (INR) for DIC was higher than that of the PT ratio and the difference between reagents in PT-INR was low. Though the difference between reagents for fibrinogen is slight, the usefulness in diagnosing DIC is also slight. Though the sensitivity of FDP for DIC was good, the difference between FDP reagents was marked. Therefore, standardization of PT and FDP seems to be necessary. Concordance of overt-DIC diagnostic criteria by the International Society of Thrombosis and Haemostasis (ISTH) and DIC diagnostic criteria of Japanese Ministry of Health and Welfare (JMHW) was about 70%, and overt-DIC diagnostic criteria of ISTH seemed to diagnose the typical type of DIC diagnosed by JMHW criteria. Finally, the diagnostic criteria of non-overt DIC are expected to become increasingly important.


Computed tomography characteristics of primary pulmonary lymphoepithelioma-like carcinoma.
Primary pulmonary lymphoepithelioma-like carcinoma is a very rare subtype of lung cancer. This report documents the CT features of 16 Chinese patients diagnosed with primary pulmonary lymphoepithelioma-like carcinoma from January 1999 to December 2005. A pre-treatment CT was used to assess the tumour site, size, borders, pleural and vascular involvement, and the presence of lymph node involvement. The majority of the patients were female non-smokers with centrally located tumours. Lymph node involvement and bronchial and vascular encasement were frequent. In an Epstein-Barr virus endemic area, primary pulmonary lymphoepithelioma-like carcinoma is an important differential diagnosis to consider.


Constraint-induced movement therapy during early stroke rehabilitation.
Limited data are available about the effectiveness of early rehabilitation after stroke. This is the 1st randomized controlled trial of constraint-induced movement therapy (CIMT) in subacute stroke to investigate neurophysiologic mechanisms and long-term outcome. Within 2 weeks after stroke, 23 patients with upper extremity (UE) weakness were randomized to 2 weeks of CIMT or traditional therapy at an equal frequency of up to 3 h/day. Motor function of the affected UE was blindly assessed before treatment, after treatment, and 3 months after stroke. Transcranial magnetic stimulation (TMS) measured the cortical area evoking movement of the affected hand. Long-term improvement in motor function of the affected UE did not differ significantly between patients who received CIMT versus intensive traditional therapy. All outcome comparisons showed trends favoring CIMT over intensive traditional therapy, but none was statistically significant except for improvements in the Fugl-Meyer (FM) UE motor scale immediately following treatment and in reported quality of hand function at 3 months. Improvement in UE motor function on the FM was associated with a greater number of sites on the affected cerebral hemisphere where responses of the affected hand were evoked by TMS. Future trials of CIMT during early stroke rehabilitation need greater statistical power, more inclusive eligibility criteria, and improved experimental control over treatment intensity. The relationship between changes in motor function and in evoked motor responses suggests that motor recovery during the 1st 3 months after stroke is associated with increased motor excitability of the affected cerebral hemisphere.


The Disruption of an OxyR-Like Protein Impairs Intracellular Magnetite Biomineralization in Magnetospirillum gryphiswaldense MSR-1.
Magnetotactic bacteria synthesize intracellular membrane-enveloped magnetite bodies known as magnetosomes which have been applied in biotechnology and medicine. A series of proteins involved in ferric ion transport and redox required for magnetite formation have been identified but the knowledge of magnetosome biomineralization remains very limited. Here, we identify a novel OxyR homolog (named OxyR-Like), the disruption of which resulted in low ferromagnetism and disfigured nano-sized iron oxide crystals. High resolution-transmission electron microscopy showed that these nanoparticles are mainly composed of magnetite accompanied with ferric oxide including α-Fe2O3 and 𝜀-Fe2O3. Electrophoretic mobility shift assay and DNase I footprinting showed that OxyR-Like binds the conserved 5'-GATA-N{9}-TATC-3' region within the promoter of pyruvate dehydrogenase (pdh) complex operon. Quantitative real-time reverse transcriptase PCR indicated that not only the expression of pdh operon but also genes related to magnetosomes biosynthesis and tricarboxylic acid cycle decreased dramatically, suggesting a link between carbon metabolism and magnetosome formation. Taken together, our results show that OxyR-Like plays a key role in magnetosomes formation.


Homotransfer of FRET Reporters for Live Cell Imaging.
Förster resonance energy transfer (FRET) between fluorophores of the same species was recognized in the early to mid-1900s, well before modern heterotransfer applications. Recently, homotransfer FRET principles have re-emerged in biosensors that incorporate genetically encoded fluorescent proteins. Homotransfer offers distinct advantages over the standard heterotransfer FRET method, some of which are related to the use of fluorescence polarization microscopy to quantify FRET between two fluorophores of identical color. These include enhanced signal-to-noise, greater compatibility with other optical sensors and modulators, and new design strategies based upon the clustering or dimerization of singly-labeled sensors. Here, we discuss the theoretical basis for measuring homotransfer using polarization microscopy, procedures for data collection and processing, and we review the existing genetically-encoded homotransfer biosensors.


The ratio of metastatic/resected lymph nodes is an independent prognostic factor in patients with node-positive pancreatic head cancer.
The aim of this study was to evaluate the prognostic value of nodal involvement in resected adenocarcinoma of the pancreatic head. For the period between 1980 and 2002, 96 patients underwent pancreaticoduodenectomy for pancreatic cancer. Lymph nodes were numbered and classified into groups according to the Japan Pancreatic Society rules. Metastatic lymph nodes were identified based on hematoxylin and eosin staining. Sixty-four (66.7%) patients had positive lymph nodes. The median number of metastatic nodes was 2 (95% confidence interval [CI], 1.0-3.0) and the median ratio of metastatic/resected nodes was 9.7% (95% CI, 7.1%-14.4%). The median survival was 14.2 months (95% CI, 10.7-17.7) and was significantly higher for node-negative than node-positive patients (27.9; 95% CI, 20.9-34.9 vs. 10.6; 95% CI, 8.7-12.5; P < 0.001). The Cox proportional hazards model, including all patients, demonstrated that nodal involvement (hazard ratio [HR], 1.461; 95% CI, 1.177-12.024), moderate or poor tumor differentiation (HR, 2.330; 95% CI, 1.181-6.949), and positive resection margins (HR, 3.838; 95% CI, 1.390-10.597) were independent negative prognostic factors. If the analysis was limited to node-positive patients, lymph node ratio of more than 20% (HR, 1.364; 95% CI, 1.116-2.599), moderate or poor tumor differentiation (HR, 3.393; 95% CI, 1.041-11.061), and positive resection margins (HR, 9.400; 95% CI, 2.235-39.536) significantly correlated with a poorer survival. Lymph node ratio seems to be a new promising prognostic factor in patients with respectable node-positive pancreatic head cancer.


[Clinical Significance of Circulating Tumor DNA and Its Future Prospects].
"Liquid biopsy"is a diagnostic medium to detect very small amount of tumor-derived molecules in blood for selecting precise clinical treatments and giving a diagnosis. This article focuses on circulating tumor DNA(ctDNA)and describes its features, clinical significance as well as future prospects with recent findings in this field. "Liquid biopsy"using ctDNAis facilitated by recent developments of highly sensitive technologies, including digital PCR. "BEAMing"is a digital PCR method that can detect rare mutations in ctDNAand will be introduced with some clinical evidences in this article. ctDNAis tumorderived fragmented DNAthat is circulating freely in the blood of a cancer patient. Tests for ctDNAare less invasive, easier than tissue-based tests to collect specimens and can be used repeatedly regardless of any cancer types. Emerging clinical evidences indicate that ctDNAtests show a high concordance rate with tissue-based tests in the identification of oncogene genotypes and can be used for real-time monitoring in vivo, such as prediction of clinical treatments, recurrence and drug resistance. "Liquid biopsy" using ctDNAcontinues to develop, but is promising to complement conventional tissue-based tests. Clinical applications of ctDNAtests are expected to expand as a useful diagnostic tools in areas of therapy selection and monitoring for drug resistance.


Proteolytic cleavage orchestrates cofactor insertion and protein assembly in [NiFe]-hydrogenase biosynthesis.
Metalloenzymes catalyze complex and essential processes, such as photosynthesis, respiration, and nitrogen fixation. For example, bacteria and archaea use [NiFe]-hydrogenases to catalyze the uptake and release of molecular hydrogen (H2). [NiFe]-hydrogenases are redox enzymes composed of a large subunit that harbors a NiFe(CN)2CO metallo-center and a small subunit with three iron-sulfur clusters. The large subunit is synthesized with a C-terminal extension, cleaved off by a specific endopeptidase during maturation. The exact role of the C-terminal extension has remained elusive; however, cleavage takes place exclusively after assembly of the [NiFe]-cofactor and before large and small subunits form the catalytically active heterodimer. To unravel the functional role of the C-terminal extension, we used an enzymatic in vitro maturation assay that allows synthesizing functional [NiFe]-hydrogenase-2 of Escherichia coli from purified components. The maturation process included formation and insertion of the NiFe(CN)2CO cofactor into the large subunit, endoproteolytic cleavage of the C-terminal extension, and dimerization with the small subunit. Biochemical and spectroscopic analysis indicated that the C-terminal extension of the large subunit is essential for recognition by the maturation machinery. Only upon completion of cofactor insertion was removal of the C-terminal extension observed. Our results indicate that endoproteolytic cleavage is a central checkpoint in the maturation process. Here, cleavage temporally orchestrates cofactor insertion and protein assembly and ensures that only cofactor-containing protein can continue along the assembly line toward functional [NiFe]-hydrogenase.


The effect of complementary and alternative medicine on quality of life, depression, anxiety, and fatigue levels among cancer patients during active oncology treatment: phase II study.
During the past decade, there has been growing interest in complementary and alternative medicine (CAM) among cancer patients and it is being integrated more frequently within conventional cancer centers. The long-term effect of mind-body therapies on quality of life (QoL), depression, anxiety, and fatigue was tested prospectively in this study. Cancer patients who received six weekly sessions of CAM during their oncological treatments participated in the study. The Hospital Anxiety and Depression Scale (HADS), Brief Fatigue Inventory (BFI) and QoL-EORTC-C30 were completed during the intervention and follow-up period. Over a two-year period, 163 patients entered the study, 135 of whom completed all six CAM sessions. An improvement was demonstrated in the median of BFI from 4.8 to 3.9 (p < 0.001), HADS-Anxiety from 8 to 7 (p < 0.001) and HADS-Depression from 7 to 6 (p < 0.001) after 12 weeks. In addition, the median of global QoL improved from 50 to 67 (p < 0.001), and a significant improvement was noticed in several parameters on the functioning and symptoms scales of the QoL-EORTC-C30. Cancer patients who completed six weekly sessions of CAM improved significantly on measured outcomes, regardless of their demographic characteristics.


Zac1 regulates cell cycle arrest in neuronal progenitors via Tcf4.
Imprinted genes play a critical role in brain development and mental health, although the underlying molecular and cellular mechanisms remain incompletely understood. The family of basic helix-loop-helix (bHLH) proteins directs the proliferation, differentiation, and specification of distinct neuronal progenitor populations. Here, we identified the bHLH factor gene Tcf4 as a direct target gene of Zac1/Plagl1, a maternally imprinted transcriptional regulator, during early neurogenesis. Zac1 and Tcf4 expression levels concomitantly increased during neuronal progenitor differentiation; moreover, Zac1 interacts with two cis-regulatory elements in the Tcf4 gene locus, and these elements together confer synergistic activation of the Tcf4 gene. Tcf4 upregulation enhances the expression of the cyclin-dependent kinase inhibitor gene p57(Kip2), a paternally imprinted Tcf4 target gene, and increases the number of cells in G1 phase. Overall, we show that Zac1 controls cell cycle arrest function in neuronal progenitors through induction of p57(Kip2) via Tcf4 and provide evidence for cooperation between imprinted genes and a bHLH factor in early neurodevelopment.


Managing strategic outsourcing.
One of the greatest challenges for companies is to know what to outsource and when. This article describes how to outsource effectively and thereby be more flexible and responsive to market demands.


Current practices and perceived implementation barriers for working with alcohol prevention in occupational health services: the WIRUS OHS study.
Alcohol is associated with detrimental health and work performance outcomes, and one to three out of ten employees may benefit from interventions. The role of occupational health services (OHS) in alcohol prevention has received little attention in research. The primary aims of this study were to explore current practices of alcohol prevention targeting employees in occupational health settings, and examine whether and which perceived implementation barriers were associated with alcohol prevention activity. The secondary aim was to explore whether barriers were differentially associated with primary, secondary and tertiary prevention activities. In this cross-sectional study, survey data were collected from 295 OHS professionals in Norway in 2018. Data were analysed by means of descriptive statistics, one-way analysis of variance, paired samples t-tests, and multivariate linear regression analyses. Overall, seven out of ten OHS professionals worked with alcohol-related cases less than monthly, while only one out of ten did so on a weekly basis. Their activities were more focused on tertiary prevention than on primary and secondary prevention. Physicians, psychologists and nurses reported to handle alcohol-related issues more often than occupational therapists and physical therapists. Higher levels of implementation barriers internal to the OHS' organisation (competence, time and resources) were associated with lower alcohol prevention activity. Barriers external to the OHS' organisation (barriers concerning employers and employees) were not. This pattern was evident for primary, secondary and tertiary prevention activities. A majority of OHS professionals agreed that employees' alcohol consumption constitute a public health challenge, and that OHS' should focus more on alcohol prevention targeting employees. Occupational health settings at workplaces may be particularly serviceable for alcohol prevention programmes since the majority of the population is employed and the majority of employees consume alcohol. An increase in overall prevention activity, and a shift from mainly focusing on tertiary prevention to an increased emphasis on primary and secondary prevention, may both hinge on increased training of OHS professionals, emphasising knowledge on the importance of working with alcohol prevention, and training in administering alcohol prevention programmes. Making alcohol prevention a priority may also require increased allocation of time and resources.


Association between home food preparation skills and behaviour, and consumption of ultra-processed foods: Cross-sectional analysis of the UK National Diet and nutrition survey (2008-2009).
'Ultra-processed foods' (UPF) have been industrially processed and tend to be higher in saturated fat, sodium and sugar than other foods. There is some evidence that consumption of UPF is associated with overweight, obesity and related diseases. In developed countries more than half of dietary energy is attributed to UPF. One reason for reliance on UPF may be poor home food preparation skills or infrequent use of these. This relationship has been previously proposed but not tested. We examined the relationship between home food preparation skills and behaviour and consumption of UPF. We used data from adults in the UK National Diet & Nutrition Survey 2008-09. Home food preparation skills and behaviours of adults (n = 509) were assessed using questions on confidence using eight cooking techniques, confidence cooking 10 foods, ability to prepare a cake or biscuits without help, and whether or not participants prepared a main meal five or more days per week. Individuals' UPF consumption was determined from four-day estimated diet diaries. Associations were adjusted for age, gender, occupational social class and household composition. In fully adjusted models, individuals who were confident with all 10 foods (adjusted beta (95% CI) = -3.76 (-6.02 to -1.50)), able to bake cakes or biscuits without help (-3.87 (-6.62 to -1.12)), and cooked a main meal at least five days a week (-2.84 (-5.43 to -0.24)) consumed a lower percentage of dietary energy from UPF. In UK adults better home food preparation skills and more frequent use of these skills tended to be cross-sectionally associated with lower UPF consumption. Greater encouragement of these skills may help reduce reliance on UPF.


Infected Thrombus on a TAVI Aortic Valve.
After a series of tests, an 86-year-old patient was shown to have an infected thrombus on a TAVI valve and was referred to urgent surgery. The valve with the infected thrombus was removed and a biological prosthetic valve was implanted in its place.


[Clinical and electroencephalogram study of 5 children with hypothalamic hamartoma].
We retrospectively studied 5 children with hypothalamic hamartoma (HH) to elucidate the clinical, neuroimaging and electroencephalogram (EEG) characteristics of this disorder. In all cases, high resolution MRI scans demonstrated an intrahypothalamic mass protruding into the 3rd ventricle. An initial symptom was epileptic attack in 4 cases and precocious puberty in the remaining one. Gelastic seizures developed in 4 of 5 patients at ranging from 2 days to 11 years of age. The ictal EEGs during the gelastic seizures showed diffuse attenuation of background activity, followed by rhythmic slow discharges either diffusely or in the central area. Gamma-knife radiosurgery was performed on 2 cases whose seizures were resistant to available antiepileptic drugs. One of the 2 patients was responded significantly to this treatment, showing the disappearance of combined attacks and a marked reduction of the generalized spike-waves discharges. A more aggressive therapy, including gamma-knife radiosurgery and surgical treatment, should be considered for patients whose seizures are resistant to the medical treatment and causing deterioration of intelligence and behavioral problem.


Modeling Localization of Amplitude-Panned Virtual Sources in Sagittal Planes.
Vector-base amplitude panning (VBAP) aims at creating virtual sound sources at arbitrary directions within multichannel sound reproduction systems. However, VBAP does not consistently produce listener-specific monaural spectral cues that are essential for localization of sound sources in sagittal planes, including the front-back and up-down dimensions. In order to better understand the limitations of VBAP, a functional model approximating human processing of spectro-spatial information was applied to assess accuracy in sagittal-plane localization of virtual sources created by means of VBAP. First, we evaluated VBAP applied on two loudspeakers in the median plane, and then we investigated the directional dependence of the localization accuracy in several three-dimensional loudspeaker arrangements designed in layers of constant elevation. The model predicted a strong dependence on listeners' individual head-related transfer functions, on virtual source directions, and on loudspeaker arrangements. In general, the simulations showed a systematic degradation with increasing polar-angle span between neighboring loudspeakers. For the design of VBAP systems, predictions suggest that spans up to 40° polar angle yield a good trade-off between system complexity and localization accuracy. Special attention should be paid to the frontal region where listeners are most sensitive to deviating spectral cues.