Mutational analysis of open reading frame E4 of bovine papillomavirus type 1.
Open reading frame (ORF) E4 is a 353-base-pair ORF of bovine papillomavirus type 1. To determine the biological activities of this ORF in mouse C127 cells, we analyzed the effects of two constructed mutations which are predicted to prevent synthesis of ORF E4 proteins while leaving the amino acid sequence encoded by the overlapping ORF E2 unchanged. Neither mutation interfered with the abilities of the mutants to efficiently induce focus formation, induce growth in soft agarose, or transactivate an inducible bovine papillomavirus type 1 enhancer. Also, neither mutation prevented establishment of the viral DNA as an extrachromosomal plasmid in transformed cells. These results suggest that ORF E4 proteins are not required for these biological activities, and they are consistent with the observation of others (J. Doorbar, D. Campbell, R. J. A. Grand, and P. H. Gallimore, EMBO J. 5:355-362, 1986) that the ORF E4 protein of a human papillomavirus is associated with late gene expression during papilloma formation.


Magnesium neuroprotection is limited in humans with acute brain injury.
Based on the results of preclinical models, magnesium sulfate (MgSO4) has gained attention as a putative neuroprotective agent. The negative results of a large-scale, randomized clinical trial using MgSO4 in acute stroke have tempered the initial enthusiasm for a neuroprotective benefit of the ion. Additional, large-scale clinical trials in stroke and other forms of brain injury are underway. This article reviews the central nervous system (CNS) physiology of Mg++, disordered Mg++ homeostasis in acute brain injury, preclinical and preliminary clinical foundations of current clinical trials, and the data regarding the CNS bio-availability of MgSO4 an important requisite for neuroprotective therapy. Although human studies have confirmed that moderate hypermagnesemia is well-tolerated and feasible, only modest elevation of cerebrospinal fluid (CSF) [Mg++] occurs. This modest increment of CSF [Mg++] in brain-injured humans occurs in the range of 10 to 19%. However, experimental evidence has yet to establish whether this modest elevation is sufficient for neuroprotection. Because of the limited CNS passage of the ion, further experimental work is needed to define the neuroprotective threshold of [Mg++] in the injured brain.


[The prevention of depression in pregnancy and the post-partum: when to intervene?].
The aim of this paper is to describe the presence of anxious-depressive symptoms and risk factors and discuss the method of intervention used with women in pregnancy and post-partum. The mood of the woman was assessed by the Edinburgh Postnatal Depression Scale (EPDS) and the Beck Depression Inventory (BDI), personality traits with the Vulnerable Personality Style Questionnaire (VPSQ) and social support through the Social Provisions Scale (PPS). 50 women have completed the evaluation. In line with the international literature, the presence of anxiety-depressive symptoms is accompanied by the presence of multiple risk factors, in particular the familiar seems to be a predisposing factor.


Probing the micellization kinetics of pyrene end-labeled diblock copolymer via a combination of stopped-flow light-scattering and fluorescence techniques.
A pyrene end-labeled double hydrophilic diblock copolymer, poly(2-(diethylamino)ethyl methacrylate)-b-poly(2-(dimethylamino)ethyl methacrylate) (Py-PDEA-b-PDMA), was synthesized by sequential monomer addition via oxyanionic polymerization using a 1-pyrenemethanol-based initiator. This diblock copolymer exhibits reversible pH-responsive micellization behavior in aqueous solution, forming PDEA-core micelles stabilized by the soluble PDMA block at neutral or alkaline pH. Taking advantage of the pyrene probe covalently attached to the end of the PDEA block, the pH-induced micellization kinetics of Py-PDEA-b-PDMA was monitored by stopped-flow light scattering using a fluorescence detector. Upon a pH jump from 4.0 to 9.0, both the scattered light intensity and excimer/monomer fluorescence intensity ratios (IE/IM) increase abruptly initially, followed by a more gradual increase to reach plateau values. Interestingly, the IE/IM ratio increases abruptly within the first 10 ms: a triple exponential function is needed to fit the corresponding dynamic trace, leading to three characteristic relaxation time constants (tau(1,fluo) < tau(2,fluo) < tau(3,fluo)). On the other hand, dynamic traces for the scattered light intensity can be well-fitted by double exponential functions: the resulting time constants tau(1,scat) and tau(2,scat) can be ascribed to formation of the quasi-equilibrium micelles and relaxation into their final equilibrium state, respectively. Most importantly, tau(1,scat) obtained from stopped-flow light scattering is in general agreement with tau(2,fluo) obtained from stopped-flow fluorescence. The fastest process (tau(1,fluo) approximately 4 ms) detected by stopped-flow fluorescence is ascribed to the burst formation of small transient micelles comprising only a few chains, which are too small to be detected by conventional light scattering. These nascent micelles undergo rapid fusion and grow into quasi-equilibrium micelles and then slowly approach their final equilibrium state. The latter two processes can be detected by both techniques.


Classical simulation of high-dimensional entanglement by non-separable angular-radial modes.
An analogous model system for high-dimensional quantum entanglement is proposed, based on the angular and radial degrees of freedom of the improved Laguerre Gaussian mode. Experimentally, we observed strong violations of the Bell-CGLMP inequality for maximally non-separable states of dimension 2 through 10. The results for violations in classical non-separable state are in very good agreement with quantum instance, which illustrates that our scheme can be a useful platform to simulate high-dimensional non-local entanglement. Additionally, we found that the Bell measurements provide sufficient criteria for identifying mode separability in a high-dimensional space. Similar to the two-dimensional spin-orbit non-separable state, the proposed high-dimensional angular-radial non-separable state may provide promising applications for classical and quantum information processing.


The use of serial betaHCG to plan surgical evacuation of retained placenta in a case of placenta accreta.
Placenta accreta is a rare condition. Its management is always a dilemma. Traditionally, hysterectomy has been the treatment of choice. However, with appropriate case selection, conservative management is possible with or without using methotrexate. This case report describes conservative management of placenta accreta with serial monitoring of ssHCG.


Effect of tetracyclines on collagenase activity in patients with recurrent aphthous ulcers.
Human neutrophil-type (MMP-8) and fibroblast-type (MMP-1) interstitial collagenase, and their inhibition by tetracyclines in saliva from patients with recurrent aphthous ulcers (RAU) or aphthae, were studied by means of sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and enzymological analyses. In the salivary specimens obtained from patients with aphthae, collagenase was found in endogenously active form and was predominantly of MMP-8 type. Topical rinsing treatment with chlortetracycline (Aureomycin) alleviated the discomfort caused by the lesions but did not reduce salivary collagenase amounts; however in vitro, doxycycline inhibited salivary collagenase totally.


Sites of in vivo extraction and interconversion of testosterone and androstenedione in dogs.
The interconversion and extraction of testosterone and androstenedione across and within different tissues or areas have been studied by the constant infusion technique. The results were calculated using the (3)H/(14)C ratios and radioactive concentrations of testosterone and androstenedione obtained from afferent and efferent blood and tissues at equilibrium. In each tissue studied, the interconversion between testosterone and androstenedione inside the tissue was significantly higher than the corresponding interconversion across the tissue. The pulmonary contribution to the total interconversion between testosterone and androstenedione was far more important than that of any of the other tissues studied. The hepatic metabolic clearance rates of testosterone and androstenedione were not different from their metabolic clearance rates in the mesenteric area. The extraction of each of these compounds, although not negligible, was lower in the kidney and the femoral bed compared with the extraction in the liver and the mesenteric area. Finally, with the possible exception of the liver, testosterone and androstenedione were more completely metabolized when they originated from the cells than from afferent blood. The evaluation of these different tissue transfer constants provides more precise information concerning the relative importance of different sites in the metabolism of these interconverting hormones.


A multi-centre trial comparing a sulfamethopyrazine/trimethoprim combination with co-trimoxazole in respiratory tract infections.
A double-blind, multi-centre trial was carried out in 72 patients with acute or chronic infections of the lower respiratory tract to compare the efficacy and tolerance of a sulfamethopyrazine (200 mg)/trimethoprim (250 mg) combination with that of the established combination co-trimoxazole (400 mg sulphamethoxazole plus 80 mg trimethoprim). Patients received treatment for 10 days either with 2 capsules of co-trimoxazole twice daily or in the newer combination group with 2 capsules on Day 1 but then only 1 capsule daily for the remainder of the treatment period. The results of clinical, bacteriological and functional tests showed an excellent or good response in over 90% of patients in each group. There was no statistically significant difference in effectiveness of treatment with the once-daily sulfamethopyrazine/trimethoprim regime compared with co-trimoxazole given twice daily, and both treatments were well tolerated, with only a few mild side-effects, mainly gastro-intestinal ones, being reported.


[Hyponatremia associated to pituitary adenomas. Report of three patients].
Severe hyponatremia occurring as the presenting feature of hypopituitarism secondary to pituitary adenomas is rare. We report three patients with this condition: Two elderly males (74 and 78 year-old) presenting with impaired consciousness and low plasma sodium after an episode of diarrhea and a 56-year-old male presenting with impaired consciousness after an episode of vomiting. All had clinical features of hypopituitarism and pituitary adenomas were found on imaging studies. Two were subjected to a trans sphenoidal resection of the adenoma.


Circulating vascular endothelial growth factor (VEGF) and its soluble receptors in patients with chronic lymphocytic leukemia.
The vascular endothelial growth factor (VEGF) transduction pathway may be very active in B-cell chronic lymphocytic leukemia (B-CLL) cells and contributes to their enhanced survival. Vascular endothelial growth factor receptor-1 (VEGFR-1) and receptor-2 (VEGFR-2), are the high-affinity VEGF receptors, which play an important role in de novo blood vessel formation and hematopoietic cell development. The aim of our study was to compare the concentration of VEGF, VEGFR-1 and VEGFR-2 in the serum of 83, never-treated B-CLL patients in different stage of disease according to Rai classification, and 20 healthy volunteers. Of all the cytokines only the serum concentration of VEGF was found to be significantly higher in the CLL group when compared to the control group (median 468.2 pg/mL and 246.9 pg/mL, respectively) (p = 0.01). In the group of CLL patients, the serum concentrations of VEGF and VEGFR-2 were significantly higher in patients in Rai stage III and IV (median 890.0 pg/mL and 4680.4 pg/mL respectively) than in patients in Rai stage 0-II (347.8 pg/mL and 2411.6 pg/mL respectively) (p<0.0001). In the entire group of CLL patients, we have found a strong, positive correlation between the serum level of VEGF and VEGFR-2 (p = 0.00001, R = 0.46). We have also found a positive correlation between the number of lymphocytes in the peripheral blood of CLL patients and the level of VEGF (p = 0.05, R = 0.24) and VEGFR2 (p = 0.02, R = 0.29). VEGF and VEGF R2, but not VEGF R1, may have an important influence on the course of B-CLL.


A high-performance histidine-functionalized MWCNT-GONR/Co-Ni LDH flower cluster structural composite via a microwave synthesis for supercapacitors.
A flower cluster structural histidine-functionalized multi-walled carbon nanotube-graphene oxide nanoribbon/Co-Ni LDH (His-MW/LDH) composite was synthesized via the microwave method. In this study, we used His-MW as a carbon material to synthesize the electrode because it not only has the properties of MWCNT-GONR (MW) but also completes the N doping process due to the addition of histidine. His-MW adhered to the LDH flower cluster, and the radius of the composite was found to be nearly 1 μm. The synergistic effects of His-MW and LDH could effectively increase the specific surface areas and conductivity of the composite, thereby endowing it with high specific capacitance (1674 F g-1) and admirable cycling stability (83.33% capacitance retention). Moreover, we assembled an asymmetric supercapacitor, and it possessed 39.47 W h kg-1 at 0.80 kW kg-1 as well as prominent cycling stability (93.81% capacitance retention). This study proves the feasibility of synthesizing the histidine-functionalized carbon derivative/LDH composite by the microwave method. Moreover, we are optimistic that the electrode material can be extensively used in supercapacitors because of its splendid electrochemical properties and facile synthesis.


Bone healing of tibial lengthening is enhanced by hyperbaric oxygen therapy: a study of bone mineral density and torsional strength on rabbits.
We investigated the effect of intermittent hyperbaric oxygen (HBO) therapy on the bone healing of tibial lengthening in rabbits. Twelve male rabbits were divided into two groups of six animals each. The first group went through 2.5 atmospheres absolute of hyperbaric oxygenation for 2 hours daily, and the second group did not go through hyperbaric oxygenation. Each animal's right tibia was lengthened 5 mm using an uniplanar lengthening device. Bone mineral density (BMD) study was performed for all of the animals at 1 day before operation and at 3, 4, 5, and 6 weeks after operation. All of the animals were killed at 6 weeks postoperatively for biomechanical testing. Using the preoperative BMD as an internal control, we found that the BMD of the HBO group was increased significantly compared with the non HBO group. The mean %BMD at 3, 4, 5, and 6 weeks were 69.5%, 80.1%, 87.8%, and 96.9%, respectively, in HBO group, whereas the mean %BMD were 51.6%, 67.7%, 70.5%, and 79.2%, respectively, in non-HBO group (two tailed t test, p < 0.01, p < 0.01, p < 0.01, and p < 0.01 at 3, 4, 5, and 6 weeks, respectively). Using the contralateral nonoperated tibia as an internal control, we found that torsional strength of lengthened tibia of the HBO group was increased significantly compared with the non-HBO group. The mean percent of maximal torque was 88.6% in HBO group at 6 weeks, whereas the mean percent of maximal torque was 76.0% in non-HBO group (two-tailed t test, p < 0.01). The results of this study suggest that the bone healing of tibial lengthening is enhanced by intermittent hyperbaric oxygen therapy.


Disruption of large-scale electrophysiological networks in stroke patients with visuospatial neglect.
Stroke frequently produces attentional dysfunctions including symptoms of hemispatial neglect, which is characterized by a breakdown of awareness for the contralesional hemispace. Recent studies with functional MRI (fMRI) suggest that hemineglect patients display abnormal intra- and interhemispheric functional connectivity. However, since stroke is a vascular disorder and fMRI signals remain sensitive to nonneuronal (i.e., vascular) coupling, more direct demonstrations of neural network dysfunction in hemispatial neglect are warranted. Here, we utilize electroencephalogram (EEG) source imaging to uncover differences in resting-state network organization between patients with right hemispheric stroke (N = 15) and age-matched, healthy controls (N = 27), and determine the relationship between hemineglect symptoms and brain network organization. We estimated intra- and interregional differences in cortical communication by calculating the spectral power and amplitude envelope correlations of narrow-band EEG oscillations. We first observed focal frequency-slowing within the right posterior cortical regions, reflected in relative delta/theta power increases and alpha/beta/gamma decreases. Secondly, nodes within the right temporal and parietal cortex consistently displayed anomalous intra- and interhemispheric coupling, stronger in delta and gamma bands, and weaker in theta, alpha, and beta bands. Finally, a significant association was observed between the severity of left-hemispace search deficits (e.g., cancellation test omissions) and reduced functional connectivity within the alpha and beta bands. In sum, our novel results validate the hypothesis of large-scale cortical network disruption following stroke and reinforce the proposal that abnormal brain oscillations may be intimately involved in the pathophysiology of visuospatial neglect.


[Neoplasms and congenital abnormalities of extrahepatic bile ducts].
Some problems of association of gallbladder carcinoma and congenital abnormalities of extrahepatic bile ducts are discussed in diagnostic and therapeutic aspects. Presented facts have been not quite clear to explain carcinogenesis of extrahepatic bile ducts.


Diurnal rhythms of proopiomelanocortin-derived N-terminal peptide, beta-lipotropin, beta-endorphin and adrenocorticotropin in normal subjects and in patients with Addison's disease and Cushing's disease.
In order to clarify the diurnal pattern of secretion of plasma immunoreactive (IR) proopiomelanocortin (POMC)-derived peptides, IR-N-terminal peptide (Nt), IR-beta-endorphin (Ep), IR-beta-lipotropin (LPH), and IR-ACTH (ACTH) in normal subjects and in patients with Addison's disease and Cushing's disease, we measured these 4 peptides in the same plasma obtained at 0900 h and then every three hours until 0600 h at the next day. All four peptides showed diurnal rhythms with the peaks at 0600 h, and the nadirs of ACTH, LPH, Ep and Nt were at 0000 h, 0000 h, 1800 h and 0300, respectively in normal subjects. In patients with Addison's disease, these four peptides also showed diurnal rhythms with the peaks at 0600 h for ACTH and Ep and at 0900 h for LPH and Nt, and the nadirs at 2100 h for ACTH and Ep and at 0000 h for LPH and Nt. The molar ratios of Ep/ACTH, LPH/ACTH and Nt/ACTH in plasma also presented diurnal variations in normal subjects and in patients with Addison's disease. On the other hand, in patients with Cushing's disease, ACTH, LPH and Nt showed no rhythmicity or change in molar ratios of Ep/ACTH, LPH/ACTH or Nt/ACTH. Only Ep showed diurnal variation. The molar ratios of Ep/ACTH, LPH/ACTH and Nt/ACTH in patients with Cushing's disease were significantly higher than those in normal subjects and in patients with Addison's disease at 0000 h.(ABSTRACT TRUNCATED AT 250 WORDS)


Amphiphilic corroles bind tightly to human serum albumin.
Amphiphilic 2,17-bis-sulfonato-5,10,15(trispentafluorophenyl)corrole (2) and its Ga and Mn complexes (2-Ga and 2-Mn) form tightly bound noncovalent conjugates with human serum albumin (HSA). Protein-induced changes in the electronic absorption, emission, and circular dichroism spectra of these corroles, as well as results obtained from HPLC profiles of the conjugates and selective fluorescence quenching of the single HSA tryptophan, are interpreted in terms of multiple corrole:HSA binding sites. High-affinity binding sites, close to the unique tryptophan, are fully occupied at very low concentrations. At biologically relevant HSA concentrations (2-3 orders of magnitude larger than those employed in our studies), all corroles (2, 2-Ga, and 2-Mn) may be considered as fully conjugated.


Generating Neural Stem Cells from iPSCs with Dopaminergic Neurons Reporter Gene.
Genetic reporters offer attractive approaches to investigate gene expression, gene function, and spatiotemporal assessment in vitro and in vivo. Tyrosine hydroxylase (TH) is the rate-limiting enzyme for the biosynthesis of the dopamine neurotransmitter, and thus it has been used as a reliable marker for dopaminergic neurons in vitro and in vivo. Herein we describe a method for making iPSC lines with TH-green fluorescent protein reporter gene using CRISPR/Cas9 technique.


Effect of catecholamine on central serous chorioretinopathy.
The role of catecholamine (CA) in the pathogenesis and development of macular edema of central serous chorioretinopathy (CSC) was studied, and its relations with visual acuity were investigated. Plasma concentrations of epinephrine (E) and norepinephrine (NE) were determined in 30 consecutive eyes with CSC. Central macular thickness analysis was done by RTA and all the data were compared with normal eyes and analyzed with SAS software package. Plasma concentrations of E and NE were increased to (569 +/- 123) ng/L and (721 +/- 104) ng/L respectively in active CSC patients, significantly higher than those in normal subjects (P < 0.01), and decreased to normal in convalescent stage. RTA analysis revealed that the retinal thickness of CSC patients was increased at active and recovery stage as compared with normal subjects; and the plasma concentration of E was significantly correlated with central macular thickness (t = 2.173, P < 0.05). Also, central macular thickness measured by RTA was significantly correlated with the visual acuity (r = -0.8046, P < 0.001) in CSC eyes. RTA analysis might be useful to quantitatively detect and evaluate prognosis in CSC patients. The plasma concentration of E, which was highly correlated with macular edema, might play an important role in the early damage and the pathogenesis of CSC.


European Standard Series Patch Test Results in Contact Dermatitis Patients in a Tertiary Care Hospital.
Sensitization of allergens varies among societies and also it is influenced by various factors, such as age and gender. It may even change over the years. In this study, we aimed to evaluate the patch test results in patients with contact dermatitis (CD) in our center. European standard series patch test results of patients with CD between 2017 and 2018 were evaluated retrospectively. Of the 135 patients, 65 (48.1%) were males, 70 (51.9%) were females. The mean age of patients was 41.43±14.26 (11-78) years. In 78 (57.8%) patients, a positive reaction against at least one allergen was detected. The most common allergens were nickel sulfate (27.4%), potassium dichromate (14.8%), cobalt chloride (11.9%), textile dye mix (8.1%), fragrance mix i, ii (6.7%) and balsam of Peru (4.4%). The sensitization of nickel sulfate was higher in females and sensitization of cobalt chloride and potassium dichromate in males (p=0.03, 0.05, 0.03, respectively). In the multivariate logistic regression analysis, age was independently related to a positive reaction against at least one allergen. Nickel sulfate, potassium dichromate, cobalt chloride and textile dye mix were the most common allergens. Legal regulations should be made to decrease exposure to allergens.


Investigating mosquito net durability for malaria control in Tanzania - attrition, bioefficacy, chemistry, degradation and insecticide resistance (ABCDR): study protocol.
Long-Lasting Insecticidal Nets (LLINs) are one of the major malaria vector control tools, with most countries adopting free or subsidised universal coverage campaigns of populations at-risk from malaria. It is essential to understand LLIN durability so that public health policy makers can select the most cost effective nets that last for the longest time, and estimate the optimal timing of repeated distribution campaigns. However, there is limited knowledge from few countries of the durability of LLINs under user conditions. This study investigates LLIN durability in eight districts of Tanzania, selected for their demographic, geographic and ecological representativeness of the country as a whole. We use a two-stage approach: First, LLINs from recent national net campaigns will be evaluated retrospectively in 3,420 households. Those households will receive one of three leading LLIN products at random (Olyset®, PermaNet®2.0 or Netprotect®) and will be followed up for three years in a prospective study to compare their performance under user conditions. LLIN durability will be evaluated by measuring Attrition (the rate at which nets are discarded by households), Bioefficacy (the insecticidal efficacy of the nets measured by knock-down and mortality of mosquitoes), Chemical content (g/kg of insecticide available in net fibres) and physical Degradation (size and location of holes). In addition, we will extend the current national mosquito insecticide Resistance monitoring program to additional districts and use these data sets to provide GIS maps for use in health surveillance and decision making by the National Malaria Control Program (NMCP). The data will be of importance to policy makers and vector control specialists both in Tanzania and the SSA region to inform best practice for the maintenance of high and cost-effective coverage and to maximise current health gains in malaria control.


Extensive Hair-Shaft Elongation by Isolated Mouse Whisker Follicles in Very Long-Term Gelfoam® Histoculture.
We have previously studied mouse whisker follicles in Gelfoam® histoculture to determine the role of nestin-expressing plutipotent stem cells, located within the follicle, in the growth of the follicular sensory nerve. Long-term Gelfoam® whisker histoculture enabled hair follicle nestin-expressing stem cells to promote the extensive elongation of the whisker sensory nerve, which contained axon fibers. Transgenic mice in which the nestin promoter drives green fluorescent protein (ND-GFP) were used as the source of the whiskers allowing imaging of the nestin-expressing stem cells as they formed the follicular sensory nerve. In the present report, we show that Gelfoam®-histocultured whisker follicles produced growing pigmented and unpigmented hair shafts. Hair-shaft length increased rapidly by day-4 and continued growing until at least day-12 after which the hair-shaft length was constant. By day-63 in histoculture, the number of ND-GFP hair follicle stem cells increased significantly and the follicles were intact. The present study shows that Gelfoam® histoculture can support extensive hair-shaft growth as well as hair follicle sensory-nerve growth from isolated hair follicles which were maintained over very long periods of time. Gelfoam® histoculture of hair follicles can provide a very long-term period for evaluating novel agents to promote hair growth.


Benefits of additional courses of systemic azithromycin in periodontal disease case report.
The strong association of subgingival anaerobic bacteria, such as Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, with destructive periodontal disease has been well documented in the literature. Several double-blind studies have also shown the beneficial use of systemic antimicrobials that are active against these microorganisms in conjunction with conventional periodontal treatment, especially when periodontal abscesses and/or suppuration upon probing are present. Four cases with periodontal abscesses were treated with scaling/root planing in conjunction with systemic azithromycin. Partial improvement led to retreatment with two additional courses of azithromycin. Bone formation was noted on periapical radiographs after the patients took additional courses of azithromycin. In view of the benefits of using additional courses of azithromycin in the treatment of destructive periodontal disease, we conclude that the single course of systemic antimicrobials currently used in periodontal therapy may be insufficient to reach necessary therapeutic levels in infected sites.


Metabolic deprivation: a lead to containment in bacterial releases.
Experiments were carried out in non-sterile soil, with or without several substrates (sucrose, citrate, lactose) as energy source, and with or without bacterial inoculates able or unable to utilize these substrates. The bacteria were Enterobacter agglomerans, Escherichia coli, Pseudomonas aeruginosa or Pseudomonas aureofaciens; they either did or did not contain plasmid RP4. It was found that sucrose is degraded by the indigenous microflora and/or free soil enzymes to give extracellular glucose and fructose, to support growth and plasmid transfer of all inoculated bacteria, e.g. sucrose-positive and sucrose-negative bacteria. In contrast, the growth and plasmid transfer of inoculates which do not degrade citrate is reduced in soil containing that substrate when compared to such inoculates which do degrade citrate. The growth and plasmid transfer of inoculates which do not degrade lactose is reduced strongly in soil containing that substrate, when compared to such inoculates which do degrade lactose. Lactose is degraded slowly in soil by the indigenous microflora, without giving rise to extracellular glucose. These findings indicate a possible way to achieve biological containment, via genetic defects in metabolic pathways.


DNA barcodes for biosecurity: invasive species identification.
Biosecurity encompasses protecting against any risk through 'biological harm', not least being the economic impact from the spread of pest insects. Molecular diagnostic tools provide valuable support for the rapid and accurate identification of morphologically indistinct alien species. However, these tools currently lack standardization. They are not conducive to adaptation by multiple sectors or countries, or to coping with changing pest priorities. The data presented here identifies DNA barcodes as a very promising opportunity to address this. DNA of tussock moth and fruit fly specimens intercepted at the New Zealand border over the last decade were reanalysed using the cox1 sequence barcode approach. Species identifications were compared with the historical dataset obtained by PCR-RFLP of nuclear rDNA. There was 90 and 96% agreement between the methods for these species, respectively. Improvements included previous tussock moth 'unknowns' being placed to family, genera or species and further resolution within fruit fly species complexes. The analyses highlight several advantages of DNA barcodes, especially their adaptability and predictive value. This approach is a realistic platform on which to build a much more flexible system, with the potential to be adopted globally for the rapid and accurate identification of invasive alien species.


The role of the elbow musculature, forearm rotation, and elbow flexion in elbow stability: an in vitro study.
The goal of this study was to define the relative passive contributions of the major muscle groups about the elbow to varus-valgus stability and to determine whether these contributions vary with forearm rotation and elbow flexion. Fourteen cadaveric upper extremities were tested with a custom elbow testing device. The biceps, brachialis, and triceps muscles were loaded to simulate passive tension. The origins and insertions of the remaining muscles that cross the elbow were left intact to assess the contributions of their passive tension to elbow stability. For each specimen, varus-valgus laxity was measured at 30 degrees , 50 degrees , and 70 degrees of elbow flexion with the forearm in full supination, pronation, and neutral rotation, yielding 9 total positions of assessment. Six specimens (series 1) were tested for varus-valgus laxity after the following sequence of conditions: (1) unloaded biceps, brachialis, and triceps; (2) loaded biceps, brachialis, and triceps; (3) release of lateral elbow muscle tension; (4) release of medial elbow muscle tension; and (5) transection of the anterior bundle of the ulnar collateral ligament (UCL). Eight specimens (series 2) were assessed under the same conditions, only with the order of the last 2 conditions reversed for further comparison. Release of the lateral muscles alone increased varus-valgus laxity by a mean of 0.6 degrees to 1.4 degrees , but this was statistically significant only at positions of forearm pronation in series 1 (P < .012) and only at 2 of 9 positions in series 2 (30 degrees of flexion in pronation and 50 degrees of flexion in neutral rotation, P < .049). Release of the medial muscles alone caused a further increase in varus-valgus laxity by a mean of 0.5 degrees to 1.2 degrees , but this was only statistically significant at 30 degrees , 50 degrees , and 70 degrees of flexion in supination (P < .014) and 70 degrees of flexion in pronation (P = .044) in series 1 and only at 30 degrees , 50 degrees , and 70 degrees of flexion in supination in series 2 (P < .046). Release of the anterior bundle of the UCL resulted in a statistically significant increase in elbow varus-valgus laxity at all elbow and forearm positions by a mean of 1.8 degrees to 3.2 degrees (P < .001). Unloading the biceps, triceps, and brachialis caused significant increases in varus-valgus laxity at most elbow testing positions, independent of the position of forearm rotation (P < .046). Thus, the medial elbow musculature and lateral elbow musculature affect total elbow varus-valgus stability to roughly equal magnitudes, and the anterior bundle of the UCL affects stability to over twice the magnitude of either muscle group. The medial elbow musculature mostly affects elbow stability with the arm in supination and the lateral musculature in pronation, where the passive tension in the respective muscles is increased. Furthermore, the medial elbow musculature provided stability to the elbow when the forearm was supinated even with a deficient anterior bundle of the UCL, emphasizing its role as a secondary stabilizer.


Quantitative study of the quadriceps muscles and trochlear groove geometry related to instability of the patellofemoral joint.
This was a quantitative study of the major anatomical structures associated with instability of the patellofemoral joint: the quadriceps muscles and the femoral trochlear groove. The attachments of the muscles to the patella, their lines of action, and their relative sizes (physiological cross-sectional areas) were found. On the basis of the physiological cross-sectional areas, it was estimated that the central muscles-the rectus femoris and vastus intermedius-contributed 35% of the quadriceps strength, with 40% from the vastus lateralis and 25% from the vastus medialis. The vastus lateralis had the most variable results, with the ratio of the lateralis to the medialis ranging from 0.90 to 2.18; this may be associated with patellar instability. Both the long and oblique parts of the vastus medialis were more oblique than the corresponding parts of the vastus lateralis. Photographic "skyline" views of the trochlear groove produced data on the sulcus angle and ratio of depth to width. The data showed that the trochlear groove did not deepen in the area contacted by the patella with progressive knee flexion (p > 0.53), contrary to popular belief. These data are useful for objective analysis of patellofemoral stability and related surgical interventions.


Energy storage and release of prosthetic feet. Part 1: Biomechanical analysis related to user benefits.
The energy storing and releasing behaviour of 2 energy storing feet (ESF) and 2 conventional prosthetic feet (CF) were compared (ESF: Otto Bock Dynamic Pro and Hanger Quantum; CF: Otto Bock Multi Axial and Otto Bock Lager). Ten trans-tibial amputees were selected. The study was designed as a double-blind, randomised trial. For gait analysis a VICON motion analysis system was used with 2 AMTI force platforms. A special measuring device was used for measuring energy storage and release of the foot during a simulated step. The impulses of the anteroposterior component of the ground force showed small, statistically non-significant differences (deceleration phase: 22.7-23.4 Ns; acceleration phase: 17.0-18.4 Ns). The power storage and release phases as well as the net results also showed small differences (maximum difference in net result is 0.03 J kg-1). It was estimated that these differences lead to a maximum saving of 3% of metabolic energy during walking. It was considered unlikely that the subjects would notice this difference. It was concluded that during walking differences in mechanical energy expenditure of this magnitude are probably not of clinical relevance. Ankle power, as an indicator for energy storage and release gave different results to the energy storage and release as measured with the special test device, especially during landing response. In the biomechanical model (based on inverse dynamics) used in the gait analysis the deformation of the material is not taken into consideration and hence this method of gait analysis is probably not suitable for calculation of shock absorption.


Calcium-Catalyzed Dynamic Multicomponent Reaction.
The reversible formation of covalent bonds enabled by the remarkably high Lewis acidity of our calcium-based catalyst system was used for the development of a new type of multicomponent reaction. Accordingly, a pharmacologically interesting bicyclic amine was amplified from a highly efficient dynamic equilibrium. The product is formed with full diastereoselectivity, and as typical for our calcium-catalyzed reactions, precautions for the exclusion of air and moisture are unnecessary.


[Separation and evaluation of antioxidant constituents from Carthamus tinctorius].
Bio-active components from Carthamus tinctorius were separated on the basis of antioxidant capacities in vitro. The antioxidant capacity was investigated on the basis of the ability to scavenge DPPH radical, ABTS radical and reduce Fe3+ of different polar fractions. Furthermore, the chemical compounds were isolated from bio-active fraction, and were evaluated for the antioxidative effects. Five major components were isolated and identified from water extract as 6-hydroxykaempferol 3,6,7-tri-O-β-D-glucoside(1), 6-hydroxykaempferol 3-O-β-rutinoside-6-O-β-D-glucoside (2), 6-hydroxykaempferol 3-O-β-D-glucoside (3), hydroxysafflor yellow A (4) and anhydrosafflor yellow B (5). By evaluating and comparing the antioxidative effects of different fractions and obtained compounds, the results showed that water extract displayed significantly high antioxidative activities and 6-hydroxykaempferol glycosides and quinochalcone C-glycosides were found as main contribution for antioxidant property.


Associations of CTX-II with biochemical markers of bone turnover raise questions on its tissue origin: data from CHECK, a cohort study of early osteoarthritis.
CTX-II (C-terminal telopeptide of type II collagen) has been put forward as a marker of collagen type II degradation being part of osteoarthritis. In this study, the authors describe similarities between CTX-II and bone markers arguing against CTX-II as a marker of (solely) cartilage degradation. uCTX-II, the bone markers uCTX-I, uNTX-I, sPINP, and sOC (C-terminal and N-terminal telopeptides of collagen I, aminoterminal propeptide of type I procollagen, and osteocalcin, respectively), and other (candidate) cartilage markers sCOMP, sCS846, and sPIIANP (cartilage oligomeric matrix protein, chondroitin sulphate 846 and type IIA collagen N-propeptide, respectively) were assessed by ELISA in CHECK (Cohort Hip and Cohort Knee), a cohort of 1002 individuals with early pain and/or stiffness in knee and/or hip. uCTX-II was more strongly associated with the bone markers than with the other cartilage markers, while the other cartilage markers were not so strongly associated with the bone markers. Moreover, both uCTX-II and bone markers but not the other cartilage markers showed an abrupt menopausal shift in women aged 48-53 years, also when adjusted for age and BMI. The similarities between uCTX-II and bone markers could be attributable to a link between cartilage and bone metabolism through metabolic and biomechanical mechanisms. However, other cartilage markers were hardly associated with uCTX-II and did not show such evident associations with bone markers. uCTX-II has unique relations with bone markers as compared to other cartilage markers and might reflect bone rather than cartilage metabolism. More thorough molecular validation of uCTX-II is required.


Lymphocytic adenohypophysitis accompanying occlusion of bilateral internal carotid arteries--case report.
A 45-year-old female presented with blurred vision, headache, and abnormal thirstiness. She was not pregnant nor postpartum. She had diabetes insipidus and bitemporal hemianopsia. Radiological evidence suggested a mass arising in the sella turcica with extension into the parasellar and suprasellar regions. Carotid angiography showed occlusions of bilateral internal carotid arteries at the cavernous portions. The mass was subtotally removed by the trans-sphenoidal approach and was histologically diagnosed as an adenohypophysitis. Laboratory data showed the patient to be in an active state of autoimmune disorder and hypopituitarism. When a patient presents with pituitary insufficiency and an enhanced intrasellar mass lesion on computed tomographic scan, lymphocytic adenohypophysitis must be included in the differential diagnosis.


[Optimizing primary total hip replacement--a technique to effect saving of manpower].
Development of a standardized surgical technique for total hip replacement thereby saving manpower (one assistant) by using a retractor system. Total hip replacement is performed with the patient in a true lateral position on a tunnel cushion. By means of a direct lateral approach the pelvitrochanteric muscles are partially detached using an omega-shaped cut. The Bookwalter retractor is fixed dorsally on the operating table. The ring is centered keeping the greater trochanter in the middle. The Hohmann retractors are fixed to the ring to sufficiently expose the acetabulum. To insert the femoral stem the ring needs to be opened dorsally and the patient's leg is bent 90 degrees in the hip and the knee over the tunnel cushion. The muscles inserting at the greater trochanter are retracted by a separate Hohmann retractor with weight. In a case control study with matched pairs the patients treated with this technique were compared with those treated in supine position with the transgluteal approach. The number of assistants required and the operating time were assessed. All the hip replacements with the patient in side position were performed with one assistant, in supine position with two assistants. The operating time did not differ significantly (supine position 110 min/side position 112 min). The complication rate in both groups was comparable (one secondary wound healing, one transient ischalgia). The process of total hip replacement can be optimized. The described technique allows to spare one surgical assistant without prolonging the operating time.


Intravenous gamma-globulin therapy improves hypercytokinemia in the acute phase of Kawasaki disease.
Abstract Proinflammatory cytokinemia and subsequent endothelial cell activation are the major pathological features of Kawasaki disease (KD), which progresses to systemic vasculitis and results in coronary artery lesions (CALs). We studied the serum levels of proinflammatory cytokines and of the soluble receptors before and after intravenous gamma-globulin (IVGG) treatment to investigate whether the anti-inflammatory effect of IVGG was due to the reduction of increased serum levels of their cytokines and soluble receptors. In the acute phase of KD, the serum levels of interleukin (IL)-2 and IL-5, as well as those of IL-6, IL-10, and interferon-γ, were markedly higher than those in controls. The level of tumor necrosis factor-α was higher than that in the control, but the difference was slight and not significant. The soluble IL-6 receptor levels were lower than those of the controls. After IVGG administration, the increased levels of these cytokines and soluble receptors were abruptly down-regulated to within their normal ranges. The patients enrolled in the present study were all effectively treated with IVGG, without a steroid, and improved without any residual CALs. Overall, IVGG administration to patients with KD was found to be effective in reducing inflammatory processes and in preventing CALs, and was followed by reduction of the serum levels of the proinflammatory cytokines and their receptors.


Patient baseline characteristics in an open-label multinational study of betahistine in recurrent peripheral vestibular vertigo: the OSVaLD study.
OSVaLD (Observational Study in patients suffering from recurrent peripheral vestibular Vertigo to Assess the effect of betahistine 48 mg/day on quality of Life and Dizziness symptoms) is a 3-month, open-label, multi-national post-marketing surveillance study of betahistine 48 mg/day in the management of patients with vertigo of less than 5 years in duration. The aim of the study is to examine the burden of disease associated with vertigo, as determined by scores on the Dizziness Handicap Inventory (DHI), Short Form-36 (SF-36) questionnaire and the Hospital Anxiety and Depression Scale (HADS). Changes in DHI, SF-36 and HADS scores between baseline and 3 months are used to assess the therapeutic effects of betahistine. Participants (n = 2037) have been recruited from 13 countries in four continents (North and South America, Asia and Europe), representing a wide range of cultural and linguistic traditions. Approximately two-thirds of the patients are women. Sixty per cent of patients have diagnoses of peripheral vestibular vertigo of unknown pathology or benign paroxysmal positional vertigo; 13% have a diagnosis of Ménière's disease. All three of the instruments used characterize this as a population with extensive vertigo-attributable morbidity at baseline. The mean DHI score of the population is 63.7 +/- 15.7 (DHI scale: 0 = no handicap; 100 = major self-perceived handicap), SF-36 scores in all domains are below the population average for the USA and the HADS indicated that > 50% of patients exhibit symptoms of anxiety or depression or both, including 9% who have severe manifestations of either or both conditions. This report describes the design and implementation of OSVaLD and presents baseline demographic and clinical features of the patients. Full results of the study, anticipated in 2007, will provide more details about the manifestations of vertigo in routine practice and the response to betahistine.


Genomic organization and promoter sequence of a gene encoding a rat liver-specific type-I transport protein.
We report the isolation and characterization of a rat gene (designated TI-LTP) encoding a liver-specific cell-surface glycoprotein that belongs to the type-I transporter family. This gene, including 5' and 3' flanking domains, was cloned from a rat lambda DASH genomic library and its nucleotide sequence was determined. TI-LTP is a single-copy gene which spans over 6 kb, and contains nine introns ranging in size from 90 bp to over 1.8 kb. Two transcription start points were located using a nuclease S-1 protection assay. The TI-LTP promoter (pTI-LTP) lacks a canonical TATA-box element, but does contain five TAGA elements. Several putative transcription-factor-binding sites were identified in the pTI-LTP, including activator protein 2 (AP-2) sites and a peroxisome proliferator response element (PPRE).


Access to credible information on schizophrenia patients' medication adherence by prescribers can change their treatment strategies: evidence from an online survey of providers.
Overestimating patients' medication adherence diminishes the ability of psychiatric care providers to prescribe the most effective treatment and to identify the root causes of treatment resistance in schizophrenia. This study was conducted to determine how credible patient drug adherence information (PDAI) might change prescribers' treatment decisions. In an online survey containing 8 clinical case vignettes describing patients with schizophrenia, health care practitioners who prescribe antipsychotics to patients with schizophrenia were instructed to choose a preferred treatment recommendation from a set of predefined pharmacologic and non-pharmacologic options. The prescribers were randomly assigned to an experimental or a control group, with only the experimental group receiving PDAI. The primary outcome was the prescribers' treatment choice for each case. Between-group differences were analyzed using multinomial logistic regression. A convenience sample (n=219) of prescribers completed the survey. For 3 nonadherent patient vignettes, respondents in the experimental group were more likely to choose a long-acting injectable antipsychotic compared with those in the control group (77.7% experimental vs 25.8% control; P<0.001). For 2 adherent but poorly controlled patient vignettes, prescribers who received PDAI were more likely to increase the antipsychotic dose compared with the control group (49.1% vs 39.1%; P<0.001). For the adherent and well-controlled patient vignette, respondents in both groups made similar treatment recommendations across all choices (P=0.099), but respondents in the experimental arm were more likely to recommend monitoring clinical stability (87.2% experimental vs 75.5% control, reference group). The results illustrate how credible PDAI can facilitate more appropriate clinical decisions for patients with schizophrenia.


Our experience in diagnosing and surgical treatment of traumatic intracranial hematomas. Analysis of 610 patients.
610 patients with traumatic intracranial hematomas treated in the Clinic of Neurosurgery in Plovdiv University of Medicine from 1975 to 1990 were studied. The study aimed at analyzing the most common clinical symptoms and paraclinical indicators leading to correct diagnosis and showing the possibilities of approximate determination of the hematoma location in accordance with the shift of the brain midline and the trauma biomechanics. It also recommends the most effective surgical method which yields the least number of hematoma recurrences. In the study the most common clinical symptom is shown to be the lucid interval. The most common paraclinical indicator is the shift of the brain midline caused by the pathological process. Visualization of the brain midline used in conjunction with the data from the biomechanics of the injury could guide the surgeons for the first burr hole in the exploratory trephination of the skull. It is recommended that, if possible, osteoplastic trephination of the skull on a four-burr-hole bone flap should be applied in the acute period of the craniocerebral trauma. This surgical method assures achievement of the best hemostasis, complete evacuation of the hematoma and the least percentage of recurrences of hematoma after surgery.


Stapes surgery in Sweden: evaluation of a national-based register.
The aim of the National Quality Registries is to monitor the outcome of healthcare given to patients. The Swedish Quality register for otosclerosis surgery is one of the nine official national registers for ear, nose and throat diseases in Sweden. Since 2004, surgical and audiological results and patient satisfaction scores have been systematically collected from a majority of the ear, nose and throat clinics performing stapes surgery in Sweden. The results of 1688 patients who underwent primary operations for otosclerosis were evaluated for 24 out of totally 26 clinics performing stapes surgery, between 2004 and 2010. The most common surgical technique reported was stapedotomy accomplished in an overnight stay. A majority of patients experienced improved hearing, and were satisfied with the preoperative counselling. Successful surgery, defined as an ABG closure ≤10 dB HL, was achieved in 69%, improvement in AC by ≥20 dB in 63% and BC not worsened by more than ≥5 dB in 93% of the patients. An overall low incidence of postoperative complications was reported. The outcome for ABG and BC was demonstrated to be independent of the number of operations performed by each clinic. An evaluation of the register and the results from the SQOS revealed that stapes surgery is a safe procedure with good hearing outcomes, low complication rates and a high rate of patient's satisfaction on a national level.


Alterations in capsaicin-evoked electrolyte transport during the evolution of guinea pig TNBS ileitis.
The efferent secretomotor activity of capsaicin-sensitive nerves was monitored during the evolution of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced ileitis in the guinea pig by recording changes in short-circuit current (DeltaI(sc)) in response to capsaicin, substance P (SP), and carbachol. Submucosal-mucosal preparations mounted in standard Ussing chambers were studied at time 0, at 8 h, and 1, 3, 5, 7, 14, and 30 days following the intraluminal instillation of TNBS or saline. Maximal DeltaI(sc) responses to capsaicin were dramatically attenuated (54%) by 24 h. By day 7, SP- and TTX-insensitive carbachol-stimulated DeltaI(sc) were also significantly reduced. Similar attenuation in capsaicin and carbachol responses was observed in jejunal tissue 20 cm proximal to the inflamed site at day 7. These studies demonstrate that efferent secretomotor function of capsaicin-sensitive nerves is maintained early in TNBS ileitis but significantly reduced by 24 h. By day 7, defects in enterocyte secretory function at inflamed and noninflamed sites also occurred, an effect that may be mediated by circulating cytokines.


One-Pot Reactions of N-(Mesyloxy)phthalimides with Secondary Amines to 2-Ureidobenzamides, 2-Ureidobenzoic Acids, Ethyl 2-Ureidobenzoates, or Isatoic Anhydrides.
The reaction of N-(mesyloxy)phthalimides with secondary amines was examined. Transformations are accomplished by one-pot reactions to optionally afford corresponding 2-ureidobenzamides, 2-ureidobenzoic acids, ethyl 2-ureidobenzoates, or isatoic anhydrides, respectively. The mechanism of the acid-catalyzed hydrolysis (or alcoholysis) of intermediate 2-ureidobenzamides to 2-ureidobenzoic acids (or esters) is discussed. A proton transfer mechanism involving the ureido moiety as an internal acid catalyst is proposed. Intermediate 2-ureidobenzoic acids undergo a further transformation to isatoic anhydrides. The utilization of the obtained 2-ureidobenzamides, 2-ureidobenzoic acids, and ethyl 2-ureidobenzoates to prepare 3,1-benzoxazin-4-ones is demonstrated.


IFN-alpha treatment enhances porcine Arterivirus infection of monocytes via upregulation of the porcine Arterivirus receptor sialoadhesin.
The Arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) has a specific tropism for a subset of differentiated macrophages. Porcine sialoadhesin was identified as a PRRSV internalization receptor that is, similarly to sialoadhesins from other species, only expressed on subsets of macrophages. Sialoadhesin is not expressed or only expressed at low levels on monocytes, which might explain why monocytes are largely refractory to PRRSV infection. Different molecules have been identified that regulate human, mouse, or rat sialoadhesin expression in in vitro cultivated monocytes and macrophages, but the effect of these varies greatly between species. In this study, we observed that interferon-alpha (IFN-alpha) induces sialoadhesin expression on monocytes to levels similar as those on macrophages and that it increases sialoadhesin on macrophages. IFN-alpha-induced sialoadhesin expression was shown to be functional using a red blood cell (RBC) binding assay. Furthermore, a 2 or 3 day IFN-alpha pretreatment of monocytes caused a 20-fold increase in the numbers of PRRSV-infected monocytes and increased production of infectious virus. We conclude that IFN-alpha, although it is a potent antiviral molecule, upregulated sialoadhesin infection on in vitro cultivated monocytes, which results in enhanced PRRSV infection of monocytes.


Quantitative Mapping of Chemical Defects at Charged Grain Boundaries in a Ferroelectric Oxide.
Polar discontinuities, as well as compositional and structural changes at oxide interfaces can give rise to a large variety of electronic and ionic phenomena. In contrast to earlier work focused on domain walls and epitaxial systems, this work investigates the relation between polar discontinuities and the local chemistry at grain boundaries in polycrystalline ferroelectric ErMnO3 . Using orientation mapping and scanning probe microscopy (SPM) techniques, the polycrystalline material is demonstrated to develop charged grain boundaries with enhanced electronic conductance. By performing atom probe tomography (APT) measurements, an enrichment of erbium and a depletion of oxygen at all grain boundaries are found. The observed compositional changes translate into a charge that exceeds possible polarization-driven effects, demonstrating that structural phenomena rather than electrostatics determine the local chemical composition and related changes in the electronic transport behavior. The study shows that the charged grain boundaries behave distinctly different from charged domain walls, giving additional opportunities for property engineering at polar oxide interfaces.


Arteriovenous malformation of the jejunum detected by arterial-phase enhanced helical CT, a case report.
This is a report on a case of arteriovenous malformation of the jejunum, which is a relatively rare occurrence that can be detected by helical computed tomography (helical CT). The patient was a 63-year-old man who was admitted to our hospital because of a tarry stool. He developed hypotension as a result of losing a large amount of bright-red blood through rectal bleeding and was given fluids and blood transfusions. Subsequently, a helical CT scan was performed at 10-mm slice thickness. A small high-density area in the jejunum was identified on the arterial phase, which was scanned 30 sec after an intravenous infusion of 100 mL of iopamidol at a rate 2.5 mL/sec. An emergency operation, based on the diagnosis of bleeding from the jejunum, was performed because the patient had developed hypotension once again. A small, elevated lesion, which coincided with the high-density area detected by helical CT, was found in the jejunum. A segmental resection and end-to-end anastomosis were done. The pathological diagnosis revealed an arteriovenous malformation of the jejunum. In conclusion, helical CT may be an effective noninvasive method for detecting the cause and site of gastrointestinal bleeding.


Top-down Multiscale Approach To Simulate Peptide Self-Assembly from Monomers.
Modeling peptide assembly from monomers on large time and length scales is often intractable at the atomistic resolution. To address this challenge, we present a new approach which integrates coarse-grained (CG), mixed-resolution, and all-atom (AA) modeling in a single simulation. We simulate the initial encounter stage with the CG model, while the further assembly and reorganization stages are simulated with the mixed-resolution and AA models. We have implemented this top-down approach with new tools to automate model transformations and to monitor oligomer formations. Further, a theory was developed to estimate the optimal simulation length for each stage using a model peptide, melittin. The assembly level, the oligomer distribution, and the secondary structures of melittin simulated by the optimal protocol show good agreement with prior experiments and AA simulations. Finally, our approach and theory have been successfully validated with three amyloid peptides (β-amyloid 16-22, GNNQQNY fragment from the yeast prion protein SUP35, and α-synuclein fibril 35-55), which highlight the synergy from modeling at multiple resolutions. This work not only serves as proof of concept for multiresolution simulation studies but also presents practical guidelines for further self-assembly simulations at more physically and chemically relevant scales.


BIN1 reverses PD-L1-mediated immune escape by inactivating the c-MYC and EGFR/MAPK signaling pathways in non-small cell lung cancer.
Non-small cell lung cancer (NSCLC) is one of the most common and malignant carcinoma worldwide, and the incidence and mortality are increasing rapidly. Immunotherapy targeting programmed death 1/programmed death ligand 1 (PD-L1) signaling has shown prominent clinical effects in treating NSCLC; however, a poor understanding of the associated regulating molecular mechanisms of PD-L1 has become one of the biggest obstacles for further improving efficacy. Bridging integrator-1 (BIN1) can regulate numerous cancer-related molecules to exert multiple tumor-suppressing effects by either interacting or not interacting with c-MYC. In the present study, we observed that there exists a negative correlation between the expression of PD-L1 and BIN1 in NSCLC tissues. The expression levels of BIN1 and PD-L1 were significantly related to the tumor, lymph node and metastasis grade (TNM) stage, invasion range and lymph node metastasis. Simultaneously, for NSCLC patients, the expression statuses of BIN1 and PD-L1 might be independent prognostic factors. Furthermore, the expression of tumor-infiltrating lymphocytes was positively associated with BIN1 expression and negatively related to PD-L1 expression in NSCLC tissues. Importantly, we showed that PD-L1 was under the control of BIN1. In addition, the overexpression of BIN1 could inhibit the c-MYC and epithelial growth factor receptor (EGFR)-dependent PD-L1 expression and reverse the suppressive immuno-microenvironment in vivo. Taken together, our findings indicated that BIN1 restoration in NSCLC could reverse PD-L1-mediated immune escape by inactivating the c-MYC and EGFR/mitogen-activated protein kinase pathways.


Safety and efficacy of the Silk flow diverter: Insight from the DIVERSION prospective cohort study.
Flow diverters are considered as an essential tool in the stent-based treatment of complex intracranial aneurysms. We report here a subgroup analysis of the nationwide prospective DIVERSION study to investigate the safety and efficacy of the Silk flow diverter at 12 months follow-up. We performed a subgroup analysis of patients included in the DIVERSION, a national prospective cohort study including all flow diverters placement between 2012 and 2014 in France, and treated with the Silk. The primary outcome was the morbi-mortality at 12 months, including death, morbidity event and aneurysm retreatment within 12 months post-treatment. All reported serious events were adjudicated by an independent Data Safety and Monitoring Board. Satisfactory occlusion was defined as 3 or 4 on Kamran's scale by an independent imaging core laboratory during follow-up. A total of 102 procedures involving 101 patients (mean age±standard deviation, 54.3±13.5 years) harbouring 118 aneurysms (113/118 located in the anterior circulation; mean size 8.2±7.1mm) were included. During the 12-month follow-up, 34 (33.3%) procedures experienced at least one morbi-mortality event: 3 deaths, 27 morbidity events and 4 retreatments. Overall, 1/3 deaths and 10/27 morbidity events were related to the device and/or the procedure, leading to a specific survival rate and a specific free-morbidity survival rate at 12 months of 98.98% [95% confidence interval, 92.98%-99.86%] and 89.73% [95%CI, 81.71%-94.36%], respectively. The rate of permanent-related neurological deficit was 5.9% within 12 months. One year follow-up imaging showed satisfactory occlusion in 82.2% of cases. Flow diversion with the Silk device has a reasonable safety and effectiveness profile for the endovascular treatment of intracranial aneurysms.


Meta-para-linked octaaza[1(8)]cyclophanes and their polycationic states.
Octaazacyclophanes, octaaza[1(8)]m,p,m,p,m,p,m,p-cyclophane (2) and octaaza[1(8)]m,p,p,p,m,p,p,p-cyclophane (3), as ring-size extended congeners of tetraaza[1(4)]m,p,m,p-cyclophane were synthesized, and the electronic states of their polycationic species were investigated by quantum chemical calculations, electrochemical measurements (cyclic voltammetry (CV) and differential pulse voltammetry (DPV)), UV-vis-NIR spectroelectrochemical measurements, and pulsed electron spin resonance (ESR) spectroscopy. These octaazacyclophanes exhibited multiredox activities depending on different linkage patterns along the macrocyclic molecular skeletons, and both molecules were oxidizable up to their respective octacations. Spectroelectrochemical measurements demonstrated that p-phenylenediamine (PD) moieties in 2 could be converted from the semiquinoidal structure to the quinoidal sturcture with increasing oxidation number, whereas higher oxidation states of 3 did not show definite quinoidal deformation of PD moieties. A pulsed ESR spectrum gave evidence about formation of the almost pure spin-triplet state for 3(2+), whereas the high-spin states of 2(2+) and 2(4+) are virtually degenerate with the competing low-spin states even at low temperatures, probably due to the fragility of spin-coupling pathway caused by facile conformational changes.


Activation of microtubule-associated protein kinase (Erk) and p70 S6 kinase by D2 dopamine receptors.
The ability of human and rat D2(short) and D2(long) dopamine receptors to activate microtubule-associated protein (MAP) kinase (Erk1/2) and p70 S6 kinase has been investigated in recombinant cells expressing these receptors. In cells expressing the D2(short) receptor, dopamine activated both enzymes in a transient manner but with very different time courses, with activation of Erk being much quicker. Activation of both enzymes by dopamine was dose-dependent and could be prevented by a range of selective dopamine antagonists. Excellent correlations were observed between the potencies of the antagonists for blocking enzyme activation and their affinities for the D2 dopamine receptor. Activation of Erk and of p70 S6 kinase via the D2 dopamine receptors was prevented by pretreatment of the cells with pertussis toxin, indicating the involvement of G proteins of the Gi or Go family. Inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase) were found to block substantially, but not completely, activation of p70 S6 kinase by dopamine, suggesting the involvement of PI 3-kinase-dependent and -independent signalling pathways in its control by dopamine. p70 S6 kinase activation was completely blocked by rapamycin. In the case of Erk, activation was partially blocked by wortmannin or LY294002, indicating a possible link with PI 3-kinase.


Biochemical and mutational analysis of glutamine synthetase type III from the rumen anaerobe Ruminococcus albus 8.
Two different genes encoding glutamine synthetase type I (GSI) and GSIII were identified in the genome sequence of R. albus 8. The identity of the GSIII protein was confirmed by the presence of its associated conserved motifs. The glnN gene, encoding the GSIII, was cloned and expressed in Escherichia coli BL21 cells. The recombinant protein was purified and subjected to biochemical and physical analyses. Subunit organization suggested a protein present in solution as both monomers and oligomers. Kinetic studies using the forward and the gamma-glutamyl transferase (gamma-GT) assays were carried out. Mutations that changed conserved glutamic acid residues to alanine in the four GSIII motifs resulted in drastic decreases in GS activity using both assays, except for an E380A mutation, which rather resulted in an increase in activity in the forward assay compared to the wild-type protein. Reduced GSIII activity was also exhibited by mutating, individually, two lysines (K308 and K318) located in the putative nucleotide-binding site to alanine. Most importantly, the presence of mRNA transcripts of the glnN gene in R. albus 8 cells grown under ammonia limiting conditions, whereas little or no transcript was detected in cells grown under ammonia sufficient conditions, suggested an important role for the GSIII in the nitrogen metabolism of R. albus 8. Furthermore, the mutational studies on the conserved GSIII motifs demonstrated, for the first time, their importance in the structure and/or function of a GSIII protein.


Amrubicin monotherapy may be an effective second-line treatment for patients with large-cell neuroendocrine carcinoma or high-grade non-small-cell neuroendocrine carcinoma.
There is no standard chemotherapy for pulmonary large-cell neuroendocrine carcinoma (LCNEC) and this type of cancer is difficult to diagnose using biopsy specimens. At the Shizuoka Cancer Center, when small biopsy specimens are used, they are diagnosed as high-grade non-small-cell neuroendocrine carcinoma (HNSCNEC) and the patients are treated according to the small-cell lung cancer (SCLC) guidelines. Amrubicin is an effective second-line treatment for patients with SCLC, although it remains unclear whether amrubicin monotherapy is effective for patients with LCNEC or HNSCNEC. Between September, 2004 and December, 2013, 18 patients with advanced LCNEC or HNSCNEC received amrubicin monotherapy in the second-line setting. The efficacy and toxicity of this treatment were retrospectively assessed. A total of 6 patients had LCNEC and 12 patients had HNSCNEC. The patients included 13 men, and the median age was 66 years (range, 57-82 years). A total of 16 patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. All the patients had received platinum-based chemotherapy as first-line treatment, and the median number of amrubicin cycles per patient was 4 (range, 1-9). The overall response rate was 11.1%. The median progression-free and overall survival were 4.0 and 9.1 months, respectively. Grade 3 or 4 neutropenia was observed in 44% of the patients, and grade 3 febrile neutropenia occurred in 17% of the patients. One patient developed pneumonia and succumbed to the disease. Non-hematological toxicities were generally mild and manageable. Therefore, the efficacy of amrubicin in the second-line setting for patients with LCNEC or HNSCNEC is limited. Development of new drugs and/or treatment strategies is warranted.


The effect of estrogen on muscle damage biomarkers following prolonged aerobic exercise in eumenorrheic women.
This study assessed the influence of estrogen (E2) on muscle damage biomarkers [skeletal muscle - creatine kinase (CK); cardiac muscle - CK-MB] responses to prolonged aerobic exercise. Eumenorrheic women (n=10) who were physically active completed two 60-minute treadmill running sessions at ∼60-65% maximal intensity during low E2 (midfollicular menstrual phase) and high E2 (midluteal menstrual phase) hormonal conditions. Blood samples were collected prior to exercise (following supine rest), immediately post-, 30 min post-, and 24 hours post-exercise to determine changes in muscle biomarkers. Resting blood samples confirmed appropriate E2 hormonal levels Total CK concentrations increased following exercise and at 24 hours post-exercise were higher in the midfollicular low E2 phase (p<0.001). However, CK-MB concentrations were unaffected by E2 level or exercise (p=0.442) resulting in the ratio of CK-MB to total CK being consistently low in subject responses (i.e., indicative of skeletal muscle damage). Elevated E2 levels reduce the CK responses of skeletal muscle, but had no effect on CK-MB responses following prolonged aerobic exercise. These findings support earlier work showing elevated E2 is protective of skeletal muscle from exercise-induced damage associated with prolonged aerobic exercise.


Spinal glial activation in a new rat model of bone cancer pain produced by prostate cancer cell inoculation of the tibia.
Studies suggest that astrocytes and microglia in the spinal cord are involved in the development of persistent pain induced by tissue inflammation and nerve injury. However, the role of glial cells in bone cancer pain is not well understood. The present study evaluated the spinal glial activation in a novel rat model of bone cancer pain produced by injecting AT-3.1 prostate cancer cells into the unilateral tibia of male Copenhagen rats. The structural damage to the tibia was monitored by radiological analysis. The thermal hyperalgesia, mechanical hyperalgesia and allodynia, and spontaneous flinch were measured. The results showed that: (1) inoculation of prostate cancer cells, but not the vehicle Hank's solution, induced progressive bone destruction at the proximal epiphysis of the tibia from day 7-20 post inoculation; (2) the inoculation also induced progressive thermal hyperalgesia, mechanical hyperalgesia, mechanical allodynia, and spontaneous flinches; (3) astrocytes and microglia were significantly activated in the spinal cord ipsilateral to the cancer leg, characterized by enhanced immunostaining of both glial fibrillary acidic protein (GFAP, astrocyte marker) and OX-42 (microglial marker); (4) IL-1beta was up-regulated in the ipsilateral spinal cord, evidenced by an increase of IL-1beta immunostained astrocytes. These results demonstrate that injection of AT-3.1 prostate cancer cells into the tibia produces progressive hyperalgesia and allodynia associated with the progression of tibia destruction, indicating the successful establishment of a novel male rat model of bone cancer pain. Further, bone cancer activates spinal glial cells, which may release IL-1beta and other cytokines and contribute to hyperalgesia.


Professional ethics for infectious disease control: moral conflict management in modern public health practice.
Despite scientific evidence that confirms their effectiveness, use of vaccines and microbiological mass testing during the COVID-19 pandemic has been associated with social and moral controversies. In this commentary, it is suggested how such conflicts originating from moral/normative imperatives can be managed in infectious disease control. This was a commentary analysis. A case example of scientific and public debate regarding infectious disease control and policy-making during the early pandemic response is first presented. The case is used to characterize how conflicts arising from moral constraints occurred during the COVID-19 pandemic. These features are thereafter used as a basis for outlining a strategy for moral conflict prevention and management. A challenge for infectious disease control throughout the pandemic was how to manage persuasive initiatives originating from social forces competing with science for influence. Purposively maneuvered information distributed through social media and internet websites could predispose population factions to contest legitimate (evidence and legally based) pandemic response measures. During the pandemic, fact-based criticism of professionals responsible for infectious disease control was mixed with a critique of their moral standards and intentions so as to diminish effectiveness and credibility. Such blending could be curtailed if infectious disease control professionals are made accountable for public health decisions made in the light of prevalent scientific evidence and legislation. If the infectious disease control community would embrace the international code of medical professional ethics, this would help to deal with moral conflicts, especially ones arising from external threats, in modern public health.


Human tibia bone marrow: defining a model for the study of haemodynamics as a function of age by near infrared spectroscopy.
A human model allowing the non-invasive study of bone marrow haemodynamics has been developed. A decrease in postischaemic tissue reperfusion capability (postischaemic hyperaemia) as a function of age (range 25-72 years) was observed both in the human tibia and tibialis anterior muscle. In the tibia bone marrow the reperfusion capability started to decrease after 50 years and was lower than for muscle for all the age range. Mean basal muscle O(2) saturation (80.8% at 25 years) decreases as a function of age (-0.35%+/-0.13% per year) whereas it remains constant for bone marrow (84.8+/-2.8%). A Monte Carlo simulation has been performed to evaluate the accuracy of the derived O(2) saturation measurements and has shown that this parameter is robust even in the presence of substantial noise. It has also been demonstrated that it is necessary to use a multi wavelength NIR spectrometer and a second derivative based fitting algorithm to obtain reliable measurements from the bone marrow, and that the tissue scattering changes occurring during the protocol do not allow the use of the standard near infrared spectroscopy algorithms. The human tibia bone marrow model presented here and the related measurement technique should enable access to new areas of physiological research.


Delivery of stents to target lesions: techniques of intraoperative stent implantation and intraoperative angiograms.
Mullins et al. [6] reported the first use of stent implantation to treat stenotic branch pulmonary arteries in 1988. In the early to mid-1990s, numerous reports confirmed its safety and efficacy, but there were limited stent and balloon designs and stent implantations were performed using relatively large delivery systems (10- to 12-Fr sheaths) [7, 8]. The general accepted patient size was limited to those weighing 12 kg or greater. Intraoperative stent implantation for branch pulmonary artery stenosis was reported in the early to mid-1990s [1-3, 5, 9]. Indications in these early reports included small patient size or difficult anatomy or patients who had additional cardiac lesions and needed surgery independent of the branch stenosis. The idea was to take advantage of the open-heart exposure provided in the operating room to permit direct access to the stenotic segment. Hence, all intraoperative stent implants were performed under direct visualization on bypass. There were no discussions on advantages over the routine percutaneous approach. Currently, with advances in stent and balloon technology as well as increased operator experience, many of those reported cases probably would have undergone cardiac catheterization for a percutaneous stent implant rather than open-heart surgery. The purpose of this report is to review the current indications, advantages, and disadvantages of intraoperative stent implantation as well as to discuss the techniques that are helpful to optimize intraoperative stent positioning. The role and advantages of intraoperative angiography will also be presented.


Evaluative and Experienced Well-being of Caregivers of Parents and Caregivers of Children.
Informal caregiving is an important source of support for aging parents and children. Yet the timing and nature of caring for parents versus children may result in different levels of well-being. Despite extensive studies on the well-being of caregivers of parents and of children, it remains elusive as to how evaluative and experienced well-being vary by caregiver type. Using data from the 2012 and 2013 rounds of the American Time Use Survey, we examined how 216 caregivers of parents and 1,989 caregivers of children reported their evaluative well-being (life satisfaction) and experienced well-being (happiness, meaning, pain, sadness, stress, and tiredness). Caregivers of parents reported lower evaluative and experienced well-being than caregivers of children. The association between caregiver type and life satisfaction dissipated, whereas the associations of caregiver type with happiness, meaning, and sadness persisted after accounting for caregivers' demographic characteristics, socioeconomic resources, and time intensity. Experienced well-being appears to be more sensitive than evaluative well-being in detecting differences in well-being between these two types of caregivers. Given that the caregivers of parents do not receive the same level of institutional support as caregivers of children, social policies should aim to provide caregivers of parents with additional support.


Relationship between early follicular serum estrone level and other hormonal or ultrasonographic parameters in women with polycystic ovary syndrome.
The aim of this study was to investigate the relationship between serum estrone (E1) level and other cardinal features in women with polycystic ovary syndrome (PCOS). 133 Korean women aged 18-35 years who were newly diagnosed with PCOS at a university hospital were included in the present study. Blood samples were collected from all participants during the early follicular phase to determine the serum E1 level and other biochemical hormonal parameters. The total antral follicle count (TFC) and the total ovarian volume (TOV) were assessed using transvaginal or transrectal ultrasound. A significant correlation was found between serum E1 and luteinizing hormone (LH) levels in women with PCOS. In addition, statistically significant correlations were observed between serum E1 level and other hormonal parameters, including testosterone, free testosterone, dehydroepiandrosterone sulfate, and 17α-hydroxyprogesterone. With respect to the ultrasound features, serum E1 levels were significantly correlated with TFC and TOV. All results did not change after adjusting for body mass index (BMI). In conclusion, serum E1 level is significantly correlated with serum LH and androgen levels, and it may be a useful marker for representing the status of the ovarian volume in women with PCOS.


Dynamics of the O + ClO reaction: reactive and vibrational relaxation processes.
Classical trajectories have been integrated to study the O + ClO reaction, both reactive and vibrational energy transfer processes, for the range of temperatures 100 ≤ T/K ≤ 500 using momentum Gaussian binning. The employed potential energy surface is the recently proposed single-sheeted double many-body expansion potential energy surface for the (2)A" ground-state of ClO2 based on multireference ab initio data. A capture-type regime with a room-temperature rate constant of (17.8 ± 0.5) × 10(-12) cm(3) s(-1) and temperature dependence of k(T/K)/cm(3) s(-1) = 22.4 × 10(-12) × T(-0.81) exp(-39.2/T) has been found. Although the value reported here is half of the experimental and recommended one, tentative explanations are given. Other dynamical attributes are also examined for the title reaction, with state-to-all and state-to-state vibrational relaxation and excitation rate constants reported for temperatures of relevance in stratospheric chemistry.


The Effect of Malignancy on Outcomes Following Revascularization for Critical Limb Ischemia: A Case-Control Study.
Malignancy is common in patients presenting with critical lower limb ischemia (CLI). However, outcomes in patients with concomitant active malignancy and CLI have not been well defined in comparative prospective analyses. Using contemporary prospective data, we aimed to assess outcomes following revascularization in patients with CLI and active malignancy. A nested case-control study was performed using data from 2 tertiary referral centers for vascular disease. A total of 48 consecutive patients undergoing intervention for CLI who had a diagnosis of active malignancy were identified and matched to patients with CLI but no malignancy for age, sex, diabetes, and smoking. Patency rates and morbidity/mortality were assessed using duplex ultrasonography and regular clinical review. A total of 48 consecutive patients (median age: 74.5 years; interquartile range: 68-80 years) with active malignancy and CLI were identified and case-matched (age, sex, diabetes, and smoking) to 48 patients undergoing intervention for CLI who had no malignancy. Major cardiovascular risk factors did not differ. All-cause mortality was 23% versus 12% ( P = .41) at 6 months and 54% versus 15% ( P < .001) at 12 months. None of the patients died due to complications relating directly to the lower limb intervention or within 30 days of the intervention. A total of 4 (8.3%) patients had required a major limb amputation at 6 months in both groups, compared with 5 (10.4%) patients with malignancy versus 4 (8.3%) patients without ( P = .73) at 12 months. Patency rates were similar at 12 months (73% vs 80%). Three patients had required reintervention in both groups (endovascular in all cases) at 12 months. Revascularization can be offered safely in selected patients with active malignancy; patency rates in those surviving to 1 year are similar to patients without malignancy.


Sampling tissue volumes using frequency-domain photon migration.
We demonstrate the use of Monte Carlo simulations to generate photon scattering density functions (PSDFs) that represent the tissue volume sampled by steady-state and frequency-domain photon migration. We use these results to illustrate how scaling laws can be developed to determine the mean sampling depth of the multiply scattered photons detected by photon migration methods that remain valid outside the bounds of the standard diffusion approximation, i.e., at small source-detector separations and in media where the optical absorption is significant relative to scattering. Using both the PSDF computation and the newly formulated scaling laws, we focus on a comprehensive description of the effects of source modulation frequency, optical absorption, and source-detector separation on the depth of the sampled tissue volume as well as the sensitivity of frequency-domain photon migration measurements to the presence of a localized absorption heterogeneity.


Development and validation of a liquid chromatography-tandem mass spectrometry method to determine ulifloxacin, the active metabolite of prulifloxacin in rat and rabbit plasma: application to toxicokinetic study.
A simple, high-throughput and specific high-performance liquid chromatography-tandem mass spectrometry method has been developed and validated according to the FDA guidelines for quantification of ulifloxacin in rat and rabbit plasma. The analyte was separated on a Peerless basic C(18) column (33 × 4.6 mm, 3 µm) with an isocratic mobile phase of methanol-water containing formic acid (0.5%, v/v; 9:1, v/v) at a flow rate of 0.5 mL/min. The MS/MS detection was carried out by monitoring the fragmentation of m/z 350.500 → 248.500 for ulifloxacin and m/z 332.400 → 231.400 for ciprofloxacin (internal standard; IS) on a triple quadrupole mass spectrometer. The response to ulifloxacin was linear over the range 0.010-2.500 µg/mL in both plasma. The limit of detection and lower limit of quantification of ulifloxacin were determined in both species to be 0.0025 and 0.010 µg/mL, respectively. The method was successfully applied to quantitatively assess the toxicokinetics of ulifloxacin in rat and rabbit following a single 400 mg/kg (in rat) and 200 mg/kg (in rabbit) oral dose of the prulifloxacin.


Epigenetic dynamics of monocyte-to-macrophage differentiation.
Monocyte-to-macrophage differentiation involves major biochemical and structural changes. In order to elucidate the role of gene regulatory changes during this process, we used high-throughput sequencing to analyze the complete transcriptome and epigenome of human monocytes that were differentiated in vitro by addition of colony-stimulating factor 1 in serum-free medium. Numerous mRNAs and miRNAs were significantly up- or down-regulated. More than 100 discrete DNA regions, most often far away from transcription start sites, were rapidly demethylated by the ten eleven translocation enzymes, became nucleosome-free and gained histone marks indicative of active enhancers. These regions were unique for macrophages and associated with genes involved in the regulation of the actin cytoskeleton, phagocytosis and innate immune response. In summary, we have discovered a phagocytic gene network that is repressed by DNA methylation in monocytes and rapidly de-repressed after the onset of macrophage differentiation.


Mortality in Cancer Patients With COVID-19 Who Are Admitted to an ICU or Who Have Severe COVID-19: A Systematic Review and Meta-Analysis.
There are scarce data to aid in prognostication of the outcome of critically ill cancer patients with COVID-19. In this systematic review and meta-analysis, we investigated the mortality of critically ill cancer patients with COVID-19. We searched online databases and manually searched for studies in English that reported on outcomes of adult cancer patients with COVID-19 admitted to an intensive care unit (ICU) or those with severe COVID-19 between December 2019 and October 2020. Risk of bias was assessed by the Modified Newcastle-Ottawa Scale. The primary outcome was all-cause mortality. We also determined the odds of death for cancer patients versus noncancer patients, as also outcomes by cancer subtypes, presence of recent anticancer therapy, and presence of one or more comorbidities. Random-effects modeling was used. In 28 studies (1,276 patients), pooled mortality in cancer patients with COVID-19 admitted to an ICU was 60.2% (95% CI, 53.6 to 6.7; I2 = 80.27%), with four studies (7,259 patients) showing higher odds of dying in cancer versus noncancer patients (odds ratio 1.924; 95% CI, 1.596 to 2.320). In four studies (106 patients) of patients with cancer and severe COVID-19, pooled mortality was 59.4% (95% CI, -39.4 to 77.5; I2 = 72.28%); in one study, presence of hematologic malignancy was associated with significantly higher mortality compared with nonhematologic cancers (odds ratio 1.878; 95% CI, 1.171 to 3.012). Risk of bias was low. Most studies were reported before the results of trials suggesting the benefit of dexamethasone and tocilizumab, potentially overestimating mortality. The observed mortality of 60% in cancer patients with COVID-19 admitted to the ICU is not prohibitively high, and admission to the ICU should be considered for selected patients (registered with PROSPERO, CRD42020207209).


Chemical pathology of krabbe's disease. IV. Studies of galactosylceramide and lactosylceramide BETA-galactosidases in brain, white blood cells and aminotic fluid cells.
Galactosylceramide beta-galactosidase and lactosylceramide beta-galactosidase activities were investigated in normal human brain, leu-kocytes and amniotic fluid cells. The enzymatic assays were performed on brains from 11 patients with Krabbe's disease, on leukocytes from 16 patients and 18 obligate heterozygotes, and on amniotic fluid cells from 9 foetuses at risk. The brain enzyme was solubilized from a 900 g-100000 g pellet. With this enzyme preparation a profound deficiency of galactosylceramide beta-galactosidase activity in brain, approximately 1% of that in age-matched controls was shown. The lactosylceramide beta-galactosidase activity of brain was also strongly reduced, but not to the same extent as the other beta-galactosidase. Galactosylceramide beta-galactosidase activity in leukocytes from patients with Krabbe's disease was generally less than 5% of that in age-matched controls and there was no overlap between the patients and the obligate heterozygotes. Carrier detection by the leukocyte enzyme was, however, not possible because of considerable overlap between heterozygotes and normal controls. The lactosylceramide beta-galactosidase activity was only moderately reduced in leukocytes, but strongly reduced in cerebral tissue from patients with Krabbe's disease. The changes in the glycolipid pattern of cerebral tissue, recently described by us in patients with Krabbe's disease, offers an explanation to the serious glycolipid beta-galactosidase deficiency in CNS.


Paroxetine for the treatment of interferon-alpha-induced depression in chronic hepatitis C.
Psychiatric side-effects may require dose reduction or premature discontinuation of interferon therapy in chronic hepatitis C. New strategies are needed in order to prevent the premature termination of interferon therapy. To evaluate prospectively the efficacy and tolerability of antidepressant therapy (paroxetine, a selective serotonin reuptake inhibitor) in patients with chronic hepatitis C treated with interferon-alpha who have developed interferon-induced major depression. A sub-group of 14 individuals from 121 consecutively treated hepatitis C patients developed substance-induced major depression without suicidal ideation during interferon-alpha treatment. The individuals in this sub-group received paroxetine after the occurrence of depression (20 mg daily until termination of interferon therapy). Diagnostic scores for depression (and anger-hostility) were obtained in a repeated measures design (Hospital Anxiety and Depression Scale and Symptom Checklist 90 Items Revised). Eleven of the 14 patients (78.6%) with interferon-induced major depression were able to complete interferon-alpha therapy as scheduled under concomitant paroxetine treatment (three dropouts: insufficient improvement of depression, occurrence of epileptic seizures, paroxetine-induced nausea/dizziness). Within 4 weeks after the start of paroxetine medication, depression scores declined significantly in all patients. Our data suggest that concomitant therapy with paroxetine is an effective way to treat interferon-induced depression in patients with chronic hepatitis C.


Characteristics and quantities of HIV host cells in human genital tract secretions.
Human immunodeficiency virus (HIV)-infected leukocytes have been detected in genital secretions from HIV-infected men and women and may play an important role in the sexual transmission of HIV. However, they have been largely overlooked in studies on mechanisms of HIV transmission and in the design and testing of HIV vaccine and microbicide candidates. This article describes the characteristics and quantities of leukocytes in male and female genital secretions under various conditions and also reviews evidence for the involvement of HIV-infected cells in both horizontal and vertical cell-associated HIV transmission. Additional research is needed in this area to better target HIV prevention strategies.


Clinical Evaluation for Sublingual Immunotherapy With Dermatophagoides farinae in Polysensitized Allergic Asthma Patients.
Background: Many studies have demonstrated the efficacy of single-allergen sublingual immunotherapy (SLIT) in polysensitized patients with allergic rhinitis (AR), but less is reported in polysensitized patients with allergic asthma (AS). Method: Data of 133 adult patients with house dust mite (HDM)-induced AS who had been treated for 3 years were collected. These patients were divided into the control group (treated with low to moderate dose of inhaled glucocorticoids and long-acting β2 agonists, n = 37) and the SLIT group (further treated with Dermatophagoides farinae drops, n = 96). The SLIT group contained three subgroups: the single-allergen group (only sensitized to HDM, n = 35), the 1- to 2-allergen group (HDM combined with one to two other allergens, n = 32), and the 3-or-more-allergen group (HDM combined with three or more other allergens, n = 29). The total asthma symptom score (TASS), total asthma medicine score (TAMS), and asthma control test (ACT) were assessed before treatment and at yearly visits. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) was assessed before treatment and at the end of SLIT. Results: TASS and ACT scores in the control group were significantly higher than that in the single-allergen group and the 1- to 2-allergen group after 1, 2, and 3 years of SLIT and significantly higher than that in the 3-or-more-allergen group after 3-year SLIT (all p < 0.05). TAMS of the control group was significantly higher than that of the other three groups after 0.5, 1, 2, and 3 years of SLIT (all p < 0.05). FEV1/FVC in the control group was significantly higher than baseline after 3 years of immunotherapy (p < 0.05). Conclusion: Patients sensitized to HDM with/without other allergens showed similar efficacy after 3 years of SLIT. However, the initial response of patients with three or more allergens was slower during immunotherapy process.


One-donor, two-recipient extracranial-intracranial bypass series for moyamoya and cerebral occlusive disease: rationale, clinical and angiographic outcomes, and intraoperative blood flow analysis.
Cerebral extracranial-intracranial (EC-IC) direct bypass is a commonly used procedure for ischemic vasculopathy. A previously described variation of this technique is to utilize one donor artery to supply two recipient arteries, which the authors designate as 1D2R. The purpose of this study is to present a single surgeon's series of 1D2R direct bypasses for moyamoya and ischemia using detailed clinical, angiographic, and intraoperative blood flow measurement data. To the authors' knowledge, this is the largest series reported to date. Hospital, office, and radiographic imaging records for all patients who underwent cerebral revascularization using a 1D2R bypass by the senior author were reviewed. The patients' demographic information, clinical presentation, associated medical conditions, intraoperative information, and postoperative course were obtained from reviewing the medical records. A total of 21 1D2R bypasses were performed in 19 patients during the study period. Immediate bypass patency was 100% and was 90% on delayed follow-up. The mean initial cut flow index (CFI(i)) was 0.64 ± 0.33 prior to the second anastomosis and the mean final value (CFI(f)) was 0.94 ± 0.38 after the second anastomosis (p < 0.001). The overall bypass flow increased on average by 50% (mean 17.9 ml/min, range -10 to 40 ml/min) with the addition of the second anastomosis. There was no significant difference in the overall flow measurements when the end-to-side anastomosis or side-to-side anastomosis was performed first. There was a statistically significant difference in the proportion of patients with a modified Rankin Scale (mRS) score of 0 or 1 postoperatively compared to preoperatively (p < 0.01). Through the application of Poiseuille's law, the authors analyzed flow dynamics, deduced the component vascular resistances based on an analogy to electrical circuits and Ohm's law, and introduced the new concepts of "second anastomosis relative augmentation" and "second anastomosis sink index" in the evaluation of 1D2R bypasses. The application of the 1D2R technique in a series of 19 consecutive patients undergoing direct EC-IC bypass for flow augmentation demonstrated high patency rates, statistically significantly higher CFIs compared to 1D1R, and improved mRS scores at last clinical follow-up. Additionally, the technique allows a shorter dissection time and preserves blood flow to the scalp. The routine utilization of intraoperative volumetric flow measurements in such surgeries allows a deeper understanding of the hemodynamic impact on individual patients.