Discovery of AZD3514, a small-molecule androgen receptor downregulator for treatment of advanced prostate cancer.
Removal of the basic piperazine nitrogen atom, introduction of a solubilising end group and partial reduction of the triazolopyridazine moiety in the previously-described lead androgen receptor downregulator 6-[4-(4-cyanobenzyl)piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (1) addressed hERG and physical property issues, and led to clinical candidate 6-(4-{4-[2-(4-acetylpiperazin-1-yl)ethoxy]phenyl}piperidin-1-yl)-3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazine (12), designated AZD3514, that is being evaluated in a Phase I clinical trial in patients with castrate-resistant prostate cancer.


Measures of sleep are not routinely captured in trials assessing treatment outcomes in knee osteoarthritis - A scoping systematic review and call to action.
To identify and map the extent to which trials for pain interventions in individuals with knee osteoarthritis (OA) track measures of sleep, characterize the type of sleep measure assessed, and assess their influence on pain-related effect sizes. A scoping review was conducted, searching seven bibliometric databases from 2000 to 2022. We included all randomized controlled trials with a primary purpose of assessing non-surgical pain management interventions for adults with knee OA. All non-surgical interventions and any comparator or control were included. Demographic data were pooled from all trials. 926 trials conducted in 61 countries met eligibility. Nineteen trials (2.1%) recorded some form of sleep assessment. Eleven trials (1.2%) assessed a formal index of sleep disturbance collected at multiple time points. No trials formally assessed the influence of sleep on the primary pain outcome (e.g., as a potential mediator), nor met the most recent guidelines for core data element recommendations regarding sleep assessment. This review highlights the paucity of sleep data captured and reported in randomized controlled trials for knee OA. The vast majority of trials addressing symptomatic knee OA do not capture sleep measures, significantly limiting the ability to accurately determine an intervention's effect on pain. Future research should include formal sleep-centric assessments measured at multiple time points to analyze sleep dysfunction and its relationship on treatment effects.


Bile deficiency induces changes in intestinal Cl(-) and HCO3 (-) secretions in mice.
Biliary tract obstruction is a common clinical lesion. However, the effect of biliary tract obstruction on intestinal secretion is poorly understood. In this study, we made an investigation on intestinal HCO3 (-) and Cl(-) secretions in an experimental model of murine biliary duct ligation. Murine intestinal mucosal HCO3 (-) and Cl(-) secretions were examined in vitro in Ussing chambers by pH-stat and short-circuit current (Isc ) techniques. The mRNA and protein expressions of the cystic fibrosis transmembrane conductance regulator (CFTR) and the Na(+) -K(+) -2Cl(-) cotransporter (NKCC1) were analysed by real-time PCR, western blot and immunohistochemistry. Basal Cl(-) secretion and forskolin-stimulated duodenal and jejunal mucosal HCO3 (-) and Cl(-) secretions in mice with common biliary duct ligation were markedly elevated, compared with controls (P < 0.05 and P < 0.01). Further experiments showed that basal Cl(-) secretion and forskolin-stimulated duodenal and jejunal mucosal HCO3 (-) and Cl(-) secretions in mice with external bile drainage were also markedly elevated. CFTRinh -172 inhibited forskolin-stimulated HCO3 (-) and Cl(-) secretions. The mRNA and protein expression levels of CFTR and NKCC1 in the intestinal mucosa with both biliary duct ligation and external bile drainage were markedly higher than those in controls (P < 0.001). Bile acid administration restored the changes in function and expression of CFTR and NKCC1 in the intestinal mucosa. Bile deficiency in the intestine up-regulates the expressions of intestinal mucosal CFTR and NKCC1 and enhances intestinal mucosal HCO3 (-) and Cl(-) secretion capacity, which contributes to the understanding of intestinal physiological function for patients with biliary duct obstruction.


The use of Bioceramics as root-end filling materials in periradicular surgery: A literature review.
Periradicular surgery involves the placement of a root-end filling following root-end resection, to provide an apical seal to the root canal system. Historically several materials have been used in order to achieve this seal. Recently a class of materials known as Bioceramics have been adopted. The aim of this article is to provide a review of the outcomes of periradicular surgery when Bioceramic root-end filling materials are used on human permanent teeth in comparison to "traditional" materials. An electronic literature search was performed in the databases of Web of Science, PubMed and Google Scholar, between 2006 and 2017, to collect clinical studies where Bioceramic materials were utilised as retrograde filling materials, and to compare such materials with traditional materials. In this search, 1 systematic review and 14 clinical studies were identified. Of these, 8 reported the success rates of retrograde Bioceramics, and 6 compared treatment outcomes of mineral trioxide aggregate (MTA) and traditional cements when used as root-end filling materials. Bioceramic root-end filling materials are shown to have success rates of 86.4-95.6% (over 1-5 years). Bioceramics has significantly higher success rates than amalgam, but they were statistically similar to intermediate restorative material (IRM) and Super ethoxybenzoic acid (Super EBA) when used as retrograde filling materials in apical surgery. However, it seems that the high success rates were not solely attributable to the type of the root-end filling materials. The surgical/microsurgical techniques and tooth prognostic factors may significantly affect treatment outcome.


Modulins: a new class of cytokine-inducing, pro-inflammatory bacterial virulence factor.
Despite the fact that the inflammatory and immune responses have evolved to combat microorganisms, the present generation of inflammation researchers has evinced relatively little interest, with the exception of septic shock, in microbially-induced inflammation. This in spite of the fact that the Gram-negative cell wall constituent, lipopolysaccharide, has been widely used as a tool in inflammation research. The reason for such lack of interest has been due to the therapeutic efficacy of antibiotics which are the treatment of choice for infections and their inflammatory sequelae. However, this is likely to change within the next decade or so, with the relentless increase in the incidence of antibiotic-resistant strains of bacteria. This will return therapy to the stage where clinicians will have to treat the inflammatory symptoms of infection. Many of these symptoms are due to the stimulation of cytokine synthesis. The capacity of bacteria to induce cytokine synthesis has, until the past few years, centred exclusively on lipopolysaccharide. However, it has been established during the past 5-10 years that a range of other molecules, mainly associated with the surface of bacteria, have the capacity to induce cytokine production. Some of these are exquisitely potent stimulators of pro-inflammatory cytokine synthesis. The nature and mechanism of action of these various cytokine-inducing molecules, for which we have devised the name modulins, is the subject of this review. It is clear that bacteria still have many surprises for us, as exemplified by the recent discovery of the role played by Helicobacter pylori in gastritis, gastric ulceration and gastric cancer.


Psychoactive substances and the political ecology of mental distress.
The goal of this paper is to both understand and depathologize clinically significant mental distress related to criminalized contact with psychoactive biotic substances by employing a framework known as critical political ecology of health and disease from the subdiscipline of medical geography. The political ecology of disease framework joins disease ecology with the power-calculus of political economy and calls for situating health-related phenomena in their broad social and economic context, demonstrating how large-scale global processes are at work at the local level, and giving due attention to historical analysis in understanding the relevant human-environment relations. Critical approaches to the political ecology of health and disease have the potential to incorporate ever-broadening social, political, economic, and cultural factors to challenge traditional causes, definitions, and sociomedical understandings of disease. Inspired by the patient-centered medical diagnosis critiques in medical geography, this paper will use a critical political ecology of disease approach to challenge certain prevailing sociomedical interpretations of disease, or more specifically, mental disorder, found in the field of substance abuse diagnostics and the related American punitive public policy regimes of substance abuse prevention and control, with regards to the use of biotic substances. It will do this by first critically interrogating the concept of "substances" and grounding them in an ecological context, reviewing the history of both the development of modern substance control laws and modern substance abuse diagnostics, and understanding the biogeographic dimensions of such approaches. It closes with proposing a non-criminalizing public health approach for regulating human close contact with psychoactive substances using the example of cannabis use.


Organic ligand induced release of vanadium from the dissolution of stone coal oxide ore.
The effects of low-molecular-weight dissolved organic matters (LMWDOMs) on the release of vanadium (V) under environmental conditions are part of a broader study on the environmental geochemistry behavior of V. Eight typical naturally occurring LMWDOMs with carboxyl, hydroxyl, and amidogen groups were chosen: citric acid, oxalic acid, EDTA, salicylic acid, catechol, glycine, cysteine, and glucose. The results showed that the release of V was largely promoted by LMWDOMs with carboxyl functional groups under acidic conditions and with catechol under basic conditions. In the presence of citric acid, oxalic acid, or EDTA at pH 4.0, the initial release rates of V were approximately 25-39 times greater than the rates in the control experiments; the steady release rates were 164, 95, and 49 times than the rates in the control experiments, respectively. For catechol, the release rate at pH 8.0 was approximately 20 times the rate at pH 4.0. Amino acids and alcohols had a minimal effect on the release of V. Ligand-promoted release rates of V were found primarily due to the faster detachment of surface complexes, the protonated sites from the mineral surface and the reduction of dissolved V (V) in the presence of citric acid, oxalic acid, EDTA, and catechol. This study helps understand the pollution risk of V in some mine areas and the fate of V in the environment.


Emergency department lumbar puncture: clinical application and utility of laboratory testing.
Lumbar puncture is an emergency department procedure for evaluating patients with suspected central nervous system infection or hemorrhage. To determine whether extensive testing of cerebrospinal fluid (CSF) obtained from emergency department patients was useful, charts of 104 adult patients who underwent lumbar puncture in a university hospital emergency department were reviewed. Examination of the CSF disclosed pleocytosis in 25 (24%) of the patients; the presence of red blood cells was considered to be clinically significant in two patients. An abnormal level of CSF protein was present in 62% of patients, and abnormal levels of glucose in 32%. Fungal element testing was negative each of the 72 times it was performed; Gram stain disclosed a bacterial pathogen in one patient. Cultures for fungus and tuberculosis were uniformly negative, as were all immunologic tests. Bacterial cultures grew a pathogen in one patient. No patient with a normal neurologic examination and normal initial CSF analysis was diagnosed subsequently as having acute central nervous system disease. The preponderance of negative or normal results of testing of CSF suggests that extensive testing may not be necessary for all patients. Limitation of sophisticated testing to only those samples with abnormal cell counts or chemistries or from patients at high risk should result in substantial cost saving without compromising patient care.


Helical (spiral) CT of the musculoskeletal system.
Helical (spiral) CT scanning of the musculoskeletal system is a valuable adjunct in patients with complex disease processes where standard radiography may prove to be of limited use. When CT scans are ordered, the use of helical (spiral) acquisition provides specific advantages in terms of ease of performance of the study, potential successful completion of the study, and in quality of the CT data set. Future advances in technology will enhance these advantages.


Effects of Pilates in children and adolescents - A systematic review and meta-analysis.
Pilates can be performed by children as a form of exercise to promote healthy growth and development. The increasing use of Pilates as a type of exercise for children or as an adjunct tool in pediatric rehabilitation should be supported by evidence of its benefits. The aim of this systematic review and meta-analysis was to assess the effects of Pilates as an exercise prescription for children and adolescents. Five electronic databases were searched to identify trials (randomized controlled clinical trials or quasi-experimental studies) with a population of children or adolescents in which Pilates (mat or equipment) was performed as a form of exercise. Studies that investigated outcomes related to health and physical performance was analyzed. Individual trial effects were extracted and pooled for meta-analysis whenever possible. To evaluate the external and internal validity of the studies, we assessed their risk of bias. Fifteen studies (from 945 records), including 1235 participants, met the eligibility criteria, and were included. The reported outcomes were heterogeneous, so only the effect on flexibility could be included in the meta-analysis (n = 4 studies). A significant positive trend toward improved flexibility for the control group compared with the Pilates group was found (Std. mean difference, 0.54; 95%CI: 0,18, 0.91; p = 0.003). Few studies have assessed the effect of Pilates on children and adolescents. The lack of appropriate methodological descriptions/controls made it impossible to determine if all of the included studies were of good quality.


High affinity phenylglycinol-based NK1 receptor antagonists.
Heterocyclic replacements for the carboxamido group of the previously disclosed phenylglycinol-based human NK1 (hNK1) receptor antagonists have been investigated, ultimately leading to acyclic compounds with sub-nanomolar affinity for the hNK1 receptor.


Neural substrates of conditioned-cued relapse to drug-seeking behavior.
Relapse to drug use following abstinence is a significant impediment in the long-term treatment of drug abuse and dependence. Conditioned stimuli are believed to be critically involved in activating drug craving and relapse to compulsive drug-taking behavior. Studies in humans and animal models have recently begun to identify the fundamental neural circuitry that mediates relapse following withdrawal from chronic drug self-administration. The current review summarizes key findings in this area that have converged on the amygdalar complex and regions of the frontal lobe as critical structures in conditioned-cued relapse. It is proposed that the amygdala is a key regulator of discrete stimulus-reinforcer associations, while the anterior cingulate and orbitofrontal cortex are critical regulators of relapse evoked by conditioned stimuli that predict drug availability. This corticolimbic circuitry may form the neural basis of multiple long-term conditioned associations produced by a variety of drugs of abuse ranging from psychostimulants to opiates. Future studies aimed at discerning the functional roles of these pathways will provide critical direction for the development of treatments for the prevention of relapse.


[Metabolic syndrome and its components in patients with sleep apnea syndrome].
Sleep Apnea Syndrome (SAHS) represents a significant risk factor for the development of cardiovascular disease and evidence suggests a relation with Metabolic Syndrome (MS). The aim of this study was to determine the prevalence of individual components of MS and of MS as an entity, in patients with clinical suspicion of SAHS, and their relation to central obesity. We examined the records of 486 consecutive patients, 359 (73.9%) men, with a mean age of 57.3 ± 13.5 years and a mean body mass index (BMI) of 32.1 ± 6.5 kg/m(2)), with clinical suspicion of SAHS. SAHS was diagnosed from the nocturnal register. An Apnea-Hipopnea Index (AHI) > 5 was considered SAHS. MS was evaluated according to the diagnostic criteria of the International Diabetes Federation. Three hundred and twenty-five (66.9%) of the entire group were moderate-severe SAHS. The mean of AHI was 30.2 ± 23.8. We had sufficient data available on 456 patients (93.8%) for MS diagnosis and its prevalence was 64.7% (295 patients). Multivariate analysis showed that age and abdominal perimeter were predictors of SAHS and MS (p<0.05). Patients with SAHS have a high prevalence of MS and their prevalence is greater in patients with major levels of SAHS. The rate of central obesity, measured by abdominal perimeter, predicts SAHS and MS.


Developmental risk of depression: experience matters.
This article focuses on discussing risks for depression onset and the role of environmental factors in promoting resilience in children and adolescents. The authors review the current literature on specific (eg, family history of depression) and nonspecific (eg, poverty, stressful life events) risk factors for youth depression to underscore the need for prevention efforts promoting resiliency in this population.


The relationship between OXT gene polymorphisms and reproductive hormones in pregnant and lactating Awassi Ewes.
Numerous genetic loci interact intricately to control reproduction in mammals. The oxytocin gene (OXT) is a promising candidate for reproductive traits in mammals. Previously, sheep and goats have been studied for the presence of the OXT polymorphism. As of yet, no polymorphisms have been identified in the OXT gene of Awassi sheep. Thus, this study was conducted to determine the effects of OXT polymorphism and litter size on reproductive hormones in pregnant and lactating Awassi ewes. This study evaluated 232 ewes aged 3 and 4 years (123 single-progeny ewes and 109 twin-producing ewes). Serum was collected to measure reproductive hormones using ELISA kits manufactured by ELK Biotechnology. DNA was extracted from sheep blood for genotyping and sequencing to identify variations in OXT gene (exon 2, 266 bp). Genotyping analysis revealed three genotypes within 266 bp: CC, CA, and AA. Sequence analysis revealed a novel mutation in exon 2: 188 C > A. Statistical analysis showed significant associations between the 188 C > A SNP and phenotypic traits. Twin-pregnant ewes carrying CC genotypes had higher estrogen, progesterone, and follicle-stimulating hormone/luteinizing hormone levels (65.86 ± 3.87) (pg/mL), (6.51 ± 0.39) (ng/mL), and (20.22 ± 1.27) (ng/mL)/( 23.37 ± 2.14) (ng/mL) respectively, compared to CA and AA genotypes in the fourth month of twin-pregnant ewes compared to single-pregnant ewes. This study found that the 188 C > A SNP negatively affected reproductive hormone levels in Awassi sheep. These findings provide breeders with a new insight into the sheep OXT gene, useful for future breeding.


Sodium accumulation has minimal effect on metabolite profile of onion bulbs.
Onions (Allium cepa L.) are considered a salt-sensitive crop. However, to date, little evidence supports this claim and information about the physiological and metabolomic effects of Na+ accumulation in onion plants is lacking. The purpose of our research has been to assess changes in onion bulbs of three different cultivars after soil and foliar applications with moderate doses of chloride-free Na2SO4. The antioxidative defense mechanism in onion and the accumulation of Na+ within the plant has also been analyzed. Based on Na+ leaf and bulb concentrations, our findings demonstrate that Na+ is only transported from bulbs to leaves not vice versa, therefore foliar application does not lead to Na+ accumulation in the bulbs. Soil application with Na2SO4 results in an accumulation of Na+ in the leaves and bulbs, but with the exception of one onion variety this accumulation does not alter the metabolite profile of onions significantly. Even the K+ concentration and organic solute levels are unchanged after accumulation of Na+. Nevertheless, after Na2SO4 treatment, the antioxidative defense system moderately increases in onion bulbs. This study demonstrates that onion plants have the ability to exclude Na+ at moderate Na2SO4 treatment, and that the potential for quality onion production in soils with increased sodium concentration is much higher than previously assumed.


Promotional effects of Nb5+ and Fe3+ co-doping on catalytic performance and SO2 resistance of MnOx-CeO2 low-temperature denitration catalyst.
As we know, SO2 can cause MnOx-CeO2 (MnCeOx) catalyst poisoning, which seriously shortens the service life of the catalyst. Therefore, to enhance the catalytic activity and SO2 tolerance of MnCeOx catalyst, we modified it by Nb5+ and Fe3+ co-doping. And the physical and chemical properties were characterized. These results illustrate that the Nb5+ and Fe3+ co-doping can optimally improve the denitration activity and N2 selectivity of MnCeOx catalyst at low temperature by improving its surface acidity, surface adsorbed oxygen as well as electronic interaction. What's more, NbOx-FeOx-MnOx-CeO2 (NbFeMnCeOx) catalyst possesses an excellent SO2 resistance due to less SO2 being adsorbed and the ammonium bisulfate (ABS) formed on its surface tends to decompose, as well as fewer sulfate species formed on its surface. Finally, the possible mechanism that Nb5+ and Fe3+ co-doping enhances the SO2 poisoning resistance of MnCeOx catalyst is proposed.


3-D reconstruction of neurons from multichannel confocal laser scanning image series.
A confocal laser scanning microscope (CLSM) collects information from a thin, focal plane and ignores out-of-focus information. Scanning of a specimen, with stepwise axial (Z-) movement of the stage in between each scan, produces Z-series of confocal images of a tissue volume, which then can be used to 3-D reconstruct structures of interest. The operator first configures separate channels (e.g., laser, filters, and detector settings) for each applied fluorochrome and then acquires Z-series of confocal images: one series per channel. Channel signal separation is extremely important. Measures to avoid bleaching are vital. Post-acquisition deconvolution of the image series is often performed to increase resolution before 3-D reconstruction takes place. In the 3-D reconstruction programs described in this unit, reconstructions can be inspected in real time from any viewing angle. By altering viewing angles and by switching channels off and on, the spatial relationships of 3-D-reconstructed structures with respect to structures visualized in other channels can be studied. Since each brand of CLSM, computer program, and 3-D reconstruction package has its own proprietary set of procedures, a general approach is provided in this protocol wherever possible.


Sequence-universal recognition of duplex DNA by oligonucleotides via pseudocomplementarity and helix invasion.
The well-known Watson-Crick complementarity rules, which were discovered 50 years ago, elegantly direct the specific pairing of two DNA single strands. On the contrary, once formed, the double-stranded (ds) DNA lacks such a simple and sequence-universal recognition principle, since most of the characteristic chemical groups of nucleobases are now buried deep inside the double helix, the major DNA form. We report a promising versatile approach for highly selective recognition of designated sites within dsDNA featuring considerable practical potential for a variety of molecular-biological, biotechnological, gene-therapeutic, and diagnostic applications. It may also have implications for prebiotic evolution of genetic machinery at the primordial stages of the origin of life. Our design synergistically employs the robust helix-invasion ability of recently developed DNA mimics and analogs, pseudocomplementary peptide nucleic acids and pseudocomplementary oligonucleotides, thus enabling the sequence-unrestricted recognition of chosen DNA duplexes by nucleobase oligomers. Using this basically general approach, we selectively tagged a unique mixed-base site on the target dsDNA fragment with streptavidin and/or multiply labeled this site with fluorophores via the primer-extension reaction.


Paraphenylene diamine hair dye poisoning: an uncommon cause of rhabdomyolysis.
Paraphenylene daimine (PPD) is a kind of aromatic amine that is widely used in several industrial products. Women also use PPD added to henna (Lawasonia alba) as a hair dye. Though rare in Western countries, PPD poisoning is quite common in East Africa, India and Middle Eastern countries because it is a traditional product at these countries. Different pathologies were described as caused by PPD ingestion including angioedema of head and neck, rhabdomyolysis, and acute renal failure. The authors report a case of systemic poisoning with PPD that lead to angioedema resulting in tracheostomy and rhabdomyolysis.


Delivery of a lentiviral vector in a Pluronic F127 gel to cells of the central nervous system.
Lentiviral vectors have been demonstrated as efficient tools for gene delivery to the CNS. We describe a novel approach for vector delivery using the thermoresponsive Gel, Pluronic F127 as a carrier. A HIV-1 lentiviral vector expressing GFP was contained in various concentrations of gel (15, 30 and 40%) and applied to cultures of 293T cells. FACS analysis of cells transduced with 8ng of lentiviral vector revealed a similar transduction efficiency for each Gel concentration compared to vector added to cells without PF127. Primary Rat CNS mixed glial cultures were also transduced with lentiviral vector in 15% Pluronic F127 and results demonstrated a similar transduction efficiency of astrocytes compared to virus without gel and no evidence of cell toxicity or death. Stereotaxic delivery of viral vector in 15% PF127 to the rat brain resulted in transduction of cells, predominantly astrocytes close to the injection site. Pluronic F127 gel delivery of viral vectors to the CNS may provide a platform for localised release particularly in areas of brain or spinal cord injury.


Crystal structure of bis-[(oxalato-κ2O1,O2)(1,4,8,11-tetra-aza-cyclo-tetra-decane-κ4N)chromium(III)] dichromate octa-hydrate from synchrotron X-ray data.
The asymmetric unit of the title compound, [Cr(C2O4)(C10H24N4)]2[Cr2O7]·8H2O (C10H24N4 = 1,4,8,11-tetra-aza-cyclo-tetra-decane, cyclam; C2O4 = oxalate, ox) contains one [Cr(ox)(cyclam)]+ cation, one half of a dichromate anion that lies about an inversion centre so that the bridging O atom is equally disordered over two positions, and four water mol-ecules. The terminal O atoms of the dichromate anion are also disordered over two positions with a refined occupancy ratio 0.586 (6):0.414 (6). The CrIII ion is coordinated by the four N atoms of the cyclam ligand and one bidentate oxalato ligand in a cis arrangement, resulting in a distorted octa-hedral geometry. The Cr-N(cyclam) bond lengths are in the range 2.069 (2)-2.086 (2) Å, while the average Cr-O(ox) bond length is 1.936 Å. The macrocyclic cyclam moiety adopts the cis-V conformation. The dichromate anion has a staggered conformation. The crystal structure is stabilized by inter-molecular hydrogen bonds involving the cyclam N-H groups and water O-H groups as donors, and the O atoms of oxalate ligand, water mol-ecules and the Cr2O72- anion as acceptors, giving rise to a three-dimensional network.


Clearance of bromosulphthalein by the liver of sheep.
The application of a serial sampling technique for assessing bromosulphthalein (BSP) clearance by the liver of sheep is described. After a single intravenous injection BSP was almost completely cleared by the liver into the bile. Clearance by the liver was in two phases which allowed the calculation of the proportionality transfer constants a (from plasma to liver), h (from liver to bile) and b (from liver back to plasma). The ratio of a:h was approximately 4:1 in sheep. The proportionality transfer constants had the advantage over fractional clearance and retention tests of relating the test more precisely to the condition of the liver at the cellular level. The single injection method was simple, non-invasive and repeatable and suitable for conscious animals.


Trial of a quantitative method for evaluating hemangioma of the liver and hepatocellular carcinoma using a radio-frequency signal.
In recent years, advances in ultrasonographic techniques have allowed the detection of even small hepatocellular carcinomas. However, many cases do not show distinctive ultrasonographic features. A quantitative ultrasonographic procedure for making the diagnosis would therefore be desirable. It is recognized that radio-frequency (RF) signals from hepatic tumors conform to the K distribution. The K distribution is used for the characterization of the statistical properties of backscattering signals from heterogeneous regions. In this study, RF signals were acquired from hemangioma of the liver (hemangioma) and hepatocellular carcinoma (HCC), and parameters of the K distribution, i.e., φ (the mean square of the amplitude of RF signals) and α (the number of effective scatterers), were calculated for the quantitative ultrasonographic evaluation of hepatic tumors. This study included 10 nodules of 10 patients with hemangioma and 27 nodules of 24 patients with HCC. The A-mode RF signals passing through the hepatic tumors were acquired with an Aloka SSD-1000 ultrasound system, and measurement units comprising 279 points were set on the RF signals corresponding to the tumor lesion. The parameters of the K distribution that were most consistent with the histogram were calculated and assessed. With regard to φ, the values were high in hemangioma, and there was a significant (P < 0.05) difference in the φ value between hemangioma and HCC. On the other hand, there was no significant difference in the α value between hemangioma and HCC. The α values of hemangioma were equivalent to those of HCC, while the φ values for hemangioma were higher than those for HCC. It was deduced from these observations that a situation in which an electron beam is likely to scatter exists in the tumor. This is also consistent with the pathological findings reported from previous studies. The use of these parameters is expected to allow quantitative ultrasonographic evaluation of hepatic tumors.


Isozyme specificity of novel glutathione-S-transferase inhibitors.
A systematically diversified set of peptide analogs of the reaction product of glutathione with an electrophilic substrate have been tested as isozyme-specific inhibitors of human glutathione-S-transferase (GST). The potency of the best of the inhibitors is in the 0.5 to 20 micromolar range, with kinetics indicative of competitive inhibition with glutathione at the active site. The specificity observed among three recombinant-derived GST isozymes at both low and high potency ranged from negligible to high (at least 20-fold over the next most sensitive isozyme). These results define a novel strategy for the design of drugs targeting cells with elevated levels of particular GST isozymes, such as tumor cells for which elevated levels of GST are believed to be an important cause of chemotherapeutic drug resistance.


Cesium transfer to millet and mustard as a function of Cs availability in soils.
137Cs is one of the most persistent radioactive contaminants in soil after a nuclear accident. It can be taken up by plants and enter the human food chain generating a potential human health hazard. Although a large amount of literature has highlighted the role of the different processes involved in Cs uptake by plants, there is still no simple way to predict its transfer for a specific plant from a particular soil. Based on the assumption that the concentration ratio (CR) of Cs can be predicted from one plant taxon if the CR of another taxon is known and taken as reference, whatever the supporting soils, a series of plant/soil Cs transfer experiments were performed on Rhizotest during 21 days using three soils with different textures, clay and organic matter contents and two plants (millet and mustard) with potentially contrasting Cs uptake capacity based on their phylogeny. CRs of each plant varied by 2-3 orders of magnitude depending on the soil and contrary to expectations, the CRs of mustard were either higher (for clay soil), equal (for clay-loam soil) or lower (for sandy soil) than the one of millet. Considering Cs availability in soils and defining a new CR based on the amount of Cs available in the soil (CRavail) decreased the range of variation in CR between the different soil types for a given plant by one order of magnitude. Differences in Cs (and K) translocation to shoots, possibly specific to millet within Poales, could partly explain the relative CRs of millet and mustard as a function of soils.


High-touch care leads to better outcomes and lower costs in a senior population.
There are several models of primary care. A form of high-intensity care is a high-touch model that uses a high frequency of encounters to deliver preventive services. The aim of this study is to compare the healthcare utilization of patients receiving 2 models of primary care, 1 with high-touch care and 1 without. Retrospective cohort study. We conducted a retrospective cohort study of 2 models of care used among Medicare Advantage populations. Model 1 is a high-touch care model, and model 2 is a standard care model. Compared with model 2, model 1 has smaller panel sizes and a higher frequency of encounters. We compared patients' healthcare utilization and hospitalizations between both models using a propensity score-matched analysis, matching by Charlson Comorbidity Index (CCI) score, age, and gender. We included 17,711 unmatched Medicare Advantage primary care patients and matched 5695 patients from both models of care. CCI scores, age, and gender were similar between both matched groups (P >.05). The median total per member per month healthcare costs in model 1 were $87 (95% CI, $26-$278) compared with $121 (95% CI, $52-$284) in model 2 (P <.01). The mean number of hospital admissions was lower in model 1 (0.10 ± 0.40) compared with model 2 (0.20 ± 0.58). The number of primary care physician visits and preventive medication use were higher in model 1 (P <.05 for both). In a propensity-matched sample of Medicare Advantage patients, those receiving high-touch care had lower healthcare costs and fewer hospitalizations. Potential explanations are higher preventive medication use and more frequent visits.


Skeletal Muscle Transcriptomic Comparison between Long-Term Trained and Untrained Men and Women.
To better understand the health benefits of lifelong exercise in humans, we conduct global skeletal muscle transcriptomic analyses of long-term endurance- (9 men, 9 women) and strength-trained (7 men) humans compared with age-matched untrained controls (7 men, 8 women). Transcriptomic analysis, Gene Ontology, and genome-scale metabolic modeling demonstrate changes in pathways related to the prevention of metabolic diseases, particularly with endurance training. Our data also show prominent sex differences between controls and that these differences are reduced with endurance training. Additionally, we compare our data with studies examining muscle gene expression before and after a months-long training period in individuals with metabolic diseases. This analysis reveals that training shifts gene expression in individuals with impaired metabolism to become more similar to our endurance-trained group. Overall, our data provide an extensive examination of the accumulated transcriptional changes that occur with decades-long training and identify important "exercise-responsive" genes that could attenuate metabolic disease.


Symmetries in Muscle Torque and Landing Kinematics Are Associated With Maintenance of Sports Participation at 5 to 10 Years After ACL Reconstruction in Young Men.
Long-term maintenance of sports participation is important for young men undergoing anterior cruciate ligament (ACL) reconstruction. Identifying biomechanical characteristics in patients who achieve this goal can assist in elaborating rehabilitation programs and in identifying successful recovery, but this has rarely been investigated. To test the association between maintenance of sports participation at 5 to 10 years after ACL reconstruction and measures of force production and landing biomechanics in men. Cross-sectional study; Level of evidence, 3. A total of 30 men who underwent isolated ACL reconstruction were examined. At 5- to 10-year follow-up, associations were tested between reported outcomes of sports maintenance and objective biomechanical measures. The biomechanical tests included isokinetic knee torque and lower limb kinetics and kinematics during landing tasks. Measurements for each limb were conducted separately, and side-to-side symmetry indices (SI) were calculated. Subgroups included SI greater than +10% (ie, extreme positive), SI lower than -10% (ie, extreme negative), and SI between -10% and +10% (ie, symmetric). At follow-up, concentric knee torque in the operated limb correlated with Tegner and Marx scores (r = 0.42-0.47; P ≤ .05). Regarding the SI of knee torque, the highest Tegner, Marx, and KOOS (Knee injury and Osteoarthritis Outcome Score) results were associated with symmetry, as opposed to patients with extreme positive or extreme negative SIs (P < .05). As for landing kinematics, Tegner score negatively correlated with knee range of motion (ROM) in the operated limb (r = -0.38; P ≤ .05). With regard to SI, hip and knee ROM correlated with Tegner, IKDC, and KOOS scores (r = 0.41-0.51; P ≤ .05). Specifically, the highest sports participation levels were associated with achieving symmetric hip and knee ROM but also with extreme positive SIs, as opposed to patients with extreme negative SIs (P < .03), indicating substantially higher ROM in the uninjured limb as compared with the operated limb. At 5 to 10 years after ACL reconstruction, maintenance of sports participation was associated with symmetric side-to-side concentric knee torque and with producing greater attenuation of hip and knee ROM during the drop jump landing in the operated limb. Therefore, eccentric load programs that can improve attenuation-phase kinematics during landing tasks may be valuable in addition to concentric training and may facilitate enhanced long-term outcomes.


Host-extract induced changes in the secretome of the plant pathogenic bacterium Pectobacterium atrosepticum.
Pectobacterium atrosepticum is a Gram-negative plant pathogenic bacterium that causes rotting in potato stems and tubers. The secreted proteins of this pathogen were analyzed with proteomics from culture supernatant of cells grown in minimal medium supplemented with host extracts. More than 40 proteins were identified, among them known virulence determinants, such as pectic enzymes, metalloprotease, and virulence protein Svx, along with flagella proteins, GroEL and cyclophilin-type chaperones and several hypothetical proteins or proteins with unknown function. Some of the identified proteins may be involved in utilization of nutrients or transport of minerals. Northern and real-time RT-PCR analyses suggested that most of the proteins upregulated by plant extract were transcriptionally regulated. Among the identified proteins were VgrG and four homologs of hemolysin-coregulated proteins (Hcps). A mutant strain lacking one of the hcp genes was not affected in virulence, while a bacterial strain overexpressing the same gene was shown to have increased virulence, which suggests that these proteins may be new virulence determinants of P. atrosepticum. Comparison of the secretomes of wild type cells and hrcC mutant defective in Type III secretion suggested that the production of the identified proteins was independent of functional Type III secretion system.


Scanning electron microscopy of removed intraocular lenses.
During a six-year period, 27 intraocular lenses (2%) were removed from a population of 1,794 implanted eyes. The frequency of and reasons for removal of the lenses, as well as patient information, dates of insertion and removal, types of surgery, and lens manufacturers, were recorded. Twelve of 15 lenses obtained for study were examined by scanning electron microscopy. These revealed poor finish quality, molding defects, and loop degradation. In the first four years the incidence of lens removal was approximately 3.8%. During the following three years, there was a dramatic reduction in the number of lenses removed, suggesting that increased experience and better lens design led to fewer lens removals.


Fibrillin-rich microfibrils of the extracellular matrix: ultrastructure and assembly.
Fibrillin-rich microfibrils are a unique class of extensible connective tissue macromolecules. Their critical contribution to the establishment and maintenance of diverse extracellular matrices was underlined by the linkage of their principal structural component fibrillin to Marfan syndrome, a heritable connective tissue disorder with pleiotropic manifestations. Microscopy and preparative techniques have contributed substantially to the understanding of microfibril structure and function. The supramolecular organisation of microfibrillar assemblies in tissues has been examined by tissue sectioning and X-ray diffraction methods. Published findings are discussed and new information reported on the organisation of microfibrils in the ciliary zonular fibrils by environmental scanning electron microscopy. This review summarises microscopy and X-ray diffraction studies that are informing current understanding of the ultrastructure of fibrillin-rich microfibrils.


The occurrence of neurological symptoms in currently abstinent misusers of alcohol.
Significant neurological symptoms may be overlooked because of the traditional view that the non-Korsakoff's psychosis, middle aged alcoholic misuser is neurologically preserved. In this study, we wanted to investigate the presence of neurological symptoms in individuals with misuse or dependence on alcohol who were abstinent for at least 1 month. We used two scales from the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) to ascertain the presence of both neurological symptoms (HEA-2) and symptoms of general health concern (HEA-3) in 70 individuals who had a diagnosis of alcohol misuse or dependence, who were abstinent for greater than 1 month. Individuals reported significantly more neurological symptoms than general health difficulties (p < 0.001). We detected neurological symptoms, unlike general health difficulties in individuals who were abstinent from alcohol for 12 months. When we examined diagnostic subgroups, general health difficulties were most present in individuals with anxiety disorders; however, neurological difficulties were present across diagnostic groups. Neurological symptoms persist to a greater extent than general health concerns in individuals who previously were dependent or misused alcohol.


Cortical Somatosensory Neurons in WAG/Rij Rats Transform Firing Evoked by Simulation of Posterior Thalamic Nucleus from Tonic to Phasic at Age of 6 Months.
Functional peculiarities of paralemniscal subdivision of the thalamocortical system were examined in normal Wistar and in WAG/Rij rats genetically prone to absence epilepsy. In 6-7-month-old WAG/Rij characterized by developed epileptic activity, the response of cortical somatosensory neurons to single electrical stimulation of the posterior thalamic nucleus was phasic, whereas in normal Wistar rats, similar reaction was tonic. The study views this phasic response as neural equivalent of spike-wave discharges known as typical EEG symptom of absence epilepsy.


Thick methacrylate sections devoid of lost caps simplify stereological quantifications based on the optical fractionator design.
In neuroscience, the optical fractionator technique is frequently used for unbiased cell number estimations. Although unbiased in theory, the practical application of the technique is often biased by the necessity of introducing a guard zone at one side of the disector to counter lost caps and/or optical limitations. Restricting the disector within the section thickness potentially introduces bias in two ways. First, the need to measure section thickness in order to obtain the disector height/section thickness fraction is challenging since both microcator measurements, microtome block advance, and measurements on re-embedded sections are potentially biased. Second, disector placement is not uniform random within the section thickness resulting in a bias in most sections with inhomogeneous cell distribution along the z axis. Re-embedded 2-hydroxyethylmethacrylate (hereafter methacrylate) sections were inspected for lost caps to evaluate the possibility of whole section thickness counting with the optical fractionator technique and hippocampal granular cell nucleoli density differences along the z axis were assessed with a z axis analysis. No lost caps were found in the examined re-embedded tissue and an inhomogeneous cell distribution through the section thickness was observed. In thick methacrylate sections devoid of lost caps sampling through the entire section thickness could be an acceptable alternative to the use of guard zones and the consequent biases associated with section thickness measurement and non-random placement of disectors.


Effect of general and epidural anaesthesia on thyroid hormones and immunity in neonates.
The aim of this study was to verify if variations of thyroid hormones related to circumstances of delivery and mode of maternal anaesthesia can contribute to neonatal neutrophil respiratory burst and natural killer cell activity. We evaluated 10 infants born by vaginal delivery (group A), 10 infants born by caesarean section after epidural anaesthesia with lidocaine (group B) and 10 infants born by caesarean section after general anaesthesia with sevoflurane (group C). A significant reduction of neutrophil respiratory burst test was found in groups A and C compared with group B. Natural killer cell (NK) activity with an effector : target ratio of 30 : 1 (NK30) and 10 : 1 (NK10) was significantly higher in group A compared with the B and C groups. In addition, thyroid stimulating hormone (TSH) concentration was significantly reduced in group A compared with the B and C groups. A significant negative correlation was found between TSH and NK30 or NK10. Our results suggest that the mode of delivery and anaesthesia can significantly modify the endocrine-immune system in the newborn. Caesarean section delivery with regional anaesthesia seems to produce fewer modifications of neonatal immune function compared with general anaesthesia.


Impairment of intradimensional shift in an attentional set-shifting task in rats with chronic bilateral common carotid artery occlusion.
Studies of rats with chronic bilateral common carotid artery occlusion (BCCAo), an animal model for vascular dementia (VaD), have reported hippocampus-dependent memory impairment and associated neuropathologies. Patients with VaD also experience attentional shifting dysfunction. However, animal models of VaD have not been used to study attentional function. Therefore, the present study examined attentional function in rats with BCCAo, using attentional set-shifting task (ASST) that required rats to choose a food-baited pot from 2 possible pots. ASST included 6 consecutive sessions including simple discrimination, compound discrimination, intradimensional shifting, extradimensional shifting, and reversals. The BCCAo rats were significantly slower at learning the intradimensional set-shifting task compared to control rats. Previous studies have demonstrated that the cingulate cortex and medial prefrontal cortex are critical to intradimensional and extradimensional set-shifting, respectively. Additionally, inflammatory responses and neuronal dysfunction were observed in rats with chronic BCCAo. In addition, OX-6 positive microglia significantly increased in the forceps minor white matter of BCCAo rats, and glutamate decarboxylase signals co-localized with NeuN were reduced in the anterior cingulate cortex of BCCAo rats, compared to control rats. Impaired neuronal and GABAergic neuronal integrity in the anterior cingulate cortex, damage to white matter, and attentional impairments observed in BCCAo rats suggest dysfunction of brain structures that are associated with attentional impairments observed in patients with VaD.


Spinal CCL2 Promotes Pain Sensitization by Rapid Enhancement of NMDA-Induced Currents Through the ERK-GluN2B Pathway in Mouse Lamina II Neurons.
Previous studies have shown that CCL2 (C-C motif chemokine ligand 2) induces chronic pain, but the exact mechanisms are still unknown. Here, we established models to explore the potential mechanisms. Behavioral experiments revealed that an antagonist of extracellular signal-regulated kinase (ERK) inhibited not only CCL2-induced inflammatory pain, but also pain responses induced by complete Freund's adjuvant. We posed the question of the intracellular signaling cascade involved. Subsequent experiments showed that CCL2 up-regulated the expression of phosphorylated ERK (pERK) and N-methyl D-aspartate receptor [NMDAR] subtype 2B (GluN2B); meanwhile, antagonists of CCR2 and ERK effectively reversed these phenomena. Whole-cell patch-clamp recordings revealed that CCL2 enhanced the NMDAR-induced currents via activating the pERK pathway, which was blocked by antagonists of GluN2B and ERK. In summary, we demonstrate that CCL2 directly interacts with CCR2 to enhance NMDAR-induced currents, eventually leading to inflammatory pain mainly through the CCL2-CCR2-pERK-GluN2B pathway.


Quantifying genotoxicity and non-genotoxicity.
Since the ability to induce genotoxicity is often equated with the potential for initiating the carcinogenic process, a method for quantitating genotoxicity would provide a useful measure for this potential. It is demonstrated herein that CPBS, the Carcinogenicity Prediction and Battery Selection method, provides a useful quantitative measure of genotoxicity as well as allowing for the detailed evaluation of the performance of batteries of short-term tests in order to select those predictive of carcinogenic potential.


Effects of sympathectomy on the in vitro alpha and beta-responses of the parotid gland.
Amylase and K+ resease were measured in slices obtained from innervated and sympathetically denervated rat parotid glands. Amylase release induced by noradrenaline was found to be increased after chronic denervation. The postjunctional component of supersensitivity to noradrenaline was evidenced by an increase in the maximal response to this agonist. The maximal response of denervated glands was blocked by propranolol 10(-5) M. On the other hand, chronic denervation did not modify the alpha-adrenoceptor-mediated response, K+ release, either in the presence or in the absence of ouabain. It is concluded that, after sympathetic denervation, postjunctional supersensitivity develops for the beta-adrenoceptor-mediated but not for the alpha-adrenoceptors-mediated effects of noradrenaline.


A simple, inexpensive method of unilateral sternal retraction.
A method of unilateral sternal retraction for the dissection of internal mammary artery is described. The procedure is safe, simple, and inexpensive.


Regenerating retinal fibers of the goldfish make temporary and unspecific but functional synapses before forming the final retinotopic projection.
Many investigators have examined the retinotectal projection following regeneration, but the mapping technique used in these studies mainly involved recording action potentials from presynaptic terminals. Hence it was not possible to analyse the postsynaptic phenomena underlying the target finding process of the retinal fibers. In the present study, the process of making functional synapses was examined using field potentials generated by small spots of light fixed in the visual field. The results show that regenerating retinal fibers first make functional but temporary, unspecific and diffuse synapses before reaching the target area to form a sharpened retinotopic projection. It is suggested that the formation of synapses subserves an important role in the target finding process.


Effect of prevascularization on in vivo vascularization of poly(propylene fumarate)/fibrin scaffolds.
The importance of vascularization in the field of bone tissue engineering has been established by previous studies. The present work proposes a novel poly(propylene fumarate) (PPF)/fibrin composite scaffold for the development of vascularized neobone tissue. The effect of prevascularization (i.e., in vitro pre-culture prior to implantation) with human mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) on in vivo vascularization of scaffolds was determined. Five conditions were studied: no pre-culture (NP), 1 week pre-culture (1P), 2 week pre-culture (2P), 3 week pre-culture (3P), and scaffolds without cells (control, C). Scaffolds were implanted subcutaneously in a severe combined immunodeficiency (SCID) mouse model for 9 days. During in vitro studies, CD31 staining showed a significant increase in vascular network area over 3 weeks of culture. Vascular density was significantly higher in vivo when comparing the NP and 3P groups. Immunohistochemical staining of human CD-31 expression indicated spreading of vascular networks with increasing pre-culture time. These vascular networks were perfused with mouse blood indicated by perfused lectin staining in human CD-31 positive vessels. Our results demonstrate that in vitro prevascularization supports in vivo vascularization in PPF/fibrin scaffolds.


Exorbitantly enhanced protein gyration and erroneous membrane modification programs in spermatozoa after vasectomy: a biophysical basis for low infertility revival after vasectomy.
Vasectomy induces an immediate biophysical incompetence in epididymal spermatozoa in terms of the erroneous execution of membrane configuration processes, premature membrane melting and untimely protein gyration. Disturbances in the planned expression 'foreign proteins' and the possible 'swinging off' of these molecules from the membrane crystals might tease the immune system and might deprive the spermatozoa of the essential recognizing terminals.


Susceptibility of nosocomial isolates of Candida species to LY121019 and other antifungal agents.
LY121019 is a novel analog of the polypeptide antifungal antibiotic echinocandin B. We investigated the in vitro activity of LY121019, amphotericin B, ketoconazole and 5-fluorocytosine against 131 nosocomial isolates of Candida species: C. albicans (n = 50), C. tropicalis (n = 30), C. rugosa (n = 12), C. parapsilosis (n = 11), C. lusitaniae (n = 10), C. guillermondii (n = 9), and C. krusei (n = 9). In vitro susceptibility testing was performed using a broth microdilution method. The minimal inhibitory concentrations (MIC) of LY121019 were less than or equal to that of the other antifungal agents against C. albicans and C. tropicalis but were generally higher for the other species of Candida. Paradoxical growth at high concentrations, but not at low concentrations, of LY121019 was observed with isolates of C. albicans and C. tropicalis.


Amplification and overexpression of CKS1B at chromosome band 1q21 is associated with reduced levels of p27Kip1 and an aggressive clinical course in multiple myeloma.
The molecular basis for aggressive transformation of multiple myeloma (MM) and other cancers is not completely understood. Global gene expression profiling on highly purified malignant plasma cells from 351 newly diagnosed patients with MM treated with autologous stem cell transplantation revealed a statistically significant over-representation of chromosome 1 genes in a group of 70 genes whose expression was linked to poor outcome. In particular, over-expression of CKS1B, which maps to an amplicon at 1q21 in myeloma and regulates SCF(Skp2)-mediated ubquitination and proteolysis of the cyclin dependent kinase inhibitor p27Kip1 was significantly over-expressed in patients with poor survival. Interphase fluorescence in-situ hybridization revealed that CKS1B expression was strongly correlated with DNA copy number in a subset of 197 cases (P<0.0001) with both measurements. Validated in 224 patients lacking expression analysis, CKS1B gene amplification conferred a poor prognosis (P<0.0001) and was an independent predictor of outcome in multivariate analyses (P=0.002). CKS1B mRNA and protein expression were correlated and both were inversely correlated with p27(Kip1) protein levels. RNA interference of CKS1B messenger RNA in myeloma cell lines led to reduced CKS1B mRNA and protein, an accumulation of p27Kip1, and profound growth inhibition. Based on these data we conclude that over-expression of CKS1B, mainly due to gene amplification, imparts a poor prognosis in MM, possibly as a result of enhanced degradation of p27Kip1.


Characterization of a high-molecular-weight phosphoprotein synthesized by the human malarial parasite Plasmodium falciparum.
During its intra-erythrocytic cycle, Plasmodium falciparum synthesizes a protein of apparent Mr 250,000-300,000. Its precise size is dependent on the P. falciparum isolate examined. This protein contains phosphate covalently bound to one or more serine residues and hence is termed PP300. Monoclonal antibody, McAb4-1F, binds to PP300 on immunoblots of protein extracts from all parasite isolates tested, both those exhibiting and those lacking the knob phenotype. Using McAb4-1F, the polypeptide was shown to be physically associated with the plasma membrane in a membrane-isolation procedure. However, in an indirect immunofluorescence assay the McAb appeared to bind to antigen associated with the erythrocyte plasma membrane in parasitized cells. However, it reacted only to fixed, not unfixed, parasitized erythrocytes indicating that the epitope is not normally exposed to extracellular antibodies. Clone 29-2 was isolated by a McAb4-1F immunoscreen of a P. falciparum complementary DNA (cDNA) expression library created in pUC8. Rat anti-clone serum which was raised to the purified protein encoded by the lacZ-29-2 fusion in pUC8 reacted with PP300 in immunoblots of parasite antigen. In Southern-blot analyses of parasite DNA digested with EcoRI, HindIII, or EcoRV, the 29-2 DNA insert hybridized to more than one fragment even though the insert lacked internal sites for these enzymes. In addition, hybridization studies were conducted using two oligodeoxy-nucleotides which were constructed based on the sequence of a cDNA clone which encoded part of a similar high-molecular-weight P. falciparum protein [Coppel et al., Mol. Biochem. Parasitol. 20 (1986) 265-277]. Analysis of these results indicates that the two cDNA sequences are parts of the same gene or a family of related genes.


Unusual cause of acute abdomen --- ruptured retroperitoneal paraganglioma.
Ruptured retroperitoneal paraganglioma is a rare cause of acute abdomen. Its clinical presentation and laparoscopic features have seldom been reported in the literature. Herein, we report a case of ruptured retroperitoneal paraganglioma that presented as acute abdomen, and its subsequent management.


Cellular and subcellular localization of the 2B-subunit of the NMDA receptor in the adult rat telencephalon.
NMDA receptors (NR) are encoded by a family of genes including those of the NR1 and NR2A-D subunits. In situ hybridization has revealed that NR1, comprising eight splice variants, is ubiquitously expressed in the central nervous system (CNS) while the expression of NR2 isoforms is restricted to particular CNS regions. We report on the cellular and ultrastructural distribution of the NR2B polypeptide in rat telencephalon. In the telencephalon, the hippocampus represented the most intensively immunolabeled region. Here, predominantly the CA pyramidal neurons were heavily stained. Intense immunoreactivity (IR) was also detected in cortical neurons, in particular in pyramidal-like ones of layers II/III and V. On the ultrastructural level, the NR2B subunit was present not only in synaptic complexes where it usually was present in postsynaptic sites but in addition could be located at extrasynaptic sites. Furthermore, preliminary evidence indicates a presynaptic location of NR2B in some rare cases. NR2B antigen distribution is consistent with that of corresponding transcripts. Indeed, NR2B immunoreactivity coincides largely with that for NR1, indicating that both subunits are coexpressed in numerous cortical and hippocampal neurons.


Patterns of sport participation for youth with autism spectrum disorder and intellectual disability.
Little is known about sport participation in youth with Autism Spectrum Disorder (ASD). The current study examined sport characteristics (frequency, diversity, positive social experiences [PSE]) for youth with ASD and intellectual disability compared to youth with intellectual disability alone and explored the personal and contextual correlates of involvement. Parents (N = 409) completed an online survey, and multiple mediation analyses were used to examine the factors that explained the relationships between sport involvement in youth with ASD and intellectual disability. No significant main effects of ASD status were found for frequency or diversity, but youth with intellectual disability alone had higher scores for PSE compared to youth with ASD and intellectual disability. Sociocommunicative abilities, coach relationship and resources mediated the relationship between ASD status and PSE. A better understanding of the factors related to sport is essential for allowing families, service providers and policy makers to improve involvement for youth with ASD.


p27Kip1 knockdown induces proliferation in the organ of Corti in culture after efficient shRNA lentiviral transduction.
The cells in the organ of Corti do not exhibit spontaneous cell regeneration; hair cells that die after damage are not replaced. Supporting cells can be induced to transdifferentiate into hair cells, but that would deplete their numbers, therefore impairing epithelium physiology. The loss of p27Kip1 function induces proliferation in the organ of Corti, which raises the possibility to integrate it to the strategies to achieve regeneration. Nevertheless, it is not known if the extent of this proliferative potential, as well as its maintenance in postnatal stages, is compatible with providing a basis for eventual therapeutic manipulation. This is due in part to the limited success of approaches to deliver tools to modify gene expression in the auditory epithelium. We tested the hypothesis that the organ of Corti can undergo significant proliferation when efficient manipulation of the expression of regulators of the cell cycle is achieved. Lentiviral vectors were used to transduce all cochlear cell types, with efficiencies around 4 % for hair cells, 43 % in the overall supporting cell population, and 74 % within lesser epithelial ridge (LER) cells. Expression of short hairpin RNA targeting p27Kip1 encoded by the lentiviral vectors led to measurable proliferation in the organ of Corti and increase in LER cells number but not hair cell regeneration. Our results revalidate the use of lentiviral vectors in the study and in the potential therapeutic approaches for inner ear diseases, as well as demonstrate that efficient manipulation of p27Kip1 is sufficient to induce significant proliferation in the postnatal cochlea.


Gallium67 scanning compared with physical examination in the preoperative staging of malignant melanoma.
Sixty patients with Stage II malignant melanoma were evaluated in order to compare preoperative gallium67 total body scan, physical examination findings, and ultimate histologic findings in regard to the site of the primary lesion and status of the regional lymph nodes. Physical examination was a more efficient and a more sensitive method of evaluation compared to gallium67 scanning in these patients when assessing nodal involvement.


Segmental splenectomy using the ultrasonic surgical aspirator.
The technique described seems to significantly decrease blood loss in segmental splenectomy. Resection of the damaged splenic segments offers the potential advantage of reducing rebleeding and secondary hemorrhage from sites of repaired lacerations. Also, the viable splenic fragment that is left behind may afford protection from postsplenectomy sepsis. The ultrasonic surgical aspirator seems well suited for the purpose of segmental splenectomy in both the trauma and staging laparotomy setting.


Molecular cloning, characterization and expression analysis of F-type lectin from pearl oyster Pinctada fucata.
F-type lectin is an important type of pattern recognition receptor that can recognize and bind carbohydrate moieties on the surface of potential pathogens through its carbohydrate recognition domains (CRDs). This paper reports the cloning of an F-type lectin (designated as pfF-type lectin) from the pearl oyster (Pinctada fucata) using rapid amplification of cDNA ends (RACE) PCR. The full-length cDNA of this pfF-type lectin contains an open reading frame (ORF) of 588 bp coding for196 amino acids. A signal peptide at the N-terminus of the deduced polypeptide was predicted by the signal P program and the cleavage site is located between the positions of Gly(19)and Tyr(20). Conserved domain search at NCBI revealed the pfF-type lectin domain extends from Lys(55)to Val(192). Semi-quantitative analysis in adult tissues showed that the pfF-type lectin mRNA was abundantly expressed in haemocytes and gill and rarely expressed in other tissues tested. After challenge with lipopolysaccharide (LPS), expression of pfF-type lectin mRNA in haemocytes was increased, reaching the highest level at 4 h, then dropping to basal levels at 36 h. These results suggest that F-type lectin play a critical role in the innate immune system of the pearl oyster P. fucata.


Duration of Antimuscarinic Administration for Treatment of Overactive Bladder Before Which One Can Assess Efficacy: An Analysis of Predictive Factors.
To determine the duration of antimuscarinic therapy for overactive bladder syndrome (OAB) appropriate for assessment of the efficacy of treatment, and to evaluate the possible predictive factors for response to therapy. All OAB patients who visited a urology outpatient clinic of a tertiary referral center and who were prescribed 5 mg of solifenacin or 4 mg of tolterodine extended release capsules daily were enrolled in the study. Patients were asked to continue therapy for 6 months. All enrolled patients completed the patient perception of bladder condition, overactive bladder symptom score (OABSS), and the modified Indevus Urgency Severity Scale questionnaires. All patients underwent uroflowmetry. A total of 164 patients were enrolled and 125 patients (76%) had at least one follow-up visit. The mean follow-up interval was 1 month (range, 0.5-6 months). Sixty-two patients (49.6%; 95% confidence interval [CI], 40.7-58.5) responded to antimuscarinic treatment. The median time for the onset of response was 3 months (95% CI, 1-6). Multivariate Cox proportional-hazards model revealed that elevated baseline OABSS was an independent predictor of responsiveness to therapy. Receiver operating characteristic (ROC) curve analysis revealed an optimal OABSS cutoff value of ≥7, with an area under the ROC curve of 0.79 (95% CI, 0.70-0.88; sensitivity, 91.9%; specificity, 60.7%). The median time for a therapeutic response was 3 months, and OABSS was the only predictor for responsiveness. These findings may serve as a guideline when prescribing antimuscarinic treatment for OAB patients.


Clinical experience with the video-assisted saphenectomy procedure for coronary bypass operations.
Leg wound complications after saphenectomy are frequent after coronary bypass operations and have a detrimental effect on postoperative quality of life and treatment cost. To reduce morbidity, we evaluated a new technique of video-assisted vein harvest. Between March 1996 and October 1996, 50 patients had video-assisted saphenectomy (VAS) and 40 patients had the standard open technique (control group). An additional 13 patients had both procedures (hybrid group). Level of pain, edema, and wound complications were evaluated at discharge and at 2, 4, and 6 weeks postoperatively. The mean operating time for VAS patients was slightly higher than for control (60.6+/-24.7 minutes versus 53.2+/-21.1 minutes; p > 0.05). The average incision length in VAS patients was 13.8+/-8.8 cm for an average of 3.3 grafts per patient. Three VAS procedures were aborted, two because of time constraints, and one because of bleeding, and a segment of vein was lost to injury. The VAS group had considerably less early postoperative pain than the control group (1.7+/-1.2 versus 4.1+/-1.4 [1 = mild, 10 = severe]; p < 0.005) and edema was similar for both groups. Patients in the hybrid group reported less pain in the VAS-operated leg. Serious wound infection occurred in 4 patients, with 2 patients in the control group requiring reoperation for drainage and flap reconstruction. Based on this initial experience, VAS harvesting, although initially more time consuming, is a rapidly mastered technique, results in shorter overall incision length, and is associated with considerably less postoperative pain than the standard open technique.


Determination of the leakage from Phenyl-Sepharose Cl-4B, Phenyl-Sepharose FF and Phenyl-Superose in bulk and column experiments.
The release of ligands from Phenyl-Sepharose CL-4B, Phenyl-Sepharose FF and Phenyl-Superose has been studied in bulk and column experiments. The leakage products have been identified and quantified by liquid chromatography, fluorescence spectroscopy and proton NMR spectroscopy. It is demonstrated that the leakage occurs primarily through hydrolysis of the agarose support. However, leakage via ether cleavage of the spacer arm-ligand moiety is also observed especially for Phenyl-Superose. The release of ligands at acidic pH is in agreement with a first-order reaction and correspondingly the rate constants have been estimated for all three gels at pH 1 and 2. These show that 50% of the ligands are intact after 15 years of incubation at pH 2. Phenyl-Superose is the most stable gel at acidic pH, whereas Phenyl-Sepharose CL-4B and Phenyl-Sepharose FF are the most stable at neutral and basic pH.


Lower Extremity Movement Quality and the Internal Training Load Response of Male Collegiate Soccer Athletes.
Training load and movement quality are associated with injury risk in athletes. Given these associations, it is important to understand how movement quality may moderate the training load so that appropriate injury-prevention strategies can be used. To determine how absolute and relative internal training loads change during a men's National Collegiate Athletic Association (NCAA) soccer season and how movement quality, assessed using the Landing Error Scoring System (LESS), moderates the relative internal training load. Prospective cohort study. Division I athletics. One NCAA Division I male collegiate soccer team was recruited and followed over 2 consecutive seasons. Fifty-two athletes (age = 19.71 ± 1.30 years, height = 1.81 ± 0.06 m, mass = 75.74 ± 6.64 kg) consented to participate, and 46 met the criteria to be included in the final statistical analysis. Daily absolute internal training load was tracked over 2 seasons using a rated perceived exertion scale and time, which were subsequently used to calculate the absolute and relative internal training loads. Movement quality was assessed using the LESS and participants were categorized as poor movers (LESS score ≥5) or good movers (LESS score ≤4). The 46 athletes consisted of 29 poor movers and 17 good movers. Absolute (P < .001) and relative (P < .001) internal training loads differed across the weeks of the season. However, movement quality did not moderate the relative internal training load (P = .264). Absolute and relative training loads changed across weeks of a male collegiate soccer season. Movement quality did not affect the relative training load, but future researchers need to conduct studies with larger sample sizes to confirm this result.


High-Throughput Screening to Identify Modulators of Sarcospan.
High-throughput screening enables the discovery of disease-modifying small molecules. Here, we describe the development of a scalable, cell-based assay to screen for small molecules that modulate sarcospan for the treatment of Duchenne muscular dystrophy. We detail the hit validation pipeline, which includes secondary screening, gene/protein quantification, and an in vitro membrane stability assay.


Follicular Dynamics during Estrous Cycle of Pubertal, Mature and Postpartum Crossbred (Nili Ravi × Jianghan) Buffaloes.
The follicular dynamics is used as a reliable indicator for reproductive management in livestock. However, the follicular dynamics (follicle wave emergence, estrus cycle length, diameter of dominant follicle, follicular growth and atretic phases) during the estrous cycle of crossbred (Nili Ravi-Jianghan) buffalo is still unexplored. Therefore, the present study aimed to observe the follicular dynamics in estrous cycle of crossbred buffaloes at different physiological stages (pubertal; n = 28, sexual mature; n = 22 and postpartum; n = 18). In the present study, the follicular dynamics were ultrasonically examined at 12 h intervals throughout an estrous cycle during the breeding season. The results indicate that about 86.76% (59/68) crossbred buffaloes, irrespective of physiological stage, exhibited two follicular waves in estrous cycle with an average estrus cycle length was 20.7 ± 0.4 days. The estrus cycle length was significantly shorter (p < 0.05) in pubertal buffaloes (19.4 ± 0.4 days) compared with sexual mature (21.5 ± 0.3 days) and postpartum (21.9 ± 0.4 days) buffaloes. The first follicular wave emerged on same day during one- (pubertal vs. postpartum), two- (pubertal vs. mature vs. postpartum) or three-wave (mature vs. postpartum) estrous cycle buffaloes. The maximum diameter of dominant follicle (DF) in pubertal, sexually mature and postpartum crossbred buffaloes was 9.6 ± 2.0 mm, 10.6 ± 0.5 mm and 12.6 ± 0.7 mm with growth rate of 1.08 ± 0.04 mm/day, 0.92 ± 0.04 mm/day, and 0.9 ± 0.07 mm/day, respectively. In conclusion, similar to other buffalo breeds, Nili Ravi-Jianghan crossbred buffaloes showed the two-wave follicular pattern dominantly with an average duration of ~20 days estrous cycle. The observed follicular dynamics can be used as a reliable indicator for synchronization and fixed-time artificial insemination (FTAI) programs to improve the fertility of crossbred buffaloes.


Oxalate stone disease after intestinal resection.
There have been 543 jejuno-ileal bypass patients screened for the presence of urinary calculi 1 to 6 years postoperatively. Of these patients 9 per cent have had 1 to 2 calculi during the followup and 3 per cent have had multiple calculi. Ninety-four per cent of the recovered calculi consisted entirely of calcium oxalate. Seven patients had a history of stones before the bypass, 6 of whom have had additional stones postoperatively. To define the conditions associated with stone formation in these patients measurements of serum and urinary oxalate concentration, urinary calcium oxalate saturation, urinary crystal size distribution, and the rates of intestinal oxalate absorption and urinary crystallization have been performed on patients who did and did not have stones postoperatively. On the basis of these studies it appears that the patients in whom stones formed differ from those in whom they did not form only in the rate of urinary crystallization and in the number of large crystal particles present in the urine. Evaluation of current therapeutic modalities in terms of the capability to correct these stone-forming characteristics and to reduce actual calculus formation reveals that the only successful regimen is that which includes an extreme reduction of oxalate ingestion.


Effects of automatic mechanical peripheral stimulation on gait biomechanics in older adults with Parkinson's disease: a randomized crossover clinical trial.
Automated mechanical peripheral stimulation (AMPS) is a rehabilitation technique suggested to correct gait abnormalities on Parkinson's disease. Although previous studies have suggested increments in functional performance and gait speed after AMPS intervention, little is known about its effect on gait biomechanics. To analyze the effect of an AMPS session on functional performance and gait biomechanics in subjects with Parkinson's disease. Twenty-eight subjects aged 67±3 years old participated in this study. Kinematics and muscle activation were recorded during walking at a preferred gait speed before and after AMPS and sham interventions. Footswitches sensors were used to record the kinematic parameters. Electromyographic (EMG) signals of tibialis anterior (TA) and gastrocnemius lateralis (GL) were recorded. Timed up and go (TUG) test and Short Physical Performance Battery (SPPB) were performed to assess functional performance. GL activation increased after AMPS intervention before and after heel strike (p = 0.04; p < 0.01) and before and after toe-off (p = 0.013; p = 0.038). Also, after AMPS intervention, TA activation increased after heel strike (p = 0.007); and after sham intervention, TA activation reduced before and after heel strike (p = 0.038; and p = 0.007) and before toe-off (p = 0.013). The time of TUG test was shorter after AMPS intervention (p = 0.015). AMPS intervention changed the EMG activation of ankle muscles during walking and functional performance. However, AMPS intervention did not change gait kinematics.


A web-based clinical pedagogy program to enhance registered nurse preceptors' teaching competencies - An innovative process of development and pilot program evaluation.
Registered Nurse Preceptors guide students to integrate theory into practice, assess clinical competencies, and enhance problem-solving skills. Researches have indicated that the teaching competencies of nurse preceptors can be transferred to students' clinical learning. The aims of the study are to develop a web-based clinical pedagogy (WCP) program for Registered Nurse Preceptors and conduct pilot program evaluation. A three-step process was applied to integrate the theoretical framework, evidence from the systematic review, and content validity by the experts and pilot test with the Registered Nurse Preceptors in the content and technical development of the program. The WCP program has unique features including use of dashboard, interactive videos, consultation with experts, discussion forum and backend data analysis. A committee of six content experts evaluated the comprehensiveness, appropriateness, and relevancy of the program. The item-Content Validity Index (CVI) score ranged from 0.83 to 1.00 and the scale-CVI score was 0.87, which indicated that the WCP program had a strong content validity. Ten nurse preceptors were invited to use the WCP program. Preceptors shared that the website was easy to use and navigate. They commented that the videos in each module are beneficial for nurses to understand the real situation in the clinical setting. This feature also makes the website more interactive. Feedback from preceptors was subsequently used to further refine the program. The WCP program is an evidence-based program that provides a comprehensive coverage on clinical teaching pedagogy and assessment strategies. The unique web-based technology and interactive features provide a platform for nurse preceptors to discuss clinical encounters with peers and consult experts. The flexible and resource-rich nature of web-based learning encourages nurses to use it for continuing education.


Two Decades of Cardiac Amyloidosis: A Danish Nationwide Study.
Cardiac amyloidosis (CA) has been associated with poor outcomes. Screening studies suggest that CA is overlooked-especially in the elderly. Recent advances in treatment have brought attention to the disease, but data on temporal changes in CA epidemiology are sparse. The aim of this work was to describe all patients with CA in Denmark, examining changes in patient characteristics from 1998 to 2017. All patients with any form of amyloidosis diagnosed from 1998 to 2017, as well as their comorbidities and pharmacotherapy, were identified in Danish nationwide registries. CA was defined as any diagnosis code for amyloidosis combined with a diagnosis code for heart failure, cardiomyopathy, or atrial fibrillation or a procedural code for pacemaker implantation, regardless of the order. The index date was defined as the date of meeting those criteria. Patients were divided into 5-year periods by index date. For comparison, we also included control subjects (1:4 ratio) from the general population. CA criteria were met by 619 patients. Comparing 1998-2002 vs 2013-2017, the median age at baseline increased from 67.4 years (interquartile range [IQR]: 53.9-75.2 years) to 72.3 years (IQR: 66.0-79.3 years). The frequency of male patients increased from 62.1% to 66.2%. The incidence of CA rose from 0.88 to 3.56 per 100,000 person-years in the Danish population aged ≥65 years, and the 2-year mortality decreased from 82.6% (IQR: 69.9%-90.5%) to 50.2% (IQR: 43.1%-56.9%). Compared with control subjects, the mortality among CA patients was significantly higher (log-rank test: P < 0.0001). CA, as defined in this study, was increasingly diagnosed on a national scale. The increasing frequency of male patients and median age suggest that wild-type transthyretin amyloidosis is driving this increase. Greater recognition of earlier, less advanced cases might explain decreasing mortality.


Cytologic characteristics of congenital mesoblastic nephroma in fine-needle aspiration cytology: a case report.
The cytologic features of congenital mesoblastic nephroma (CMN) as recognized in smears of fine-needle aspirated cytology (FNAC) are reported. These included spindle- and tadpole-shaped cells with round to oval nuclei having small nucleoli and a smooth contour. The cytoplasm of these cells was dense and homogeneously stained. The background was composed of mucoid fibrillar material. The findings appear to be different from other types of renal tumors in infancy and specific enough for this tumor to allow diagnosis by FNAC.


Neurosyphilis.
Syphilis and its consequent central nervous system sequelae remain clinical problems, especially when presenting in the unfamiliar acute meningeal forms of syphilitic meningitis and meningovascular syphilis. The diagnosis of neurosyphilis of all types depends on evaluation of spinal fluid reactivity as evidenced by pleocytosis and increased protein content with reactive serology. The cerebrospinal fluid is always abnormal in active disease, and only active disease responds to treatment. Penicillin remains the drug of choice for all forms of neurosyphilis, but disease progression has been frequently reported following the use of penicillin G benzathine. Documentation of cerebrospinal fluid resolution over the months following penicillin therapy is required to confirm curative treatment.


Tooth caries detection by curve fitting of laser-induced fluorescence emission: a comparative evaluation with reflectance spectroscopy.
Nitrogen laser-induced fluorescence (LIF) spectra of sound tooth consists of two broad bands centered at 440 and 490 nm, with two apparent side bands on either side. In order to locate the exact peak position of these bands and to effectively utilize the LIF spectral signatures for detection of tooth caries, the LIF spectra were curve-fitted using Gaussian spectral functions and the results were compared with those from diffuse reflectance spectral measurements. The excitation light at 337.1 nm was guided to the sound and caries-affected tooth samples through the central fiber of the fiber-optic probe of a laser-induced fluorescence reflectance spectroscopy (LIFRS) system. Six surrounding fibers of the probe collect tooth fluorescence or diffuse reflectance from the lesion and direct it to a miniature spectrometer. The in vitro spectra were obtained from healthy enamel, dentin, and pulp level tooth caries. As compared to sound tooth, the caries tooth showed lower fluorescence and reflectance intensities in the 350-700 nm region. The deconvoluted peaks in the LIF spectra of sound tooth were found centered at 403.80, 434.20, 486.88, and 522.45 nm, whereas in the case of pulp level caries, a new peak was observed at 636.78 nm. Curve-fitted parameters, such as peak center, Gaussian curve area, full width at half intensity maximum (FWHM), and their ratios, were also found to vary with the stage of tooth caries. The ratios involving the 435 nm band, such as F405/F435, F435/F490, and F435/F525 ratios derived from curve-fitted areas and amplitudes, were found to be sensitive to discriminate between sound, dentin, and pulp level caries. Among the various diffuse reflectance spectral intensity ratios, the R500/R700 was found to be most sensitive to distinguish between pulp and dentin level caries. Nitrogen laser-excited fluorescence spectral studies were found to be more suited for detection of caries lesions. The LIF measurement with spectral analysis, done by curve fitting, outscores the diffuse reflectance methodology and shows the potential to screen different levels of tooth decay in a clinical setting.


LuFLA1PRO and LuBGAL1PRO promote gene expression in the phloem fibres of flax (Linum usitatissimum).
Cell type-specific promoters were identified that drive gene expression in an industrially important product. To identify flax (Linum usitatissimum) gene promoters, we analyzed the genomic regions upstream of a fasciclin-like arabinogalactan protein (LuFLA1) and a beta-galactosidase (LuBGAL1). Both of these genes encode transcripts that have been found to be highly enriched in tissues bearing phloem fibres. Using a beta-glucuronidase (GUS) reporter construct, we found that a 908-bp genomic sequence upstream of LuFLA1 (LuFLA1PRO) directed GUS expression with high specificity to phloem fibres undergoing secondary cell wall development. The DNA sequence upstream of LuBGAL1 (LuBGAL1PRO) likewise produced GUS staining in phloem fibres with developing secondary walls, as well as in tissues of developing flowers and seed bolls. These data provide further evidence of a specific role for LuFLA1 in phloem fibre development, and demonstrate the utility of LuFLA1PRO and LuBGAL1PRO as tools for biotechnology and further investigations of phloem fibre development.


Cyclin G2 upregulation impairs migration, invasion, and network formation through RNF123/Dvl2/JNK signaling in the trophoblast cell line HTR8/SVneo, a possible role in preeclampsia.
Disruption of extravillous trophoblast (EVT) migration and invasion is considered to be responsible for pathological placentation in preeclampsia (PE). Cyclin G2 (CCNG2) is an atypical cyclin that inhibits cell cycle progression. However, its biological function and underlying molecular mechanism in PE are poorly understood. In this study, clinical data demonstrated that CCNG2 was significantly upregulated in PE placenta and associated with invasive EVT dysfunction. Additionally, Ccng2 knockout led to an attenuation of PE-like symptoms in the PE mouse model produced via treatment with NG-nitro-L-arginine methyl ester (L-NAME). In vitro, CCNG2 inhibited the migration, invasion, and endothelial-like network formation of human trophoblast cell line HTR8/SVneo. Mechanically, CCNG2 suppressed JNK-dependent Wnt/PCP signaling and its downstream indicators including epithelial-to-mesenchymal transition (EMT) markers and matrix metalloproteinases (MMPs) via promoting the polyubiquitination degradation of dishevelled 2 (Dvl2) protein in HTR8/SVneo cells. We also discovered that the E3 ligase Ring finger protein 123 (RNF123), as a novel CCNG2 target among HTR8/SVneo cells, interacted with Dvl2 and participated in CCNG2-induced polyubiquitination degradation of Dvl2. Moreover, we verified that the treatment of HTR8/SVneo cells with RNF123-specific siRNA improved polyubiquitination-induced degradation of Dvl2 and the activity of Wnt/PCP-JNK signaling mediated by CCNG2. Taken together, our results reveal that the CCNG2/RNF123/Dvl2/JNK axis may be involved in the pathogenesis and progression of PE through trophoblastic cell function modulation, thus probably providing us with new therapeutic strategies for PE treatment.


Double-barrel stenting of distal left main stenosis in a patient with acute coronary syndrome: intravascular ultrasound and optical coherence tomography follow-up at six months.
A 58-year-old man presented with frequent episodes of angina at rest. A diagnosis of anterior non-ST elevation myocardial infarction was made. Coronary angiography performed on the day of admission revealed a significant stenosis (50% to 60%) of the distal left main stem (LMS) extending to the ostia of the left anterior descending and left circumflex arteries. Coronary artery bypass graft surgery was advised; however, the patient consistently declined this option. Kissing balloon predilation was performed at the LMS bifurcation, and two stents of the same diameter and length (4.0 mm × 18 mm) were simultaneously deployed at the same high pressure (18 atm) spanning the entire length of the LMS, and extending into the left anterior descending and left circumflex arteries beyond the bifurcation lesion. Six months later, intravascular ultrasound and optical coherence tomography revealed neointimal hyperplasia, especially in the artificial septum.


A dilatancy assay for nucleoid denaturation: the centrifugation-dependent clumping of denatured spermidine nucleoids.
The ability of low centrifugal forces to convert denatured spermidine nucleoids from Escherichia coli into nonsedimentable macroscopic clumps is the basis of a rapid and simple, nonisotopic assay for nucleoid denaturation.


A harmony search-based H-infinity control method for islanded microgrid.
This paper proposes a harmony search (HS) based H-infinity (H∞) control method to promote the conventional droop control method. The proposed method is used to enhance the performance of the voltage/frequency (V/F), controller. It can regulate both voltage and frequency to their rated values while enhancing autonomous microgrid (MG) power quality. The results gained from the proposed controller were compared with the results achieved by using the model predictive control (MPC) technique to show the applicability of the proposed controller. On top of that, a comparison between different controllers presented in this paper is performed.


Accuracy of noninvasive fibrosis scores in predicting advanced fibrosis in pediatric patients after liver transplantation.
Liver biopsy is the gold standard to stage fibrosis in liver disease. Several scoring systems have been studied to predict advanced fibrosis in liver disease. Those scores have not been validated in pediatric liver transplant patients. Evaluate the performance of three fibrosis scores (FSc) in assessing the presence of advanced fibrosis (AF) in children after orthotopic liver transplantation (OLT). Patients < 20 years of age who underwent liver biopsy post-OLT with laboratory values within 1 month of the biopsy were included. Fibrosis was determined by an experienced pathologist (F0-4). We defined AF as F3-4. The following FSc were calculated: AST/ALT ratio, APRI, and FIB-4 index. Receiver operating characteristic curve analysis was done to assess the FSc performance in predicting AF. A total of 232 biopsies were analyzed, of those 42 (18.1%) showed AF (F3-4). FIB-4 was significantly higher in patients with AF compared to those without AF [median value of 1.1 [0.7, 3.0] and 0.6 [0.2, 1.4], respectively (p = .02)]; however, FIB-4 had satisfactory accuracy to diagnose AF with significant overlap and AUC of 0.68 (CI 0.56-0.81). Cutoff points of 0.2 and 3.03 were used to rule in and rule out AF, respectively. AST/ALT and APRI were not significantly different between patients with and without AF. Even though FIB-4 had satisfactory accuracy in detecting AF in pediatric transplant patients, noninvasive hepatic FSc developed in adults still performed poorly. Our results highlight the need to develop a reliable pediatric FSc.


A history of randomized task designs in fMRI.
In the early days of fMRI, data were acquired using methods adapted mainly from PET imaging. Sets of similar stimuli were presented in extended blocks, with stimulus conditions changing from block to block. While this method provided optimum statistical power, it also presented a variety of potential confounds, including changes in attention, alertness, expectancy, and practice effects within and between blocks. Event-related paradigms using unpredictable, randomized stimulus sequences had been used in EEG studies for over 50 years before the development of fMRI, and provided a means to overcome these issues. However, the temporal dispersion of BOLD fMRI activity resulted in responses to successive stimuli adding together, making it difficult to perform rapid event-related paradigms using fMRI. Here we describe the background and history of methods developed to overcome this limitation, allowing rapid, randomized stimulus sequences to be used with fMRI. The advantages and disadvantages of this technique and how these methods have been applied in a variety of experimental settings are discussed.


A new treatment for urethral strictures: a permanently implanted urethral stent.
We describe a new urethral stent, originally developed for endovascular use, that we have implanted into 8 patients with urethral strictures. The stent is woven in the form of a tubular mesh from surgical grade stainless steel wire and is self-expanding when released from its small diameter delivery catheter. All patients have been treated successfully with a good caliber urethra visible on urethrography and direct endoscopy, and with improved urine flow rates. Mean followup of these patients is 8 months (range 6 months to 1 year). Urethroscopy had demonstrated complete epithelial covering of the implant at 4 to 6 months. Although the followup is short it seems that this simple technique may offer a lasting treatment for many urethral strictures.


Income inequality, illiteracy rate, and life expectancy in Brazil.
The link between income disparities and health has been studied mostly in developed nations. This study assesses the relationship between income disparities and life expectancy in Brazil and measures the impact of illiteracy rates on the association. The units of analysis (n = 27) are all the Brazilian states and the federal capital. Simple and multiple linear regressions were performed to measure the association between income disparity, measured by the Gini coefficient, gross domestic product (GDP) per capita, and illiteracy rate. Data came from publicly available sources at the Brazilian Ministry of Health and the Brazilian Institute of Geography and Statistics. Income disparities and illiteracy rates were negatively associated with life expectancy in Brazil. GDP per capita was positively associated with life expectancy. The inclusion of illiteracy rates in the regression model removed the effect of income disparities. Illiteracy rate is strongly associated with life expectancy in Brazil. This finding is in accord with reports from the United States and has implications for health policy and planning for both developed and developing countries.


Interaction of prazosin with model membranes--a Langmuir monolayer study.
In this study, the effect of prazosin on the molecular interactions between cholesterol and 1,2-dipalmitoylphosphatidylcholine (DPPC) within a monolayer at an air-water interface was studied. A mixed cholesterol/DPPC monolayer was employed as a model lipid membrane. From a detailed analysis of surface pressure-area isotherms, it was concluded that DPPC and cholesterol were miscible and formed non-ideal monolayers on prazosin solution. The thermodynamic stability of the mixed monolayers was investigated by analyzing the free energy of mixing. It was found that the mixed monolayers were more stable than the single component monolayers. Monolayers spread over a subphase with prazosin were more compressible than those spread on pure water. To quantify the effect of prazosin on the monolayer stability, the Gibbs free energy due to the presence of prazosin in the water subphase was calculated. It was found that prazosin penetrated and destabilized mixed cholesterol/DPPC monolayers. However, a comparison of the drug penetration into the pure DPPC monolayer and the mixed cholesterol/DPPC monolayer showed that the presence of cholesterol in the DPPC monolayer considerably restricted the drug penetration.